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Biomedical subjects

M Stuschke

Publications and source records attributed to M Stuschke.

At least 73 records · Page 4Linked to original sources
PubMed1997

Chemo-radiotherapy for locally advanced head and neck cancer--long-term results of a phase II trial.

The feasibility and effectiveness of a combined chemo-radiotherapy treatment modality for locally advanced head and neck cancer was tested in a phase II trial. Between 1990 and 1993, 74 patients (20 female/54 male) with head and neck cancer stage III (n = 12) and IV (n = 62) were treated with accelerated radiotherapy (72 Gy) and simultaneous chemotherapy (5-FU, folinic acid, mitomycin C). The median follow-up time was 43 months (1-72). Complete remission (CR) was absent in 76% (56/74) of patients and, after subsequent resection of residual lymph nodes, another 8 patients achieved CR. The cumulative local control rate was 72% and disease-specific survival rate was 59% at 4 years. Two patients died with treatment-related conditions (pancytopenia, larynx oedema). By multivariate analysis, only lymph node status was an independent parameter for local control (P = 0.04). This treatment was feasible and toxicity was not a treatment-limiting factor. As a consequence, a German multicentre phase III trial was initiated in 1995.

Adult↗
PubMed1997

Ultrastructural evidence for divergent and alternating differentiations in spindle cell sarcoma xenografts.

Seven spindle cell sarcomas, 5 poorly differentiated ones and 2 moderately well differentiated ones, were established on nude mice and long term passaging was done. Sarcoma strains were analysed electron microscopically in an attempt to get further insight in spindle cell sarcoma differentiation pathways. Ultrastructurally, the tumours were classified as malignant peripheral nerve sheath tumour (3/7), leiomyosarcoma (2/7), rhabdomyosarcoma (1/7), and spindle cell sarcoma not otherwise classifiable (1/7). Undifferentiated tumour cells including fibroblastoid ones predominated in most xenografts, whereas cells harbouring cytoplasmic specificities tended to be few in number. Nevertheless, divergent differentiations exhibiting unusual double or triple patterns could be documented ultrastructurally in 12/30 xenografts with juxtaposed myomatous as well as nerve sheath-like cells and, in addition, histiocytoid (MFH-like) elements in 3 of the xenografts. Moreover, sarcoma strains alternated fine structural constellations in the course of passaging, whereby different phenotypes, myomatous, nerve sheath-like, unspecific, or mixed ones, succeeded one another. These findings pursue recent immunohistochemical data on multidirectional sarcoma differentiation by means of electron microscopy. They, furthermore, fit well into the concept of multipotential stem cells as progenitors in mesenchymal differentiation and suggest microenvironment to play a modifying role in the expression of cell differentiation.

Adult↗
PubMed1997

[CT angiography of the pulmonary artery in patients with bronchial carcinoma].

The aim of the study was to evaluate 3D computed tomography (3D-CT) for the visualization of tumor extent with respect to the infiltration of the pulmonary arteries in patients with locally advanced small and nonsmall-cell lung cancer. A total 61 examinations in 40 patients with bronchial carcinoma were performed with contrast-enhanced (150 ml injected with 4 ml/s after bolus tracking) 2 mm spiral CT (pitch 1.5, increment 1 mm) (Somatom Plus4, Siemens AG, Germany). Using the implemented software cine mode, surface shaded display (SSD), and maximum intensity projection (MIP), reconstructions of the pulmonary arteries and the tumors were generated. In comparison to conventional spiral thoracic CT, the optimized cross-sectional images of the mediastium represented a benefit with the technique described, and this can help to diagnose vessel infiltration and may therefore be of value for pre- and post-therapeutic staging in modern stage-adapted multimodality treatment programs.

Angiography↗
PubMed1996

Differentiated thyroid cancer. Impact of adjuvant external radiotherapy in patients with perithyroidal tumor infiltration (stage pT4).

