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Biomedical subjects

J Gellermann

Publications and source records attributed to J Gellermann.

30 records · Page 2Linked to original sources
PubMed1998

[Phase II study on preoperative radio-chemo-thermotherapy in locally advanced rectal carcinoma].

BACKGROUND: Recent studies show that preoperative radio-chemotherapy can increase resectability and local control of locally advanced rectal carcinomas. Additional regional hyperthermia might increase remission rates and tumor response. We therefore tested regional hyperthermia together with radio-chemotherapy in a phase-II study on locally advanced rectal carcinomas. PATIENTS AND METHODS: Thirty-seven patients with primary advanced stage uT3/T4 rectal carcinomas were treated with preoperative radio-chemo-thermo-therapy. The initial tumor depth was determined using endosonography, CT, and MRI. Radiotherapy was carried out in prone position (on a belly board) using standard techniques, with 5 x 1.8 Gy per week up to 45 Gy at the reference point. 5-Fluorouracil (300 to 500 mg/m2) was administered with low doses of leucovorin (50 mg) on days 1 to 5 and 22 to 28. The patients were treated with regional hyperthermia each week prior to radiotherapy and simultaneously with chemotherapy, using the Sigma 60 ring from the BSD-2000 system. Temperature/position curves and temperature/time curves were recorded in endocavitary (endorectal) catheters in tumor contact and as well in bladder and vagina. Following endosonographic restaging, the operation was carried out 4 to 6 weeks after the end of preoperative therapy and adjuvant chemotherapy continued in four cycles. In cases where tumors were non-resectable, a boost up to 64 Gy was aimed. RESULTS: Thirty-one of the 37 patients (84%) with primary carcinoma proved locally R0-resectable. In addition we had 1 R1-resection (3%) and 5 non-resectable tumors (13%). Among the resected tumors, 53% experienced a reduction of depth infiltration from the initial endosonographic stage during preoperative therapy. The actuarial survival rate after 4 years is 65% (free of progression 57%). The actuarial 4-year survival rate was particularly favorable for the group of responders. Overall, the preoperative multimodal therapy was well tolerated, and premature termination was only necessary in 1 case (3%). Grade III/IV toxicities in the intestine and skin were reduced as far as possible by field blockings and cooling of the perineal region. They occurred only in 5/37 patients (13%) at the intestine and in 6/37 patients (16%) at the skin. The thermal data were subjected to a statistical analysis. The quality of temperature distribution (T90, cum min T90 > or = 40.5 degrees C) depends on the power level and relative power density. The response (reduction of tumor size or depth infiltration) correlated significantly with quality parameters of the temperature distributions. This dependency is found as a trend for progression-free survival, too. CONCLUSIONS: Preoperative radio-chemo-thermo-therapy proved to be practical and effective, with encouraging remission rates and excellent local control rates. For this reason, a phase-III study to test regional hyperthermia has been initiated. At the same time, certain technical improvements are still under development for regional hyperthermia.

Adult↗
PubMed1998

Combined treatment of inoperable carcinomas of the uterine cervix with radiotherapy and regional hyperthermia. Results of a phase II trial.

