Background
The aim was to define the pathological response in lymph nodes following neoadjuvant chemotherapy for oesophageal adenocarcinoma and to quantify any associated survival benefit.
Methods
...Lymph nodes retrieved at oesophagectomy were examined retrospectively by two pathologists for evidence of a response to chemotherapy. Patients were classified as lymph node‐negative (either negative nodes with no evidence of previous tumour involvement or negative with evidence of complete regression) or positive (allocated a lymph node regression score based on the proportion of fibrosis to residual tumour). Lymph node responders (score 1, complete response; 2, less than 10 per cent remaining tumour; 3, 10–50 per cent remaining tumour) and non‐responders (score 4, more than 50 per cent viable tumour; 5, no response) were compared in survival analyses using Kaplan–Meier and Cox regression analysis.
Results
Among 377 patients, 256 had neoadjuvant chemotherapy. Overall, 68 of 256 patients (26·6 per cent) had a lymph node response and 115 (44·9 per cent) did not. The remaining 73 patients (28·5 per cent) had negative lymph nodes with no evidence of regression. Some patients had a lymph node response in the absence of a response in the primary tumour (27 of 99, 27 per cent). Lymph node responders had a significant survival benefit (P < 0·001), even when stratified by patients with or without a response in the primary tumour. On multivariable analysis, lymph node responders had decreased overall (hazard ratio 0·53, 95 per cent c.i. 0·36 to 0·78) and disease‐specific (HR 0·42, 0·27 to 0·66) mortality, and experienced reduced local and systemic recurrence.
Conclusion
Lymph node regression is a strong prognostic factor and may be more important than response in the primary tumour.
Nodal response predicts survival
Following neoadjuvant chemotherapy for operable gastroesophageal cancer, lymph node metastasis is the only validated prognostic variable; however, within lymph node groups there is still ...heterogeneity with risk of relapse. We hypothesized that gene profiles from neoadjuvant chemotherapy treated resection specimens from gastroesophageal cancer patients can be used to define prognostic risk groups to identify patients at risk for relapse.
The Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial (n = 202 with high quality RNA) samples treated with perioperative chemotherapy were profiled for a custom gastric cancer gene panel using the NanoString platform. Genes associated with overall survival (OS) were identified using penalized and standard Cox regression, followed by generation of risk scores and development of a NanoString biomarker assay to stratify patients into risk groups associated with OS. An independent dataset served as a validation cohort.
Regression and clustering analysis of MAGIC patients defined a seven-Gene Signature and two risk groups with different OS hazard ratio (HR) 5.1; P < 0.0001. The median OS of high- and low-risk groups were 10.2 95% confidence interval (CI) of 6.5 and 13.2 months and 80.9 months (CI: 43.0 months and not assessable), respectively. Risk groups were independently prognostic of lymph node metastasis by multivariate analysis (HR 3.6 in node positive group, P = 0.02; HR 3.6 in high-risk group, P = 0.0002), and not prognostic in surgery only patients (n = 118; log rank P = 0.2). A validation cohort independently confirmed these findings.
These results suggest that gene-based risk groups can independently predict prognosis in gastroesophageal cancer patients treated with neoadjuvant chemotherapy. This signature and associated assay may help risk stratify these patients for post-surgery chemotherapy in future perioperative chemotherapy-based clinical trials.
Abstract Introduction EURECCA (EUropean REgistration of Cancer CAre) is a network aiming to improve cancer care by auditing outcome. EURECCA initiated an international survey to share and compare ...patient outcome for oesophagogastric cancer. The present study assessed how a uniform dataset could be introduced for oesophagogastric cancer in Europe. Methods Participating countries presented data using common data items describing patients', disease, strategies, and outcome characteristics. Patients treated with curative surgery for squamous cell carcinoma (SCC) or adenocarcinoma (ACA) were included. Results United Kingdom, the Netherlands, France, Spain and Ireland participated. There were differences in data source ranging from national registries to large collaborative groups. 4668 oesophagogastric cancer cases over a 12 months period were included. The predominant histological type was ACA. Disease stage tended to be earlier in France and Ireland. In oesophageal and junctional cancers neoadjuvant chemoradiotherapy was preferred in the Netherlands and Ireland contrasting with chemotherapy in the UK and France. All countries used perioperative chemotherapy in gastric cancer but 1/3 of patients received this treatment. The mean R0 resection rate was 86% for oesophageal and junctional resections and 88% for gastric resections. Postoperative mortality varied from 1% to 7%. Conclusion This European survey shown that implementing a uniform treatment and outcome data format of oesophagogastric cancer is feasible. It identified differences in disease presentation, treatment approaches and outcome, which need to be investigated, especially by increasing the number of participating countries. Future comparisons will facilitate developments in treatment for the benefit of patient outcomes.