BACKGROUND: The role of adjuvant external radiotherapy in the survival of patients with differentiated thyroid cancer (DTC) is controversial. To our knowledge, no attempt has been undertaken thus far to assess the impact of this therapy with respect to the papillary and follicular types of thyroid cancer as separate entities. METHODS: Between 1979 and 1992, 238 patients with differentiated papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) with Stage pT4 have been treated and followed in our clinic. One hundred sixty-nine patients free of metastases at the final staging, which was performed after the second radioiodine therapy, were included in this study. The standard treatment comprised total thyroidectomy, ablative radioiodine therapy, and thyroid-stimulating hormone-suppressive therapy with levothyroxin. Ninety-nine patients free of disease after the final staging received additional external radiotherapy to the neck (with a dose of 50-60 Gy), whereas the remaining 70 patients were treated with the standard treatment protocol only. Distributions of age, sex, and follow-up time were comparable in both irradiated and nonirradiated groups. Multivariate analysis of the influence of age, sex, histologic subtype, and lymph node status as well as of external radiotherapy on the time to first locoregional and distant failure (LDF), and the time to locoregional recurrence (LR), was accomplished using Cox's proportional hazard model. RESULTS: In patients with DTC, external radiotherapy was a predictive factor for improvement of both LR (P = 0.004) and locoregional and distant failure (P = 0.0003). When the time to first locoregional and distant failure was calculated separately for patients with PTC and FTC, there was a significant difference in the PTC group in favor of irradiated patients (P = 0.0001), whereas there was no effect of external radiotherapy in the FTC group (P = 0.38). Further analyses disclosed that this effect was significantly present only in patients with PTC and lymph node involvement (P = 0.002), whereas those without lymph node involvement did not benefit from an additional adjuvant radiotherapy (P = 0.27). Because none of the patients younger than age 40 years died due to the disease nor had progressive disease during follow-up, we reassessed our results in patients older than age 40 years. The effect of external radiotherapy could be confirmed in this subgroup of patients (P = 0.0009) and in the subgroup of lymph node positive patients older than age 40 years with invasive PTC (P = 0.01). CONCLUSIONS: In addition to total thyroidectomy, treatment with radioiodine, and TSH-suppressive therapy with thyroid hormone, adjuvant external radiotherapy improves the recurrence-free survival in patients older than age 40 years with invasive PTC and lymph node involvement.

Adenocarcinoma, Follicular↗
PubMed1996

Induction of DNA double-strand breaks by ionizing radiation at the c-myc locus compared with the whole genome: a study using pulsed-field gel electrophoresis and gene probing.

Ionizing radiation-induced double-strand breaks (dsb) in a human colon carcinoma-derived cell line COLO320HSR were determined from the fragment size distribution of non-specifically labelled DNA and Sfi I restriction enzyme-digested DNA uniformly labelled with a c-myc probe. The dose-effect relation for the induction of DNA dsb was linear with no significant difference between slopes for the curves in the whole genome (7.2 +/- 0.3 x 10(-9) dsb/bp/Gy) and in the 130 kbp restriction fragments containing c-myc (6.5 +/- 0.5 x 10(-9) dsb/bp/Gy). The size distribution of the c-myc fragments showed deviations from the random-breakage model, indicating heterogeneity of dsb induction at this locus.

DNA↗
PubMed1996

Combined preoperative chemotherapy and radiotherapy in patients with locally advanced esophageal cancer. Interim analysis of a phase II trial.

