Children's Oncology Group's 2023 blueprint for research: Radiation oncology.

Radiation oncology is an integral part of the multidisciplinary team caring for children with cancer. The primary goal of our committee is to enable the delivery of the safest dose of radiation therapy (RT) with the maximal potential for cure, and to minimize toxicity in children by delivering lower doses to normal tissues using advanced technologies like intensity-modulated RT (IMRT) and proton therapy. We provide mentorship for y ators and are actively involved in educating the global radiation oncology community. We are leaders in the effort to discover novel radiosensitizers, radioprotectors, and advanced RT technologies that could help improve outcomes of children with cancer.

Development of a log file analysis tool for proton patient QA, system performance tracking, and delivered dose reconstruction.

PURPOSE/OBJECTIVE(S): To describe a log file-based patient-specific quality assurance (QA) method and develop an in-house tool for system performance tracking and dose reconstruction in pencil-beam scanning proton therapy that can be used for pre-treatment plan review. MATERIALS/METHODS: The software extracts beam-specific information from the treatment delivery log file and automatically compares the monitor units (MU), lateral position, and size of each spot against the intended values in the treatment plan to identify any discrepancies in the beam delivery. The software has been used to analyze 992 patients, 2004 plans, 4865 fields, and more than 32 million proton spots from 2016 to 2021. The composite doses of 10 craniospinal irradiation (CSI) plans were reconstructed based on the delivered spots and compared with the original plans as an offline plan review method. RESULTS: Over the course of 6 years, the proton delivery system has proved stable in delivering patient QA fields with proton energies of 69.4-221.3 MeV and an MU range of 0.003-1.473 MU per spot. The planned mean and standard deviation (SD) of the energy and spot MU were 114.4 ± 26.4 MeV and 0.010 ± 0.009 MU, respectively. The mean and SD of the differences in MU and position between the delivered and planned spots were 9.56 × 10-8 ± 2.0 × 10-4 MU and 0.029/-0.007 ± 0.049/0.044 mm on the X/Y-axis for random differences and 0.005/0.125 ± 0.189/0.175 mm on the X/Y-axis for systematic differences. The mean and SD of the difference between the commissioning and delivered spot sizes were 0.086/0.089 ± 0.131/0.166 mm on the X/Y-axis. CONCLUSION: A tool has been developed to extract crucial information about the performance of the proton delivery and monitor system and provide a dose reconstruction based on delivered spots for quality improvement. Each patient's plan was verified before treatment to ensure accurate and safe delivery within the delivery tolerance of the machine.

Treatment-planning approaches to intensity modulated proton therapy and the impact on dose-weighted linear energy transfer.

PURPOSE: We quantified the effect of various forward-based treatment-planning strategies in proton therapy on dose-weighted linear energy transfer (LETd). By maintaining the dosimetric quality at a clinically acceptable level, we aimed to evaluate the differences in LETd among various treatment-planning approaches and their practicality in minimizing biologic uncertainties associated with LETd. METHOD: Eight treatment-planning strategies that are achievable in commercial treatment-planning systems were applied on a cylindrical water phantom and four pediatric brain tumor cases. Each planning strategy was compared to either an opposed lateral plan (phantom study) or original clinical plan (patient study). Deviations in mean and maximum LETd from clinically acceptable dose distributions were compared. RESULTS: In the phantom study, using a range shifter and altering the robust scenarios during optimization had the largest effect on the mean clinical target volume LETd, which was reduced from 4.5 to 3.9 keV/µm in both cases. Variations in the intersection angle between beams had the largest effect on LETd in a ring defined 3 to 5 mm outside the target. When beam intersection angles were reduced from opposed laterals (180°) to 120°, 90°, and 60°, corresponding maximum LETd increased from 7.9 to 8.9, 10.9, and 12.2 keV/µm, respectively. A clear trend in mean and maximum LETd variations in the clinical cases could not be established, though spatial distribution of LETd suggested a strong dependence on patient anatomy and treatment geometry. CONCLUSION: Changes in LETd from treatment-plan setup follow intuitive trends in a controlled phantom experiment. Anatomical and other patient-specific considerations, however, can preclude generalizable strategies in clinical cases. For pediatric cranial radiation therapy, we recommend using opposed lateral treatment fields to treat midline targets.

