GTV Volume Research Articles

Improved Dosimetry and Plan Quality for Accelerated Partial Breast Irradiation Using Online Adaptive Radiation Therapy: A Single Institutional Study

PurposeAccelerated partial breast irradiation (APBI) is an attractive treatment modality for eligible patients as it has been shown to result in similar local control and improved cosmetic outcomes compared to whole breast radiotherapy. The use of online adaptive radiotherapy (OART) for APBI is promising as it allows for a reduction of PTV margins since breast motion and lumpectomy cavity volume changes are accounted for in daily imaging. Here we present a retrospective, single-institution evaluation on the adequacy of kV-cone beam computed tomography (CBCT) OART for APBI treatments. Methods and Materials19 patients (21 treatment sites) were treated to 30 Gy in 5 fractions between January of 2022 and May of 2023. Time between simulation and treatment, change in gross tumor (i.e. lumpectomy cavity) volume (GTV), and differences in dose volume histogram (DVH) metrics with adaption were analyzed. The Wilcoxon paired, non-parametric test was utilized to test for DVH metric differences between the scheduled plans (initial plans recalculated on daily CBCT anatomy) and delivered plans, either the scheduled or adapted plan, which was re-optimized using daily anatomy. ResultsMedian (inter-quartile range) time from simulation to first treatment was 26 days (21-32 days). During this same time, median GTV volume reduction was 16.0% (7.3-23.9%) relative to simulation volume. Adaptive treatments took 31.3 min (27.4-36.6 min) from start of CBCT to treatment session end. At treatment, the adaptive plan was selected for 86% (89/103) of evaluable fractions. In evaluating plan quality, 78% of delivered plans met all target, OAR, and conformity metrics evaluated, compared to 34% of scheduled plans. ConclusionsUse of OART for stereotactic linac-based APBI allowed for safe, high-quality treatments in this cohort of 21 treatment courses. Although treatment delivery times were longer than traditional stereotactic body treatments, there were notable improvements in plan quality for APBI using OART.

RADT-17. SINGLE INSTITUTION REVIEW OF OUTCOMES FOLLOWING STEREOTACTIC RADIOSURGERY FOR SIX TO EIGHTEEN BRAIN METASTASES: INTRACRANIAL FAILURE RATES AND NEED FOR FURTHER CRANIAL RADIOTHERAPY

Abstract BACKGROUND A single centre retrospective review of outcomes following linear accelerator - based stereotactic radiosurgery (SRS) for patients with 6 to 18 brain metastases was conducted. METHODS Patients receiving SRS to multiple metastatic sites were identified from our institutional database and subsequently stratified into those with 6-9 metastases (group 1) and 10 or more metastases (group 2). RESULTS 45 patients were evaluated in total with a mean number of metastases of 7 for group 1 and 14 for group 2. Mean total GTV volumes for each SRS treatment were 1.92cc (group 1) and 2.70cc (group 2). Median overall survival was 8 months for group 1 (0 -51 months) and 7 months (3-36 months) for group 2 . Following SRS, median time to intracranial progression was 3 months for both groups, occurring in 59% and 64% of group 1 and group 2 patients respectively. Following relapse, more patients in group 2 received whole brain/posterior fossa radiotherapy rather than SRS when compared with those in group 1 (80% vs 40%). The majority of patients surviving more than 1 year following SRS for ≥6 brain metastases had a targetable mutation (defined as any of ALK/EGFR/ROS1/BRAF mutation, ER+, HER 2+, PDL1 expression ≥ 1) in their primary tumour; 75% of group 1 and 100% of group 2. CONCLUSIONS Although this study represents small patient numbers, we show that long term survival can be achieved for some patients following SRS for more than 5 brain metastases. However, many patients with more than 10 brain metastases develop intracranial relapse shortly after SRS and require whole brain/posterior fossa radiotherapy, indicating these patients are less likely to benefit from SRS. The presence of a targetable mutation in the primary tumour may indicate a better outcome following SRS for more than 5 brain metastases and warrants further investigation.

Phase 2 Clinical Trial of Simultaneous Boost Intensity Modulated Radiation Therapy With 3 Dose Gradients in Patients With Stage I-II Nasal Type Natural Killer/T-Cell Lymphoma: Long-Term Outcomes of Survival and Quality of Life

The aim of this study was to investigate the treatment results and long-term quality of life in patients with early-stage extranodal natural killer/T-cell lymphoma who were prospectively treated with simultaneous boost intensity modulated radiation therapy (SIB-IMRT) with 3 dose gradients. Sixty patients with stage I-II nasal cavity natural killer/T-cell lymphoma (NKTCL) and Waldeyer's ring NKTCL were enrolled in a single-arm, prospective, phase 2 clinical trial from August 2011 to April 2015. All patients were treated with definitive radiation therapy combined with short-course induction chemotherapy. A newly designed SIB-IMRT scheme was uniformly adopted, with 54.6 Gy for the gross tumor volume (GTV) of the primary tumor and GTV of the positive lymph nodes, 50.7 Gy for the high-risk clinical target volume (CTV), and 45.5 Gy for the low-risk CTV, all delivered in 26 daily fractions. Before SIB-IMRT, L-asparaginase-based induction chemotherapy was used in 95.0% (57/60) of patients. With a median follow-up time of 95.8 months, the 5-year locoregional recurrence-free survival, progression-free survival, and overall survival rates were 83.3%, 81.7%, and 88.3%, respectively. Dosimetric analysis in the first 21 patients showed satisfying conformality for planning target volume of GTV, high-risk CTV, and low-risk CTV, while the organs at risk were well protected. The results of long-term quality-of-life investigations in patients without progression were favorable, and nasal discomfort was the most common symptom. No grade 3 or 4 acute or late toxicities were observed. The scheme of target volume delineation and dose setting that we designed has favorable clinical effects with mild side effects in treating patients with stage I-II nasal cavity NKTCL and Waldeyer's ring NKTCL.

Impact of attenuation correction of radiotherapy hardware for positron emission tomography-magnetic resonance in ano-rectal radiotherapy patients.

