ABSTRACT
AIM: Laparoscopic surgery is widely used for small gastric gastrointestinal stromal tumors (GISTs) (≤ 5 cm) but remains a controversial approach for larger gastric GISTs (> 5 cm). This study aims to compare short- and long-term outcomes of laparoscopic resection in comparison with open resection for gastric GISTs measuring over 5 cm. METHOD: All patients receiving surgery for gastric GIST > 5 cm between 2000 and 2021 in a single tertiary hospital were included. Data were collected from prospectively maintained records. Kaplan-Meier method and log rank test were used to compare survival outcomes. RESULTS: Among 108 included patients, 59 patients had minimally invasive (MI) surgery (54.6%) whereas 49 patients had open surgery (46.4%). The rate of overall postoperative morbidity was 14.8% and the median length was significantly shorter in the MI group [4 (range 2-30) vs. 7 (range 4-33) days; P = 0.007]. The overall R0 resection rate was 98.2% and the rate of tumor rupture was 13%, not different between the two groups. Recurrence occurred in 24% of the whole population without any difference between groups (20.3% vs. 28.7%, p = 0.31). Minimally invasive surgery was not found as a negative prognostic disease-free survival factor. CONCLUSION: Laparoscopic surgery could be a safe and feasible alternative to open surgery in large gastric GIST, bringing the benefits of minimally invasive surgery without compromising oncologic results.
Subject(s)
Gastrectomy , Gastrointestinal Stromal Tumors , Laparoscopy , Stomach Neoplasms , Humans , Gastrointestinal Stromal Tumors/surgery , Gastrointestinal Stromal Tumors/pathology , Gastrointestinal Stromal Tumors/mortality , Laparoscopy/methods , Female , Male , Middle Aged , Aged , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Stomach Neoplasms/mortality , Adult , Gastrectomy/methods , Treatment Outcome , Retrospective Studies , Aged, 80 and over , Postoperative Complications/epidemiology , Postoperative Complications/etiologySubject(s)
Antibodies, Monoclonal, Humanized , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Antibodies, Monoclonal, Humanized/therapeutic use , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma/drug therapy , Male , Antineoplastic Agents, Immunological/therapeutic use , Antineoplastic Agents, Immunological/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Middle Aged , AgedABSTRACT
The prognostic significance of positive peritoneal cytology still varied between cancer types and geographical origin. However, because of the lack of sensitivity of this biomarker, conventional cytology is not routinely performed in every country. Here, we wanted to test a new biomarker, peritoneal tumour DNA, using NGS technique, in order to compare it with the historical one, in patients having peritoneal metastases of gastrointestinal or ovarian cancer.
Subject(s)
Dihydropyrimidine Dehydrogenase Deficiency , Fluorouracil , Humans , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Dihydropyrimidine Dehydrogenase Deficiency/complications , Fatal Outcome , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Male , Antimetabolites, Antineoplastic/adverse effects , Antimetabolites, Antineoplastic/administration & dosage , Middle Aged , FemaleABSTRACT
BACKGROUND: Trifluridine/tipiracil (FTD/TPI) is approved in third-line treatment of patients with advanced/metastatic gastric and gastroesophageal junction adenocarcinomas (aGA/GEJA). The association of oxaliplatin with FTD/TPI is promising and the combination of FTD/TPI + oxaliplatin + nivolumab has shown a predictable and manageable safety profile. AIMS: The aim is to evaluate the efficacy and safety of FTD/TPI plus oxaliplatin with or without nivolumab in patients, with HER2 negative aGA/GEJA, unfit for triplet chemotherapy (TFOX/mFLOT regimen), in the first-line metastatic setting in comparison with the standard of care FOLFOX with or without nivolumab. METHODS: This study is a prospective randomised, open label, comparative, multicentre, phase II trial designed to include 118 patients. The primary objective is to evaluate the superiority of FTD/TPI plus oxaliplatin with or without nivolumab over FOLFOX regimen with or without nivolumab in terms of PFS in a population of patients non candidate for triplet chemotherapy. Nivolumab will be used for patients whose tumour express PD-L1 with a CPS score ≥5. DISCUSSION: PRODIGE73-UCGI40-LOGICAN study will provide efficacy and safety data on the association of FTD/TPI plus oxaliplatin with or without nivolumab versus FOLFOX regimen with or without nivolumab in first-line palliative setting, in patients with aGA/GEJA (NCT05476796).