Design of a novel 5-camera surface guidance system with multiple imaging isocenters.

PURPOSE/OBJECTIVE(S): Surface-guided radiation therapy (SGRT) can track the patient surface noninvasively to complement radiographic image-guided radiation therapy with a standard 3-camera system and a single radiation/image isocenter. Here we report the commissioning of a novel SGRT system that monitors three imaging isocenters locations in a proton half-gantry room with a unique 5-camera configuration. MATERIALS/METHODS: The proton half-gantry room has three image isocenters, designated ISO-0, ISO-1, and ISO-2, to cover various anatomical sites via a robotic ceiling-mounted cone-beam CT. Although ISO-0 and ISO-1 are used to image the cranium, head and neck, and thoracic regions, ISO-2 is often used to image body and extremity sites and contiguous craniospinal target volumes. The five-camera system was calibrated to the radiographic isocenter by using a stereotactic radiosurgery cube phantom for each image isocenter. RESULTS: The performance of this 5-camera system was evaluated for 6 degrees of freedom in three categories: (1) absolute setup accuracy relative to the radiographic kV image isocenter based on the DICOM reference; (2) relative shift accuracy based on a reference surface capture; and (3) isocenter tracking accuracy from one isocenter to another based on a reference surface capture. The evaluation revealed maximum deviations of 0.8, 0.2, and 0.6 mm in translation and 0.2°, 0.1°, and 0.1° in rotation for the first, second, and third categories, respectively. Comparing the dosimetry and latency with static and gated irradiation revealed a 0.1% dose difference and positional differences of 0.8 mm in X and 0.9 mm in Y with less than 50 ms temporal accuracy. CONCLUSION: The unique 5-camera system configuration provides SGRT at the treatment isocenter (ISO-0) and also imaging isocenter locations (ISO-0, ISO-1, and ISO-2) to ensure correct patient positioning before and after radiographic imaging, especially during transitions from the offset imaging isocenters to the treatment isocenter.

Acute lymphoblastic leukemia.

The survival of patients with acute lymphoblastic leukemia (ALL) has improved significantly with the use of intensive multimodality treatment regimens including chemotherapy, high-dose chemotherapy and stem cell rescue, and radiation therapy when indicated. This report summarizes the treatment strategies, especially radiation therapy in the Children's Oncology Group for children with ALL. Currently, radiation therapy is only indicated for children with high-risk CNS involvement at diagnosis or relapse, testicular relapse and as part of the conditioning regimen for hematopoietic stem cell transplantation. Future research strategies regarding the indications for and dosages of radiation therapy and novel radiation techniques are discussed.

Advances in radiotherapy technology for pediatric cancer patients and roles of medical physicists: COG and SIOP Europe perspectives.

Over the last two decades, rapid technological advances have dramatically changed radiation delivery to children with cancer, enabling improved normal-tissue sparing. This article describes recent advances in photon and proton therapy technologies, image-guided patient positioning, motion management, and adaptive therapy that are relevant to pediatric cancer patients. For medical physicists who are at the forefront of realizing the promise of technology, challenges remain with respect to ensuring patient safety as new technologies are implemented with increasing treatment complexity. The contributions of medical physicists to meeting these challenges in daily practice, in the conduct of clinical trials, and in pediatric oncology cooperative groups are highlighted. Representing the perspective of the physics committees of the Children's Oncology Group (COG) and the European Society for Paediatric Oncology (SIOP Europe), this paper provides recommendations regarding the safe delivery of pediatric radiotherapy. Emerging innovations are highlighted to encourage pediatric applications with a view to maximizing the therapeutic ratio.

