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Purpose: Thermoradiotherapy combines radiation therapy with hyperthermia to increase therapeutic effectiveness. Currently, both modalities are optimized separately and in state-of-the-art research the enhanced therapeutic effect is evaluated using equivalent radiation dose in 2-Gy fractions (EQD2). This study proposes a novel thermoradiotherapy treatment planning framework with voxelwise EQD2 radiation therapy optimizing including thermal radiosensitization and direct thermal cytotoxicity., Methods and Materials: To demonstrate proof-of-concept of the planning framework, 3 strategies consisting of 20 radiation therapy fractions were planned for 4 prostate cancer cases with substantially different temperature distributions: (1) Conventional radiation therapy plan of 60 Gy combined with 4 hyperthermia sessions (RT 60 + HT), (2) standalone uniform dose escalation to 68 Gy without hyperthermia (RT 68 ), and (3) uniform target EQD2 that maximizes the tumor control probability (TCP) accounting for voxelwise thermal effects of 4 hyperthermia sessions without increasing normal tissue doses (RT HT + HT). Assessment included dose, EQD2, TCP, and rectal normal tissue complication probability (NTCP), alongside robustness analyses for TCP and NTCP against parameter uncertainties., Results: The estimated TCP of around 76% for RT 60 without hyperthermia was increased to an average of 85.9% (range, 81.3%-90.5%) for RT 60 + HT, 92.5% (92.4%-92.5%) for RT 68 , and 94.4% (91.7%-96.6%) for RT HT + HT . The corresponding averaged rectal NTCPs were 8.7% (7.9%-10.0%), 14.9% (13.8%-17.1%), and 8.4% (7.5%-9.7%), respectively. RT 68 and RT HT + HT exhibited slightly enhanced TCP robustness against parameter uncertainties compared with RT 60 + HT, and RT 68 presented higher and less robust rectal NTCP values compared with the other planning strategies., Conclusions: This study introduces an innovative thermoradiotherapy planning approach, integrating thermal effects into EQD2-based radiation therapy optimization. Results demonstrate an ability to achieve enhanced and uniform target EQD2 and TCP across various temperature distributions without elevating normal tissue EQD2 or NTCP compared with conventional methods. Although promising for improving clinical outcomes, realizable enhancements depend on accurate tumor- and tissue-specific data and precise quantification of hyperthermic effects, which are seamlessly integrable in the planning framework as they emerge., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Clinical evidence is limited regarding palliative radiation therapy for relieving pancreatic cancer-related pain. We prospectively investigated pain response after short-course palliative radiation therapy in patients with moderate-to-severe pancreatic cancer-related pain., Methods and Materials: In this prospective phase 2 single center nonrandomized trial, 30 patients with moderate-to-severe pain (5-10, on a 0-10 scale) of pancreatic cancer refractory to pain medication, were treated with a short-course palliative radiation therapy; 24 Gy in 3 weekly fractions (2015-2018). Primary endpoint was defined as a clinically relevant average decrease of ≥2 points in pain severity, compared with baseline, within 7 weeks after the start of treatment. Secondary endpoint was global quality of life (QoL), with a clinically relevant increase of 5 to 10 points (0-100 scale). Pain severity reduction and QoL were assessed 9 times using the Brief Pain Inventory and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C15-PAL, respectively. Both outcomes were analyzed using joint modeling. In addition, acute toxicity based on clinician reporting and overall survival (OS) were assessed., Results: Overall, 29 of 30 patients (96.7%) received palliative radiation therapy. At baseline, the median oral morphine equivalent daily dose was 129.5 mg (range, 20.0-540.0 mg), which decreased to 75.0 mg (range, 15.0-360.0 mg) after radiation (P = .021). Pain decreased on average 3.15 points from baseline to 7 weeks (one-sided P = .045). Patients reported a clinically relevant mean pain severity reduction from 5.9 to 3.8 points (P = .011) during the first 3 weeks, which further decreased to 3.2 until week 11, ending at 3.4 (P = .006) in week 21 after the first radiation therapy fraction. Global QoL significantly improved from 50.5 to 60.8 during the follow-up period (P = .001). Grade 3 acute toxicity occurred in 3 patients and no grade 4 to 5 toxicity was observed. Median OS was 11.8 weeks, with a 13.3% 1-year actuarial OS rate., Conclusions: Short-course palliative radiation therapy for pancreatic cancer-related pain was associated with rapid, clinically relevant reduction in pain severity, and clinically relevant improvement in global QoL, with mostly mild toxicity., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: The combination of hyperthermia (HT) with radio(chemo)therapy or chemotherapy (CT) is an established treatment strategy for specific indications. Its application in routine clinical practice in Europe depends on regulatory and local conditions. We conducted a survey among