Biomedical subjects
Publications and source records attributed to N Keldsen.
We describe three cases of women who have been treated with radiotherapy for cervical cancer and then many years later develop cancer of the uterine endometrium. Apparently there may be active endometrium left in the uterus after radiotherapy, for which reason we recommend combined hormone therapy with oestrogen and progesterone.
Chemotherapy and irradiation it combination or alone have been employed in the treatment of oesophageal carcinomas for many years. However, their place in curative treatment is not definitively clarified. Several non-randomized studies indicate an effect from combined chemotherapy and irradiation possibly followed by surgery. Randomized studies published during the last few years confirm an increased curability in patients who have received combined treatment. New multicentre trials show that a more aggressive attitude is indicated in selected groups of patients with oesophageal carcinoma. Due to the variable spectrum of the disease and complexity of the treatment the treatment should be given in centres which master the different modalities.
OBJECTIVE: To evaluate the effect of oral treosulfan in patients with platinum-resistant ovarian cancer. METHODS: A phase II trial of oral treosulfan 500 mg per day in 30 females with platinum resistant ovarian cancer. All patients had measurable or evaluable disease. RESULTS: The treatment was well tolerated. One patient (3%) achieved a partial response lasting 12+ months. Seven patients had stable disease for 5.3 months (median) range 4.4-7.5 months. Median time to progression was 11.5 weeks (95% C.L. 11-12 weeks). Median survival was 31 weeks (95% C.L. 30-35 weeks). CONCLUSION: Oral treosulfan in the present schedule is not recommended in platinum resistant ovarian cancer.
The pathology, etiology and epidemiology of anal cancer (CA) and the treatment and prognostic factors are reviewed. CA is a rare disease. However, the incidence is rising and is now 0.7 per 100,000 women and 0.4 per 100,000 men in Denmark. The median age is 60 years. Smoking and infection with human papillomavirus or HIV increases the risk of CA. The most important prognostic factors are tumour size, depth of invasion, inquinal lymph node involvement, differentiation and DNA ploidy. Previously CA was treated with abdominoperineal resection. Now sphincter preserving treatment with radiotherapy either alone or in combination with chemotherapy is preferred in most centers. Its is unsettled whether combined treatment is superior to radiotherapy only. Careful follow-up is warranted in order to perform salvage surgery in case of recurrent disease.
A consecutive cohort of patients with NHL was examined to identify the factors predictive of CNS-involvement with Cox's proportional hazards model in a multivariate analysis. Twenty-seven cases of CNS-involvement were found among 498 patients with NHL. Only 3 of 96 patients with low-grade lymphomas had CNS involvement, all occurring after transformation into high-grade lymphoma. In univariate analysis of 402 patients with intermediate or high-grade lymphoma, lymphoblastic histology (including Burkitt's lymphoma), age <35 years, B-symptoms, stage IV disease, testis involvement and bone marrow involvement were found to be statistically significant risk factors. Lymphoblastic histology was found to be strongly correlated to age younger than 35 years. In the multivariate analysis only lymphoblastic histology, stage IV disease and B-symptoms were found to be significantly associated with CNS involvement. It is concluded that CNS prophylaxis should be considered in all patients with lymphoblastic histology and in patients with stage IV B lymphomas other than those of low-grade types.
Attitudes towards autopsy were investigated by a questionnaire given to 60 cancer patients, 30 patients with severe cardiac disease and 132 healthy people without known disease. Eighty-five percent of the patients and 82% of the healthy people had a positive attitude towards autopsy. A majority (65-72%) found that permission should be given by the patient rather than the family. Only 6% of patients and 13% of the healthy people would refuse to give permission to autopsy, 71% and 47% would give permission and 10% and 25% would consent to autopsy under certain conditions. both groups were more reluctant to give consent to the performance of an autopsy on a relative. It is concluded that hospital routine should be changed so that patients should be asked whether they would permit an autopsy to be performed in event of their decease.
One-hundred-and-fifty-one patients with previously untreated multiple myeloma were allocated to treatment with either NOP regimen (mitoxantrone 16 mg/m2 and vincristine 2 mg day 1 and prednisolone 250 mg day 1-4 and 17-20) or M+P regimen (melphalan 0.25 mg/kg and prednisolone 100-200 mg/day day 1-4). Both regimens were repeated every 4 weeks and were scheduled for 1 year. Seventy-seven patients were treated with NOP and 74 patients with M+P. No major clinical differences were recorded between the groups before treatment. Sixty percent of the patients responded (CR+PR) to NOP versus 64% to M+P (NS). The time to progression was 16 months (95% C.L. 14-51) in the NOP group versus 21 months (95% C.L. 15-27) in the M+P group (NS). The median survival was 14 months (7-21) in the NOP group and 31 months (21-43) in the M+P group (p = 0.02). NOP was significantly more toxic than M+P. Seven patients treated with NOP died due to infection and neutropenia and 1 patient died of cardiac toxicity, in contrast to 1 death due to infection and neutropenia in the M+P group. Gastrointestinal toxicity was acceptable in both groups. In conclusion, NOP was inferior to M+P as primary treatment of multiple myeloma.