AIM: The disappointing results for inoperable, advanced tumors of the uterine cervix after conventional radiotherapy alone necessitates improving of radiation therapy. Simultaneous chemotherapy or altered radiation fractionation, such as accelerated regimen, increase acute toxicity and treatment is often difficult to deliver in the planned manner. The purpose of this phase II study was to investigate the toxicity and effectiveness of a combined approach with radiotherapy and regional hyperthermia. PATIENTS AND METHODS: From January 1994 to October 1995 18 patients with advanced carcinomas of the uterine cervix were treated in combination with radiotherapy and hyperthermia. The patients were treated with 6 to 20 MV photons delivered by a linear accelerator in a 4-field-box technique to a total dose of 50.4 Gy in 28 fractions. In the first and fourth week 2 regional hyperthermia treatments were each applied with the Sigma-60 applicator from a BSD-2000 unit. After this a boost to the primary tumor was given with high-dose-rate iridium-192 brachytherapy by an afterloading technique with 4 x 5 Gy at point A to a total of 20 Gy and for the involved parametrium anterioposterior-posterioanterior to 9 Gy in 5 fractions. RESULTS: The acute toxicity was low and similar to an external radiotherapy alone treatment. No Grade III/IV acute toxicity was found. The median age was 47 years (range 34 to 67 years). In 16 of 18 patients a rapid tumor regression was observed during combined thermo-radiotherapy, which allowed the use of intracavitary high-dose-rate brachytherapy in these cases. Complete and partial remission were observed in 13 and 4 cases, respectively. One patient did not respond to the treatment. The median follow-up was 24 months (range 17 to 36 months). The local tumor control rate was 48% at 2 years. Median T20, T50 and T90 values were 41.7 degrees C (range 40.3 to 43.2 degrees C), 41.1 degrees C (range 39.2 to 42.5 degrees C) and 39.9 degrees C (range 37.7 to 41.9 degrees C), respectively. Cumulative minutes of T90 > 40 degrees C (Cum40T90) and cumulative minutes, which were isoeffective to 43 degrees C, were calculated (CEM43T90, CEM43T50, CEM43T20). CEM43T90 was found to be a significant parameter in terms of local tumor control for the 4 hyperthermia treatments (p = 0.019). CONCLUSIONS: This treatment modality has proved to be feasible and well tolerable. The rapid tumor shrinkage in the combined approach of radiotherapy with hyperthermia before beginning brachytherapy seems to be a good prerequisite for improving of the disappointing results in cure of advanced cancer of the uterine cervix.

Adult↗
PubMed1998

Evaluation of segmentation algorithms for generation of patient models in radiofrequency hyperthermia.

Time-efficient and easy-to-use segmentation algorithms (contour generation) are a precondition for various applications in radiation oncology, especially for planning purposes in hyperthermia. We have developed the three following algorithms for contour generation and implemented them in an editor of the HyperPlan hyperthermia planning system. Firstly, a manual contour input with numerous correction and editing options. Secondly, a volume growing algorithm with adjustable threshold range and minimal region size. Thirdly, a watershed transformation in two and three dimensions. In addition, the region input function of the Helax commercial radiation therapy planning system was available for comparison. All four approaches were applied under routine conditions to two-dimensional computed tomographic slices of the superior thoracic aperture, mid-chest, upper abdomen, mid-abdomen, pelvis and thigh; they were also applied to a 3D CT sequence of 72 slices using the three-dimensional extension of the algorithms. Time to generate the contours and their quality with respect to a reference model were determined. Manual input for a complete patient model required approximately 5 to 6 h for 72 CT slices (4.5 min/slice). If slight irregularities at object boundaries are accepted, this time can be reduced to 3.5 min/slice using the volume growing algorithm. However, generating a tetrahedron mesh from such a contour sequence for hyperthermia planning (the basis for finite-element algorithms) requires a significant amount of postediting. With the watershed algorithm extended to three dimensions, processing time can be further reduced to 3 min/slice while achieving satisfactory contour quality. Therefore, this method is currently regarded as offering some potential for efficient automated model generation in hyperthermia. In summary, the 3D volume growing algorithm and watershed transformation are both suitable for segmentation of even low-contrast objects. However, they are not always superior to user-friendly manual programs for contour generation. When the volume growing algorithm is used, the contours have to be postprocessed with suitable filters. The watershed transformation has a large potential if appropriately developed to 3D sequences and 3D interaction features. After all, the practicality and feasibility of every segmentation method critically depend on various details of the user software as pointed out in this article.

Algorithms↗
PubMed1998

Preoperative hyperthermia combined with radiochemotherapy in locally advanced rectal cancer: a phase II clinical trial.

