CLINICAL REPORT

Guidance for the Clinician in Rendering Long-term Follow-up Care for Pediatric Pediatric Care Survivors

AMERICAN ACADEMY OF Section on Hematology/ CHILDREN؅S ONCOLOGY GROUP

ABSTRACT Progress in therapy has made survival into adulthood a reality for most children, adolescents, and young adults diagnosed with cancer today. Notably, this growing www.pediatrics.org/cgi/doi/10.1542/ peds.2008-3688 population remains vulnerable to a variety of long-term therapy-related sequelae. Systematic ongoing follow-up of these patients, therefore, is important for pro- doi:10.1542/peds.2008-3688 viding for early detection of and intervention for potentially serious late-onset All clinical reports from the American Academy of Pediatrics automatically expire complications. In addition, health counseling and promotion of healthy lifestyles 5 years after publication unless reaffirmed, are important aspects of long-term follow-up care to promote risk reduction for revised, or retired at or before that time. health problems that commonly present during adulthood. Both general and The guidance in this report does not subspecialty pediatric health care providers are playing an increasingly important indicate an exclusive course of treatment role in the ongoing care of childhood cancer survivors, beyond the routine preventive or serve as a standard of medical care. Variations, taking into account individual care, health supervision, and anticipatory guidance provided to all patients. This report circumstances, may be appropriate. is based on the guidelines that have been developed by the Children’s Oncology This document is copyrighted and is Group to facilitate comprehensive long-term follow-up of childhood cancer survivors property of the American Academy of Pediatrics and its Board of Directors. All (www.survivorshipguidelines.org). Pediatrics 2009;123:906–915 authors have filed conflict of interest statements with the American Academy of Pediatrics. Any conflicts have been resolved through a process approved by the Board of Directors. The American INTRODUCTION Academy of Pediatrics has neither solicited Cancer is diagnosed in approximately 12 400 children and adolescents younger nor accepted any commercial involvement than 20 years each year in the .1 Before 1970, almost all children with in the development of the content of this cancer died as a result of their primary disease. However, rapid improvements in publication. multimodal treatment regimens (, , and surgery), Key Words childhood cancer, treatment, survival, late coupled with aggressive supportive-care regimens, have resulted in survival rates effects, guidelines, long-term follow-up that continue to increase at a fast pace. The current overall survival rate for Abbreviations 2 childhood malignancies is estimated at 79%. This translates into approximately COG—Children’s Oncology Group 300 000 childhood cancer survivors now in the United States, many of whom may COG LTFU guidelines—Children’s seek ongoing care from pediatricians and other pediatric subspecialty providers.3 Oncology Group’s Long-term Follow-up Guidelines for Survivors of Childhood, As the number of childhood cancer survivors continues to grow, there is a Adolescent, and Young Adult concomitant increase in the number of survivors being cared for in the primary PEDIATRICS (ISSN Numbers: Print, 0031-4005; care setting. The Childhood Study (CCSS), the largest and most Online, 1098-4275). Copyright © 2009 by the extensively characterized cohort of 5-year childhood cancer survivors in North American Academy of Pediatrics America, reported that survivors receive most of their care from primary care providers.4 Furthermore, the proportion of survivors reporting a cancer-related visit decreases with increasing time from cancer diagnosis. Thus, the general pediatrician is likely to have an increasingly vital role in caring for this rapidly growing population. Cancer and its treatment may result in a variety of physical and psychosocial effects that predispose childhood cancer survivors to excess morbidity and early mortality when compared with the general population.5–12 Virtually every organ system can be affected by the chemotherapy, radiation, and/or surgery required to achieve cure of pediatric malignancies. Late complications of treatment may include problems with organ function, growth and development, neurocognitive function and academic achievement, and the potential for additional cancers. Cancer and its treatment also have psychosocial consequences that may adversely affect family/peer relationships, vocational and employment opportunities, and insurance and health care access. A child’s life is forever changed when touched by the cancer experience, and it is critical to assist the child and his or her family with rehabilitation into a society that places high value on good health and proper performance. Moreover, late effects after childhood cancer are common. Two of every 3 childhood cancer survivors will develop at least 1 late-onset therapy-related complication;

