Biomedical subjects
W Duncan
Publications and source records attributed to W Duncan.
Lactate dehydrogenase as a marker for testicular germ-cell tumours.
One hundred and eighty-four patients with testicular germ-cell tumours, 92 with seminoma and 92 with non-seminomatous germ-cell tumours (NSGCT) had total lactate dehydrogenase (LD) assay performed at the time of initial staging following orchidectomy. The proportion of patients with elevated plasma LD and the mean plasma LD increased with advancing stage and increasing tumour bulk for both seminoma and NSGCT. Of patients receiving cytotoxic chemotherapy, 87.5% with seminoma and 63% with NSGCT had elevated plasma LD with subsequent levels reflecting regression or progression of disease. Elevated plasma LD levels were seen in four of seven seminoma, and in 18 of 30 NSGCT patients relapsing after primary treatment. The LD assay provides useful information, and complements the routine measurement of alphafetoprotein (AFP) and beta human chorionic gonadotrophin (beta hCG) in the management of patients with testicular germ-cell tumours.
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 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.
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.
Influence of computed tomography scanning and lymphography on the management of testicular germ-cell tumours.
Seventy-eight patients with seminoma and 66 patients with teratoma had computed tomography (CT) of the thorax and abdomen performed as part of initial staging following orchidectomy. Four of 65 (6%) seminoma and 13 of 66 (20%) teratoma patients were upstaged by the addition of CT scanning. No seminoma patients with Stage I disease according to abdominal CT and lymphography had an abnormal thoracic CT scan. Seven of 52 (13%) seminoma and 4 of 21 (19%) teratoma patients who were Stage I according to the CT scan had their staging altered by lymphography. CT was of particular value for defining the exact extent and bulk of metastatic disease prior to and following chemotherapy and radiotherapy, prior to surgical excision of residual disease following chemotherapy, and for investigating potential sites of disease relapse. For all patients with teratoma, we recommend CT of the thorax and abdomen, with bipedal lymphography for those with normal CT scans. For seminoma patients, we suggest lymphography followed by abdominal CT and if either is abnormal, thoracic CT.
Radical treatment of prostatic carcinoma by megavoltage X-ray therapy.
The case records of 116 patients treated with radical megavoltage X-ray therapy for carcinoma of the prostate have been reviewed. The age-corrected actuarial 5-year survival rate was 60.0% and the 10-year rate was 31.5%. Multivariate analysis demonstrated that T classification was the strongest prognostic variable but a long delay between diagnosis and radiotherapy also had a detrimental effect on prognosis. The incidence of severe acute and late radiation morbidity was low. Radical radiotherapy has been shown to be a safe and effective form of management for localised carcinoma of the prostate.
The Edinburgh experience of treating sarcomas of soft tissues and bone with neutron irradiation.
The experience of treating 30 patients with sarcomas of soft tissue and bone with d(15)+Be neutron irradiation is reported. The local control of measurable soft-tissue sarcomas was 38.5% (minimum follow-up 2 years), which is similar to that expected after photon therapy. The radiation morbidity was unacceptably high (50%). Bone tumours did not respond well; in only one out of nine was lasting local tumour control achieved.
Bilateral testicular plasmacytoma.
A case is reported of a 55-year-old man with asynchronous bilateral testicular plasmacytoma. Despite chemotherapy and radiotherapy he died seven and a half years after the original diagnosis of testicular plasmacytoma, and 13 months after developing evidence of disseminated myeloma. The testicular plasmacytomas may have arisen as a result of seeding from a systemic myelomatous process.
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 growth and histological characteristics of a series of human bladder cancer xenografts.
Xenografts from human transitional cell carcinoma of the bladder (TCC) have been successfully established in CBA mice which had previously been immune-deprived by thymectomy and whole body irradiation with cytosine arabinoside pre-treatment. Xenografts were established from 3/17 patients with histological grade 2 tumours, 3/19 patients with histological grade 3 tumours, and one from a patient with a mixed transitional cell and squamous cell carcinoma. No xenografts were established from patients with histological grade 1 tumours. All the xenografts maintained the histological characteristics of their parent tumours in early passage, but some developed more prominent squamous features in later generations. Many of the xenografts were cystic.
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.
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.
Report of a randomised pilot study of the treatment of patients with supratentorial gliomas using neutron irradiation.
A randomised pilot study is reported of d(15)+Be neutrons compared with 4 MV photons in the treatment of patients with astrocytoma. Sixteen patients were treated by photons and 18 by neutrons. Both treatments were well tolerated by patients. The median survival after photons was 11 months and after neutrons, 7 months. It was demonstrated that four of nine patients treated by neutrons had evidence at autopsy of radiation-induced brain damage. All had residual cancer. No patient treated by photons had signs of radiation-related morbidity. The trial was, therefore, discontinued prematurely.
The results of a randomised trial of mixed-schedule (neutron/photon) irradiation in the treatment of supratentorial Grade III and Grade IV astrocytoma.
A randomised trial is reported of mixed-schedule (neutron/photon) irradiation compared with photon therapy for patients with Grade III or Grade IV astrocytoma. Thirty-one patients were allocated to be treated by the neutron/photon regime and 30 patients by photons. The median survival was 4 months in the mixed-schedule group and 8 months in the photon group. The survival rates were not significantly different. All patients who died had evidence of residual brain tumour. None had signs of radiation-related morbidity.
A phase I study of mixed (neutron and photon) irradiation using two fractions per day in the treatment of high-grade astrocytomas.
A Phase I study of the treatment of 50 patients with high-grade astrocytomas by mixed schedule (neutron and photon) irradiation given in 12 fractions over 4 weeks is reported. The neutron and photon fractions were separated each day by 2-3 h. A total neutron dose of 6.36 Gy (8% gamma) and 20.40 Gy of photons was prescribed. Treatment was well tolerated and there was no clinical evidence of radiation-related morbidity in the brain. The median survival was 6.9 months, similar to that expected after photon irradiation alone. A multivariate analysis of prognostic variables in presented.