A comparison of remote afterloading and manually inserted caesium in the treatment of carcinoma of cervix.

Between 1982 and 1985, 240 patients with carcinoma of cervix were treated by radical radiotherapy, 140 using the selectron at the Royal Beatson Memorial Hospital (RBMH) and 100 with conventional caesium at the Western Infirmary. To allow for the increased dose rate to point A (1.2-1.4 Gy/h) during selectron treatment the overall intracavity dose was reduced by a mean value of 25%. Local recurrence rates were similar: 15% (selectron) against 14% (conventional). Three-year survival with local control was somewhat worse in the selectron group (77% against 81%) mainly because of an increased frequency of metastatic disease with local control (19.3% against 12.0%. The use of remote afterloading has not increased late morbidity (15.7% selectron, 15.0% conventional). The introduction of the selectron has brought about a marked reduction in staff radiation exposure. At the RBMH the mean recorded dose to nurses fell from 19 mSv in 1981 to 2.4 mSv in 1985.

Survival of younger cervical carcinoma patients treated by radical radiotherapy in the west of Scotland 1964-1984.

Between 1964 and 1984, 2011 patients in the West of Scotland were treated by radical radiotherapy for carcinoma of cervix. In keeping with the rise in incidence amongst younger patients nationally, the number of women aged less than 35 years seen during the 20-year period has doubled. Younger women (aged less than 35 or less than 45) have a better prognosis mainly because more present with earlier disease. Stage for stage there has been no change in survival of women of all ages treated by identical radiotherapy during this period. The rise in mortality of younger patients from carcinoma of cervix may be due to the increased incidence of the condition rather than a more virulent form of the disease.

Does adenocarcinoma of uterine cervix have a worse prognosis than squamous carcinoma when treated by radiotherapy?

Between 1964 and 1980, 1878 patients were considered for radiotherapy at the Western Infirmary, Glasgow, of whom 1673 (91.8%) had squamous tumors and 120 (6.6%) adenocarcinomas. Of these, 1505 squamous carcinomas (92.5%) and 95 (5.8%) adenocarcinomas were treated by radical radiotherapy. The treatment given to either histological type assigned to the same tumor stage was identical. The actuarial 5-year survival (all stages) for squamous (Sq) tumors was 54.6% and adenocarcinomas (Ad) was 54.0%. When analyzed by tumor stage 5-year survival is similar for patients with either tumor type-Stage I Sq 79.9%, Ad 81.8%; Stage II Sq 61.9%, Ad 65.9%; Stage III Sq 39.9%, Ad 29.8%; and Stage IV Sq 14.3%, Ad 21%.

The prognostic value of a response to chemotherapy given before radiotherapy in advanced cancer of cervix.

Forty patients with stage III and 15 patients with stage IVa carcinoma of cervix have been treated with two pulses of cisplatin, vincristine and bleomycin combination chemotherapy before full dose radical radiotherapy. Twenty-seven of 51 (53%, 95% confidence interval 40-67%) had an objective response to chemotherapy and all chemotherapy responders had a complete response to radiotherapy. The actuarial survival at 24 months of responders to chemotherapy is 71% against 37% for non-responders. The responding patients had an estimated reduction in mortality to 36% (P = 0.014, 95% CI 15-81%) of that of the non-responders to chemotherapy. The incidence of tumour recurrence or distant metastases showed a similar reduction to 34% (P = 0.006, 95% CI 14-73%) of that of the non-responders. The data strongly suggest that response to chemotherapy in the initial treatment of advanced cervical cancer is associated with an improvement in survival following subsequent radical radiotherapy.

The treatment of stage IV carcinoma of cervix by radical dose radiotherapy.

During 1974-1979, 92 patients (14% of all carcinoma cervix cases) were assigned to Stage IV; 68 (10%) to Stage IVa and 24 (4%) to Stage IVb. Fifty-five patients were treated radically using 4 MeV X-rays (42.5 Gy in 20 fractions) followed by a 137Cs insertion (33.5 Gy to the A points). Twenty-six patients were treated palliatively and 11 received no treatment. Sixteen per cent of radically treated patients were alive at 5 years, whereas all patients treated palliatively were dead in 18 months. Pelvic tumour was eliminated in 22/55 (40%) treated radically, but in only 1/26 treated palliatively. The 5-year survival for Stage IVa treated radically was 18% and 19/44 (43%) had local tumour control. Only one patient in Stage IVb (involvement of vulva) was alive at 5 years. The overall 5-year survival for Stage IV patients in this series was 11/92 (12%).

