Organs At Risk Constraints Research Articles

Prospective In Silico Evaluation of Cone-Beam Computed Tomography-Guided StereoTactic Adaptive Radiation Therapy (CT-STAR) for the Ablative Treatment of Ultracentral Thoracic Disease

PurposeWe conducted a prospective, in silico study to evaluate the feasibility of cone-beam computed tomography (CBCT)-guided stereotactic adaptive radiation therapy (CT-STAR) for the treatment of ultracentral thoracic cancers (NCT04008537). We hypothesized that CT-STAR would reduce dose to organs at risk (OARs) compared with nonadaptive stereotactic body radiation therapy (SBRT) while maintaining adequate tumor coverage. Methods and MaterialsPatients who were already receiving radiation therapy for ultracentral thoracic malignancies underwent 5 additional daily CBCTs on the ETHOS system as part of a prospective imaging study. These were used to simulate CT-STAR, in silico. Initial, nonadaptive plans (PI) were created based on simulation images and simulated adaptive plans (PA) were based on study CBCTs. 55 Gy/5 fractions was prescribed, with OAR constraint prioritization over PTV coverage under a strict isotoxicity approach. PI were applied to patients’ anatomy of the day and compared with daily PA using dose-volume histogram metrics, with selection of superior plans for simulated delivery. Feasibility was defined as completion of the end-to-end adaptive workflow while meeting strict OAR constraints in ≥80% of fractions. CT-STAR was performed under time pressures to mimic clinical adaptive processes. ResultsSeven patients were accrued, 6 with intraparenchymal tumors and 1 with a subcarinal lymph node. CT-STAR was feasible in 34 of 35 simulated fractions. In total, 32 dose constraint violations occurred when the PI was applied to anatomy-of-the-day across 22 of 35 fractions. These violations were resolved by the PA in all but one fraction, in which the proximal bronchial tree dose was still numerically improved through adaptation. The mean difference between the planning target volume and gross total volume V100% in the PI and the PA was –0.24% (–10.40 to 9.90) and –0.62% (–11.00 to 8.00), respectively. Mean end-to-end workflow time was 28.21 minutes (18.02-50.97). ConclusionsCT-STAR widened the dosimetric therapeutic index of ultracentral thorax SBRT compared with nonadaptive SBRT. A phase 1 protocol is underway to evaluate the safety of this paradigm for patients with ultracentral early-stage NSCLC.

The role of adaptive planning in margin-reduced, MRI-guided stereotactic body radiotherapy to the prostate bed following radical prostatectomy: Post-hoc analysis of a phase II clinical trial

Background and purposeWe examined the interfractional variations of clinical target volumes (CTVs), planning target volumes (PTVs), and organs-at-risk (OARs) in patients receiving MRI-guided stereotactic body radiotherapy (SBRT) to the prostate bed and evaluated the potential role of adaptive planning. Materials and Methods31 patients received 30–34 Gy in five fractions to the prostate bed on a phase II clinical trial. OARs, CTVs, and PTVs were retrospectively contoured on daily pretreatment MRIs (n = 155). Geometric comparisons were made between initial planning contours and daily pretreatment contours. Predicted treatment plans for each fraction were evaluated using the following constraints: CTV V95%>93%, PTV V95%>90%, bladder Dmax < 36.7 Gy, bladder V32.5 Gy < 35%, rectum Dmax < 36.7 Gy, rectum V27.5 Gy < 45%, rectum 32.5 Gy < 30%, and rectal wall V24Gy < 50%. Adaptive planning was simulated for all fractions that failed to meet these criteria. Plans were then re-evaluated. ResultsMedian change in volume was 0.48% for CTV, −24.5% for bladder, and 6.95% for rectum. Median DSC was 0.89 for CTV, 0.79 for bladder, and 0.76 for rectum. 145/155 fractions (93.5%) met CTV V95%>93%. 75/155 fractions (48.4%) failed at least one OAR dose constraint. Overall, 83/155 fractions (53.5%) met criteria for adapting planning. This affected 24/31 patients (77.4%). Following adaptive planning, all fractions met CTV V95%>93% and PTV V95%>90% and 120/155 fractions (77.4%) met all OAR constraints. ConclusionDue to significant interfractional variations in anatomy, a majority of fractions failed to meet both target volume and OAR constraints. However, adaptive planning was effective in overcoming these anatomic changes. Adaptive planning should be routinely considered in prostate bed SBRT.

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.

Prioritizing sufficient dose to gross tumor volume over normal tissue sparing in intensity-modulated radiotherapy treatment of T4 nasopharyngeal carcinoma.

In intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC), priority is often given minimize dose to the critical organs at risk (OARs) to avoid potential morbid sequelae. However, in T4 NPC, dosimetric inadequacy enforced by dose constraints on OARs may significantly impact tumor control. This was a single-institute cohort that patients diagnosed between July 2005 and December 2010 with T4 NPC treated with IMRT. All patients were re-classification according to the 7th-AJCC stage. Overall, the average doses such as Dmax , D1% , D2% and D1cc for various Central nervous system (CNS) OARs including brainstem, optic nerve, chiasm, temporal lobes and spinal cord were found to exceed published guidelines as RTOG0225. However, no clinical toxicities were seen during the follow-up period except for 13% patients with temporal lobe necrosis. Our retrospective review showed that its feasible to maximize gross tumor volume dose coverage while exceeding most CNS OAR constraint standards, with ideal local control and no obvious increase of craniocerebral toxicity.

The effect of integrating knowledge-based planning with multicriteria optimization in treatment planning for prostate SBRT.

Knowledge-based planning (KBP) and multicriteria optimization (MCO) are two powerful tools to assist treatment planners in achieving optimal target coverage and organ-at-risk (OAR) sparing. The purpose of this work is to investigate if integrating MCO with conventional KBP can further improve treatment plan quality for prostate cancer stereotactic body radiation therapy (SBRT). A two-phase study was designed to investigate the impact of MCO and KBP in prostate SBRT treatment planning. The first phase involved the creation of a KBP model based on thirty clinical SBRT plans, generated by manual optimization (KBP_M). A ten-patient validation cohort was used to compare manual, MCO, and KBP_M optimization techniques. The next phase involved replanning the original model cohort with additional tradeoff optimization via MCO to create a second model, KBP_MCO. Plans were then generated using linear integration (KBP_M+MCO), non-linear integration (KBP_MCO), and a combination of integration methods (KBP_MCO+MCO). All plans were analyzed for planning target volume (PTV) coverage, OAR constraints, and plan quality metrics. Comparisons were generated to evaluate plan and model quality. Phase 1 highlighted the necessity of KBP and MCO in treatment planning, as both optimization methods improved plan quality metrics (Conformity and Heterogeneity Indices) and reduced mean rectal dose by 2Gy, as compared to manual planning. Integrating MCO with KBP did not further improve plan quality, as little significance was seen over KBP or MCO alone. Principal component score (PCS) fitting showed KBP_MCO improved bladder and rectum estimated and modeled dose correlation by 5% and 22%, respectively; however, model improvements did not significantly impact plan quality. KBP and MCO have shown to reduce OAR dose while maintaining desired PTV coverage in this study. Further integration of KBP and MCO did not show marked improvements in treatment plan quality while requiring increased time in model generation and optimization time.

Should organs at risk (OARs) be prioritized over target volume coverage in stereotactic ablative radiotherapy (SABR) for oligometastases? a secondary analysis of the population-based phase II SABR-5 trial

Background and PurposeStereotactic ablative radiotherapy (SABR) for oligometastases may improve survival, however concerns about safety remain. To mitigate risk of toxicity, target coverage was sacrificed to prioritize organs-at-risk (OARs) during SABR planning in the population-based SABR-5 trial. This study evaluated the effect of this practice on dosimetry, local recurrence (LR), and progression-free survival (PFS). MethodsThis single-arm phase II trial included patients with up to 5 oligometastases between November 2016 and July 2020. Theprotocol-specified planning objective was to cover 95 % of the planning target volume (PTV) with 100 % of the prescribed dose, however PTV coverage was reduced as needed to meet OAR constraints. This trade-off was measured using the coverage compromise index (CCI), computed as minimum dose received by the hottest 99 % of the PTV (D99) divided by the prescription dose. Under-coverage was defined as CCI < 0.90. The potential association between CCI and outcomes was evaluated. Results549 lesions from 381 patients were assessed. Mean CCI was 0.88 (95 % confidence interval [CI], 0.86–0.89), and 196 (36 %) lesions were under-covered. The highest mean CCI (0.95; 95 %CI, 0.93–0.97) was in non-spine bone lesions (n = 116), while the lowest mean CCI (0.71; 95 % CI, 0.69–0.73) was in spine lesions (n = 104). On multivariable analysis, under-coverage did not predict for worse LR (HR 0.48, p = 0.37) or PFS (HR 1.24, p = 0.38). Largest lesion diameter, colorectal and ‘other’ (non-prostate, breast, or lung) primary predicted for worse LR. Largest lesion diameter, synchronous tumor treatment, short disease free interval, state of oligoprogression, initiation or change in systemic treatment, and a high PTV Dmax were significantly associated with PFS. ConclusionPTV under-coverage was not associated with worse LR or PFS in this large, population-based phase II trial. Combined with low toxicity rates, this study supports the practice of prioritizing OAR constraints during oligometastatic SABR planning.

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.

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.

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.

