A comparison of the palliative effects of strontium-89 and external beam radiotherapy in metastatic prostate cancer.

From 1988 to 1991, 284 patients with prostatic cancer and painful bone metastases were treated with either radiotherapy or strontium-89 (200 MBq). Patients were first stratified according to suitability for local or hemibody radiotherapy, then randomly allocated that form of treatment or strontium-89 (i.v. injection). After 4, 8 and 12 weeks pain sites were mapped, toxicity monitored, and all additional palliative treatments recorded. There was no significant difference in median survival (after > 80% had died); 33 weeks following strontium-89 and 28 weeks following radiotherapy (p = 0.1). All treatments provided effective pain relief; improvement was sustained to 3 months in 63.6% after hemibody radiotherapy compared with 66.1% after strontium-89, and in 61% after local radiotherapy compared with 65.9% in the comparable strontium-89 group. Fewer patients reported new pain sites after strontium-89 than after local or hemibody radiotherapy (p < 0.05). Radiotherapy to a new site was required by 12 patients in the local radiotherapy group compared with 2 after strontium-89 (p < 0.01), although there was no significant difference between hemibody radiotherapy (6 patients) and strontium-89 (9 patients) in this respect. Platelets and leukocytes fell by an average 30-40% after strontium-89 but sequelae were uncommon, and other symptoms rare.

A report of late rectosigmoid morbidity in patients with advanced cancer of the cervix, treated by a six week pelvic brick technique.

An increased incidence of late rectosigmoid complications, with no improvement in local control, was observed after the introduction of a 6 week technique of external beam pelvic irradiation (55.0 Gy in 30 fractions) in Edinburgh. This increase in morbidity did not appear to be related to the use of a single intracavitary caesium insertion or to the introduction of a Selectron for remote afterloading. A 5% dose reduction was subsequently instituted.

Bladder cancer following low or high dose pelvic irradiation.

Eleven women presenting to this department since 1971 with bladder cancer have had previous pelvic irradiation. The tumours were generally of high grade and advanced T-category. Prognosis was poor and only 32% survived for one year. The interval observed between low dose pelvic irradiation and subsequent bladder cancer was longer than after high dose pelvic irradiation (mean interval of 30 years compared with 16.5 years).

Extramedullary plasmacytoma of the rectum: two cases treated by radiotherapy.

Two cases of extramedullary plasmacytoma of the rectum treated by radiotherapy are reported. In one patient local control of disease was achieved at 36 months. A second patient treated by a palliative course of radiotherapy had initial good local regression and control of symptoms at 3 months. In view of the radiosensitivity of this tumour, consideration should be given to treating extramedullary plasmacytoma of the rectum by primary radiotherapy.

Do normal mucosal biopsies predict prognosis in patients with transitional cell carcinoma of bladder treated by radical radiotherapy?

A biopsy of normal-looking mucosa showed mucosal abnormalities in 48.9% of patients with transitional cell carcinoma of the bladder. The presence of dysplasia or carcinoma in situ was significantly associated with grade but not with tumour category. In 100 patients who completed a course of radical megavoltage X-ray therapy, the result of mucosal biopsy gave no significant prognostic information about tumour regression, durable local control, survival or the risk of subsequent metastases.

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.

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.

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 patient's 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%).

The influence of hemoglobin level on the regression and long term local control of transitional cell carcinoma of the bladder following photon irradiation.

Patients with transitional cell carcinoma of the bladder treated by radical megavoltage X ray therapy are analyzed. There was a significant correlation between tumor T stage classification and the hemoglobin level at the start of radical radiotherapy. A hemoglobin level of 12g/dl or more was associated with a significant improvement in complete local tumor regression at 6 months and durable local tumor control for patients with T3 cancer or a cancer of grade 3 histology. Hemoglobin level did not influence survival for patients with T1 or grade 1 cancer. Those patients with T2-T4 cancer, grade 2-3 cancer, or a cancer of solid or mixed appearance had a significantly better survival probability if their hemoglobin level was more than 13g/dl. Hemoglobin level would appear to exert its influence on survival by an effect on local tumor control. It has no significant independent effect on the hazard of distant metastases.

Results of surgery following radical radiotherapy for invasive bladder cancer.

Five hundred and ninety-one of 889 patients with T1 to T4 transitional cell carcinoma of the bladder had persistent or recurrent cancer after radical radiotherapy. Durable local control was significantly poorer for patients with grade 1 or T4 cancer before radiotherapy. Three hundred and twenty-two patients received additional surgical treatment: 211 were endoscopically managed and 111 had secondary cystectomy. The survival of patients with residual or recurrent cancer after radiotherapy was significantly improved by secondary local treatment (P less than 0.0001). A comparison was made between endoscopic treatment and cystectomy after radiotherapy. Patients having secondary cystectomy were younger (mean age 60.0 years) than those managed endoscopically (66.8 years). The 5-year actuarial survival rate (from the date of radiotherapy) for patients who had endoscopic treatment was 47.1% compared with 62.5% for those who had cystectomy (P = 0.16). After both treatments survival was significantly correlated with the T category of the tumour before radiotherapy. Local tumour control was better after cystectomy; 85.6% of patients were locally tumour-free at the end of follow-up compared with 44.5% of those managed endoscopically. There was no overall difference in the subsequent risk of metastases between the two forms of surgery. However, seven of 12 patients managed endoscopically prior to secondary cystectomy died of their cancer. Five of these patients died from metastases even though they were locally disease-free. There was a significantly increased risk of metastases in patients managed endoscopically who were not locally disease-free after treatment (P = 0.0003). Caution is advised in persisting with endoscopic treatment after radiotherapy if local control is not readily achieved.

