Continuous versus intermittent prednimustine treatment of non-Hodgkin's lymphoma.

Seventy-eight patients with advanced non-Hodgkin's lymphomas were randomized for treatment with prednimustine (Sterecyt) in two different schedules: either receiving continuous treatment at a dosage of 60 mg daily, or intermittent two-week courses with 200 mg daily for five days. The aim of the study was to compare efficacy and side effects of the two different schedules. Forty patients received continuous, and 38 patients intermittent treatment. Objective response was achieved in 66% of 71 evaluable patients, equally distributed between the two treatment arms. The 10-year survival rate was 20% (SE = 6%; continuous treatment) and 11% (SE = 5%; intermittent treatment), respectively (logrank p = 0.26). Median time to response, duration of response and time to progression showed no significant difference between the treatment groups. Median time on treatment was longer for patients treated continuously, probably due to more easily performed dose adjustments in such patients. There was a significant decrease of the white blood cell counts in patients who received prednimustine continuously compared with those treated according to the intermittent schedule (p = 0.02). No significant differences were found regarding the thrombocyte levels. The response rate was closely related to haematological toxicity (p = 0.01). Our results suggest that prednimustine in non-Hodgkin's lymphomas has similar effectiveness both in daily treatment and in a two-weekly intermittent schedule. Continuously given treatment may be easier to govern and, thereby, allow for higher treatment intensity. With respect to toxicity, daily doses of approximately 30-40 mg in previously untreated patients may be recommended.

Prognostic factors in unselected patients with nonseminomatous metastatic testicular cancer: a multicenter experience.

Between 1981 and 1986, 200 consecutive patients with metastatic nonseminomatous testicular cancer were entered into the Swedish Norwegian Testicular Cancer (SWENOTECA) project from 14 hospitals. The treatment plan was four chemotherapy cycles (cisplatin, vinblastine, and bleomycin) followed by surgical resection of residual tumor masses. After a median observation time of 75 months, the overall 5-year survival rate was 82%. In a univariate analysis, the following parameters influenced the prognosis significantly: the extent of the disease (Medical Research Council [MRC] grouping); the prechemotherapy levels of serum alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), and lactate dehydrogenase (LDH); the patients' age; the presence of extrapulmonary hematogeneous metastases; and/or particularly large lymph node metastases. Patients fared better when more than 3 weeks elapsed between orchiectomy and start of chemotherapy as compared with those who were treated within this interval. The place of treatment (a large oncology unit v smaller units) also represented a significant prognostic factor for patients with large-volume (LV) and very-large-volume (VLV) disease combined. Multivariate analysis (Cox regression proportional hazards model) performed in all 193 assessable patients showed the following adverse prognostic factors: high-volume metastatic burden, age older than 35 years, prechemotherapy AFP greater than 500 micrograms/L and/or HCG greater than 1,000 U/L, and an interval between orchiectomy and start of chemotherapy of less than 3 weeks. The place of treatment also significantly influenced the final outcome. If patients with LV and VLV disease were combined, the presence of two of the following risk factors represented an additional prognostic factor: AFP greater than 1,000 micrograms/L, HCG greater than 10,000 U/L, liver metastases, brain metastases, bone metastases, retroperitoneal tumor greater than or equal to 10 cm, and mediastinal tumor greater than or equal to 5 cm.

Effects of repeated mammographic screening on breast cancer stage distribution. Results from a randomised study of 92 934 women in a Swedish county.

A randomised controlled trial of mass screening for breast cancer by single-view mammography was begun in Sweden in 1977. All women aged 40 and older and resident in the counties of Kopparberg and Ostergötland were enrolled. The present report is confined to the Ostergötland study, which started in 1978 and comprised 92 934 women. After randomisation, which was done on the basis of communities rather than individuals, 47 001 women were allocated to the study group and offered repeated mammographic screening; 45 933 were allocated to the control group. As compliance among women over 74 years of age was poor these were excluded from the present report. The yearly incidence of stage II or more advanced breast cancers after the initial screening round up to and including the second was reduced by 40 per cent in the study group compared with the controls. This effect was less marked in the age group 40-49. After 5.5 years average from the date of entry the absolute number of women with stage II-IV disease in the control group exceeded that for the study group by 44, whereas there was a large excess of cancer in situ and stage I cancer in the study group.

Effect of repeat irradiation on the tracheal ciliary cell activity.

