Organs At Risk Dose Constraints Research Articles

CT-guided online adaptive stereotactic body radiotherapy for pancreas ductal adenocarcinoma: Dosimetric and initial clinical experience

Purpose/ObjectivesRetrospective analysis suggests that dose escalation to a biologically effective dose of more than 70 Gy may improve overall survival in patients with pancreatic ductal adenocarcinoma (PDAC), but such treatments in practice are limited by proximity of organs at risk (OARs). We hypothesized that CT-guided online adaptive radiotherapy (OART) can account for interfraction movement of OARs and allow for safe delivery of ablative doses. Materials/MethodsThis is a single institution retrospective analysis of patients with PDAC treated with OART on the Ethos platform (Varian Medical Systems, a Siemens Healthineers Company, Palo Alto). All patients were treated to 40 Gy in 5 fractions. PTV overlapping with a 5 mm planning risk volume expansion on the stomach, duodenum and bowel received 25 Gy. Initial treatment plans were created conventionally. For each fraction, PTV and OAR volumes were recontoured with AI assistance after initial cone beam CT (CBCT). The adapted plan was calculated, underwent QA, and then compared to the scheduled plan. A second CBCT was obtained prior to delivery of the selected plan. Total treatment time (first CBCT to end of radiation delivery) and active physician time (first to second CBCT) were recorded. PTV_4000 V95 %, PTV_2500 V9 5%, and D0.03 cc to stomach, duodenum and bowel were reported for scheduled (S) and adapted (A) plans. CTCAEv5.0 toxicities were recorded. Statistical analysis was performed using a two-sided T test and α of 0.05. Results21 patients with unresectable or locally-recurrent PDAC were analyzed, with a total of 105 fractions. Average total time was 29 min and 16 s (16:36–49:40) and average active physician time was 19:41 min (9:25–39:34). All fractions were treated with adapted plans. 97 % of adapted plans met PTV_4000 V95.0 % >95.0 % coverage goal and 100 % of adapted plans met OAR dose constraints. Median follow up was 6.6 months. Only 1 patient experienced acute grade 3+ toxicity directly attributable to radiation. Only 1 patient experienced late grade 3+ toxicity directly attributable to radiation. ConclusionsDaily CT-based OART was associated with significantly reduced dose OARs while achieving superior PTV coverage. Given the relatively quick total treatment time, radiation delivery was generally well tolerated and easily incorporated into the clinic workflow. Our initial clinical experience demonstrates OART allows for safe dose escalation in the treatment of PDAC.

Feasibility and constraints of Bragg peak FLASH proton therapy treatment planning.

FLASH proton therapy (FLASH-PT) requires ultra-high dose rate (≥40 Gy/s) protons to be delivered in a short timescale whilst conforming to a patient-specific target. This study investigates the feasibility and constraints of Bragg peak FLASH-PT treatment planning, and compares the in silico results produced to plans for intensity modulated proton therapy (IMPT). Bragg peak FLASH-PT and IMPT treatment plans were generated for bone (n=3), brain (n=3), and lung (n=4) targets using the MIROpt research treatment planning system and the Conformal FLASH library developed by Applications SA from the open-source version of UCLouvain. FLASH-PT beams were simulated using monoenergetic spot-scanned protons traversing through a conformal energy modulator, a range shifter, and an aperture. A dose rate constraint of ≥ 40 Gy/s was included in each FLASH-PT plan optimisation. Space limitations in the FLASH-PT adapted beam nozzle imposed a maximum target width constraint, excluding 4 cases from the study. FLASH-PT plans did not satisfy the imposed target dose constraints (D95% ≥ 95% and D2%≤ 105%) but achieved clinically acceptable doses to organs at risk (OARs). IMPT plans adhered to all target and OAR dose constraints. FLASH-PT plans showed a reduction in both target homogeneity (p < 0.001) and dose conformity (non-significant) compared to IMPT. Without accounting for a sparing effect, IMPT plans were superior in target coverage, dose conformity, target homogeneity, and OAR sparing compared to FLASH-PT. Further research is warranted in treatment planning optimisation and beam delivery for clinical implementation of Bragg peak FLASH-PT.

Dosimetric comparison of hippocampal-sparing technologies in patients with low-grade glioma.

Radiotherapy (RT) plays an integral role in the management of low-grade gliomas (LGG). Late toxicity from RT can cause progressive neurocognitive dysfunction. Radiation-induced damage to the hippocampus (HCP) plays a considerable role in memory decline. Advancements in photon planning software have resulted in the development of multi-criteria optimization (MCO) and HyperArc technologies which may improve HCP sparing while maintaining planning target volume (PTV) target coverage. Three planning methods for hippocampal sparing (HS) were compared, volumetric modulated arc therapy (VMAT) without HS (VMAT_noHS), VMAT with HS (VMAT_HS), MCO with HS (MCO_HS), and HyperArc with HS (HyperArc_HS). Twenty-five patients were identified. The contralateral HCP was spared in 16 patients and bilateral HCP in 9 patients with superiorly located tumors. All 3 HS planning techniques showed significant reductions in dose to the spared HCP in contralateral cases but only VMAT_HS and MCO_HS achieved this in bilateral cases (P < .008). Only MCO_HS was superior to VMAT_HS in lowering the dose to both contralateral HCP and bilateral HCP in all measured metrics (P < .008). PTV and OAR (organ at risk) dose constraints were achieved for all plans. This retrospective dosimetric study demonstrated the feasibility of HS for low-grade glioma. All 3 HS planning techniques achieved significant dose reductions to the spared contralateral hippocampus, but only MCO_HS and VMAT_HS achieved this in bilateral cases. MCO was superior to other planning techniques for sparing both bilateral and contralateral hippocampi.

