Chemotherapy For Resectable Gastric Cancer Research Articles

Pathological complete response achieved with FLOT chemotherapy in two patients with MSI-H esophagogastric junction and gastric adenocarcinoma.

Globally, more than 1 million new cases of gastric cancer were estimated in 2020, ranking fourth in cancer mortality. Currently although in resectable gastric cancer and esophagogastric junction (EGJ) adenocarcinoma a perioperative triplet chemotherapy regimen including a fluoropyrimidine, a platinum compound and docetaxel (FLOT) demonstrated a better overall survival, the survival rate is still very low, and a massive effort is still required to improve clinical prognosis. High microsatellite instability (MSI-H) status in gastric cancer is a favorable prognostic factor but poor data are available on its predictive role for perioperative FLOT chemotherapy in resectable gastric cancer. Here, we presented the case of two patients with advanced MSI-H gastric cancer/EGJ adenocarcinoma who had no residual tumor following neoadjuvant FLOT chemotherapy maintaining a complete response for more than 30 months, suggesting MSI-H status to be a positive prognostic marker also in patients treated with a taxane-containing triplet in this setting. We also discuss the future perspectives including the opportunity to achieve excellent clinical outcomes with immune checkpoint inhibitor (ICI)-based regimens.

Neoadjuvant chemotherapy for resectable gastric cancer is associated with better outcomes than neoadjuvant chemoradiation.

National Comprehensive Cancer NetworkGuidelines recommend neoadjuvant chemotherapy (CTx) or chemoradiation (CRTx) for advanced resectable gastric cancer, irrespective of the tumor location. The aim of this study is to compare survival benefits between neoadjuvant CTx and CRTx using the National Cancer Database (NCDB). Using the NCDB, we retrospectively reviewed patients who underwent gastrectomy after neoadjuvant CRTx or CTx between 2004 and 2018. The cohort included 14 266 patients, with 6458 (45.3%) receiving neoadjuvant CTx and 7808 (54.7%) receiving neoadjuvant CRTx. Both treatment groups exhibited significant differences in various demographic and clinical factors, including sex, age, race, tumor locations, stages, and adjuvant treatment (all p < 0.001). While the complete pathological response was more prevalent in the CRTx group (p < 0.001), overall survival (OS) was significantly extended in the CTx group (p < 0.001). Subgroup survival analyses, accounting for tumor location and clinical/pathological stage, consistently revealed longer OS in the CTx group (p < 0.001). The direct comparison showed an approximately 20%-30% improved 5-year OS in the CTx group across the majority of American Joint Committee on Cancer (AJCC) T/N category tables. Multivariate analysis confirmed neoadjuvant CTx was an independent protective factor (hazard ratio = 0.811; p < 0.001). A nomogram for OS based on multivariate analysis was also proposed, revealing a significant improvement in the c-index compared to the current AJCC staging (0.654 vs. 0.596). Patients undergoing neoadjuvant CRTx demonstrated significantly shorter survival compared to patients undergoing CTx at the same stage. The current AJCC staging may lead to an overestimation of survival in patients with neoadjuvant CRTx.

Evaluation of Pathological Response Rate and Complications of FOLFOX versus FLOT Regimen in Perioperative Chemotherapy for Resectable Gastric Cancer: A Prospective Study.

Previous studies have shown that the perioperative and postoperative chemotherapy can lead to an improvement in the prognosis of patients with resectable gastric cancer (GC). There is no preference for postoperative chemotherapy with the two common treatment regimens, FLOT and FOLFOX, in these patients. The aim of this study was to compare FOLFOX and FLOT regimens in perioperative chemotherapy in resectable GC based on pathological response and complications. This prospective cohort study was conducted on 112 patients with resectable GC who were admitted to Firozgar Hospital affiliated with Iran University of Medical Sciences, Tehran, Iran between 2021 to 2022. Given the inclusion criteria, 80 patients were enrolled in the present study. Patients were divided into 2 groups based on the type of treatment regimen, FOLFOX (40 patients) and FLOT (40 patients). Tumor response was classified using Mandard Tumor regression grading system criteria into five categories of TRG1 to 5. Also, the side effects were classified according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0. The rate of complete pathological response in FOLT group was significantly higher than FOLFOX group (35.0% vs 2.5%, p: 0.001). The frequency of neurological complications and hair loss in the FOLT group was significantly higher than the FOLFOX group (P<0.05). While no significant difference was observed in the frequency of hematological, Gastroenterological, hepatic, renal and stomatitis complications in the both groups (p>0.05). Our study showed that perioperative FLOT regimen has a better pathological response than FOLFOX regimen. The frequency of neurological complications and hair loss was significantly higher in patients treated with FLOT regimen. Thus, perioperative FLOT regimen may be recommended for treating GC patients.

