Background Non-surgical management of anal cancer by radiotherapy alone or combined with chemotherapy has, in uncontrolled studies, yielded similar local tumour control and survival rates to surgery. However, whether the addition of chemotherapy improves outcome without adding to morbidity is not known. Our trial was designed to compare combined modality therapy (CMT) with radiotherapy alone in patients with epidermoid anal cancer.Methods From 856 patients considered for entry to our multicentre trial, 585 patients were randomised to receive initially either 45 Gy radiotherapy in twenty or twenty-five fractions over 4-5 weeks (290 patients) or the same regimen of radiotherapy combined with 5-fluorouracil (1000 mg/m(2) for 4 days or 750 mg/m(2) for 5 days) by continuous infusion during the first and the final weeks of radiotherapy and mitomycin (12 mg/m(2)) on day 1 of the first course (295 patients). We assessed clinical response 6 weeks after initial treatment: good responders were recommended for boost radiotherapy and poor responders for salvage surgery. The main endpoint was local-failure rate (greater than or equal to 6 weeks after initial treatment); secondary endpoints were overall and cause-specific survival. Analysis was by intention-to-treat.Findings In the radiotherapy and CMT arms, respectively, five and three were ineligible, and six and nine died 6 weeks after initial treatment. After a median follow-up of 42 months (interquartile range 28-62), 164 of 279 (59%) radiotherapy patients had a local failure compared with 101 of 283 (36%) CMT patients. This gave a 46% reduction in the risk of local failure in the patients receiving CMT (relative risk 0.54, 95% CI 0.42-0.69, p<0.0001). The risk of death from anal cancer was also reduced in the CMT arm (0.71, 0.53-0.95, p=0.02). There was no overall survival advantage (0.86, 0.67-1.11, p=0.25). Early morbidity was significantly more frequent in the CMT arm (p=0.03), but late morbidity occurred at similar rates.Interpretation Our trial shows that the standard treatment for most patients with epidermoid anal cancer should be a combination of radiotherapy and infused 5-fluorouracil and mitomycin, with surgery reserved for those who fail on this regimen.

Background Although surgery is the treatment of choice for rectal cancer, local recurrence is common even after apparently curative resection. We aimed to assess the role of postoperative radiotherapy in reducing rates of local recurrence, and improving disease-free and overall survival in patients with mobile Dukes' stage B and C rectal cancers.Methods We carried out a prospective, randomised trial of surgery alone (n=235) versus surgery followed 4-6 weeks later by radiotherapy (n=234), of 40 Gy in 20 fractions of 2 Gy over 4 weeks. The 469 patients, from 46 hospitals in the UK and the Republic of Ireland, were randomised between 1984 and 1989, and followed up for a minimum of 5 years or to death.Findings 284 patients died, 145 of 235 allocated surgery alone and 139 of 234 allocated postoperative radiotherapy. The hazard ratio for overall survival was 0.84 (95% CI 0.65-1.07, p=0.17). At 5 years' follow-up 79 patients who received surgery alone and 48 who received postoperative radiotherapy had had local recurrence (hazard ratio 0.54 [0.38-0.77], p=0.001). The corresponding numbers with distant recurrence were 83 and 75 (hazard ratio 0.85 [0.63-1.114], p=0.18). The hazard ratio for disease-free survival was 0.85 (0.65-1.08; p=0.18). Radiotherapy was generally well tolerated; assessment of late events showed serious late bowel complications to be rare and not significantly increased after radiotherapy, even when this followed anterior resection.Interpretation Our results have provided further evidence of the ability of postoperative radiotherapy to delay and prevent local recurrence of rectal cancer. Although the local recurrence rate in the control group is in keeping with other multicentre trials of the mid to late 1980s, it is undoubtedly higher than would be regarded as acceptable now. The combination of larger trials required to provide definitive answers on the impact that postoperative radiotherapy will have on survival.

In 178 consecutive oesophageal squamous carcinoma cases, 5% (9 cases) had had thyrotoxicosis, hypothyroidism or thyroid carcinoma. The incidence in males was 1% (1 case) and in females 8% (8 cases). This incidence was in excess of other known associations of oesophageal cancer and in this series, it was exceeded only by previous gastric surgery for peptic ulceration.