906 AMERICAN ACADEMY OF PEDIATRICS Downloaded from www.aappublications.org/news by guest on September 30, 2021 in 1 of every 4 cases, the complication will be severe or ateness of screening recommendations on the basis of life-threatening.13 Childhood cancer survivors, there- collective clinical experience of the expert panel. The fore, require ongoing comprehensive long-term fol- COG LTFU guidelines, therefore, are a hybrid of evi- low-up care to optimize long-term outcomes by success- dence-based and consensus-driven approaches to guide- fully monitoring for and treating the late effects that may line development. Task forces within the COG monitor occur as a result of previous cancer therapies. the literature on an ongoing basis and provide recom- Because health risks associated with cancer are mendations for guideline revision as new information unique to the age at treatment and specific therapeutic becomes available. These task forces include general pe- modality, follow-up evaluations and health screening diatricians and other primary care providers to incorpo- should be individualized on the basis of treatment his- rate a primary care perspective and facilitate effective tory. To facilitate comprehensive and systematic fol- dissemination of these guidelines into the “real-world” low-up of childhood cancer survivors, the Children’s setting. Table 1 provides a summary of selected treat- Oncology Group (COG) organized exposure-based ment exposures and associated late effects according to health screening guidelines. This clinical report presents organ system as outlined in the COG LTFU guidelines. the pediatrician with guidance in providing high-quality Fig 1 provides an example of an exposure-based recom- long-term follow-up care and health supervision for sur- mendation from the COG LTFU guidelines. vivors of pediatric malignancies by incorporating long- The COG LTFU guidelines are designed for use in term follow-up guidelines developed by the COG into asymptomatic survivors presenting for routine health their practice14 and by maintaining ongoing interaction maintenance at least 2 years after completion of thera- with pediatric oncology subspecialists to facilitate com- py.15 They are not designed for disease-related surveil- munication regarding any changes in follow-up recom- lance, which generally continues under the guidance of mendations specific to the childhood cancer survivors the treating oncologist throughout the period when the under their care. patient remains at risk of relapse from his or her primary disease. This period of risk varies depending on diagnosis METHODS: DEVELOPMENT OF LONG-TERM FOLLOW-UP and is generally highest in the first few years, with the GUIDELINES risk decreasing significantly as time from diagnosis The COG is a cooperative clinical trials group supported lengthens. by the National Cancer Institute with more than 200 member institutions. In January 2002, at the request of CLINICAL APPLICATION OF THE COG LTFU GUIDELINES the Institute of , a multidisciplinary panel Malignancies that present in the pediatric age range within the COG initiated the process of developing com- encompass a spectrum of diverse histologic subtypes that prehensive risk-based, exposure-related recommenda- have been managed with heterogeneous and evolving tions for screening and management of late treatment- treatment approaches. Over the last 20 years, treatment related complications potentially resulting from therapy protocols for localized and biologically favorable presen- for childhood cancers. The resulting comprehensive re- tations of pediatric cancers have been modified substan- source, the COG’s Long-term Follow-up Guidelines for Sur- tially to reduce the risk of therapy-related complications. vivors of Childhood, Adolescent, and Young Adult Cancers Conversely, therapy has been intensified for many ad- (COG LTFU guidelines),14 is designed to raise awareness vanced and biologically unfavorable pediatric cancers to of the risk of late treatment-related sequelae to facilitate optimize disease control and long-term survival. Thus, early identification and intervention for these complica- not all childhood cancer survivors have similar risks of tions, standardize follow-up care, improve quality of life, late treatment effects, including those with the same and provide guidance to health care professionals, in- diagnosis. The diversity and potential interplay of factors cluding pediatricians, who supervise the ongoing care of contributing to cancer-related morbidity are illustrated childhood cancer survivors. in the case presentations summarized in Table 2. In The methodology used in developing these guidelines general, the risk of late effects is directly proportional to has been described elsewhere.15 Briefly, evidence for the intensity of therapy required to achieve and main- development of the COG LTFU guidelines was collected tain disease control. Longer treatment with higher cu- by conducting a complete search of the medical litera- mulative doses of chemotherapy and radiation, multi- ture for the previous 20 years via Medline. After the modal therapy, and relapse therapy increases the risk of screening recommendations were developed, a multidis- late treatment effects. Specifically, the risk of late effects ciplinary panel (including experts from pediatric oncol- is related to the type and intensity of cancer therapy (eg, ogy and other pediatric subspecialties, nursing, radiation surgery, radiation therapy, chemotherapy, hematopoi- oncology, behavioral medicine, and patient advocacy) etic stem cell transplantation) and the patient’s age at reviewed and revised the guidelines. A panel of experts the time of treatment. Chemotherapy most often results in the late effects of childhood and adolescent cancer in acute effects, some of which may persist and cause treatment then reviewed and scored the guidelines by problems as the survivor ages. Many radiation-related using a modified version of the National Comprehensive effects on growth and development, organ function, and Cancer Network “Categories of Consensus” system.16 may not manifest until many years after Each score reflects the strength of data from the litera- cancer treatment. The young child is especially at risk of ture linking specific late complications with therapeutic delayed treatment toxicity affecting linear growth, skel- exposures, coupled with an assessment of the appropri- etal maturation, intellectual function, sexual develop-

