[Treatment sequelae following definitive percutaneous radiotherapy of prostatic neoplasms].
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Humans↗
Biomedical subjects
H Sack
Publications and source records attributed to H Sack.
Changes in oxygenation patterns of locally advanced recurrent tumors under thermoradiotherapy.
Oxygen tension distributions (pO2) were measured in 10 patients with recurrent soft tissue sarcoma (n = 4), recurrent rectal cancer (n = 2), recurrent breast cancer (n = 3) and recurrent neck nodes (n = 1) using computerized pO2 histography. Measurements were performed pretherapeutically and 24 hours after the first cytotoxic hyperthermic treatment. In one patient an increase of the mean pO2 value was evident after hyperthermia. The other 9 patients showed a significant decrease in the mean pO2 values after hyperthermia. Pooled pO2 distributions of measurements before and after hyperthermia differ statistically significant (p < 0.01). The median pO2 from 1248 measurements before hyperthermia is 18.9 mmHg, whereas the median pO2 from 1263 measurements after hyperthermia is 9.4 mmHg.
Aged↗
Preoperative radiochemotherapy and radical surgery of advanced head and neck cancers--results of a prospective, multicenter DOSAK study.
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Adult↗
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↗
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↗
[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↗
[German radio-oncologists and Europe].
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Europe↗
[Does adjuvant radiotherapy after mastectomy shorten the life expectancy of patients?].
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Breast Neoplasms↗
[Studies on oxygen partial pressure in tumor tissue under radiotherapy and thermoradiotherapy].
PURPOSE: Detection of radiation resistant hypoxic cells in poorly vascularized regions of tumors could facilitate selection of therapeutic schedules for the combination of radiotherapy and hyperthermia. PATIENTS AND METHODS: In 29 patients (9 breast carcinomas, 8 soft tissue sarcomas, 8 lymph node metastases of head and neck cancers and 4 different other tumors) the oxygenation status was examined before, during and after radio- and partially thermoradiotherapy. It was registered using a needle electrode under local anesthesia. The pO2-values obtained from about 100 to 200 sites of an individual tumor were displayed as histograms (Eppendorf-pO2-Histograph, Hamburg). RESULTS: Hypoxic tissue areas (pO2 < 5 mm Hg) was found more in sarcomas (10.2%) than in lymph node metastases of head and neck cancers (5.8%) and breast carcinomas (3.3%). We observed in the course of therapy increasing pO2 values (reoxygenation) only partially in the groups of breast carcinomas and cervical lymph node metastases, decreasing in the soft tissue sarcomas. CONCLUSIONS: In future the selection of patients for hyperthermia could be done on the base of pO2-measurements.
Breast Neoplasms↗
[Surgery of locally advanced non-small-cell bronchial cancer after intensive preoperative chemo-/radiotherapy].
From March 1991 to June 1993 50 patients with local advanced NSCLC (mediastinoscopy obligatory) have been entered into an ongoing trial with preoperative chemotherapy and simultaneous chemo-/radiotherapy, followed by re-mediastinoscopy and surgery. Clinical response rates after chemotherapy amounted to 66.8% after chemo/radiotherapy 77.5%, no severe toxicity was observed. 36 patients ultimately underwent operation, 29 with a curative, 5 with a palliative resection and 2 with an explorative thoracotomy. Pathological complete remission rates of the primary tumor were found in 11 (32.3%), R0-resection in 18 (52.9%) and R1-resection in 5 (14.7%) cases. Sterilisation rates of mediastinal nodes were found in 86.3% of N2 tumors and 66.6% of N3 tumors. Median survival time ranged between 21 months for stage III a and 16 months for III b disease. This intensive preoperative neoadjuvant treatment is tolerable and effective, the requirements for a randomised comparative trial was met.
Adult↗
Radioresponsiveness of human glioma, sarcoma, and breast cancer spheroids depends on tumor differentiation.
