W. Duncan

The results of a series of 963 patients with transitional cell carcinoma of the urinary bladder primarily treated by radical megavoltage X-ray therapy

The results are reported of a large series of patients with transitional cell cancer of the bladder, treated in Edinburgh between 1971 and 1982. Analysis of pre-treatment characteristics for patients with transitional cell bladder cancer showed that tumour category was significantly associated with grade and tumour size. Complete local tumour regression at follow-up cystoscopy was achieved in 45.9% of patients who completed radical megavoltage X-ray therapy. Patients with grade 2 or 3 cancer, a solid cancer or a tumour of less than 8 cm in size had significantly improved complete regression rates. Lasting local tumour control after initial complete regression was better in patients with grade 3 cancer. Complete regression was associated with improved survival for all but patients with T1 cancer. The poorest (uncorrected) survival rates were seen in patients over 79 years of age, those with T4 cancer, an ulcerated cancer, a grade 3 cancer or a tumour of more than 7 cm in size. Metastases were more often seen in patients with grade 3 or T3/T4 cancer. Severe late radiation-related complications were seen in 14.8% of patients.

Low dose preoperative radiotherapy for carcinoma of the oesophagus: results of a randomized clinical trial

One-hundred-and-seventy-six patients with potentially operable squamous cell carcinoma or adenocarcinoma of the middle or lower thirds of the oesophagus were randomly assigned to preoperative radiotherapy or surgery alone. Patients assigned to the radiotherapy arm received 20 Gy in 10 treatments over 2 weeks, using parallel opposed 4 MV beams. The preoperative radiotherapy was not associated with any significant acute morbidity or any increase in operative complications. The median survival of the overall group of 176 patients was 8 months, and the 5-year survival was 13%. There was no significant difference in the survival of the 90 patients who received preoperative radiotherapy and the 86 who were managed by surgery alone. Proportional hazards analysis identified lymph node involvement, high tumour grade and male sex as significant adverse prognostic features, but the treatment option assigned had no prognostic significance. It was concluded that low dose preoperative radiotherapy offered no advantage over surgery alone.

Preoperative radiotherapy in esophageal carcinoma: A meta-analysis using individual patient data (oesophageal cancer collaborative group)

PURPOSE The existing randomized evidence has failed to conclusively demonstrate the benefit or otherwise of preoperative radiotherapy in treating patients with potentially resectable esophageal carcinoma. This meta-analysis aimed to assess whether there is benefit from adding radiotherapy prior to surgery. METHODS AND MATERIALS This quantitative meta-analysis included updated individual patient data from all properly randomized trials (published or unpublished) comprising 1147 patients (971 deaths) from five randomized trials. RESULTS With a median follow-up of 9 years, the hazard ratio (HR) of 0.89 (95% CI 0.78-1.01) suggests an overall reduction in the risk of death of 11% and an absolute survival benefit of 3% at 2 years and 4% at 5 years. This result is not conventionally statistically significant (p = 0.062). No clear differences in the size of the effect by sex, age, or tumor location were apparent. CONCLUSION Based on existing trials, there was no clear evidence that preoperative radiotherapy improves the survival of patients with potentially resectable esophageal cancer. These results indicate that if such preoperative radiotherapy regimens do improve survival, then the effect is likely to be modest with an absolute improvement in survival of around 3 to 4%. Trials or a meta-analysis of around 2000 patients would be needed to reliably detect such an improvement (15-->20%).

Similar decreases in local tumor control are calculated for treatment protraction and for interruptions in the radiotherapy of carcinoma of the larynx in four centers

PURPOSE Data on patients with cancer of the larynx are analyzed using statistical models to estimate the effect of gaps in the treatment time on the local control of the tumor. METHODS AND MATERIALS Patients from four centers, Edinburgh, Glasgow, Manchester, and Toronto, with carcinoma of the larynx and treated by radiotherapy were followed up and the disease-free period recorded. In all centers the end point was control of the primary tumor after irradiation alone. The local control rates at > or = 2 years, Pc, were analyzed by log linear models, and Cox proportional hazard models were used to model the disease-free period. RESULTS T stage, nodal involvement, and site of the tumor were important determinants of the disease-free interval, as was the radiation schedule used. Elongation of the treatment time by 1 day, or a gap of 1 day, was associated with a decrease in Pc of 0.68% per day for Pc = 0.80, with a 95% confidence interval of (0.28, 1.08)%. An increase of 5 days was associated with a 3.5% reduction in Pc from 0.80 to 0.77. At Pc = 0.60 an increase of 5 days was associated with an 7.9% decrease in Pc. The time factor in the Linear Quadratic model, gamma/alpha, was estimated as 0.89 Gy/day, 95% confidence interval (0.35, 1.43) Gy/day. CONCLUSIONS Any gaps (public holidays are the majority) in the treatment schedule have the same deleterious effect on the disease free period as an increase in the prescribed treatment time. For a schedule, where dose and fraction number are specified, any gap in treatment is potentially damaging.

Results of radical radiotherapy of squamous cell carcinoma of the oesophagus

A retrospective study was undertaken of 444 patients who were referred with squamous cell carcinoma of the oesophagus during the period January 1956 to December 1974 and who were treated by radical radiotherapy. The overall crude survival rate at 5 years was 9.0% which is similar to the results of most series reported from other centres and compares favourably with the results of radical surgery. The crude 5 year survival rate was 5.7% for males and 11.6% for females, a significant difference (P less than 0.05). Survival is analysed in terms of sex, site, size and histological grade. Patients (males and females) with the best 5-year survival rates had tumours no more than 5.0 cm in length (11.9%) or confined to the cervical oesophagus (18.9%). Histological grade appeared to have no influence on prognosis. The principal morbidity associated with radical radiotherapy is fibrous stricture formation. This occurred in 43.7% of the patients but was usually effectively managed by bouginage.

