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

Abstract

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.

Prognostic impact of lymph node involvement and loss of heterozygosity of 1p or 16q in stage III favorable histology Wilms tumor: A report from Children’s Oncology Group Studies AREN03B2 and AREN0532

“…Historically, patients relapsing after DD4A have a 4-year EFS of 42.3%, 14 and therapy for survivors confers a significant risk of late effects in longterm survivors, such as cardiac and pulmonary toxicities, secondary malignancies, and infertility. 15 Assignment of these patients to more intensive therapy upfront confers some immediate risks, but these may be preferable compared with the increased risks of intensive therapy delivered at relapse. Intensification may be particularly warranted with respect to irinotecan because this is an active agent with minimal long-term toxicities.…”

“…Although the prognostic effects of LN and LOH status (alone or in combination) on OS were not statistically significant, there exists strong motivation to tailor therapy through better risk stratification with the goal to avoid the medical and psychological burdens of relapse on children with FHWT and their families. Historically, patients relapsing after DD4A have a 4‐year EFS of 42.3%, 14 and therapy for survivors confers a significant risk of late effects in long‐term survivors, such as cardiac and pulmonary toxicities, secondary malignancies, and infertility 15 . Assignment of these patients to more intensive therapy upfront confers some immediate risks, but these may be preferable compared with the increased risks of intensive therapy delivered at relapse.…”

Children's Oncology Group's 2023 blueprint for research: Renal tumors

“…Alongside a focus on cure, careful attention is being paid to survivorship issues. This includes focus on cardiac toxicity, renal function, secondary malignancy, and fertility preservation 12–16 . An additional emerging area of focus is better understanding the impact of social determinants of health on outcomes for children with renal tumors.…”

“…This includes focus on cardiac toxicity, renal function, secondary malignancy, and fertility preservation. [12][13][14][15][16] An additional emerging area of focus is better understanding the impact of social determinants of health on outcomes for children with renal tumors. Current data indicate that children with WT who suffer from more social deprivation, experience worse survival.…”

Late health outcome among survivors of Wilms tumor

“…It is a pleasure to write the editorial commentary on a landmark paper by Weil and colleagues recently published in the Journal of Clinical Oncology ( 1 ). The improvement in Wilms tumor (WT) survival, with 85–90% 5-year survivals, can be attributed to risk adjusted standardization of therapy based on protocols developed by the Children’s Oncology Group (COG) in the United States (USA) and SIOP (Societie International Oncology Pediatrique) in Europe over the last half century.…”