OBJECTIVE: A prospective phase II study was performed to determine the feasibility and efficacy in terms of response rate, resectability, and morbidity in patients with locally advanced rectal cancer who received preoperative regional hyperthermia combined with radiochemotherapy (HRCT). SUMMARY BACKGROUND DATA: Recent studies suggest that preoperative radiochemotherapy in locally advanced rectal cancer can induce downstaging, but after resection the incidence of local recurrences remains high. Hyperthermia (HT) may add tumoricidal effects and improve the efficacy of radiochemotherapy in a trimodal approach. PATIENTS AND METHODS: Thirty-seven patients with histologically proven rectal cancer and T3 or T4 lesions, as determined by endorectal ultrasound and computed tomography, entered the trial. 5-Fluorouracil (300-350 mg/m2) and leucovorin (50 mg) were administered on days 1 to 5 and 22 to 26. Regional HT using the SIGMA 60 applicator (BSD-2000) was given once a week before radiotherapy (45 Gy with 1.8-Gy fractions for 5 weeks). Surgery followed 4 to 6 weeks after completion of HRCT. RESULTS: Preoperative treatment was generally well tolerated, with 16% of patients developing grade III toxicity. No grade IV complications were observed. The overall resectability rate was 32 of 36 patients (89%), and 31 resection specimens had negative margins (R0). One patient refused surgery. In 5 patients (14%), the histopathologic report confirmed no evidence of residual tumor (pCR). A partial remission (PR) was observed in 17 patients (46%). The survival rate after 38 months was 86%. In none of the patients was local recurrence detected after R0(L), but five patients developed distant metastases. CONCLUSION: Preoperative HRCT is feasible and effective and may contribute to locoregional tumor control of advanced rectal cancer, which is to be proven in an ongoing phase III trial.

Adenocarcinoma↗
PubMed1997

Twenty-four-hour ambulatory blood pressure monitoring in young children.

Twenty-four-hour ambulatory blood pressure monitoring (ABPM) has many advantages for the diagnosis and follow-up of hypertension at all ages. This technique has so far not been documented as applicable to the very young. We studied the feasibility of ABPM in 61 healthy children and in 40 patients with renal diseases and/or hypertension, aged less than 6 years. A satisfactory ABPM profile (recording time = 24 h and > 30 good recordings) was obtained in 77% of the healthy children. The mean number of good blood pressure (BP) measurements per 24 h increased with age from 46 (3-4 years) to 58 (6 years). The mean (+/- SD) systolic and diastolic BPs of healthy 3- to 6-year-old children (n = 47) were 110 +/- 5/67 +/- 5 mmHg during the day-time and 100 +/- 5/58 +/- 5 mmHg at night. In addition to the nocturnal decrease in BP, ABPM detected a second, day-time dip in BP during bed rest after lunch. Ninety percent of patients with renal disease and/or hypertension had successful ABPM recordings for 24 h, with an age-dependent increase in the mean number of reliable readings from 34 (< 2 years) to 48 (4 years). In 5 of 10 children with hypertensive results obtained by casual BP measurements, elevated BP was not confirmed by ABPM. We conclude that ABPM is a useful tool for the diagnosis and evaluation of hypertension in children under 6 years of age.

Aging↗
PubMed1997

Oscillometric twenty-four-hour ambulatory blood pressure values in healthy children and adolescents: a multicenter trial including 1141 subjects.

Ambulatory blood pressure (ABP) monitoring is increasingly used to evaluate the blood pressure of children and adolescents. The upper normal ABP values in the pediatric age group are still unknown, because reference values based on a sufficiently high number of healthy children have not yet been published. In this multicenter trial, we pooled ABP records of 1141 healthy children and adolescents with a body height between 115 and 185 cm. The study was carried out by seven centers according to a common protocol. The 50th percentile for 24-hour systolic ABP increased moderately with height, from 103 to 113 mm Hg in girls and from 105 to 120 mm Hg in boys. The 50th percentile for diastolic 24-hour means was 66 +/- 1 mm Hg, irrespective of height or gender. Diastolic daytime means were 73 +/- 1 mm Hg, which is remarkably high compared with reference values for casual blood pressure. The mean nocturnal systolic and diastolic ABP (midnight to 6 AM) was 13% +/- 6% and 23% +/- 9% lower compared with the daytime means (8 AM to 8 PM), respectively. This multicenter study provides well-based limits of normal ABP in mid-European children.

