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Recklitis, Christopher J., Lisa R. Diller, Xiaochun Li, Julie Najita, Leslie L. Robison, and Lonnie Zeltzer. "Suicide Ideation in Adult Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study." Journal of Clinical Oncology 28, no. 4 (February 1, 2010): 655–61. http://dx.doi.org/10.1200/jco.2009.22.8635.
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Purpose To evaluate risk of suicide ideation (SI) after childhood cancer, prevalence of SI in a cohort of adult survivors of pediatric cancers was compared with prevalence in a sibling comparison group. The relationship of SI to cancer treatment and current health was examined, and the hypothesis that poor physical health is significantly associated with suicidality, after adjusting for depression, was specifically tested. Methods Nine thousand one hundred twenty-six adult survivors of childhood cancer and 2,968 siblings enrolled onto the Childhood Cancer Survivor Study completed a survey describing their demographics and medical and psychological functioning, including SI in the prior week. Results Of survivors, 7.8% reported SI compared with 4.6% of controls (odds ratio = 1.79; 95% CI, 1.4 to 2.4). Suicidality was unrelated to age, age at diagnosis, sex, cancer therapy, recurrence, time since diagnosis, or second malignancy. SI was associated with primary CNS cancer diagnosis, depression, and poor health outcomes including chronic conditions, pain, and poor global health rating. A logistic regression analysis showed that poor current physical health was significantly associated with SI even after adjusting for cancer diagnosis and depression. Conclusion Adult survivors of childhood cancers are at increased risk for SI. Risk of SI is related to cancer diagnosis and post-treatment mental and physical health, even many years after completion of therapy. The association of suicidal symptoms with physical health problems is important because these may be treatable conditions for which survivors seek follow-up care and underscores the need for a multidisciplinary approach to survivor care.
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Yu, Chu-Ling, Emily S. Tonorezos, Chiung-Yu Huang, Brian C.-H. Chiu, Chun-Ju Chiang, Hui-Ju Ch'ang, Yen-Lin Liu, James S. Miser, Hung-Yi Chiou, and Yun Yen. "Second malignant neoplasms in a nationwide population-based cohort of childhood cancer survivors in Taiwan." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 10569. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.10569.
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10569 Background: Childhood cancer survivors have excess risk of second malignant neoplasms, but data are limited in Asian populations. We established a nationwide retrospective cohort of childhood cancer survivors in Taiwan to study the risk of second malignant neoplasms in the population. Methods: Children and adolescents diagnosed with cancer before age 21 years between 1990 and 2011 were identified from the Taiwan Cancer Registry, the national cancer registry in Taiwan. One-year survivors of childhood cancer were ascertained through data linkage with the national death registry. Survivors were followed up through December 2012. Standardized incidence ratios (SIRs), absolute excess risks (AERs), and cumulative incidence of second malignant neoplasms were calculated. Results: A total of 186 second malignant neoplasms occurred among 15,263 1-year survivors of childhood cancer after a mean follow-up time of 8.0 years (SIR = 5.4, 95% confidence interval [CI] = 4.6-6.2; AER = 12.4 per 10,000 person-years). The most common types of second malignant neoplasms were gastrointestinal cancers (n = 37), leukemia (n = 28), endocrine cancers (n = 18), and brain cancer (n = 17). Cancers in the liver (n = 11, including 9 hepatocellular carcinoma) and colorectum (n = 16) accounted for 73% of second gastrointestinal malignant neoplasms in this population. The cumulative incidence of second malignant neoplasms at 10 and 20 years from follow-up was 1.0% (95% CI = 0.8-1.2%) and 3.0% (95% CI = 2.3-3.6%), respectively. Conclusions: Childhood cancer survivors in Taiwan experience excess risk of second malignant neoplasms, in particular gastrointestinal cancers, compared with the general population.
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Moskowitz, Chaya S., Joanne F. Chou, Joseph P. Neglia, Ann H. Partridge, Rebecca M. Howell, Lisa R. Diller, Danielle Novetsky Friedman, et al. "Mortality After Breast Cancer Among Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study." Journal of Clinical Oncology 37, no. 24 (August 20, 2019): 2120–30. http://dx.doi.org/10.1200/jco.18.02219.
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PURPOSE Female survivors of childhood cancer have a high risk of subsequent breast cancer. We describe the ensuing risk for mortality and additional breast cancers. PATIENTS AND METHODS Female participants in the Childhood Cancer Survivor Study, a cohort of 5-year survivors of cancer diagnosed between 1970 and 1986 before age 21 years, and subsequently diagnosed with breast cancer (n = 274; median age at breast cancer diagnosis, 38 years; range, 20 to 58 years) were matched to a control group (n = 1,095) with de novo breast cancer. Hazard ratios (HRs) and 95% CIs were estimated from cause-specific proportional hazards models. RESULTS Ninety-two childhood cancer survivors died, 49 as a result of breast cancer. Overall survival after breast cancer was 73% by 10 years. Subsequent risk of death as a result of any cause was higher among childhood cancer survivors than among controls (HR, 2.2; 95% CI, 1.7 to 3.0) and remained elevated after adjusting for breast cancer treatment (HR, 2.4; 95% CI, 1.7 to 3.2). Although breast cancer–specific mortality was modestly elevated among childhood cancer survivors (HR, 1.3; 95% CI, 0.9 to 2.0), survivors were five times more likely to die as a result of other health-related causes, including other subsequent malignant neoplasms and cardiovascular or pulmonary disease (HR, 5.5; 95% CI, 3.4 to 9.0). The cumulative incidence of a second asynchronous breast cancer also was elevated significantly compared with controls ( P < .001). CONCLUSION Mortality after breast cancer was higher in childhood cancer survivors than in women with de novo breast cancer. This increased mortality reflects the burden of comorbidity and highlights the need for risk-reducing interventions.
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Bhatia, Smita, and Charles Sklar. "Second cancers in survivors of childhood cancer." Nature Reviews Cancer 2, no. 2 (February 2002): 124–32. http://dx.doi.org/10.1038/nrc722.
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Smith, Helin, and Bob Phillips. "Childhood Cancer." InnovAiT: Education and inspiration for general practice 5, no. 10 (September 14, 2012): 595–603. http://dx.doi.org/10.1093/innovait/ins133.
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Childhood cancers are uncommon, accounting for only 0.5% of all cancers in the UK. Approximately, 1500 children are diagnosed with cancer in the UK every year. Despite it being a rare occurrence, cancer still remains the largest cause of death in the 1–14 year age group, amongst whom it counts for 20% of all deaths. Although most adult cancers affect the lung, breast, bowel and prostate, the majority of childhood cancers are haematological and central nervous system (CNS) tumours. The primary care physician's role is vital across the disease trajectory, requiring them to recognize the signs and symptoms of childhood cancer, understand treatment, provide support to children and families, and finally consider the issues affecting survivors of childhood cancer.
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Ford, Jennifer S., Toana Kawashima, John Whitton, Wendy Leisenring, Caroline Laverdière, Marilyn Stovall, Lonnie Zeltzer, Leslie L. Robison, and Charles A. Sklar. "Psychosexual Functioning Among Adult Female Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study." Journal of Clinical Oncology 32, no. 28 (October 1, 2014): 3126–36. http://dx.doi.org/10.1200/jco.2013.54.1086.
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Purpose Childhood cancer survivors may be at risk for impaired psychosexual functioning as a direct result of their cancer or its treatments, psychosocial difficulties, and/or diminished quality of life. Patients and Methods Two thousand one hundred seventy-eight female adult survivors of childhood cancer and 408 female siblings from the Childhood Cancer Survivor Study (CCSS) completed a self-report questionnaire about their psychosexual functioning and quality of life. On average, participants were age 29 years (range, 18 to 51 years) at the time of the survey, had been diagnosed with cancer at a median age of 8.5 years (range, 0 to 20) and were most commonly diagnosed with leukemia (33.2%) and Hodgkin lymphoma (15.4%). Results Multivariable analyses suggested that after controlling for sociodemographic differences, survivors reported significantly lower sexual functioning (mean difference [MnD], −0.2; P = .01), lower sexual interest (MnD, −0.2; P < .01), lower sexual desire (MnD, −0.3; P < .01), lower sexual arousal (MnD, −0.3; P < .01), lower sexual satisfaction (MnD, −0.2; P = .01), and lower sexual activity (MnD, −0.1; P = .02) compared with siblings. Risk factors for poorer psychosexual functioning among survivors included older age at assessment, ovarian failure at a younger age, treatment with cranial radiation, and cancer diagnosis during adolescence. Conclusion Decreased sexual functioning among female survivors of childhood cancers seems to be unrelated to emotional factors and is likely to be an underaddressed issue. Several risk factors among survivors have been identified that assist in defining high-risk subgroups who may benefit from targeted screening and interventions.
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Nathan, P. C., K. K. Ness, M. M. Hudson, M. Mahoney, J. S. Ford, W. Landier, G. Armstrong, T. Henderson, L. L. Robison, and K. C. Oeffinger. "Cancer screening in adult survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS)." Journal of Clinical Oncology 27, no. 18_suppl (June 20, 2009): CRA6501. http://dx.doi.org/10.1200/jco.2009.27.18_suppl.cra6501.
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CRA6501 Background: Childhood cancer survivors may develop a second malignant neoplasm (SMN) and require surveillance to detect new cancers. Methods: We surveyed survivors and siblings from the CCSS, a cohort study of patients who have survived ≥5 years after a diagnosis of childhood cancer from 1970–86. We assessed compliance with the American Cancer Society's (ACS) guidelines for surveillance mammography, colonoscopy and PAP smears, and compared them to a matched population comparison group drawn from the 2003 National Health Interview Survey. Further, we examined compliance with the Children's Oncology Group (COG) guidelines for more frequent colonoscopy, mammography and skin exams in survivors at high risk for cancers of the colon (≥30 Gy pelvic, abdominal or spinal radiation), breast (≥ 20 Gy breast radiation in females) or skin (any radiation). Proportions screened were compared between groups with adjusted generalized estimating equations or log-binomial regression models. Results: There were 8318 survivors (50.6% male, mean age at interview 31.2 ± 7.3 years), 2661 siblings and 8318 population controls. 141/829 (17.6%), 592/855 (70.4%) and 3362/3690 (92.6%) eligible survivors reported a colonoscopy, mammogram, or PAP smear per ACS guidelines. Survivors were less likely than siblings (odds ratio [OR] 0.30; 95% confidence interval [CI] 0.18–0.49) and population controls (OR 0.63; CI 0.50–0.80) to have a colonoscopy, and less likely than siblings to have a PAP smear (risk ratio [RR] 0.98; CI 0.97–0.99). However, they were more likely than siblings (RR 1.14; CI 1.03–1.27) and population controls (RR 1.05; CI 1.01–1.10) to have a mammogram. Among survivors at increased risk for a SMN, only 92/809 (11.4%) reported a colonoscopy within the COG recommended 5-year period, 164/537 (30.5%) reported a mammogram within a 1-year period and 1288/4833 (26.7%) reported a skin exam. Care at a cancer center was associated with mammography (RR 1.91; 95% CI 1.02–1.27) and skin exam (RR 1.55; 95% CI 1.22–196) in high-risk patients. Conclusions: Childhood cancer survivors are not screened adequately for SMNs. Surveillance is very poor amongst those at highest risk for colon, breast, or skin cancer. Survivors and their physicians need education about the importance of surveillance. No significant financial relationships to disclose.
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Aung, LeLe, Yiong Huak Chan, Eng Juh Yeoh, Poh Lin Poh Lin, and Thuan Chong Quah. "A Report from the Singapore Childhood Cancer Survivor Study (SG-CCSS): A Multi-institutional Collaborative Study on Long-term Survivors of Childhood Cancer, Initial Analysis Reporting for the SG-CCSS." Annals of the Academy of Medicine, Singapore 38, no. 8 (August 15, 2009): 684–89. http://dx.doi.org/10.47102/annals-acadmedsg.v38n8p684.