Positron Emission Tomography-Magnetic Resonance (PET-MR) scanners could improve ano-rectal radiotherapy planning through improved Gross Tumour Volume (GTV) delineation and enabling dose painting strategies using metabolic measurements. This requires accurate quantitative PET images acquired in the radiotherapy treatmentposition. This study aimed to evaluate the impact on GTV delineation and metabolic parameter measurement of using novel Attenuation Correction (AC) maps that included the radiotherapy flat couch, coil bridge and anterior coil to see if they werenecessary. Seventeen ano-rectal radiotherapy patients received a -FluoroDeoxyGlucose PET-MR scan in the radiotherapy position. PET images were reconstructed without ( ) and with ( ) the radiotherapy hardware included. Both AC maps used the same Computed Tomography image for patient AC. Semi-manual and threshold GTVs were delineated on both PET images, the volumes compared and the Dice coefficient calculated. Metabolic parameters: Standardized Uptake Values , and Total Lesion Glycolysis (TLG) were compared using paired t-tests with a Bonferroni corrected significance level of . Differences in semi-manual GTV volumes between and were approaching statistical significance (difference , ), with larger differences in low FDG-avid tumours ( ). The and GTVs were concordant with Dice coefficients (manual) and (threshold). Metabolic parameters were significantly different, with , and TLG differences of ( ), ( ) and ( ) respectively. The TLG difference resulted in 1/8 rectal cancer patients changing prognosis group, based on literature TLG cut-offs, when using rather than . This study suggests that using AC maps with the radiotherapy hardware included is feasible for patient imaging. The impact on tumour delineation was mixed and needs to be evaluated in larger cohorts. However using AC of the radiotherapy hardware is important for situations where accurate metabolic measurements are required, such as dose painting and treatmentprognostication.

Development of an automated treatment planning approach for lattice radiation therapy.

Lattice radiation therapy (LRT) alternates regions of high and low doses within the target. The heterogeneous dose distribution is delivered to a geometrical structure of vertices segmented inside the tumor. LRT is typically used to treat patients with large tumor volumes with cytoreduction intent. Due to the geometric complexity of the target volume and the required dose distribution, LRT treatment planning demands additional resources, which may limit clinical integration. We introduce a fully automated method to (1) generate an ordered lattice of vertices with various sizes and center-to-center distances and (2) perform dose optimization and calculation. We aim to report the dosimetry associated with these lattices to help clinical decision-making. Sarcoma cancer patients with tumor volume between 100 cm3 and 1500 cm3 who received radiotherapy treatment between 2010 and 2018 at our institution were considered for inclusion. Automated segmentation and dose optimization/calculation were performed by using the Eclipse Scripting Application Programming Interface (ESAPI, v16, Varian Medical Systems, Palo Alto, USA). Vertices were modeled by spheres segmented within the gross tumor volume (GTV) with 1cm/1.5cm/2cm diameters (LRT-1cm/1.5cm/2cm) and 2 to 5cm center-to-center distance on square lattices alternating along the superior-inferior direction. Organs at risk were modeled by subtracting the GTV from the body structure (body-GTV). The prescription dose was that 50% of the vertice volume should receive at least 20Gy in one fraction. The automated dose optimization included three stages. The vertices optimization objectives were refined during optimization according to their values at the end of the first and second stages. Lattices were classified according to a score based on the minimization of body-GTV max dose and the maximization of GTV dose uniformity (measured with the equivalent uniform dose [EUD]), GTV dose heterogeneity (measured with the GTV D90%/D10% ratio), and the number of patients with more than one vertex inserted in the GTV. Plan complexity was measured with the modulation complexity score (MCS). Correlations were assessed with the Spearman correlation coefficient (r) and its associated p-value. Thirty-three patients with GTV volumes between 150 and 1350 cm3 (median GTV volume=494 cm3 , IQR=272-779 cm3 were included. The median time required for segmentation/planning was 1min/21min. The number of vertices was strongly correlated with GTV volume in each LRT lattice for each center-to-center distance (r>0.85, p-values<0.001 in each case). Lattices with center-to-center distance=2.5cm/3cm/3.5cm in LRT-1.5cm and center-to-center distance=4cm in LRT-1cm had the best scores. These lattices were characterized by high heterogeneity (median GTV D90%/D10% between 0.06 and 0.19). The generated plans were moderately complex (median MCS ranged between 0.19 and 0.40). The automated LRT planning method allows for the efficacious generation of vertices arranged in an ordered lattice and the refinement of planning objectives during dose optimization, enabling the systematic evaluation of LRT dosimetry from various lattice geometries.

Implementation Science in Radiation Oncology: Case Study for Liver SBRT.

The translation of research into clinical practice is challenging and implementation science is becoming as important as the trial design and development. Implementation science methodologies have been shown to reduce research-to-practice gap in other clinical settings. This is especially true for the field of Radiation Oncology where modern hypofractionated techniques, like Stereotactic Ablative Body Radiotherapy for Liver are at a high risk of over enthusiastic implementation as well as underutilization. We present the results of a multicomponent implementation methodology utilized to develop our Liver SBRT program as a model to safely translate a complex technology into clinical practice. After review of literature and market research a setup was created with focus on machine requirements, immobilization devices, motion management techniques and QA techniques. Clinical tools in the form of checklists were developed for patient selection, simulation along with image fusion, target delineation, planning (conformity indices, dose constraint criteria) and treatment delivery. All patients were treated on Truebeam® after Bodyfix® immobilization with plastic wrap. Planning was completed on Eclipse TPS with dose constraints and conformity guidelines defined per the RTOG 1112 and TG 101. Clinical outcomes including clinical and imaging follow-up for tumor control and toxicity were recorded. For this report, all patients treated were reviewed and compared to published data to assess the success of the implementation methodology. A total of 64 consecutive Patients treated with liver SBRT at Dignity Health Cancer Institute (DHCI) were eligible for the study. 58 patients treated for primary liver malignancies were included in this analysis to assess outcomes including control of disease and toxicity to compare to the published literature. Median follow up for these patients 6.5 months (4-46mnths). Median GTV volume was 38.7cc (0.1cc-2056.1 cc), median PTV volume was 159.35 cc (21.5cc-2673.5cc). Median SBRT prescription dose was 50 Gy/5 fractions (35-50 Gy). Median Liver- GTV was 1595.8 cc(770.7cc-2983.0cc). Following toxicities were noted- Grade 1- 10.3%, Grade 2 - 1.72%, Grade 3- 3.44%. No Grade 4 toxicity was noted. 1 year LC rate was 96.6%. 8.6% showed out of field liver failure and 6.9% developed distant metastasis. These results were compared to the current published literature and are shown to be comparable. Strong and well thought out Implementation methodologies can ensure reproducing results in clinical practice, comparable to the controlled environment of trials. These are crucial in translation of clinical trials utilizing advanced technologies to promote the culture of safety in clinical practice of Radiation Oncology. Regular assessment and tracking of clinical outcomes can be used as Quality markers for directing care and reimbursements for future.

