Development of a smartphone virtual reality game to support the radiation therapy of children and adolescents in proton centers

IntroductionFor most patients, cancer therapy with radiation is a new experience coming with many unknown challenges. This can be stressful, particularly for children and adolescents. With the aim of reducing this stress and anxiety, a virtual-reality (VR) game, which can be used by patients prior to treatment, was developed and evaluated in a proton therapy center.MethodsThe specifications were derived from literature and from interviews with medical staff and patients. The gantry including the sound of its moving components and the sound of the interlock and safety system were identified as the main features relevant for preparation of a radiation course. Potential implementation difficulties were identified in a literature study and regarded in the design. Within the VR game, patients could interact with modeled equipment of the treatment room and hear the reportedly stress-inducing sounds in a stress-free environment prior to the treatment. The VR game was evaluated in a second series of interviews with patients.Results and DiscussionThis exploratory study demonstrated the specification, implementation and safe application of a VR game dedicated to young proton therapy patients. Initial anecdotal evidence suggested that the VR gaming experience was well received and found to be helpful when preparing young patients for radiation therapy

Protonentherapie mit "Spot-Scanning" bei Rhabdomyosarkomen im frühen Kindesalter: Erste Erfahrungen am PSI

Ziel:: Die Durchführbarkeit und Verträglichkeit der Spot-Scanning-Protonentherapie in tiefer Sedierung bei Kindern mit Rhabdomyosarkomen (RMS) sollten geprüft werden. Patienten und Methodik:: Seit 2004 werden junge Kinder am Paul Scherrer Institut (PSI), Villigen, Schweiz, auch in tiefer Sedierung mit Protonen bestrahlt. Ausgewertet wurden Kinder unter 5 Jahren mit RMS im Bereich des Kopfes und Körperstamms. Alle Kinder waren in eine Therapieoptimierungsstudie eingeschlossen und wurden prospektiv hinsichtlich der Verträglichkeit der Bestrahlung untersucht. Ergebnisse:: Neun Kinder im medianen Alter von 1,9 Jahren wurden untersucht (sechs embryonale RMS und je ein alveoläres, undifferenziertes und nicht klassifizierbares RMS). Die Lokalisationen waren parameningeal (n = 4), orbital (n = 3), Kopf-Hals-Bereich (n = 1) und Prostata (n = 1). Bei allen Kindern lag ein IRS-Stadium III vor. Die Bestrahlung erfolgte ausschließlich mit Protonen (Gesamtdosen 46-54 CGE [Cobalt-Gray-Äquivalent]). Akuttoxizitäten Grad 3 oder 4 nach RTOG/EORTC traten ausschließlich im Bereich des Knochenmarks auf. Schlussfolgerung:: Die Protonentherapie bei RMS im frühen Kindesalter war problemlos durchführbar und hervorragend verträglich. Prospektive, standardisierte Erhebungen von Spättoxizität und Lebensqualität sind essentiel

Characterization of pixelated silicon detectors for daily quality assurance measurements in proton therapy

The advanced imaging and delivery techniques in proton therapy allow conformal high-dose irradiation of the target volume with high accuracy using pencil beam scanning or beam shaping apertures. These irradiation methods increasingly include small radiation fields with large dose gradients, which require detector systems with high spatial resolution for quality assurance. In addition the measurement of all success parameters for daily quality assurance with only one proton field and one simple detector system would save a lot of time in clinical usage. Based on their good spatial resolution and high rate compatibility, pixelated silicon detectors could meet the new requirements. To assess their applicability in proton therapy, ATLAS pixelated silicon detectors are used to measure the lateral beam profile with high spatial resolution. Furthermore, a dose dependent detector calibration is presented to allow the measurement of the requested output constancy. A strategy to verify the proton energy during the daily quality assurance is under study. Promising results from proof-of-principle measurements at the West German Proton Therapy Centre in Essen, Germany, have been obtained.Comment: 5 pages, 6 figures, accepted for publication in the proceedings of TIPP 2021 to be published in Journal of Physics: Conference Serie