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Introduction: Worldwide, the survival rates among childhood cancer patients are increasing. As such, assessing the risk of late effects and complications are increasingly becoming more important. The degree of risk of late effects may be influenced by various treatment-related factors. Materials and Methods: The Singapore Childhood Cancer Survivor Study (SG- CCSS) consists of all individuals who survived at least 2 or more years after treatment for cancer diagnosed during childhood or adolescence. Phase I of SG-CCSS is the identification of all eligible patients between 1981 and 2005. Results: There were a total of 1440 patients registered in the Singapore Childhood Cancer Registry. Among these, 704 (48.9%) patients were from the KK Women’s and Children’s Hospital (KKH) and 626 (43.5%) were from the National University Hospital (NUH). Of all the registered patients, the most common cancer in childhood was leukaemia [42.6% (n = 613)] and the second most common was brain tumour [14.9% (n = 215)]. A total of 1043 (72.4%) patients were surviving, of whom 839 (80.4%) were long-term survivors. Haematological malignancies were found in 492 (58.6%) survivors whilst 347 (41.4%) were diagnosed with various solid tumours. Among leukaemic patients (n = 613), 65.6% (n = 402) were long-term survivors. Acute lymphoblastic leukaemia (ALL) (n = 484) had the highest percentage of [80.9% (n = 392)] of surviving patients, of whom 73.4% were long term-survivors. For brain tumour (n = 215), there were 95 (44.2%) long-term survivors. Conclusion: Preliminary analysis revealed that 58.3% of patients were long-term survivors. Our hope is to tailor all future therapy for childhood cancers, optimising cure rates whilst minimising long-term side-effects. Key words: Late effects
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Hudson, Melissa M., Daniel A. Mulrooney, Daniel C. Bowers, Charles A. Sklar, Daniel M. Green, Sarah S. Donaldson, Kevin C. Oeffinger, Joseph P. Neglia, Anna T. Meadows, and Leslie L. Robison. "High-Risk Populations Identified in Childhood Cancer Survivor Study Investigations: Implications for Risk-Based Surveillance." Journal of Clinical Oncology 27, no. 14 (May 10, 2009): 2405–14. http://dx.doi.org/10.1200/jco.2008.21.1516.
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Childhood cancer survivors often experience complications related to cancer and its treatment that may adversely affect quality of life and increase the risk of premature death. The purpose of this manuscript is to review how data derived from Childhood Cancer Survivor Study (CCSS) investigations have facilitated identification of childhood cancer survivor populations at high risk for specific organ toxicity and secondary carcinogenesis and how this has informed clinical screening practices. Articles previously published that used the resource of the CCSS to identify risk factors for specific organ toxicity and subsequent cancers were reviewed and results summarized. CCSS investigations have characterized specific groups to be at highest risk of morbidity related to endocrine and reproductive dysfunction, pulmonary toxicity, cerebrovascular injury, neurologic and neurosensory sequelae, and subsequent neoplasms. Factors influencing risk for specific outcomes related to the individual survivor (eg, sex, race/ethnicity, age at diagnosis, attained age), sociodemographic status (eg, education, household income, health insurance) and cancer history (eg, diagnosis, treatment, time from diagnosis) have been consistently identified. These CCSS investigations that clarify risk for treatment complications related to specific treatment modalities, cumulative dose exposures, and sociodemographic factors identify profiles of survivors at high risk for cancer-related morbidity who deserve heightened surveillance to optimize outcomes after treatment for childhood cancer.
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Chemaitilly, Wassim, Ann C. Mertens, Pauline Mitby, John Whitton, Marilyn Stovall, Yutaka Yasui, Leslie L. Robison, and Charles A. Sklar. "Acute Ovarian Failure in the Childhood Cancer Survivor Study." Journal of Clinical Endocrinology & Metabolism 91, no. 5 (May 1, 2006): 1723–28. http://dx.doi.org/10.1210/jc.2006-0020.
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Context: Defined as the loss of ovarian function within 5 yr of diagnosis, acute ovarian failure (AOF) is known to develop in a subset of survivors of pediatric and adolescent cancers. Its precise incidence is unknown, and data concerning its risk factors are limited. Objective: Our objective was to determine the incidence of and patient/treatment factors associated with AOF in a large cohort of pediatric cancer survivors. Design and Setting: We conducted a retrospective cohort, multicenter study. Patients: Female participants from the Childhood Cancer Survivor Study who were greater than 18 yr of age were considered for inclusion. We excluded survivors who received cranial irradiation at doses of more than 3000 cGy, those with hypothalamic/pituitary tumors, and survivors who underwent bilateral oophorectomy. Survivors who reported never menstruating or who had ceased having menses within 5 yr after their cancer diagnosis were considered to have AOF. Main Outcome: We assessed incidence and risk factors for AOF. Results: Of a total of 3390 eligible survivors, 215 cases (6.3%) developed AOF. Survivors with AOF were older at diagnosis and more likely to have been diagnosed with Hodgkin’s lymphoma or to have received abdominal or pelvic radiotherapy than survivors without AOF. Among survivors with AOF, 116 (54%) had received at least 1000-cGy ovarian irradiation. In a multivariable logistic regression model, increasing doses of ovarian irradiation, exposure to procarbazine, and exposure to cyclophosphamide at ages 13–20 yr were independent risk factors for AOF. Conclusions: AOF develops in a small subset of survivors, especially those treated with at least 1000-cGy ovarian radiation. These results will facilitate patient counseling and selection of candidates for newer fertility preservation techniques.
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Morton, Lindsay M., Kenan Onel, Rochelle E. Curtis, Eric A. Hungate, and Gregory T. Armstrong. "The Rising Incidence of Second Cancers: Patterns of Occurrence and Identification of Risk Factors for Children and Adults." American Society of Clinical Oncology Educational Book, no. 34 (May 2014): e57-e67. http://dx.doi.org/10.14694/edbook_am.2014.34.e57.
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As the population of cancer survivors has increased and continues to age, the occurrence of second cancers has risen dramatically—from 9% of all cancer diagnoses in 1975–1979 to 19% in 2005–2009. The Childhood Cancer Survivor Study, a cohort of more than 14,000 childhood cancer survivors with detailed exposure data and long-term follow-up, has substantially contributed to our understanding of the roles of radiotherapy and chemotherapy in second cancer occurrence. In particular, dose-related risks have been demonstrated for second cancers of the breast, thyroid, central nervous system, gastrointestinal tract, and sarcomas following radiation. Cytotoxic chemotherapy—which has long been known to be leukemogenic—also appears to contribute to risk for a range of other second cancer types. Individuals who develop a second cancer are at particularly high risk for developing additional second cancers. A genome-wide association study of survivors of Hodgkin lymphoma who received radiotherapy identified a locus on chromosome 6q21 as being associated with second cancer risk, demonstrating that recent advances in genomics are likely to prove invaluable for elucidating the contribution of genetic susceptibility to second cancer etiology. Among adults, risk of second cancers varies substantially by type of first and second cancer, patient age, and prevalence of second cancer risk factors, including primary cancer treatments, environmental and lifestyle exposures, and genetic susceptibility. Further research is needed to quantify second cancer risks associated with specific etiologic factors and to identify the patients at highest risk of developing a second cancer to target prevention and screening efforts.
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Oeffinger, Kevin C., and Smita Bhatia. "Second primary cancers in survivors of childhood cancer." Lancet 374, no. 9700 (October 2009): 1484–85. http://dx.doi.org/10.1016/s0140-6736(09)61885-7.
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Wasilewski-Masker, K., W. Leisenring, L. R. Meacham, S. Hammond, A. T. Meadows, L. L. Robison, and A. C. Mertens. "Late recurrence in survivors of childhood and adolescent cancer: A report from the Childhood Cancer Survivor Study (CCSS)." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 9534. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.9534.
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9534 Background: An increasing percentage of childhood cancer patients are surviving their disease, but limited research suggests that late recurrences may impact overall survival. The goal of this study is to estimate late recurrence rates for the most common pediatric cancers and to determine additional risk factors for late recurrence. Methods: CCSS is a retrospective cohort study of five-year survivors of childhood cancer diagnosed before 21 years of age, between 1970 and 1986 at one of 26 consortium centers. Late recurrence was defined as first recurrence occurring > five years post-diagnosis. Recurrences were determined by self-report questionnaire or by confirmation through medical record, death certificate or pathologic review. Probability of late recurrence was calculated using cumulative incidence. Adjusted hazard ratios (HR) were obtained using Cox proportional hazards regression. Results: In 12,948 survivors with no recurrence = five years from diagnosis, 670 (5.2%) subjects had a first recurrence > five years after their primary diagnosis. Late recurrences ranged from 5 to 28.9 years from diagnosis (median 7.9 years). Cumulative incidence varied by diagnosis ( table ). In multivariate analysis, significant risk factors for increased late recurrence included a primary diagnosis of Ewing's sarcoma or CNS tumors (HR of 2.3 and 2.7 respectively vs. leukemia survivors), age = 10 years at diagnosis (HR 1.4 vs. age < 10 years), chemotherapy exposure (HR 1.5 vs. none), and radiation exposure (HR 1.4 vs. none) (p < 0.001 for all). At the time of last follow-up, 51.6% of subjects with a late recurrence had died versus 6.4% of those with no history of recurrence. Conclusions: Late recurrences occur in survivors of childhood cancers with a significant risk of mortality. This emphasizes the importance of long-term survivor follow-up into adulthood, particularly for adolescents and patients with Ewing's sarcoma and CNS tumors. [Table: see text] No significant financial relationships to disclose.
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Quillen, Joanne, Yimei Li, Michele Demski, Claire Carlson, Holli Bradley, Lisa Schwartz, Jill P. Ginsberg, and Wendy Hobbie. "Comparing the Knowledge of Parents and Survivors Who Attend a Survivorship Clinic." Journal of Pediatric Oncology Nursing 35, no. 1 (November 2, 2017): 56–64. http://dx.doi.org/10.1177/1043454217735828.
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Background: This study underscores the importance of the survivor/parent dynamic in understanding the knowledge level of childhood cancer survivors and their parents with regard to cancer diagnosis, treatments, and potential late effects, and to assess the impact of parental knowledge on survivor’s knowledge. Procedure: A convenience sample (N = 219 dyads) consisting of childhood cancer survivors with a parent match was used. Survivors 2 years out from completion of therapy, aged 16 to 25 years, and fluent in English or Spanish completed 2 questionnaires to assess adolescent and young adult and parental knowledge regarding diagnosis, treatment, and long-term risks. Results: Data from the survivor/parent dyad confirm that parents are more knowledgeable than their child regarding treatment specifics. However, survivors are more accurate when assessing second tumor and fertility risk. More knowledgeable parents led to more knowledgeable survivors. Conclusions: Although parents were well-informed about treatment specifics, they were not as accurate in identifying risks appropriately. Therefore, education must be directed at both parent and survivors to maximize knowledge.
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Smitherman, Andrew Brian, Danielle Mohabir, Tania Wilkins, Julie Blatt, Hazel Nichols, and Stacie Dusetzina. "Early post-therapy prescription drug usage among survivors of childhood cancers." Journal of Clinical Oncology 35, no. 5_suppl (February 10, 2017): 147. http://dx.doi.org/10.1200/jco.2017.35.5_suppl.147.
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147 Background: Childhood cancer survivors often develop treatment-associated morbidities. We hypothesized that emerging treatment-related medical morbidities would be reflected in patterns of prescription drug usage among survivors in the first three years after therapy completion. Methods: Using the Truven Health MarketScan Commercial Claims database, we identified survivors of childhood (0-21 years-old at diagnosis) leukemia, lymphoma, central nervous system (CNS), bone, or gonadal tumors who completed therapy during 2000 - 2011. Patients were identified using diagnosis codes and cancer-specific procedure codes for chemotherapy, surgery, or radiation therapy. Prescription fills during the first three years following therapy completion were examined and categorized by drug class. Median numbers of prescriptions per survivor were compared to age- and sex-matched children without cancer. Relative risks (RR) for any prescription and for prescriptions by drug class were calculated comparing survivors to children without cancer. Results: We identified 1,414 survivors and 14,140 children without cancer. The median number of unique drug class prescriptions among survivors ranged from 4 [gonadal] to 8 [CNS] in year 1 and from 2 [gonadal] to 6 [CNS] in year 3 compared to a median of 1 among children without cancer (p < 0.001 for all comparisons). Increased risks for fills of antibiotics (RR in year 1: 1.5 [CNS, gonadal], 1.7 [bone], and 1.8 [leukemia, lymphoma]) and opioids (RR in year 1: 2.4 [lymphoma], 2.7 [gonadal], 4.0 [CNS], and 4.8 [leukemia, bone]) persisted throughout the three years among all cancer groups. Survivors of leukemia, lymphoma, CNS, and bone tumors had 2-4 times the risk for antidepressant prescriptions and 4-10 times the risk for anxiolytics. Survivors of leukemia, lymphoma, and bone tumors had 8-10 times the risk for ACE inhibitor prescriptions by the third year off therapy. Conclusions: Compared to children without cancer, childhood cancer survivors have higher rates of prescription drug use across many drug classes indicative of their higher burden of medical morbidities. Careful attention should be given to emerging morbidities during the early off-therapy period.
