A patterns of care analysis of hyperthermia in combination with radio(chemo)therapy or chemotherapy in European clinical centers.

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.

A randomized phase-II study of reirradiation and hyperthermia versus reirradiation and hyperthermia plus chemotherapy for locally recurrent breast cancer in previously irradiated area.

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/m2. 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.

Comparison of the clinical performance of a hybrid Alba 4D and the AMC-4 locoregional hyperthermia systems.

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.

Improved unsupervised physics-informed deep learning for intravoxel incoherent motion modeling and evaluation in pancreatic cancer patients.

PURPOSE: Earlier work showed that IVIM-NETorig , 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-NEToptim , 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 (CVNET ), respectively. The best performing network, IVIM-NEToptim was compared to least squares (LS) and a Bayesian approach at different SNRs. IVIM-NEToptim '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-NEToptim outperformed IVIM-NETorig 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 (CVNET (D) = 0.013 vs 0.104; CVNET (f) = 0.020 vs 0.054; CVNET (D*) = 0.036 vs 0.110). IVIM-NEToptim showed superior performance to the LS and Bayesian approaches at SNRs < 50. In vivo, IVIM-NEToptim showed significantly less noisy parameter maps with lower wSD for D and f than the alternatives. In the treated cohort, IVIM-NEToptim detected the most individual patients with significant parameter changes compared to day-to-day variations. CONCLUSION: IVIM-NEToptim is recommended for accurate, informative, and consistent IVIM fitting to DWI data.

Transceive phase mapping using the PLANET method and its application for conductivity mapping in the brain.

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 T1 , T2 , B0 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 T1 , T2 , and B0 maps.

Deep learning-based reconstruction of in vivo pelvis conductivity with a 3D patch-based convolutional neural network trained on simulated MR data.

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 B1+ and transceive phase (ϕ± ). Simulated B1+ 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 90th and 10th 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.

Advanced patient-specific hyperthermia treatment planning.

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.

Locoregional peritoneal hyperthermia to enhance the effectiveness of chemotherapy in patients with peritoneal carcinomatosis: a simulation study comparing different locoregional heating systems.

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.

Accuracy and precision of electrical permittivity mapping at 3T: the impact of three B1+ mapping techniques.

PURPOSE: To investigate the sequence-specific impact of B1+ amplitude mapping on the accuracy and precision of permittivity reconstruction at 3T in the pelvic region. METHODS: B1+ 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 B1+ 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 B1+ bias relative to the true B1+ 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 B1+ of 0.2% of the B1+ average value. As regards B1+ precision, in vivo and phantom measurements were comparable. CONCLUSIONS: Our simulation framework quantitatively predicts the different impact of B1+ mapping techniques on permittivity reconstruction and shows high sensitivity of permittivity reconstructions to sequence-specific bias and noise perturbation in the B1+ map. These findings are supported by the experimental results.

Temperature and thermal dose during radiotherapy and hyperthermia for recurrent breast cancer are related to clinical outcome and thermal toxicity: a systematic review.

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.

Reirradiation + hyperthermia for recurrent breast cancer en cuirasse.

BACKGROUND AND PURPOSE: Patients with irresectable locoregional recurrent breast cancer en cuirasse (BCEC) do not have effective curative treatment options. Hyperthermia, the elevation of tumor temperature to 40-45 °C, is a well-established radio- and chemotherapy sensitizer. A total of 196 patients were treated with reirradiation and hyperthermia (reRT+HT) at two Dutch institutes from 1982-2005. The palliative effect was evaluated in terms of clinical outcome and toxicity. PATIENTS AND METHODS: All patients received previous irradiation to a median dose of 50 Gy. In all, 75% of patients received 1-6 treatment modalities for previous tumor recurrences. ReRT consisted of 8 × 4 Gy given twice a week or 12 × 3 Gy given four times a week. Superficial hyperthermia was added once or twice a week. Tumor area comprised ≥½ of the ipsilateral chest wall. RESULTS: Overall clinical response rate was 72% (complete response [CR] 30%, partial response [PR] 42%, stable disease [SD] 22%, progressive disease [PD] 6%). The local progression-free rate at 1 year was 24%. Median survival was 6.9 months. Forty-three percent of our patients with CR, PR, SD after treatment remained infield progression-free until death or last follow-up. Acute ≥grade 3 toxicity occurred in 33% of patients, while late ≥grade 3 toxicity was recorded in 14% of patients. Tumor ulceration prior to treatment had a negative impact on both clinical outcome and toxicity. CONCLUSION: ReRT+HT provides sustainable palliative tumor control, despite refractory, extensive tumor growth. Compared to currently available systemic treatment options, reRT+HT is more effective with less toxicity.

