The breast radiation injury litigation and the clinical oncologist.

A number of women with breast cancer believed they were suffering injury because radiotherapy had been given negligently. In March 1995, their solicitors were permitted by the High Court, to select 10 cases in order to further a group action. In the legal exchanges which followed, the principal issues put forward by the plaintiffs went through a number of modifications until finally, in December 1997, they were abandoned. Two cases came to trial and after a hearing of 21 days, the Judge found no negligence. Clinical oncologists should be aware of the course of the litigation and consider the lessons to be learned.

Dosimetric considerations in the treatment of inoperable endometrial carcinoma by a high dose rate afterloading packing technique.

A series of 23 patients with early adenocarcinoma of the endometrium who underwent a total of 37 modified Heyman packings treated on a high dose rate Microselectron has been reviewed. Using computed tomography (CT), the uterine wall thickness was measured retrospectively and doses calculated at a number of points on the uterine serosa and related normal tissues. The mean and maximum fundal serosal doses were found to be highest posteriorly and the sigmoid colon was adjacent to the posterior surface of the uterus in all instances. By superimposing the isodose distribution on CT sections of the uterus, it is now possible to prescribe to a serosal dose, or, in patients too heavy for the CT scanner, a dose can be prescribed to a point S, which is a reasonable approximation to the serosal position. Since the initial study, a further ten patients have been treated by the same method and, where relevant, data from all 33 patients have been used.

Physiological effect of endobronchial radiotherapy in patients with major airway occlusion by carcinoma.

BACKGROUND: Endobronchial radiotherapy by a high dose rate remote after-loading technique (high dose rate brachytherapy) has become an established treatment for major airway occlusion by inoperable carcinoma of the bronchus. Only limited objective data on its effect on pulmonary physiology and on radiographic and bronchoscopic appearances are available. The aim of this study was to make a detailed assessment of patients before and after high dose rate brachytherapy to determine which investigations were useful and to generate data for comparing this with other methods of treatment. METHODS: Twenty patients with major airway obstruction by inoperable lung cancer underwent a detailed assessment before receiving endobronchial radiotherapy (15 Gy at 1 cm in a single fraction) and six weeks after treatment. This included chest radiography, computed tomography of the thorax, bronchoscopy including an obstruction index, five minute walking tests, isotope ventilation and perfusion lung scanning, and full lung function tests with maximum inspiratory and expiratory flow-volume loops. RESULTS: Nineteen patients (mean age 69 years) completed the study. Symptomatic improvement occurred in 17 patients. A collapsed lobe or lung, seen on the chest radiograph in 13, reexpanded in nine. Bronchoscopic appearances improved in 18, the mean obstruction index decreasing from 6.2 to 2.8. The isotope scans showed significant increases in the percentage of total lung ventilation (V) and perfusion (Q) measured over the abnormal lung (V 17.7% to 27.7%, Q 15.1 to 21.9%). Five minute walking distance (305 to 329 m), forced expiratory volume in one second (FEV1 1.45 to 1.61 l), forced vital capacity (FVC 2.17 to 2.48 l) and ratio of forced expiratory to forced inspiratory flow rate at 50% vital capacity (FEF50/FIF50 0.58 to 0.88) all increased significantly. CONCLUSIONS: Endobronchial radiotherapy led to subjective benefit in most cases in terms of symptoms and bronchoscopic and radiological appearances. There was objective improvement in spirometric indices and in exercise tolerance with increased pulmonary ventilation and perfusion and evidence of decreased intrathoracic airway obstruction.

Long term results of Cathetron high dose rate intracavitary radiotherapy in the treatment of carcinoma of the cervix.

