Early treatment discontinuation in patients with deficient mismatch repair or microsatellite instability high metastatic colorectal cancer receiving immune checkpoint inhibitors.

Background: Immune checkpoint inhibitors (ICIs) are recommended to treat patients with deficient mismatch repair/microsatellite instability high (dMMR/MSI-H) metastatic colorectal cancer (mCRC). Pivotal trials have fixed a maximum ICI duration of 2 years, without a compelling rationale. A shorter treatment duration has the potential to improve patients' quality of life and reduce both toxicity and cost without compromising efficacy.

ERBB2 Comprehensive Profiling and Prognostication in Stage III Colon Cancer: Findings From PETACC8 and IDEA-France Cohorts.

Background & Aims: ERBB2 pathway activation, through amplification or activating mutations, represents a new target for colon cancer (CC) treatment. Molecular methods were compared with the gold standard for assessing ERBB2 status, and the prognostic value of ERBB2 amplification, mutations, and expression was determined using data from 2 phase 3 trials involving nearly 3000 patients with stage III CC.

Methods: In the PETACC8 trial, immunohistochemistry and fluorescence in situ hybridization, DNA, and RNA analysis were performed on 1813, 1719, and 1733 samples, respectively.

Oxaliplatin-Based Versus Alkylating Agent in Neuroendocrine Tumors According to the O-Methylguanine-DNA Methyltransferase Status: A Randomized Phase II Study (MGMT-NET).

Purpose: Alkylating agents (ALKY) are the main chemotherapies used for advanced neuroendocrine tumors (NETs). O-Methylguanine-DNA methyltransferase (MGMT) status, as proficient (p) or deficient (d), may predict the response to ALKY.

Patients And Methods: MGMT-NET (ClinicalTrials.

[Practice-changing clinical trials in gastrointestinal radiation oncology].

Current events in radiotherapy oncology are marked by the results of strategic trials, particularly for esophageal and rectal cancers. For resectable esophageal adenocarcinoma, results of the ESOPEC study showed a benefit in overall survival from the perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin and docetaxel compared to chemoradiotherapy (41.4Gy radiotherapy and carboplatin/paclitaxel chemotherapy).

Olaparib as maintenance therapy in non resectable pancreatic adenocarcinoma associated with homologous recombination deficiency profile: A French retrospective multicentric AGEO real-world study.

Background: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. The POLO trial showed that olaparib (PARP inhibitor) improved progression-free survival (PFS) but not overall survival (OS), when used as maintenance therapy after ≥ 16 weeks of disease control with first-line platinum-based chemotherapy in patients with germline (g) BRCA 1 or 2 pathogenic variants (PV) metastatic PDAC. However, real-world data on the effectiveness of olaparib are missing.

BRAF + EGFR +/- MEK inhibitors after immune checkpoint inhibitors in BRAF V600E mutated and deficient mismatch repair or microsatellite instability high metastatic colorectal cancer.

Background: Immune checkpoint inhibitors (ICIs) are the guideline endorsed first choice for patients with deficient mismatch repair or microsatellite instability high (dMMR/MSI-H) mCRC, however a significant proportion experience primary or secondary resistance. BRAF V600E mutated (BRAFm) and dMMR/MSI-H mCRC can be treated with BRAF + EGFR inhibitors but specific data on the efficacy after progression to ICIs are missing.

Methods: We collected consecutive patients with BRAFm dMMR/MSI-H mCRC treated from 2017 to 2024 with a combination of BRAFi+EGFRi+/-MEKi, after disease progression on ICIs.

Neoadjuvant radiotherapy combined with fluorouracil-cisplatin plus cetuximab in operable, locally advanced esophageal carcinoma: Results of a phase I-II trial (FFCD-0505/PRODIGE-3).

Background: Radiotherapy combined with fluorouracil (5FU) and cisplatin for locally advanced esophageal cancer is associated with a 20-25% pathologic complete response (pCR) rate. Cetuximab increases the efficacy of radiotherapy in patients with head and neck carcinomas. The aim of this phase I/II trial was to determine the optimal doses and the pCR rate with chemoradiotherapy (C-RT) plus cetuximab.

