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A randomized trial compared standard chemotherapy plus dostarlimab or placebo. Patients with mismatch repair–deficient tumors had 2-year progression-free survival of 61.4% with dostarlimab and 15.7% with placebo.

Among patients with endoscopically resected early gastric cancers who were infected with Helicobacter pylori , the incidence of metachronous gastric cancer was 50% lower among those who received active treatment with antibiotics than among controls.

Whole breast irradiation (WBI) after conservative surgery for ductal carcinoma in situ (DCIS) reduces local recurrence. We investigated whether a tumour bed boost after WBI improved outcomes, and examined radiation dose fractionation sensitivity for non-low-risk DCIS. The study was an international, randomised, unmasked, phase 3 trial involving 136 participating centres of six clinical trials organisations in 11 countries (Australia, New Zealand, Singapore, Canada, the Netherlands, Belgium, France, Switzerland, Italy, Ireland, and the UK). Eligible patients were women aged 18 years or older with unilateral, histologically proven, non-low-risk DCIS treated by breast-conserving surgery with at least 1 mm of clear radial resection margins. They were assigned to one of four groups (1:1:1:1) of no tumour bed boost versus boost after conventional versus hypofractionated WBI, or randomly assigned to one of two groups (1:1) of no boost versus boost after each centre prespecified conventional or hypofractionated WBI. The conventional WBI used was 50 Gy in 25 fractions, and hypofractionated WBI was 42·5 Gy in 16 fractions. A boost dose of 16 Gy in eight fractions, if allocated, was delivered after WBI. Patients and clinicians were not masked to treatment allocation. The primary endpoint was time to local recurrence. This trial is registered with ClinicalTrials.gov (NCT00470236). Between June 25, 2007, and June 30, 2014, 1608 patients were randomly assigned to have no boost (805 patients) or boost (803 patients). Conventional WBI was given to 831 patients, and hypofractionated WBI was given to 777 patients. Median follow-up was 6·6 years. The 5-year free-from-local-recurrence rates were 92·7% (95% CI 90·6–94·4%) in the no-boost group and 97·1% (95·6–98·1%) in the boost group (hazard ratio 0·47; 0·31–0·72; p<0·001). The boost group had higher rates of grade 2 or higher breast pain (10% [8–12%] vs 14% [12–17%], p=0·003) and induration (6% [5–8%] vs 14% [11–16%], p<0·001). In patients with resected non-low-risk DCIS, a tumour bed boost after WBI reduced local recurrence with an increase in grade 2 or greater toxicity. The results provide the first randomised trial data to support the use of boost radiation after postoperative WBI in these patients to improve local control. The international scale of the study supports the generalisability of the results. National Health and Medical Research Council of Australia, Susan G Komen for the Cure, Breast Cancer Now, OncoSuisse, Dutch Cancer Society, Canadian Cancer Trials Group.

