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Background and Purpose: Dose-escalation in rectal cancer (RCa) may result in an increased complete response rate and thereby enable omission of surgery and organ preservation. In order to implement dose-escalation, it is crucial to develop a technique that allows for accurate image-guided radiotherapy. The aim of the current study was to determine the performance of a novel liquid fiducial marker (BioXmark®) in RCa patients during the radiotherapy course by assessing its positional stability on daily cone-beam CT (CBCT), technical feasibility, visibility on different imaging modalities and safety., Materials and Methods: Prospective, non-randomized, single-arm feasibility trial with inclusion of twenty patients referred for neoadjuvant chemoradiotherapy for locally advanced RCa. Primary study endpoint was positional stability on CBCT. Furthermore, technical aspects, safety and clinical performance of the marker, such as visibility on different imaging modalities, were evaluated., Results: Seventy-four markers from twenty patients were available for analysis. The marker was stable in 96% of the cases. One marker showed clinically relevant migration, one marker was lost before start of treatment and one marker was lost during treatment. Marker visibility was good on computed tomography (CT) and CBCT, and moderate on electronic portal imaging ( EPI ). Marker visibility on magnetic resonance imaging (MRI) was poor during response evaluation., Conclusion: The novel liquid fiducial marker demonstrated positional stability. We provide evidence of the feasibility of the novel fiducial marker for image-guided radiotherapy on daily cone beam CT for RCa patients., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Authors Berbée, Verhaegen and Van Limbergen hold a patent for a rectal brachytherapy applicator: “Endorectal probe device for effecting radiation treatment of colorectal cancerous tissue in the rectum of a human or animal subject.”, filed December 2016, F. Verhaegen, M. Bellezzo, E. van Limbergen, M. Berbée, B. Reniers, G. Fonseca, EP16204735. The patent has been licensed to Varian Medical Systems, Inc. The conduction of the trial was funded by Nanovi and the BioXmark® fiducials were provided without costs. Nanovi was not involved in the study design, collection, analysis and interpretation of data, writing of the manuscript or the decision to submit the manuscript for publication., (© 2022 MAASTRO.)

Background/purpose: Electronic portal imaging device (EPID) dosimetry aims to detect treatment errors, potentially leading to treatment adaptation. Clinically used threshold classification methods for detecting errors lead to loss of information (from multi-dimensional EPID data to a few numbers) and cannot be used for identifying causes of errors. Advanced classification methods, such as deep learning, can use all available information. In this study, convolutional neural networks (CNNs) were trained to detect and identify error type and magnitude of simulated treatment errors in lung cancer patients. The purpose of this simulation study is to provide a proof-of-concept of CNNs for error identification using EPID dosimetry in an in vivo scenario., Materials and Methods: Clinically realistic ranges of anatomical changes, positioning errors and mechanical errors were simulated for lung cancer patients. Predicted portal dose images (PDIs) containing errors were compared to error-free PDIs using the widely used gamma analysis. CNNs were trained to classify errors using 2D gamma maps. Three classification levels were assessed: Level 1 (main error type, e.g., anatomical change), Level 2 (error subtype, e.g., tumor regression) and Level 3 (error magnitude, e.g., >50% tumor regression)., Results: CNNs showed good performance for all classification levels (training/test accuracy 99.5%/96.1%, 92.5%/86.8%, 82.0%/72.9%). For Level 3, overfitting became more apparent., Conclusion: This simulation study indicates that deep learning is a promising powerful tool for identifying types and magnitude of treatment errors with EPID dosimetry, providing additional information not currently available from EPID dosimetry. This is a first step towards rapid, automated models for identification of treatment errors using EPID dosimetry., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: To investigate the feasibility of in vivo dosimetry using microMOSFET dosimeters in patients treated with brachytherapy using two types of gynecological applicators., Methods and Materials: In this study, a microMOSFET was placed in an empty needle of an Utrecht Interstitial Fletcher applicator or MUPIT (Martinez Universal Perineal Interstitial Template) applicator for independent verification of treatment delivery. Measurements were performed in 10 patients, with one to three microMOSFETs per applicator and repeated for one to four fractions, resulting in 50 in vivo measurements. Phantom measurements were used to determine characteristics of the microMOSFETs., Results: Phantom measurements showed a linear relationship between dose and microMOSFET threshold voltage, and a calibration coefficient (mV/cGy) was determined. Reproducibility of repeated 50 cGy irradiations was 2% (1 standard deviation). Distance and angle dependencies were measured and correction factors were determined. Subsequently, three microMOSFETs were placed in a phantom to measure a validation plan. The difference between predicted and measured dose was less than the measurement uncertainty (±9%, 2 standard deviations). In vivo measurements were corrected for distance and angle dependencies. Differences between predicted and measured dose in the patients were smaller than the measurement uncertainty for the majority of the measurements., Conclusions: In vivo dosimetry using microMOSFETs in MUPIT and Utrecht Interstitial Fletcher applicators has proved to be feasible. Reimaging should be performed after detection of differences larger than 10% between predicted and measured dose to verify the applicator configuration. Movement of the applicator relative to the target or organs at risk is undetectable with this method., (Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

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.