Combination chemotherapy prior to radical radiotherapy for stage III and IV carcinoma of the cervix.

Twenty-three patients with Stage III and seven patients with Stage IVa carcinoma of cervix were treated with two pulses of cisplatin, vincristine and bleomycin combination chemotherapy prior to radical radiotherapy. Seventeen of the 30 patients (57%) had a partial response to chemotherapy; 25 had a complete response following radiotherapy. Currently, 16 patients are tumour-free 6 to 31 months after treatment, eight are dead and six are alive, with tumour. The actuarial survival at 30 months is 66%. Acute and late effects of radiation upon normal tissue have not been increased. Pelvic tumour was eliminated in 21 of the 30 patients (70%). The high local control rate may be due to the initial tumour shrinkage after chemotherapy.

Improved control of primary vaginal tumours by combined external-beam and interstitial radiotherapy.

In 20 years we have seen only 78 cases of primary vaginal cancer. 61 patients had squamous carcinoma, three had adenocarcinoma, 10 had clear-cell carcinoma, four of which may have been metastatic from carcinoma of the kidney, and four had malignant melanoma. The actuarial 5-year survival of patients with squamous cancer was: Stage I, 68%; Stage II, 34%; Stage III, 29% and Stage IV, 14%. Patients treated by combined external and intracavitary or interstitial radiotherapy had increased local control and superior survival to those treated by interstitial methods alone. The improved tumour control offered by combination treatment may be due to the elimination of small tumour deposits in lymph nodes within the treated volume and the sterilisation of carcinoma in situ in the vagina some distance from obvious tumour.

Carcinoma of the cervix--anaemia, radiotherapy and hyperbaric oxygen.

Further analyses of the material contained in trials of the hyperbaric oxygen chamber in the radiotherapy of carcinoma of the cervix have shown that patients who were severely anaemic prior to radiotherapy, and who required blood transfusion, showed very poor local tumour control when conventionally treated after transfusion, but very good local tumour control when treated in hyperbaric oxygen. The finding of a special sub-group where hypoxia would seem to be an important cause of radiation failure, and where hyperbaric oxygen was successful in overcoming it, may have importance in the evaluation of other methods for overcoming the hypoxia, including the use of chemical sensitising agents.

Selectron: rectal dose-rate measurements and modified applicators.

A procedure for estimating the rectal dose-rate in patients treated by a Selectron remote-afterloading machine is described. This entails dose-rate measurements using low-activity test sources whilst the patient is still in theatre. The standard applicators were modified to enable the rectal dose to be reduced.

Hyperbaric oxygen and radiotherapy: a Medical Research Council trial in carcinoma of the bladder.

In a randomized controlled clinical trial of hyperbaric oxygen in the radiotherapy of carcinoma of the bladder a total of 241 cases were contributed by four radiotherapy centres in the United Kingdom. In this trial where in each centre identical radiotherapy was employed for both oxygen and air cases, no benefit was shown with the use of hyperbaric oxygen.

Hyperbaric oxygen and radiotherapy: a Medical Research Council trial in carcinoma of the cervix.

In a randomized controlled clinical trial of hyperbaric oxygen in the radiotherapy of advanced carcinoma of the uterine cervix a total of 320 cases were contributed by four radiotherapy centres in the United Kingdom. The use of hyperbaric oxygen resulted in improved local control and survival. The benefit was greatest in patients under the age of 55 who presented with stage III disease. There was a slight increase in radiation morbidity but it seemed that the benefit of hyperbaric oxygen outweighed this increase in morbidity and that there was a true improvement in the therapeutic ratio.

Cumulative radiation effect. Part VI: simple nomographic and tabular methods for the solution of practical problems.

