Improved patient-specific hyperthermia planning based on parametrized electromagnetic and thermal models for the SIGMA-30 applicator.

OBJECTIVE: To create an improved planning method for pediatric regional hyperthermia (RHT) using the SIGMA-30 applicator (SIGMA-30). MATERIALS AND METHODS: An electromagnetic model of SIGMA-30 was generated for use with the finite-difference time-domain (FDTD) method. Applying special MATLAB-based algorithms, voxel models of a pediatric patient with pelvic rhabdomyosarcoma were created from Computed-Tomography (CT) contours for use with the FDTD method and the finite-difference (FD) method capable of using either temperature-independent or temperature-dependent perfusion models for solving the Bioheat Transfer Equation (BHTE). Patient models were parametrized regarding, first, the positioning in the applicator, second, the absorbed power range and, third, different perfusion models, resulting in the so-called Parametrized Treatment Models (PTMs). A novel dedicated optimization procedure was developed based on quantitative comparison of numerical calculations against temperature and power measurements from two RHT therapies. RESULTS: Using measured data, a realistic absorbed power range in the patient model was estimated. Within this range, several FDTD and BHTE runs were performed and, applying the aforementioned optimization scheme, the best PTMs and perfusion models were identified for each therapy via a retrospective comparison with measurements in 14 temperature sensor positions: 5 in the tumor, 8 in rectum and one in bladder. CONCLUSION: A novel dedicated optimization procedure for identification of suitable patient-specific electromagnetic and thermal models, which can be used for improved patient planning, was developed and evaluated by comparison with treatment-derived measurements using SIGMA-30. The optimization procedure can be extended to other hyperthermia applicators and to other patient types, including adults.

Radiofrequency applicator concepts for thermal magnetic resonance of brain tumors at 297 MHz (7.0 Tesla).

Purpose: Thermal intervention is a potent sensitizer of cells to chemo- and radiotherapy in cancer treatment. Glioblastoma multiforme (GBM) is a potential clinical target, given the cancer's aggressive nature and resistance to current treatment options. The annular phased array (APA) technique employing electromagnetic waves in the radiofrequency (RF) range allows for localized temperature increase in deep seated target volumes (TVs). Reports on clinical applications of the APA technique in the brain are still missing. Ultrahigh field magnetic resonance (MR) employs higher frequencies than conventional MR and has potential to provide focal temperature manipulation, high resolution imaging and noninvasive temperature monitoring using an integrated RF applicator (ThermalMR). This work examines the applicability of RF applicator concepts for ThermalMR of brain tumors at 297 MHz (7.0 Tesla).Methods: Electromagnetic field (EMF) simulations are performed for clinically realistic data based on GBM patients. Two algorithms are used for specific RF energy absorption rate based thermal intervention planning for small and large TVs in the brain, aiming at maximum RF power deposition or RF power uniformity in the TV for 10 RF applicator designs.Results: For both TVs , the power optimization outperformed the uniformity optimization. The best results for the small TV are obtained for the 16 element interleaved RF applicator using an elliptical antenna arrangement with water bolus. The two row elliptical RF applicator yielded the best result for the large TV.Discussion: This work investigates the capacity of ThermalMR to achieve targeted thermal interventions in model systems resembling human brain tissue and brain tumors.

Spinal cord constraints in the era of high-precision radiotherapy : Retrospective analysis of 62 spinal/paraspinal lesions with possible infringements of spinal cord constraints within a minimal volume.

OBJECTIVE: Current constraints aim to minimize the risk of radiation myelitis by the use of restrictive maximal spinal cord doses, commonly 50 Gy. However, several studies suggested that a dose-volume effect could exist. Based on these observations, we evaluated patients receiving potentially excessive doses to the spinal cord within minimal volumes. PATIENTS AND METHODS: Patients receiving radiotherapy between June 2010 and May 2015 using the NovalisTM (Varian, Palo Alto, CA, USA; Brainlab, Heimstetten, Germany) radiosurgery system were retrospectively analyzed. A total of 56 patients with 62 treated lesions that had been prescribed radiation doses close to the spinal cord potentially higher than the common 50 Gy 2­Gy equivalent-dose (EQD2) constraint were selected for further analysis. Of these patients, 26 with 31 lesions had no history of previous irradiation, while 30 patients with 31 lesions had been previously irradiated within the treatment field. RESULTS: According to different dose evaluation approaches (spinal canal, spinal cord contour), 16 and 10 out of 31 primary irradiated lesions infringed constraints. For the 16 lesions violating spinal canal doses, the maximum doses ranged from 50.5 to 61.9 Gy EQD2. Reirradiated lesions had an average and median cumulative dose of 70.5 and 69 Gy, respectively. Dose drop-off was steep in both groups. Median overall survival was 17 months. No radiation myelitis or radiomorphological alterations were observed during follow-up. CONCLUSION: This study adds to the increasing body of evidence indicating that excessive spinal cord doses within a minimal volume, especially in a reirradiation setting with topographically distinct high-point doses, may be given to patients after careful evaluation of treatment- and tumor-associated risks.

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.

Hyperthermia classic commentary: 'Simulation studies promote technological development of radiofrequency phased array hyperthermia' by Peter Wust et al., International Journal of Hyperthermia 1996;12:477-494.