European clinical centers to determine current practice of HT., Methods: A questionnaire with 22 questions was sent to 24 European HT centers. The questions were divided into two main categories. The first category assessed how many patients are treated with HT in combination with radio(chemo)therapy or CT for specific indications per year. The second category addressed which hyperthermia parameters are recorded. Analysis was performed using descriptive methods., Results: The response rate was 71% (17/24) and 16 centers were included in this evaluation. Annually, these 16 centers treat approximately 637 patients using HT in combination with radio(chemo)therapy or CT. On average, 34% (range: 3-100%) of patients are treated in clinical study protocols. Temperature readings and the time interval between HT and radio(chemo)therapy or CT are recorded in 13 (81%) and 9 (56%) centers, respectively. The thermal dose quality parameter "cumulative equivalent minutes at 43 °C" (CEM43°C) is only evaluated in five (31%) centers for each HT session. With regard to treatment sequence, 8 (50%) centers administer HT before radio(chemo)therapy and the other 8 in the reverse order., Conclusion: There is a significant heterogeneity among European HT centers as to the indications treated and the recording of thermometric parameters. More evidence from clinical studies is necessary to achieve standardization of HT practice., (© 2022. The Author(s).)

Mutations in the isocitrate dehydrogenase 1 (IDH1MUT) gene occur in various types of malignancies, including ~60% of chondrosarcomas, ~30% of intrahepatic cholangiocarcinomas and >80% of low-grade gliomas. IDH1MUT are causal in the development and progression of these types of cancer due to neomorphic production of the oncometabolite D-2-hydroxyglutarate (D-2HG). Intracellular accumulation of D-2HG has been implicated in suppressing homologous recombination and renders IDH1MUT cancer cells sensitive to DNA-repair-inhibiting agents, such as poly-(adenosine 5′-diphosphate−ribose) polymerase inhibitors (PARPi). Hyperthermia increases the efficacy of DNA-damaging therapies such as radiotherapy and platinum-based chemotherapy, mainly by inhibition of DNA repair. In the current study, we investigated the additional effects of hyperthermia (42 °C for 1 h) in the treatment of IDH1MUT HCT116 colon cancer cells and hyperthermia1080 chondrosarcoma cancer cells in combination with radiation, cisplatin and/or a PARPi on clonogenic cell survival, cell cycle distribution and the induction and repair of DNA double-strand breaks. We found that hyperthermia in combination with radiation or cisplatin induces an increase in double-strand breaks and cell death, up to 10-fold in IDH1MUT cancer cells compared to IDH1 wild-type cells. This vulnerability was abolished by the IDH1MUT inhibitor AGI-5198 and was further increased by the PARPi. In conclusion, our study shows that IDH1MUT cancer cells are sensitized to hyperthermia in combination with irradiation or cisplatin and a PARPi. Therefore, hyperthermia may be an efficacious sensitizer to cytotoxic therapies in tumors where the clinical application of hyperthermia is feasible, such as IDH1MUT chondrosarcoma of the extremities.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is an MRI technique for quantifying perfusion that can be used in clinical applications for classification of tumours and other types of diseases. Conventionally, the non-linear least squares (NLLS) methods is used for tracer-kinetic modelling of DCE data. However, despite promising results, NLLS suffers from long processing times (minutes-hours) and noisy parameter maps due to the non-convexity of the cost function. In this work, we investigated physics-informed deep neural networks for estimating physiological parameters from DCE-MRI signal-curves. Three voxel-wise temporal frameworks (FCN, LSTM, GRU) and two spatio-temporal frameworks (CNN, U-Net) were investigated. The accuracy and precision of parameter estimation by the temporal frameworks were evaluated in simulations. All networks showed higher precision than the NLLS. Specifically, the GRU showed to decrease the random error on v e by a factor of 4.8 with respect to the NLLS for noise (SD) of 1/20. The accuracy was better for the prediction of the v e parameter in all networks compared to the NLLS. The GRU and LSTM worked with arbitrary acquisition lengths. The GRU was selected for in vivo evaluation and compared to the spatio-temporal frameworks in 28 patients with pancreatic cancer. All neural network approaches showed less noisy parameter maps than the NLLS. The GRU had better test-retest repeatability than the NLLS for all three parameters and was able to detect one additional patient with significant changes in DCE parameters post chemo-radiotherapy. Although the U-Net and CNN had even better test-retest characteristics than the GRU, and were able to detect even more responders, they also showed potential systematic errors in the parameter maps. Therefore, we advise using our GRU framework for analysing DCE data., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: In patients with inoperable local