SO-11 Response evaluation after neoadjuvant chemotherapy for resectable gastric cancer: Downsizing vs downstaging

Response evaluation following neoadjuvant chemotherapy (NAC) in resectable gastric cancer is debated. The aims of the present study were to investigate the value of strict radiologic methods, hence UICC-downstaging and RECIST, as mode of response evaluation following a MAGIC-style regimen of NAC applied to a large Western cohor. Further to explore a composite radiologic/pathologicdownstaging comparing radiologic stage at diagnosis (rTNM) to pathologic stage following chemotherapy (ypTNM). Population-based study (2007-2016) on 171 consecutive patients with gastric adenocarcinoma, receiving a MAGIC style neoadjuvant chemotehrapi (NAC). Three methods of response evaluation are investigated, two strict radiologic methodes; one comparing initialt rTNM-stage and radiologic stage following NAC (yrTNM) and one using RECIST (downsizing), and a composite radiologic/pathologic comparing initial rTNM-stage to pathologic ypTNM-stage (downstaging). Of 171 patients receiving NAC, 169 were available for response evaluation. For radiologic TNM response mode, 43% responded, 50% had stable disease and 7% progressed at CT. Crosstabulating yrTNM stage to ypTNM stage, 24% had concordant stages, with CT overstaging 38% and understaging 38% of the tumours, Cohen kappa ƙ=0,06 (95%CI 0,004-0,12). Similar patterns of discordance were found for T-stages and N-stages separately. For M-category, restaging CT detected 12 patients with carcinomatosis, with an additional 14 diagnosed with carcinomatosis only at operation. No patient developed parenchymal or extra abdominal metastases, and none developed locally non-resectable tumour during delivery of NAC. Restaging CT with response evaluation was not able to stratify patients into groups of different long-term survival rates based on response mode. RECIST failed to identify half of the patients progressing to metastatic disease, and were not able to assign patients to subsets with different long-term survival rates. The compositeTNM response mode, comparing initialt radiologic stage (rTNM) to the pathologic TNM stage (ypTNM) did achieve this objective. A totale of 78/164 (48%) were downstaged, 25/164 (15%) had stable disease and 61/164 (37%) were upstaged. Histopathologic complete response was found in 15/164 (9%). The 5-year overall survival was 65.3% (95% CI 54.7% - 75.9%) for responders, 40.0% (95 CI 20.8% - 59.2%) for stable disease and 14.8% (95% CI 6.0% - 23.6%) for patients with progression, p < 0.001. In a multivariable ordinal regression Lauren category and tumour location were the only significant determinants of response mode. Routine CT-scan following NAC is of limited value. Accuracy of CT staging compared to final pathologic stage is poor, and strict radiologic downstaging as measure of response evaluation is unreliable and unable to discriminate long-term survival rates based on response mode. RECIST as method of response evaluation following NAC in gastric cancer is also discouraged. Comparing CT-stage at diagnosis to pathologic stage following NAC appears as a useful method of response evaluation serving the every-day situation well.