Background and Purpose: In Rotterdam, patient-specific hyperthermia (HT) treatment planning (HTP) is applied for all deep head and neck (H&N) HT treatments. In this paper we introduce VEDO (the Visualisation Tool for Electromagnetic Dosimetry and Optimisation), the software tool required, and demonstrate its value for HTP-guided online complaint-adaptive (CA) steering based on specific absorption rate (SAR) optimisation during a H&N HT treatment., Materials and Methods: VEDO integrates CA steering, visualisation of the SAR patterns and mean tumour SAR (SAR(target)) optimisation in a single screen. The pre-calculated electromagnetic fields are loaded into VEDO. During treatment, VEDO shows the SAR pattern, overlaid on the patients' CT-scan, corresponding to the actually applied power settings and it can (re-)optimise the SAR pattern to minimise SAR at regions where the patient senses discomfort while maintaining a high SAR(target)., Results: The potential of the quantitative SAR steering approach using VEDO is demonstrated by analysis of the first treatment in which VEDO was used for two patients using the HYPERcollar. These cases show that VEDO allows response to power-related complaints of the patient and to quantify the change in absolute SAR: increasing either SAR(target) from 96 to 178 W/kg (case 1); or show that the first SAR distribution was already optimum (case 2)., Conclusion: This analysis shows that VEDO facilitates a quantitative treatment strategy allowing standardised application of HT by technicians of different HT centres, which will potentially lead to improved treatment quality and the possibility of tracking the effectiveness of different treatment strategies.

Adding hyperthermia to standard radiotherapy (RT+HT) improves treatment outcome for patients with locally advanced cervical cancer (LACC). We investigated the effect of hyperthermia dose on treatment outcome for patients with LACC treated with RT+HT. We collected treatment and outcome data of 420 patients with LACC treated with hyperthermia at our institute from 1990 to 2005. Univariate and multivariate analyses were performed on response rate, local control, disease-specific survival and toxicity for these patients to search for a thermal dose response relationship. Besides commonly identified prognostic factors in LACC like tumour stage, performance status, radiotherapy dose and tumour size, thermal parameters involving both temperature and duration of heating emerged as significant predictors of the various end-points. The more commonly used CEM43T90 (cumulative equivalent minutes of T90 above 43 degrees C) was less influential than TRISE (based on the average T50 increase and the duration of heating, normalised to the scheduled duration of treatment). CEM43T90 and TRISE measured intraluminally correlate significantly and independently with tumour control and survival. These findings stimulate further technological development and improvement of deep hyperthermia, as they strongly suggest that it might be worthwhile to increase the thermal dose for LACC, either by treatment optimisation or by prolonging the treatment time. These results also confirm the beneficial effects from hyperthermia as demonstrated in our earlier randomised trial, and justify applying radiotherapy and hyperthermia as treatment of choice for patients with advanced cervical cancer.

Purpose: To report response rate, pelvic tumor control, survival, and late toxicity after treatment with combined radiotherapy and hyperthermia (RHT) for patients with locally advanced cervical carcinoma (LACC) and compare the results with other published series., Methods and Materials: From 1996 to 2005, a total of 378 patients with LACC (International Federation of Gynecology and Obstetrics Stage IB2-IVA) were treated with RHT. External beam radiotherapy (RT) was applied to 46-50.4 Gy and combined with brachytherapy. The hyperthermia (HT) was prescribed once weekly. Primary end points were complete response (CR) and local control. Secondary end points were overall survival, disease-specific survival, and late toxicity. Patient, tumor, and treatment characteristics predictive for the end points were identified in univariate and multivariate analyses., Results: Overall, a CR was achieved in 77% of patients. At 5 years, local control, disease-specific survival, and incidence of late toxicity Common Terminology Criteria for Adverse Events Grade 3 or higher were 53%, 47%, and 12%, respectively. In multivariate analysis, number of HT treatments emerged as a predictor of outcome in addition to commonly identified prognostic factors., Conclusions: The CR, local control, and survival rates are similar to previously observed results of RHT in the randomized Dutch Deep Hyperthermia Trial. Reported treatment results for currently applied combined treatment modalities (i.e., RT with chemotherapy and/or HT) do not permit definite conclusions about which combination is superior. The present results confirm previously shown beneficial effects from adding HT to RT and justify the application of RHT as first-line treatment in patients with LACC as an alternative to chemoradiation.