Perioperative Modified FLOT Versus EOX in Locally Advanced Resectable Gastric and Gastro-Oesophageal Junction Adenocarcinoma: Results of a Matched-Pair Analysis.

BACKGROUND AND OBJECTIVES: There is limited real-world data on the efficacy of 2-weekly cycles of docetaxel, oxaliplatin, leucovorin, and fluorouracil (FLOT) compared to epirubicin, oxaliplatin, and capecitabine (EOX) as perioperative therapy in esophagogastric adenocarcinomas (EGAC). METHODS: The data of 611 patients with EGAC treated with perioperative chemotherapy and planned for curative resection between January 2013 and December 2019 were retrieved. Patients receiving EOX and a dose-modified version of FLOT (mFLOT) were evaluated. A 1:1 matching, using age, tumour location, signet ring histology, and Eastern Cooperative Oncology Group performance status, without replacement was performed by using nearest neighbour matching method. The primary endpoint of the study was 3-year event-free survival (EFS). RESULTS: A total of 593 patients (261 with EOX and 332 with mFLOT) were matched. One hundred and nighty-eight patients (76%) and 285 patients (86%) in the EOX and mFLOT cohorts underwent curative resection, respectively (p = 0.002). With a median follow-up of 35 and 53 months, respectively, the primary outcome of 3-year EFS was statistically superior in patients receiving mFLOT as compared to the EOX regimen (60% vs. 39%; p < 0.001). There was a greater incidence of grade 3 and grade 4 neutropenia (neoadjuvant: 18% vs. 2%; p < 0.001, adjuvant: 18% vs. 1%; p = 0.001) and febrile neutropenia (neoadjuvant: 8% vs. 1.1%; p < 0.001, adjuvant: 6% vs. 0; p = 0.001) with mFLOT. INTERPRETATION AND CONCLUSION: mFLOT is associated with improved resection rates and survival in comparison to EOX as perioperative therapy in gastric adenocarcinomas in this large real-world cohort, with manageable increase in clinically relevant toxicities such as grade 3 and grade 4 febrile neutropenia and neutropenia.

Surgical Feasibility, Determinants, and Overall Efficacy of Neoadjuvant 177Lu-DOTATATE PRRT for Locally Advanced Unresectable Gastroenteropancreatic Neuroendocrine Tumors.

We assessed 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) in the neoadjuvant setting in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). We also evaluated the variables associated with resectability of the primary tumor after PRRT. Methods: This study included 57 GEP-NET patients who had a primary tumor that was unresectable (because of vascular involvement as defined using the pancreatic ductal adenocarcinoma criteria of the National Comprehensive Cancer Network) and who underwent 177Lu-DOTATATE therapy without any prior surgery. They were categorized into 2 groups: 23 patients without liver metastases (group 1) and 34 patients with potentially resectable liver metastases (group 2). 177Lu-DOTATATE was administered with mixed amino acid-based renal protection at a dose of 7.4 GBq (200 mCi) per cycle. Surgical resectability was evaluated using triphasic contrast-enhanced abdominal CT imaging at 3 different time points during the PRRT course. Four broad categories of overall PRRT response were evaluated. The Kaplan-Meier product-limit method was used to calculate progression-free survival (PFS) and overall survival (OS). Associations between variables and a resectable primary tumor after PRRT were analyzed using the χ2 test, with a P value of less than 0.05 considered statistically significant. Results: After 177Lu-DOTATATE therapy, the unresectable primary tumor became resectable in 15 of 57 (26.3%) patients (7 patients in group 1 and 8 patients in group 2). A complete or partial response to PRRT was seen in 48 patients (84%), 23 patients (40%), 18 patients (31%), and 23 patients (40%) using symptomatic, biochemical, molecular imaging, and anatomic imaging criteria, respectively. Estimated rates of PFS were 95% and 90% at 2 y in groups 1 and 2, respectively. The 2-y OS of the 2 groups combined was 92.1%. The rate at which the primary tumor was resectable after PRRT was significantly higher in patients who had duodenal neuroendocrine tumors, patients who had GEP-NETs with no regional lymph node involvement, patients for whom the primary tumor was smaller than 5 cm, patients for whom liver metastases were no larger than 1.5 cm, patients for whom there were no more than 3 liver metastases, and patients for whom 18F-FDG uptake in the primary tumor had an SUVmax of less than 5. Conclusion: In a moderate fraction of GEP-NET patients, with or without liver metastases, whose primary tumor was unresectable because of vascular involvement, the primary tumor converted from unresectable to resectable after 177Lu-DOTATATE therapy, signifying that neoadjuvant PRRT can be considered in such patients. The effective control of symptoms, favorable morphologic and functional imaging response, and durable PFS and OS that we observed after 177Lu-DOTATATE PRRT may lead to less morbidity and mortality in these patients.

