High-dose definitive concomitant chemoradiotherapy in non-metastatic locally advanced esophageal cancer: toxicity and outcome

Abstract

This study is a retrospective analysis of high-dose definitive concomitant chemoradiotherapy in locally advanced esophageal cancer in a single institution. The aim of the study was to identify and quantify the toxicity associated with the high-dose treatment and to analyze the outcome of this treatment. Forty-six patients (41 men and 5 women, median age of 67.5 years) with disease stage IIA-III esophageal cancer were treated with high-dose definitive chemoradiotherapy. Thirty patients had squamous cell carcinomas and 16 had adenocarcinomas. The patients were treated with three courses of chemotherapy. Each chemotherapy course consisted of cisplatin 100 mg/m(2), day 1 and 5-Fluorouracil 1000 mg/m(2)/day, day 1-5. One course was given every 3 weeks. Concurrent radiotherapy (66 Gy/33 fractions) was administered during the last two courses of chemotherapy. Toxicity grades three and four were seen in 47.5% and 40% of the patients, respectively. Treatment related mortality occurred in one patient (2.5%) due to neutropenic septicemia. Follow-up time for surviving patients (2/46) was 45 and 112 months. For the entire study population, the median time to local recurrence in the radiotherapy field was 33 months and the median time to distant metastasis was 8.7 months, whereas median overall survival was 10.8 months and median disease-specific survival 11 months. For responders to chemoradiotherapy, the median time to local recurrence was 76 months, the median time to distant metastasis 16.8 months, the median overall survival and the median disease-specific survival for the responders were both 17 months. The 2, 3 and 5-year survival rates were 22%, 15% and 11% for the entire study population, and 31%, 24% and 17% for the responders to chemoradiotherapy, respectively. By multivariate analysis response to chemoradiotherapy and lower disease stage were positive prognostic factors for survival. The results of our study have shown that concurrent high-dose chemoradiotherapy provides long-term local tumor control in locally advanced esophageal cancer. However, toxicities following this high-dose treatment, while manageable, were significant. Survival rates were not improved by high-dose chemoradiotherapy compared with what is reported in previous studies applying lower doses of definitive chemoradiotherapy.