Ultra wideband microwave hyperthermia for brain cancer treatment

Despite numerous clinical trials demonstrating that microwave hyperthermia is a powerful adjuvant modality in the treatment of cancers, there have been few instances where this method has been applied to brain tumors. The reason is a combination of anatomical and physiological factors in this site that require an extra degree of accuracy and precision in the thermal dose delivery. Current clinical applicators are not able to provide such control, partly because they are designed to operate at a single fixed frequency. In terms of treatment planning, the use of a single frequency is limiting as the size of the focal spot cannot be modified to accommodate the specific tumor volume and location. The introduction of ultra wide-band (UWB) systems opens up an opportunity to overcome these limitations, as they convey the possibility of adapting the focal spot and obtaining different power deposition patterns to reduce the heating of healthy tissues.In this thesis, we explore whether the current SAR-based treatment planning methods can be meaningfully translated to the UWB setting and propose new solutions for deep UWB microwave hyperthermia. We analyze the most commonly used cost functions for treatment planning optimization and discuss their suitability for use with UWB systems. Then, we propose a novel SAR-based cost function (HCQ) for UWB optimization that exhibits a high correlation with the resulting tumor temperature. To solve for the HCQ, we describe a novel, time-reversal-based, iterative scheme for a rapid and efficient optimization of UWB treatment plans. Next, we investigate the design possibilities of UWB brain applicators and introduce a fast E-field approximation scheme to quickly explore a large number of array configurations. The method determines the best antenna arrangement around the head with respect to the multiple objectives and requirements of clinical hyperthermia. Together, the proposed solutions manage to achieve the level of tumor coverage and hot-spot suppression that is necessary for a successful treatment. Finally, we investigate the benefit of integrating hyperthermia delivered by an optimized UWB applicator into the radiation therapy plan for a pediatric medulloblastoma patient. The results suggest that UWB microwave hyperthermia for brain cancer treatment is feasible and motivate efforts for further development of UWB applicators and systems

Towards UWB microwave hyperthermia for brain cancer treatment

Despite numerous clinical trials demonstrating that microwave hyperthermia is a powerful adjuvant modality in the treatment of cancers, there have been few instances where this method has been applied to brain tumors. The reason is a combination of anatomical and physiological factors in this site that require an extra degree of accuracy and control in the thermal dose delivery which current systems are not able to provide. All clinical applicators available today are in fact based on a single-frequency technology. In terms of treatment planning options, the use of a single frequency is limiting as the size of the focal spot cannot be modified to accommodate the specific tumor volume and location. The introduction of UWB systems opens up an opportunity to overcome these limitations, as they convey the possibility to adapt the focal spot and to use multiple operating frequencies to reduce the power deposition in healthy tissues.In this thesis, we explore whether the current treatment planning methods can be meaningfully translated to the UWB setting and propose new solutions for UWB microwave hyperthermia. We analyze the most commonly used cost-functions for treatment planning optimization and discuss their suitability for use with UWB systems. Then, we propose a novel cost-function specifically tailored for UWB optimization (HCQ). To solve for the HCQ, we further describe a novel, time-reversal based, iterative scheme for the rapid and efficient optimization of UWB treatment plans. We show that the combined use of these techniques results in treatment plans that better exploit the benefits of UWB systems, yielding increased tumor coverage and lower peak temperatures outside the target. Next, we investigate the design possibilities of UWB applicators and introduce a fast E-field approximation scheme. The method can be used for the global optimization of the array parameters with respect to the multiple objectives and requirements of hyperthermia treatments. Together, the proposed solutions represent a step forward in the implementation of patient-specific hyperthermia treatments, increasing their accuracy and precision. The results suggest that UWB microwave hyperthermia for brain cancer treatment is feasible, and motivate the efforts for further development of UWB applicators and systems

Suitability of eigenvalue beam-forming for discrete multi-frequency hyperthermia treatment planning

