OBJECTIVE:Despite their established clinical benefits, breast cancer screening examinations expose women to ionizing radiation (IR) and call for vigilance regarding protocols and practices. This study estimates the population attributable risk (PAR) of radiation-induced breast cancer in France in 2019 that is attributable to past exposure to IR through screening performed in women aged 40 to 74 years old. METHODS:Breast cancer screening practices were reconstituted for the period 1980 to 2019. Records of recent years were built based on French National Health Data System. An estimation was made for earlier years based on the available literature and expert knowledge. Women diagnosed with a history of breast cancer before mammography were excluded. Absorbed glandular doses to the breast were modeled based on existing literature and reports on French practices. Excess breast cancer cases were estimated using 2 radiation-risk models (Biologic Effects of Ionizing Radiation VII and the International Commission on Radiological Protection). RESULTS:Of roughly 55 000 new breast cancer cases diagnosed in 2019 in women at least 40 years old, we estimate that approximately 27 might be attributable to past exposures to IR associated with breast cancer screening between the ages of 50 and 74 years. This leads to a PAR of 0.048%. In addition, about 16 cases might be attributable to screening between ages 40 and 49 years, with a PAR of approximately 0.030%. CONCLUSION:The contribution of breast cancer screening to the breast cancer burden in France is limited. Efforts to limit the dose delivered to the breast must continue.
BACKGROUND:Hypofractionated radiotherapy is standard for whole-breast radiotherapy, but 50 Gy in 25 fractions (5-week radiotherapy) is still standard in many countries when nodal radiotherapy is needed for morbidity concerns. The UNICANCER HypoG-01 trial aimed to assess morbidity and efficacy of hypofractionated locoregional radiotherapy delivering 40 Gy in 15 fractions (3-week radiotherapy) versus 5-week radiotherapy. METHODS:This non-inferiority, open-label, multicentre, randomised phase 3 trial, conducted in 29 centres in France, included female patients 18 years and older, with invasive breast carcinoma requiring nodal irradiation after complete microscopic resection of the primary tumour. Patients were randomly allocated in a 1:1 ratio to either 3-week radiotherapy (experimental group) or 5-week radiotherapy (control group) to the regional nodes and thoracic wall or breast. The primary endpoint was ipsilateral arm lymphoedema, defined as a 10% or greater increase in arm circumference at 15 cm proximal, 10 cm distal, or both, to the ipsilateral olecranon relative to baseline and contralateral arm, with a non-inferiority margin on the hazard ratio (HR) of 1·545. This trial was registered at ClinicalTrials.gov (NCT03127995) and is closed to recruitment. FINDINGS:Between Sept 26, 2016, and March 27, 2020, 1265 patients were enrolled, and 1221 were included in per-protocol analysis (median follow-up 4·8 years [IQR 4·01-5·02]), 614 assigned to 3-week radiotherapy and 607 to 5-week radiotherapy. The median age was 58 years (IQR 49-68). Arm lymphoedema occurred in 275 (25%) patients (143 with 3-week radiotherapy and 132 with 5-week radiotherapy). 3-week radiotherapy was non-inferior to 5-week radiotherapy regarding arm lymphoedema risk (HR 1·02 [95% CI 0·79-1·31] pnon-inferiority<0·001), with a 3-year cumulative incidence of 23·4% (95% CI 19·7-27·6) and 22·2% (95% CI 19·5-26·3), respectively. Safety profiles were similar between groups; grade 3 or worse adverse events frequencies were 8% and 13%, respectively. Following French regulation, data on race and ethnicity were not collected. INTERPRETATION:3-week radiotherapy (40 Gy in 15 fractions) was found to be non-inferior to 5-week radiotherapy (50 Gy in 25 fractions) for arm lymphoedema risk and was comparably safe regarding other late normal tissue effects for patients prescribed locoregional radiotherapy for early-breast cancer. FUNDING:French National Cancer Institute.
PURPOSE:There is no standard second-line therapy for gastroenteropancreatic (GEP) and lung large-cell neuroendocrine carcinoma (NEC) after the failure of platinum-based chemotherapy. This study aimed to investigate the efficacy of nivolumab ± ipilimumab. METHODS:The GCO-001-NIPINEC (ClinicalTrials.gov identifier: NCT03591731) trial was a noncomparative, open-label, phase II trial. The main inclusion criteria were age ≥18 years, performance status (PS) ≤2, advanced large- and small-cell GEP-NEC and large-cell lung NEC, and second- or third-line treatment for NECs refractory to platinum-based chemotherapy. Patients were randomly assigned (1:1) and stratified by age and PS to receive nivolumab (3 mg/kg/once every 2 weeks) ± ipilimumab (1 mg/kg/once every 6 weeks) for 2 years or until progression or unacceptable toxicity. The primary end point was objective response rate (ORR) at 8 weeks, assessed by investigators. RESULTS:A total of 185 patients (91 in the nivolumab arm and 94 in the nivolumab-ipilimumab arm) were enrolled between December 2018 and March 2021; 169 were analyzed (median age of 64.5 years, 71% male, 91% PS 0-1). The main primary tumor locations were lungs (50%), colorectal (15%), gastroesophageal (14%), and pancreatic (13%) regions. The ORR at 8 weeks was 7.2% (95% CI, 2.7 to 15.1]) in the nivolumab arm and 14.0% (95% CI, 7.4 to 23.1) in the nivolumab-ipilimumab arm. The best ORR was 9.6% and 20.9%, respectively, whereas the median progression-free and overall survival were approximately 2 months and 6 months in both arms. One treatment-related death occurred, in the nivolumab arm. The grade 3-4 adverse events (≥5%) were asthenia (13%), gamma-glutamyl transferase increase (10%), alkaline phosphatase increase (9%), dyspnea (7%), and anemia (6%) in the nivolumab-ipilimumab arm. CONCLUSION:Nivolumab-ipilimumab could be a second-/third-line treatment option for patients with NECs. However, given the limited magnitude of benefit, studies are warranted to evaluate its use earlier and/or associated with chemotherapy.
Stereotactic radiotherapy (SRT), including stereotactic radiosurgery (SRS) and hypofractionated stereotactic radiotherapy (hfSRT), plays a key role in the management of brain metastases (BM). As advances in systemic therapies prolong survival, local recurrence of BM has become more frequent, prompting interest in salvage reirradiation strategies. This systematic review aimed to evaluate the efficacy and safety of a second course of stereotactic radiotherapy (SRT2) for in-field recurrent brain metastases. Data on local control, overall survival, and radionecrosis were extracted and pooled using random-effects models. Eleven retrospective studies published between 2020 and 2025 were included, comprising 914 patients and 2,352 brain metastases, with 389 lesions treated with salvage SRS2/SRT2. Patients who had received prior whole-brain radiotherapy were excluded. The pooled 1-year local failure rate was 24