Handcrafted Radiomics, Deep Learning Radiomics in the Prediction of Radiation Pneumonitis for NSCLC Patients Treated with Immunotherapy Followed with Thoracic Radiotherapy

Our previous study has shown that NSCLC patients previously received immune checkpoint inhibitors (ICIs) underwent thoracic intensity modulated radiotherapy have a higher risk of acute radiation pneumonitis (RP). This study aimed to establish machine learning models using handcrafted radiomics (HCR), deep learning-based radiomics (DLR) and clinical characteristics to improve the prediction of symptomatic radiation pneumonitis (RP) (grade ≥ 2) status for NSCLC patients treated with immunotherapy followed with thoracic radiotherapy. This study retrospectively collected data of 61 NSCLC patients meeting the requirements of study enrollment. Of these 61 patients, 35 developed symptomatic graded ≥ 2 RP. We defined 3 regions of interest (ROIs) in planning CT images including gross tumor volume (GTV), planning tumor volume (PTV), PTV-GTV. We calculated the mean dose, V5, V10, V20, and V30 within TL-GTV, and the volume of GTV, PTV and total lung. A total of 516 handcrafted radiomics features and 512 deep features were extracted from each 3 ROIs. Person Correlation Analysis and Least Absolute Shrinkage and Selection Operator (LASSO) were used to reduce the dimension of features. The HCR models, DLR models and the fusion models across different ROIs with machine learning classifiers were built and compared. In multi-classifier modeling, models with PTV under logistic regression (LR) classifiers showed better prediction than other ROIs under different machine learning algorithms. Based on PTV with LR, HCR+ DLR model had better performance, with an area under the curve (AUC) of 0.95 (95% confidence interval (CI): 0.893-1) in the training cohort and 0.87 (95% CI: 0.698-1) in the test cohort, which was higher than that of HCR model, with an AUC of 0.86 (95% CI: 0.755-0.9) in the training cohort and 0.82 (95% CI: 0.624-1) in the test cohort, the results of fusion model with HCR, DLR and 7 clinical characteristics including T, N, clinical stage, age, smoking, radiotherapy alone/combined and V30, demonstrated the best distinguishing performance, with an AUC of 0.99 (95% CI: 0.970-1) in the training cohort and 0.91 (95% CI: 0.784-1) in the test cohort. The combination of HCR, DLR and clinical characteristic underwent machine learning algorithms can improve the prediction of symptomatic RP in NSCLC patients treated with ICIs followed with thoracic radiotherapy.

Evaluation of 68Ga-Fibroblast Activation Protein Inhibitor vs. 18F-FDG as a Novel Radiotracer for Biologically Guided Radiation Therapy

Real-time biology guided radiation therapy (BgRT) uses real-time positron emissions from a PET tracer during treatment to guide targeted radiation to cancerous lesions. Fibroblast activation protein alpha (FAP) is highly expressed on cancer-associated fibroblasts in tumors with low expression in normal tissues. While 18F-FDG-PET requires fasting and has background in the liver and brain, 68-Gallium labeled FAP inhibitor (FAPI) does not require fasting and has less background uptake. The goal of this study was to investigate the utility of FAPI as a potential universal fiducial for BgRT. We hypothesized that 68Ga-FAPI would be a better radiotracer than 18F-FDG, as assessed by the Normalized Minimal kBq/mL and the Normal Target Signal (NTS), two parameters used to gauge the suitability of BgRT. PET-CTs were obtained for 50 patients with pancreatic, liver, lung, head & neck, and cervical cancer using 18F-FDG and 68Ga-FAPI (n = 10 for each). Four DICOM images were obtained per patient (FDG PET + CT, FAPI PET + CT). Radiation oncologists delineated the gross tumor volume (GTV) on PET images. A separate set of auto-contours were generated from the PET using an auto-threshold of 40% maximum SUV for all tumors. A 1 cm expansion was added to the GTV to create a ring around the physician-generated contours and auto-contours. The following parameters were measured: GTV volume, SUV max of GTV, SUV mean of GTV, Normalized Minimal kBq/mL within the GTV, and NTS (= SUV max/Ring SUV mean). Values were compared using paired t-test. For the BgRT product with similar calculations, the required Normalized Minimal kBq/mL is > 5 kBq/mL; the required NTS is > 2.7 for treatment planning and > 2.0 for BgRT delivery. The Normalized Minimal kBq/mL for FAPI was > 5 kBq/mL for all tumors and greater for auto-contoured GTVs compared to physician-contoured GTVs. The mean NTS for the auto-contours for all tumor sites was > 2.0. In addition, there was a statistically significant increase in the NTS for FAPI compared to FDG in pancreatic, liver and head & neck cancers. In pancreatic cancer, there was a statistically significant increase in Normalized Minimal kBq/mL for FAPI compared to FDG (26.0 vs 14.2) (p = 0.01) and the SUVmax of FAPI was almost double that of FDG (15.9 vs 8.2) (p = 0.01). FAPI had no background in the liver, but had high background in the uterus, suggesting it may have a role in liver cancer but not cervical cancer. This is the first study demonstrating the potential superiority of 68Ga-FAPI compared to 18F-FDG as a biologic fiducial for BgRT when treating pancreatic, liver and head & neck cancers, with a similar efficacy for lung cancer. Our results indicate that auto-contoured GTVs generate a higher NTS than physician-contoured GTVs but all are > 2.0. In addition, the Normalized Minimal kBq/mL for auto-contours is > 5 kBq/mL for all tumors. As hypothesized, FAPI-based BgRT is most likely to be successful when treating tumors with significant desmoplastic stroma, such as pancreatic cancer.

