Olav Kaalhus

Radiotherapy for testicular seminoma stage I: treatment results and long-term post-irradiation morbidity in 365 patients

After infradiaphragmatic radiotherapy the cancer-related 10 year survival was 99% in 365 patients with seminoma Stage I referred to the Norwegian Radium Hospital between 1970 and 1982. Thirteen patients relapsed, 11 of them within the first 3 years after treatment. Nine of the recurrent patients were cured by radiotherapy alone (4) or in combination with chemotherapy (5). There is no need to include the inguinal lymph nodes into the irradiation field or to give scrotal irradiation, not even to patients with tumor infiltration beyond the testicular tissue, or to those with prior scrotal or inguinal surgery. At least 1 year after radiotherapy moderate or more severe dyspepsia was observed in 16 patients. Nine patients developed a peptic ulcer. In general, there was no increased risk for development of a second non-germ cell cancer after radiotherapy. However, 4 patients developed a pulmonary cancer indicating a border-line significance of increased risk for this type of malignancy. (p:0.05). In conclusion, infradiaphragmatic radiotherapy remains the optimal routine treatment in seminoma patients with Stage I.

Histology of tumor residuals following chemotherapy in patients with advanced nonseminomatous testicular cancer

A total of 111 patients with advanced nonseminomatous testicular cancer underwent cisplatin-based combination chemotherapy, followed by surgical removal of residual masses in 101. Surgery included retroperitoneal lymph node dissection in 92 patients, thoracotomy in 19 and hepatic resection in 1 (11 patients underwent 2 operations). Complete necrosis and/or fibrosis was found in 52 operative specimens, mature teratoma in 37 and vital malignant tumor in 12. Of the 11 patients who underwent 2 operations 4 had complete necrosis and/or fibrosis in both histological specimens. After a median observation of 55 months 83 of 89 patients with complete necrosis and/or fibrosis or mature teratoma were without evidence of disease. Only 7 of 12 patients with vital malignant tumor in the operative specimen survived without evidence of disease. Relapses were observed in 16 patients, 4 of them in the retroperitoneal space. Of the 16 relapses 5 were in 12 patients with residual vital malignant tumor, 5 in 37 patients with post-chemotherapy mature teratoma and 4 in 52 patients with complete necrosis and/or fibrosis after chemotherapy. Two patients with recurrence did not undergo an operation. In patients in whom post-chemotherapy retroperitoneal lymph node dissection is considered complete necrosis and/or fibrosis can be predicted by the combination of several factors, including absence of teratomatous elements in the testicular tumor, complete response on post-chemotherapy computerized tomography, and normal alpha-fetoprotein and human chorionic gonadotropin levels after chemotherapy (sensitivity 83%, specificity 76% and correctly predicted 79%). With the knowledge of these factors it seems possible to omit post-chemotherapy retroperitoneal lymph node dissection in approximately 20% of the patients with advanced metastatic nonseminomatous testicular cancer with initial retroperitoneal tumors.

Salivary gland malignant neoplasms: treatment and prognosis

A retrospective analysis of 183 patients with malignant salivary gland tumors treated between 1955 and 1978 is presented. The analysis showed that radiation therapy lowered the recurrence rates after surgery and controlled approximately one-third of the inoperable tumors. A dose-response relationship exists and the data suggest that the radiation dose should not be less than that corresponding to a CRE-value of 1950 reu (70 Gy/7 weeks). Histology, location and clinical stage are important prognostic factors.

Estrogen receptors and long‐term prognosis in breast cancer

The long‐term prognosis in 233 primary breast cancer patients, most of whom had received ovarian irradiation, has been related to the estrogen‐receptor status of the primary tumors. The median observation time was 9 years. The receptor status did influence disease‐free interval and survival only in patients having metastases in axillary nodes. Thus, in the postmenopausal patients with axillary metastases, the disease‐free interval and survival time were longer in receptor‐positive than in receptor‐negative patients during the first few years of observation. However, this difference disappeared in the course of the subsequent years. in the premenopausal women with axillary metastases the receptor status did not influence the short‐term prognosis, and, unexpectedly, seemed to affect adversely the long‐term prognosis. It is concluded that the long‐term prognosis is no better in breast cancer patients having estrogen receptors in their primary tumors than in those with receptor‐negative tumors.

Prognostic factors in liposarcoma

In a series of 99 liposarcomas, the prognostic impact of the various diagnostic and therapeutic factors was analyzed. The analysis indicated that the tumor size, histologic subtype, and x‐ray density are important prognostic factors. The prognosis is also influenced by operability and treatment modalities employed. Treatment strategy should be radical, irrespective of the actual prognostic factors.

