The Value of Perioperative Chemotherapy for Patients With Hepatoid Adenocarcinoma of the Stomach Undergoing Radical Gastrectomy

BackgroundHepatoid adenocarcinoma of the stomach (HAS) is a rare type of gastric cancer, but the role of perioperative chemotherapy is still poorly understood. The aim of this retrospective study was to investigate the associations between perioperative chemotherapy and prognosis of HAS.MethodWe retrospectively analyzed patients with locally advanced HAS who received radical surgery in Peking University Cancer Hospital between November 2009 and October 2020. Patients were divided into neoadjuvant chemotherapy-first (NAC-first) group and surgery-first group. The relationships between perioperative chemotherapy and prognosis of HAS were analyzed using univariate, multivariate survival analyses and propensity score matching analysis (PSM).ResultsA total of 100 patients were included for analysis, including 29 in the NAC-first group and 71 in the surgery-first group. The Her-2 amplification in HAS patients was 22.89% (19/83). For NAC-first group, 4 patients were diagnosed as tumor recession grade 1 (TRG1), 4 patients as TRG 2, and 19 patients as TRG 3. No significant difference in prognosis between the surgery-first group and the NAC-first group (P=0.108) was found using PSM analysis. In the surgery-first group, we found that the survival rate was better in group of ≥6 cycles of adjuvant chemotherapy than that of <6 cycles (P=0.013).ConclusionNAC based on platinum and fluorouracil may not improve the Overall survival (OS) and Disease-free survival time (DFS) of patients with locally advanced HAS. Patients who received ≥6 cycles of adjuvant chemotherapy had better survival. Therefore, the combination treatment of radical gastrectomy and sufficient adjuvant chemotherapy is recommended for patients with locally advanced HAS.

Eribulin improved the overall survival from the initiation of first-line chemotherapy for HER2-negative advanced breast cancer: a multicenter retrospective study

Background Eribulin methylate (eribulin) improved the overall survival (OS) of eribulin-treated patients with HER2-negative advanced breast cancer (ABC) in prospective and retrospective studies. However, the effect of eribulin on OS as first-line chemotherapy and the characteristics of the patients who benefited from eribulin remain unclear. Methods Between January 2011 and December 2016, 301 patients with HER2-negative ABC who started first-line chemotherapy at 3 institutions were retrospectively evaluated for OS from the initiation of first-line chemotherapy. Results We identified 172 patients (119 estrogen receptor-positive [ER+], 47 ER−, 6 unknown) who received eribulin (eribulin group) and 129 patients (92 ER+, 31 ER−, 6 unknown) who did not receive eribulin (non-eribulin group). The median OS from the initiation of first-line chemotherapy in the two groups was not statistically significant (869 vs. 744 days, P = 0.47, log-rank); however, in patients who received eribulin in later lines (≥3rd-line) and who had a history of perioperative chemotherapy with anthracycline- and/or taxane-based regimens, the median OS improved (1001 vs. 744 days, P = 0.037; and 834 vs. 464 days, respectively P = 0.032, respectively; Wilcoxon). Multivariate analyses revealed that a history of perioperative chemotherapy with anthracycline- and/or taxane-based regimens was a predictive factor (hazard ratio, 0.39; 95% confidence interval, 0.21–0.70) for OS. Conclusions This study successfully identified subgroups of HER2− ABC patients with improved OS by eribulin therapy. Selecting patients according to their background and line of treatment will maximize the efficacy of eribulin therapy.

Mismatch Repair Deficiency, Chemotherapy and Survival for Resectable Gastric Cancer: an Observational Study from the German staR Cohort and a Meta-Analysis