Practice patterns and recommendations for pediatric image-guided radiotherapy: A Children's Oncology Group report.

This report by the Radiation Oncology Discipline of Children's Oncology Group (COG) describes the practice patterns of pediatric image-guided radiotherapy (IGRT) based on a member survey and provides practice recommendations accordingly. The survey comprised of 11 vignettes asking clinicians about their recommended treatment modalities, IGRT preferences, and frequency of in-room verification. Technical questions asked physicists about imaging protocols, dose reduction, setup correction, and adaptive therapy. In this report, the COG Radiation Oncology Discipline provides an IGRT modality/frequency decision tree and the expert guidelines for the practice of ionizing image guidance in pediatric radiotherapy patients.

Automatic image processing pipeline for tracking longitudinal vessel changes in magnetic resonance angiography.

BACKGROUND: Cerebral vessel diameter changes objectively and automatically derived from longitudinal magnetic resonance angiography (MRA) facilitate quantification of vessel changes and further modeling. PURPOSE: To characterize longitudinal changes in intracranial vessel diameter using time-of-flight (TOF) MRA. STUDY TYPE: Retrospective longitudinal study. SUBJECT POPULATION: IN all, 112 pediatric patients, aged 9.96 ± 4.59 years, with craniopharyngioma from 2006-2011 scanned annually. FIELD STRENGTH/SEQUENCE: 1.5T and 3T TOF MRA. STATISTICAL TESTS: Chi-square and Wilcoxon-Mann-Whitney tests. ASSESSMENT: Manual measurements using interventional angiography was established as a reference standard for diameter measurements. Constant and linear quantile regression with absolute difference, percentage difference, and relative difference was used for outlier detection. RESULTS: Major vessels surrounding the circle of Willis were successfully segmented except for posterior communicating arteries, mostly due to disease-related hypoplasia. Diameter measurements were calculated at 1-mm segments with a median computed vessel diameter of 1.25 mm. Diameter distortion due to registration was within 0.04 mm for 99% of vessel segments. Outlier detection using quantile regression detected less than 4.34% as being outliers. Outliers were more frequent in smaller vessels and proximity to bifurcations (P < 0.001). DATA CONCLUSION: Using the proposed method, objective changes in vessel diameter can be acquired noninvasively from routine longitudinal imaging. High-throughput analyses of imaging-derived vascular trees combined with clinical and treatment parameters will allow rigorous modeling of vessel diameter changes. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1063-1074.

Nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) in pediatric and young adult patients: Results from a prospective study using limited-margin radiotherapy.

BACKGROUND: Indications for and delivery of adjuvant therapies for pediatric nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) have been derived largely from adult studies; therefore, significant concern remains regarding radiation exposure to normal tissue. The authors report long-term treatment outcomes and toxicities for pediatric and young adult patients with high-grade NRSTS who were treated on a prospective trial using limited-margin radiotherapy. METHODS: Sixty-two patients (ages 3-22 years) with predominantly high-grade NRSTS requiring radiation were treated on a phase 2 institutional study of conformal external-beam radiotherapy and/or brachytherapy using a 1.5-cm to 2-cm anatomically constrained margin. The estimated cumulative incidence of local failure, Gray's method estimated cumulative incidence of local failure, Kaplan-Meier method estimated survival, competing-risk regression model determined predictors of disease outcome, and toxicity was reported according to CTCAE v2.0. RESULTS: At a median follow-up of 5.1 years (range, 0.2-10.9 years), 9 patients had experienced local failure. The 5-year overall cumulative incidence of local failure was 14.8% (95% confidence interval [CI], 7.2%-25%), and all but 1 local failure occurred outside the highest-dose irradiation volume. The 5-year Kaplan-Meier estimates for event-free and overall survival were 49.3% (95% CI, 36.3%-61.1%) and 67.9% (95% CI, 54.2%-78.3%), respectively. Multivariable analysis indicated that younger age was the only independent predictor of local recurrence (P = .004). The 5-year cumulative incidence of grade 3 or 4 late toxicity was 15% (95% CI, 7.2%-25.3%). CONCLUSIONS: The delivery of limited-margin radiotherapy using conformal external-beam radiotherapy or brachytherapy provides a high rate of local tumor control without an increase in marginal failures and with acceptable treatment-related morbidity. Cancer 2017;123:4419-29. © 2017 American Cancer Society.