Short-term efficacy and toxicity of total neoadjuvant chemotherapy in patients with resectable gastric cancer

Background. Currently, perioperative chemotherapy is the standard treatment option for resectable gastric cancer (GC ) at stages higher than T1. Preoperative chemotherapy was shown do not adversely affect the course of the postoperative period in gastric cancer patients. However, approximately 60 % of radically operated patients complete adjuvant chemotherapy. In this regard, the problem arises of postponing all courses of chemotherapy for operable gastric cancer to the preoperative period.The purpose of the study was to analyze short-term efficacy and toxicity of total neoadjuvant chemotherapy with FLOT regimen in patients with resectable gastric cancer.Material and Methods. Since 2020, the Research Cancer Institute of Tomsk National Research Medical Center has been conducting a pilot study, which included 25 patients with resectable gastric cancer (T2–4N0–2M0) who received 8 cycles of neoadjuvant chemotherapy with FLOT regimen followed by radical surgery (gastrectomy or distal subtotal resection of the stomach).Results. Preoperative chemotherapy was completed in 25 (100 %) patients. Side effects that occurred during chemotherapy did not require cancellation or interruption of treatment and reduction in the initial dose of drugs. The most common adverse events were emetogenic reactions (92 %), peripheral neuropathy (60 %), and neutropenia (48 %). All patients had no greater than grade II toxicity, which was reversed with standard maintenance therapy. Radical surgeries were performed 6 weeks after completion of chemotherapy cycle 8. There were no significant postoperative complications (grade III or higher according to the Clavien–Dindo scale) and deaths. The histological examination revealed pathological response of TG R2–3 grade in 21 (84%) patients. Downstaging in both T and N categories was found in 13 (52%) patients.Conclusion. Eight cycles of total neoadjuvant chemotherapy for resectable gastric cancer demonstrates high efficacy, moderate toxicity, and do not adversely affect the course of the perioperative period.

The value of restaging CT following neoadjuvant chemotherapy for resectable gastric cancer. A population-based study

BackgroundResponse evaluation following neoadjuvant chemotherapy (NAC) in gastric cancer is debated. The aim of this study was to investigate the value of UICC-downstaging as mode of response evaluation following a MAGIC-style regimen of NAC.MethodsRetrospective, population-based study on consecutive patients with resectable gastric adenocarcinoma receiving NAC from 2007 to 2016. CT-scan was obtained at diagnosis (rTNM) and repeated following NAC (yrTNM) to evaluate response in terms of downstaging. Further, yrTNM stage was crosstabulated to pathologic stage (ypTNM) to depict correlation between radiologic and pathologic assessment.ResultsOf 171 patients receiving NAC, 169 were available for response evaluation. For TNM-stages, 43% responded, 50% had stable disease and 7% progressed at CT. Crosstabulating yrTNM stage to ypTNM stage, 24% had concordant stages, with CT overstaging 38% and understaging 38% of the tumours, Cohen kappa ƙ = 0,06 (95%CI 0.004–0.12). Similar patterns of discordance were found for T-stages and N-stages separately. For M-category, restaging CT detected 12 patients with carcinomatosis, with an additional 14 diagnosed with carcinomatosis only at operation. No patient developed parenchymal or extra abdominal metastases, and none developed locally non-resectable tumour during delivery of NAC. Restaging CT with response evaluation was not able to stratify patients into groups of different long-term survival rates based on response mode.ConclusionsRoutine CT-scan following NAC is of limited value. Accuracy of CT staging compared to final pathologic stage is poor, and radiologic downstaging as measure of response evaluation is unreliable and unable to discriminate long-term survival rates based on response mode.

Current treatment and recent progress in gastric cancer.

Gastric cancer is not a top-10 malignancy in the United States but represents one of the most common causes of cancer death worldwide. Biological differences between tumors from Eastern and Western countries add to the complexity of identifying standard-of-care therapy based on international trials. Systemic chemotherapy, radiotherapy, surgery, immunotherapy, and targeted therapy all have proven efficacy in gastric adenocarcinoma; therefore, multidisciplinary treatment is paramount to treatment selection. Triplet chemotherapy for resectable gastric cancer is now accepted and could represent a plateau of standard cytotoxic chemotherapy for localized disease. Classification of gastric cancer based on molecular subtypes is providing an opportunity for personalized therapy. Biomarkers, in particular microsatellite instability (MSI), programmed cell death ligand 1 (PD-L1), human epidermal growth factor receptor 2 (HER2), tumor mutation burden, and Epstein-Barr virus, are increasingly driving systemic therapy approaches and allowing for the identification of populations most likely to benefit from immunotherapy and targeted therapy. Significant research opportunities remain for the less differentiated histologic subtypes of gastric adenocarcinoma and those without markers of immunotherapy activity.