PURPOSE: Differences in the intrinsic radiosensitivity within and between different tumor classes have been noticed for human tumor cell lines using the clonogenic assay. By far, most of the cell lines studied up to now were derived from poorly differentiated tumors. In this study, the influence of tumor differentiation on the radiation doses necessary to control 50% of small oxic spheroids (SCD50) was determined. Evidence of a distinct dependence of radioresponsiveness on tumor progression provides a background for an investigation of the underlying mechanisms. METHODS AND MATERIALS: Spheroids were aggregated from 1000-1500 cells in agarose coated 24 multi-well plates. Their diameters ranged from 156 to 405 microns, depending on the cell line. Spheroids were irradiated with graded 60Co single doses using spheroid control as end point and a minimum follow-up period of 3 months. RESULTS: Cell lines from three low grade gliomas and 10 malignant gliomas were studied in the spheroid control assay. The group mean SCD50 values were 6.1 +/- 1.6 Gy and 13.1 +/- 3.3 Gy, respectively. Four cell lines from grade 2 soft tissue sarcomas had a mean SCD50 value of 6.2 +/- 0.5 Gy and one undifferentiated sarcoma line of 11.0 Gy. Three well-differentiated breast cancer lines expressed the cell adhesion molecule E-cadherin, had an epithelioid morphology in monolayer culture, were estrogen receptor positive or contact inhibited in multicellular spheroids. Two undifferentiated breast cancer lines had a fibroblastoid morphology and were marker negative. The mean SCD50 value of the former was 10.5 +/- 1.0 Gy while that of the undifferentiated lines was 14.8 +/- 2.8 Gy. Analysis of variance revealed a significant effect of the tumor type as well as the grade of dedifferentiation on the SCD50 after irradiation with one fraction or 2Gy/fraction. The surviving fractions at 2 Gy (SF2), obtained from the spheroid control rates after different fractionation schedules by approximation of the linear quadratic model assuming Poisson statistics were significantly dependent on tumor type (p = 0.001, ANOVA F-test) but not on tumor differentiation (p = 0.27). The alpha/beta ratios did not depend on tumor type (p = 0.08, ANOVA F-Test) but significantly increased with the grade of tumor cell dedifferentiation (p = 0.03). CONCLUSION: The spheroid model is suitable for measuring the radioresponsiveness of differentiated cell lines with very low colony forming efficiencies. Tumor cell differentiation is an important factor for the radioresponsiveness and recovery capacity of human tumor cells.
Breast Neoplasms↗
Deep regional hyperthermia: comparison between the annular phased array and the sigma-60 applicator in the same patients.
PURPOSE: Several institutions have accumulated clinical experience with the annular array as well as with the Sigma applicator. There exist only limited data in comparison of both heating devices possibly favoring the annular array over the Sigma applicator with regard to tumor temperatures and acute toxicity. The objective of this study was to record temperature distributions at identical sites in tumor and normal tissue in the same patients treated with each device. METHODS AND MATERIALS: Eighteen patients with advanced pelvic tumors were treated on successive occasions with regional hyperthermia using the annular phased array applicator usually driven at 60-80 MHz or the Sigma applicator usually driven at 70-90 MHz. In all patients detailed thermal mapping and temperature analysis for tumor and normal tissues could be performed. RESULTS: Regardless the device used the acute toxicity was treatment limiting in nearly 50% of the treatments. Systemic stress was treatment limiting in 30% of the treatments with both devices although systemic parameters (core temperature, heart rate, changes in blood pressure) were higher with the annular array. The overall mean minimum, average and maximum tumor temperature observed were 39.5 +/- 1.0 degrees C, 40.9 +/- 1.4 degrees C, 42.7 +/- 2.3 degrees C for the annular array and 39.3 +/- 0.9 degrees C, 40.9 +/- 1.4 degrees C, and 42.5 +/- 1.7 degrees C for the Sigma applicator. The time-averaged temperatures achieved in 20% (T20), 50% (T50) and 90% (T90) of all measured sites were 41.7 +/- 2.1 degrees C, 40.8 +/- 1.4 degrees C, 39.9 +/- 1.2 degrees C for the annular array and 41.7 +/- 1.4 degrees C, 41.0 +/- 1.3 degrees C, and 40.1 +/- 1.0 degrees C, for the S-60. The difference was not statistically significant. With regard to normal tissue temperatures a trend to higher maximum temperatures in the deep muscle and fat tissue was evident for the Sigma applicator. The overall minimum and average normal tissue temperatures in the deep muscle and fat tissue and the rectum and the time-averaged temperatures achieved in 20% (T20), 50% (T50) and 90% (T90) of the measured sites differ not statistically significant. CONCLUSION: These results indicate that there continue to be unresolved limitations in achieving temperature elevation in deep seated tumors of the pelvis with radiative coherent EM wave techniques using amplitude and phase steering capabilities without any special optimization procedure.
