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.
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
BACKGROUND:In patients with hormone receptor (HR)-positive early breast cancer (BC), the POSITIVE trial demonstrated that temporary interruption of adjuvant endocrine therapy (ET) for pregnancy is feasible and safe in early follow-up (median 41 months). In this article, we report updated results from a preplanned analysis with 2.5 years of additional follow-up. PATIENTS AND METHODS:POSITIVE, a single-arm prospective trial evaluating temporary interruption of adjuvant ET (after 18-30 months and for up to 2 years) to attempt pregnancy in young patients with BC, enrolled 518 eligible women (≤42 years of age, stage I-III BC, desiring pregnancy) from December 2014 to December 2019. Using the bootstrap-matching method, 5-year breast cancer-free interval (BCFI) and distant recurrence-free interval (DRFI) event rates were compared with those of the SOFT/TEXT trials as external controls. RESULTS:At a median follow-up of 71 months in the POSITIVE cohort and 80 months in the SOFT/TEXT cohort, the 5-year cumulative incidence of BCFI events was 12.3% in POSITIVE and 13.2% in SOFT/TEXT [-0.9% difference, 95% confidence interval (CI) -4.2% to 2.6%]. The 5-year cumulative incidence of DRFI events was 6.2% and 8.3%, respectively (-2.1% difference, 95% CI -4.5% to 0.4%). Among 497 women followed for nondisease outcomes, 377 (76%) had ≥1 documented pregnancy on trial, and 343 of 497 (69%) had ≥1 live birth, totaling 440 offspring. In an unadjusted analysis comparing the 180 women (36%) who had pre-enrollment embryo/oocyte cryopreservation with those who did not, the 5-year cumulative incidence of BCFI events was 14.0% (95% CI 9.6% to 20.2%) and 11.5% (95% CI 8.4% to 15.7%), respectively. CONCLUSION:Longer-term follow-up of the POSITIVE trial demonstrates that temporary interruption of ET for pregnancy, including use of fertility preservation, does not increase the risk of BC events. Continued follow-up is warranted given the known risk of late recurrence in this population.
