Eeva Nordman

Prognosis of patients treated for intracranial metastases with whole-brain irradiation

Seventy-five patients with brain metastases from solid tumours were treated with whole-brain irradiation at our institution between 1990 and 1993. The primary cancers included 35 cases of lung cancer, 19 cases of breast cancer, nine cases of renal-cell cancer, six cases of melanoma and six cases of other primary sites. In each case the total dose to the whole brain was at least 25 gray (Gy). The primary site, age, performance status, number of brain metastases and the presence of extracranial disease were studied as prognostic factors for survival. The median survival for the whole population was 4 months (range 1-62 months). The patients with the brain as the only metastatic site had significantly better survival (P = 0.019) than those with both intracranial and extracranial metastatic sites. Poor performance status at the time of diagnosis of brain metastases was also related to short survival (P = 0.001). None of the other studied variables had prognostic significance. Four of the 75 patients with primary tumour sites in the breast (two patients) and the kidney (two patients) survived for more than 2 years. In general, patients with breast cancer had better survival than patients with other primary cancers. Our study confirms the generally poor prognosis of cancer with brain metastases, although individual patients may survive several years after whole-brain irradiation. Approximately two-thirds of the patients experienced a relief in symptoms allowing a reduction in the dose of corticosteroid medication, which clearly supports the use of whole-brain radiotherapy as a palliative treatment.

Estimation of Long-Term Salivary Gland Damage Induced by Radiotherapy

A classification is proposed for estimating salivary gland damage induced by radiotherapy to the head and neck. The volume of salivary glands irradiated was evaluated, and their relative proportions of whole saliva output were calculated. Stimulated salivary flow rate was measured in 61 patients treated with radiotherapy for head and neck malignancies. A highly significant negative correlation was found between the classification of salivary gland damage and stimulated salivary flow rate. The volume of the major salivary glands irradiated seems to be the most important factor affecting the postirradiation salivary flow after a curative dose of radiotherapy. If possible, partial sparing of the salivary glands may help to keep the patients salivary secretion at an acceptable level and promote protection against dental caries. Most patients irradiated to the head and neck, however, need an effective prophylactic programme for the rest of their lives in order to preserve their teeth.

Imaging of head and neck tumors with positron emission tomography and [11C]methionine

PURPOSE To evaluate the value of positron emission tomography and [11C]methionine in imaging of malignant tumors of the head and neck region. METHODS AND MATERIALS Forty-seven tumors of the head and neck were investigated with 11C-labeled methionine and positron emission tomography before treatment. Because of the resolution limits of the positron emission tomography scanner, all tumors selected for the study were larger than 1 cm in diameter. RESULTS Forty-two (91%) of the 46 malignant tumors were clearly visible in the positron emission tomography image (squamous cell carcinoma, n = 26; lymphoma, n = 9; adenocystic carcinoma, n = 2; lymphoepithelioma, n = 1; adenocarcinoma, n = 1; transitional cell carcinoma, n = 1; esthesioneuroblastoma, n = 1; plasmocytoma, n = 1), while three (7%) squamous cell carcinomas were visible, but less easy to detect due to physiological accumulation of the tracer in the area under observation. Only one (2%) squamous cell carcinoma could not be delineated from the positron emission tomography image, and there was no uptake of [11C]methionine in a benign pleomorphic adenoma. No correlation was found between the uptake of [11C]methionine and the histological grade in the subset of squamous cell carcinoma (n = 30). High physiological uptake of [11C]methionine was observed in the salivary glands and the bone marrow. CONCLUSIONS Malignant head and neck tumors can be effectively imaged with positron emission tomography using [11C]methionine as the tracer.

A flow cytometric analysis of 23 carcinoid tumors.

Twenty‐three carcinoid tumors were investigated from paraffin‐embedded tissue with flow cytometry (FCM) in order to correlate the DNA ploidy with clinical variables. DNA aneuploidy was found in ten tumors (45%) and one tumor was classified as tetraploid. Diurnal urinary excretion of 5‐hydroxy indolic acetic acid (5‐HIAA) was known to be elevated in seven of eight diploid tumors and in four of seven aneuploid carcinoids with distant metastases. Six (55%) of the diploid tumors had not given rise to metastases at the time of diagnosis, compared with three (30%) of the aneuploid tumors. Six of seven patients with an aneuploid tumor and three of five patients with a diploid tumor, observed for at least 10 years, died of the disease. It was concluded that, unlike in earlier studies with static DNA cytometry, DNA aneuploidy is common in human carcinoid tumors and may occur in tumors secreting biogenic amines.

Lymphocyte subpopulations in patients with breast cancer after postoperative radiotherapy

The effects of radiotherapy on the immune competence of patients with mammary cancer was studied using enumeration of the various lymphocyte subpopulations as detected by monoclonal OKT antisera, lymphocyte proliferative responses to phytohemagglutinin, concanavalin A, purified protein derivative to tuberculin (PPD), and serum immunoglobulin levels. The tests were carried out in nine patients with newly diagnosed and operated mammary cancer before and after the radiation therapy, and 6 months later, and in ten patients whose mammary cancer had been diagnosed and treated at least 3 years earlier and who had remained tumor‐free. The number of lymphocytes in the peripheral blood and the various T‐cell subpopulations as well as the OKIa1 cells mostly representing B‐cells decreased. The only population increasing were the OKM1‐positive cells, mostly representing monocytes and null cells. As also described earlier, the responses to mitogens decreased because of the radiotherapy but recovered, except for the responses to PPD which remained low.

