A multicenter analysis of 123 patients with recurrent rectal cancer within the pelvis.
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Adult↗
Biomedical subjects
P Wust
Publications and source records attributed to P Wust.
Treatment of locally recurrent rectal cancer with special focus on regional pelvic hyperthermia.
Progress in surgery and adjuvant therapy has markedly improved local control and survival rates in patients with primary, non-metastatic rectal cancer. However, the prognosis of patients with locally recurrent disease is still poor, and a realistic chance for repeated treatment with curative intent is still restricted to the minority of cases. Therefore, effective palliation of symptoms and preservation of a good quality of life are the major goals of therapy for most patients with local recurrence of rectal cancer. Here we give a short overview on the options available for the treatment of pelvic recurrence of rectal cancer, with special focus on adjunctive regional pelvic radiofrequency hyperthermia.
Combined Modality Therapy↗
[Hyperthermia: current status and therapeutic results].
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Combined Modality Therapy↗
Impact of overall treatment time on local control of anal cancer treated with radiochemotherapy.
Between 1987 and 2000, 111 patients with epidermoid anal cancer (T1-T4 Nx M0) were assigned to primary simultaneous radiochemotherapy (RCT) with a radiation dose of 45 Gy, performed either as a split course with 2-Gy single fractions (schedule A, 1987-1996, n = 65 patients) or continuously with fractions of 1.8 Gy (schedule B, 1996-2000; n = 38 patients). The chemotherapy consisted of continuous infusions of 5-fluorouracil (5-FU; 800/1,000 mg/m(2)/day, on 4/5 consecutive days, during weeks 1 and 5) together with one (schedule A) or two (schedule B) short infusions of mitomycin C (10 mg/m(2)) during the first course of 5-FU. Associations between clinical outcome and various prognostic factors were assessed in 103 patients who completed these schedules. For both patient groups combined, 5-year local control rate was 67% and 5-year survival rate 71%. Advanced tumor stage, size, and nodal status significantly decreased the 5-year local control rate as well as the overall treatment time (OTT) >41 days (58% for OTT >41 days vs. 79% for OTT < or =41 days; p = 0.04). However, we did not find a correlation with the prescribed radiotherapy schedule (A or B). In conclusion, in patients with anal carcinomas treated with RCT with a radiation dose of 45 Gy, the predominant determinant of local control is the resulting OTT and not the administration schedule (split course or continuous radiotherapy).
Adult↗
Current and potential role of thermoradiotherapy for solid tumours.
The disappointing results for inoperable, locally advanced or recurrent solid tumours of the uterine cervix, rectum, chest wall, liver and deep seated, high-risk sarcomas after conventional radiotherapy alone necessitate the search for improved treatments. A benefit from simultaneous radiochemotherapy with regard to local tumour control and survival has been shown for a rising number of tumour entities. Radiofrequency hyperthermia is established in only a few centres, and represents another option to intensify the effect of radio- and chemotherapy. Altogether 11 randomised phase III trials with more than 1,000 patients proved the combination of hyperthermia (40-42 degrees C for at least 1 h) and radiation therapy in reference to local tumour control. Two of these trials could demonstrate a survival benefit; e.g. in locally advanced cervical cancer, stage FIGO IIB-IVa, the 3-year survival was improved from 27 to 51% with the addition of hyperthermia. Frequently trial design (main endpoint local tumour control), a low number of patients or a short follow- up period are the reasons why most trials of thermoradiotherapy failed to demonstrate a survival benefit. Disadvantageous effects of hyperthermia like an increased rate of distant metastases as a result of hyperthermia-induced elevated perfusion can be largely ruled out. While at the moment the equivalence of thermoradiotherapy and radiochemotherapy is still under evaluation, future studies have to investigate the question whether hyperthermia can add benefits when used in combination with simultaneous radiochemotherapy. An ongoing investigation of hyperthermia in multimodal treatment strategies for locally advanced solid tumours is warranted. These trials will help to improve temperature monitoring and temperature distribution and define particular groups of patients who will profit from the addition of hyperthermia. The 'Interdisziplinäre Arbeitsgruppe Hyperthermie', a working group of the German Cancer Society, introduces clinical protocols, treatment devices, and provides information for patients at www.hyperthermie.org.