PEDIATRICS Volume 123, Number 3, March 2009 907 Downloaded from www.aappublications.org/news by guest on September 30, 2021 TABLE 1 Potential Late Effects of Selected Therapeutic Interventions for Childhood Cancer According to Organ System Organ System Therapeutic Exposures Potential Late Effect Chemotherapy Radiation Therapy Field Surgery Skin — All fields — Dysplastic nevi; skin cancer Ocular Busulfan; Cranial; orbital/eye; TBI Neurosurgery Cataracts; retinopathy (XRT doses Ն 30 corticosteroids Gy only); ocular nerve palsy (neurosurgery only) Auditory Cisplatin; carboplatin Ն30 Gy to: cranial, ear/infratemporal, — Sensorineural hearing loss; conductive (in myeloablative nasopharyngeal hearing loss (XRT only); Eustachian doses only) tube dysfunction (XRT only) Dental Any chemotherapy Head and neck fields that include the — Dental maldevelopment (tooth/root before oral cavity or salivary glands (eg, agenesis, microdontia, enamel development of cranial, oropharyngeal, mantle, dysplasia); periodontal disease; secondary TBI) dental caries; osteoradionecrosis (XRT dentition doses Ն 40 Gy) Cardiovascular Anthracycline agents Chest (eg, mantle, mediastinal); — Cardiomyopathy; congestive heart (eg, doxorubicin, upper abdominal failure; arrhythmia; subclinical left daunorubicin) ventricular dysfunction; XRT only: valvular disease, atherosclerotic heart disease, myocardial infarction, and pericarditis, pericardial fibrosis Pulmonary Bleomycin; busulfan; Chest (mantle, mediastinal, whole Pulmonary resection; Pulmonary fibrosis; interstitial carmustine; lung); TBI lobectomy pneumonitis; restrictive/obstructive lomustine lung disease; pulmonary dysfunction Breast — Chest (mantle, mediastinal, axillary, — Breast tissue hypoplasia; breast cancer whole lung, TBI) (XRT doses Ն 20 Gy) Gastrointestinal — Abdominal, pelvic (doses Ն 30 Gy) Laparotomy; pelvic/ Chronic enterocolitis; gastrointestinal spinal surgery tract strictures; adhesions/ obstruction; fecal incontinence; colon cancer (XRT only; doses Ն 30 Gy) Liver Antimetabolites Abdominal (doses Ն 30 Gy) — Hepatic dysfunction; veno-occlusive (mercaptopurine, disease (VOD); hepatic fibrosis, thioguanine, cirrhosis; cholelithiasis methotrexate) Renal Cisplatin; Abdominal (including ) Nephrectomy Glomerular toxicity; tubular dysfunction; carboplatin; renal insufficiency; hypertension ifosfamide; methotrexate Bladder Cyclophosphamide; Pelvic (including bladder); lumbar- Spinal surgery; Hemorrhagic cystitis; bladder fibrosis; ifosfamide sacral spine cystectomy dysfunctional voiding; neurogenic bladder; bladder malignancy (cyclophosphamide, XRT) Sexual/reproductive Males Alkylating agents Hypothalamic-pituitary; testicular; Pelvic/spinal surgery; Delayed/arrested puberty; (eg, busulfan, pelvic; TBI orchiectomy hypogonadism; infertility; erectile/ carmustine, ejaculatory dysfunction lomustine, cyclophosphamide, mechlorethamine, melphalan, procarbazine) Females Alkylating agents Hypothalamic-pituitary; pelvic; Oophorectomy Delayed/arrested puberty; premature (eg, busulfan, ovarian; lumbar-sacral spine; TBI menopause; infertility; uterine carmustine, vascular insufficiency (XRT only); lomustine, vaginal fibrosis/stenosis (XRT only) cyclophosphamide, mechlorethamine, melphalan, procarbazine)

