Our study demonstrates that proton therapy for patients with medulloblastoma reduces dose to normal brain tissues, which is associated with better intellectual outcomes. Children with medulloblastoma who undergo RT should be treated with proton therapy, if available.

Purpose/Objective(s) The role of SBRT in the treatment of HCC is not well established. The hypothesis of this study was that overall survival (OS) would improve with SBRT followed by sorafenib (SBRT/S) vs. sorafenib alone (S), in patients with advanced HCC. Materials/Methods Eligible patients had new or recurrent HCC, unsuitable for resection, transplant, ablation or TACE, with Zubrod performance status (PS) 0-2, Child-Pugh A, intermediate (B) or advanced (C) Barcelona Clinic Liver Cancer Stage (BCLC), ≤ 5 HCCs, sum of hepatic HCCs ≤ 20 cm, and sum of extrahepatic metastases ≤ 3 cm. Patients were randomized 1:1 to S 400 mg BID vs. SBRT (27.5-50Gy in 5 fractions, with dose individualized based on mean liver dose and other dose constraints) followed by S 200 mg BID then increased to 400 mg BID after 28 days if appropriate. Primary endpoint was OS. Reported secondary endpoints were progression-free survival (PFS), time to progression (TTP), and adverse events (AEs - CTCAEv4). Planned sample size was 292 patients (238 OS events, HR=0.72, 80% power, 1-sided alpha=0.05). Accrual closed early, primarily due to a change in HCC standard of care systemic therapy. Statistics were amended to report data as of 7/1/2022, projecting 155 OS events providing 65% power for the original hypothesis, with the same alpha. OS and PFS were estimated by Kaplan-Meier and arms compared using log-rank test. Cox proportional hazards models were used to analyze treatment effect. TTP was estimated with cumulative incidence and arms compared using Gray's test. Secondary endpoints were tested with 2-sided alpha=0.05. Results Of 193 patients accrued from April 2013 to March 2021 from 23 sites, 177 eligible patients were randomized to S (n=92) vs. SBRT/S (n=85). Median age was 66 years (27-84); 41% had Hepatitis C and 19% had Hepatitis B or B/C. The majority were stage BCLC C (82%), with macrovascular invasion (74%). 4% had metastases. Median follow-up for all and alive patients was 13.2 and 33.7 months, respectively. With 153 OS events, median OS was improved from 12.3 months (90% CI 10.6, 14.3) with S to 15.8 months (90% CI 11.4-19.2) with SBRT/S (HR=0.77, 1-sided p=0.0554). After adjusting for PS, M stage, Child Pugh A5 vs. 6, and degree of vascular HCC, OS was statistically significantly improved for SBRT/S (HR=0.72, 95% CI 0.52-0.99, 2-sided Cox p=0.042). Median PFS was improved from 5.5 months (95% CI 3.4-6.3) with S to 9.2 months (95% CI 7.5-11.9) with SBRT/S (HR=0.55, 95% CI 0.40-0.75, 2-sided p=0.0001). TTP was also improved with SBRT/S (HR=0.69, 95% CI 0.48-0.998, 2-sided Gray's p=0.034). Treatment-related grade 3+ AEs were not significantly different (S - 42%, SBRT/S - 47%; p=0.52). There was one grade 5 treatment-related AE, in the S arm. Conclusion Adding SBRT improved OS, PFS, and TTP in patients with advanced HCC, compared to Sorafenib alone, with no significant increase in AEs.

Dose escalation to mpMRI-defined GTV provided high rates of local and biochemical control with limited severe late toxicity. Intraprostatic failures outside the boost volume appeared to correlate with BCR, which suggests that dose escalation to other subclinical intraprostatic regions may be required. Further characterization using molecular classification, beyond usual clinical parameters, may be warranted in order to improve local control.

