Background: Adjuvant abemaciclib combined with endocrine therapy (ET) previously demonstrated clinically meaningful improvement in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) in hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive, high-risk early breast cancer at the second interim analysis, however follow-up was limited. Here, we present results of the prespecified primary outcome analysis and an additional follow-up analysis. Patients and methods: This global, phase III, open-label trial randomized (1 : 1) 5637 patients to adjuvant ET for !5 years AE abemaciclib for 2 years. Cohort 1 enrolled patients with !4 positive axillary lymph nodes (ALNs), or 1-3 positive ALNs and either grade 3 disease or tumor !5 cm. Cohort 2 enrolled patients with 1-3 positive ALNs and centrally determined high Ki-67 index (!20%). The primary endpoint was IDFS in the intent-to-treat population (cohorts 1 and 2). Secondary endpoints were IDFS in patients with high Ki-67, DRFS, overall survival, and safety. Results: At the primary outcome analysis, with 19 months median follow-up time, abemaciclib þ ET resulted in a 29% reduction in the risk of developing an IDFS event [hazard ratio (HR) ¼ 0.71, 95% confidence interval (CI) 0.58-0.87; nominal P ¼ 0.0009]. At the additional follow-up analysis, with 27 months median follow-up and 90% of patients off treatment, IDFS (HR ¼ 0.70, 95% CI 0.59-0.82; nominal P < 0.0001) and DRFS (HR ¼ 0.69, 95% CI 0.57-0.83; nominal P < 0.0001) benefit was maintained. The absolute improvements in 3-year IDFS and DRFS rates were 5.4% and 4.2%, respectively. Whereas Ki-67 index was prognostic, abemaciclib benefit was consistent regardless of Ki-67 index. Safety data were consistent with the known abemaciclib risk profile. Conclusion: Abemaciclib þ ET significantly improved IDFS in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive, high-risk early breast cancer, with an acceptable safety profile. Ki-67 index was prognostic, but abemaciclib benefit was observed regardless of Ki-67 index. Overall, the robust treatment benefit of abemaciclib extended beyond the 2-year treatment period.

IMPORTANCEThe COVID-19 pandemic has been associated with substantial reduction in screening, case identification, and hospital referrals among patients with cancer. However, no study has quantitatively examined the implications of this correlation for cancer patient management.OBJECTIVE To evaluate the association of the COVID-19 pandemic lockdown with the tumor burden of patients who were diagnosed with metastatic colorectal cancer (mCRC) before vs after lockdown. DESIGN, SETTING, AND PARTICIPANTSThis cohort study analyzed participants in the screening procedure of the PANIRINOX (Phase II Randomized Study Comparing FOLFIRINOX + Panitumumab vs FOLFOX + Panitumumab in Metastatic Colorectal Cancer Patients Stratified by RAS Status from Circulating DNA Analysis) phase 2 randomized clinical trial. These newly diagnosed patients received care at 1 of 18 different clinical centers in France and were recruited before or after the lockdown was enacted in France in the spring of 2020. Patients underwent a blood-sampling screening procedure to identify their RAS and BRAF tumor status. EXPOSURES mCRC. MAIN OUTCOMES AND MEASURESCirculating tumor DNA (ctDNA) analysis was used to identify RAS and BRAF status. Tumor burden was evaluated by the total plasma ctDNA concentration. The median ctDNA concentration was compared in patients who underwent screening before (November 11, 2019, to March 9, 2020 vs after (May 14 to September 3, 2020) lockdown and in patients who were included from the start of the PANIRINOX study. RESULTS A total of 80 patients were included, of whom 40 underwent screening before and 40 others underwent screening after the first COVID-19 lockdown in France. These patients included 48 men (60.0%) and 32 women (40.0%) and had a median (range) age of 62 (37-77) years. The median ctDNA concentration was statistically higher in patients who were newly diagnosed after lockdown compared with those who were diagnosed before lockdown (119.2 ng/mL vs 17.3 ng/mL; P < .001).Patients with mCRC and high ctDNA concentration had lower median survival compared with those with lower concentration (14.7 [95% CI,.0] months vs 20.0 [95% CI, 14.1-32.0] months). This finding points to the potential adverse consequences of the COVID-19 pandemic and related lockdown.CONCLUSIONS AND RELEVANCE This cohort study found that tumor burden differed between patients who received an mCRC diagnosis before vs after the first COVID-19 lockdown in France. The (continued) Key Points Question What is the implication of the COVID-19 lockdown for the tumor burden of patients with a newly diagnosed metastatic colorectal cancer? Findings In this cohort study of 80 patients with metastatic colorectal cancer, the tumor burden, which was evaluated using the circulating tumor DNA in plasma, appeared to be significantly higher in patients who received a diagnosis after lockdown compared with those who were diagnosed before lockdown (119.2 ng/mL vs 17.3 ng/mL). Patients with greater tumor burden had lower median survival than those with lower tumor burden.M...

