June 24, 2014 Dr. Bernice Hecker, MD, MHA, FACC Contractor Medical

June 24, 2014

Dr. Bernice Hecker, MD, MHA, FACC Contractor Medical Director Noridian Healthcare Solutions, LLC 900 42nd Street S. P.O. Box 6740 Fargo, ND 58108-6740

Re: LCD DL35236- Draft LCD for Stereotactic Radiation Therapy: Stereotactic Radiosurgery (SRS) and Stereotactic Body Radiation Therapy (SBRT)

Dear Dr. Hecker:

The American Society for Radiation Oncology* (ASTRO) appreciates the opportunity to review and provide comments on the Noridian Healthcare Solutions, LLC Jurisdiction E, draft LCD DL35236 on Stereotactic Radiosurgery (SRS) and Stereotactic Body Radiation Therapy (SBRT). Noridian accepted some of ASTRO’s previous recommendations sent on April 17, 2012, but in light of recently published data, ASTRO respectfully submits the following comments.

Stereotactic Radiosurgery (SRS) Indications

The draft LCD states that patients with more than three primary or metastatic brain lesions must be enrolled in an IRB-approved clinical trial or appropriate clinical registry for coverage. ASTRO recommends the removal of the limit on the number of primary or metastatic lesions to determine medical necessity. We recommend a more nuanced approach in which the number of intracranial lesions is not the essential consideration in making a determination to use SRS.

A large body of published literature shows that patients presenting with greater than three lesions and excellent performance status also benefit from SRS1-5. Recent studies found Karnofsky Performance Status (KPS) score, not the number of brain metastases, significantly correlated with overall survival2-4. The total intracranial volume rather than the number of metastases has been demonstrated to be an important predictor of survival in two major series4,5. While ASTRO supports the accrual of additional data and research, including the creation of a national SRS

* ASTRO is the premier radiation oncology society in the world, with more than 10,000 members who are physicians, nurses, biologist, physicists, radiation therapists, dosimetrists and other health care professionals that specialize in treating patients with radiation therapies. As the leading organization in radiation oncology, the Society is dedicated to improving patient care through professional education and training, support for clinical practice and health policy standards, advancement of science and research, and advocacy. ASTRO publishes two medical journals, International Journal of Radiation Oncology, Biology, Physics (www.redjournal.org) and Practical Radiation Oncology (www.practicalradonc.org); developed and maintains an extensive patient website, www.rtanswers.org; and created the Radiation Oncology Institute (www.roinstitute.com), a non-profit foundation to support research and education efforts around the world that enhance and confirm the critical role of radiation therapy in improving cancer treatment. To learn more about ASTRO, visit www.astro.org.

ASTRO Comments – Noridian Draft LCD (DL35236) for SRS and SBRT Page 2

registry, which we anticipate joining with another professional society, we believe that the limiting criteria listed in items 7,8,and 9 under “Indications for SRS/SBRT (for Cranial Lesions only)” to be unnecessary and overly restrictive. Likewise, item #3 should be deleted.

Additionally, the draft policy declares cobalt-60 pallidotomy a non-covered service. In Chapter 13 of the “ASTRO/ACR Guide to Radiation Oncology Coding 2010” under Common Clinical Indications, ASTRO states that SRS may be used as a course of treatment in movement disorders such as Parkinson’s disease, essential tremor, and other disabling tremors when open neurosurgical thalamotomy cannot be performed and medical therapy is unsatisfactory. Several studies support this approach6-8. The draft policy also does not include ICD-9-CM code 333.1 (Essential and Other Specified Forms of Tremor) in the list of codes that support medical necessity. ASTRO’s SRS Model Policy recommends coverage for ICD-9-CM code 333.1 “be limited to the patient who cannot be controlled with medications, has major systemic disease or coagulopathy, and who is unwilling or unsuited for open surgery. Coverage should further be limited to unilateral thalamotomy.” While ASTRO agrees that SRS is not the primary treatment for all patients suffering from functional disorders, stereotactic radiotherapy offers an appropriate alternative for select cases. Thus, we recommend removing the cobalt-60 pallidotomy non- coverage statement and adding ICD-9-CM code 333.1 to the final policy.

Stereotactic Body Radiation Therapy (SBRT) Indications

ASTRO proposes Noridian remove the requirement that prostate cancer patients be enrolled in an IRB-approved clinical trial or registry. ASTRO updated its SBRT Model Policy in April 2013 to reflect the many clinical studies now supporting SBRT in the treatment of prostate cancer. The clinical data has matured to a point where SBRT represents an appropriate alternative for select patients with low to intermediate risk prostate cancer.

A recently published pooled analysis of 1100 patients enrolled on prospective trials of SBRT for prostate cancer demonstrates biochemical relapse-free survival rates and quality of life outcomes that compare favorably with other definitive treatments for prostate cancer 9,10. After a median dose of 36.25 Gy in 4-5 fractions, the 5-year biochemical relapse free survival rate was 93% for all patients; 95%, 83% and 78% for GS 6, 7 and 8, respectively; and 95%, 84% and 81% for low-, intermediate- and high-risk patients, respectively. A transient decline in the urinary and bowel domains was observed within the⩽ first 3 months⩾ after SBRT which returned to baseline status or better within 6 months and remained so beyond 5 years. In addition, SBRT’s cost effectiveness relative to other forms of radiation therapy of prostate cancer11,12 in this is appealing in this setting.

Additionally, the draft policy lacks crucial ICD-9-CM codes indicated for SBRT including those for “recurrent pelvic and head and neck tumors that have recurred after primary irradiation”, listed on page seven of the LCD. SBRT may also treat patients with recurrent nodal metastasis who have already undergone prior conventionally fractionated radiotherapy and thus the corresponding diagnosis codes should be included in the policy. ASTRO recommends the following ICD-9-CM codes be added to the final LCD:

• 147.0-149.9 Malignant neoplasms of the pharynx

ASTRO Comments – Noridian Draft LCD (DL35236) for SRS and SBRT Page 3

• 160.0-161.9 Malignant neoplasms of the nasal cavities, accessory sinuses, and larynx • 154.0-154.8 Malignant neoplasms of the rectum and anus • 179-184.9 Malignant neoplasms of the female reproductive system • 195.2 Malignant neoplasm of abdomen • 195.3 Malignant neoplasm of pelvis • 196.0-196.9 Secondary and unspecified malignant nodal neoplasms

Stereotactic Radiotherapy Coding

Historically, in the hospital outpatient environment, CMS utilized G-codes to distinguish between robotic and non-robotic SBRT and SRS. The agency recently reviewed current radiotherapy equipment technology and found that most linac-based treatment platforms incorporate some type of robotic capability. CMS therefore concluded that it is no longer necessary to continue distinguishing robotic and non-robotic linear accelerators. Beginning January 1, 2014, CMS replaced the existing four HCPCS codes: G0173, G0251, G0339, and G0340 with the SRS CPT® code 77372 and SBRT code 77373. The chart below provides a summary of these changes:

2013 Descriptor 2014 Descriptor ® CPT CPT Code Code

G0173 Linear accelerator stereotactic Radiation treatment delivery, radiosurgery, complete course of therapy in stereotactic radiosurgery (SRS), one session. 77372 complete course of treatment of cranial lesion(s) consisting of 1 session; linear accelerator based. G0251 Linear accelerator based stereotactic radiosurgery, delivery including collimator changes and custom plugging, fractionated treatment, all lesions, per session, maximum five sessions per course of treatment. G0339 Image-guided robotic linear accelerator- Stereotactic body radiation therapy, based stereotactic radiosurgery, course of treatment delivery, per fraction to 1 therapy in one session, or first session of 77373 or more lesions, including image fractionated treatment guidance, entire course not to G0340 Image-guided robotic linear accelerator- exceed 5 fractions. based stereotactic radiosurgery, delivery including collimator changes and custom plugging, fractionated treatment, all lesions, per session, second through fifth sessions, maximum five sessions per course of treatment

ASTRO Comments – Noridian Draft LCD (DL35236) for SRS and SBRT Page 4

The draft coverage policy lists G-codes in the “CPT/HCPCS Code” section. In order to avoid any confusion, ASTRO recommends Noridian remove all G-codes from the final LCD. Enclosed for your reference are the current version of ASTRO’s SRS and SBRT Model Coverage Policies. ASTRO recently mailed Noridian complimentary copies of the ASTRO/ACR Guide to Radiation Oncology Coding 2010: 2014 Supplement. Chapters 13 and 14 provide extensive coding information for these technologies including the codes integral to the process of care. Since no specific codes for SRS planning or for the professional component of SBRT planning exist, other codes such as CPT code 77295 (3-dimensional radiotherapy plan, including dose-volume histograms) or IMRT CPT code 77301 (Intensity modulated radiotherapy plan, including dose-volume histograms for target and critical structure partial tolerance specifications) are appropriate.

Thank you for your consideration of our comments. Should you have any questions or wish to discuss SRS/SBRT and our recommendations further, please contact ASTRO’s Assistant Director of Health Policy, Anne Hubbard, at (703) 839-7394 or via email at [email protected].

Sincerely,

Laura I Thevenot Chief Executive Officer cc: Arthur Lurvey, MD Richard Whitten, MD, MBA, FACP

Enclosures: ASTRO SRS Model Policy ASTRO SBRT Model Policy ASTRO/ACR Guide to Radiation Oncology Coding – Chapter 13 and 14 Radiotherpetuic and surgical management for newly diagnosed brain metastasis(es): an American Society for Radiaion Oncology evidence based guideline

References: 1. Serizawa T, Hirai T, Nagano O, et al. Gamma knife surgery for 1–10 brain metastases without prophylactic whole-brain radiation therapy: analysis of cases meeting the Japanese prospective multi-institute study (JLGK0901) inclusion criteria. J Neurooncol. 2010; 98(2): 163-167. 2. Hunter GK, Suh JH, Reuther AM, et al. Treatment of five or more brain metastases with stereotactic radiosurgery. Int J Radiat Oncol Biol Phys. 2012; 83(5): 1394-1398. 3. Raldow AC, Chiang VL, Knisely JP, et al. Survival and intracranial control of patients with 5 or more brain metastases treated with gamma knife stereotactic radiosurgery. Am J Clin Oncol. 2013; 36(5): 486-490. 4. Bhatnagar AK, Flickinger JC, Kondziolka D, Lunsford LD. Stereotactic radiosurgery for four or more intracranial metastases. Int J Radiat Oncol Biol Phys. 2006; 64(3):898-903. 5. Likhacheva A, Pinnix CC, Parikh NR, et al. Predictors of survival in contemporary practice after initial radiosurgery for brain metastases, Int J Radiat Oncol Biol Phys. 2013; 85(3): 656-661.

ASTRO Comments – Noridian Draft LCD (DL35236) for SRS and SBRT Page 5

6. Kooshkabadi A, Lunsford LD, Tonetti D, et al. Gamma Knife thalamotomy for tremor in the magnetic resonance imaging era. J Neurosurg. 2013; 118(4):713-8. 7. Ohye C1, Higuchi Y, Shibazaki T, et al. Gamma knife thalamotomy for Parkinson disease and essential tremor: a prospective multicenter study. Neurosurgery. 2012; 70(3):526-535. 8. Young RF, Li F, Vermeulen S, Meier R. Gamma Knife thalamotomy for treatment of essential tremor: long-term results. J Neurosurg. 2010; 112(6):1311-1317. 9. King CR, Freeman D, Kaplan I, et al. Stereotactic body radiotherapy for localized prostate cancer: pooled analysis from a multi-institutional consortium of prospective phase II trials. Radiother and Oncol. 2013; 109(2): 217-221. 10. King CR, Collins S, Fuller D, et al. Health-related quality of life after stereotactic body radiation therapy for localized prostate cancer: results from a multi-institutional consortium of prospective trials. Int J Radiat Oncol Biol Phys. 2013; 87(5): 939-945. 11. Hodges JC, Lotan Y, Boike TP, et al. Cost-effectiveness analysis of stereotactic body radiation therapy versus intensity-modulated radiation therapy: an emerging initial radiation treatment option for organ-confined prostate cancer. J Oncol Practice. 2012; 8(3 Suppl):e31s-37s. 12. Parthan A, Pruttivarasin N, Davies D, et al. Comparative cost-effectiveness of stereotactic body radiation therapy versus intensity-modulated and proton radiation therapy for localized prostate cancer. Front Oncol. 2012; 2:81.

American Society for Radiation Oncology (ASTRO) Stereotactic Radiosurgery (SRS) Model Coverage Policy

AMA CPT / Copyright Statement

CPT® codes, descriptions and other data only are copyright 2010 American Medical Association (or such other date of publication of CPT). CPT is a registered trademark of the American Medical Association. All Rights Reserved.

Indications and Limitations of Coverage and/or Medical Necessity

This Model Policy1 addresses coverage for Stereotactic Radiosurgery (SRS).

Stereotactic Radiosurgery (SRS) is a distinct discipline that utilizes externally generated ionizing radiation in certain cases to inactivate or eradicate a defined target(s) in the head or spine without the need to make an incision. The target is defined by high-resolution stereotactic imaging. To assure quality of patient care, the procedure involves a multidisciplinary team consisting of a neurosurgeon, radiation oncologist, and medical physicist. (For a subset of tumors involving the skull base, the multidisciplinary team may also include a head and neck surgeon with training in stereotactic radiosurgery).

The adjective “Stereotactic” describes a procedure during which a target lesion is localized relative to a fixed three dimensional reference system, such as a rigid head frame affixed to a patient, fixed bony landmarks, a system of implanted fiducial markers, or other similar system. This type of localization procedure allows physicians to perform image-guided procedures with a high degree of anatomic accuracy and precision.

Stereotactic radiosurgery (SRS) couples this anatomic accuracy and reproducibility with very high doses of highly precise, externally generated, ionizing radiation, thereby maximizing the ablative effect on the target(s) while minimizing collateral damage to adjacent tissues. SRS requires computer-assisted, three-dimensional planning and delivery with stereotactic and convergent-beam technologies, including, but not limited to: multiple convergent cobalt sources (e.g. Gamma Knife®); protons; multiple, coplanar or non-coplanar photon arcs or angles (e.g. XKnife®); fixed photon arcs; or image-directed robotic devices (e.g. CyberKnife®) that meet the criteria.

SRS typically is performed in a single session, using a rigidly attached stereotactic guiding device, other immobilization technology and/or a stereotactic-guidance system, but can be performed in a limited number of sessions, up to a maximum of five.

Regardless of the number of sessions, all SRS procedures include the following components:

1. Position stabilization (attachment of a frame or frameless) 2. Imaging for localization (CT, MRI, angiography, PET, etc.) 3. Computer assisted tumor localization (i.e. “Image Guidance”)

1 ASTRO model policies were developed as a means to efficiently communicate what ASTRO believes to be correct coverage policies for radiation oncology services. The ASTRO Model Policies do not serve as clinical guidelines and they are subject to periodic review and revision without notice. The ASTRO Model Policies may be reproduced and distributed, without modification, for noncommercial purposes.

4. Treatment planning - number of isocenters, number, placement and length of arcs or angles, number of beams, beam size and weight, etc. 5. Isodose distributions, dosage prescription and calculation 6. Setup and accuracy verification testing 7. Simulation of prescribed arcs or fixed portals

Radiation oncologists and neurosurgeons have separate CPT billing codes for SRS. CPT Codes 61781–61783, 61796-61800 and 63620 and 63621 are reported for the work attributed to the neurosurgeon. These codes are mutually exclusive with the radiation oncology CPT codes 77432 and 77435; therefore the same physician should not bill for both of these codes.

A radiation oncologist may bill the SRS management code 77432 (stereotactic radiation treatment management of cranial lesion(s) (complete course of treatment consisting of one session) for single fraction intracranial SRS (and only once per treatment course) when and only when fully participating in the management of the procedure. CPT 77432 will be paid only once per course of treatment for cranial lesions regardless of the number of lesions. When SRS is administered in more than one but not more than five fractions to the brain or in one through five fractions to the spine, the radiation oncologist should instead bill the Stereotactic Body Radiation Therapy (SBRT) code 77435 to cover patient management during that course of therapy. CPT 77435 will be paid only once per course of therapy regardless of the number of sessions, lesions or days of treatment. The radiation oncologist may not bill 77432 and 77435 for the same course of therapy. In addition to the management codes, a radiation oncologist may bill other appropriate radiation oncology (77xxx) codes for services performed prior to the delivery of SRS as indicated by the pattern of care and other Medicare policies.

No one physician may bill both the neurosurgical codes 61781-83, 61796–61800, 63620 or 63621 and the radiation oncology 77XXX codes. If either the radiation oncologist or the neurosurgeon does not fully participate in the patient’s care, that physician must take care to indicate this change by use of the appropriate -54 modifier (followed by any appropriate -55 modifier) on the global procedure(s) submitted. As the services are collegial in nature with different specialties providing individual components of the treatment, surgical assistants will not be reimbursed.

The technical charges used by hospital-based and outpatient facilities for SRS delivery are described by the CPT codes listed below. It is not appropriate to bill more than one treatment delivery code on the same day of service, even though some types of delivery may have elements of several modalities (for example, a stereotactic approach with IMRT). Only one delivery code is to be billed.

Other radiation oncology professional and technical services required prior to the delivery of SRS are coded separately and may be appropriately billed by the radiation oncologist, when necessary.

ASTRO SRS Model Coverage Policy Page 2 Final Approval 1-14-11 Updated 7-25-11 Indications for SRS: 1. Primary central nervous system malignancies, generally used as a boost or salvage therapy for lesions <5cm. 2. Primary and secondary tumors involving the brain or spine parenchyma, meninges/dura, or immediately adjacent bony structures. 3. Benign brain tumors and spinal tumors such as meningiomas, acoustic neuromas, other schwannomas, pituitary adenomas, pineocytomas, craniopharyngiomas, glomus tumors, hemangioblastomas 4. Arteriovenous malformations and cavernous malformations. 5. Other cranial non-neoplastic conditions such as trigeminal neuralgia and select cases of medically refractory epilepsy. As a boost treatment for larger cranial or spinal lesions that have been treated initially with external beam radiation therapy or surgery (e.g. sarcomas, chondrosarcomas, chordomas, and nasopharyngeal or paranasal sinus malignancies). 6. Metastatic brain or spine lesions, with stable systemic disease, Karnofsky Performance Status 40 or greater (and expected to return to 70 or greater with treatment), and otherwise reasonable survival expectations, OR an Eastern Cooperative Oncology Group (ECOG) Performance Status of 3 or less (or expected to return to 2 or less with treatment). 7. Relapse in a previously irradiated cranial or spinal field where the additional stereotactic precision is required to avoid unacceptable vital tissue radiation.

Limitations:

SRS is not considered medically necessary under the following circumstances:

1. Treatment for anything other than a severe symptom or serious threat to life or critical functions. 2. Treatment unlikely to result in functional improvement or clinically meaningful disease stabilization, not otherwise achievable. 3. Patients with wide-spread cerebral or extra-cranial metastases with limited life expectancy unlikely to gain clinical benefit within their remaining life. 4. Patients with poor performance status (Karnofsky Performance Status less than 40 or ECOG Performance greater than 3) - see Karnofsky and ECOG Performance Status scales below. 5. For ICD-9-CM code 333.1, essential tremor, coverage should be limited to the patient who cannot be controlled with medication, has major systemic disease or coagulopathy, and who is unwilling or unsuited for open surgery. Coverage should further be limited to unilateral thalamotomy.

ASTRO SRS Model Coverage Policy Page 3 Final Approval 1-14-11 Updated 7-25-11 Karnofsky Performance Status Scale 100 Normal; no complaints, no evidence of disease 90 Able to carry on normal activity; minor signs or symptoms of disease 80 Normal activity with effort; some signs or symptoms of disease 70 Cares for self; unable to carry on normal activity or to do active work 60 Requires occasional assistance but is able to care for most needs 50 Requires considerable assistance and frequent medical care 40 Disabled; requires special care and assistance 30 Severely disabled; hospitalization is indicated although death not imminent 20 Very sick; hospitalization necessary; active supportive treatment is necessary 10 Moribund, fatal processes progressing rapidly 0 Dead

Karnofsky DA, Burchenal JH. (1949). "The Clinical Evaluation of Chemotherapeutic Agents in Cancer." In: MacLeod CM (Ed), Evaluation of Chemotherapeutic Agents. Columbia Univ Press. Page 196.

ECOG Performance Status Scale Grade 0: Fully active, able to carry on all pre-disease performance without restriction. Grade 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g. light house work, office work. Grade 2: Ambulatory and capable of all self-care but unable to carry out and work activities. Up and about more than 50% of waking hours. Grade 3: Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. Grade 4: Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. Grade 5: Dead

Eastern Cooperative Oncology Group, Robert Comis M.D., Group Chair.

* As published in Am. J. Clin. Oncol.:Oken, M.M., Creech, R.H., Tormey, D.C., Horton, J., Davis, T.E., McFadden, E.T., Carbone, P.P.: Toxicity And Response Criteria Of The Eastern Cooperative Oncology Group. Am J Clin Oncol 5:649-655, 1982.

CPT/HCPCS Codes

Note: Uses of 77435 and 77373 are addressed in both this Model Policy and in the Stereotactic Body Radiation Therapy Model Policy.

