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Introduction: This article is a summary of the French intergroup guidelines regarding the management of non-metastatic colon cancer (CC), revised in November 2022., Methods: These guidelines represent collaborative work of all French medical and surgical societies involved in the management of CC. Recommendations were graded in three categories (A, B, and C) according to the level of evidence found in the literature published up to November 2022., Results: Initial evaluation of CC is based on clinical examination, colonoscopy, chest-abdomen-pelvis computed tomography (CT) scan, and carcinoembryonic antigen (CEA) assay. CC is usually managed by surgery and adjuvant treatment depending on the pathological findings. The use of adjuvant therapy remains a challenging question in stage II disease. For high-risk stage II CC, adjuvant chemotherapy must be discussed and fluoropyrimidine monotherapy or oxaliplatin-based chemotherapy proposed according to the type and number of poor prognostic features. Oxaliplatin-based chemotherapy (FOLFOX or CAPOX) is the current standard for adjuvant therapy of patients with stage III CC. However, these regimens are associated with significant oxaliplatin-induced neurotoxicity. The results of the recent IDEA study provide evidence that 3 months of treatment with CAPOX is as effective as 6 months of oxaliplatin-based therapy in patients with low-risk stage III CC (T1-3 and N1). A 6-month oxaliplatin-based therapy remains the standard of care for high-risk stage III CC (T4 and/or N2). For patients unfit for oxaliplatin, fluoropyrimidine monotherapy is recommended., Conclusion: French guidelines for non-metastatic CC management help to offer the best personalized therapeutic strategy in daily clinical practice. Each individual case must be discussed within a multidisciplinary tumor board and then the treatment option decided with the patient., Competing Interests: Conflict of interest T. Lecomte: Amgen, Merck Serono, Pierre Fabre, and Servier. D. Tougeron: Amgen, Merck Serono, Pierre Fabre, Servier, MSD, BMS, Astra Zeneca, Sanofi, and Roche. F. Bibeau: Astellas, Astra-Zeneca, BMS, Incyte, MSD, Pierre Fabre, and Sanofi. R. Cohen: MSD Oncology, Pierre Fabre, Bristol-Myers Squibb, Mylan Medical, Servier, Exeliom Biosciences, and Enterome Bioscience. T. Aparicio: MSD, Pierre Fabre, BMS, Servier, and Amgen. O. Bouché: Amgen, Apmomia Therapeutics Bayer, Grunenthal, Merck KGaA, MSD, Pierre Fabre, and Servier. The other authors have reported no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: In case of locally advanced and/or non-metastatic unresectable esophageal cancer, definitive chemoradiotherapy (CRT) delivering 50 Gy in 25 daily fractions in combination with platinum-based regimen remains the standard of care resulting in a 2-year disease-free survival of 25% which deserves to be associated with new systemic strategies. In recent years, several immune checkpoint inhibitors (anti-PD1/anti-PD-L1, anti-Program-Death 1/anti-Program-Death ligand 1) have been approved for the treatment of various solid malignancies including metastatic esophageal cancer. As such, we hypothesized that the addition of an anti-PD-L1 to CRT would provide clinical benefit for patients with locally advanced oesophageal cancer. To assess the efficacy of the anti-PD-L1 durvalumab in combination with CRT and then as maintenance therapy we designed the randomized phase II ARION (Association of Radiochemotherapy with Immunotherapy in unresectable Oesophageal carciNoma- UCGI 33/PRODIGE 67)., Methods: ARION is a multicenter, open-label, randomized, comparative phase II trial. Patients are randomly assigned in a 1:1 ratio in each arm with a stratification according to tumor stage, histology and centre. Experimental arm relies on CRT with 50 Gy in 25 daily fractions in combination with FOLFOX regimen administrated during and after radiotherapy every two weeks for a total of 6 cycles and durvalumab starting with CRT for a total of 12 infusions. Standard arm is CRT alone. Use of Intensity Modulated radiotherapy is mandatory. The primary endpoint is to increase progression-free survival at 12 months from 50 to 68% (HR = 0.55) (power 90%; one-sided alpha-risk, 10%). Progression will be defined with central external review of imaging., Ancillary Studies Are Planned: PD-L1 Combined Positivity Score on carcinoma cells and stromal immune cells of diagnostic biopsy specimen will be correlated to disease free survival. The study of gut microbiota will aim to determine if baseline intestinal bacteria correlates with tumor response. Proteomic analysis on blood samples will compare long-term responder after CRT with durvalumab to non-responder to identify biomarkers., Conclusion: Results of the present study will be of great importance to evaluate the impact of immunotherapy in combination with CRT and decipher immune response in this unmet need clinical situation., Trial Registration: ClinicalTrials.gov, NCT: 03777813.Trial registration date: 5 th December 2018., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Although patients with microsatellite instable metastatic colorectal cancer (CRC) benefit from immune checkpoint blockade, chemotherapy with targeted therapies remains the only therapeutic option for microsatellite stable (MSS) tumors. The single-arm, phase 1b/2 MEDITREME trial evaluated the safety and efficacy of durvalumab plus tremelimumab combined with mFOLFOX6 chemotherapy in first line, in 57 patients with RAS-mutant unresectable metastatic CRC. Safety was the primary objective of phase Ib; no safety issue was observed. The phase 2 primary objective of efficacy in terms of 3-month progression-free survival (PFS) in patients with MSS tumors was met, with 3-month PFS of 90.7% (95% confidence interval (CI): 79.2-96%). For secondary objectives, response rate was 64.5%; median PFS was 8.2 months (95% CI: 5.9-8.6); and overall survival was not reached in patients with MSS tumors. We observed higher tumor mutational burden and lower genomic instability in responders. Integrated transcriptomic analysis underlined that high immune signature and low epithelial-mesenchymal transition were associated with better outcome. Immunomonitoring showed induction of neoantigen and NY-ESO1 and TERT blood tumor-specific T cell response associated with better PFS. The combination of durvalumab-tremelimumab with mFOLFOX6 was tolerable with promising clinical activity in MSS mCRC. Clinicaltrials.gov identifier: NCT03202758 ., (© 2023. The Author(s).)