Stereotactic magnetic resonance-guided online adaptive radiotherapy of adrenal metastases combines high ablative doses with optimized sparing of organs at risk

Purpose/ObjectiveTo evaluate the potential of stereotactic magnetic resonance-guided online adaptive radiotherapy (SMART) to fulfill dose recommendations for stereotactic body radiotherapy (SBRT) of adrenal metastases and spare organs at risk (OAR). Materials and methodsIn this subgroup analysis of a prospective registry trial, 22 patients with adrenal metastases were treated on a 0.35 T MR-Linac in 5–12 fractions with fraction doses of 4–10 Gy. Baseline plans were re-calculated to the anatomy of the day. These predicted plans were reoptimized to generate adapted plans. Baseline, predicted and adapted plans were compared with regard to PTV objectives, OAR constraints and published dose recommendations. ResultsThe cohort comprised patients with large GTV (median 36.0 cc) and PTV (median 66.6 cc) and predominantly left-sided metastases. 179 of 181 fractions (98.9 %) were adapted because of PTV and/or OAR violations. Predicted plans frequently violated PTV coverage (99.4 %) and adjacent OAR constraints (bowel: 32.9 %, stomach: 32.8 %, duodenum: 10.4 %, kidneys: 10.8 %). In the predicted plans, the volume exposed to the maximum dose was exceeded up to 16-fold in the duodenum and up to 96-fold in the spinal cord. Adapted plans significantly reduced OAR violations by 96.4 % for the bowel, 98.5 % for the stomach, 85.6 % for the duodenum and 83.3 % for the kidneys. Plan adaptation improved PTV coverage from 82.7 ± 8.1 % to 90.6 ± 4.9 % (p < 0.001). Furthermore, recently established target volume thresholds could easily be fulfilled with SMART. No toxicities > grade II occurred. ConclusionSMART fulfills established GTV and PTV dose recommendations while simultaneously sparing organs at risk even in a challenging cohort.

Dosimetric Implications of Margin-Reduced MRI-Guided Stereotactic Body Radiotherapy to the Prostate Bed Following Radical Prostatectomy: Post-Hoc Analysis of a Phase II Study

<h3>Purpose/Objective(s)</h3> Due to the highly deformable and mobile nature of the target volume and adjacent organs at risk (OARs), generous planning target volume (PTV) margins have historically been used in the context of radiotherapy after radical prostatectomy. MRI-guided radiotherapy systems have improved on-board imaging capabilities and the ability to perform automatic beam holds based on pre-specified structures. Herein, we evaluate the dosimetric implications of interfraction variations in the clinical target volumes (CTV) and OARs in patients receiving margin-reduced MRI-guided stereotactic body radiotherapy (SBRT) to the prostate bed. <h3>Materials/Methods</h3> 31 consecutive patients received MRI-guided SBRT to the prostate bed (30 – 34 Gy in 5 fractions) without adaptive planning on a phase II study. The OAR volumes, CTV, and PTV (created using a 3 mm isotropic expansion of the CTV) were retrospectively contoured on on-board 0.35T MRIs obtained prior to each fraction (n=155). Geometric comparisons were made between the initial planning contours and the 5 daily contours for each patient using change in volume and Dice similarity coefficient (DSC) calculations. Coverage of the CTV and PTV was assessed (CTV V95% >93% and PTV V95% >90%), as were bladder and rectal dose constraints (Bladder Dmax <36.7 Gy, Bladder V32.5 Gy <35%, Rectum Dmax <36.7 Gy, Rectum V27.5 Gy <45%, Rectum 32.5 Gy <30%, and Rectal Wall V24 <50%). <h3>Results</h3> The median change in volume was -24.5% (interquartile range [IQR], -35.5 – -2.2%) for the bladder, 6.95% (IQR, -6.94 – 23.0%) for the rectum, -0.2% (IQR, -8.3 – 8.7%) for the rectal wall, 0.48% (IQR, -3.87 – 7.6%) for the CTV, and -0.48% (IQR, -5.12 – 6.53%) for the PTV. The median DSC was 0.79 (IQR, 0.73 – 0.84) for the bladder, 0.76 (IQR, 0.69 – 0.81) for the rectum, 0.35 (IQR, 0.28 – 0.44) for the rectal wall, 0.89 (IQR, 0.83 – 0.93) for the CTV, and 0.90 (IQR, 0.87 – 0.95) for the PTV. 145/155 fractions (93.5%) met the CTV V95% >93% target and 134/155 fractions (86.5%) met both the CTV V95% >93% and PTV V95% >90% targets. When calculated over 5 cumulative fractions, 29/31 patients (93.5%) met the CTV goal of V95% >93%. 62/155 fractions (40%) failed at least one OAR constraint. The mean number of fractions per patient that failed at least one OAR constraint was 2/5 (median, 1; range, 0 – 5). <h3>Conclusion</h3> With MRI-guidance, a reduction of the PTV margin to 3 mm isotropically allows for adequate CTV coverage in over 90% of patients without the need for adaptive planning. However, OAR constraints are not met in 40% of delivered fractions despite meeting all dose constraints at the time of treatment planning. Online dose prediction and, if indicated, adaptive radiotherapy can optimize this to allow for improved OAR protection and potentially allow for further reductions in the PTV expansion while maintaining adequate CTV coverage.

