Multidisciplinary treatment strategy for locally advanced gastric cancer: A systematic review

BackgroundMultidisciplinary management of patients with locally advanced gastric cancer (LAGC) remains unstandardized worldwide. We performed a systemic review to summarize the advancements, regional differences, and current recommended multidisciplinary treatment strategies for LAGC.MethodsEligible studies were identified through a comprehensive search of PubMed, Web of Science, Cochrane Library databases and Embase. Phase 3 randomized controlled trials which investigated survival of patients with LAGC who underwent gastrectomy with pre-/perioperative, postoperative chemotherapy, or chemoradiotherapy were included.ResultsIn total, we identified 11 studies of pre-/perioperative chemotherapy, 38 of postoperative chemotherapy, and 14 of chemoradiotherapy. In Europe and the USA, the current standard of care is perioperative chemotherapy for patients with LAGC using the regimen of 5-FU, folinic acid, oxaliplatin and docetaxel (FLOT). In Eastern Asia, upfront gastrectomy and postoperative chemotherapy is commonly used. The S-1 monotherapy or a regimen of capecitabine and oxaliplatin (CapOx) are used for patients with stage II disease, and the CapOx regimen or the S-1 plus docetaxel regimen are recommended for those with stage III Gastric cancer (GC). The addition of postoperative radiotherapy to peri- or postoperative chemotherapy is currently not recommended. Additionally, clinical trials testing targeted therapy and immunotherapy are increasingly performed worldwide.ConclusionsRecent clinical trials showed a survival benefit of peri-over postoperative chemotherapy and chemoradiotherapy. As such, this strategy may have a potential as a global standard for patients with LAGC. Outcome of the ongoing clinical trials is expected to establish the global standard of multidisciplinary treatment strategy in patients with LAGC.     

Hepatic Artery Infusion Chemotherapy Using Fluorouracil,Leucovorin, and Oxaliplatin versus Transarterial Chemoembolization as Initial Treatment for Locally Advanced Hepatocellular Carcinoma: A Propensity Score–Matching Analysis

PurposeTo compare the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) with a modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX) regimen with that of transarterial chemoembolization as a locoregional treatment for patients with locally advanced hepatocellular carcinoma (HCC).MethodsThis retrospective study included adult patients with locally advanced HCC who received first-line treatment with either HAIC-mFOLFOX or conventional transarterial chemoembolization monotherapy from January 2015 to December 2016. The outcomes, including tumor response rates, evaluated via imaging assessment using the modified response evaluation criteria in solid tumors; overall survival; progression-free survival; and safety, were compared. The propensity score–matching methodology was used to reduce the influence of confounding factors on the outcomes.ResultsThe study included 131 patients with locally advanced HCC who underwent transarterial chemoembolization and 101 who received HAIC-mFOLFOX as initial treatment. After propensity score matching (n = 67 in each group), patients who received HAIC-mFOLFOX had a higher objective response rate (43.3% vs 13.4%, P = .001), longer median overall survival (13.9 vs 6.0 months, P < .001), and longer median progression-free survival (6.4 vs 2.8 months, P = .001) than those who underwent transarterial chemoembolization. The survival benefit with HAIC-mFOLFOX was strengthened in patients with HCC with vascular invasion (hazard ratio: 0.379; 95% confidence interval: 0.237–0.607). HAIC-mFOLFOX was associated with lower incidences of severe adverse events (8.9% vs 22.9%) and liver toxicity than transarterial chemoembolization.ConclusionsCompared with transarterial chemoembolization, HAIC-mFOLFOX is a potentially safer and more effective locoregional therapy for patients with locally advanced HCC.     

胃癌腹膜转移病人腹腔化疗港并发症发生及危险因素分析

目的:分析腹腔化疗港并发症发生及相关危险因素。方法:回顾性分析我院323例放置腹腔化疗港病人的临床资料,纳入261例胃癌腹膜转移病人。分析腹腔化疗港在胃癌腹膜转移病人腹腔化疗时发生的并发症及其危险因素。结果:261例中59例(22.6%)发生化疗港相关并发症。其中,皮下积液(25例,42.4%)和化疗港感染(16例,27.1%)是发生较多的并发症。其他是港体倾斜翻转(9例,15.3%),化疗港局部切口裂开(7例,11.9%),导管堵塞(1例,1.7%),和皮下转移(1例,1.7%)。化疗港并发症发生的中位时间为化疗港放置后3.0个月。结合Clavien-Dindo分级方法,将化疗港发生的并发症分为1~4个等级。ECOG评分、血清白蛋白水平、置港流程优化及专业团队放置为化疗港并发症发生的独立危险因素(P<0.05)。ECOG评分为唯一影响并发症分级的关联因素(P<0.05)。结论:腹腔化疗港在胃癌腹膜转移病人腹腔化疗中的应用安全可行,发生并发症可控。ECOG评分、血清白蛋白水平、置港方式是否优化及是否专业团队放置为化疗港并发症发生的独立危险因素。     

