Deep regional hyperthermia with preoperative radiochemotherapy in locally advanced rectal cancer, a prospective phase II trial.

PURPOSE: The goal of the present study was to investigate the effect of deep regional hyperthermia on early and long-term oncological outcomes in the context of preoperative radiochemotherapy in rectal cancer. METHODS: In this prospective phase II trial, patients with locally advanced rectal cancer were treated with 5-fluorouracil based preoperative radiochemotherapy with 50.4 Gy in 28 fractions. Deep regional hyperthermia was scheduled twice weekly. Pathological tumor regression was scored according to the Dworak regression system. The primary endpoint was pathological complete response (pCR). Further endpoints were local control (LC), distant control (DC), disease-free survival (DFS) and overall survival (OS). Hyperthermia was defined as feasible if 70% of patients received at least eight treatments. Quality of life was assessed at follow-up by the EORTC-QLQ-C30 and QLQ-CR29 questionnaires. Time to event data was analyzed according to Kaplan-Meier based on first-events. The study was registered on clinicaltrials.gov (NCT02353858). RESULTS: From 2012 until 2017, 78 patients were recruited. Median follow-up was 54 months. Based on magnetic resonance imaging, the mesorectal fascia was involved or threatened in 60% of the patients. Compliance with radiotherapy was 99%, 91% received both cycles of chemotherapy and 77% had eight or more hyperthermia treatments. Median time from the end of radiotherapy to surgery was 6.7 weeks. A pathological complete response was reported in 14% of the patients, 50% had either Dworak 4 (complete regression) or Dworak 3 regression (scattered tumor cells only). Three year estimates for OS, DFS, LC and DC were 94%, 81%, 96% and 87%. Patients with higher hyperthermia related cumulative temperatures showed stronger tumor regression. Global health status based on EORTC-QLQ-C30 was comparable with data from the general population. CONCLUSION: Deep regional hyperthermia was feasible, did not compromise standard treatments and resulted in promising long-term oncological outcomes and QoL.

Compact self-grounded Bow-Tie antenna design for an UWB phased-array hyperthermia applicator.

Using UWB hyperthermia systems has the potential to improve the heat delivery to deep seated tumours. In this paper, we present a novel self-grounded Bow-Tie antenna design which is to serve as the basis element in a phased-array applicator. The UWB operation in the frequency range of 0.43-1 GHz is achieved by immersing the antenna in a water bolus. The radiation characteristics are improved by appropriate shaping the water bolus and by inclusion of dielectric layers on the top of the radiating arms of the antenna. In order to find the most appropriate design, we use a combination of performance indicators representing the most important attributes of the antenna. These are the UWB impedance matching, the transmission capability and the effective field size. The antenna was constructed and experimentally validated on muscle-like phantom. The measured reflection and transmission coefficients as well as radiation characteristics are in excellent agreement with the simulated results. MR image acquisitions with antenna located inside MR bore indicate a negligible distortion of the images by the antenna itself, which indicates MR compatibility.

Quality assurance guidelines for superficial hyperthermia clinical trials: I. Clinical requirements.

Quality assurance guidelines are essential to provide uniform execution of clinical trials and treatment in the application of hyperthermia. This document provides definitions for a good hyperthermia treatment and identifies the clinical conditions where a certain hyperthermia system can or cannot adequately heat the tumour volume. It also provides brief description of the characteristics and performance of the current electromagnetic (radiative and capacitive), ultrasound and infra-red heating techniques. This information helps to select the appropriate heating technique for the specific tumour location and size, and appropriate settings of the water bolus and thermometry. Finally, requirements of staff training and documentation are provided. The guidelines in this document focus on the clinical application and are complemented with a second, more technical quality assurance document providing instructions and procedure to determine essential parameters that describe heating properties of the applicator for superficial hyperthermia. Both sets of guidelines were developed by the ESHO Technical Committee with participation of senior STM members and members of the Atzelsberg Circle.

Unsupervised Segmentation of Head Tissues from Multi-modal MR Images for EEG Source Localization.

