Multidisciplinary therapy for scirrhous gastric cancer: a retrospective analysis and proposal of new treatment strategy

Abstract

BackgroundScirrhous gastric cancer (SGC) is highly invasive and metastatic because of its interactions with stromal cells, such as fibroblasts and macrophages, and extracellular matrix, leading to a higher incidence of peritoneal metastasis (PM) than other gastric cancers (GCs). Taxane-based intraperitoneal chemotherapy (IPC) is a promising therapy for PM. We retrospectively analyzed outcomes of multidisciplinary therapies that included IPC for SGC.Patients and therapyOf 1,679 GC patients treated between 1990 and 2012, we analyzed 119 patients who underwent multidisciplinary therapy for SGC. Patients without PM received gastrectomy with lymphadenectomy and resection of involved adjacent organs followed by intraoperative IPC using cisplatin. Patients with PM received chemotherapy using fluorouracil, with or without methotrexate plus IPC using cisplatin before 2000, and S-1 plus IPC using paclitaxel or docetaxel since 2000.ResultsOf the 119 patients, 73 (61%) had PM and 63 (53%) had positive peritoneal lavage cytology. Of the 89 gastrectomy patients, 30 (34%) had macroscopic residual tumors (R2). Of the patients treated since 2000, 66 (100%) received S-1 plus taxanes and 44 patients (67%) received taxane-based IPC. Median survival time was significantly longer in the post-2000 group (22.8 months) than in the pre-2000 group (9.5 months). In univariate analysis, lavage cytology, PM, taxane-based IPC, gastrectomy, and R2 resection were significant prognostic factors. However, only R2 resection was an independent prognostic factor in multivariate analysis (hazard ratio: 5.53, 95% CI: 2.05–14.93).ConclusionAs use of taxane-based IPC is not an independent prognostic factor, new multidisciplinary therapies are necessary to avoid R2 resections.

The Genomic Signatures of Linitis Plastica Signal the Entrance into a New Era: Novel Approaches for Diagnosis and Treatment

“…Intraperitoneal chemotherapy is also being investigated as an alternative to conventional IV chemotherapy for peritoneal carcinomatosis. Taxanebased IPC takes advantage of the antifibrotic properties of the agent [1]. Adipocytes found around tumors, along their borders, or within the tumor itself, serve a function similar to CAFs.…”

“…Gastric cancer (GC) ranks as the fifth most common malignancy worldwide, with approximately 1.1 million new cases annually. It stands out as having one of the highest mortality rates with the third most deaths [1][2][3][4]. Linitis Plastica (LP), a subtype of gastric cancer, constitutes 10% of all GC cases [2,5,6].…”

High CD8/CD33 ratio in peritoneal metastatic lesions is associated with favorable prognosis in gastric cancer

“… 17 Patients received the chemotherapy of physician's choice including taxane‐based intraperitoneal chemotherapy. 4 Immune checkpoint inhibitor was not used in all cases. Among the patients who were judged as resectable, gastrectomy was performed 4 to 8 weeks after their last day of chemotherapy.…”

“…Importantly, molecular mechanisms of peritoneal metastasis are poorly understood. Although various treatments have been developed for peritoneal metastasis, including systemic chemotherapy, intraperitoneal chemotherapy, sufficiently satisfactory outcomes have yet to be achieved 3 , 4 , 5 ; this indicates the need for novel treatment strategies, in addition to conventional surgery and chemotherapy.…”

Serine threonine kinase 11/liver kinase B1 mutation in sporadic scirrhous-type gastric cancer cells

“…It has been reported that the neoadjuvant chemotherapy for patients with SGC (JCOG0501) could not find a survival benefit (4). One of the reasons for the poor prognosis of SGC is the lack of effective therapeutic agents based on the characteristic molecular biology of SGC (5,6). Then, in this study, we aimed to find the characteristic features and useful therapeutic targets for SGC.…”