Correlation between postoperative chemotherapy regimen and survival in patients with resectable gastric adenocarcinoma accompanied with vascular cancer thrombus

BACKGROUND Patients with resectable gastric adenocarcinoma accompanied by vascular cancer thrombus(RGAVCT)have a poor prognosis,with a 5-year survival rate ranging from 18.42%-53.57%.These patients need a reasonable postoperative treatment plan to improve their prognosis.AIM To determine the most effective postoperative chemotherapy regimen for patients with RGAVCT.METHODS We retrospectively collected the clinicopathological data of 530 patients who un-derwent radical resection for gastric cancer between January 2017 and January 2022 and who were pathologically diagnosed with gastric adenocarcinoma with a choroidal cancer embolus.Fur-thermore,we identified the high-risk variables that can influence the prognosis of patients with RGAVCT by asse-ssing the clinical and pathological features of the patients who met the inclusion criteria.We also assessed the significance of survival outcomes using Mantel-Cox univariate and multivariate analyses.The subgroups of pa-tients with stages Ⅰ,Ⅱ,and Ⅲ disease who received single-,dual-,or triple-drug regimens following surgery were analyzed using SPSS 25.0 and the ggplot2 package in R 4.3.0.RESULTS In all,530 eligible individuals with RGAVCT were enrolled in this study.The median overall survival(OS)of patients with RGAVCT was 24 months,and the survival rates were 80.2%,62.5%,and 42.3%at 12,24,and 59 months,respectively.Preoperative complications,tumor size,T stage,and postoperative chemotherapy were identified as independent factors that influenced OS in patients with RGAVCT according to the Cox multivariate analysis model.A Kaplan-Meier analysis revealed that chemotherapy had no effect on OS of patients with stage Ⅰ or Ⅱ RGAVCT;however,chemotherapy did have an effect on OS of stage Ⅲ patients.Stage Ⅲ patients who were treated with chemotherapy consisting of dual-or triple-agent regimens had better survival than those treated with single-agent regimens,and no significant difference was observed in the survival of patients treated with chemo-therapy consisting of dual-or triple-agent regimens.CONCLUSION For patients with stage Ⅲ RGAVCT,a dual-agent regimen of postoperative chemotherapy should be recom-mended rather than a triple-agent treatment,as the latter is associated with increased frequency of adverse events.

Current Status and Research Progress of Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer

Gastric cancer is one of the most common malignant tumours worldwide, with a high degree of malignancy and a poor prognosis. While early gastric cancer can be cured by surgical treatment, locally advanced gastric cancer requires neoadjuvant therapy to shrink the tumour, suppress potential metastases, achieve down-staging, and provide patients with the opportunity for radical surgery to prolong their survival. This article reviews the current status and progress of neoadjuvant chemotherapy for locally advanced gastric cancer.

Effect of postoperative adjuvant chemotherapyon the prognosis of patients with ypT0-3N0 rectalcancer undergoing neoadjuvant chemoradiotherapy

Objective The aim of this study was to investigate the effect of adjuvant chemotherapy (AC) on theprognosis of patients with ypT0-3N0 rectal cancer undergoing neoadjuvant chemoradiotherapy.Methods The study participants were 110 patients with locally advanced rectal cancer. Thirty-fourpatients did not receive postoperative AC treatment, and the other 76 patients received postoperative ACtreatment. The differences in the 5-year overall survival (OS) and disease-free survival (DFS) between thetwo groups were compared.Results Age was an important determinant of the patients’ decision to undergo postoperative treatment.Patients who did not receive AC treatment were significantly older than those who received AC treatment(P < 0.05). The tumor location (distance above anal margin) in the AC group was significantly larger thanthat in the non-AC group (P < 0.05). Moreover, there was no significant difference in the 5-year DFS andOS between the two groups. Postoperative AC did not significantly improve the prognosis of patients withrectal cancer. Age, tumor differentiation, and the number of resected lymph nodes were independent factorsaffecting the OS of patients (P < 0.05). Older patients, patients with lower degree of tumor differentiation,and patients with <12 resected lymph nodes showed worse prognosis (P < 0.05).Conclusion Patients with rectal cancer whose ypT0-3N0 stage is reduced after neoadjuvantchemoradiotherapy, especially those without adverse prognostic factors, do not need AC after surgery.

