A. Rodger

Pain relief and quality of life following radiotherapy for bone metastases: a randomised trial of two fractionation schedules

BACKGROUND The optimum dose and fractionation schedule for the palliative irradiation of painful bone metastases is controversial. PURPOSE To compare the efficacy, side-effects and effect on quality of life of two commonly used radiotherapy schedules in the management of painful bone metastases. MATERIALS AND METHODS In a prospective trial, 280 patients were randomised to receive either a single 10 Gy treatment or a course of 22.5 Gy in five daily fractions for the relief of localised metastatic bone pain. RESULTS Response rates have been calculated from 240 assessable treated sites of pain. The overall response rates were 83.7% (single treatment) and 89.2% (five fractions). The complete response rates were 38.8% (single treatment) and 42.3% (five fractions). The median duration of pain control was 13.5 weeks (single treatment) and 14.0 weeks (five fractions). None of these differences was statistically significant. There were no differences between the groups in the effect of treatment on a variety of quality of life parameters. CONCLUSIONS It is concluded that a single 10 Gy treatment is as effective as a course of 22.5 Gy in five fractions in the management of painful bone metastases.

Prognostic factors for survival in soft tissue sarcoma.

Between 1975 and 1984, 125 cases of histologically confirmed soft tissue sarcomata (STS) were registered in the Department of Clinical Oncology in Edinburgh. Of these, 100 were eligible for analysis of prognostic factors. The overall 5-year survival rate was 21.5%. Univariate analysis demonstrated that extent of surgery, radical versus palliative or no radiotherapy, mass as a presenting symptom, metastases at presentation, site, histological type, mitotic activity, grade and UICC stage all had a statistically significant effect on survival. Analysis using the proportional hazard regression model was performed on the 87 patients for whom all variables were recorded. When all histological and clinical features and treatment modalities were included in the model then radiotherapy, surgery, necrosis, sex and mitoses were identified as independent prognostic variables. When symptoms and treatment were excluded then the multivariate analysis identified sex and mitotic activity as independent parameters. For the 33 superficial STS with tumour size recorded multivariate analysis revealed size, necrosis and cellularity as independent prognostic variables. For the 31 deep STS histological type, sex, surgery and radiotherapy were identified as independent prognostic parameters.

Multiple primary tumours in patients treated with radiotherapy for breast cancer

Between January 1954 and March 1964, 3926 patients with primary breast cancer were referred to The Department of Clinical Oncology, Edinburgh. One hundred and eighty patients developed 195 malignancies subsequent to the treatment of their initial breast cancer. Overall, the total number of second tumours was not significantly in excess of the expected incidence in the general population. However, statistical analysis revealed a significant increase in the incidence of rectal, skin and bone tumours. The excess of bone tumours was likely due to radiation exposure. There was not an overall excess of tumours within the irradiated or scattered radiation volume.

The value of internal fixation and radiotherapy in the management of upper and lower limb bone metastases

Fifty-four consecutive patients underwent 61 orthopaedic operations for metastatic bone disease affecting the upper and lower limbs. These patients were subsequently managed using a consistent postoperative radiotherapy (RT) policy. There were 27 prophylactic internal fixations and 34 internal fixations of pathological fractures. There was a marked difference in survival between these groups. The median postoperative survival of the prophylactic (P) group was 15 months whereas that of the fracture (F) group was 2 months (P less than 0.0001). Ninety-three per cent of the P group and 59% of the F group were able to be discharged home following treatment. Subsequent local fracture requiring further surgical intervention occurred in 11% of the P group and in none of the F group. Seventy-eight per cent of the P group and 62% of the F group did not suffer any further sequelae at the operation site until the time of death or last follow-up. Patient mobility following surgery and RT for metastatic lesions occurring in the lower limb was significantly improved in both the P group (P less than 0.05) and in the F group (P less than 0.0001) such that 91% and 58%, respectively, of these patients were subsequently able to walk.

Brain Metastases from Carcinoma of Breast: A Review of 90 Cases

The case records of 90 patients developing brain metastases from carcinoma of the breast have been reviewed. Brain metastases developed more commonly in those patients who had Stage III disease at first diagnosis of breast cancer and in those who were pre- or perimenopausal at that time. Patients given whole-brain irradiation for brain metastases lived longer, from the date of central nervous system involvement, than those not given radiotherapy.

