Radiotherapy for Primary and Metastatic Spinal Tumors O. Kenneth Macdonald, MD,* and Christopher M. Lee, MD† Primary and metastatic spinal tumors as a group represent a heterogeneous mixture of benign and malignant processes. In general, primary tumors of the spine remain relatively uncommon, and the majority of spinal tumors that are treated annually represent systemic spread of extraosseous primary malignancy. The management of spinal tumors requires meticulous yet expedient attention as the consequences of failed or inappropriate treat- ment can be devastating. Radiotherapy has proven beneficial in many tumors of the spine, particularly metastatic lesions, Ewing’s sarcoma, and myeloid malignancies. A review of the use of radiotherapy for the more common primary spinal malignancies and metastasis is presented. Semin Spine Surg 21:121-128 © 2009 Elsevier Inc. All rights reserved. KEYWORDS radiotherapy, spine, malignancy, metastasis lthough relatively uncommon, primary spinal tumors from breast, prostate, lung, kidney, and hematopoietic can- Arepresent a heterogeneous mixture of benign and malig- cers.10-18 nant processes. These result in a broad spectrum of symp- No matter the etiology, the management of spinal tumors toms ranging from a minor backache to severe weakness that requires meticulous but expedient attention as the conse- prevents one from walking (due to neurologic structure im- quences of failed or inappropriate or careless treatment can pingement). Common benign tumors that develop in the be neurologically devastating and potentially irreversible. spine include aneurysmal bone cysts, hemangiomas, giant Surgical intervention has been established as a beneficial cell tumors of bone, osteoid osteomas, meningiomas, and treatment with durable results in the setting of primary and osteoblastomas. There are many primary malignant pro- secondary tumors of the spine.13,16,19-22 The application of cesses that can also develop in the spine, including chordo- radiotherapy (RT) can serve as an adjunct to surgery or at mas, chondrosarcomas, osteosarcomas, Ewing’s sarcomas, times might be used in place of surgery or as a preparative plasmacytomas, multiple myeloma, and lymphoma. Al- regimen to make a tumor more readily resectable. RT is used though the differential diagnosis for a spinal tumor may ap- extensively in tumors of the spine, both in primary and in pear lengthy, these primary disease processes only account metastatic lesions, and this review addresses options, tech- for a minority of all spinal tumors diagnosed annually.1-6 niques, and results of modern-day RT applications. The majority of spinal tumors treated annually represent systemic spread of an extraosseous primary malignancy. Skeletal metastases represent one of the most common man- Radiotherapy ifestations of metastatic malignancy, and vertebral column for Primary Tumors involvement is the most common site for bony metastases to 7 As mentioned previously, there are a variety of primary ma- be located. Although difficult to quantify, estimates suggest lignant tumors of the spine. The most recognized and treated that over 100,000 patients develop osseous metastasis in the malignancies typically derive from 1 of 2 tissue types, soft USA annually. In these patients, it is estimated that 20% have tissues (sarcomas) or hematopoietic cells (hematopoietic can- spinal column involvement.8,9 Most spine metastases derive cers). The frequency of use and effectiveness of primary and adjuvant RT approaches vary greatly among these primary *Department of Radiation Oncology, Mayo Clinic, Rochester, MN. cancers even within tumors of similar cell-level progenitors. †Department of Radiation Oncology, Cancer Care Northwest, Spokane, WA. Address reprint requests to O. Kenneth Macdonald, MD, Department of Chordoma Radiation Oncology, Mayo Clinic, Desk R, Charlton Subway Level, 200 First St. SW, Rochester, MN 55905. E-mail: Macdonald.Orlan@mayo. These rare, slow-growing tumors often arise in the sacrum or edu base of skull.23 Men are more commonly affected than 1040-7383/09/$-see front matter © 2009 Elsevier Inc. All rights reserved. 