908 AMERICAN ACADEMY OF PEDIATRICS Downloaded from www.aappublications.org/news by guest on September 30, 2021 TABLE 1 Continued Organ System Therapeutic Exposures Potential Late Effect Chemotherapy Radiation Therapy Field Surgery Endocrine/metabolic — Hypothalamic-pituitary; neck Thyroidectomy Growth hormone deficiency; precocious (thyroid) puberty; hypothyroidism; thyroid nodules/cancer; XRT doses Ն 40 Gy: hyperprolactinemia, central adrenal insufficiency, gonadotropin deficiency, and hyperthyroidism Musculoskeletal Corticosteroids; — — Osteopenia/osteoporosis; osteonecrosis methotrexate — All fields — Reduced/uneven growth; reduced function/mobility; hypoplasia, fibrosis; radiation-induced fracture (doses Ն 40 Gy); scoliosis/kyphosis (trunk fields only); secondary benign or malignant neoplasm — — Amputation; limb Reduced/uneven growth; reduced sparing function/mobility Neurocognitive Methotrexate Cranial; ear/infratemporal; total body Neurosurgery Neurocognitive deficits (executive (intrathecal irradiation function, attention, memory, administration or processing speed, visual motor IV doses Ն 1000 integration); learning deficits; mg/m2); diminished IQ cytarabine (IV doses Ն 1000 mg/m2) Central Methotrexate, Doses Ն 18 Gy to: cranial, orbital/eye, Neurosurgery Leukoencephalopathy (spasticity, cytarabine ear/infratemporal, nasopharyngeal ataxia, dysarthria, dysphagia, (intrathecal hemiparesis, seizures ͓chemotherapy administration or and XRT͔); motor and sensory deficits; IV doses Ն 1000 cerebrovascular complications mg/m2) (stroke, Moya Moya, occlusive cerebral; vasculopathy ͓XRT and surgery͔) (any XRT dose) Peripheral nervous system Plant alkaloids — Spinal surgery Peripheral sensory or motor neuropathy (vincristine, vinblastine); cisplatin, carboplatin Immunologic Abdomen, left upper quadrant, Splenectomy Life-threatening infection related to spleen (doses Ն 40 Gy) functional or anatomic asplenia (note: functional asplenia can also occur as a consequence of active chronic graft-vs-host disease after hematopoietic stem cell transplant) Psychosocial Any Any Any Social withdrawal; educational problems; depression; anxiety; posttraumatic stress This table briefly summarizes potential late effects for selected therapeutic exposures only; the complete set of long-term follow-up guidelines from the Children’s Oncology Group, including screening recommendations, is available at www.survivorshipguidelines.org. XRT indicates radiation therapy; TBI, total body irradiation; IV, intravenous. ment, and organ function. Because pediatricians provide includes the date of cancer diagnosis, cancer histology, care across a continuum of developmental periods, they organs/tissues affected by cancer, and specific treatment must also recognize that childhood cancer survivors face modalities such as surgical procedures, chemotherapeutic unique vulnerabilities related to their age at diagnosis agents and radiation treatment fields and doses, and his- and treatment. tory of bone marrow or stem cell transplant and blood- Risk-based care involving a systematic plan for lifelong product transfusion. Knowledge of cumulative chemother- screening, surveillance, and prevention that incorporates apy dosages (eg, for anthracycline agents), or dose intensity risks on the basis of previous cancer, cancer therapy, ge- of administration (eg, for methotrexate), also is important netic predispositions, lifestyle behaviors, and comorbid in estimating risk and screening frequency. This pertinent health conditions is recommended for all survivors.10,17 In- clinical information can be organized into a treatment formation critical to the coordination of risk-based care summary that interfaces with the COG LTFU guidelines to

PEDIATRICS Volume 123, Number 3, March 2009 909 Downloaded from www.aappublications.org/news by guest on September 30, 2021 FIGURE 1 Example of an exposure-based recommendation from the COG LTFU guidelines. (Reproduced with permission from the Children’s Oncology Group. Long-term Follow-up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers. Version 3.0. Arcadia, CA: Children’s Oncology Group; 2008:73.) facilitate identification of potential late complications and resource for this treatment information. Furthermore, the recommended follow-up care (Fig 2). Because of the di- need for ongoing, open lines of communication between versity and complexity of pediatric cancer therapies, the the pediatric cancer center and the primary care provider is treating pediatric oncology center represents the optimal critical.

TABLE 2 Examples of 2 Survivors: Factors Contributing to Cancer-Related Morbidity Factor Example 1: Leukemia Example 2: Solid Tumor Host 3-y-old white male 16-y-old black female Tumor Acute lymphoblastic leukemia, B lineage, average risk, Embryonal of the chest wall, without CNS involvement stage II Treatment Vincristine; corticosteroids; antimetabolites (PO, IV, Vincristine; dactinomycin; chest radiation (36 Gy) intrathecal); asparaginase; cyclophosphamide (moderate dose); doxorubicin (low dose) Potential late effects Peripheral neuropathy; osteopenia/osteoporosis; Peripheral neuropathy; cardiac complications osteonecrosis; cataracts; hepatic dysfunction; renal (cardiomyopathy, congestive heart failure, insufficiency; neurocognitive deficits; arrhythmia, subclinical left ventricular leukoencephalopathy; hemorrhagic cystitis, dysfunction, valvular disease, atherosclerotic bladder malignancy; secondary myelodysplasia or heart disease, myocardial infarction, myeloid leukemia; gonadal dysfunction; pericarditis, pericardial fibrosis); pulmonary cardiomyopathy, congestive heart failure, complications (fibrosis, interstitial arrhythmia; dental maldevelopment, periodontal pneumonitis, restrictive/obstructive lung disease, excessive dental caries disease); esophageal stricture; breast tissue hypoplasia; breast cancer; scoliosis/kyphosis; shortened trunk height; secondary benign or malignant neoplasms in radiation field Genetics/familial Diabetes mellitus, type 2 Hypertension; early coronary artery disease Comorbid Obesity Hypertension conditions Health behaviors Sedentary lifestyle Smoker Aging Bone mineral density (osteoporosis) Cardiomyopathy CNS indicates ; PO, oral; IV, intravenous.

