Radiation dose and volume to the pancreas and subsequent risk of diabetes mellitus: A report from the Childhood Cancer Survivor study.

Purpose This study was undertaken to determine the effect of treatment for childhood cancer on male fertility. Patients and Methods We reviewed the fertility of male Childhood Cancer Survivor Study survivor and sibling cohorts who completed a questionnaire. We abstracted the chemotherapeutic agents administered, the cumulative dose of drug administered for selected drugs, and the doses and volumes of all radiation therapy from medical records. Risk factors for siring a pregnancy were evaluated using Cox proportional hazards models. Results The 6,224 survivors age 15 to 44 years who were not surgically sterile were less likely to sire a pregnancy than siblings (hazard ratio [HR], 0.56; 95% CI, −0.49 to 0.63). Among survivors, the HR of siring a pregnancy was decreased by radiation therapy of more than 7.5 Gy to the testes (HR, 0.12; 95% CI, −0.02 to 0.64), higher cumulative alkylating agent dose (AAD) score or treatment with cyclophosphamide (third tertile HR, 0.42; 95% CI, −0.31 to 0.57) or procarbazine (second tertile HR, 0.48; 95% CI, −0.26 to 0.87; third tertile HR, 0.17; 95% CI, −0.07 to 0.41). Compared with siblings, the HR for ever siring a pregnancy for survivors who had an AAD score = 0, a hypothalamic/pituitary radiation dose = 0 Gy, and a testes radiation dose = 0 Gy was 0.91 (95% CI, 0.73 to 1.14; P = .41). Conclusion This large study identified risk factors for decreased fertility that may be used for counseling male cancer patients.

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Congenital Anomalies in the Children of Cancer Survivors: A Report From the Childhood Cancer Survivor Study

Journal of Clinical Oncology ◽

10.1200/jco.2011.37.2938 ◽

2012 ◽

Vol 30 (3) ◽

pp. 239-245 ◽

Cited By ~ 93

Author(s):

Lisa B. Signorello ◽

John J. Mulvihill ◽

Daniel M. Green ◽

Heather M. Munro ◽

Marilyn Stovall ◽

...

Keyword(s):

Radiation Dose ◽

Cancer Survivors ◽

Childhood Cancer ◽

Cancer Survivor ◽

Congenital Anomalies ◽

Alkylating Agents ◽

Childhood Cancer Survivor ◽

Individual Treatment ◽

Increased Risk ◽

Childhood Cancer Survivor Study

Purpose Children with cancer receive mutagenic treatments, which raises concern about the potential transmissibility of germline damage to their offspring. This question has been inadequately studied to date because of a lack of detailed individual treatment exposure assessment such as gonadal radiation doses. Methods Within the Childhood Cancer Survivor Study, we performed a retrospective cohort analysis of validated cases of congenital anomalies among 4,699 children of 1,128 male and 1,627 female childhood cancer survivors. We quantified chemotherapy with alkylating agents and radiotherapy doses to the testes and ovaries and related these exposures to risk of congenital anomalies using logistic regression. Results One hundred twenty-nine children had at least one anomaly (prevalence = 2.7%). For children whose mothers were exposed to radiation or alkylating agents versus neither, the prevalence of anomalies was 3.0% versus 3.5% (P = .51); corresponding figures were 1.9% versus 1.7% (P = .79) for the children of male survivors. Neither ovarian radiation dose (mean, 1.19 Gy; odds ratio [OR] = 0.59; 95% CI, 0.20 to 1.75 for 2.50+ Gy) nor testicular radiation dose (mean, 0.48 Gy; OR = 1.01; 95% CI, 0.36 to 2.83 for 0.50+ Gy) was related to risk of congenital anomalies. Treatment with alkylating agents also was not significantly associated with anomalies in the children of male or female survivors. Conclusion Our findings offer strong evidence that the children of cancer survivors are not at significantly increased risk for congenital anomalies stemming from their parent's exposure to mutagenic cancer treatments. This information is important for counseling cancer survivors planning to have children.