Oxaliplatin plus S-1 or capecitabine as neoadjuvant or adjuvant chemotherapy for locally advanced gastric cancer with D2lymphadenectomy: 5-year follow-up results of a phase II-III randomized trial

Objective： To compare the effect of neoadjuvant chemotherapy （NACT） with adjuvant chemotherapy （ACT） using oxaliplatin plus S-1 （sex） or capecitabine （CapeOX） on gastric cancer patients with D2 lymphadenectomy. Methods： This was a two-by-two factorial randomized phase Ⅱ-Ⅲ trial, and registered on ISRCTN registry （No. ISRCTN12206108）. Locally advanced gastric cancer patients were randomized to neoadjuvant sex, neoadjuvant CapeOX, adjuvant sex, or adjuvant CapeOX arms. Primary analysis was performed on an intention- to-treat （ITT） basis using overall survival （OS） as primary endpoint. Results： This trial started in September 2011 and closed in December 2012 with 100 patients enrolled. Treatment completion rate was 56%, 52%, 38% and 30% in the four arms, respectively. NACT group had fewer dropouts due to unacceptable toxicity （P=0.042）. Surgical complication rate did not differ by the four groups （P=0.986）. No survival signifcant difference was found comparing NACT with ACT （P=0.664; 5-year-OS： 70% vs. 74% respectively）, nor between the sex and CapeOX groups （P=0.252; 5-year-OS： 78% vs. 66% respectively）. Subgroup analysis showed sex significantly improved survival in patents with diffuse type （P=0.048）. Conclusions： No significant survival difference was found between NACT and ACT. sex and CapeOX had good safety and efficacy as neoadjuvant regimens. Diffuse type patients may survive longer due to sex.

Adjuvant chemotherapy for gastric cancer:Current evidence and future challenges

Gastric cancer still represents one of the major causes of cancer mortality worldwide.Patients survival is mainly related to stage,with a high proportion of patients with metastatic disease at presentation.Thus,the cure rate largely depend upon surgical resection.Despite the additional,albeit small,benefit of adjuvant chemotherapy has been clearly demonstrated,no general consensus has been reached on the best treatment option.Moreover,the narrow therapeutic index of adjuvant chemotherapy(i.e.,limited survival benefit with considerable toxicity)requires a careful assessment of expected risks and benefits for individual patients.Treatment choices vary widely based on the different geographic areas,with chemotherapy alone more often preferred in Europe or Asia and chemoradiotherapy in the United States.In the present review we discuss the current evidence and future challenges regarding adjuvant chemotherapy in curatively resected gastric cancer with particular emphasis on the recently completed landmark studies and meta-analyses.The most recent patient-level meta-analysis demonstrated the benefit of adjuvant chemotherapy over curative surgery;the same Authors also showed that disease free survival may be used as a surrogate end-point for overall survival.We finally discuss future research issues such as the need of economic evaluations,development of prognostic or predictive biomarkers,and the unmet clinical need of trials comparing perioperative chemotherapy with adjuvant treatment.

Pilot study of postoperative adjuvant chemoradiation for advanced gastric cancer:Adjuvant 5-FU/cisplatin and chemoradiation with capecitabine

