Thelma D. Bates

The 10-year results of a prospective trial of post-operative radiotherapy delivered in 3 fractions per week versus 2 fractions per week in breast carcinoma

The 10-year results are presented of a prospective trial of 411 patients with breast carcinoma treated by mastectomy and post-operative radiotherapy given in either 2 or 3 fractions per week (i.e. a comparison of 6 fractions in 18 days with 12 fractions in 28 days). The early radiation effects on the normal tissues were similar and acceptable. The late skin changes in the chest wall (treated with 70 kV X rays) were progressive and by 10 years were slightly more marked with 6 fractions. Late subcutaneous fibrosis in the axilla (treated with cobalt-60 teletherapy), however, was much less in the 6-fraction group. Twelve fractions resulted in greater restriction of shoulder movement and an increased incidence of lymphoedema of the arm. Doses were selected on the basis of past clinical experience. The dose used to treat the axilla in 6 fractions was 35 Gy, 14.99% less than that predicted by NSD. The dose predicted by alpha:beta, using a value of 2 Gy for late reactions, is 38.14 Gy. Thus simple theory, which omits time, still predicts too high a dose for 6 fractions, although it is closer than NSD. In this trial, the 6-fraction technique showed an advantage over the 12-fraction technique. It was equally effective in controlling local recurrence and had fewer late sequelae. It was also convenient for patients and economic in the use of radiotherapy resources.

A prospective clinical trial of post-operative radiotherapy delivered in three fractions per week versus two fractions per week in breast carcinoma

The results are presented of a five-year prospective trial of 411 patients with breast carcinoma treated by mastectomy and post-operative radiotherapy. Twice or thrice weekly dose-fractionation techniques were used, i.e. 12 fractions in 28 days and six fractions in 18 days. The results show that, in terms of survival and control of local disease, the two techniques are very similar. The early and late radiation effects on the normal tissues up to five years are similar and acceptable. Dose levels thought to be biologically equivalent on the basis of experience at St Thomass Hosiptal were selected. It is stressed that there is a narrower margin of normal tissue tolerance when six fractions over 18 days are used, that it is essential to treat all fields on each treatment occasion and that the total maximum tissue dose of 3600 R is not exceeded. Attention is drawn to the fact that the dose for six fractions, derived from the NSD formula which would be predicted to be equivalent to the 12-fraction dose is, in fact, over 10% higher than the dose used here and likely to produce unacceptable late radiation changes.

The treatment of stage 3 carcinoma of the cervix by external radiotherapy and high-pressure oxygen

Abstract The results of treatment are presented in 21 patients with stage 3 carcinoma of the cervix, treated since 1963 by external radiotherapy in six fractions over 18 days while breathing high-pressure oxygen. The encouraging results are associated with a relatively high incidence of fracture of the neck of the femur in those patients treated with wide pelvic fields. Limiting the width of the anterior and posterior fields to 12 cm when possible is suggested to avoid this complication. Attention is drawn to the importance of a period of oxygen saturation at full pressure before treatment and of treating all fields at each treatment session.

Carcinoma of the breast, the effect of dose fractionation and radiotherapeutic technique on survival

The results are presented of a retrospective survey of 1207 patients with operable carcinoma of the breast treated by mastectomy and post-operative radiotherapy between 1953–1962. A significant increase in the 10 year survival rate, associated with a fall in the incidence of metastases, is shown in patients treated by radiotherapy given in three fractions per week over a period of four to five weeks compared with patients receiving a biologically equivalent dose in the conventional five fractions per week over the same time. The incidence of local recurrence and morbidity in patients treated with these two methods of dose fractionation are the same. The radiotherapeutic techniques used are described and comparisons made between them in terms of survival and morbidity.

Further experience in treating cervical cancer with a central source vaginal applicator

Abstract Further experience is described in the treatment of cancer of the cervix with a colpostat, consisting of a transparent shell, attached to the intrauterine tube and containing central radioactive sources. The colpostat allows inspection of the vault, prior to insertion of the vaginal radioactive sources and metal screens designed for rectal protection. The vaginal sources may be “after loaded” with consequent reduction in radiation exposure to staff. Physical estimations show that γ ray doses to important regions in the pelvis differ only very slightly from standard techniques, differences which disappear when supplementary external irradiation is used. Of the 69 patients reviewed, in whom all stages of the disease were represented, 43 had remained apparently free of recurrence in the treated volume of tissue up to over five years prior to this analysis. Our observations show that doses received by the rectum and bladder from this technique are within the limits of safety. This is reflected by the...

Hyperbaric oxygen combined with radiotherapy for carcinoma of the cervix

We, as must also a great many others, were extremely interested in Dr. Stanley Disches excellent article on “The hyperbaric oxygen chamber in the radiotherapy of carcinoma of the uterine cervix” (Dische, 1974). Our trial is uncontrolled, but we feel that it might be of interest to up-date the results as published by one of us in The British Journal of Radiology almost five years ago (Bates, 1969).