Combined Modality Therapy↗
[T4 rectal carcinoma. Surgical and multimodal therapy].
BACKGROUND: In locally advanced rectal cancer with infiltration of neighbouring organs (uT4), resectability and local control are difficult to achieve. Combined preoperative radiochemotherapy may result in increased resectability and reduced local recurrence rates. PATIENTS AND METHODS: Thirty-four patients with biopsy-proven locally advanced rectal cancer were treated by preoperative radiochemotherapy. All tumours had been staged as uT4 lesions by endorectal ultrasound or computed tomography. Radiotherapy was applied in standard blocks, 5 x 1.8 Gy up to 45 Gy. Chemotherapy consisted of two cycles of 5-fluorouracil (300-350 mg/m2/day) and leucovorin (50 mg). In 20 patients, additional thermotherapy was carried out using the Sigma 60 applicator BSD 2000 once a week prior to radiotherapy. Surgery was performed 4-6 weeks after radiochemotherapy. Postoperatively, all patients received four cycles of 5-fluorouracil and leucovorin. RESULTS: Treatment-induced toxicity occurred in 26% of the patients (WHO grade III (n = 6) and IV (n = 3)). The resectability rate was 76% (26/34 patients) (R0 resectability n = 21; 62%). The pathological complete response rate was 6% (n = 2) and the partial response rate was 47% (n = 16). A local failure was observed in six patients after median time of 16 months (range 7-36 months). Patients with R0 resection achieved a 5-year disease-free survival rate of 55% and a survival rate of 71%. The overall 5-year survival rate for all patients with advanced uT4 rectal cancer was 49%. CONCLUSIONS: Our data on preoperative combined treatment in locally advanced T4 rectal cancer revealed encouraging downstaging, local control, and survival rates.
Adult↗
Hyperthermia in combined treatment of cancer.
Hyperthermia, the procedure of raising the temperature of tumour-loaded tissue to 40-43 degrees C, is applied as an adjunctive therapy with various established cancer treatments such as radiotherapy and chemotherapy. The potential to control power distributions in vivo has been significantly improved lately by the development of planning systems and other modelling tools. This increased understanding has led to the design of multiantenna applicators (including their transforming networks) and implementation of systems for monitoring of E-fields (eg, electro-optical sensors) and temperature (particularly, on-line magnetic resonance tomography). Several phase III trials comparing radiotherapy alone or with hyperthermia have shown a beneficial effect of hyperthermia (with existing standard equipment) in terms of local control (eg, recurrent breast cancer and malignant melanoma) and survival (eg, head and neck lymph-node metastases, glioblastoma, cervical carcinoma). Therefore, further development of existing technology and elucidation of molecular mechanisms are justified. In recent molecular and biological investigations there have been novel applications such as gene therapy or immunotherapy (vaccination) with temperature acting as an enhancer, to trigger or to switch mechanisms on and off. However, for every particular temperature-dependent interaction exploited for clinical purposes, sophisticated control of temperature, spatially as well as temporally, in deep body regions will further improve the potential.
Animals↗
Monitoring arterial blood pressure during whole body hyperthermia.
BACKGROUND: For monitoring of arterial blood pressure (ABP) during whole body hyperthermia (WBH) different methods have been recommended. This investigation was performed to evaluate the agreement of invasive measurements at various sites, and to compare invasive and non-invasive methods of ABP monitoring under conditions of a heat-induced extreme vasodilation. METHODS: In 19 patients, 48 treatments with WBH were performed. Measurements of ABP in the radial and femoral artery by oscillometry and by sphygmomanometry were taken at four temperature levels during WBH (37, 40, 41.8 and 39 degrees C). RESULTS: Significant differences were observed between invasive and non-invasive methods for systolic ABP, with higher values for non-invasive measurements. When compared with both invasive measurements for diastolic blood pressures, sphygmomanometry gave higher values and oscillometry gave lower values. Sphygmomanometry also showed higher values for mean ABP compared with all other techniques, while measurements in radial and femoral artery and by oscillometry only differed by approximately 5 mmHg. CONCLUSION: The mean arterial pressure and not the systolic and/or diastolic pressure should guide hemodynamic management during WBH. The sphygmomanometric technique is not recommended for use during hyperthermia.