A multidisciplinary approach to improving the quality of tangential chest wall and breast irradiation for carcinoma of the breast

Physicists, radiotherapists and radiographers have worked together to enhance the quality and accuracy of radiotherapy for tangential irradiation of the chest wall and breast. Each stage of the process has been reassessed and improved. A technique has been developed on the treatment simulator which determines the required beam directions and sizes in a straightforward manner. A computerised tomography facility has also been developed on the simulator and this provides one or more slices for planning through the treatment volume, thus allowing accurate determination of external contour and lung position with the patient in the treatment position. The beam edge entry points and the isocentre position can be seen from radiation opaque markers placed on the skin surface, allowing accurate reproduction of the treatment beam positions as set on the simulator. A photon beam algorithm that corrects for the changes in scatter dose in a 3-dimensional (3-D) inhomogeneous situation has been developed and applied to tangential chest wall irradiation. This has shown large differences (up to 10%) in dose compared to a conventional 2-dimensional algorithm. The changes in dose distribution due to the accurate determination of lung position have also been investigated. A method has been developed of measuring the volume of ipsilateral lung irradiated. Dose-area histograms are used to evaluate the fraction of the lung area irradiated in the central slice, and an estimate of the volume irradiated can be made using a beams eye radiograph and the simulator CT image.

Locally advanced breast cancer: report of phase II study and subsequent phase III trial

Twenty-four evaluable patients with stage T4 breast cancer were entered into a phase II study and received chemotherapy comprising cyclophosphamide 1,000 mg m-2 i.v., doxorubicin 50 mg m-2 i.v., vincristine 1.4 mg m-2 i.v. and prednisolone 40 mg orally for 5 days, given 3 weekly for four cycles prior to undergoing loco-regional radiotherapy. All patients completed treatment as planned with no major acute toxicity from either chemotherapy or radiotherapy. Subsequently 52 patients with stage T4 breast cancer were randomised in a phase III trial to receive either radiotherapy alone (RT) or this chemotherapy and radiotherapy (CHOP + RT). A significantly higher complete response rate was achieved in the CHOP + RT treatment arm (P = 0.03). However a larger proportion of the RT arm achieved loco-regional control after salvage treatment for relapse such that 50% of the RT arm and 57% of the CHOP + RT arm had no evidence of loco-regional disease at the time of last follow-up or death. There was no statistical difference in time to distant relapse or overall survival. Analysis of the pilot study showed results comparable to the trial CHOP + RT arm. This trial suggests that this cytotoxic therapy used in conjunction with radiotherapy has only marginal value in improving prognosis in locally advanced breast cancer.

A change in postmastectomy radiotherapy fractionation: an audit of tumour control, acute and late morbidity

Abstract In order to determine if a change in radiotherapy fractionation, which reduced the radiation dose per fraction without changing total overall dose, would reduce acute and late morbidity without reducing local control of disease or survival in patients who had undergone mastectomy for breast cancer, a non-randomized retrospective study of case records and measurement of late radiation morbidity both clinically (generally by one clinician) and radiologically was performed. This audit was performed in the Department of Clinical Oncology in Edinburgh, a centre serving a population of approximately 1.2 million and receiving at that time approximately 500 new breast cancer patient referrals each year. The patients studied were those referred between January 1979 and December 1984 with the fractionation change occurring in April 1982. The case record reviews were carried out in both 1987 and 1993. Between 1979 and 1984, 2739 patients with breast cancer were referred to the department. Of these 821 underwent simple mastectomy as primary treatment followed by radiotherapy. Forty-eight of those were excluded (44 received non-standard radiotherapy and 4 case records could not be found). Of the 773 remaining, 484 underwent 10 fraction radiotherapy, and 289 underwent 20 fractions. The two groups were matched well by menstrual status, clinical stage, and histology. In each group the radiation therapy dose was generally 45 Gray. Late morbidity could be assessed in 79 of the 10 fraction cohort and 92 of the 20 fraction cohort. Locoregional relapse and survival were not affected by this change. Acute skin morbidity was significantly decreased in the 20 fraction cohort while late skin, subcutaneous and rib morbidity were also markedly reduced in this group. There was a slight increase in acute pneumonitis. Arm oedema was not significantly affected.

The staging of breast cancer: a comparison of four staging systems in a cohort of 3800 patients

Abstract Four staging systems for breast cancer have been introduced in turn and have been in general use in the United Kingdom since 1948. Each of these systems has been applied to a cohort of nearly 4000 patients treated in the Radiotherapy Department in Edinburgh between 1954 and 1964 to determine the effect of such changes on prognosis and, presumably, also on management for the various stage groupings. The changes in staging systems over the years have highlighted the importance of some factors, e.g. tumour size and extent of nodal involvement. However, the overall effect on survival of these changes is minimal and the value of frequent changes in staging systems at less than 10-year intervals is questionable. Even the most recent changes in the UICC staging system make assumptions which are not validated by this review.

Lactation after breast conserving therapy, including radiation therapy, for early breast cancer

Two patients who underwent breast conservation including radiotherapy for early breast carcinoma are described and who subsequently delivered healthy newborn infants. One of the two patients lactated from both the irradiated and the non-irradiated breast; whereas the other patient did not lactate from the irradiated side. The treatment and implications are discussed.