Novel Technique of Craniospinal Axis Proton Therapy with the Spot-Scanning System: Avoidance of Patching Multiple Fields and Optimized Ventral Dose Distribution

Background and Purpose:: Conventional craniospinal irradiation (CSI) is a complex procedure carrying a high risk of adverse side effects. Still, it is indispensable for cure in a number of pediatric brain tumors. In this study, the feasibility and the potential advantage of spot-scanning proton therapy for CSI are investigated. Material and Methods:: A boy (5.5 years of age) with a recurrent medulloblastoma received CSI with a single posterior field using the spot-scanning system at Paul Scherrer Institute. Dose distribution to the targets and the organs at risk, treatment time, reproducibility of patient positioning, toxicity (according to EORTC/RTOG score), and treatment outcome were evaluated. Results:: The plan achieved a homogeneous coverage of the target volume, even using a single field. The doses to the organs ventral to the target were minimized. During treatment, grade 1 skin reaction and grade 2 central nervous system toxicity were observed. After 2 months, the boy presented with a transitory fatigue. After 24 months, he is alive and free of disease. Growth hormones and thyroid hormones are reduced. Conclusion:: These results, based on a single patient, suggest that spot-scanning proton therapy for craniospinal treatment is feasible and safe. By applying a single dorsal field, difficulties of multiple-field patching can be avoided and the ventral dose spread can be minimize

Comparing biological effectiveness guided plan optimization strategies for cranial proton therapy: potential and challenges

Background: To introduce and compare multiple biological effectiveness guided (BG) proton plan optimization strategies minimizing variable relative biological effectiveness (RBE) induced dose burden in organs at risk (OAR) while maintaining plan quality with a constant RBE. Methods: Dose-optimized (DOSEopt) proton pencil beam scanning reference treatment plans were generated for ten cranial patients with prescription doses ≥ 54 Gy(RBE) and ≥ 1 OAR close to the clinical target volume (CTV). For each patient, four additional BG plans were created. BG objectives minimized either proton track-ends, dose-averaged linear energy transfer (LETd), energy depositions from high-LET protons or variable RBE-weighted dose (DRBE) in adjacent serially structured OARs. Plan quality (RBE = 1.1) was assessed by CTV dose coverage and robustness (2 mm setup, 3.5% density), dose homogeneity and conformity in the planning target volumes and adherence to OAR tolerance doses. LETd, DRBE (Wedenberg model, α/βCTV = 10 Gy, α/βOAR = 2 Gy) and resulting normal tissue complication probabilities (NTCPs) for blindness and brainstem necrosis were derived. Differences between DOSEopt and BG optimized plans were assessed and statistically tested (Wilcoxon signed rank, α = 0.05). Results: All plans were clinically acceptable. DOSEopt and BG optimized plans were comparable in target volume coverage, homogeneity and conformity. For recalculated DRBE in all patients, all BG plans significantly reduced near-maximum DRBE to critical OARs with differences up to 8.2 Gy(RBE) (p < 0.05). Direct DRBE optimization primarily reduced absorbed dose in OARs (average ΔDmean = 2.0 Gy; average ΔLETd,mean = 0.1 keV/µm), while the other strategies reduced LETd (average ΔDmean < 0.3 Gy; average ΔLETd,mean = 0.5 keV/µm). LET-optimizing strategies were more robust against range and setup uncertaintes for high-dose CTVs than DRBE optimization. All BG strategies reduced NTCP for brainstem necrosis and blindness on average by 47% with average and maximum reductions of 5.4 and 18.4 percentage points, respectively. Conclusions: All BG strategies reduced variable RBE-induced NTCPs to OARs. Reducing LETd in high-dose voxels may be favourable due to its adherence to current dose reporting and maintenance of clinical plan quality and the availability of reported LETd and dose levels from clinical toxicity reports after cranial proton therapy. These optimization strategies beyond dose may be a first step towards safely translating variable RBE optimization in the clinics