Sunday, June 19, 202211:30 AM - 12:30 PMPSOR1 Presentation Time: 11:30 AM: MRI-Guided Neurovascular Bundle Avoidance in HDR Prostate Brachytherapy

<h3>Purpose</h3> Ultrasound or computed tomography (CT) are typically used for treatment planning in HDR prostate brachytherapy. However, the neurovascular bundles (NVB), which are hypothesized to have a role in erectile function, are not well visualized in these studies. Our group has shown that magnetic resonance imaging (MRI) can be used to segment the NVB as an avoidance structure for external beam radiation. In this study we hypothesize that treatment planning MRI will allow avoidance of the NVB during HDR prostate brachytherapy. <h3>Materials and Methods</h3> A retrospective chart review of all individuals with prostate cancer treated with radiation therapy at a single institution was used to identify patients who had HDR brachytherapy as monotherapy. All patients underwent TRUS-guided HDR catheter placement followed by CT and MRI for treatment planning. Patients were treated with two 13.5 Gy fractions utilizing standard clinical plans that optimized prostate coverage and minimized irradiation of the standard organs at risk (OARs) - bladder, rectum, and urethra. When applicable, MRI-defined GTVs were targeted for dose escalation to 150%. Experimental NVB-sparing plans were generated to maintain target coverage and OAR constraints but also to add avoidance of the NVBs. The left and right NVB were contoured on the treatment planning MRI and used as avoidance structures with 0 margin. Differences between target and OAR doses in the original and NVB-sparing plans were assessed pairwise using a two-tailed t-test. <h3>Results</h3> 15 prostate cancer patients at a single institution were treated with HDR monotherapy were included. Segmentation of the left and right NVB was feasible for all patients and 13 MRI-defined GTVs were targeted for dose escalation in 11 patients. Compared to their paired original plans, NVB-sparing plans reduced NVB D0.01cc (18.2 vs 14.6 Gy, p<0.01) and V100 (0.1 cc vs 0.0 cc, p<0.01). There was no difference in prostate D90 (108% vs 108%, p=0.19) and V100 (96.7 vs 95.9%, p=0.17) between plans; prostate V150% (36.5% vs. 34.3%, p<0.01) and V200% (14.4% vs 13.5%, p<0.01) slightly decreased in the NVB-sparing plans. Bladder V75 (0.3 cc vs 0.3 cc, p=1.0), rectum V75 (0.2 cc vs. 0.2 cc, p=0.75), and urethra V125 (0.03 cc vs. 0.03 cc, p=0.33) were similar between plans. In the subset of patients with GTVs, the mean GTV V150 decreased from 80.9% to 74.8% (p = 0.04) in the NVB-sparing plans; in one case NVB-sparing led to GTV min dose less than 100%. <h3>Conclusions</h3> NVB-sparing prostate HDR brachytherapy is feasible. Treatment planning MRI should be considered for NVB delineation. NVB-sparing should be approached with caution if GTVs are in close proximity. Evaluation of the clinical impact of MRI-delineated NVB irradiation is underway.

Does Compromising Target Coverage Impact Overall Survival when Treating Oligometastatic Disease with Stereotactic Ablative Radiotherapy (SABR)?

<h3>Purpose/Objective(s)</h3> SABR may improve survival in patients with oligometastases, but for some lesions, safe delivery of SABR may require a reduction in delivered dose or target coverage. This study assessed the association between target coverage compromise and oncologic and survival outcomes through a secondary analysis of the SABR-COMET Phase II Randomized Trial. <h3>Materials/Methods</h3> Patients with a controlled primary malignancy and 1 to 5 oligometastases were randomized (1:2) between standard of care (SOC) treatment and SOC plus SABR. In patients receiving SABR, the target dose coverage was reduced to meet organ at risk (OAR) constraints, if necessary. The D99 value (minimum dose received by the hottest 99% of the planning target volume [PTV]) was used as a measure of PTV coverage for each treatment plan, and the relationship between the coverage compromise index (CCI, defined as D99/prescription dose) and patient outcomes were assessed. <h3>Results</h3> Sixty-two patients in the SABR arm had dosimetric information available and a total of 109 lesions were evaluated. The mean CCI per lesion was 0.96 (95% CI, 0.56-1.61). Of the 109 lesions evaluated, 29.4% (n = 32) required coverage compromise (CCI <0.9). Adrenal metastases required coverage compromise in 100% of analyzed lesions (n = 7). CCI was not significantly associated with lesional control, adverse events, overall survival (OS), or progression-free survival (PFS). <h3>Conclusion</h3> Target compromise was required in a substantial minority of cases, but PTV coverage was not associated with OS, progression-free survival, or lesional control. This suggests that OAR constraints used for SABR treatments in the oligometastatic setting should continue to be prioritized during planning.

