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Biomedical subjects

W Budach

Publications and source records attributed to W Budach.

At least 55 records · Page 3Linked to original sources
PubMed1997

Postoperative limited volume irradiation in a child with a solitary brain metastasis from Wilms tumor: a case report.

An 11-year-old boy presented with a solitary cerebral metastasis 2.5 years after initial diagnosis and 4 months after successful combined modality treatment of a stage II recurrent Wilms tumor in the chest. Resection of the brain metastasis was followed by limited volume irradiation with 30.0 Gy total dose. After a follow-up of 2.5 years the boy is in complete remission and shows no neurological or neuropsychological deficits indicating the possibility of curative postoperative radiotherapy of low toxicity and restricted to the tumor site in the presence of solitary brain metastases.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

[Genetic predisposition and radiation sensitivity of tumors].

BACKGROUND: Studies on normal tissue radiation sensitivity have demonstrated profound differences of individual sensitivities. A number of genetic syndromes associated with abnormal radiation sensitivity have been described. Significant differences have also been detected in persons without known genetic disorders. The question arises as to whether tumors originating from normal tissues with abnormal radiation sensitivity share this abnormal sensitivity and as to whether a general correlation between normal tissue sensitivity and tumor tissue sensitivity can be substantiated. METHODS: Experimental and clinical data derived from own investigations and an extensive review of the literature was used to answer the question. RESULTS: Experimental studies on normal and tumor tissues of SCID-and C3H-mice demonstrated that the 2.7-fold enhanced radiation sensitivity of SCID normal tissues is also found in SCID tumors. Clinical investigations on cervical carcinoma and breast cancer patients revealed higher local control rates in patients with more pronounced acute side effects. A weak trend towards the same relationship was found in head and neck cancer patients. Case reports on unusually severe acute radiation side effects or unexpected tumor remissions as well as few reports on radiotherapy in ataxia telangiectasia (AT) patients suggest a correlation between normal- and tumor-tissue radiation sensitivity. Studies on fibroblasts and tumor cells from the same patient support this hypothesis in soft tissue sarcoma patients, but do not so for head and neck cancer patients. Tumor cells exhibit a considerably higher variation of radiation sensitivities than normal tissue cells. CONCLUSIONS: Experimental and clinical data are compatible with the hypothesis that normal tissue radiation sensitivity predicts for tumor tissue sensitivity. However, in view of the larger heterogeneity of tumor cell radiation sensitivity as compared to normal tissue radiation sensitivity, the development of a clinically useful predictive test for tumor sensitivity based on normal cell sensitivity appears to be unrealistic.

Animals↗
PubMed1997

Correlation between primary chemo- and radiation sensitivity in a panel of highly malignant human soft tissue sarcoma xenografts.

BACKGROUND AND PURPOSE: Sensitivity to radiation and sensitivity to cytotoxic drugs have been proposed to be independent properties of tumour cells. However, very few clinical or experimental studies have tested this hypothesis. Therefore, we evaluated the response to ionizing radiation and to four cytotoxic drugs in a panel of 12 human soft tissue sarcoma cell lines using the xenograft system. MATERIAL AND METHODS: NMRI-nu/nu nude mice with subcutaneous tumours received at a tumour volume of 120-200 mm3 either single dose, single agent chemotherapy with 350 mg/kg ifosfamide, 200 mg/kg dacarbazine, 10 mg/kg doxorubicin, 6.6 mg/kg cisplatin, or 24 Gy local tumour irradiation under acutely hypoxic conditions from a cobalt-60 source. Tumour response to radiotherapy and chemotherapy was measured as specific growth delay (SGD). RESULTS: A significant correlation was found between SGD after radiotherapy and SGD after decarbazine (P < 0.001) and doxorubicin (P = 0.05), whereas no correlation could be demonstrated for cisplatin. For ifosfamide, the correlation reached borderline significance. The maximal response to any of the four tested chemotherapeutic drugs correlated very well with the response to radiotherapy (P < 0.001). CONCLUSION: The results suggest that radiation sensitivity and chemosensitivity are not independent properties of soft tissue sarcoma cell lines.

Animals↗
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

Paclitaxel in simultaneous radiochemotherapy of head and neck cancer: preclinical and clinical results.

Several studies have presented evidence that paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) displays a radiation-sensitizing effect. We therefore analyzed the influence of paclitaxel and concomitant radiation on the proliferation kinetics of head and neck tumor cells and normal fibroblasts. Our data clearly support the notion that paclitaxel given with radiation exerts an additive effect on the clonogenic survival of squamous cell carcinoma cells and normal fibroblasts. Since concomitant radiochemotherapy has proven to be beneficial for the treatment of locally advanced head and neck cancer, we are testing the feasibility of simultaneous paclitaxel plus radiotherapy. Paclitaxel is given on a one-time weekly basis. Up to now, 13 evaluable patients have been treated, and the maximum tolerable dose has not been reached at 40 mg/m2. Mucositis is expected to be the dose-limiting toxicity.

Adult↗
PubMed1995

In vivo radiation sensitivity of glioblastoma multiforme.