Dosimetric Predictors of Toxicities and Quality of Life Following Two-Fraction Stereotactic Body Radiotherapy for Prostate Cancer.

There is emerging interest in two-fraction stereotactic body radiotherapy (2#SBRT) for localized prostate cancer. However, there is limited data to guide organs at risk (OAR) dose constraints in 2#SBRT. We aim to identify dosimetric predictors of toxicities and quality of life (QoL) using real life patient data from two prospective 2#SBRT trials. We included 60 patients who had 2#SBRT in the 2STAR (NCT02031328) and 2SMART (NCT03588819) phase 2 trials. The prescribed dose was 26Gy to the prostate +/- focal boost of 32Gy to the dominant intraprostatic lesions. Toxicities and QoL data were prospectively collected using CTCAEv4 and EPIC26 questionnaires. For QoL, we reported the minimal clinical important changes (MCIC), defined as changes in QoL score of >0.5 standard deviation from baseline QoL score. We evaluated the bladder, urethra, rectum, and penile bulb dosimetry (urethra dosimetry only available in 30 patients in 2SMART trial). Some of the dosimetric parameters were log-transformed to normalize the distribution. Cox regression was used to identify dosimetric predictors for acute and late grade ≥2 GU toxicities. Logistic regression was used to identify dosimetric predictors for late MCIC in urinary, bowel and sexual QoL domains. Backward stepwise selection was used to identify significant dosimetric parameters. For GU toxicities and urinary QoL, three additional clinical factors (age, prostate volume and IPSS) were included in the final model as confounding factors. Receiver operating characteristics curve was used to identify cut-off for significant dosimetric parameters. The median follow-up for the cohort was 56 months (range: 39-78 months). The cumulative acute and late grade ³2 GU toxicities were 62% (37/60) and 57% (34/60) respectively. No bladder or urethra dosimetric parameter was associated with acute grade ≥2 GU toxicities. Bladder D0.5cc was significant predictor of late grade ≥2 GU toxicities in univariate model (P = 0.05), but not in multivariate model. Baseline IPSS score was the single strongest predictor for late grade ≥2 GU toxicities (HR = 1.9; 95% CI = 1.1-3.4; P = 0.03). For late QoL outcomes, there were 36% (21/58), 28% (16/58), and 29% (17/58) of patients with MCIC in urinary, bowel and sexual QoL domains respectively. Bladder V10Gy was associated with late urinary MCIC in multivariate model after adjusting for clinical confounders (HR = 2.6, 95% CI = 1.1-6.6; P = 0.04). 48% (14/29) and 24% (7/29) of patients with bladder V10Gy>13.9% and V10Gy≤13.9% respectively had late urinary MCIC. No rectum and penile bulb dosimetry parameters was identified to be associated with late bowel or sexual QoL. Using real life patient data from prospective clinical trials with medium term follow-up, we identified statistically significant bladder dosimetry parameter predictive of late urinary QoL. This finding could be useful to guide OAR dose constraints in prostate 2#SBRT trials.

Dosimetric Impact of Systematic Mediastinal Staging via Endobronchial Ultrasound for Patients with Locally Advanced Lung Cancer: The SEISMIC Trial

The SEISMIC trial aims to find the best method for mediastinal staging in patients with lung cancer receiving chemoradiotherapy. Currently, CT or PET-CT scans are standard in clinical practice, but histological evaluation of the mediastinum is performed on a case-by-case basis. The study will examine the effect of systematic histological evaluation using Endobronchial Ultrasound (EBUS) on radiotherapy target volumes. The hypothesis of this study is that differences in staging between the diagnostic PET-CT and EBUS would result in reduced tumor coverage and/or increased doses to organs at risk (OAR). SEISMIC is a prospective multicenter international cohort study. Patients were enrolled from Australia, the Netherlands, USA and Canada after regional IRB approvals. Patients were treated with 4DCT simulation. Two iGTV and PTV target volumes were delineated for each patient with discordant staging according to both PET-CT and EBUS, as were OARs. Two VMAT plans were generated for each patient based on either PET-CT or EBUS target volumes using knowledge-based planning methodology. Plans aimed to achieve institutional guidelines for target coverage and OAR dose constraints, with a prescribed dose of 60 Gy in 30 fractions. Target coverage and OAR doses for the PET- and EBUS-defined volumes were compared. In 156 patients, EBUS showed a larger extent of disease than PET in 18 (11.5%) and a smaller extent of lymph node (LN) involvement than PET in 49 (31.4%). Out of 67 patients with PET-EBUS discordant results, 25 underwent upfront radiotherapy and were included in the study. EBUS revealed PET-occult LN involvement in 11/25 patients (44%). In these patients, 10/11 patients received <95% of the prescribed dose to PET-occult LN iGTVs; the median [range] minimum dose to the EBUS iGTV was 9.2 Gy [0.1 - 57.9 Gy]. When planning based on EBUS LN involvement, all patients received ≥95% of the prescribed dose to the iGTV (the median [range] minimum dose to the EBUS iGTV was 58.9 Gy [58.1 - 60.5 Gy]). This resulted in increased median [range] doses to OARs; mean lung dose increased by 1.1 Gy [0.3 - 8.4 Gy], esophagus mean dose increased by 3.6 Gy [0.2 - 24.8 Gy], and mean heart dose increased by 0.5 Gy [-0.6 - 8.5 Gy]. Systematic endoscopic evaluation of the mediastinum had a significant effect on tumor coverage in a clinically meaningful proportion of cases and consequent plan adaptation impacted on organ-at-risk (OAR) doses. Results suggest systematic mediastinal LN staging should be considered in all patients prior to curative-intent radiotherapy. ACTRN12617000333314.