Analysis of clinical data to determine the minimum number of sensors required for adequate skin temperature monitoring of superficial hyperthermia treatments.

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 cm2). 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 (Tmin) and maximum (Tmax) 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 Tmax 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 Tmax, with a 95%CI of -0.2 °C and 0.4 °C, respectively. The detection rate of Tmax ≥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 cm2 applicator. Thermal mapping is a valid alternative.

Clinical validation of a novel thermophysical bladder model designed to improve the accuracy of hyperthermia treatment planning in the pelvic region.

PURPOSE: Hyperthermia treatment planning for deep locoregional hyperthermia treatment may assist in phase and amplitude steering to optimize the temperature distribution. This study aims to incorporate a physically correct description of bladder properties in treatment planning, notably the presence of convection and absence of perfusion within the bladder lumen, and to assess accuracy and clinical implications for non muscle invasive bladder cancer patients treated with locoregional hyperthermia. METHODS: We implemented a convective thermophysical fluid model based on the Boussinesq approximation to the Navier-Stokes equations using the (finite element) OpenFOAM toolkit. A clinician delineated the bladder on CT scans obtained from 14 bladder cancer patients. We performed (1) conventional treatment planning with a perfused muscle-like solid bladder, (2) with bladder content properties without and (3) with flow dynamics. Finally, we compared temperature distributions predicted by the three models with temperature measurements obtained during treatment. RESULTS: Much higher and more uniform bladder temperatures are predicted with physically accurate fluid modeling compared to previously employed muscle-like models. The differences reflect the homogenizing effect of convection, and the absence of perfusion. Median steady state temperatures simulated with the novel convective model (3) deviated on average -0.6 °C (-12%) from values measured during treatment, compared to -3.7 °C (-71%) and +1.5 °C (+29%) deviation for the muscle-like (1) and static (2) models, respectively. The Grashof number was 3.2 ± 1.5 × 105 (mean ± SD). CONCLUSIONS: Incorporating fluid modeling in hyperthermia treatment planning yields significantly improved predictions of the temperature distribution in the bladder lumen during hyperthermia treatment.

A flexible 70 MHz phase-controlled double waveguide system for hyperthermia treatment of superficial tumours with deep infiltration.

PURPOSE: Superficial tumours with deep infiltration in the upper 15 cm of the trunk cannot be treated adequately with existing hyperthermia systems. The aim of this study was to develop, characterise and evaluate a new flexible two-channel hyperthermia system (AMC-2) for tumours in this region. MATERIALS AND METHODS: The two-channel AMC-2 system has two horizontally revolving and height adjustable 70 MHz waveguides. Three different interchangeable antennas with sizes 20 × 34, 15 × 34 and 8.5 × 34 cm were developed and their electrical properties were determined. The performance of the AMC-2 system was tested by measurements of the electric field distribution in a saline water filled elliptical phantom, using an electric field vector probe. Clinical feasibility was demonstrated by treatment of a melanoma in the axillary region. RESULTS: Phantom measurements showed a good performance for all waveguides. The large reflection of the smallest antenna has to be compensated by increased forward power. Field patterns become asymmetrical when using smaller top antennas, necessitating phase corrections. The clinical application showed that tumours deeper than 4 cm can be heated adequately. A median tumour temperature of 42 °C can be reached up to 12 cm depth with adequate antenna positioning and phase-amplitude steering. CONCLUSIONS: This 70 MHz AMC-2 waveguide system is a useful addition to existing loco-regional hyperthermia equipment as it is capable of heating axillary tumours and other tumours deeper than 4 cm.

