NEOADJUVANT CONCURRENT CHEMORADIOTHERAPY FOLLOWED BY DEFINITIVE HIGH-DOSE RADIOTHERAPY OR SURGERY FOR OPERABLE THORACIC ESOPHAGEAL-CARCINOMA

Purpose: A prospective clinical trial was undertaken to investigate th e feasibility of concurrent chemoradiotherapy for esophageal carcinoma s. Materials and Methods: Between June 1989 and May 1996, forty patien ts with operable squamous cell carcinoma of the thoracic esophagus (St age 0 to III: UICC 1987), ages 45 to 78 years (mean: 64), were enrolle d in a study of neoadjuvant concurrent chemoradiotherapy followed by d efinitive 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 cispl atin (80-100 mg/body, mean: 60 mg/m(2), Day 1, bolus injection) and 5- fluorouracil (500-1000 mg/body/day, mean: 400 mg/m(2), Days 1-4, conti nuous infusion). After completion of neoadjuvant chemoradiotherapy, an intermediate clinical response was assessed by barium swallow, esopha goscopy with/without biopsy, EUS in most cases, thoracic and upper abd ominal CT scan, and cervical US. Definitive chemoradiotherapy was perf ormed in patients when regression of more than 75% was evident (CRT Gr oup), 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 intral uminal brachytherapy and a total of 3 courses of chemotherapy were pla nned. In CRT-S Group, intraoperative radiotherapy for abdominal lympha tic system and postoperative supraclavicular irradiation were added. R esults: At the time of intermediate assessment, complete response (CR) was observed in 16 patients, a partial response (PR) in 22, and no ch ange (NC) in 2. Thirty responding patients (CR, 16; PR, 14) entered th e CRT Group, and 10 nonresponding patients (PR, 8; NC, 2) were followe d 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% i n CRT Group, and pathologic CR rate 10% in CRT-S Group. The overall me dian 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 i n 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 t hat almost all early disease (Stage 0-I) and about half of advanced di sease (Stage II-III) could be conserved, their esophagus treated by th e multidisciplinary approach centering on high-dose radiotherapy and c oncurrent chemotherapy. (C) 1998 Elsevier Science Inc.