910 AMERICAN ACADEMY OF PEDIATRICS Downloaded from www.aappublications.org/news by guest on September 30, 2021 FIGURE 2 Sample template for cancer treatment summary containing essential data elements necessary for generating long-term follow-up guidelines. (Reproduced with permission from the Children’s Oncology Group. Long-term Follow-up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers. Version 3.0. Arcadia, CA: Children’s Oncology Group; 2008:Appendix 1.)

PEDIATRICS Volume 123, Number 3, March 2009 911 Downloaded from www.aappublications.org/news by guest on September 30, 2021 Coordination of risk-based care for childhood cancer The COG LTFU guidelines should be used to guide survivors requires a working knowledge about cancer- development of individualized follow-up plans for related health risks and appropriate screening evalua- each patient on the basis of his or her particular risk of tions or access to a resource that contains this informa- late complications, which should be developed tion. Individualized recommendations for long-term through a shared partnership that includes the general follow-up care of childhood cancer survivors can be pediatric and pediatric oncology subspecialty provid- customized from the COG LTFU guidelines on the basis ers, the child, and the family. The COG LTFU guide- of each patient’s treatment history, age, and gender into lines can assist the clinician in maintaining a balance a “survivorship care plan” that is ideally developed by, or between overscreening (which could potentially cause in coordination with, the pediatric oncology subspecial- undue fear of unlikely but remotely plausible compli- ist. In addition, the COG LTFU guidelines provide infor- cations as well as higher medical costs resulting from mation to assist with risk stratification, allowing the unnecessary screening) and underscreening (which health care provider to address specific treatment-re- could miss potentially life-threatening complications, lated health risks that may be magnified in individual thus resulting in lost opportunities for early interven- patients because of familial or genetic predisposition, tion that could minimize morbidity). Ultimately, as sociodemographic factors, or maladaptive health behav- with all clinical practice guidelines, decisions regard- iors. The patient education materials (known as “health ing specific screening and ongoing clinical manage- links”) that accompany the COG LTFU guidelines are ment for individual patients should be tailored to take specifically tailored to enhance health supervision and all relevant factors (such as therapeutic exposures, promotion in this population by providing simplified medical and psychosocial history, and comorbidities) explanations of guideline-specific topics in lay lan- into consideration. guage.18 The COG LTFU guidelines, associated patient The pediatrician must also be aware that the childhood education materials, and supplemental resources to cancer experience is unique in that some survivors, given enhance guideline application, including clinical sum- their young age at diagnosis, may not remember their mary templates, can be downloaded from www. cancer diagnosis or the treatment that they received. For survivorshipguidelines.org. A Web-based platform others, parents may not have told the child about his or her that will allow online generation of therapeutic sum- cancer history. Therefore, it is not surprising that when maries with simultaneous output of patient-specific childhood cancer survivors have been questioned regard- guidelines on the basis of exposure history, age, and ing knowledge of their diagnosis and treatment, important gender is currently under development.19 deficits have been identified.22 The pediatrician may need to request a cancer treatment summary and “survivorship DISCUSSION/RECOMMENDATIONS care plan” from the pediatric oncology center if one is not Pediatricians are uniquely qualified to deliver ongoing provided at the time that the child transitions back to the health care to childhood cancer survivors, because primary care setting. Many pediatric oncology centers offer they are already familiar with health maintenance and ongoing multidisciplinary follow-up care for childhood supervision for healthy children and adolescents and cancer survivors on an annual, 1-time, or as-needed basis. also provide care for patients with complex chronic Some follow-up clinics are comprehensive and offer ongo- medical conditions. The concept of the “medical ing care and risk-based screening for childhood cancer home” has been endorsed by the American Academy survivors, and other follow-up clinics are consultative in of Pediatrics as an effective model for coordinating the nature and develop risk-based recommendations for ongo- complex health care requirements of children with ing follow-up (included in survivorship care plans) that can special needs, such as childhood cancer survivors, to be conducted in the primary care setting. In any case, the provide care and preventive services that are accessi- components of a survivorship care plan should include ble, continuous, comprehensive, family centered, co- recommendations for late-effects screening generated from ordinated, compassionate, and culturally effective.20,21 the COG LTFU guidelines on the basis of therapeutic ex- Within this framework, the pediatrician is able to view posures, identification of the provider(s) who will be coor- the cancer survivor in the context of the family and to dinating the indicated screening evaluations, and identifi- assist not only the survivor but also the parents and cation of the provider(s) responsible for communicating siblings in adapting to the “new normal” of cancer and explaining the results to the patient and/or caregivers. survivorship. The focus of care for the childhood can- In addition to screening for late effects on the basis of cer survivor seen in the general pediatric practice is previous therapeutic exposures, health counseling and not the cancer from which the patient has now recov- promotion of healthy lifestyles are important aspects of ered but, rather, the actual and potential sequelae of long-term follow-up care in this population. Oeffinger and cancer and its therapy. Childhood cancer survivors are colleagues13 have shown that survivors of childhood cancer at a substantially increased risk of morbidity and mor- have a high rate of chronic health conditions when fol- tality when compared with the general population.5–12 lowed long-term. For this reason, it is essential for the Their follow-up evaluations should be individualized pediatrician to provide anticipatory guidance regarding on the basis of their treatment history and may in- health promotion and disease prevention aimed at mini- clude screening for such potential complications as mizing the risk of future morbidity and mortality. For thyroid or cardiac dysfunction, second malignant neo- example, survivors who are at risk of obesity, cardiovas- plasms, neurocognitive difficulties, and many others.13 cular disease, and osteoporosis should be counseled re-