77371 Radiation treatment delivery, stereotactic radiosurgery (SRS), complete course of treatment of cranial lesion(s) consisting of 1 session; multi-source Cobalt 60 based

ASTRO SRS Model Coverage Policy Page 4 Final Approval 1-14-11 Updated 7-25-11 77372 Radiation treatment delivery, stereotactic radiosurgery (SRS), complete course of treatment of cranial lesion(s) consisting of 1 session; linear accelerator based

77373 Stereotactic body radiation therapy, treatment delivery, per fraction to 1 or more lesions, including image guidance, entire course not to exceed 5 fractions. (Do not report 77373 in conjunction with 77401-77416, 77418). (For single fraction cranial lesion, see 77371, 77372)

77432 Stereotactic radiation treatment management of cranial lesion(s) (complete course of treatment consisting of 1 session)

(The same physician should not report both stereotactic radiosurgery services [61796-61800] and radiation treatment management [77432 or 77435] for cranial lesions)

(For stereotactic body radiation therapy treatment, use 77435)

77435 Stereotactic body radiation therapy, treatment management, per treatment course, to 1 or more lesions, including image guidance, entire course not to exceed 5 fractions (Do not report 77435 in conjunction with 77427-77432) (The same physician should not report both stereotactic radiosurgery services [63620, 63621] and radiation treatment management [77435] for extracranial lesions)

G0173 Linear accelerator based stereotactic radiosurgery, complete course of therapy in one session

G0339 Image-guided robotic linear accelerator-based stereotactic radiosurgery, complete course of therapy in one session or first session of fractionated treatment

ICD-9 Codes that Support Medical Necessity

Note: Diagnosis codes are based on the current ICD-9-CM codes that are effective at the time of Model Policy publication. Any updates to ICD-9-CM codes will be reviewed by ASTRO, and coverage should not be presumed until the results of such review have been published/posted. These ICD-9-CM codes support medical necessity under this Model Policy:

147.0 MALIGNANT NEOPLASM OF SUPERIOR WALL OF NASOPHARYNX 147.1 MALIGNANT NEOPLASM OF POSTERIOR WALL OF NASOPHARYNX 147.2 MALIGNANT NEOPLASM OF LATERAL WALL OF NASOPHARYNX 147.3 MALIGNANT NEOPLASM OF ANTERIOR WALL OF NASOPHARYNX

ASTRO SRS Model Coverage Policy Page 5 Final Approval 1-14-11 Updated 7-25-11 147.8 MALIGNANT NEOPLASM OF OTHER SPECIFIED SITES OF NASOPHARYNX 147.9 MALIGNANT NEOPLASM OF NASOPHARYNX UNSPECIFIED SITE 160.0 MALIGNANT NEOPLASM OF NASAL CAVITIES 160.1 MALIGNANT NEOPLASM OF AUDITORY TUBE MIDDLE EAR AND MASTOID AIR CELLS 160.2 MALIGNANT NEOPLASM OF MAXILLARY SINUS 160.3 MALIGNANT NEOPLASM OF ETHMOIDAL SINUS 160.4 MALIGNANT NEOPLASM OF FRONTAL SINUS 160.5 MALIGNANT NEOPLASM OF SPHENOIDAL SINUS 160.8 MALIGNANT NEOPLASM OF OTHER ACCESSORY SINUSES 160.9 MALIGNANT NEOPLASM OF ACCESSORY SINUS UNSPECIFIED 191.0 MALIGNANT NEOPLASM OF CEREBRUM EXCEPT LOBES AND VENTRICLES 191.1 MALIGNANT NEOPLASM OF FRONTAL LOBE 191.2 MALIGNANT NEOPLASM OF TEMPORAL LOBE 191.3 MALIGNANT NEOPLASM OF PARIETAL LOBE 191.4 MALIGNANT NEOPLASM OF OCCIPITAL LOBE 191.5 MALIGNANT NEOPLASM OF VENTRICLES 191.6 MALIGNANT NEOPLASM OF CEREBELLUM NOS 191.7 MALIGNANT NEOPLASM OF BRAIN STEM 191.8 MALIGNANT NEOPLASM OF OTHER PARTS OF BRAIN 191.9 MALIGNANT NEOPLASM OF BRAIN UNSPECIFIED SITE 192.0 MALIGNANT NEOPLASM OF CRANIAL NERVES 192.1 MALIGNANT NEOPLASM OF CEREBRAL MENINGES 194.3 MALIGNANT NEOPLASM OF PITUITARY GLAND AND CRANIOPHARYNGEAL DUCT 194.4 MALIGNANT NEOPLASM OF PINEAL GLAND 194.6 MALIGNANT NEOPLASM OF AORTIC BODY AND OTHER PARAGANGLIA 198.3 SECONDARY MALIGNANT NEOPLASM OF BRAIN AND SPINAL CORD 198.4* SECONDARY MALIGNANT NEOPLASM OF OTHER PARTS OF NERVOUS SYSTEM 198.5* SECONDARY MALIGNANT NEOPLASM OF BONE AND BONE MARROW 198.89* SECONDARY MALIGNANT NEOPLASM OF OTHER SPECIFIED SITES 225.0 BENIGN NEOPLASM OF BRAIN 225.1 BENIGN NEOPLASM OF CRANIAL NERVES 225.2 BENIGN NEOPLASM OF CEREBRAL MENINGES 227.3 BENIGN NEOPLASM OF PITUITARY GLAND AND CRANIOPHARYNGEAL DUCT 227.4 BENIGN NEOPLASM OF PINEAL GLAND 227.5 BENIGN NEOPLASM OF CAROTID BODY 227.6 *BENIGN NEOPLASM OF AORTIC BODY AND OTHER PARAGANGLIA 228.02 HEMANGIOMA OF INTRACRANIAL STRUCTURES 237.0 NEOPLASM OF UNCERTAIN BEHAVIOR OF PITUITARY GLAND AND CRANIOPHARYNGEAL DUCT 237.1 NEOPLASM OF UNCERTAIN BEHAVIOR OF PINEAL GLAND 237.3* NEOPLASM OF UNCERTAIN BEHAVIOR OF PARAGANGLIA 237.5* NEOPLASM OF UNCERTAIN BEHAVIOR OF BRAIN AND SPINAL CORD 237.6* NEOPLASM OF UNCERTAIN BEHAVIOR OF MENINGES

ASTRO SRS Model Coverage Policy Page 6 Final Approval 1-14-11 Updated 7-25-11 239.6* NEOPLASM OF UNSPECIFIED NATURE OF BRAIN 239.7* NEOPLASM OF UNSPECIFIED NATURE OF ENDOCRINE GLANDS AND OTHER PARTS OF NERVOUS SYSTEM 332.0 PARALYSIS AGITANS 333.1** ESSENTIAL AND OTHER SPECIFIED FORMS OF TREMOR 345.11 GENERALIZED CONVULSIVE EPILEPSY WITH INTRACTABLE EPILEPSY 345.3 GRAND MAL STATUS EPILEPTIC 345.91 EPILEPSY UNSPECIFIED WITH INTRACTABLE EPILEPSY 350.1 TRIGEMINAL NEURALGIA 350.8 OTHER SPECIFIED TRIGEMINAL NERVE DISORDERS 350.9 TRIGEMINAL NERVE DISORDER UNSPECIFIED 351.0 BELL'S PALSY 351.1 GENICULATE GANGLIONITIS 351.8 OTHER FACIAL NERVE DISORDERS 351.9 FACIAL NERVE DISORDER UNSPECIFIED 352.0* DISORDERS OF OLFACTORY (1ST) NERVE 352.1* GLOSSOPHARYNGEAL NEURALGIA 352.2* OTHER DISORDERS OF GLOSSOPHARYNGEAL (9TH) NERVE 352.3* DISORDERS OF PNEUMOGASTRIC (10TH) NERVE 352.4* DISORDERS OF ACCESSORY (11TH) NERVE 352.5* DISORDERS OF HYPOGLOSSAL (12TH) NERVE 352.6* MULTIPLE CRANIAL NERVE PALSIES 352.9* UNSPECIFIED DISORDER OF CRANIAL NERVES 747.81* CONGENITAL ANOMALIES OF CEREBROVASCULAR SYSTEM 990*** EFFECTS OF RADIATION UNSPECIFIED

* ICD-9-CM codes 198.4, 198.5, 198.89, 234.8, 237.5, 237.6, 239.6, 239.7, 333.1, 352.0, 352.1, 352.2, 352.3, 352.4, 352.5, 352.6, 352.9 and 747.81 are all limited to use for lesions occurring either above the neck or in the spine.

** ICD-9-CM 333.1 code is limited to the patient who cannot be controlled with medication, has major systemic disease or coagulopathy, and who is unwilling or unsuited for open surgery.

*** ICD-9-CM 990 may only be used where prior radiation therapy to the site is the governing factor necessitating SRS in lieu of other radiotherapy. An ICD-9-CM code for the anatomic diagnosis must also be used.

General Information

Documentation Requirements

The patient's record must support the necessity and frequency of treatment. Medical records should include not only the standard history and physical but also the patient's functional status and a description of current performance status (Karnofsky Performance Status or ECOG Performance Status). See Karnofsky Performance Status or ECOG Performance Status listed under Indications and Limitation of Coverage above.

ASTRO SRS Model Coverage Policy Page 7 Final Approval 1-14-11 Updated 7-25-11

Documentation should include the date and the current treatment dose. A radiation oncologist and a neurosurgeon must evaluate the clinical aspects of the treatment, and document and sign this evaluation as well as the resulting management decisions. A radiation oncologist and medical physicist must evaluate the technical aspects of the treatment and document and sign this evaluation as well as the resulting treatment management decisions.

For Medicare claims, the HCPCS/CPT code(s) may be subject to Correct Coding Initiative (CCI) edits. This policy does not take precedence over CCI edits. Please refer to the CCI for correct coding guidelines and specific applicable code combinations prior to billing Medicare.

ASTRO SRS Model Coverage Policy Page 8 Final Approval 1-14-11 Updated 7-25-11 SRS References

1. Adler JR Jr, Gibbs IC, Puataweepong P, Chang SD. Visual field preservation after multisession cyberknife radiosurgery for perioptic lesions. Neurosurgery. 2006 Aug; 59(2):244-54; discussion 244-54.

2. American College of Radiology ACR Appropriateness Criteria Brain Metastasis. 2006. Accessed April 2009. Available at: http://www.acr.org/SecondaryMainMenuCategories/quality_safety/app_criteria/pdf/Expert

3. American College of Radiology Practice Guideline for the performance of Stereotactic Radiosurgery. Effective 10/01/2006. Accessed April 2009. Available at URL address: http://www.acr.org/ SecondaryMainMenuCategories/ quality_safety/guidelines/ro/ stereotactic_radiosurgery.aspx

4. American College of Radiology Practice Guideline for the Performance of Stereotactic Body Radiation Therapy. Amended 2006 Accessed April 2009. Available at: http://www.acr.org /Secondary MainMenuCategories /quality_safety/ guidelines /ro/stereo_body_radiation.aspx

5. American Society for Radiation Oncology (ASTRO). Report of the ASTRO Emerging Technology Committee (ETC) September 19, 2008 Stereotactic Body Radiotherapy (SBRT) For Primary Management of Early-Stage, Low-Intermediate Risk Prostate Cancer Available at: http://www.astro.org/HealthPolicy/EmergingTechnology/EvaluationProjects/documents/SBR Tpros.pdf. Accessed April 2009.

6. American Society for Therapeutic Radiation and Oncology (ASTRO). The ASTRO/ACR Guide to Radiation Oncology Coding 2007. Fairfax, VA: ASTRO; 2007.

7. Andrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC, et al. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet. 2004 May 22; 363(9422):1665-72.

8. Aoyama H, Shirato H, Tago M, Nakagawa K, Toyoda T, Hatano K, et al. Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA. 2006 Jun 7; 295(21):2483-91.

9. Barajas MA, Ramirez-Guzman MG, Rodriguez-Vazquez C, Toledo-Buenrostro V, Cuevas-Solorzano A, Rodriguez-Hernandez G. Gamma Knife surgery for hypothalamic hamartomas accompanied by medically intractable epilepsy and precocious puberty: experience in Mexico. J Neurosurg. 2005 Jan; 102 Suppl: 53-5.

10. Barbaro NM, Quigg M, Broshek DK, et al. A multicenter, prospective pilot study of gamma knife radiosurgery for mesial temporal lobe epilepsy: seizure response, adverse ASTRO SRS Model Coverage Policy Page 9 Final Approval 1-14-11 Updated 7-25-11 events, and verbal memory. Ann Neurol. 2009 Feb;65(2):167-75.

11. Barcia-Salorio JL, Barcia JA, Hernandez G, Lopez-Gomez L. Radiosurgery of epilepsy. Long-term results. Acta Neurochir Suppl (Wien). 1994; 62:111-113.

12. Barnett GH, Linskey ME, Adler JR, Cozzens JW, Friedman WA, Heilbrun MP, Lunsford LD, Schulder M, Sloan AE; American Association of Neurological Surgeons; Congress of Neurolofical Surgeons Washington Committee Stereotactic Radiosurgery Task Force. Stereotactic radiosurgery--an organized neurosurgery-sanctioned definition. J Neurosurg. 2007 Jan; 106(1):1-5.

13. Bhatnagar AK, Flickinger JC, Kondziolka D, Lunsford LD. Stereotactic radiosurgery for four or more intracranial metastases. Int J Radiat Oncol Biol Phys. 2006 Mar 1; 64(3):898- 903.

14. Brisman R. Microvascular decompression vs. Gamma Knife radiosurgery for typical trigeminal neuralgia: preliminary findings. Stereotact Funct Neurosurg. 2007; 85(2-3):94-8.

15. Chang SD, Gibbs IC, Sakamoto GT, Lee E, Oyelese A, Adler JR Jr. Staged stereotactic irradiation for acoustic neuroma. Neurosurgery. 2005 Jun; 56(6):1254-61; discussion 1261-3.

16. Chougule PB, Burton-WilliamsM, Saris S, Zheng Z, Ponte B, Noren G, et al. Randomized treatment of brain metastases with Gamma Knife radiosurgery, whole brain radiotherapy or both (abstract). International Journal of Radiation Oncology, Biology, Physics 2000; 48: 114.

17. Chua DT, Sham JS, Hung KN, Leung LH, Au GK. Predictive factors of tumor control and survival after radiosurgery for local failures of nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2006 Dec 1; 66(5):1415-21.

18. Cohen VM, Carter MJ, Kemeny A, Radatz M, Rennie IG. Metastasis-free survival following treatment for uveal melanoma with either stereotactic radiosurgery or enucleation. Acta Ophthalmol Scand. 2003 Aug; 81(4):383-8.

19. Dieckmann K, Georg D, Bogner J, Zehetmayer M, Petersch B, Chorvat M, et al. Optimizing LINAC based stereotactic radiotherapy of uveal melanomas: 7 years' clinical experience. Int J Radiat Oncol Biol Phys. 2006 Nov 15; 66(4 Suppl):S47-52.

20. Donnet A, Tamura M, Valade D, RJ. Trigeminal nerve radiosurgical treatment in intractable chronic cluster headache: unexpected high toxicity. Neurosurgery. 2006 Dec; 59(6):1252-7; discussion 1257.

21. Dodd RL, Ryu MR, Kamnerdsupaphon P, Gibbs IC, Chang SD Jr, Adler JR Jr. CyberKnife radiosurgery for benign intradural extramedullary spinal tumors. Neurosurgery. 2006 Apr; 58(4):674-85; discussion 674-85.

ASTRO SRS Model Coverage Policy Page 10 Final Approval 1-14-11 Updated 7-25-11 22. Duma CM. Movement disorder radiosurgery--planning, physics and complication avoidance. Prog Neurol Surg. 2007; 20:249-66.

23. ECRI Institute Health Technology Assessment Information Service (HTAIS). CyberKnife and Gamma Knife Radiosurgery for Trigeminal Neuralgia. Hotline Response. May 2007. Archived

24. Elia AE, Shih HA, Loeffler JS. Stereotactic radiation treatment for benign meningiomas. Neurosurg Focus. 2007; 23(4):E5.

25. Friehs GM, Park MC, Goldman MA, Zerris VA, NorG, Sampath P. Stereotactic radiosurgery for functional disorders. Neurosurg Focus. 2007; 23(6):E3.

26. Gagnon GJ, Henderson FC, Gehan EA, Sanford D, Collins BT, Moulds JC, Dritschilo A. Cyberknife radiosurgery for breast cancer spine metastases: a matched-pair analysis. Cancer. 2007 Oct 15; 110(8):1796-802.

27. Gerszten PC, Burton SA, Ozhasoglu C, Welch WC. Radiosurgery for spinal metastases: clinical experience in 500 cases from a single institution. Spine. 2007 Jan 15; 32(2):193-9.

28. Gerszten PC, Burton SA. Clinical Assessment of Stereotactic IGRT: Spinal Radiosurgery. Med Dosim. 2008 summer; 33(2):107-16.

29. Gerszten PC, Burton SA, Ozhasoglu C, McCue KJ, Quinn AE. Radiosurgery for benign intradural spinal tumors. Neurosurgery. 2008 Apr; 62(4):887-95; discussion 895-6.

30. Gerszten PC, Ozhasoglu C, Burton SA, Vogel WJ, Atkins BA, Kalnicki S, Welch WC. CyberKnife frameless stereotactic radiosurgery for spinal lesions: clinical experience in 125 cases. Neurosurgery. 2004 Jul; 55(1):89-98; discussion 98-9.

31. Gerszten PC, Ozhasoglu C, Burton SA, Vogel WJ, Atkins BA, Kalnicki S, Welch WC. CyberKnife frameless single-fraction stereotactic radiosurgery for benign tumors of the spine. Neurosurg Focus. 2003 May 15; 14(5):e16.

32. Gerszten PC, Burton SA, Welch WC, Brufsky AM, Lembersky BC, Ozhasoglu C, Vogel WJ. Single-fraction radiosurgery for the treatment of spinal breast metastases. Cancer. 2005a Nov 15; 104(10):2244-54.

33. Gerszten PC, Burton SA, Ozhasoglu C, Vogel WJ, Welch WC, Baar J, Friedland DM. Stereotactic radiosurgery for spinal metastases from renal cell carcinoma. J Neurosurg Spine. 2005b Oct; 3(4):288-95.

34. Gerszten PC, Burton SA, Quinn AE, Agarwala SS, Kirkwood JM Radiosurgery for the treatment of spinal melanoma metastases. Stereotact Funct Neurosurg. 2005c; 83(5-6):213- 21.

ASTRO SRS Model Coverage Policy Page 11 Final Approval 1-14-11 Updated 7-25-11 35. Gerszten PC, Germanwala A, Burton SA, Welch WC, Ozhasoglu C, Vogel WJ. Combination kyphoplasty and spinal radiosurgery: a new treatment paradigm for pathological fractures. J Neurosurg Spine. 2005d Oct; 3(4):296-301.

36. Gerszten PC, Burton SA, Belani CP, Ramalingam S, Friedland DM, Ozhasoglu C, Quinn AE, McCue KJ, Welch WC. Radiosurgery for the treatment of spinal lung metastases. Cancer. 2006 Dec 1; 107(11):2653-61.

37. Gibbs IC, Kamnerdsupaphon P, Ryu MR, Dodd R, Kiernan M, Chang SD, Adler JR Jr. Image-guided robotic radiosurgery for spinal metastases. Radiother Oncol. 2007 Feb; 82(2):185-90.

38. Giller CA, Berger BD, Fink K, Bastian E. A volumetric study of CyberKnife hypofractionated stereotactic radiotherapy as salvage for progressive malignant brain tumors: initial experience. Neurol Res. 2007 Sep; 29(6):563-8.

39. Gopalan R, Dassoulas K, Rainey J, Sherman JH, Sheehan JP. Evaluation of the role of Gamma Knife surgery in the treatment of craniopharyngiomas. Neurosurg Focus. 2008; 24(5):E5.

40. Gottfried ON, Liu JK, Couldwell WT. Comparison of radiosurgery and conventional surgery for the treatment of glomus jugulare tumors. Neurosurg Focus. 2004 Aug 15; 17(2):E4.

41. Grabenbauer GG, Reinhold Ch, Kerling F, et al. Fractionated stereotactically guided radiotherapy of pharmacoresistant temporal lobe epilepsy. Acta Neurochir Suppl. 2002; 84: 65-70.

42. Gronseth G, Cruccu G, Alksne J, Argoff C, Brainin M, Burchiel K, Nurmikko T, Zakrzewska JM. Practice parameter: the diagnostic evaluation and treatment of trigeminal neuralgia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the European Federation of Neurological Societies. Neurology. 2008 Oct 7; 71(15):1183-90.

43. Han JH, Kim DG, Chung HT, et al. Clinical and neuroimaging outcome of cerebral arteriovenous malformations after Gamma Knife surgery: analysis of the radiation injury rate depending on the arteriovenous malformation volume. J Neurosurg. 2008; 109(2):191-198.

44. Hara W, Loo BW Jr, Goffinet DR, Chang SD, Adler JR, Pinto HA, et al. Excellent Local Control with Stereotactic Radiotherapy Boost After External Beam Radiotherapy in Patients with Nasopharyngeal Carcinoma. Int J Radiat Oncol Biol Phys. 2007 Dec 28.

45. Hayes, Inc. HAYES Medical Technology Directory. Stereotactic Radiosurgery for Arteriovenous Malformations and Intracranial Tumors. Lansdale, PA: Hayes, Inc. January 2009.

ASTRO SRS Model Coverage Policy Page 12 Final Approval 1-14-11 Updated 7-25-11 46. Ikeda H, Jokura H, Yoshimoto T. Transsphenoidal surgery and adjuvant Gamma Knife treatment for growth hormone-secreting pituitary adenoma. J Neurosurg. 2001 Aug; 95(2):285-91.

47. International RadioSurgery Association. Radiosurgery practice guideline initiative: stereotactic radiosurgery for patients with vestibular schwannomas. Issued May 2006. Accessed April 2009. Available at: http://www.irsa.org/AN%20Guideline.pdf.

48. International RadioSurgery Association. Radiosurgery practice guideline initiative: stereotactic radiosurgery for patients with intractable typical trigeminal neuralgia who have failed medical management. Issued: September 2003. Accessed April 2009. Available at: http://www.irsa.org/ TN%20Guideline.pdf.

49. International RadioSurgery Association. Radiosurgery practice guideline initiative: stereotactic radiosurgery for patients with pituitary adenomas. Issued: April 2004. Accessed April 2009. Available at: http://www.irsa.org /Pituitary%20 Guideline.pdf

50. International RadioSurgery Association, The. Radiosurgery practice guideline initiative: stereotactic radiosurgery for patients with intracranial arteriovenous malformations. Issued September 2003. Accessed April 2009. Available at: http://www.irsa.org/AVM%20Guideline.pdf

51. Ishihara H, Saito K, Nishizaki T, Kajiwara K, Nomura S, Yoshikawa K, Harada K, Suzuki M. CyberKnife radiosurgery for vestibular schwannoma. Minim Invasive Neurosurg. 2004 Oct; 47(5):290-3.

52. Kajiwara K, Saito K, Yoshikawa K, Kato S, Akimura T, Nomura S, Ishihara H, Suzuki M. Image-guided stereotactic radiosurgery with the CyberKnife for pituitary adenomas. Minim Invasive Neurosurg. 2005 Apr; 48(2):91-6.

53. Karpinos M, Teh BS, Zeck O, Carpenter LS, Phan C, Mai WY, Lu HH, Chiu JK, Butler EB, Gormley WB, Woo SY. Treatment of acoustic neuroma: stereotactic radiosurgery vs. microsurgery. Int J Radiat Oncol Biol Phys. 2002 Dec 1; 54(5):1410-21. Stereotactic radiotherapy. Front Radiat Ther Oncol. 2007; 40:415-26.

54. Kim SH, Weil RJ, Chao ST, Toms SA, Angelov L, Vogelbaum MA, Suh JH, Barnett GH. Stereotactic radiosurgical treatment of brain metastases in older patients. Cancer. 2008 Aug 15; 113(4):834-40.

55. Kondziolka D, Ong JG, Lee JY, Moore RY, Flickinger JC, Lunsford LD. Gamma Knife thalamotomy for essential tremor. J Neurosurg. 2008 Jan; 108(1):111-7.

56. Kondziolka D, Patel A, Lunsford LD, Kassam A, Flickinger JC. Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases. Int J Radiat Oncol Biol Phys. 1999 Sep 1; 45(2):427-34.

ASTRO SRS Model Coverage Policy Page 13 Final Approval 1-14-11 Updated 7-25-11 57. Kong DS, Lee JI, Lim do H, Kim KW, Shin HJ, Nam DH, et al. The efficacy of fractionated radiotherapy and stereotactic radiosurgery for pituitary adenomas: long-term results of 125 consecutive patients treated in a single institution. Cancer. 2007 Aug 15; 110(4):854-60.

58. Lee M, Kalani MY, Cheshier S, Gibbs IC, Adler JR, Chang SD. Radiation therapy and CyberKnife radiosurgery in the management of craniopharyngiomas. Neurosurg Focus. 2008; 24(5):E4.

59. Lee JY, Kondziolka D, Flickinger JC, Lunsford LD. Radiosurgery for intracranial meningiomas. Prog Neurol Surg. 2007; 20:142-9.

60. Lim M, Bower R, Nangiana JS, Adler JR, Chang SD. Radiosurgery for glomus jugulare tumors. Technol Cancer Res Treat. 2007 Oct; 6(5):419-23.

61. Lim M, Cotrutz C, Romanelli P, Schaal D, Gibbs I, Chang SD, Adler JR. Stereotactic radiosurgery using CT cisternography and non-isocentric planning for the treatment of trigeminal neuralgia. Comput Aided Surg. 2006 Jan; 11(1):11-20.

62. Lim M, Villavicencio AT, Burneikiene S, Chang SD, Romanelli P, McNeely L,McIntyre M, Thramann JJ, Adler JR. CyberKnife radiosurgery for idiopathic trigeminal neuralgia. Neurosurg Focus. 2005 May 15; 18(5):E9.

63. Linskey ME, Davis SA, Ratanatharathorn V. Relative roles of microsurgery and stereotactic radiosurgery for the treatment of patients with cranial meningiomas: a single- surgeon 4-year integrated experience with both modalities. J Neurosurg. 2005 Jan; 102 Suppl: 59-70.

64. Lipani JD, Jackson PS, Soltys SG, Sato K, Adler JR. Survival Following CyberKnife Radiosurgery and Hypofractionated Radiotherapy for Newly Diagnosed Glioblastoma Multiforme. Technol Cancer Res Treat. 2008 Jun; 7(3):249-56.

65. Madsen BL, Hsi RA, Pham HT, Fowler JF, Esagui L, Corman J. Stereotactic hypofractionated accurate radiotherapy of the prostate (SHARP), 33.5 Gy in five fractions for localized disease: first clinical trial results. Int J Radiat Oncol Biol Phys. 2007 Mar 15; 67(4):1099-105.