Neoadjuvant chemotherapy with docetaxel plus oxaliplatin and S-1 for locally advanced, resectable gastric or gastro-esophageal junction adenocarcinoma: Short-term results from a phase II trial.

397 Background: In locally advanced, resectable gastric or gastro-oesophageal junction (EGJ) adenocarcinoma, perioperative the docetaxel-based triplet FLOT (fluorouracil plus leucovorin, oxaliplatin and docetaxel) is the standard chemotherapy in Europe. However, there is no evidence of neoadjuvant chemotherapy for resectable gastric cancer in Japan. Therefore, we conducted a phase II trial of neoadjuvant chemotherapy with docetaxel plus oxaliplatin, and S-1 (DOS) for locally advanced, resectable gastric or EGJ adenocarcinoma. Methods: Eligible patients had histologically confirmed gastric or EGJ adenocarcinoma of a clinical Stage III according to the 14th Edition of Japanese Classification of Gastric Carcinoma. DOS was administered for two or three preoperative cycles followed by eight postoperative cycles of S-1. Each 3-week cycle of DOS consisted of docetaxel 40 mg/m2 and oxaliplatin 100 mg/m2 on day 1 plus S-1 80-120 mg/body on days 1 to 14. Primary endpoint was 3-year progression-free survival rate, and secondary endpoints included overall survival, progression-free survival, response rate, histological response rate, R0 resection rate, and adverse events. Results: Of 50 enrolled patients, 48 (37 gastric and 11 EGJ) were eligible for the analysis. 42 (88%) patients completed two or three preoperative cycles of DOS. The most common grade 3-4 adverse events of DOS were neutropenia (69%), leukopenia (56%), diarrhea (19%), and febrile neutropenia (13%). Of 45 patients who underwent gastrectomy, postoperative morbidities (Clavien-Dindo ≥Grade II) occurred in 12 (27%) patients. R0 resection could be achieved in 43 (90%) patients. 12 (27%) and 30 (67%) of 45 patients achieved pathological response rate of Grade2-3 and Grade1b-3, respectively. There was no treatment-related death. Conclusions: Neoadjuvant DOS for locally advanced, resectable gastric or EGJ adenocarcinoma might be favorable. Long-term results will be published in two years. Clinical trial information: 000017652.

What is the most useful body composition parameter for predicting toxicities of preoperative chemotherapy for gastric cancer?

Preoperative chemotherapy is an effective treatment option for resectable gastric cancer, but it is associated with various adverse events (AEs). This study aimed to identify the body composition parameters that most accurately predicted the incidence of AEs in preoperative chemotherapy for gastric cancer. The present study included a total of 114 patients who received preoperative chemotherapy for resectable gastric cancer. We estimated various body composition parameters using computed tomography images obtained before preoperative chemotherapy. Their associations with the incidence of hematological (grade ≥ 3) and non-hematological (grade ≥ 2) AEs were analyzed by multivariate logistic regression analyses. Seventy-two of the 114 (63.2%) patients experienced hematological AEs (grade ≥ 3), specifically neutropenia in 68 (59.6%), anemia in 5 (4.9%), and thrombocytopenia in 3 (2.6%). Meanwhile, 59 patients (51.8%) experienced non-hematological AEs (grade ≥ 2), namely hypoalbuminemia in 31 (27.2%), anorexia in 24 (21.1%), and febrile neutropenia in 17 (14.9%). Multivariate analyses revealed that a low psoas muscle index (PMI) was an independent risk factor for the incidence of both hematological and non-hematological AEs. Patients with a low PMI experienced an increased incidence of hematological and non-hematological toxicities during preoperative chemotherapy for gastric cancer. Clinicians should be aware of these risks in this population.

Individual Patient Data Meta-Analysis of the Value of Microsatellite Instability As a Biomarker in Gastric Cancer.

