Efficacy and safety of systemic chemotherapy for radically resectable esophago-gastric adenocarcinoma in older patients: A systematic review and meta-analysis.

INTRODUCTION: A significant proportion of locally-advanced esophago-gastric adenocarcinoma (EGA) is diagnosed in patients ≥70 years old (y.o.) who are commonly underrepresented in clinical trials. MATERIALS AND METHODS: The PubMed database was searched for phase 2/3 clinical trials enrolling patients ≥70 y.o and reporting efficacy/safety information of chemotherapy for resectable EGA. The main outcomes were overall survival (OS) and recurrence-free survival (RFS). RESULTS: Among 6,128 records, only seven studies reported these outcomes (three peri-operative, three adjuvant, and one neoadjuvant), including 1004 older patients, <20% of the overall population. No significant benefit in terms of OS and RFS was observed for perioperative or adjuvant chemotherapy vs surgery alone. No trial reported safety endpoints in this subgroup. DISCUSSION: This work did not show any significant benefit in OS or RFS for chemotherapy vs surgery alone or conventional vs de-escalated chemotherapy in the curative setting of EGA in ≥70 y.o patients. Specific ad hoc trials should be performed to derive reliable data.

Role of microsatellite instability and HER2 positivity in locally advanced esophago-gastric cancer patients treated with peri-operative chemotherapy

Purpose Neoadjuvant chemotherapy (NAC) significantly improved the prognosis of patients with locally advanced gastric cancer (LAGC). Several biomarkers, including HER2 and MMR/MSI are crucial for treatment decisions in the advanced stage but, currently, no biomarkers can guide the choice of NAC in clinical practice. Our aim was to evaluate the role of MSI and HER2 status on clinical outcomes. Methods We retrospectively collected LAGC patients treated with NAC and surgery +/- adjuvant chemotherapy from 2006 to 2018. HER2 and MSI were assessed on endoscopic and surgical samples. Pathologic complete response (pCR) rate, overall survival (OS), and event‐free survival (EFS) were estimated and evaluated for association with downstaging and MSI. Results We included 76 patients, 8% were classified as MSI-H, entirely consistent between endoscopic and surgical samples. Six percent of patients were HER2 positive on endoscopic and 4% on surgical samples. Tumor downstaging was observed in 52.5% of cases, with three pCR (5.1%), none in MSI-H cancers. According to MSI status, event-free survival (EFS) and overall survival (OS) were higher for MSI-H patients to MSS [EFS not reached vs 30.0 months, p = 0.08; OS not reached vs 39.6 months, p = 0.10]. Conclusion Our work confirms the positive prognostic effect of MSI-H in the curative setting of LAGC, not correlated with pathologic tumor downstaging. Prospective ad-hoc trial and tumor molecular profiling are eagerly needed (AU)

Role of microsatellite instability and HER2 positivity in locally advanced esophago-gastric cancer patients treated with peri-operative chemotherapy.

PURPOSE: Neoadjuvant chemotherapy (NAC) significantly improved the prognosis of patients with locally advanced gastric cancer (LAGC). Several biomarkers, including HER2 and MMR/MSI are crucial for treatment decisions in the advanced stage but, currently, no biomarkers can guide the choice of NAC in clinical practice. Our aim was to evaluate the role of MSI and HER2 status on clinical outcomes. METHODS: We retrospectively collected LAGC patients treated with NAC and surgery +/- adjuvant chemotherapy from 2006 to 2018. HER2 and MSI were assessed on endoscopic and surgical samples. Pathologic complete response (pCR) rate, overall survival (OS), and event-free survival (EFS) were estimated and evaluated for association with downstaging and MSI. RESULTS: We included 76 patients, 8% were classified as MSI-H, entirely consistent between endoscopic and surgical samples. Six percent of patients were HER2 positive on endoscopic and 4% on surgical samples. Tumor downstaging was observed in 52.5% of cases, with three pCR (5.1%), none in MSI-H cancers. According to MSI status, event-free survival (EFS) and overall survival (OS) were higher for MSI-H patients to MSS [EFS not reached vs 30.0 months, p = 0.08; OS not reached vs 39.6 months, p = 0.10]. CONCLUSION: Our work confirms the positive prognostic effect of MSI-H in the curative setting of LAGC, not correlated with pathologic tumor downstaging. Prospective ad-hoc trial and tumor molecular profiling are eagerly needed.

