Neoadjuvant concurrent chemoradiotherapy followed by definitive high-dose radiotherapy or surgery for operable thoracic esophageal carcinoma

Abstract Purpose: A prospective clinical trial was undertaken to investigate the feasibility of concurrent chemoradiotherapy for esophageal carcinomas. Materials and Methods: Between June 1989 and May 1996, forty patients with operable squamous cell carcinoma of the thoracic esophagus (Stage 0 to III: UICC 1987), ages 45 to 78 years (mean: 64), were enrolled in a study of neoadjuvant concurrent chemoradiotherapy followed by definitive high-dose radiotherapy (CRT group) or surgery (CRT-S group). Neoadjuvant chemoradiotherapy consisted of 44 Gy in 40 fractions for 4 weeks (2.2 Gy/2 Fr/day) through 10-MVX rays, with 2 courses of cisplatin (80–100 mg/body, mean: 60 mg/m2, Day 1, bolus injection) and 5-fluorouracil (500–1000 mg/body/day, mean: 400 mg/m2, Days 1–4, continuous infusion). After completion of neoadjuvant chemoradiotherapy, an intermediate clinical response was assessed by barium swallow, esophagoscopy with/without biopsy, EUS in most cases, thoracic and upper abdominal CT scan, and cervical US. Definitive chemoradiotherapy was performed in patients when regression of more than 75% was evident (CRT Group), and esophageal resection was indicated in those who remained at less than 75% (CRT-S Group). In CRT Group, a cumulative dose of 60–70 Gy for Tis, T1 and 65–75 Gy for T2–T4 tumor with high-dose–rate intraluminal brachytherapy and a total of 3 courses of chemotherapy were planned. In CRT-S Group, intraoperative radiotherapy for abdominal lymphatic system and postoperative supraclavicular irradiation were added. Results: At the time of intermediate assessment, complete response (CR) was observed in 16 patients, a partial response (PR) in 22, and no change (NC) in 2. Thirty responding patients (CR, 16; PR, 14) entered the CRT Group, and 10 nonresponding patients (PR, 8; NC, 2) were followed by surgery (CRT-S Group). Radiotherapy was completed satisfactorily, but chemotherapy was suspended in 26 patients (65%) because of acute toxicity. Clinical CR rate at the completion of treatment showed 90% in CRT Group, and pathologic CR rate 10% in CRT-S Group. The overall median survival was 45 months, survival at 1, 2, and 3 years being 100%, 72%, and 56%, respectively. Local-regional failure was observed in 7 patients (all in CRT Group), distant failure in 6 (3 in CRT Group, 3 in CRT-S Group) and local-regional with distant failure in 1 (CRT Group). Four patients with local-regional recurrence in the CRT Group were salvaged by surgery. Overall survival at 2 and 3 years for CRT vs. CRT-S Group was 72%, 64% vs. 75%, 38%, respectively. No treatment-related mortality was observed. The rate of the ’esophagus conservation’ was 65% (Stage 0: 1 of 1, 100%; Stage I: 11 of 12, 92%; Stage II: 8 of 17, 47%; Stage III: 6 of 10, 60%). Conclusion: Our results demonstrated that almost all early disease (Stage 0–I) and about half of advanced disease (Stage II–III) could be conserved, their esophagus treated by the multidisciplinary approach centering on high-dose radiotherapy and concurrent chemotherapy.