Late Health Outcomes Among Survivors of Wilms Tumor Diagnosed Over Three Decades: A Report From the Childhood Cancer Survivor Study.

2023

JCO2202111

01/2023

1527-7755

PURPOSE: To evaluate long-term morbidity and mortality among unilateral, nonsyndromic Wilms tumor (WT) survivors according to conventional treatment regimens.

METHODS: Cumulative incidence of late mortality (≥ 5 years from diagnosis) and chronic health conditions (CHCs) were evaluated in WT survivors from the Childhood Cancer Survivor Study. Outcomes were evaluated by treatment, including nephrectomy combined with vincristine and actinomycin D (VA), VA + doxorubicin + abdominal radiotherapy (VAD + ART), VAD + ART + whole lung radiotherapy, or receipt of ≥ 4 chemotherapy agents.

RESULTS: Among 2,008 unilateral WT survivors, 142 deaths occurred (standardized mortality ratio, 2.9, 95% CI, 2.5 to 3.5; 35-year cumulative incidence of death, 7.8%, 95% CI, 6.3 to 9.2). The 35-year cumulative incidence of any grade 3-5 CHC was 34.1% (95% CI, 30.7 to 37.5; rate ratio [RR] compared with siblings 3.0, 95% CI, 2.6 to 3.5). Survivors treated with VA alone had comparable risk for all-cause late mortality relative to the general population (standardized mortality ratio, 1.0; 95% CI, 0.5 to 1.7) and modestly increased risk for grade 3-5 CHCs compared with siblings (RR, 1.5; 95% CI, 1.1 to 2.0), but remained at increased risk for intestinal obstruction (RR, 9.4; 95% CI, 3.9 to 22.2) and kidney failure (RR, 11.9; 95% CI, 4.2 to 33.6). Magnitudes of risk for grade 3-5 CHCs, including intestinal obstruction, kidney failure, premature ovarian insufficiency, and heart failure, increased by treatment group intensity.

CONCLUSION: With approximately 40% of patients with newly diagnosed WT currently treated with VA alone, the burden of late mortality/morbidity in future decades is projected to be lower than that for survivors from earlier eras. Nevertheless, the risk of late effects such as intestinal obstruction and kidney failure was elevated across all treatment groups, and there was a dose-dependent increase in risk for all grade 3-5 CHCs by treatment group intensity.

10.1200/JCO.22.02111

J Clin Oncol

36693221

Predicting acute ovarian failure in female survivors of childhood cancer: a cohort study in the Childhood Cancer Survivor Study (CCSS) and the St Jude Lifetime Cohort (SJLIFE).

2020

2020 Feb 14

1474-5488

<p><strong>BACKGROUND: </strong>Cancer treatment can cause gonadal impairment. Acute ovarian failure is defined as the permanent loss of ovarian function within 5 years of cancer diagnosis. We aimed to develop and validate risk prediction tools to provide accurate clinical guidance for paediatric patients with cancer.</p>

<p><strong>METHODS: </strong>In this cohort study, prediction models of acute ovarian failure risk were developed using eligible female US and Canadian participants in the Childhood Cancer Survivor Study (CCSS) cohort and validated in the St Jude Lifetime Cohort (SJLIFE) Study. 5-year survivors from the CCSS cohort were included if they were at least 18 years old at their most recent follow-up and had complete treatment exposure and adequate menstrual history (including age at menarche, current menstrual status, age at last menstruation, and menopausal aetiology) information available. Participants in the SJLIFE cohort were at least 10-year survivors. Participants were excluded from the prediction analysis if they had an ovarian hormone deficiency, had missing exposure information, or had indeterminate ovarian status. The outcome of acute ovarian failure was defined as permanent loss of ovarian function within 5 years of cancer diagnosis or no menarche after cancer treatment by the age of 18 years. Logistic regression, random forest, and support vector machines were used as candidate methods to develop the risk prediction models in the CCSS cohort. Prediction performance was evaluated internally (in the CCSS cohort) and externally (in the SJLIFE cohort) using the areas under the receiver operating characteristic curve (AUC) and the precision-recall curve (average precision [AP; average positive predictive value]).</p>

