Overview of bladder heating technology: matching capabilities with clinical requirements.

Moderate temperature hyperthermia (40-45°C for 1 h) is emerging as an effective treatment to enhance best available chemotherapy strategies for bladder cancer. A rapidly increasing number of clinical trials have investigated the feasibility and efficacy of treating bladder cancer with combined intravesical chemotherapy and moderate temperature hyperthermia. To date, most studies have concerned treatment of non-muscle-invasive bladder cancer (NMIBC) limited to the interior wall of the bladder. Following the promising results of initial clinical trials, investigators are now considering protocols for treatment of muscle-invasive bladder cancer (MIBC). This paper provides a brief overview of the devices and techniques used for heating bladder cancer. Systems are described for thermal conduction heating of the bladder wall via circulation of hot fluid, intravesical microwave antenna heating, capacitively coupled radio-frequency current heating, and radiofrequency phased array deep regional heating of the pelvis. Relative heating characteristics of the available technologies are compared based on published feasibility studies, and the systems correlated with clinical requirements for effective treatment of MIBC and NMIBC

Comparison of intratumor and intraluminal temperatures during locoregional deep hyperthermia of pelvic tumors

Purpose: To investigate whether intraluminal thermometry provides sufficient information to apply high quality deep hyperthermia in pelvic tumors. Patients and Methods: The intratumor and intraluminal temperatures of 48 patients were analyzed per cancer type: rectum (21 male, 14 female), cervix (n = 8), and bladder (n = 5). Temperature-dose parameters were calculated, temperature curves within each treatment session were compared, and correlation between intratumor and intraluminal temperatures was analyzed. Results: Intratumor and intraluminal temperatures at the same time points during individual treatments were highly correlated (mean correlation coefficient: 0.93). However, the quantitative level differed from 0.1 to 1.1 degrees C and the differences of the timetemperature graphs varied per tumor group. Average intratumor and intraluminal temperatures were not different in the four groups. Intratumor thermometry was found not superior over intraluminal thermometry to improve tumor temperature level and homogeneity by SAR steering. Conclusion: Intraluminal thermometry provides sufficient information to apply deep hyperthermia to individual patients with centrally located rectum, cervix or bladder cancer

Assessment of the thermal tissue models for the head and neck hyperthermia treatment planning

Purpose: To compare different thermal tissue models for head and neck hyperthermia treatment planning, and to assess the results using predicted and measured applied power data from clinical treatments. Methods: Three commonly used temperature models from literature were analysed: “constant baseline”, “constant thermal stress” and “temperature dependent”. Power and phase data of 93 treatments of 20 head and neck patients treated with the HYPERcollar3D applicator were used. The impact on predicted median temperature T50 inside the target region was analysed with maximum allowed temperature of 44 °C in healthy tissue. The robustness of predicted T50 for the three models against the influence of blood perfusion, thermal conductivity and the assumed hotspot temperature level was analysed. Results: We found an average predicted T50 of 41.0 ± 1.3 °C (constant baseline model), 39.9 ± 1.1 °C (constant thermal stress model) and 41.7 ± 1.1 °C (temperature dependent model). The constant thermal stress model resulted in the best agreement between the predicted power (P = 132.7 ± 45.9 W) and the average power measured during the hyperthermia treatments (P = 129.1 ± 83.0 W). Conclusion: The temperature dependent model predicts an unrealistically high T50. The power values for the constant thermal stress model, after scaling simulated maximum temperatures to 44 °C, matched best to the average measured powers. We consider this model to be the most appropriate for temperature predictions using the HYPERcollar3D applicator, however further studies are necessary for developing of robust temperature model for tissues during heat stress.</p

Adapting temperature predictions to MR imaging in treatment position to improve simulation-guided hyperthermia for cervical cancer

Hyperthermia treatment consists of elevating the temperature of the tumor to increase the effectiveness of radiotherapy and chemotherapy. Hyperthermia treatment planning (HTP) is an important tool to optimize treatment quality using pre-treatment temperature predictions. The accuracy of these predictions depends on modeling uncertainties such as tissue properties and positioning. In this study, we evaluated if HTP accuracy improves when the patient is imaged inside the applicator at the start of treatment. Because perfusion is a major uncertainty source, the importance of accurate treatment position and anatomy was evaluated using different perfusion values. Volunteers were scanned using MR imaging without (&amp;#x201C;planning setup&amp;#x201D;) and with the MR-compatible hyperthermia device (&amp;#x201C;treatment setup&amp;#x201D;). Temperature-based quality indicators were used to assess the differences between the standard, apparent and the optimized hyperthermia dose. We conclude that pre-treatment imaging can improve HTP predictions accuracy but also, that tissue perfusion modelling is crucial if temperature-based optimization is applied.</p

Exposure of the human body to professional and domestic induction cooktops compared to the basic restrictions

We investigated whether domestic and professional induction cooktops comply with the basic restrictions defined by the International Commission on Non-Ionizing Radiation Protection (ICNIRP). Based on magnetic field measurements, a generic numerical model of an induction cooktop was derived in order to model user exposure. The current density induced in the user was simulated for various models and distances. We also determined the exposure of the fetus and of young children. While most measured cooktops comply with the public exposure limits at the distance specified by the International Electrotechnical Commission (standard IEC 62233), the majority exceeds them at closer distances, some of them even the occupational limits. The maximum current density in the tissue of the user significantly exceeds the basic restrictions for the general public, reaching the occupational level. The exposure of the brains of young children reaches the order of magnitude of the limits for the general public. For a generic worst-case cooktop compliant with the measurement standards, the current density exceeds the 1998 ICNIRP basic restrictions by up to 24 dB or a factor of 16. The brain tissue of young children can be overexposed by 6 dB or a factor of 2. The exposure of the tissue of the central nervous system of the fetus can exceed the limits for the general public if the mother is exposed at occupational levels. This demonstrates that the methodology for testing induction cooktops according to IEC 62233 contradicts the basic restrictions. This evaluation will be extended considering the redefined basic restrictions proposed by the ICNIRP in 2010