regional recurrences of breast cancer in previously irradiated areas, local control is difficult to maintain and treatment options are limited. The Dutch standard treatment for such recurrences is reirradiation combined with hyperthermia. Apart from enhancing the effect of reirradiation, hyperthermia is also known to improve local effects of chemotherapy like cisplatin. This randomized phase-II trial compares reirradiation and hyperthermia versus the same treatment combined with cisplatin., Patients and Methods: From December 2010 up to January 2019, 49 patients were randomized, 27 in the standard arm and 22 in the combined arm. A total of 32 Gy was given in eight fractions of 4 Gy in 4 weeks, at two fractions per week. After January 2015, the radiation schedule was changed to 46 Gy in 23 fractions of 2 Gy, at five fractions per week. Hyperthermia was added once a week after radiotherapy. The combined arm was treated with four cycles of weekly cisplatin 40 mg/m 2 ., Results: Complete response rate was 60.9% in the standard arm and 61.1% in the combined arm ( p  = 0.87). Partial response rate was 30.4% in the standard arm and 33.3% in the combined arm ( p  = 0.79). One-year overall survival was 63.4% in the standard arm and 57.4% in the combined arm. One-year local progression-free interval was 81.5% in the standard arm and 88.1% in the combined arm ( p  = 0.95). Twenty-five percentage of patients in the standard arm experienced grade 3 or 4 acute toxicity and 29% of patients in the combined arm ( p  = 0.79)., Conclusion: No potential benefit could be detected of adding cisplatin to reirradiation and hyperthermia in patients with recurrent breast cancer in a previously irradiated area. With or without cisplatin, most patients had subsequent local control until last follow-up or death.

Purpose: To investigate the impact of hyperthermia thermal dose (TD) on locoregional control (LRC), overall survival (OS) and toxicity in locoregional recurrent breast cancer patients treated with postoperative re-irradiation and hyperthermia., Methods: In this retrospective study, 112 women with resected locoregional recurrent breast cancer treated in 2010-2017 with postoperative re-irradiation 8frx4Gy (n = 34) or 23frx2Gy (n = 78), combined with 4-5 weekly hyperthermia sessions guided by invasive thermometry, were subdivided into 'low' (n = 56) and 'high' TD (n = 56) groups by the best session with highest median cumulative equivalent minutes at 43 °C (Best CEM43T50) < 7.2 min and ≥7.2 min, respectively. Actuarial LRC, OS and late toxicity incidence were analyzed. Backward multivariable Cox regression and inverse probability weighting (IPW) analysis were performed., Results: TD subgroups showed no significant differences in patient/treatment characteristics. Median follow-up was 43 months (range 1-107 months). High vs. low TD was associated with LRC (p = 0.0013), but not with OS (p = 0.29) or late toxicity (p = 0.58). Three-year LRC was 74.0% vs. 92.3% in the low and high TD group, respectively (p = 0.008). After three years, 25.0% and 0.9% of the patients had late toxicity grade 3 and 4, respectively. Multivariable analysis showed that distant metastasis (HR 17.6; 95%CI 5.2-60.2), lymph node involvement (HR 2.9; 95%CI 1.2-7.2), recurrence site (chest wall vs. breast; HR 4.6; 95%CI 1.8-11.6) and TD (low vs. high; HR 4.1; 95%CI 1.4-11.5) were associated with LRC. TD was associated with LRC in IPW analysis (p = 0.0018)., Conclusions: High thermal dose (best CEM43T50 ≥ 7.2 min) was associated with significantly higher LRC for patients with locoregional recurrent breast cancer treated with postoperative re-irradiation and hyperthermia, without augmenting toxicity., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Hyperthermia (HT) is a cancer treatment modality which targets malignant tissues by heating to 40-43 °C. In addition to its direct antitumor effects, HT potently sensitizes the tumor to radiotherapy (RT) and chemotherapy (CT), thereby enabling complete eradication of some tumor entities as shown in randomized clinical trials. Despite the proven efficacy of HT in combination with classic cancer treatments, there are limited international standards for the delivery of HT in the clinical setting. Consequently, there is a large variability in reported data on thermometric parameters, including the temperature obtained from multiple reference points, heating duration, thermal dose, time interval, and sequence between HT and other treatment modalities. Evidence from some clinical trials indicates that thermal dose, which correlates with heating time and temperature achieved, could be used as a predictive marker for treatment efficacy in future studies. Similarly, other thermometric parameters when chosen optimally are associated with increased antitumor efficacy. This review summarizes the existing clinical evidence for the prognostic and predictive role of the most important thermometric parameters to guide the combined treatment of RT and CT with HT. In conclusion, we call for the standardization of thermometric parameters and stress the importance for their validation in future prospective clinical studies.

