For superficial hyperthermia a custom-built multi-applicator multi-amplifier superficial hyperthermia system operating at 433 MHz is utilised. Up to 6 Lucite Cone applicators can be used simultaneously to treat an area of 600 cm2. Temperatures are measured continuously with fibre optic multi-sensor probes. For patients with non-standard clinical problems, hyperthermia treatment planning is used to support decision making with regard to treatment strategy. In 74% of our patients with recurrent breast cancer treated with a reirradiation scheme of 8 fractions of 4 Gy in 4 weeks, combined with 4 or 8 hyperthermia treatments, a complete response is achieved, approximately twice as high as the CR rate following the same reirradation alone. The CR rate in tumours smaller than 30 mm is 80-90%, for larger tumours it is 65%. Hyperthermia appears beneficial for patients with microscopic residual tumour as well. To achieve high CR rates it is important to heat the whole radiotherapy field, and to use an adequate heating technique.
Clinical trials have shown that hyperthermia is a potent adjuvant to conventional cancer treatments, but the temperatures currently achieved in the clinic are still suboptimal. Hyperthermia treatment planning simulations have potential to improve the heating profile of phased-array applicators. An important open challenge is the development of an effective optimization procedure that enables uniform heating of the target region while keeping temperature below a threshold in healthy tissues. In this work, we analyzed the effectiveness and efficiency of a recently proposed optimization approach, i.e. focusing via constrained power optimization (FOCO), using 3D simulations of twelve clinical patient specific models. FOCO performance was compared against a clinically used particle swarm based optimization approach. Evaluation metrics were target coverage at the 25% iso-SAR level, target hotspot quotient, median target temperature (T50) and computational requirements. Our results show that, on average, constrained power focusing performs slightly better than the clinical benchmark (T50 °C), but outperforms this clinical benchmark for large target volumes (40 cm, T50 °C). In addition, the results are achieved in a shorter time (%) and are repeatable because the approach is formulated as a convex optimization problem.
Biological studies and clinical trials show that addition of hyperthermia stimulates conventional cancer treatment modalities and significantly improves treatment outcome. This supra-additive stimulation can be optimized by adaptive hyperthermia to counteract strong and dynamic thermoregulation. The only clinically proven method for the 3D non-invasive temperature monitoring required is by magnetic resonance (MR) temperature imaging, but the currently available set of MR compatible hyperthermia applicators lack the degree of heat control required. In this work, we present the design and validation of a high-frequency (433 MHz ISM band) printed circuit board antenna with a very low MR-footprint. This design is ideally suited for use in a range of hyperthermia applicator configurations. Experiments emulating the clinical situation show excellent matching properties of the antenna over a 7.2% bandwidth (S < -15 dB). Its strongly directional radiation properties minimize inter-element coupling for typical array configurations (S < -23 dB). MR imaging distortion by the antenna was found negligible and MR temperature imaging in a homogeneous muscle phantom was highly correlated with gold-standard probe measurements (root mean square error: RMSE = 0.51 °C and R = 0.99). This work paves the way for tailored MR imaging guided hyperthermia devices ranging from single antenna or incoherent antenna-arrays, to real-time adaptive hyperthermia with phased-arrays.
Purpose: Hyperthermia treatment quality determines treatment effectiveness as shown by the clinically derived thermal-dose effect relations. SAR based optimization factors are used as possible surrogate for temperature, since they are not affected by thermal tissue properties uncertainty and variations. Previously, target coverage (TC) at the 25% and 50% iso-SAR level was shown predictive for treatment outcome in superficial hyperthermia and the target-to-hot-spot-quotient (THQ) was shown to highly correlate with predictive temperature in deep pelvic hyperthermia. Here, we investigate the correlation with temperature for THQ and TC using an 'intermediate' scenario: semi-deep hyperthermia in the head & neck region using the HYPERcollar3D. Methods: Fifteen patient-specific models and two different planning approaches were used, including random perturbations to circumvent optimization bias. The predicted SAR indicators were compared to predicted target temperature distribution indicators T50 and T90, i.e., the median and 90th percentile temperature respectively. Results: The intra-patient analysis identified THQ, TC25 and TC50 as good temperature surrogates: with a mean correlation coefficient R 2 T50 ¼ 0.72 and R 2 T90 ¼0.66. The inter-patient analysis identified the highest correlation with TC25 (R 2 T50 ¼ 0.76, R 2 T90 ¼0.54) and TC50 (R 2 T50 ¼ 0.74, R 2 T90 ¼ 0.56). Conclusion: Our investigation confirmed the validity of our current strategy for deep hyperthermia in the head & neck based on a combination of THQ and TC25. TC50 was identified as the best surrogate since it enables optimization and patient inclusion decision making using one single parameter. ARTICLE HISTORY