Rabbit tracheas were initially irradiated with 10 Gy in vitro. A second irradiation of 10 Gy was administered 2 hours later. The initial exposure caused a 25 per cent increase of the ciliary beat frequency during the irradiation--a response which was not found during the second irradiation. Between the exposures, the beat frequency dropped to 20 per cent below the reference level, followed by an 11 per cent overshooting before the second irradiation. Tracheas placed untreated in the experimental chamber for 2 hours and subsequently irradiated with 10 Gy showed a similar pattern of ciliary activity as induced by the initial radiation exposure in the first experiment. The storage during 2 hours did thus not affect the condition of the ciliae. The absence of a great increase of the beat frequency during a second irradiation period may be explained by damages caused by the initial exposure, morphologically seen first a few days later.

Reduction in mortality from breast cancer after mass screening with mammography. Randomised trial from the Breast Cancer Screening Working Group of the Swedish National Board of Health and Welfare.

A randomised controlled trial to investigate the efficacy of mass screening with single-view mammography in reducing mortality from breast cancer was started in Sweden in 1977. 162 981 women aged 40 years or more and living in the counties of Kopparberg and Ostergötland were enrolled in the study and divided at random into 2 groups. Each woman in the study group was offered screening every 2 or 3 years depending on age. Women in the control group were not offered screening. This report is confined to the 134 867 women aged 40-74 years at date of entry. The results to the end of 1984 show a 31% reduction in mortality from breast cancer and a 25% reduction in the rate of stage II or more advanced breast cancers in the group invited to screening. 7 years after the start of the study the excess of stage I cancers in the study group largely outweighs the deficit of advanced cancers.

Malignant lymphoma of the testis.

Lymphoma presenting in the testis was evaluated in 24 patients. The tumours were classified according to both the Rappaport and the Kiel classification. The Rappaport classification yielded only two tumour types--15 diffuse histiocytic and 9 diffuse mixed histiocytic-lymphocytic, with no pure lymphocytic lymphoma. No difference in survival time was found between these two tumour types. According to the Kiel classification there were four histological tumour types--immunoblastic (11 cases), centroblastic (2), centroblastic/centrocytic (6) and polymorphic immunocytic (5). In comparison with the other tumour types, the centroblastic/centrocytic lymphomas seemed to be advantageous as regards survival. It is concluded that systemic treatment with chemotherapy in accordance with current principles for malignant lymphoma is indicated following orchiectomy in localised testicular lymphoma as well as in disseminated disease. The value of post-operative radiotherapy to regional nodes is questionable.

Changes in circulating immune complexes in tumour patient serum after in vitro or ex vivo affinity chromatography of blood plasma or whole blood over immunoglobulin-binding staphylococcal protein A-Sepharose.

Circulating immune complexes (CIC) were determined in tumour patient sera using three methods. One is based on PEG-precipitation, one on C1q-reactivity, and one on protein A-reactivity. About 25-30% of the sera were positive in at least one of the tests. Incubation of serum with protein A-Sepharose in vitro removed PEG-precipitable CIC from most sera, whereas C1q-reactive CICs had a much lower affinity to protein A. The protein A-reactive complexes showed considerable variation in their binding to protein A-Sepharose, and in some sera the amount of these CICs was actually increased. Similar changes in protein A-reactive CIC were also found during ex vivo treatment of tumour patients with immune adsorption. It is proposed that the binding of immune complexes to protein A can result in remodelling of protein A itself. Results from ultracentrifugation and fractionated PEG-precipitation support this hypothesis.

Intracellular recording of potential oscillations in ciliated cells exposed to ionizing radiation.

Intracellular potential oscillations of the ciliated cells of the rabbit's trachea have been measured by means of glass capillary microelectrodes during exposure of the cells to ionizing radiation. The electrophysiologic activity was fairly stable during the entire exposure at a total administered dose of 10.0 Gy. This finding is contradictory to the change in mucociliary activity obtained under the same conditions when measured with a light beam reflex method, but is in agreement with the findings regarding the influence of radiation on the membrane potentials as far as nerves and muscles are concerned.

Urinary excretion of inorganic sulfate, ester sulfate, total sulfur and taurine in cancer patients.

The urinary excretion of inorganic sulfate, ester sulfate, taurine and total sulfur has been estimated in 18 patients with malignancy, and compared with those of an age-matched reference group. The absolute amount of inorganic sulfate was significantly lower in the cancer group, whereas an increased ester sulfate excretion was observed. Reduced excretion of total sulfate (inorganic plus ester sulfate) and increased excretion of "neutral sulfur" (total sulfur minus total sulfate) in the cancer group was calculated from these data. If these values were recalculated with respect to creatinine, no significant differences were found for inorganic and total sulfate between the two patient groups, whereas ester sulfate and the "neutral sulfur" fractions were still increased. The enlarged "neutral sulfur" could to a large extent be explained by an increased excretion of taurine. The mechanism behind these findings is discussed.