Objective: The in-house developed 70 MHz AMC-4 locoregional hyperthermia system has been in clinical use since 1984. This device was recently commercialized as the Alba 4D (Medlogix ® , Rome, Italy), with a similar geometrical 4-waveguide design. At the time of this study a hybrid Alba 4D was installed at our center, which incorporated elements of the AMC-4. This study aims to compare clinical performance of both devices., Methods: During one year after clinical acceptance of the hybrid Alba 4D, both devices were used for treatment delivery in patients scheduled for locoregional hyperthermia. Each patient started with the AMC-4, next sessions were allocated to either device. Possible differences between Alba 4D and AMC-4 sessions in power, achieved temperature T0, T10, T50, T90, T100, treatment time and complaints per session, were evaluated using linear mixed models (LMMs) for repeated measures with patient as random effect., Results: From March 2018 to April 2019, eleven patients with cervical, pancreatic, vaginal carcinoma and uterine leiomyosarcoma received 27 locoregional hyperthermia sessions with the Alba 4D and 34 sessions with the AMC-4. Median number of sessions per patient was 5 (range 3-13). Treatment results for both devices were not significantly different: T50 was 40.5 ± 1.0 °C vs. 40.8 ± 0.7 °C, applied power was 500 ± 79 W vs. 526 ± 108 W, for the Alba 4D vs. AMC-4, respectively., Conclusion: Results of the first patients treated with the hybrid Alba 4D demonstrated comparable clinical performance of the Alba 4D and AMC-4 locoregional hyperthermia systems, and both devices are expected to yield similar favorable clinical results.

Purpose: Earlier work showed that IVIM-NET orig , an unsupervised physics-informed deep neural network, was faster and more accurate than other state-of-the-art intravoxel-incoherent motion (IVIM) fitting approaches to diffusion-weighted imaging (DWI). This study presents a substantially improved version, IVIM-NET optim , and characterizes its superior performance in pancreatic cancer patients., Method: In simulations (signal-to-noise ratio [SNR] = 20), the accuracy, independence, and consistency of IVIM-NET were evaluated for combinations of hyperparameters (fit S0, constraints, network architecture, number of hidden layers, dropout, batch normalization, learning rate), by calculating the normalized root-mean-square error (NRMSE), Spearman's ρ, and the coefficient of variation (CV NET ), respectively. The best performing network, IVIM-NET optim was compared to least squares (LS) and a Bayesian approach at different SNRs. IVIM-NET optim 's performance was evaluated in an independent dataset of 23 patients with pancreatic ductal adenocarcinoma. Fourteen of the patients received no treatment between two repeated scan sessions and nine received chemoradiotherapy between the repeated sessions. Intersession within-subject standard deviations (wSD) and treatment-induced changes were assessed., Results: In simulations (SNR = 20), IVIM-NET optim outperformed IVIM-NET orig in accuracy (NRMSE(D) = 0.177 vs 0.196; NMRSE(f) = 0.220 vs 0.267; NMRSE(D*) = 0.386 vs 0.393), independence (ρ(D*, f) = 0.22 vs 0.74), and consistency (CV NET (D) = 0.013 vs 0.104; CV NET (f) = 0.020 vs 0.054; CV NET (D*) = 0.036 vs 0.110). IVIM-NET optim showed superior performance to the LS and Bayesian approaches at SNRs < 50. In vivo, IVIM-NET optim showed significantly less noisy parameter maps with lower wSD for D and f than the alternatives. In the treated cohort, IVIM-NET optim detected the most individual patients with significant parameter changes compared to day-to-day variations., Conclusion: IVIM-NET optim is recommended for accurate, informative, and consistent IVIM fitting to DWI data., (© 2021 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Cancer treatments based on mild hyperthermia (39-43 °C, HT) are applied to a widening range of cancer types, but several factors limit their efficacy and slow down more widespread adoption. These factors include difficulties in adequate heat delivery, a short therapeutic window and the acquisition of thermotolerance by cancer cells. Here, we explore the biological effects of HT, the cellular responses to these effects and their clinically-relevant consequences. We then identify the heat stress response-the cellular defense mechanism that detects and counteracts the effects of heat-as one of the major forces limiting the efficacy of HT-based therapies and propose targeting this mechanism as a potentially universal strategy for improving their efficacy.