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.

Rib fractures after reirradiation plus hyperthermia for recurrent breast cancer: Predictive factors.

BACKGROUND: Combining reirradiation (reRT) and hyperthermia (HT) has shown high therapeutic value for patients with locoregional recurrent breast cancer (LR). However, additional toxicity of reirradiation (e.g., rib fractures) may occur. The aim of this study is to determine the impact of potential risk factors on the occurrence of rib fractures. PATIENTS AND METHODS: From 1982-2005, 234 patients were treated with adjuvant reRT + HT after surgery for LR. ReRT consisted typically of 8 fractions of 4 Gy twice a week, or 12 fractions of 3 Gy four times a week. A total of 118 patients were irradiated with abutted photon and electron fields. In all, 60 patients were irradiated using either one or alternating combinations of abutted AP electron fields. Hyperthermia was given once or twice a week. RESULTS: The 5-year infield local control (LC) rate was 70 %. Rib fractures were detected in 16 of 234 patients (actuarial risk: 7 % at 5 years). All rib fractures occurred in patients treated with a combination of photon and abutted electron fields (p = 0.000); in 15 of 16 patients fractures were located in the abutment regions. The other significant predictive factors for rib fractures were a higher fraction dose (p = 0.040), large RT fields, and treatment before the year 2000. DISCUSSION AND CONCLUSION: ReRT + HT results in long-term LC. The majority of rib fractures were located in the photon/electron abutment area, emphasizing the disadvantage of field overlap. Large abutted photon/electron fields combined with 4 Gy fractions increase the number of rib fractures in this study group. However, as these factors were highly correlated no relative importance of the individual factors could be estimated. Increasing the number of HT sessions a week does not increase the risk of rib fractures.

Chemohyperthermia in non-muscle-invasive bladder cancer: An overview of the literature and recommendations.

Non-muscle-invasive bladder cancer (NMIBC) is characterised by a high risk of recurrence for the present standard treatment of transurethral resection of the bladder (TURB) followed by intravesical instillation of Mitomycin-C (MMC) or bacillus Calmette-Guérin (BCG). To decrease this high recurrence rate, alternative treatments are studied. Intravesical MMC combined with hyperthermia could be an interesting alternative active treatment for intermediate- and high-risk NMIBC, and has been investigated in the past years. Hyperthermia, raising tumour temperatures to 40-44 °C, can be achieved with several hyperthermia systems, based on three different techniques: 1) intravesical microwave induced heating, 2) conductive heating, and 3) loco-regional, using external radiofrequency antennas. In this review an overview is given of the available hyperthermia systems and the reported outcomes. Future directions are discussed. Optimal implementation of a combined regimen of MMC and hyperthermia requires further clinical trials to identify patients who will benefit most from this treatment, to optimise treatment schedules and to compare the efficacy of different hyperthermia devices.

Thermoradiotherapy planning: Integration in routine clinical practice.

