Abstract
PurposeChildhood cancer survivors are at increased risk of developing subsequent malignant neoplasms (SMNs). We compared survival and clinical characteristics of survivors with SMNs (sarcoma, breast cancer, or melanoma) and a population-based sample of similar first malignant neoplasm (FMN) patients.MethodsWe assembled three case series of solid SMNs observed in a cohort of 5-year Dutch childhood cancer survivors diagnosed 1963–2001 and followed until 2014: sarcoma (n = 45), female breast cancer (n = 41), and melanoma (n = 17). Each SMN patient was sex-, age-, and calendar year-matched to 10 FMN patients in the population-based Netherlands Cancer Registry. We compared clinical and histopathological characteristics by Fisher’s exact tests and survival by multivariable Cox regression and competing risk regression analyses.ResultsAmong sarcoma-SMN patients, overall survival [hazard ratio (HR) 1.88, 95% confidence interval (CI) 1.23–2.87] and sarcoma-specific mortality (HR 1.91, 95% CI 1.16–3.13) were significantly worse compared to sarcoma-FMN patients (foremost for soft-tissue sarcoma), with 15-year survival rates of 30.8% and 61.6%, respectively. Overall survival did not significantly differ for breast-SMN versus breast-FMN patients (HR 1.14, 95% CI 0.54–2.37), nor for melanoma-SMN versus melanoma-FMN patients (HR 0.71, 95% CI 0.10–5.00). No significant differences in tumor characteristics were observed between breast-SMN and breast-FMN patients. Breast-SMN patients were treated more often with mastectomy without radiotherapy/chemotherapy compared to breast-FMN patients (17.1% vs. 5.6%).ConclusionsSurvival of sarcoma-SMN patients is worse than sarcoma-FMN patients. Although survival and tumor characteristics appear similar for breast-SMN and breast-FMN patients, treatment differs; breast-SMN patients less often receive breast-conserving therapy. Larger studies are necessary to substantiate these exploratory findings.
Highlights
Survivors of childhood cancer are at increased risk of developing long-term health problems even decades after treatment [1,2,3,4]
In analyses per specific sarcoma morphology type, we found no difference in survival between osteosarcomaSMN and first malignant neoplasm (FMN) patients, but we found a statistically significant difference between synovial sarcoma Subsequent malignant neoplasms (SMNs) and FMN patients
Survival and characteristics of three types of solid SMNs from a large cohort of childhood cancer survivors were compared to FMNs of the same type in the general population
Summary
Survivors of childhood cancer are at increased risk of developing long-term health problems even decades after treatment [1,2,3,4]. Since the majority of these type of studies focused on breast-SMN, most were conducted in Hodgkin lymphoma or other adolescent and young adult (AYA) cancer survivors. We examined clinical characteristics, overall survival, and cause-specific survival of patients in the Dutch Childhood Cancer Oncology Group—Long-Term Effects After Childhood Cancer (DCOG-LATER) cohort who developed SMNs of sarcoma, breast, or melanoma and compared those outcomes with matched patients having similar FMNs in the general population, based on the Netherlands Cancer Registry (NCR). We hypothesized that survival of SMNs may be different from survival of FMNs for several reasons: earlier detection due to surveillance efforts among survivors (favorable), variability of tumor characteristics due to different pathogenesis (favorable or unfavorable), limited treatment options due to previous childhood cancer treatment (unfavorable), and a higher frequency of other potentially lethal long-term chronic health conditions (unfavorable)
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