Doxorubicin‐induced normal breast epithelial cellular aging and its related breast cancer growth through mitochondrial autophagy and oxidative stress mitigated by ginsenoside Rh2

Clinical dose of doxorubicin (100 nM) induced cellular senescence and various secretory phenotypes in breast cancer and normal epithelial cells. Herein, we reported the detailed mechanism underlying ginsenoside Rh2‐mediated NF‐κB inhibition, and mitophagy promotion were evaluated by antibody array assay, western blotting analysis, and immunocytostaining. Ginsenoside Rh2 suppressed the protein levels of TRAF6, p62, phosphorylated IKK, and IκB, which consequently inactivated NF‐κB activity. Rh2‐mediated secretory phenotype was delineated by the suppressed IL‐8 secretion. Senescent epithelial cells showed increased level of reactive oxygen species (ROS), which was significantly abrogated by Rh2, with upregulation on SIRT 3 and SIRT 5 and subsequent increase in SOD1 and SOD2. Rh2 remarkably favored mitophagy by the increased expressions of PINK1 and Parkin and decreased level of PGC‐1α. A decreased secretion of IL‐8 challenged by mitophagy inhibitor Mdivi‐1 with an NF‐κB luciferase system was confirmed. Importantly, secretory senescent epithelial cells promoted the breast cancer (MCF‐7) proliferation while decreased the survival of normal epithelial cells demonstrated by co‐culture system, which was remarkably alleviated by ginsenoside Rh2 treatment. These data included ginsenoside Rh2 regulated ROS and mitochondrial autophagy, which were in large part attributed to secretory phenotype of senescent breast epithelial cells induced by doxorubicin. These findings also suggested that ginsenoside Rh2 is a potential treatment candidate for the attenuation of aging related disease.     

Population-based study on practice variation regarding preoperative systemic chemotherapy in patients with colorectal liver metastases and impact on short-term outcomes

IntroductionDefinitions regarding resectability and hence indications for preoperative chemotherapy vary. Use of preoperative chemotherapy may influence postoperative outcomes. This study aimed to assess the variation in use of preoperative chemotherapy for CRLM and related postoperative outcomes in the Netherlands.Materials and methodsAll patients who underwent liver resection for CRLM in the Netherlands between 2014 and 2018 were included from a national database. Case-mix factors contributing to the use of preoperative chemotherapy, hospital variation and postoperative outcomes were assessed using multivariable logistic regression. Postoperative outcomes were postoperative complicated course (PCC), 30-day morbidity and 30-day mortality.ResultsIn total, 4469 patients were included of whom 1314 patients received preoperative chemotherapy and 3155 patients did not. Patients receiving chemotherapy were significantly younger (mean age (+SD) 66.3 (10.4) versus 63.2 (10.2) p < 0.001) and had less comorbidity (Charlson scores 2+ (24% versus 29%, p = 0.010). Unadjusted hospital variation concerning administration of preoperative chemotherapy ranged between 2% and 55%. After adjusting for case-mix factors, three hospitals administered significantly more preoperative chemotherapy than expected and six administered significantly less preoperative chemotherapy than expected. PCC was 12.1%, 30-day morbidity was 8.8% and 30-day mortality was 1.5%. No association between preoperative chemotherapy and PCC (OR 1.24, 0.98–1.55, p = 0.065), 30-day morbidity (OR 1.05, 0.81–1.39, p = 0.703) or with 30-day mortality (OR 1.22, 0.75–2.09, p = 0.467) was found.ConclusionSignificant hospital variation in the use of preoperative chemotherapy for CRLM was present in the Netherlands. No association between postoperative outcomes and use of preoperative chemotherapy was found.     

Disqualification of Neoadjuvant Rectal Score Based on Data of 6596 Patients From the Netherlands Cancer Registry

BackgroundThe neoadjuvant rectal score (NAR) was developed as a surrogate endpoint for overall survival in patients with rectal cancer after neoadjuvant treatment. We aimed to validate the NAR score in patients from the Netherlands Cancer Registry database.Patients and MethodsWe studied patients with rectal cancer treated with long-course neoadjuvant therapy followed by surgery in the Netherlands between 2007 and 2014. The probability of concordance with overall survival and the goodness of fit of several models were evaluated using Harrell's concordance index (c index) and the Akaike information criterion (AIC), which is used to compare the quality of statistical models.ResultsThe NAR score resulted in a c index of 0.665. We found that single pathologic parameters (pT or pN) have similar concordance as the NAR formula (c index of 0.663 and 0.655, respectively). A combination of pT and pN resulted in better concordance with the true endpoint, overall survival (c index 0.684), and a simple Cox regression model with the 3 parameters included in the NAR formula (cT, pT, and pN) improved the concordance even more (c index 0.689). When the AIC index was compared for all models, the NAR score model showed the worst fit to the true endpoint.ConclusionWe found no additional value for using the NAR formula as a surrogate endpoint for overall survival in rectal cancer patients treated with neoadjuvant therapy.