PURPOSE: The prognosis of patients with locally advanced esophageal cancer (LAEC) remains poor when treated with local modalities. An intensive preoperative program with chemoradiotherapy was used to evaluate the curative resection rate, pathologic response, and survival of patients with LAEC. PATIENTS AND METHODS: Ninety patients with LAEC were treated preoperatively with chemotherapy (three courses of fluorouracil, leucovorin, etoposide, and cisplatin [FLEP]) followed by concurrent chemoradiotherapy (one course of cisplatin plus etoposide in combination with 40 Gy of radiation). Transthoracic esophagectomy was performed 4 weeks after the end of radiation. RESULTS: Seventy-two patients were included in this evaluation. Forty-four (61%) underwent a complete tumor resection, and 16 (22%) had no tumor in the resected specimen (pathologic complete response [PCR]). The operative mortality rate was 15%. At a median follow-up time of 22 months (range, 12 to 41), the median survival duration of all 72 patients was 17 months (range, 1 to 41+). The calculated survival rates at 3 years were 33%, 42%, and 68% for all patients, patients after complete resection, and patients with PCR, respectively. CONCLUSION: This combined treatment modality is active in LAEC, with a PCR in 33% of the patients undergoing surgery. The results appear improved compared with those reported with surgery alone, by approximately doubling the 3-year survival rate. The high efficacy of preoperative chemoradiation warrants evaluation of the role of surgery in LAEC.

Adenocarcinoma↗
PubMed1996

[Radiotherapy of primary extranodal non-Hodgkin's lymphoma of the head and neck region. Results of a prospective multicenter study. Study Group NHL: early studies].

PURPOSE: To evaluate the long-term outcome of patients with limited-stage primary extranodal lymphoma of head and neck treated with definitive radiotherapy in low-grade and a combined radio- and chemotherapy in high-grade lymphoma. PATIENTS AND METHODS: Between January 1986 and August 1993, 63 patients with primary extranodal Non-Hodgkin lymphoma of head and neck region, stages IE and IIE were treated with radiotherapy. The histological classification followed the Kiel classification, staging the Ann Arbor classification. PATIENT CHARACTERISTICS: 33 male, 30 female; age 18 to 84 years; tumor localisation: tonsils 26, nasopharynx 7, oropharynx 8, paranasal sinus 11, salivary glands 7, floor of mouth/gingiva 3, larynx 1. Mean follow-up is 74 months. Low-grade lymphoma in stages I and II CS were treated with definitive radiation therapy according to the concepts of epithelial tumors of the same localisation (target volume and technique). The adjuvant dose was 30 Gy and in the tumor volume 40 Gy, 2 Gy daily. 28 patients were registered, 18 in stage I and 10 in stage II. High-grade lymphoma were treated with definitive radiation therapy according to the concepts of epithelial tumors of the same localisation, too. The dose was 40 respectively 50 Gy, followed by 4 courses of adjuvant chemotherapy with CHOP. Thirty-five patients were enrolled, of whom only 10 received chemotherapy. RESULTS: The overall 5-year survival rates were for low-grade 67% and for high grade lymphoma 88%. The corresponding relapse-free survival rates were 54/68%, respectively. Only 1 patient failed within the irradiated target volume. Recurrences occurred at sites distant to the irradiated volume in nodal and extranodal regions. Prognosis was influenced by histologic grade. Significant trends were not observed for other potential pretreatment parameters (age, stage, localisation, bulk). CONCLUSIONS: In stage I or II patients with low malignant non-Hodgkin's lymphoma of the head and neck, initial management with definitive external radiotherapy is appropriate and probably curative. In high-grade lymphoma of clinical stage IE with nonextensive tumor size definitive radiotherapy is possible in curative intention. Primary chemotherapy followed by radiation is probably preferable.

Adolescent↗
PubMed1996

[Water-filtered infrared-A-hyperthermia combined with radiotherapy in advanced and recurrent tumors. Initial results of a multicenter phase I-II study].