In this paper, we present and evaluate an automatic unsupervised segmentation method, hierarchical segmentation approach (HSA)-Bayesian-based adaptive mean shift (BAMS), for use in the construction of a patient-specific head conductivity model for electroencephalography (EEG) source localization. It is based on a HSA and BAMS for segmenting the tissues from multi-modal magnetic resonance (MR) head images. The evaluation of the proposed method was done both directly in terms of segmentation accuracy and indirectly in terms of source localization accuracy. The direct evaluation was performed relative to a commonly used reference method brain extraction tool (BET)-FMRIB's automated segmentation tool (FAST) and four variants of the HSA using both synthetic data and real data from ten subjects. The synthetic data includes multiple realizations of four different noise levels and several realizations of typical noise with a 20% bias field level. The Dice index and Hausdorff distance were used to measure the segmentation accuracy. The indirect evaluation was performed relative to the reference method BET-FAST using synthetic two-dimensional (2D) multimodal magnetic resonance (MR) data with 3% noise and synthetic EEG (generated for a prescribed source). The source localization accuracy was determined in terms of localization error and relative error of potential. The experimental results demonstrate the efficacy of HSA-BAMS, its robustness to noise and the bias field, and that it provides better segmentation accuracy than the reference method and variants of the HSA. They also show that it leads to a more accurate localization accuracy than the commonly used reference method and suggest that it has potential as a surrogate for expert manual segmentation for the EEG source localization problem.

Fast PRF-based MR thermometry using double-echo EPI: in vivo comparison in a clinical hyperthermia setting.

OBJECTIVE: To develop and test in a clinical setting a double-echo segmented echo planar imaging (DEPI) pulse sequence for proton resonance frequency (PRF)-based temperature monitoring that is faster than conventional PRF thermometry pulse sequences and not affected by thermal changes in tissue conductivity. MATERIALS AND METHODS: Four tumor patients underwent between one and nine magnetic resonance (MR)-guided regional hyperthermia treatments. During treatment, the DEPI sequence and a FLASH PRF sequence were run in an interleaved manner to compare the results from both sequences in the same patients and same settings. Temperature maps were calculated based on the phase data of both sequences. Temperature measurements of both techniques were compared using Passing and Bablok regression and the Bland-Altman method. RESULTS: The temperature results from the DEPI and FLASH sequences, on average, do not differ by more than ΔT = 1 °C. DEPI images showed typically more artifacts and approximately a twofold lower signal-to-noise ratio (SNR), but a sufficient temperature precision of 0.5°, which would theoretically allow for a fivefold higher frame rate. CONCLUSION: The results indicate that DEPI can replace slower temperature measurement techniques for PRF-based temperature monitoring during thermal treatments. The higher acquisition speed can be exploited for hot spot localization during regional hyperthermia as well as for temperature monitoring during fast thermal therapies.

On the fully automatic construction of a realistic head model for EEG source localization.

Accurate multi-tissue segmentation of magnetic resonance (MR) images is an essential first step in the construction of a realistic finite element head conductivity model (FEHCM) for electroencephalography (EEG) source localization. All of the segmentation approaches proposed to date for this purpose require manual intervention or correction and are thus laborious, time-consuming, and subjective. In this paper we propose and evaluate a fully automatic method based on a hierarchical segmentation approach (HSA) incorporating Bayesian-based adaptive mean-shift segmentation (BAMS). An evaluation of HSA-BAMS, as well as two reference methods, in terms of both segmentation accuracy and the source localization accuracy of the resulting FEHCM is also presented. The evaluation was performed using (i) synthetic 2D multi-modal MRI head data and synthetic EEG (generated for a prescribed source), and (ii) real 3D T1-weighted MRI head data and real EEG data (with expert determined source localization). Expert manual segmentation served as segmentation ground truth. The results show that HSA-BAMS outperforms the two reference methods and that it can be used as a surrogate for manual segmentation for the construction of a realistic FEHCM for EEG source localization.

Thermal modelling using discrete vasculature for thermal therapy: A review.