Biomarkers to improve the risk–benefit of extended adjuvant endocrine therapy for late recurrence in patients with oestrogen-receptor-positive breast cancer would be clinically valuable. We compared the prognostic ability of the breast-cancer index (BCI) assay, 21-gene recurrence score (Oncotype DX), and an immunohistochemical prognostic model (IHC4) for both early and late recurrence in patients with oestrogen-receptor-positive, node-negative (N0) disease who took part in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) clinical trial. In this prospective comparison study, we obtained archival tumour blocks from the TransATAC tissue bank from all postmenopausal patients with oestrogen-receptor-positive breast cancer from whom the 21-gene recurrence score and IHC4 values had already been derived. We did BCI analysis in matched samples with sufficient residual RNA using two BCI models—cubic (BCI-C) and linear (BCI-L)—using previously validated cutoffs. We assessed prognostic ability of BCI for distant recurrence over 10 years (the primary endpoint) and compared it with that of the 21-gene recurrence score and IHC4. We also tested the ability of the assays to predict early (0–5 years) and late (5–10 years) distant recurrence. To assess the ability of the biomarkers to predict recurrence beyond standard clinicopathological variables, we calculated the change in the likelihood-ratio χ2 (LR-Δχ2) from Cox proportional hazards models. Suitable tissue was available from 665 patients with oestrogen-receptor-positive, N0 breast cancer for BCI analysis. The primary analysis showed significant differences in risk of distant recurrence over 10 years in the categorical BCI-C risk groups (p<0·0001) with 6·8% (95% CI 4·4–10·0) of patients in the low-risk group, 17·3% (12·0–24·7) in the intermediate group, and 22·2% (15·3–31·5) in the high-risk group having distant recurrence. The secondary analysis showed that BCI-L was a much stronger predictor for overall (0–10 year) distant recurrence compared with BCI-C (interquartile HR 2·30 [95% CI 1·62–3·27]; LR-Δχ2=22·69; p<0·0001). When compared with BCI-L, the 21-gene recurrence score was less predictive (HR 1·48 [95% CI 1·22–1·78]; LR-Δχ2=13·68; p=0·0002) and IHC4 was similar (HR 1·69 [95% CI 1·51–2·56]; LR-Δχ2=22·83; p<0·0001). All further analyses were done with the BCI-L model. In a multivariable analysis, all assays had significant prognostic ability for early distant recurrence (BCI-L HR 2·77 [95% CI 1·63–4·70], LR-Δχ2=15·42, p<0·0001; 21-gene recurrence score HR 1·80 [1·42–2·29], LR-Δχ2=18·48, p<0·0001; IHC4 HR 2·90 [2·01–4·18], LR-Δχ2=29·14, p<0·0001); however, only BCI-L was significant for late distant recurrence (BCI-L HR 1·95 [95% CI 1·22–3·14], LR-Δχ2=7·97, p=0·0048; 21-gene recurrence score HR 1·13 [0·82–1·56], LR-Δχ2=0·48, p=0·47; IHC4 HR 1·30 [0·88–1·94], LR-Δχ2=1·59, p=0·20). BCI-L was the only significant prognostic test for risk of both early and late distant recurrence and identified two risk populations for each timeframe. It could help to identify patients at high risk for late distant recurrence who might benefit from extended endocrine or other therapy. Avon Foundation, National Institutes of Health, Breast Cancer Foundation, US Department of Defense Breast Cancer Research Program, Susan G Komen for the Cure, Breakthrough Breast Cancer through the Mary-Jean Mitchell Green Foundation, AstraZeneca, Cancer Research UK, and the National Institute for Health Research Biomedical Research Centre at the Royal Marsden (London, UK).

BackgroundThis trial investigated the hypothesis that the treatment with trabectedin/PLD (TP) to extend the platinum-free interval (TFIp) can improve overall survival (OS) in patients with recurrent ovarian cancer (OC).MethodsPatients with OC (up to two previous platinum-based lines), with a TFIp of 6–12 months, were randomised to receive carboplatin/PLD (CP) or TP followed by platinum therapy at relapse. The primary endpoint was OS (HR: 0.75).ResultsThe study enrolled 617 patients. The median TFIp was 8.3 months and 30.3% of patients had received two previous platinum lines. 74% and 73.9% of patients, respectively, received a subsequent therapy (ST) in the CP and TP arm; in the latter TP arm 87.2% of ST was platinum-based, as per protocol. The median OS was 21.4 for CP and 21.9 months for TP (HR 1.13; 95% CI: 0.94–1.35; p = 0.197). Grade 3–5 adverse reactions occurred in 37.1% of patients in the CP arm and 69.7% of patients in the TP arm, and the most frequent were neutropenia (22.8% CP, 39.5% TP), gastrointestinal (7.1% CP, 17.4% TP), hepatic (0.7% CP, 19.1% TP).ConclusionsThis study did not meet the primary endpoint. CP combination remains the standard for patients with recurrent OC and a 6–12 months TFIp; TP is an effective treatment in patients suffering from persistent platinum toxicities.Clinical trial registrationClinicalTrials.gov, number NCT01379989.