BACKGROUND: Water-filtered infrared-A-radiation (IR/A-HT) can be used to heat superficial malignant tumors. A prospective multicenter phase I-II study was conducted to evaluate toxicity and efficacy of IR/A-HT combined with external beam radiotherapy (RT). PATIENTS, MATERIAL AND METHODS: From December 1991 to June 1994, a total of 53 patients with 58 malignant lesions were entered in the study. There were 14 primary, 36 recurrent and 8 metastatic tumors which were located in the head and neck region (14), chest wall (31), abdominal wall (2) and the extremities (11). The mean tumor volume was 100 cm3. IR/A-HT was applied 1 to 2 times per week with up to 3 IR/A-HT-radiators directly before or after external RT for 1 hour at 40.5 to 44 degrees C. Temperatures were controlled at various locations at the skin surface and invasively at depth. RESULTS: IR/A-HT was well tolerated: in 31 (53%) lesions acute (pain, pulse or blood pressure changes, increased skin reaction etc.) and in 25 (43%) chronic side-effects (atrophy, telangiectasis, fibrosis etc.) were noted; usually the toxicity was minor and temporary. At 3 months FU, 32 (55%) lesions achieved a local CR and 19 (35%) a PR; at 12 months FU, 25 (43%) had persistent CR; 16 patients (18 lesions) were deceased and 3 (4 lesions) not yet in FU. In univariate analysis the following prognostic factors for CR at 3 or 12 months FU were found: Karnofsky, metastatic status, tumor size, total RT-dose, thermal parameters T min(av) and T mean. For acute toxicity maximum temperature Tmax(av) was prognostically decisive. Significant differences were also found when considering the "quality of the HT-application". The microwave technique was superior to the infrared-A-HT-technique with regard to the penetration depth of energy deposition. CONCLUSIONS: Water-filtered infrared-A-radiation can be safely and effectively applied to heat localized superficial tumors (up to 1 cm depth). To increase the area of HT application multiple infrared-A-radiators have to be combined. A multi-element-system is in progress.

Abdominal Muscles↗
PubMed1995

Radiation-induced apoptosis in human sarcoma and glioma cell lines.

Six human soft-tissue sarcoma and 14 glioma cell lines, exhibiting considerable differences in radioresponsiveness and histological grade of differentiation of the parental tumour, were examined with respect to apoptosis development after irradiation with 60Co gamma-rays. After test doses of 6 and 25 Gy, significant changes characteristic of apoptosis occurring within 6 to 30 hr were exhibited by only 2 differentiated sarcoma cell lines, EL7 and ESS2. The characteristic internucleosomal fragmentation of DNA was detected as early as 6 hr after exposure of subconfluent monolayer cultures to 6 Gy. It was limited to cells that had detached from the culture plate, whereas adherent cells showed random degradation of DNA, namely after higher doses (25Gy) or longer incubation times (30 hr). As assessed by fluorescence microscopy of unfixed cultures stained with Hoechst 33342 and propidium iodide, the proportion of cells showing apoptotic bodies in non-irradiated controls was < 0.1% and 0.3% for EL7 and ESS2, respectively. The dose-response relationship for apoptosis was determined at 9 hr post-irradiation. After 2 Gy, the percentage of apoptotic cells was elevated to 3.4% in EL7 and 4.5% in ESS2 cultures. Saturation was obtained above 6 Gy, with 8.4% apoptosis in EL7 and 15% in ESS2 after 25 Gy. Taken together, rapid ionizing-radiation-induced apoptosis seems to be limited to a subgroup of sarcomas and is unlikely to occur in gliomas.

Animals↗
PubMed1995

Heterogeneity in the fractionation sensitivities of human tumor cell lines: studies in a three-dimensional model system.