Subject(s)
Adenocarcinoma , Antineoplastic Combined Chemotherapy Protocols , Drug Combinations , Esophagogastric Junction , Fluorouracil , Leucovorin , Nivolumab , Pyrrolidines , Stomach Neoplasms , Thymine , Trifluridine , Humans , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Prospective Studies , Trifluridine/administration & dosage , Trifluridine/therapeutic use , Leucovorin/therapeutic use , Leucovorin/administration & dosage , Fluorouracil/administration & dosage , Fluorouracil/therapeutic use , Nivolumab/administration & dosage , Nivolumab/adverse effects , Nivolumab/therapeutic use , Esophagogastric Junction/pathology , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Pyrrolidines/administration & dosage , Pyrrolidines/therapeutic use , Female , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/therapeutic use , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/pathology , Receptor, ErbB-2/metabolism , Male , Middle Aged , Oxaliplatin/administration & dosage , Oxaliplatin/therapeutic use , Adult , Aged , Multicenter Studies as TopicABSTRACT
BACKGROUND: Small bowel adenocarcinoma is a rare disease. The genomic profiling tumours according to clinical characteristics and its impact on the prognosis remains unclear. METHODS: A pooled analysis of clinical data, genomic profiling and MisMatch Repair (MMR) status from three databases was performed. RESULTS: A total of 188 tumour samples were analysed. A predisposing disease was reported in 22.3%, mainly Lynch syndrome and Crohn's disease. The tumours were localized in 80.2% and metastatic in 18.8%. The most frequent mutations were KRAS (42.0%) among them 7/79 are G12C, TP53 (40.4%), APC (19.1%), PIK3CA (18.6%), SMAD4 (12.8%) and ERBB2 (9.6%). Mutation distribution differed according to predisposing disease for TP53, ERBB2, IDH1, FGFR3, FGFR1 and KDR. KRAS and SMAD4 mutations were more frequent in metastatic tumour, whereas ERBB2 mutations were absent in metastatic tumour. For localized tumour, APC mutation was independently associated with a poor overall survival (OS) (p = 0.0254). 31.8% of localized tumours and 11.3% of metastatic tumours were dMMR (29.8% of the entire cohort). A dMMR status was associated with a better OS (HR = 0.61 [0.39-0.96], p = 0.0316). CONCLUSIONS: There is a different genomic profile according to the stage and predisposing disease. dMMR and APC mutation in localized tumour predict a better prognosis.
Subject(s)
Adenocarcinoma , Intestinal Neoplasms , Mutation , Humans , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Intestinal Neoplasms/genetics , Intestinal Neoplasms/pathology , Intestinal Neoplasms/mortality , Male , Female , Middle Aged , Aged , Intestine, Small/pathology , Adult , Prognosis , Aged, 80 and over , Gene Expression Profiling , DNA Mismatch Repair/geneticsABSTRACT
Importance: Efficacy of second-line chemotherapy in advanced gastric or gastrooesphageal junction (GEJ) adenocarcinoma remains limited. Ojectives: To determine the efficacy of 1 or 2 immune checkpoint inhibitors combined with FOLFIRI (leucovorin [folinic acid], fluorouracil, and irinotecan) in the treatment of advanced gastric/GEJ adenocarcinoma. Design, Setting, and Participants: The PRODIGE 59-FFCD 1707-DURIGAST trial is a randomized, multicenter, noncomparative, phase 2 trial, conducted from August 27, 2020, and June 4, 2021, at 37 centers in France that included patients with advanced gastric/GEJ adenocarcinoma who had disease progression after platinum-based first-line chemotherapy. Intervention: Patients were randomized to receive FOLFIRI plus durvalumab (anti-programmed cell death 1 [PD-L1]) (FD arm) or FOLFIRI plus durvalumab and tremelimumab (anti-cytotoxic T-lymphocyte associated protein 4 [CTLA-4]) (FDT arm). The efficacy analyses used a clinical cutoff date of January 9, 2023. Main outcome and Measures: The primary end point was progression-free survival (PFS) at 4 months according to RECIST 1.1 criteria evaluated by investigators. Results: Overall, between August 27, 2020, and June 4, 2021, 96 patients were randomized (48 in each arm). The median age was 59.7 years, 28 patients (30.4%) were women and 49 (53.3%) had GEJ tumors. Four month PFS was 44.7% (90% CI, 32.3-57.7) and 55.6% (90% CI, 42.3-68.3) in the FD and FDT arms, respectively. The primary end point was not met. Median PFS was 3.8 and 5.4 months, objective response rates were 34.7% and 37.7%, and median overall survival was 13.2 and 9.5 months in the FD and FDT arms, respectively. Disease control beyond 1 year was 14.9% in the FD arm and 24.4% in the FDT arm. Grade 3 to 4 treatment-related adverse events were observed in 22 (47.8%) patients in each arm. A combined positive score (CPS) PD-L1 of 5 or higher was observed in 18 tumors (34.0%) and a tumor proportion score (TPS) PD-L1 of 1% or higher in 13 tumors (24.5%). Median PFS according to CPS PD-L1 was similar (3.6 months for PD-L1 CPS ≥5 vs 5.4 months for PD-L1 CPS <5) by contrast for TPS PD-L1 (6.0 months for PD-L1 TPS ≥1% vs 3.8 months for PD-L1 TPS <1%). Conclusions and Relevance: Combination of immune checkpoint inhibitors with FOLFIRI in second-line treatment for advanced gastric/GEJ adenocarcinoma showed an acceptable safety profile but antitumor activity only in a subgroup of patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03959293.