Purpose: In this study, we investigated the differences in hyperthermia treatment (HT) quality between treatments applied with different hyperthermia systems for sub-superficial tumours in the head and neck (H&N) region. Materials and methods: In 24 patients, with a clinical target volume (CTV) extending up to 6 cm from the surface, we retrospectively analysed the predicted HT quality achievable by two planar applicator arrays or one phased-array hyperthermia system. Hereto, we calculated and compared the specific absorption rate (SAR) and temperature distribution coverage of the CTV and gross tumour volume (GTV) for the Lucite cone applicator (LCA: planar), current sheet applicator (CSA: planar) and the HYPERcollar (phased-array). Results: The HYPERcollar provides better SAR coverage than planar applicators if the target region is fully enclosed by its applicator frame. For targets extending outside the HYPERcollar frame, sufficient SAR coverage (25% target coverage, i.e. TC25 ! 75%) can still be achieved using the LCA when the target is fully under the LCA aperture and not deeper than 50 mm from the patient surface. Conclusion: Simulations predict that the HYPERcollar (hence also its successor the HYPERcollar3D) is to be preferred over planar applicators such as LCA and current sheet applicator in sub-superficial tumours in the H&N region when used within specifications. ARTICLE HISTORY
Hyperthermia is an emerging cancer treatment modality, which involves applying heat to the malignant tumor. The heating can be delivered using electromagnetic (EM) energy, mostly in the radiofrequency (RF) or microwave range. Accurate patient-specific hyperthermia treatment planning (HTP) is essential for effective and safe treatments, in particular, for deep and loco-regional hyperthermia. An important aspect of HTP is the ability to focus microwave energy into the tumor and reduce the occurrence of hot spots in healthy tissue. This paper presents a method for optimizing the specific absorption rate (SAR) distribution for the head and neck cancer hyperthermia treatment. The SAR quantifies the rate at which localized RF or microwave energy is absorbed by the biological tissue when exposed to an EM field. A differential evolution (DE) optimization algorithm is proposed in order to improve the SAR coverage of the target region. The efficacy of the proposed algorithm is demonstrated by testing with the Erasmus MC patient dataset. DE is compared to the particle swarm optimization (PSO) method, in terms of average performance and standard deviation and across various clinical metrics, such as the hot-spot-tumor SAR quotient (HTQ), treatment quantifiers, and temperature parameters. While hot spots in the SAR distribution remain a problem with current approaches, DE enhances focusing microwave energy absorption to the target region during hyperthermia treatment. In particular, DE offers improved performance compared to the PSO algorithm currently deployed in the clinic, reporting a range of improvement of HTQ standard deviation of between 40.1-96.8% across six patients.
Clinical studies have shown that hyperthermia sensitizes tumor cells for conventional therapies. During phased-array microwave hyperthermia, an array of antennas is used to focus the electromagnetic waves at the target region. Selective heating, while preserving the healthy tissue, is a demanding challenge and currently patient specific pre-treatment planning is used to optimize the amplitudes and phases of the waves. In addition, when needed, this single optimal heat distribution is adapted using the simulations based on the feedback from thermo-sensors and the patient. In this paper, we hypothesize that sequential, i.e. 'time-multiplexed', application of multiple Pareto optimal heating patterns provides a better time-averaged treatment quality. To test the benefit of such a time-multiplexed approach, a multi-objective genetic algorithm was introduced to balance two objectives that both focus the specific absorption rate (SAR) delivered to the target region but differ in the suppressing of pre-defined hotspots. This step leads to two Pareto optimal distributions. These 'diverse' antenna settings are then applied sequentially and thermal simulations are used to evaluate the effectiveness of the time-multiplexed steering. The proposed technique is tested using treatment planning data of a representative dataset of five head and neck patients for the HYPERcollar3D. Steering dynamics are analysed and the time-multiplexed steering is compared to the current static solution used in the clinic, i.e. hotspot-target SAR quotient optimization using particle swarm optimization. Our results demonstrate that realistic steering periods of 10s suffice to stabilize temperatures within 0.04 °C and the ability to enhance target heating while reducing hotspots, i.e. 0.3 °C-1.2 °C improvement in T while reducing hotspot temperatures by 0.6 °C-1.5 °C.
Purpose: A port-a-cath is a device implanted under the skin for continuous drug administration. It is composed of a catheter and a silicone or metal reservoir. A simulation study was done to assess the impact of a port-a-cath implant on the quality of superficial hyperthermia treatments applied using the Lucite cone applicator (LCA). Methods: Specific absorption rate (SAR) and temperature distributions were predicted using SEMCAD-X (version 14.8). We simulated 72 arrangements: two LCA-implant set-ups (central port-a-cath or at an edge below the LCA footprint), six translations of the LCA per set-up, two LCA orientations (Parallel or perpendicular electric field direction) per set-up, two implant materials (silicon or metal) and a control without port-a-cath. Treatment quality was quantified by the average 1 g SAR coverage (CV 25% ), i.e. volume within the 25% iso-SAR surface, and the volume within the 40 C iso-temperature surface (CV 40 C ). Results: CV 25% reduced with a silicon port-a-cath located below the LCA footprint. In the worst scenario, only 64% of the CV 25% of the control set-up was achieved. For a metal port-a-cath below the LCA aperture, dramatic reductions of CV 25% were predicted: worst scenario down to 12.1% of the control CV 25% . For the CV 40 C the worst case values were 74.5% and 6.5%, for silicon and metal implants, respectively. Conclusions: A silicone port-a-cath below the LCA had a smaller effect on treatment quality than a metal implant. Based on this study we recommend verifying heating quality by 3D patient-specific treatment planning when a port-a-cath is located below the footprint of the applicator.
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