PURPOSE: Current concepts to optimize the therapeutic gain of radiotherapy by hyperfractionation assume that human tumors are less sensitive to fractionation than late reacting normal tissues. The aim of this study was to investigate the extent of the intercell line heterogeneity of fractionation sensitivity of a wide variety of human tumor cell lines in a three-dimensional model system under fully oxic conditions using schedules with one to eight fractions. Biological characteristics of the tumors that correlate with fractionation sensitivity should be identified. METHODS AND MATERIALS: A total of 21 cell lines from human tumors maintained as multicellular spheroids consisting of 1000-1500 cells were given fractionated irradiation within a total treatment time of maximally 50 h. Complete dose-spheroid control curves were determined for each fractionation scheme. The spheroid control data were adequately described by the linear quadratic model assuming Poisson statistics. In addition, the induction of a G2 block by a fractionated test dose of seven 3 Gy fractions given at 6-h intervals was determined in spheroid cells using flow cytometry of propidium bromide stained cell nuclei. RESULTS: The fractionation sensitivities of human tumor cells in multicellular spheroids could be characterized by alpha/beta values, ranging from 2.8-37 Gy in dependence on the cell line. The log normally distributed alpha/beta values were positively correlated with the percentage increase in G2/M phase after the fractionated test dose compared to the controls (r = 0.72, p < 0.01), and were associated with the degree of tumor differentiation (p = 0.01, ANOVA F-test). No significant correlation between the log (alpha/beta) values and the surviving fractions at 2 Gy (SF2) or the total doses with 2 Gy per fraction necessary to control 50% of the spheroids (SCD50) was observed. Despite the intercell line variability of the alpha/beta values, the SCD50 values of the different cell lines, given with one and eight fractions or one fraction and 2 Gy per fraction, were closely associated (Spearman rank correlation coefficients: r = 0.89 or r = 0.90, p < 0.0001). CONCLUSION: Human tumor cell lines showed a marked heterogeneity in the fractionation sensitivity when irradiated as multicellular spheroids and assayed in situ using the spheroid control end point. Therefore, the therapeutic gain of altered fractionation also depends on those biological characteristics of each individual tumor that affects its fractionation sensitivity. Parameters that correlate with fractionation sensitivity of the tumor lines in the spheroid system were identified as grade of tumor differentiation and percentage increase in G2/M cells at the end of an eight-fraction schedule.

Humans↗
PubMed1994

Local recurrences of soft tissue sarcomas in adults: a retrospective analysis of prognostic factors in 102 cases after surgery and radiation therapy.

Between 1974 and 1990, 102 adult patients (age 18-86 years) with the diagnosis of a soft tissue sarcoma (STS) were treated with photons and/or electrons in combination with surgery. The total doses in the initial treatment volume (second order target volume) was 40-50 Gy. For the coning down volume (first order target volume) the median total dose was 59 Gy (range 45-72 Gy). A total of 18% (18/102) local failures was observed. In multivariate analysis, prognostic factors for the occurrence of a local failure were identified as follows: treatment of a primary or recurrent STS (P = 0.02), total dose (P = 0.025) and tumour grade (P = 0.05). Mode of surgery, tumour size (trunk versus extremity), pre- or postoperative radiotherapy, combined chemotherapy and tumour size (T1 versus T2) had no significant impact on the local relapse-free survival. These data give further evidence that combined surgery and radiotherapy is an effective modality in treatment of soft tissue sarcomas.

Adolescent↗
PubMed1994

DNA content as a predictor of clinical outcome in soft tissue sarcoma patients.

The prognostic relevance of cellular DNA content has been shown for a variety of human malignancies. However, only a few studies concerning soft tissue sarcomas have been published. Biopsies of 81 patients with soft tissue sarcomas, referred for primary or secondary surgery, were analysed by flow cytometry to determine cellular DNA content of tumours. Most patients (60/81) already had one or more local recurrences at the time of first presentation at Essen University. The median age of the patients was 45 years (range 14-79). 44 (54%) patients had euploid and 37 (46%) had aneuploid tumours. Age, sex, and tumour localisation (trunk versus extremity) were equally distributed between euploid and aneuploid sarcoma patients. The median follow-up was 69 months (range 9-312). The median survival time for euploid and aneuploid tumours was 84 and 30 months, respectively (P < 0.0005). In the univariate analysis, ploidy, S-phase percentage, localisation and tumour grading were significant predictors of survival, whereas in the multivariate analysis, only DNA content and tumour localisation were independent prognostic variables for survival.

Adolescent↗
PubMed1994

Efficacy of ifosfamide, dacarbazine, doxorubicin and cisplatin in human sarcoma xenografts.