In the CLASSIC and MAGIC trials, microsatellite instability (MSI)-high status was a favorable prognostic and potential negative predictive factor for neoadjuvant/adjuvant chemotherapy in resectable gastric cancer (GC). Given the low prevalence of MSI-high status in GC and its association with other positive prognostic variables, large data sets are needed to draw robust evidence of its prognostic/predictive value. We performed a multinational, individual-patient-data meta-analysis of the prognostic/predictive role of MSI in patients with resectable GC enrolled in the MAGIC, CLASSIC, ARTIST, and ITACA-S trials. Prognostic analyses used multivariable Cox models (MVM). The predictive role of MSI was assessed both in an all-comer population and in MAGIC and CLASSIC trials by MVM testing of the interaction of treatment (chemotherapy plus surgery v surgery) with MSI. MSI status was available for 1,556 patients: 121 (7.8%) had MSI-high status; 576 were European, and 980 were Asian. In MSI-high versus MSI-low/microsatellite stable (MSS) comparisons, the 5-year disease-free survival (DFS) was 71.8% (95% CI, 63.8% to 80.7%) versus 52.3% (95% CI, 49.7% to 55.1%); the 5-year overall survival (OS) was 77.5% (95% CI, 70.0% to 85.8%) versus 59.3% (95% CI, 56.6% to 62.1%). In MVM, MSI was associated with longer DFS (hazard ratio [HR], 1.88; 95% CI, 1.28 to 2.76; P < .001) and OS (HR, 1.78; 95% CI, 1.17 to 2.73; P = .008), as were pT, pN, ethnicity, and treatment. Patients with MSI-low/MSS GC benefitted from chemotherapy plus surgery: the 5-year DFS compared with surgery only was 57% versus 41% (HR, 0.65; 95% CI, 0.53 to 0.79), and the 5-year OS was 62% versus 53% (HR, 0.75; 95% CI, 0.60 to 0.94). Conversely, those with MSI-high GC did not: the 5-year DFS was 70% versus 77% (HR, 1.27; 95% CI, 0.53 to 3.04), and the 5-year OS was 75% versus 83% (HR, 1.50; 95% CI, 0.55 to 4.12). In patients with resectable primary GC, MSI is a robust prognostic marker that should be adopted as a stratification factor by clinical trials. Chemotherapy omission and/or immune checkpoint blockade should be investigated prospectively in MSI-high GCs according to clinically and pathologically defined risk of relapse.

Poor compliance with perioperative chemotherapy for resectable gastric cancer and its impact on survival

BackgroundIn several Western European countries it is recommended to treat gastric cancer patients with perioperative chemotherapy if they are eligible for surgery. However, little is known about its use in daily clinical practice. This study examines the use of perioperative treatment and its impact on survival in the Netherlands. MethodsPatients diagnosed with potentially resectable gastric cancer (cT1N+/cT2-T3,X any cN, cM0,X) between 2006 and 2014 were selected from the Netherlands Cancer Registry (N = 5824). Treatment trends were examined. Propensity score matching was used to create a subsample to reduce selection bias. Cox regression analysis was used to assess differences in overall survival. ResultsThe percentage of patients treated with perioperative treatment increased from 3% in 2006 to 26% in 2014 and the use of only surgery decreased from 60% to 26%. 35% of all patients did not undergo surgery. Of the patients who underwent preoperative chemotherapy and surgery, 43% did not commence postoperative treatment. Cox regression analysis showed a better overall survival for patients who underwent perioperative treatment compared to patients who underwent preoperative treatment only (HR = 0.80 95%CI 0.70–0.93; propensity matched sample: HR = 0.84 95%CI 0.71–0.99), whereas survival was comparable for patients who underwent preoperative chemotherapy versus surgery alone (HR = 0.89 95%CI 0.77–1.02, propensity matched sample: HR = 0.85 95%CI 0.72–1.01). ConclusionThis population-based study highlights that a significant proportion of the patients did not receive perioperative treatment. More research is necessary to elucidate the importance of the individual components of perioperative treatment.

Perioperative Treatment in Resectable Gastric Cancer: Current Perspectives and Future Directions.

