Herman Høst

Postoperative radiotherapy in breast cancer--long-term results from the Oslo study

The long-term results of a randomized clinical trial evaluating the effect of postoperative radiotherapy as an adjuvant to radical mastectomy are presented. There were 1115 patients including 27 protocol deviants. The follow-up time is 11-20 years. In the first part a conventional roentgen unit was used, and in the second part a 60Co unit, with considerably increased dosage and altered treatment plan. Both types of radiation techniques lowered the incidence of loco-regional recurrences significantly, but had no significant influence on the overall survival. The relapse-free survival was significantly improved by 60Co radiation in Stage II patients, but was unaffected by radiation in the other subgroups. Regarding survival, Stage II patients with medially located tumors seemed to benefit more from 60Co radiation than those with lateral tumors. A significant increase in the number of deaths caused by myocardial infarction was observed in Stage I patients having 60Co radiation, indicating that the radiation dose to the heart is of significance.

The effect of post-operative radiotherapy in breast cancer.

Abstract The results of a randomized clinical trial concerning the value of post-operative radiotherapy as an adjuvant to radical mastectomy, are presented in this manuscript. A total of 1090 patients have entered the study. In the first part a conventional roentgen unit was used, and in the second part a 60 Co unit, with considerably increased dosage and altered treatment plan. No effect of post-operative radiation was demonstrated in Stage I regarding survival, disease-free survival, local recurrence, regional and distant metastases. In Stage II roentgen irradiation reduced the incidence of local recurrences and regional metastases, whereas the survival was not affected. Besides reduction of local and regional metastases 60 Co radiation in patients with Stage II disease also reduced significantly the relapse rate as well as the cumulative survival rate up to 5 years. Thus, the results indicate that the radiation dose is of significance. Further analyses suggest, particularly in patients with medially located tumors who have 4 or more axillary lymph nodes involved, that the prognosis will be improved by post-operative radiotherapy in adequate doses.

Symptomatic treatment versus combination chemotherapy for patients with extensive non‐small cell lung cancer

In a randomized clinical trial, 87 patients with inoperable, extensive non‐small cell lung cancer (NSCLC) were randomized to receive either combination chemotherapy (cisplatin at 70 mg/m2 intravenously [IV] on day 1 and etoposide at 100 mg/m2 IV on day 1 and 200 mg/m2 orally on days 2 and 3) or symptomatic treatment. No statistically significant differences in survival time were found between the two treatment techniques. A major problem in the interpretation of the results was the use of semicurative radiation therapy (3000 to 4200 cGy) to the primary tumor and mediastinum, which was given with symptomatic intent. Three long‐term survivors were seen in the latter group.

Myelopathy following radiotherapy of bronchial carcinoma with large single fractions: A retrospective study

A series of 387 patients with bronchial carcinoma treated with a concentrated split course regimen was surveyed for radiation myelitis. The total dose was 38 Gy. Three fractions of 6 Gy were given the first week. After a three-week interval the patients had a second course of radiotherapy with fractions of 4 Gy on 5 consecutive days. A spinal shield was used in 230 patients for the last two fractions of radiotherapy. The median survival for all patients was 9.4 months. Seventeen cases of radiation myelopathy were found. The life table method was used to calculate the risk of myelopathy in surviving patients, showing risk levels of 30 +/- 15% in patients surviving three years or more. The average age of the patients with myelopathy was 57.6 years, compared to 62.9% years in the total population. Statistical analysis showed a borderline significant increased risk for myelopathy in females, and a significant increased risk in younger patients (P = 0.03). No difference in the incidence of myelopathy was found in patients treated with or without a spinal shield.

Combined Surgery and Radiation Therapy Versus Surgery Alone in Primary Mammary Carcinoma: I. The effect of orthovoltage radiation

The effect of routine postoperative irradiation in the treatment of carcinoma of the breast has been evaluated. Postoperative irradiation had no effect on the proportion of patients free of disease nor on the survival rate, but the incidence of local recurrence and homolateral supraclavicular lymph node metastasis was reduced. In stage II patients homolateral axillary lymph node metastases were also encountered less frequently in the irradiated group. Distant metastases occurred either in stage II patients with postoperative irradiation as compared with controls.