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Chemaitilly, Wassim, and Charles A. Sklar. "Endocrine complications in long-term survivors of childhood cancers." Endocrine-Related Cancer 17, no. 3 (September 2010): R141—R159. http://dx.doi.org/10.1677/erc-10-0002.
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Endocrine disturbances are among the most frequently reported complications in childhood cancer survivors, affecting between 20 and 50% of individuals who survive into adulthood. Most endocrine complications are the result of prior cancer treatments, especially radiotherapy. The objective of the present review is to discuss the main endocrine complications observed in this population, including disorders of the hypothalamic–pituitary axis, disorders of pubertal development, thyroid dysfunction, gonadal dysfunction, decreased bone mineral density, obesity, and alterations in glucose metabolism with a special focus on recent findings reported from the Childhood Cancer Survivor Study.
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Gurney, James G., Kevin R. Krull, Nina Kadan-Lottick, H. Stacy Nicholson, Paul C. Nathan, Brad Zebrack, Jean M. Tersak, and Kirsten K. Ness. "Social Outcomes in the Childhood Cancer Survivor Study Cohort." Journal of Clinical Oncology 27, no. 14 (May 10, 2009): 2390–95. http://dx.doi.org/10.1200/jco.2008.21.1458.
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Difficulties with negotiating and achieving desired social outcomes in life may be exacerbated by the experience of childhood cancer, including adverse effects from therapies used to achieve a cure. This review of previous publications from the Childhood Cancer Survivor Study (CCSS) and other relevant literature provides insight into the prevalence of, and risk factors for, poor educational attainment, less than optimal employment status, and interpersonal relationship issues among long-term survivors of childhood cancer. The impacts of emotional health and physical disability on social outcomes are also examined. Study results suggest that childhood cancer survivors generally have similar high school graduation rates, but are more likely to require special education services than sibling comparison groups. Survivors are slightly less likely than expected to attend college, and are more likely to be unemployed and not married as young adults. Cancers and treatments that result in impairment to the CNS, particularly brain tumors, or that impact sensory functioning, such as hearing loss, are associated with greater risk for undesirable social outcomes, as are emotional health problems and physical disability. This review of relevant data from CCSS and other studies provides information on risk factors for social problems into adulthood. A greater understanding of the long-term social impacts from the diagnosis and treatment of childhood cancer is critically important for developing targeted interventions to prevent or ameliorate adverse psychosocial effects.
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Janitz, Amanda, Weiyu Qiu, Jeremy M. Schraw, Sogol Mostoufi-Moab, Lisa Mirabello, Douglas R. Stewart, Kevin C. Oeffinger, et al. "Congenital anomalies and health outcomes among survivors of childhood cancer: A report from the childhood cancer survivor study." Journal of Clinical Oncology 41, no. 16_suppl (June 1, 2023): e22021-e22021. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.e22021.
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e22021 Background: Although congenital anomalies are established risk factors for developing childhood cancer, less is known about health outcomes among survivors of childhood cancer with known congenital anomalies. Therefore, we estimated the risk of chronic health conditions (CHCs) and subsequent malignant neoplasms (SMNs) among survivors of childhood cancer by congenital anomaly status in the Childhood Cancer Survivor Study (CCSS). Methods: Overall, 22,247 five-year survivors self-reported congenital anomalies. We included 16 conditions present at birth, excluding self-reported genetic conditions. Patient-reported CHCs were graded using the Common Terminology Criteria for Adverse Events (CTCAE v. 4.03). Self-reported SMNs were confirmed through pathology report review. Hazard ratios (HR) of CHCs comparing survivors with vs. without congenital anomalies and their 95% confidence intervals (CI) were estimated using Cox regression with age as the time scale, adjusted for race/ethnicity, education, household income, health insurance, and original cancer treatment. Results: Among survivors (median age at cancer diagnosis 6 years (range 3-12), age at follow-up 31 years (range 25-39)), 16.9% (n = 3880) reported a congenital anomaly. The most common anomalies included: large/multiple birth marks (n = 1540, 40.4%); congenital heart defects (n = 693, 18.4%); and kidney, bladder, or genital abnormalities (n = 607, 14.6%). Relative to survivors without anomalies, those with anomalies more commonly had astrocytoma, Wilms tumor, and neuroblastoma primary cancers (p < 0.001), treated with radiation (p = 0.011), cyclophosphamide (p < 0.001), anthracyclines (p < 0.001), and epipodophyllotoxins (p = 0.044), and younger age at cancer diagnosis (11.3% vs. 5.7% diagnosed prior to one year of age, p < 0.001). Survivors with anomalies were more likely to develop any CHC (CTCAE grades 1-5 HR: 1.31, 95% CI: 1.23, 1.39); severe, disabling, life-threatening or fatal CHCs (grades 3-5 HR: 1.42 (95% CI: 1.28, 1.58); and multiple CHCs (≥2 conditions HR: 1.36, 95% CI: 1.27, 1.46; ≥3 conditions HR: 1.49, 95% CI: 1.37, 1.63). Survivors with anomalies had increased risk for adverse outcomes across multiple systems (all p < 0.001), including: hearing/vision/speech (HR: 1.37); urinary (HR: 1.42); hormonal/endocrine (HR: 1.24); heart/circulatory (HR: 1.35); digestive (HR: 1.49); and brain systems (HR: 1.42). We observed no differences in the risk of any SMN by congenital anomaly status (HR: 1.12, 95% CI: 0.90, 1.38). Conclusions: In our assessment, survivors of childhood cancer with self-reported congenital anomalies had an increased risk of developing CHCs compared to survivors without reported anomalies, but no increased risk of SMNs. Evaluating congenital anomalies allows identification of a population of childhood cancer survivors at high risk for poor long-term health outcomes.
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Bassal, Mylène, Ann C. Mertens, Leslie Taylor, Joseph P. Neglia, Brian S. Greffe, Sue Hammond, Cécile M. Ronckers, et al. "Risk of Selected Subsequent Carcinomas in Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study." Journal of Clinical Oncology 24, no. 3 (January 20, 2006): 476–83. http://dx.doi.org/10.1200/jco.2005.02.7235.
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Purpose To determine the risk of subsequent carcinomas other than breast, thyroid, and skin, and to identify factors that influence the risk among survivors of childhood cancer. Patients and Methods Subsequent malignant neoplasm history was determined in 13,136 participants (surviving ≥ 5 years postmalignancy, diagnosed from 1970 to 1986 at age < 21 years) of the Childhood Cancer Survivor Study to calculate standardized incidence ratios (SIRs), using Surveillance, Epidemiology, and End Results data. Results In 71 individuals, 71 carcinomas were diagnosed at a median age of 27 years and a median elapsed time of 15 years in the genitourinary system (35%), head and neck area (32%), gastrointestinal tract (23%), and other sites (10%). Fifty-nine patients (83%) had received radiotherapy, and 42 (59%) developed a second malignant neoplasm in a previous radiotherapy field. Risk was significantly elevated following all childhood diagnoses except CNS neoplasms, and was highest following neuroblastoma (SIR = 24.2) and soft tissue sarcoma (SIR = 6.2). Survivors of neuroblastoma had a 329-fold increased risk of renal cell carcinomas; survivors of Hodgkin's lymphoma had a 4.5-fold increased risk of gastrointestinal carcinomas. Significantly elevated risk of head and neck carcinoma occurred in survivors of soft tissue sarcoma (SIR = 22.6), neuroblastoma (SIR = 20.9), and leukemia (SIR = 20.9). Conclusion Young survivors of childhood cancers are at increased risk of developing subsequent carcinomas typical of later adulthood, underscoring the importance of long-term follow-up and risk-based screening. Follow-up of the cohort is ongoing to determine lifetime risk and delineate individual characteristics that contribute to risk.
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Kurkure, Purna Arun, Saroj Prasad Panda, Maya Prasad, and Savita Goswami. "Adolescent and young adult (AYA) survivors of childhood cancers: A challenge in after completion of therapy (ACT) clinic in resource-constrained country." Journal of Clinical Oncology 34, no. 3_suppl (January 20, 2016): 19. http://dx.doi.org/10.1200/jco.2016.34.3_suppl.19.
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19 Background: To assess the evaluation of late effects in childhood cancer survivors who have transitioned to AYA age group on longitudinal follow up in After Completion of Therapy (ACT) clinic at Tata Memorial Hospital, Mumbai. Methods: ACT clinic database was analyzed for childhood cancer survivors who have attained age 15-30 yrs at last follow up in the clinic for demographics, grade of late effects &pattern of follow up. Results: Of 1720 childhood cancer Survivors ( > , 2 yrs off therapy & disease free) registered in ACT clinic from Feb 91-Feb15, 976(56.7%) are in AYA group, M.F = 707/269 (2.6:1), Hematolymphoid : Solid tumours = 543/433 (1.3:1), Mumbai based: Non Mumbai = 306/670 (1:2.2).Median age at diagnosis 8 yrs, current median age 20 yrs, median duration of ACT clinic follow up is 6 yrs. At registration 448 (47%) had no late effects. 230(24%) had grade I, 81(8.4%) grade II 195 (20%) had grade III. Only 9(1%) had grade IV late effects which increased to 53 (6%) at last follow up due to recurrence & second neoplasia. Only 29(3%) were at low risk of developing potential late effects. 466(48.5%) were in intermediate risk & 48.5% (466) fell in high risk category requiring at least annual follow up. 72% of survivors registered in ACT clinic from 1991-2001 had stopped follow up as compared to 36% registered in subsequent decade (p < 0.01). Conclusions: AYA survivors of childhood cancers form major (56.7%) group in Long Term Follow up clinic. The increasing incidence of life threatening late effects on longitudinal follow up combined with statistically significant increasing trend of stopping follow up over period of time since ACT registration is alarming & calls for innovative approaches for maintaining good follow up through survivor centric approaches such as use of IT based communication technologies & formation of childhood cancer survivors support groups like Ugam.
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Teepen, Jop C., Flora E. van Leeuwen, Wim J. Tissing, Eline van Dulmen-den Broeder, Marry M. van den Heuvel-Eibrink, Helena J. van der Pal, Jacqueline J. Loonen, et al. "Long-Term Risk of Subsequent Malignant Neoplasms After Treatment of Childhood Cancer in the DCOG LATER Study Cohort: Role of Chemotherapy." Journal of Clinical Oncology 35, no. 20 (July 10, 2017): 2288–98. http://dx.doi.org/10.1200/jco.2016.71.6902.
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Purpose Childhood cancer survivors (CCSs) are at increased risk for subsequent malignant neoplasms (SMNs). We evaluated the long-term risk of SMNs in a well-characterized cohort of 5-year CCSs, with a particular focus on individual chemotherapeutic agents and solid cancer risk. Methods The Dutch Childhood Cancer Oncology Group–Long-Term Effects After Childhood Cancer cohort includes 6,165 5-year CCSs diagnosed between 1963 and 2001 in the Netherlands. SMNs were identified by linkages with the Netherlands Cancer Registry, the Dutch Pathology Registry, and medical chart review. We calculated standardized incidence ratios, excess absolute risks, and cumulative incidences. Multivariable Cox proportional hazard regression analyses were used to evaluate treatment-associated risks for breast cancer, sarcoma, and all solid cancers. Results After a median follow-up of 20.7 years (range, 5.0 to 49.8 years) since first diagnosis, 291 SMNs were ascertained in 261 CCSs (standardized incidence ratio, 5.2; 95% CI, 4.6 to 5.8; excess absolute risk, 20.3/10,000 person-years). Cumulative SMN incidence at 25 years after first diagnosis was 3.9% (95% CI, 3.4% to 4.6%) and did not change noticeably among CCSs treated in the 1990s compared with those treated earlier. We found dose-dependent doxorubicin-related increased risks of all solid cancers ( Ptrend < .001) and breast cancer ( Ptrend < .001). The doxorubicin-breast cancer dose response was stronger in survivors of Li-Fraumeni syndrome–associated childhood cancers (leukemia, CNS, and non-Ewing sarcoma) versus survivors of other cancers ( Pdifference = .008). In addition, cyclophosphamide was found to increase sarcoma risk in a dose-dependent manner ( Ptrend = .01). Conclusion The results strongly suggest that doxorubicin exposure in CCSs increases the risk of subsequent solid cancers and breast cancer, whereas cyclophosphamide exposure increases the risk of subsequent sarcomas. These results may inform future childhood cancer treatment protocols and SMN surveillance guidelines for CCSs.