The authors regret that the incorrect photo was uploaded for Figure 1. The authors would like to apologise for any inconvenience caused. Below is the correct photo. Can Conformity-Based Volumetric Modulated Arc Therapy Improve Dosimetry and Speed of Delivery in Radiation Therapy to Lumbosacral Spine Compared with Conventional Techniques?Journal of Medical Imaging and Radiation SciencesVol. 51Issue 3PreviewVolumetric modulated arc therapy (VMAT) has generally been perceived as too time and resource intensive for palliative radiation therapy mainly because of the need for extensive organs at risk contouring. Dose-limiting conformity-based objectives can be automatically generated and are commonly used to conform isodoses closely around the target volumes during inverse planning. The aim of this study was to determine if conformity-based objectives can be used to create VMAT plans for lumbosacral spine palliative radiation therapy without organs at risk contours, which will improve conformity, dose homogeneity, and speed of delivery compared with standard forward planning approaches. Full-Text PDF

NRG Oncology trial RTOG 1112 is a randomized study of sorafenib with or without stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma. Image-guided radiation therapy (IGRT) credentialing is essential for this study due to the high doses, respiratory motion, and variety of delivery technologies. This analysis examines the IGRT credentialing experience. Credentialing of volumetric IGRT for RTOG 1112 requires submission of planning and localization images, planning structures, and resulting IGRT shifts consistent with the study. A study reviewer uses this data to repeat the registrations and compare to the actual clinical registrations. Agreement within 5 mm was considered acceptable for credentialing. Deviations of greater than 10 mm were confirmed with the submitting institution. Images of 130 fractions from the initial and repeat submissions from 42 institutions between June 2013 to present were reviewed. The median agreement between clinical registrations and study reviewer was 3 mm, with 95% of all fractions within 5 mm. A sub-analysis investigated differences between use of low contrast soft tissue (n=63 images) or high-contrast surrogates (n=67) (e.g. implanted fiducial markers, surgical clips, metallic stents) for registration. Soft tissue registrations agreed within 3 mm in 50% of fractions and 9 mm in 95%, while high-contrast surrogate registrations agreed within 3 mm in 50% and 5 mm in 95%. Soft tissue registrations exceeded 10 mm in 3% of fractions, while no high-contrast surrogate registrations exceeded 5 mm. The RTOG 1112 credentialing experience suggests most institutions perform liver IGRT with sufficient accuracy to deliver SBRT safely. Both soft tissue and high-contrast surrogates appear adequate for consistent registration in most instances; however, some mis-registrations were observed when using soft-tissue registration targets. The use of high-contrast surrogates appears to reduce the small risk of substantial geographic miss due to mis-registration in liver IGRT. Funding: This project was supported by grants U10CA180868 (NRG Oncology Operations), U24CA180803 (IROC), CTEP from the National Cancer Institute (NCI).

and functional outcomes.We consider this bladder sparing treatment as the gold standard in bladder preserving therapies.A multidisciplinary collaboration is indispensable.

We have developed a novel voxel- and machine learning-based automated planning method that requires the planning image dataset, target contours, relevant organ at risk (OAR) volumes as inputs for dose distribution prediction, and a voxel dose dose-mimicking step that generates a complete treatment plan in 20-25 minutes. As the method has automated determination of appropriate clinical trade-offs, user input during the optimization process is not required. Herein, we validate our method for clinical application in prostate volumetric arc radiotherapy (RT). A dose prediction algorithm was trained and tested using 116 consecutive clinically used plans for prostate cancer radical RT. An independent dataset of 20 patients with localized prostate cancer was randomly selected and the dose prediction algorithm was used to generate RT plans. These were evaluated alongside the original clinical plans by three expert reviewers (2 GU radiation oncologists and 1 medical physicist) blinded to the plan origin. Three plans were excluded prior to any review as they contained hip prosthesis. Evaluation criteria included acceptability and preference with regards to target coverage, dose conformity, dose gradient at rectum/prostate interface, lateral symmetry, OAR sparing, and overall approval. Of the 17 patients reviewed, automated plans were deemed superior in target coverage and OAR sparing, similar in gradient at rectum/prostate interface, and inferior in high-dose conformity and lateral dose symmetry. Both automated and clinical plans were deemed clinically acceptable in 49 of 51 instances across the three reviewers. One automated plan was deemed clinically unacceptable by two reviewers, and two different clinical plans were deemed clinically unacceptable by one reviewer. When compared head-to-head by the three reviewers, automated plans were deemed superior in 38 (74.5%) and equivalent to clinical plans in 3 (5.9%) reviews. Overall, in 15 of 17 (88.2%) patients, automated plans were deemed superior or equivalent to the delivered clinical plans. Our machine learning-based automated planning framework has the potential for clinical application in prostate RT, providing and opportunity to improve efficiency and consistency in the planning process. Furthermore, without the need for user interaction during plan optimization process, can enable increased throughput and liberate human resources for being allocated elsewhere within the RT process. Integration into our clinical practice including prospective performance evaluation of the proposed method is ongoing.