AIM： To evaluate the efficacy and toxicity of postoperative chemoradiation using FP chemotherapy and oral capecitabine during radiation for advanced gastric cancer following curative resection. METHODS： Thirty-one patients who had underwent a potentially curative resection for Stage Ⅲ and Ⅳ （M0） gastric cancer were enrolled. Therapy consists of one cycle of FP （continuous infusion of 5-FU 1000 mg/m^2 on d 1 to 5 and cisplatin 60 mg/m^2 on d 1） followed by 4500 cGy （180 cGy/d） with capecitabine （1650 mg/m daily throughout radiotherapy）. Four wk after completion of the radiotherapy, patients received three additional cycles of FP every three wk. The median follow-up duration was 22.2 mo. RESULTS： The 3-year disease free and overall survival in this study were 82.7% and 83.4%, respectively. Four patients （12.9%） showed relapse during follow-up. Eight patients did not complete all planned adjuvant therapy. Grade 3/4 toxicities included neutropenia in 50.2%, anemia in 12.9%, thrombocytopenia in 3.2% and nausea/ vomiting in 3.2%. Neither grade 3/4 hand foot syndrome nor treatment related febrile neutropenia or death were observed. CONCLUSION： These preliminary results suggest that this postoperative adjuvant chemoradiation regimen of FP before and after capecitabine and concurrent radiotherapy appears well tolerated and offers a comparable toxicity profile to the chemoradiation regimen utilized in INTo0116. This treatment modality allowed successful Ioco-regional control rate and 3-year overall survival.

Current status of adjuvant chemotherapy for gastric cancer

Although radical gastrectomy is a standard treatment for advanced gastric cancer,recurrence remains high.After several large-scale controlled studies have shown the beneficial effects of adjuvant chemotherapy,that treatment emerged as a standard option for advanced gastric cancer after gastrectomy.However,various guidelines from different countries have suggested different adjuvant chemotherapies.Understanding the differences between guidelines is very important for investigating further therapeutic strategies.Fortunately,because there are many ongoing studies about new regimens for adjuvant treatment,it is expected that patients with gastric cancer after surgery will have better outcome.

Implications of clinical research on adjuvant chemotherapy for gastric cancer: Where to go next?

Postoperative adjuvant chemotherapy(ACT)confers superior gastric cancer(GC)survival in the Eastern cohort.However,is the current standard of ACT already excessive,or is it still necessary to increase its intensity for specific subgroups?Tailored ACT strategies for GC depend on gradual exploration by clinical trials in selected patients.Thus,understanding the implications of previous and current research can help us respond wisely and design effective,rational trials,save medical resources and make better decisions in clinical practice.After reviewing and analyzing studies on ACT for GC patients undergoing curative resection,we found that research strategies for conducting"addition""ACT for specific stages of the disease have achieved great progress in making ACT more tailored and personalized in consideration of pathology stages.Furthermore,trials indicate that"addition"ACT strategies for GC patient subgroups based on histological characteristics might be helpful to move toward a more specific tailored and personalized management approach.Designing ACT research focused on different node statuses should also be conducted according to the biological specificity of lymph node(LN)metastasis.Therefore,future trials designed to determine tailored treatment based on histological and biological characteristics for specific subgroups are urgently needed and conducted as the theme of the 2019 American Society of Clinical Oncology(ASCO):Caring for Every Patient,Learning from Every Patient.

Retrospective analysis of adjuvant chemotherapy for curatively resected gastric cancer

AIM: To determine the efficacy of adjuvant chemotherapy for gastric cancer in clinical practice, a retrospective analysis was conducted in a high-volume Chinese cancer center.

Is adjuvant chemotherapy necessary for early gastric cancer?

Objective:To quantify the potential benefit of adjuvant chemotherapy(ACT)with respect to survival,and to identify factors for predicting prognoses in early gastric cancer patients.Methods:Patients with pT1 gastric cancer(GC)who underwent radical resection with D2 lymphadenectomy were retrospectively analyzed.Based on lymph node metastasis(LNM)status and treatment regimens,patients were classified into groups,and clinicopathological variables,overall survival(OS),and disease-specific survival(DSS)were compared.Results:Of 1,050 enrolled patients,151 patients(14.4%)had a positive LNM status.Submucosal invasion,undifferentiated state,tumor size>2 cm,ulceration,and lymphovascular invasion were independent risk factors for LNM using multivariate analyses.The 5-year OS of all patients was 96.4%.HER2 positive,perineural invasion,and LNM were independent factors for worse survival.Patients with pT1N3 GC had a worse 5-year OS and DSS than pT1N0,pT1N1,and pT1N2 patients(P<0.001).The 5-year OS and DSS for pT1N1 patients showed no significant difference between ACT and surgery only patients.For pT1N2 patients,the 5-year OS and DSS showed no significant difference between S-1 and Xelox treatments.For pT1N3 patients,7(36.8%)received S-1,while 12(63.2%)received Xelox treatment.Patients receiving Xelox treatment showed a better 5-year OS(75.0%vs.14.3%)and DSS(81.8%vs.20.0%)than patients receiving S-1(P<0.05).Conclusions:Curative surgery only was adequate for patients with pT1N0 and pT1N1.Xelox showed no survival benefits for pT1N2 patients.Therefore,S-1 is the optimal choice for pT1N2 patients,when considering adverse effects.Xelox is recommended for pT1N3 patients.

