Association of COVID-19 Lockdown With the Tumor Burden in Patients With Newly Diagnosed Metastatic Colorectal Cancer.

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.

[Localized MSI/dMMR gastric cancer patients, perioperative immunotherapy instead of chemotherapy: The GERCOR NEONIPIGA phase II study is opened to recruitment]. / Patients atteints d'un cancer gastrique localisé MSI/dMMR, pas de chimiothérapie mais une immunothérapie périopératoire : l'essai de phase II GERCOR NEONIPIGA vient d'être ouvert au recrutement.

INTRODUCTION: Perioperative chemotherapy is the standard strategy for localized gastric cancers. Nevertheless, this strategy seems to be inefficient, if not deleterious, for patients with tumors harboring microsatellite instability (MSI) and/or mismatch repair deficiency (dMMR), a tumor phenotype predictive for the efficacy of immune checkpoint inhibitors (ICKi). AIM: The GERCOR NEONIPIGA single-arm phase II study (NCT04006262; EUDRACT 2018-004712-22) aims at evaluating the efficacy of a peri-operative strategy with nivolumab and ipilimumab in neoadjuvant setting, then nivolumab alone after surgery for patients with resectable MSI/dMMR gastric cancer. MATERIAL AND METHODS: Main inclusion criteria are: gastric and oesogastric junction adenocarcinoma (GOA), T2-T4, all N stage and M0, MSI/dMMR. Patients will be treated with nivolumab 240mg Q2W, 6 infusions, and ipilimumab 1mg/kg Q6W, 2 infusions in neoadjuvant setting. Following surgery, patients with TRG 1-2-3 (Mandard tumor regression grade), acceptable tolerance of neoadjuvant treatment and postoperative ECOG performance status 0-1, will be treated with adjuvant nivolumab 480mg Q4W, 9 infusions. RESULTS: The primary endpoint is pathological complete response rate (pCR-R). Based on a Fleming design, with α=5% and ß=20%, 27 patients have to be evaluated (H0=5%; H1=20%). Secondary endpoints include disease-free survival, overall survival and safety. CONCLUSION: This study is planned to include 32 patients to evaluate the pCR-R with the combination of nivolumab and ipilimumab in neoadjuvant setting for MSI/dMMR localized GOA. The MSI/MMR status should be systematically assessed on diagnostic biopsies of all GOA. If it meets its primary endpoint, the GERCOR NEONIPIGA study might mark a turning point in the management of localized MSI/dMMR GOA patients.

Tolerance and outcomes of sorafenib in elderly patients treated for advanced hepatocellular carcinoma.

INTRODUCTION: Use of sorafenib remains debated in elderly patients treated for advanced hepatocellular carcinoma (HCC). METHODS: This was a bicentric retrospective study including all patients ≥75years and treated with sorafenib for advanced HCC between January 2010 and March 2014. RESULTS: Of the 51 patients included (median age: 78 years, range: 75-92; performance status (PS) 0-1: 98%; cirrhosis: 88.2%; Child-Pugh A: 95.6%) all experienced at least one adverse event (AE). About 2/3 of them (66.7%) had grade 3-4 toxicities, including fatigue (43.1%), hand foot skin syndrome (11.8%), anorexia (9.8%) or diarrhea (9.8%). After adjustment for arterial hypertension, heart failure, other(s) cardiovascular history(ies), and sorafenib dose at baseline, only patients ≥80 years were associated with severe AE (OR: 13.3; p=0.009). Discontinuation for toxicity was reported in 31 (60.8%) patients, mainly within the 3rd months, especially in those who had PS ≥1 at baseline (OR: 10.4; p=0.01), or other cardiovascular histories (OR: 30.9; p=0.016). In this setting, overall survival was significantly reduced (HR: 4.5; p<0.0001). CONCLUSION: Tolerance of Sorafenib seems to be low in elderly, especially for patients aged ≥80 years or with PS ≥1. Starting with reduced dose of sorafenib does not seem to impact results. Some of these patients may truly benefit from the treatment in terms of survival.

The level of epidermal growth factor receptors expression is correlated with the advancement of colorectal adenoma: validation of a surface biomarker.