Adult↗
The TCD50 and regrowth delay assay in human tumor xenografts: differences and implications.
The response to irradiation of five human xenograft cell lines--a malignant paraganglioma, a neurogenic sarcoma, a malignant histiocytoma, a primary lymphoma of the brain, and a squamous cell carcinoma--were tested in nude mice. All mice underwent 5 Gy whole body irradiation prior to xenotransplantation to minimize the residual immune response. The subcutaneous tumors were irradiated at a tumor volume of 120mm3 under acutely hypoxic conditions with single doses between 8 Gy and 80 Gy depending on the expected radiation sensitivity of the tumor line. Endpoints of the study were the tumor control dose 50% (TCD50) and the regrowth delay endpoints growth delay, specific growth delay, and the tumor bed effect corrected specific growth delay. Specific growth delay and corrected specific growth delay at 76% of the TCD50 was used in order to compare the data to previously published data from spheroids. The lowest TCD50 was found in the lymphoma with 24.9 Gy, whereas the TCD50 of the soft tissue sarcomas and the squamous cell carcinoma ranged from 57.8 Gy to 65.6 Gy. The isoeffective dose levels for the induction of 30 days growth delay, a specific growth delay of 3, and a corrected specific growth delay of 3 ranged from 15.5 Gy (ECL1) to 37.1 Gy (FADU), from 7.2 Gy (ENE2) to 45.6 Gy (EPG1) and from 9.2 Gy (ENE2) to 37.6 Gy (EPG1), respectively. The corrected specific growth delay at 76% of the TCD50 was correlated with the number of tumor rescue units per 100 cells in spheroids, which was available for three tumor lines, and with the tumor doubling time in xenografts (n = 5). The TCD50 values corresponded better to the clinical experience than the regrowth delay data. There was no correlation between TCD50 and any of the regrowth delay endpoints. This missing correlation was most likely a result of large differences in the number of tumor rescue units in human xenografts of the same size.
Animals↗
Thermoradiotherapy in locally advanced deep seated tumours--thermal parameters and treatment results.
From October 1987 to December 1990 a total of 37 patients with deep seated tumours of the pelvis (n = 34), the abdomen (n = 2), or lower leg (n = 1) were treated with radiotherapy and regional hyperthermia. Hyperthermia was produced by the BSD-1000 system and the annular phased array (AA) applicator usually driven at 60-80 MHz, or the BSD-2000 system and the Sigma-60 (S 60) applicator usually driven at 70-90 MHz. Detailed thermal mapping and temperature analysis was performed on 29 patients. The overall mean maximum, average and minimum temperature observed was 42.9 +/- 2.4 degrees C, 40.9 +/- 1.5 degrees C, and 39.3 +/- 0.9 degrees C for all treatments. The time-averaged tumour temperatures achieved in 20%, 50% and 90% of all measured temperature sites were 41.8 +/- 2.1 degrees C (T20), 40.9 +/- 1.6 degrees C (T50), and 39.9 +/- 1.2 degrees C (T90). In addition, the overall mean maximum, average and minimum temperature measured in normal tissue was 42.4 +/- 1.4 degrees C, 40.6 +/- 1.0 degrees C, and 39.2 +/- 0.9 degrees C. The time averaged normal tissue temperatures achieved in 20%, 50% and 90% of all measured temperature sites were 41.3 +/- 1.1 degrees C, 40.6 +/- 1.1 degrees C, and 39.6 +/- 1.0 degrees C. In 36 assessable patients, the overall objective response rate was 31%: 2 complete responses (CR) and 9 partial responses (PR).
Adult↗
Spheroid control of malignant glioma cell lines after fractionated irradiation: relation to the surviving fractions at 2 Gy and colony forming efficiencies in a soft agar clonogenic assay.
Spheroid control doses (SCD50) were determined for ten human glioma lines after fractionated irradiation under oxic conditions. In addition, SF2 values and colony forming efficiencies (CFE) were measured in a soft agarose clonogenic assay. A significant relationship existed between the SCD50 values and the SF2-CFE data pairs (p = 0.01) but the SCD50 values were higher than expected from the SF2 and CFE values. This comparison shows the influence of environmental factors (different in both model systems) on reproductive tumour cell death after irradiation.
