Search PubMed⌕ Search

Biomedical subjects

H J Feldmann

Publications and source records attributed to H J Feldmann.

At least 55 records · Page 3Linked to original sources
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

Hyperthermia--its actual role in radiation oncology. Part III: Clinical rationale and results in deep seated tumors.

PURPOSE: Combined hyperthermia and radiation therapy has been reported to yield higher complete and durable responses than radiotherapy alone in superficial tumors. In deep seated tumors the effect of the combined treatment is still under research. METHODS: The literature and own clinical data are reviewed with regard to biological and physical fundamentals and clinical results. RESULTS: Clinical phase I to II studies have applied regional hyperthermia in the abdomen, the pelvic region and the extremities. Usually primary advanced, persistent or local recurrent and metastatic tumors were selected for treatment either due to poor response to conventional therapy or for effective palliation. The clinical data are presented concerning the following topics: invasive thermometry, temperature parameter in tumor and normal tissue, toxicity, tumor response, treatment planning, clinical trials and prognostic factors. Clinical results of thermoradiotherapy for advanced or recurrent rectal cancer, cervical cancer and soft tissue sarcomas are reviewed in detail. In addition, the prognostic relevance of temperature parameters and physiological conditions such as global tumor perfusion are discussed. CONCLUSION: Clinical issues of optimization of regional thermoradiotherapy are: improvement of hyperthermia technique, analysis of biological effects and mechanisms involved in temperature elevation, selection of appropriate study concepts for specific tumor sites. Part I has covered biological and technical fundamentals of clinical hyperthermia and has been published in Strahlenther. Onkol. 168 (1992), 183-190. Part II has covered clinical fundamentals and results in superficial tumors of clinical hyperthermia and has been published in Strahlenther.

Algorithms↗
PubMed1995

Hyperthermia--its actual role in radiation oncology. Part IV: Thermo-radiotherapy for malignant brain tumors.

BACKGROUND: High-grade malignant gliomas have a dismal prognosis. Only achievement of long-term local control improves overall survival. Conventional treatments have not been successful, but thermoradiotherapy appears to be a promising new approach to this disease. PATIENTS AND METHODS: The review addresses the various HT techniques applied for brain heating, the biological rationale and experimental studies supporting the use of heat in addition to radiotherapy for brain tumors. Normal brain damage exposed to heat is critically evaluated. Clinical trials implementing HT for tumors of the brain accumulating more than 400 patients are discussed. RESULTS: HT is a feasible and effective approach to brain tumors. Important selection criteria are tumor size (< 6 cm) and location (supratentorial, peripheral). Acute treatment toxicity is relatively low and long-term side effects are similar to those observed for RT alone. In some studies a high response rate and improvement of survival was achieved. Tumor control and survival depend on histology (anaplastic astrocytoma vs. glioblastoma multiforme), extent of surgery (complete vs. incomplete), tumor status (primary vs. recurrent), age and performance status. Satisfactory heating also correlates significantly with favourable treatment outcome. CONCLUSIONS: The encouraging results of clinical trials may be biased by favourable tumor and patient selection. Randomized clinical trials comparing RT alone versus combined RT-HT for advanced and recurrent brain tumors are justified. Part I has covered biological and technical fundamentals of clinical hyperthermia and has been published in Strahlenther. Onkol. 168 (1992), 183-190. Part II has covered clinical fundamentals and results in superficial tumors of clinical hyperthermia and has been published in Strahlenther. Onkol. 169 (1993), 633-654. Part III has covered clinical rationale and results in deep seated tumors and has been published in Strahlenther. Onkol. 171 (1995), 251-264.

Animals↗
PubMed1994

Oxygenation of locally advanced recurrent rectal cancer, soft tissue sarcoma and breast cancer.

Oxygen tension distributions (pO2) were measured in 20 patients with recurrent soft tissue sarcoma (n = 8), recurrent breast cancer (n = 9) and recurrent rectal cancer (n = 3) using computerized pO2 histography. A total of 35 measurements could be performed pretherapeutically. In 8 measurements there exist some problems with regard to clinical relevant bleeding or uncertainties of the tumor/normal tissue boundary. In general, there is a marked tumor-to-tumor variability even for tumors of the same histology. 5 of 8 soft tissue sarcomas, 1 of 3 recurrent rectal cancers, 4 of 9 breast cancers exhibited pO2 values between zero and 2.5 mmHg, i.e. tissue areas with less than half-maximum radiosensitivity.