During the ten-year period from 1.1.1980 to 31.12.1989, thoracotomy was found performed on 22 patients with malignant sarcoma on account of suspected pulmonary metastases. Fourteen patients were submitted to operation on one occasion, nine patients were submitted to operation twice and one patient was operated upon six times. The median age was 21 years (range 7-68 years). The median interval without illness from the primary treatment was 65 weeks (range 7 weeks to 5.8 years). At the first operation, 13 patients had one metastasis, seven had two metastases and one had five metastases. In one patient, a benign lesion was found. Six patients were submitted to renewed thoracotomy on account of pulmonary metastases from 16 to 75 weeks after the first recurrence. The median survival after the first operation was 1.4 years (range 0.4-5.7 years). Five patients (24%) are still free from recurrences from 0.9 to 5 years after the last operation. It is concluded that patients with malignant sarcoma should be followed-up regularly with radiography of the thorax and should be offered operation in cases of pulmonary metastases.
Intracavitary irradiation (ICI) of esophageal cancer is a technique where the radioactive source is placed in the lumen of the esophagus thereby delivering a high local radiation dose to the tumor. ICI is used as single modality therapy for palliation of dysphagia or as a supplement to external irradiation. Dysphagia is hereby relieved in more than 90% of the patients and it appears that survival is improved. The side effects are dose dependent and consist of esophagitis, esophageal ulceration and benign stricture. Fistulae do not seem to occur with increased frequency after ICI, but an existing fistula is claimed to be a contraindication to ICI. The mortality connected with ICI is considerably lower than with tubulation or laser extirpation. It is concluded that ICI is a promising treatment in esophageal cancer both as palliative and curative treatment in combination with other treatment modalities.
In a phase II study, patients with refractory myelomatosis were treated with a combination chemotherapy (NOP regimen): mitoxantrone (bolus injection of 4 mg/m2 on days 1-4), vincristine (continuous infusion of 0.4 mg/24 h on days 1-4) and prednisone (250 mg/d on days 1-4 and 17-20). The treatment was repeated every 4 weeks. Ninety-two patients were treated after they were found refractory to treatment with melphalan and prednisone (and occasionally vincristine) (n = 50) or more intensive treatment regimens (n = 42) including anthracyclines (n = 18). Response (greater than or equal to 50% reduction of M protein) was obtained in 23 patients and minor response (clinical improvement but less than 50% reduction in M protein) in 22 patients. The median duration of the response was 7.5 months. Equal response rates were observed irrespective of the type of previous treatment. The major toxicity was myelosuppression with severe granulocytopenia and infections. However, the frequency decreased throughout the cycles. The NOP treatment is recommended in refractory myelomatosis, especially in patients refractory to other intensive regimens. Patients in a poor clinical condition or with thrombocytopenia before treatment should have a reduced mitoxantrone dose in the first treatment cycles.
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A phase II study of cisplatin and tegafur in recurrent epidermoid head and neck cancer is presented. All patients were treated with cisplatin 100 mg/m2 every 4 weeks. Twenty-nine received tegafur 750 mg/m2 days 2-28 orally and 18 patients, who were unable to take tegafur orally, were treated with tegafur 1,500 mg/m2 intravenously days 2-5. The response rate in the oral group was 28.5% and the median survival 29 weeks. The response rate in the intravenous group was 6% and the median survival was 17 weeks. We conclude that cisplatin and oral tegafur is active against head and neck cancer.
The changes in peripheral blood counts and number of colony forming cells (CFU-c) in the bone marrow after 131I treatment for thyroid cancer were followed in 24 patients. The median WBC declined to 78% and the median blood platelet count to 69% of the pretreatment values after 4 treatments. In 4 patients a moderate pancytopenia developed and in 1 patient additionally treated with chemotherapy and preleukaemia was suspected. In 19 bone marrow samples obtained from 13 patients no difference in number of CFU-c could be found related to cumulated 131I activities given to those patients. In 5 of 7 patients examined between the 9th and the 19th day afer a treatment the number of CFU-c had declined by 50% or more. It is concluded that radioiodine exerts a protracted suppressive effect on the bone marrow which is seldom severe. Agar culture of bone marrow cells with counting of CFU-c was not found to be more sensitive than the peripheral blood counts in predicting bone marrow damage and cannot be recommended for routine use.
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Six of 70 (8.6%) consecutive cases with therapy-related acute nonlymphocytic leukemia (ANLL) or preleukemia had a translocation or deletion with a breakpoint on 21q. Such aberrations were seen in only one of 200 (0.5%) consecutive cases of de novo ANLL examined at our laboratory. The figures reflect a 17.1-fold increased incidence of 21q aberrations in therapy-related ANLL or preleukemia, compared with ANLL de novo. The difference is highly significant (p = 0.003). The increased incidence of 21q aberrations in therapy-related myelodysplastic syndromes was confirmed by literature studies. Band 21q22 was most often involved. Cases with t(8;21), which is strongly associated with the M2 variant of ANLL, or cases with i(21q), which is supposedly due to a centromeric misdivision, were not included in the count. It is concluded that the 21q aberrations are associated with treatment-related ANLL or preleukemia with at least the same degree of specificity as aberrations of #5 and #7.
Thirty-two patients with advanced or recurrent carcinoma of the head and neck were treated with cis-dichlorodiaminoplatinum II (CDDP) 75 mg/m2 every third week as second line chemotherapy. The response rate was 3 per cent with one complete and no partial responders, 16 patients with no change and 10 with progressive disease. Five were not evaluated concerning response. Median time to progression was 12 weeks (confidence limits 10-17 weeks) and median survival time 21 weeks (confidence limits 10 to 33 weeks, range 4 to 109). No severe hematologic toxicity was seen. Two patients had progressive polyneuropathy, one had a severe decline in Cr-EDTA-clearance and in one decline in auditory function was suspected. It is concluded that CDDP in this schedule has no role as second line chemotherapy in advanced cancer of head and neck.