Initial Experience Using Daily Artificial Intelligence-Assisted Adaptive Radiotherapy on Cone-Beam CT for Bladder Cancer

<h3>Purpose/Objective(s)</h3> Adaptive radiation therapy (ART) provides a method to observe daily changes in the patient's internal anatomy and revise the radiation plan. In patients undergoing radiation for bladder cancer, changes in the bladder contour due to bladder filling result in significant changes in the radiation dose distribution potentially reducing the target coverage. Large margins are required in order to account for these anatomic changes, increasing the dose to the nearby organs at risk (OARs). Daily ART is an attractive method for bladder cancer in an attempt to reduce treatment margins. Herein we report our initial experience using commercially available, online adaptive platform with Artificial Intelligence (AI)-assisted workflows on daily cone-beam computed tomography (CBCT) for bladder cancer. <h3>Materials/Methods</h3> 9 consecutive patients eligible for bladder conserving radiotherapy underwent CT-simulation (CT-sim) and planned for ART. Clinical Target Volume included the bladder and proximal prostatic urethra +/- pelvic lymph nodes with an additional 0.5-1cm margin for the planning target volume (PTV). Fractionation schemas utilized included 64Gy/32 fractions, 55Gy/20 fractions, and 36Gy/6 fractions. A reference IMRT plan was created and approved using institutional target goals and OAR constraints. For treatment, the patient was aligned and CBCT acquired. The CT-sim was registered to the CBCT using deformable registration and a synthetic CT scan was generated. AI-based auto-contour and structure deformation of OARs and Targets on CBCT were reviewed and edited by the treating physician. 2 plans were generated including, a CT sim-based plan with deformed structures (scheduled) and a re-optimized plan (adaptive) of which both plans evaluated and the best one approved and delivered. Statistical analyses were performed comparing PTV coverage and OAR constraints between adaptive versus scheduled plans and a dosimetric comparison of ART compared to non-ART large-margin (1.5cm) treatment. <h3>Results</h3> 174 comparative adaptive and scheduled plans were generated of which the adaptive plan was chosen in 91.0% of sessions. V95 PTV mean coverage was improved with adaptation 97.0% versus 86.9% (p<.001). Average PTV volume change during ART was 16.4% (Range:0.4%-98.0%). All completed ART courses met institutional OAR constraints. With adaptation, there was a mean decrease in rectal V45%, V75%, V100% by 6% (95% CI 4.2%-7.6%, p<.003), 2.3% (95% CI 1.6%-3%, p<.003), 0.7% (95% CI 0.5%-0.8%, p<.001) respectively, and an increase in bowel V85%, V90% by 0.5% (95% CI 0.3%-0.8%, p<.04), 0.6% (95% CI 0.4%-0.8%, p<.01), respectively. Compared to a plan with large margins, there was a significant reduction in all bowel and rectal parameters with daily ART and smaller PTV margins. <h3>Conclusion</h3> Daily AI-assisted ART using CBCT for bladder cancer appears feasible and may potentially improve the therapeutic index by reducing the need for large PTV margins while ensuring acceptable target coverage.

Whole Tumor vs. FDG-Directed Dose Escalation in Patients with Locally Advanced NSCLC: Evaluation of Isotoxic Treatment Plans from the Randomized ARTFORCE PET-Boost Trial

<h3>Purpose/Objective(s)</h3> In the phase II ARTFORCE PET-Boost trial, two individualized dose escalation strategies, utilizing hypofractionation and functional imaging, were tested aiming to improve local control in patients with locally advanced non-small cell lung cancer (LA-NSCLC). Before randomization, plans for both arms were optimized and normalized to the mean lung dose, approximating isotoxicity. The purpose of this study is to assess the isotoxicity of the two treatment plans for each patient, by comparing planned dose to organs at risk (OAR). <h3>Materials/Methods</h3> The PET-Boost trial included patients with stage II-III NSCLC, with a large primary tumor >4cm. Patients received an escalated dose either to the primary tumor as a whole (arm A), or the FDG-avid areas within the primary tumor (>50% SUV_max) (arm B). Before randomization, two treatment plans were created for each patient, one for each arm, with equal mean lung dose (max 20 Gy). In both arms, the escalated dose was delivered in 24 fractions of 3.0-5.4 Gy, defined by OAR constraints. As the PET-subvolume is smaller than the whole tumor, the dose per fraction could be escalated further. Involved lymph nodes received 66 Gy (24 × 2.75 Gy) in both arms. In this analysis, dose metrics were compared for OARs in the whole tumor vs PET-subvolume arm for each patient. Difference was calculated as metric_armB – metric_armA. Wilcoxon sign rank tests were applied to assess intrapatient differences. <h3>Results</h3> Between 2010 and 2017, 107 patients were randomized in seven European centers. For 87 patients, data from both treatment plans was available for current analysis. The median (+IQR) differences in dose to OARs between arm A and B were as follows: lung Dmean EQD2_α/β=3 -0.3 Gy (-0.5 – 0; p<0.005), lung V5_physical +1.1% (0.2 - 2.7; p < 0.005), lung V20_physical +0.5% (0.1 – 1.3; p<0.005), esophagus Dmean EQD2_α/β=10 +0.1 Gy (-0.9 – 0.6; p = 0.76), esophagus V36_physical +0.1% (-0.7 – 1.2; p = 0.45), esophagus Dmax EQD2_α/β=10 -0.2 Gy (-2.85 – 0.8; p = 0.05), heart Dmax -0.5 Gy EQD2_α/β=3 (-2.1 – 0.6; p = 0.04), heart Dmean -0.1 Gy EQD2_α/β=3 (-1.5 – 0.1; p < 0.005), brachial plexus Dmax_physical -0.3 Gy (-2.1 – 0.1; p=0.01), and spinal cord Dmax_physical -0.4 Gy (-2.1 – 0.8; p=0.03). We found that outliers with larger differences tended to have either very large primary tumors, or relatively small (≤ 70 cm³) tumor volumes. <h3>Conclusion</h3> An international trial was performed which randomized LA-NSCLC patients between two dose-escalation strategies that aimed to be isotoxic. Though most statistically significance, we found generally small differences in dose to OAR between the two plans. Our results confirm by aiming at an equal mean lung dose, doses to heart, esophagus, brachial plexus and spinal cord were also to a large extent kept isotoxic. Analyses of dose volume histograms in relation to adverse events reported in the trial is ongoing. This study has the ClinicalTrials.gov identifier NCT01024829.

