Search

Purpose: The development of online-adaptive proton therapy (PT) is essential to overcome limitations encountered by day-to-day variations of the patient's anatomy. Range verification could play an essential role in an online feedback loop for the detection of treatment deviations such as anatomical changes. Here, we present the results of the first systematic patient study regarding the detectability of anatomical changes by a prompt-gamma imaging (PGI) slit-camera system., Methods and Materials: For 15 patients with prostate cancer, PGI measurements were performed during 105 fractions (201 fields) with in-room control computed tomography (CT)acquisitions. Field-wise doses on control CT scans were manually classified as whether showing relevant or non-relevant anatomical changes. This manual classification of the treatment fields was then used to establish an automatic field-wise ground truth based on spot-wise dosimetric range shifts, which were retrieved from integrated depth-dose (IDD) profiles. To determine the detection capability of anatomical changes with PGI, spot-wise PGI-based range shifts were initially compared with corresponding dosimetric IDD range shifts. As final endpoint, the agreement of a developed field-wise PGI classification model with the field-wise ground truth was determined. Therefore, the PGI model was optimized and tested for a subcohort of 131 and 70 treatment fields, respectively., Results: The correlation between PGI and IDD range shifts was high, ρ pearson  = 0.67 (p < 0.01). Field-wise binary PGI classification resulted in an area under the curve of 0.72 and 0.80 for training and test cohorts, respectively. The model detected relevant anatomical changes in the independent test cohort, with a sensitivity and specificity of 74% and 79%, respectively., Conclusions: For the first time, evidence of the detection capability of anatomical changes in prostate-cancer PT from clinically acquired PGI data is shown. This emphasizes the benefit of PGI-based range verification and demonstrates its potential for online-adaptive PT., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Current risk-stratification systems for prostate cancer (PCa) do not sufficiently reflect the disease heterogeneity. Genomic classifiers (GC) enable improved risk stratification after surgery, but less data exist for patients treated with definitive radiation therapy (RT) or RT in oligo-/metastatic disease stages. To guide future perspectives of GCs for RT, we conducted (1) a systematic review on the evidence of GCs for patients treated with RT and (2) a survey of experts using the Delphi method, addressing the role of GCs in personalized treatments to identify relevant fields of future clinical and translational research. We performed a systematic review and screened ongoing clinical trials on ClinicalTrials.gov. Based on these results, a multidisciplinary international team of experts received an adapted Delphi method survey. Thirty-one and 30 experts answered round 1 and round 2, respectively. Questions with ≥75% agreement were considered relevant and included in the qualitative synthesis. Evidence for GCs as predictive biomarkers is mainly available to the postoperative RT setting. Validation of GCs as prognostic markers in the definitive RT setting is emerging. Experts used GCs in patients with PCa with extensive metastases (30%), in postoperative settings (27%), and in newly diagnosed PCa (23%). Forty-seven percent of experts do not currently use GCs in clinical practice. Expert consensus demonstrates that GCs are promising tools to improve risk-stratification in primary and oligo-/metastatic patients in addition to existing classifications. Experts were convinced that GCs might guide treatment decisions in terms of RT-field definition and intensification/deintensification in various disease stages. This work confirms the value of GCs and the promising evidence of GC utility in the setting of RT. Additional studies of GCs as prognostic biomarkers are anticipated and form the basis for future studies addressing predictive capabilities of GCs to optimize RT and systemic therapy. The expert consensus points out future directions for GC research in the management of PCa., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the results of the radiation therapy (RT) quality assurance (QA) program of the phase 3 randomized SAKK 09/10 trial in patients with biochemically recurrent prostate cancer after prostatectomy., Methods and Materials: Within the Schweizerische Arbeitsgemeinschaft für Klinische Krebsforschung (SAKK) 09/10 trial testing 64-Gy versus 70-Gy salvage RT, a central collection of treatment plans was performed and thoroughly reviewed by a dedicated medical physicist and radiation oncologist. Adherence to the treatment protocol and specifically to the European Organization for the Research and Treatment of Cancer (EORTC) guidelines for target volume definition (classified as deviation observed yes vs no) and its potential correlation with acute and late toxicity (Common Terminology Criteria for Adverse Events version 4.0) and freedom from biochemical progression (FFBP) were investigated., Results: The treatment plans for 344 patients treated between February 2011 and April 2014 depicted important deviations from the EORTC guidelines and the recommendations per trial protocol. For example, in up to half of the cases, the delineated structures deviated from the protocol (eg, prostate bed in 48.8%, rectal wall [RW] in 41%). In addition, variations in clinical target volume (CTV) and planning target volume (PTV) occurred frequently (eg, CTV and PTV deviations in up to 