PubMed HealthSearch

Biomedical subjects

E Dühmke

Publications and source records attributed to E Dühmke.

At least 19 recordsLinked to original sources

Influence of clodronate on breast cancer cells in vitro.

UNLABELLED: One of the major therapies of bone metastasis is administration of clodronate. But the influence of clodronate alone on tumour cells is not quite clear. Radiotherapy and administration of clodronate increasingly are used in combination. The influence of clodronate on radiosensitivity of tumour cells is not known. METHODS: We used MDA-MB-435S and MCF-7 cells (breast cancer) in vitro and exposed the cells to clodronate in different concentrations and different short application times. In a second experiment we added graded doses of radiotherapy to the cell cultures. All experiments were done under standard conditions of the colony test. RESULTS: At different concentrations and different incubation times clodronate is able to reduce the cell survival of MDA-MB-435S cells, but not of MCF-7 cells. Even very low concentrations of clodronate in the cell culture medium are sufficient to reduce the tumour cell survival of MDA-MB-435S down to 59%. This reduction is time and concentration dependent. Using irradiation, clodronate has definitively no influence on the radiosensitivity of MDA-MB-435S cells in vitro, but the shoulder of the survival curve of MCF-7 cells is markedly reduced, demonstrating reduced repair of sublethal radiation damage.

Aged

[Indication and technic of radiation therapy in advanced high malignancy non-Hodgkin lymphoma].

The role of radiotherapy in the treatment of advanced high-grade NHL is not defined. Most experiences come from retrospective analyses or prospective randomized studies not evaluating primarily the indication of radiotherapy. Longtime results of the German-Austrian Multicenter Study are lacking. Possibilities of the radiotherapy consists of the radiotherapy of prior involved or bulky or slow responding regions in the adjuvant situation. In high risk groups, prophylactic brain irradiation may be useful. In recurrent patients, radiotherapy offers many possibilities of local palliation.

Female

[Use of G-CSF (Neupogen) in multimodal treatment in radiotherapy].

BACKGROUND: Therapy-induced leukopenias with corresponding consequences repeatedly occur in radiotherapy using combined modalities treatment. In radiotherapy, where G-CSF (granulocyte-colony-stimulating-factor) is not licensed, G-CSF has been used successfully under individual circumstances. These results were confirmed in several studies with small patient groups. The aim of this study was to check former results in a larger patient group, to verify postulated side effects and specially to define a cost-effective schedule in the treatment with G-CSF (Neupogen). PATIENTS AND METHODS: In this surveillance trial 50, partially previously treated patients with different malignant tumors were treated with G-CSF. According to the probability of a leucocytosis lower than 1000/mm3, G-CSF (Neuropogen) was already given at leukocyte values lower than 2500/mm3 (500/mm3 bis 2450/mm3). It administered subcutaneously every other day, based on body weight until reaching normal leucocyte levels. RESULTS: In 92% of the patients the increase of leucocytes occurred in the first 24 hours. On average G-CSF was given 4.9 times per patient. Patients without prior therapies or less complex therapies needed less G-CSF applications (3.5 to 5.8 applications). Due to individually varying leucocyte courses the G-CSF therapy was started with leucocyte values between 500/mm3 and 2450/mm3. Patients who were treated with up to 3 G-CSF applications had higher leucocyte levels than those with 4 or more applications (1620/mm3 to 1250/mm3). Leucopenia related infections, therapy interruptions or break-offs did not occur. Besides light "flu like" symptoms in 14% of the patients, no side effects were observed. CONCLUSIONS: When a decrease of leucocyte values lower than 1000/mm3 is expected, the most cost-effective treatment is given when starting the interventional G-CSF administration already at leucocyte values around 1600/mm3. Leucopenias can be treated effectively, with little side effects and in a cost-effective way when G-CSF is given on time.

Adult

BEACOPP: a new regimen for advanced Hodgkin's disease. German Hodgkin's Lymphoma Study Group.