Adult↗
[Comparison between endorectal MRI (EMRTI) and endorectal sonography (ES) after surgery or therapy for rectal tumors to exclude recurrent or residual tumor].
PURPOSE: This study was designed to evaluate the accuracy and limitations for staging of contrast-enhanced endorectal MR imaging comparing with transrectal US for restaging of rectal lesions after surgery or after therapeutic radiation. Both methods were correlated with histologic findings. METHOD/MATERIALS: The efficacy of these both methods was evaluated in 30 patients with supposed residual or recurrent rectal neoplasms. Contrast enhanced (bolus injection of 0.1 mmol/kg b.w. Gd-DTPA) endorectal MR imaging was performed using a 1.5 Tesla Magnetom. In addition endosonography (7.5 x or 10-MHz transducer) was used. RESULTS: In 8 patients with rectal adenoma after electro-laser resection, 8 patients with rectal carcinoma stage pT1 after transanal resection, 8 patients with rectal carcinoma stage pT2 and 6 patients with rectal carcinoma stage pT3 after regional hyperthermia with radiochemo-therapy, the following results were obtained during the postsurgical or posttherapeutical follow-up with respect to histopathological evaluation: exact staging in 86.6 % with EMRI and 63.3 % in ES, overstaging in 8 % (EMRI) and 23 % (ES), understaging in 0 % (EMRI) and 7 % (ES). The highest diagnostic accuracy was shown in EMRT in patients with rectal adenoma and rectal carcinoma (pT1) and after electro-laser resection or transanal resection during follow-up. CONCLUSIONS: Contrast enhanced endorectal MR imaging appears to be very promising for accurate posttherapeutical staging of rectal cancer and helpful in the diagnosis of recurrence or the differentiation between scar tissue and residual rectal tumor.
Adenoma↗
[Radiochemotherapy plus hyperthermia in rectal carcinoma].
In locally advanced rectal cancer (uT3/uT4) resectability as well as local control is reduced. In the patients combined preoperative radiochemotherapy demonstrated an increase of resectability and a reduction of local recurrence. Radiotherapy was applied in standard blocks, 5 x 1.8 Gy up to 45 Gy. Chemotherapy consisted out of two cycles of 5-Fluorouracil (300-350 mg/m2/d) and Leucovorin (50 mg). Prior to radiotherapy additionally thermotherapy was carried out using the SIGMA 60 applicator BSD 2000 once a week. The hyperthermia method is based on heating up affected tissue compartments to temperature above 42 degrees Celsius without damaging surrounding tissue compartments. In regional hyperthermia tumors in the abdominal region are treated by emitting radio waves into the patient. 4-6 weeks after radiochemotherapy, surgery was performed. The therapeutic toxicity was acceptable and the resectability rate was up to 90%. Response rate to treatment was 60%. Our data with preoperative combined treatment in locally advanced rectal cancer revealed encouraging downstaging, local control, and survival rates.
Chemotherapy, Adjuvant↗
Calibrated electro-optic E-field sensors for hyperthermia applications.
E-field measurements are an important task for the investigation of newly developed hyperthermia applicators as well as for online control of hyperthermia treatments. Compact and non-perturbing integrated optical E-field sensors based on LiNbO3 as well as optical E-field sensors based on infrared emitting diodes and light bulbs are suitable for nearfield measurements of hyperthermia antennas. In order to investigate their properties a calibration cell with transverse electromagnetic (TEM) waves has been constructed. By using this cell, calibration curves and directional patterns for all sensors have been measured. Due to the threshold behaviour of the IRED and light bulb sensor, only the LiNbO3 sensor is capable of measuring weak fields inside an applicator or a homogeneous phantom.
Biophysical Phenomena↗
A fast algorithm to find optimal controls of multiantenna applicators in regional hyperthermia.