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Nathan, Paul C., Tara O. Henderson, Anne C. Kirchhoff, Elyse R. Park, and K. Robin Yabroff. "Financial Hardship and the Economic Effect of Childhood Cancer Survivorship." Journal of Clinical Oncology 36, no. 21 (July 20, 2018): 2198–205. http://dx.doi.org/10.1200/jco.2017.76.4431.
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In addition to the long-term physical and psychological sequelae of cancer therapy, adult survivors of childhood cancer are at an elevated risk for financial hardship. Financial hardship can have material, psychological, and behavioral effects, including high out-of-pocket medical costs, asset depletion and debt, limitations in or inability to work, job lock, elevated stress and worry, and a delaying or forgoing of medical care because of cost. Most financial hardship research has been conducted in survivors of adult cancers. The few studies focused on childhood cancer survivors have shown that these individuals are at elevated risk for having difficulties with affording needed health care and report high out-of-pocket medical expenses, difficulty with paying medical bills, or consideration of filing for bankruptcy. Childhood cancer survivors are more likely to be unable to work or to have missed work because of poor health. They are more likely to report difficulties with obtaining insurance coverage and rely more frequently on government-sponsored insurance. Globally, countries able to provide curative cancer therapies have witnessed a growing population of survivors, which places a burden on their health care systems because survivors are more likely to require hospitalization and experience a higher burden of chronic illness than the general population. Guidelines for surveillance for late effects are intended to reduce the burden of morbidity, but research is needed to determine whether such surveillance is cost effective. Of note, risk-based survivor care should include routine surveillance for financial hardship. Improved measures of financial hardship, enhanced data infrastructure, and research studies to identify survivors and families most vulnerable to financial hardship and adverse health outcomes will inform the development of targeted programs to serve as a safety net for those at greatest risk.
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Gupta, Sumit, Rinku Sutradhar, Sarah Alexander, Michelle Science, Cindy Lau, Chenthila Nagamuthu, Mohammad Agha, Paul C. Nathan, and David Hodgson. "Risk of COVID-19 Infections and of Severe Complications Among Survivors of Childhood, Adolescent, and Young Adult Cancer: A Population-Based Study in Ontario, Canada." Journal of Clinical Oncology 40, no. 12 (April 20, 2022): 1281–90. http://dx.doi.org/10.1200/jco.21.02592.
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PURPOSE Survivors of childhood, adolescent, and young adult cancer are at risk of late effects, including pulmonary and infectious complications. Whether survivors are at increased risk of COVID-19 infection and severe complications is unknown. METHODS Population-based registries in Ontario, Canada, identified all 5-year survivors of childhood cancer diagnosed age 0-17 years between 1985 and 2014, and of six common adolescent and young adult cancers diagnosed age 15-21 years between 1992 and 2012. Each survivor alive on January 1, 2020, was randomly matched by birth year, sex, and residence to 10 cancer-free population controls. Individuals were linked to population-based laboratory and health care databases to identify COVID-19 tests, vaccinations, infections, and severe outcomes (emergency department [ED] visits, hospitalizations, intensive care unit admissions, and death within 60 days). Demographic, disease, and treatment-related variables were examined as possible predictors of outcomes. RESULTS Twelve thousand four hundred ten survivors were matched to 124,100 controls. Survivors were not at increased risk of receiving a positive COVID-19 test (386 [3.1%] v 3,946 [3.2%]; P = .68) and were more likely to be fully vaccinated (hazard ratio, 1.23; 95 CI, 1.20 to 1.37). No increase in risk among survivors was seen in emergency department visits (adjusted odds ratio, 1.2; 95 CI, 0.9 to 1.6; P = .19) or hospitalization (adjusted odds ratio, 1.8; 95 CI, 1.0 to 3.5; P = .07). No survivor experienced intensive care unit admission or died after COVID-19 infection. Pulmonary radiation or chemotherapies associated with pulmonary toxicity were not associated with increased risk. CONCLUSION Cancer survivors were not at increased risk of COVID-19 infections or severe sequelae. These results can inform risk-counseling of survivors and their caregivers. Further study is warranted to determine risk in older survivors, specific subsets of survivors, and that associated with novel COVID-19 variants.
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Shuldiner, Jennifer, Nida Shah, Catherine Reis, Ian Chalmers, Noah Ivers, and Paul Nathan. "Developing a Provincial Surveillance and Support System for Childhood Cancer Survivors: Multiphase User-Centered Design Study." JMIR Human Factors 9, no. 3 (September 13, 2022): e37606. http://dx.doi.org/10.2196/37606.
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Background Survivors of childhood cancer are at lifelong risk of morbidity (such as new cancers or heart failure) and premature mortality due to their cancer treatment. These are termed late effects. Therefore, they require lifelong, risk-tailored surveillance. However, most adult survivors of childhood cancer do not complete recommended surveillance tests such as mammograms or echocardiograms. Objective In partnership with survivors, family physicians, and health system partners, we are designing a provincial support system for high-priority tests informed by principles of implementation science, behavioral science, and design thinking. Methods Our multiphase process was structured as follows. Step 1 consisted of a qualitative study to explore intervention components essential to accessing surveillance tests. Step 2 comprised a workshop with childhood cancer survivors, family physicians, and health system stakeholders that used the Step 1 findings and “personas” (a series of fictional but data-informed characters) to develop and tailor the intervention for different survivor groups. Step 3 consisted of intervention prototype development, and Step 4 involved iterative user testing. Results The qualitative study of 30 survivors and 7 family physicians found a high desire for information on surveillance for late effects. Respondents indicated that the intervention should help patients book appointments when they are due in addition to providing personalized information. Insights from the workshop included the importance of partnering with both family physicians and survivorship clinics and providing emotional support for survivors who may experience distress upon learning of their risk for late effects. In our user-testing process, prototypes went through iterations that incorporated feedback from users regarding acceptability, usability, and functionality. We sought to address the needs of survivors and physicians while balancing the capacity and infrastructure available for a lifelong intervention via our health system partners. Conclusions In partnership with childhood cancer survivors, family physicians, and health system partners, we elucidated the barriers and enablers to accessing guideline-recommended surveillance tests and designed a multifaceted solution that will support survivors and their family physicians. The next step is to evaluate the intervention in a pragmatic randomized controlled trial.
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Ou, Judy, Heidi Hanson, Joemy Ramsay, Claire Leiser, Yue Zhang, James VanDerslice, C. Pope, and Anne Kirchhoff. "Fine Particulate Matter and Respiratory Healthcare Encounters among Survivors of Childhood Cancers." International Journal of Environmental Research and Public Health 16, no. 6 (March 26, 2019): 1081. http://dx.doi.org/10.3390/ijerph16061081.
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Some chemotherapies that treat childhood cancers have pulmonary-toxic properties that increase risk for adverse respiratory-health outcomes. PM2.5 causes similar outcomes but its effect among pulmonary compromised cancer survivors is unknown. This case-crossover study identified the PM2.5-associated odds for primary-respiratory hospitalizations and emergency department visits among childhood cancer survivors in Utah. We compared risk among chemotherapy-treated survivors to a cancer-free sample. We calculated 3-day-average PM2.5 by ZIP code and county for event and control days. Conditional logistic regression estimated odds ratios. Models were stratified by cause of admission (infection, respiratory disease, asthma), previous chemotherapy, National Ambient Air Quality Standard (NAAQS), and other variables. Results are presented per 10 µg/m3 of PM2.5. 90% of events occurred at 3-day PM2.5 averages <35.4 µg/m3, the NAAQS 24-h standard. For survivors, PM2.5 was associated with respiratory hospitalizations (OR = 1.84, 95% CI = 1.13–3.00) and hospitalizations from respiratory infection (OR = 2.09, 95% CI = 1.06–4.14). Among chemotherapy-treated survivors, the PM2.5-associated odds of respiratory hospitalization (OR = 2.03, 95% CI = 1.14–3.61) were significantly higher than the cancer-free sample (OR = 0.84, 95% CI = 0.57–1.25). This is the first study to report significant associations between PM2.5 and respiratory healthcare encounters in childhood cancer survivors. Chemotherapy-treated survivors displayed the highest odds of hospitalization due to PM2.5 exposure and their risk is significantly higher than a cancer-free sample.
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Pradhan, Kamnesh R., Yan Chen, Sogol Moustoufi-Moab, Kevin Krull, Kevin C. Oeffinger, Charles Sklar, Gregory T. Armstrong, et al. "Endocrine and Metabolic Disorders in Survivors of Childhood Cancers and Health-Related Quality of Life and Physical Activity." Journal of Clinical Endocrinology & Metabolism 104, no. 11 (July 9, 2019): 5183–94. http://dx.doi.org/10.1210/jc.2019-00627.
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Abstract Context Childhood cancer survivors experience chronic health conditions that impact health-related quality of life (HRQOL) and participation in optimal physical activity. Objective The study aimed to determine independent effects of endocrine and metabolic disorders on HRQOL and physical activity. Design, Setting, and Patients Retrospective cohort with longitudinal follow-up of survivors of childhood cancer enrolled in the North American Childhood Cancer Survivor Study. Main Outcome Measures Medical Outcomes Short Form-36 estimated HRQOL, and participation in physical activity was dichotomized as meeting or not meeting recommendations from the Centers for Disease Control and Prevention. Log binomial regression evaluated the association of each endocrine/metabolic disorder with HRQOL scales and physical activity. Results Of 7287 survivors, with a median age of 32 years (range, 18 to 54 years) at their last follow-up survey, 4884 (67%) reported one or more endocrine/metabolic disorders. Survivors with either disorder were significantly more likely to be male, older, have received radiation treatment, and have experienced other chronic health conditions. After controlling for covariates, survivors with any endocrine/metabolic disorder were more likely to report poor physical function risk ratio (RR, 1.25; 95% CI, 1.05 to 1.48), increased bodily pain (RR, 1.27; 95% CI, 1.12 to 1.44), poor general health (RR, 1.49; 95% CI, 1.32 to 1.68), and lower vitality (RR, 1.21; 95% CI, 1.09 to 1.34) compared with survivors without. The likelihood of meeting recommended physical activity was lower among survivors with growth disorders (RR, 0.90; 95% CI, 0.83 to 0.97), osteoporosis (RR, 0.87; 95% CI, 0.76 to 0.99), and overweight/obesity (RR, 0.92; 95% CI, 0.88 to 0.96). Conclusion Endocrine and metabolic disorders are independently associated with poor HRQOL and suboptimal physical activity among childhood cancer survivors.
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MacDonald, Tamara. "Pediatric Cancer: A Comprehensive Review. Part I: Biology, Epidemiology, Common Tumours, Principles of Treatment and Late Effects." Canadian Pharmacists Journal / Revue des Pharmaciens du Canada 143, no. 4 (July 2010): 176–83. http://dx.doi.org/10.3821/1913-701x-143.4.176.
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The incidence rates of pediatric cancer, like adult cancer, are increasing, though to a lesser degree. Options for the treatment of childhood cancers are continually changing and improving and overall survival has increased dramatically over the last 60 years. This paper discusses the incidence and survival trends of childhood cancer. The biology and epidemiology of the most common cancers seen in children and the late effects of treatment for childhood cancer will also be discussed. A basic understanding of childhood cancer is important for both hospital and community pharmacists, since many young adults in North America are now survivors of childhood cancer and may experience long-term consequences of chemotherapy.
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Meadows, Anna T., Debra L. Friedman, Joseph P. Neglia, Ann C. Mertens, Sarah S. Donaldson, Marilyn Stovall, Sue Hammond, Yutaka Yasui, and Peter D. Inskip. "Second Neoplasms in Survivors of Childhood Cancer: Findings From the Childhood Cancer Survivor Study Cohort." Journal of Clinical Oncology 27, no. 14 (May 10, 2009): 2356–62. http://dx.doi.org/10.1200/jco.2008.21.1920.