Study protocol of the German "Registry for the Detection of Late Sequelae after Radiotherapy in Childhood and Adolescence" (RiSK)

<p>Abstract</p> <p>Background</p> <p>Late effects after radiotherapy in childhood and adolescence have mainly been characterized retrospectively with small patient numbers. However, these analyses are limited due to little information regarding organ dose levels in many cases. To overcome this limitation, the German Group of Paediatric Radiation Oncology (APRO) established the „Registry for the evaluation of late side effects after radiation in childhood and adolescence” (RiSK). The study protocol and the documentation forms are given in this publication.</p> <p>Methods/Design</p> <p>Radiation parameters including detailed organ doses as well as toxicity evaluations are collected prospectively from centres all over Germany. Standardized documentation forms are used. These forms are given in an English and German version as additional files to this publication. Documentation is planned for all children who receive radiotherapy in one of the therapy trials of the "German Society of Paediatric Oncology and Haematology (GPOH)". The study started in a pilot phase in June 2001 in few centres. Since 2004 documentation has been performed all over Germany and is still on-going.</p> <p>Discussion</p> <p>To our knowledge, "RiSK" is the only multi-centre study that evaluates radiation associated side effects prospectively with detailed information about organ dose levels. With ongoing recruitment and prolongation of follow-up powerful data will be obtained in a few years. A broad use and international cooperation are welcome.</p

Comprehensive investigation of lateral dose profile and output factor measurements in small proton fields from different delivery techniques

Background and purpose: As a part of the commissioning and quality assurance in proton beam therapy, lateral dose profiles and output factors have to be acquired. Such measurements can be performed with point detectors and are especially challenging in small fields or steep lateral penumbra regions as the detector's volume effect may lead to perturbations. To address this issue, this work aims to quantify and correct for such perturbations of six point detectors in small proton fields created via three different delivery techniques. Methods: Lateral dose profile and output measurements of three proton beam delivery techniques (pencil beam scanning, pencil beam scanning combined with collimators, passive scattering with collimators) were performed using high-resolution EBT3 films, a PinPoint 3D 31022 ionization chamber, a microSilicon diode 60023 and a microDiamond detector 60019 (all PTW Freiburg, Germany). Detector specific lateral dose response functions K(x,y) acting as the convolution kernel transforming the undisturbed dose distribution D(x,y) into the measured signal profiles M(x,y) were applied to quantify perturbations of the six investigated detectors in the proton fields and correct the measurements. A signal theoretical analysis in Fourier space of the dose distributions and detector's K(x,y) was performed to aid the understanding of the measurement process with regard to the combination of detector choice and delivery technique. Results: Quantification of the lateral penumbra broadening and signal reduction at the fields center revealed that measurements in the pencil beam scanning fields are only compromised slightly even by large volume ionization chambers with maximum differences in the lateral penumbra of 0.25 mm and 4% signal reduction at the field center. In contrast, radiation techniques with collimation are not accurately represented by the investigated detectors as indicated by a penumbra broadening up to 1.6 mm for passive scattering with collimators and 2.2 mm for pencil beam scanning with collimators. For a 3 mm diameter collimator field, a signal reduction at field center between 7.6% and 60.7% was asserted. Lateral dose profile measurements have been corrected via deconvolution with the corresponding K(x,y) to obtain the undisturbed D(x,y). Corrected output ratios of the passively scattered collimated fields obtained for the microDiamond, microSilicon and PinPoint 3D show agreement better than 0.9% (one standard deviation) for the smallest field size of 3 mm. Conclusion: Point detector perturbations in small proton fields created with three delivery techniques were quantified and found to be especially pronounced for collimated small proton fields with steep dose gradients. Among all investigated detectors, the microSilicon diode showed the smallest perturbations. The correction strategies based on detector's K(x,y) were found suitable for obtaining unperturbed lateral dose profiles and output factors. Approximation of K(x,y) by considering only the geometrical averaging effect has been shown to provide reasonable prediction of the detector's volume effect. The findings of this work may be used to guide the choice of point detectors in various proton fields and to contribute toward the development of a code of practice for small field proton dosimetry.</p