Primary radical radiotherapy for T3 transitional cell cancer of the bladder: an analysis of survival and control

Patients who completed a course of radical radiotherapy for T3 bladder cancer are reviewed. A follow up cystoscopy where tumor response was assessed, was carried out in 272 of the 333 patients of whom 41.2% had complete local regression. Significant factors correlated with complete local tumor regression are described, the most significant being histological grade of the tumor. A higher proportion of patients with complete regression were found among those with Grade 3 cancer (55.7%). Patients who received a central tumor absorbed dose of 55.0 gray or 57.5 gray in 20 fractions over 4 weeks had a significantly higher probability of complete local regression and lasting local control than those who received lower doses. Patients with initial complete local regression had a significantly better probability of survival than those with incomplete regression (p less than 0.0001). There was a significant association between the hemoglobin level at the start of radiotherapy and both local regression and survival. Patients with T3 cancer are more critically selected for treatment by primary radical radiotherapy on the basis of primary tumor size, tumor grade and the patients plasma urea level. Primary cystectomy may be the more appropriate treatment for a patient with a tumor of more than 7 cm in diameter, a Grade 1 cancer or a plasma urea level of more than 10 mmol/l.

ADVERSE EFFECT OF TREATMENT GAPS IN THE OUTCOME OF RADIOTHERAPY FOR LARYNGEAL CANCER

BACKGROUND AND PURPOSE A correlation has been demonstrated between unplanned prolongation of radiotherapy and increased local relapse. This review was performed to assess the importance of overall time on the outcome of curative radiotherapy of larynx cancer. MATERIALS AND METHODS Retrospective analysis was performed of 383 patients with laryngeal cancer managed by elective radiotherapy between 1976-1988 in the Department of Clinical Oncology, University of Edinburgh, Western General Hospital, Edinburgh All cancers were confirmed histologically to be squamous cell carcinomas. All subjects received radiotherapy in 20 daily fractions (except Saturdays and Sundays), employing individual beam direction techniques and computer dose distribution calculations. Main outcome measures were complete resolution of the cancer in the irradiated volume; local relapse; survival and cause-specific survival rates. RESULTS Radiotherapy was completed without any unplanned interruption (28 +/- 2 days) in 230/383 (60%) of patients. A statistically significant two-fold increase in local relapse rates was observed when treatment was given in 31 days or more. There also was a statistically significant four-fold increase in laryngeal cancer deaths when the treatment time exceeded 30 days. CONCLUSIONS In patients with laryngeal cancer, accelerated repopulation of cancer cells probably occurs after the start of radiotherapy. When the overall treatment time is 4 weeks or less, gaps at weekends are not detrimental. However, long holiday periods or gaps in treatment longer than 4 days increase the risk of laryngeal cancer relapse and cancer-related mortality. Significant gaps in treatment should be avoided. If treatment has to be prolonged, additional radiation dose should be prescribed to compensate for increased tumour cell proliferation.

Prognostic indices for bladder cancer: An analysis of patients with transitional cell carcinoma of the bladder primarily treated by radical megavoltage X-ray therapy

A group of 889 patients who completed radical X-ray therapy for transitional cell carcinoma of the bladder during a 12 year period were analysed by a multivariate technique. The patients age, tumour category, tumour size and haemoglobin level were shown to be independent prognostic covariates. A prognostic index was derived and four prognostic subgroups were identified. The prognostic index could divide patients within each T category into those with good, moderate, fair or poor prognosis. The 5 year actuarial survival rate for patients in the poor prognosis group was 5.8% compared to 69.8% for patients in the good prognosis group. Durable local tumour control after radical radiotherapy was also analysed by a multivariate technique. Tumour category, grade, haemoglobin and urea level were found to be significant covariates. A tumour control index was derived and two groups were identified corresponding to a high probability of lasting local control after radical radiotherapy (47.8% of patients) or a low probability of control (52.2%).

Fast neutrons in the treatment of head and neck cancers: The results of a multi-centre randomly controlled trial

The results are presented of a multi-centre randomly controlled trial of fast neutron irradiation and mega-voltage X-rays in the treatment of patients with locally advanced squamous cell carcinoma of the head and neck region. No significant difference was observed in local tumour control rates. Salvage surgery was performed in a similar number of patients in the two groups. Late morbidity was also similar in the two treatment groups. Patients in a subgroup with cancer of the larynx treated by photons had a significantly better survival than those in the neutron treated group.

An analysis of the radiation related morbidity observed in a randomized trial of neutron therapy for bladder cancer.

This report is an analysis of the morbidity in the bladder and bowel observed in a randomized trial of d(15)+Be neutrons versus megavoltage photons in the treatment of bladder cancer. Acute reactions in the bladder and bowel were significantly worse after photon therapy. Of the patients treated with photons 45.7% had severe reactions in the bladder compared with 10.6% after neutron therapy (p less than 0.001). Severe acute bowel reactions were observed in 8.5% of the patients after photon therapy compared with 3.8% after neutron therapy (p less than 0.05). Late reactions were significantly worse after neutrons. Severe late reactions in the bladder were seen in 58.5% of patients after neutron therapy and in 40.5% after photon therapy (p less than 0.05). In the bowel they were observed in 53.3% of patients after neutron therapy compared with 8% after photon therapy (p less than 0.0001). The disparity in the degree of early and late complications makes assessment of RBE values difficult. It is estimated that for bladder morbidity the RBE value, for photon dose fractions of 2.75 Gy, is less than 3.3 for early reactions and equal to 3.4 for late effects. The respective RBE values for early and late effects in the bowel are less than 3.4 and 3.8.