Planning of combined radiotherapy and hyperthermia treatments should be performed taking the synergistic action between the two modalities into account. This work evaluates the available experimental data on cytotoxicity of combined radiotherapy and hyperthermia treatment and the requirements for integration of hyperthermia and radiotherapy treatment planning into a single planning platform. The underlying synergistic mechanisms of hyperthermia include inhibiting DNA repair, selective killing of radioresistant hypoxic tumour tissue and increased radiosensitivity by enhanced tissue perfusion. Each of these mechanisms displays different dose-effect relations, different optimal time intervals and different optimal sequences between radiotherapy and hyperthermia. Radiosensitisation can be modelled using the linear-quadratic (LQ) model to account for DNA repair inhibition by hyperthermia. In a recent study, an LQ model-based thermoradiotherapy planning (TRTP) system was used to demonstrate that dose escalation by hyperthermia is equivalent to ∼10 Gy for prostate cancer patients treated with radiotherapy. The first step for more reliable TRTP is further expansion of the data set of LQ parameters for normally oxygenated normal and tumour tissue valid over the temperature range used clinically and for the relevant time intervals between radiotherapy and hyperthermia. The next step is to model the effect of hyperthermia in hypoxic tumour cells including the physiological response to hyperthermia and the resulting reoxygenation. Thermoradiotherapy planning is feasible and a necessity for an optimal clinical application of hyperthermia combined with radiotherapy in individual patients.

Feasibility of electric property tomography of pelvic tumors at 3T.

PURPOSE: Investigation of the validity of the "transceive phase assumption" for Electric Property Tomography of pelvic tumors at 3T. The acquired electric conductivities of pelvic tumors are beneficial for improved specific absorption rate determination in hyperthermia treatment planning. METHODS: Electromagnetic simulations and magnetic resonance imaging measurements of a pelvic-sized phantom and the human pelvis of a volunteer and a cervix cancer patient. RESULTS: The reconstructed conductivity values of the phantom tumor model are in good quantitative agreement (mean deviation: 1-10%) with the probe measurements. Furthermore, the average reconstructed conductivity of a pelvic tumor model was in close agreement with the input conductivity (0.86 S/m vs. 0.90 S/m). The reconstructed tumor conductivity of the presented patient (cervical carcinoma, Stage: IVA) was 1.16 ± 0.40 S/m. CONCLUSION: This study demonstrates the feasibility of electric property tomography to measure quantitatively the conductivity of centrally located tumors in a pelvic-sized phantom and human pelvis with a standard magnetic resonance (MR) system and MR sequences. A good quantitative agreement was found between the reconstructed σ-values and probe measurements for a wide range of σ-values and for off-axis located spherical compartment. As most pelvic tumors are located in the central region of the pelvis, these results can be exploited in hyperthermia treatment planning systems.

Hyperthermia-related clinical trials on cancer treatment within the ClinicalTrials.gov registry.

PURPOSE: Hyperthermia has been shown to improve the effectiveness of chemotherapy and radiotherapy in the treatment of cancer. This paper summarises all recent clinical trials registered in the ClinicalTrials.gov registry. MATERIALS AND METHODS: The records of 175,538 clinical trials registered at ClinicalTrials.gov were downloaded on 29 September 2014 and a database was established. We searched this database for hyperthermia or equivalent words. RESULTS: A total of 109 trials were identified in which hyperthermia was part of the treatment regimen. Of these, 49 trials (45%) had hyperthermic intraperitoneal chemotherapy after cytoreductive surgery (HIPEC) as the primary intervention, and 14 other trials (13%) were also testing some form of intraperitoneal hyperthermic chemoperfusion. Seven trials (6%) were testing perfusion attempts to other locations (thoracic/pleural n = 4, limb n = 2, hepatic n = 1). Sixteen trials (15%) were testing regional hyperthermia, 13 trials (12%) whole body hyperthermia, seven trials (6%) superficial hyperthermia and two trials (2%) interstitial hyperthermia. One remaining trial tested laser hyperthermia. CONCLUSIONS: In contrast to the general opinion, this analysis shows continuous interest and ongoing clinical research in the field of hyperthermia. Interestingly, the majority of trials focused on some form of intraperitoneal hyperthermic chemoperfusion. Despite the high number of active clinical studies, HIPEC is a topic with limited attention at the annual meetings of the European Society for Hyperthermic Oncology and the Society of Thermal Medicine. The registration of on-going clinical trials is of paramount importance for the achievement of a comprehensive overview of available clinical research activities involving hyperthermia.