A new scoring system to evaluate adjuvant chemotherapy for patients with T2N0M0 gastric cancer after D2 gastrectomy

BACKGROUND At present,there is insufficient medical evidence to determine whether adjuvant chemotherapy is necessary for T2N0M0 gastric cancer.AIM To obtain a risk score to assess the need for adjuvant chemotherapy in patients with T2N0M0 gastric cancer.METHODS We identified 325 patients with pathological T2N0M0 stage primary gastric cancer at the National Cancer Center between 2011 and 2018.Univariate and multivariate Cox regression analyses were performed to predict factors affecting prognosis.Vascular invasion,tumor site,and body mass index were assessed,and a scoring system was established.We compared the survival outcomes and benefits of adjuvant chemotherapy between the different subgroups.RESULTS Five-year survival rates of the score 0,1,2,and 3 groups were 92%,95%,80%,and 50%,respectively(P<0.001).In the score 2-3 group,five-year survival rates for patients in the adjuvant chemotherapy group and postoperative observation group were 95%and 61%,respectively(P=0.021).CONCLUSION For patients with T2N0M0 stage gastric cancer and two or more risk factors,adjuvant chemotherapy after D2 gastrectomy may have a survival benefit.

A pilot clinical study to evaluate feasibility of using single patient classifier as a prognostic test in stage Ⅱ-Ⅲ gastric cancer patients

Objective:Precision medicine approaches emphasize the importance of reliable prognostic tools for guiding individualized therapy decisions.In this study,we evaluated the clinical feasibility of the single patient classifier(SPC)test,a new clinical-grade prognostic assay,in stageⅡ-Ⅲgastric cancer patients.Methods:A prospective multicenter study was conducted,involving 237 patients who underwent gastrectomy between September 2019 and August 2020 across nine hospitals.The SPC test was employed to stratify patients into risk groups,and its feasibility and performance were evaluated.The primary endpoint was the proportion of the cases in which the test results were timely delivered before selecting postoperative treatment.Furthermore,3-year disease-free survivals of risk groups were analyzed.Results:The SPC test met the primary endpoint criteria.The 99.5%of SPC tests were timely delivered to hospitals before the postoperative treatment started.In a clinical setting,the median time from the specimen transfer to laboratory to the result delivery to hospital was 4 d.Furthermore,3-year disease-free survivals were significantly different between risk groups classified with SPC tests.Conclusions:This study highlights the SPC test's feasibility in offering crucial information timely delivered for making informed decisions regarding postoperative treatment strategies.It also provides evidence to support the implementation of a future prospective clinical trial aimed at evaluating the clinical utility of the SPC test in guiding personalized treatment decisions for gastric cancer patients.