121 doi:10.1053/j.semss.2009.03.006 122 O.K. Macdonald and C.M. Lee women and are more commonly identified in the fifth to myeloma. Both of these hematologic malignancies are more seventh decades.24 Surgical resection is the mainstay of treat- common in men. Although multiple myeloma is more com- ment but can be fraught with difficulty due to the complexity mon in the sixth and seventh decades of life, solitary plasma- of removing tumors that commonly are intimately associated cytoma typically presents at a younger age.48 Solitary plasma- with nerve roots. Recurrence, although typically indolent in cytoma is a rare entity and by definition is a single tumor its course, can be common.25 RT has been found to be useful involving a specific area of the spine or bone. In a good in the adjuvant and primary setting because of the difficulty proportion of patients, they are thought to predispose the of achieving a complete resection.26-31 The most favorable individual to the subsequent development of multiple my- reported results with RT combine high-dose proton beam eloma regardless of local therapy. Multiple myeloma repre- therapy (PT) with an aggressive surgical approach.32-35 There sents systemic involvement of the marrow space with likely are multiple potential reasons for the improved outcomes diffuse involvement of the spinal column. Both malignancies with PT, but it is likely that the greatest component of success are exquisitely sensitive to RT. Plasmacytoma is commonly derives from the ability to optimize the therapeutic ratio with treated with a 4- to 6-week course of tumor-directed RT with PT to a higher degree than traditional RT with photons (see excellent results in local control.49-52 However, evidence in- below for further explanation). dicates a high, albeit variable, risk of progression to myeloma with 10-year rates commonly reported as greater than Osteosarcoma 50%.53-55 RT is commonly used in multiple myeloma as a Osteosarcoma is a highly malignant tumor that commonly palliative tool to help improve patients’ quality of life, de- develops in young males. In osteosarcoma of the extremity, crease pain, and prevent pathologic fracture. Palliative RT in neoadjuvant chemotherapy followed by complete surgical this situation is commonly delivered with a shorter 2- to 56,57 resection represents the gold standard.36,37 Investigations 3-week course with good results. into adequate therapy without surgery using contemporary chemotherapy are controversial and uncommon.38 RT as a Lymphoma single modality has not been shown to be particularly effec- Lymphoma is described as a “small round blue-cell malig- tive in the primary management of osteosarcoma.39,40 RT nancy” that can develop primarily in the bones of the spine. combined with systemic agents have been infrequently inves- Resection is not typically required or recommended (unless tigated but have shown potential for improving local control necessary for prophylactic measures in stabilizing or rein- and limb preservation following induction with chemother- forcing the vertebrae). Various subtypes of lymphoma can apy.38,41,42 Typically, RT is not administered in the primary involve the bone primarily. Although generally rare, best ev- management of osteosarcoma (including in spinal presenta- idence reveals that primary lymphoma of the spine should be tions) but could be considered in the palliative setting. treated with induction chemotherapy tailored to the lym- phoma cell type, followed by consolidative RT. Several ran- Chondrosarcoma domized studies have demonstrated a significantly improved Chondrosarcomas were first described in 1943 by Lichten- disease-free survival with the combination of chemotherapy stein and Jaffe.43 Although relatively uncommon, they repre- and radiation compared to chemotherapy alone or RT alone sent the second most common primary bone tumor. Oppo- in the primary management of intermediate grade non- site of osteosarcomas, chondrosarcomas typically develop in Hodgkin’s lymphoma.58,59 Although little data regarding RT adulthood (commonly in the fourth to seventh decades). dose for spinal lymphoma are available, it is reasonable to Further, chondrosarcoma is a slow-growing tumor that can extrapolate information from the doses implemented in the develop in any portion of the bony spine. The gold standard above trials for bony primary sites. of therapy for these indolent tumors remains surgical resec- tion and this alone results in a relatively favorable prognosis Ewing’s Sarcoma 44 for patients with newly diagnosed, resectable disease. How- Another “small round blue-cell tumor,” Ewing’s sarcoma is ever, a complete resection can be hampered by the size, lo- the second most common primary tumor of bone in children cation, and extent of the tumor. Historically, it has been (behind osteosarcoma). Ewing’s class of tumor has a charac- believed that chondrosarcomas are typically resistant to both teristic age distribution with presentations uncommon in chemotherapy and RT. Studies investigating the administra- children younger than 8 years of age and in adults older than tion of RT during a course of care for a patient with chondro- 25 years.60 Although primary disease in the spine occurs in a sarcoma indicate that statistically significant improvements relative minority of patients, it historically has represented a in local control can be achieved with 3-dimensional (3D) relatively