Simulation studies can estimate the potentials of regional hyperthermia based on the multi-antenna principle. They postulate an optimal parameter setup (phases, amplitudes) that should increase temperatures in heat treatments by 1 degrees C or more. However in praxi, slight inaccuracies and uncertainties accumulate in a way that the optimal adjustment is typically missed during a real treatment. The reasons for these errors are electrical and geometrical. A way out is an on-line control, which adapts the plans to the actual distributions. Magnetic resonance thermography is employed for on-line control, and control software has been developed. However, there is still a long way to reach the technological endpoint of multi-antenna systems for clinical applications.

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.

Regional hyperthermia of the abdomen, a pilot study towards the treatment of peritoneal carcinomatosis.

BACKGROUND: Peritoneal carcinomatosis occurs in different cancer subtypes and is associated with a dismal prognosis. Some doubts remain whether the whole abdomen can be treated by regional hyperthermia, therefore we analyzed feasibility conducting a pilot study. METHODS: A simulation of the abdominopelvic heat distribution in 11 patients with peritoneal carcinomatosis was done using the HyperPlan software and the SIGMA-60 and SIGMA-Eye applicators. Tissue-specific region-related electrical and thermal parameters were used to solve the Maxwell's equations and the bioheat-transfer equation. Three-dimensional specific absorption rate (SAR) distributions and, additionally, estimated region-related perfusion rates were used to solve the bioheat-transfer equation. The predicted SAR and temperature distributions were compared with minimally invasive measurements in pelvic reference points. RESULTS: In 11 patients (7 of them treated in the SIGMA-60 and 4 in the SIGMA-Eye applicator) the measured treatment variables (SAR, temperatures in the pelvic reference points) indicated that the heated volumes were higher for the SIGMA-Eye applicator. The mean computed abdominal SARs were less for the SIGMA-Eye (33 versus 44 W/kg). Nevertheless, the temperature distributions in the abdomen (peritoneal cavity) were more homogeneous in the SIGMA-Eye applicator as compared to the SIGMA-60 as indicated by higher values of T90 (mean 40.2 versus 38.2 °C) and T50 (mean 41.1 versus 40.2 °C), while the maximum temperatures were similar (in the range 41 to 43 °C). Even though the mean abdominal SAR was lower in the SIGMA-Eye, the heat distribution covered a larger volume of the abdomen (in particular the upper abdomen). For the SIGMA-60 applicator the achieved T90 appeared to be limited between 41 and 42 °C, for the SIGMA Eye applicator more effective T90 in the range 42 to 43 °C were obtained. CONCLUSION: Our results suggest that an adequate heating of the abdomen and therefore abdominal regional hyperthermia in PC patients appears feasible. The SIGMA-Eye applicator appears to be superior compared to the SIGMA-60 applicator for abdominal hyperthermia.

Which technique for radiation is most beneficial for patients with locally advanced cervical cancer? Intensity modulated proton therapy versus intensity modulated photon treatment, helical tomotherapy and volumetric arc therapy for primary radiation - an intraindividual comparison.

BACKGROUND: To compare highly sophisticated intensity-modulated radiotherapy (IMRT) delivered by either helical tomotherapy (HT), RapidArc (RA), IMRT with protons (IMPT) in patients with locally advanced cervical cancer. METHODS AND MATERIALS: Twenty cervical cancer patients were irradiated using either conventional IMRT, VMAT or HT; ten received pelvic (PEL) and ten extended field irradiation (EFRT). The dose to the planning-target volume A (PTV_A: cervix, uterus, pelvic ± para-aortic lymph nodes) was 1.8/50.4 Gy. The SIB dose for the parametrium (PTV_B), was 2.12/59.36 Gy. MRI-guided brachytherapy was administered with 5 fractions up to 25 Gy. For EBRT, the lower target constraints were 95% of the prescribed dose in 95% of the target volume. The irradiated small bowel (SB) volumes were kept as low as possible. For every patient, target parameters as well as doses to the organs at risk (SB, bladder, rectum) were evaluated intra-individually for IMRT, HT, VMAT and IMPT. RESULTS: All techniques provided excellent target volume coverage, homogeneity, conformity. With IMPT, there was a significant reduction of the mean dose (Dmean) of the SB from 30.2 ± 4.0 Gy (IMRT); 27.6 ± 5.6 Gy (HT); 34.1 ± 7.0 (RA) to 18.6 ± 5.9 Gy (IMPT) for pelvic radiation and 26.3 ± 3.2 Gy (IMRT); 24.0 ± 4.1 (HT); 25.3 ± 3.7 (RA) to 13.8 ± 2.8 Gy (IMPT) for patients with EFRT, which corresponds to a reduction of 38-52% for the Dmean (SB). Futhermore, the low dose bath (V10Gy) to the small bowel was reduced by 50% with IMPT in comparison to all photon techniques. Furthermore, Dmean to the bladder and rectum was decresed by 7-9 Gy with IMPT in patents with pelvic radiation and EFRT. CONCLUSION: All modern techniques (were proved to be dosimetrically adequate regarding coverage, conformity and homogeneity of the target. Protons offered the best sparing of small bowel and rectum and therefore could contribute to a significant reduction of acute and late toxicity in cervical cancer treatment.

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.