11C-Methionine positron emission tomography delineates non-contrast enhancing tumor regions at high risk for recurrence in pediatric high-grade glioma.

We assessed the prognostic utility of 11C-Methionine positron emission tomography (MET-PET) in pediatric high-grade glioma (HGG). Thirty-one children had 62 MET-PET studies. Segmented tumor volumes from co-registered magnetic resonance studies were assessed for concordance with MET-PET uptake using Boolean operations. The tumor volume at diagnosis and treatment failure was assessed relative to MET-PET avid volume. The prognostic impact of MET-PET-delineated non-contrast enhancing tumor (NCET) was assessed. NCET was defined as the region of tumor defined by defined by FLAIR which did not enhance but showed MET-PET avidity. MET-PET concordance varied according to magnetic resonance sequence. MET-PET rarely added to the tumor volume in most cases. The volume of MET-PET with standardized uptake value >3.0 was differentially distributed at diagnosis, post treatment, and at recurrence. The initial MET-PET region overlapped with recurrent tumor in 90% of the cases. When the proportion of tumor which was NCET was >10%, an earlier time to progression (5.8 months; 95% CI, 1-8.2 vs. 10.5 months; 95% CI, 0.9-NR; p = 0.035) was noted. MET-PET delineates regions at increased risk for recurrence and may improve the definition of failure, prognostic assessment, and target definition for radiotherapy.

Performance analysis and knowledge-based quality assurance of critical organ auto-segmentation for pediatric craniospinal irradiation.

Craniospinal irradiation (CSI) is a vital therapeutic approach utilized for young patients suffering from central nervous system disorders such as medulloblastoma. The task of accurately outlining the treatment area is particularly time-consuming due to the presence of several sensitive organs at risk (OAR) that can be affected by radiation. This study aimed to assess two different methods for automating the segmentation process: an atlas technique and a deep learning neural network approach. Additionally, a novel method was devised to prospectively evaluate the accuracy of automated segmentation as a knowledge-based quality assurance (QA) tool. Involving a patient cohort of 100, ranging in ages from 2 to 25 years with a median age of 8, this study employed quantitative metrics centered around overlap and distance calculations to determine the most effective approach for practical clinical application. The contours generated by two distinct methods of atlas and neural network were compared to ground truth contours approved by a radiation oncologist, utilizing 13 distinct metrics. Furthermore, an innovative QA tool was conceptualized, designed for forthcoming cases based on the baseline dataset of 100 patient cases. The calculated metrics indicated that, in the majority of cases (60.58%), the neural network method demonstrated a notably higher alignment with the ground truth. Instances where no difference was observed accounted for 31.25%, while utilization of the atlas method represented 8.17%. The QA tool results showed that the two approaches achieved 100% agreement in 39.4% of instances for the atlas method and in 50.6% of instances for the neural network auto-segmentation. The results indicate that the neural network approach showcases superior performance, and its significantly closer physical alignment to ground truth contours in the majority of cases. The metrics derived from overlap and distance measurements have enabled clinicians to discern the optimal choice for practical clinical application.

Reporting Standards for Complication Studies of Radiation Therapy for Pediatric Cancer: Lessons From PENTEC.

