scholarly journals Perioperative chemotherapy for locally advanced gastric cancer in Japan: current and future perspectives

Surgery Today ◽  
2019 ◽  
Vol 50 (1) ◽  
pp. 30-37 ◽  
Author(s):  
Masanori Tokunaga ◽  
Yuya Sato ◽  
Masatoshi Nakagawa ◽  
Tomoki Aburatani ◽  
Takatoshi Matsuyama ◽  
...  

Abstract The standard treatment for locally advanced gastric cancer differs across the world. In western countries, perioperative chemotherapy or postoperative adjuvant chemoradiotherapy are the preferred treatment options, whereas in Asia, D2 gastrectomy followed by postoperative adjuvant chemotherapy is standard. In Japan, adjuvant chemotherapy with S-1 is the standard treatment for pStage II gastric cancer, whereas adjuvant chemotherapy with a doublet regimen is preferred for pStage III gastric cancer. The efficacy of preoperative neoadjuvant chemotherapy using S-1 plus cisplatin, has been investigated in selected patients with expected poor survival outcomes. To expand the indications for neoadjuvant chemotherapy, a clinical trial investigating the efficacy of preoperative S-1 plus oxaliplatin in patients with cStage III (cT3-4N1-3) gastric cancer (JCOG1509) is ongoing in Japan. The addition of immune checkpoint inhibitors to cytotoxic chemotherapy also seems promising and is being investigated in international randomized clinical trials. Although we have to await the final results of these studies, preoperative neoadjuvant chemotherapy is a promising treatment strategy and likely to become standard treatment for locally advanced gastric cancer in Japan.

2020 ◽  
Vol 50 (5) ◽  
pp. 528-534 ◽  
Author(s):  
Masanori Terashima ◽  
Takaki Yoshikawa ◽  
Narikazu Boku ◽  
Seiji Ito ◽  
Akira Tsuburaya ◽  
...  

Abstract Perioperative treatment for locally advanced gastric cancer has been inconsistent between Japan and the Western countries. In Japan, D2 gastrectomy followed by adjuvant chemotherapy is regarded as standard treatment, while neoadjuvant or perioperative chemotherapy is considered to be a standard in the Western countries. Stomach Cancer Study Group of Japan Clinical Oncology Group (JCOG) has conducted many perioperative chemotherapy trials. After the publishing of positive results of ACTS-GC trial, stage-specific adjuvant chemotherapy protocols are planned. JCOG1104 was conducted as to demonstrate the non-inferiority of four courses of S-1 to standard eight courses of S-1, because the efficacy of S-1 appears to be sufficient in stage II. The trial failed to demonstrate the non-inferiority of four courses of S-1. S-1 for 1 year is still recognized to be a standard for stage II gastric cancer. For stage III, studies with more intensive treatments were planned as the efficacy of S-1 monotherapy seems to be insufficient. As in the Western countries, JCOG planned the perioperative chemotherapy. However, the clinical staging is a serious issue to select optimal patients for perioperative chemotherapy. JCOG conducted a prospective cohort study to evaluate the validity of clinical staging in JCOG1302A. From the results of this study, cT3-4 and cN1–3 are selected as optimal candidate for perioperative chemotherapy. JCOG1509 was conducted to demonstrate the superiority of perioperative chemotherapy to adjuvant chemotherapy in these cohorts. Perioperative chemotherapy for marginally resectable tumours such as linitis plastica or extensive nodal disease and special type of cancer like HER2 positive are also conducted.


2013 ◽  
Vol 50 (3) ◽  
pp. 236-242 ◽  
Author(s):  
Thales Paulo BATISTA ◽  
Candice Amorim de Araujo Lima SANTOS ◽  
Gustavo Fernandes Godoy ALMEIDA

Gastric cancer is one of the most common cancers and a main cause of cancer-related death worldwide, since the majority of patients suffering of this malignancy are usually faced with a poor prognosis due to diagnosis at later stages. In order to improve treatment outcomes, the association of surgery with chemo and/or radiotherapy (multimodal therapy) has become the standard treatment for locally advanced stages. However, despite several treatment options currently available for management of these tumors, perioperative chemotherapy has been mainly accepted for the comprehensive therapeutic strategy including an appropriated D2-gastrectomy. This manuscript presents a (nonsystematic) critical review about the use of perioperative chemotherapy, with a special focus on the drugs delivery.


2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 244-244
Author(s):  
Elvira Lise Vos ◽  
Steven Brad Maron ◽  
Robert Wallace Krell ◽  
Masaya Nakauchi ◽  
Megan Fiasconaro ◽  
...  

244 Background: Subgroup analysis of trials data suggested a favorable prognostic role for microsatellite instability high (MSI-high) status in resectable gastric cancer, but a lack of survival benefit from neoadjuvant/adjuvant chemotherapy; questioning current standard of care for MSI-high locally advanced gastric cancer. To help guide treatment decision making, we retrospectively studied the interaction between MSI status and chemotherapy on survival in a single institution. Methods: All clinically advanced (tumor stage 3-4 or positive lymph nodes) gastric cancer patients that underwent gastrectomy between 2000-2018 with MSI status available from immunohistochemistry (IHC, deficient mismatch repair protein expression (dMMR) vs proficient (pMMR)) or DNA next generation sequencing testing (NGS, MSI-high vs low/stable (MSS)) were included. Clinicopathological characteristics and overall survival (OS) was compared between patients with neoadjuvant/adjuvant chemotherapy and without, stratified for MSI status, by Kaplan-Meier and Cox regression analysis. Results: From a total of 1,844 clinically advanced patients with resection, MSI status was available in 559 as determined by IHC in 420, NGS in 88, and both in 51 with a concordance rate of 50/51 (98%). Tumors were dMMR/MSI-high in 84 (15%) and pMMR/MSS in 475 (85%). Patients with dMMR/MSI-high tumors were more often older, female, and had distal tumors with intestinal subtype. Neoadjuvant and/or adjuvant chemotherapy was administered in 53 (63%) in the dMMR/MSI-high group and 367 (77%) in the pMMR/MSS (p = 0.006). Median (interquartile range) time of follow-up was 32 (19-57) months. In the total cohort, OS after 3 years was 82% in the dMMR/MSI-high and 59% in pMMR/MSS (p < 0.001). In the patients with neoadjuvant/adjuvant chemotherapy only, the dMMR/MSI-high had improved OS (3-years OS: 80% vs 60%, p = 0.001), and after adjustment for age and clinical tumor stage in multivariable analysis, dMMR/MSI-high status was associated with improved OS (HR 0.38 95%CI 0.22-0.68). In the dMMR/MSI-high group only, 3-year OS was 80% with chemotherapy vs 86% without (p = 0.374), and chemotherapy was not associated with a difference in OS after multivariable analysis (HR 1.03 95%CI 0.40-2.66). In case of neoadjuvant chemotherapy, grade 1 pathological response ( > 90%) was observed in 1/41 (2.4%) of the dMMR/MSI-high tumors vs 43/278 (16%) of the pMMR/MSS tumors respectively (p = 0.026). Conclusions: The incidence of MSI-high tumors in our cohort of clinically locally advanced, resectable, gastric cancers was 15%. Patients with MSI-high tumors had worse pathological treatment response to neoadjuvant chemotherapy, but better OS, compared to microsatellite stable tumors. However, in patients with MSI-high tumors, OS was not altered by neoadjuvant/adjuvant chemotherapy. We recommend assessing MSI status in locally advanced gastric cancer.


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