Paediatric radiation therapy across Europe: A European questionnaire survey supported by the SIOPe, ESTRO, PROS and several national paediatric hematology-oncology societies (NAPHOS)

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Subsequent female breast cancer risk associated with anthracycline chemotherapy for childhood cancer.

Anthracycline-based chemotherapy is associated with increased subsequent breast cancer (SBC) risk in female childhood cancer survivors, but the current evidence is insufficient to support early breast cancer screening recommendations for survivors treated with anthracyclines. In this study, we pooled individual patient data of 17,903 survivors from six well-established studies, of whom 782 (4.4%) developed a SBC, and analyzed dose-dependent effects of individual anthracycline agents on developing SBC and interactions with chest radiotherapy. A dose-dependent increased SBC risk was seen for doxorubicin (hazard ratio (HR) per 100 mg m-2: 1.24, 95% confidence interval (CI): 1.18-1.31), with more than twofold increased risk for survivors treated with ≥200 mg m-2 cumulative doxorubicin dose versus no doxorubicin (HR: 2.50 for 200-299 mg m-2, HR: 2.33 for 300-399 mg m-2 and HR: 2.78 for ≥400 mg m-2). For daunorubicin, the associations were not statistically significant. Epirubicin was associated with increased SBC risk (yes/no, HR: 3.25, 95% CI: 1.59-6.63). For patients treated with or without chest irradiation, HRs per 100 mg m-2 of doxorubicin were 1.11 (95% CI: 1.02-1.21) and 1.26 (95% CI: 1.17-1.36), respectively. Our findings support that early initiation of SBC surveillance may be reasonable for survivors who received ≥200 mg m-2 cumulative doxorubicin dose and should be considered in SBC surveillance guidelines for survivors and future treatment protocols

Cohort profile: Risk and risk factors for female breast cancer after treatment for childhood and adolescent cancer: an internationally pooled cohort.

PURPOSE The International Consortium for Pooled Studies on Subsequent Malignancies after Childhood and Adolescent Cancer was established in 2018 to address gaps in knowledge of risk and risk factors for breast cancer subsequent to childhood/adolescent cancer by pooling individual patient data from seven cohorts. Initially, the pooled cohort will focus on three clinically relevant questions regarding treatment-related subsequent breast cancer risk in female survivors, which are the risk related to low-dose radiotherapy exposure to the chest, specific chemotherapy agents and attained age. PARTICIPANTS The consortium database includes pooled data on 21 892 female survivors from seven cohorts in North America and Europe with a primary cancer diagnosis at <21 years of age, and survival ≥5 years from diagnosis. FINDINGS TO DATE This is a newly established pooled study. The cohort profile summarised the data collected from each included cohort, including childhood cancer diagnosis information and treatment details (ie, radiotherapy fields and cumulative doses, and chemotherapy agents and cumulative doses for each agent). Included cohorts' follow-up started 1951-1981 and ended 2013-2021, respectively, for a median follow-up duration of 24.3 (IQR 18.0-32.8) years since primary cancer diagnosis. The median age at primary cancer diagnosis was 5.4 (IQR 2.5-11.9) years. And the median attained age at last follow-up was 32.2 (IQR 24.0-40.4) years. In all, 4240 (19.4%) survivors were treated with radiotherapy to the chest and 9308 (42.5%) with anthracyclines. At the end of the follow-up, 835 females developed a first subsequent breast cancer, including 635 invasive breast cancer only, 184 carcinomas in situ only (172 ductal carcinomas in situ and 12 lobular carcinomas in situ), and 16 with both an invasive and in situ diagnosis at the same moment. The cumulative incidences of subsequent breast cancer (both invasive and in situ) 25 and 35 years after primary cancer diagnosis were 2.2% and 6.2%, respectively. FUTURE PLANS The consortium is intended to serve as a model and robust source of childhood/adolescent cancer survivor data for elucidating other knowledge gaps on subsequent breast cancer risk, and risk of other subsequent malignancies (including data on males) in the future

Risk of Renal or Urinary Related Hospitalization in Survivors of Childhood Cancer: Results from the French Childhood Cancer Survivor Study

International audienceBACKGROUND: Hospitalization rates can be used as an indirect indicator of the burden and severity of adverse health outcomes in childhood cancer survivors (CCS). We aimed to determine the long-term risks of hospitalization related to renal and urinary diseases among 5-year CCS. METHODS: The French Childhood Cancer Survivor Study cohort was linked with data from the French National Healthcare System database, which enabled the identification of hospitalizations related to renal or urinary diseases. Clinical and detailed treatment data were collected from medical records. Dose-volume histograms were estimated for all patients treated with radiotherapy. Standardized Hospitalization Ratios and absolute excess risks (AER) were calculated. Relative risks were estimated using Poisson regression. RESULTS: A total of 5,498 survivors were followed for 42,118 person-years (PY). Survivors experience 2.9 times more renal hospitalizations than expected in the general population, with an AER of 21.2/10,000 PY. Exposing more than 10% of the kidneys' volume to at least 20 Gray increases the risk of being hospitalized for renal causes by 2.2 (95% confidence interval, 1.3-3.6). Nephrectomized survivors treated with high doses of ifosfamide (>60 g/m²) have an extremely high risk of hospitalization for renal causes. Patients with comorbidities have about a 3-fold higher risk, and nephrectomized patients a 2-fold higher risk of being hospitalized for renal causes compared with other subjects. In the case of hospitalization for urinary causes, treatment by anthracycline administration was found to be associated with an almost 2-fold higher risk of hospitalization compared with the general population. CONCLUSIONS: These results support the need for careful monitoring of long-term renal diseases in survivors who have undergone nephrectomy, those treated with high doses of radiation (≥20 Gy) even to small volumes of the kidneys, and those with predisposing risk factors. IMPACT: This study provides new evidence with potential impact on surveillance guidelines related to dose-volume indicators associated with renal toxicity