Complete patient exposure during paediatric brain cancer treatment for photon and proton therapy techniques including imaging procedures

BackgroundIn radiotherapy, especially when treating children, minimising exposure of healthy tissue can prevent the development of adverse outcomes, including second cancers. In this study we propose a validated Monte Carlo framework to evaluate the complete patient exposure during paediatric brain cancer treatment.Materials and methodsOrgan doses were calculated for treatment of a diffuse midline glioma (50.4 Gy with 1.8 Gy per fraction) on a 5-year-old anthropomorphic phantom with 3D-conformal radiotherapy, intensity modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT) and intensity modulated pencil beam scanning (PBS) proton therapy. Doses from computed tomography (CT) for planning and on-board imaging for positioning (kV-cone beam CT and X-ray imaging) accounted for the estimate of the exposure of the patient including imaging therapeutic dose. For dose calculations we used validated Monte Carlo-based tools (PRIMO, TOPAS, PENELOPE), while lifetime attributable risk (LAR) was estimated from dose-response relationships for cancer induction, proposed by Schneider et al.ResultsOut-of-field organ dose equivalent data of proton therapy are lower, with doses between 0.6 mSv (testes) and 120 mSv (thyroid), when compared to photon therapy revealing the highest out-of-field doses for IMRT ranging between 43 mSv (testes) and 575 mSv (thyroid). Dose delivered by CT ranged between 0.01 mSv (testes) and 72 mSv (scapula) while a single imaging positioning ranged between 2 μSv (testes) and 1.3 mSv (thyroid) for CBCT and 0.03 μSv (testes) and 48 μSv (scapula) for X-ray. Adding imaging dose from CT and daily CBCT to the therapeutic demonstrated an important contribution of imaging to the overall radiation burden in the course of treatment, which is subsequently used to predict the LAR, for selected organs.ConclusionThe complete patient exposure during paediatric brain cancer treatment was estimated by combining the results from different Monte Carlo-based dosimetry tools, showing that proton therapy allows significant reduction of the out-of-field doses and secondary cancer risk in selected organs

Quality-of-life evaluations in children and adolescents with Ewing sarcoma treated with pencil-beam-scanning proton therapy.

BACKGROUND With improved survival rates for children with cancer, quality-of-life (QoL) issues have increasingly become the focus of attention. We report the QoL of children with Ewing sarcoma (EWS) treated with pencil-beam-scanning proton therapy (PT). METHODS A PEDQOL (QoL questionnaire for children 4-18 years) self/proxy questionnaire was used to prospectively assess the QoL of 23 children <18 years with EWS treated with PT. This questionnaire evaluates eight different domains. Children (self-rating) and parents (proxy-rating) filled out the questionnaire at the start of PT (E1), 2 months after treatment (E2), and thereafter once yearly (E≥3). RESULTS Compared with healthy controls, parents rated the QoL of their children at E1 significantly worse in all but two (cognition and social functioning-family) domains. At E4, significant differences between the two groups only remained in three of eight domains. At E1, children self-rated their QoL significantly worse in the domain Physical functioning (p = .004) and significantly better in the domain Body image (p = .044) compared to healthy controls, whereas no significant differences were observed at E4. For the longitudinal comparison E1 versus E4, according to parents, Emotional functioning, Cognition and Social functioning-peers were slightly decreased 2 years after PT. The children rated Emotional functioning and Body image poorly 2 years after PT. CONCLUSIONS Children with EWS usually recovered seemingly well to normal QoL levels 2 years after the end of PT. They tended to rate their QoL substantially higher than their parents. However, in the longitudinal analysis at 2 years, children rated their Emotional functioning and Body image scores poorly