912 AMERICAN ACADEMY OF PEDIATRICS Downloaded from www.aappublications.org/news by guest on September 30, 2021 garding the importance of eating a well-balanced diet lescent and young adult survivors should be well versed (high in calcium, low in fat) and participating in regular regarding their own health maintenance needs, their po- exercise. The COG LTFU guidelines can be used to facil- tential health risks, necessary ongoing screening related to itate targeted education regarding health promotion. In their cancer therapy, and health-related behaviors that can addition to the verbal counseling completed in the office reduce their risk of potential adverse sequelae. They need setting, survivors should also receive written and/or to be aware of the importance of maintaining continuous Web-based educational material that can be used to health insurance coverage to ensure access to screening for further reinforce their knowledge about their risks for their late effects. This can be challenging, because many specific late effects. These written and Web-based health adolescent and young adult survivors are still defining ca- education materials are called health links and are avail- reer goals and, therefore, have not yet attained employer- able with the COG LTFU guidelines at www.survivor- based health insurance coverage. The adolescent or young shipguidelines.org. They can be printed for distribution adult cancer survivor may be grappling with unique treat- in the primary care office setting and are available for ment-related health issues, such as infertility, at a time viewing by patients and their caregivers on the Inter- when their sexual maturity and personal relationships are net.18 developing. Some may also be at risk of early death be- Again, it must be emphasized that the pediatrician is not cause of primary disease recurrence or second malignant alone in caring for the childhood cancer survivor. There are neoplasms,25 which in turn may require frank discussions numerous multidisciplinary long-term follow-up programs regarding advanced directives. Therefore, adolescent and for childhood cancer survivors, and most of these programs young adult survivors should leave the pediatric health will work collaboratively with pediatricians to assist with care environment equipped with a comprehensive survi- the development of individualized survivorship care plans. vorship care plan, along with the knowledge and skills Depending on geographic location, insurance coverage, required to keep abreast of new information relating to and other considerations, some patients may return to the their potential health risks as that information emerges. primary oncology center for annual or periodic visits, and Although late treatment effects can be anticipated in their long-term follow-up care may be partially or entirely many cases on the basis of therapeutic exposures, the risk accomplished through these specialized centers, with the to an individual patient is modified by multiple factors. The pediatrician providing the primary pediatric health care for patient with cancer may present with premorbid health those patients. However, for many survivors, long dis- conditions that influence tolerance to therapy and increase tances or other barriers may make specialized long-term the risk of treatment-related toxicity. Cancer-related fac- follow-up impractical, and the pediatrician is often called tors, including histology, tumor site, and tumor genetics, on to provide both long-term follow-up and primary care often dictate treatment modality and intensity. Host-re- for childhood cancer survivors in the community setting. lated factors such as age at diagnosis, race, and gender may Telephone consultation with the primary oncology team or affect the risk of several treatment-related complications. associated long-term follow-up center is generally available Sociodemographic factors such as household income, ed- to facilitate this ongoing care. For survivors who are iden- ucational attainment, and socioeconomic status often in- tified as having chronic health problems as a result of their fluence access to health insurance, remedial services, and previous cancer therapy, the pediatrician can also work appropriate risk-based health care. Organ senescence in with the primary oncology center to obtain assistance with aging survivors may accelerate presentation of age-related referrals to subspecialists knowledgeable in issues related to health conditions in survivors with subclinical organ injury childhood cancer survivorship. In addition, a listing of or dysfunction resulting from cancer treatment. Genetic or COG-affiliated subspecialty survivorship clinics is available familial characteristics may also enhance susceptibility to (www.childrensoncologygroup.org). These clinics are also treatment-related complications. Problems experienced excellent venues for pediatric residents to learn about the during and after treatment may further increase morbidity. unique health care needs of childhood cancer survivors Health behaviors, including and alcohol use, sun and of the long-term therapy-related risks that they con- exposure, and dietary and exercise habits, may increase the tinue to face across their life span; however, there are risk of specific therapy-related complications. Although currently no formal mechanisms for including cancer sur- much is known about factors predisposing to cancer-re- vivorship in the training of medical students or pediatric lated morbidity and mortality in this growing population, residents. there is still much to learn to inform the development of Ensuring a smooth transition from pediatric to adult- interventions that will optimize survival rates for pediatric oriented health care services poses additional challenges in malignancies while limiting or eliminating therapy-related the care of childhood cancer survivors as they age out of toxicities. This fact underscores the importance of long- the pediatric health care system. Pretransition planning is a term follow-up for childhood cancer survivors to accu- critical element in the successful transition from pediatric rately define health outcomes, characterize groups at high to adult-oriented health care for all adolescents and young risk, and implement risk-reducing interventions. adults with special health care needs, including childhood cancer survivors, and the medical home model provides a SUMMARY strong foundation for this planning.23,24 The pretransition Given the high incidence of late effects experienced by plan should outline the roles of patient, family, subspe- childhood cancer survivors, it is essential that individuals cialty and community health care providers in the ongoing who were treated for cancer during childhood receive care of the survivor to ensure a successful transition. Ado- long-term follow-up care from knowledgeable providers so