Quantitative, Multi-institutional Evaluation of MR Thermometry Accuracy for Deep-Pelvic MR-Hyperthermia Systems Operating in Multi-vendor MR-systems Using a New Anthropomorphic Phantom

Clinical outcome of hyperthermia depends on the achieved target temperature, therefore target conformal heating is essential. Currently, invasive temperature probe measurements are the gold standard for temperature monitoring, however, they only provide limited sparse data. In contrast, magnetic resonance thermometry (MRT) provides unique capabilities to non-invasively measure the 3D-temperature. This study investigates MRT accuracy for MR-hyperthermia hybrid systems located at five European institutions while heating a centric or eccentric target in anthropomorphic phantoms with pelvic and spine structures. Scatter plots, root mean square error (RMSE) and Bland–Altman analysis were used to quantify accuracy of MRT compared to high resistance thermistor probe measurements. For all institutions, a linear relation between MRT and thermistor probes measurements was found with R2 (mean ± standard deviation) of 0.97 ± 0.03 and 0.97 ± 0.02, respectively for centric and eccentric heating targets. The RMSE was found to be 0.52 ± 0.31 °C and 0.30 ± 0.20 °C, respectively. The Bland-Altman evaluation showed a mean difference of 0.46 ± 0.20 °C and 0.13 ± 0.08 °C, respectively. This first multi-institutional evaluation of MR-hyperthermia hybrid systems indicates comparable device performance and good agreement between MRT and thermistor probes measurements. This forms the basis to standardize treatments in multi-institution studies of MR-guided hyperthermia and to elucidate thermal dose-effect relations

Heat-induced BRCA2 degradation in human tumours provides rationale for hyperthermia-PARP-inhibitor combination therapies

Purpose: Hyperthermia (40–44 °C) effectively sensitises tumours to radiotherapy by locally altering tumour biology. One of the effects of heat at the cellular level is inhibition of DNA repair by homologous recombination via degradation of the BRCA2-protein. This suggests that hyperthermia can expand the group of patients that benefit from PARP-inhibitors, a drug exploiting homologous recombination deficiency. Here, we explore whether the molecular mechanisms that cause heat-mediated degradation of BRCA2 are conserved in cell lines from various origins and, most importantly, whether, BRCA2 protein levels can be attenuated by heat in freshly biopted human tumours. Experimental design: Cells from four established cell lines and from freshly biopsied material of cervical (15), head- and neck (9) or bladder tumours (27) were heated to 42 °C for 60 min ex vivo. In vivo hyperthermia was studied by taking two biopsies of the same breast or cervical tumour: one before and one after treatment. BRCA2 protein levels were measured by immunoblotting. Results: We found decreased BRCA2-levels after hyperthermia in all established cell lines and in 91% of all tumours treated ex vivo. For tumours treated with hyperthermia in vivo, technical issues and intra-tumour heterogeneity prevented obtaining interpretable results. Conclusions: This study demonstrates that heat-mediated degradation of BRCA2 occurs in tumour material directly derived from patients. Although BRCA2-degradation may not be a practical biomarker for heat deposition in situ, it does suggest that application of hyperthermia could be an effective method to expand the patient group that could benefit from PARP-inhibitors

Thermoradiotheraphy of cancer: an effective approach

Hyperthermia (HT) means using controlled temperatures of 40-45°C for cancer treatment. HT is applied with differentmethods e.g. superficial-HT, locoregional deep-HT, interstitial-HT, intracavity-HT, and whole body-HT. HT can apply indifferent tumor sites such as breast cancer, melanoma, head and neck, cervix cancer, and glioblastoma. The Literature suggests that addition of HT to radiotherapy, chemotherapy, or both, will result better tumor response rate, local control, and survival rate; without increasing toxicity. HT can also improve palliative effects in patient. In recent years, due to substantial technical improvements made in achieving selected increaseof temperatures in superficial and deep-seated tumors,thermometry, and treatment planning; HT is becoming moreclinically accepted in Europe and the USA. HT, as an adjunctcancer treatment modality, is certainly a promising approach;however, it is not well known yet worldwide. Therefore, itseems there is need to know more about that. The purpose of this review is to provide an overview on the application of HT combined with conventional cancer treatment modalities,mainly radiotherapy. The article also introduces mechanism of HT, heating delivery modes, thermometry, and it summarizes results of randomized trials from Western research groups

Impact of segmentation detail in hyperthermia treatment planning: comparison between detailed and clinical tissue segmentation

Treatment planning for deep pelvic hyperthermia is currently based on tissue models comprising four tissue categories. For head and neck hyperthermia, we earlier found that more tissues are required for an accurate representation. Hence, we studied the accuracy of the clinical tissue segmentation (4 tissues) using a full detailed tissue list segmentation (80 tissues) as benchmark. The SAR and temperature distributions were evaluated and relevant differences were found. Also, the large and unknown variation in blood perfusion results in a large uncertainty in the predicted temperature distributions. In summary, this study showed that the number of tissues segmented is relevant for both SAR and the temperature prediction accuracy