Epidemiology and prognostic nomogram for locally advanced gastric signet ring cell carcinoma:A population-based study

BACKGROUND Gastric signet ring cell carcinoma(GSRC)represents a specific subtype of gastric cancer renowned for its contentious epidemiological features,treatment principles,and prognostic factors.AIM To investigate the epidemiology of GSRC and establish an improved model for predicting the prognosis of patients with locally advanced GSRC(LAGSRC)after surgery.METHODS The annual rates of GSRC incidence and mortality,covering the years 1975 to 2019,were extracted from the Surveillance,Epidemiology,and End Results(SEER)database to explore the temporal trends in both disease incidence and mortality rates using Joinpoint software.The clinical data of 3793 postoperative LAGSRC patients were collected from the SEER database for the analysis of survival rates.The Cox regression model was used to explore the independent prognostic factors for overall survival(OS).The risk factors extracted were used to establish a prognostic nomogram.RESULTS The overall incidence of GSRC increased dramatically between 1975 and 1998,followed by a significant downward trend in incidence after 1998.In recent years,there has been a similarly optimistic trend in GSRC mortality rates.The trend in GSRC showed discrepancies based on age and sex.Receiver operating characteristic curves,calibration curves,and decision curve analysis for 1-year,3-year,and 5-year OS demonstrated the high discriminative ability and clinical utility of this nomogram.The area under the curve indicated that the performance of the new model outperformed that of the pathological staging system.CONCLUSION The model we established can aid clinicians in the early prognostication of LAGSRC patients,resulting in improved clinical outcomes by modifying management strategies and patient health care.

Perioperative chemotherapy for resectable gastric cancer:MAGIC and beyond

Over the last 15 years, there have been major advances in the multimodal treatment of gastric cancer, in large part due to several phase Ⅲ studies showing the treatment benefits of neoadjuvant and adjuvantchemotherapy and chemoradiation protocols. The objective of this editorial is to review the current highlevel evidence supporting the use of chemotherapy, chemoradiation and anti-HER2 agents in both the neoadjuvant and adjuvant settings, as well as to provide a clinical framework for use of this data based on our own institutional protocol for gastric cancer. Major studies reviewed include the SWOG/INT 0116, Medical Research Council Adjuvant Gastric Infusional Chemotherapy(MAGIC), CLASSIC, ACTS-GC, Adjuvant Chemoradiation Therapy in Stomach Cancer(ARTIST) and Trastuzumab for Gastric Cancer trials. Although these studies have demonstrated that multiple approaches in terms of the timing and therapy for gastric cancer are effective, no standard of care is widely accepted and questions regarding the optimal timing of chemotherapy, the benefit of radiotherapy, the minimum required extent of lymphadenectomy and optimal chemotherapy regimen still exist. Protocols from the upcoming ARTIST Ⅱ, CRITICS, TOPGEAR, Neo-AEGIS and MAGIC-B studies are outlined, and results from these studies will provide critical information regarding optimal timing and treatment regimen. Additionally, the future directions of gastric cancer research predicated on molecular profiling and tailored therapies based on targetable genetic alterations in individual patient's tumors are addressed.

Neoadjuvant plus adjuvant chemotherapy benefits overall survival of locally advanced gastric cancer

Neoadjuvant chemotherapy (NAC) has drawn more attention to the treatment of locally advanced gastric cancer (AGC) in the current multidisciplinary treatment model. EORTC trial 40954 has recently reported that NAC plus surgery without postoperative adjuvant chemotherapy could not benefit the locally AGC patients in their overall survival. We performed a meta-analysis of 10 studies including 1518 gastric cancer patients. Stratified subgroups were NAC plus surgery and NAC plus both surgery and adjuvant chemotherapy (AC), while control was surgery alone. The results showed that NAC plus surgery did not benefit the patients with locally AGC in their overall survival [odds ratio (OR) = 1.20, 95% CI 0.80-1.80, P = 0.37] and the number needed to treat (NNT) was 74. However, the NAC plus both surgery and AC had a slight overall survival benefit (OR = 1.33, 95% CI 1.03-1.71, P = 0.03) and NNT was 14, which is superior to the NAC plus surgery. Therefore, we recommend that combined NAC and AC should be used to improve the overall survival of the locally AGC patients.