42.4% and 25.9%, respectively). The detected deviations showed a significant association with a lower risk of grade ≥2 gastrointestinal acute toxicity when the CTV did not overlap the RW versus when the CTV overlapped the RW (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.22-0.85; P = .014), and a higher rate of grade ≥2 late genitourinary (GU) toxicity when the CTV overlapped the RW (OR, 2.58; 95% CI, 1.17-5.72; P = .019). A marginally significant lower risk of grade ≥2 late GU toxicity was observed when the prostate bed did not overlap versus did overlap the RW (OR, 0.51; 95% CI, 0.25-1.03; P = .06). In addition, a marginally significant decrease in FFBP was observed in patients with PTV not including surgical clips as potential markers of the limits of the prostate bed (hazard ratio, 1.44; 95% CI, 0.96-2.17; P = .07)., Conclusions: Despite a thorough QA program, the central review of a phase 3 trial showed limited adherence to treatment protocol recommendations, which was associated with a higher risk of toxicity by means of acute or late gastrointestinal or GU toxicity and showed a trend toward worse FFBP. Data from this QA review might help to refine future QA programs and prostate bed delineation guidelines., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Uncertainty in computed tomography (CT)-based range prediction substantially impairs the accuracy of proton therapy. Direct determination of the stopping-power ratio (SPR) from dual-energy CT (DECT) has been proposed (DirectSPR), and initial validation studies in phantoms and biological tissues have proven a high accuracy. However, a thorough validation of range prediction in patients has not yet been achieved by any means. Here, we present the first systematic validation of CT-based proton range prediction in patients using prompt gamma imaging (PGI)., Methods and Materials: A PGI slit camera system with improved positioning accuracy, using a floor-based docking station, was used. Its overall uncertainty for range prediction validation was determined experimentally with both x-ray and beam measurements. The accuracy of range prediction in patients was determined from clinical PGI measurements during hypofractionated treatment of 5 patients with prostate cancer - in total 30 fractions with in-room control-CTs. For each pencil-beam-scanning spot, the range shift was obtained by comparing the PGI measurement to a control-CT-based PGI simulation. Three different SPR prediction approaches were applied in simulations: a standard CT-number-to-SPR conversion (Hounsfield look-up table [HLUT]), an adapted HLUT (DECT optimized), and DirectSPR. The spot-wise weighted mean range shift from all spots served as a measure for the accuracy of the respective range prediction approach., Results: A mean range prediction accuracy of 0.0% ± 0.5%, 0.3% ± 0.4%, and 1.8% ± 0.4% was obtained for DirectSPR, adapted HLUT, and standard HLUT, respectively. The overall validation uncertainty of the second-generation PGI slit camera is about 1 mm (2σ) for all approaches, which is smaller than the range prediction uncertainty for deep-seated tumors., Conclusions: For the first time, range prediction accuracy was assessed in clinical routine using PGI range verification in prostate cancer treatments. Both DECT-derived range prediction approaches agree well with the measured proton range from PGI verification, whereas the standard HLUT approach differs relevantly. These results endorse the recent reduction of clinical safety margins in DirectSPR-based treatment planning in our institution., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Different international target volume delineation guidelines exist and different treatment techniques are available for salvage radiation therapy (RT) for recurrent prostate cancer, but less is known regarding their respective applicability in clinical practice., Methods and Materials: A randomized phase III trial testing 64 Gy vs 70 Gy salvage RT was accompanied by an intense quality assurance program including a site-specific and study-specific questionnaire and a dummy run (DR). Target volume delineation was performed according to the European Organisation for the Research and Treatment of Cancer guidelines, and a DR-based treatment plan was established for 70 Gy. Major and minor protocol deviations were noted, interobserver agreement of delineated target contours was assessed, and dose-volume histogram (DVH) parameters of different treatment techniques were compared., Results: Thirty European centers participated, 43% of which were using 3-dimensional conformal RT (3D-CRT), with the remaining centers using intensity modulated RT (IMRT) or volumetric modulated arc technique (VMAT). The first submitted version of the DR contained major deviations in 21 of 30 (70%) centers, mostly caused by inappropriately defined or lack of prostate bed (PB). All but 5 centers completed the DR successfully with their second submitted version. The interobserver agreement of the PB was moderate and was improved by the DR review, as indicated by an increased κ value (0.59 vs 0.55), mean sensitivity (0.64 vs 0.58), volume of total agreement (3.9 vs 3.3 cm(3)), and decrease in the union volume (79.3 vs 84.2 cm(3)). Rectal and bladder wall DVH parameters of IMRT and VMAT vs 3D-CRT plans were not significantly different., Conclusions: The interobserver agreement of PB delineation was moderate but was improved by the DR. Major deviations could be identified for the majority of centers. The DR has improved the acquaintance of the participating centers with the trial protocol., (Copyright © 2013 Elsevier Inc. All rights reserved.)