The BEACOPP chemotherapy regimen for advanced Hodgkin's disease employs a rearranged schedule permitting a shortened three-week cycle. With haematological growth factor support, the dosages of cyclophosphamide, etoposide and adriamycin could be moderately escalated. The 3-armed multicentre HD9 trial (recruitment 1993-1998; 1300 patients randomised) aimed to compare BEACOPP with the standard COPP/ABVD chemotherapy and to detect and measure the gain in efficacy, if any, due to moderate dose escalation of BEACOPP. Eight cycles were given, followed by local irradiation. The most recent interim analysis, with 689 evaluable patients, circa 40% of all expected events and a median observation time of 27 months, showed significant differences in progression rate (P) and in two-year freedom from treatment failure (F) between the treatment arms, with escalated BEACOPP (P = 2%, F = 89%) better than baseline BEACOPP (P = 9%, F = 81%) better than COPP/ABVD (P = 13%, F = 72%). Survival was not significantly different. Acute toxicity was more severe due to dose escalation, but remained manageable. These preliminary results suggest that BEACOPP improves efficacy. Moderate dose escalation is feasible with G-CSF support and appears likely to make a worthwhile improvement in the cure rate. The results must await confirmation (or otherwise) by the final analysis including all randomised patients and sufficiently mature data.

Adolescent

Biomodulative effects induced by 805 nm laser light irradiation of normal and tumor cells.

The influence of light emitted from a diode laser centred at lambda = 805 nm was investigated on murine skeletal myotubes (C2), normal urothelial cells (HCV29), human squamous carcinoma cells of the gingival mucosa (ZMK) and urothelial carcinoma cells (J82) in a computer-controlled irradiation chamber. Cells were treated with varying fluences between 0 and 20 J cm-2. The response was tested by analysis of the mitotic index using single cell counting after Orcein staining and proliferation index based on BrdU incorporation during DNA synthesis. While the mitotic index of C2, HCV29 and J82 cells increased at a fluence of 4 J cm-2, irradiation with fluences of 20 J cm-2 resulted in a slight decrease. ZMK tumor cells showed a decrease of the mitotic index with both fluences. No significant differences could be determined when using irradiances between 10 mW cm-2 and 150 mW cm-2. The BrdU test after irradiation showed no significant effects compared to the controls in each cell line.

Animals

Randomized trial with early-stage Hodgkin's disease testing 30 Gy vs. 40 Gy extended field radiotherapy alone.

PURPOSE: To evaluate whether or not a total dose (TD) of 30 Gy is sufficient for treatment of assumed subclinical Hodgkin's Disease compared to 40 Gy TD with early stage Hodgkin's Disease (ESHD). METHODS AND MATERIALS: In a prospective multicenter trial, 376 patients with laparotomy-proven ESHD stages PS IA to PS IIB without risk factors such as large mediastinum, massive splenic involvement, extranodal disease, elevated erythrocyte sedimentation rate (ESR), and/or three or more involved lymph node areas were randomly allocated either to receive (ARM A) 40 Gy TD extended field-radiotherapy (EF-RT) or (ARM B) 30 Gy TD EF-RT plus 10 Gy TD involved field-radiotherapy (IF-RT), both arms without any chemotherapy. Three hundred sixty-six of these patients were evaluable for early and long-term response, such as remission status, freedom from treatment failure (FFTF), and overall survival (OAS). For quality control, all planning and verification films as well as dose charts were prospectively reviewed by a panel of four experts, all heads of a radiotherapy department, where protocol violations (PV) were seen either with regard to errors in treatment technique, treatment volume, in TD and/or in dose/time-relationship. RESULTS: Treatment resulted in a complete remission (CR) of 98%; in a 5-year FFTF of 76%, and a 5-year OAS of 97%. There was no difference between the two arms in favor of 40 Gy EF compared to 30 Gy EF regarding FFTF and OAS, without any in field relapse throughout the EF volumes. Expectedly, 5-years FFTF was significantly influenced by the quality of radiotherapeutical procedures: 70% with protocol violations (PV) vs. 82% without PV. CONCLUSION: Subclinical involvement in ESHD without risk factors is sufficiently treated by a TD of 30 Gy without chemotherapy, leading to a 5-years FFTF of 82% and a 5-year OAS of 97% in a multicenter treatment setting, where quality assurance is mandatory.