66. Mathieu D, Kondziolka D, Niranjan A, Flickinger J, Lunsford LD. Gamma knife radiosurgery for refractory epilepsy caused by hypothalamic hamartomas. Stereotact Funct Neurosurg. 2006; 84(2-3):82-7.

67. McClelland S 3rd, Gerbi BJ, Higgins PD, Orner JB, Hall WA. Safety and efficacy of fractionated stereotactic radiotherapy for acoustic neuromas. J Neurooncol. 2008 Jan; 86(2):191-4.

68. Meijer OW, Vandertop WP, Baayen JC, Slotman BJ. Single-fraction vs. fractionated

ASTRO SRS Model Coverage Policy Page 14 Final Approval 1-14-11 Updated 7-25-11 linac-based stereotactic radiosurgery for vestibular schwannoma: a single-institution study. Int J Radiat Oncol Biol Phys. 2003 Aug 1; 56(5):1390-6.

69. Muacevic A, Wowra B, Siefert A, Tonn JC, Steiger HJ, Kreth FW. Microsurgery plus whole brain irradiation versus Gamma Knife surgery alone for treatment of single metastases to the brain: a randomized controlled multicentre phase III trial. J Neurooncol. 2008 May; 87(3):299-307.

70. Muragaki Y, Nakamura R, Iseki H, Hori T, Takakura K. Outcome after pituitary radiosurgery for thalamic pain syndrome. Int J Radiat Oncol Biol Phys. 2007 Nov 1; 69(3):852-7.

71. Myrseth E, MP, Pedersen PH, Vassbotn FS, Wentzel-Larsen T, Lund-Johansen M. Vestibular schwannomas: clinical results and quality of life after microsurgery or Gamma Knife radiosurgery. Neurosurgery. 2005 May; 56(5):927-35; discussion 927-35.

72. National Comprehensive Cancer Network (NCCN).Web site. Clinical Practice Guidelines in Oncology. Central Nervous System Cancers V.1.2008. Accessed April 2009. Available at http://www.nccn.org/professionals/physician_gls/PDF/cns.pdf.

73. National Comprehensive Cancer Network (NCCN).Web site. Clinical Practice Guidelines in Oncology. Soft Tissue Sarcoma. V.1.2009. Accessed April 2009. Available at: http://www.nccn.org/professionals/physician_gls/PDF/sarcoma.pdf.

74. National Institute for Clinical Excellence. Stereotactic radiosurgery for trigeminal neuralgia using the Gamma Knife. August 2004.

75. National Institute for Health and Clinical Excellence. Interventional procedure Guidance IPG085 Stereotactic radiosurgery for trigeminal neuralgia using the Gamma Knife - guidance. August 2004. Accessed April 2009. Available at: http://www.nice.org.uk/nicemedia/pdf/ip/IPG085guidance .pdf.

76. National Institute for Health and Clinical Excellence. Systematic review of the clinical efficacy and safety of stereotactic radiosurgery (Gamma Knife) in the treatment of trigeminal neuralgia. 27 April 2004. Accessed April 2009. Available at: http://www.nice.org.uk /nicemedia /pdf/ip/173 systematic review.pdf.

77. Niranjan A, Jawahar A, Kondziolka D, Lunsford LD. A comparison of surgical approaches for the management of tremor: radiofrequency thalamotomy, Gamma Knife thalamotomy and thalamic stimulation. Stereotact Funct Neurosurg. 1999; 72(2-4):178-84.

78. Nishizaki T, Saito K, Jimi Y, Harada N, Kajiwara K, Nomura S, Ishihara H, Yoshikawa K, Yoneda H, Suzuki M, Gibbs IC. The role of cyberknife radiosurgery/radiotherapy for brain metastases of multiple or large-size tumors. Minim Invasive Neurosurg. 2006 Aug; 49(4):203-9.

ASTRO SRS Model Coverage Policy Page 15 Final Approval 1-14-11 Updated 7-25-11 79. Ogilvy CS, Stieg PE, Awad I, Brown RD Jr, Kondziolka D, Special Writing Group of the Stroke Council, American Stroke Association, et al. AHA Scientific Statement: Recommendations for the management of intracranial arteriovenous malformations: a statement for healthcare professionals from a special writing group of the Stroke Council, American Stroke Association. Stroke. 2001 Jun; 32(6):1458-71.

80. Okun MS, Stover NP, Subramanian T, Gearing M, Wainer BH, Holder CA, Watts RL, Juncos JL, Freeman A, Evatt ML, Schuele SU, Vitek JL, DeLong MR. Complications of Gamma Knife surgery for Parkinson disease. Arch Neurol. 2001 Dec; 58(12):1995-2002.

81. Pan DH, Guo WY, Chung WY, et al. Gamma knife radiosurgery as a single treatment modality for large cerebral arteriovenous malformations. J Neurosurg. 2000; 93(suppl 3):113-119.

82. Patil CG, Veeravagu A, Bower RS, Li G, Chang SD, Lim M, Adler JR Jr. CyberKnife radiosurgical rhizotomy for the treatment of atypical trigeminal nerve pain. Neurosurg Focus. 2007; 23(6):E9.

83. Picozzi P, Losa M, Mortini P, Valle MA, Franzin A, Attuati L, Ferrari da Passano C, Giovanelli M. Radiosurgery and the prevention of regrowth of incompletely removed nonfunctioning pituitary adenomas. J Neurosurg. 2005 Jan; 102 Suppl: 71-4.

84. Pollock BE, Stafford SL, Utter A, Giannini C, Schreiner SA. Stereotactic radiosurgery provides equivalent tumor control to Simpson Grade 1 resection for patients with small- to medium-size meningiomas. Int J Radiat Oncol Biol Phys. 2003 Mar 15; 55(4):1000-5.

85. Pollock BE. Stereotactic radiosurgery in patients with glomus jugulare tumors. Neurosurg Focus. 2004 Aug 15; 17(2):E10.

86. Pollock, BE. An evidence-based medicine review of stereotactic radiosurgery. Prog Neurol Surg. 2006; 19152-170.

87. Pollock BE, Lunsford LD, Flickinger JC, Clyde BL, Kondziolka D. Vestibular schwannoma management. Part I. Failed microsurgery and the role of delayed stereotactic radiosurgery. J Neurosurg. 1998 Dec; 89(6):944-8.

88. Quigg M, Barbaro NM. Stereotactic radiosurgery for treatment of epilepsy. Arch Neurol. 2008 Feb; 65(2):177-83.

89. Rades D, Bohlen G, Pluemer A, Veninga T, Hanssens P, Dunst J, Schild SE. Stereotactic radiosurgery alone versus resection plus whole-brain radiotherapy for 1 or 2 brain metastases in recursive partitioning analysis class 1 and 2 patients. Cancer. 2007 Jun 15; 109(12):2515- 21.

90. Regis J, Arkha Y, Yomo S, Bartolomei F, Peragut JC, Chauvel P. Radiosurgery for drug- resistant epilepsies: state of the art, results and perspectives. Neurochirurgie. 2008 May;

ASTRO SRS Model Coverage Policy Page 16 Final Approval 1-14-11 Updated 7-25-11 54(3):320-31.

91. Regis J, Bartolomei F, Rey M, et al. Gamma knife surgery for mesial temporal lobe epilepsy. J Neurosurg. 2000; 93(Suppl 3):141-146.

92. Regis J, Pellet W, Delsanti C, Dufour H, Roche PH, Thomassin JM, Zanaret M, Peragut JC. Functional outcome after Gamma Knife surgery or microsurgery for vestibular schwannomas. J Neurosurg. 2002 Nov; 97(5):1091-100.

93. Regis J, Rey M, Bartolomei F, Vladyka V, Liscak R, Schrottner O, Pendl G. Gamma knife surgery in mesial temporal lobe epilepsy: a prospective multicenter study. Epilepsia. 2004 May;45(5):504-15.

94. Regis J, Scavarda D, Tamura M, et al. Epilepsy related to hypothalamic hamartomas: Surgical management with special reference to Gamma Knife surgery. Childs Nerv Syst. 2006; 22(8):881-895.

95. Regis J, Bartolomei F, de Toffol B, Genton P, Kobayashi T, Mori Y, et al. Gamma knife surgery for epilepsy related to hypothalamic hamartomas. Neurosurgery. 2000 Dec; 47(6):1343-51; discussion 1351-2.

96. Regis J, Rey M, Bartolomei F, Vladyka V, Liscak R, Schrottner O, Pendl G. Gamma knife surgery in mesial temporal lobe epilepsy: a prospective multicenter study. Epilepsia. 2004 May; 45(5):504-15.

97. Roche PH, Robitail S, Delsanti C, Marouf R, Pellet W, RJ. Radiosurgery of vestibular schwannomas after microsurgery and combined radio-microsurgery Neurochirurgie. 2004 Jun; 50(2-3 Pt 2):394-400.

98. Romanelli P, Anschel DJ. Radiosurgery for epilepsy. Lancet Neurol. 2006 Jul; 5(7):613- 20.

99. Romanelli P, Heit G, Chang SD, Martin D, Pham C, Adler J. Cyberknife radiosurgery for trigeminal neuralgia. Stereotact Funct Neurosurg. 2003; 81(1-4):105-9.

100. Ryu S, Jin R, Jin JY, Chen Q, Rock J, Anderson J, Movsas B. Pain control by image- guided radiosurgery for solitary spinal metastasis. J Pain Symptom Manage. 2008 Mar; 35(3):292-8.

101. Sahgal A, Chou D, Ames C, Ma L, Lamborn K, Huang K, Chuang C, Aiken A, Pett P, Weinstein P, Larson D .Image-guided robotic stereotactic body radiotherapy for benign spinal tumors: the University of California San Francisco preliminary experience. Technol Cancer Res Treat. 2007 Dec; 6(6):595-604.

102. Schaeuble B, Cascino GD, Pollock BE, Gorman DA, Weigand S, Cohen-Gadol AA, McClelland RL. Seizure outcomes after stereotactic radiosurgery for cerebral arteriovenous

ASTRO SRS Model Coverage Policy Page 17 Final Approval 1-14-11 Updated 7-25-11 malformations. Neurology. 2004 Aug 24; 63(4):683-7.

103. Selch MT, Gorgulho A, Mattozo C, Solberg TD, Cabatan-Awang C, DeSalles AA. Linear accelerator stereotactic radiosurgery for the treatment of gelastic seizures due to hypothalamic hamartoma. Minim Invasive Neurosurg. 2005 Oct; 48(5):310-4.

104. Serizawa, Toru; Hirai, Tatsuo; Nagano, Osamu; Higuchi, Yoshinori; Matsuda, Shinji; Ono, Junichi; Saeki, Naokatsu. Gamma knife surgery for 1–10 brain metastases without prophylactic whole-brain radiation therapy: analysis of cases meeting the Japanese prospective multi-institute study (JLGK0901) inclusion criteria. Journal of Neuro-Oncology (2010) 98: 163-167, June 10, 2010

105. Sinclair J, Chang SD, Gibbs IC, Adler JR Jr. Multisession CyberKnife radiosurgery for intramedullary spinal cord arteriovenous malformations. Neurosurgery. 2006 Jun; 58(6):1081-9; discussion 1081-9.

106. Souhami L, Seiferheld W, Brachman D, Podgorsak EB, Werner-Wasik M, Lustig R, Schultz CJ, Sause W, Okunieff P, Buckner J, Zamorano L, Mehta MP, Curran WJ Jr. Randomized comparison of stereotactic radiosurgery followed by conventional radiotherapy with carmustine to conventional radiotherapy with carmustine for patients with glioblastoma multiforme: report of Radiation Therapy Oncology Group 93-05 protocol. Int J Radiat Oncol Biol Phys. 2004 Nov 1; 60(3):853-60.

107. Steinvorth S, Wenz F, Wildermuth S, et al. Cognitive function in patients with cerebral arteriovenous malformations after radiosurgery: prospective long-term follow-up. Int J Radiat Oncol Biol Phys. 2002; 54(5):1430-7.

108. Tsao MN, Lloyd N, Wong R, Chow E, Rakovitch E, Laperriere N. Whole brain radiotherapy for the treatment of multiple brain metastases. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD003869.

109. Tsao MN, Mehta MP, Whelan TJ, Morris DE, Hayman JA, Flickinger JC, Mills M, Rogers CL, Souhami L. The American Society for Therapeutic Radiology and Oncology (ASTRO) evidence-based review of the role of radiosurgery for malignant glioma. Int J Radiat Oncol Biol Phys. 2005 Sep 1; 63(1):47-55.

110. Villavicencio AT, Lim M, Burneikiene S, Romanelli P, Adler JR, McNeely L, Chang SD, Fariselli L, McIntyre M, Bower R, Broggi G, Thramann JJ. Cyberknife radiosurgery for trigeminal neuralgia treatment: a preliminary multicenter experience. Neurosurgery. 2008 Mar; 62(3):647-55; discussion 647-55.

111. Whang CJ, Kwon Y. Long-term follow-up of stereotactic Gamma Knife radiosurgery in epilepsy. Stereotact Funct Neurosurg. 1996; 66(Suppl 1):349-356.

112. Weil M. Stereotactic Radiosurgery for Brain Tumors. Hematology/Oncology Clinics of North America. 2001; 15(6).

ASTRO SRS Model Coverage Policy Page 18 Final Approval 1-14-11 Updated 7-25-11

113. Wu SX, Chua DT, Deng ML, Zhao C, Li FY, Sham JS, Wang HY, Bao Y, Gao YH, Zeng ZF. Outcome of fractionated stereotactic radiotherapy for 90 patients with locally persistent and recurrent nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2007 Nov 1; 69(3):761-9.

114. Yang KJ, Wang KW, Wu HP, Qi ST. Radiosurgical treatment of intractable epilepsy with low radiation dose. Di Yi Jun Yi Da Xue Xue Bao. 2002; 22(7):645-647.

115. Yoshikawa K, Saito K, Kajiwara K, Nomura S, Ishihara H, Suzuki M. CyberKnife stereotactic radiotherapy for patients with malignant glioma. Minim Invasive Neurosurg. 2006 Apr; 49(2):110-5.

116. Young RF, Jacques S, Mark R, Kopyov O, Copcutt B, Posewitz A, Li F. Gamma knife thalamotomy for treatment of tremor: long-term results. J Neurosurg. 2000 Dec; 93 Suppl 3:128-35.

117. Young RF, Vermeulen S, Posewitz A, Shumway-Cook A. Pallidotomy with the Gamma Knife: a positive experience. Stereotact Funct Neurosurg. 1998 Oct; 70 Suppl 1:218- 28.

118. Young RF, Vermeulen SS, Grimm P, Posewitz AE, Jacques DB, Rand RW, Copcutt BG. Gamma Knife thalamotomy for the treatment of persistent pain. Stereotact Funct Neurosurg. 1995; 64 Suppl 1:172-81.

119. Zesiewicz TA, Elble R, Louis ED, Hauser RA, Sullivan KL, Quality Standards Subcommittee of the American Academy of Neurology, et al. Practice parameter: therapies for essential tremor: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2005 Jun 28; 64(12):2008-20.

ASTRO SRS Model Coverage Policy Page 19 Final Approval 1-14-11 Updated 7-25-11 Model Policies

STEREOTACTIC BODY RADIATION THERAPY (SBRT)

This Model Policy1 addresses coverage for Stereotactic Body Radiation Therapy (SBRT).

Description

SBRT is a treatment that couples a high degree of anatomic targeting accuracy and reproducibility with very high doses of extremely precise, externally generated, ionizing radiation, thereby maximizing the cell-killing eff ect on the target(s) while minimizing radiation-related injury in adjacent normal tissues. SBRT is used to treat extra-cranial sites as opposed to stereotactic radiosurgery (SRS) which is used to treat intra-cranial and spinal targets. However, some of the CPT® codes discussed here are also utilized in the billing process for SRS and are discussed accordingly in the SRS model policy.

The adjective “stereotactic” describes a procedure during which a target lesion is localized relative to a known three- dimensional reference system that allows for a high degree of anatomic accuracy and precision. Examples of devices used in SBRT for stereotactic guidance may include a body frame with external reference markers in which a patient is positioned securely, a system of implanted fi ducial markers that can be visualized with low-energy (kV)X-rays and CT-imaging-based systems used to confi rm the location of a tumor immediately prior to treatment.

Treatment of extra-cranial sites requires accounting for internal organ motion as well as for patient motion. Thus, reliable immobilization or repositioning systems must often be combined with devices capable of decreasing organ motion or accounting for organ motion e.g. respiratory gating. Additionally, all SBRT is performed with at least one form of image guidance to confi rm proper patient positioning and tumor localization prior to delivery of each fraction. The ASTRO/ACR Practice Guidelines for SBRT outline the responsibilities and training requirements for personnel involved in the administration of SBRT.

SBRT may be delivered in one to fi ve sessions (fractions). Each fraction requires an identical degree of precision, localization and image guidance. Since the goal of SBRT is to maximize the potency of the radiotherapy by completing an entire course of treatment within an extremely accelerated time frame, any course of radiation treatment extending beyond fi ve fractions is not considered SBRT and is not to be billed using these codes. SBRT is meant to represent a complete course of treatment and not be used as a boost following a conventionally fractionated course of treatment.

1 ASTRO model policies were developed as a means to effi ciently communicate what ASTRO believes to be correct coverage policies for radiation oncology services. The ASTRO model policies do not serve as clinical guidelines and they are subject to periodic review and revision without notice. The ASTRO Model Policies may be reproduced and distributed, without modifi cation, for noncommercial purposes.

Approved 8-2-10 Updated 4-17-13 STEREOTACTIC BODY RADIATION THERAPY (SBRT) MODEL POLICY Page 2

Indications and Limitations of Coverage and/or Medical Necessity

This Model Policy addresses only the CPT® codes for SBRT treatment management - 77435, and SBRT treatment delivery -77373, G0251, G0339 and G0340.

When billing for SBRT delivery, it is not appropriate to bill more than one treatment delivery code on the same day of service, even though some types of delivery may have elements of several modalities (for example, a stereotactic approach with intensity-modulated static beams or arcs). Also, only one delivery code is to be billed even if multiple lesions are treated on the same day.

Indications for SBRT:

SBRT is indicated for primary tumors of and tumors metastatic to the lung, liver, kidney, adrenal gland or pancreas as well as for pelvic and head and neck tumors that have recurred after primary irradiation when and only when each of the following criteria are met, and each specifi cally documented in the medical record. Multiple ICD diagnosis codes (ICD-9 or ICD-10) fi t this description and are listed in this coverage policy.

1. The patient’s general medical condition (notably, the performance status) justifi es aggressive treatment to a primary cancer or, for the case of metastatic disease, justifi es aggressive local therapy to one or more discrete deposits of cancer within the context of eff orts to achieve total clearance or clinically benefi cial reduction in the patient’s overall burden of systemic disease. 2. The tumor burden can be completely targeted with acceptable risk to critical normal structures.

Other Neoplasms Prostate Cancer:

Many clinical studies supporting the effi cacy and safety of SBRT in the treatment of prostate cancer have been published. At least one study has shown excellent fi ve year biochemical control rates with very low rates of serious toxicity. Additionally, numerous studies have demonstrated the safety of SBRT for prostate cancer after a follow-up interval long enough (two to three years) to provide an opportunity to observe the incidence of late GU or GI toxicity. While it is necessary to observe patients treated for prostate cancer for extended intervals to gauge the rate of long term (beyond 10 years) biochemical control and overall survival, the interim results reported appear at least as good as other forms of radiotherapy administered to patients with equivalent risk levels followed for the same duration post-treatment.

It is ASTRO’s opinion that data supporting the use of SBRT for prostate cancer have matured to a point where SBRT could be considered an appropriate alternative for select patients with low to intermediate risk disease.

Bone Metastases:

SBRT has been demonstrated to achieve durable tumor control when treating lesions in vertebral bodies or the paraspinous region, where extra care must be taken to avoid excess irradiation of the spinal cord when tumor-ablative doses are administered. There is an important clinical distinction between the status of patients described above and a patient with widely metastatic disease for whom palliation is the major objective. In one setting, a patient with limited metastatic disease and good performance status is treated with the intention of eradicating all known active disease or greatly reducing the total disease burden in a manner that can extend progression-free survival. For such a patient, SBRT can be a reasonable therapeutic intervention. However, for uncomplicated, previously untreated bone metastases in a patient with widespread progressive disease in the spine or elsewhere, where the prognosis is unfavorable, it is generally appropriate to use a less technically complex form of palliative radiotherapy rather than SBRT. CPT copyright 2012 American Medical Association. All rights reserved. STEREOTACTIC BODY RADIATION THERAPY (SBRT) MODEL POLICY Page 3

Other Indications for SBRT:

For patients with tumors of any type arising in or near previously irradiated regions, SBRT may be appropriate when a high level of precision and accuracy is needed to minimize the risk of injury to surrounding normal tissues. Also, in other cases where a high dose per fraction treatment is indicated SBRT may be appropriate. The necessity should be documented in the medical record.

Limitations:

SBRT is not considered medically necessary under the following circumstances:

1. Treatment unlikely to result in clinical cancer control and/or functional improvement. 2. The tumor burden cannot be completely targeted with acceptable risk to critical normal structures. 3. Patients with poor performance status (Karnofsky Performance Status less than 40 or Eastern Cooperative Oncology Group (ECOG) Status of 3 or worse) - see Karnofsky Performance Status and ECOG Status below.

Karnofsky Performance Status Scale 100 Normal; no complaints, no evidence of disease 90 Able to carry on normal activity; minor signs or symptoms of disease 80 Normal activity with eff ort; some signs or symptoms of disease 70 Cares for self; unable to carry on normal activity or to do active work 60 Requires occasional assistance but is able to care for most needs 50 Requires considerable assistance and frequent medical care 40 Disabled; requires special care and assistance 30 Severely disabled; hospitalization is indicated although death not imminent 20 Very sick; hospitalization necessary; active supportive treatment is necessary 10 Moribund, fatal processes progressing rapidly 0 Dead

Karnofsky DA, Burchenal JH. (1949). “The Clinical Evaluation of Chemotherapeutic Agents in Cancer.” In: MacLeod CM (Ed), Evaluation of Chemotherapeutic Agents. Columbia Univ Press. Page 196. STEREOTACTIC BODY RADIATION THERAPY (SBRT) MODEL POLICY Page 4

ECOG Performance Status Scale

Grade 0: Fully active, able to carry on all pre-disease performance without restriction. Grade 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g. light house work, offi ce work. Grade 2: Ambulatory and capable of all self-care but unable to carry out and work activities. Up and about more than 50% of waking hours. Grade 3: Capable of only limited self-care, confi ned to bed or chair more than 50% of waking hours. Grade 4: Completely disabled. Cannot carry on any self-care. Totally confi ned to bed or chair. Grade 5: Dead

Eastern Cooperative Oncology Group, Robert Comis MD, Group Chair.

* As published in Am. J. Clin. Oncol.: Oken, M.M., Creech, R.H., Tormey, D.C., Horton, J., Davis, T.E., McFadden, E.T., Carbone, P.P.: Toxicity And Response Criteria Of The Eastern Cooperative Oncology Group. Am J Clin Oncol 5:649-655, 1982.

PHYSICIANS’ CURRENT PROCEDURAL TERMINOLOGY (CPT®)/HCPCS SECTION [(Note – CPT is a trademark of the American Medical Association (AMA)]

CPT/HCPCS Codes: 77435 Stereotactic body radiation therapy, treatment management, per treatment course, to 1 or more lesions, including image guidance, entire course not to exceed 5 fractions (The same physician should not report both the stereotactic radiosurgery services [32701, 63620, 63621] and radiation treatment management [77435]) This code will be paid only once per course of treatment and should not be reported in conjunction with any other treatment management codes (77427-77432).

77373 Stereotactic body radiation therapy, treatment delivery, per fraction to 1 or more lesions, including image guidance, entire course not to exceed 5 fractions (For single fraction cranial lesions, see 77371, 77372) This code should not be reported in conjunction with any other treatment delivery codes e.g. 77401-77416, 77418. This code will be paid only once per day of treatment regardless of the number of sessions or lesions.

