No abstract available

[en] Objective: To investigate if the occurrence of subcutaneous fibrosis after radiotheraphy in an unselected group of breast cancer patients is related to cellular radiosensitivity of skin fibroblasts as measured in a clonogenic assay. Materials and methods: An in vitro colony-forming assay of normal fibroblast radiosensitivity was applied to primary skin biopsies from 31 breast cancer patients who received post-mastectomy radiotherapy with large doses per fraction (2.7-3.9 Gy) more than 10 years earlier. Three clinical normal-tissue endpoints were assessed. Two late endpoints, subcutaneous fibrosis and telangiectasia, were evaluated in three treatments fields by a single experienced clinician. In addition, skin erythema had been assessed at the end of treatment by members of the staff and junior staff. >From previous analyses of normal tissue response, individual clinical radiosensitivity could be assessed as 'excess risk' of each of the three reactions. This was defined as the difference between the actual observed response in the patient and the expected response estimated from individual treatment characteristics in a linear quadratic (LQ) mixture model and, for the two late endpoints, with correction for the follow-up time. This clinical radioresponsiveness was compared with the in vitro radiosensitivity of the skin fibroblasts. To this end, the fractions of colony-forming cells after graded single doses were fitted by an LQ survival curve using non-linear and linear regression from which the surviving fraction at 3.5 Gy (SF_3.5) was estimated. Assessment at 3.5 Gy was chosen to reflect the fraction size during clinical radiotherapy. Results: A statistically significant variability of in vitro radiosensitivity between patients could be detected for both SF₂ (P = 0.0095) and SF_3.5 (P = 0.0008). A significant correlation was observed between SF_3.5 and excess risk of fibrosis (r_s -0.46, P = 0.009) while no association was found between fibroblast radiosensitivity and either the occurrence of severe skin telangiectasia or the acute endpoint skin erythema. Conclusion: These results suggest that variability in the occurrence of subcutaneous fibrosis, but not telangiectasia or erythema, after radiotherapy is partly accounted for by differences in cellular radiosensitivity of normal skin fibroblasts

[en] 78 patients with inoperable lung cancer of various histologic types were treated with split course x-ray therapy to the primary and nodal areas and combination chemotherapy with CCNU, adriamycin and vinblastine. 84 per cent of patients responded to therapy. The median survival time was 11 months; 21.5 per cent of patients survived more than 2 years mostly free of disease

No abstract available

[en] Nimorazole, a 5-Nitromidazole compound has been shown in animal studies to have similar radiosensitizing properties to misonidazole at clinically acceptable dose levels. The drug is well absorbed in humans after oral administration with peak plasma levels occurring around 90 min after ingestion (range 35-135 min) and a plasma half life between 2 and 4.8 hours. Total doses of Nimorazole up to 60 grams given in daily doses with conventional radiation therapy have demonstrated a significant lack of side effects, in particular no demonstrable neurotoxicity

[en] The present investigation has been carried out to evaluate the sensitivity of the inner ear to irradiation. Cochlear function was tested in a cohort of 22 patients before and 7-84 months after receiving external irradiation for nasopharyngeal carcinoma. The pre-irradiation sensori-neural hearing threshold at 500, 1000, 2000, and 4000 Hz was used as a baseline for the individual patient, and the observed sensori-neural hearing loss (SNHL) was calculated as the difference between pre- and post-irradiation values. The pre-irradiation hearing level or patient age was not correlated with the actual SNHL. In contrast, there was a significant correlation between the total radiation dose to the inner ear and the observed hearing impairment. SNHL was most pronounced in the high frequencies, with values up to 35 dB (4000 Hz) and 25 dB (2000 Hz) in some patients. The latent period for the complication appeared to be 12 months or more. The deleterious effect of irradiation on the hearing should be kept in mind both in treatment planning and in the follow-up after radiotherapy