Predictors of Tumor Dynamics during a 6-Week Course of Chemoradiotherapy for Glioblastoma

Our prior imaging studies have shown geometrically meaningful inter-fraction tumor dynamics specific to glioblastoma (GBM). We aim to identify predictors associated with tumor dynamics during a 6-week course of concurrent chemoradiotherapy (CRT) for GBM. Patients enrolled in a prospective serial magnetic resonance imaging (MRI) study were reviewed. All patients were treated with 54-60 Gy in 30 fractions. The gross tumor volume (GTV) included the surgical cavity and T1c enhanced residual tumor; clinical tumor volume (CTV) included GTV with a 15mm isotropic expansion, respecting anatomical boundaries; planning target volume (PTV) was 4mm expansion. MRIs were obtained at RT planning (F0), fraction 10 (F10), and fraction 20 (F20). Tumor dynamic metrics (relative to F0) assessed included the GTV volume (Vrel), Hausdorff distance (dH) and migration distance (dM). dH is the average distance between two datasets in metric space. dM is the maximum linear displacement of the GTV in any direction. Factors to be determined associated with tumor dynamics included: age, sex, corpus callosum (CC) involvement, extent of surgery (gross total resection (GTR), subtotal resection (STR) or biopsy alone (Bx)), MGMT methylation and IDH mutation status. A total of 129 patients were reviewed. Median GTV was 20.9cc at F0, 17.6cc at F10 (Vrel 0.85), and 16.1cc at F20 (Vrel 0.78). Patients without CC involvement had more marked GTV volume reduction: Vrel 0.82 vs 1.02 with CC involvement at F10 (P = 0.05), and Vrel 0.77 vs 0.88 with CC involvement at F20 (P = 0.03). Patients with GTR (vs STR vs Bx) had more marked GTV volume reduction across all time points: Vrel 0.78, 0.85 and 1.07 respectively at F10 (P = 0.001), and Vrel 0.69, 0.80, 1.04 respectively at F20 (P = 0.001). The median dH was 8.1mm at F10 and 9.2mm at F20. Patients with CC involvement (vs without CC involvement) had a larger dH: 54% vs 25% had dH>10mm respectively at F10 (P = 0.03), and 73% vs 28% had dH>10mm respectively at F20 (P<0.005). Patients with a GTR had smaller dH at both F10 (P = 0.02) and F20 (P = 0.006). At F20, 20%, 47% and 37% of patients with GTR, STR and Bx had dH>10mm (P = 0.04). The median dM were 4.7mm at F10 and 4.7mm at F20. Patients with CC involvement (vs without CC involvement) had larger dM: 41% vs 12% had dM >10mm respectively at F10 (P = 0.01), and 45% vs 9% had dM >10mm respectively at F20 (P<0.001). Patients with GTR had smaller dM at F10 (P = 0.03) and F20 (P0.002). At F20, 0%, 25% and 19% of patients with GTR, STR and Bx had dM>10mm (P = 0.002). Age, sex, MGMT methylation and IDH mutation status were not associated with Vrel, dH and dM at F10 and F20. We identified CC involvement and extent of surgery to be associated with tumor dynamics at F10 and F20 over the course of CRT for GBM. This offers opportunities to better select patients who may benefit from earlier/ more frequent RT replan/ adaptation to ensure adequate tumor coverage, or to reduce RT toxicities.

Target Volumes Comparison between Postoperative Simulation MRI and Preoperative Diagnostic MRI for Prone Breast Radiotherapy after Breast-Conserving Surgery

To investigate the correlation and difference between target volumes determined by postoperative prone positioning magnetic resonance imaging (MRI) and preoperative prone diagnostic MRI for breast radiotherapy after breast-conserving surgery (BCS) based on deformable image registration (DIR). A total of 17 patients undergoing prone whole breast-irradiation after BCS were enrolled, all these patients were undergoing preoperative and postoperative prone MRI scans. The gross tumor volume (GTV) was delineated on the preoperative MRI images, then expanding 10 mm to simulate the preoperative lumpectomy cavity (LC). The LC were expended to clinical target volume (CTV), and planning target volume (PTV) on preoperative and postoperative MRI sequences, respectively. Preoperative and postoperative MRI was registered based on DIR by a commercially available software system. The target volume, the distance between the centers of mass (dCOM), conformity index (CI), degree of inclusion (DI) were compared to explore the target volume variation for pre- and post-surgery delineation. And evaluated the relationship between CILC/CIPTV and clinical factors. The volume of GTVpre was 3.05cm3(range, 1-23.63cm3). The median volume of LCpre were 26.84 cm3 (range, 11.75-102.28 cm3). 0.85cm3 smaller than the LCpre, the LCpost were 25.99 cm3 (range, 5.98-41.95) (P = 0.04). The dCOM, CI, and DI between LCpre and LCpost were 1.371cm (range, 0.533-5.447), 0.221 (range, 0.041-0.516), and 0.472 (range, 0.108-0.804). There was no significant statistically difference between PTVpre and PTVpost (120.73cm3 vs 131.67cm3, p = 0.723). Compared with LC, the CI and DI between PTVpre and PTVpost were increased to 0.446 (range, 0.233-0.700), 0.636 (range, 0.362-0.834), respectively. Meanwhile, the dCOM was reduced to 1.239cm (range, 0.413-3.642). There was no obvious linear correlation between the CI with the GTV volume, the ratio of the primary tumor volume to the breast volume, the distance from the primary tumor to the nipple and chest wall, and the Body Mass Index (BMI), respectively. For prone breast irradiation, even based on DIR, the spatial correspondence of the target volumes between preoperative and postoperative MRI images were still poor. Therefore, it is not reasonable to delineate postoperative LC refer to preoperative diagnostic MRI based on DIR. Preoperative MRI also cannot provide individualized guidance for LC delineation according to tailored patient.

Outcomes of Patients Treated with Re-Irradiation for Recurrent Head and Neck Cancer Using Pencil Beam Scanning Proton Therapy