CT-Guided Online Adaptive Stereotactic Body Radiotherapy for Pancreas Ductal Adenocarcinoma: Dosimetric and Initial Clinical Experience

Retrospective analysis suggests that dose escalation to a biologically effective dose of more than 70 Gy may improve overall survival in patients with pancreatic ductal adenocarcinoma (PDAC), but such treatments in practice are limited by proximity of organs at risk (OARs). We hypothesized that CT-guided online adaptive radiotherapy (OART) can account for interfraction movement of OARs, reduce dose to OARs, and improve coverage of targets. This is a single institution retrospective analysis of patients with PDAC treated with OART on a CBCT-based OART platform. All patients were treated to 40 Gy in 5 fractions. PTV overlapping with a 5 mm planning risk volume expansion on the stomach, duodenum and bowel received 25 Gy. Initial treatment plans were created conventionally. For each fraction, PTV and OAR volumes were recontoured with AI assistance after initial cone beam CT (CBCT). The adapted plan was calculated, underwent QA, and then compared to the scheduled plan. A second CBCT was obtained prior to delivery of the selected plan. Total treatment time (first CBCT to end of radiation delivery) and active physician time (first to second CBCT) were recorded. PTV_4000 V95%, PTV_2500 V95%, and D0.03 cc to stomach, duodenum and bowel were reported for scheduled (S) and adapted (A) plans. CTCAEv5.0 toxicities were recorded. Statistical analysis was performed using a two-sided T test and α of 0.05. Seven patients with unresectable or locally-recurrent PDAC were analyzed, with a total of 35 fractions. Average total time was 33:00 minutes (22:25-49:40) and average active time was 22:48 minutes (14:15-39:34). All fractions were treated with adapted plans. All adapted plans met PTV_4000 V95.0% > 95.0% coverage goal and OAR dose constraints. Dosimetric data for scheduled and adapted plans per fraction are in Table 1. Median follow up was 1.7 months. 5 (71%) patients experienced either Grade 1 or 2 toxicities. No patients experienced Grade 3+ toxicities. Daily OART significantly reduced dose OARs while achieving superior PTV coverage. Treatment was generally well tolerated with no grade 3+ acute toxicity, and required only 22:48 minutes on average of active physician time. Our initial clinical experience demonstrates OART allows for safe dose escalation in the treatment of PDAC.

Dosimetric Plan Evaluation of Biology Guided Radiotherapy Using [18F]-DCFPyL PSMA Radiotracer in Patients with Prostate Cancer

The X1 system represents a cutting-edge solution in radiotherapy delivery, with its capability to perform Biology Guided Radiotherapy (BgRT). The system utilizes real-time positron emission tomography (PET) signal as biological fiducials to provide tracked dose delivery and is initially available for use with [18F]-Fluorodeoxyglucose (FDG). The aim of this research study is to assess the quality of BgRT treatment plans for prostate cancer using patients' PSMA PET images obtained on the X1 system. Sixteen patients with at least one PET-avid tumor identified on their whole-body diagnostic PSMA PET scan were selected. These patients were scanned on X1 following their diagnostic scan without additional radiotracer administration. Based on the X1 PET images, a BgRT plan was created for each patient, with the prescription dose determined by the location of treatment sites. The planning objectives of organs-at-risk (OARs) were established in accordance with the 2018 Timmerman guidelines. Target coverage objective was the dose covering 95% (D95%) of the planning target volume (PTV) to be higher than 100%. The following parameters were analyzed: PTV D95%, the minimal dose (Dmin) of gross tumor volume (GTV), plan maximum dose (Dmax), conformity index (CI), gradient index (GI), and maximum point dose (D0.03cc) to the nearest OARs. The X1 BgRT planning system also generated dose volume histogram (DVH) bounds, which model variations in BgRT delivery. The low boundary of GTV Dmin, representing the minimum GTV dose in the worst-case scenario, was recorded. BgRT plans were created for all patients, except for one where the target signal was indistinguishable from the bladder. The prescription dose was 2700 cGy or 3000 cGy in 3 fractions for lymph node lesions, 2400 cGy to 3000 cGy in 3 fractions for bone metastasis, and 4500 cGy in 5 fractions for lesions in prostate. All plans met the dose constraints for OARs as per the Timmerman guidelines. The Dmax of all plans was 129.9% ± 6.9% (mean ± standard deviation). The PTV D95% and GTV Dmin were 101.7% ± 1.0% and 111.0% ± 7.6%, respectively. The low boundary of GTV Dmin was 95.9% ± 5.8%. The CI and GI were 1.22 ± 0.11 and 9.40 ± 2.12, respectively. The D0.03cc to nearest OARs was 84.6% ± 25.4%. The estimated treatment time was 699 ± 228 seconds. This study is a pioneering effort to evaluate the quality of BgRT plans for prostate cancer patients using the [18F]-DCFPyL PSMA radiotracer. Our results showed that all BgRT plans met the planning objectives defined in the Timmerman protocol. BgRT with [18F]-DCFPyL represents a promising treatment modality for patients with prostate cancer. Further research is needed to validate this approach, including a comprehensive assessment of the dosimetric and tracking accuracy through physical measurements.