The primary chemosensitivity of 16 highly malignant xenografted human soft-tissue sarcomas to ifosfamide, dacarbazine, adriamycin and cisplatin and the development of secondary drug resistance in two chemosensitive sarcoma cell lines was tested in the xenograft system. Single-dose, single-agent treatments with 350 mg kg-1 ifosfamide, 200 mg kg-1 dacarbazine, 10 mg kg-1 doxorubicin and 6.6 mg kg-1 cisplatin were administered and response measured as specific growth delay. Since ifosfamide induced unexpectedly higher toxicity, response was corrected based on the shape of the dose-response curve for ifosfamide. Taking a specific growth delay > 3 as the cut-off point for chemosensitivity, ifosfamide, dacarbazine, doxorubicin and cisplatin were effective in 10/16, 4/16, 2/16 and 1/16 sarcoma cell lines respectively. Five out of 16 sarcoma cell lines were resistant to all tested drugs. Ifosfamide-resistant sarcoma lines were also resistant to doxorubicin and cisplatin, indicating a high degree of cross-resistance. Dacarbazine was still effective in 1/6 ifosfamide-resistant sarcoma cell lines. Secondary drug resistance developed slowly after doxorubicin and ifosfamide pretreatments at moderate selection pressure and developed rapidly after dacarbazine pretreatment at high selection pressure.

Animals↗
PubMed1994

[Accelerated hyperfractionated radiotherapy combined with simultaneous chemotherapy in locally advanced pharyngeal and oral carcinomas].

PURPOSE: To evaluate the feasibility and effectiveness of a concurrent radio-chemotherapy regimen for locally advanced carcinomas of the pharynx and floor of the mouth. PATIENTS AND METHODS: Since January 1990, 97 patients with locally advanced carcinomas of the naso-, oro-, hypopharynx and the oral cavity in UICC stages III and IV were treated according to an accelerated hyperfractionated radiotherapy schedule with concurrent chemotherapy. The primary tumor and positive lymph nodes received a total dose of 72 Gy in 6 weeks. In the first 3 weeks, large fields were irradiated 5 times per week with 2 Gy per fraction. Thereafter, treatment was accelerated, giving 2 daily fractions of 1.4 Gy with minimal intervals of 6 hours. Target volumes were reduced after 49.6 and 59.4 Gy, excluding clinically uninvolved lymph node regions of low and high risk. On day 1, 350 mg/m2 5-FU and 50 mg/m2 folinic acid were given as intravenous bolus followed by continuous infusion of 350 mg/m2 5-FU and 100 mg/m2 folinic acid, days 1 to 5. 10 mg/m2 mitomycin C was given on day 5 and 36 of the treatment. Salvage surgery was offered for residual disease 5 to 6 weeks after the end of radiotherapy. PATIENT CHARACTERISTICS: 70 male, 27 female; age: 27 to 81 years; T2/T3/T4: 7/30/60; N0/N1/N2/N3: 20/18/53/6; nasopharynx/oropharynx/hypopharynx/oral cavity: 16/33/36/12. Median follow-up is 26 months. RESULTS: Overall survival and recurrence-free survival at 2 years were RESULTS: Overall survival and recurrence-free survival at 2 years were 68 +/- 5% and 74 +/- 5%. Multivariate analysis revealed a significant influence of the geometric mean neck node diameter or the N-stage on loco-regional control and survival. T-stage, tumor volume, or tumor localisation did not become significant. Acute toxicity of this schedule was acceptable but required optimised supportive care. Treatment related grade 4+ late toxicity of mucosa, soft tissue and bone were observed with a cumulative frequency of 13% at 2 years. Two patients died during a phase of severe leuko- or thrombocytopenia. CONCLUSION: This phase I to II trial shows favourable results using an intensified treatment radio-chemotherapy protocol. A phase III study is now planned, comparing this regime with an accelerated hyperfractionated radio-therapy alone to an increased total dose of 77.6 Gy.

Adult↗