Chemotherapy for gastric cancer

Metastatic gastric cancer remains a non-curative disease. Palliative chemotherapy has been demonstrated to prolong survival without quality of life compromise. Many single-agents and combinations have been confirmed to be active in the treatment of metastatic disease. Objective response rates ranged from 10-30% for single-agent therapy and 30-60% for polychemotherapy. Results of phase Ⅱ and Ⅲ studies are reviewed in this paper as well as the potential efficacy of new drugs. For patients with localized disease, the role of adjuvant and neoadjuvant chemotherapy and radiation therapy is discussed. Most studies on adjuvant chemotherapy failed to demonstrate a survival advantage, and therefore, it is not considerecl as standard treatment in most centres. Adjuvant immunochemotherapy has been developed fundamentally in Korea and Japan. A meta-analysis of phase Ⅲ trials with OK-432 suggested that immunochemotherapy may improve survival of patients with curatively resected gastric cancer. Based on the results of US Intergroup 0116 study, postoperative chemoradiation has been accepted as standard care in patients with resected gastric cancer in North America. However, the results are somewhat confounded by the fact that patients underwent less than a recommended D1 lymph node dissection and the pattern of recurrence suggested a positive effect derived from local radiotherapy without any effect on micrometastatic disease. Neoadjuvant chemotherapy or chemoradiation therapy remains experimental, but several phase Ⅱ studies are showing promising results. Phase Ⅲ trials are needed.

Adjuvant chemotherapy with S-1 plus oxaliplatin improves survival of patients with gastric cancer after D2 gastrectomy: A multicenter propensity score-matched study

AIM To investigate the safety and efficacy of S-1 plus oxaliplatin(SOX) as an adjuvant chemotherapy regimen in gastric cancer(GC) after D2 dissection.METHODS GC Patients who underwent D2 gastrectomy from September 2009 to December 2011 in four Chinese institutions were enrolled. Patients with stage ⅠB-ⅢC GC, who received adjuvant SOX treatment were matched by propensity scores with those who underwent surgery alone and those who conducted capecitabine plus oxaliplatin(XELOX) regimen. Disease-free survival(DFS) and overall survival(OS) were compared among the groups. In addition, adverse events in SOX patients were analyzed.Of 1944 GC patients who underwent D2 dissection, 867 were included for analysis. One hundred and seventeen patients treated with SOX were matched to 234 patients who conducted surgery alone. Fifty-seven patients treated with SOX were matched to 57 patients who received XELOX. The estimated five-year DFS was 57.5% in the adjuvant SOX group which was higher than that(44.6%) in the surgery alone group(P = 0.001); and the estimated five-year OS was 68.3% which was higher than that(45.8%) of surgery alone group(P < 0.001). Survival benefit was also revealed in stage III and > 60 years old subgroups(P < 0.001 and P = 0.015, respectively). Compared with XELOX regimen, SOX showed no significant difference in DFS(P = 0.340) and OS(P = 0.361). The most common ≥ 3 grade adverse events of SOX regimen were neutropenia(22.6%), leukopenia(8.9%) and thrombocytopenia(5.6%).CONCLUSION Compared with surgery alone, SOX regimen significantly improves the long-term survival and has acceptable toxicity in patients with stage ⅠB-ⅢC GC after D2 dissection. It may be a novel adjuvant chemotherapy regimen in GC patients.

Impact of duration of adjuvant chemotherapy in radically resected patients with T4bN1-3M0/TxN3bM0 gastric cancer