G0339 Image-guided robotic linear accelerator-based stereotactic radiosurgery, complete course of therapy in one session, or fi rst session of fractionated treatment This code includes all image guidance on the days of treatment delivery, so do not report G0339 in conjunction with 77421 or 77014 on the days of treatment delivery. This code will be paid only once per day of treatment regardless of the number of sessions or lesions.

G0340 Image-guided robotic linear accelerator-based stereotactic radiosurgery, delivery including collimator changes and custom plugging, fractionated treatment, all lesions, per session, second through fi fth sessions, maximum fi ve sessions per course of treatment For reporting fractions 2 through 5 after reporting G0339 for the fi rst fraction. This code includes all image guidance on the days of treatment delivery, so do not report G0340 in conjunction with 77421 or 77014 on the days of treatment delivery. This code will be paid only once per day of treatment regardless of the number of sessions or lesions.

G0251 Linear accelerator based stereotactic radiosurgery, delivery including collimator changes and custom plugging, fractionated treatment, all lesions, per session, maximum fi ve sessions per course of treatment This code should be utilized only by hospital outpatient departments to report non-robotic Linac based treatments for fractions two through fi ve. This code is excluded from MPFS by regulation.

The CPT® codes discussed in this Model Policy are applicable to all diagnoses listed in the ASTRO SRS Model Policy, a companion document to the SBRT model policy.

ICD Diagnosis Codes that Support Medical Necessity Note: Diagnosis codes are based on the current ICD-9-CM codes that are eff ective at the time of Model Policy publication. Any updates to ICD-9-CM or ICD-10-CM codes will be reviewed by ASTRO, and coverage should not be presumed until the results of such review have been published/posted. These ICD diagnosis codes support medical necessity under this Model Policy:

Diagnosis ICD-9 Code(s) ICD-10 Code(s) Comment Primary lung cancer 162.2 – 162.9 C34.00 – C34.92 Thoracic lymph nodes 196.1 C77.1 Lung metastasis 197.0 C78.00 – C78.02 Primary liver or bile duct 155.0, 155.1, 155.2 C22.0 – C22.9 cancer Liver metastasis 197.7 C78.7 Primary Pancreas cancer 157.0 – 157.9 C25.0 – C25.9 Kidney cancer or 189.0, 189.1, C64.1 – C65.9, metastasis 198.0 C79.00 – C79.02

Adrenal Gland primary or 194.0, C74.00 – C74.92, metastasis 194.6, C75.5, 198.7 C79.70 – C79.72

Prostate cancer 185 C61 Pelvic cancer recurrent after prior . Abdomen and Pelvis . 195.2, 195.3 . C76.2, C76.3 conventionally fractionated . Gynecological . 179 – 184.9 . C51.0 – C58 RT . Rectum and Anus . 154.0 – 154.8 . C19 – C21.8 . Eff ects of Radiation . 990* . T66.XXXA* Head & Neck cancer, 140.0 – 146.8, C00.0 – C10.8, recurrent after prior multiple primary sites 990* T66.XXXA* conventionally fractionated RT Nodal metastasis 196.0 – 196.9 C77.0 – C77.9 recurrent after prior conventionally fractionated RT

*ICD-9-CM 990 or ICD-10-CM T66.XXXA (Eff ects of Radiation, Unspecifi ed) may only be used where prior radiation therapy to the site is the governing factor necessitating SBRT in lieu of other radiotherapy. An ICD diagnosis code for the anatomic diagnosis must also be used. CPT copyright 2012 American Medical Association. All rights reserved. STEREOTACTIC BODY RADIATION THERAPY (SBRT) MODEL POLICY Page 6

General Information Documentation Requirements The patient’s record must support the necessity and frequency of treatment. Medical records should include not only the standard history and physical but also the patient’s functional status and a description of current performance status (Karnofsky Performance Status or ECOG Performance Status). See Karnofsky Performance Status or ECOG Performance Status listed under Limitations above. A radiation oncologist must evaluate the clinical and technical aspects of the treatment, and document this evaluation as well as the resulting management decisions. Documentation of the technical aspects of treatment planning and delivery should include details of target dose and relevant dose-limiting normal structures. Documentation should include the date and the current treatment dose. All documentation must be available upon request of the insurer. For Medicare claims, the HCPCS/CPT® code(s) may be subject to Correct Coding Initiative (CCI) edits. This policy does not take precedence over CCI edits. Please refer to the CCI for correct coding guidelines and specifi c applicable code combinations prior to billing Medicare.

References

General 17. Nelson JW, Yoo DS, Sampson JH, et al. Stereotactic body radiotherapy for lesions of the spine and paraspinal regions. Int J Radiat Oncol Biol 1. Benedict SH, Yenice KM, Followill D, et al. Stereotactic body radiation Phys. 2009; 73(5): 1369–1375. therapy: The report of AAPM Task Group 101. Med Phys. 2010; 37(8): 4078-4101. 18. Papatheofanis F, Williams E, Chang S. Cost-utility analysis of the cyberknife system For metastatic spinal tumors. Neurosurgery. 2009; 2. Chang R, Timmerman R. Stereotactic Body Radiation Therapy : A 64(2 Suppl): A73-A82. Comprehensive Review. Am J Clin Oncol. 2007; 30(6): 637-644. 19. Parikh S, Heron D. Fractionated radiosurgical management of 3. Corbin KS, Hellman S, Weichselbaum RR. Extracranial oligometastases: a intramedullary spinal cord metastasis: A case report and review of the subset of metastases curable with stereotactic radiotherapy. literature. Clin Neurol Neurosurg. 2009; 111(10): 858-861. J Clin Oncol. 2013; 31(11):1384-1390. 20. Sahgal A, Ames C, Chou D, et al. Stereotactic Body Radiotherapy Is 4. Halperin EC, Perez, CA, Brady LW. Principles and Practice of Radiation Eff ective Salvage Therapy for Patients with Prior Radiation of Spinal Therapy, 5th edition. Philadelphia, PA: Lippincott Williams & Wilkins; 2008. Metastases. Int J Radiat Oncol Biol Phys. 2008; 71: 652–665.

5. Kavanagh BD and Timmerman RD (Eds.) Stereotactic Body Radiation Breast Therapy, Philadelphia, PA: Lippincott Williams & Wilkins; 2005. 21. Milano MT, Zhang H, Metcalfe SK, et al. Oligometastatic breast cancer 6. Lo S, Fakiris A, Chang E, et al. Stereotactic body radiation therapy: a novel treated with curative-intent stereotactic body radiation therapy. treatment modality. Nat Rev Clin Oncol. 2010; 7(1): 44-54. Breast Cancer Res Treat. 2009; 115(3): 601-608.

7. Martin A, Gaya A, Stereotactic Body Radiotherapy: A Review. Clin Oncol Head and Neck (R Coll Radiol). 2010; 22(3): 157-172. 22. Chen HH, Tsai ST, Wang MS, et al. Experience in fractionated stereotactic 8. Milano MT, Katz A, Muhs, AG et al. A prospective pilot study of body radiation therapy boost for newly diagnosed nasopharyngeal curative-intent stereotactic body radiation therapy in patients with 5 or carcinoma. Int J Radiat Oncol Biol Phys. 2006; 66(5): 1408-1414. fewer oligometastatic lesions. Cancer. 2008; 112(3): 650-658. 23. Kawaguchi K, Sato K, Horie A, et al. Stereotactic radiosurgery may 9. Potters L, Kavanagh B, Galvin JM, et al. American Society for Therapeutic contribute to overall survival for patients with recurrent head and neck Radiology and Oncology (ASTRO) and American College of Radiology carcinoma. Radiat Oncol. 2010; 5:51. (ACR) practice guideline for the performance of stereotactic body radiation therapy. Int J Radiat Oncol Biol Phys. 2010; 76(2): 326-332. 24. Rwiegema J, Heron D, Ferris R, et al. Fraactionated stereotactic body radiation therapy in the treatment of previously-irradiated recurrent 10. Timmerman RD, Kavanagh BD, Cho LC, et al. Stereotactic Body Radiation head and neck carcinoma. Updated report of the University of Pittsburgh Therapy in Multiple Organ Sites. J Clin Oncol. 2007; 25(8): 947-952. experience. Am J Clin Oncol. 2009; 33(3): 286-293.

Bone Metastasis 25. Unger KR, Lominska CE, Deeken JF, et al. Fractionated Stereotactic Radiosurgery for Reirradiation of Head-and-Neck Cancer. Int J Radiat Oncol 11. Chang EL, Shiu AS, Lii MF, et al. Phase I clinical evaluation of near- Biol Phys. 2010; 77(5): 1411-1419. simultaneous computed tomographic image-guided stereotactic body radiotherapy for spinal metastases. Int J Radiat Oncol Biol Phys. 2004; 5 9(5): 1288-1294. Kidney

12. Chang EL, Shiu AS, Mendel E, et al. Phase I/II study of stereotactic body 26. Svedman C, Karlsson K, Rutkowska E, et al. Stereotactic body radiotherapy radiotherapy for spinal metastasis and its pattern of failure. J Neurosurg of primary and metastatic renal lesions for patients with only one Spine. 2007; 7(2): 151-160. functioning kidney. Acta Oncol. 2008; 47(8): 1578-1583.

13. Choi CY, Adler JR, Gibbs IC, et al. Stereotactic Radiosurgery for Liver Treatment of Spinal Metastases Recurring in Close Proximity to Previously Irradiated Spinal Cord. Int J Radiat Oncol Biol Phys. 2010; 27. Choi BO, Choi IB, Jang HS, et al. Stereotactic body radiation therapy with or 78(2): 499-506. without transarterial chemoembolization for patients with primary hepatocellular carcinoma: preliminary analysis. BMC Cancer. 2008; 8: 351. 14. Gagnon GJ, Nasr NM, Liao JJ, et al. Treatment of spinal tumors using CyberKnife fractionated stereotactic radiosurgery: pain and quality of 28. Katz AW, Carey-Sampson M, Muhs AG, et al. Hypofractionated stereotactic life assessment after treatment in 200 patients. Neurosurgery. 2009; body radiation therapy (SBRT) for limited hepatic metastases. Int J Radiat 64(2): 297–306. Oncol Biol Phys. 2007; 67(3): 793-798.

15. Haley M, Gerszten P. Stereotactic Radiosurgery in the Management of 29. Kavanagh BD, Schefter TE, Cardenes HR, et al. Interim analysis of a Cancer Pain. Curr Pain Headache Rep. 2009; 13(4): 277–281. prospective phase I/II trial of SBRT for liver metastases. Acta Oncol. 2006; 45(7): 848-855. 16. Janjan N, Lutz S, Bedwinek J, et al. Therapeutic Guidelines for the Treatment of Bone Metastasis: A Report from the American College of Radiology Appropriateness Criteria Expert Panel on Radiation Oncology. J Palliat Med. 2009; 12(5): 417-426. STEREOTACTIC BODY RADIATION THERAPY (SBRT) MODEL POLICY Page 8

30. Lee MT, Kim JJ, Dinniwell R, et al. Phase I study of individualized stereotactic 47. Fakiris, AJ, McGarry RC, Yiannoutsos CT, et al. Stereotactic body body radiotherapy for liver metastases. J Clin Oncol. 2009; 27: 1585–1591. radiation therapy for early-stage non-small-cell lung carcinoma: four-year results of a prospective phase II study. Int J Radiat Oncol Biol 31. McCammon R, Schefter TE, Gaspar LE, et al. Observation of a dose-control Phys. 2009; 75(3): 677–682. relationship for lung and liver tumors after stereotactic body radiation therapy. Int J Radiat Oncol Biol Phys. 2009; 73(1): 112-118. 48. Fritz P, Kraus HJ, Blaschke T, et al. Stereotactic, high single-dose irradiation of stage I non-small cell lung cancer (NSCLC) using four- 32. Méndez Romero A, Wunderink W, Hussain SM, et al. Stereotactic body dimensional CT scans for treatment planning. Lung Cancer. 2008; radiation therapy for primary and metastatic liver tumors: A single 60(2): 193-199. institution phase i-ii study. Acta Oncol. 2006; 45(7): 831-837. 49. Guckenberger M, Wulf J, Mueller G, et al. Response Relationship for 33. Méndez Romero A, Wunderink W, van Os RM, et al. Quality of life Image-Guided Stereotactic Body Radiotherapy of Pulmonary Tumors: after stereotactic body radiation therapy for primary and metastatic liver Relevance of 4d Dose Calculation. Int J Radiat Oncol Biol Phys. 2009; tumors. Int J Radiat Oncol Biol Phys. 2008; 70(5): 1447-1452. 73(2): 442-448.

34. Rusthoven KE, Kavanagh BD, Cardenes H, et al. Multi-institutional 50. Henderson M, McGarry R, Yiannoutsos C, et al. Baseline pulmonary phase I/II trial of stereotactic body radiation therapy for liver metastases. function as a predictor for survival and decline in pulmonary J Clin Oncol. 2009; 27: 1579–1584. function over time in patients undergoing stereotactic body radiotherapy for the treatment of stage I non-small-cell lung cancer. 35. Rusthoven KE, Kavanagh BD, Cardenes H, et al. Multi-institutional phase I/ Int J Radiat Oncol Biol Phys. 2008; 72(2): 404-409. II trial of stereotactic body radiation therapy for liver metastases. J Clin Oncol. 2009; 27(10): 1572-1578. 51. Hiraoka M, Matsuo Y, Nagata Y. Stereotactic body radiation therapy (SBRT) for early-stage lung cancer. Cancer Radiother. 2007; 11(1-2): 36. Schefter TE, Kavanagh BD, Timmerman RD, Cardenes HR, Baron A, Gaspar 32-35. LE. A phase I trial of stereotactic body radiation therapy (SBRT) for liver metastases. Int J Radiat Oncol Biol Phys. 2005; 62(5): 1371-1378. 52. Joyner M, Salter BJ, Papanikolaou N, et al. Stereotactic body radiation therapy for centrally located lung lesions. Acta Oncol. 2006; 45(7): 802- 37. Tse RV, Hawkins M, Lockwood G, Kim JJ, Cummings B, Knox J, Sherman M, 807. Dawson LA. Phase I study of individualized stereotactic body radiotherapy for hepatocellular carcinoma and intrahepatic cholangiocarcinoma. 53. Koto M, Takai Y, Ogawa Y, et al. A phase II study on stereotactic body J Clin Oncol. 2008; 26(4):657-664. radiotherapy for stage I non-small cell lung cancer. Radiother Oncol. 2007; 85(3): 429-434. Lung 54. McCammon R, Schefter TE, Gaspar LE, et al. Observation of a 38. Collins BT, Vahdat S, Erickson K, et al. Radical cyberknife radiosurgery with dose-control relationship for lung and liver tumors after stereotactic tumor tracking: an eff ective treatment for inoperable small peripheral body radiation therapy. Int J Radiat Oncol Biol Phys. 2009; 73(1): 112- stage I non-small cell lung cancer. J Hematol Oncol. 2009; 2: 1. 118.

39. Banki F, Luketich JD, Chen H, et al. Stereotactic radiosurgery for lung cancer. 55. McGarry RC, Papiez L, Williams M, et al. Stereotactic body radiation Minerva Chir. 2009; 64(6): 589-598. therapy of early-stage non-small-cell lung carcinoma: phase I study. Int J Radiat Oncol Biol Phys. 2005; 63(4): 1010-1015. 40. Baumann P, Nyman J, Hoyer M, et al. Outcome in a prospective phase II trial of medically inoperable stage I non-small-cell lung cancer patients treated 56. Norihisa Y, Nagata Y, Takayama K, et al. Stereotactic body radiotherapy with stereotactic body radiotherapy. J Clin Oncol. 2009; 27(20): 3290–3296. for oligometastatic lung tumors. Int J Radiat Oncol Biol Phys. 2008; 72(2): 398-403. 41. Baumann P, Nyman J, Hoyer M, et al. Stereotactic body radiotherapy for medically inoperable patients with stage I non-small cell lung cancer - 57. Okunieff P, Petersen AL, Philip A, et al. Stereotactic Body Radiation a fi rst report of toxicity related to COPD/CVD in a non-randomized Therapy (SBRT) for lung metastases. Acta Oncol. 2006; 45(7): 808-817. prospective phase II study. Radiother Oncol. 2008; 88(3): 359-367. 58. Pennathur A, Luketick J, Heron D, et. al. Stereotactic radiosurgery for 42. Baumann P, Nyman J, Lax I, et al. Factors important for effi cacy of the treatment of lung neoplasm: experience in 100 consecutive stereotactic body radiotherapy of medically inoperable stage I lung cancer. patients. Ann Thorac Surg. 2009; 88: 1594-1600. A retrospective analysis of patients treated in the Nordic countries. Acta Oncol. 2006; 45(7): 787-795. 59. Rusthoven KE, Kavanagh BD, Burri SH, et al. Multi-institutional phase I/II trial of stereotactic body radiation therapy for lung metastases. J 43. Chang JY, Balter PA, Dong L, et al. Stereotactic body radiation therapy in Clin Oncol. 2009; 27(10): 1579-1584. centrally and superiorly located stage I or isolated recurrent non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2008; 72(4): 967–971. 60. Salazar OM, Sandhu TS, Lattin PB, et al. Once-weekly, high-dose stereotactic body radiotherapy for lung cancer: 6-year analysis of 60 44. Chang JY, Balter PA, Dong L, et al. Stereotactic body radiation therapy in early-stage, 42 locally advanced, and 7 metastatic lung cancers. Int J centrally and superiorly located stage I or isolated recurrent non-small-cell Radiat Oncol Biol Phys. 2008; 72(3): 707-715. lung cancer. Int J Radiat Oncol Biol Phys. 2008; 72(4): 967-971. 61. Schefter TE, Kavanagh BD, Raben D, et al. A Phase I/II trial of 45. Chen Y, Guo W, Lu Y,et al. . Dose-individualized stereotactic body Stereotactic Body Radiation Therapy (SBRT) for Lung Metastases: radiotherapy for T1-3N0 non-small cell lung cancer: long-term results and Initial report of dose escalation and early toxicity. Int J Radiat Oncol effi cacy of adjuvant chemotherapy. Radiother Oncol. 2008; 88(3): 351-358. Biol Phys. 2006; 66(4 Suppl): S120-S127.

46. Coons D, Gokale A, Burton A, et al. Fractionated stereotactic body radiation therapy in the treatment of primary, recurrent, and metastatic lung tumors: the role of positron emission tomography/computed tomography-based treatment planning. Clin Lung Cancer. 2008; 9(4): 217-221. STEREOTACTIC BODY RADIATION THERAPY (SBRT) MODEL POLICY Page 9

62. Scorsetti M, Navarria P, Facoetti A, et al. Eff ectiveness of Prostate stereotactic body radiotherapy in the treatment of inoperable early-stage lung cancer. Anticancer Res. 2007; 27(5B): 3615-3619. 76. Buyyounouski MK, Price RA, Harris EER, et al. Stereotactic body radiotherapy for primary management of early-stage, low-to 63. Senan S, Lagerwaard F. Stereotactic radiotherapy for stage I lung intermediate-ris prostate cancer: Report of the American Society for cancer: Current results and new developments. Cancer Radiother. Therapeutic Radiology and Oncology Emerging Technology 2010; 14(2): 115-118. Committee. Int J Radiat Oncol Biol Phys. 2010; 76(5): 1297-1304.

64. Sonke JJ, Rossi M, Wolthaus J,. et al. Frameless stereotactic body 77. Freeman DF, King CR. Stereotactic body radiation for low-risk prostate radiotherapy for lung cancer using four dimensional cone beam CT cancer: fi ve year outcomes. Radiat Oncol. 2011; 6:3. guidance. Int J Radiat Oncol Biol Phys. 2009; 74(2): 567–574. 78. Ishiyama H, Teh BS, Lo SS, et al. Stereotactic body radiation therapy 65. Takeda A, Sanuki N, Kunieda E, et al. Stereotactic Body Radiotherapy for prostate cancer. Future Oncol. 2011; 7(9): 1077-1086. for Primary Lung Cancer at a Dose of 50 Gy Total in Five Fractions to the Periphery of the Planning Target Volume Calculated Using a 79. King CR, Brooks JD, Gill H, et al. Long-term outcomes from a Superposition Algorithm. Int J Radiat Oncol Biol Phys. 2009; 73(2): prospective trial of stereotactic body radiotherapy for low-risk 442-448. prostate cancer. Int J Radiat Oncol Biol Phys. 2012; 82(2); 877-882.

66. van der Voort van Zyp NC, Prevost J-B, Hoogeman MS, et al. 80. King CR, Brooks JD, Gill H, et al. Stereotactic body radiotherapy for Stereotactic radiotherapy with real-time tumor tracking for non-small localized prostate cancer: interim results of a prospective phase II ` cell lung cancer: clinical outcome. Radiother Oncol. 2009; 91(3): clinical trial. Int J Radiat Oncol Biol Phys. 2009; 73(4): 1043–1048. 296–300. 81. Katz AJ, Santoro M, Ashley R, et al. Stereotactic body radiotherapy 67. van der Voort van Zyp NC, van der Holt B, van Klaveren RJ, et al. for organ-confi ned prostate cancer. BMC Urol. 2010; 10(1) Stereotactic body radiotherapy using real-time tumor tracking in (doi:10.1186/1471-2490-10-1). octogenarians with non-small cell lung cancer. Lung Cancer. 2010; 69(3): 296-301. 82. Madsen BL, Hsi RA, Pham HT, et al. Stereotactic hypofractionated accurate radiotherapy of the prostate (SHARP), 33.5 Gy in fi ve 68. Zimmermann F, Wulf J, Lax I, et al. Stereotactic Body Radiation fractions for localized disease: fi rst clinical trial results. Int J Radiat Therapy for Early Non-Small Cell Lung Cancer. Front Radiat Ther Oncol Biol Phys. 2007; 67(4): 1099-1105. Oncol. 2010; 42: 94-114. 83. Parthan A, Pruttivarasin N, Davies D, et al. Comparative Pancreas cost-eff ectiveness of stereotactic body radiation therapy versus intensity-modulated and proton radiation therapy for localized 69 . Chang DT, Schellenberg D, Shen J, et al. Stereotactic radiotherapy prostate cancer. Front Oncol. 2012; 2:81. for unresectable adenocarcinoma of the pancreas. Cancer. 2009; 115(3): 665-672.

70. Mahadevan A, Jain S, Goldstein M, et al. Stereotactic Body Radiotherapy and Gemcitabine for Locally Advanced Pancreatic Cancer. Int J Radiat Oncol Biol Phys. 2010; 78(3): 735-742.

71. Rwigema J, Parihk S, Heron D, et al. Stereotactic body radiotherapy in the treatment of advanced adenocarcinoma of the pancreas. Am J Clin Oncol. 2011; 34(1): 63-69.

72. Schellenberg D, Goodman KA, Lee F, et al. Gemcitabine chemotherapy and single-fraction stereotactic body radiotherapy for locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2008; 72: 678–686.

73. Schellenberg D, Quon A, Yuriko Minn A et al. 18 Fluorodeoxyglucose PET is prognostic of progression-free and overall survival in locally advanced pancreas cancer treated with stereotactic radiotherapy. Int J Radiat Oncol Biol Phys. 2010; 77(5): 1420- 1425.

Pelvic

74. Choi C, Cho C, Yoo S, et al. Image-guided Stereotactic Body Radiation Therapy in Patients with Isolated Para-aortic Lymph Node Metastases from Uterine Cervical and Corpus Cancer. Int J Radiat Oncol Biol Phys. 2009; 74(1): 147-153.