Adolescent↗
PubMed1997

[Magnetic resonance tomography and endosonography in the preoperative staging of advanced rectal carcinomas after hyperthermoradiochemotherapy].

PURPOSE: Comparison of diagnostic accuracy of staging of endorectal sonography (ES) and body coil MRI after preoperative hyperthermoradiochemotherapy in patients with advanced rectal cancer. METHODS: Prospective analysis of MRI and ES in 30 patients after hyperthermoradiochemotherapy and correlation with histopathological patterns. RESULTS: T-staging by MRI was correct in 47% and by ES in 53% of the cases. Despite similar accuracy of staging in T0- and T1-tumours, we found different accuracies concerning T2-tumour staging about 63% versus 73% (MRI/ES), concerning perirectal infiltration 70% for both techniques, concerning invasion of adjacent organs 90% versus 87%, and concerning lymph node metastases without respect to the N-stage 63% versus 63%. CONCLUSION: Both imaging modalities provide useful information for operation planning despite limited accuracy after hyperthermoradiochemotherapy. The body coil MRI does not seem to be severely inferior to ES in post-therapeutic staging, despite better contour line imaging by ES. With respect to the determination of invasion of other organs, MRI seems to be more useful.

Adult↗
PubMed1996

Hyperthermia in the multimodal therapy of advanced rectal carcinomas.

The synergistic effects of hyperthermia (raising temperatures to 40 degrees C and above) when combined with radiotherapy and cytotoxic drugs and a modulation of immunological phenomena have been demonstrated in the laboratory. Pre-clinical data relating to hyperthermia are summed up, along with their implications for clinical application. Controlled studies of local and regional hyperthermia have been performed during recent years, and these show us that the adjunction of hyperthermia provides at least an improvement of local control compared with radiotherapy alone. Current clinical results are summarized. Therapy systems based on radiowave irradiation have been commercially available for regional hyperthermia of the pelvis since the mid 1980s. This technology allows us to perform sufficiently tolerable and effective regional hyperthermia on rectal carcinomas. Used as part of curative preoperative and postoperative multimodal therapeutic strategies, hyperthermia can lead to improvement in local control (resectability, down-staging, progression-free time, recurrence rate), at least for certain risk groups. The preoperative radio-chemo-thermotherapy of advanced primary and recurring rectal carcinoma, uT3/4, was tested in a phase-I/II study of 20 patients. Therapy procedure, acute toxicity, thermal parameters, and response are described and discussed for this patient group. The regimen proved to be sufficiently tolerable, and complications did not occur. Tumor resection was performed on 14 of the 20 patients; 13 of the procedures were R0-resections and one was an R2 resection. In 64% of the resected rectal carcinomas, histopathological down-staging of the pretherapeutic endosonographical stadium was achieved; in three of the patients, despite continued non-resectability, local control has now been maintained for more than 12 months. In two patients with nonresectable rectal carcinomas, local progress was seen during the neoadjuvant combination therapy.

Clinical Trials as Topic↗
PubMedDate not supplied

Electromagnetic phased arrays for regional hyperthermia: optimal frequency and antenna arrangement.

This paper investigates the effects of the three-dimensional arrangement of antennae and frequency on temperature distributions that can be achieved in regional hyperthermia using an electromagnetic phased array. It compares the results of power-based and temperature-based optimization. Thus, one is able to explain the discrepancies between previous studies favouring more antenna rings on the one hand and more antennae per ring on the other hand. The sensitivity of the results is analysed with respect to changes in amplitudes and phases, as well as patient position. This analysis can be used for different purposes. First, it provides additional criteria for selecting the optimal frequency. Secondly, it can be used for specifying the required phase and amplitude accuracy for a real phased array system. Furthermore, it may serve as a basis for technological developments in order to reduce both types of sensitivities described above.

Electromagnetic Fields↗
PubMedDate not supplied

Temperature data and specific absorption rates in pelvic tumours: predictive factors and correlations.