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Purpose To review the reports of subsequent neoplasms (SNs) in the Childhood Cancer Survivor Study (CCSS) cohort that were made through January 1, 2006, and published before July 31, 2008, and to discuss the host-, disease-, and therapy-related risk factors associated with SNs. Patients and Methods SNs were ascertained by survivor self-reports and subsequently confirmed by pathology findings or medical record review. Cumulative incidence of SNs and standardized incidence ratios for second malignant neoplasms (SMNs) were calculated. The impact of host-, disease-, and therapy-related risk factors was evaluated by Poisson regression. Results Among 14,358 cohort members, 730 reported 802 SMNs (excluding nonmelanoma skin cancers). This represents a 2.3-fold increase in the number of SMNs over that reported in the first comprehensive analysis of SMNs in the CCSS cohort, which was done 7 years ago. In addition, 66 cases of meningioma and 1,007 cases of nonmelanoma skin cancer were diagnosed. The 30-year cumulative incidence of SMNs was 9.3% and that of nonmelanoma skin cancer was 6.9%. Risk of SNs remains elevated for more than 20 years of follow-up for all primary childhood cancer diagnoses. In multivariate analyses, risks differ by SN subtype, but include radiotherapy, age at diagnosis, sex, family history of cancer, and primary childhood cancer diagnosis. Female survivors whose primary childhood cancer diagnosis was Hodgkin's lymphoma or sarcoma and who received radiotherapy are at particularly increased risk. Analyses of risk associated with radiotherapy demonstrated different dose-response curves for specific SNs. Conclusion Childhood cancer survivors are at a substantial and increasing risk for SNs, including nonmelanoma skin cancer and meningiomas. Health care professionals should understand the magnitude of these risks to provide individuals with appropriate counseling and follow-up.
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Chowdhury, Tanzina, and Gill A. Levitt. "Late Complications of Cancer in Childhood and Adolescence." Oncology & Hematology Review (US) 09, no. 01 (2013): 52. http://dx.doi.org/10.17925/ohr.2013.09.1.52.
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Overall survival for all childhood cancers has substantially increased with nearly 80 % of children surviving to five years following diagnosis, compared with 30 % 50 years ago. Unfortunately this comes at a cost; the overall Standardised Mortality Ratio (SMR) was 8.4 for childhood cancer survivors compared with the general population and increases in cause-specific mortality were seen for deaths due to second malignancy and cardiotoxicity. The incidence of chronic morbidities in the US Childhood Cancer Survivor Study (CCSS) cohort was 62.3 % after follow-up for 26.6 years. While many children will escape these organ toxicities, a significant proportion will require surveillance and management of treatment morbidities. It is the responsibility of those who treat childhood cancer to understand the effects of treatment and provide effective services to maximise the potential of these young people.
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Nathan, Paul C., Mark L. Greenberg, Kirsten K. Ness, Melissa M. Hudson, Ann C. Mertens, Martin C. Mahoney, James G. Gurney, et al. "Medical Care in Long-Term Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study." Journal of Clinical Oncology 26, no. 27 (September 20, 2008): 4401–9. http://dx.doi.org/10.1200/jco.2008.16.9607.
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Purpose To evaluate whether childhood cancer survivors receive regular medical care focused on the specific morbidities that can arise from their therapy. Patients and Methods We conducted a cross-sectional survey of health care use in 8,522 participants in the Childhood Cancer Survivor Study, a multi-institutional cohort of childhood cancer survivors. We assessed medical visits in the preceding 2 years, whether these visits were related to the prior cancer, whether survivors received advice about how to reduce their long-term risks, and whether screening tests were discussed or ordered. Completion of echocardiograms and mammograms were assessed in patients at high risk for cardiomyopathy or breast cancer. We examined the relationship between demographics, treatment, health status, chronic medical conditions, and health care use. Results Median age at cancer diagnosis was 6.8 years (range, 0 to 20.9 years) and at interview was 31.4 years (range, 17.5 to 54.1 years). Although 88.8% of survivors reported receiving some form of medical care, only 31.5% reported care that focused on their prior cancer (survivor-focused care), and 17.8% reported survivor-focused care that included advice about risk reduction or discussion or ordering of screening tests. Among survivors who received medical care, those who were black, older at interview, or uninsured were less likely to have received risk-based, survivor-focused care. Among patients at increased risk for cardiomyopathy or breast cancer, 511 (28.2%) of 1,810 and 169 (40.8%) of 414 had undergone a recommended echocardiogram or mammogram, respectively. Conclusion Despite a significant risk of late effects after cancer therapy, the majority of childhood cancer survivors do not receive recommended risk-based care.
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Recht, Lawrence D., Griffith Harsh IV, and Harvey J. Cohen. "The rationale for early detection and treatment of brain tumors in survivors of childhood cancer." Oncology Reviews 3, no. 1 (December 14, 2011): 51. http://dx.doi.org/10.4081/oncol.2009.51.
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Survivors of childhood cancer have a relatively high risk of developing second cancers. The incidence of brain tumor in these patients approaches 1% at 10 years, over 80-fold that in the general population. This high incidence increases the likelihood that early detection of brain tumors in survivors of childhood cancer is feasible. By analogy with other epithelial cancers, detection and treatment of brain tumors at a pre-neoplastic or premalignant stage may render screening and treatment cost effective for certain high-risk populations. Our animal studies with a clinically appropriate model of this condition suggest that there is a pre-neoplastic, pre-malignant brain tumor lesion that is potentially both detectable and effectively treated. The possibility of detecting such a treatable antecedent to brain tumors provides the rationale for genomic and proteomic screening of tumor tissue, CSF, plasma and urine in this animal model, of tumor tissue and body fluids of patients with known brain tumors at various stages, and of body fluids of survivors of childhood cancer.
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Bhandari, Rusha, Yan Chen, Eric Jessen Chow, Rebecca M. Howell, Lisa Brazzamano Kenney, Kevin R. Krull, Wendy M. Leisenring, et al. "Mortality and the burden of subsequent malignant neoplasms in survivors of childhood cancer beyond age 50: A report from the Childhood Cancer Survivor Study (CCSS)." Journal of Clinical Oncology 41, no. 16_suppl (June 1, 2023): 10052. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.10052.
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10052 Background: The first generation of survivors of childhood cancer is now older than 50 years (y) of age. There is a paucity of information on the risk for late mortality and the evolving burden of subsequent malignant neoplasms (SMNs) in these aging survivors. Methods: We assessed cause-specific mortality (National Death Index) and self-reported SMNs (excluding nonmelanoma skin cancers) among CCSS participants diagnosed between 1970-1999, conditional on having survived to 50y by 12/31/2017. There were 4,772 survivors alive at 50y eligible for mortality analyses. Of the 3,355 who completed a baseline CCSS questionnaire, 2,273 also completed a follow-up questionnaire at ≥50y and were included in the SMN analyses. Cumulative mortality, standardized mortality ratios (SMRs), and, for SMNs, cumulative burden, standardized incidence ratios (SIRs), and relative rate (RR) with 95% confidence intervals (CIs) were calculated, compared with the general US population and by survivor subgroups. Piecewise-exponential multivariable regression was used to identify risk factors associated with the development of SMNs after 50y. Results: Mean age at diagnosis was 14y (standard deviation 4.2y). Mortality: Among survivors who attained 50y of age, the subsequent 5y, 10y, and 15y incidences of all-cause mortality were 9%, 19%, and 35%, respectively, (overall SMR 3.7 [95% CI 3.4-4.1]). SMRs were highest for SMN (SMR 5.1 [95% CI 4.4-5.9]), pulmonary (SMR 4.7 [95% CI 3.3-6.5]) and cardiovascular (SMR 3.9 [95% CI 3.2-4.8]) causes of death. The highest SMR (SMR 9.2 [95% CI 7.7-10.8]) was seen in female survivors of Hodgkin lymphoma. SMN: By age 50y, 14% of CCSS participants reported >1 SMN. History of SMN <50y was independently associated with the rate of developing another SMN at >50y (RR 1.6 [95% CI 1.1-2.3]). The most frequent SMNs ≥50y were breast (41%) in females and prostate (21%) in males, followed by gastrointestinal cancers in both (14% [females], 19% [males]). The cumulative burden of SMNs in survivors treated with radiation therapy (RT) increased sharply with age and exceeded 50 per 100 survivors by 65y (SIR 3.3 95%CI 2.0-5.2]). Survivors who did not receive RT had a SMN rate comparable to the general population (Table). Conclusions: This sentinel population of survivors of childhood cancer is at high risk for poor outcomes as they enter older adulthood. RT exposure and history of SMN <50y are associated with increased risk for developing SMNs after 50y. The evolving burden of late morbidity attributed to SMNs may be lower for contemporary survivors projected to have less RT exposure. [Table: see text]
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Perkins, Joanna L., Yan Liu, Pauline A. Mitby, Joseph P. Neglia, Sue Hammond, Marilyn Stovall, Anna T. Meadows, et al. "Nonmelanoma Skin Cancer in Survivors of Childhood and Adolescent Cancer: A Report From the Childhood Cancer Survivor Study." Journal of Clinical Oncology 23, no. 16 (June 1, 2005): 3733–41. http://dx.doi.org/10.1200/jco.2005.06.237.
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Purpose Nonmelanoma skin cancer (NMSC) has become the most common type of cancer in many populations throughout the world. Ultraviolet and ionizing radiation are known risk factors. Because NMSCs are rarely lethal and most cancer registries do not routinely report data regarding these cancers, they have received little attention in studies evaluating long-term effects of cancer therapy. This article reports on the occurrence of secondary NMSC as a long-term effect of cancer therapy in survivors of childhood cancer. Patients and Methods The Childhood Cancer Survivor Study (CCSS) is a cohort study of 5-year survivors of childhood and adolescent cancer from 25 participating institutions in North America. NMSC patients were defined by a history of basal cell or squamous cell carcinoma of the skin after primary malignancy treatment. Demographic and treatment data were collected and analyzed. Results Among the 13,132 eligible CCSS participants, 213 have reported NMSC; 99 patients (46%) have had multiple occurrences. Median age of occurrence was 31 years (range, 7 to 46 years). Location of NMSC included head and neck (43%), back (24%), chest (22%), abdomen and pelvis (5%), extremity (3%), and unknown (4%). Ninety percent of patients had previously received radiation therapy (RT); 90% of tumors occurred within the RT field. RT was associated with a 6.3-fold increase in risk (95% CI, 3.5- to 11.3-fold). Conclusion Long-term survivors of childhood and adolescent cancer who were treated with RT are at highest risk for developing NMSC. Educational efforts need to be directed to this population to facilitate early diagnosis of NMSC and reduction in sun exposure.
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Arsenault, Valerie, Weiyu Qiu, Qi Liu, Jennifer Yeh, Wendy Leisenring, Kirsten K. Ness, Gregory T. Armstrong, et al. "Emergency department (ED) visits and hospitalizations in survivors of childhood cancer in the Childhood Cancer Survivor Study." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 10056. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.10056.
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10056 Background: Chronic health conditions are frequent among childhood cancer survivors and lead to increased health care resource utilization. We compared rates of ED visits and hospitalizations between survivors and siblings. Methods: Analyses included 10,762 ≥5-year survivors and 2,069 siblings who completed a questionnaire from 2014-2016. We calculated ED visits and non-obstetric hospitalizations in the last 12 months per 1,000 person-years (PY) and evaluated cause-specific hospitalization rates using ICD-10 categories. Multivariable Poisson regression models evaluated predictors of survivor visits. Results: Median age in survivors and siblings was 35.3 years (interquartile range [IQR] 29.0-43.1) and 42.9 years (IQR 35.6-50.2), respectively; time from cancer diagnosis was 27.8 years (IQR 21.7-34.1). 24.2% of survivors and 16.2% of siblings had ≥1 ED visit (p < 0.001); rates were 521/1,000 PY for survivors and 246/1,000 PY for siblings (age/sex-adjusted relative rate [RR] 2.0; 95% confidence interval [CI] 1.7 - 2.3). Factors associated with increased survivor ED visits were black race (RR 1.6, CI 1.2-2.0), being obese (RR 1.4, CI 1.2-1.7) or underweight (RR 1.9, CI 1.2-3.0), female sex (RR 1.3, CI 1.1-1.5), younger age (p = 0.02) or abdomen/pelvis (RR 1.2, CI 1.1-1.4) or brain irradiation (RR 1.2, CI 1.0-1.4). 13.3% of survivors and 8.3% of siblings had ≥1 hospitalization (p < 0.001); rates were 219/1,000 PY for survivors and 130/1,000 PY for siblings (RR 1.9; CI 1.3 - 2.9). Factors associated with increased survivor hospitalizations were female sex (RR 1.3, 1.1-1.5), younger age (p < 0.0001), being obese (RR 1.3, CI 1.0-1.6) or underweight (RR 1.5, 95% CI 1.1-2.2) or platinum chemotherapy exposure (RR 1.6, CI 1.3-2.0). The most common indications for hospitalization were diseases of the digestive (21.9/1,000 PY; CI 18.7 - 25.7) and circulatory (20.9/1,000 PY; CI 17.8 – 24.4) systems. Leukemia survivors had the highest ED visit and hospitalization rates. Conclusions: Childhood cancer survivors had a 2-fold increased likelihood of an ED visit or hospitalization compared with their siblings. This increases the economic burden on survivors and the health care system.