Evaluation of a blood miRNA/mRNA signature to follow-up Lu-PRRT therapy for G1/G2 intestinal neuroendocrine tumors.

Background: Lu-oxodotreotide peptide receptor therapy (LuPRRT) is an efficient treatment for midgut neuroendocrine tumors (NETs) of variable radiological response. Several clinical, biological, and imaging parameters may be used to establish a relative disease prognosis but none is able to predict early efficacy or toxicities. We investigated expression levels for mRNA and miRNA involved in radiosensitivity and tumor progression searching for correlations related to patient outcome during LuPRRT therapy.

Survival of patients managed in France for duodenal neuroendocrine tumors (D-NET): a 20-year multicenter cohort study from the GTE group: a cohort study.

Introduction: Duodenal neuroendocrine tumours (D-NETs) have a low incidence; however, their diagnosis has been increasing. Features such as tumour location, size, type, histological grade, and stage were used to adapt the treatment to either endoscopic (ER) or surgical (SR) resections. There is no consensus regarding the definitive treatment.

A multicenter study evaluating efficacy of immune checkpoint inhibitors in advanced non-colorectal digestive cancers with microsatellite instability.

Background: One randomized phase III trial comparing chemotherapy (CT) with immune checkpoint inhibitors (ICI) has demonstrated significant efficacy of ICI in deficient DNA mismatch repair system/microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer. However, few studies have compared ICI with CT in other advanced dMMR/MSI-H digestive tumors.

Methods: In this multicenter study, we included patients with advanced dMMR/MSI-H non-colorectal digestive tumors treated with chemotherapy and/or ICIs.

Triplet chemotherapy plus cetuximab as first-line treatment in extended RAS wild-type metastatic colorectal cancer patients.

Background: Triplet chemotherapy plus cetuximab showed promising results in phase II trials in unsystematically selected RAS population. We evaluated FOLFIRINOX+cetuximab efficacy as first-line treatment in extended RAS wild-type metastatic colorectal cancer (mCRC) patients.

Methods: We retrospectively analyzed patients treated with FOLFIRINOX+cetuximab, using data from clinical trials and real-life practice.

[The French National College of Oncology Teachers (CNEC): Missions, organization, and projects].

The National College of Cancerology Teachers (CNEC) was created in September 1986. Its missions are to develop the teaching of oncology, to promote educational actions in the discipline, to participate in the development of teaching content and the definition of curricula and the control of knowledge for the training of medical students and specialists, to develop and validate educational documents relating to the above teaching, to ensure the representation of oncology teaching to of the National University Council (CNU) and administrative authorities, to ensure and coordinate relations with other university disciplines, scientific societies, national, European, and international professional groups, and to contribute to the development of research in the discipline. The current office was elected in September 2022 for three years.

Primary resistance to immunotherapy in patients with a dMMR/MSI metastatic gastrointestinal cancer: who is at risk? An AGEO real-world study.

Background: The outstanding efficacy of immunotherapy in metastatic dMMR/MSI gastro-intestinal (GI) cancers has led to a rapid increase in the number of patients treated. However, 20-30% of patients experience primary resistance to immune checkpoint inhibitors (ICIPR) and need better characterization.

Methods: This AGEO real-world study retrospectively analyzed the efficacy and safety of ICIs and identified clinical variables associated with ICIPR in patients with metastatic dMMR/MSI GI cancers treated with immunotherapy between 2015 and 2022.

Metastatic site and clinical outcome of patients with deficient mismatch repair metastatic colorectal cancer treated with an immune checkpoint inhibitor in the first-line setting.

Purpose: Only one-half of deficient mismatch repair (d-MMR) metastatic colorectal cancers (mCRC) demonstrate durable responses to immune checkpoint inhibitors (ICIs). Given preclinical data indicating that liver metastases sequester activated CD8 T cells from systemic circulation, we examined clinical outcome by metastatic site.

Patients And Methods: In a retrospective cohort of patients with d-MMR mCRCs treated at multiple centers in France (n = 66), we sought to validate data from a U.