Re-irradiation (re-RT) for recurrent head and neck cancer (HNC) after prior HNC radiation therapy (RT) is clinically challenging given prior radiation of nearby organs at risk (OARs). We describe clinical outcomes and toxicity of pencil beam scanning proton therapy (PBS-PT) for recurrent HNC. We performed a retrospective analysis of recurrent HNC patients treated at a single institution with PBS-PT. Baseline demographic, disease and treatment characteristics were recorded. Local control (LC), locoregional control (LRC), progression free survival (PFS), distant metastasis free survival (DMFS), and overall survival (OS) were estimated using the Kaplan-Meier method. UVA was completed using logistic regression, and MVA was performed using a backward elimination model. We also report acute and late grade 3+ toxicity outcomes, graded per CTCAE v5.0. A total of 89 patients treated with PBS-PT for recurrent HNC between 2016 and 2022 were included. Primary sites included oropharynx (30.0%), oral cavity (22.5%), sinonasal cavity (15.7%), larynx (12.4%) and nasopharynx (6.7%). The most common tumor histology was SCC (73.0%). Median time to re-RT was 47 months. Median dose of PBS-PT was 60 Gy (range: 40-72) with 50.6% receiving BID treatment. Median GTV volume was 30cc (range 4.8-1083cc). 24% of patients received concurrent systemic therapy (46% cytotoxic, 4.5% immunotherapy). Median follow-up after PBS-PT was 8 months (range: 0-71), and median OS was 13 months (95% CI: 9.3-16.7). The median PFS and DMFS were 7 months (95% CI 5.0-9.0) and 9 months (95% CI 5.3-12.7) respectively. The 1- and 2-year LC rates were 80.8% (95% CI: 70.8-90.8) and 66.2% (95% CI: 50.7-81.7). The 1- and 2-year DMFS were 41.0% (95% CI: 30.0-52.0) and 26.3% (95% CI: 15.7-36.9). On UVA and MVA, smaller GTV volume was associated with improved OS (HR 1.002, p = .004), DMFS (HR 1.002, p = 0.004) and PFS (HR 1.002, p = 0.014). In addition, shorter time to re-RT was associated with worse LRC (HR 1.003, p = 0.002), and higher KPS was associated with improved PFS (HR 0.57, p = 0.04). There were 31 acute grade 3 toxicity events (21 patients), the most common being odynophagia (9.0%) followed mucositis (5.6%), dehydration and dermatitis (both 4.5%). One patient had grade 4 toxicity, laryngeal edema requiring intubation 40 days after completion of re-RT. One patient had acute grade 5 toxicity, an oropharyngeal bleed 74 days after completion of re-RT. There were 35 late toxicity events (n = 27), the most common being dysphagia (n = 7, 7.9%). One patient suffered late grade 5 osteoradionecrosis, which resulted in sepsis. PBS-PT for recurrent HNC results in effective disease control and favorable toxicity. Patients with smaller GTV volume appear to have improved OS, PFS and DMFS, and may be better candidates. Those with shorter time to re-RT also have worse LRC. However, distant failure (DF) comprises a major failure pattern, and biomarkers to identify patients at risk for DF may improve clinical decision making.

Efficacy and Safety of Multifraction Stereotactic Radiation Therapy with Volumetric Modulated Arc Therapy Technique for Multiple Brain Metastases

Multifraction stereotactic radiotherapy (MF-SRT) with volumetric modulated arc therapy (VMAT) is the standard treatment option for patients with multiple brain metastases. VMAT has superior physical accessibility and economic accessibility compared with advanced radiotherapy technologies such as Tomo or Proton radiotherapy. However, existing studies has mainly focused on comparing the dosimetric parameters between distinct radiotherapy techniques. Moreover, single fraction stereotactic radiosurgery is preferentially recommended for treatment of brain metastases with maximum diameter <2cm compared with MF-SRT. There is a lack of clinical results of its efficacy and subgroup analyses according to diameter. Thus, we first report the detailed analysis of clinical results of SRT using VMAT for brain metastases. This study is a retrospective analysis of SRT for multiple brain metastasis using VMAT. The clinical efficacy of VMAT was evaluated by local control (LC) in 6-months, 1-year, and 2-year. A total of 63 patients with 214 brain metastases were enrolled. The most common fractionation schemes were 40 Gy/8F and 48 Gy/12F. In all, LC rates at 6-month, 1-year, and 2-year were 95.5%, 90.6%, and 76.8%, respectively. Using univariate and multivariate analyses according to stratification factors including maximum diameter, GTV volume, dose per fraction, fractions, inner structure, and BED (α/β = 10), we found that no factors were associated with 6-month LC, 1-year LC, and 2-year LC. 1-year LC rates for maximum diameter ≥1 and <2, ≥2 and <3, and ≥3 cm were 89.2%, 90.7%, and 95.7%, respectively. The 1-year LC rates for tumors with GTV <3, ≥3 and <5, ≥5 and <10, and ≥10 cc were 87.0%, 91.7%, 94.7%, and 96.6%, respectively. Interestingly, 1year-LC in GTV ≥3 cc tends to higher than those in GTV <3 cc, but there was no significant difference (94.4% vs 87%, P = 0.162). Brain radionecrosis (RN) was the most significant toxicity occurring in 10 (4.7%) out of the 214 treated brain metastases. Among 6 patients with RN, 4 (66.7%) had been treated with tyrosine kinase inhibitors. The use of MF-SRT with VMAT for multiple brain metastases showed a comparable clinical efficacy to other techniques described in the literature. And the LC rate for maximum diameter <2cm treated with MF-SRT VMAT was comparable to single fraction stereotactic radiosurgery as previously reported. The treatment-related toxicity was acceptable.

Feasibility and Safety of Single-Isocenter/Multi-Lesion (SIML) HyperArc Brain SRT: Clinical Implementation and Early Outcomes

Patients with multiple brain metastases may not tolerate relatively longer treatment times for traditional stereotactic radiation therapy (SRT) with individual isocenter plans for each lesion due to discomfort or co-morbidities. SRT using a single-isocenter/multi-lesion (SIML) HyperArc volumetric modulated arc therapy (VMAT) plan with flattening filter free (FFF) beam could significantly shorten overall treatment time, and improve patient comfort, compliance, and clinic efficiency. We report early clinical results of treating multiple brain metastases with SIML HyperArc SRT. Twenty-three patients with multiple brain metastatic tumors (range, 2-9 lesions; total treated lesions, n = 96) were simulated using Encompass support and Q-fix mask, and treated with a highly-conformal SIML VMAT SRT plans via non-coplanar HyperArc geometry. Mean tumor distance to isocenter was 5.3 cm, maximum up to 7 cm. Common prescriptions were 25-30 Gy/5 fractions, 24-27 Gy/3 fractions, and 20 Gy/1 fraction prescribed to each planning target volume (PTV) using 2 mm margin around standard gross tumor volume (GTV) delineated on contrasted enhanced MP-RAGE MRI fusion. Acuros dose calculation for 6MV-FFF beam was used for tissue heterogeneity corrections. Alliance A071801 criteria was used for dose constraints to organs at risk (OAR) and target conformality. Treatment was delivered every other day with CBCT-guidance, adjustments made with 6DOF couch corrections on a medical linear accelerator, and treatment delivery time within 15 minutes. Local control rates were reported, and toxicity profile rated based on CTCAE v5.0 for brain radionecrosis, optic neuropathy, and brainstem dysfunction. All plans met Alliance A071801 requirements for each tumor coverage, dose to OAR including optic apparatus, brainstem, and spinal cord. Mean GTV and PTV volume were 9.4 cc (range, 0.3-54.8 cc) and 16.13 cc (range, 1.0-80.2 cc). Patient-specific quality assurance results were 98.3% for gamma passing criteria of 2%/2mm. Independent in-house Monte Carlo physics second check agreed with HyperArc plans by ±3.0%. Mean follow up was 6 months (range, 0.0-18.6 months). Of the 23 patients treated, 17 (74%) had post-treatment MRI imaging to assess local control and toxicity. Local control was achieved in 69/73 (95%) of treated and followed lesions. CTCAE grade 2 radionecrosis occurred in 2 patients and were managed with dexamethasone. No CTCAE grade 3+ events of radionecrosis, optic pathway dysfunction, or brainstem toxicity were observed. SIML HyperArc Brain SRT for multiple brain metastases has excellent local control and low toxicity profile in our patients. It can significantly reduce treatment delivery time as compared to traditional multiple-isocenter brain SRT or chronologically separate treatment courses and thus, help to improve patient comfort, compliance, ease of care, and clinic workflow. Longer median follow up of SIML brain SRT on larger patient cohort is warranted.