Adaptive Dose-Staged Stereotactic Ablative Body Radiotherapy for Treatment of Large Central NSCLC Lung Tumors: A Dosimetric Simulation Study

Adaptive dose-staged Stereotactic Radiosurgery (SRS) treatment of cranial AVM and personalized ultrafractionated stereotactic ablative radiotherapy (PULSAR) proposed by Timmerman et al. for lung cancer has been shown to be an effective technique with lower toxicities in the management of large lesions. The PULSAR technique requires periodic functional PET imaging or tumor biopsy more than one week apart post stereotactic ablative body radiotherapy (SABR) PULSE to utilize the tumor biological response feedback to delineate the residual active disease for subsequent (SABR) PULSES' adaptive treatment planning. The purpose of this study is to explore dosimetrically the benefit of SABR PULSES for the treatment of large central lungs tumors. A retrospective simulation study of five anonymized patients with large NSCLC was performed. Tumors were located centrally in left (N = 3) and right (N = 2) lungs. The PTVs generated by 5mm symmetric margin to the ITV, the ITV and PTV volumes were 30.0±21.4cc (10.6-64.5cc) and 65.4±35.2cc (30.7-121.0cc), respectively. Depending on the total PTV volume, 4 other adaptive PTVs were simulated by generating a symmetric reduction of the PTV volumes by 2 or 3mm assuming given enough time shrinking the original volume after each PULSE due to biological response during the time between the initial and subsequent SABR PULSES. The organs-at-risk (OARs) were contoured and 3 VMAT arcs plans were generated and optimized for each PTV with the same VMAT objective functions. The original PTV plan with 50 Gy in 5 consecutive fractions was compared with the sum of the 5 PULSES in 10 Gy per PULSE with adaptive volumes. A statistical analysis and a paired t-test of the 50 Gy plan in 5 consecutive fractions were compared with the 5 PULSES summed dose for the ITV, PTV, and the OARs. The t-test showed the 5 PULSES plans significantly lowered the doses to the ipsilateral, and contralateral lungs and heart when compared to 5 consecutive 10 Gy/fraction plans (p-Values, 0.031, 0.01, 0.02, respectively). The 11 Gy ipsilateral lung volume, a precursor for developing normal lung tissue fibrosis about one-year post SABR was significantly lower for the 5 PULSES (136±44cc Vs. 241±83cc) (p-Value, 0.01). The mean and maximum dose to the original PTV was significantly lower in 5 PULSES technique (p-Value, 0.0001, 0.046). The dose to the spinal canal was not statistically different between the two techniques (p-Value, 0.12). The current management of large central lung tumors is conventional fractionation with chemotherapy or delivering lower fractional SABR dose to meet the OAR dose constraints that may hinder the successful radioablation and local control. The PULSAR treatments using SABR dosimetrically provides significant sparing of normal tissue. Dose escalation for larger central lung tumors may be possible using this technique for effective local control and better overall survivorship.

Stereotactic body radiation therapy (SBRT) following Yttrium-90 (90Y) selective internal radiation therapy (SIRT): a feasibility planning study using 90Y delivered dose

Objective. 90Y selective internal radiation therapy (SIRT) treatment of hepatocellular carcinoma (HCC) can potentially underdose lesions, as identified on post-therapy PET/CT imaging. This study introduces a methodology and explores the feasibility for selectively treating SIRT-underdosed HCC lesions, or lesion subvolumes, with stereotactic body radiation therapy (SBRT) following post-SIRT dosimetry. Approach. We retrospectively analyzed post-treatment PET/CT images of 20 HCC patients after 90Y SIRT. Predicted tumor response from SIRT was quantified based on personalized post-therapy dosimetry and corresponding response models. Predicted non-responding tumor regions were then targeted with a hypothetical SBRT boost plan using a framework for selecting eligible tumors and tumor subregions. SBRT boost plans were compared to SBRT plans targeting all tumors irrespective of SIRT dose with the same prescription and organ-at-risk (OAR) objectives. The potential benefit of SIRT followed by a SBRT was evaluated based on OAR dose and predicted toxicity compared to the independent SBRT treatment. Main results. Following SIRT, 14/20 patients had at least one predicted non-responding tumor considered eligible for a SBRT boost. When comparing SBRT plans, 10/14 (71%) SBRTboost and 12/20 (60%) SBRTalone plans were within OAR dose constraints. For three patients, SBRTboost plans were within OAR constraints while SBRTalone plans were not. Across the 14 eligible patients, SBRTboost plans had significantly less dose to the healthy liver (decrease in mean dose was on average ± standard deviation, 2.09 Gy ± 1.99 Gy, ) and reduced the overall targeted PTV volume (39% ± 21%) compared with SBRTalone. Significance. A clinical methodology for treating HCC using a synergized SIRT and SBRT approach is presented, demonstrating that it could reduce normal tissue toxicity risk in a majority of our retrospectively evaluated cases. Selectively targeting SIRT underdosed HCC lesions, or lesion subvolumes, with SBRT could improve tumor control and patient outcomes post-SIRT and allow SIRT to function as a target debulking tool for cases when SBRT is not independently feasible.