Adaptive strategies in bladder cancer radiotherapy allow excellent target coverage but may be associated with differences in rectal sparing. We examined 3 adaptive radiotherapy techniques using deformable image registration and dose accumulation. Fifteen patients who had radiotherapy for muscle invasive bladder cancer (simulated and treated with comfortably full bladder and empty rectum) were identified. RayStation 4.7 was used for planning, image registration and dose accumulation. New treatment plans to a dose of 55Gy in 20 fractions were created using 7-field IMRT. CTV (whole bladder) and rectum were outlined on planning CT (PCT) and 20 daily cone beam CTs (CBCT). PTVs derived from 3 adaptive strategies were compared (geometric expansions in all directions unless otherwise stated): 1. Patient specific (PS-PTV): Union of CTV from PCT and first 5 CBCT formed an “occupancy volume” (OV). PS-PTV = 0.3 cm + OV 2. Multi-image plan of day (MI-POD): 3 library plans were created; Small (2 smallest of CTV from PCT and first 5 CBCT used to create OV. PTV = OV + 3 mm), Medium (same as PS-PTV) and Large (1.5 cm + CTV from PCT) 3. Single image plan of day (SI-POD): Plan library created using PCT alone. Small (1.5 cm to CTV in all directions except -1.0 cm superiorly), Medium (1.5 cm in all directions except -0.5 cm superiorly) and Large (1.5 cm in all directions except 0 cm superiorly) Standard PTV (1.5 cm + CTV from PCT) was used for dose accumulation for first 5 fractions in PS-PTV & MI-POD. PTV in each strategy that fully contained the bladder on registered CBCT/fraction was recorded. Daily CBCTs were registered using deformable image registration with PCT; dose was computed on each CBCT and deformably accumulated on PCT. The PTV, CTV D99 and rectum D30 for each strategy were compared using Wilcoxon Signed Rank test or paired Student’s t test (where appropriate) with a 2-tailed p≤0.05 considered statistically significant. Median PTV for each strategy was: SI-POD 480.9 cc, PS-PTV 391.8 cc and MI-POD 451.8. CTV D99 and median of difference in the PTV are shown below:Abstract 2636StrategyMean CTV D99 in Gy with 95% CI p values compared to SI-PODMedian of difference in the PTVcc compared to SI-POD [IQR]SI-POD52.9 [95% CI 52.2 – 53.7]PS-PTV53.0 [95% CI 52.2 – 53.7, p=0.88]113 [82.5 – 145.7, p<0.001]MI-POD53.0 [95% CI 52.3 – 53.7, p=0.61]76.5 [50.3 – 110.2, p<0.001] Open table in a new tab Median rectum D30 was: SI-POD 36.7 Gy, PS-PTV 26.2 Gy and MI-POD 26.8 Gy. Rectal sparing was significantly better with PS-PTV and MI-POD compared to SI-POD; median of difference in rectum D30 compared to SI-POD was: PS-PTV 5Gy [p=0.002] and MI-POD 5.3 Gy [p=0.001] with no difference in median between PS-PTV and MI-POD, 0Gy [p=0.509]. Our study demonstrated that a PTV based on multiple images (PS-PTV and MI-POD) provided superior rectal sparing while maintaining adequate target dose compared to single image strategy (SI-POD). However as MI-POD is relatively resource intensive, PS-PTV may be a preferred adaptive strategy for bladder cancer radiotherapy.

The performance of CT-CBCT (Cone Beam CT) Deformable Image Registration (DIR) for prostate propagation for dose tracking purposes can be improved by including bladder and rectum as guiding structures. Currently, these volumes are manually delineated on CBCT. This study quantified the interobserver variability in delineating bladder and rectum on CBCT and to assess its impact on the propagated prostate. Bladder and rectum were delineated as solid structures by 3 observers on the reference CT and 13 CBCTs from each of 10 prostate patients. Intensity-based DIR was performed 3 times on each CBCT, using the 3 different sets of volumes as additional guiding structures. ProstateDIR was propagated from the reference CT onto CBCTs using the deformation vector fields of the corresponding DIR from each observer for comparison. Mean Distance between Surfaces (DSS) was calculated to assess interobserver variability and its impact on ProstateDIR. A DSS < 2mm was considered as having good agreement among the volumes. A total of 390 ProstateDIR was included for analysis. Interobserver variability in bladder delineation was low, with 96% of DSS < 2mm. However, high variability was noted in the delineation of rectum, with only 35% of DSS < 2mm for one observer. Despite a low agreement in one of the guiding structures for DIR, there was good agreement in ProstateDIR among observers, with ≥ 91% of DSS < 2mm. Upon image review, a DSS of > 2mm for ProstateDIR was attributed to a significant difference in defining the rectum among observers in the anterior direction, where the rectum-prostate interface is. Variation in defining rectum in other directions has no impact on ProstateDIR. Interobserver variability in defining the rectum in the anterior direction has an impact on the geometry of the propagated prostate when rectum is used as a guiding structure for CT-CBCT DIR. Further investigation is needed to assess its impact on estimating the accumulated delivered dose to the prostate.