75. Kim MS, Choi C, Yoo S, et al. Stereotactic body radiation therapy in patients with pelvic recurrence from rectal carcinoma. Jpn J Clin Oncol. 2008; 38(10): 695-700. Practical Radiation Oncology (2012) 2, 210–225 CME

www.practicalradonc.org

Special Article Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es): An American Society for Radiation Oncology evidence-based guideline May N. Tsao MDa,⁎, Dirk Rades MDb, Andrew Wirth MDc, Simon S. Lo MDd, Brita L. Danielson MDe, Laurie E. Gaspar MD, MBAf, Paul W. Sperduto MD, MPPg, Michael A. Vogelbaum MD, PhDh, Jeffrey D. Radawski MDi, Jian Z. Wang PhDn, Michael T. Gillin PhD j, Najeeb Mohideen MDk, Carol A. Hahn MDl, Eric L. Chang MDm aDepartment of Radiation Oncology, University of Toronto, Odette Cancer Centre, Toronto, Ontario, Canada bDepartment of Radiation Oncology, University Hospital Schleswig-Holstein, Luebeck, Germany (ESTRO representative) cPeter MacCallum Cancer Center, Trans Tasman Radiation Oncology Group (TROG), East Melbourne, Australia dDepartment of Radiation Oncology, Case Western Reserve University, University Hospitals Case Medical Center, Cleveland, Ohio eDepartment of Radiation Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Canada (CARO representative) fDepartment of Radiation Oncology, University of Colorado, Aurora, Colorado gUniversity of Minnesota Gamma Knife Center and Minneapolis Radiation Oncology, Minneapolis, Minnesota hDepartment of Neurological Surgery, Cleveland Clinic, Cleveland, Ohio iDepartment of Radiation Oncology, Ohio State University, Columbus, Ohio jDepartment of Radiation Oncology, M.D. Anderson Cancer Center, Houston, Texas kDepartment of Radiation Oncology, Northwest Community Hospital, Arlington Heights, Illinois lDepartment of Radiation Oncology, Duke University Medical School, Durham, North Carolina mDepartment of Radiation Oncology, University of Southern California Keck School of Medicine, Los Angeles, California nDepartment of Radiation Oncology, Ohio State University, Columbus, Ohio (deceased)

Received 27 October 2011; revised 9 December 2011; accepted 15 December 2011

Note: An online CME test for this article can be taken at http://astro.org/MOC. Conflicts of interest: Before initiation of this Guideline, all members of the Guidelines Task Group were required to complete disclosure statements. These statements are maintained at the American Society for Radiation Oncology (ASTRO) headquarters in Fairfax, Virginia and pertinent disclosures are published with the report. The ASTRO Conflict of Interest Disclosure Statement seeks to provide a broad disclosure of outside interests. Where a potential conflict is detected, remedial measures to address any potential conflict are taken and will be noted in the disclosure statement. Dirk Rades has received research grants from Merck Serono and Novartis, and serves as a consultant for Amgen and Astra Zeneca. Michael Vogelbaum has received research funding from Schering-Plough, Genentech, Brainlab, and Astra Zeneca; he owns stock in Johnson and Johnson. Jian Wang has received a prostate cancer research grant from the Ohio Cancer Research Associates. Expert reviewers were also required to complete disclosure statements, which are maintained at ASTRO Headquarters. The Task Group Chairs reviewed all disclosures and determined that they were not relevant to the subject matter of the Guideline. ⁎ Corresponding author. Odette Cancer Centre, 2075 Bayview Ave, Toronto, ON M4N 3M5. E-mail address: [email protected] (M.N. Tsao).

1879-8500/$ – see front matter © 2012 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.prro.2011.12.004 Practical Radiation Oncology: July-September 2012 Brain metastases: An ASTRO guideline 211

Abstract Purpose: To systematically review the evidence for the radiotherapeutic and surgical management of patients newly diagnosed with intraparenchymal brain metastases. Methods and Materials: Key clinical questions to be addressed in this evidence-based Guideline were identified. Fully published randomized controlled trials dealing with the management of newly diagnosed intraparenchymal brain metastases were searched systematically and reviewed. The U.S. Preventative Services Task Force levels of evidence were used to classify various options of management. Results: The choice of management in patients with newly diagnosed single or multiple brain metastases depends on estimated prognosis and the aims of treatment (survival, local treated lesion control, distant brain control, neurocognitive preservation). Single brain metastasis and good prognosis (expected survival 3 months or more): For a single brain metastasis larger than 3 to 4 cm and amenable to safe complete resection, whole brain radiotherapy (WBRT) and surgery (level 1) should be considered. Another alternative is surgery and radiosurgery/ radiation boost to the resection cavity (level 3). For single metastasis less than 3 to 4 cm, radiosurgery alone or WBRT and radiosurgery or WBRT and surgery (all based on level 1 evidence) should be considered. Another alternative is surgery and radiosurgery or radiation boost to the resection cavity (level 3). For single brain metastasis (less than 3 to 4 cm) that is not resectable or incompletely resected, WBRT and radiosurgery, or radiosurgery alone should be considered (level 1). For nonresectable single brain metastasis (larger than 3 to 4 cm), WBRT should be considered (level 3). Multiple brain metastases and good prognosis (expected survival 3 months or more): For selected patients with multiple brain metastases (all less than 3 to 4 cm), radiosurgery alone, WBRT and radiosurgery, or WBRT alone should be considered, based on level 1 evidence. Safe resection of a brain metastasis or metastases causing significant mass effect and postoperative WBRT may also be considered (level 3). Patients with poor prognosis (expected survival less than 3 months): Patients with either single or multiple brain metastases with poor prognosis should be considered for palliative care with or without WBRT (level 3). It should be recognized, however, that there are limitations in the ability of physicians to accurately predict patient survival. Prognostic systems such as recursive partitioning analysis, and diagnosis- specific graded prognostic assessment may be helpful. Conclusions: Radiotherapeutic intervention (WBRT or radiosurgery) is associated with improved brain control. In selected patients with single brain metastasis, radiosurgery or surgery has been found to improve survival and locally treated metastasis control (compared with WBRT alone). © 2012 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Introduction that they are modality-based, it was also felt important to develop guidelines from an international perspective Brain metastases represent a significant health care with international representation on the Brain Metastases problem. It is estimated that 20% to 40% of cancer Task Group. Additional key questions are posed (not patients will develop brain metastases during the course necessarily previously addressed) such as prognostic of their illness.1 classification systems, radiotherapy fractionation schemes, Systematic reviews based on randomized phase III comparison of surgery and radiosurgery, neurocognition controlled trials for the management of single or as an outcome variable in decision-making, palliative multiple brain metastases in adult patients have been supportive care, and radiation sensitizers. published.1-8 Various treatment modalities exist, includ- Treatment recommendations are based on patient ing whole brain radiotherapy (WBRT), resection, stereo- factors (such as age, performance status), tumor factors tactic radiosurgery, and best supportive care with the use (such as number and size of brain metastases, tumor of dexamethasone. A series of articles performing a type, extracranial disease activity), and available treat- systematic review and evidence-based clinical practice ment options (such as access to neurosurgery or guidelines have been published from the perspective of stereotactic radiosurgery). the modalities listed above under the auspices of the This Guideline builds on the previous ASTRO Health American Association of Neurological Surgeons/Congress Services Research Committee publication, “The American of Neurosurgeons (AANS/CNS).4-8 The conclusions from Society for Therapeutic Radiology and Oncology this American Society for Radiation Oncology (ASTRO) (ASTRO) evidence-based review of the role of radiosur- Guideline are congruent with the conclusions put forth gery for brain metastases.”1 This present guideline has by the AANS/CNS. While these articles are important in been endorsed by the CNS. 212 M.N. Tsao et al Practical Radiation Oncology: July-September 2012

Methods and materials As a result of feedback received from public comments, the literature search was further expanded to include Process nonrandomized studies (prospective or retrospective) dealing with the use of either radiosurgery or fractionated radiation to the postoperative surgical cavity. The MED- The Guidelines Subcommittee of the Clinical Affairs LINE (1947 to May week 2, 2011) search resulted in 1549 and Quality Committee, in accordance with established nonrandomized publications and EMBASE (1980-2011 ASTRO policy, recruited a Task Group composed of recognized experts in the fields of radiotherapy, surgery, week 20) gave 3721 nonrandomized publications. The CENTRAL search resulted in 0 randomized controlled and radiosurgery for brain metastases. These experts trials. Titles and abstracts were screened and a final total of represent radiation oncology, neurosurgery, physics, out- 15 relevant publications were retrieved. comes, and health services research. The Task Group was Of note, all the radiosurgery trials used frame-based asked to systematically review the literature on the single fraction radiosurgery techniques with either a linear radiotherapeutic and surgical management for patients accelerator or gamma knife unit. with newly diagnosed metastatic disease to the brain. Management options were graded by the level of In June 2009, the ASTRO Board of Directors approved a proposal to develop a Guideline on radiotherapeutic and evidence available using the U.S. Preventative Services Task Force levels.12 Due to the lack of high-quality surgical management for newly diagnosed brain metasta- studies, management of patients with recurrent metastatic ses. In January 2010, the Board authorized the Task Group disease to the brain is not included in this report. membership. The Task Group participated in a series of The U.S. Preventative Services Task Force levels of communications by e-mail and conference calls to review evidence12 are as follows. the relevant publications, to discuss controversial issues, and formulate the Guidelines contained herein. The Task Level I: Evidence obtained from at least 1 properly designed Group agreed by consensus on the various recommenda- randomized controlled trial. tions based on the randomized trials and relevant Level II-1: Evidence obtained from well-designed controlled publications. The initial draft of the manuscript was trials without randomization. reviewed by 3 expert reviewers and was placed on the Level II-2: Evidence obtained from well-designed cohort or ASTRO website during the month of April 2011 for public case-controlled analytic studies, preferably from more than 1 comment. Upon integration of the feedback, the document center or research group. was then submitted to the ASTRO Board of Directors for Level II-3: Evidence obtained from multiple time series with their final review and approval in October 2011. or without the intervention.

Dramatic results from uncontrolled trials might also be Literature search regarded as this type of evidence.

MEDLINE (1966-Nov. 3, 2010), EMBASE (1980- Level III: Opinions of respected authorities, based on clinical 2010 week 46), and the CENTRAL databases (issue 4, experience, descriptive studies or reports of expert committees. 2010) were searched (Appendix 1). The search strategies resulted in 1826 publications, 597 publications, and 425 The medical management issues associated with brain publications from MEDLINE, EMBASE, and CENTRAL, metastases will not be addressed by this Guideline as they respectively (search strategy courtesy of the Cochrane are outside the scope of this review. Optimal follow-up Library). Only randomized phase III trials pertinent to the brain imaging for patients with brain metastases has not management of newly diagnosed brain metastases were been evaluated using high-quality trials. Based on expert included. Trials dealing with the use of WBRT, surgery, opinion, in patients with good prognostic features and radiosurgery, chemotherapy, radiosensitizers, and pallia- where there is potential for future salvage brain metastases tive care alone were considered. Trials that examined the treatment, enhanced magnetic resonance imaging follow- use of prophylactic cranial irradiation were excluded. A up every 2 to 4 months should be considered. total of 36 randomized controlled trials were retrieved. One trial was excluded as it was published in abstract form in the year 2000 but never fully reported.9 Two duplicate Results publications of the same trial10,11 were included. Lead representatives from international radiation on- Table 1 and Table 2 summarize common scenarios cology groups, ASTRO, Canadian Association of Radia- related to patients presenting initially with either single or tion Oncology (CARO), European Society for Therapeutic multiple brain metastasis(es). These tables include not Radiology and Oncology (ESTRO), and Trans-Tasman only the level 1 evidence but also other treatment options Radiation Oncology Group (TROG), reviewed the 36 based on panel opinion and supported by literature of retrieved trials. lower quality evidence. Practical Radiation Oncology: July-September 2012 Brain metastases: An ASTRO guideline 213

Table 1 Single brain metastasis—initial management Prognostic Other Treatment options (evidence grade) Clinical benefit a category ( ) features references S LC WB control Neurocognition Good prognosis Complete If brain metastasis ≤3-4 cm: resection • Surgery and WBRT (level 1)10,11,22,23,42,43,b ✓✓ ✓ possible • Radiosurgery and WBRT (level 1)51,53 ✓✓ ✓ Expected survival • Radiosurgery alone (Level 1)23,54 ✓✓ 3 mo or more • Surgery with radiosurgery/radiation boost ✓✓(with WBRT) to the resection cavity with or without WBRT (level 3)26-41,b

If brain metastasis N3-4 cm: • Surgery and WBRT (level 1)10,11,22,23,42,43,b ✓✓ ✓ • Surgery with radiosurgery/radiation ✓✓(with WBRT) boost to the resection cavity with or without WBRT (level 3)26-41,b

Good prognosis Not If brain metastasis ≤3-4 cm: resectable • Radiosurgery and WBRT (level 1)51,53 ✓✓ ✓ Expected survival • Radiosurgery alone (level 1)23,54 ✓✓ 3 mo or more If brain metastasis N3-4 cm: • WBRT (level 3), with consideration of ✓✓ ✓ biopsy, if primary unknown59,85,86

Poor prognosis • WBRT (level 3)59,85 ✓✓ Expected survival • Palliative care without WBRT (level 3)59,85 less than 3 mo KPS, Karnofsky performance status; LC, local control; S, survival; WB, whole brain; WBRT, whole brain radiotherapy. Surgery may be favored if the diagnosis is uncertain (eg, no known primary cancer or remote history of cancer and no known extracranial metastases or metastasis). a Prognostic category based on known prognostic factors (see clinical question 1, references 13-21). b Excluding radiosensitive histologies (eg, small cell lung cancer, leukemia, lymphoma, germ cell tumor). A 6%-9% minority of patients in Radiation Therapy Oncology Group (RTOG) 9508 trial had small cell lung cancer.

The questions and guideline statements regarding the radiosensitizers: class I, patients with Karnofsky perfor- radiotherapeutic and surgical management for newly mance status (KPS) ≥70 years, less than 65 years of age diagnosed brain metastases are listed below. with controlled primary (3-month stability on imaging or newly diagnosed), and no extracranial metastases; class b 1. What prognostic factors are important for III, KPS 70; class II, All others. Median survival was 7.1 months, 4.2 months, and 2.3 months for class I, II, and III, assessing and managing patients with newly respectively. diagnosed brain metastases? Brain metastases are a heterogeneous population. The purpose of the graded prognostic assessment Interpretative summary (GPA) was to identify significant diagnosis-specific prognostic factors in an updated era (1985-2007) as Several prognostic indices have been reported in the compared with the RTOG recursive partitioning literature13-21 for survival duration among patients with analysis (RPA) (1979-1993). The original GPA was newly diagnosed brain metastases. These are useful in based on 4 criteria15: age, KPS, number of brain categorizing patients into survival time strata for treatment metastases, and presence or absence of extracranial decisions, for predicting the results of therapeutic in- metastases. Each of the 4 criteria is given a score of 0, terventions, and for comparing treatment results. 0.5, or 1.0 and these 4 scores are summed to determine the The Radiation Therapy Oncology Group (RTOG) GPA score. Patients with the best prognosis have a GPA devised 3 prognostic groups using recursive partitioning score of 4.0. The authors established this prognostic index analysis13,14 based on 1200 patients treated on prospec- based on 1960 patients treated with WBRT alone, WBRT tive clinical trials with WBRT alone or additionally with and radiosensitizers, or WBRT and radiosurgery in the 214 M.N. Tsao et al Practical Radiation Oncology: July-September 2012

Table 2 Multiple brain metastases-initial management Prognostic Other features Treatment options Clinical benefit a category ( ) (evidence grade) references S LC WB control Neurocognition Good prognosis All brain • Radiosurgery and WBRT (level 1)51,53 ✓✓ Expected survival metastases • Radiosurgery alone23,54 (level 1) ✓✓ 3 mo or more ≤3-4 cmb • WBRT (level 1)59,85 ✓✓

Good prognosis Brain metastasis/ • Safe surgical resection of the ✓✓ metastases brain metastasis/metastases causing causing significant significant mass effect and mass effect c postoperative WBRT (level 3)25,b Expected survival • WBRT (level 3)59,85 ✓✓ ✓ 3 mo or more

Poor prognosis • WBRT (level 3)59,85 ✓✓ Expected survival • Palliative care without less than 3 mo WBRT (level 3)59,85 KPS, Karnofsky performance status; LC, local control; S, survival; WB, whole brain; WBRT, whole brain radiotherapy. Surgery may be favored if the diagnosis is uncertain (eg, no known primary cancer or remote history of cancer and no known extracranial metastases or metastasis). a Prognostic category based on known prognostic factors (see clinical question 1, references 13-21). b Excluding radiosensitive histologies (eg, small cell lung cancer, leukemia, lymphoma, germ cell tumor). A 6%-9% minority of patients in RTOG 9508 trial had small cell lung cancer. c The maximum number or total volume of brain metastases best treated with radiosurgery (or surgery) is unknown. Randomized trials which have examined the use of radiosurgery, included selected patients with up to 4 brain metastases, while retrospective reports document use of radiosurgery that exceed 4 brain metastases.52,55 A retrospective study25 suggested that surgery significantly improves survival if all brain metastases can be removed.

RTOG database, with all patients and data coming from metastases treated with surgery, WBRT, radiosurgery, prospective clinical trials. or various treatment combinations. New diagnosis- The GPA was then refined based on a multi- specific prognostic indices (diagnosis-specific graded institutional analysis of 4259 other patients with brain prognostic assessment) were defined based only on the

Table 3 Diagnosis-specific GPA15,20,21 GPA Significant prognostic GPA scoring criteria factors NSCLC/SCLC 0 0.5 1 Age N60 50-60 b50 KPS b70 70-80 90-100 ECM Present — Absent #BM N3 2-3 1

Melanoma/RCC 0 1 2 KPS b70 70-80 90-100 #BM N3 2-3 1

Breast cancer 0 0.5 1.0 1.5 2.0 KPS b60 60 70-80 90-100 ER/PR/Her2 Triple negative ER/PR + Her2 - ER/PR – Her2 + Triple positive Age ≥ 70 b70

GI 0 1 2 3 4 KPS b70 70 80 90 100 ECM, extracranial metastases; ER, estrogen receptor; GPA, graded prognostic assessment; Her2, human epidermal growth factor receptor 2; KPS, Karnofsky performance status; #BM, number of brain metastases; NSCLC, non-small cell lung cancer; PR, progesterone receptor; RCC, renal cell carcinoma; SCLC, small cell lung cancer. Practical Radiation Oncology: July-September 2012 Brain metastases: An ASTRO guideline 215

Table 4 Median survivals stratified by diagnosis and diagnosis-specific GPA score for patients with newly diagnosed brain metastases15,20,21 DiagnosisOverall median Diagnosis-specific GPA survival (mo) GPA: 0-1 GPA: 1.5-2.0 GPA: 2.5-3.0 GPA: 3.5-4.0 Median Median Median Median survival (mo) survival (mo) survival (mo) survival (mo) NSCLC 7.0 3.0 5.5 9.4 14.8 SCLC 4.9 2.8 4.9 7.7 17.1 Melanoma 6.7 3.4 4.7 8.8 13.2 Renal cell 9.6 3.3 7.3 11.3 14.8 GI 5.4 3.1 4.4 6.9 13.5 Breast 13.8 3.4 7.7 15.1 25.3 Total 7.2 3.1 5.4 9.6 16.7 GI, gastrointestinal; GPA, graded prognostic assessment; NSCLC, non-small cell lung cancer; SCLC, small cell lung cancer. statistically significant prognostic factors for each Newly diagnosed brain metastases: Single individual diagnosis.20 A subsequent analysis of 400 brain metastasis, role for surgery breast cancer patients refined the breast-GPA scoring system.21 2. For patients with single brain metastasis Table 3 shows the GPA scoring criteria for each of the significant prognostic factors by diagnosis. Table 4 (excluding radiosensitive histologies such as shows the associated range of median survival by GPA small cell lung cancer, leukemia, lymphoma, and diagnosis. and germ cell tumor), does surgical resection Other prognostic indices such as the score index for and whole brain radiotherapy improve survival radiosurgery, the basic score for brain metastases, the or brain control compared with whole brain Golden grading system, and the Rades prognostic scoring radiotherapy alone or compared with surgical system have also been published.16-19 resection alone?

Caveats Interpretative summary For selected patients with good performance status Most published randomized trials that deal with the (eg, KPS ≥70), limited extracranial disease, and a management of patients with brain metastases included resectable brain metastasis, complete resection of the patients with various primary cancers (non-small cell lung single brain metastasis improves the probability of cancer, breast cancer, etc). Physicians should consider extended survival. The addition of postoperative whole histology-specific indices in regard to clinical decision brain radiotherapy improves treated brain metastasis making. The use of histology-specific indices help guide control and overall brain control without improving estimated prognosis, useful in deciding on whether overall survival or duration of functional independence. aggressive therapies (eg, radiosurgery, surgery) for These interpretations are consistent with the AANS selected patients should be considered (Tables 1 and 2). guidelines on the use of surgery.5 At present, there are insufficient level 1 data to recommend protracted WBRT schedules for certain histologies or higher radiosurgery doses for “radioresistant” lesions Phase III randomized trials evidence summary (such as melanoma, renal cell carcinoma). Future clinical trials should consider these histology-specific indices for WBRT and surgery versus WBRT alone purposes of stratification. Three randomized controlled trials10,11,42,43 examined It should be noted that the original RTOG RPA the use of WBRT with or without resection for a single system did not find histology to be statistically brain metastasis. [References 10 and 11 are duplicate significant for survival prediction. However, the revised publications of the same trial]. Two of the 3 trials10,11,43 GPA has found histology to be statistically significant found significant improvement in survival with the based on retrospective data in a more recent era (1985- addition of surgery to WBRT as compared with 2007) compared with the database used to derive the WBRT alone. RTOG RPA (1979-1993). The difference may be due to The benefit for surgery may be lost in patients with newer and more effective chemotherapy used to treat poor prognostic factors such as advanced extracranial systemic disease. disease or lower performance status. Decreased median 216 M.N. Tsao et al Practical Radiation Oncology: July-September 2012 survival was reported in 2 randomized trials10,11,42 in suggests the hypothesis that resection of multiple metas- patients with a greater systemic involvement of their tases may convey a similar benefit as conferred by primary malignancy. Noordijk et al10 reported a 5-month resection of a single brain metastasis.25 Furthermore, the median survival in patients with progressive systemic benefit of excising multiple brain metastases causing mass disease in both the WBRT plus surgery versus WBRT effect has not been definitively proven with level 1 alone arms. Patients with stable systemic disease had a evidence. However, it was felt by the guideline authors 12-month survival with WBRT and surgery versus 7 that safe resection of multiple brain metastases causing months with WBRT alone. Mintz et al42 reported a mass effect should be included as an option for good significant difference (P = .009) in the Cox regression prognosis patients. analysis for mortality in patients having extracranial There is a lack of level 1 evidence relating to the use metastases versus no evidence of primary tumor (risk of surgery and radiation boost to the surgical cavity with ratio 2.3). Forty-five percent of the patients in the study or without WBRT, although there are publications (with by Mintz et al42 had extracranial metastases compared lower level of evidence) supporting its use.26-41 Fourteen with only 37.5% in the trial by Patchell et al43 and publications27-40 reported on the use of surgery and local 31.7% in the trial by Vecht et al.11 radiation (radiosurgery in 10 series and conformal fractionated radiation therapy in 4 series), with the WBRT and surgery versus surgery alone rationale to defer or avoid WBRT, without compromis- Two randomized trials22,23 have been completed that ing survival. One publication reported on the use of found a significant improvement in brain control (primary surgery, WBRT, and radiosurgery to the surgical cavity, endpoint) in patients treated with WBRT and surgery as with the rationale to maximize whole brain and local compared with surgery alone. The first trial22 showed that tumor bed control.26 postoperative WBRT significantly prevented brain recur- However, due to the paucity of randomized data, it is rence at the site of the original metastasis (10% vs 46%, unknown whether the omission of postoperative WBRT P b .001) and at other sites in the brain (14% vs 37%, P b (with a strategy of close radiographic and clinical .01). The authors found no difference in survival with the follow-up and the use of salvage radiosurgery or use of WBRT and surgery versus surgery alone, although WBRT at relapse) reduces neurocognitive decline the study was not powered for survival (a secondary compared with patients undergoing immediate postoper- endpoint of this trial).22 ative WBRT. On the other hand, in a post hoc analysis The second trial,23 the European Organization for of a randomized trial, distant brain metastases recurrence Research and Treatment of Cancer (EORTC) 22952- (a higher risk with radiosurgery alone) may have a 26001 study, found that WBRT reduced the 2-year relapse bigger impact on neurocognitive decline.57 at the initial site of surgery from 59% to 27% (P b .001), and at new sites from 42% to 23% (P = .008). In addition, salvage therapies were used more frequently after Newly diagnosed brain metastases: Single observation, compared with after WBRT.23 brain metastasis, surgery versus radiosurgery

Caveats 3. Is survival or brain control different in selected There are 2 completed randomized trials that examine patients with single brain metastasis (excluding WBRT and surgery versus surgery alone.22,23 The first radiosensitive histologies such as small cell lung trial22 was small and not powered for survival. The second cancer, leukemia, lymphoma, and germ cell trial by the EORTC23 included patients randomized to tumor) treated with surgery or radiosurgery? receive postoperative WBRT. A total dose of 30 Gy in 10 fractions at 3 Gy per fraction within 6 weeks of surgery Interpretative summary was administered. There have been no high quality randomized trials that The Trans-Tasman Radiation Oncology Group trial have assessed whether selected patients with a small single (TROG 98.05) was closed early due to poor accrual.24 The brain metastasis, in surgically accessible sites, should accrual target was a total of 130 patients. The authors undergo radiosurgery or resection. Adding WBRT did not reported on the 9 patients randomized to observation after improve overall survival or functional independence. surgery or radiosurgery and 10 patients randomized to WBRT after surgery or radiosurgery for single brain Evidence summary metastasis. However, no conclusions could be made from this severely underpowered study. WBRT and surgery versus radiosurgery alone No prospective studies have evaluated whether resec- One trial44 randomized patients with single (less than tion of more than one metastasis conveys meaningful 3 cm) resectable brain metastasis to resection plus WBRT clinical benefit. A retrospective case control series versus radiosurgery alone. Due to poor patient accrual, the Practical Radiation Oncology: July-September 2012 Brain metastases: An ASTRO guideline 217 trial was stopped early and reported 33 patients in the Newly diagnosed brain metastases: Single or surgery and WBRT arm and 31 patients in the radiosur- multiple brain metastasis(es), WBRT with or gery alone arm. This trial was too underpowered for any without radiosurgery boost conclusions to be made.