The goal of regional hyperthermia is to heat up deeply located tumours to temperatures above 42 C while keeping the temperatures in normal tissues below tissue-dependent critical values. The aim of this paper is to describe and analyse functions which can be used for computing hyperthermia treatment plans in line with these criteria. All the functionals considered here can be optimized by efficient numerical methods. We started with the working hypothesis that maximizing the quotient of integral absorbed power inside the tumour and a weighted energy norm outside the tumour leads to clinically useful power distributions which also yield favourable temperature distributions. The presented methods have been implemented and tested with real patient data from the Charité Berlin. Campus Virchow-Klinikum. The results obtained by these fast routines are comparable with those obtained by relatively expensive global optimization techniques. Thus the described methods are very promising for online optimization in a hybrid system for regional hyperthermia where a fast response to MR-based information is important.
Algorithms↗
Antenna arrays in the SIGMA-eye applicator: interactions and transforming networks.
OBJECTIVES: In multiantenna applicators such as the SIGMA-60 or SIGMA-Eye, which consist of 4 or 12 pairs of antennas shunt to 4 or 12 amplifiers ("antenna couplets"), phases and amplitudes in the feed points of these antennas under certain conditions can significantly differ from the values selected at the multichannel amplifier (forward parameters), mainly due to coupling. In the SIGMA-Eye, this interaction is particularly affected by the transforming networks between the generators and the feed points, thus hampering the control of the feed point parameters. In this work, we perform measurements at existing applicators, present a formalism to describe the facts numerically, and investigate modifications of the transforming networks to improve the performance. METHODS AND MATERIALS: We prepared an experimental setup for the SIGMA-Eye applicator that is fed by forward waves of a 12-channel amplifier system. In this setup, we made the water bolus, the interior of the tissue-equivalent phantom, and the entire transforming network accessible for measuring probes. Then, we constructed various alternative transforming networks such as Pawsey loops, LC matching networks, and power dividers and compared them with the original matching network of the SIGMA-Eye applicator. In particular, we utilized a high-resistive probe to determine the disturbances and influences caused by some channels with respect to some selected feed points of the SIGMA-Eye dipoles. RESULTS: In the original SIGMA-Eye applicator, the influences of coupling channels on the phases and voltages in the feed point of a particular antenna are largest for adjacent longitudinal channels. Here, the +/- 10 degrees phase shift and +/- 30% voltage change were observed if the reference channel (i.e., the disturbed channel) and disturbing channel are equally powered. The changes eminently increased to -30 degrees to + 100 degrees phase shift and -80% to +50% voltage change if the reference channel is fed with much lower power (four to eight-fold) than the disturbing channel. The disturbance from distant channels is less but still significant, reaching shifts of -10 degrees to +50 degrees and -50% to +20%, respectively. Using Pawsey loops instead of the original ferrite rings in the SIGMA-Eye network, the efficacy of the baluns was improved by a more than a factor of 4. Using an LC matching network, dependencies on frequency and external arrangements can be reduced significantly. Applying a power divider circuit, the coupling between antennas combined to one channel is considerably diminished (down to <-25 dB). CONCLUSION: Coupling between resonators (pairs of antennas including the matching network) reduces the control of the SIGMA-Eye applicator, i.e., it causes deviations between the selection of forward parameters at the amplifier and the total actual parameters in the feed points of the antennas. Modified transformation networks can improve the control, in particular by reducing sheath currents and asymmetries. There is a linear but variable relationship between selected (amplifiers) and actually given (feed points) parameters. This linear mapping (described by a matrix) and its characteristics need further investigation.
Hyperthermia, Induced↗
Preoperative radiochemotherapy in locally advanced or recurrent rectal cancer: regional radiofrequency hyperthermia correlates with clinical parameters.