Reliable temperature information during clinical hyperthermia and thermal ablation is essential for adequate treatment control, but conventional temperature measurements do not provide 3D temperature information. Treatment planning is a very useful tool to improve treatment quality, and substantial progress has been made over the last decade. Thermal modelling is a very important and challenging aspect of hyperthermia treatment planning. Various thermal models have been developed for this purpose, with varying complexity. Since blood perfusion is such an important factor in thermal redistribution of energy in in vivo tissue, thermal simulations are most accurately performed by modelling discrete vasculature. This review describes the progress in thermal modelling with discrete vasculature for the purpose of hyperthermia treatment planning and thermal ablation. There has been significant progress in thermal modelling with discrete vasculature. Recent developments have made real-time simulations possible, which can provide feedback during treatment for improved therapy. Future clinical application of thermal modelling with discrete vasculature in hyperthermia treatment planning is expected to further improve treatment quality.

Virus-induced hepatocellular carcinomas cause antigen-specific local tolerance.

T cell surveillance is often effective against virus-associated tumors because of their high immunogenicity. It is not clear why surveillance occasionally fails, particularly against hepatitis B virus- or hepatitis C virus-associated hepatocellular carcinoma (HCC). We established a transgenic murine model of virus-induced HCC by hepatocyte-specific adenovirus-induced activation of the oncogenic SV40 large T antigen (TAg). Adenovirus infection induced cytotoxic T lymphocytes (CTLs) targeted against the virus and TAg, leading to clearance of the infected cells. Despite the presence of functional, antigen-specific T cells, a few virus-infected cells escaped immune clearance and progressed to HCC. These cells expressed TAg at levels similar to HCC isolated from neonatal TAg-tolerant mice, suggesting that CTL clearance does not select for cells with low immunogenicity. Virus-infected mice revealed significantly greater T cell infiltration in early-stage HCC compared with that in late-stage HCC, demonstrating progressive local immune suppression through inefficient T cell infiltration. Programmed cell death protein-1 (PD-1) and its ligand PD-L1 were expressed in all TAg-specific CD8+ T cells and HCC, respectively, which contributed to local tumor-antigen-specific tolerance. Thus, we have developed a model of virus-induced HCC that may allow for a better understanding of human HCC.

Quality assurance for clinical studies in regional deep hyperthermia.

BACKGROUND: A guideline is provided for the implementation of regional deep hyperthermia treatments under strict rules of quality assurance. The objective is to guarantee a comparable and comprehensible method in the treatment and scientific analysis of hyperthermia. The guideline describes regional deep hyperthermia (RHT) and MR-controlled partial body hyperthermia (PBH) of children, young and adult patients. According to this guideline, hyperthermia treatment is always applied in combination with chemotherapy and/or radiotherapy. METHODS: The guideline is based on practical experience from several hyperthermia centers. The procedure allows applying jointly coordinated standards and quality control in hyperthermia for studies. RESULTS: The guideline contains recommendations for hyperthermia treatments, including indication, preparation, treatment, and standardized analysis.

Long term combination treatment with bevacizumab, pegylated liposomal doxorubicin and regional abdominal hyperthermia in platinum refractory ovarian cancer: a case report and review of the literature.

BACKGROUND: Platinum resistance constitutes a therapeutic challenge in the treatment of ovarian cancer, with overall unsatisfactory response rates to standard chemotherapy and correspondingly low survival. Regional abdominal hyperthermia and bevacizumab are treatment options that have both shown the capacity to improve the results of standard chemotherapy in the platinum-resistant situation, when added to the treatment schedule. CASE REPORT: We report on a 29-year-old patient with primary platinum-refractory ovarian cancer, who was treated with a combination of pegylated liposomal doxorubicin, regional abdominal hyperthermia and bevacizumab in a four-week cycle over a long-term period of 38 months. Due to an excellent clinical and radiologic response resulting in stable disease, with a concomitant mild toxicity profile consisting only of intermitted diarrhoea and mild fatigue [corrected] , the treatment was continued in an ambulatory setting. DISCUSSION: To our knowledge we describe the first experience with combination treatment of pegylated liposomal doxorubicin with regional abdominal hyperthermia and bevacizumab in a long term setting of almost 2 years. Excellent response with comparably low toxicity was demonstrated. Further evaluation as a therapeutic option in this heavily pretreated and highly palliative patient population is warranted.