Dose Escalation for Pancreas SBRT: Potential and Limitations of using Daily Online Adaptive Radiation Therapy and an Iterative Isotoxicity Automated Planning Approach

To determine the dosimetric limitations of daily online adaptive pancreas stereotactic body radiation treatment by using an automated dose escalation approach. We collected 108 planning and daily computed tomography (CT) scans from 18 patients (18 patients×6 CT scans) who received 5-fraction pancreas stereotactic body radiation treatment at MD Anderson Cancer Center. Dose metrics from the original non-dose-escalated clinical plan (non-DE), the dose-escalated plan created on the original planning CT (DE-ORI), and the dose-escalated plan created on daily adaptive radiation therapy CT (DE-ART) were analyzed. We developed a dose-escalation planning algorithm within the radiation treatment planning system to automate the dose-escalation planning process for efficiency and consistency. In this algorithm, the prescription dose of the dose-escalation plan was escalated before violating any organ-at-risk (OAR) dose constraint. Dose metrics for 3 targets (gross target volume [GTV], tumor vessel interface [TVI], and dose-escalated planning target volume [DE-PTV]) and 9 OARs (duodenum, large bowel, small bowel, stomach, spinal cord, kidneys, liver, and skin) for the 3 plans were compared. Furthermore, we evaluated the effectiveness of the online adaptive dose-escalation planning process by quantifying the effect of the interfractional dose distribution variations among the DE-ART plans. The median D95% dose to the GTV/TVI/DE-PTV was 33.1/36.2/32.4 Gy, 48.5/50.9/40.4 Gy, and 53.7/58.2/44.8 Gy for non-DE, DE-ORI, and DE-ART, respectively. Most OAR dose constraints were not violated for the non-DE and DE-ART plans, while OAR constraints were violated for the majority of the DE-ORI patients due to interfractional motion and lack of adaptation. The maximum difference per fraction in D95%, due to interfractional motion, was 2.5 ± 2.7 Gy, 3.0 ± 2.9 Gy, and 2.0 ± 1.8 Gy for the TVI, GTV, and DE-PTV, respectively. Most patients require daily adaptation of the radiation planning process to maximally escalate delivered dose to the pancreatic tumor without exceeding OAR constraints. Using our automated approach, patients can receive higher target dose than standard of care without violating OAR constraints.

Delivery of a VMAT technique with flattening filter (FF) and flattening filter free (FFF) mode for whole breast irradiation with five fractions (FAST-Forward trial).

To investigate the feasibility of volumetric modulated arc therapy (VMAT) delivery for whole breast irradiation with a 5-fraction regimen according to the FAST-Forward trial. Recently, we treated 10 patients with carcinoma of the left breast after breast conserving surgery. The dose prescription to the PTV was 26 Gy in 5 fractions. Treatment plans were produced using a VMAT technique with the Eclipse treatment planning system for 6 MV flattening filter (FF) and FF free (FFF) beams. Dose volume histograms (DVHs) for the PTV and the organs at risk (OARs), the ipsilateral lung and heart, were compared with the dose constraints specified in the FAST-Forward trial (PTV, D95 > 95%, D5 < 105%, D2 < 107% and Dmax < 110%; ipsilateral lung, D15 < 8Gy; Heart, D30 < 1.5Gy and D5 < 7Gy). Furthermore, conformity index (CI), homogeneity index (HI) and dose to the heart, contralateral lung, contralateral breast, and left anterior descending artery (LAD), were also assessed. Mean ± SD D95(%), D5(%), D2(%), and Dmax (%) for PTV were 97.75 ± 1.12, 105.2 ± 0.82, 105.90 ± 0.89, 109.36 ± 1.00 (FF) and 96.46 ± 0.75, 103.97 ± 0.97, 104.70 ± 1.09, 108.58 ± 1.33 (FFF) respectively. The mean ± SD CI was 1.07 ± 0.05 (FF), 1.048 ± 0.06 (FFF) and HI was 0.11 ± 0.02 (FF), 0.10 ± 0.02 (FFF). Dose constraints for OARs were met for both treatment techniques. However, D15 (Gy) for ipsilateral lung was 3.0% lower with FFF beams. In contrast, D5 (Gy) for heart was 9.0% higher with FFF beams. The dose difference between FF and FFF beams for other OARs such as contralateral lung-D10 (Gy) contralateral breast-D5 (Gy) and LAD was up to 6.0%. Both FF and FFF methods met the acceptable criteria. However, the treatment plans with FFF mode were more conformal and provided greater target homogeneity.

Comparing Ultra-hypofractionated Proton versus Photon Therapy in Extremity Soft Tissue Sarcoma.

Recent single institution, phase II evidence has demonstrated the feasibility and efficacy of ultra-hypofractionated, preoperative photon therapy in 5 fractions for the treatment of soft tissue sarcoma (STS). Our purpose was to evaluate the dosimetric benefits of modern scanning beam proton therapy compared with conventional photon radiation therapy (RT) for the neoadjuvant treatment of adult extremity STS. Existing proton and photon plans for 11 adult patients with STS of the lower extremities previously treated preoperatively with neoadjuvant RT at our center were used to create proton therapy plans using Raystation Treatment Planning System v10.A. Volumes were delineated, and doses reported consistent with International Commission on Radiation Units and Measurements reports 50, 62, and 78. Target volumes were optimized such that 100% clinical target volume (CTV) was covered by 99% of the prescription dose. The prescribed dose was 30 Gy for PT and RT delivered in 5 fractions. For proton therapy, doses are reported in GyRBE = 1.1 Gy. The constraints for adjacent organs at risk (OARs) within 1 cm of the CTV were the following: femur V30Gy ≤ 50%, joint V30Gy < 50%, femoral head V30Gy ≤ 5 cm3, strip V12 ≤ 10%, and skin V12 < 50%. Target coverage goals, OAR constraints, and integral dose were compared by Student t test with P < .05 significance. A minimum 99% CTV coverage was achieved for all plans. OAR dose constraints were achieved for all proton and photon plans; however, mean doses to the femur (10.7 ± 8.5 vs 16.1 ± 7.7 GyRBE), femoral head (2.0 ± 4.4 vs 3.6 ± 6.4 GyRBE), and proximal joint (1.8 ± 2.4 vs 3.5 ± 4.4 GyRBE) were all significantly lower with PT vs intensity-modulated radiation therapy (IMRT) (all P < .05). Integral dose was significantly reduced for proton vs photon plans. Conformity and heterogeneity indices were significantly better for proton therapy. Proton therapy maintained target coverage while significantly reducing integral and mean doses to the proximal organs at risk compared with RT. Further prospective investigation is warranted to validate these findings and potential benefit in the management of adult STS.