4. Is there a survival or brain control difference in WBRT and radiosurgery versus WBRT and surgery One randomized trial examined the use of radiosur- patients treated with WBRT and radiosurgery gery and WBRT versus surgery and WBRT.45 This trial boost versus WBRT alone? was closed due to slow accrual. Results were reported for 11 patients randomized to radiosurgery and WBRT Interpretative summary and 10 patients randomized to surgery and WBRT. For good prognosis patients with single brain metasta- Unfortunately, the trial was too underpowered to make ses (less than 4 cm in size, in patients with good any conclusions. performance status and controlled extracranial disease), There have been 2 retrospective series46,47 and 2 the use of radiosurgery added to WBRT improves retrospective matched pair analyses48,49 that examined survival, treated brain lesion control, and overall brain the use of WBRT and radiosurgery versus WBRT and control as compared with WBRT alone. surgery for a single brain metastasis. These publications In good prognosis patients with multiple brain suggested no difference in overall survival between the metastases (all less than 4 cm in size and up to 4 brain 2 study groups. metastases in number), radiosurgery boost when added to WBRT improves treated brain lesion and overall brain control as compared with WBRT alone. As there is no Radiosurgery for “radioresistant” histologies survival advantage with radiosurgery added to WBRT in A phase II trial of radiosurgery for 1 to 3 newly patients with multiple brain metastases, WBRT alone diagnosed brain metastases (4 cm or less in maximum may be considered. dimension) from histologies (renal cell carcinoma, mela- One randomized trial51 (RTOG 9508) that included noma, and sarcoma) that historically have been deemed patients with up to 3 brain metastases found an radioresistant to fractioned external beam radiotherapy, improvement in KPS and decreased steroid use at 6 was reported by the Eastern Cooperative Oncology months with the use of radiosurgery boost added to Group.50 Thirty-one eligible patients were treated with WBRT. These interpretations are consistent with the radiosurgery alone. Three-month intracranial failure with AANS guidelines on the use of radiosurgery boost.7 radiosurgery alone was 25.8%; in-field failure rate at 3 months was 19.3%. Phase III randomized trials evidence summary Distant intracranial failure rate at 3 months was 32.2%. Survival was consistent with other published WBRT alone versus WBRT and radiosurgery boost series of similar patients treated with surgery, radiosur- The multi-institutional, cooperative RTOG 9508 trial51 gery, WBRT, or a combination of these therapies. The examined the use of WBRT and radiosurgery boost (n = intracranial relapse rate was moderately high in this study 167) versus WBRT alone (n = 164). This trial included of patients treated with radiosurgery alone. Whether selected patients with 1 to 3 newly diagnosed brain surgery has better local control or survival as compared metastases with a maximum diameter of 4 cm (for the with radiosurgery for “radioresistant” single brain largest lesion) and additional lesions not exceeding 3 cm in metastasis could not be answered by this study due to diameter. Median survival was significantly improved in lack of direct comparisons with a surgical group. patients with single brain metastasis treated with radiosurgery boost (6.5 months) as compared with 4.9 months Caveats in patients treated with WBRT alone. Higher response rates at 3 months and better control of treated lesions at 1 In good prognosis patients with single brain year were observed in the WBRT and radiosurgery group metastasis (less than 3 to 4 cm in maximum dimension versus WBRT alone (82% vs 71%, P = .01). and amenable to gross total resection), either surgery or One single institution fully published trial53 stopped at radiosurgery may be considered. Surgery may be an interim evaluation of 60% accrual (14 patients favored in patients with unknown primary, or in randomized to WBRT alone and 13 patients randomized patients with single brain metastasis causing significant to WBRT plus radiosurgery). There was no survival mass effect. In good prognosis patients with single brain benefit with the use of radiosurgery boost as compared metastasis less than 3 to 4 cm in maximum dimension with WBRT alone in patients with multiple brain (in eloquent brain areas not amenable to safe total metastases. Patients treated with WBRT and radiosurgery resection or in patients who are unfit for surgery), boost were reported to have better brain control versus radiosurgery may be considered. those patients treated with WBRT alone. 218 M.N. Tsao et al Practical Radiation Oncology: July-September 2012

Caveats Evidence summary

None of the trials have examined validated quality of Radiosurgery alone versus WBRT and radiosurgery life outcomes with patients managed with WBRT alone versus WBRT and radiosurgery boost. Given no One fully published trial56 reported on the use of expected survival benefit, either option of WBRT radiosurgery alone versus WBRT and radiosurgery in alone with possible salvage treatment or upfront selected patients with 1 to 4 brain metastases. The number WBRT and radiosurgery boost may be offered for of patients with single brain metastases (n = 68) was too selected patients with multiple brain metastases. It is small to perform meaningful subset analyses. unclear from these published trials whether there is As such, results were reported for both single and benefit with radiosurgery boost to more than 4 lesions. multiple brain metastases patients. No overall survival However, there are level 3 data on patients undergoing difference between the 2 groups was found, with a median radiosurgery for 4 or more intracranial metastases survival of 7.5 months (WBRT and radiosurgery) versus suggesting a survival benefit, and that total intracranial 8 months (radiosurgery alone) (P = .42). volume rather than number of brain metastases may be the However, the 12-month brain tumor recurrence rate was more important predictor of survival.52 At present, there 48.6% in the WBRT and the radiosurgery group compared are insufficient high-quality data on whether certain with 76.4% for the radiosurgery alone group (P b .001). histologies benefit from the use of radiosurgery to treat Deterioration in mini-mental score examination more than 4 intracranial metastases. (MMSE) occurred in 14 of 36 WBRT and radiosurgery When new brain metastases are seen on the planning patients (39%) versus 12 of 46 radiosurgery alone patients scan the day of radiosurgery, it may be reasonable to (26%; P = .21), and there was no difference in actuarial proceed and complete the radiosurgical procedure to all the curves of freedom-from-3-point drop in MMSE (P = .73). lesions visualized even if they exceed a total of 4 brain Among patients with MMSE decline, the average duration metastases. Alternatively, not performing radiosurgery and until deterioration of the MMSE was 16.5 months in the proceeding with WBRT would also be considered a WBRT and radiosurgery group as compared with 7.6 reasonable option in these patients. months in the radiosurgery alone group (P = .05). The shorter duration to neurocognitive decline (as measured by the MMSE) was felt by the authors to be attributable to Newly diagnosed brain metastases: Single or the increased risk of brain relapse in the radiosurgery 57 multiple brain metastasis(es), radiosurgery alone group. It should be noted, however, that the MMSE is a poor measure of neurocognition as it lacks alone versus WBRT and radiosurgery adequate sensitivity.58 Chang et al54 reported a randomized trial that examined 5. Is there survival, brain control difference, or patients with 1 to 3 brain metastases treated with WBRT neurocognitive difference in patients treated and radiosurgery versus radiosurgery alone. The study was with radiosurgery alone versus WBRT stopped according to early stopping rules on the basis that and radiosurgery? there was a high probability (96%) that patients randomly assigned to receive WBRT and radiosurgery were more Interpretative summary likely to show a decline in learning and memory at 4 months Selected patients with brain metastasis(es) may be compared with patients assigned to receive radiosurgery treated with radiosurgery alone. A further alternative is alone. At 4 months, patients treated with WBRT and WBRT and radiosurgery boost. A third option for selected radiosurgery had measurable decline in learning and patients with multiple brain metastases is WBRT alone. memory as compared with patients treated with radiosur- There have been no convincing survival differences gery alone (52% vs 24%, respectively) despite higher rates among the 3 options listed above, although none of the of local and distant brain control in patients treated with trials have been adequately powered to detect anything WBRT and radiosurgery. It remains to be reported whether other than very large survival differences. neurocognitive outcomes are different between the strategy More trials are needed to assess whether there are of radiosurgery alone versus WBRT and radiosurgery at differences in neurocognitive and quality of life outcomes different time points (other than 4 months). when WBRT is omitted in selected patients who are Additionally, there was a survival difference between treated with radiosurgery alone. There is level 3 evidence the 2 arms not readily explained by treatment selection, that the increased risk of brain recurrence with a strategy raising the possibility of inadvertent randomization or of radiosurgery alone (if patients are not monitored and selection differences between the 2 groups. An imbalance followed adequately) may be associated with symptom- in the arms of the trial with respect to medications (such as atic recurrence, which may not recover fully despite anti-seizure medications and benzodiazepines) may also salvage treatment.88 affect neurocognitive outcomes. Practical Radiation Oncology: July-September 2012 Brain metastases: An ASTRO guideline 219

The subset of patients with single brain metastasis was A phase II trial of radiosurgery for 1 to 3 newly not analyzed separately. diagnosed brain metastases from histologies (renal cell carcinoma, melanoma, and sarcoma), which historically Radiosurgery or surgery alone versus WBRT and have been deemed radioresistant to fractioned external radiosurgery or surgery beam radiotherapy, was reported by the Eastern Cooper- The EORTC 22952-26001 trial23 included patients ative Oncology Group50 (ECOG) as discussed previously. with 1 to 3 brain metastases. Three hundred fifty-nine Because the intracranial relapse rate was moderately high patients were recruited. One hundred ninety-nine patients in this study using radiosurgery alone (25.8% at 3 months underwent radiosurgery and 160 underwent surgery. For and 48.3% at 6 months), the authors concluded that the radiosurgery group, 100 patients were allocated to delaying WBRT may be appropriate for some subgroups post-radiosurgery observation and 99 patients were of patients with “radioresistant” histologies, but routine allocated to post-radiosurgery WBRT. In the surgery avoidance of WBRT should be approached judiciously. group, 79 patients were allocated to postsurgery Whether WBRT should be routinely omitted in radiosur- observation and 81 patients were allocated to adjuvant gery eligible patients with “radioresistant” histologies WBRT. Patients eligible for radiosurgery had 1 to 3 remains controversial. There is level 3 evidence that the metastases of solid tumors (small cell lung cancer, increased risk of brain relapse with radiosurgery alone may lymphoma, leukemia, myeloma, and germ cell tumors be associated with symptomatic recurrences that may not were excluded) and brain metastasis size ≤3.5 cm in be reversible with salvage brain treatment.88 In this ECOG diameter for a single lesion (≤2.5 cm for 2 to 3 lesions). trial, the actuarial incidence of failure within the A complete resection was required for patients who radiosurgery field at 3 months was 19.3% and at 6 months underwent surgery. was 32.2%. The brain relapse rate and radiosurgery failure Overall survival (10.9 months vs 10.7 months) was rate in the ECOG trial were similar to the radiosurgery similar in both arms (P = .89). WBRT reduced the 2-year alone arm in the Aoyama et al,56 Kocher et al,23 and relapse rate both at initial sites (surgery: 59% to 27%, P b Chang et al54 trials. .001; radiosurgery: 31% to 19%, P = .040) and at new sites The trials reported have examined the use of (surgery: 42% to 23%, P = .008; radiosurgery: 48% to radiosurgery alone versus WBRT and radiosurgery 33%, P = .023). In well-performing patients with stable boost. There have been no trials that have examined systemic disease and 1 to 3 brain metastases, treated with patients treated with radiosurgery alone versus initial radiosurgery or surgery, WBRT can be withheld if WBRT alone. serial imaging for follow-up is performed. For patients undergoing surgery for a single brain metastasis, postop- Newly diagnosed brain metastases: Multiple erative local irradiation is an option that should be brain metastases investigated as adjuvant irradiation substantially reduces the risk of tumor bed recurrence. 6. What is the role of comfort measures or Caveats palliative supportive care alone versus WBRT in patients with multiple brain metastases? There is a suggestion based on 1 randomized trial54 that omission of WBRT after radiosurgery for single brain Interpretative summary metastasis is associated with better neurocognitive out- For selected patients with poor life expectancy (less comes based on formal neurocognitive testing. More trials than 3 months), the use of whole brain radiotherapy may or addressing the question of neurocognitive outcomes in the may not significantly improve symptoms from brain setting of radiosurgery alone and omission of upfront metastases. Comfort measures only, or short course (20 WBRT are needed. Gy in 5 daily fractions) whole brain radiotherapy, are These radiosurgery trials assessed selected patients with reasonable options. small oligometastases to the brain (up to 4 metastases). It is unknown if there is a cutoff for the maximum number of Evidence summary targets appropriate for radiosurgery. Total target volume as well as number of targets may be important for safety and WBRT plus supportive care versus supportive efficacy. A prospective nonrandomized series of patients55 care alone with1to10brainmetastasestreatedwithinitial Only 1 older randomized trial,59 performed in the pre- radiosurgery (without WBRT) required less than 10 cc computed tomographic era, compared WBRT plus volume for the largest tumor and less than 15 cc total supportive care versus supportive care alone (oral tumor volume. Median survival was 0.83 years, 0.69 prednisone). Median survival in the prednisone alone years, 0.69 years, 0.59 years, and 0.62 years for 1, 2, 3-4, arm was 10 weeks as compared with 14 weeks in the 5-6, and 7-10 metastases, respectively. combined arm (P value not stated). 220 M.N. Tsao et al Practical Radiation Oncology: July-September 2012

There is 1 on-going Medical Research Council trial These trials also did not examine different dose (Quartz)87 that randomizes patients to optimal supportive fractionation schedules in the setting of single brain care using dexamethasone versus optimal supportive care metastasis treated with surgery. In addition, optimal using dexamethasone and whole brain radiotherapy for dose fractionation schedules of WBRT were not patients with inoperable brain metastases from non-small examined in the setting of upfront WBRT with cell lung cancer. Outcomes of interest include quality of radiosurgery or in the setting of WBRT at the time life, overall survival, and side effects. of salvage after radiosurgery alone.

Caveats 8. What is the role of WBRT and radiosensitizers There are consistent predictors for poor survival of brain versus WBRT alone in the management of metastases patients that include poor performance status patients with brain metastases? and active uncontrolled disease.13-21 Until better therapy is available for these poor prognostic patients, supportive Interpretative summary comfort measures without WBRT can be considered. There is no evidence of survival benefit with the use of radiosensitizers and whole brain radiotherapy. 7. What is the optimal WBRT dose Evidence summary fractionation schedule? WBRT plus radiosensitizers versus WBRT alone Interpretative summary There have been a few randomized trials70-76 that have No differences in overall survival or symptom control examined the use of radiosensitizers (lonidamine, metro- have been demonstrated among the commonly used nidazole, misonidazole, bromodeoxyuridine, motexafin fractionation schemes, including 30 Gy in 10 daily gadolinium, and efaproxyn or RSR-13). Overall, no fractions or 20 Gy in 5 daily fractions. Other common radiosensitizer has improved survival. dose fractionation schedules of WBRT are 37.5 Gy in 15 Although, the use of motexafin gadolinium was daily fractions and 40 Gy in 20 daily (or twice daily) reported to reduce neurologic progression in patients fractions. This interpretation is consistent with the AANS with non-small cell lung cancer metastatic to the brain,76 4 guideline on whole brain radiotherapy. the U.S. Food and Drug Administration did not approve the use of motexafin gadolinium for non-small cell lung Evidence summary cancer patients with brain metastases in 2007. A subset analysis of breast cancer patients treated with Altered WBRT dose fractionation schedules RSR-13 and WBRT was reported to show an improvement Numerous trials have examined various dose fraction- in survival and quality of life as compared with WBRT ation schedules of WBRT.60-69 No altered dose fraction- alone.70 However, the subsequent larger trial designed ation scheme has shown improvement in either survival or specifically with breast cancer patients failed to show symptom control (neurologic functional status, neurologic benefit with the use of RSR-13 and WBRT.71 In 2004, the symptom relief, palliative index, or performance status) as U.S. Food and Drug Administration Oncologic Drugs compared with 20 Gy in 5 fractions or 30 Gy in 10 fractions Advisory committee did not recommend approval of RSR- of daily WBRT. One trial randomized patients of good 13 as an adjunct to WBRT in patients with brain performance status with brain metastases not suitable for metastases from breast cancer. surgical excision to either 40 Gy in 20 fractions of 2 Gy twice daily versus 20 Gy in 5 daily fractions.68 There was Caveats no difference in median survival (19 weeks in both arms). Another randomized trial examined the use of 40 Gy in 20 More trials are needed to assess the role (if any) of 69 twice daily fractions versus 20 Gy in 4 daily fractions. novel radiosensitizers in patients with brain metastases. The primary endpoint of brain progression favored patients treated with 40 Gy in 20 twice daily fractions (44% vs 64%, 9. What is the role of chemotherapy and WBRT? P = .03). The secondary endpoint of death from brain progression was no different between the 2 groups, P = .17. Interpretative summary The authors concluded that intracranial disease control was Although chemotherapy trials reported improved improved in patients treated with 40 Gy in 20 twice daily brain response rates with the use of combined chemo- fractions as compared with 20 Gy in 4 daily fractions. therapy and WBRT, this was at the cost of toxicity and Caveats no overall survival advantage was found with the addition of chemotherapy.77-82 There currently is no Differences in neurocognitive outcomes have not been high quality evidence to support the routine use of well studied among the different fractionation schemes. chemotherapy in the management of brain metastases. Practical Radiation Oncology: July-September 2012 Brain metastases: An ASTRO guideline 221

Evidence summary Numerous research opportunities exist to improve outcomes (survival, quality of life, brain control, and Chemotherapy and WBRT neurocognitive function) not only in the initial manage- There have been 8 trials examining the use of ment of patients with brain metastases but also in the area chemotherapy for brain metastases.77-84 The chemother- of salvage treatment. apy agents used were chloroethylnitrosoureas, teniposide, fotemustine, temozolomide, thalidomide, and topotecan. Acknowledgments One trial examined the use of early versus delayed WBRT with chemotherapy in patients with metastatic non-small cell lung cancer.83 No survival difference was seen The authors would like to thank the following in- between early versus delayed WBRT with chemotherapy. dividuals who served as expert reviewers of the manu- Another trial84 examined the use of primary chemotherapy script: Steven N. Kalkanis, MD, Penny K. Sneed, MD, and for newly diagnosed non-small cell lung cancer with Minesh Mehta, MB, ChB. This paper is dedicated and in synchronous brain metastases (with delayed WBRT at memoriam of Jian Z. Wang, PhD. We also acknowledge brain relapse) versus WBRT administered first. No Shari Siuta for her administrative assistance. survival difference was reported between the 2 arms. This document was prepared by the Guidelines Subcommittee of the Clinical Affairs and Quality Committee (CAQC) of ASTRO in coordination with Caveats the Third International Consensus Conference on Palliative Radiotherapy. Further trials are needed to assess the role of ASTRO Guidelines present scientific, health, and chemotherapy (including novel systemic agents) in the safety information and may to some extent reflect management of patients with brain metastases. scientific or medical opinion. They are made available to ASTRO members and to the public for educational and informational purposes only. Any commercial use of any Conclusions content in this Guideline without the prior written consent of ASTRO is strictly prohibited. Treatment options for brain metastases more than 30 Adherence to this Guideline will not ensure successful years ago were limited to steroids and whole brain treatment in every situation. radiotherapy and rarely surgery. Management options Furthermore, this Guideline should not be deemed today have expanded to include comfort measures inclusive of all proper methods of care or exclusive of (including the use of steroids), WBRT and, in selected other methods of care reasonably directed to obtaining patients, surgery or radiosurgery. Optimal management the same results. The ultimate judgment regarding the depends on patient factors (such as age, performance propriety of any specific therapy must be made by the status), tumor factors (such as extracranial cancer activity, physician and the patient in light of all circumstances as well as number, size, location, and histopathology of presented by the individual patient. ASTRO assumes no brain metastases) and available treatment options (such as liability for the information, conclusions, and findings experienced radiosurgery services and neurosurgeons). contained in its Guidelines. In addition, this Guideline The most important endpoint should be the deciding cannot be assumed to apply to the use of these factor for which treatment is most appropriate. For selected interventions performed in the context of clinical trials, patients with single brain metastasis, the use of surgery or given that clinical studies are designed to evaluate or radiosurgery has been shown to improve survival and this validate innovative approaches in a disease for which should be the primary consideration. improved staging and treatment are needed or are Treatment options which have been shown to improve being explored. whole brain control (such as the use of WBRT) or local This Guideline was prepared on the basis of informa- brain control (such as the use of radiosurgery) without tion available at the time the Task Group was conducting survival benefit for selected multiple brain metastases its research and discussions on this topic. There may be patients are more difficult in terms of best treatment new developments that are not reflected in this Guideline, choice. The most important outcome likely is quality of and that may, over time, be a basis for ASTRO to consider life (taking into account the morbidity of symptomatic revisiting and updating the Guideline. brain recurrence and the morbidity of treatment such as neurocognitive decline, which may be associated with the use of WBRT or the side effects associated with the Appendix 1 prolonged use of dexamethasone). Quality of life has inconsistently been measured in these trials and drop-outs MEDLINE search strategy: are a problem with assessing this endpoint. Medline Ovid 1966 to Nov. 3, 2010 222 M.N. Tsao et al Practical Radiation Oncology: July-September 2012