The Incidence of Severe Radiation-Induced Lymphopenia during Chemoradiotherapy for Stage Ⅲ Non-Small Cell Lung Cancer: A Comparative Study of Proton Versus Photon-Based Radiotherapy

To investigate the incidence of severe radiation-induced lymphopenia (SRL) and the survival in patients with stage Ⅲ non-small cell lung cancer treated with concurrent chemoradiotherapy with passive scattering proton beam (PSPT) or photon-based radiotherapy (XRT) including 3D-CRT and IMRT. We conducted a retrospective cohort study including 355 patients who received definitive concurrent chemoradiotherapy with PSPT (n = 38) or XRT (n = 317) at our institution between January 2010 and December 2020. SRL during concurrent chemoradiotherapy was defined as absolute lymphocyte counts (ALCs) of <500 cells/mm3. Propensity score matching (PSM) analysis was performed to adjust for the patient characteristics between the PSPT and XRT groups. Propensity scores were calculated using age, sex, PS (0-1 vs. 2), primary tumor location (upper/middle vs. lower lobe), pathology (Adeno vs. Others), PTV volume, ALCs at pretreatment, year of treatment (before vs. after July 2018, when durvalumab approved in Japan), and platinum-based chemotherapy regimen (CDDP based vs. CBDCA based). After PSM, the incidence of SRL and the overall survival (OS) were analyzed. The GTV and PTV volumes were significantly lower in the PSPT group than in the XRT group (median, 57 vs. 103 mm3; p < 0.05, 322 vs. 399 mm3; p < 0.05, respectively). ALCs at pretreatment were significantly lower in the PSPT group than in the XRT group (median, 1531 vs. 1718 cells/mm3; p < 0.05). SRL was observed in 275 patients (87%) in the XRT group and 27 patients (71%) in the PSPT group (p < 0.05). After PSM, PSPT significantly reduced the incidence of SRL compared to XRT (68.6 % vs. 88.6 %, p < 0.05), and the patients without SRL may have better 3-year OS than those with SRL (71.1 % vs. 55.3 %; p = 0.062). Compared with XRT, PSPT significantly reduced the incidence of SRL, and the patients without SRL had a good prognosis.

Patterns of Locoregional Failure After Ablative 5-Fraction Stereotactic MR-Guided on-Table Adaptive Radiation Therapy for Pancreatic Cancer

SBRT for pancreatic ductal adenocarcinoma (PDAC) is routinely delivered with non-ablative dose to only gross disease resulting in locoregional failure (LRF) rates of >50%, most commonly near the celiac artery (CA) and/or superior mesenteric artery (SMA). It is unclear whether an alternative approach of prescribing ablative dose to gross disease plus elective coverage prevents and/or delays LRF. The study objective was to describe the incidence and anatomic distribution of LRF using this treatment approach. A single institution retrospective analysis was performed of non-metastatic PDAC patients who received ablative stereotactic MR-guided on-table adaptive radiation therapy (A-SMART) on a 0.35T MR-Linac from 2018-2022. Median prescribed dose was 50 Gy/5 fractions. Elective coverage (EC), including a margin around the primary tumor, CA, and SMA, to 33-35 Gy/5 fractions became routine in 2019 using a simultaneous integrated boost; the porta hepatis was not routinely covered. LRFs were contoured and defined as out-of-field (OOF), marginal (M), or in-field (IF) if >80%, 20-80%, or <20% of it was outside of the most peripheral prescription isodose line. One hundred four patients were evaluated (87% head tumors). 94% had induction chemotherapy (median 4 months), usually FOLFIRINOX (66%) or gemcitabine/nab-paclitaxel (27%). 88% received EC. Median GTV, CTV, PTVgrosstumor, and PTVelective volumes were 29 cc, 90 cc, 64 cc, and 127 cc, respectively. 16 patients (15%) had LRF after a median of 17 months (range: 2.4-30.8) from A-SMART; 13 had scans available for delineating LRF. Median follow-up from A-SMART for the entire cohort vs. LRF was 12 vs. 24 months. LRF involved the primary tumor (31%), retroperitoneal lymph nodes (25%), SMA (19%), porta hepatis (19%), and CA (6%). LRF was OOF, M, or IF in 30.8% (n = 4), 61.5% (n = 8), and 7.7% (n = 1). Distance from the 3 SMA failures to SMA origin was 10 cm (EC used), 9.3 cm (EC used), and 3 cm (no EC). The 1 CA failure involved the CA origin (no EC). Median mean, maximum, and minimum dose of the contoured LRF region on the original plan was 33.3 Gy (range: 9.7-50.3 Gy), 56 Gy (range: 44.2-71.4 Gy), and 11.4 Gy (range: 1.2-22.7 Gy), respectively. Median V20, V25, V30, V35, and V40 of the contoured LRF was 84.3% (range: 16.1-100%), 69.2% (range: 12.5-99.7%), 57.5% (range: 9.3-95.5%), 41.2% (range: 6.8-84.0%), and 32.7% (range: 4.8-71.8%). This study represents the first patterns of LRF analysis after ablative 5-fraction SBRT for PDAC. Although EC is not currently endorsed by published pancreas SBRT guidelines, our low LRF incidence especially involving the CA/SMA demonstrates that EC should be considered, even when delivering ablative dose. Furthermore, given that nearly all LRF were M or OOF we have considered expanding our institutional elective volumes. While the optimal EC dose is uncertain, 33-35 Gy appears effective in limiting IF LRF and therefore has been standardized within ongoing ablative SBRT trials for PDAC at our institution.

