Effect of Pathologic Tumor Response and Nodal Status on Survival in the Medical Research Council Adjuvant Gastric Infusional Chemotherapy Trial

Abstract

PurposeThe 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 MethodsPathologic 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.ResultsThree 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).ConclusionLymph 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.

Perioperative Chemotherapy in Elderly Patients with Locally Advanced Adenocarcinoma of the Stomach and the Esophagogastric Junction: A Retrospective Cohort Analysis of Toxicity and Efficacy at the National Center for Tumor Diseases, Heidelberg

“…In the majority of our cohort, patient refusal or cardiopulmonary comorbidities rather than systemic disease progression during neoadjuvant treatment led to a change in the treatment procedure (e.g., switch to a definitive [chemo-]radiation). A good histological response (grade 1a or 1b according to the classification by Becker et al [21]) was observed in about 30% of our patients, which is in good accordance with other recent analyses [26,27]. A tendency for a better histological response with a triplet combination therapy was observed in our patients, although it did not reach statistical significance.…”

ypTNM staging after neoadjuvant chemotherapy in the Chinese gastric cancer population: an evaluation on the prognostic value of the AJCC eighth edition cancer staging system

“…For instance, studies have found that up to 50% of patients in stage ypT3 and ypT4 can have residual tumor cells of less than 10%, whereas the percentage of residual tumor cells was not necessarily smaller than 10% in those patients with stage ypT1 [12]. Therefore, a few studies have proposed that the ypN stage, combined with pathologic regression grade, may be helpful in stratifying the prognosis of esophageal cancer patients who undergo preoperative chemotherapy or chemoradiotherapy [6,13]. This proposition may also hold true for gastric cancer.…”

Neoadjuvant therapy for esophageal cancer: Who, when, and what?

“…18 N0 rates of approximately 30% to 40% were reported for the combination of cisplatin and 5-FU and ECX in the UK MRC OEO5 and FLOT4-AIO studies, respectively, versus an N0 rate of 49% in the FLOT arm. 19 Given that lymph node negativity appears to be strongly prognostic, this further justifies the use of chemoradiation in these patients. 8,13 In a retrospective review of the MAGIC study, multivariate analysis demonstrated that lymph node status was the only independent predictor of survival in patients treated with chemotherapy.…”