Hippocampal-sparing whole-brain radiotherapy under coplanar or noncoplanar VMAT.

Whole-brain radiotherapy (WBRT) can alleviate symptoms in patients with brain metastases. However, WBRT may damage the hippocampus. Volumetric modulated arc therapy (VMAT) can achieve a suitable coverage of the target region and a more conforming dose distribution whereas decreasing the dose to organs-at-risk (OARs). Herein, we aimed to compare the differences between treatment plans utilizing coplanar VMAT and noncoplanar VMAT in hippocampal-sparing WBRT (HS-WBRT). Ten patients were included in this study. For each patient, the Eclipse A10 treatment planning system was used to generate 1 coplanar VMAT (C-VMAT) and 2 noncoplanar VMAT treatment plans with various beam angles (noncoplanar VMAT A [NC-A] and noncoplanar VMAT B [NC-B]) for HS-WBRT. The prescribed dose was 30 Gy in 12 fractions. Treatment plans were established based on the OAR dose constraints of the Radiation Therapy Oncology Group 0933 (RTOG 0933). Parameters such as the global maximum dose, dose conformity, dose homogeneity of plans, and OAR doses were evaluated. The maximum biologically equivalent doses in 2-Gy fractions (EQD2) of OARs in C-VMAT were 9.17 ± 0.61, 42.79 ± 2.00, and 42.84 ± 3.52 Gy in the hippocampus, brain stem, and optic chiasm, respectively, which were the lowest among the 3 treatment plans. There was no significant difference in dose conformity among the 3 treatment plans. However, NC-A had a slightly better conformity than C-VMAT and NC-B. NC-A had the best homogeneity, and NC-B had the worst homogeneity (p = 0.042). NC-A and NC-B had the lowest and highest global dose maximum, respectively. Therefore, NC-A, which had an intermediate performance in terms of OAR doses, had the best quality parameters. We used the quality score table based on the p-value to evaluate the significant difference between each treatment technique from the multiparameter results. In terms of treatment plan parameters, only NC-A received a score of 2; for OAR doses, C-VMAT, NC-A, and NC-B received a score of 6, 3, and 5, respectively. For the overall evaluation, C-VMAT, NC-A, and NC-B received a total score of 6, 5, and 5, respectively. Rather than noncoplanar VMAT, 3 full-arc C-VMATs should be utilized in HS-WBRT. C-VMAT can simultaneously maintain treatment plan quality and decrease patient alignment time and total treatment time.

PO31 Presentation Time: 10:30 AM: Dosimetric Evaluation of Normal Tissue Sparing in MRI Guided Adaptive Brachytherapy with Replan at Each Treatment Fraction in Cervix HDR Brachytherapy

<h3>Purpose</h3> Evaluate target and organ at risk (OAR) dosimetric benefit with replan at each treatment fraction in MRI guided adaptive brachytherapy (MRIGABT) for cervix cancer. <h3>Materials and Methods</h3> Radiotherapy treatment planning MRI (RTPMRI) were acquired before each brachytherapy fraction (1-4), in 10 patients treated with intrauterine brachytherapy (IUB) using the Venezia^TM applicator. Each patient had 2 IUB applicator insertions and received 28 Gy/4# following EBRT 25 Gy/25# (EMBRACE II protocol)¹. A replan based on anatomy on MRI acquired on day 2 (D2) of each IUB applicator insertion was planned and delivered (D2-replan). Total target and OAR dose was compared to conventional treatment where the treatment plan on day 1 of IUB applicator insertion is also delivered on day 2 (no replan). Total biologically equivalent doses for EBRT and brachytherapy were calculated in 2 Gy equivalents using the EQD2 equation and reported as total dose (Gy). <h3>Results</h3> Forty RTPMRI and IUB HDR treatment plans were analysed in 10 patients. The mean (±SD) total dose (EBRT + HRCTV 90) received for D2-replan and D2-no replan was 91.9 Gy (±2.3) and 90.5 Gy (±2.8). There was no statistically significant difference in target and OAR dose between D2-replan and no replan. But in individual patients there were clinically significant differences. No OAR dose constraints were exceeded with D2-replan, OAR dose constraints were exceeded in 5-20% of fractions when there was no replan (rectum 8/40#, sigmoid 2/40#, bowel 2/40# and bladder 2/40#). <h3>Conclusions</h3> Daily MRIGABT replan at each treatment fraction results in improved HRCTV dose and reduced OAR dose in some patients. With a replan, we saw consistent HRCTV D90 of >87 Gy, which is significantly associated with better disease control^2,3 especially in asymmetrical tumours. The additional resources required will not benefit all patients and selection criteria for patients who will benefit is required.