Cell Aggregation↗
[The value of dynamic MRT in the perfusion evaluation of pelvic tumors under hyperthermia].
For the purpose of assessing perfusion of deep seated pelvic tumours 22 dynamic MR studies were carried out and correlated with relevant CT studies as well as with the intratumoural distribution of temperature under hyperthermia in different areas. Using changes of signal intensity, dynamic MR could thus distinguish between well and poorly perfused tumours, besides supplying reliable information on inhomogeneities in tumour perfusion. Altogether, a correlation of 0.92 (p < 0.001) was found between MR and CT and 0.72 (p < 0.001) between MR and the steady state determination of intratumoural temperature. Thus, dynamic MR provides prognostic information concerning therapeutic temperatures (> = 42 degrees C) in tumours and therefore their response to hyperthermia.
Chemotherapy, Cancer, Regional Perfusion↗
[Malignant paragangliomas--the results of radiotherapy in 6 patients].
Between February 1984 and May 1989, six patients (four male, two female) with malignant paragangliomas of the carotid body (n = 4) and glomus jugulare (n = 2) were irradiated in the Department of Radiation Oncology at Essen University. All patients had macroscopic (residual) tumor at the start of treatment. Five out of six paragangliomas had to be considered malignant, since histological lymph node involvement or distant metastasis was confirmed. In the sixth case extra- and intracranial tumor growth was observed. Total doses between 40 and 55 Gy using cobalt 60, 10 or 15 MeV photons were administered. Radiation therapy was canceled at 30.6 Gy in one patient because of multiple distant metastasis. Three out of four patients, who received curative treatments, were locally controlled (25 to 91 months). A local recurrence in one patient was detected 18 months after irradiation; this patient died of distant metastasis 23 months after treatment. In one out of two palliatively irradiated patients, local control could be achieved until the patient died of distant metastasis twelve months after treatment. Grade III- or grade IV-treatment toxicity was not observed. Radiation therapy of malignant paragangliomas with doses between 45 and 54 Gy in five to six weeks is an effective treatment with low toxicity and should be preferred to surgery in glomus jugulare and advanced carotid body tumors.
Adult↗
Radiosensitivity, repair capacity, and stem cell fraction in human soft tissue tumors: an in vitro study using multicellular spheroids and the colony assay.
Radiation doses necessary to control 50% of spheroids (SCD50) were determined for five human soft tissue tumor lines after single dose and fractionated irradiation. Spheroids with 1000-1500 cells were used throughout. A similar number of cells per spheroid resulted in different sized spheroids for the respective cell lines. The parameters alpha, beta, and the number of regenerating cellular units per spheroid (SRU) were estimated from the spheroid control data using a direct fit according to the linear quadratic model assuming Poisson statistics. The number of spheroid regenerating cellular units was also determined from the growth delay at doses required for 10% spheroid control. In addition, alpha, beta, and the fraction of clonogenic cells of the five cell lines were obtained from a soft agar colony forming assay. The most precise parameter for radiation sensitivity was the SCD50, with a coefficient of variation smaller than 5%. SCD50 values ranged from 5.9 to 11.0 Gy for the five soft tissue tumor lines. Two of the five cell lines showed significantly higher alpha values and lower calculated survival fractions after 2 Gy (SF2) in the soft agar clonogenic assay than in the spheroid control assay. This points to a resistance-enhancing effect in the spheroid system. Whereas the fractions of SRU from the number of cells per spheroid, estimated from the spheroid control and growth delay assays, agreed well, no significant correlation existed between the fraction of SRU and the fraction of clonogenic cells in the soft agar colony forming assay. The alpha/beta ratios as a descriptive measure of the fractionation sensitivity of the tumor cell spheroids in the spheroid control assay corresponded well with those derived from the dose-cell survival data using a soft agar colony forming assay. Two of the five cell lines showed high fractionation sensitivities with alpha/beta values smaller than 5 Gy while those of the remaining three ranged from 7.8 to 10.8 Gy. Spheroids are structurally more similar to in vivo tumors than monolayer cultures. From the observed lack of correlation in the radiosensitivity parameters alpha and SF2 as well as in the fraction of SRU or clonogenic cells obtained from the spheroid control assay or the colony forming assay, one would expect even greater differences between results from colony forming assays and the radiosensitivity of in vivo tumors, at least for human soft tissue sarcomas.
Cell Aggregation↗