Background: Accurate monitoring of skin surface temperatures is necessary to ensure treatment quality during superficial hyperthermia. A high-resolution thermal monitoring sheet (TMS) was developed to monitor the skin surface temperature distribution. The influence of the TMS on applicator performance was investigated, feasibility and ability to reliably monitor the temperature distribution were evaluated in a clinical study. Methods: Phantom experiments were performed to determine the influence of the TMS on power deposition patterns, applicator efficiency, and heat transfer of the water bolus for 434 and 915 MHz applicators. Clinical feasibility was evaluated in 10 women with locoregional recurrent breast cancer. Skin surface temperatures during consecutive treatments were monitored alternatingly with either standard Amsterdam UMC thermometry or TMS. Treatments were compared using (generalized) linear mixed models. Results: The TMS did not significantly affect power deposition patterns and applicator efficiency (1-2%), the reduced heat transfer of the water boluses (51-56%) could be compensated by adjusting the water bolus flow. Skin surface temperatures were monitored reliably, and no alteration of thermal toxicity was observed compared to standard Amsterdam UMC thermometry. Conclusion: Clinical application of the TMS is feasible. Power deposition patterns and applicator efficiency were not affected. Surface temperatures were monitored reliably.

Purpose: To demonstrate that mapping pelvis conductivity at 3T with deep learning (DL) is feasible., Methods: 210 dielectric pelvic models were generated based on CT scans of 42 cervical cancer patients. For all dielectric models, electromagnetic and MR simulations with realistic accuracy and precision were performed to obtain B 1 + and transceive phase (ϕ ± ). Simulated B 1 + and ϕ ± served as input to a 3D patch-based convolutional neural network, which was trained in a supervised fashion to retrieve the conductivity. The same network architecture was retrained using only ϕ ± in input. Both network configurations were tested on simulated MR data and their conductivity reconstruction accuracy and precision were assessed. Furthermore, both network configurations were used to reconstruct conductivity maps from a healthy volunteer and two cervical cancer patients. DL-based conductivity was compared in vivo and in silico to Helmholtz-based (H-EPT) conductivity., Results: Conductivity maps obtained from both network configurations were comparable. Accuracy was assessed by mean error (ME) with respect to ground truth conductivity. On average, ME < 0.1 Sm -1 for all tissues. Maximum MEs were 0.2 Sm -1 for muscle and tumour, and 0.4 Sm -1 for bladder. Precision was indicated with the difference between 90 th and 10 th conductivity percentiles, and was below 0.1 Sm -1 for fat, bone and muscle, 0.2 Sm -1 for tumour and 0.3 Sm -1 for bladder. In vivo, DL-based conductivity had median values in agreement with H-EPT values, but a higher precision., Conclusion: Anatomically detailed, noise-robust 3D conductivity maps with good sensitivity to tissue conductivity variations were reconstructed in the pelvis with DL., (© 2020 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Moderate hyperthermia at temperatures between 40 and 44°C is a multifaceted therapeutic modality. It is a potent radiosensitizer, interacts favorably with a host of chemotherapeutic agents, and, in combination with radiotherapy, enforces immunomodulation akin to " in situ tumor vaccination." By sensitizing hypoxic tumor cells and inhibiting repair of radiotherapy-induced DNA damage, the properties of hyperthermia delivered together with photons might provide a tumor-selective therapeutic advantage analogous to high linear energy transfer (LET) neutrons, but with less normal tissue toxicity. Furthermore, the high LET attributes of hyperthermia thermoradiobiologically are likely to enhance low LET protons; thus, proton thermoradiotherapy would mimic 12 C ion therapy. Hyperthermia with radiotherapy and/or chemotherapy substantially improves therapeutic outcomes without enhancing normal tissue morbidities, yielding level I evidence reported in several randomized clinical trials, systematic reviews, and meta-analyses for various tumor sites. Technological advancements in hyperthermia delivery, advancements in hyperthermia treatment planning, online invasive and non-invasive MR-guided thermometry, and adherence to quality assurance guidelines have ensured safe and effective delivery of hyperthermia to the target region. Novel biological modeling permits integration of hyperthermia and radiotherapy treatment plans. Further, hyperthermia along with immune checkpoint inhibitors and DNA damage repair inhibitors could further augment the therapeutic efficacy resulting in synthetic lethality. Additionally, hyperthermia induced by magnetic nanoparticles coupled to selective payloads, namely, tumor-specific radiotheranostics (for both tumor imaging and radionuclide therapy), chemotherapeutic drugs, immunotherapeutic agents, and gene silencing, could provide a comprehensive tumor-specific theranostic modality akin to "magic (nano)bullets." To get a realistic overview of the strength (S), weakness (W), opportunities (O), and threats (T) of hyperthermia, a SWOT analysis has been undertaken. Additionally, a TOWS analysis categorizes future strategies to facilitate further integration of hyperthermia with the current treatment modalities. These could gainfully accomplish a safe, versatile, and cost-effective enhancement of the existing therapeutic armamentarium to improve outcomes in clinical oncology., (Copyright © 2020 Datta, Kok, Crezee, Gaipl and Bodis.)