Adolescent

[Radiotherapy of lymphogranulomatosis in adulthood].

Hodgkin's disease is a highly curable disease. In clinical stages I to II (A and B) of Hodgkin's disease radiotherapy alone is curative in more than 80% of the patients. Challenges remain, however, to further refine our therapy, identify and cure the minority of patients who continue to succumb to this disease. Innovative therapies or significant modifications of current standard therapies are very much needed. The sequential approach of drugs and radiation therapy could reduce the length (not the dose!) of primary chemotherapy as well as the extent and the dose of additive radiation. An effective polydrug regimen not including alkylating agents may avoid the risk of infertility and second malignancies. In patients with Hodgkin's disease presenting with massive mediastinal involvement the efficacy of combined modality therapy has been proven by all research groups. In patients with clinical stage III (A and B) as well as selected stage IV Hodgkin's disease the percentage of nodal relapse is not negligible even after a very effective chemotherapy. Radiotherapy limited to the initial site(s) of bulky lymphoma is not enough to avoid the risk of nodal relapse in adjacent nodal areas. And here, too, avoiding the administration of alkylating agents may drastically reduce some of the serious long-term toxicities.

Antineoplastic Combined Chemotherapy Protocols

[Total skin electron beam irradiation in cutaneous T-cell lymphoma].

PURPOSE: Patients with cutaneous T-cell lymphoma are treated in Germany mostly by dermatological local therapy like corticosteroids or PUVA-irradiation. Total skin electron beam irradiation is used rarely, even though it has a potentially curative character. We present an analysis of patients, who received a total skin electron beam irradiation after having progressive disease following other treatment modalities. PATIENTS AND METHODS: Twenty-one patients (mean age 58.9 years) in different stages were treated (stage IB and IIA n = 4, stage IIB n = 8, stage III n = 3, stage IV n = 6). All patients had progressive disease under other forms of local therapy. The irradiation was performed from 6 directions per hemibody using 2 axial fields which have each an 18 degree angle to the horizontal level. Six and 7 MeV fast electrons were used. Total dose was between 8 and 36 Gy in single dosis of 1 x 4 up to 5 x 2 Gy per week. In underdosed areas and areas of tumors of the skin boost irradiation with small fields was given. RESULTS: All patients had a good tumor regression (complete remission: n = 10, partial remission: n = 11). With the follow-up between 4 and 93 months total- and recurrence-free survival was 18 and 7 months (median). Patients in early stages with slow but complete remission of the symptoms had the best prognosis. Because of the small case number there was no significant difference between the groups. There were no severe side effects of the radiotherapy noted. CONCLUSION: Our analysis shows on a small patient number, that total skin electron beam irradiation has a good palliative effect on patients who have progressive disease following other types of treatment like PUVA or corticosteroids. The recurrence-free survival of 2 out of 4 patients with early stage disease (I-IIA) up to 93 month shows the potentially curative character of the treatment.

Adult

[Adjuvant intraoperative radiotherapy of stomach carcinoma].

In order to evaluate the role of adjuvant IORT in the treatment of resectable gastric carcinoma, we carried out a randomized trial comparing surgery and surgery+adjuvant IORT. The study included 115 patients within a 74-month period, 51 of them received a single application of 28 Gy to the celiac axis. Patients were comparable with regard to age, sex, tumor stage and operative morbidity. The difference in mean survival time (IORT: 26.9 months vs. non-IORT, 30.8 months) and tumor-related death in the long-term course (mean follow-up period 29.2 months) with 29.4% (15/51) in the IORT-treated patients vs. 31.2% (20/64) in non-irradiated patients did not reach significance.

Combined Modality Therapy

Use of surface markers for MR radiotherapy planning.