AIM To provide evidence regarding the postoperative treatment of patients with T4 b N1-3 M0/Tx N3 b M0 gastric cancer, for which guidelines have not been established. METHODS Patients who had undergone curative resection between 1996 and 2014 with a pathological stage of T4 b N1-3 M0/Tx N3 b M0 for gastric cancer were retrospectively analyzed; staging was based on the 7 th edition of the American Joint Committee on Cancer staging system. The clinicopathological characteristics, administration of adjuvant chemotherapy, and patterns of recurrence were studied. Univariate and multivariate analyses of prognostic factors were conducted. The chemotherapeutic agents mainly included fluorouropyrimidine, platinum and taxanes, used as monotherapy, doublet, or triplet regimens. Patterns of first recurrence were categorized as locoregional recurrence, peritoneal dissemination, or distant metastasis.RESULTS The 5-year overall survival(OS) of the whole group(n = 176) was 16.8%, and the median OS was 25.7 mo(95%CI: 20.9-30.5). Lymphovascular invasion and a node positive rate(NPR) ≥ 0.8 were associated with a poor prognosis(P = 0.01 and P = 0.048, respectively). One hundred forty-seven(83.5%) of the 176 patients eventually experienced recurrence; the most common pattern of the first recurrence was distant metastasis. The prognosis was best for patients with locoregional recurrence and worst for those with peritoneal dissemination. Twelve(6.8%) of the 176 patients did not receive adjuvant chemotherapy, while 164(93.2%) patients received adjuvant chemotherapy. Combined chemotherapy, including doublet and triplet regimens, was associated with a better prognosis than monotherapy, with no significant difference in 5-year OS(17.5% vs 0%, P = 0.613). The triplet regimen showed no significant survival benefit compared with the doublet regimen for 5-year OS(18.5% vs 17.4%, P = 0.661). Thirty-nine(22.1%) patients received adjuvant chemotherapy for longer than six months; the median OS in patients who received adjuvant chemotherapy for longer than six months was 40.2 mo(95%CI: 30.6-48.2), significantly longer than the 21.6 mo(95%CI: 19.1-24.0) in patients who received adjuvant chemotherapy for less than six months(P = 0.001).CONCLUSION Patients with T4 b N1-3 M0/Tx N3 b M0 gastric cancer showed a poor prognosis and a high risk of distant metastasis. Adjuvant chemotherapy for longer than six months improved outcomes for them.

ERCC1 polymorphism, expression and clinical outcome of oxaliplatin-based adjuvant chemotherapy in gastric cancer

AIM： TO determine the influence of excision repair cross complementing group 1 （ERCC1） codon 118 polymorphism and mRNA level on the clinical outcome of gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy. METHODS： Eighty-nine gastric cancer patients treated with oxalipatin-based adjuvant chemotherapy were included in this study. ERCC1 codon 118 C/T polymorphism was tested by polymerase chain reaction-ligation detection reaction （PCR-LDR） method in peripheral blood lymphocytes of those patients; and the intratumoral ERCC1 mRNA expression was measured using reverse transcription PCR in 62 patients whose tumor tissue specimens were available. RESULTS： No significant relationship was found between ERCC1 codon 118 polymorphism and ERCC1 mRNA level. The median relapse-free and overall survival period was 20.1 mo and 28.4 too, respectively. The relapse-free and overall survivals in patients with lOW levels of ERCC1 mRNA were significantly longer than those in patients with high levels （P 〈 0.05）, while there was no significant association found between ERCC1 118 genotypes and the disease prognosis. Multivariate analysis also showed that ERCC1 mRNA level was a potential predictor for relapse and survival in gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy （P 〈 0.05）. CONCLUSION： ERCC1 codon 118 polymorphisrn has no significant impact on ERCC1 rnRNA expression, and the intraturnoral ERCC1 rnRNA level but not codon 118 polymorphisrn may be a useful predictive parameter for the relapse and survival of gastric cancer patients receiving oxaliplatin-based adjuvant chemotherapy.

Adjuvant therapy for gastric cancer:Current and future directions

The management of gastric cancer continues to evolve. Whilst surgery alone is effective when tumours present early,a large proportion of patients are diagnosed with loco-regionally advanced disease,resulting in high locoregional and distant relapse rates,with subsequent poor survival. Early attempts at improving outcomes following resection were disappointing;however,randomized trials have now established either post-operative chemoradiotherapy(INT0116) or peri-operative chemotherapy as standard adjuvant therapies in the Western world. There remain,however,significant differences in the approach to management between the West and East. In Asia,where there is the highest incidence of gastric cancer,extended resection followed by adjuvant chemotherapy represents the standard of care. This review discusses current standard adjuvant therapy in gastric adenocarcinoma,as well as recent and ongoing trials investigating novel(neo)adjuvant approaches,which hope to build on the successes of previous studies.