Dose escalation has successfully improved cancer outcomes for patients with localized prostate cancer. Targeting subprostatic regions of tumor burden for dose-intensification may further improve tumor control and reduce dose to surrounding normal tissues. Quantitative MRI may provide a clinically useful evaluation of early radiation response to enable the adaptation of dose. Our objective is to determine whether the ADC derived from diffusion-weighted imaging (DWI) of prostate tumors may be used as a biomarker for evaluation of early radiation response and dose adaptation. Patients with biopsy proven prostate adenocarcinoma visualized on MRI prior to radiotherapy were recruited to participate in a prospective trial in which patients received 76 Gy in 38 fractions to the prostate and either an integrated boost (IB) (19 Gy/38#) or an HDR boost (10 Gy/1#) to the dominant tumor. Patients underwent endorectal coil multiparametric MRI (3T Verio, Siemens) at baseline and during week 6 of treatment. ADC was calculated from in-line processing of DWI (b values of 0, 100, 600, and 1000 s/mm2). Dominant tumors, prostate, and common reference points were defined on the baseline T2 weighted (T2w) image (Pinnacle). The prostate and common reference points were again defined on the week 6 T2w image. Deformable registration (Morpheus) was applied to the baseline prostate and reference contours to guide segmentation of the tumor volumes (no longer clearly visible) in the week 6 ADC maps. Volume of interest (VOI) voxel based histogram analysis of mean, skewness, and kurtosis were used to assess ADC response. Of 80 enrolled patients, the first 17 were analyzed. 8 patients received IB and 9 patients received HDR. Tumor volumes were small (baseline mean 2.0 cm3, 95% CI 1.6-2.9 cm3). For all 17 patients, there was a statistically significant increase in tumor ADC from baseline (mean 1.12x10-3 mm2/s, 95% CI 1.04-1.19 x10-3 mm2/s) to week 6 of treatment (mean 1.34x10-3 mm2/s, 95% CI 1.29-1.39 x10-3 mm2/s, p<0.001). Tumor ADC kurtosis increased significantly from 3.1 to 4.0 (95% CI 2.7-3.6 at baseline, 3.3-4.8 at week 6, p=0.04). Mean tumor ADC increased by 24.5% (95% CI 10-39%) in the IB-VMAT arm and 20% (95% CI 6-34%) in the VMAT+HDR arm (p=0.6). Our preliminary data confirm a statistically significant increase in tumor ADC during radiotherapy, worthy of further investigation. Complete analysis of the study cohort will elucidate relationships between early changes in tumor ADC and subsequent response to treatment.

A phase I trial of liver SBRT and Sorafenib (pre-concurrent and post) resulted in serious toxicities in HCC patients, but not in a parallel trial in liver metastases. Unanticipated reductions in liver volume were also observed during SBRT potentially impacting dosimetry. Delivered SBRT doses were reconstructed to investigate if the differential toxicity profiles were related to delivered doses or underlying patient biology. HCC (N=14) and metastases (N=14) patients treated on the Phase I trials with individualized SBRT (30-54 Gy in 6 fractions, determined by liver and luminal gastrointestinal (GI) tissue doses) and concurrent Sorafenib were investigated. Daily SBRT doses were retrospectively recalculated on each density-corrected cone-beam CT (accuracy <2%) acquired for image-guidance. Biomechanical deformable registration (accuracy