Purpose: Thermal dose delivery in microwave hyperthermia for cancer treatment is expected to benefit from the introduction of ultra-wideband (UWB)-phased array applicators. A full exploitation of the combination of different frequencies to improve the deposition pattern is, however, a nontrivial problem. It is unclear whether the cost functions used for hyperthermia treatment planning (HTP) optimization in the single-frequency setting can be meaningfully extended to the UWB case. Method: We discuss the ability of the eigenvalue (EV) and a novel implementation of iterative-EV (i-EV) beam-forming methods to fully exploit the available frequency spectrum when a discrete set of simultaneous operating frequencies is available for treatment. We show that the quadratic power deposition ratio solved by the methods can be maximized by only one frequency in the set, therefore rendering EV inadequate for UWB treatment planning. We further investigate whether this represents a limitation in two realistic test cases, comparing the thermal distributions resulting from EV and i-EV to those obtained by optimizing for other nonlinear cost functions that allow for\ua0multi-frequency. Results: The classical EV-based single-frequency HTP yields systematically lower target SAR deposition and temperature values than nonlinear HTP. In a larynx target, the proposed single-frequency i-EV scheme is able to compensate for this and reach temperatures comparable to those given by global nonlinear optimization. In a meninges target, the multi-frequency setting outperforms the single-frequency one, achieving better target coverage and (Formula presented.) higher (Formula presented.) in the tumor than single-frequency-based\ua0HTP. Conclusions: Classical EV performs poorly in terms of resulting target temperatures. The proposed single-frequency i-EV scheme can be a viable option depending on the patient and tumor to be treated, as long as the proper operating frequency can be selected across a UWB range. Multi-frequency HTP can bring a considerable benefit in regions typically difficult to treat such as the\ua0brain

Iterative time-reversal for multi-frequency hyperthermia

Time-reversal (TR) is a known wideband array beam-forming technique that has been suggested as a treatment planning alternative in deep microwave hyperthermia for cancer treatment. While the aim in classic TR is to focus the energy at a specific point within the target, no assumptions are made on secondary lobes that might arise in the healthy tissues. These secondary lobes, together with tissue heterogeneity, may result in hot-spots (HSs), which are known to limit the efficiency of the thermal dose delivery to the tumor. This paper proposes a novel wideband TR focusing method that iteratively shifts the focus away from HSs and towards cold-spots from an initial TR solution, a procedure that improves tumor coverage and reduces HSs. We verify this method on two different applicator topologies and several target volume configurations. The algorithm is deterministic and runs within seconds, enabling its use for real-time applications. At the same time, it yields results comparable to those obtained with global stochastic optimizers such as Particle Swarm

The hot-to-cold spot quotient for SAR-based treatment planning in deep microwave hyperthermia

BACKGROUND: A necessary precondition for a successful microwave hyperthermia (HT) treatment delivered by phased arrays is the ability of the HT applicator to selectively raise the temperature of the entire tumor volume. SAR-based treatment plan (HTP) optimization methods exploit the correlation between specific absorption rate (SAR) and temperature increase in order to determine the set of steering parameters for optimal focusing, while allowing for lower model complexity. Several cost functions have been suggested in the past for this optimization problem. However, their correlation with high and homogeneous tumor temperatures remains sub-optimal in many cases. Previously, we proposed the hot-to-cold spot quotient (HCQ) as a novel cost function for SAR-based HTP optimization and showed its potential to address these issues. MATERIALS AND METHODS: In this work, we validate the HCQ on a standard ESHO patient repository within single and multi-frequency contexts. We verify its correlation with clinical SAR and temperature indexes, and compare it to HTPs obtained using a commonly accepted cost-function for SAR-based HTP (hot-spot to target quotient, HTQ). RESULTS AND DISCUSSION: The results show that low HCQ values produce better SAR (TC50, TC75) and temperature metrics (T50, T90) than HTQ in most patient models and frequency settings. For the deep-seated tumors, the correlation between the clinical indicators and 1/HCQ is more favorable than the correlation exhibited by 1/HTQ. CONCLUSION: The validation confirms the ability of HCQ to promote target coverage and hot-spot suppression in SAR-based HTP optimization, resulting in higher SAR and temperature indexes for deep-seated tumors

Antenna Arrangement in UWB Helmet Brain Applicators for Deep Microwave Hyperthermia

