Definitive Concurrent Chemotherapy and High Dose (60-70Gy) Radiation Therapy for Esophageal Cancer

Abstract

Based on the results of the intergroup-0123/RTOG 94-05 trial that demonstrated no benefit of dose escalation over 50.4 Gy in definitive chemoradiation therapy (CRT) for esophageal carcinoma, 50.4 Gy appears to be accepted as a standard dose. Radiobiologically, however, higher radiation doses, if safely delivered, could lead to better local control. We have used combination of standard FP (5-fluorouracil [5-FU] and cisplatin) chemotherapy and radiation with doses >60 Gy in the treatment of non-metastatic esophageal cancer. We report clinical outcome of the treatment protocol. Between 2002 and 2014, 78 patients with stage I-III or IV (M1 LYM) esophageal cancer were treated with CRT. Median age of the patients was 68 years (range: 46 to 84); 66 were men and 12 were women. Histology was squamous cell carcinoma in 96%. Patients were divided into 4 groups according to the stage and operability; Group 1: stage I patients (n = 10); Group 2: stage II-III operable patients (n = 16); Group 3: stage II-III (non-T4) inoperable patients (n = 19); and Group 4: stage III-IV (T4/M1 LYM) patients (n = 33). Chemotherapy protocols were either cisplatin (70 mg/m2) plus 5-FU (700 mg/m2 x 4 days) administered every 4 weeks or low-dose daily cisplatin (10 mg/m2) and 5-FU (175 mg/m2). Radiation was given by 10-MV X rays with a daily fraction of 1.8-2 Gy. Treatment volume included primary tumor plus regional lymph nodes. A total dose between 60 and 70 Gy was chosen depending on the treatment volume. Median radiation dose was 64 Gy (range: 14-70 Gy; 4 patients could not complete planned treatment). Failure was confirmed by pathology or findings of progressive disease on serial endoscopy and/or imaging studies. Overall survival (OS) and local control (LC) rates were calculated by the Kaplan-Meier method. Toxicities were evaluated by the Common Terminology Criteria for Adverse Events version 4.0. For all 78 patients, the 3-year LC and OS rates were 62% and 26%, respectively; they were 100% and 100%, respectively, in Group 1, and 76% and 40%, respectively, in Group 2. The 2-year LC and OS were 63% and 15%, respectively, in Group 3, and 62% and 16%, respectively, in Group 4. Overall response rate was 76% (complete response in 28 and partial response in 31). Grade 3 or higher acute toxicities, mainly hematological, were observed in 45% of the patients and 10% experienced grade 3-4 late toxicities. CRT with standard FP and 60-70 Gy of radiation appears to be tolerable for patients with esophageal cancer. Although outcome of this treatment in inoperable patients is not satisfactory, the 3-year LC of 100% for stage I patients and 76% for stage II-III operable patients appear promising. Further investigation is warranted to clarify the optimal radiation dose in CRT for esophageal cancer.