Background Folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) or modified FOLFIRINOX (mFFX) is the first-line standard of care for metastatic pancreatic adenocarcinoma; effective and safe treatment strategies are needed as survival remains poor. Sintilimab, a human immunoglobulin G4 monoclonal antibody for programmed cell death-1, has shown efficacy in various cancers. We evaluated the efficacy and safety of sintilimab with mFFX for metastatic/recurrent pancreatic ductal adenocarcinoma in China. Patients and Methods This was a single-center, randomized, controlled, open-label phase II study. Patients were assigned 1:1 to sintilimab + mFFX or mFFX ( n = 55, each). Results In the intention-to-treat population, median overall survivals (primary endpoint) were similar in the sintilimab + mFFX and mFFX groups: 10.9 and 10.8 months, respectively [hazard ratio (HR) 1.07, 95% confidence interval (CI) 0.69–1.68]. The objective response rate was higher [50.0% (95% CI 34.6–65.4%) versus 23.9% (95% CI 11.1–36.7%)] in the sintilimab + mFFX group ( P < 0.05). Median (HR, 95% CI) progression-free survival and disease control rates (95% CI) were also similar at 5.9 and 5.7 months (0.93, 0.62–1.40), and 84.1% (72.8–95.3%) and 71.7%, (58.2–85.3%), respectively. Incidences of grade ≥ 3 treatment-emergent adverse events were 84.9% (45/53) and 74.1% (40/54), and that of grade ≥ 3 immune-related adverse events were 5.7% (3/53) and 0 in each group, respectively. Conclusions The study did not meet its primary endpoint, no clear survival benefit was observed, and the benefit of sintilimab + mFFX for advanced pancreatic cancer was not supported; however, the findings suggest that using this regimen for pancreatic cancer is feasible, has an acceptable safety profile, and leads to an objective response rate of 50%. Trial registration ClinicalTrials.Gov; NCT03977272

Background The minimally invasive esophagectomy (MIE) is widely being implemented for esophageal cancer in order to reduce morbidity and improve quality of life. Non-randomized studies investigating the mid-term quality of life after MIE show conflicting results at 1-year follow-up. Therefore, the aim of this study is to determine whether MIE has a continuing better mid-term 1-year quality of life than open esophagectomy (OE) indicating both a faster recovery and less procedure-related symptoms. Methods A one-year follow-up analysis of the quality of life was conducted for patients participating in the randomized trial in which MIE was compared with OE. Late complications as symptomatic stenosis of anastomosis are also reported. Results Quality of life at 1 year was better in the MIE group than in the OE group for the physical component summary SF36 [50 (6; 48–53) versus 45 (9; 42–48) p .003]; global health C30 [79 (10; 76–83) versus 67 (21; 60–75) p .004]; and pain OES18 module [6 (9; 2–8) versus 16 (16; 10–22) p .001], respectively. Twenty six patients (44 %) in the MIE and 22 patients (39 %) in the OE group were diagnosed and treated for symptomatic stenosis of the anastomosis. Conclusions This first randomized trial shows that MIE is associated with a better mid-term one-year quality of life compared to OE.

Background It has been suggested that selective sentinel node (SN) biopsy alone can be used to manage early breast cancer, but definite evidence to support this notion is lacking. The aim of this study was to investigate whether refraining from completion axillary lymph node dissection (ALND) suffices to produce the same prognostic information and disease control as proceeding with completion ALND in early breast cancer patients showing micrometastasis at SN biopsy. Methods This prospective, randomized clinical trial included patients with newly diagnosed early-stage breast cancer ( T  < 3.5 cm, clinical N0, M0) who underwent surgical excision as primary treatment. All had micrometastatic SN. Patients were randomly assigned to one of the two study arms: complete ALND (control arm) or clinical follow-up (experimental arm). Median follow-up was 5 years, recurrence was assessed, and the primary end point was disease-free survival. Results From a total sample of 247 patients, 14 withdrew, leaving 112 in the control arm and 121 in the experimental arm. In 15 control subjects (13 %), completion ALND was positive, with a low tumor burden. Four patients experienced disease recurrence: 1 (1 %) of 108 control subjects and 3 (2.5 %) of 119 experimental patients. There were no differences in disease-free survival ( p  = 0.325) between arms and no cancer-related deaths. Conclusions Our results strongly suggest that in early breast cancer patients with SN micrometastasis, selective SN lymphadenectomy suffices to control locoregional and distant disease, with no significant effects on survival.