Purpose:To make Image Guided Radiation Therapy (IGRT) credentialing a more unified, consistent and efficient process across the entire National Clinical Trial Network (NCTN).Methods:IGRT plays a role in several advanced NCTN trials. Previously an institution had to be IGRT credentialed for each protocol. When institutions were allowed to use previous credentials for new protocols it was limited to the same disease site as the original credentialing. The credentialing was analyzed by the physics PI of the protocol. We consulted with several of these physicists to determine what is important to consider when reviewing submissions and to learn ways to apply credentialing more broadly.Results:For trials open in 2016, IGRT credentialing can be simplified to cover either boney anatomy or soft tissue. This revised credentialing will cover all disease sites based on the type of anatomy, unless otherwise stated within the protocol. Institutions will submit will complete an online questionnaire about their IGRT procedures. Boney anatomy requirements will include submission of data from 2 sequential fraction of both a patient aligned with boney anatomy and pelvic patient. Soft tissue will require similar submissions for a patient aligned using soft tissue and a pelvic patient. Institutions will only be required to submit the pelvic patient once. Data should be in DICOM format and includes planning CT set, RT structure set, RT plan file, RT dose file, localization images and spatial registration file (if available). Reviews will be done by IROC‐Houston staff who will continue to provide feedback to the sites.Conclusion:This revised IGRT credentialing process will bring consistency, a savings in time and effort for both the IROC Houston QA office and to those institutions wanting to be credentialed to participate in NCTN Trials.Sponsored by NIH/NCI CA10953

Toxicity following SBRT for liver metastases (LM) appears low but dose/volumetric correlations have not clearly been established. We describe dosimetry and hepatic toxicity for patients with LM treated with SBRT. Cumulative dose volume histograms (DVHs) and dosimetric parameters for patients with LM treated on two sequential prospective trials of 6 fraction SBRT, were correlated with hepatic toxicity defined as an increase in Child Pugh (CP) score or CTCAEv3.0 grade in ALT, AST or ALP at 1 and 3 months. Patients with local progressive disease (PD) within 3 months of SBRT were excluded due to potential confounding effect. Dose to 700ml spared liver (calculated as dose at absolute volume minus 700cc) was analyzed as previous data has shown an association with liver toxicity. Univariate and multivariate binary logistic regression was performed to identify predictors of toxicity. Eighty-eight patients were identified, with 18 excluded due to PD (4) or lacking dosimetric data (14). Patient characteristics included; median age 63 (30-90) years, 40 (57%) male, 49 (70%) colorectal carcinoma primary, one (1%) underlying untreated Hepatitis B, 41 (57%) extrahepatic disease, 44 (62%) prior chemotherapy, 20 (28%) previously treated with hepatic resection (13) and/or RFA (7), 67 (96%) baseline Child-Pugh A5, median number LM 2 (1-7), median GTV volume 50 (1-722) cc, median liver - GTV volume 1564 (882-3029) cc, median SBRT prescription 42 (30-60) Gy median mean liver -GTV dose 16.2 (3-22.7) Gy, median Veffliver37% (5-80%), median physical and biologically normalized NTCP 15.8% (0-69%), and 0.07% (0-18.8%), median dose for all patients to 700cc of spared liver minus GTV 10.5 (0.2 – 38.2) Gy, with 58 patients (82.8%) meeting the Colorado dose sparing guideline – equivalent dose 19.5 Gy in 6 fractions (α/β 3). Two patients' albumin decreased (CP score increase from A5 to A6) at 1 month, reversed at 3 months. Another developed a sustained decrease in albumin at 3 months. Liver enzyme toxicity up to 3 months post SBRT (Table 1) occurred in 43 patients (61%). There were no incidences of radiation induced liver disease. One patient had grade 3 ALP toxicity at 1 month that resolved at 3 months. On univariate analysis there was a trend to significance for dose to spared 700cc of liver and enzyme toxicity (P = 0.08). On multivariate analysis dose to spared 700cc was statistically significant (P = 0.025) and there was a trend to significance for prior liver surgery (P = 0.29) or BioNTCP (P = 0.21) and toxicity. No factors correlated with worsening of CP score. These results suggest that dose to 700cc of spared liver may be associated with acute liver enzyme abnormality. This dosimetric parameter has potential implications for future liver SBRT planning and ongoing clinical management.Tabled 1Abstract 2494; Table 1. Liver enzyme toxicityGradeBaseline Number of events1 month Number of events3 months Number of eventsAST/ALT0989267139443022553100ALP0514628116202022333110 Open table in a new tab