Comparison of Short Term Clinical and Dosimetric Outcomes of Fast Forward vs. Hypofractionated Radiotherapy for Early Breast Cancer – A Single Center Experience

<h3>Purpose/Objective(s)</h3> To share the experience of planning, dosimetric evaluation and delivery of ultra-hypofractionated (fast forward-FF) versus hypofractionated (HF) radiotherapy in breast cancers treated at our center. <h3>Materials/Methods</h3> 60 patients (average age 44 years- range 32-65 years) of early [T1, T2N0] breast cancer (BC) treated between October 2020 and October 2021 were included. Plans of 15 patients of left BC by FF, left BC by HF, right BC by FF and right BC by HF were evaluated in terms of coverage and organs at risk (OAR) constraints. Patients were planned by field within field [FIF] planning for phase I (42.5 Gy/16# for HF and 26 Gy/5# for FF). Boost plans were generated by FIF/electron/conformal planning to a dose of 10-16 Gy @ 2 Gy/fraction. Deep inspiratory breath hold (DIBH) was used for left sided BC patients who were able to hold breath. PTV coverage goal was V95 more than or equal to 95%, V105 <7%, V107 < 2%. Constraints for FF were – lung V8<15%, heart V1.5<30%, V7<5%. Constraints for HF plans were – lung V20<20%, heart avg <3 Gy. 15 right sided BC patients were treated with FF and 15 by HF plans. For left sided BC, plans were generated for dosimetric comparison between FF and HF plans, but all patients were treated by HF plans. <h3>Results</h3> For left sided BC cases, high heart dose was seen in those with more heart volume, precordial location of boost volume and patients unable to do DIBH. All patients treated by FF had grade I skin reaction and 1/15 had wet desquamation in inframammary fold. Among patients treated by HF, majority patients had dry desquamation, 3/45 had wet desquamation in folds. Edema developed in FF by 2-3^rd fraction and by 7-9^th fraction in HF. Edema was milder in HF. The edema and skin changes resolved in 2-3 weeks. At 3 and 6 months, mild skin discoloration and minimal induration at post op site was seen which was similar in those treated by FF and HF. <h3>Conclusion</h3> Adequate coverage and OAR constraints can be met for FF as for HF plans. Radiation dermatitis is milder in FF arm and the edema is milder in the HF arm. Radiation of early breast cancer by FF is executable at independent centers with diligent planning with tight constraints and precise delivery.

Dosimetric Comparison between a Frameless Robotic Radiosurgery System and HyperArc Treatment Plans for Trigeminal Neuralgia: Cone-Based Robotic System vs. High-Definition MLC Based Linac System