Nutritional deficiency post esophageal and gastric cancer surgery: A quality improvement study.

BACKGROUND: Esophagectomy or gastrectomy for malignant tumors can have a profound effect on nutritional status of patients undergoing the procedure. Hence, postoperative nutritional status is an important prognostic factor to consider in ensuring optimal recovery. In this study, we looked at assessing the prevalence of micronutrient deficiencies post esophagectomy or gastrectomies and the efficiency of Allied Health Professionals (AHP) led clinics in identifying and appropriately managing the deficiencies. METHOD: Between February 2017 and February 2018, all patients who attended the AHP clinic, had micronutrient screening, which includes ferritin, folate, vitamin B12 and vitamin D. Patients were screened for exocrine pancreatic insufficiency (EPI) through series of questions related to symptoms of EPI including steatorrhea, flatulence and urgency to defecate. All patients included in the study were started on A-Z multivitamin tablets from their first visit. Patients reporting symptoms indicative of EPI were started on Creon. Patients found deficient in any micronutrients were invited for a follow-up measurement of the respective deficiency. RESULTS: A total of 63 patients were included in the study period with a median follow-up of 18 months (range: 2-60 months) post esophagectomy and/or subtotal/total gastrectomy for malignant tumors. Proportion of patients with deficiency in ferritin, folate, vitamin B12 and vitamin D were 42.86%, 9.52%, 6.35% and 36.67% respectively. The proportion of patients identified with symptoms indicative of EPI was 31.75%. At re-test follow-up, 66.67% patient noticed settlement of symptoms of EPI. Ferritin, Folate, Vitamin B12 and D levels significantly improved post initial AHP follow-up (significance level p < 0.05). CONCLUSION: This study highlights that nutritional deficiencies post esophagectomy and/or subtotal/total gastrectomy for malignant tumors are prevalent. AHP run follow-up clinics in our unit helps identify these deficiencies and manage them accordingly. This study shows statistically significant improvement in deficiencies thereby making AHP led follow-up clinics to be cost effective and improve patient outcome.

Neoadjuvant chemotherapy in advanced gastric and esophago-gastric cancer. Meta-analysis of randomized trials.

INTRODUCTION: Even in after curative surgery and adequate linfoadenectomy the survival of advanced gastric cancer (AGC) remains poor. At present some data have been published on the effects of NACT and perioperative chemotherapy on AGC and Esophago-gastric cancer (EGC) but not definitive ones. The present meta-analysis aims to evaluate the effects of neoadjuvant chemotherapy (NACT) on the AGC and EGC. MATERIAL AND METHODS: A systematic review with meta-analysis of randomized controlled trials (RCTs) of NACT + surgery vs. Surgery in patients with AGC and EGC was performed. RESULTS: 15 RCTs have been included (2001 patients: 977 into NACT + surgery arm and 1024 into control arm). NACT + Surgery reduces the overall mortality at 1, 3 and 5-year in cumulative analysis (RR = 0.78; 0.81; 0.88 respectively), at 1, 2, 3 and 5-years in EGC (RR = 0.79; 0.83; 0.84; 0.91 respectively) and at 3 and 5-years in AGC (RR = 0.74; 0.82 respectively). Morbidity and perioperative mortality rate are not influenced by NACT. Recurrence rate is reduced by NACT + surgery in EGC (RR = 0.80). CONCLUSIONS: NACT reduces the mortality in gastric and esophago-gastric cancer. Morbidity and perioperative mortality are not influenced by NACT. The overall recurrence rate is reduced by NACT in esophago-gastric cancer.