BackgroundKnowledge of patients’ height is essential for daily practice in the intensive care unit. However, actual height measurements are unavailable on a daily routine in the ICU and measured height in the supine position and/or visual estimates may lack consistency. Clinicians do need simple and rapid methods to estimate the patients’ height, especially in short height and/or obese patients. The objectives of the study were to evaluate several anthropometric formulas for height estimation on healthy volunteers and to test whether several of these estimates will help tidal volume setting in ICU patients.MethodsThis was a prospective, observational study in a medical intensive care unit of a university hospital. During the first phase of the study, eight limb measurements were performed on 60 healthy volunteers and 18 height estimation formulas were tested. During the second phase, four height estimates were performed on 60 consecutive ICU patients under mechanical ventilation.ResultsIn the 60 healthy volunteers, actual height was well correlated with the gold standard, measured height in the erect position. Correlation was low between actual and calculated height, using the hand’s length and width, the index, or the foot equations. The Chumlea method and its simplified version, performed in the supine position, provided adequate estimates. In the 60 ICU patients, calculated height using the simplified Chumlea method was well correlated with measured height (r = 0.78; ∂ < 1 %). Ulna and tibia estimates also provided valuable estimates. All these height estimates allowed calculating IBW or PBW that were significantly different from the patients’ actual weight on admission. In most cases, tidal volume set according to these estimates was lower than what would have been set using the actual weight.ConclusionWhen actual height is unavailable in ICU patients undergoing mechanical ventilation, alternative anthropometric methods to obtain patient’s height based on lower leg and on forearm measurements could be useful to facilitate the application of protective mechanical ventilation in a Caucasian ICU population. The simplified Chumlea method is easy to achieve in a bed-ridden patient and provides accurate height estimates, with a low bias.Electronic supplementary materialThe online version of this article (doi:10.1186/s13613-016-0154-4) contains supplementary material, which is available to authorized users.

IntroductionTrastuzumab in combination with platinum-based chemotherapy is the standard first-line regimen in HER2-positive advanced gastric cancer. However, there are very few data concerning efficacy of continuing trastuzumab beyond first-line progression.MethodsThis retrospective multicenter study included all consecutive patients with HER2-positive advanced gastric or gastro-esophageal junction (GEJ) adenocarcinoma who received a second-line of chemotherapy with or without trastuzumab after progression on platinum-based chemotherapy plus trastuzumab. Progression-free survival (PFS) and overall survival (OS) were estimated from the start of second-line chemotherapy using the Kaplan-Meier method and compared using log-rank test. The prognostic variables with P values ≤ 0.05 in univariate analysis were eligible for the Cox multivariable regression model.ResultsFrom May 2010 to December 2015, 104 patients were included (median age, 60.8 years; male, 78.8%; ECOG performance status [PS] 0-1, 71.2%). The continuation (n=39) versus discontinuation (n=65) of trastuzumab beyond progression was significantly associated with an improvement of median PFS (4.4 versus 2.3 months; P=0.002) and OS (12.6 versus 6.1 months; P=0.001. In the multivariate analysis including the ECOG PS, number of metastatic sites and measurable disease, the continuation of trastuzumab beyond progression remained significantly associated with longer PFS (HR, 0.56; 95% CI, 0.35-0.89; P=0.01) and OS (HR, 0.47; 95% CI, 0.28-0.79; P=0.004).ConclusionThis study suggests that continuation of trastuzumab beyond progression has clinical benefit in patients with HER2-positive advanced gastric cancer. These results deserve a prospective randomized validation.

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