Introduction: Small rectal neuroendocrine tumours are good candidates for endoscopic resection provided that complete pathological resection (R0) is obtained and their risk of metastatic progression is low. We conducted a large multicentre nationwide study to evaluate the outcomes of the management of non‐metastatic rectal neuroendocrine tumours ≤2 cm diagnosed endoscopically.Patients and methods: The medical records, the endoscopic and pathological findings of patients with non‐metastatic rectal neuroendocrine tumours ≤2 cm managed from January 2000–June 2018 in 16 French hospitals, were retrospectively analysed. The primary objective was to describe the proportion of R0 endoscopic resections.Results: A total of 329 patients with 345 rectal neuroendocrine tumours were included, 330 (96%) tumours were managed by local treatments: 287 by endoscopy only and 43 by endoscopy followed by transanal endoscopic microsurgery. The final endoscopic R0 rate was 134/345 (39%), which improved from the first endoscopy (54/225, 24%), to the second (60/100, 60%) and the third endoscopy (20/26, 77%). R0 was associated with endoscopic technique (90% for advanced techniques, 40% for mucosectomy and 17% for polypectomy), but not with tumour or patient characteristics. Twenty patients had metastatic disease, which was associated with tumour size ≥10 mm (odds ratio: 9.1, 95% confidence interval (3.5–23.5)), tumour grade G2–G3 (odds ratio: 4.2, (1.5–11.7)), the presence of muscular (odds ratio: ∞, (11.9–∞)) and lymphovascular invasion (odds ratio: 57.2, (5.6–578.9)).Conclusions: The resection of small rectal neuroendocrine tumours often requires multiple procedures. Training of endoscopists is necessary in order to better recognise these tumours and to perform the appropriate resection technique.

Immunotherapy demonstrated remarkable efficacy in metastatic colorectal cancers (mCRCs) with mismatch repair deficiency (MMRd)/microsatellite instability (MSI). However, data regarding efficacy and safety of immunotherapy in the routine clinical practice are scarce. This is a retrospective, multicenter study aiming to evaluate efficacy and safety of immunotherapy in routine clinical practice and to identify predictive markers for long-term benefit. Long-term benefit was defined as progression-free survival (PFS) exceeding 24 months. All patients who received immunotherapy for an MMRd/MSI mCRC were included. Patients who received immunotherapy in combination with another known effective therapeutic class agent (chemotherapy or tailored therapy) were excluded. Overall, 284 patients across 19 tertiary cancer centers were included. After a median follow-up of 26.8 months, the median overall survival (mOS) was 65.4 months [95% confidence interval (CI) 53.8 months-not reached (NR)] and the median PFS (mPFS) was 37.9 months (95% CI 30.9 months-NR). There was no difference in terms of efficacy or toxicity between patients treated in the real-world or as part of a clinical trial. Overall, 46.6% of patients had long-term benefit. Independent markers associated with long-term benefit were Eastern Cooperative Oncology Group-performance status (ECOG-PS) 0 (P = 0.025) and absence of peritoneal metastases (P = 0.009). Our study confirms the efficacy and safety of immunotherapy in patients with advanced MMRd/MSI CRC in the routine clinical practice. ECOG-PS score and absence of peritoneal metastases provide simple markers that could help identify patients who benefit the most from this treatment.

PURPOSE: Alkylating agents (ALKY) are the main chemotherapies used for advanced neuroendocrine tumors (NETs). O ⁶ -Methylguanine-DNA methyltransferase (MGMT) status, as proficient (p) or deficient (d), may predict the response to ALKY. PATIENTS AND METHODS: MGMT-NET (ClinicalTrials.gov identifier: NCT03217097 ) was a phase II trial randomly assigning 1:1 for pMGMT or 2:1 for dMGMT-NETs to either ALKY or oxaliplatin (Ox). Inclusion criteria were a confirmed advanced pancreatic, thoracic, or unknown primary NETs with an indication for chemotherapy and tissue available. The primary aim was to detect a difference of 35% between the 3-month objective response rate (ORR) in pMGMT-NETs versus in dMGMT-NETs when treated with ALKY. A biomarker-stratified design was performed to compare ALKY and Ox in the dMGMT and pMGMT strata for the secondary end points. dMGMT was defined using pyrosequencing (PSQ; methylated MGMT ≥9%) and using immunochemistry ( H -score of MGMT <50) when PSQ was not interpretable. RESULTS: From October 2018 to October 2021, 105 patients (55 pancreas, 38 thorax, 12 unknown) started either ALKY (n = 62) or Ox (n = 43). The median age was 63 years (range, 30-84), and 59% were males. NETs were G1 (19%), G2 (69%), or G3 (10%). Among patients with interpretable MGMT status, 56.9% (58 of 102) had a dMGMT-NET. The primary end point was not reached; the 3-month ORR was 10 (29.4%) versus 2 (8%), and the odds ratio was 3.5 (0.58-21.16), P = .172. However, best ORR (18 [52.9%] v 3 [11.5%]) and median progression-free survival (14.6 [95% CI, 7.2 to 22.1] v 11.3 [9.4 to 13.2] months) were higher for dMGMT-NETs versus pMGMT-NETs. MGMT status does not seem to affect the Ox efficacy. CONCLUSION: Despite the fact that the primary end point was not reached, ALKY has clinical activity in patients with dMGMT-NETs.

Management of ampullary tumors (AT) is challenging because of a low level of scientific evidence. This document is a summary of the French intergroup guidelines regarding the management of AT, either adenoma (AA) or carcinoma (AC), published in July 2023, available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org). A collaborative work was conducted under the auspices of French medical, endoscopic, oncological and surgical societies involved in the management of AT. Recommendations are based on recent literature review and expert opinions and graded in three categories (A, B, C), according to quality of evidence. Accurate diagnosis of AT requires at least duodenoscopy and EUS. All patients should be discussed in multidisciplinary tumor board before treatment. Surveillance may only be proposed for small AA in familial adenomatous polyposis. For AA, endoscopic papillectomy is the preferred option only if R0 resection can be achieved. When not possible, surgical papillectomy should be considered. For AC beyond pT1a N0, pancreaticoduodenectomy is the procedure of choice. Adjuvant monochemotherapy (gemcitabine, 5FU) may be proposed. For aggressive tumors (pT3/T4, pN+, R1, poorly differentiated AC, pancreatobiliary differentiation) with high risk of recurrence, 6 months polychemotherapy (CAPOX/FOLFOX for the intestinal subtype and mFOLFIRINOX for the pancreatobiliary or the mixed subtype) may be a valid alternative. Clinical and radiological follow up is recommended for 5 years. These guidelines help to homogenize and highlight unmet needs in the management of AA and AC. Each individual case should be discussed by a multidisciplinary team.