Gastric cancer (GC) is the fifth-most common cancer worldwide and an important cause of cancer-related-death. The growing knowledge of its molecular pathogenesis has shown that GC is not a single entity, but a constellation of different diseases, each with its own molecular and clinical characteristics. Currently, surgery represents the only curative approach for localized GC, but only 20% of patients (pts) showed resectable disease at diagnosis and, even in case of curative resection, the prognosis remains poor due to the high rate of disease relapse. In this context, multimodal perioperative approaches were developed in western and eastern countries in order to decrease relapse rates and improve survival. However, there is little consensus about the optimal treatment for non-metastatic GC. In this review, we summarize the current status and future developments of perioperative chemotherapy in resectable GC, attempting to find clear answers to the real problems in clinical practice.

Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer: per protocol analysis of the CRITICS trial

Background: The American Intergroup 0116 study (Macdonald et al; NEJM; 2001) and the British MAGIC trial (Cunningham et al; NEJM; 2006) changed clinical practice for resectable gastric cancer. It was shown that overall survival after surgery improved with postoperative chemoradiotherapy and perioperative chemotherapy, respectively. Intention-to-treat analysis of the data in the CRITICS trial (chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer; Lancet Oncology; 2018) did not show a survival difference between the two treatment arms. Due to comorbidity, the aging society, treatment related toxicity and major surgery, compliance is a problem in clinical studies. A per protocol analysis was performed acknowledging the limitations of such analysis.

Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial

Both perioperative chemotherapy and postoperative chemoradiotherapy improve survival in patients with resectable gastric cancer from Europe and North America. To our knowledge, these treatment strategies have not been investigated in a head to head comparison. We aimed to compare perioperative chemotherapy with preoperative chemotherapy and postoperative chemoradiotherapy in patients with resectable gastric adenocarcinoma. In this investigator-initiated, open-label, randomised phase 3 trial, we enrolled patients aged 18 years or older who had stage IB- IVA resectable gastric or gastro-oesophageal adenocarcinoma (as defined by the American Joint Committee on Cancer, sixth edition), with a WHO performance status of 0 or 1, and adequate cardiac, bone marrow, liver, and kidney function. Patients were enrolled from 56 hospitals in the Netherlands, Sweden, and Denmark, and were randomly assigned (1:1) with a computerised minimisation programme with a random element to either perioperative chemotherapy (chemotherapy group) or preoperative chemotherapy with postoperative chemoradiotherapy (chemoradiotherapy group). Randomisation was done before patients were given any preoperative chemotherapy treatment and was stratified by histological subtype, tumour localisation, and hospital. Patients and investigators were not masked to treatment allocation. Surgery consisted of a radical resection of the primary tumour and at least a D1+ lymph node dissection. Postoperative treatment started within 4-12 weeks after surgery. Chemotherapy consisted of three preoperative 21-day cycles and three postoperative cycles of intravenous epirubicin (50 mg/m2 on day 1), cisplatin (60 mg/m2 on day 1) or oxaliplatin (130 mg/m2 on day 1), and capecitabine (1000 mg/m2 orally as tablets twice daily for 14 days in combination with epirubicin and cisplatin, or 625 mg/m2 orally as tablets twice daily for 21 days in combination with epirubicin and oxaliplatin), received once every three weeks. Chemoradiotherapy consisted of 45 Gy in 25 fractions of 1·8 Gy, for 5 weeks, five daily fractions per week, combined with capecitabine (575 mg/m2 orally twice daily on radiotherapy days) and cisplatin (20 mg/m2 intravenously on day 1 of each 5 weeks of radiation treatment). The primary endpoint was overall survival, analysed by intention-to-treat. The CRITICS trial is registered at ClinicalTrials.gov, number NCT00407186; EudraCT, number 2006-004130-32; and CKTO, 2006-02. Between Jan 11, 2007, and April 17, 2015, 788 patients were enrolled and randomly assigned to chemotherapy (n=393) or chemoradiotherapy (n=395). After preoperative chemotherapy, 372 (95%) of 393 patients in the chemotherapy group and 369 (93%) of 395 patients in the chemoradiotherapy group proceeded to surgery, with a potentially curative resection done in 310 (79%) of 393 patients in the chemotherapy group and 326 (83%) of 395 in the chemoradiotherapy group. Postoperatively, 233 (59%) of 393 patients started chemotherapy and 245 (62%) of 395 started chemoradiotherapy. At a median follow-up of 61·4 months (IQR 43·3-82·8), median overall survival was 43 months (95% CI 31-57) in the chemotherapy group and 37 months (30-48) in the chemoradiotherapy group (hazard ratio from stratified analysis 1·01 (95% CI 0·84-1·22; p=0·90). After preoperative chemotherapy, in the total safety population of 781 patients (assessed together), there were 368 (47%) grade 3 adverse events; 130 (17%) grade 4 adverse events, and 13 (2%) deaths. Causes of death during preoperative treatment were diarrhoea (n=2), dihydropyrimidine deficiency (n=1), sudden death (n=1), cardiovascular events (n=8), and functional bowel obstruction (n=1). During postoperative treatment, grade 3 and 4 adverse events occurred in 113 (48%) and 22 (9%) of 233 patients in the chemotherapy group, respectively, and in 101 (41%) and ten (4%) of 245 patients in the chemoradiotherapy group, respectively. Non-febrile neutropenia occurred more frequently during postoperative chemotherapy (79 [34%] of 233) than during postoperative chemoradiotherapy (11 [4%] of 245). No deaths were observed during postoperative treatment. Postoperative chemoradiotherapy did not improve overall survival compared with postoperative chemotherapy in patients with resectable gastric cancer treated with adequate preoperative chemotherapy and surgery. In view of the poor postoperative patient compliance in both treatment groups, future studies should focus on optimising preoperative treatment strategies. Dutch Cancer Society, Dutch Colorectal Cancer Group, and Hoffmann-La Roche.