The system BSD 2000 has been in clinical use for regional hyperthermia for more than 10 years. Several technical details of this hyperthermia system, as well as the results of clinical studies employing this system have been investigated. The intention of this paper is to investigate the correlation between technical efficiency or feasibility of hyperthermia with the BSD 2000, in terms of power densities and temperatures depending upon parameters such as tumour histology, tumour location, patient age, patient sex, and patient cross section. The possible conclusions of predictive factors derived from the above correlations were closely scrutinized. Data acquired from 772 treatment sessions of 190 patients with pelvic tumours, mainly sarcomas and carcinomas of the rectum, cervix, prostate and anus, have been evaluated. For every session, index temperatures T90 (temperature attained at 90% of tumour related measurement points), cumulative minutes for T90 > Tref, tumour related power density (SAR: specific absorption rate, in W/kg) and the effective perfusion Weff (in ml/100 g min) were calculated. Temperatures were measured either invasively or endoluminally. The statistics software SPSS was employed subsequently for univariate, as well as multivariate analyses. The results exhibit that index temperatures mainly depend on the power density SAR and the hyperthermia induced effective perfusion. The total power P (in 100 W) and, complementarily, the relative power density absolute value(SAR) (= SAR/P) seem to have lesser influence. Clear differences between the tumour entities were established regarding their index temperatures and temperature distributions. SAR, Weff and P were correlated with several anatomical, biological and clinical factors. Sessions rendering low index temperatures and SAR values also revealed decreased individual tolerance to the treatment. This clearly displays that power-induced side effects define the limits of the efficiency of regional hyperthermia. Equivalent relationships and correlations are derived from intratumoural and endoluminal thermometry. Individual limitations of regional hyperthermia caused by anatomical, biological and clinical factors are liable to be difficult to overcome with the rather restricted potentials of the BSD 2000 system to control the SAR distribution.

Analysis of Variance↗
PubMedDate not supplied

Influence of patient models and numerical methods on predicted power deposition patterns.

BACKGROUND: A hyperthermia planning system has been developed for generating patient and applicator models as well as calculating and visualizing E-field and temperature distributions. Significant dependencies on models and algorithms have been found. METHODS: Computerized tomography (CT) data sets are first transformed into so called 'labelled CT-volume'-data sets of equal resolution, which are used for segmentation. The first type of patient model obtained subsequently is based on regions with specified electrical properties representing tissues or organs (so called 'region-based model'). The second patient model renders a direct transformation of Hounsfield Units (HU) to electrical constants (so called 'HU-based model'). The FDTD-method (finite difference time domain) is then applied on a cubic lattice employing either an auxiliary 'sub-cubic lattice' (for HU-based segmentation) or a tetrahedron grid (for region-based segmentation) to assign the electrical properties, both representing the anatomy of the patient. E-field distributions are corrected by a post-processing procedure with respect to the geometry of interfaces defined by the tetrahedron grid. For comparison, the VSIE method (volume surface integral equation) is performed on the same tetrahedron grid. The applicator model assumes eight half-wavelength dipole antennas fed with constant voltages with water as background medium. RESULTS: For both numerical methods (FDTD, VSIE) the resulting antenna input impedances as well as the current distributions along the antennas were quite similar and almost insensitive to the particular geometry model (region-based, HU-based). In contrast to that, the power deposition patterns in the interior of the patient depended strongly on those models. Major differences can be related to different labels of the tissue type bone in the HU-based model in comparison to the definition via regions. Conversely, comparable results were obtained using the VSIE method and the FDTD method on the region-based patient model with a posteriori correction at the tetrahedron grid points. SAR (specific absorption rate) elevations up to a factor of 10 were predicted when employing region-based models. Those peaks might correspond to specific toxicity of electromagnetic radiation clinically known as hot spot phenomena or musculo-skeletal syndromes. Conversely, HU-based models generated quite homogeneous power deposition patterns with fluctuations of at most factor 2. CONCLUSION: The methods employing region-based geometry models such as the VSIE method and FDTD method in conjunction with a posteriori correction at tissue interfaces result in comparable E-field distributions for regional hyperthermia. Due to its shorter calculation time, the FDTD method is currently used in the clinic. Predictions derived from HU-based models without prior corrections of tissue specifications are not always supported by clinical experience.

Humans↗