[en] A colony-forming assay of human skin fibroblast radiosensitivity was established in our laboratory and applied to primary skin biopsies from 12 women belonging to an unselected group of patients who received postmastectomy radiotherapy 10-12 years prior to this study. The aim was to investigate the relationship between in vitro radiosensitivity and the occurrence of subcutaneous fibrosis after radiotherapy. Early generations of normal skin fibroblasts in exponential growth were irradiated at room temperature at a high dose-rate to estimate the surviving fraction of colony-forming cells after single doses ranging from 1 to 8 Gy. A linear-quadratic cell survival curve was fitted to the data and from these fits the surviving fraction at 3.5 Gy (SF_3.5) was estimated. Replicate experiments of different cell generations were made to validate the assay, and the between-patients variability was significantly larger than the assay variability for both SF₂(p=0.002) and SF_3.5(p=0.04). Patients were treated in the period 1978-1982 with a dose per fraction between 2.7 and 3.9 Gy, a total of 12 fractions at two fractions per week. They were evaluated with respect to the occurence of marked subcutaneous fibrosis in a total of 36 independent treatment fields. In each treatment field the total dose and dose per fraction at the relevant dosimetric reference depth as well as the length of follow-up were recorded. (Author)

[en] Late treatment-related morbidity after mastectomy and adjuvant systemic treatment with and without postoperative irradiation was assessed in 84 patients randomized in the Danish Breast Cancer Cooperative Group Trials 82b and c. A structured interview and physical examination, using a standardized assessment sheet, constructed on the basis of the late effects normal tissues (LENT) scoring system, was used. The median length of follow-up from mastectomy was 9 years (range 6-13 years). Lymphedema was measured in 14%, of the irradiated patients versus 3% of the non-irradiated patients (NS). Slightly decreased shoulder morbidity was measured in 45% of the irradiated women versus 15% of the non-irradiated patients, but moderate or more severe impairment was seen in only 5% of the irradiated patients and in none of the non-irradiated patients (p = 0.004). Seventeen percent of the irradiated patients and 2% of the non-irradiated patients found that impairment of shoulder movement caused symptoms (p = 0.001)

[en] In 1978-1980, inclusive, all breast cancer patients referred for postmastectomy irradiation were treated by 2 fractions per week (73 patients) but due to a high incidence of late complications this fractionation schedule was changed from early 1981 to 5 fractions per week (66 patients) with dose adjustment according to the nominal standard dose (NSD) concept. The dose aim in both regimens was 1345 ret minimum target dose. This allowed a comparison of acute and late complications in the two patient groups treated to the same NSD value, but with different fractionation. The patients have been analysed with respect to acute and late reaction in the skin, subcutaneous tissue, lung and bone, as well as related complications, such as arm oedema and impairment of shoulder movement. Except for the acute skin reactions, all other endpoints could not be adequately predicted by the NSD formula. The data clearly demonstrates the danger by using the NSD formula in equation of two different fractionation schedules. This formula as well as other mathematical models can only be used with caution within the limitations defined by the underlying clinical and experimental data on which they have been derived. 26 refs.; 3 figs.; 7 tabs

[en] The purpose of this study was to quantify the time course of radiological lung changes in patients after post mastectomy radiotherapy assessed from routine follow-up chest x-rays. Radiological density changes in the apex of the irradiated lung were quantified by a recent lung densitometry assay. Lung changes were expressed as the so-called Relative change in Equivalent Absorber Thickness (REAT). The clinical series comprised 329 patients treated with post mastectomy radiotherapy between 1978 and 1982. Of these patients 100 were treated with chemotherapy (CTX or CMF) and 41 were given tamoxifen as an additional adjuvant treatment; 290 patients (88.2%) had pretreatment x-rays and at least one x-ray after completion of radiotherapy and these were included in the study. A total of 2,209 chest x-rays was taken during follow-up, and among these 1921 x-rays (86.9%) were judged to be assessable. Late changes were defined as changes occurring more than a year after radiotherapy. A total of 280 patients had at least one chest x-ray taken more than one year after radiotherapy and these were evaluable with respect to late changes. There were 1,390 follow-up x-rays in these patients and 207 patients (73.9%) had three or more follow-up x-rays. Linear regression of REAT vs. observation time was used to identify three patterns of time changes: progressive, regressive, and stable. The results were as follows. Two phases of lung changes were observed. The early phase peaks around 6 months and the density changes may subsequently resolve, completely or in part. In most cases (173 patients or 84%), the lung density changes reached a stable level 12 months after irradiation. Yet, in 16 patients (7.7%) the lung changes progressed for five or more years. Regression of the density changes was seen in 18 patients (8.7%), and in some cases there were signs that this apparent regression was caused by contraction of the fibrotic tissue. We conclude that two phases of lung response can be distinguished and can be graded according to severity using this assay. Early lung changes reach a maximum around 6 months after RT. Late reactions reach a plateau in most patients after one year, but progress in some cases for five or more years