166 Current Pediatric Reviews, 2012, 8, 166-178 1573-7829/12 $58.00+.00 © 2012 Bentham Science Publishers Long-Term Survivors of Cancer in Childhood and Adolescence Stacey L. Urbach 1 , Sharon Guger 2 and Paul C. Nathan *,3 Divisions of Endocrinology 1 and Hematology/Oncology 3 , Department of Pediatrics, Department of Psychology 2 , The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada Abstract: Significant improvements in the treatment of many pediatric malignancies have led to a growing population of long-term survivors of childhood cancer. Many of these survivors are at significant risk for late physical and psychosocial sequelae (“late effects”) as a result of their prior disease and its therapy. In some survivors (such as children treated for a brain tumor), late effects including endocrine dysfunction and neurocognitive challenges can develop during therapy and persist throughout life. In others (such as children and adolescents treated for Hodgkin’s lymphoma), late effects including congestive heart failure, pulmonary fibrosis and secondary breast cancers may not occur for many years, often once survivors have reached adulthood. During childhood, survivor care usually occurs at the pediatric cancer center, often in a specialized long-term follow-up clinic. However, adult survivors are usually cared for by primary care practitioners in their own communities. It is essential that the health care providers who will care for childhood cancer survivors as they age be aware of each survivor’s treatment exposures, long-term risks, and the surveillance strategies suggested for monitoring for these late effects. Strategies for effective transition from pediatric care and for ongoing communication between primary care practitioners and pediatric cancer centers need to be implemented to ensure that childhood cancer survivors receive appropriate care focused on their specific risks throughout their lifespan. Keywords: Childhood cancer, late effects, endocrine and neurocognitive dysfunction. INTRODUCTION The evolution of therapy for childhood cancer represents one of the major medical successes of the past half century. Whereas only 10% of children diagnosed with cancer in the 1950s became long term survivors [1], over 80% of children diagnosed today will survive their disease [2]. For acute lymphoblastic leukemia, the most prevalent pediatric malig- nancy, survival rates have risen from 60% in the 1970s to almost 90% today [3]. Improved survival of childhood cancer has been achieved by better stratification of therapy (offering more intensive therapy to those children at higher risk of relapse while decreasing toxic therapies in those children at lower risk), improvements in supportive care that allow for the delivery of intensive multi-modal therapies and more recently, by the introduction of novel therapies such as hematopoietic stem cell transplantation and molecularly targeted agents [4, 5]. As a consequence of improved survi- val, the population of survivors of childhood cancer is growing steadily. In 2005, there were over 325,000 survivors of childhood cancer alive in the United States (US) [6]. Although one quarter of these had survived 30 or more years from their original cancer diagnosis, many were still in their pediatric or adolescent years. When compared to diagnoses of cancer during adulthood, childhood cancer is relatively uncommon. Of the estimated 1,529,560 new cases of cancer that will be diagnosed in the US in 2010, only 10,700 (0.7%) will occur in children aged 0 to 14 years [7]. However, since children who survive their cancer have the potential for many future years of life, childhood cancers (as a group) impact more person-years than all adult malignancies except breast and lung cancer [8]. *Address correspondence to this author at the Divisions of Hematology/Oncology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Tel: 416-813-8795; Fax: 416- 813-5327; E-mail: paul.nathan@sickkids.ca Unfortunately, cure of cancer during childhood fre- quently comes at a cost to the patient. In addition to the acute (usually reversible) side effects of therapy (e.g. alopecia, nausea and vomiting, immune suppression), survivors are at risk for chronic sequelae of therapy that may develop during treatment (“long-term effects”) or months to years after the conclusion of therapy (“late effects”). Cytotoxic chemo- therapy agents, radiation therapy, surgery and the local effect of the tumor are all associated with chronic morbidities in childhood cancer survivors. The Childhood Cancer Survivor Study (CCSS), a longitudinal cohort study of over 10,000 adult survivors of childhood cancer treated between 1970 and 1986, revealed that 62% of survivors had developed one or more chronic physical health conditions, and that 28% had developed a severe or life threatening condition [9]. When compared to their siblings, survivors were more than three times as likely to have developed a chronic health condition. Childhood cancer survivors diagnosed and treated more recently appear to be at similar risk for chronic morbidity [10], although an understanding of long-term outcomes in children treated in the current era will require further follow- up. The more common physical sequelae of cancer and its therapy include endocrine, cardiac, neurologic, renal and pulmonary dysfunction (Table 1) [10]. In addition to an increased risk of morbidity, childhood cancer survivors are at increased risk for early mortality. Among survivors who have lived for five or more years after their cancer diagnosis, there is a nine-fold increased risk of early mortality com- pared to their peers. This elevated risk does not diminish over time [11]. Although death from recurrence or progres- sion of the original cancer is the leading cause of early mortality in 5-year cancer survivors, this population is also at increased risk of death from treatment-related causes such as new neoplasms, cardiac and pulmonary disease [12]. The impact of specific therapies is modified by patient factors (e.g. age at treatment, gender) and lifestyle factors (e.g.