Preoperative Treatment with Radiochemotherapy for Locally Advanced Gastroesophageal Junction (GEJ) Cancer and Unresectable Locally Advanced Gastric Cancer

Abstract

Introduction: Recent evidences highlight the importance of radiotherapy in addition to neoadjuvant chemotherapy regimens in GEJ cancers and also in gastric cancers. Data demonstrating survival benefits of preoperative radiochemotherapy in GEJ carcinomas are quite strong, but in gastric cancer are less clear. In both cases preoperative radiochemotherapy increases rates of radical resection, pathological complete response and patients survival, with no increase in postoperative morbidity and mortality. Methods: In the period from January 2004 to July 2012, 90 patients (24 male and 66 females, aged 30-79 years, mean age 60.5 years) were treated with preoperative radiation in 25 daily fractions of 1.8 Gy in 5 weeks with concomitant 5-fluorouracil in 96h continuous infusion and cisplatin. All patients had locally and/or regionally advanced GEJ cancer or unresectable locally advanced gastric cancer. Surgery was performed 4-6 weeks after radiochemotherapy. The main endpoints of this study were histopathological R0 resection rate and pathological response rate. The effect of preoperative chemoradiotherapy on tumor down-staging was assessed by comparing the pretreatment radiologicaly determined TNM stage with the postoperative pathologic TNM stage. The rates of acute side effects were also estimated. Results: Only 63.4% of patients underwent surgery with the aim of complete removal of the tumor. Radical resection (R0) was achieved in 50 (55.6%) patients and the remaining seven (7.8%) patients underwent non-radical surgery (R1 in five and R2 in two patients). Pathological complete response of tumor was achieved in 8.8% patients who underwent surgery and 5.6% of all treated patients. Down-staging was recorded in 86% of patients, in 1,8% the stage after radiochemotherapy was unchanged while in 12.3% of patients the pathological stage was higher than clinical, mainly due to higher pN stage. Seven percent of patients did not complete the preoperative treatment according to the protocol, because of disease progression or serious side effects of treatment and deterioration of performance status. No death occurred due to the therapy. Most grade 3 and 4 toxicities were due to vomiting, nausea and bone marrow suppression. Despite intensive nutritional support the weight loss was observed in 58% of patients during treatment, but more than 10% of weight loss was seen in only 13.9% of patients. Twenty-six (45.6%) patients died due to GEJ or gastric carcinoma, one died because of septic shock following the surgery and a reason for two deaths was unknown. Twenty-eight patients (49.1%) were disease free, the rest twenty-nine patients (50.9%) developed the recurrence: one patient (1.8%) only local, one patient (1.8%) loco-regional, 24 patients (42.1%) only distant metastases and other three patients (5.4%) loco-regional recurrence in combination with distant metastases. Conclusion: We believe that treatment with preoperative radiochemotherapy is feasible, with acceptable toxicity, and it provides good down-staging with even the possibility of complete pathological complete response of the disease.