The prevalence of total CHDs, primarily common, less severe types, are increasing, with some racial/ethnic differences. Further studies could clarify the possible reasons for such variations including differences in ascertainment, risk factors, or susceptibility.

Innovations in the understanding of childhood cancer biology, treatment and supportive care have dramatically improved cure rates such that 84% of newly diagnosed children and adolescents in high-income countries are expected to survive beyond 5-years from diagnosis. 1 As a result, the number of childhood cancer survivors living in the USA surpassed 420 000 in 2013 1 and is anticipated to approach 500 000 by 2020. 2 The medical success manifest by this growing population has been realized at a cost, however, as many survivors experience adverse health outcomes related to cancer and its treatment. [3][4][5][6] In addition to chronic morbidity, survivors experience premature mortality compared to age-and sex-matched controls. [7][8][9][10] Current understanding of late health outcomes in adult survivors of childhood cancer has largely been the result of a number of cohort studies that have been instrumental in identifying, quantifying and characterizing cancer treatment-related health risks. [11][12][13][14][15][16][17] Health outcomes research findings have had a major influence on changes in paediatric cancer therapy and have informed health-screening strategies of childhood cancer survivors.

Peripheral neuropathy is a well recognised treatment-related toxicity in children with cancer, associated with exposure to neurotoxic chemotherapy agents. Acute damage can occur in sensory, motor, or autonomic neurons, with symptoms that are rarely life threatening, but often severe enough to interfere with function during therapy and after treatment ends. The type of neuropathy and specific symptoms are associated with multiple factors including age at time of therapy, genetic predisposition, chemotherapy type and cumulative dose, and exposure to other agents during therapy. In this Review, we describe the peripheral neuropathy phenotype in children during cancer therapy and among survivors who have completed therapy, to summarise genetic and treatment-related risk factors for neuropathy, and to outline strategies to monitor and detect neuropathy during and after therapy. Additionally, we outline strategies for medical management of neuropathy during treatment and potential rehabilitation interventions to prevent or remediate functional loss.

Context Data on hypothalamic-pituitary (HP) disorders in systematically evaluated childhood cancer survivors are limited. Objective To describe prevalence, risk factors, and associated adverse health outcomes of deficiencies in GH deficiency (GHD), TSH deficiency (TSHD), LH/FSH deficiency (LH/FSHD), and ACTH deficiency (ACTHD), and central precocious puberty (CPP). Design Retrospective with cross-sectional health outcomes analysis. Setting Established cohort; tertiary care center. Patients Participants (N = 3141; median age, 31.7 years) were followed for a median 24.1 years. Main Outcome Measure Multivariable logistic regression was used to calculate ORs and 95% CIs for associations among HP disorders, tumor- and treatment-related risk factors, and health outcomes. Results The estimated prevalence was 40.2% for GHD, 11.1% for TSHD, 10.6% for LH/FSHD, 3.2% for ACTHD, and 0.9% for CPP among participants treated with HP radiotherapy (n = 1089), and 6.2% for GHD, and <1% for other HP disorders without HP radiotherapy. Clinical factors independently associated with HP disorders included HP radiotherapy (at any dose for GHD, TSHD, LH/FSHD, >30 Gy for ACTHD), alkylating agents (GHD, LH/FSHD), intrathecal chemotherapy (GHD), hydrocephalus with shunt placement (GHD, LH/FSHD), seizures (TSHD, ACTHD), and stroke (GHD, TSHD, LH/FSHD, ACTHD). Adverse health outcomes independently associated with HP disorders included short stature (GHD, TSHD), severe bone mineral density deficit (GHD, LH/FSHD), obesity (LH/FSHD), frailty (GHD), impaired physical health-related quality of life (TSHD), sexual dysfunction (LH/FSHD), impaired memory, and processing speed (GHD, TSHD). Conclusion HP radiotherapy, central nervous system injury, and, to a lesser extent, chemotherapy are associated with HP disorders, which are associated with adverse health outcomes.

The population of adult survivors of childhood cancer continues to grow as survival rates improve. Although it is well established that these survivors experience various complications and comorbidities related to their malignancy and treatment, this risk is modified by many factors that are not directly linked to their cancer history. Research evaluating the influence of patient-specific demographic and genetic factors, premorbid and comorbid conditions, health behaviors, and aging has identified additional risk factors that influence cancer treatment-related toxicity and possible targets for intervention in this population. Furthermore, although current long-term follow-up guidelines comprehensively address specific therapyrelated risks and provide screening recommendations, the risk profile of the population continues to evolve with ongoing modification of treatment strategies and the emergence of novel therapeutics. To address the multifactorial modifiers of cancer treatment-related health risk and evolving treatment approaches, a patient-centered and risk-adapted approach to care that often requires a multidisciplinary team approach, including medical and behavioral providers, is necessary for this population. CA Cancer J Clin 2018;68:133-152.