A Survey of Pediatric Clinical Trial Radiotherapy Dose Constraints

<h3>Purpose/Objective(s)</h3> Radiation therapy normal tissue dose constraints are critical when treating children with cancer due to the vulnerability of developing organs to toxicity and the many years over which these effects can evolve. Guidelines in international clinical trials have been instrumental in shaping how treatment plans are designed; however, consistency among organs at risk (OARs) constraints has not been previously evaluated. In this study we identify the variations in OAR-specific dose constraints within pediatric trials both in the United States (US) and in Europe. <h3>Materials/Methods</h3> All US pediatric trials from the COG website were included up until 1/1/2020 along with a sampling of European trials accessible in the Netherlands. Dose constraints were identified and built into an interactive web application with filters to display data by OAR, protocol, dose, volume, and fractionation scheme. Dose constraints were compared between pediatric US and European trials by graphical intercomparison and by comparing high dose constraints (maximum dose [Dmax] or dose to a volume ≤ 20%) and by dose metrics that were commonly used across protocols. <h3>Results</h3> Sixty-five trials were included with the US trials (53) represented by the COG/CCG/POG and the European trials (12) represented by the SIOP, EURAMOS, GPOH, DCOG, and EpSSG. Thirty-three separate OARs were found with high variability within the trials for each OAR, ranging from different maximum tolerable doses to variations of volumetric dose constraints. Seven organs had 10 to 18 different constraints and included serial organs such as the spinal cord, optic chiasm, optic nerves, and brainstem as well as parallel organs including the lungs, liver, and heart. An example of dose variability can be seen with the spinal cord Dmax constraint ranging from 50 Gy to V59 < 10%, the optic nerves constraint ranging from a Dmax of 45 Gy to 60 Gy, the heart V30 constraint ranging from 40-100%, and the kidney D50% constraint ranging from 8-24 Gy. When comparing high dose tolerances between US and European trials, US constraints were higher for four OARs—bladder (V70 < 20% vs Dmax < 60), lungs (V20 < 20% vs Dmax < 18), mandible (V77 < 1cc vs Dmax < 60), and spinal cord (V57 < 10% vs Dmax < 54); lower for four OARs—brainstem (V63 < 10% vs V64 < 10%), heart (Dmax < 30 vs Dmax < 30.6), kidneys (Dmax < 15 vs Dmax < 19.8), and liver (Dmax < 15 vs Dmax < 23.4); and identical in four OARs—brain, optic chiasm, optic nerves, and bowel. <h3>Conclusion</h3> Review of pediatric dose-volume constraints in clinical trials showed substantial variability for all OARs. Continued focus on standardization of OAR dose constraints and risk profiles are essential to improving clinical trial consistency and improving understanding of dose-response in the pediatric population.

Impact of Using Unedited CT-Based DIR-Propagated Autocontours on Online ART for Pancreatic SBRT.

PurposeTo determine the dosimetric impact of using unedited autocontours in daily plan adaptation of patients with locally advanced pancreatic cancer (LAPC) treated with stereotactic body radiotherapy using tumor tracking.Materials and MethodsThe study included 98 daily CT scans of 35 LAPC patients. All scans were manually contoured (MAN), and included the PTV and main organs-at-risk (OAR): stomach, duodenum and bowel. Precision and MIM deformable image registration (DIR) methods followed by contour propagation were used to generate autocontour sets on the daily CT scans. Autocontours remained unedited, and were compared to MAN on the whole organs and at 3, 1 and 0.5 cm from the PTV. Manual and autocontoured OAR were used to generate daily plans using the VOLO™ optimizer, and were compared to non-adapted plans. Resulting planned doses were compared based on PTV coverage and OAR dose-constraints.ResultsOverall, both algorithms reported a high agreement between unclipped MAN and autocontours, but showed worse results when being evaluated on the clipped structures at 1 cm and 0.5 cm from the PTV. Replanning with unedited autocontours resulted in better OAR sparing than non-adapted plans for 95% and 84% plans optimized using Precision and MIM autocontours, respectively, and obeyed OAR constraints in 64% and 56% of replans.ConclusionFor the majority of fractions, manual correction of autocontours could be avoided or be limited to the region closest to the PTV. This practice could further reduce the overall timings of adaptive radiotherapy workflows for patients with LAPC.

Predicting personalised and progressive adaptive dose escalation to gross tumour volume using knowledge-based planning models for inoperable advanced-stage non-small cell lung cancer patients treated with volumetric modulated arc therapy

Objectives. Increased radiation doses could improve local control and overall survival of lung cancer patients, however, this could be challenging without exceeding organs at risk (OAR) dose constraints, especially for patients with advanced-stage disease. Increasing OAR doses could reduce the therapeutic ratio and quality of life. It is therefore important to investigate methods to increase the dose to target volume without exceeding OAR dose constraints. Methods. Gross tumour volume (GTV) was contoured on synthetic computerised tomography (sCT) datasets produced using the Velocity adaptive radiotherapy software for eleven patients. The fractions where GTV volume decreased compared to that prior to radiotherapy (reference plan) were considered for personalised progressive dose escalation. The dose to the adapted GTV (GTVAdaptive) was increased until OAR doses were affected (as compared to the original clinical plan). Planning target volume (PTV) coverage was maintained for all plans. Doses were also escalated to the reference plan (GTVClinical) using the same method. Adapted, dose-escalated, plans were combined to estimate accumulated dose, D99 (dose to 99%) of GTVAdapted, PTV D99 and OAR doses and compared with those in the original clinical plans. Knowledge-based planning (KBP) model was developed to predict D99 of the adapted GTV with OAR doses and PTV coverage kept similar to the original clinical plans; prediction accuracy and model verification were performed using further data sets. Results. Compared to the original clinical plan, the dose to GTV was significantly increased without exceeding OAR doses. Adaptive dose-escalation increased the average D99 to GTVAdaptive by 15.1Gy and 8.7Gy compared to the clinical plans. The KBP models were verified and demonstrated prediction accuracy of 0.4% and 0.7% respectively. Conclusion. Progressive adaptive dose escalation can significantly increase the dose to GTV without increasing OAR doses or compromising the dose to microscopic disease. This may increase overall survival without increasing toxicities.