Between 1967 and 1974, 371 patients with carcinoma of the cervix have been treated by a combination of external beam radiotherapy and fractionated high dose rate brachytherapy using the Cathetron. A retrospective review was undertaken in 1986 and median follow-up time was 6 years. Life table analysis of survival and complications to 16 years was undertaken. International Federation of Gynaecology and Obstetrics (FIGO) stage distribution was 26%, 46% and 28% for Stages I, II and III, respectively, and 5 year survival was likewise 94% 63% and 37%. Age and histological type or grade were not found to influence survival. Recurrent disease was recorded in 142 patients; the first site was within the pelvis in 25% and as distant metastases in 17%. Following development of pelvic recurrence median survival was 28 weeks. Salvage surgery was performed in 32 patients, of whom five probably obtained survival benefit. Significant late morbidity was seen in a total of 71 patients (19%); in seven patients this was at more than one site. Late morbidity to the small bowel was recorded as Grade 2 in 10 patients and Grade 3 in 13; to the rectum, Grade 2 in 10 patients and Grade 3 in two patients; to the bladder, Grade 2 in 15 patients and to the vagina Grade 2 in 29 patients. Median time to onset for small bowel morbidity was 14 months, for rectum 18 months, for vagina 20 months and for bladder 52 months. 82% of all late morbidity had been seen by 5 years of follow-up, no case of late morbidity of recurrence was seen between 11 and 18 years of follow-up. These results are comparable to those reported for other methods in use at the time the patients were treated.

Cancer of the cervix in women under 40 years of age, a regional survey, 1975-1984.

OBJECTIVE: To review the method and results of treatment of carcinoma of the cervix in women less than 40 years old. DESIGN: Retrospective review of all available case records. SETTING: Yorkshire Regional Health Authority. SUBJECTS: 428 women less than 40 years old treated for stage IB-IV carcinoma of the cervix between 1975 and 1984 inclusive. MAIN OUTCOME MEASURES: Overall survival by stage, effect of age, identifiable factors of prognostic significance, survival, grade 3 morbidity and pattern of recurrence in relation to treatment. RESULTS: The 5-year actuarial percentage survival by stage was 78.4 (IB), 54.4 (II), 18.4 (III) and 0 (IV). Identifiable factors of prognostic importance were stage, nodal metastases (P less than 0.001) and tumour grade (P less than 0.01). CONCLUSION: Primary surgical treatment for young women with early disease allows ovarian conservation and the avoidance of radiotherapy in 80% of them. Such treatment results in less local recurrence, particularly evident in patients with moderate or poorly differentiated tumours and a lower incidence of serious morbidity.

Concomitant pelvic irradiation, 5-fluorouracil and mitomycin C in the treatment of advanced cervical carcinoma.

This was a Phase II study of 24 late (FIGO) Stage IIb and 39 Stage III patients. External beam radiotherapy was given daily, five days a week, using 15 x 15 cm parallel opposed pelvic fields. The first 20 patients had 45.00 Gy mid-plane dose in 20 fractions, Days 1-28, the last 43 patients had 50.40 Gy in 28 fractions, Days 1-43. This was followed by an intracavitary boost of 17.00 Gy to Point A in two fractions over seven days. The first seven patients had concomitant 5-fluorouracil (5FU) 1 g/m2/day (maximum 1.5 g/day) Days 2-5, 30-33 and 57-60, with mitomycin C 10 mg/m2 (maximum 15 mg) Days 2 and 57. Two patients had WHO Grade 4 cytopenia, and only two were able to have full dose intensity. The 5FU dose was reduced to 0.8 g/m2/day, for Days 2-5 and 30-33; mitomycin C was given on Day 2 only. Treatment morbidity with the reduced chemotherapy intensity was comparable with that of radiotherapy alone. Median follow-up was 16 months (range 6-44). Median survival was 35 months. The results were compared with historical controls treated using the same radiation method alone. Two-year survival for late Stage IIb patients was 67% with the combination and 72% with radiotherapy alone; for Stage III, 67% and 49% respectively. Two-year pelvic control for late Stage IIb was 87% (combination) and 84% (radiotherapy alone) and for Stage III, 61% and 55% respectively. In contrast to reports from other centres, these results do not show an overall significant improvement on radiotherapy alone. A Phase III study may not be practicable.

Treatment of recurrent and metastatic carcinoma of cervix: a comparison of low dose methotrexate with adriamycin plus methotrexate.

Sixty-six patients with recurrent or metastatic cervical cancer were treated with two different chemotherapy regimens in the last 11 years. Thirty-three patients received weekly low-dose methotrexate (MTX) regimen A and the other 33 patients were treated with a combination of adriamycin and MTX, regimen B. Response rates were 15.2% and 42.4% with regimens A and B respectively (P = 0.014). Symptomatic relief, duration of response and median survival were similar in both groups. General and haematological toxicities were higher including one toxic death with regimen B. Considering the quality of remaining life of the patient low dose MTX is preferred for the treatment of symptomatic recurrent and metastatic cervical cancer.

Primary malignant melanoma of the uterine cervix.