<h3>Purpose/Objective(s)</h3> SRS is an effective and safe treatment option for trigeminal neuralgia (TN). Good dosimetric distribution has made HyperArc (HA) an attractive SRS/FRST technique for treating benign brain lesions. This study aims to evaluate the feasibility of HA for TN by comparing it with the dose distribution of frameless robotic radiosurgery systems. <h3>Materials/Methods</h3> Twenty patients with TN treated by cone-based CK were enrolled. The treatment location was targeted on the whole trigeminal nerve root entry zone (REZ) segment, leaving a 2-mm sparing from the brainstem. The prescription dose was 65 Gy in a single fraction, prescribing to the 80% isodose line with the highest dose of 81.25 Gy in the REZ. The segment of the trigeminal nerve encompassed by the 80% isodose line averaged 7.2 mm in length. Dose to brainstem surface was constrained with a maximum dose of 40 Gy. The corresponding HA plans were generated for the 20 patients to meet the same CK treatment plan criteria, using the high-definition MLC (2.5mm at the center) and SRS NTO optimization algorithm. The CK and HA treatment plans were compared with target coverage, sparing of organs at risk (OARs), and dose distribution metrics. <h3>Results</h3> All the OAR constraints were met in the HA treatment plans. The HA plans exhibited higher coverage of the PTVs than the CK plans, with statistically significant differences (HA vs. CK, 97.2% vs. 92.2%, P = 0.008). The HA plans consistently demonstrate better sparing of the OARs than the CK plans. The mean brain doses were 0.83 Gy and 1.15 Gy for HA and CK (P < 0.001), respectively. The brain V12 was significantly smaller with HA plans than with CK plans (5.9 c.c. in HA vs. 6.9 c.c. in CK, P = 0.019). Significant differences in the maximal and mean doses of the ipsilateral/contralateral CN VII/VIII were observed between the HA and CK plans. The HA plans exhibited a significantly greater conformity index than the CK plans (HA vs. CK, 1.59 vs. 1.71, P = 0.001). The dose gradient radius was similar in the CK and HA plans (HA, 0.28 vs. CK, 0.29). <h3>Conclusion</h3> Excellent sparing of OARs and good dosimetric distribution demonstrated HA is a feasible SRS technique for the treatment of TN. Further clinical studies using HA for TN would be necessary to confirm the therapeutic benefits and toxicity profiles.

Verification Studies Confirm Reproducibility of Post-Hysterectomy Pelvic Proton Radiotherapy

<h3>Purpose/Objective(s)</h3> Post-hysterectomy radiotherapy (RT) is associated with urinary, gastrointestinal, and hematologic toxicity. Concern for organ and target motion has limited exploration of proton RT as a tool to reduce toxicity. Attention to planning and treatment delivery is paramount given sensitivity of protons to small changes in soft tissue in the beam path. We sought to evaluate the consistency of target coverage and organ at risk (OAR) sparing in post-hysterectomy proton RT. <h3>Materials/Methods</h3> The first 10 patients treated with proton RT on an institutional prospective non-randomized trial of proton post-hysterectomy RT for endometrial cancer were included. CT simulation was performed with pelvic immobilization and a rectal balloon, which was also used for treatment. Full and empty bladder and IV contrast scans were obtained. Clinical target volumes (CTV) included the vaginal cuff, proximal 3 cm of vagina, and pelvic lymph nodes to the level of L4/L5. Prescription was 45 Gy (relative biological effectiveness (RBE) 1.1) in 25 fractions. Planning was multi-field optimization with two posterior oblique beams and a posterior beam. Plans were evaluated for robustness to ensure CTV coverage in worst case scenarios of ±5 mm isocenter shifts in x, y, and z directions and ±5% range uncertainty. A variable RBE calculation assuming a linear relationship between RBE and linear energy transfer was used to evaluate for target coverage and increased RBE within OARs. If needed, the plan was modified to limit hot spots without compromising coverage in the calculation with uniform 1.1 RBE. Patients underwent weekly CT-on-rails verification scans. Target coverage and dose to OARs were assessed at each verification and replanning was done if target coverage or OAR constraints did not meet original planning objectives. <h3>Results</h3> The first patient on the study required replan after first verification due to excess air in the rectum at simulation and verification, resulting in rectum V30Gy 90% and V40Gy 81%. After replan, subsequent verifications met objectives. Subsequent patients were planned with air in the rectum or bowel accounted for by evaluation of plans with air overridden to HU = -300 to -450 and HU = 0. Target coverage met acceptable planning parameters in all cases (Table 1). There was no statistical difference in bladder mean, V30Gy, and V45Gy; sigmoid V45Gy; rectum mean, V30Gy, and V40Gy; and small bowel V40% and V45Gy. All patients were successfully treated with protons for all planned fractions. <h3>Conclusion</h3> Proton post-hysterectomy pelvic RT with robust optimization is feasible, reproducible, and associated with appropriate target coverage and acceptable dose to organs at risk as assessed with weekly verification scans.

Correlation of Left Anterior Descending Coronary Artery Radiation Dose with Major Adverse Cardiac Events and Feasibility of Coronary Artery Sparing Treatment Planning in Lung Cancer