Dosimetric Analysis of Local Failure Outcomes and Vertebral Compression Fracture Risk in Single-Fraction Spine Stereotactic Radiosurgery for Metastatic Sarcoma

Sarcoma spinal metastases (SSM) are particularly difficult to manage given their poor response rates to chemotherapy and their inherent radioresistance. We sought to analyze dosimetric parameters impacting local failure and vertebral compression fracture outcomes in a homogenously treated cohort of patients with SSM treated with single-fraction spine stereotactic radiosurgery (SSRS). A retrospective review was conducted on a cohort of patients with SSM treated with definitive SSRS at a single tertiary institution. 16-24 Gy was delivered to the GTV and 16 Gy uniformly to the CTV. Kaplan-Meier analysis was conducted to assess time to local failure (LF). The log-rank test was utilized to examine group differences. Patients were censored at time of last follow-up or death. Cox proportionate hazards modeling was used to determine hazard ratios (HR) and their respective 95% confidence intervals (CI). A total of 66 patients with 96 lesions underwent SSRS for SSM. Median follow-up was 17 months (IQR 8-28). Median age was 55 years (IQR 41-63). The most common histological subtype was leiomyosarcoma (41%) followed by liposarcoma (9%). 81 lesions received 24 Gy to the GTV, 12 received 18 Gy and 3 received 16 Gy. Median GTV and CTV volume was 13.6cc (IQR 5-27) and 51.6cc (IQR 30-80) respectively. 27% of patients had Bilsky 1b or greater disease. 16 of 96 lesions demonstrated progression representing a crude local failure rate of 17% with median time to failure of 8 months (IQR 5-18). The 1-year actuarial progression free survival (PFS) was 89% with a median PFS of 13 months (IQR 16-63). Median overall survival (OS) was 15 months (IQR 8-28) from SSRS. 8% of patients developed vertebral compression fractures at a median of 13 months post SSRS (IQR 7-25). Every 1 Gy increase in GTV minimum dose (DMin) across the range (5.8-25cc) was associated with a reduced risk of local failure (HR = 0.875 [95% CI 0.787-0.974], p = 0.01). Stratifying thresholds for GTV DMin, a local control benefit was seen as low as 12 Gy and higher (HR = 0.329 [95% CI 0.11-0.97, p = 0.044) with a significantly greater magnitude benefit seen at 14 Gy (HR = 0.267 [95% CI 0.09-0.77, p = 0.014) and above 15 Gy (HR = 0.091 [95% CI 0.03-0.41], p = 0.0018). There were no other queried variables besides GTV Dmin associated with local control including: GTV: volume, mean, Dmax, D90, CTV: volume, Dmin, Dmean, Dmax, or D90. There was an increased risk of VCF with increasing CTV DMean (HR = 2.4 [95% CI 1.4-4.1], p = 0.002) and CTV D90 (HR = 2.2 [95% CI 1.2-4.0], p = 0.01); however, no association with GTV parameters. This study represents one of the most homogenously treated and the largest cohorts of patients with sarcoma spinal metastases treated with single-fraction SSRS. Despite inherent radioresistance, SSRS confers durable and high rates of local control in SSM without unexpected long-term toxicity rates. Increasing GTV minimum dose is significantly associated with superior local control with no corresponding increased risk of VCF.

Clinical Feasibility of Daily Online Adaptive Bladder Cancer Radiotherapy with Cone Beam CT, Using Fiducial Makers

Radiotherapy (RT) for muscle invasive bladder cancer is challenging due to varying bladder filling. We assessed the efficacy and feasibility of online adaptive RT (oART), applying a focal boost to the tumor, in terms of dose and workflow. Bladder cancer patients (N = 15) were treated with oART on a ring-shaped Linac. This system integrates imaging (CBCT) with AI-based organ and tumor segmentation, adaptive treatment planning and delivery. Before treatment the GTV was demarcated with liquid markers. On the planning CT organs-at-risk and the GTV were contoured. The reference treatment plan was optimized with total dose for PTV (elective bladder, lymph nodes) 40Gy/20 fractions and an integrated focal boost to the GTV (15Gy). Margins were 3mm (GTV-CTV) and 5mm (CTV-PTV). Before each daily treatment, a CBCT was acquired. Bladder, rectum and GTV were determined by the AI. Planning CT and CBCT were registered to generate other organs at risk. Subsequently, the dose of the reference plan was calculated for this anatomy (scheduled plan). An adaptive plan was generated by reoptimization. Subsequently, a second pretreatment CBCT (CBCT2) was made to verify and correct the position, when necessary. Target coverage for PTV and GTV (V95%) and dose outside the target were evaluated on CBCT2. Radiation therapists (RTTs) executed the oART workflow with medical physicists (MPs) and radiation oncologists (ROs) on call. The time (median [range]) and personnel involvement were monitored. For all adaptive plans V95%>98% for CTV and GTV (boost) volumes. For scheduled plans this was 53.5% (CTV boost) and 98.5% (bladder+lymph nodes). For adaptive vs scheduled plans, the volume of dose (40Gy) to tissue outside the PTV reduced with 150cm3(p<0. 01). Median session time (patient entering-leaving) was 32 [25-45] min for the first 5 patients and reduced to 27 [20-61] min for subsequent patients. About 30% of this time was reoptimization. AI-generated GTVs were corrected in 75% for the first 5 patients and 40% for subsequent patients (taking 5min). Fiducial markers were clearly visible on CBCTs supporting GTV localization. ROs and MPs were consulted during each first fraction (5% of total) and 12% of the remaining fractions. The adaptive procedure is well feasible in clinical practice with an RTT-only workflow. The procedure takes longer than conventional RT, with reoptimization as a main factor. Dosimetric result are clearly favorable compared to delivery of non-adaptive plans.

