Efficacy analysis of neoadjuvant chemotherapy for resectable locally advanced adenocarcinoma of the esophageal-gastric junction

Abstract

Objective To investigate the clinical efficacy of neoadjuvant chemotherapy (oxaliplatin + capecitabine, XELOX) for the resectable locally advanced adenocarcinoma of esophageal-gastric junction (AEG). Methods The prospective study was conducted. The clinicopathological data of 106 locally advanced AEG patients who were admitted to the Cancer Hospital of Shantou University Medical College from January 2011 to December 2014 were collected. All the patients were divided into the treatment group and control group by single blind, randomized, controlled random number table. Patients underwent preoperative neoadjuvant chemotherapy (XELOX) + surgery + postoperative adjuvant chemotherapy (XELOX) in the treatment group and surgery + postoperative adjuvant chemotherapy (XELOX) in the control group. Total gastrectomy + Roux-en-Y esophagojejunostomy + D2 lymphadenectomy were applied to patients by the same team of doctors. Observation indicators: (1) treatment situations; (2) results of postoperative pathological examination; (3) follow-up and survival situations. Follow-up using outpatient examination was performed to detect the postoperative tumor recurrence or metastasis and patients′ survival up to February 2017. Measurement data with normal distribution were represented as ±s, and comparisons between groups were evaluated with the t test. Measurement data with skewed distribution were described as M (range) and analyzed by the nonparametric test. Comparisons of count data were analyzed using the chi-square test. The ordinal data were compared using the nonparametric test. Survival rate and curve were respectively calculated and drawn by the Kaplan-Meier method and survivals were compared using the Long-rank method. Results One hundred and six patients were screened for eligibility, including 54 in the treatment group and 52 in the control group. (1) Treatment situations: ① preoperative neoadjuvant chemotherapy: 54 in the treatment group received 2-4 cycle neoadjuvant chemotherapy. During the chemotherapy, gastrointestinal reaction, grade 1-2 granulocytopenia, elevated alanine transaminase (ALT) and grade 3 granulocytopenia were detected in 21, 17, 8, 1 patients, and 7 patients had no adverse reaction. The complete response(CR), partial response (PR), stable disease (SD) and progressive disease (PD) of neoadjuvant chemotherapy in the treatment group were detected in 4, 27, 20 and 3 patients, respectively. Of 54 patients in the treatment group, 4, 13, 25 and 12 were in grade 0, 1, 2 and 3 of response to preoperative chemotherapy, respectively. ② Surgical situations: preoperative carcinoembryonic antigen (CEA) in the treatment and control groups were respectively 4.71 μg/L (range, 0.20-36.19 μg/L) and 14.09 μg/L (range, 0.71-178.20 μg/L), with a statistically significant difference between groups (Z=-1.92, P 0.05). ③ Postoperative adjuvant chemotherapy: all the patients completed the postoperative adjuvant chemotherapy. The granulocytopenia, elevated ALT and gastrointestinal reaction occurred in 25, 5, 28 patients in the treatment group and 21, 7, 30 patients in the control group, respectively, with no statistically significant difference between groups (χ2=0.38, 0.47, 0.36, P>0.05). Some of the patients were merged with multiple adverse reactions. (2) Results of postoperative pathological examination: maximum tumor dimension, cases with lymphovascular invasion, perineural invasion, T0, T2, T3, T4 (T stage), stage 0, Ⅰ, Ⅱ and Ⅲ (TNM stage) were respectively (3.6±1.4)cm, 5, 10, 4, 10, 20, 20, 4, 7, 15, 28 in the treatment group and (4.5±1.7)cm, 24, 30, 0, 2, 13, 37, 0, 1, 12, 39 in the control group, with statistically significant differences between groups (t=-2.88, χ2=18.14, 17.30, Z=14.74, 8.13, P 0.05). There was a statistically significant difference in cases with local recurrence between groups (χ2=4.41, P<0.05) The tumor-free survival time and overall survival time in the treatment group were respectively 29 months (range, 8-72 months), 38 months (range, 10-72 months) in 31 patients with CR and PR and 11 months (range, 3-68 months), 18 months (range, 4-68 months) in 23 patients with SD and PD, showing statistically significant differences in tumor-free and overall survival times (χ2=5.27, 7.72, P<0.05). Conclusion Neoadjuvant chemotherapy with oxaliplatin and capecitabine is safe and effective for patients with the resectable locally advanced AEG, it can also decrease tumor stage and reduce local recurrence, but fail to demonstrate a survival benefit. Key words: Adenocarcinoma of esophagogastric junction; Locally advanced; Neoadjuvant chemotherapy