Abstract This study was designed to investigate the prognostic impact of elevated platelet to lymphocyte ratio (PLR) on survival for oesophageal and junctional adenocarcinoma (OJA) treated with ...neoadjuvant chemotherapy in a curative intent. From 2004 to 2014, 153 consecutive patients with OJA were included. PLR was measured at first diagnosis. Receiver Operating Characteristic curve analysis was performed to determinate PLR threshold. Cox multivariate model was used to assess correlation between PLR and survival. Cut-off value for PLR was 192, which identified 2 groups of patients: low (n = 122) and high PLR value (n = 31). Both groups were comparable by patient (age, sex, ASA score) and tumour characteristics (differentiation, TNM stage, location). Five year overall survival (OS) was 65%. OS and DFS were reduced in the high PLR group: p = 0.019 and p = 0.016, respectively. PLR was associated with increased recurrence (54.8% vs . 35.2%, p = 0.046) and cancer-related death (41.9% vs . 23.8%, p = 0.043) rates. On multivariate analysis, elevated PLR was associated with decreased DFS (HR = 2.85, 95%CI = 1.54–5.26, p = 0.001) and OS (HR = 2.47, 95%CI = 1.21–5.01, p = 0.012). This study demonstrates that elevated PLR is associated with poor OS and DFS for OJA treated with a curative intent and has the potential to be a useful prognostic biomarker for treatment planning.
Peri-operative chemotherapy and surgery is a standard treatment of localised oesophagogastric adenocarcinoma; however, the outcomes remain poor.
ST03 is a multicentre, randomised, phase II/III study ...comparing peri-operative ECX with or without bevacizumab (ECX-B). The primary outcome measure of phase II (n = 200) was safety, specifically gastrointestinal (GI) perforation rates and cardiotoxicity.
Two hundred patients were randomised between October 2007 and April 2010. Ninety-one/101 (90%) ECX and 86/99 (87%) ECX-B patients completed pre-operative chemotherapy; 7 ECX and 9 ECX-B patients stopped due to toxicity. Gastrointestinal perforations (3 ECX, 1 ECX-B), cardiac events (1 ECX, 4 ECX-B) and venous thromboembolic events (VTEs, 8 ECX, 7 ECX-B) were uncommon. Arterial thromboembolic events (ATEs, myocardial infarction (MI) or cerebrovascular accident) were more frequent with ECX-B (5 versus 1 with ECX). Delayed wound healing, anastomotic leaks and GI bleeding rates were similar.
More asymptomatic left ventricular ejection fraction (LVEF) falls (≥15% and/or to <50%) occurred with ECX-B (21.2% versus 11.1% with ECX). Clinically significant falls (≥10% to below lower limit of normal, LLN) occurred in (15.3%) and (8.9%) respectively, with no associated cardiac failure (median 22 months follow-up).
Addition of bevacizumab to peri-operative ECX chemotherapy is feasible with acceptable toxicity and no negative impact on surgical outcomes.
The aim of this project was to evaluate the current practice of D2 in Europe.
In the first part of the study, 18 European high volume gastric cancer centres completed a questionnaire, designed to ...evaluate their preferred lymphadenectomy in a series of clinical scenarios. Surgeon compliance with international guidelines for lymphadenectomy was evaluated.
In the second part, information on 381 gastrectomies performed for primary gastric cancer by participating surgeons from January to December 2015, was retrospectively collected.
Surgical choice in clinical scenarios was affected by tumour stage and to a lesser extent, site and histotype. In particular, in early gastric cancer with diffuse histology D2 was recommended by >70% of surgeons, while this percentage dropped to 44% in intestinal histotypes. When surgeons selected a D2 dissection, the procedure was rarely fully compliant with the Japanese guidelines.