En-bloc irradiation of unresectable bronchogenic carcinomas and their regional lymphatics.

Patients with unresectable or inoperable bronchial carcinoma were treated with en-bloc irradiation of the tumour and the mediastinal lymph nodes to a total target absorbed dose of 40 Gy in 20 fractions. The first 52 patients were treated in one series and the last 45 patients in two series (split-course). Radiation adverse effects were only mild. The two regimens gave the same palliative results. The median survival was the same for the 2 groups (8 months). Most patients died in disseminated disease.

Effect of 50 kV roentgen rays and cobalt-60 gamma rays on the activity of ciliated cells.

A method capable of continuously recording the changes in the physiologic activity of ciliated cells during irradiation has been used to analyse the importance of photon energy for the early biologic effects of ionizing radiation. Gamma rays from 60Co and 50 kV roentgen rays were used. Important differences were demonstrated and conventional RBE values are not valid for early effects. The results are discussed and RBE for 50 kV roentgen rays has been calculated in respect to early effects of irradiation.

Response of ciliated cells during irradiation at different dose rates.

Early radiation effects on the physiologic activity of ciliated cells during exposure have been investigated at 0.34Gy/s and 0.05 Gy/s. The results obtained indicate a more intense early biologic effect at a higher dose rate. The mechanisms of radiation injury are discussed.

Ultrastructural alterations in ciliary cells exposed to ionizing radiation. A scanning and transmission electron microscopic study.

Early effects of ionizing radiation were investigated in an experimental in vitro system using the ciliary cells of the tracheal mucous membrane of the rabbit, irradiated at 30 degrees C and at more than 90% humidity. The changes in physiological activities of the ciliary cells caused by irradiation were continuously registered during the irradiation. The specimens were examined immediately after irradiation electron microscopically. The morphological changes in irradiated material after 10-70 Gy are compared with normal material. After 40-70 Gy, scanning electron microscopy revealed the formation of vesicles on cilia, and club-like protrusions and adhesion of their tips. After 30-70 Gy, a swelling of mitochondrial membranes and cristae was apparent transmission electron microscopically. The membrane alterations caused by irradiation are assumed to disturb the permeability and flow of ATP from the mitochondria, which in turn leads to the recorded changes in the activity of the ciliated cells.

Mantle treatment of Hodgkin's disease. Results and side effects.

Eighty-seven patients were treated with the mantle technique for Hodgkin's disease. Usually 40 Gy in 27 fractions in two series over 71 days were given. A local recurrence was diagnosed in 3 of 87 patients. An analysis of radiation reactions of the lung tissue, heart and pericardium, and spinal cord is reported. It is recommended to give mantle treatment for Hodgkin's disease over a relatively long period of time such as in split-course in two series.

Clinical course after mantle treatment of non-laparotomized patients with Hodgkin's disease.

Forty-two patients with Hodgkin's disease were staged without laparotomy and considered to have only supradiaphragmatic disease. They were treated with the mantle technique and followed up for at least 3 years. Abdominal extension was later found in 31 per cent. It is concluded that occult abdominal disease usually in course of time will give symptoms.

Effects of ionizing radiation on the activity of the ciliated epithelium of the trachea.

The immediate effect of ionizing radiation on the activity of the ciliated epithelium of the trachea has been investigated using a light reflection method. This method enables continuous registration of the mucociliary activity both during and after irradiation. A notable increase of the mucociliary activity occurred within 5 seconds after beginning of irradiation and this activity reached its maximum 10 seconds after initial exposure with a dose rate of 0.34 Gy/s (34 rad/s). The mechanism causing the phenomena observed is not clear but theoretically it might be due to ATP, the source of energy of the cilia being freed by the irradiation, possibly through disturbances of the permeability in the mitochondrion membranes.

Tumours of the testis. A report of 128 cases.

The records of 128 patients treated between 1960 and 1971 at the University Hospital, Lund, because of tumour of the testis were analysed in respect of age at onset of the tumour, symptoms, histology, diagnosis, treatment and survival rate. Teratoma occured in 67 cases, in the majority at the age of 20-30 years. Treatment consisted in orchiectomy, lymphadenectomy, administration of cytostatics and radiation alone or combined, depending upon the histology and spread of the tumour. The 5-year survival rate was 40%. Sixty-one patients had seminoma, most of which appeared between 30 and 40 years of age. The patients were treated with orchiectomy and radiation. The 5-year survival rate was 82%.