Assessment of tumor oxygenation in human cervical carcinoma by use of dynamic Gd-DTPA-enhanced MR imaging

Increased knowledge of the physiological basis behind the signal enhancement in tumors during dynamic contrast‐enhanced magnetic resonance (MR) imaging may be useful in development of predictive assays based on this technique. In the present work, the relative signal intensity (RSI) increase in gadopentetate dimeglumine (Gd‐DTPA)‐enhanced MR images of patients with cervical carcinoma was related to tumor perfusion, vascular density, cell density, and oxygen tension (pO2). The patients were subjected to MR imaging before the start of treatment (N = 12) and after two weeks of radiotherapy (N = 8). Perfusion was determined from the kinetics of contrast agent in tumors and arteries, vascular density and cell density were determined from tumor biopsies, and pO2 was determined by polarographic needle electrodes. The maximal RSI was correlated to perfusion (P = 0.002) and cell density (P = 0.004), but was not related to vascular density. There was also a correlation between pO2 and perfusion (P < 0.001). Moreover, pO2 tended to be correlated to cell density (P = 0.1), but was not related to vascular density. There was a significant correlation between RSI and pO2, regardless of whether the median pO2 (P < 0.001) or the fraction of pO2 readings below 2.5 mmHg (P < 0.001), 5 mmHg (P < 0.0001), or 10 mmHg (P < 0.001) was considered. Our results suggest that the Gd‐DTPA‐induced signal enhancement in MR images of cervical tumors is influenced by both perfusion and cell density. These parameters are also of major importance for tumor oxygenation, leading to a correlation between signal enhancement and oxygenation. Dynamic contrast‐enhanced MR imaging may therefore possibly be useful in prediction of treatment outcome. J. Magn. Reson. Imaging 2001;14:750–756.

BLEOMYCIN AND RADIATION THERAPY IN SQUAMOUS CELL CARCINOMA OF THE UPPER AERO-DIGESTIVE TRACT: A PHASE III CLINICAL TRIAL

A group of 222 consecutive patients admitted with squamous cell carcinoma of the upper aero-digestive tract were studied in a prospectively randomized and stratified clinical trial. One-half of the patients received bleomycin injected intramuscularly 1 hour before the radiation treatment daily for 5 days a week; the other half received radiation therapy without the added chemotherapy. The total dose of radiation in both groups was about the same, and was given with curative intent even to the patients with advanced tumors who constituted the majority in both groups. Interstitial radiation as boost therapy or surgery was added in patients with residual tumor if the lesions were considered operable and the patients condition would allow surgery. The addition of bleomycin did not increase the combined local and regional tumor control rates nor did it improve the survival, but did significantly increase the morbidity and the complication rate.

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.

The bystander effect in photodynamic inactivation of cells

Treatment of MDCK II cells with the lipophilic photosensitizer tetra(3-hydroxyphenyl)porphyrin and light was found to induce a rapid apoptotic response in a large fraction of the cells. Furthermore, the distribution of apoptotic cells in microcolonies of eight cells was found to be different from the binomial distribution, indicating that the cells are not inactivated independently, but that a bystander effect is involved in cell killing by photodynamic treatment. The observation of a bystander effect disagrees with the common view that cells are inactivated only by direct damage and indicates that communication between cells in a colony plays a role in photosensitized induction of apoptosis. The degree of bystander effect was higher for cells dying by necrosis than for cell dying by apoptosis.

Intra- and intertumor heterogeneity in blood perfusion of human cervical cancer before treatment and after radiotherapy.

Knowledge of the intratumor heterogeneity in blood perfusion may lead to increased understanding of tumor response to treatment. In the present work, absolute perfusion values, in units of ml/g·min, were determined in 20 tumor subregions of patients with cervical cancer before treatment (n = 12) and after 2 weeks of radiotherapy (n = 8), by using a method based on contrast‐enhanced magnetic resonance imaging. The aims were to evaluate the intratumor heterogeneity in perfusion in relation to the intertumor heterogeneity and to search for changes in the heterogeneities during the early phase of therapy. The intra‐ and intertumor heterogeneity in perfusion were estimated from components of one‐way analyses of variance. The mean perfusion differed significantly among the patients before treatment, ranging from 0.044 to 0.12 ml/g·min. Large differences in perfusion were also observed within individual tumors. The heterogeneity was largest in the best perfused tumors, perfusion values ranging, e.g., from 0.055 to 0.29 ml/g·min were observed. The intratumor heterogeneity was similar to the intertumor heterogeneity. The mean perfusion generally increased or tended to increase during radiotherapy, ranging from 0.064 ml/g·min to 0.13 ml/g·min after 2 weeks of treatment. There was a tendency of increased intratumor heterogeneity in perfusion after therapy, consistent with the higher mean value; a difference in perfusion of more than a factor of 10 was seen within some tumors. These results suggest that cervix tumors contain a significant amount of poorly perfused subregions with high treatment resistance. Moreover, the perfusion and perfusion heterogeneity may increase during the early phase of radiotherapy and influence tumor response.