Magnetic fluids (MF) have a potential for hyperthermia due to their good power absorption capabilities. Recent in vitro experiments with the so-called 'Magnetic Fluid Hyperthermia (MFH)' have shown that human tumours cells are homogeneously inactivated after AC magnetic field excitation of extracellular MF. The aim of the present study was the evaluation of a high dose MFH on intramuscularly implanted mammary carcinoma of the mouse. The tumours originated from initial in vivo passages of a spontaneous parent tumour. Because of larger variations of tumour growth in this rather primary model, logistic regression of non-averaged volumes was performed for each treatment modality. All growing tumours were randomized 30 days after transplantation (day of treatment) with an overall size distribution between 120-400 mm3. An intratumoural steady state temperature of 47 +/- 1.0 degrees C was maintained for 30 minutes with whole-body AC magnetic fields of 6-12.5 kA/m at 520 kHz. The magnetic fluid was #P6, which is a high biocompatible dextran magnetite. #P6 was given intratumourally (1.5 x 10(-2) mg ferrite/mm3) 20-30 minutes before excitation and was combined with magnetic targeting (50 mT), which yielded a 2.5-fold enhancement of the intratumoural iron concentration. Histological examinations of tumour tissue after intralesional ferrofluid administration alone indicated deep infiltration of the fluid into the carcinoma tissue, but no evidence of tissue damage as compared with untreated controls. In contrast, widespread tumour necrosis was observed after MFH. After application of either dextran or ferrofluid alone (no difference, p = 0.665), tumour growth was slightly delayed in comparison with untreated controls (p < 0.001). In contrast to the good fit of the controls (R = 0.92-0.87), tumour growth after MFH was much more heterogeneous; some tumours showed no evidence for regrowth at 50 days whereas others had grown quite readily. This most probably reflected the critical problem of homogeneity of the intratumoural MF distribution, which was also confirmed qualitatively by Magnetic Resonance Imaging (MRI), heterogeneous pigmentation of MFH treated tumours, and up to 1 degree C differences between temperature probes in the same tumour during AC magnetic field application. However, a quantitative comparison between intratumoural MF-heterogeneity and tumour response could not be performed in this study. Despite these current limitations, the regression analysis of the MFH data yielded a smaller tumour volume of about 1000 mm3 at 50 days growth time in contrast to all three controls. In conclusion, encouraging results have been obtained, which show, that one single high dose MFH is already able to induce local tumour control in many cases within 30 days after treatment. To overcome the uncertainties of intratumoural MF heterogeneity, advanced intralesional application methods are currently under development.

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 ≥90%) and standardized thermal parameters, such as thermal dose cumulative equivalent minutes at 43°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. Cancer 2006. © 2006 American Cancer Society.

BackgroundEstablishing Total Body Irradiation (TBI) using Helical Tomotherapy (HT) to gain better control over dose distribution and homogeneity and to individually spare organs at risk. Because of their limited body length the technique seems especially eligible in juvenile patients.Patients and methodsThe cohort consisted of 10 patients, 6 female and 4 male, aged 4 - 22 y with acute lymphoblastic- (ALL) or acute myeloic leukemia (AML). All patients presented with high risk disease features. Body length in treatment position ranged from 110–180 cm. Two Gy single dose was applied BID to a total dose of 12 Gy. Dose volume constraint for the PTV was 95% dose coverage for 95% of the volume. The lungs were spared to a mean dose of [less than or equal to] 10 Gy. Patients were positioned in a vac-loc bag in supine position with a 3-point head mask.ResultsAverage D95 to the PTV was 11.7 Gy corresponding to a mean coverage of the PTV of 97.5%. Dmean for the lungs was 9.14 Gy. Grade 3–4 side effects were not observed.ConclusionsTBI using HT is feasible and well tolerated. A benefit could be demonstrated with regard to dose distribution and homogeneity and the selective dose-reduction to organs at risk.

To implement noninvasive thermometry, we installed a hybrid system consisting of a radiofrequency multiantenna applicator (SIGMA-Eye) for deep hyperthermia (BSD-2000/3D) integrated into the gantry of a 1.5 Tesla magnetic resonance (MR) tomograph Symphony. This system can record MR data during radiofrequency heating and is suitable for application and evaluation of methods for MR thermography. In 15 patients with preirradiated pelvic rectal recurrences, we acquired phase data sets (25 slices) every 10 to 15 minutes over the treatment time (60-90 minutes) using gradient echo sequences (echo time = 20 ms), transformed the phase differences to MR temperatures, and fused the color-coded MR-temperature distributions with anatomic T1-weighted MR data sets. We could generate one complete series of MR data sets per patient with satisfactory quality for further analysis. In fat, muscle, water bolus, prostate, bladder, and tumor, we delineated regions of interest (ROI), used the fat ROI for drift correction by transforming these regions to a phase shift zero, and evaluated the MR-temperature frequency distributions. Mean MR temperatures (T MR ), maximum T MR , full width half maximum (FWHM), and other descriptors of tumors and normal tissues were noninvasively derived and their dependencies outlined. In 8 of 15 patients, direct temperature measurements in reference points were available. We correlated the tumor MR temperatures with direct measurements, clinical response, and tumor features (volume and location), and found reasonable trends and correlations. Therefore, the mean T MR of the tumor might be useful as a variable to evaluate the quality and effectivity of heat treatments, and consequently as optimization variable. Feasibility of noninvasive MR thermography for regional hyperthermia has been shown and should be further investigated. (Cancer Res 2005; 65(13): 5872-80)

MR-controlled RF hyperthermia in a hybrid system is well established in phantoms and already feasible for patients in the pelvic and lower extremity region. Under optimal conditions the temperature accuracy might be in the range of 0.5 degrees C. However a variety of developments, especially sequences and post-processing modules, are still required for the clinical routine.