Deep microwave hyperthermia applicators are typically designed as narrow-band conformal antenna arrays with equally spaced elements, arranged in one or more rings. This solution, while adequate for most body regions, might be sub-optimal for brain treatments. The introduction of ultra-wide-band semi-spherical applicators, with elements arranged around the head and not necessarily aligned, has the potential to enhance the selective thermal dose delivery in this challenging anatomical region. However, the additional degrees of freedom in this design make the problem non-trivial. We address this by treating the antenna arrangement as a global SAR-based optimization process aiming at maximizing target coverage and hot-spot suppression in a given patient. To enable the quick evaluation of a certain arrangement, we propose a novel E-field interpolation technique which calculates the field generated by an antenna at any location around the scalp from a limited number of initial simulations. We evaluate the approximation error against full array simulations. We demonstrate the design technique in the optimization of a helmet applicator for the treatment of a medulloblastoma in a paediatric patient. The optimized applicator achieves 0.3\ua0 (Formula presented.) C higher T90 than a conventional ring applicator with the same number of elements

Self-calibration algorithms for microwave hyperthermia antenna arrays

In deep microwave hyperthermia (MW-HT), antenna arrays are used to generate an interference pattern which focuses energy in the tumor location. These arrays are subject to a number of disturbances which must be compensated for through calibration. This paper proposes and analyzes a pair of self-calibration algorithms, i.e. calibration procedures which rely only on S-matrix measurements of the N-port array applicator device, avoiding the need for external references and making real-time in-treatment calibration possible. Two algorithms are analyzed by means of simulations and experiments in terms of reliability and sensitivity to different kinds of disturbances. The results show that one of two implemented algorithms can converge to the same calibration values obtained when using an external calibration reference (monopole antenna)

Radiobiological evaluation of combined gamma knife radiosurgery and hyperthermia for pediatric neuro-oncology

Combining radiotherapy (RT) with hyperthermia (HT) has been proven effective in the treatment of a wide range of tumours, but the combination of externally delivered, focused heat and stereotactic radiosurgery has never been investigated. We explore the potential of such treatment enhancement via radiobiological modelling, specifically via the linear-quadratic (LQ) model adapted to thermoradiotherapy through modulating the radiosensitivity of temperature-dependent parame-ters. We extend this well-established model by incorporating oxygenation effects. To illustrate the methodology, we present a clinically relevant application in pediatric oncology, which is novel in two ways. First, it deals with medulloblastoma, the most common malignant brain tumour in children, a type of brain tumour not previously reported in the literature of thermoradiotherapy studies. Second, it makes use of the Gamma Knife for the radiotherapy part, thereby being the first of its kind in this context. Quantitative metrics like the biologically effective dose (BED) and the tumour control probability (TCP) are used to assess the efficacy of the combined plan

Prescription appropriateness of anti-diabetes drugs in elderly patients hospitalized in a clinical setting: evidence from the REPOSI Register

Diabetes is an increasing global health burden with the highest prevalence (24.0%) observed in elderly people. Older diabetic adults have a greater risk of hospitalization and several geriatric syndromes than older nondiabetic adults. For these conditions, special care is required in prescribing therapies including anti- diabetes drugs. Aim of this study was to evaluate the appropriateness and the adherence to safety recommendations in the prescriptions of glucose-lowering drugs in hospitalized elderly patients with diabetes. Data for this cross-sectional study were obtained from the REgistro POliterapie-Società Italiana Medicina Interna (REPOSI) that collected clinical information on patients aged ≥ 65 years acutely admitted to Italian internal medicine and geriatric non-intensive care units (ICU) from 2010 up to 2019. Prescription appropriateness was assessed according to the 2019 AGS Beers Criteria and anti-diabetes drug data sheets.Among 5349 patients, 1624 (30.3%) had diagnosis of type 2 diabetes. At admission, 37.7% of diabetic patients received treatment with metformin, 37.3% insulin therapy, 16.4% sulfonylureas, and 11.4% glinides. Surprisingly, only 3.1% of diabetic patients were treated with new classes of anti- diabetes drugs. According to prescription criteria, at admission 15.4% of patients treated with metformin and 2.6% with sulfonylureas received inappropriately these treatments. At discharge, the inappropriateness of metformin therapy decreased (10.2%, P < 0.0001). According to Beers criteria, the inappropriate prescriptions of sulfonylureas raised to 29% both at admission and at discharge. This study shows a poor adherence to current guidelines on diabetes management in hospitalized elderly people with a high prevalence of inappropriate use of sulfonylureas according to the Beers criteria

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population