Management of fibrolamellar hepatocellular carcinoma.

Fibrolamellar hepatocellular carcinoma (FLHCC) is a primary liver tumor. It is a pathologically distinct variety of hepatocellular carcinoma (HCC). The term 'fibrolamellar' is derived from the presence of thick fibrous collagen bands surrounding the tumor cells. It is a relatively rare tumor of unknown biology. It has a distinctive predilection for adolescents and young adults with no underlying liver disease or cirrhosis. FLHCC patients have higher incidence of lymph node involvement than conventional HCC patients probably owing to larger median tumor size at presentation. Most cases present at an advanced stage at the time of initial diagnosis, however, curative intent treatment options can still be offered to up to 70% of patients. Surgery (resection/liver transplantation) is the current mainstay of treatment and remains the only potentially curative option. As recurrences are common, alternative therapies are under investigation. FLHCCs have traditionally been considered less chemo-responsive than their conventional HCC counterparts, but in advanced cases multimodality treatments can be effective. Compared to stage-matched non-cirrhotic patients with HCC, patients with FLHCC do not have a favourable prognosis and do not respond differently to treatment. The survival advantage observed in FLHCC over conventional HCC is most likely due to younger age at presentation and absence of cirrhosis.

Peritoneal Carcinomatosis in Colorectal Cancers - Management Perspective Needs a Change.

BACKGROUND: Peritoneal carcinomatosis (PC) from colorectal cancers (CRC) either at initial presentation or at subsequent recurrence presents a significant treatment challenge. The aim of our study was to find its incidence and analyze outcomes of patients with PC from CRC origin managed by different treatment modalities. PATIENTS AND METHODS: A retrospective analysis of patients, from August 2013 to July 2014, presenting with metastatic peritoneal disease from CRC with or without metastasis to other sites was performed. PC was classified as limited (peritoneal carcinomatosis index [PCI] < 10) and widespread (PCI > 10). RESULTS: This study included 70 patients; 45 patients had peritoneum as the only site of metastasis and the remaining 25 visceral metastasis with peritoneum. Resections were performed in 23 patients (19 underwent R0 resection and 4 were R+). All patients received systemic chemotherapy (FOLFOX [Oxaliplatin with fluorouracil and folinic acid]/CAPOX [oxaliplatin and capecitabine]). At a median follow-up of 11 months, the median OS was 14 months. Patients with PCI < 10 had significantly better survival (median not reached) as compared with those with PCI > 10 (15 months). Patients undergoing R0 resection had better survival (24 months) versus those with R+ resection (16 months). The survival of patients receiving only systemic chemotherapy was 11 months. CONCLUSION: The incidence of peritoneal metastasis in CRC is about 10%. A select group of patients who have low PCI who undergo R0 resection of only the diseased portion, without entire peritonectomy, still do well. Where facilities for hyperthermic intraperitoneal chemotherapy are not available, cytoreduction followed by systemic chemotherapy should be considered. The added role of hyperthermic intraperitoneal chemotherapy in this subgroup needs to be evaluated.