Purpose: Temperature measurement during superficial hyperthermia is limited by poor spatial resolution. We investigated two sheets to improve temperature monitoring of the skin surface., Methods and Materials: Two different sheets were studied with a grid of temperature sensors with one sensor per ~5 cm2. The first was a matrix of multisensor thermocouple probes laced through a silicone sheet. The second sheet had rows of thermistors connected by meandering copper leads mounted on stretchable printed circuit board (SPCB). Accuracy, temperature resolution and two hour stability of both sheets were investigated. Furthermore, we determined the ability to follow body contours, thermal conduction errors and electromagnetic (EM) compatibility to clinically used 434 and 915 MHz hyperthermia applicators., Results: For both sheets the accuracy (≤0.2 °C), temperature resolution (≤0.03 °C) and stability (≤0.01°C hr-1) were adequate for clinical use. Thermal conduction errors ranged from 5.25 - 11.25 mm vs. 2.15 mm for the thermocouple probe and thermistor, respectively. Both sheets could follow body contours, where the ratio air/ water bolus surface was <5%. When aligned perpendicularly to the EM field the meandering copper tracks used on the SPCB did induce self-heating, while the thermocouple probes did not. Self-heating had a linear relationship with the angle of the leads with respect to the EM field direction for both sensors at both frequencies. Self-heating of the thermistor was similar for both frequencies, while it was circa two-fold higher for 915 vs. 434 MHz for the thermocouple., Conclusion: The use of SPCB technology for skin surface monitoring was promising. However, suppressing self-heating induced by the horseshoe shaped copper tracks needed for stretchability of the SPCB requires more in-depth investigation. The thermocouple matrix was the most promising for clinical application, meeting 6/7 of the major requirements for skin surface temperature monitoring when positioned perpendicular to the EM field., (© 2020 Institute of Physics and Engineering in Medicine.)

Purpose: To demonstrate feasibility of transceive phase mapping with the PLANET method and its application for conductivity reconstruction in the brain., Methods: Accuracy and precision of transceive phase (ϕ ± ) estimation with PLANET, an ellipse fitting approach to phase-cycled balanced steady state free precession (bSSFP) data, were assessed with simulations and measurements and compared to standard bSSFP. Measurements were conducted on a homogeneous phantom and in the brain of healthy volunteers at 3 tesla. Conductivity maps were reconstructed with Helmholtz-based electrical properties tomography. In measurements, PLANET was also compared to a reference technique for transceive phase mapping, i.e., spin echo., Results: Accuracy and precision of ϕ ± estimated with PLANET depended on the chosen flip angle and TR. PLANET-based ϕ ± was less sensitive to perturbations induced by off-resonance effects and partial volume (e.g., white matter + myelin) than bSSFP-based ϕ ± . For flip angle = 25° and TR = 4.6 ms, PLANET showed an accuracy comparable to that of reference spin echo but a higher precision than bSSFP and spin echo (factor of 2 and 3, respectively). The acquisition time for PLANET was ~5 min; 2 min faster than spin echo and 8 times slower than bSSFP. However, PLANET simultaneously reconstructed T 1 , T 2 , B 0 maps besides mapping ϕ ± . In the phantom, PLANET-based conductivity matched the true value and had the smallest spread of the three methods. In vivo, PLANET-based conductivity was similar to spin echo-based conductivity., Conclusion: Provided that appropriate sequence parameters are used, PLANET delivers accurate and precise ϕ ± maps, which can be used to reconstruct brain tissue conductivity while simultaneously recovering T 1 , T 2 , and B 0 maps., (© 2019 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Introduction: Intravenous chemotherapy plus abdominal locoregional hyperthermia is explored as a noninvasive alternative to hyperthermic intraperitoneal chemotherapy (HIPEC) in treatment of peritoneal carcinomatosis (PC). First clinical results demonstrate feasibility, but survival data show mixed results and for pancreatic and gastric origin results are not better than expected for chemotherapy alone. In this study, computer simulations are performed to compare the effectiveness of peritoneal heating for five