Importance: The 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 Participants: This 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 Measures: Circulating 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, 8.8-18.0] 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 findings of this study suggest that CRC is a major area for intervention to minimize pandemic-associated delays in screening, diagnosis, and treatment.

Purpose: Combining bevacizumab with paclitaxel significantly improves progression-free survival (PFS) versus paclitaxel alone in HER2-negative metastatic breast cancer (MBC). Eribulin is active and tolerable in pretreated MBC. To assess whether eribulin may offer a more tolerable yet effective combination partner for bevacizumab, we evaluated a bevacizumab/eribulin combination regimen as first-line therapy for MBC., Methods: In this single-arm phase II study, patients with histologically confirmed HER2-negative MBC and no prior chemotherapy for MBC received eribulin 1.23 mg/m 2 on days 1 and 8 every 3 weeks for ≥6 cycles plus bevacizumab 15 mg/kg on day 1 every 3 weeks until disease progression. The primary endpoint was non-progression rate at 1 year. Secondary endpoints included objective response rate (ORR), PFS, and safety., Results: The median age of the 61 treated female patients was 59 years, 16% had triple-negative MBC, 30% had ≥3 metastatic sites, and 71% had received prior (neo)adjuvant chemotherapy. Patients received a median of six eribulin and nine bevacizumab cycles. The non-progression rate at 1 year was 32% (95% confidence interval [CI]: 20-43%), ORR was 47% (95% CI: 34-60%), and median PFS was 8.3 months (95% CI: 7.0-9.6 months). The only grade ≥3 clinical adverse events in >5% of patients were hypertension (39%), neutropenia (26%), thrombosis (10%), and paresthesia/dysesthesia (7%)., Conclusion: First-line eribulin/bevacizumab combination therapy showed interesting activity in MBC with an acceptable safety profile, including a particularly low incidence of high-grade neuropathy., Competing Interests: Declaration of competing interest FC reports grants, personal fees, and non-financial support from AstraZeneca, grants from Roche Diagnostics, and personal fees and non-financial support from Roche and Lilly, outside the submitted work. BY reports consulting/advisory roles for AstraZeneca and advisory boards for Roche, GSK/Tesaro, Clovis, Novartis, MSD, BMS, Amgen, and ECS Progastrin, all outside the submitted work. GE reports personal fees and research support from Roche and Novartis, personal fees from Pfizer and Amgen, and research support from MSD, Odonate, Dompé Farmaceutici, AstraZeneca, and MacroGenics, outside the submitted work. A–CH–B, FB, AL, JG, JM-B, BL, JM, J-MF, A-MS, AMa, RD, and IM have nothing to disclose., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Trastuzumab 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., Methods: This 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., Results: From 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)., Conclusion: This 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., Competing Interests: CONFLICTS OF INTEREST Dr Tougeron has participated in consulting or/and advisory boards for Amgen, Sanofi, Ipsen and Celgene; Dr Soularue for Novartis; Dr Ben Abdelghani for Sanofi, Amgen and Merck Serono; Dr Sarabi for Sanofi, Ipsen and Roche; Dr Evesque for Sanofi; Dr Hautefeuille for Lilly, Amgen, Merck Serono, Ipsen, Novartis, Pfizer and Sanofi; Dr Bouché for Merck Serono, Amgen, Roche, Lilly and Novartis; Dr Louvet for Celgene, Roche and Sanofi; Dr Lecomte for Lilly; Dr Taieb for Merck Serono, Sanofi, Roche, Pfizer and Amgen; Dr Zaanan for Merck Serono, Amgen, Roche, Sanofi and Lilly. No other disclosures are reported.

Background: Knowledge 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., Methods: This 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., Results: In 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., Conclusion: When 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.