IntroductionSurgery (oesophagectomy), with neoadjuvant chemo(radio)therapy, is the main curative treatment for patients with oesophageal cancer. Several surgical approaches can be used to remove an oesophageal tumour. The Ivor Lewis (two-phase procedure) is usually used in the UK. This can be performed as an open oesophagectomy (OO), a laparoscopically assisted oesophagectomy (LAO) or a totally minimally invasive oesophagectomy (TMIO). All three are performed in the National Health Service, with LAO and OO the most common. However, there is limited evidence about which surgical approach is best for patients in terms of survival and postoperative health-related quality of life.Methods and analysisWe will undertake a UK multicentre randomised controlled trial to compare LAO with OO in adult patients with oesophageal cancer. The primary outcome is patient-reported physical function at 3 and 6 weeks postoperatively and 3 months after randomisation. Secondary outcomes include: postoperative complications, survival, disease recurrence, other measures of quality of life, spirometry, success of patient blinding and quality assurance measures. A cost-effectiveness analysis will be performed comparing LAO with OO. We will embed a randomised substudy to evaluate the safety and evolution of the TMIO procedure and a qualitative recruitment intervention to optimise patient recruitment. We will analyse the primary outcome using a multi-level regression model. Patients will be monitored for up to 3 years after their surgery.Ethics and disseminationThis study received ethical approval from the South-West Franchay Research Ethics Committee. We will submit the results for publication in a peer-reviewed journal.Trial registration numberISRCTN10386621.

Background We sought to investigate the prognosis of patients following curative-intent surgery for intrahepatic cholangiocarcinoma (ICC) stratified by hepatitis B (HBV-ICC), hepatolithiasis (Stone-ICC), and no identifiable cause (conventional ICC) etiologic subtype. Methods 986 patients with HBV-ICC ( n  = 201), stone-ICC ( n  = 103), and conventional ICC ( n  = 682) who underwent curative-intent resection were identified from a multi-institutional database. Propensity score matching (PSM) was used to mitigate residual bias. Results HBV-ICC patients more often had cirrhosis, earlier stage tumors, a mass-forming lesion, well-to-moderate tumor differentiation, and an R0 resection versus stone-ICC or conventional ICC patients. Five-year recurrence-free survival among HBV-ICC and conventional ICC patients was 23.9 and 17.8%, respectively, versus a recurrence-free of only 8.3% among patients with stone-ICC. Similarly, 5-year overall survival among patients with stone-ICC was only 18.3% compared with 48.9 and 38.0% for patients with HBV-ICC and conventional ICC, respectively. On PSM, patients with stone-ICC group had equivalent long-term outcomes as HBV-ICC patients. In contrast, on PSM, stone-ICC patients had a median overall survival of only 18.0 months versus 44.0 months for patients with conventional ICC. Median overall survival after intrahepatic-only recurrence among patients who had stone-ICC (6.0 months) was worse than OS among HBV-ICC (13.0 months) or conventional ICC (12.0 months) ( p  = 0.006 and p  = 0.082, respectively). Conclusions While HBV-ICC had a better prognosis on unadjusted analyses, these differences were mitigated on PSM suggesting no stage-for-stage differences in outcomes compared with stone-ICC or conventional ICC. In contrast, patients with stone-ICC had worse long-term outcomes. These data highlight the relative importance of ICC etiology relative to established clinicopathological factors in the prognosis of patients with ICC.