different locoregional heating systems. Methods: Simulations of peritoneal heating were performed for a phantom and two pancreatic cancer patients, using the Thermotron RF8, the AMC-4/ALBA-4D system, the BSD Sigma-60 and Sigma-Eye system, and the AMC-8 system. Specific absorption rate (SAR) distributions were optimized and evaluated. Next, to provide an indication of possible enhancement factors, the corresponding temperature distributions and thermal enhancement ratio (TER) of oxaliplatin were estimated. Results: Both phantom and patient simulations showed a relatively poor SAR coverage for the Thermotron RF8, a fairly good coverage for the AMC-4/ALBA-4D, Sigma-60, and Sigma-Eye systems, and the best and most homogeneous coverage for the AMC-8 system. In at least 50% of the peritoneum, 35-45 W/kg was predicted. Thermal simulations confirmed these favorable peritoneal heating properties of the AMC-8 system and TER values of ∼1.4-1.5 were predicted in at least 50% of the peritoneum. Conclusion: Locoregional peritoneal heating with the AMC-8 system yields more favorable heating patterns compared to other clinically used locoregional heating devices. Therefore, results of this study may promote the use of the AMC-8 system for locoregional hyperthermia in future multidisciplinary studies for treatment of PC.

Hyperthermia treatment planning (HTP) is valuable to optimize tumor heating during thermal therapy delivery. Yet, clinical hyperthermia treatment plans lack quantitative accuracy due to uncertainties in tissue properties and modeling, and report tumor absorbed power and temperature distributions which cannot be linked directly to treatment outcome. Over the last decade, considerable progress has been made to address these inaccuracies and therefore improve the reliability of hyperthermia treatment planning. Patient-specific electrical tissue conductivity derived from MR measurements has been introduced to accurately model the power deposition in the patient. Thermodynamic fluid modeling has been developed to account for the convective heat transport in fluids such as urine in the bladder. Moreover, discrete vasculature trees have been included in thermal models to account for the impact of thermally significant large blood vessels. Computationally efficient optimization strategies based on SAR and temperature distributions have been established to calculate the phase-amplitude settings that provide the best tumor thermal dose while avoiding hot spots in normal tissue. Finally, biological modeling has been developed to quantify the hyperthermic radiosensitization effect in terms of equivalent radiation dose of the combined radiotherapy and hyperthermia treatment. In this paper, we review the present status of these developments and illustrate the most relevant advanced elements within a single treatment planning example of a cervical cancer patient. The resulting advanced HTP workflow paves the way for a clinically feasible and more reliable patient-specific hyperthermia treatment planning.

Hyperthermia therapy (40-44 °C) is a promising option to increase efficacy of radiotherapy/chemotherapy for brain tumours, in particular paediatric brain tumours. The Chalmers Hyperthermia Helmet is developed for this purpose. Hyperthermia treatment planning is required for treatment optimisation, but current planning systems do not involve a physically correct model of cerebrospinal fluid (CSF). This study investigates the necessity of fluid modelling for treatment planning. We made treatments plans using the Helmet for both pre-operative and post-operative cases, comparing temperature distributions predicted with three CSF models: a convective "fluid" model, a non-convective "solid" CSF model, and CSF models with increased effective thermal conductivity ("high- k "). Treatment plans were evaluated by T 90 , T 50 and T 10 target temperatures and treatment-limiting hot spots. Adequate heating is possible with the helmet. In the pre-operative case, treatment plan quality was comparable for all three models. In the post-operative case, the high- k models were more accurate than the solid model. Predictions to within ±1 °C were obtained by a 10-20-fold increased effective thermal conductivity. Accurate modelling of the temperature in CSF requires fluid dynamics, but modelling CSF as a solid with enhanced effective thermal conductivity might be a practical alternative for a convective fluid model for many applications.