Impact of Irradiation Field Aperture Controller Settings on Patient-specific Quality Assurance

The aperture shape controller (ASC) is a tool on a radiation therapy planning system to reduce complexity by increasing the aperture size of multileaf collimator (MLC). The purposes of this study were to clarify the effect of the dose index on the treatment plan when the intensity of ASC is changed and then to clarify the effect on the verification result in the individual patient-specific quality assurance (QA) using the verification phantom. For four types of mock structures presented at AAPM TG-119, volumetric modulated arc therapy (VMAT) treatment plans with three dose levels were set without using the ASC for each of these four types. ASC settings were changed to very low, low, moderate, high and very high for the treatment plan, and the treatment plan was recreated without changing the planning target volume (PTV) and/or OAR dose constraints. The dose index of the treatment plan was then evaluated. The plan was also transferred by the true composite method to the assessment phantom, and patient-specific QA was evaluated. The frequency of dose constraint deviation by changing the ASC was 3.6% (2/55). In patient-specific QA, when the ASC setting was set to moderate, the γ analysis passing rate increased by 1.5% compared to the case without the ASC. In the treatment plan with a γ analysis pass rate of 95% or less without ASC, a 2.7% increase in the γ analysis pass rate was observed by setting the ASC to moderate. We found that setting the ASC tended to improve patient-specific QA. Compared to when the ASC was not set, the evaluation result of patient-specific QA was improved without violating the dose constraints of the PTV and/or organ at risk (OAR). In particular, the improvement was notable for the case where the evaluation result of patient-specific QA was 95% or less when the ASC was not used.

Comprehensive Evaluation of Carbon-Fiber-Reinforced Polyetheretherketone (CFR-PEEK) Spinal Hardware for Proton and Photon Planning.

Purpose: To evaluate a novel spine implant, carbon-fiber-reinforced polyetheretherketone (CFR-PEEK), for proton and photon treatment planning. Materials and Methods: We compared target coverage and sparing of organs-at-risk (OARs) for a spinal phantom with 4 different spine configurations: (a) normal (no implant); (b) Titanium; (c) CFR-PEEK; and (d) hybrid (CFR-PEEK with Titanium tulip head). The spinal phantom was imaged via computed tomography (CT) scan, and the iterative Metal Artifact Reduction (iMAR) CT set was used for planning. A representative spinal chordoma target and associated OARs were contoured. The prescription dose was 50 Gy to the initial target volume, followed by a 24 Gy boost, for which multi-field optimization (MFO) proton plans were developed with a 3 mm setup and 3.5% range uncertainties. For photon planning, volumetric modulated arc therapy (VMAT) plans were developed for the initial and boost plans. OAR dose constraints were set according to our institutional guidelines. Results: For the 4 spine configurations, the proton plans achieved similar nominal target coverage and OARs sparing. While evaluating coverage and OAR dose under uncertainty scenario analysis for initial clinical target volume (CTV) 50 Gy 95% and 90% coverage, higher means and the narrower band of doses variations were achieved for the normal and CFR-PEEK plans. Similarly, uncertainty analysis of spinal cord Dmax showed tighter distribution for normal and CFR-PEEK plans. Overall plan quality showed no significant difference for photon planning when compared to normal spine versus other inserts. However, for proton planning, there is a larger difference for the normal spine insert scenario versus the Titanium insert scenario. For each insert scenario comparison between photon and proton plans, there was a larger difference for OARs: heart and spinal cord. Conclusion: The CFR-PEEK implant has similar clinical properties to a normal spine for proton planning, allowing us to pass protons through the material and achieve superior target coverage and OAR sparing under nominal and uncertainty conditions.

Optimising tumour coverage and organ at risk sparing for hypofractionated re-irradiation in glioblastoma.

Background and purposeRe-irradiation may be used for recurrent glioblastoma (GBM) patients. In some cases Planning Target Volume (PTV) under-coverage is necessary to meet organ at risk (OAR) constraints. This study aimed to develop a Volumetric Modulated Arc Therapy planning solution for GBM re-irradiation including a means of assessing if target coverage would be achievable and how much PTV ‘cropping’ would be required to meet OAR constraints, based on PTV volume and OAR proximity.Materials and methodsFor 10 PTVs, 360°, 180°, two coplanar 180° and 180° + non-coplanar 45° arc arrangements were compared using 35 Gy in 10 fractions. Using the preferred arrangement, dose fall-off was modelled to determine the separation required between PTV and OAR to ensure OAR dose constraints were met, with data presented graphically. To evaluate the graph as an aid to planning, seven cases with overlap were replanned in two treatment planning systems (TPSs).ResultsThere were no significant dosimetric differences between arc arrangements. 180° was preferred due to shorter treatment times. The graph, which indicated if 95% PTV coverage would be achievable based on PTV volume and OAR proximity, was employed in seven cases to guide planning in two TPSs. Plans were deliverable.ConclusionsRe-irradiation treatment planning can be challenging, especially when PTV under-coverage is necessary. 180° was considered optimal. To assist in the planning process, graphical guidance was produced to inform planners whether PTV under-coverage would be necessary and how much PTV ’cropping’ would be required to meet constraints during optimisation.