Purpose. In a post hoc analysis of the MAGIC trial, patients with curatively resected gastric cancer (GC) and mismatch repair (MMR) deficiency (MMRd) had better median overall survival (OS) when treated with surgery alone but worse median OS when treated with additional chemotherapy. Further data are required to corroborate these findings.Methods. Between April 2013 and December 2018, 458 patients with curatively resected GC, including cancers of the esophagogastric junction Siewert type II and III, were identified in the German centers of the staR consortium. Tumor sections were assessed for expression of MLH1, MSH2, MSH6 and PMS2 by immunohistochemistry. The association between MMR status and survival was assessed. Similar studies published up to January 2021 were then identified in a MEDLINE search for a meta-analysis. Results. MMR-status and survival data were available for 223 patients (median age 66 years, 62.8% male), 23 patients were MMRd (10.3%). After matching for baseline clinical characteristics, median OS was not reached in any subgroup. Compared to perioperative chemotherapy, patients receiving surgery alone with MMRd and MMRp had a HR of 0.67 (95% CI: 0.13-3.37, P=0.63) and 1.44 (95% CI: 0.66-3.13, P=0.36), respectively. The meta-analysis included pooled data from 385 patients. Compared to perioperative chemotherapy, patients receiving surgery alone with MMRd had an improved OS with a HR of 0.36 (95% CI: 0.14-0.91, P=0.03), whereas those with MMRp had a HR of 1.18 (95% CI: 0.89-1.58, P=0.26).Conclusion. Our data support a positive prognostic effect for MMRd in GC patients treated with surgery only and a differentially negative prognostic effect in patients treated with perioperative chemotherapy. MMR status determined by preoperative biopsies may be used as a predictive biomarker to select patients for perioperative chemotherapy in curatively resectable GC.

Duration of Perioperative Chemotherapy in Locally Advanced Gastric Cancer: A “Less Is More” Question When ypN0 Is Achieved

BackgroundsPerioperative chemotherapy (PEC) and neoadjuvant chemotherapy (NAC) have become a vital part of locally advanced gastric cancer (LAGC) treatment, but the optimal duration of PEC has not been studied. The aim of this study was to demonstrate the possibility of duration reduction in PEC in the adjuvant chemotherapy (AC) phase for ypN0 patients.MethodsWe included LAGC patients who achieved ypN0 after NAC in our institution from 2005 to 2018. The risk/benefit of AC and other covariates were majorly measured by overall survival (OS) and progression-free survival (PFS). We developed a survival-tree-based model to determine the optimal PEC duration for ypN0 patients in different classes.ResultsA total of 267 R0 resection patients were included. There were 55 patients who did not receive AC. The 5-year OS was 74.34% in the non-AC group and 83.64% in the AC group with a significant difference (p = 0.012). Multivariate Cox regression revealed that both AC (AC vs. non-AC: HR, 0.49; 95%CI, 0.27–0.88; p = 0.018) and ypT stages (ypT3-4 vs. ypT0-2: HR, 2.00; 95%CI, 1.11–3.59; p = 0.021) were significant protective/risk factors on patients OS and PFS. A decision tree model for OS indicated an optimal four to six cycles of PEC, which was recommended for ypT0-2N0 patients, while a minimum of five PEC cycles was recommended for ypT3-4N0 patients.ConclusionAC treatment is still necessary for ypN0. The duration reduction could be applied for the ypT0-2N0 stage patients but may not be suitable for higher ypT stages and beyond. A multicenter-based study is required.

Perioperative Chemotherapy with FLOT Scheme in Resectable Gastric Adenocarcinoma: A Preliminary Correlation between TRG and Radiomics

Perioperative chemotherapy (p-ChT) with a fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) scheme is the gold standard of care for locally advanced gastric cancer. We aimed to test CT radiomics performance in early response prediction for p-ChT. Patients with advanced gastric cancer who underwent contrast enhanced CT prior to and post p-ChT were retrospectively enrolled. Histologic evaluation of resected specimens was used as the reference standard, and patients were divided into responders (TRG 1a-1b) and non-responders (TRG 2-3) according to their Becker tumor regression grade (TRG). A volumetric region of interest including the whole tumor tissue was drawn from a CT portal-venous phase before and after p-ChT; 120 radiomic features, both first and second order, were extracted. CT radiomics performances were derived from baseline CT radiomics alone and ΔRadiomics to predict response to p-ChT according to the TRG and tested using a receiver operating characteristic (ROC) curve. The final population comprised 15 patients, 6 (40%) responders and 9 (60%) non-responders. Among pre-treatment CT radiomics parameters, Shape, GLCM, First order, and NGTDM features showed a significant ability to discriminate between responders and non-responders (p < 0.011), with Cluster Shade and Autocorrelation (GLCM features) having AUC = 0.907. ΔRadiomics showed significant differences for Shape, GLRLM, GLSZM, and NGTDM features (p < 0.007). MeshVolume (Shape feature) and LongRunEmphasis (GLRLM feature) had AUC = 0.889. In conclusion, CT radiomics may represent an important supportive approach for the radiologic evaluation of advanced gastric cancer patients.