A case of primary malignant melanoma of the uterine cervix is presented. It demonstrates the histological findings at both light and electron microscopy, the unusual flow cytofluorometric analysis, the clinical response to irradiation and the rapid dissemination of the tumour.

Flow cytofluorometric evidence for the differential radioresponsiveness of aneuploid and diploid cervix tumours.

We are presently involved in a prospective study of the relationship between DNA content profiles, and their changes during treatment, determined by flow cytofluorometry, and patient prognosis and response to therapy for cancer of the uterine cervix. To date, 348 patients have been included in the study over a 54-month period. Data on these patients have shown that DNA aneuploid tumours are significantly more radioresponsive than diploid cervix tumours. Analysis of the data on 213 patients with a minimum follow-up time of 15 months has, however, failed to show an overall more favourable prognosis conferred by tumour DNA aneuploidy. Analysis of the relationship between clinical stage and disease state and tumour DNA ploidy, however, suggests that aneuploid tumours metastasize to distant sites at an earlier stage of the disease than diploid tumours and local recurrence rates for diploid tumours, in late stage disease, are double those for aneuploid tumours. Improved staining procedures, and instrument modification, has also shown that cervix tumour heterogeneity is of considerably greater frequency than at first appeared to be the case (approximately 75% of DNA aneuploid tumours show heterogeneity.

The growth and cellular kinetics of human cervical cancer spheroids in relation to drug response.

A methodology for culturing multicellular spheroids directly from tumour biopsy material has been established with a success rate of 82% for cervical carcinomas. Spheroids, selected for uniform size and shape, have been subjected to quantitative assay to determine their population dynamics using 3H-Tdr autoradiography and have also been treated with 13 commonly used anti-cancer drugs. Several characteristics of cervical spheroids, e.g. growth rate, labelling index, thickness of viable cell rim, were similar for drug responding and non-responding spheroids but the faster growing spheroids responded to an increased number of types of drugs. Spheroids derived from poorly differentiated tumours also showed an increased response to drugs compared to those from moderate or well differentiated tumours.

Clinical measures to assess the practice and efficiency of breast self-examination.

If women examine their breasts thoroughly and regularly they may promptly recognize abnormal tissue changes. The level of skill and motivation required for effective breast self-examination (BSE), however, is very high. In a prospective study of 304 patients with newly diagnosed breast cancer, 165 (54%) claimed to practice BSE. On comparison with the remaining 139, the BSE practitioners reported their symptoms sooner than the nonpractitioners, and presented more often with clinically early tumors. There was, however, no difference in tumor size, and pathologic status of axillary nodes between the two groups. There were 60 patients who discovered the abnormalities during self-examination. On comparison with the remaining 244, significantly more BSE discoverers had shorter patient delay in presentation, but there was no significant difference in tumor size, clinical stage, and nodal status. It is concluded that these or similar clinical measures must be used in assessing the effectiveness of population-based BSE campaigns.

Breast screening clinic versus health education session as outlets for education in breast self-examination.

A population based programme to educate women in breast self-examination (BSE) was organised as part of the UK Trial of Early Detection of Breast Cancer. Women who responded to an invitation to a meeting were educated in groups and were not routinely screened. Open access clinics offered x ray and clinical examination to all women in the study age group of 45 to 64. Women who presented for screening without prior BSE education were taught individually by clinic staff. Women taught by the two methods were surveyed by post and their BSE practice since education was compared. It was hypothesised that the women taught in clinics, who had been reassured of their breast normality, would practice BSE more regularly and correctly. Results did not confirm this hypothesis. Lower standards of practise and a higher level of anxiety at the time of survey were found in the group who presented at a free access clinic and had received individual teaching at the time of screening.

Radiation pneumonitis in patients treated for breast cancer.

An analysis of 201 breast cancer patients having post-operative radiotherapy to the chest wall between January 1981 and May 1983 has identified those patients with chest symptoms following radiotherapy and these have been critically assessed with regard to the possibility of radiation pneumonitis being their cause. The inner contour of the anterior chest wall has been reconstructed on the radiation plan and the area of lung irradiated to a significant level in the mid-plane of the tangential fields determined. The incidence and severity of pneumonitis has been shown to rise exponentially with increase in the irradiated volume. A method of measuring the thickness of the chest wall using the simulator has been devised so that this information may be incorporated into the planning process in order to reduce the area of lung at risk.