Regularized antenna profile adaptation in online hyperthermia treatment.

PURPOSE: Online optimization of annular-phased-array hyperthermia (HT) is based on planning tools and magnetic resonance (MR) thermometry. Until now, the method has been validated in phantoms. Further developments and extensions are required for clinical purposes. In particular, the problem of deducing the electric field distribution inside the patient from MR thermometry is ill-posed, which leads to an amplification of measurement errors. A method to overcome this difficulty is proposed. METHODS: The authors utilized a regularized Gauss-Newton algorithm with a fast bioheat transfer equation (BHTE) approximation to identify the field parameters. To evaluate the method, simulations with patient models are conducted and a treatment data set obtained from a heat treatment performed in the hybrid HT-MR system at the Charité Medical School is used to visualize the error amplification. RESULTS: The regularization leads to a significantly improved accuracy of the predicted electric fields and temperatures compared to an unregularized approach. The BHTE approximation enables highly accurate temperature predictions in real-time. CONCLUSIONS: Regularization proves to be necessary to identify electromagnetic field parameters. The proposed method is able to reproduce measurements without overfitting to the noise in the MR measurements and results in an improved treatment planning.

Non-invasive magnetic resonance thermography during regional hyperthermia.

Regional hyperthermia is a non-invasive technique in which cancer tissue is exposed to moderately high temperatures of approximately 43-45 degrees C. The clinical delivery of hyperthermia requires control of the temperatures applied. This is typically done using catheters with temperature probes, which is an interventional procedure. Additionally, a catheter allows temperature monitoring only at discrete positions. These limitations can be overcome by magnetic resonance (MR) thermometry, which allows non-invasive mapping of the entire treatment area during hyperthermia application. Various temperature-sensitive MRI parameters exist and can be exploited for MR temperature mapping. The most popular parameters are proton resonance frequency shift (PRFS) (Delta phi corresponding to a frequency shift of 0.011 ppm, i.e. 0.7 Hz per degrees C at 1.5 Tesla), diffusion coefficient D (Delta D/D = 2-3 % per degrees C), longitudinal relaxation time T(1) (Delta T1/T1 approximately 1% per degrees C), and equilibrium magnetisation M(0) (Delta M(0)/M=0.3% per degrees C). Additionally, MRI temperature mapping based on temperature-sensitive contrast media is applied. The different techniques of MRI thermometry were developed to serve different purposes. The PRFS method is the most sensitive proton imaging technique. A sensitivity of +/-0.5 degrees C is possible in vivo but use of PRFS imaging remains challenging because of a high sensitivity to susceptibility effects, especially when field homogeneity is poor, e.g. on interventional MR scanners or because of distortions caused by an inserted applicator. Diffusion-based MR temperature mapping has an excellent correlation with actual temperatures in tissues. Correct MR temperature measurement without rescaling is achieved using the T(1) method, if the scaling factor is known. MR temperature imaging methods using exogenous temperature indicators are chemical shift and 3D phase sensitive imaging. TmDOTMA(-) appears to be the most promising lanthanide complex because it showed a temperature imaging accuracy of <0.3 degrees C.

Regional abdominal hyperthermia combined with systemic chemotherapy for the treatment of patients with ovarian cancer relapse: Results of a pilot study.