Acute and subacute side effects due to infra-diaphragmatic radiotherapy for testicular cancer: A prospective study

Acute/subacute side effects were evaluated in 39 testicular cancer patients before infra-diaphragmatic radiotherapy, twice during therapy and 3, 6, and 12 months after treatment discontinuation. The evaluation was primarily based on questionnaires filled in by the patients. At the end of radiotherapy nausea was reported by all responding patients, and 29 patients complained of diarrhea. Two-thirds of the patients reported abdominal pain and/or meteorism, and one-half complained of retching and/or vomiting. During therapy the median weight was significantly reduced by three kilos and the median value of the performance status decreased by 20%. The hematological and biochemical toxicity was low. At the 3-month evaluation more patients complained of nausea, abdominal pain, and meteorism than before irradiation. Compared to the pretreatment situation the patients evaluated their physical condition to be reduced during treatment and at the first follow-up visit. One year posttreatment the patients had regained their physical fitness. All patients in income-producing activity were on sick leave during the period of radiotherapy and for 5 weeks (median) thereafter. In conclusion, infra-diaphragmatic radiotherapy leads to significant but reversible acute/subacute side effects lasting for a median of 9 weeks. It is hoped that better symptomatic therapy and modifications of the radiotherapy technique will reduce the side effects.

Randomized phase II trial of carminomycin versus 4'-epidoxorubicin in advanced breast cancer.

Sixty-three evaluable patients with advanced breast cancer were randomly allocated to receive three-week intravenous courses of carminomycin (18 mg/m2) or 4-epidoxorubicin (90 mg/m2). The former yielded one (3%) partial response for nine weeks among 29 patients whereas, in the other arm, nine (27%) of 34 patients achieved partial response for a median of 28 weeks (range, nine to 36 weeks; p less than 0.02). The major toxic effect of these anthracyclines was leukopenia with median white blood cell nadirs of 1,600/microL (range, 300-4,000/microL) versus 1,800/microL (range, 500-4,300/microL), respectively. Acute nonhematologic toxic effects were qualitatively similar but carminomycin produced significantly less gastrointestinal intolerance and alopecia. Patients whose disease failed to respond to first-line anthracycline received doxorubicin (60 mg/m2) every three weeks. Four partial responses were obtained among 19 patients previously treated with carminomycin. Following 4-epidoxorubicin therapy, one of 12 evaluable patients also attained partial response. Survival curves were not affected by the initial treatment option. Carminomycin has marginal activity against breast cancer whereas 4-epidoxorubicin deserves further evaluation of its therapeutic index relative to doxorubicin. The design used in this trial appears attractive for prompt phase II evaluation of anthracycline analogs.

Weekly adriamycin® vs. 4-epidoxorubicin every second week in advanced breast cancer. A randomized trial

One hundred and sixty-six patients with advanced breast cancer previously not treated with chemotherapy for metastatic disease were randomly allocated to 20 mg Adriamycin i.v. weekly (Awkly) as bolus injection or 50 mg 4-epidoxorubicin biweekly over a 3-h infusion time (EPIbiwkly). Of the 149 patients evaluable for response, the response rate was 36% for Awkly vs. 22% for EPIbiwkly (P = 0.10). There was no difference in response duration or survival. The main difference between the two regimens was in toxicity. Seventy per cent of Awkly patients virtually had no side-effects vs. 15% in the EPIbiwkly group. Significant differences in favour of Awkly were observed both for nausea/vomiting and alopecia.

Leukocyte adherence inhibition assay in human pulmonary neoplasia

The hemocytometer leukocyte adherence inhibition technique was used to study cell-mediated immuno-activity of patients with lung cancer. KCl extracts (3.5 M) from the lung cancer cell line Calu-1 and the breast cancer cell line MCF-7 were used as antigens. Of 138 patients with lung cancer, 85% showed a positive response against the Calu-1 antigen. The response was independent of the histological type of the tumor and was the same among untreated patients, patients undergoing different types of treatment and patients who died within 3 months after blood collection. Twenty-five percent of the untreated lung cancer patients also reacted against the breast cancer antigen. Among lung cancer patients undergoing different types of treatment, 36% reacted while 50% of the patients who died within 3 months after blood collection reacted against the breast cancer antigen.

HOST MARKERS AND PROGNOSIS IN RECURRENT RECTAL CARCINOMAS TREATED WITH RADIOTHERAPY

The value of blood tests as prognostic factors in patients with recurrent rectal carcinomas treated with radiotherapy was studied in one retrospective (n = 114, 1976-1984) and one prospective (n = 100, 1985-1989) group of patients. The retrospective group was used for validation of the results from the prospective group. In univariate survival analyses, 19 of totally 38 variables significantly correlated to the survival. Of 13 significant blood parameters, lactate dehydrogenase (LD), erythrocyte sedimentation rate (ESR), alpha 1-, alpha 2-globulin, fibrinogen, carcinoembryonic antigen (CEA), C-reactive protein (CRP), haptoglobin, granulocytosis and thrombocytosis were the most important ones (p < or = 0.01). In the multivariate analyses (Cox regression) of the prospective group, LD, alpha 1-globulin, diagnosed liver metastases and CEA were found to be significant predictors of survival. A prognostic index was derived from the prospective group including ESR, LD and relapse-free interval. This clearly separated the patients in the retrospective group into one low- and one high-risk group.