The major aim of Pediatric Normal Tissue Effects in the Clinic (PENTEC) was to synthesize quantitative published dose/-volume/toxicity data in pediatric radiation therapy. Such systematic reviews are often challenging because of the lack of standardization and difficulty of reporting outcomes, clinical factors, and treatment details in journal articles. This has clinical consequences: optimization of treatment plans must balance between the risks of toxicity and local failure; counseling patients and their parents requires knowledge of the excess risks encountered after a specific treatment. Studies addressing outcomes after pediatric radiation therapy are particularly challenging because: (a) survivors may live for decades after treatment, and the latency time to toxicity can be very long; (b) children's maturation can be affected by radiation, depending on the developmental status of the organs involved at time of treatment; and (c) treatment regimens frequently involve chemotherapies, possibly modifying and adding to the toxicity of radiation. Here we discuss: basic reporting strategies to account for the actuarial nature of the complications; the reporting of modeling of abnormal development; and the need for standardized, comprehensively reported data sets and multivariate models (ie, accounting for the simultaneous effects of radiation dose, age, developmental status at time of treatment, and chemotherapy dose). We encourage the use of tools that facilitate comprehensive reporting, for example, electronic supplements for journal articles. Finally, we stress the need for clinicians to be able to trust artificial intelligence models of outcome of radiation therapy, which requires transparency, rigor, reproducibility, and comprehensive reporting. Adopting the reporting methods discussed here and in the individual PENTEC articles will increase the clinical and scientific usefulness of individual reports and associated pooled analyses.

Improving Pediatric Normal Tissue Radiation Dose-Response Modeling in Children With Cancer: A PENTEC Initiative.

The development of normal tissue radiation dose-response models for children with cancer has been challenged by many factors, including small sample sizes; the long length of follow-up needed to observe some toxicities; the continuing occurrence of events beyond the time of assessment; the often complex relationship between age at treatment, normal tissue developmental dynamics, and age at assessment; and the need to use retrospective dosimetry. Meta-analyses of published pediatric outcome studies face additional obstacles of incomplete reporting of critical dosimetric, clinical, and statistical information. This report describes general methods used to address some of the pediatric modeling issues. It highlights previous single- and multi-institutional pediatric dose-response studies and summarizes how each PENTEC taskforce addressed the challenges and limitations of the reviewed publications in constructing, when possible, organ-specific dose-effect models.

Evaluating the Impact of Bowel Gas Variations for Wilms' Tumor in Pediatric Proton Therapy.

(1) Background: Proton therapy, a precise form of radiation treatment, can be significantly affected by variations in bowel content. The purpose was to identify the most beneficial gantry angles that minimize deviations from the treatment plan quality, thus enhancing the safety and efficacy of proton therapy for Wilms' tumor patients. (2) Methods: Thirteen patients with Wilms' tumor, enrolled in the SJWT21 clinical trial, underwent proton therapy. The variations in bowel gas were systematically monitored using daily Cone Beam Computed Tomography (CBCT) imaging. Air cavities identified in daily CBCT images were analyzed to construct daily verification plans and measure water equivalent path length (WEPL) changes. A worst-case scenario simulation was conducted to identify the safest beam angles. (3) Results: The study revealed a maximum decrease in target dose (ΔD100%) of 8.0%, which corresponded to a WEPL variation (ΔWEPL) of 11.3 mm. The average reduction in target dose, denoted as mean ΔD100%, was found to be 2.8%, with a standard deviation (SD) of 3.2%. The mean ΔWEPL was observed as 3.3 mm, with an SD of 2.7 mm. The worst-case scenario analysis suggested that gantry beam angles oriented toward the patient's right and posterior aspects from 110° to 310° were associated with minimized WEPL discrepancies. (4) Conclusions: This study comprehensively evaluated the influence of bowel gas variability on treatment plan accuracy and proton range uncertainties in pediatric proton therapy for Wilms' tumor.

Radiation Dose-Volume-Response Relationships for Adverse Events in Childhood Cancer Survivors: Introduction to the Scientific Issues in PENTEC.