1. exp Brain Neoplasms/ 17. factorial⁎.ti,ab. 2. ((brain or brainstem or intracranial or posterior 18. (crossover⁎ or cross over⁎ or cross-over⁎).ti,ab. fossa) adj3 (cancer⁎ or carcinom⁎ or tumor⁎ or 19. placebo⁎.ti,ab. tumour⁎ or neoplasm⁎)).mp. 20. (doubl⁎ adj blind⁎).ti,ab. 3. 3 1 or 2 21. (singl⁎ adj blind⁎).ti,ab. 4. exp Neoplasm Metastasis/ or metastas⁎.mp. 22. assign⁎.ti,ab. 5. Radiotherapy/ 23. allocat⁎.ti,ab. 6. Radiotherapy, Adjuvant/ 24. volunteer⁎.ti,ab. 7. (radiotherapy or radiat⁎ or radiosurg⁎).mp. 25. crossover procedure/ 8. Combined Modality Therapy/ 26. double blind procedure/ 9. Radiosurgery/ 27. randomized controlled trial/ 10. gamma knife.mp. 28. single blind procedure/ 11. or/5-10 29. or/16-28 12. 3 and 4 and 11 30. 15 and 29 13. randomized controlled trial.pt. 31. animal/ or nonhuman/ or animal experiment/ 14. controlled clinical trial.pt. 32. human/ 15. randomized.ab. 33. 31 and 32 16. placebo.ab. 34. 31 not 33 17. radiotherapy.fs. 35. 30 not 34 18. randomly.ab. 36. limit 35 to yr = ”1980 - 2010” 19. trial.ab. key: 20. groups.ab. mp = title, abstract, subject headings, heading word, 21. or/13-20 drug trade name, original title, device manufacturer, drug 22. 12 and 21 manufacturer name 23. limit 22 to yr = ”1966 - 2010” ti = title 24. (animals not (humans and animals)).sh. ab = abstract 25. 23 not 24 CENTRAL search strategy: key: CENTRAL Issue 4, 2010 mp = title, original title, abstract, name of substance word, subject heading word, unique identifier #1. MeSH descriptor Brain Neoplasms explode all trees pt = publication type #2. brain⁎ near/3 (cancer⁎ or carcinoma⁎ or tumor⁎ or ab = abstract tumour⁎ or neoplasm⁎) fs = floating subheading #3. brainstem near/3 (cancer⁎ or carcinoma⁎ or tumor⁎ sh = subject heading or tumour⁎ or neoplasm⁎) #4. intracranial near/3 (cancer⁎ or carcinoma⁎ or tumor⁎ EMBASE search strategy: or tumour⁎ or neoplasm⁎) Embase Ovid 1980 to 2010 week 46 #5. posterior fossa near/3 (cancer⁎ or carcinoma⁎ 1. exp Central Nervous System Tumor/ tumor⁎ or tumour⁎ or neoplasm⁎) 2. exp brain cortex/ #6. (#1 OR #2 OR #3 OR #4 OR #5) 3. ((brain or brainstem or intracranial or posterior #7. MeSH descriptor Neoplasm Metastasis explode all trees fossa) adj3 (neoplasm⁎ or cancer⁎ or carcinoma⁎ or #8. metastas⁎ tumor⁎ or tumour⁎)).mp. #9. (#7 OR #8) 4. or/1-3 #10. MeSH descriptor Radiotherapy explode all trees 5. Brain Metastasis/ or metastas⁎.mp. #11. MeSH descriptor Radiotherapy, Adjuvant explode 6. 4 and 5 all trees 7. exp radiosurgery/ #12. radiotherapy or radiat⁎ or radiosurg⁎ 8. multimodality cancer therapy/ #13. MeSH descriptor Combined Modality Therapy 9. Radiotherapy/ explode all trees 10. Cancer radiotherapy/ #14. MeSH descriptor Radiosurgery explode all trees 11. (radiotherap⁎ or radiosurg⁎).mp. #15. gamma knife 12. gamma knife.mp. #16. (#7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 13. radiat⁎.mp. OR #14 OR #15) 14. or/7-13 #17. (#6 AND #9 AND #16) 15. 6 and 14 #18. (#17), from 1980 to 2010 16. random⁎.ti,ab. (Literature search courtesy of the Cochrane Library.) Practical Radiation Oncology: July-September 2012 Brain metastases: An ASTRO guideline 223

References 18. Golden DW, Lamborn KR, McDermott MW, et al. Prognostic factors and grading systems for overall survival in patients treated with radiosurgery for brain metastases: variation by primary site. 1. Mehta MP, Tsao MN, Whelan TJ, et al. The American Society for J Neurosurg. 2008;109(Suppl):77-86. Therapeutic Radiology and Oncology (ASTRO) evidence-based 19. Rades D, Dunst J, Schild SE. A new scoring system to predicting the review of the role of radiosurgery for brain metastases. Int J Radiat survival of patients treated with whole brain radiotherapy for brain Oncol Biol Phys. 2005;63:37-46. metastases. Strahlenther Onkol. 2008;184:251-255. 2. Tsao MN, Lloyd N, Wong RKS, Chow E, Rakovitch E, Laperriere 20. Sperduto PW, Chao ST, Sneed PK, et al. Diagnosis-specific N. Whole brain radiotherapy for the treatment of multiple brain prognostic factors, indexes, and treatment outcomes for patients metastases–Full review. Cochrane Database Syst Rev. 2006;3: with newly diagnosed brain metastases: a multi-institutional CD003869. analysis of 4259 patients. Int J Radiat Oncol Biol Phys. 2010;77: 3. Tsao MN, Lloyd NS, Wong RK, et al. Clinical practice guideline on 655-661. the optimal radiotherapeutic management of brain metastases. BMC 21. Sperduto PW, Xu Z, Sneed P, et al. The graded prognostic Cancer. 2005;5:34. assessment for women with brain metastases from breast cancer 4. Gaspar LE, Mehta MP, Patchell RA, et al. The role of whole brain (GPA-Breast): a Diagnosis-Specific Prognostic Index. Int J Radiat radiation therapy in the management of newly diagnosed brain Oncol Biol Phys. 2010;78(suppl):S6-S7. metastases: a systematic review and evidence based clinical practice 22. Patchell RA, Tibbs PA, Regine WF, et al. Postoperative radiotherapy guideline. J Neurooncol. 2010;96:17-32. in the treatment of single metastasis to the brain. JAMA. 1998;280: 5. Kalkanis SN, Kondziolka D, Gaspar LE, et al. The role of surgical 1485-1489. resection in the management of newly diagnosed brain metastases: 23. Kocher M, Soffietti R, Abacioglu U, et al. Adjuvant whole-brain a systematic review and evidence-based clinical practice guideline. radiotherapy versus observation after radiosurgery or surgical J Neurooncol. 2010;96:33-43. resection of one to three cerebral metastases: results of the EORTC 6. Mehta MP, Paleologos NA, Mikkelsen T, et al. The role of 22952-26001 study. J Clin Oncol. 2011;29:134-141. chemotherapy in the management of newly diagnosed brain 24. Roos DE, Wirth A, Burmeister BH, et al. Whole brain irradiation metastases: a systematic review and evidence-based clinical practice following surgery or radiosurgery for solitary brain metastases: guideline. J Neurooncol. 2010;96:71-83. mature results of a prematurely closed randomized Trans-Tasman 7. Linskey ME, Andrews DW, Asher AL, et al. The role of stereotactic Radiation Oncology Group trial (TROG 98.05). Radiother Oncol. radiosurgery in the management of patients with newly diagnosed 2006;80:318-322. brain metastases: a systematic review and evidence-based clinical 25. Bindal RK, Sawaya R, Leavens ME, Lee JJ. Surgical treatment of practice guideline. J Neurooncol. 2010;96:45-68. multiple brain metastases. J Neurosurg. 1993;79:210-216. 8. Ryken TC, McDermott M, Robinson PD, et al. The role of steroids in 26. Roberge D, Petrecca K, El Refae M, Souhami L. Whole brain the management of brain metastases: a systematic review and radiotherapy and tumor bed radiosurgery following resection of evidence-based clinical practice guideline. J Neurooncol. 2010;96: solitary brain metastasis. J Neuro Oncol. 2009;95:95-99. 103-114. 27. Soltys SG, Adler JR, Lipani JD, et al. Stereotactic radiosurgery of the 9. Chougule PB, Burton-Williams M, Saris M, et al. Randomized postoperative resection cavity for brain metastases. Int J Radiat treatment of brain metastases with gamma knife radiosurgery, whole Oncol Biol Phys. 2008;70:187-193. brain radiotherapy or both. [Abstract] Int J Radiat Oncol Biol Phys. 28. Jagannathan J, Yen CP, Ray DK, et al. Gamma knife radiosurgery 2000;48:114. to the surgical cavity following resection of brain metastases. 10. Noordijk EM, Vecht CJ, Haaxma-Reiche H, et al. The choice of J Neurosurg. 2009;111:431-438. treatment of single brain metastasis should be based on extra- 29. Do L, Pezner R, Radany E, Liu A, Staud C, Badie B. Resection cranial tumor activity and age. Int J Radiat Oncol Biol Phys. 1994; followed by stereotactic radiosurgery to resection cavity for 29:711-717. intracranial metastases. Int J Radiat Oncol Biol Phys. 2009;73: 11. Vecht CJ, Haaxma-Reiche H, Noordijk EM, et al. Treatment of 486-491. single brain metastasis: Radiotherapy alone or combined with 30. Quigley MR, Fuhrer R, Karlovits S, Karlovits B, Johnson M. Single neurosurgery? Ann Neurol. 1993;33:583-590. session stereotactic radiosurgery boost to the post-operative site in 12. US Preventative Services Task Force Evidence Syntheses, formerly lieu of whole brain radiation in metastatic brain disease. Systematic Evidence Reviews. Rockville (MD): Agency for J Neurooncol. 2008;87:327-332. Healthcare Research and Quality (US). 1998. 31. Mathieu D, Knodziolka D, Flickinger JC, et al. Tumor bed 13. Gaspar LE, Scott C, Rotman M, et al. Recursive partitioning analysis radiosurgery after resection of cerebral metastases. Neurosurg. (RPA) of prognostic factors in three Radiation Therapy Oncology 2008;62:817-823. Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys. 32. Bahl G, White G, Alksne J, Vemuri L, Spear MA. Focal radiation 1997;37:745-751. therapy of brain metastases after complete surgical resection. Med 14. Gaspar LE, Scott C, Murray K, Curran W. Validation of Oncol. 2006;23:317-324. the RTOG recursive partitioning analysis (RPA) classification 33. Hwang SW, Abozed MM, Hale A, et al. Adjuvant Gamma Knife for brain metastases. Int J Radiat Oncol Biol Phys. 2000;47: radiosurgery following surgical resection of brain metastases: a 1001-1006. 9-year retrospective cohort study. J Neurooncol. 2010;98:77-82. 15. Sperduto PW, Berkey B, Gaspar LE, Mehta M, Curran W. A new 34. Tolentino PJ. Brain metastases secondary to breast cancer: treatment prognostic index and comparison to three other indices for patients with surgical resection and stereotactic radiosurgery. Mo Med. with brain metastases: an analysis of 1960 patients in the RTOG 2009;106:428-431. database. Int J Radiat Oncol Biol Phys. 2008;70:510-514. 35. Karlovits BJ, Quigley MR, Karlovits SM, et al. Stereotactic 16. Weltman E, Salvajoli JV, Brandt RA, et al. Radiosurgery for brain radiosurgery boost to the resection bed for oligometastatic brain metastases: a score index for predicting prognosis. Int J Radiat disease: challenging the tradition of adjuvant whole-brain radiother- Oncol Biol Phys. 2000;46:1155-1161. apy. Neurosurg Focus. 2009;27:E7. 17. Lorenzoni J, Devriendt D, Massager N, et al. Radiosurgery 36. Lindvall P, Bergström P, Löfroth PO, Tommy Bergenheim A. A treatment of brain metastases: estimation of patient eligibility comparison between surgical resection in combination with WBRT using three stratification systems. Int J Radiat Oncol Biol Phys. or hypofractionated stereotactic irradiation in the treatment of 2004;60:218-224. solitary brain metastases. Acta Neurochir. 2009;151:1053-1059. 224 M.N. Tsao et al Practical Radiation Oncology: July-September 2012

37. Limbrick Jr DD, Lusis EA, Chicoine MR, et al. Combined surgical 55. Serizawa T, Hirai T, Nagano O, et al. Gamma knife radiosurgery for resection and stereotactic radiosurgery for treatment of cerebral 1-10 brain metastases without prophylactic whole-brain radiation metastases. Surg Neurol. 2009;71:280-288. therapy: analysis of cases meeting the Japanese prospective multi- 38. Iwai Y, Yamanaka K, Yasui T. Boost radiosurgery for treatment of institute study (JLG0901) inclusion criteria. J Neurooncol. 2010;98: brain metastases after surgical resections. Surg Neurol. 2008;69: 163-167. 181-186. 56. Aoyama H, Shirato H, Tago M, et al. Stereotactic radiosurgery plus 39. Iwadate Y, Namba H, Yamaura A. Whole brain radiation therapy is whole-brain radiation therapy vs stereotactic radiosurgery alone for not beneficial as adjuvant therapy for brain metastases compared treatment of brain metastases: a randomized controlled trial. JAMA. with localized irradiation. Anticancer Res. 2002;22:325-330. 2006;295:2483-2491. 40. Coucke PA, Zouhair A, Ozsahin M, De Tribolet N, Mirimanoff RO. 57. Aoyama H, Tago M, Kato N, et al. Neurocognitive function of Focalized external radiotherapy for resected solitary brain metastasis: patients with brain metastasis who received either whole brain does the dogma stand? Radiother Oncol. 1998;47:99-101. radiotherapy plus stereotactic radiosurgery or radiosurgery alone. Int 41. Roberge D, Souhami L. Tumor bed radiosurgery following resection J Radiat Oncol Biol Phys. 2007;68:1388-1395. of brain metastases: a review. Technol Cancer Res Treat. 2010;9: 58. Meyers CA, Wefel JS. The use of the mini-mental state examination 597-602. to assess cognitive functioning in cancer trials: no ifs, ands, buts or 42. Mintz AH, Kestle J, Rathbone MP, et al. A randomized trial to assess sensitivity. [Editorial] J Clin Oncol. 2003;21:3557-3558. the efficacy of surgery in addition to radiotherapy in patients with 59. Horton J, Baxter DH, Olson KB. The management of metastases to single brain metastasis. Cancer. 1996;78:1470-1476. the brain by irradiation and corticosteroids. Am J Roentgenol Radium 43. Patchell RA, Tibbs PA, Walsh JW, et al. A randomized trial of Ther Nucl Med. 1971;111:334-336. surgery in the treatment of single metastasis to the brain. N Engl J 60. Haie-Meder C, Pellae-Cosset B, Laplanche A, et al. Results of a Med. 1990;322:494-500. randomized clinical trial comparing two radiation schedules in the 44. Muacevic A, Wowra B, Siefert A, Tonn JC, Steiger HJ, Kreth FW. palliative treatment of brain metastases. Radiother Oncol. 1993;26: Microsurgery plus whole brain irradiation versus Gamma Knife 111-116. surgery alone for treatment of single metastasis to brain: a 61. Borgelt B, Gelber R, Kramer S, et al. The palliation of brain randomized controlled multicentre phase III trial. J Neurooncol. metastases: final results of the Radiation Therapy Oncology Group. 2008;87:299-307. Int J Radiat Oncol Biol Phys. 1980;6:1-9. 45. Roos DE, Smith JG, Stephens SW, et al. Radiosurgery versus 62. Borgelt B, Gelber R, Larson M, Hendrickson F, Griffin T, Roth R. surgery, both with adjuvant whole brain radiotherapy, for solitary Ultra-rapid high dose irradiation schedules for the palliation of brain brain metastases: a randomized controlled trial. Clin Oncol (R Coll metastases: final results of the first two studies by the Radiation Radiol). 2011;23:646-651. Therapy Oncology Group. Int J Radiat Oncol Biol Phys. 1981;7: 46. Schöggl A, Kitz K, Reddy M, et al. Defining the role of stereotactic 1633-1638. radiosurgery versus microsurgery in the treatment of single brain 63. Chatani M, Teshima T, Hata K, Inoue T, Suzuki T. Whole brain metastases. Acta Neurochir (Wien). 2000;142:621-626. irradiation for metastases from lung carcinoma. A clinical investi- 47. O'Neill BP, Iturria NJ, Link MJ, Pollock BE, Ballman KV, O'Fallon gation. Acta Radiol Oncol. 1985;24:311-314. JR. A comparison of surgical resection and stereotactic radiosurgery 64. Harwood AR, Simson WJ. Radiation therapy of cerebral metastases: in the treatment of solitary brain metastases. Int J Radiat Oncol Biol a randomized prospective clinical trial. Int J Radiat Oncol Biol Phys. Phys. 2003;55:1169-1176. 1977;2:1091-1094. 48. Rades D, Kueter JD, Veninga T, Gliemroth J, Schild SE. Whole 65. Kurtz JM, Gelber R, Brady LW, Carella RJ, Cooper JS. The brain radiotherapy plus stereotactic radiosurgery (WBRT +SRS) palliation of brain metastases in a favourable patient population: A versus surgery plus whole brain radiotherapy (OP+WBRT) for 1-3 randomized clinical trial by the Radiation Therapy Oncology Group. brain metastases: results of a matched pair analysis. Eur J Cancer. Int J Radiat Oncol Biol Phys. 1981;7:891-895. 2009;45:400-404. 66. Murray KJ, Scott C, Greenberg H, et al. A randomized phase III 49. Rades D, Kueter JD, Pluemer A, Veninga T, Schild SE. A matched- study of accelerated hyperfracionation versus standard in patients pair analysis comparing whole-brain radiotherapy plus stereotactic with unresectable brain metastases: a report of the Radiation Therapy radiosurgery versus surgery plus whole-brain radiotherapy and a Oncology Group (RTOG) 9104. Int J Radiat Oncol Biol Phys. boost to the metastatic site for one to two brain metastases. Int J 1997;39:571-574. Radiat Oncol Biol Phys. 2009;73:1077-1081. 67. Priestman TJ, Dunn J, Brada M, et al. Final results of the Royal 50. Manon R, O'Neill A, Knisely J, et al. Phase II trial of College of Radiologists' trial comparing two different radiotherapy radiosurgery for one to three newly diagnosed brain metastases schedules in the treatment of cerebral metastases. Clin Oncol (R Coll from renal cell carcinoma, melanoma and sarcoma: an Eastern Radiol). 1996;8:308-315. Cooperative Oncology Group Study (E 6397). J Clin Oncol. 68. Davey P, Hoegler D, Ennis M, Smith J. A phase III study of 2005;23:8870-8876. accelerated versus conventional hypofractionated whole brain 51. Andrews DW, Scott CB, Sperduto PW, et al. Whole brain radiation irradiation in patients of good performance status with brain therapy with and without stereotactic radiosurgery boost for patients metastases not suitable for surgical excision. Radiother Oncol. with one to three brain metastases: Phase III results of the RTOG 2008;88:173-176. 9508 randomised trial. Lancet. 2004;363:1665-1672. 69. Graham PH, Bucci J, Browne L. Randomized comparison of whole 52. Bhatnagar AK, Flickinger JC, Kondziolka D, Lunsford LD. brain radiotherapy, 20 Gy in 4 daily fractions versus 40 Gy in 20 Stereotactic radiosurgery for four or more intracranial metastases. twice-daily fractions for brain metastases. Int J Radiat Oncol Biol Int J Radiat Oncol Biol Phys. 2006;64:898-903. Phys. 2010;77:648-654. 53. Kondziolka D, Patel A, Lunsford LD, Kassam A, Flickinger JC. 70. Scott C, Suh J, Stea B, Nabid A, Hackman J. Improved Stereotactic radiosurgery plus whole brain radiotherapy versus survival, quality of life, and quality adjusted survival in breast radiotherapy alone for patients with multiple brain metastases. Int cancer patients treated with efaproxiral (Efaproxyn) plus whole J Radiat Oncol Biol Phys. 1999;45:427-434. brain radiation therapy for brain metastases. Am J Clin Oncol. 54. Chang EL, Wefel JS, Hess KR, et al. Neurocognition in patients with 2007;30:580-587. brain metastases treated with radiosurgery or radiosurgery plus 71. Suh JH, Stea B, Tankel K, et al. Results of the phase III ENRICH whole-brain irradiation: a randomised controlled trial. Lancet Oncol. (RT-016) study of efaproxiral administered concurrent with whole 2009;10:1037-1044. brain radiation therapy (WBRT) in women with brain metastases Practical Radiation Oncology: July-September 2012 Brain metastases: An ASTRO guideline 225

from breast cancer. Int J Radiat Oncol Biol Phys. 2008;72(Suppl): cerebral metastases of melanoma. [Article in French] Cancer S50-S51. Radiother. 2003;7:1-8. 72. DeAngelis LM, Currie VE, Kim JH, et al. The combined use of 81. Knisely JPS, Berkey B, Chakravarti A, et al. A phase III study of radiation therapy and lonidamide in the treatment of brain conventional radiation therapy plus thalidomide versus conventional metastases. J Neurooncol. 1989;7:241-247. radiation therapy for multiple brain metastases (RTOG 0118). Int J 73. Eyre HJ, Ohlsen JD, Frank J, et al. Randomized trial of radiotherapy Radiat Oncol Biol Phys. 2008;71:79-86. versus radiotherapy plus metronidazole for the treatment of 82. Neuhaus T, Ko Y, Muller RP, et al. A phase III trial of topotecan and metastatic cancer to brain. J Neurooncol. 1984;2:325-330. whole brain radiation therapy for patients with CNS-metastases due 74. Komarnicky LT, Phillips TL, Martz K, Asbell S, Isaacson S, Urtasun to lung cancer. Br J Cancer. 2009;100:291-297. R. A randomized phase III protocol for the evaluation of 83. Robinet G, Thomas P, Breton JL, et al. Results of a phase III misonidazole combined with radiation in the treatment of patients study of early versus delayed whole brain radiotherapy with with brain metastases (RTOG -7916). Int J Radiat Oncol Biol Phys. concurrent cisplatin and vinorelbine combination in inoperable 1991;20:53-58. brain metastasis of non-small cell lung cancer: Groupe Français 75. Phillips TL, Scott CB, Leibel SA, Rotman M, Weigensberg IJ. de Pneumo-Cancérologie (GFPC) Protocol 95-1. Ann Oncol. Results of the randomized comparison of radiotherapy and 2001;12:59-67. bromodeoxyuridine with radiotherapy alone for brain metastases: 84. Lee DH, Han J-Y, Kim HT, et al. Primary chemotherapy for newly report of RTOG trial 89-05. Int J Radiat Oncol Biol Phys. 1995;33: diagnosed NSCLC with synchronous brain metastases compared 339-348. with WBRT administered first. Result of a randomized pilot study. 76. Mehta MP, Shapiro WR, Phan SC, et al. Motexafin gadolinium Cancer. 2008;113:143-149. combined with prompt whole brain radiotherapy prolongs time to 85. Komosinska K, Kepka L, Niwinska A, et al. Prospective evaluation neurologic progression in nonsmall-cell lung cancer patients with of the palliative effect of whole brain radiotherapy in patients with brain metastases: results of a phase III trial. Int J Radiat Oncol Biol brain metastases and poor performance status. Acta Oncol. 2010;49: Phys. 2009;73:1069-1076. 382-388. 77. Postmus PE, Haaxma-Reiche H, Smit EF, et al. Treatment of brain 86. Campos S, Davey P, Hird A, et al. Brain metastasis from an metastases of small-cell lung cancer: comparing teniposide and unknown primary or primary brain tumour? A diagnostic dilemma. teniposide with whole brain radiotherapy- a phase III study of the Curr Oncol. 2009;16:62-66. European Organization for the Research and Treatment of Lung 87. Cancer Research UK. A trial looking at the treatment of lung Cancer Cooperative Group. J Clin Oncol. 2000;18:3400-3408. cancer which has spread to the brain (Quartz). Available at: 78. Ushio Y, Arita N, Hayakawa T, et al. Chemotherapy of brain http://cancerhelp.cancerresearchuk.org/trials/a-trial-looking-at-the- metastases from lung carcinoma: a controlled randomized study. treatment-oflung-cancer-which-has-spread-to-the-brain. Accessed Neurosurg. 1991;28:201-205. September 19, 2011. 79. Antonadou D, Paraskevaidis M, Saris G, et al. Phase II randomized 88. Regine WF, Huhn JL, Patchell RA, et al. Risk of symptomatic trial of temozolomide and concurrent radiotherapy in patients with brain tumor recurrence and neurologic deficit after radiosurgery brain metastases. J Clin Oncol. 2002;20:3644-3650. alone in patients with newly diagnosed brain metastases: 80. Mornex F, Thomas L, Mohr P, et al. Randomized phase III trial of results and implications. Int J Radiat Oncol Biol Phys. 2002; fotemustine versus fotemustine plus whole brain irradiation in 52:333-338. 2014 GUIDE

ASTRO /ACR GUIDE TO

RADIATION ONCOLOGY CODING 2010

TARGETING CANCER CARE All rights reserved. No part of this publication covered by the copyright herein may be reproduced or cop- ied in any form or by any means – graphic, electronic or mechanical, including photocopying, taping or information storage and retrieval systems – without written permission of the publishers.

