Background
Oesophageal cancer carries a poor prognosis. The 5-year survival rate following resection ranges from 10 to 35 per cent. Recent evidence suggests that the addition of non-surgical treatments to surgery may improve resection rates, reduce the risk of recurrence and improve survival. This review examines the role of preoperative chemoradiotherapy (CRT) in oesophageal cancer.

Methods
A Medline-based literature review (1980–2000) was performed using the key words ‘neoadjuvant or preoperative’ and ‘chemoradiotherapy or radiochemotherapy’. Additional literature was obtained from original papers and published meeting abstracts.

Results
Forty-six non-randomized and six randomized trials of preoperative CRT were found. Resection rates, pathological complete response (pCR), treatment-related mortality rates and relapse patterns are documented. Improved 5-year survival rates approaching 60 per cent may be achieved following pCR. Three of the six randomized trials show a benefit in either overall survival or disease-free survival compared with surgery alone. Treatment-related toxicity can be significant.

Conclusion
Preoperative CRT may improve survival. Emerging evidence suggests that CRT alone can achieve similar survival rates to surgery alone. New imaging modalities may help to select which patients require surgery. Larger randomized trials of preoperative CRT or chemotherapy are needed to define optimal regimens and produce higher pCR rates with acceptable toxicity. © 2001 British Journal of Surgery Society Ltd

Preoperative (neoadjuvant) chemoradiotherapy in oesophageal cancer.

Purpose: To determine the outcome of neoadjuvant chemotherapy followed by concurrent chemotherapy plus high-dose radiation therapy in patients with local/regional squamous cell carcinoma of the esophagus. Methods and Materials: Forty-five patients with clinical Stage T1-4N0-1M0 squamous cell carcinoma were entered on a prospective single-arm study, of which 38 were eligible. Patients received 3 monthly cycles of 5-FU (1000 mg/m 2 /24 h × 5 days) and cisplatin (100 mg/m 2 day 1; neoadjuvant segment) followed by 2 additional monthly cycles of 5-FU (1000 mg/m 2 /24 h × 5 days) and cisplatin (75 mg/m 2 day 1) plus concurrent 6480 cGy (combined modality segment). The median follow-up in surviving patients was 59 months. Results: For the 38 eligible patients, the primary tumor response rate was 47% complete, 8% partial, and 3% stable disease. The first site of clinical failure was 39% local/regional and 24% distant. For the total patient group, there were 6 deaths during treatment, of which 9% (4/45) were treatment related. The median survival was 20 months. Actuarial survival at 3 years was 30%, and at 5 years, 20%. Conclusion: This intensive neoadjuvant approach does not appear to offer a benefit compared with conventional doses and techniques of combined modality therapy. However, high dose radiation (6480 cGy) appears to be tolerable, and is being tested further in Intergroup Trial INT 0123.

Final report of Intergroup Trial 0122 (ECOG PE-289, RTOG 90-12): Phase II trial of neoadjuvant chemotherapy plus concurrent chemotherapy and high-dose radiation for squamous cell carcinoma of the esophagus.

The use of chemoradiotherapy in oesophageal cancer.

Purpose: This retrospective study was designed to compare treatment results of the chemoradiation protocol with conventional surgery for thoracic T1-T2 esophageal squamous cell carcinoma. Methods and Materials: Sixty-six patients with esophageal carcinoma, clinically diagnosed as T1 (tumor invading lamina propria or submucosa) or T2 (tumor invading muscularis propria) were treated for 12 consecutive years, from July 1986 to January 1998. The conventional surgery group included 30 patients who underwent esophagectomy with regional lymph node dissection. Twenty-one of them received postoperative radiotherapy. Thirty-six patients were assigned to the chemoradiation protocol, consisting of neoadjuvant chemoradiotherapy (44 Gy; CDDP: 60 mg/m 2 , day 1, bolus; 5-FU: 400 mg/m 2 , day 1–4, continuous), followed by either definitive radiotherapy with high-dose-rate intraluminal brachytherapy (total 70 Gy) for responders or surgery for nonresponders as in the conventional surgery group. Surgical candidates in both groups received intraoperative radiotherapy for abdominal lymphatics since 1991. Results: In the protocol group, 4 patients underwent radical surgery after neoadjuvant chemoradiotherapy, and the remaining 32 underwent definitive chemoradiotherapy. Local control rates at 1 and 3 years were 85% and 70% in the T1/protocol group versus 91% and 80% in the T1/surgery group, and 83% and 83% in the T2/protocol group versus 94% and 80% in the T2/surgery group, respectively. There was no statistical significance. Overall 1- and 3-year survival rates were 100% and 83% in the T1/protocol group versus 82% and 72% in the T1/surgery group ( p = 0.36), and 100% and 51% in the T2/protocol group, versus 95% and 68% in the T2/surgery group ( p = 0.61), respectively. There was no treatment-related mortality in either group. The rates of esophageal conservation were 92% in the T1/protocol group and 58% in the T2/ protocol group. Conclusion: The chemoradiation protocol can result in comparable survival with conventional surgery for patients with T1-T2 esophageal carcinoma. A randomized trial between definitive chemoradiotherapy and surgery is required.

Comparison between chemoradiation protocol intended for organ preservation and conventional surgery for clinical T1-T2 esophageal carcinoma

The definition of potential curative tumors of the esophagus and gastro-esophageal junction remains problematic. This is due to a lack of accuracy in clinical staging despite recent advances in CT, endoscopic ultrasonography (EUS), positron emission tomography scan and minimally invasive staging modalities. As a result much controversy persists regarding indications for surgery and extent of resection and lymphadenectomy. Today surgery with curative option results in five-year survival of over 30%. Multimodality regimens, especially neoadjuvant chemoradiotherapy, seem to be beneficial in patients with a complete response on pathologic staging. Other indications are investigational and should be studied within carefully monitored study protocols. In early carcinoma T is – T 1a endoluminal ablation technique seem to open promising perspectives provided of discrimination between T is – T 1a and T 1b can be made by the use of 20mhz EUS probes.

Cancer of the esophagus and gastro-esophageal junction: potentially curative therapies

Combined intensive chemoradiotherapy for organ preservation in patients with resectable and non-resectable oesophageal cancer

In order to investigate the medical treatment of anal canal carcinoma (ACC), 27 patients (pts) were treated with cisplatin, fluorouracil and radiotherapy, in an alternating schedule. Eleven pts received mitomycin C, fluorouracil and radiotherapy, in a concurrent scheme. Finally, six pts were included in a new outpatient scheme with cisplatin, fluorouracil, leucovorin, mitomycin C and concurrent radiotherapy. Within the first schedule, 25 pts were evaluable and 18 achieved complete response. All of them are disease free until now. With the second scheme, 7/10 pts had a complete response and 5 of them are alive and disease free. All the pts included in the last schedule (6/6) achieved complete remission. There were no deaths related to toxicity. Our experience is one of the earliest in oncology using cisplatin as a first line drug, in the non-surgical treatment of ACC. We think that the use of cisplatin is feasible, its toxicity is manageable, and its effectivity is similar to other schedules, as observed in our last scheme.

Medical treatment of 44 patients with anal canal carcinoma. Argentinian Intergroup for the treatment of gastrointestinal tumors (IATTGI)

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Combined intensive chemoradiotherapy for organ preservation in patients with resectable and non-resectable oesophageal cancer

Medical treatment of 44 patients with anal canal carcinoma. Argentinian Intergroup for the treatment of gastrointestinal tumors (IATTGI)