PURPOSE: Preoperative radiochemotherapy (RCT) is a widely used means of treatment for patients suffering from primary, locally advanced, or recurrent rectal cancer. We evaluated the efficacy of treatment due to additional application of regional hyperthermia (HRCT) to this conventional therapy regime in a Phase II study, employing the annular phased-array system BSD-2000 (SIGMA-60 applicator). The clinical results of the trial were encouraging. We investigated the relationship between a variety of thermal and clinical parameters in order to assess the adequacy of thermometry, the effectiveness of hyperthermia therapy, and its potential contribution to clinical endpoints. METHODS AND MATERIALS: A preoperative combination of radiotherapy (1.8 Gy for 5 days a week, total dose 45 Gy applied over 5 weeks) and chemotherapy (low-dose 5-fluorouracil [5-FU] plus leucovorin in the first and fourth week) was administered to 37 patients with primary rectal cancer (PRC) and 18 patients with recurrent rectal cancer (RRC). Regional hyperthermia (RHT) was applied once a week prior to the daily irradiation fraction of 1.8 Gy. Temperatures were registered along rectal catheters using Bowman thermistors. Measurement points related to the tumor were specified after estimating the section of the catheter in near contact with the tumor. Three patients with local recurrence after abdominoperineal resection, had their catheters positioned transgluteally under CT guidance, where the section of the catheter related to the tumor was estimated from the CT scans. Index temperatures (especially T(max), T(90)) averaged over time, cumulative minutes (cum min) (here for T(90) > reference temperature 40.5 degrees C), and equivalent minutes (equ min) (with respect to 43 degrees C) were derived from repetitive temperature-position scans (5- to 10-min intervals) utilizing software specially developed for this purpose on a PC platform. Using the statistical software package SPSS a careful analysis was performed, not only of the variance of thermal parameters with respect to clinical criteria such as toxicity, response, and survival but also its dependency on tumor characteristics. RESULTS: The rate of resectability (89%) and response (59%) were high for the PRC group, and a clear positive correlation existed between index temperatures (T(90)) and thermal doses (cum min T(90) >/= 40.5 degrees C). Even though the overall 5-year survival was encouraging (60%) and significantly associated with response, there was no statistically significant relationship between temperature parameters and long-term survival for this limited number of patients. However, nonresectable tumors with higher thermal parameters (especially cum min T(90) >/= 40.5 degrees C) had a tendency for better overall survival. We found even higher temperatures in patients with recurrences (T(90) = 40.7 degrees C versus T(90) = 40.2 degrees C). However, these conditions for easier heating did not involve a favorable clinical outcome, since surgical resectability (22%) and response rate (28%) for the RRC group were low. We did not notice any other dependency of thermal parameters to a specific tumor or patient characteristics. Finally, neither acute toxicity (hot spots) induced by hyperthermia or RCT nor perioperative morbidity were correlated with temperature-derived parameters. Only a higher probability for the occurrence of hot spots was found during treatment with elevated power levels. CONCLUSION: In this study with two subgroups, i.e., patients with PRC (n = 37) and RRC (n = 18), there exists a positive interrelationship between thermal parameters (such as T(90), cum min T(90) >/= 40,5 degrees C) and clinical parameters concerning effectiveness. Additional hyperthermia treatment does not seem to enhance toxicity or subacute morbidity. Procedures to measure temperatures and to derive thermal parameters, as well as the hyperthermia technique itself appear adequate enough to classify heat treatments in
Age Factors↗
Regional hyperthermia for rectal cancer.
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Combined Modality Therapy↗
Clinical evaluation and verification of the hyperthermia treatment planning system hyperplan.
PURPOSE: A prototype of the hyperthermia treatment planning system (HTPS) HyperPlan for the SIGMA-60 applicator (BSD Medical Corp., Salt Lake City, Utah, USA) has been evaluated with respect to clinical practicability and correctness. MATERIALS AND METHODS: HyperPlan modules extract tissue boundaries from computed tomography (CT) images to generate regular and tetrahedral grids as patient models, to calculate electric field (E-field) distributions, and to visualize three-dimensional data sets. The finite difference time-domain (FDTD) method is applied to calculate the specific absorption rate (SAR) inside the patient. Temperature distributions are calculated by a finite-element code and can be optimized. HyperPlan was tested on 6 patients with pelvic tumors. For verification, measured SAR values were compared with calculated SAR values. Furthermore, intracorporeal E-field scans were performed and compared with calculated profiles. RESULTS: The HTPS can be applied under clinical conditions. Measured absolute SAR (in W/kg), as well as relative E-field scans, correlated well with calculated values (+/-20%) using the contour-based FDTD method. Values calculated by applying the FDTD method directly on the voxel (CT) grid, were less well correlated with measured data. CONCLUSION: The HyperPlan system proved to be clinically feasible, and the results were quantitatively and qualitatively verified for the contour-based FDTD method.