Fee schedules, relative value units, conversion factors and/or related components are not assigned by the AMA, are not part of CPT© and the AMA is not recommending their use. The AMA does not directly or indirectly practice medicine or dispense medical services. The AMA assumes no liability for data contained or not contained herein.

The responsibility for the content of any “National Correct Coding Policy” included in this product is with the Centers for Medicare and Medicaid Services, and no endorsement by the AMA is intended or should be implied. The AMA disclaims responsibility for any consequences or liability attributable to or related to any use, nonuse or interpretation of information contained in this product. 13STEREOTACTIC RADIOSURGERY Stereotactic radiosurgery (SRS) is a technique for delivering a high dose of radiation to a specifi c target.

STEREOTACTIC RADIOSURGERY (SRS) IS A TECHNIQUE FOR DELIVERING A HIGH DOES OF RADIATION TO A SPECIFIC TARGET while delivering a minimal dose to surrounding tissues. This technique is used to treat defined target(s) in the head and spine. It is typically performed in a single session, but can be performed in a limited number of sessions, up to a maximum of five. Stereotactic treatment depends on the accurate and reproducible spatial correlation of the target and the radiation source using three-dimensional CT and/or MR simulation. Extreme precision of patient positioning is essential for accurate treatment delivery. This additional precision is achieved through rigid immobilization, such as with a rigid frame, or with image-based techniques.

Stereotactic treatments can be given with either photon or particle therapy. In both approaches, multiple beams converge on the target. Thus, the target gets a much higher dose than surrounding tissues, and a steep dose gradient can be obtained close to the periphery of the target. This technique is capable of great accuracy and precision and can deliver radiation dosages within 1 mm of the planned position.

The radiation oncologist is responsible for target volume delineation, treatment planning, supervising the patient positioning, proper alignment of treatment beams and management of the patient during treatment. From a billing and coding perspective, there is a difference in the codes used for single fraction cranial SRS and fractionated cranial SRS (2- 5 fractions) and all spinal SRS (1-5 fractions) as further explained in the section Radiation Treatment Management in this chapter.

COMMON CLINICAL INDICATIONS SRS is appropriate for the treatment of certain malignant and benign neoplasms of the brain and spine, cranial nerves and meninges, arteriovenous malformations of cerebral vessels and other non-neoplastic conditions for which it has been established to be effective. This includes both primary and metastatic diseases. Movement disorders such as Parkinson's disease, essential tremor and other disabling tremors may be treated with stereotactic radiosurgery when stereotactic thalamotomy cannot be performed. SRS is often effective therapy for trigeminal neuralgia refractory to medical management.

Coding Guidance for Stereotactic Radiosurgery (SRS) Coding guidance for each phase of the process of care is described below. Where there is no specific guidance for SRS, there is a reference to the earlier chapter in this Guide where general guidance for that phase of the process of care is given. There are specific codes for SRS radiation treatment delivery and treatment management. When stereotactic radiosurgery is furnished to Medicare beneficiaries in a hospital outpatient department, the technical component is paid under the hospital outpatient prospective payment system (OPPS).

Consultation/Clinical Management See Chapter 6.

Preparing For Treatment SRS planning is a separate process from SRS delivery. There are no specific codes for SRS planning; the current recommendation is to use all appropriate CPT codes normally associated with the process of SRS planning. Appropriate treatment planning codes may include CPT code 77295 (3-dimensional radiotherapy plan, including dose-volume histogram) or IMRT CPT code 77301 (Intensity modulated radiotherapy plan, including dose-volume histograms for target and critical structure partial tolerance specifications), CPT code 77300 (Basic radiation dosimetry calculation, central axis depth dose calculation, TDF, NSD, gap calculation, off axis factor, tissue inhomogeneity factors, calculation of non-ionizing radiation surface and depth dose, as required during course of treatment, only when prescribed by the treating physician) and CPT code 77370 (Special medical radiation physics consultation). Treatment devices are billed separately from the planning and delivery codes if appropriate. Whether one treats one or more lesions, treatment planning CPT code 77295 or CPT code 77301 should only be used once for the entire episode.

CPT® DESCRIPTION SRS-SPECIFIC GUIDELINES CODE 77263 Therapeutic radiology treatment planning; complex Given the complexity of SRS, a complex treatment planning code is justified. 77295 3-dimensional radiotherapy plan, including dose-volume At a minimum, three-dimensional histogram simulation is essential to provide accurate stereotactic treatment OR delivery.

77301 Intensity modulated radiotherapy plan, including dose-volume Report once per course of therapy. histograms for target and critical structure partial tolerance specifications

(Dose plan is optimized using inverse planning technique for modulated beam delivery [eg, binary, dynamic MLC] to create highly conformal dose distribution. Computer plan distribution

must be verified for positional accuracy based on dosimetric verification of the intensity map with verification of treatment setup and interpretation of verification methodology)

Medical Radiation Physics, Dosimetry, Treatment Devices and Special Services There are no SRS-specific codes for medical radiation physics, dosimetry, treatment devices and special services. However, the codes for basic dosimetry CPT® code 77300, CPT code 77370 and complex devices CPT code 77334 can be used as described below. See Chapter 8 for further guidance.

CPT® DESCRIPTION SRS-SPECIFIC GUIDELINES CODE 77300 Basic radiation dosimetry calculation, central axis depth dose One unit for each arc in linear calculation, TDF, NSD, gap calculation, off axis factor, tissue accelerator system. inhomogeneity factors, calculation of non-ionizing radiation One unit for each shot in Cobalt- surface and depth dose, as required during course of treatment, 60. only when prescribed by the treating physician Maximum of 10 units. 77370 Special medical radiation physics consultation May be reasonable and necessary if ordered by the Radiation Oncologist. 77334 Treatment devices, design and construction; complex (irregular One unit for each unique blocks, special shields, compensators, wedges, molds or casts) combination of beam angle and collimator pattern or each unique arc; certain carrier limitations may apply. One unit for each helmet in Cobalt- 60. 77338 Multi-leaf collimator (MLC) device(s) for intensity modulated If IMRT planning code 77301 is radiation therapy (IMRT), design and construction, per IMRT used for coding treatment planning plan then one CPT 77338 should be used to code for the devices.

Radiation Treatment Delivery CMS has historically used HCPCS G-codes to distinguish between robotic and non-robotic SRS delivery methods. In the CY 2014 Hospital Outpatient Prospective Payment System (HOPPS) final regulations, CMS announced that as of January 1, 2014, the agency will no longer differentiate between robotic and non-robotic linac-based SRS through HCPCS G-codes. For CY 2014, CMS will replace the existing four HCPCS codes: G0173, G0251, G0339 and G0340 with the SRS CPT® codes 77372 and 77373. The chart below provides a summary of these changes.

® 2013 CPT ® 2014 CPT OR HCPCS DESCRIPTOR DESCRIPTOR Code Code

77371 Radiation treatment 77371 Radiation treatment delivery, stereotactic radiosurgery delivery, stereotactic (SRS), complete course of treatment of cranial lesion(s) radiosurgery (SRS), consisting of 1 session; multi-source Cobalt-60 based complete course of

treatment of cranial lesion(s) consisting of 1 session; multi-source Cobalt-60 based

G0173 Linear accelerator 77372 Radiation treatment delivery, stereotactic radiosurgery stereotactic radiosurgery, (SRS), complete course of treatment of cranial lesion(s) complete course of therapy consisting of 1 session; linear accelerator based in one session

G0339 Image-guided robotic linear accelerator- based stereotactic radiosurgery, course of Stereotactic body radiation therapy, treatment delivery, per therapy in one session, or 77373 fraction to 1 or more lesions, including image guidance, first session of fractionated entire course not to exceed 5 fractions. treatment

As of 2009, on the OPPS side the payment for CPT® code 20660 (Application of cranial tongs, caliper or stereotactic frame, including removal [separate procedure]) is included in payment for 77371; therefore, hospitals should not report 20660 separately.

CPT® DESCRIPTION SRS-SPECIFIC GUIDELINES CODE 77371 Radiation treatment delivery, stereotactic radiosurgery (SRS), Technical charge for single fraction complete course of treatment of cranial lesion(s) consisting of 1 treatment delivery using cobalt-60. session; multi-source Cobalt-60 based.

(For radiation treatment management, use 77432) 77372 Radiation treatment delivery, stereotactic radiosurgery (SRS), Technical charge for single fraction complete course of treatment of cranial lesion(s) consisting of 1 treatment delivery using a Linac (linear accelerator).

session; linear accelerator based.

(For radiation treatment management, use 77432) Stereotactic body radiation therapy, or stereotactic cranial radiosurgery 2-5 fractions-treatment delivery, per fraction to 1 or more lesions, including image guidance, entire course not to exceed 5 fractions Technical charge for multi fraction 77373 (2-5) treatment delivery for cranial lesions and all SBRT lesions.

(CPT code 77435 reports SBRT treatment management per treatment course (not to exceed five fractions).

Change in Payment for Stereotactic Radiosurgery in Hospital Outpatient Department Effective April 1, 2013 On January 2, 2013, the President signed the American Taxpayer Relief Act of 2012 into law, a partial resolution to the US fiscal cliff situation which also included a one-year patch to planned 27 percent Medicare physician payment cuts for CY 2013. Reductions to hospital outpatient radiosurgery rates were implemented to help partially offset the costs of averting these cuts to Medicare physician payments. The legislation mandated that as of April 1, 2013, the payment rate for multi-source Cobalt 60-based stereotactic surgery in the hospital outpatient department (CPT code 77371) (APC 0127) would be lowered to the level of linear accelerator based stereotactic radiosurgery (APC 0067).

Radiation Treatment Management There is one radiation treatment management code specific to SRS, CPT® code 77432 (see table) and this code can only be used for single fraction cranial SRS. If cranial SRS is delivered in 2–5 fractions use the SBRT management CPT code 77435 (Stereotactic body radiation therapy, treatment management, per treatment course, to 1 or more lesions, including image guidance, entire course not to exceed 5 fractions) for the entire course of treatment. One can no longer bill CPT® 77432 (Stereotactic radiation treatment management of cranial lesion(s) [complete courseof treatment consisting of 1 session]) for the first fraction and CPT code 77427 (Radiation tx management, x5) or 77431 (Radiation therapy management [one or two fractions only]) for the remaining fractions, for the same treatment volume. For all spinal radiosurgery (1- 5 fractions) use the SBRT management CPT code 77435 once for the entire course of treatment. CPT® code 77432 and CPT code 77435 cannot be billed for the same patient for the same episode of care (see Chapter 14) and Medicare does not reimburse CPT code 77432 and CPT code 77470 (Special radiation treatment) on the same day of service. A prolonged (4-6 week) course of cranial radiation therapy should be billed using appropriate codes for conventionally fractionated radiotherapy. Fractionated stereotactic cranial and body radiotherapy codes apply only to hypo-fractionated (1-5 fractions) radiosurgery using large doses per fraction.

SRS treatments are to be performed under the direct supervision of a qualified medical physicist and a radiation oncologist.

CPT® SRS-SPECIFIC DESCRIPTION CODE GUIDELINES 77432 Stereotactic radiation treatment management of cranial lesion(s) For use of single fraction, (complete course of treatment consisting of 1 session) complete course of therapy.

(The same physician should not report both stereotactic radiosurgery services [61796-61800] and radiation treatment management [77432 or 77435] for cranial lesions).

(For stereotactic body radiation therapy treatment, use 77435

CPT® code 77435 is discussed in more detail in Chapter 14.

Other Related Codes Usually a radiation oncologist will work with a neurosurgeon to perform SRS. The following codes may be used by the neurosurgeon to code for involvement in the procedure.

CPT® DESCRIPTION CODE 61796 Stereotactic radiosurgery (particle beam, gamma ray, or linear accelerator); 1 simple cranial lesion

61797 each additional cranial lesion, simple (List separately in addition to code for primary procedure)

61798 1 complex cranial lesion

61799 additional cranial lesion, complex (List separately in addition to code for primary procedure)

61800 Application of stereotactic headframe for stereotactic radiosurgery (List separately in addition to code for primary procedure) 63620 Stereotactic radiosurgery (particle beam, gamma ray, or linear accelerator); 1 spinal lesion

63621 each additional spinal lesion

FREQUENTLY ASKED QUESTIONS QUESTION: What is the correct billing procedure when treating a patient with acoustic neuroma with fractionated cranial radiosurgery (2-5 fractions) in the hospital setting?

ADVICE: When fractionated cranial SRS is used as the sole treatment for lesions like acoustic neuroma or pituitary adenoma in the hospital setting, it should be billed using CPT code 77373. The radiation oncologist’s work for treatment management for fractionated cranial SRS will be

reported with CPT code 77435 for the whole course of treatment, and not with CPT code 77432 or 77427. This only applies to a complete course of radiosurgery treatment for up to five fractions.

QUESTION: How should a provider treat a patient with 4 metastatic brain lesions? Is it appropriate to treat the patient using sequential single-fraction SRS?

ADVICE: For synchronous brain metastases that will be treated with single fraction SRS on Linac-based, the correct code for treatment delivery would be 77372. The code for treatment management is 77432. Each of the 4 lesions is treated fully in a single fraction. Depending on the size and location of some synchronous brain metastases, they may need to be treated with fractionated stereotactic radiosurgery, for which the SBRT codes apply for treatment delivery and radiation oncologist professional codes. The correct code for treatment delivery would be 77373. The code for treatment management is 77435. All of the 4 lesions will be treated fully in up to 5 fractions over a 10 day period.

14SSOCCTEREOTACTIC BODY RADIATION THERAPY Stereotactic body radiation therapy (SBRT) describes the delivery of potent doses of radiation using numerous carefully directed fi elds to extracranial sites.

STEREOTACTIC BODY RADIATION THERAPY (SBRT) describes the delivery of potent doses of radiation using numerous carefully directed fields to extracranial sites.23 It has been considerably difficult translating stereotactic treatments in the brain to treating tumors in the body. The major obstacles to such an approach are related to motion and fixation. Unlike the brain, organ motion in the body is the rule due to breathing and filling or emptying of hollow viscous structures such as bladder and intestines. Using conventionally fractionated (low daily dose) radiation, radiation oncologists identify a "margin" of normal tissue around tumor targets to account for daily variations in the position of the target to avoid missing target portions on any given day. These margins range from 2 to 3 centimeters (cm) depending on the location of the target. SBRT utilizes significantly higher daily doses per fraction, a treatment biologically very different from conventionally fractionated radiation. Wide margins of 2 to 3 cm would result in unacceptable damage to surrounding normal tissue. To successfully accomplish stereotactic treatments outside of the brain with significantly smaller margins, one must utilize a combination of reliable immobilization or repositioning systems, devices capable of decreasing internal organ motion or accounting for organ motion, along with image guidance. SBRT is defined and billed on the basis of the number of fractions employed (total course of therapy consisting of five fractions or less), assuming all other required parameters are met for guidance, precision and medical necessity, and is unrelated to the equipment utilized. The term "robotic" is not limited to any one vendor but rather represents the delivery of SBRT under computer control. The SBRT codes discussed in this chapter are also used to code all spinal stereotactic radiosurgery (SRS) treatments and all cranial SRS treatments given in 2-5 fractions.

The process of care for SBRT has now been established, as SBRT has been performed since the early 1990s and is distinct from conventional radiation therapy. SBRT may be used as an alternative to conventional open surgery for treating various lesions and may be an effective and safer alternative than conventional radiation therapy for certain presentations of cancers and other non-cancer targets. Direct physician involvement, image guidance and immobilization are integral to stereotactic treatment for these diverse body sites.

The medical physicist should perform a second check calculation before initiating the first treatment to ensure the monitor units used to deliver the planned treatment are correct. With a radiation oncologist, the medical physicist should ensure all of the treatment parameters are

CPT COPYRIGHT © 2013 AMERICAN MEDICAL ASSOCIATION ALL RIGHTS RESERVED Page 154 correct, including image guidance, respiratory motion compensation, or any other complex positioning aids that may be employed to accurately treat the patient. This highly intense work usually will justify a 77370, special physics report if requested by the physician. SBRT treatments are to be performed under the direct supervision of a qualified medical physicist and radiation oncologist.

To report the SBRT codes, the patient must be treated with SBRT as a complete course of therapy. More specifically, if the treatment plan includes more than five fractions, the SBRT codes may not be submitted. For example, it would not be appropriate to submit SBRT charges for the first five fractions of radiation therapy treatment and an additional 25 fractions of conventional treatment delivery codes (i.e., CPT® codes 77401- 77418) for the remainder of the treatment.

Common Clinical Indications To bill appropriately for SBRT, the radiation oncologist must determine the treatment to be "medically necessary." This means that services are proper and needed for the diagnosis or treatment of a medical condition; are provided for the diagnosis, direct care and treatment of a medical condition; and meet the standards of good medical practice in the local area. SBRT can be applied to very localized malignant conditions in the body and is appropriate for treatment of the following conditions: • Medically inoperable early-stage lung cancer. • Recurrent lung cancer amenable to salvage therapy. • Primary liver cancer. • Lung or liver metastases. • Pancreatic tumors not amenable to surgery. • Adrenal gland tumors. • Retroperitoneal tumors, e.g. renal, adrenal and paraspinous. • Pelvic tumors recurrent after primary irradiation. • Spinal and paraspinous tumors. • Other recurrent cancers or tumors.

Please check with your local Contractor for all approved indications.

Consultation and Follow-up Care Management See Chapter 6.

Preparing For Treatment There are no specific codes for the professional component of clinical treatment planning and simulation for SBRT. However, because of the complexity of SBRT and the need for three- dimensional simulation, the following codes are usually appropriate for SBRT cases. See Chapter 8 for further guidance.

CPT® DESCRIPTION SRBT-SPECIFIC CODE GUIDELINES 77263 Therapeutic radiology treatment planning; complex Given the complexity of SBRT, a complex treatment planning code is justified. 77295 3-dimensional radiotherapy plan, including dose-volume Three-dimensional simulation is histograms essential to provide accurate OR stereotactic treatment delivery.

77301 Intensity modulated radiotherapy plan, including dose-volume Report once per course of histograms for target and critical structure partial tolerance therapy. specifications (Dose plan is optimized using inverse planning technique for modulated beam delivery [eg, binary, dynamic MLC] to create highly conformal dose distribution. Computer plan distribution must be verified for positional accuracy based on dosimetric verification of the intensity map with verification of treatment setup and interpretation of verification methodology) 77470 Special treatment procedure Given the complexity, and additional time and effort required of SBRT, a special treatment procedure code may be justified with appropriate specific documentation.

Medical Radiation Physics, Dosimetry, Treatment Devices and Special Services There are no SBRT specific codes for medical radiation physics, dosimetry, treatment devices and special services. However, the codes for basic dosimetry CPT® code 77300 (Basic radiation dosimetry calculation) and complex devices CPT code 77334 (Radiation treatment devices; complex) and CPT code 77338 (MLC used in IMRT) can be used as described below. See Chapter 8 for further guidance.

CPT® DESCRIPTION SRBT-SPECIFIC GUIDELINES CODE 77300 Basic radiation dosimetry calculation, central axis depth One unit for each arc in linear dose calculation, TDF, NSD, gap calculation, off axis factor, accelerator system. tissue inhomogeneity factors, calculation of non-ionizing One unit for each shot in Cobalt-60. radiation surface and depth dose, as required during course of treatment, only when prescribed by the treating physician Maximum limit of 10 units. 77370 Special medical radiation physics consultation May be reasonable and necessary if ordered by the radiation oncologist. 77334 Treatment devices, design and construction; complex One unit for each unique combination (irregular blocks, special shields, compensators, wedges, of beam angle and collimator pattern or molds or casts) each unique arc; certain carrier limitations may apply. One unit for each helmet in Cobalt-60. 77338 Multi-leaf collimator (MLC) device(s) for intensity modulated If IMRT planning code 77301 is used radiation therapy (IMRT), design and construction, per IMRT for coding treatment planning then one plan CPT 77338 should be used to code for the devices.

Radiation Treatment Delivery Codes The table below includes the radiation treatment delivery codes specific to SBRT.

CPT® DESCRIPTION SRBT-SPECIFIC GUIDELINES CODE 77373 Stereotactic body radiation therapy, Technical code for up to but no more than 5 fractions in the treatment delivery, per fraction to 1 freestanding setting. This code may also be used for or more lesions, including image fractionated stereotactic cranial treatments of 2 to 5 fractions. guidance, entire course not to This code includes all image guidance on the days of exceed 5 fractions treatment delivery; therefore, do not report 77373 in conjunction with 77421 or 77014 on the days of treatment (Do not report 77373 in conjunction delivery. with 77401- 77416, 77418)

(For single fraction cranial lesion[s], see 77371, 77372)

SBRT treatment delivery in both the freestanding facility and hospital outpatient setting should be reported using CPT code 77373 (Stereotactic body radiation therapy, treatment delivery, per fraction to 1 or more lesions, including image guidance, entire course not to exceed 5 fractions).

Radiation Treatment Management The table below includes the radiation treatment management code specific to SBRT.

CPT® DESCRIPTION SRBT-SPECIFIC GUIDELINES CODE 77435 Stereotactic body radiation therapy, Professional charge for treatment management performed treatment management, per treatment by the radiation oncologist. course, to one or more lesions, including image guidance, entire course not to This code can be reported only once for the entire course exceed 5 fractions of treatment and not per fraction. This will apply to all extracranial SBRT up to a maximum of 5 fractions and all (Do not report 77435 in conjunction with fractionated cranial SRS up to a maximum of 5 fractions. It 77427- 77432) will apply to all lesions treated during that entire course of treatment. (The same physician should not report both stereotactic radiosurgery services (32701, 63620, 63621) and radiation treatment management (77435)

As of January 1, 2007, CPT® Category I code 77435 (SBRT treatment management) should be used by the radiation oncologist for stereotactic body radiation therapy, treatment management. This code is billed per treatment course with the entire course not to exceed 5 fractions and it includes the work of image guidance during treatment.

The physician work for 77435 can be summarized as follows: The radiation oncologist evaluates the patient prior to the procedure. Under the direct supervision of the radiation oncologist, the patient is set up on the treatment table and all the treatment parameters are verified. Image

CPT COPYRIGHT © 2013 AMERICAN MEDICAL ASSOCIATION ALL RIGHTS RESERVED Page 157 guidance, and respiratory correlation if required, may be achieved through a variety of methods, all of which are supervised, corrected and approved in real time by the physician. The physician assesses and approves all of the ongoing images used for localization, tumor tracking, any gating application, as well as any complementary single (beam's eye) view localization images for any of the fields or arcs that are arranged to deliver a dose. The radiation oncologist remains available throughout SBRT treatment to manage the execution of the treatment and make real- time adjustments in response to patient motion, target movement, or equipment issues to ensure accuracy and safety. The physician also evaluates the patient post-procedure. All other work generally associated with CPT code 77427 (Radiation treatment management, five treatments) is included and should not be separately coded.

Much of the radiation oncologist's work in establishing the above treatment parameters is performed in conjunction with the qualified medical physicist, who should be present and participate in delivering SBRT treatment.

FREQUENTLY ASKED QUESTIONS QUESTION: What are the appropriate and/or reasonable units of service for CPT 77300 for an SBRT case?

ADVICE: The radiation dose per field is routinely independently calculated and verified before the course of radiation treatment, and reported using CPT code 77300. Some systems may use a dataset of 100 - 200 beams to treat a lesion and many of them may undergo independent calculations to ensure accuracy for the patient treatment. A proportion of the beams may have a variance of over 10 percent on independent calculations and these may be evaluated by the physician for assessing the dose contribution from these beams. ASTRO does not recommend that all 100 – 200 beams be billed individually as a separate CPT 77300 charge. While more may be medically indicated under certain circumstances, the American Society for Radiation Oncology does not recommend routinely coding CPT code 77300 more than ten times per course when using SBRT.