An Attempt to Reduce Lung Dose-Volume in the Era of Radiotherapy Combined Immunotherapy

In immunotherapy era, the safety of thoracic radiotherapy, especially pneumonia is a concern of clinical and patients. The incidence of pneumonia in KEYNOTE 799 is higher than that in PACIFIC and GEMSTONE301, and the incidence of pneumonia is related to V20 Gy. This study aims to explore how to reduce the lung dose of immunotherapy plus concurrent chemoradiation therapy (cCRT). We prospectively selected 32 patients treat with IMRT for untreated, locally advanced, stage III NSCLC. They all received immunochemotherapy in the first cycle treatment and completed the first CT-based simulation. In the second cycle treatment, all patients received cCRT plus ICIs and each patient received the second radiotherapy location after 10 or 20 fractions of radiotherapy. The initial and second treatment plan based on CT image are Plan1 and Plan2. The volume changes of gross tumor volume (GTV) between primary and secondary CT scans were compared, and the dose-volume parameters such as lung volume (V5 Gy, V20 Gy, V30 Gy) and heart volume (V30 Gy) in Plan2 were compared with those of Plan1. Compared with the first and second CT scan, the mean volume of GTV is decreased by 34%. The dose-volume parameters of total lung and heart were significantly lower than those in Plan1.Among them the V20 Gy, V30 Gy of total lung have statistical difference (Z = -2.068, P = 0.039; Z = -3.008, P = 0.003; respectively) and decreased by 31%, 33%, respectively. Additionally, the V20 resected after the 10-fraction radiotherapy is less than the 20th (V20 Gy = 25.1%, 26.3%; respectively). Meanwhile, for treatment-related pneumonitis, there is only one case (5%) in grade 3 or higher pneumonitis, and most of pneumonitis can be relieved after symptomatic treatment. In the mode of immunotherapy plus cCRT, timely reduction measures in the process of radiotherapy will effectively reduce lung dose-volume (V20 Gy), so as to decrease pulmonary toxicity. Two-cycle induction therapy were followed by radiotherapy may be a potent treatment candidate.

Agreement among Radiation Oncologists and Radiologist in Contouring GTV on Planning and Mid-Treatment MRI for Locally Advanced Oropharynx Cancer

Over the 7-week radiotherapy course, patients with head and neck cancers undergo significant anatomical changes, including weight loss and tumor shrinkage (with complete response at mid-treatment in as high as 50% of patients). The current standard of care is to maintain the same plan for the entire treatment duration, unless major dosimetric deviations are suspected. The use of MRI for treatment adaptation has the advantage of increased soft tissue contrast and is being integrated into several clinical practices with the recent implementation of the MR-Linac technology. In this interim secondary analysis of a phase 2, randomized trial, we assessed inter-observer variability (IOV) in the delineation of GTV at planning and mid-treatment in locally advanced oropharynx cancer (OPC). Three expert radiation oncologists (RO) and 1 expert radiologist, with a minimum of 5 years' experience in MRI contouring, blinded to each other's volumes, were provided with planning and mid-treatment MRI (T1 gadolinium, T2-weighted and DWI) of 9 patients with locally advanced OPC. Primary gross tumor volume (GTV) was independently contoured by all 3 ROs and the radiologist. Contouring agreement was analyzed using the dice similarity coefficient (DSC) index and the average Hausdorff distance. Nine cases of locally advanced OPC were included. Fifty percent of the patients were stage 3 (AJCC 8th edition) and all were p16+ OPC. There was moderate IOV in the delineation of GTV on planning MRI as evidenced by mean DSC index and Hausdorff distance of 0.75 (range 0.53 - 0.87) and 0.30 cm (max 2.14 cm). At mid-treatment, the GTV IOV had a mean DSC index and Hausdorff distance of 0.30 (range 0.19 - 0.76) and 0.55 cm (max 2.83), respectively. The contours of the radiologist compared to RO shown a mean DSC index and Hausdorff distance on planning MRI 0.63 (range 0.53 - 0.69) and 0.41 cm (max 2.14 cm), and on mid-treatment MRI of 0.36 (range 0.19 - 0.59) and 0.68 cm (max 1.08 cm). Although this study demonstrates the presence of moderate IOV between 3 experienced head and neck ROs and one radiologist in an academic institution for the delineation of GTV on planning MRI, we observed a higher IOV between the 4 experts on mid-treatment MRI. We also experienced a higher IOV between the radiologist and RO on planning and mid-treatment images. These results show high degree of GTV volume variability on mid-treatment MRI. Therefore, peer review of contours is important and guidelines for MR adaptive tumor delineation are needed.

KV-CBCT-Guided Daily Adaptation Improves Target Coverage and Spares Normal Tissue for Accelerated Partial Breast Irradiation

Linear accelerator based accelerated partial breast irradiation (APBI) in early-stage breast cancer necessitates a reduction in non-target breast tissue to decrease long term toxicity and adverse cosmetic outcome. In particular, lumpectomy cavity seromas may decrease in size and deform in shape during the course of short course APBI. Online adaptive RT (oART) offers considerable prospect for treating mobile targets through pendulous breast anatomy. However, there are limited studies outlining the methods and outcomes of CBCT-based oART for APBI. Here we present a retrospective, single institutional study analyzing the treatment process for patients receiving stereotactic kV-CBCT guided oART APBI. Fourteen patients were treated to 30 Gy in 5 fractions for a total of 70 fractions. Time between simulation and treatment, change in gross tumor volume (GTV), and differences in DVH metrics with adaption were analyzed. The Wilcoxon paired, non-parametric test was utilized to test for DVH metric differences between the scheduled plans (initial plans recalculated on daily CBCT anatomy) and treated plans, which were either the scheduled or adapted plan (initial plans re-optimized using daily anatomy), depending on the preference of the treating physician or physicist. Median (inter-quartile range) time from simulation to first treatment was 28 days (21-33 days). During this same time, GTV volume reduced to 72.5% (57.8-87.3%) of the simulation lumpectomy cavity volume. Adaptive treatments required 31.1 min (27.2-37.1 min) from start of CBCT to treatment session end. Table 1 summarizes differences between scheduled and treated plan metrics for 70 fractions, 62 (89%) of which were treated adaptively and 8 (11%) of which were treated using the scheduled plan. Significant improvement in prescription planning target volume coverage (p = 0.003), significant reduction in 5/6 organ-at-risk metrics evaluated (p ≤ 0.003), and significant improvement in conformity index and high dose spillage (p ≤ 0.001) were realized with adaption. Table 1: Scheduled versus treated plan metrics. APBI using oART decreased most organs at risk DVH metrics, improved plan quality metrics, and increased target coverage, justifying the use of kV-CBCT-guided oART for APBI.