Aged↗
PubMed1994

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↗
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

[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↗
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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

Evaluation of tumor blood perfusion by dynamic MRI and CT in patients undergoing thermoradiotherapy.

In 18 patients who were treated with combined regional hyperthermia and radiation for recurrent pelvic tumors, blood flow related data were obtained using dynamic computed tomography and dynamic magnetic resonance imaging. The enhancement of contrast material (delta HU) and Gadolinium DTPA (delta SI) over baseline in the early phase (15-30 s) after bolus injection is dependent upon perfusion. With both methods significant differences in global perfusion have been observed between tumor center and tumor periphery. With regard to the mean perfusion values we are able to separate high, medium and low perfused pelvic tumors. Flow rates expressed as delta HU for dynamic CT and delta SI for dynamic MRI show a significant inverse correlation with the achieved steady state temperatures above baseline. Values of enhancement of contrast material higher than 15-35 delta HU or 300-700 delta SI indicate flow rates which were limiting in achieving steady state temperatures higher than 3 degrees C above baseline (core temperature).

Combined Modality Therapy↗
PubMed1993

[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↗
PubMed1993

Hyperthermia--its actual role in radiation oncology. Part II: Clinical fundamentals and results in superficial tumors.

This overview summarizes the most important clinical fundamentals to implement combined hyperthermia (HT) and radiotherapy (RT) in clinical trials and reviews clinical HT-RT data obtained in superficial and medium depth tumors treated with external heating devices. In the first part we discuss the following clinical fundamentals: selection of appropriate clinical sites for HT-RT studies, selection of suitable HT-devices, principle design of clinical HT-RT studies, requirements for treatment prescription, relevant treatment endpoints, definition and assessment of a thermal enhancement ratio (TER) and therapeutic gain factor (TGF), impact of prognostic parameters on treatment stratification and statistical evaluation. In the second part we review and discuss clinical results of thermoradiotherapy (HT-RT) for advanced breast carcinoma, recurrent breast cancer, advanced head and neck tumors, cervical neck node metastases, malignant melanomas and residual microscopic disease. In addition, clinical results of pilot studies are reviewed, which have applied a triple modality approach of thermo-radiochemotherapy (HRC) for various tumors. Finally, possible future perspectives of clinical HT-RT research are outlined.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Clinical investigations on blood perfusion in human malignancies of the pelvis and abdomen: significance for tumor therapy.

Blood flow of deep pelvic and abdominal tumors was investigated with the thermal clearance method, dynamic CT and dynamic MRI. There are good correlations between the measurement values obtained by these methods. A low flow was observed in rectal cancer and soft tissue sarcoma in contrast to pancreatic cancer and hypernephroma. The temperature increase induced by regional hyperthermia was dependent on the individual tumor blood flow. Dynamic CT can be used pretherapeutically and predict the quality of a heat treatment, which is important with regard to concepts consisting in radiotherapy or chemotherapy plus hyperthermia.

Abdominal Neoplasms↗
PubMed1992

Blood flow and steady state temperatures in deep-seated tumors and normal tissues.

Blood flow related data obtained in different deep-seated tumors and adjacent normal tissues were analyzed in 28 patients who were treated with combined regional hyperthermia and radiation for recurrent or metastatic tumors. The evaluation of blood flow related data has been made using the thermal clearance/thermal cooling coefficient technique and dynamic computed tomography. With both methods significant differences in global perfusion have been observed between tumor center and tumor periphery, between tumor and normal tissue (deep muscle and fat tissue), and between tumor entities. Washout rates or thermal cooling coefficient values, as well as the enhancement of contrast material over baseline (expressed in delta Hounsfield Units), correlated significantly with the achieved steady state temperatures for different tissue categories (i.e., tumor center, tumor periphery, different tumor entities, normal tissue). Thermal cooling coefficient values higher than 63000-83000 W/m3-K (washout rates higher than 15-20 ml/100 g-min) or values of enhancement of contrast material higher than delta 20-25 HU coincide with a limitation in achieving therapeutic temperatures higher than 40 degrees C.

Abdominal Neoplasms↗