PEDIATRICS Volume 123, Number 3, March 2009 913 Downloaded from www.aappublications.org/news by guest on September 30, 2021 that their care is appropriately tailored to their specific Support (CORE) grant CA 21765 from the National Can- treatment-related risk factors. This is an exciting time for cer Institute and by the American Lebanese Syrian As- providing care to childhood cancer survivors. Discussion sociated Charities (ALSAC). Dr Casillas is also supported regarding the best models for providing survivorship care by The Harold Amos Medical Faculty Development Pro- are emerging concomitantly with the availability of the gram funded by the Robert Wood Johnson Foundation. COG LTFU guidelines. A recent review by Oeffinger and McCabe26 proposed a “shared-care model” that includes roles for both the primary care provider and the cancer REFERENCES subspecialist in the care of cancer survivors. In this model, 1. Ries LAG, Eisner MP, Kosary CL, et al. 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Health care of and specialist to optimize the follow-up care for childhood young adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Ann Fam Med. 2004;2(1): cancer survivors. 61–70 Ultimately, the goal of this clinical report from the 5. Hudson MM, Mertens AC, Yasui Y, et al. Health status of adult American Academy of Pediatrics is to increase the long-term survivors of childhood cancer: a report from the awareness of general pediatricians to the readily avail- Childhood Cancer Survivor Study. JAMA. 2003;290(12): able resource of the COG LTFU guidelines. These guide- 1583–1592 lines can, in turn, be used to develop a comprehensive 6. Gurney JG, Kadan-Lottick NS, Packer RJ, et al. Endocrine and yet individualized survivorship care plan for each child- cardiovascular late effects among adult survivors of childhood hood cancer survivor. The pediatrician works collabora- brain tumors: Childhood Cancer Survivor Study. 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Obesity in adult survivors of childhood acute lymphoblastic leukemia: a report AAP SECTION ON HEMATOLOGY/ONCOLOGY EXECUTIVE COMMITTEE, from the Childhood Cancer Survivor Study. J Clin Oncol. 2003; 2007–2008 21(7):1359–1365 Stephen A. Feig, MD, FAAP, Chairperson 10. Oeffinger KC, Hudson MM. Long-term complications follow- Alan S. Gamis, MD, FAAP ing childhood and adolescent cancer: foundations for providing Jeffrey D. Hord, MD, FAAP risk-based health care for survivors. CA Cancer J Clin. 2004; Eric D. Kodish, MD 54(4):208–236 Brigitta U. Mueller, MD, FAAP 11. Sklar CA, Mertens AC, Walter A, et al. Changes in body mass Eric J. Werner, MD, FAAP index and prevalence of overweight in survivors of childhood Roger L. Berkow, MD, FAAP, Past Chairperson acute lymphoblastic leukemia: role of cranial irradiation. Med Pediatr Oncol. 2000;35(2):91–95 STAFF 12. Wallace WH, Blacklay A, Eiser C, et al. Developing strategies Laura Laskosz, MPH for long term follow up of survivors of childhood cancer. BMJ. 2001;323(7307):271–274 CHILDREN’S ONCOLOGY GROUP 13. Oeffinger KC, Mertens AC, Sklar CA, et al. Chronic health *Smita Bhatia, MD, MPH conditions in adult survivors of childhood cancer. Childhood *Jacqueline Casillas, MD, MSHS Cancer Survivor Study. N Engl J Med. 2006;355(15):1572–1582 14. Children’s Oncology Group. Long-term Follow-up Guidelines for *Melissa M. Hudson, MD Survivors of Childhood, Adolescent, and Young Adult Cancers. Ver- *Wendy Landier, RN, MSN, CPNP sion 3.0. Arcadia, CA: Children’s Oncology Group; 2008 15. Landier W, Bhatia S, Eshelman DA, et al. Development of *Lead authors risk-based guidelines for pediatric cancer survivors: the Chil- dren’s Oncology Group Long-term Follow-up Guidelines from ACKNOWLEDGMENTS the Children’s Oncology Group Late Effects Committee and This work was supported in part by Children’s Oncology Nursing Discipline. J Clin Oncol. 2004;22(24):4979–4990 Group grant U10 CA098543 from the National Cancer 16. Winn RJ, Botnick WZ. The NCCN guideline program: a concep- Institute. Dr Hudson is also supported by Cancer Center tual framework. Oncology (Williston Park). 1997;11(11A):25–32