PURPOSE: Due to the poor prognosis of patients with ovarian cancer relapse (OCR), newer strategies are warranted to improve the therapeutic index. We performed a prospective phase I/II-study of regional abdominal hyperthermia (RHT) combined with systemic chemotherapy in OCR patients in order to evaluate outcome, efficacy and tolerance. MATERIALS AND METHODS: OCR patients with an Eastern Cooperative Oncology Group status <2, without any thromboembolic disease or severe cardiovascular co-morbidities, and pre-treated with at least one systemic chemotherapy regimen due to epithelial ovarian cancer were enrolled into the present study. RHT was applied using a SIGMA 60 applicator and a Hybrid-System SIGMA-Eye/MRT composed of a 1.5T-MRT and a Sigma-Eye-applicator. RESULTS: Overall, 36 OCR patients were enrolled. The majority of the patients (>80%) were classified as platinum resistant. The most common chemotherapeutic agent applied was pegylated-liposomal-doxorubicin (47.2%) followed by carboplatin (16.6%) and topotecan (13.9%). One patient (2.8%) achieved a complete remission (CR), 12 patients (33.3%) yielded a partial remission (PR) and 16 patients (44.4%) developed a progressive disease (PD). In platinum-sensitive patients we observed higher response (57.1% versus 31%) and lower progression rates (28.6% versus 48.3%) than in platinum-resistant patients. Eleven patients (30.5%) discontinued treatment due to toxicity. The main toxicity was a haematological one with grade 3/4 anaemia, leucopenia and thrombocytopenia occurring in 13.9%, 5.6% and 8.3%, respectively. Median overall survival was 12 months (range: 1-48), while median progression-free survival was 5 months (range: 0.5-34). CONCLUSIONS: Our results demonstrate the feasibility of RHT combined with systemic treatment. Prospective phase III trials are warranted to evaluate the benefit and efficacy in heavily pre-treated patients with OCR.

Immunogenicity of premalignant lesions is the primary cause of general cytotoxic T lymphocyte unresponsiveness.

Cancer is sporadic in nature, characterized by an initial clonal oncogenic event and usually a long latency. When and how it subverts the immune system is unknown. We show, in a model of sporadic immunogenic cancer, that tumor-specific tolerance closely coincides with the first tumor antigen recognition by B cells. During the subsequent latency period until tumors progress, the mice acquire general cytotoxic T lymphocyte (CTL) unresponsiveness, which is associated with high transforming growth factor (TGF) beta1 levels and expansion of immature myeloid cells (iMCs). In mice with large nonimmunogenic tumors, iMCs expand but TGF-beta1 serum levels are normal, and unrelated CTL responses are undiminished. We conclude that (a) tolerance to the tumor antigen occurs at the premalignant stage, (b) tumor latency is unlikely caused by CTL control, and (c) a persistent immunogenic tumor antigen causes general CTL unresponsiveness but tumor burden and iMCs per se do not.

Perfusion measurement using DCE-MRI: implications for hyperthermia.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is today the most popular method to assess perfusion in the body. Unfortunately, the technique is mostly used to determine semiquantitative parameters like time to peak enhancement. Perfusion quantification remains challenging using DCE-MRI. The method suffers from two major limitations. First, no standardized imaging technique is available. Secondly, no standard evaluation technique for perfusion quantification has been established which accurately describes the tracer kinetics of available contrast agents. Different imaging techniques using spoiled gradient echo sequences and the basics of the evaluation are presented. To assess perfusion changes due to hyperthermia using DCE-MRI one has to take into account the systematic variation of the arterial input function required for perfusion quantification. Hyperthermia modifies the contrast agent bolus in that a shorter and more highly concentrated bolus appears earlier in the tissue.

Simulation of different applicator positions for treatment of a presacral tumour.