Algorithms↗
Is absolute noninvasive temperature measurement by the Pr[MOE-DO3A] complex feasible.
Recently, the feasibility of the praseodymium complex of 10-(2-methoxyethyl)-1,4,7,10-tetraaza-cyclododecane-1,4,7-tr iacetate (Pr[MOE-DO3A]) for non-invasive temperature measurement via 1H spectroscopy has been demonstrated. Particularly the suitability of the complex for non-invasive temperature measurements including in vivo spectroscopy without spatial resolution as well as first spectroscopic imaging measurements at low temporal resolution (> or = 4 min) and high temporal resolution (breath hold, approximately 20 s) has been shown. As of today, calibration curves according to the particular experimental conditions are necessary. This work aims to clarify whether the Pr[MOE-DO3A] probe in conjunction with 1H-NMR spectroscopy allows non-invasive absolute temperature measurements with high accuracy. The measurement results from two different representative media, distilled water and human plasma, show a slight but significant dependence of the calibration curves on the surrounding medium. Calibration curves in water and plasma were derived for the temperature dependence of the chemical shift difference (F) between Pr[MOE-DO3A]'s OCH3 and water with F = -(27.53 +/- 0.04) + (0.125 +/- 0.001) x T and F = -(27.61 +/- 0.02) + (0.129 +/- 0.001) x T, respectively, with F in ppm and T in degrees C. However, the differences are minuscule even for the highest spectral resolution of 0.001 ppm/pt, so that they are indistinguishable under practical conditions. The estimated temperature errors are +/- 0.18 degrees C for water and +/- 0.14 degrees C for plasma and with that only slightly worse than the measurement accuracy of the fiber-optical temperature probe (+/- 0.1 degrees C). It can be concluded that the results obtained indicate the feasibility of the 1H spectroscopy method in conjunction with the Pr[MOE-DO3A] probe for absolute temperature measurements, with a maximum accuracy of +/- 0.2 degrees C.
Agar↗
[The importance of delay in patients with tumors exemplified by pretreatment of locally advanced rectal carcinoma].
BACKGROUND: With the intention to achieve tumor reduction and thereby increase R0-resection rate, preoperative radiochemotherapy is increasingly applied in locally advanced rectum cancer. Along with the advantages of prior therapy, a delay of surgical treatment occurs which might despite continuing therapy give way to local tumor progression or metastatic disease. PATIENTS AND METHODS: Since 1993 we have treated locally advanced rectum carcinomas by preoperative radiotherapy according to a preoperative study protocol. We analyzed the incidence of local tumor progression or metastases during the 12 weeks of preoperative treatment. Hundred and fifteen patients with histologically proven primary rectum carcinoma without evidence of regional or distant metastases and endosonographically determined infiltration depth of stage T3 or more underwent preoperative radiochemotherapy between 3/1993 and 10/1999. Hundred and eight patients (88 times uT3 and (20 times uT4) have been operated and examined afterwards with respect to response to prior treatment. Before and after preoperative therapy, endorectal ultrasound was performed to evaluate local response. Distant metastatic manifestations were excluded by radiography and ultrasound scanning. RESULTS: A reduction of the infiltration depth was observed in 55 patients (51%). Tumor size remained unchanged in 50 patients (46%). Only 3 patients (3%) showed tumor growth in histological assessment. Fifty-seven patients (53%) showed no change in lymph node status after preoperative therapy, whereas lymph node metastases were detected in 11 patients (10%) who were judged uN0 preoperatively. We discovered metastases in 6 patients (6%) after preoperative therapy. CONCLUSION: During preoperative therapy, tumor progress is not entirely evitable. Considering the lack of precision in pretherapeutic staging diagnostics, we conclude that delays due to therapeutic regimen are responsible for prognostic disadvantage in only a small number of patients.
Antimetabolites, Antineoplastic↗