SummaryBackgroundConcurrent chemoradiotherapy is the standard of care in limited-stage small-cell lung cancer, but the optimal radiotherapy schedule and dose remains controversial. The aim of this study was to establish a standard chemoradiotherapy treatment regimen in limited-stage small-cell lung cancer.MethodsThe CONVERT trial was an open-label, phase 3, randomised superiority trial. We enrolled adult patients (aged ≥18 years) who had cytologically or histologically confirmed limited-stage small-cell lung cancer, Eastern Cooperative Oncology Group performance status of 0–2, and adequate pulmonary function. Patients were recruited from 73 centres in eight countries. Patients were randomly assigned to receive either 45 Gy radiotherapy in 30 twice-daily fractions of 1·5 Gy over 19 days, or 66 Gy in 33 once-daily fractions of 2 Gy over 45 days, starting on day 22 after commencing cisplatin–etoposide chemotherapy (given as four to six cycles every 3 weeks in both groups). The allocation method used was minimisation with a random element, stratified by institution, planned number of chemotherapy cycles, and performance status. Treatment group assignments were not masked. The primary endpoint was overall survival, defined as time from randomisation until death from any cause, analysed by modified intention-to-treat. A 12% higher overall survival at 2 years in the once-daily group versus the twice-daily group was considered to be clinically significant to show superiority of the once-daily regimen. The study is registered with ClinicalTrials.gov (NCT00433563) and is currently in follow-up.FindingsBetween April 7, 2008, and Nov 29, 2013, 547 patients were enrolled and randomly assigned to receive twice-daily concurrent chemoradiotherapy (274 patients) or once-daily concurrent chemoradiotherapy (273 patients). Four patients (one in the twice-daily group and three in the once-daily group) did not return their case report forms and were lost to follow-up; these patients were not included in our analyses. At a median follow-up of 45 months (IQR 35–58), median overall survival was 30 months (95% CI 24–34) in the twice-daily group versus 25 months (21–31) in the once-daily group (hazard ratio for death in the once daily group 1·18 [95% CI 0·95–1·45]; p=0·14). 2-year overall survival was 56% (95% CI 50–62) in the twice-daily group and 51% (45–57) in the once-daily group (absolute difference between the treatment groups 5·3% [95% CI −3·2% to 13·7%]). The most common grade 3–4 adverse event in patients evaluated for chemotherapy toxicity was neutropenia (197 [74%] of 266 patients in the twice-daily group vs 170 [65%] of 263 in the once-daily group). Most toxicities were similar between the groups, except there was significantly more grade 4 neutropenia with twice-daily radiotherapy (129 [49%] vs 101 [38%]; p=0·05). In patients assessed for radiotherapy toxicity, was no difference in grade 3–4 oesophagitis between the groups (47 [19%] of 254 patients in the twice-daily group vs 47 [19%] of 246 in the once-daily group; p=0·85) an...

Purpose: The uptake of risk-reducing surgery in women at increased risk of breast and ovarian cancer is highly variable between countries and centers within countries. We have investigated the rate, timing, and age of uptake of surgery in the northwest of England to report the results after up to 7 years in a Regional Genetics center. Methods: Uptake was documented in 211 known unaffected BRCA1/2 mutation carriers from 509 families and in 3,515 women at >25% lifetime risk of breast cancer without known mutations. Results: Of the 211 mutation carriers, 40% opted for bilateral risk-reducing mastectomy (BRRM) and 45% underwent bilateral risk-reducing salpingo-oophorectomy (BRRSPO). Uptake of BRRM was significantly related to lifetime risk and age but continued over several years. In women not known to carry a BRCA mutation, 6.4% of women at 40% to 45% lifetime risk, 2.5% of women at 33% to 39% lifetime risk, and 1.8% of women at 25% to 32% lifetime risk underwent BRRM (P < 0.005). BRRSPO uptake was greater in BRCA1 (52%) than BRCA2 (28%) carriers but in both groups tended to occur within the first 2 years after gene test (except in the youngest age group) and in women between the ages of 35 and 45. Conclusion: To truly assess the uptake of risk-reducing surgery, longer-term follow-up is necessary particularly in younger women who are likely to delay BRRSPO. Careful risk counseling does seem to influence women's decisions for surgery, although the effect is not immediate. (Cancer Epidemiol Biomarkers Prev 2009;18(8): 2318-24)