Outcomes of patients with nonmetastatic gastric adenocarcinoma according to perioperative treatment strategy: a real-world, population-based study

Aim: To assess the survival outcomes of patients with nonmetastatic gastric cancer according to the type of perioperative treatment strategy used (surgery-only, adjuvant chemo-radiotherapy, adjuvant chemotherapy, perioperative chemotherapy) in a population-based setting. Materials & methods: Surveillance, Epidemiology and End Results research-plus database was explored, and patients with nonmetastatic gastric cancer who were treated with an oncologic surgery were reviewed. Multivariable Cox regression analysis was used to examine the impact of treatment strategy on overall and cancer-specific survival. Results: A total of 11,526 patients were found to be eligible and they were included in the current analysis. Looking at the percentages of different treatment strategies throughout the study years (2006–2017), the use of the following strategies increased: adjuvant chemotherapy (20.1 vs 10.6%), and perioperative chemotherapy (21.3 vs 0.5%); while the use of the following strategies decreased: surgery only (36.2 vs 58.2%), and adjuvant chemo-radiotherapy (22.4 vs 30.6%). Using multivariable Cox regression analysis, the following factors were associated with worse overall survival: older age (hazard [HR]: 1.021; 95% CI: 1.018–1.023), males (HR: 1.09; 95% CI: 1.04–1.14), Black race (HR: 1.11; 95% CI: 1.04–1.19), cardia subsite (HR: 1.09; 95% CI: 1.02–1.17), grade 3–4 (HR:1.32; 95% CI: 1.25–1.40), diffuse histology (HR: 1.46; 95% CI: 1.35–1.58), clinically node positive (HR:1.43; 95% CI: 1.34–1.53), total gastrectomy (HR: 1.20; 95% CI: 1.13–1.28), and surgery-only approach (HR: 1.65; 95% CI: 1.55–1.75). Conclusion: Among patients with localized gastric cancer, patients who were treated with surgery-only, and to a less extent, patients who were treated with surgery followed by adjuvant chemotherapy have worse survival outcomes; while those treated with perioperative chemotherapy have the best survival outcomes.

Efficacy and Safety of mFOLFOX6 as Perioperative Chemotherapy for Resectable Liver Metastases from Colorectal Cancer: as Case–Control Study

Background: Although resection is effective for managing resectable liver metastases from colorectal cancer, the clinical significance of chemotherapy for such metastases has remained undetermined. Therefore, we conducted a phase II trial of perioperative chemotherapy with mFOLFOX6 to examine its efficacy.Methods: A total of 41 patients were examined. The liver resection rate was the primary endpoint, whereas the response rate, adverse events, completion rate, liver injury rate, R0 resection rate, and histological results were the secondary endpoints.Results: Overall, 34 (82.9%) patients underwent liver resection, and 77.4% and 100% had synchronous and metachronous liver metastases, respectively. The seven remaining patients did not undergo resection because of a progressive disease. Moreover, 2, 15, 17, and 7 patients had a complete response, partial response, stable disease, and progressive disease, respectively, which indicated that the response rate was 41.5%. Regarding adverse events, three patients exhibited Grade 3 myelosuppression and one patient had gastrointestinal symptoms. On the basis of histopathological examination, 27, 5, and 2 patients belonged to grades 1a:1b, 2, and 3, respectively. Regarding liver injury, 29.4% had liver sinusoidal injury, whereas 11.7% had steatohepatitis. Meanwhile, all patients underwent postoperative chemotherapy.Conclusions: mFOLFOX6 is safe and yields favorable therapeutic effects. The indication for liver resection after a certain waiting period is clinically significant.Trial registration；UMIN,UMIN000009725,Registered 01/08/2013 ,URL; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000011399