In five previous papers, the concept of the Cumulative Radiation Effect (CRE) has been presented as a scale of accumulative sub-tolerance radiation damage. The biological effect generated in normal connective tissue by fractionated or continuous radiation therapy given in any temporal arrangement is described by the CRE on a unified scale of assessment, so that a unique value of the CRE describes a specific level of radiation effect. The basic methods of evaluating CREs were shown in these papers to facilitate a full understanding of the fundamental aspects of the CRE-system, but these methods can be time-consuming and tediuous for complex situations. In this paper, simple nomographic and tabular methods for the solution of practical problems are presented. An essential feature of solving a CRE problem is firstly to present it in a concise and readily appreciated form, and, to do this, nomenclature is introduced to describe schedules and regimes as compactly as possible. Simple algebraic equations are derived to describe the CRE achieved by multi-schedule regimes. In these equations, the equivalence conditions existing at the junctions between schedules are not explicit and the equations are based on the CREs of the constituent schedules assessed individually without reference to their context in the regime as a whole. This independent evaluations of CREs for each schedule results in a considerable simplification in the calculation of complex problems. The calculations are further simplified by the use of suitable tables and nomograms, so that the mathematics involved is reduced to simple arithmetical operations which require at the most the use of a slide rule but can be done by hand. The order of procedure in the presentation and calculation of CRE problems can be summarised in an evaluation procedure sheet. The resulting simple methods for solving practical problems of any complexity on the CRE-system are demonstrated by a number of examples.

High-dose effects in the treatment of carcinoma of the bladder under air and hyperbaric oxygen conditions.

Twenty-seven patients with carcinoma of the bladder were treated at the Glasgow Institute of Radiotherapeutics as part of a national hyperbaric oxygen trial. These patients were treated on a 4 MeV linear accelerator either in air or in 3 atm, absolute, of oxygen, by random selection. Of these patients, one-third were found to have high-dose effects to an extent which necessitated surgery. No association was found between the incidence of high-dose effects and treatment in air or hyperbaric oxygen. The treatment protocol used in all cases was to give an intended modal tumour dose of 6000 rad in 24 fractions in approximately 5 weeks. As all patients had received the same modal dose, there was no apparent reason why some had developed high-dose effects. However, on the basis of a Cumulative Radiation Effect (CRE) analysis of the treatment regimes given, a close correlation was found between the maximum CRE achieved and the occurrence of high-dose effects. Above a threshold level of 1910 reu in the maximum CRE achieved, there was a high incidence and rapid onset of high-dose effects. The reasons for the occurrence of the exceptionally high CRE values found in some patients are discussed. From a review of clinical results of bladder treatments, it is apparent that at a CRE level of 1910 reu, the tumour control rate is still increasing with CRE. It is proposed that by choosing the dose given on any treatment schedule to keep the maximum value of the CRE achieved just below 1910 reu, the greatest probability of cure would be obtained with minimum complication rate.

Cumulative radiation effect. part IV. Normalisation of fractionated and continuous therapy - area and volume correction factors.

In three previous papers, a scale of accumulated sub-tolerance radiation damage, the Cumulative Radiation Effect (CRE), was described for fractionated treatment regimes and continuous radiation therapy from both long-lived and short-lived sources. This scale provides a means of assessing and comparing the biological effects of various treatments. In this paper, it is intended to further the scope of application of the CRE-system by describing in detail the normalisation between the assessments of fractionated and continuous therapy. To do this, it is necessary to consider area and volume correction factors, whose roles are to modify the values of uncorrected CREs so that a specific biological effect, regardless of the area or volume treated, is described by a unique value of the corrected CRE. The problem arising when the CRE achieved by a treatment regime is not constant over a volume is briefly discussed and a simple hypothesis is proposed which may stimulate interest in this problem. The establishment of a normalisation procedure between fractionated treatment regimes and continuous radiation therapy, which is the primary aim of this paper, serves to integrate the concept of the CRE into a unified system of assessment of biological damage, so that a unique value of the CRE describes a specific level of biological damage regardless of the area or volume treated, or the time course of administration of the radiation employed.