Benefit of Adjuvant Traditional Herbal Medicine With Chemotherapy for Resectable Gastric Cancer.

Introduction: Stomach cancer, historically, has a low survival rate advances in curative resection procedures. Objectives: To assess the potential benefits of traditional herbal medicines in conjunction with chemotherapy in postoperative gastric cancer patients in terms of overall survival and disease-free survival. Data Sources: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, a Chinese database (CNKI), a Korean database, a Japanese database, AMED, and CINAHL up to September 2016. We summarized survival data from all RCTs. Study Selection: All RCTs of oral traditional medicines for resectable gastric cancer compared with chemotherapy alone were eligible. Data Extraction: Thirteen eligible trials with survival data (1075 patients) were deemed eligible for inclusion. Results: There were 217 documented deaths of the 574 patients assigned to adjuvant traditional medicines groups and 319 documented deaths of the 501 patients assigned to the chemotherapy-only groups. Adjuvant traditional medicines were associated with a statistically significant benefit in terms of overall survival rate (hazard ratio = 0.56; 95% confidence interval = 0.47-0.66; P < .00001) and disease-free survival (hazard ratio = 0.54; 95% confidence interval = 0.43-0.66; P < .00001). Conclusion: Among the RCTs included, the inclusion of postoperative adjuvant traditional medicines was associated with reduced risk of death in gastric cancer patients, when survival rates were compared with the group of patients who received chemotherapy alone. However, most of the included studies utilized are thought to be of low quality, so it would certainly appear that more trials are both advisable and necessary to arrive at correct and convincing conclusions.

Chemotherapy versus chemoradiotherapy following surgery and neoadjuvant chemotherapy for resectable gastric cancer (CRITICS): an editorial

Gastric cancer is a malignancy with a strong global distribution, being more common in Asian countries like Japan and South Korea. As such, treatment algorithms differ significantly between the Eastern countries and Western. According to the Japanese Gastric Cancer Guidelines, neoadjuvant therapy is not utilized, even for advanced stage cancers (1).

Validity of studies suggesting postsurgical chemotherapy for resectable gastric cancer: critical appraisal of randomised trials

Background and aimIn 2013, Diaz-Nieto et al published a Cochrane review to summarise the impact of postsurgical chemotherapy versus surgery alone on survival for resectable gastric cancer. The authors concluded...