At its very core, radiation oncology involves a trade-off between the benefits and risks of exposing tumors and normal tissue to relatively high doses of ionizing radiation. This trade-off is particularly critical in childhood cancer survivors (CCS), in whom both benefits and risks can be hugely consequential due to the long life expectancy if the primary cancer is controlled. Estimating the normal tissue-related risks of a specific radiation therapy plan in an individual patient relies on predictive mathematical modeling of empirical data on adverse events. The Pediatric Normal-Tissue Effects in the Clinic (PENTEC) collaborative network was formed to summarize and, when possible, to synthesize dose-volume-response relationships for a range of adverse events incident in CCS based on the literature. Normal-tissue clinical radiation biology in children is particularly challenging for many reasons: (1) Childhood malignancies are relatively uncommon-constituting approximately 1% of new incident cancers in the United States-and biologically heterogeneous, leading to many small series in the literature and large variability within and between series. This creates challenges in synthesizing data across series. (2) CCS are at an elevated risk for a range of adverse health events that are not specific to radiation therapy. Thus, excess relative or absolute risk compared with a reference population becomes the appropriate metric. (3) Various study designs and quantities to express risk are found in the literature, and these are summarized. (4) Adverse effects in CCS often occur 30, 50, or more years after therapy. This limits the information content of series with even very extended follow-up, and lifetime risk estimates are typically extrapolations that become dependent on the mathematical model used. (5) The long latent period means that retrospective dosimetry is required, as individual computed tomography-based radiation therapy plans gradually became available after 1980. (6) Many individual patient-level factors affect outcomes, including age at exposure, attained age, lifestyle exposures, health behaviors, other treatment modalities, dose, fractionation, and dose distribution. (7) Prospective databases with individual patient-level data and radiation dosimetry are being built and will facilitate advances in dose-volume-response modeling. We discuss these challenges and attempts to overcome them in the setting of PENTEC.

Imaging Assessment of Radiation Therapy-Related Normal Tissue Injury in Children: A PENTEC Visionary Statement.

The Pediatric Normal Tissue Effects in the Clinic (PENTEC) consortium has made significant contributions to understanding and mitigating the adverse effects of childhood cancer therapy. This review addresses the role of diagnostic imaging in detecting, screening, and comprehending radiation therapy-related late effects in children, drawing insights from individual organ-specific PENTEC reports. We further explore how the development of imaging biomarkers for key organ systems, alongside technical advancements and translational imaging approaches, may enhance the systematic application of imaging evaluations in childhood cancer survivors. Moreover, the review critically examines knowledge gaps and identifies technical and practical limitations of existing imaging modalities in the pediatric population. Addressing these challenges may expand access to, minimize the risk of, and optimize the real-world application of, new imaging techniques. The PENTEC team envisions this document as a roadmap for the future development of imaging strategies in childhood cancer survivors, with the overarching goal of improving long-term health outcomes and quality of life for this vulnerable population.

Toward Systematic Assessment and Improvement of Radiation Therapy Plan Quality of Cooperative Group Trial Submissions: A Report From the Children's Oncology Group.

PURPOSE: This study evaluates the quality of plans used for the treatment of patients in the Children's Oncology Group study ACNS1123. Plan quality is quantified based on a scoring system specific to the protocol. In this way, the distribution of plan quality scores is determined that can be used to identify plan quality issues for this study and for future plan quality improvement. METHODS AND MATERIALS: ACNS1123 stratum 1 patients (70) were evaluated. This included 50 photon and 20 proton plans. Digital Imaging and Communications in Medicine (DICOM) structure and dose data were obtained from the Children's Oncology Group. A commercially available plan quality scoring algorithm was used to create a scoring system we designed using the protocol dosimetric requirements. The whole ventricle and boost planning target volumes (PTVs) could earn a maximum of 70 points, whereas the organs at risk could earn 30 points (total maximum score of 100 points). The scoring algorithm adjusted scores based on the difficulty in achieving the structure dose requirements, which depended on the proximity of the PTVs and the dose gradients achieved relative to the organs at risk. The distribution of plan scores was used to determine the mean, median, and range of scores. RESULTS: The median adjusted plan quality scores for the 20 proton and 50 photon plans were 83.3 and 86.9, respectively. The range of adjusted scores (maximum to minimum) was 50 points. The average score adjustment was 7.4 points. Photon and proton plans performed almost equally. Average plan quality by individual structure revealed that the brain stem, PTV boost, and cochlea lost the most points. CONCLUSIONS: This report is the first to systematically analyze overall radiation therapy plan quality scores for an entire cohort of patients treated in a cooperative group clinical trial. The methodology demonstrated a large variation in plan quality in this trial. Future clinical trials could potentially use this method to reduce plan quality variability, which may improve outcomes.