PURPOSE: For the precise planning of radiotherapy treatment ports, the delineation and control of their borders has to be performed with X-ray and other imaging procedures before and during the therapy. MATERIALS AND METHODS: Conventional planned therapy ports are checked with the help of MR-imaging with new gel-markers, as a further development to formerly used fluid filled tubes, on the skin of the patient in different regions. We describe the essentials of these gels and report about their first practical use. RESULTS: Principal considerations to the technique and practical applications are given with imaging examples. The essential physical qualities of the gels are introduced with separate NMR experiments. It turns out, that multiplanar MR-imaging in combination with field markers on the skin is a fast simple and useful help for the control and the improvement of treatment planning. CONCLUSION: MR-imaging with gel-markers on the skin in many cases can show the tumor and the field-ports in one picture. Thus the therapy planning is refined with simple means. On the one hand the target volume can be seized completely and on the other hand sensitive organs can better be protected.

Humans

[A comparative consideration of para-aortic fields within the framework of the German Hodgkin's Disease Study].

In 33 patients of the multicenter German Hodgkin's Lymphoma Study Group the field borders of the paraaortic field were compared computer-assisted. It was seen that fields are chosen often too small or too large, though precise description of the fields is given in the protocol. In these patients the para-aortics were irradiated exclusively as extended field region. In addition to the above observation the clipping of the spleen pedicle provides the optimal help for correct positioning of this field. Overall a very low frequency of lymphatic clipping is observed, though clinical needs are obvious.

Aorta

Quality control review for radiotherapy of small breast cancer: analysis of 708 patients in the GBSG I trial. German Breast Study Group (GBSG).

Within six years between November 1983 and December 1989 the German Breast Cancer Study Group (GBSG) conducted a prospective multicenter trial on the treatment of pT1 pN0 M0 breast carcinoma. Out of 1036 eligible patients from 69 hospitals, a total of 733 underwent breast preservation surgery and postoperative radiotherapy. A detailed quality control (QC) screening of 708 available radiotherapy records was performed by the radiotherapy reference center. The following quality control scoring system was used for all radiotherapy variables: Radiotherapy treatment "completely according to study protocol" (QC score = 0); "acceptable protocol deviations" (QC score = 1); "unacceptable protocol violations" (QC score = 2); the "overall QC score" was the worst judgement for any single quality control criterion, while the "total QC score" was the summation of all single quality control scores (range: 0 to 14). 292 (41.2%) patients were treated per protocol; 290 (41.0%) had acceptable protocol deviations; and 126 (17.8%) had unacceptable protocol violations. 107 (84.9%) single violations, 15 (11.9%) combinations of two, three (2.4%) combinations of three, and one (0.8%) combination of four unacceptable violations were observed. 564 (79.4%) patients achieved a total QC score of < or = 2, 124 (17.5%) of 3 to 5, and 20 (2.8%) of > or = 6. The criterion "radiotherapy treatment duration" had the highest rate of protocol violations, 67/708 (9.5%); other quality control criteria with protocol violations were "radiotherapy reference dose" (27 = 3.8%), "radiotherapy treatment initiation" (15 = 2.1%) and "other protocol violations" (33 = 4.7%). No protocol violations were observed for the criterion "target volume coverage". The protocol compliance improved slightly during the conduct of the study. Institutional differences in protocol compliance were observed depending upon the accrual rate, the institutional treatment preference and between academic and non-academic hospitals. After a short median follow-up of 48 months, differences in protocol compliance, i.e. protocol violations, have not resulted in a reduced disease-free survival; however, the final prognostic evaluation of the quality control review may require longer follow-up and eventually different treatment endpoints to be analyzed.

Breast Neoplasms

[Diabetes insipidus and breast carcinoma--the importance of NMR tomography (MRT) in therapy planning].

In patients with advanced breast cancer the incidence of diabetes insipidus is between 0.1% and 0.9%. Satisfactory symptomatic relief can be obtained with Desmopressin-acetate. In the presence of this symptom complex magnetic resonance imaging (MRI) can aid in the detection of metastases to the posterior pituitary. By the use of magnetic resonance imaging, the incidence for and implementation of local radiotherapy can be firmly grounded.

Adult