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Biomedical subjects

U Nestle

Publications and source records attributed to U Nestle.

24 records · Page 2Linked to original sources

A palliative accelerated irradiation regimen (PAIR) for advanced non-small-cell lung cancer (NSCLC).

In order to avoid overtreatment in advanced NSCLC we developed a palliative accelerated irradiation regimen (PAIR) applying a total dose of 32 Gy in 10 days with two daily fractions of 2 Gy. This paper reports on a 1-year pilot study carried out in preparation of a randomised trial. Data for the 34 patients receiving PAIR were compared to 179 conventionally irradiated historical controls selected from a pre-existing database according to identical inclusion criteria. Statistical analysis showed that PAIR patients had a significantly longer survival than controls (P = 0.0029). Median survival was 11.8 and 5.8 months, respectively, while 1-year survival was 45.6% vs. 21.2%. Compared to the subgroup of controls who had received the full planned dose of 60 Gy (n = 104) PAIR patients showed no significant difference in survival. In order to adjust for possible imbalances we used a comprehensive blinded prognostic rating design creating one score value per patient out of several known prognostic factors. After adjustment for the resulting prognostic score by means of the Cox proportional hazards model PAIR patients still showed significantly longer survival. We conclude that in advanced NSCLC survival after a palliative short-term regimen appears to be at least equivalent to that following conventional high-dose irradiation.

Carcinoma, Non-Small-Cell Lung↗

[Primary cerebral non-Hodgkin's lymphomas. The results of radiotherapy].

BACKGROUND: In the last years many therapeutic attempts were made to improve the poor prognosis of primary cerebral non Hodgkin's lymphoma. The aim of this study was to report on own experiences concerning this rare disease. PATIENTS AND METHODS: In 1986 to 1994 26 patients were treated for primary cerebral non Hodgkin's lymphoma. 15% were HIV-positive. High-grade non-Hodgkin's lymphomas were diagnosed in 62%. 46% of all cases showed multiple lesions. 23% of our patients received a dose less than 25.5 Gy, 27% received 37.5 Gy (whole brain) and 39% were treated with 51 Gy (37.5 Gy whole brain and 13.5 Gy boost dose). Radiation technique included regular and irregular fields (single dose: 1.5 Gy). RESULTS: 62% of patients achieved a complete or partial remission directly after irradiation, in 4% no change or progression was seen. 31% could not be examined due to their bad status or death. The mean follow-up time for all patients was 19.6 months, the median survival was 3.6 months. The 1-year-survival rate was 41%, 3-year survival rate was 28%. Patients who received a tumor dose of 51 Gy had better survival times in comparison to patients who received less (p = 0.01). Prognostic parameters (Cox regression analysis) were: tumor dose, grading and local result after irradiation. The Karnofsky performance status was not an independent parameter (p = 0.12). Side effects were low. Long-term survivors had relatively good quality of life. CONCLUSION: Taking into consideration the small numbers of patients in all studies all results or conclusions have to be made with great reservations. Despite the high proportion of HIV-positive patients our results are in compliance with other authors using similar therapy protocols. Reports dealing with combined radio-chemotherapy have published good results concerning survival time. But long-term morbidity due to these protocols needs further investigation and has to be awaited.

Adult↗

Relation between local result and total dose of radiotherapy for brain metastases.

PURPOSE: Some studies published recently focused on the improvement of the treatment results of patients with brain metastases who underwent radiation therapy. They evaluated survival as a measure for the expected improvement, but failed to demonstrate a significant benefit from an increased total dose of radiotherapy. This study was targeted to investigate the effect of dose escalation with a different endpoint, the local response. METHODS AND MATERIALS: As a first step, a retrospective analysis of 164 patients treated with a standard regimen of 10 x 3 Gy was performed to find factors correlating with the local result. All patients were systematically followed and underwent regular computed tomography (CT) examinations of the brain after irradiation. The second step was to compare, with respect to local control and survival, 39 patients treated with a total dose of 40-60 Gy with 39 patients treated with the standard regimen selected by means of a matched cohort pairs method. RESULTS: The retrospective analysis showed a dependence of the local result after irradiation on three parameters: diameter of brain metastases, primary tumor, and tumor histology. Small-cell and adenocarcinoma were found to be more radiosensitive than squamous-cell carcinoma. The highest radiosensitivity was found in breast cancer metastases. The matching procedure was performed with respect to those parameters and also the number of brain metastases and total cerebral tumor volume. The resulting groups were absolutely equivalent and differed only with regard to the total dose applied. The local response (complete or partial remission) was 48-52% after 30 Gy vs. 77% after 40-60 Gy (p < or = 0.05). Survival was not significantly different. A further analysis of the dose-response relationships showed the tendency of control probability to increase with total dose. CONCLUSION: This study suggests that there is a rationale for dose escalation in the treatment of brain metastases with radiotherapy, when local control is the aim. However, it seems questionable whether an improvement in survival results.

