Maarten Paulides

Simulation techniques in hyperthermia treatment planning

Abstract Clinical trials have shown that hyperthermia (HT), i.e. an increase of tissue temperature to 39–44 °C, significantly enhance radiotherapy and chemotherapy effectiveness [1]. Driven by the developments in computational techniques and computing power, personalised hyperthermia treatment planning (HTP) has matured and has become a powerful tool for optimising treatment quality. Electromagnetic, ultrasound, and thermal simulations using realistic clinical set-ups are now being performed to achieve patient-specific treatment optimisation. In addition, extensive studies aimed to properly implement novel HT tools and techniques, and to assess the quality of HT, are becoming more common. In this paper, we review the simulation tools and techniques developed for clinical hyperthermia, and evaluate their current status on the path from ‘model’ to ‘clinic’. In addition, we illustrate the major techniques employed for validation and optimisation. HTP has become an essential tool for improvement, control, and assessment of HT treatment quality. As such, it plays a pivotal role in the quest to establish HT as an efficacious addition to multi-modality treatment of cancer.

Local hyperthermia combined with radiotherapy and-/or chemotherapy: Recent advances and promises for the future

Hyperthermia, one of the oldest forms of cancer treatment involves selective heating of tumor tissues to temperatures ranging between 39 and 45°C. Recent developments based on the thermoradiobiological rationale of hyperthermia indicate it to be a potent radio- and chemosensitizer. This has been further corroborated through positive clinical outcomes in various tumor sites using thermoradiotherapy or thermoradiochemotherapy approaches. Moreover, being devoid of any additional significant toxicity, hyperthermia has been safely used with low or moderate doses of reirradiation for retreatment of previously treated and recurrent tumors, resulting in significant tumor regression. Recent in vitro and in vivo studies also indicate a unique immunomodulating prospect of hyperthermia, especially when combined with radiotherapy. In addition, the technological advances over the last decade both in hardware and software have led to potent and even safer loco-regional hyperthermia treatment delivery, thermal treatment planning, thermal dose monitoring through noninvasive thermometry and online adaptive temperature modulation. The review summarizes the outcomes from various clinical studies (both randomized and nonrandomized) where hyperthermia is used as a thermal sensitizer of radiotherapy and-/or chemotherapy in various solid tumors and presents an overview of the progresses in loco-regional hyperthermia. These recent developments, supported by positive clinical outcomes should merit hyperthermia to be incorporated in the therapeutic armamentarium as a safe and an effective addendum to the existing oncological treatment modalities.

Benefit of replacing the Sigma-60 by the Sigma-Eye applicator. A Monte Carlo-based uncertainty analysis.

Background and purposeTo investigate the clinical benefit of replacing the BSD-2000 Sigma-60 with the Sigma-Eye applicator, taking into account effects of uncertainties in tissue and water bolus parameters.Patients and methodsFor 20 patients, specific absorption rate (SAR) and temperature distributions were calculated and optimized, based on computed tomography (CT) scans in treatment position. The impact of uncertainties on predicted distributions was studied using a Monte Carlo uncertainty assessment.ResultsReplacing the Sigma-60 by the Sigma-Eye applicator resulted in a higher SAR in the tumor [on average a decrease of the hotspot tumor quotient (HTQ) by 24%; p < 0.001], and higher temperatures (T90: +0.4°C, p < 0.001; T50: +0.6°C, p < 0.001) using literature values and SAR optimization. When temperature optimization (T90) was used, a larger average increase was found (T90: +0.7°C, p < 0.001; T50: +0.8°C, p < 0.001). When taking into account uncertainties, a decrease of 23% in median HTQ (p < 0.001) and an increase in T50 and T90 of 0.4°C (p < 0.001) could be demonstrated.ConclusionBased on this uncertainty analysis, significant and clinically relevant improvements in HTQ and tumor temperature were achieved when replacing the Sigma-60 by the Sigma-Eye applicator.ZusammenfassungZielUntersuchung des Ersatzes des Sigma-60-Applikators des BSD-2000-Hyperthermiesystems durch den Sigma-Eye-Applikator, unter Berücksichtigung der Auswirkungen der Unsicherheiten in den Gewebeparametern.MethodeModelle von 20 Patienten wurden aus den CT-Scans in Behandlungsposition erstellt und für die Berechnung und Optimierung von spezifischen Absorptionsraten(SAR)- und Temperaturverteilungen verwendet. Die klinische Relevanz von Unsicherheiten wurde mithilfe der Monte-Carlo-Methode ausgiebig untersucht.ErgebnisseDer Ersatz des Sigma-60 durch den Sigma-Eye führt zu erhöhten SAR-Werten im Tumor [durchschnittliche Verbesserung der HTQ um 24% (p < 0,001)] und zu erhöhten Temperaturen (T90: +0,4°C, p < 0,001; T50: +0,6°C, p < 0,001). Durch Verwendung der Temperaturoptimierung (T90) wird eine größere Zunahme festgestellt (T90: + 0,7°C, p < 0,001; T50: + 0,8°C, p < 0,001). Wenn die Unsicherheiten berücksichtigt werden, ergibt sich eine Verbesserung der mittleren HTQ um 23% (p < 0,001) und eine Erhöhung der mittleren T50 und T90 um 0,4°C (p < 0,001).SchlussfolgerungAuf Basis einer Unsicherheitsanalyse ergibt sich eine signifikante und klinisch relevante Verbesserung der Tumor-SAR und der Tumortemperatur, wenn der Sigma-60- durch den Sigma-Eye-Applikator ersetzt wird.

Hyperthermia by electromagnetic fields to enhanced clinical results in oncology

Confining treatment to the tumor to improve therapeutic outcome and reduce toxicity, is a hot issue in cancer research. Hyperthermia is recognized as a strong sensitizer for radiotherapy and chemotherapy enhancing tumor control without increasing toxicity. Todays electromagnetic hyperthermia systems heat large tissue volumes with limited ability to selectively heat the tumor. Fortunately, tremendous improvements in 3-dimensional electromagnetic & temperature modelling provide an exciting opportunity to design advanced multi-element electromagnetic applicator systems. Together with feedback control using MR non-invasive thermometry and smart E-field sensors, this paves the way for selective tumor heating and potentially prescription of a thermal dose. A technological advanced hyperthermia system, with guaranteed delivery of high quality hyperthermia lowers the threshold for newcomers to apply hyperthermia. Combined with recent proof that hyperthermia blocks DNA repair and new, exciting, ways for controlled drug delivery using temperature sensitive liposome encapsulated drugs, this is expected to increase interest of the medical community in hyperthermia.Confining treatment to the tumor to improve therapeutic outcome and reduce toxicity, is a hot issue in cancer research. Hyperthermia is recognized as a strong sensitizer for radiotherapy and chemotherapy enhancing tumor control without increasing toxicity. Todays electromagnetic hyperthermia systems heat large tissue volumes with limited ability to selectively heat the tumor. Fortunately, tremendous improvements in 3-dimensional electromagnetic & temperature modelling provide an exciting opportunity to design advanced multi-element electromagnetic applicator systems. Together with feedback control using MR non-invasive thermometry and smart E-field sensors, this paves the way for selective tumor heating and potentially prescription of a thermal dose. A technological advanced hyperthermia system, with guaranteed delivery of high quality hyperthermia lowers the threshold for newcomers to apply hyperthermia. Combined with recent proof that hyperthermia blocks DNA repair and new, exciting, ways for controlled drug delivery using temperature sensitive liposome encapsulated drugs, this is expected to increase interest of the medical community in hyperthermia.