914 AMERICAN ACADEMY OF PEDIATRICS Downloaded from www.aappublications.org/news by guest on September 30, 2021 17. Oeffinger KC. Longitudinal risk-based health care for adult cancer survivors’ knowledge about their past diagnosis and survivors of childhood cancer. Curr Probl Cancer. 2003;27(3): treatment: Childhood Cancer Survivor Study. JAMA. 2002; 143–167 287(14):1832–1839 18. Eshelman D, Landier W, Sweeney T, et al. Facilitating care for 23. American Academy of Pediatrics; American Academy of Fam- childhood cancer survivors: integrating children’s oncology ily Physicians; American College of Physicians-American Soci- group long-term follow-up guidelines and health links in clin- ety of Internal Medicine. A consensus statement on health care ical practice. J Pediatr Oncol Nurs. 2004;21(5):271–280 transitions for young adults with special health care needs. 19. National Cancer Institute. Passport for care: an internet-based Pediatrics. 2002;110(6 pt 2):1304–1306 survivorship care plan. NCI Cancer Bull. 2006;3(23):8 24. Kelly AM, Kratz B, Bielski M, Rinehart PM. Implementing 20. American Academy of Pediatrics, Medical Home Initiatives for transitions for youth with complex chronic conditions using Children With Special Needs Project Advisory Committee. The the medical home model. Pediatrics. 2002;110(6 pt 2): medical home. Pediatrics. 2002;110(1):184–186 1322–1327 21. American Academy of Pediatrics National Center of Medical 25. Mertens AC. Cause of mortality in 5-year survivors of child- Home Initiatives for Children With Special Needs. Available at: hood cancer. Pediatr Blood Cancer. 2007;48(7):723–726 www.medicalhomeinfo.org. Accessed April 8, 2008 26. Oeffinger KC, McCabe MS. Models for delivering survivorship 22. Kadan-Lottick NS, Robison LL, Gurney JG, et al. Childhood care. J Clin Oncol. 2006;24(32):5117–5124

PEDIATRICS Volume 123, Number 3, March 2009 915 Downloaded from www.aappublications.org/news by guest on September 30, 2021 Long-term Follow-up Care for Pediatric Cancer Survivors AMERICAN ACADEMY OF PEDIATRICS Section on Hematology/Oncology CHILDREN'S ONCOLOGY GROUP Pediatrics 2009;123;906 DOI: 10.1542/peds.2008-3688

Updated Information & including high resolution figures, can be found at: Services http://pediatrics.aappublications.org/content/123/3/906 References This article cites 22 articles, 7 of which you can access for free at: http://pediatrics.aappublications.org/content/123/3/906#BIBL Subspecialty Collections This article, along with others on similar topics, appears in the following collection(s): Current Policy http://www.aappublications.org/cgi/collection/current_policy Section on Hematology/Oncology http://www.aappublications.org/cgi/collection/section_on_hematolog y_oncology Hematology/Oncology http://www.aappublications.org/cgi/collection/hematology:oncology_ sub Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.aappublications.org/site/misc/Permissions.xhtml Reprints Information about ordering reprints can be found online: http://www.aappublications.org/site/misc/reprints.xhtml

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Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. Pediatrics is owned, published, and trademarked by the American Academy of Pediatrics, 345 Park Avenue, Itasca, Illinois, 60143. Copyright © 2009 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.

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