Antimetastatic effect of cimetidine on mice bearing a C3H mouse mammary adenocarcinoma: survival and lymphocyte function studies

It has been reported that treatment with cimetidine, a histamine H2-receptor antagonist, increased survival and decreased the number of lung metastases in mice bearing the Lewis Lung carcinoma [29]. It was suggested that this effect was due to the ability of cimetidine to block histamine activation of suppressor lymphocytes and hence allow host defence mechanisms to inhibit tumour growth. In the present studies, C3H/He mice were implanted with a C3H mouse mammary adenocarcinoma on Day 0. This tumour metastasizes to the lungs in 30–50 days. Primary tumours were ablated with X-rays when they had grown to about 0·2g and animals were given drinking water with or without cimetidine (10 mg ml−1) until the end of the experiment. Cimetidine reduced the number of mice dying from metastatic disease from 7/15 (controls) to 3/13. Cimetidine treatment also prolonged survival of mice that did succumb to metastatic disease by about 12 days. The response of spleen lymphocytes to the mitogens phytohaemagglutinin and lipopolysaccharide was assessed in vitro by uptake of 3H-thymidine 0, 16, 45 and 58 days after tumour implantation. Lymphocyte responsiveness was depressed by tumour burden. The influence of cimetidine treatment was equivocal being dependent upon time after tumour implantation and dose of mitogen. In this mouse-tumour system, the mechanism of the antimetastic effect of cimetidine is different from that previously suggested [29].

A clinical evaluation of ICRF 159 as a radiosensitising agent

Abstract There is evidence that the drug ICRF 159 is a radiosensitising agent. This clinical investigation suggests, however, that ICR:F 159 is not a clinically useful radiosensitiser in that it also increases the damage done to normal tissues. Two groups of patients were studied. The first group, 12 patients who had sarcomas generally regarded as radioresistant, treated by radiotherapy with ICRF 159. They responded well to treatment, but three of them subsequently developed unusually severe post-irradiation soft tissue fibrosis. The second group, had multiple skin metastases and bilateral lung metastases from breast carcinomas. These patients were given radiotherapy with ICRF 159 to one lesion and radiotherapy alone to another similar lesion, thus each patient acted as their own control. There was a slightly better response in three of six skin tumours irradiated with ICRF 159 but more intense late skin changes in four of them. The tumour response in the patient with bilateral lung metastases was similar on each side but the lung which was irradiated with ICRF 159 subsequently developed a severe radiation pneumonitis.

A randomized, prospective, comparative, multicentre trial of a single combination versus alternating combinations of antitumour drugs in advanced breast cancer

A prospective, multicentre trial was conducted in 262 patients with advanced breast cancer randomized to receive every 3 weeks either: (i) a single five-drug combination of adriamycin (50 mg), vincristine (1.5 mg) and 5-fluorouracil (750 mg) given intravenously; with methotrexate (50 mg) intramuscularly and chlorambucil (10 mg) orally all at time zero, followed by three further doses of chlorambucil (10 mg) at 6-h intervals, or (ii) one course of two alternating three-drug combinations consisting of regimen A--vincristine (1.5 mg), adriamycin (70 mg) and methotrexate (50 mg) and regimen B--5-fluorouracil (750 mg) and vindesine (5 mg) intravenously with cyclophosphamide (50 mg) orally at time zero, followed by three further doses of cyclophosphamide (50 mg) at 6-h intervals. Results show that overall response rates to chemotherapy were comparable in the two arms of this study being 63% (83 of 131 patients) for the single combination and 64% (84 of 131 patients) for the alternating combinations. Response rates according to menopausal status indicate no significant difference for the two arms of this study. However overall, combining all patients treated with either the single or the alternating combinations, post-menopausal patients had a significantly lower response rate (57%) compared with pre-menopausal patients (76%), P less than 0.05. Overall serious side-effects were minimal and were similar in both treatment groups. Response durations and overall survival data, which are essentially similar for the two treatment groups, proved disappointing with a median response duration of only approx. 6 months and overall median survival only slightly in excess of 1 year. Alternative treatment approaches are needed to maintain the remissions initially achieved in metastatic breast cancer.

The management of cervical lymph node metastases by hyperbaric oxygen and radiotherapy

The results of treatment of 102 patients with secondary squamous carcinoma in cervical lymph nodes from head and neck primary tumours by means of radiotherapy combined with hyperbaric oxygen are compared with previously reported results from conventional radiotherapy, also with surgery in the case of operable nodes. Although there is no improvement in survival rates, greatly improved local clearance rates enhance the quality of survival by avoiding the distressing symptoms so often associated with advanced secondary neck nodes. If hyperbaric oxygen is used, the stage of the lymph node involvement appears to make very little difference to the chance of sterilising the tumour.