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Tseloval'nikova, Tat'yana Yur'evna, Mariya Gennadievna Pavlova, Aleksey Vadimovich Zilov, Nadezhda Aleksandrovna Mazerkina, Ol'ga Grigor'evna Zheludkova, Irina Alekseevna Aref'eva, and Ol'ga Aleksandrovna Medvedeva. "Metabolic disorders in medulloblastoma and acute lymphoblastic leukemia survivors." Obesity and metabolism 12, no. 3 (August 3, 2015): 3–9. http://dx.doi.org/10.14341/omet201533.
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The childhood cancer morbidity has been steadily increasing over the last few decades. However, the recent more effective complex treatment approaches have led to a dramatic improvements in the survival rate in childhood cancers. Currently many childhood cancer survivors require a life-long follow-up. Therefore, today doctors of various specialties are faced with different long-term consequences after the complex treatment for cancer. Among the various complications metabolic disorders should be eparately identified as risk factors for cardiovascular diseases, which are the most frequent causes of death. This article describes the current understanding of the various metabolic changes in the patients after treatment for medulloblastoma and acute lymphoblastic leukemia in childhood, the mechanisms of their development and treatment issues.
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Casillas, Jacqueline N., Qi Liu, Melissa M. Hudson, Mark Greenberg, Mark W. Yeazel, Kirsten K. Ness, Leslie L. Robison, et al. "Longitudinal changes in health care utilization by adult survivors of childhood cancer in the Childhood Cancer Survivor Study (CCSS)." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 6030. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.6030.
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6030 Background: The incidence of late effects increases as childhood cancer survivors age. Survivors require lifelong care focused on the risks arising from prior cancer therapy (survivor-focused care). Methods: We assessed longitudinal changes in health care utilization in adult survivors of childhood cancer participating in the CCSS. Utilization at baseline and most recent follow-up was classified into one of three mutually exclusive hierarchical categories: no health care, general medical care, or survivor-focused care. Relative risk (RR) and 95% confidence intervals (CI) were calculated for predictors of reduction in care over time from survivor-focused to general or no care. Multivariable models, adjusted for key treatment exposures, were created to assess the risk factors for reductions in level of care over time. Results: Among 8591 eligible survivors, mean age at last follow-up was 35.1 years (SD=7.8) with a mean of 11.6 years (SD=2.2) since baseline. Of 3993 (46%) survivors who reported survivor-focused care at baseline, 2383 (59.7%) reported a lower level of care at follow-up. Among 4598 (54%) not receiving survivor-focused care at baseline, 915 (20%) reported survivor-focused care at follow-up. Baseline predictors of a decreased level of care were no health insurance (RR=1.5, 95% CI 1.2-1.9), male sex (RR=1.4, 95% CI 1.2-1.6), being 10-19 years from diagnosis compared with 20+ years (RR=1.4, 95% CI 1.1-1.7). In contrast, factors associated with a maintenance in survivor-focused care were Canadian residency compared to U.S. residency with insurance (RR=0.7, 95% CI 0.6-0.9), unemployment (RR=0.8, 95% CI 0.7-0.9), physical limitations (RR=0.7, 95% CI 0.6-0.9), cancer-related pain (RR=0.7, 95% CI 0.5-0.8), poor emotional health (RR=0.7, 95% CI 0.5-0.9), having mild-moderate (RR=0.5, 95% CI 0.4-0.6) or severe-disabling chronic health condition (RR=0.6, 95% CI 0.5-0.7). Conclusions: Less than a third of adult survivors of childhood cancer report survivor-focused care. Rates decrease over time. Targeted interventions to maximize survivor-focused care in at-risk survivors should be tested so preventive and risk-reducing opportunities are not lost.
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Harper, Andrew, Fiona Schulte, Gregory M. T. Guilcher, Tony H. Truong, Kathleen Reynolds, Maria Spavor, Natalie Logie, Joon Lee, and Miranda M. Fidler-Benaoudia. "Alberta Childhood Cancer Survivorship Research Program." Cancers 15, no. 15 (August 2, 2023): 3932. http://dx.doi.org/10.3390/cancers15153932.
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Adverse outcomes after childhood cancer have been assessed in a range of settings, but most existing studies are historical and ascertain outcomes only after 5-year survival. Here, we describe the Alberta Childhood Cancer Survivorship Research Program and its foundational retrospective, population-based cohort of Albertan residents diagnosed with a first primary neoplasm between the ages of 0 and 17 years from 1 January 2001 to 31 December 2018. The cohort was established in collaboration with the Alberta Cancer Registry and Cancer in Young People in Canada program and has been linked to existing administrative health databases and patient-reported outcome questionnaires. The cohort comprised 2580 survivors of childhood cancer, 1379 (53.4%) of whom were 5-year survivors. Approximately 48% of the cohort was female, 47% of the cohort was diagnosed between 0 and 4 years of age, and the most frequent diagnoses were leukemias (25.4%), central nervous system tumors (24.0%), and lymphomas (14.9%). Detailed treatment information was available for 1741 survivors (67.5%), with manual abstraction ongoing for those with missing data. By the study exit date, the median time since diagnosis was 5.5 years overall and 10.4 years for 5-year survivors. During the follow-up time, 82 subsequent primary cancers were diagnosed, 20,355 inpatient and 555,425 ambulatory/outpatient events occurred, 606,773 claims were reported, and 437 survivors died. The results from this research program seek to inform and improve clinical care and reduce cancer-related sequelae via tertiary prevention strategies.
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Yavvari, Siddhartha, Yasaswi Makena, Sahithi Sukhavasi, and Monish Ram Makena. "Large Population Analysis of Secondary Cancers in Pediatric Leukemia Survivors." Children 6, no. 12 (November 29, 2019): 130. http://dx.doi.org/10.3390/children6120130.
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Introduction: Survivors of childhood cancer have an increased risk of developing a subsequent secondary malignant neoplasm (SMN). Among five-year survivors of primary cancer, SMNs account for nearly half of non-relapse deaths, which make them the most frequent cause of non-relapse mortality. Leukemia is the most common childhood cancer and the five-year survival rate of leukemia has drastically improved over the past two decades. Therefore, the chances of developing SMNs are higher in pediatric (0–19 years) leukemia survivors. Methods: The US based Surveillance, Epidemiology, and End Results (SEER-18) database (1973–2014) was probed for SMNs in the pediatric population (age ≤ 19). Variables Sequence-number central, primary site and ICCC3WHO were used to identify the first and second cancers among patients who developed SMN. Results: Our SEER database analysis found 99,380 cases of pediatric primary malignancies (0–19 years), of which 1803 (1.81%) patients developed SMN. The breakdown of SMNs in pediatric leukemia survivors (n = 251) showed thyroid carcinoma (18.33% of cases) as the most common second cancer, followed by sarcoma (15.14%), astrocytoma (10.36%), lymphoma (9.56%), salivary gland carcinoma (7.17%), melanoma (4.38%), and breast cancer (3.98%). Interestingly, we found that over 76% of SMNs that were developed by leukemia patients occurred within 20 years after initial leukemia diagnosis. However, some SMNs occur during later age, for example, the mean age for breast cancer occurrence in leukemia survivors is 26.20 ± 8.53 years after initial leukemia diagnosis. Conclusions: Our study presented comprehensive rates of SMNs among pediatric cancers survivors, and the potential SMNs for pediatric leukemia survivors. This information could we used by oncologists, patients, patient families, and cancer researchers to understand the long-term risks that are associated with the development of SMNs in pediatric leukemia survivors.
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Park, Elyse R., Frederick P. Li, Yan Liu, Karen M. Emmons, Arthur Ablin, Leslie L. Robison, and Ann C. Mertens. "Health Insurance Coverage in Survivors of Childhood Cancer: The Childhood Cancer Survivor Study." Journal of Clinical Oncology 23, no. 36 (December 20, 2005): 9187–97. http://dx.doi.org/10.1200/jco.2005.01.7418.
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Purpose To examine the prevalence and predictors of health insurance coverage and the difficulties obtaining coverage in a large cohort of childhood cancer survivors. Patients and Methods This study included 12,358 5-year survivors of childhood cancer and 3,553 sibling controls participating in the Childhood Cancer Survivor Study. Data were collected by surveys distributed in 1994 (baseline) and 2000 (follow-up). Results At baseline, 83.9% of adult survivors, compared with 88.3% of siblings, had health insurance coverage (P < .01); 6 years later, small but significant survivor-sibling differences remained (88% v 91%; P < .01). Twenty-nine percent of survivors reported having had difficulties obtaining coverage, compared with only 3% of siblings (P < .01). In multivariate analysis of survivors 18 years of age or older, factors associated with being uninsured included younger age at diagnosis (diagnosis age of 0 to 4 years; odds ratio [OR] = 1.7; 95% CI, 1.3 to 2.2), male sex (OR = 1.3; 95% CI, 1.2 to 1.5), age at baseline survey (age 22 to 24 years; OR = 1.6; 95% CI, 1.2 to 2.1), lower level of attained education (less than high school, OR = 2.6, 95% CI, 2.1 to 3.3; high school graduate, OR = 2.1, 95% CI, 1.8 to 2.5), income less than $20,000 (OR = 5.6, 95% CI, 4.5 to 7.1), marital status (widowed/divorced/separated; OR = 1.3; 95% CI, 1.1 to 1.6), smoking status (current smoker, OR = 2.0, 95% CI, 1.7 to 2.3; former smoker, OR = 1.4, 95% CI, 1.2 to 1.8), and treatment that included cranial radiation (OR = 1.3, 95% CI, 1.0 to 1.6). Conclusion Compared with siblings, adult survivors of childhood cancer had significantly lower rates of health insurance coverage and more difficulties obtaining coverage. Since lack of coverage likely has serious health and financial implications for this at-risk population, any disparity in availability and quality of coverage is of great concern.
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Belle, Fabiën Naomi, Maja Beck Popovic, Marc Ansari, Maria Otth, Claudia Elisabeth Kuehni, and Murielle Bochud. "Nutritional Assessment of Childhood Cancer Survivors (the Swiss Childhood Cancer Survivor Study-Nutrition): Protocol for a Multicenter Observational Study." JMIR Research Protocols 8, no. 11 (November 18, 2019): e14427. http://dx.doi.org/10.2196/14427.