<p><strong>FINDINGS: </strong>Data from the CCSS cohort were collected for participants followed up between Nov 3, 1992, and Nov 25, 2016, and from the SJLIFE cohort for participants followed up between Oct 17, 2007, and April 16, 2012. Of 11 336 female CCSS participants, 5886 (51·9%) met all inclusion criteria for analysis. 1644 participants were identified from the SJLIFE cohort, of whom 875 (53·2%) were eligible for analysis. 353 (6·0%) of analysed CCSS participants and 50 (5·7%) of analysed SJLIFE participants had acute ovarian failure. The overall median follow-up for the CCSS cohort was 23·9 years (IQR 20·4-27·9), and for SJLIFE it was 23·9 years (19·0-30·0). The three candidate methods (logistic regression, random forest, and support vector machines) yielded similar results, and a prescribed dose model with abdominal and pelvic radiation doses and an ovarian dose model with ovarian radiation dosimetry using logistic regression were selected. Common predictors in both models were history of haematopoietic stem-cell transplantation, cumulative alkylating drug dose, and an interaction between age at cancer diagnosis and haematopoietic stem-cell transplant. External validation of the model in the SJLIFE cohort produced an estimated AUC of 0·94 (95% CI 0·90-0·98) and AP of 0·68 (95% CI 0·53-0·81) for the ovarian dose model, and AUC of 0·96 (0·94-0·97) and AP of 0·46 (0·34-0·61) for the prescribed dose model. Based on these models, an online risk calculator has been developed for clinical use.</p>

<p><strong>INTERPRETATION: </strong>Both acute ovarian failure risk prediction models performed well. The ovarian dose model is preferred if ovarian radiation dosimetry is available. The models, along with the online risk calculator, could help clinical discussions regarding the need for fertility preservation interventions in girls and young women newly diagnosed with cancer.</p>

<p><strong>FUNDING: </strong>Canadian Institutes of Health Research, Women and Children's Health Research Institute, National Cancer Institute, and American Lebanese Syrian Associated Charities.</p>

10.1016/S1470-2045(19)30818-6

Lancet Oncol.

32066539

Radiation Dose and Volume to the Pancreas and Subsequent Risk of Diabetes Mellitus.

2019

2019 Jul 22

1460-2105

<p><strong>BACKGROUND: </strong>Childhood cancer survivors exposed to abdominal radiation (abdRT) are at increased risk for diabetes mellitus but the association between risk and radiation dose and volume is unclear.</p>

<p><strong>METHODS: </strong>Participants included 20,762 five-year survivors of childhood cancer (4,568 exposed to abdRT) and 4,853 siblings. For abdRT, we estimated maximum dose to abdomen, mean doses for whole pancreas, pancreatic head, body, tail, and percent pancreas volume receiving ≥10, ≥20, and ≥30Gy. Relative risks (RRs) were estimated with a Poisson model using generalized estimating equations, adjusted for attained age. All statistical tests were two-sided.</p>

<p><strong>RESULTS: </strong>Survivors exposed to abdRT (median age=31.6 years, range=10.2-58.3) were 2.92-fold more likely than siblings (95% confidence interval [CI]=2.02 to 4.23) and 1.60-times more likely than survivors not exposed to abdRT (95%CI=1.24 to 2.05) to develop diabetes. Among survivors treated with abdRT, greater attained age (RR(per 10 years)=2.11, 95%CI=1.70 to 2.62), higher body mass index (RR(BMI 30+)=5.00, 95%CI=3.19 to 7.83 with reference(BMI 18.5-24.9)), and increasing pancreatic tail dose were associated with increased diabetes risk in a multivariable model; an interaction was identified between younger age at cancer diagnosis and pancreatic tail dose with much higher diabetes risk associated with increasing pancreatic tail dose among those diagnosed at the youngest ages (p&lt;.001). Radiation dose and volume to other regions of the pancreas were not statistically significantly associated with risk.</p>

<p><strong>CONCLUSIONS: </strong>Among survivors treated with abdRT, diabetes risk was associated with higher pancreatic tail dose, especially at younger ages. Targeted interventions are needed to improve cardiometabolic health among those at highest risk.</p>

10.1093/jnci/djz152

J. Natl. Cancer Inst.

31329225