INTRODUCTION: Data about the expression of Epidermal Growth Factor Receptors (EGFRs) in colorectal adenomas remain scarce. RESULTS: 101 patients were enrolled including 53 controls. All adenomas (n = 38) and CRC (n = 5) were EGFR positive. Hyperplastic polyps (HP) (n = 8) and control colons (n = 53) were EGFR negative in half of cases (p < 0.0001). A well significant gradient of increased EGFR expression was observed between adjacent mucosa, hyperplastic lesions, low grade dysplasia (LGD) (n = 30), high grade dysplasia (HGD) adenomas (n = 9) and cancers (p < 0.0001). EGFR overexpression was reported in 100% of cancers, 77.8% of HGD, and 10% of LGD adenomas. By multivariate analysis in adenomas, associated factors with EGFR overexpression were HGD and tubulo-villous feature. MATERIALS AND METHODS: All patients undergoing colonoscopy in the university center of Saint-Etienne were eligible to the study from December 2015 to March 2016. In patients with colorectal neoplasia (lesions group), biopsies were performed on the lesion before its resection, and on the adjacent and distal colon mucosa. In control group, biopsies were performed in the right and left side colon. The EGFR expression was assessed by immunohistochemical scores (Goldstein grade, intensity of staining, composite score), using a primary mouse monoclonal antibody (EGFR, clone 113, Novocastra). Outcomes were compared using Kruskal-Wallis and/or Mann-Whitney-U tests, appropriately. The associated clinical, endoscopic and histological factors with EGFR overexpression (composite score ≥ 6) were assessed for adenomas by logistic regression. CONCLUSIONS: EGFR are early involved in colorectal carcinogenesis, and their expression is strongly correlated to the neoplasia stage, leading to validate EGFR as an interesting surface biomarker of adenomas.

Laparoscopy could be the best approach to treat colorectal cancer in selected patients aged over 80 years: Outcomes from a multicenter study.

BACKGROUND: The efficacy and safety of treating elderly patients with colorectal cancer (CRC) is of concern. This study aimed to compare the short- and long-term outcomes of elective laparoscopic vs. open surgery to treat CRC in very elderly patients. METHODS: All patients aged >80 years and who had undergone a colectomy for CRC without metastasis between July 2005 and April 2012 were considered for inclusion. Demographic, clinical, operative, and postoperative data, plus overall and disease-free survival rates, were retrospectively collected and compared between two groups of patients that underwent an open procedure (OP group) or laparoscopy (LG). RESULTS: 123 patients were enrolled (55 OPG, 68 LG). Median age was similar between the groups (84 vs. 83 years, respectively; NS). Duration of surgery was significantly lower in OPG (170 vs. 200min; p=0.030). Overall mortality at 3 months was 8.3%: it tended to be greater in the OPG (16.5% vs. 1.5%, NS). Morbidity was significantly greater in the OPG compared to the LG (52.7% vs. 27.5%; p=0.021), resulting in significantly longer hospital stay (12 vs. 8 days, respectively; p<0.001). Pathological findings were similar between the two groups. Cumulative overall survival rates at 3 and 5 years were significantly greater after laparoscopy (85% and 72%) compared to open surgery (58.2% and 48%, respectively; p<0.001). CONCLUSIONS: Our study suggests that laparoscopy is safe and could increase overall survival compared to open surgery in elderly patients suffering from CRC. SUMMARY: This retrospective study compared the short- and longer-term outcomes of patients aged >80 years and undergoing elective laparoscopic or open surgery for CRC between 2005 and 2012.

[Biomarkers in inflammatory bowel diseases]. / Intérêt des biomarqueurs dans la prise en charge des MICI.

Fecal calprotectine is of interest for diagnosis of IBD at the beginning. CRP and fecal calprotectine are predictive of long-term response in patients treated by anti-TNF therapy. Trough levels of anti-TNF are associated to clinical remission and mucosal healing. Detectable antibodies to anti-TNF are associated with lower response to treatment. Interventional studies are waiting before optimization of treatment in function of biomarkers. Trough levels of anti-TNF help to modify our treatment (optimization or de-escalation).