D2 versus D1 Lymph Node Dissection: Results of the Medical Research Council and the Dutch Trial

Purpose The Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial established perioperative epirubicin, cisplatin, and fluorouracil chemotherapy as a standard of care for patients with resectable esophagogastric cancer. However, identification of patients at risk for relapse remains challenging. We evaluated whether pathologic response and lymph node status after neoadjuvant chemotherapy are prognostic in patients treated in the MAGIC trial. Materials and Methods Pathologic regression was assessed in resection specimens by two independent pathologists using the Mandard tumor regression grading system (TRG). Differences in overall survival (OS) according to TRG were assessed using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate analyses using the Cox proportional hazards method established the relationships among TRG, clinical-pathologic variables, and OS. Results Three hundred thirty resection specimens were analyzed. In chemotherapy-treated patients with a TRG of 1 or 2, median OS was not reached, whereas for patients with a TRG of 3, 4, or 5, median OS was 20.47 months. On univariate analysis, high TRG and lymph node metastases were negatively related to survival (Mandard TRG 3, 4, or 5: hazard ratio [HR], 1.94; 95% CI, 1.11 to 3.39; P = .0209; lymph node metastases: HR, 3.63; 95% CI, 1.88 to 7.0; P < .001). On multivariate analysis, only lymph node status was independently predictive of OS (HR, 3.36; 95% CI, 1.70 to 6.63; P < .001). Conclusion Lymph node metastases and not pathologic response to chemotherapy was the only independent predictor of survival after chemotherapy plus resection in the MAGIC trial. Prospective evaluation of whether omitting postoperative chemotherapy and/or switching to a noncross-resistant regimen in patients with lymph node-positive disease whose tumor did not respond to preoperative epirubicin, cisplatin, and fluorouracil may be appropriate.

Download Full-text

Next Generation intraoperative Lymph node staging for Stratified colon cancer surgery (GLiSten): a multicentre, multinational feasibility study of fluorescence in predicting lymph node-positive disease

Efficacy and Mechanism Evaluation ◽

10.3310/eme03060 ◽

2016 ◽

Vol 3 (6) ◽

pp. 1-122

Author(s):

Helen Andrew ◽

Gemma Gossedge ◽

Julie Croft ◽

Neil Corrigan ◽

Julia M Brown ◽

...

Keyword(s):

Colon Cancer ◽

Lymph Node ◽

Medical Research ◽

Feasibility Study ◽

Research Council ◽

Medical Research Council ◽

Cancer Surgery ◽

Lymph Node Staging ◽

Next Generation ◽

Colon Cancer Surgery

Background5-aminolevulinic acid (5-ALA) is used for fluorescence diagnosis (FD) in neurological, gynaecological and urological malignancies. The Medical Research Council/Efficacy and Mechanism Evaluation (EME) programme/National Institute for Health Research’s Next Generation intraoperative Lymph node staging for Stratified colon cancer surgery (GLiSten) study investigated its use to predict lymph node (LN)-positive disease in colon cancer as an aid to stratified surgery.ObjectivesThe primary objective was to optimise the dose of oral 5-ALA for intraoperative FD of metastatic LNs in colon cancer. Secondary objectives included standardisation of pre-operative computerised tomography (CT) LN reporting, intraoperative fluorescence detection, surgical resection with D3 lymphadenectomy and histopathological examination of resected specimens.DesignThis was a feasibility study to determine optimal strategies for 5-ALA positive LN detection. Patients with locally advanced disease identified using the Fluoropyrimidine, Oxaliplatin and Targeted-Receptor pre-Operative Therapy for patients with high-risk, operable colon cancer (FOxTROT) criteria were recruited from two sites between October 2013 and June 2015. Cohort 1 received 20 mg/kg and cohort 2 received 30 mg/kg of oral 5-ALA, 1–6 hours preoperatively. Laparoscopic assessment of fluorescence was performed using the Storz D-Light system (KARL STORZ GmbH & Co. KG; Tuttlingen, Germany), with marking of fluorescent LNs, followed by oncological resection. The specimen was subjected to histological analysis with step sectioning of marked fluorescent LNs. Progression to an evaluation phase using the optimal dosing schedule was dependent on positively identifying at least 2 out of 10 patients with metastatic LN disease in either cohort.ResultsA total of 44 patients were recruited with a male to female ratio of 26 : 18 and a mean age of 71 years (range 52–88 years). Cohort 1 consisted of 18 patients, of whom six had fluorescent primary cancers and three of these had fluorescent LNs. One out of 10 patients with metastatic LN disease had a fluorescent involved LN. Cohort 2 consisted of 26 patients, of whom eight had fluorescent primary cancers and four of these had fluorescent LNs. None of the fluorescent LNs contained disease in this cohort. No serious adverse events (SAEs) occurred but two mild, self-limiting, photosensitivity reactions were observed in cohort 2. The sensitivity and specificity for 5-ALA detection of LN-positive disease were: cohort 1 11.1%, 75%; and cohort 2 0%, 75%.LimitationsThis was a feasibility study exploring the use of 5-ALA for LN disease in a select cohort of patients with advanced colorectal cancer. The study population was small and generalisation to other cancers is not possible. The study was limited by the ability to determine LN-positive patients on the basis of pre-operative CT staging, which is often inaccurate, resulting in our cohorts containing several patients without LN disease.Conclusions5-ALA fluorescent diagnosis has poor sensitivity for discriminating LN-positive colon cancer. Its use as an aid to stratified colon cancer surgery is not supported. No SAEs were observed, suggesting that photosensitisers may be useful for intraoperative FD.Future work5-ALA has poor sensitivity for detecting LN metastases and cannot be recommended for intraoperative staging. Other, more sensitive fluorescent probes are required if this strategy is to be used.Study registrationCurrent Controlled Trials ISRCTN79949827 and EudraCT number 2012–002623–15.Funding detailsThis project was funded by the EME programme, a Medical Research Council and National Institute for Health Research partnership.

Download Full-text