PURPOSE: Human glioblastoma (GBM) is one of the most resistant tumors to radiation. In previous reports, we have demonstrated a wide range of radiation sensitivity of GBM in vitro; that is, SF2 values of 0.2 to 0.8. The great sensitivity of some of the cell lines is not in accord with the almost invariably fatal clinical outcome of patients with GBM. The sensitivity of cells in vitro pertains to cells cultured in optimal nutritional conditions. The TCD50 (the radiation dose necessary to control 50% of the tumors locally) determined in lab animals is analogous to the use of radiation with curative intent in clinical radiation oncology. The aim of the present study was (a) to evaluate the sensitivity of GBM in vivo relative to that of other tumor types and (b) assess the relationship between the single dose TCD50 of the xenografts and the sensitivity of the corresponding cell lines in vitro. METHODS AND MATERIALS: The TCD50 assay was used to study twelve human tumor lines. Four previously published values were added. A total of 10 GBM, 4 squamous cell carcinoma (SCC), 1 soft tissue sarcoma (STS), and 1 cancer colon (CC) are included in the analysis. For further suppression of the residual immune system, all the animals received 6 Gy whole-body irradiation 1 day before transplantation. Local tumor irradiations were given as a single dose, under conditions of clamp hypoxia using a Cs irradiator. RESULTS: The TCD50 values for the 10 GBM xenografts varied between 32.5 and 75.2 Gy, with an average of 47.2 +/- 13.1 Gy. The TCD50 values for the SCC were similar to those of the GBM and ranged from 40.7 and 54.4 Gy, with a mean of 46.8 +/- 6.4. The difference between the average TCD50 of GBM and SCC was not significant. The STS and CC xenografts had TCD50 values of 46.0 and 49.2 Gy, respectively. No correlation was found between the TCD50 in vivo and the SF2 or D0 in vitro. CONCLUSIONS: Our data on GBM xenografts showed a wide range of sensitivities to single dose irradiation in vivo, which does not correlate with the almost invariably fatal clinical outcome of these patients. No correlation was observed between the TCD50 in vivo and the in vitro SF2/D0 of the corresponding cell lines. Our in vivo and in vitro data on GBM suggest that radiation sensitivity alone does not explain the cause of the poor clinical response of GBM to radiation, and other factors could contribute to this response.

Animals↗
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↗
PubMed1994

Influence of experimental factors on intrinsic radiosensitivity assays at low doses of radiation: cell multiplicity.

Evaluation of the probability of biological phenomena per cell by colony formation, requires knowledge not only of the number of cells at risk but also of their microdistribution. In the present study, the influence of cellular multiplicity (number of cells per potential colony-forming unit) on the determination of radiation sensitivity is evaluated for a range of multiplicity distributions. Cell surviving fraction was calculated using no multiplicity correction, an average multiplicity correction or the fractional distribution of multiplicities of the control and irradiated population. The results obtained show that: (a) multiplicity corrections are required when the number of cells per potential colony-forming unit is greater than 1.00 either immediately after plating or at the time of irradiation; (b) both the control and irradiated populations must be corrected for multiplicity; (c) multiplicity errors are most pronounced in the low-dose range, e.g. in the survival range with 2 Gy; and (d) the error introduced by using an average vs fractional distribution of multiplicities increases with the multiplicity dispersion. Seemingly small errors due to uncorrected multiplicity effects lead to markedly different predicted isoeffect doses when amplified through multiple (e.g. 30) fractions.

Carcinoma, Squamous Cell↗
PubMed1994

A time-saving system for irradiations of experimental tumors.

PURPOSE: Experimental in vivo radiotherapy frequently aims at the imitation of clinically applied fractionation schedules. However, the reliability of the anesthetic procedure and limited access to the treatment machines in clinical departments are major factors complicating the practical realisation of the experiment. Therefore, a reliable and time saving system for irradiations of xenografted tumors has been developed, which allows repeated irradiations, even in relatively short intervals available for experimental irradiations. MATERIAL AND METHODS: The system presented here consists of an acrylic distributor for an anesthetic gas mixture employing enflurane (Ethrane) in the center of the set-up. Ten mice are positioned radially around the midpoint of the set-up so that they can be irradiated simultaneously. The xenotransplanted tumors growing on the right hind leg of mice are placed in a predefined position, which was found to be of advantage in order to position the tumors for fractionated treatments in identical setting. Tumor-bearing mice are irradiated with 15 MeV photons generated by a linear accelerator at a dose rate of 2.5 Gy/min. One of the significant feature of the setup is the ability to irradiate in acute hypoxia which is obtained by use of an integrated tourniquet. The dose modifying effects of different gases can be investigated by simply using them as carrier for the enflurane. RESULTS: With the use of the set-up several different experiments were performed so far. At most ten fractions were given, one fraction per day. Even after these repeated treatment the loss of animals due to narcosis was less than 2%. The dose variation within the treatment field was found to be less than 4% as measured with TLD dosimetry. The remaining body of the mice is shielded effectively from the direct beam as the whole body dose of mice is 8% of the total tumor absorbed dose. The efficacy of the tourniquet technique for acute hypoxic irradiations was illustrated with the use of 99mTc-labelled albumin showing a complete stop of blood flow in the clamped leg. The steep dose-response curve obtained for single dose irradiation of a neurogenic sarcoma is based on the physical and experimental precision which can be reached with the technique suggested here. CONCLUSION: Due to the high dose rate and the possibility to irradiate ten animals simultaneously the set-up introduced here is greatly time saving. The versatile applicability makes the new set-up a valuable tool for tumor radiobiology.

Anesthesia, Inhalation↗