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Fertility of Female Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study

Journal of Clinical Oncology ◽

10.1200/jco.2008.20.1541 ◽

2009 ◽

Vol 27 (16) ◽

pp. 2677-2685 ◽

Cited By ~ 314

Author(s):

Daniel M. Green ◽

Toana Kawashima ◽

Marilyn Stovall ◽

Wendy Leisenring ◽

Charles A. Sklar ◽

...

Keyword(s):

Radiation Dose ◽

Childhood Cancer ◽

Cancer Survivor ◽

Medical Records ◽

Chemotherapeutic Agents ◽

Childhood Cancer Survivor ◽

Multivariate Models ◽

Female Survivors ◽

Childhood Cancer Survivor Study ◽

Survivors Of Childhood Cancer

Purpose This study was undertaken to determine the effect, if any, of treatment for cancer diagnosed during childhood or adolescence on fertility. Patients and Methods We reviewed the fertility of female participants in the Childhood Cancer Survivor Study (CCSS), which consisted of 5-year survivors, and a cohort of randomly selected siblings who responded to a questionnaire. Medical records of all members of the cohort were abstracted to obtain chemotherapeutic agents administered; the cumulative dose of drug administered for several drugs of interest; and the doses, volumes, and dates of administration of all radiation therapy. Results There were 5,149 female CCSS participants, and there were 1,441 female siblings of CCSS participants who were age 15 to 44 years. The relative risk (RR) for survivors of ever being pregnant was 0.81 (95% CI, 0.73 to 0.90; P < .001) compared with female siblings. In multivariate models among survivors only, those who received a hypothalamic/pituitary radiation dose ≥ 30 Gy (RR, 0.61; 95% CI, 0.44 to 0.83) or an ovarian/uterine radiation dose greater than 5 Gy were less likely to have ever been pregnant (RR, 0.56 for 5 to 10 Gy; 95% CI, 0.37 to 0.85; RR, 0.18 for > 10 Gy; 95% CI, 0.13 to 0.26). Those with a summed alkylating agent dose (AAD) score of three or four or who were treated with lomustine or cyclophosphamide were less likely to have ever been pregnant. Conclusion This large study demonstrated that fertility is decreased among female CCSS participants. The risk factors identified may be utilized for pretreatment counseling of patients and their parents.

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Comparison of Radiation Dose Reconstruction Methods to Investigate Late Adverse Effects of Radiotherapy for Childhood Cancer: A Report from the Childhood Cancer Survivor Study

Radiation Research ◽

10.1667/rr15308.1 ◽

2019 ◽

Vol 193 (2) ◽

pp. 95

Author(s):

Sara J. Schonfeld ◽

Rebecca M. Howell ◽

Susan A. Smith ◽

Joseph P. Neglia ◽

Lucie M. Turcotte ◽

...

Keyword(s):

Radiation Dose ◽

Adverse Effects ◽

Childhood Cancer ◽

Cancer Survivor ◽

Childhood Cancer Survivor ◽

Dose Reconstruction ◽

Reconstruction Methods ◽

Late Adverse Effects ◽

Childhood Cancer Survivor Study

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Endocrine Abnormalities in Aging Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study

Journal of Clinical Oncology ◽

10.1200/jco.2016.66.6545 ◽

2016 ◽

Vol 34 (27) ◽

pp. 3240-3247 ◽

Cited By ~ 60

Author(s):

Sogol Mostoufi-Moab ◽

Kristy Seidel ◽

Wendy M. Leisenring ◽

Gregory T. Armstrong ◽

Kevin C. Oeffinger ◽

...

Keyword(s):

Diabetes Mellitus ◽

High Risk ◽

Childhood Cancer ◽

Cancer Survivor ◽

Primary Hypothyroidism ◽

Childhood Cancer Survivor ◽

Increased Risk ◽

Childhood Cancer Survivor Study ◽

Survivors Of Childhood Cancer

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.

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