INTRODUCTION: Proximally located presacral recurrences of rectal carcinomas are known to be difficult to heat due to the complex anatomy of the pelvis, which reflect, shield and diffract the power. This study is to clarify whether a change of position of the Sigma-Eye applicator in this region can improve the heating. MATERIAL AND METHODS: Finite element (FE) planning calculations were made for a phantom model with a proximal presacral tumour using a fixed 100 MHz radiofrequency radiation. Shifts of the applicator were simulated in 1 cm steps in x-(lateral), y-(posterior) and z-(longitudinal) direction. Computations also considered the network effects of the Sigma-Eye applicator. Optimisation of the phases and amplitudes for all positions were performed after solving the bioheat-transfer-equation. The parameters T90, T50, sensitivity, hot spot volume and total deposited power have been sampled for every applicator position with optimised plans and a standard plan. RESULTS: The ability to heat a presacral tumour clearly depends on the applicator position, for standard antenna adjustment and also for optimised steering of the Sigma-Eye applicator. The gamma-direction (anterior-posterior) is very sensitive. Using optimised steering for each position, in z-direction (longitudinal), we found an unexpected additional optimum at 8 cm cranial from the middle position of the phantom. The x-direction (lateral) is in a clinical setting less important and shows only smaller changes of T90 with an expected optimum in the central position. A positioning of the applicator in the axial and anterior position of the mid-pubic symphysis should be avoided for treatment of the presacral region, regardless of the used adjustment. Use of amplitude and phase optimisation yields better T90 values than plans optimised only by phases, but they are much more sensitive for small variations of phases and amplitudes during a treatment, and the total power of the Sigma-Eye applicator can be restricted by the treatment software. CONCLUSIONS: Complex geometry of the human pelvis seems to be the reason for the difficulties to warm up the proximal presacral region. The assumption that every position can be balanced by a proper phase adaption, is true only in a small range. A centring of the applicator on the mid-pubic symphysis to heat this region should be avoided. From the practical point of view improved warming should be performed by optimisation of phases only.

Implications of clinical RF hyperthermia on protection limits in the RF range.

The systemic temperature is meticulously regulated to 37-37.5 degrees C. Organ systems (skin, digestive system, muscles) have a considerable potential to regulate the perfusion for thermal regulation, physical activity, or digestion. While the regulation of the systemic temperature (37.5 degrees C) is quite strict, the tolerance and regulation potential with respect to local heat is more variable. Laboratory studies provided the relationship between thermal doses and cytotoxic effects. Tissue damage for short-term expositions (in the range of minutes) is only possible for temperatures above 50 degrees C. Radiofrequency radiation is utilized in cancer therapy, inducing local tissue temperatures in the range of 40-45 degrees C for 30-60 min. During local hyperthermia (with heated volumes <1 L) specific absorption rates (SARs) of 100-200 W kg, reactive perfusions of 20-40 mL/100 g/min, and tumor temperatures of 42-43 degrees C are achieved. Normally no side effects or damage in the normal tissue, such as muscle or skin, have been seen. During regional hyperthermia, SARs of 30-40 W kg are found in heated volumes of 10 L with temperatures of 41-42 degrees C in tumor-related measurement points. Then the reactive average perfusion is 6-9 mL/100 g/min (mean value 8 mL/100 g/min). Local temperatures even for higher SAR are regulated to values of not more than 40-42 degrees C. For these temperatures no damages in normal tissues have been found after regional hyperthermia in hundreds of patients. We conclude that the thermoregulatory potential for the whole body or large body regions is limited by the cardiac output, which can at least double the output from 5 to 10 L min. Even higher is the potential to compensate in smaller volumes. Here the perfusion in muscle can be increased from the basal value of 2-4 mL/100 g/min more than 5-10-fold.

Adaptation of antenna profiles for control of MR guided hyperthermia (HT) in a hybrid MR-HT system.

A combined numerical-experimental iterative procedure, based on the Gauss-Newton algorithm, has been developed for control of magnetic resonance (MR)-guided hyperthermia (HT) applications in a hybrid MR-HT system BSD 2000 3D-MRI. In this MR-HT system, composed of a 3-D HT applicator Sigma-Eye placed inside a tunnel-type MR tomograph Siemens MAGNETOM Symphony (1.5 T), the temperature rise due to the HT radiation can be measured on-line in three dimensions by use of the proton resonance frequency shift (PRFS) method. The basic idea of our iterative procedure is the improvement of the system's characterization by a step-by-step modification of the theoretical HT antenna profiles (electric fields radiated by single antennas). The adaptation of antenna profiles is efficient if the initial estimates are radiation fields calculated from a good a priori electromagnetic model. Throughout the iterative procedure, the calculated antenna fields (FDTD) are step-by-step modified by comparing the calculated and experimental data, the latter obtained using the PRFS method. The procedure has been experimentally tested on homogeneous and inhomogeneous phantoms. It is shown that only few comparison steps are necessary for obtaining a dramatic improvement of the general predictability and quality of the specific absorption rate (SAR) inside the MR-HT hybrid system.