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Background Childhood cancer survivors are at high risk of developing adverse late health effects. Poor nutritional intake may contribute to this risk, but information about dietary intake is limited. Objective This study will assess childhood cancer survivors’ dietary intake and compare two dietary assessment tools: a self-reported food frequency questionnaire, and dietary measurements from urine spot samples. Methods In a substudy of the Swiss Childhood Cancer Survivor Study (SCCSS), SCCSS-Nutrition, we assessed childhood cancer survivors’ dietary intake via a validated food frequency questionnaire. We sent a urine spot collection kit to a subset of 212 childhood cancer survivors from the French-speaking region of Switzerland to analyze urinary sodium, potassium, urea, urate, creatinine, and phosphate content. We will compare the food frequency questionnaire results with the urine spot analyses to quantify childhood cancer survivors’ intake of various nutrients. We collected data between March 2016 and March 2018. Results We contacted 1599 childhood cancer survivors, of whom 919 (57.47%) returned a food frequency questionnaire. We excluded 11 childhood cancer survivors who were pregnant or were breastfeeding, 35 with missing dietary data, and 71 who had unreliable food frequency questionnaire data, resulting in 802 childhood cancer survivors available for food frequency questionnaire analyses. To a subset of 212 childhood cancer survivors in French-speaking Switzerland we sent a urine spot collection kit, and 111 (52.4%) returned a urine sample. We expect to have the results from analyses of these samples in mid-2019. Conclusions The SCCSS-Nutrition study has collected in-depth dietary data that will allow us to assess dietary intake and quality and compare two dietary assessment tools. This study will contribute to the knowledge of nutrition among childhood cancer survivors and is a step toward surveillance guidelines and targeted nutritional recommendations for childhood cancer survivors in Switzerland. Trial Registration ClinicalTrials.gov NCT03297034; https://clinicaltrials.gov/ct2/show/NCT03297034 International Registered Report Identifier (IRRID) DERR1-10.2196/14427
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Patel, Pranali G., Chaitali S. Dagli, Nosayaba Osazuwa-Peters, Mrudula Nair, Dina K. Abouelella, Oluwole A. Babatunde, Shreya P. Ramkumar, and Eric Adjei Boakye. "Abstract B021: Trends in psychological distress among adult survivors of childhood, adolescent and young adult cancers: Analysis of 2008-2018 National Health Interview Survey data." Cancer Epidemiology, Biomarkers & Prevention 32, no. 12_Supplement (December 1, 2023): B021. http://dx.doi.org/10.1158/1538-7755.disp23-b021.
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Abstract Background: Cancer survivors diagnosed at childhood, adolescent and young adults age face psychological distress in the form of depression, anxiety, and panic attacks. In addition, psychological distress has been found to have an impact on the medical expenditures of cancer survivors. Previous studies have examined psychological distress in survivors of childhood, and young adult cancers (AYA) and found them to be high, whether this increasing or decreasing over the years is unknown. The aim of our study was to examine trends in psychological distress among survivors of childhood AYA cancers. Methods: We analyzed the 2008-2018 National Health Interview Survey (NHIS) data, a cross-sectional household interview survey of the US civilian, non-institutionalized population that uses a multistage area probability design. We identified individuals (n=6,175) who were diagnosed with cancer between 0 to 39 years of age. Psychological distress was assessed using the validated Kessler 6-item scale. Using a 30-day reference period, respondents’ rate how often they felt nervous, hopeless, restless or fidgety, so sad that nothing could cheer them up, that everything was an effort, and worthless. Response options include ‘never’, ‘a little of the time’, ‘some of the time’, ‘most of the time’, and ‘all of the time’. Responses were scored and added to produce a range of 0–24. We defined mild distress as a score of less <5, moderate distress as a score between 5-13 and severe distress as a score of >13. Joinpoint regression estimated yearly increases/decreases in psychological distress using annual percent changes. Results: Overall, the proportion of childhood and AYA cancer survivors with moderate distress decreased slightly between 2008 and 2014 but increased from 2014-2018 by 5% per year, though not statistically significant. However, the proportion of childhood and AYA cancer survivors with mild and severe distress remained relatively stable throughout the study period. The proportion of females and males with moderate distress increased by an average of 5% and 6% annually from 2014-2018 respectively, however, the increase was not statistically significant. The proportion of childhood and AYA cancer survivors who were married with moderate distress increased by 8% from 2014-2018 whereas survivors who were never married with severe distress decreased by 29% in the same time range. Conclusion: There is an increase in the number of survivors with moderate psychological distress while mild psychological distress has declined from 2014-15 onwards. Severe distress has remained relatively stable in all the years. Citation Format: Pranali G. Patel, Chaitali S Dagli, Nosayaba Osazuwa-Peters, Mrudula Nair, Dina K. Abouelella, Oluwole A. Babatunde, Shreya P. Ramkumar, Eric Adjei Boakye. Trends in psychological distress among adult survivors of childhood, adolescent and young adult cancers: Analysis of 2008-2018 National Health Interview Survey data [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B021.
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Nair, Mrudula, Chaitali S. Dagli, Betelihem B. Tobo, Samantha H. Tam, Nada Al-Antary, Nosayaba Osazuwa-Peters, and Eric Adjei Boakye. "Abstract 753: HPV vaccine uptake in survivors of childhood and adolescent and young adult (AYA) cancer." Cancer Research 83, no. 7_Supplement (April 4, 2023): 753. http://dx.doi.org/10.1158/1538-7445.am2023-753.
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Abstract Introduction: There will be an estimated 110,000 children and adolescents’ cancer survivors in the United States (US) in 2022. Previous studies have argued for the establishment of a specialized adolescent and young adult (AYA) oncology service to better serve their needs. Studies have demonstrated that survivors of childhood and AYA cancers remain at higher risk of developing second primary cancers over their lifetime. AYA cancer survivors are a growing part of the population and will benefit from HPV vaccination. Documenting HPV vaccine uptake among cancer survivors will facilitate interventions to improve vaccination rates in this population. Despite evidence supporting the efficacy of HPV vaccination, AYA vaccination rates are low. Furthermore, studies assessing HPV vaccination coverage in survivors of AYA cancer are lacking. Therefore, we assessed HPV vaccine initiation and completion between survivors of AYA cancer and respondents without a cancer diagnosis among 18-35-year-old in the US. Methods: We analyzed data from the 2017-2018 National Health Interview Survey, an annual cross-sectional national survey that provides information on the health of the noninstitutionalized US population. The outcome variables were HPV vaccine initiation (receipt of ≥1 dose) and completion (receipt of ≥3 doses). Exposure was cancer survivorship (AYA cancer survivors [respondents who were diagnosed with cancer as a child, adolescent, or young adult] vs. respondents without a cancer diagnosis). Weighted multivariable logistic regression models were used to examine the association between cancer survivorship and HPV vaccine initiation and completion, controlling for socioeconomic and healthcare access related factors. Results: A total of 2,942 respondents were included in the study, of which 242 (7.1%) were AYA cancer survivors. HPV vaccine initiation (22.5%) and completion (16.3%) among AYA cancer survivors were comparable to respondents without cancer diagnosis (initiation: 25.5%, completion: 15.3%). In the adjusted analyses, there were no significant differences in HPV vaccine initiation (P=0.6770) or completion (P=0.2001) between AYA cancer survivors and respondents without cancer diagnosis. Conclusions: HPV vaccine series initiation and completion were comparably low among AYA cancer survivors and respondents without a cancer diagnosis in our study. Low uptake of HPV vaccine among AYA cancer survivors is a more notable public health concern given their heightened immunocompromised status and elevated risk for second primary cancers. There is a need for primary care and oncology providers to encourage HPV vaccination and raise awareness of its crucial role among families of AYA cancer survivors. Citation Format: Mrudula Nair, Chaitali S. Dagli, Betelihem B. Tobo, Samantha H. Tam, Nada Al-Antary, Nosayaba Osazuwa-Peters, Eric Adjei Boakye. HPV vaccine uptake in survivors of childhood and adolescent and young adult (AYA) cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 753.
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Casano-Sancho, Paula, and Ana Carolina Izurieta-Pacheco. "Endocrine Late Effects in Childhood Cancer Survivors." Cancers 14, no. 11 (May 26, 2022): 2630. http://dx.doi.org/10.3390/cancers14112630.
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Childhood cancer management has improved considerably over the years, leading to a significant improvement in survival of up to 80%. However, childhood cancer survivors are at the highest risk of developing sequelae resulting from treatment, with endocrine complications being frequently observed among survivors. Multiple predisposing factors for endocrine sequelae have been identified, including age at diagnosis, treatment received, radiation, tumor type, and genetic polymorphisms, which could explain the individual predisposition to develop drug toxicity. Novel agents targeting tumor growth and immune checkpoint inhibitors have recently become the cornerstone for the treatment of different cancers, triggering a myriad of immune-related endocrinopathies. Endocrine sequelae of cancer therapy will have an impact on not only childhood but also on the survival and quality of life of these highly complex patients. Therefore, lifelong monitoring of childhood cancer survivors at risk of endocrine diseases is paramount. Encouraging oncologists and endocrinologists to develop new follow-up and early detection guidelines that minimize sequelae among these patients has become a priority, promoting integration between pediatric and adult units since many sequelae may manifest only after years to decades of follow-up.
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Lemmen, Jesse, Susan Mageto, Festus Njuguna, Nancy Midiwo, Sandra Langat, Terry Vik, Gertjan Kaspers, and Saskia Mostert. "Self-Reported Late Effects in Childhood Cancer Survivors in Kenya." African Health Sciences 24, no. 3 (October 6, 2024): 230–41. http://dx.doi.org/10.4314/ahs.v24i3.27.
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Background: The number of children surviving cancer in low and middle-income countries is expected to grow in the coming years. Knowledge about late effects and follow-up preferences in Kenya is lacking.Objectives: This study assessed self-reported late effects in Kenyan childhood cancer survivors and explored their preferences for survivorship care.Methods: Childhood cancer survivors, having successfully completed treatment for at least one year, were interviewed using semi-structured questionnaires during clinic or home visits between 2021-2022. Medical records were reviewed for patient and treatment characteristics.Results: Twenty-six survivors of hematological malignancies (n=19, 73%), solid tumors (n=6, 23%), unknown tumor type (n=1, 4%), were interviewed. Most survivors (n=19, 73%) solely received chemotherapy and one survivor (4%) was irradiated. Median time since treatment completion was seven years. Fifteen survivors (58%) were previously lost to follow-up. Many survivors (n=19; 73%) self-reported late effects, predominantly pain and fatigue. Survivors (n=11, 42%) were limited in daily life activities: physical work (n=10, 38%), personal care (n=6, 23%), social activities (n=6, 23%). Eight survivors (31%) recalled being informed about late effects. Some survivors experienced a negative attitude toward cancer in regional hospitals. Follow-up duration was longer among informed patients (p=0.043). Survivors recommended education and survivor meetings and preferred their follow-up to be done at the referral center.Conclusions: Kenyan childhood cancer survivors self-report late effects, comparable in frequency, nature and severity to other survivors worldwide. Survivors and healthcare providers require education about the lifelong impact of childhood cancer and should have access to survivorship expertise to continue follow-up. Keywords: Pediatrics; survivorship; neoplasms; aftercare.
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Effinger, Karen E., Wendy M. Leisenring, Kevin C. Oeffinger, Melissa M. Hudson, Kirsten K. Ness, Neyssa Marina, Marilyn Stovall, et al. "Longitudinal Evaluation Of Health Status In Aging Pediatric Hodgkin Lymphoma Survivors: Report From The Childhood Cancer Survivor Study." Blood 122, no. 21 (November 15, 2013): 769. http://dx.doi.org/10.1182/blood.v122.21.769.769.
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Abstract Background Hodgkin lymphoma (HL) is one of the most treatable pediatric cancers; however, long-term survivors have many therapy-related late effects. As the number of survivors expands and ages, it is important to determine how aging affects the health status of pediatric HL survivors. Methods The study included 1,469 5-year HL survivors and 3,206 siblings enrolled in the Childhood Cancer Survivor Study, a multi-center study of childhood cancer survivors and siblings. Six health status domains (general health, functional impairment, activity limitation, mental health, cancer-related pain, and cancer-related anxiety) were analyzed from data longitudinally collected on the baseline and 2 follow-up surveys. Prevalence of poor outcomes (as defined by Hudson et al. JAMA 2003) for survivors and siblings in each domain were compared using multiple logistic regression models and generalized estimating equations. Separate regressions were performed by sex and included survivor/sibling status, age, race, and interaction between age and survivor status. Models were then adjusted for body mass index (BMI) and number of severe, disabling, or life-threatening medical conditions (Common Terminology Criteria for Adverse Events [CTCAE] Grade 3 or 4). Treatment effects were evaluated in survivors in subsequent analyses. Results Survivors had higher odds of poor health status outcomes than siblings across all domains, which persisted after adjustment for the number of grade 3 or 4 medical conditions (Table 1). The gap between survivors and siblings increased significantly with age in females in the domains of functional impairment (Figure 1) and mental health (Figure 2), but not in males. The odds ratios (OR) for functional impairment in female survivors versus similarly aged female siblings were 0.8 (95% confidence interval [CI] 0.3-1.9) for 18 - 29 year olds, 2.5 (95% CI 1.6-3.7) for 30 - 39 year olds, and 3.1 (95% CI 2.0-4.8) for 40 year olds and older. Female survivors also reported higher prevalence of grade 3 or 4 conditions than male survivors, with 42% of male and 70% of female survivors 40 years and older reporting 1 or more conditions. These conditions increased the odds of poor health status in both sexes (Table 1). BMI in females and race other than non-Hispanic white in males were also significant predictors of poor health status. No treatment variables were consistently associated with poor health status. Conclusions Pediatric HL survivors have increased odds of poor health status compared to siblings. Aging further increases this burden for female survivors in the domains of functional impairment and mental health. Survivors of both sexes continue to develop serious medical conditions with aging, which increase the odds of poor health status. Pediatric HL survivors require early interventions to improve health status and close screening to diagnose medical conditions before they negatively impact quality of life. Disclosures: No relevant conflicts of interest to declare.