Brain Neoplasms↗

Low-dose radiotherapy for stage I seminoma: early results.

One hundred and one patients with stage I seminoma were irradiated with total doses of 30, 25.5 and 20 Gy to gradually reduced target volumes (paraaortic, pelvic, and inguinal regions to paraaortic only). Low doses and small target volumes resulted in excellent survival and freedom of recurrence but in more frequent nausea.

Adult↗

[Tumor markers as prognostic factors in non-small-cell bronchial carcinoma].

PURPOSE: Considerations of different therapeutic approaches require a realistic estimation of the prognosis. The usefulness of tumor markers as prognostic indicators was evaluated by means of a multivariate analysis. PATIENTS AND METHODS: The data of 300 patients who had been irradiated for their primary tumor were analysed retrospectively. The serum concentrations of CEA, SCCA, NSE, and LDH were available before treatment and 3 months thereafter in a sufficient number of cases. The prognostic factors for survival and progression-free survival resulting from univariate tests were further evaluated by a Cox-proportional-hazards model. RESULTS: The serum levels of the particular tumor markers were pathologically elevated in 25 to 36.5% of the cases. Their values correlated with the stage of the disease and separately the N-stage too. A normalization of increased marker levels after irradiation occurred in 37.5 to 67% of the cases. Survival of patients with increased pretherapeutic values of CEA, SCCA, and LDH was significantly worse compared to those with normal values. In the case of a post-therapeutic return to normal levels, prognosis was significantly better than for those where the elevation persisted. However, after inclusion of all other parameters in multivariate analysis the tumor markers were meaningless. Karnofsky-performance status, total dose of radiotherapy, stage of the disease, and weight-loss evolved as independent prognostic factors for survival. For progression-free survival only stage of the disease was important. All subgroup analyses (restriction on patients with favorable prognosis) showed the same results. CONCLUSIONS: A prognostic importance of NSE could not be demonstrated. CEA, SCCA, and LDH were univariate predictors for survival and progression-free survival. But they proved to be dependent on the stage of the disease and were not confirmed as independent variables in the Cox-model. Their importance during the follow-up is diminished by the frequent lack of therapeutic approaches in the case of disease progression. Certainly a more favorable prognosis in case of a post-therapeutic normalization of previously elevated values was found.

Biomarkers, Tumor↗

Chromosomal aberrations in patients with primary biliary cirrhosis.

Chromosomal aberrations in untreated lymphocyte cultures, bleomycin (BLM)-induced aberrations and sister chromatid exchanges (SCE) in the peripheral blood lymphocytes of 11 patients suffering from primary biliary cirrhosis (PBC) and 14 matched control individuals were analysed. The lymphocytes of the PBC patients had on average a lower mitotic index (2.3) compared with controls (3.5) in the untreated cultures. The mean baseline rate of aberrations of the cultured lymphocytes of the patients was 5.3 aberrations per 100 metaphases (%); this was significantly different (P = 0.0291) from that of the controls with a mean of 2.3%. In lymphocytes of the patients and controls, most of the aberrations observed took the form of gaps; there was an almost equal breakage rate in both groups (0.5% and 0.4%, respectively). The average number of mitoses with aberrations in the PBC patients studied was double that of the controls (4.9% and 2.3% respectively, P = 0.0323). The mean number of the BLM-induced aberrations was 54.0% and 27.7% for the lymphocytes of the patients and controls, respectively. The mean number of the aberrant mitoses in the BLM cultures was 6 times higher than that of the untreated cultures for both groups, 25.7% and 14.6% respectively (P = 0.018). The chromosomal distribution of baseline and induced aberrations was not random. The PBC patients had a mean number of 8.7 SCE per mitosis, which was significantly higher than the SCEs in the controls (6.3 SCE per mitosis; P = 0.0156). The evidence suggests that the chromosomes of the lymphocytes of PBC patients may be less stable than those of the control individuals in this study.

Adult↗