Validation of thermal dynamics during Hyperthermic IntraPEritoneal Chemotherapy simulations using a 3D-printed phantom.

Introduction: CytoReductive Surgery (CRS) followed by Hyperthermic IntraPeritoneal Chemotherapy (HIPEC) is an often used strategy in treating patients diagnosed with peritoneal metastasis (PM) originating from various origins such as gastric, colorectal and ovarian. During HIPEC treatments, a heated chemotherapeutic solution is circulated through the abdomen using several inflow and outflow catheters. Due to the complex geometry and large peritoneal volume, thermal heterogeneities can occur resulting in an unequal treatment of the peritoneal surface. This can increase the risk of recurrent disease after treatment. The OpenFoam-based treatment planning software that we developed can help understand and map these heterogeneities. Methods: In this study, we validated the thermal module of the treatment planning software with an anatomically correct 3D-printed phantom of a female peritoneum. This phantom is used in an experimental HIPEC setup in which we varied catheter positions, flow rate and inflow temperatures. In total, we considered 7 different cases. We measured the thermal distribution in 9 different regions with a total of 63 measurement points. The duration of the experiment was 30 minutes, with measurement intervals of 5 seconds. Results: Experimental data were compared to simulated thermal distributions to determine the accuracy of the software. The thermal distribution per region compared well with the simulated temperature ranges. For all cases, the absolute error was well below 0.5°C near steady-state situations and around 0.5°C, for the entire duration of the experiment. Discussion: Considering clinical data, an accuracy below 0.5°C is adequate to provide estimates of variations in local treatment temperatures and to help optimize HIPEC treatments.

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.

Clinical Feasibility of a High-Resolution Thermal Monitoring Sheet for Superficial Hyperthermia in Breast Cancer Patients.

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.

HyCHEED System for Maintaining Stable Temperature Control during Preclinical Irreversible Electroporation Experiments at Clinically Relevant Temperature and Pulse Settings.

Electric permeabilization of cell membranes is the main mechanism of irreversible electroporation (IRE), an ablation technique for treatment of unresectable cancers, but the pulses also induce a significant temperature increase in the treated volume. To investigate the therapeutically thermal contribution, a preclinical setup is required to apply IRE at desired temperatures while maintaining stable temperatures. This study's aim was to develop and test an electroporation device capable of maintaining a pre-specified stable and spatially homogeneous temperatures and electric field in a tumor cell suspension for several clinical-IRE-settings. A hydraulically controllable heat exchange electroporation device (HyCHEED) was developed and validated at 37 °C and 46 °C. Through plate electrodes, HyCHEED achieved both a homogeneous electric field and homogenous-stable temperatures; IRE heat was removed through hydraulic cooling. IRE was applied to 300 µL of pancreatic carcinoma cell suspension (Mia PaCa-2), after which cell viability and specific conductivity were determined. HyCHEED maintained stable temperatures within ±1.5 °C with respect to the target temperature for multiple IRE-settings at the selected temperature levels. An increase of cell death and specific conductivity, including post-treatment, was found to depend on electric-field strength and temperature. HyCHEED is capable of maintaining stable temperatures during IRE-experiments. This provides an excellent basis to assess the contribution of thermal effects to IRE and other bio-electromagnetic techniques.

Two high-resolution thermal monitoring sheets for clinical superficial hyperthermia.

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.