Purpose: To investigate the sequence-specific impact of B 1 + amplitude mapping on the accuracy and precision of permittivity reconstruction at 3T in the pelvic region., Methods: B 1 + maps obtained with actual flip angle imaging (AFI), Bloch-Siegert (BS), and dual refocusing echo acquisition mode (DREAM) sequences, set to a clinically feasible scan time of 5 minutes, were compared in terms of accuracy and precision with electromagnetic and Bloch simulations and MR measurements. Permittivity maps were reconstructed based on these B 1 + maps with Helmholtz-based electrical properties tomography. Accuracy and precision in permittivity were assessed. A 2-compartment phantom with properties and size similar to the human pelvis was used for both simulations and measurements. Measurements were also performed on a female volunteer's pelvis., Results: Accuracy was evaluated with noiseless simulations on the phantom. The maximum B 1 + bias relative to the true B 1 + distribution was 1% for AFI and BS and 6% to 15% for DREAM. This caused an average permittivity bias relative to the true permittivity of 7% to 20% for AFI and BS and 12% to 35% for DREAM. Precision was assessed in MR experiments. The lowest standard deviation in permittivity, found in the phantom for BS, measured 22.4 relative units and corresponded to a standard deviation in B 1 + of 0.2% of the B 1 + average value. As regards B 1 + precision, in vivo and phantom measurements were comparable., Conclusions: Our simulation framework quantitatively predicts the different impact of B 1 + mapping techniques on permittivity reconstruction and shows high sensitivity of permittivity reconstructions to sequence-specific bias and noise perturbation in the B 1 + map. These findings are supported by the experimental results., (© 2019 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Objective: Hyperthermia therapy (HT), heating tumors to 40-45 °C, is a known radiotherapy (RT) and chemotherapy sensitizer. The additional benefit of HT to RT for recurrent breast cancer has been proven in multiple randomized trials. However, published outcome after RT + HT varies widely. We performed a systematic review to investigate whether there is a relationship between achieved HT dose and clinical outcome and thermal toxicity for patients with recurrent breast cancer treated with RT + HT. Method: Four databases, EMBASE, PubMed, Cochrane library and clinicaltrials.gov, were searched with the terms breast, radiotherapy, hyperthermia therapy and their synonyms. Final search was performed on 3 April 2019. Twenty-two articles were included in the systematic review, reporting on 2330 patients with breast cancer treated with RT + HT. Results: Thirty-two HT parameters were tested for a relationship with clinical outcome. In studies reporting a relationship, the relationship was significant for complete response in 10/15 studies, in 10/13 studies for duration of local control, in 2/2 studies for overall survival and in 7/11 studies for thermal toxicity. Patients who received high thermal dose had on average 34% (range 27%-53%) more complete responses than patients who received low thermal dose. Patients who achieved higher HT parameters had increased odds/probability on improved clinical outcome and on thermal toxicity. Conclusion: Temperature and thermal dose during HT had significant influence on complete response, duration of local control, overall survival and thermal toxicity of patients with recurrent breast cancer treated with RT + HT. Higher temperature and thermal dose improved outcome, while higher maximum temperature increased incidence of thermal toxicity.

Purpose: Tumor response and treatment toxicity are related to minimum and maximum tissue temperatures during hyperthermia, respectively. Using a large set of clinical data, we analyzed the number of sensors required to adequately monitor skin temperature during superficial hyperthermia treatment of breast cancer patients., Methods: Hyperthermia treatments monitored with >60 stationary temperature sensors were selected from a database of patients with recurrent breast cancer treated with re-irradiation (23 × 2 Gy) and hyperthermia using single 434 MHz applicators (effective field size 351-396 cm 2 ). Reduced temperature monitoring schemes involved randomly selected subsets of stationary skin sensors, and another subset simulating continuous thermal mapping of the skin. Temperature differences (ΔT) between subsets and complete sets of sensors were evaluated in terms of overall minimum (T min ) and maximum (T max ) temperature, as well as T90 and T10., Results: Eighty patients were included yielding a total of 400 hyperthermia sessions. Median ΔT was <0.01 °C for T90, its 95% confidence interval (95%CI) decreased to ≤0.5 °C when >50 sensors were used. Subsets of <10 sensors result in underestimation of T max up to -2.1 °C (ΔT 95%CI), which decreased to -0.5 °C when >50 sensors were used. Thermal profiles (8-21 probes) yielded a median ΔT < 0.01 °C for T90 and T max , with a 95%CI of -0.2 °C and 0.4 °C, respectively. The detection rate of T max  ≥43 °C is ≥85% while using >50 stationary sensors or thermal profiles., Conclusions: Adequate coverage of the skin temperature distribution during superficial hyperthermia treatment requires the use of >50 stationary sensors per 400 cm 2 applicator. Thermal mapping is a valid alternative.