Noninvasive magnetic resonance thermography of soft tissue sarcomas during regional hyperthermia: correlation with response and direct thermometry.

BACKGROUND: The objective of this study was to evaluate noninvasive magnetic resonance (MR) thermography for the monitoring of regional hyperthermia (RHT) in patients with soft tissue sarcomas of the lower extremities and pelvis. METHODS: Noninvasive MR monitoring during RHT was performed in 9 patients who had high-risk soft tissue sarcomas of the lower extremities or pelvis during neoadjuvant chemotherapy plus RHT in the scope of the European Organization for Research and Treatment of Cancer 62961/European Society for Hyperthermic Oncology RHT-95 study. Anatomic and temperature-sensitive data sets were acquired every 10 minutes before and during RHT (using gradient-echo-sequences with variable echo times). MR temperature distributions were derived from the phase differences by using the proton-resonance frequency shift method. A phase convolution setting phase shifts to zero in the fat tissue was performed as a drift correction. The mean MR temperatures in the tumor and muscles and the index temperatures (e.g., T90, which covers 90% of the target volume) and thermal doses were determined and compared with pathohistologic responses and direct temperature measurements if available. RESULTS: Thirty of 72 MR-thermography data sets (>40% of heat sessions) were evaluable. A significant correlation was observed between pathohistologic response (defined as a necrosis rate >or=90%) and standardized thermal parameters, such as thermal dose cumulative equivalent minutes at 43 degrees C to 90% of the target volume (T90) (P = .050), mean T90 (P = .048), or T50 (P = .050). The correlation of 13 conventional temperature measurements performed in selected patients and sessions invasively in the tumor or noninvasively in rectum and bladder revealed an excellent correlation with MR temperatures (R2 = .96). CONCLUSIONS: Noninvasive MR thermography of soft tissue sarcoma was feasible and suitable for validating the quality of heating during RHT.

Thermal monitoring: invasive, minimal-invasive and non-invasive approaches.

BACKGROUND: Thermal treatments need verification of effectiveness. Invasive intra-tumoural thermometry was established as a standard method several years ago. However, in deep heating, invasive techniques have disadvantages. Therefore, alternatives have been suggested and are under development. METHODS: In three phase II studies treating rectal cancer, cervical cancer and prostate cancer, this study replaced invasive (intra-tumoural) thermometry by tumour-related reference points or catheter sections in the rectum, vagina or urethra. Index temperatures and thermal dose parameters were determined. Two recent studies treated patients with recurrent rectal cancer and soft tissue sarcoma using non-invasive MR-thermometry employing the SIGMA-Eye applicator. The proton resonance frequency shift (PRFS) method was employed to generate MR-temperature distributions during the entire heat treatment in 10 min intervals (via phase differences). Fat correction (nulling specified regions in the fat tissue) was utilized to calibrate the method, in particular with respect to the B0-drift. RESULTS: Statistically significant correlations were found between response (downstaging, WHO) and thermal parameters in rectal cancer (37 patients, rectum measurement, T90, cum min T90 >or= 40.5 degrees C) and cervical cancer (30 patients, vagina, mean temperature and equ min 43 degrees C in a reference point). In prostate cancer (14 patients), a clear correlation was verified between long-term PSA control (or= 40.5 degrees C). The mean MR-temperature in the tumour at steady-state as well as the mean T90 were significantly correlated with response for recurrent rectal carcinoma regarding palliation and analgesia (15 patients) and with pathohistological regression rate in soft tissue sarcoma (nine patients). CONCLUSIONS: For tumours in the pelvis and in the lower extremities, invasive measurements can be replaced by minimally-invasive or non-invasive techniques, which provide equivalent or even more complete information. Extending the application of these surveillance methods to abdominal tumours or liver metastases is a challenge, but strongly desirable for clinical reasons.