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 patient's 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.

Radiotherapy for squamous carcinoma of the urinary bladder.

One hundred and seven patients with squamous cell carcinoma of the bladder were reviewed. They form 6.8% of patients with bladder cancer seen in this department. There were more females than males, 1.28 to 1. The patients had a mean age of 67.5 years. Patients were found to have tumors that invariably invaded to the muscle. Almost all tumors were solitary and described as ulcerated or solid (non-papillary) in appearance. Forty-nine patients completed a course of radical megavoltage X ray therapy of whom 35 had T3 cancers, with a complete regression rate of 42.3%. The actuarial local control rate for patients with T3 squamous cancer was 33.7% at 3 years. Their survival, however, was poor, being only 18.3% at 3 years.

Treatment of superficial (T1) tumours of the bladder by radical radiotherapy.

Local tumour control and survival is reported for 190 patients with T1 transitional cell cancer of the bladder who received a radical course of X-ray therapy. There was no difference in survival by the histological grade of the cancer but patients with grade 3 cancers had the highest probability of local control. After initial complete local tumour regression there was a similar probability of subsequent distant metastases irrespective of the grade of the cancer. Radical small field beam directed radiotherapy is commended for patients with T1/pT1 grade 3 transitional cell cancer of the bladder.

A report of a randomized trial of d(15)+Be neutrons compared with megavoltage X ray therapy of bladder cancer.

The results of a randomized trial of d(15)+Be neutrons compared with 4 or 6 MV photons for the treatment of transitional cell carcinoma of the bladder. Between December 1978 and December 1981, 113 patients were accrued, 53 allocated to be treated by neutrons and 60 by photons. Complete local tumor regression was observed in 64% of patients treated by neutrons and 62% treated by photons. Recurrent cancer was subsequently confirmed in 31% of patients, similar in both treatment groups. There was no significant difference in the control rates by T stage between the two treatment groups. Late morbidity was significantly worse in patients treated by neutrons. Following neutron therapy, 78% of patients had serious late morbidity in at least one tissue compared with 38% in the group treated by photons. Survival was significantly better in the photon treated group 45.3% (+/- 11%) at 5 years compared with 12% (+/- 6%) after neutron therapy.

The role of endoscopic treatment after radical radiotherapy for invasive bladder cancer.

In a 6-year period 232 patients were treated by radical radiotherapy for transitional cell cancer of the bladder. Fifty-eight patients had secondary surgical management to control either locally persistent or recurrent tumour. Endoscopic treatment alone was used in 31 patients with down-staged tumours and the survival of this group compared favourably with that of 27 patients selected for salvage cystectomy (5-year survival rate 88% cf. 44%). A group of patients with favourable prognostic factors may be identified in whom cystectomy can be avoided without prejudice to survival.

Cisplatin-containing chemotherapy in advanced head and neck cancer.

Sixty-two patients with previously untreated advanced head and neck cancer were admitted to a study of pre-radiotherapy combination chemotherapy containing cisplatin. After two courses only 3% were in complete response but 47% had achieved a partial response. Ninety per cent of patients completed radical radiotherapy and at least one course of chemotherapy; 54% of these achieved a complete response at 1 month post-therapy. The overall actuarial survival rate at 2 years was 40.3%, with a median survival of 12 months. The median survival of those with complete response 1 month after therapy has not yet been reached. The toxicity of the chemotherapy was low and no increase in morbidity from the subsequent radiotherapy was noted. Comparison with historical data from this hospital does not suggest any improvement in overall survival for the use of cisplatin-containing chemotherapy prior to radiotherapy.

Results of a randomised study to evaluate influence of dose on morbidity in radiotherapy for bladder cancer.

Ninety-four patients with invasive transitional-cell carcinoma of the bladder were randomised to receive three different doses of megavoltage X-rays. Doses of 50.0 Gy, 52.5 Gy and 57.5 Gy were given in 20 daily fractions. Patients were stratified into two groups by tumour size: less than 5.0 cm and 5.0-7.0 cm in diameter. The large tumours were more advanced (higher T stage) and included a larger number of patients with less well differentiated tumours. Comparisons of morbidity are made in each dose group defined by tumour size. Early and late morbidity was carefully assessed during follow-up and was found to be unacceptably high in the group who received 57.5 Gy in 20 daily fractions.