Combined Bleomycin Treatment and Radiation Therapy in Squamous Cell Carcinoma of the Head and Neck Region

Forty-six patients with squamous cell carcinoma of the head and neck region were randomized to either irradiation or irradiation plus bleomycin. If possible, the patients later underwent radical surgery. In the bleomycin group, significantly fewer patients had remaining tumour cells in the tissue removed at operation, and a longer time elapsed before recurrences occurred. However, bleomycin had no significant effect on the 3-and 5-year survival rates, and it did not significantly reduce the incidence of local recurrences.

Combined interferon and vinblastine treatment of advanced melanoma: evaluation of the treatment results and the effects of the treatment on immunological functions.

SummaryThirteen patients with metastatic malignant melanoma received interferon α-2a (Roferon-A) and vinblastine. The interferon dosage was increased from 3×106 IU to 9×106 IU daily in 10 weeks and thereafter 9×106 IU was administered three times weekly intrasmuscularly. Vinblastine (0.075–0.15 mg/kg) was given every third week intravenously. One of the ten evaluable patients had partial remission (PR) (11%) for 10 months. The diseases was stabilized (NC) in three patients (30%) for 3, 6 and 9 months. Progression (PD) occurred in six patients. The treatment time varied from 5 weeks to 44 weeks. The median survial time from the beginning of this combination treatment was 5 months. The most common side-effects were fever, fatigue, loss of taste, weight loss and neutropenia.The mitogen response to phytohemagglutinin and purified protein derivative of tuberculin decreased in all patients. The response to concanavalin A decreased less and began to increase again in the patients with PR and NC. The natural killer cell activity in PD patients decreased more than in the patients with PR and NC. The ratio of T4/T8-positive cells was restored in PR + NC patients but rose in PD patients indicating a difference in the immunomodulatory effect of the combination or of the advanced disease itself on T-cell function in PD patients.This combination of daily interferon and vinblastine did not prove to be effective in melanoma. The depression of immunological functions, which was more marked in patients with PD, might indicate that vinblastine in this combination counteracts the immunostimulatory effect of interferon.

Long-Term Effect of Postoperative Irradiation on the Immune Functions in Patients with Mammary Carcinoma

The effect of postoperative irradiation on the immune functions of 13 patients with breast carcinoma is reported, using as parameters the peripheral blood lymphocyte count, percentages of E and EAC rosette forming cells, and lymphocyte proliferative responses to PHA, Con A and PPD. After irradiation the number of peripheral blood lymphocytes was reduced during 8 months. The percentages of E and EAC rosette forming cells were not altered during the observation time of 7 to 36 months. In the proliferative responses of lymphocytes to PHA, Con A and PPD, the postoperative irradiation caused a decrease which, regarding PHA and Con A, lasted up to 8 months and then recovered. The decrease in the proliferative responses to PPD was stronger and lasted during the whole observation time. In the mitogenic responses of patients with recurrent or disseminating disease no difference could be demonstrated as compared with the patients living recurrence-free.

Interferon Combined with Irradiation in the Treatment of Operable Head and Neck Carcinoma; A pilot study

Twenty-two patients with operable head and neck cancer were randomized to receive natural leukocyte alpha interferon (IFN) and radiotherapy, or radiotherapy alone (control) before operation. IFN was administered at 6 MU i.m. daily for 4 weeks and thereafter 3 times per week for 2 months. IFN treatment was introduced simultaneously with radiotherapy (2 Gy daily, 5 fractions per week). The preoperative dose was 30-32 Gy. Tumor response and side-effects were registered. The patients underwent radical surgery 3 weeks after the preoperative irradiation, followed by postoperative irradiation with 22-32 Gy. After preoperative treatment there were one complete response and 4 partial responses among 10 patients receiving IFN and 2 partial responses among 12 patients treated with irradiation alone. No difference in survival was demonstrated between the 2 groups. In the histologic examination of the surgical samples malignant cells were found in 6 of the IFN patients and in 8 of the control patients. The IFN patients had considerably more pronounced mucosal radiation reactions than the controls. The accrual of patients to the study was discontinued due to the side-effects.

Ultrastructural effects of irradiation on squamous cell carcinoma of the head and neck

Tissue samples taken before and during the radical irradiation of the squamous cell carcinoma of the head and neck region were studied by light and electron microscopic examination. Radiation‐induced cellular changes of which nuclear atypia was most pronounced. The tumor invasion pattern remained unchanged but the number of mitoses decreased. The lymphocytic infiltration increased at the beginning of the therapy (from 10–30 Gy) but decreased at the end of radiotherapy. The amount of neutrofils and the keratinization pattern remained almost unchanged at the light microscopic level, but intracellular filaments and desmosomes slightly increased in electron microscopic study. The changes in nuclear morphologic features pointing in a more undifferentiated direction are considered to be due to cell damage rather than to the more aggressive behavior of the tumor cells. This is in agreement with the decrease of mitoses which is due to radiation‐induced arrest of tumor cells to the G2 phase. These changes might be related to the disappearance of tumors during irradiation. The leukocyte compartment seen in the samples might take part in the destruction of the tumor cells and in the removal of the cell debris.