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Rebholz, Cornelia E., Raoul C. Reulen, Andrew A. Toogood, Clare Frobisher, Emma R. Lancashire, David L. Winter, Claudia E. Kuehni, and Michael M. Hawkins. "Health Care Use of Long-Term Survivors of Childhood Cancer: The British Childhood Cancer Survivor Study." Journal of Clinical Oncology 29, no. 31 (November 1, 2011): 4181–88. http://dx.doi.org/10.1200/jco.2011.36.5619.
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Purpose Survivors of childhood cancer are at high risk of chronic conditions, but few studies investigated whether this translates into increased health care utilization. We compared health care service utilization between childhood cancer survivors and the general British population and investigated potential risk factors. Methods We used data from the British Childhood Cancer Survivor Study, a population-based cohort of 17,981 individuals diagnosed with childhood cancer (1940-1991) and surviving ≥ 5 years. Frequency of talks to a doctor, hospital outpatient visits, and day-patient and inpatient hospitalizations were ascertained by questionnaire in 10,483 survivors and were compared with the General Household Survey 2002 data by using logistic regression. Results Among survivors, 16.5% had talked to a doctor in the last 2 weeks, 25.5% had attended the outpatient department of a hospital in the last 3 months, 11.9% had been hospitalized as a day patient in the last 12 months, and 9.8% had been hospitalized as an inpatient in the last 12 months. Survivors had talked slightly more often to a doctor than the general population (odds ratio [OR], 1.2; 95% CI, 1.1 to 1.3) and experienced increased hospital outpatient visits (OR, 2.5; 95% CI, 2.3 to 2.8), day-patient hospitalizations (OR, 1.4; 95% CI, 1.3 to 1.6) and inpatient hospitalizations (OR, 1.9; 95% CI, 1.7 to 2.2). Survivors of Hodgkin's lymphoma, neuroblastoma, and Wilms tumor had the highest ORs for day-patient care, whereas survivors of CNS tumors and bone sarcomas had the highest OR for outpatient and inpatient care. The OR of health care use did not vary significantly with age of survivor. Conclusion We have quantified how excess morbidity experienced by survivors of childhood cancer translates into increased use of health care facilities.
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Vankina, Srilakshmi P., Rachel I. Vogel, Patricia I. Jewett, Alexander A. Boucher, Sanyukta K. Janardan, Alicia Kunin-Batson, Karim Thomas Sadak, and Anne Blaes. "Body mass index (BMI) and quality of life among long-term survivors of childhood acute lymphoblastic leukemia." F1000Research 10 (March 4, 2021): 178. http://dx.doi.org/10.12688/f1000research.44641.1.
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Background: Adult survivors of childhood cancers such as acute lymphoblastic leukemia (ALL) are at risk of overweight and related chronic morbidities. As childhood cancer survival has been improving, long-term quality of life (QOL) among cancer survivors becomes more important. We examined the association of body mass index with physical and psychosocial QOL among childhood ALL survivors who returned for long-term follow-up after end of therapy. Methods: Using a cross-sectional survey (2006-2012), we assessed the association between body mass index and quality of life in 58 long-term survivors of childhood ALL (ages 9 to 43 at the time of survey/measurement) using age-appropriate QOL instruments (Health-Related Quality of Life Short Form – SF-36 or Child Health Questionnaire-PF-50). Results: Half of the participants were overweight or obese at the time of survey. Mean QOL scores were similar to population norms. Compared to underweight/healthy weight status, being overweight/obese was not significantly associated with poorer physical QOL, but with poorer psychosocial QOL (47.1±13.2 vs. 54.0±6.0, P=0.01, effect size Cohen’s d=0.67), which remained statistically significant after adjusting for age and sex. Conclusions: Weight management should be the target of timely interventions among survivors of childhood ALL.
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Russell, K. Brooke, Erin L. Merz, Kathleen Reynolds, Fiona Schulte, and Lianne Tomfohr-Madsen. "Sleep Disturbances in Survivors of Pediatric Acute Lymphoblastic Leukemia and Their Siblings." Journal of Pediatric Psychology 45, no. 7 (June 17, 2020): 707–16. http://dx.doi.org/10.1093/jpepsy/jsaa043.
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Abstract Objective Sleep disturbances have been identified by patients with cancer as common and distressing; however, conflicting evidence about the prevalence of these outcomes exists for survivors of childhood cancers. Additionally, little is known about how the experience of cancer might impact survivor siblings’ sleep. The current study compared the sleep of survivors of acute lymphoblastic leukemia who were 2–7 years off therapy and their siblings to healthy control/sibling dyads. Methods Participants (survivors, n = 45; survivor siblings, n = 27; controls, n = 45; control siblings, n = 41; 58% male) aged 8–18 (m = 11.64) completed a 7-day sleep diary and seven consecutive days of actigraphy. Parents (n = 90) completed the Children’s Sleep Habits Questionnaire for each of their children. Results No between-group differences were found on measures of sleep diaries or actigraphy. Parents reported that survivor siblings had significantly poorer sleep habits than survivors or controls. For survivors, greater time off treatment and younger age at diagnosis were associated with less total sleep time, more wake after sleep onset, and decreased sleep efficiency via actigraphy. Conclusion Sleep across all groups was consistent and below national guidelines. Although the survivor group did not have poorer sleep compared to their siblings or matched controls, within the survivor group, those who were diagnosed at an earlier age and those who were further off treatment had more disrupted sleep. Parent reports suggested that survivor siblings may be at risk for sleep problems.
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Wang, Amy Yuan, Yan Chen, Yutaka Yasui, Wendy Stock, Wendy M. Leisenring, Gregory T. Armstrong, Kevin C. Oeffinger, Eric Jessen Chow, Kevin R. Krull, and Tara O. Henderson. "Neurocognitive outcomes in survivors of early adolescent and young adult (eAYA) hematologic cancers from the Childhood Cancer Survivor Study (CCSS)." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 10029. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.10029.
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10029 Background: Neurocognitive impairment in eAYA hematologic cancer survivors has not been well described, despite intensive neurotoxic therapies. We examined prevalence and risk for such impairment in hematologic cancer survivors diagnosed during eAYA compared to a younger age. Methods: We identified 1,213 eAYA (diagnosed at 15-21 years; median [range] follow-up age 40 [30-54]) and 4,538 childhood (diagnosed at <15 years; median age 30 [17-48]) survivors of ALL (n= 301 vs 3274), AML (n= 77 vs 424), and Hodgkin lymphoma (HL; n= 835 vs 840) from the CCSS (diagnosed 1970-1999) who completed the Neurocognitive Questionnaire. Impairment was defined as a score >90% of normative data in task efficiency (TE), organization (Org), memory (Mem), and emotional regulation (ER) domains. 1,014 age-matched siblings were controls. Treatment by diagnosis group, chronic health conditions, health status and health behaviors were examined as risk factors for neurocognitive impairment using multivariable logistic regression. Adjusted odds ratios (ORs) and corresponding 95% CI are reported. Results: Prevalence of neurocognitive impairment (≥1 impaired domain) was similar for eAYAs and childhood survivors of HL (31.0% vs 29.6%, p=0.54) and AML (36.4% vs 40.3%, p=0.51), although eAYA AML survivors were more likely to have impaired Mem (OR=2.3, 95% CI 1.0-5.4). eAYA ALL survivors were less likely to have neurocognitive impairment than childhood ALL survivors (28.2% vs 38.5%, p<.001) due to lower risk for impaired TE (OR=0.7, 95% CI 0.4-1.0) and Org (OR=0.5, 95% CI 0.4-0.9). No factors, including cranial radiation (RT), explained the rate differences. Treatment by diagnosis group (including cranial RT in ALL, chest RT in HL, and salvage therapy use) was not consistently associated with neurocognitive impairment in eAYA survivors. However, anthracycline dose ≥120mg/m2 was a risk factor for impaired ER (OR=6.0, 95% CI 2.0-17.9) only in eAYA ALL survivors. Presence of a neurologic health condition was associated with impairment in all 4 domains in eAYA (ORs ranged 1.7-2.9) and childhood cancer survivors (ORs ranged 1.9-5.3). eAYA survivors with a respiratory condition were more likely to have impaired TE (OR=2.1, 95% CI 1.2-3.8). Being in good general health was associated with less impairment across all 4 domains for eAYA (ORs ranged 0.2-0.4) and childhood survivors (ORs ranged 0.3-0.5). eAYA survivors who never smoked were less likely to have impaired ER (OR=0.4, 95% CI 0.2-0.6) than those who smoke. Conclusions: Survivors of hematologic cancers diagnosed during eAYA are susceptible to neurocognitive impairment at rates similar to those diagnosed at younger ages. Having comorbidities and being in fair/poor general health are risk factors for impairment. Higher anthracycline exposure in ALL survivors diagnosed during eAYA was the only therapy associated with impairment rates.
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Mostoufi-Moab, Sogol, Kristy Seidel, Wendy M. Leisenring, Gregory T. Armstrong, Kevin C. Oeffinger, Marilyn Stovall, Lillian R. Meacham, et al. "Endocrine Abnormalities in Aging Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study." Journal of Clinical Oncology 34, no. 27 (September 20, 2016): 3240–47. http://dx.doi.org/10.1200/jco.2016.66.6545.
Full textAbstract:
Purpose The development of endocrinopathies in survivors of childhood cancer as they age remains understudied. We characterized endocrine outcomes in aging survivors from the Childhood Cancer Survivor Study on the basis of therapeutic exposures. Patients and Methods We analyzed self-reported conditions in 14,290 5-year survivors from the Childhood Cancer Survivor Study, with a median age 6 years (range, < 1 to 20 years) at diagnosis and 32 years (range, 5 to 58 years) at last follow-up. Identification of high-risk therapeutic exposures was adopted from the Children’s Oncology Group Long-Term Follow-Up Guidelines. Cumulative incidence curves and prevalence estimates quantified and regression models compared risks of primary hypothyroidism, hyperthyroidism, thyroid neoplasms, hypopituitarism, obesity, diabetes mellitus, or gonadal dysfunction between survivors and siblings. Results The cumulative incidence and prevalence of endocrine abnormalities increased across the lifespan of survivors (P < .01 for all). Risk was significantly higher in survivors exposed to high-risk therapies compared with survivors not so exposed for primary hypothyroidism (hazard ratio [HR], 6.6; 95% CI, 5.6 to 7.8), hyperthyroidism (HR, 1.8; 95% CI, 1.2 to 2.8), thyroid nodules (HR, 6.3; 95% CI, 5.2 to 7.5), thyroid cancer (HR, 9.2; 95% CI, 6.2 to 13.7), growth hormone deficiency (HR, 5.3; 95% CI, 4.3 to 6.4), obesity (relative risk, 1.8; 95% CI, 1.7 to 2.0), and diabetes mellitus (relative risk, 1.9; 95% CI, 1.6 to 2.4). Women exposed to high-risk therapies had six-fold increased risk for premature ovarian insufficiency (P < .001), and men demonstrated higher prevalence of testosterone replacement (P < .001) after cyclophosphamide equivalent dose of 20 g/m2 or greater or testicular irradiation with 20 Gy or greater. Survivors demonstrated an increased risk for all thyroid disorders and diabetes mellitus regardless of treatment exposures compared with siblings (P < .001 for all). Conclusion Endocrinopathies in survivors increased substantially over time, underscoring the need for lifelong subspecialty follow-up of those at risk.