In the review of gastrectomy experience an adequate number of nodes (≥15 nodes) was retrieved in 97% after D2. The number of retrieved nodes varied with median values ranging from 17 to 35 (p < 0.001) after D2. D2/D2+ was more frequently performed in mixed (80%) and diffuse (78%) cases than in intestinal cases (69%) (p = 0.016).
Although an adequate lymphadenectomy was achieved in almost all cases in dedicated centres, there is still variation in the number of retrieved nodes. Tumor histology largely affects surgeon’s choice as regards the extent of lymphadenectomy; however, the role of histology in planning surgical procedures needs to be verified in prospective trials.
Background
The optimal surgical approach to tumours of the oesophagus and oesophagogastric junction remains controversial. The principal randomized trial comparing transhiatal (THO) and transthoracic ...(TTO) oesophagectomy showed no survival difference, but suggested that some subgroups of patients may benefit from the more extended lymphadenectomy typically conducted with TTO.
Methods
This was a cohort study based on two prospectively created databases. Short‐ and long‐term outcomes for patients undergoing THO and TTO were compared. The primary outcome measure was overall survival, with secondary outcomes including time to recurrence and patterns of disease relapse. A Cox proportional hazards model provided hazard ratios (HRs) and 95 per cent confidence intervals (c.i.), with adjustments for age, tumour stage, tumour grade, response to chemotherapy and lymphovascular invasion.
Results
Of 664 included patients (263 THO, 401 TTO), the distributions of age, sex and histological subtype were similar between the groups. In‐hospital mortality (1·1 versus 3·2 per cent for THO and TTO respectively; P = 0·110) and in‐hospital stay (14 versus 17 days respectively; P < 0·001) favoured THO. In the adjusted model, there was no difference in overall survival (HR 1·07, 95 per cent c.i. 0·84 to 1·36) or time to tumour recurrence (HR 0·99, 0·76 to 1·29) between the two operations. Local tumour recurrence patterns were similar (22·8 versus 24·4 per cent for THO and TTO respectively). No subgroup could be identified of patients who had benefited from more radical surgery on the basis of tumour location or stage.
Conclusion
There was no difference in survival or tumour recurrence for TTO and THO.
Surgical approach makes little difference to long‐term outcomes
Neoadjuvant chemotherapy is established in the management of most resectable esophageal and esophagogastric junction adenocarcinomas. However, assessing the downstaging effects of chemotherapy and ...predicting response to treatment remain challenging, and the relative importance of tumor stage before and after chemotherapy is debatable.
We analyzed consecutive resections for esophageal or esophagogastric junction adenocarcinomas performed at two high-volume cancer centers in London between 2000 and 2010. After standard investigations and multidisciplinary team consensus, all patients were allocated a clinical tumor stage before treatment, which was compared with pathologic stage after surgical resection. Survival analysis was conducted using Kaplan-Meier analysis and Cox regression analysis.
Among 584 included patients, 400 patients (68%) received neoadjuvant chemotherapy. Patients with downstaged tumors after neoadjuvant chemotherapy experienced improved survival compared with patients without response (P < .001), and such downstaging (hazard ratio, 0.43; 95% CI, 0.31 to 0.59) was the strongest independent predictor of survival after adjusting for patient age, tumor grade, clinical tumor stage, lymphovascular invasion, resection margin status, and surgical resection type. Patients downstaged by chemotherapy, compared with patients with no response, experienced lower rates of local recurrence (6% v. 13%, respectively; P = .030) and systemic recurrence (19% v. 29%, respectively; P = .027) and improved Mandard tumor regression scores (P = .001). Survival was strongly dictated by stage after neoadjuvant chemotherapy, rather than clinical stage at presentation.
The stage of esophageal or esophagogastric junction adenocarcinoma after neoadjuvant chemotherapy determines prognosis rather than the clinical stage before neoadjuvant chemotherapy, indicating the importance of focusing on postchemotherapy staging to more accurately predict outcome and eligibility for surgery. Patients who are downstaged by neoadjuvant chemotherapy benefit from reduced rates of local and systemic recurrence.
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