Hepatic arterial oxaliplatin plus intravenous 5-fluorouracil and cetuximab for first-line treatment of colorectal liver metastases: A multicenter phase II trial.

Background: The efficacy and tolerability of hepatic arterial infusion (HAI) oxaliplatin plus systemic 5-fluorouracil and cetuximab as frontline treatment in patients with colorectal liver metastases (CRLM) are unknown.

Methods: In this multicenter, single-arm phase II study, patients with CRLM not amenable to curative-intent resection or requiring complex/major liver resection, and no prior chemotherapy for metastatic disease, received HAI oxaliplatin and intravenous 5-fluorouracil, leucovorin and cetuximab, every two weeks until disease progression, limiting toxicity or at least 3 months after complete response or curative-intent resection/ablation. The primary endpoint was overall response rate (ORR).

Exploring the basis of heterogeneity of cancer aggressiveness among the mutated POLE variants.

Germline pathogenic variants in the exonuclease domain of the replicative DNA polymerase Pol ε encoded by the gene, predispose essentially to colorectal and endometrial tumors by inducing an ultramutator phenotype. It is still unclear whether all the alterations influence similar strength tumorigenesis, immune microenvironment, and treatment response. In this review, we summarize the current understanding of the mechanisms and consequences of mutations in human malignancies; we highlight the heterogeneity of mutation rate and cancer aggressiveness among POLE variants, propose some mechanistic basis underlining such heterogeneity, and discuss novel considerations for the choice and efficacy of therapies of POLE tumors.

Association of Radiochemotherapy to Immunotherapy in unresectable locally advanced Oesophageal carciNoma-randomized phase 2 trial ARION UCGI 33/PRODIGE 67: the study protocol.

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.

Image-Guided Precision Medicine in the Diagnosis and Treatment of Pheochromocytomas and Paragangliomas.

In this comprehensive review, we aimed to discuss the current state-of-the-art medical imaging for pheochromocytomas and paragangliomas (PPGLs) diagnosis and treatment. Despite major medical improvements, PPGLs, as with other neuroendocrine tumors (NETs), leave clinicians facing several challenges; their inherent particularities and their diagnosis and treatment pose several challenges for clinicians due to their inherent complexity, and they require management by multidisciplinary teams. The conventional concepts of medical imaging are currently undergoing a paradigm shift, thanks to developments in radiomic and metabolic imaging.

Evaluation of the relevance of the growth modulation index (GMI) from the FFCD 0307 randomized phase III trial comparing the sequence of two chemotherapeutic regimens.

Background: Precision medicine trials disrupted the paradigm of randomized controlled trials in large populations. Patient selection may be based on molecular alterations rather than on primary tumor location. In small patient populations, the growth modulation index (GMI) has been developed to evaluate treatment efficacy by using each patient as its own control.

Complete pathological response after chemotherapy or immune checkpoint inhibitors in deficient MMR metastatic colorectal cancer: Results of a retrospective multicenter study.

About 5% of the patients with metastatic colorectal cancers (mCRC) present microsatellite instability (MSI)/deficient mismatch repair system (dMMR). While metastasectomy is known to improve overall and progression-free survival in mCRC, specific results in selected patients with dMMR/MSI mCRC are lacking. Our study aimed to describe metastasectomy results, characterize histological response and evaluate pathological complete response (pCR) rate in patients with dMMR/MSI mCRC.

Special features of sarcomas developed in patients with Lynch syndrome: A systematic review.

Lynch syndrome (LS) is a genetic predisposition leading to colorectal and non-colorectal tumors such as endometrial, upper urinary tract, small intestine, ovarian, gastric, biliary duct cancers and glioblastoma. Though not classically associated with LS, growing literature suggests that sarcomas might develop in patients with LS. This systematic review of literature identified 44 studies (N = 95) of LS patients who developed sarcomas.

Efficacy of immunotherapy in mismatch repair-deficient advanced colorectal cancer in routine clinical practice. An AGEO study.

Background: 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.

Patients And Methods: 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.