Role of systemic immune-inflammatory index, tumor infiltrating neutrophils and PD-1+ T cells to predict the postoperative recurrence after S-1 adjuvant chemotherapy for gastric cancer: A retrospective study.

74 Background: The adjuvant chemotherapy with S-1 is the standard treatment for Stage II/III gastric cancer in Japan. Immunological status of host is critical for treatment outcome. Several investigators showed that systemic immune-inflammaotry indexes including neutrophil lymphocyte ratio (NLR) and modified Glasgow Prognostic Score (mGPS) well reflected the tumor progression. Methods: We analyzed clinical data obtained from 170 patients with pathological stage II/III gastric cancer who underwent surgery followed by S-1 adjuvant chemotherapy at Osaka City University Hospital between 2006 and 2015. Tumor infiltrating cells were detected by immunohistochemistry. Results: We found recurrent diseases in 70 (41%) patients including 15 in stage II and 55 in stage III. In univariate analysis using Cox proportion model, 2 grade of mGPS, the increase value of post-operative CEA, CA19-9, number of lymphocytes and NLR were associated with recurrence. Post-operative elevation of CEA and NLR were identified as independent risk factors for recurrence in multivariate analysis. Increase value of pre-operative NLR and CEA was significantly associated with early recurrent within one year after surgery. Tumor infiltrating neutrophils and PD-1+ T cells had correlated with the increase of pre-operative NLR and CEA value, respectively. Patients with low PD-1+T cells and low neutrophils had better prognosis than those with high infiltration. Conclusions: Post-surgical elevation of CEA and NLR value were useful as a predictive marker for recurrence in patients treated with S-1 adjuvant chemotherapy after surgery for gastric cancer. Early recurrence had correlated with tumor infiltrating neutrophils and PD-1+T cells. Our results suggested that systemic and local immune suppression should be an important element to exacerbate prognosis after chemotherapy for resectable gastric cancer.

Adjuvant intraperitoneal chemotherapy for the treatment of gastric cancer at risk for peritoneal carcinomatosis: A systematic review.

The peritoneal surface is a frequent site of recurrence following surgery for gastric cancer. A systematic review and random effect analysis was undertaken to analyze current literature regarding the role of adjuvant intraperitoneal chemotherapy in gastric cancer. While pooled analysis supports the use of adjuvant IP chemotherapy in resectable gastric cancer, maximal benefit occured with intra-operative delivery, and possibly the use of MMC. J. Surg. Oncol. 2017;115:192-201. © 2016 Wiley Periodicals, Inc.

Phase II study of docetaxel, cisplatin and capecitabine as preoperative chemotherapy in resectable gastric cancer.

AIMTo investigate the feasibility of preoperative docetaxel, cisplatin and capecitabine (DCC) in patients with resectable gastric cancer.METHODSPatients with resectable gastric cancer fulfilling the inclusion criteria, were treated with 4 cycles of docetaxel (60 mg/m2), cisplatin (60 mg/m2) and capecitabine (1.875 mg/m2 orally on day 1-14, two daily doses) repeated every three weeks, followed by surgery. Primary end point was the feasibility and toxicity/safety profile of DCC, secondary endpoints were pathological complete resection rate and pathological complete response (pCR) rate.RESULTSAll of the patients (51) were assessable for the feasibility and safety of the regimen. The entire preoperative regimen was completed by 68.6% of the patients. Grade III/IV febrile neutropenia occurred in 10% of all courses. Three patients died due to treatment related toxicity (5.9%), one of them (also) because of refusing further treatment for toxicity. Of the 45 patients who were evaluable for secondary endpoints, four developed metastatic disease and 76.5% received a curative resection. In 3 patients a pCR was seen (5.9%), two patients underwent a R1 resection (3.9%).CONCLUSIONFour courses of DCC as a preoperative regimen for patients with primarily resectable gastric cancer is highly demanding. The high occurrence of febrile neutropenia is of concern. To decrease the occurrence of febrile neutropenia the prophylactic use of granulocyte colony-stimulating factor (G-CSF) should be explored. A curative resection rate of 76.5% is acceptable. The use of DCC without G-CSF support as preoperative regimen in resectable gastric cancer is debatable.