Novel Monthly Quality Assurance Regimen and 5-Year Analysis Using a Proton Metrology System.

Purpose: To develop a novel, monthly quality assurance (QA) regimen for a proton therapy system that uses 2 custom phantoms, each housing a commercial scintillator detector and a charge-coupled device camera. The novel metrology system assessed QA trends at a pediatric proton therapy center from 2018 to 2022. Materials and Methods: The measurement system was designed to accommodate horizontal and vertical positioning of the commercial device and to enable gantry and couch isocentricity measurements (using a star shot procedure), proton spot profile verification, and imaging and radiation congruence tests to be performed simultaneously in the dual-phantom setup. Gantry angles and proton beam energies were varied and alternated each month, using gantry angles of 0°, 30°, 60°, 90°, 120°, 150°, and 180° and discrete beam energies of 69.4, 84.5, 100, 139.1, 180.4, 200.4, and 221.3 MeV after radiographic verification. A total of 1176 individual monthly QA measurements of gantry and couch isocentricity, spot size, and congruence were analyzed. Results: Gantry and couch star shot measurements showed beam isocentricities of 0.3 ± 0.2 mm and 0.2 ± 0.2 mm, respectively, which were within the threshold of 1.0 mm. Spot sizes for each discrete energy were within the threshold of ± 10% of the baseline values for all 3 proton rooms. The imaging and radiation coincidence test results for the 1176 individual monthly QA measurements were 0.5 mm for the 50th percentile and 1.2 mm (the clinical threshold) for the 97.6th percentile. Conclusions: Integrating a commercial device with custom phantoms improved the quality of proton system checks compared with previous methods using radiochromic films, loose ball bearings, and foam. The scheme of alternating beam angles with discrete energies in the monthly QA-enabled, clinically meaningful verification of beam energy and gantry angle combinations while the machine performance and accuracy were being checked.

Monitoring of Interfractional Proton Range Verification and Dosimetric Impact Based on Daily CBCT for Pediatric Patients with Pelvic Tumors.

(1) Background: Synthetic CT images of the pelvis were generated from daily CBCT images to monitor changes in water equivalent path length (WEPL) and determine the dosimetric impact of anatomy changes along the proton beam's path; (2) Methods: Ten pediatric patients with pelvic tumors treated using proton therapy with daily CBCT were included. The original planning CT was deformed to the same-day CBCT to generate synthetic CT images for WEPL comparison and dosimetric evaluation; (3) Results: WEPL changes of 20 proton fields at the distal edge of the CTV ranged from 0.1 to 12 mm with a median of 2.5 mm, and 75th percentile of 5.1 mm for (the original CT-rescanned CT) and ranged from 0.3 to 10.1 mm with a median of 2.45 mm and 75th percentile of 4.8 mm for (the original CT-synthetic CT). The dosimetric impact was due to proton range pullback or overshoot, which led to reduced coverage in CTV Dmin averaging 12.1% and 11.3% in the rescanned and synthetic CT verification plans, respectively; (4) Conclusions: The study demonstrated that synthetic CT generated by deforming the original planning CT to daily CBCT can be used to quantify proton range changes and predict adverse dosimetric scenarios without the need for excessive rescanned CT scans during large interfractional variations in adaptive proton therapy of pediatric pelvic tumors.