<h3>Purpose/Objective(s)</h3> Radiation dose to the left anterior descending (LAD) coronary artery is associated with major adverse cardiac events (MACE) in patients with locally advanced non-small cell lung cancer (LA-NSCLC). However, the newly identified LAD metric (percent volume receiving 15 Gy [LAD V15Gy]) has not been independently validated and the extent to which modern radiotherapy (RT) planning techniques can reduce LAD V15Gy without exceeding dose tolerances to other critical organs at risk (OAR) remains uncertain. <h3>Materials/Methods</h3> This is a single institution retrospective study of 98 patients with LA-NSCLC treated with RT between 2005-2020. The LAD was manually delineated for each patient. MACE (unstable angina, myocardial infarction, heart failure, coronary revascularization, and cardiac death) cumulative incidence was estimated and Fine and Gray regressions were performed, adjusting for non-cardiac death as a competing risk. Patients who received LAD V15Gy ≥10% and experienced MACE were re-planned with volumetric-modulated arc therapy (VMAT) to optimize reduction of LAD V15Gy while maintaining target coverage and meeting standard OAR constraints. <h3>Results</h3> The median follow up was 23.2 months. The median age was 69 years, 30.6% of patients had pre-existing coronary heart disease (CHD) or a CHD risk-equivalent. The mean LAD V15Gy was 32% (standard deviation [SD] 27.8%). Ten patients developed at least one MACE, with a 2-year cumulative incidence of 10.2% (95% CI: 3.1-17.0%). Adjusting for pre-existing CHD there was an increased risk of MACE with LAD V15Gy (subdistribution hazard ratio 1.03; 95% CI 1.00-1.06; p=.034), with a significant interaction between LAD V15Gy and CHD (p=.005). Among the 10 patients who developed a MACE, 6 (60%) had an LAD V15Gy ≥ 10% (mean 52%, range 10-100%). The original planning techniques included: 3-dimensional conformal RT (3D-CRT; n=2), static intensity-modulated RT (IMRT; n=2), and VMAT (n=2). In 4 of these plans (n=2 IMRT, n=1 3D-CRT, n=1 VMAT), the re-planned LAD V15Gy was reduced to <10%, however all 6/6 plans achieved some degree of LAD V15Gy reduction (range, 9-100%). Specifically, optimization with LAD-sparing VMAT achieved a mean absolute decrease of 35.1% for LAD V15Gy (SD 32.4%) and 6.2 Gy mean heart dose (SD 10.9 Gy), with a concomitant mean increase of 0.8 Gy mean lung dose (SD 1.8 Gy), and mean lung V20Gy of 0.2% (SD 4.1%). All re-plans achieved similar target coverage and remained within national guideline OAR constraints. <h3>Conclusion</h3> LAD V15Gy is associated with an increased risk of MACE in this independent retrospective cohort. VMAT-based LAD-sparing RT plan optimization is feasible and can achieve meaningful reductions in LAD V15Gy with potentially clinically acceptable tradeoffs in lung dose. Together, these findings underscore the need for more aggressive LAD-sparing RT planning approaches.

Daily Artificial Intelligence-Assisted Adaptive Radiotherapy on Cone-Beam CT for Cancer of the Head and Neck

<h3>Purpose/Objective(s)</h3> Adaptive radiation therapy (ART) provides a method to modify the radiation treatment plan secondary to structural and spatial changes that occur during a treatment course. Specifically, ART is relevant in head and neck cancers as many patients will experience changes of the target volumes and organs-at-risk (OARs) during treatment due to combination of treatment response, weight loss, inflammation and effects on normal tissues. Our institution recently began performing daily ART for select cases of definitive Head and Neck cancers using a commercially available, online adaptive platform with AI-assisted workflows on daily cone-beam computed tomography (CBCT). Herein we report our initial dosimetric experience using this novel technique. <h3>Materials/Methods</h3> Twelve consecutive head and neck cancer patients (nasopharynx, oropharynx, larynx) underwent CT-simulation and planned for adaptive treatments. A reference IMRT plan was created and approved using institutional dose/fractionation schema, target goals and OAR constraints. For treatment, the patient was aligned and CBCT acquired. The simulation CT scan was subsequently registered to the CBCT using deformable registration and a synthetic CT scan was generated. AI-based auto-contour and structure deformation of OARs and Targets on CBCT were reviewed and edited by the treating physician. Two plans were generated including, a CT sim-based plan with deformed structures (scheduled) and a re-optimized plan (adaptive) of which both plans evaluated and the best one approved and delivered. Statistical analyses were performed comparing adaptive versus scheduled plans using a paired student's t-test. <h3>Results</h3> 419 adaptive and scheduled radiotherapy plans were generated of which 82.2% adaptive plans were chosen with an average time per session of 19.4 minutes. Adaptive plans demonstrated superior V95 PTV70, PTV60, PTV56 mean coverage by 0.8 (95% CI 0.5%-1.1%, p < 0.001), 2.4% (95% CI 2%-3%, p < 0.001), and 5.9% (95% CI 5.4%-6.5%, p < 0.001). Compared to scheduled plans, high priority OARs demonstrated a reduction in: mean parotid gland right and left dose by 3.2 Gy (95% CI 1.9-4.4, p < 0.001) and 2.7 Gy (95% CI 1-4.4, p < 0.001), respectively and brainstem max dose was reduced by 5.2% (95% CI 3.7%-6.7%, p < 0.001). <h3>Conclusion</h3> Daily AI-assisted adaptive radiation therapy for head and neck cancer may potentially improve the therapeutic index for different tumor types by improving the target coverage and reducing OAR dose. Prospective clinical evaluation is indicated to further this novel approach.