Stereotactic Body Radiation Therapy Treatment Research Articles

Outcomes of Stereotactic Body Radiation Therapy (SBRT) for Femur Oligometastases

Stereotactic body radiation therapy (SBRT) is increasingly used for oligometastatic bone disease, but there is limited data regarding the clinical outcomes of utilizing SBRT in treatment for femur metastases, which was excluded from SABR-COMET. We aimed to identify patient or treatment factors associated with clinical outcomes among patients treated with SBRT to femur metastases for oligometastatic disease control or re-irradiation. We identified 50 patients with 56 femur lesions consecutively treated with SBRT at a single institution May 2017-June 2022. The Kaplan-Meier method was used to characterize time-to-event endpoints and Cox proportional hazards models were performed to evaluate the associations between baseline factors and clinical outcomes. Local control was defined as the absence of regional tumor progression at treated area or need for surgical fixation post radiation. Most patients had ECOG 0-1 (90%), prostate (50%) or breast/lung (16%) cancer, and 1-3 lesions (100%), including 30 proximal and 5 distal. 55% of lesions received concurrent systemic therapy, including ADT (n = 18) or immunotherapy (n = 6). Median PTV volume was 54.7cc (range, 6.6 to 387cc). PTV V100(%) was 99% (range 71.5-100). Fractionation included 18-20 Gy/1F, 27-30 Gy/3F, 25-40 Gy/5F, and 50 Gy/10F. 43% of lesions had Mirel's score ≥ 7 and 91% of lesions did not have extraosseous bone extension on diagnostic CT and/or MRI. Acute toxicities included grade 1 fatigue (14.3%), pain flare (7.1%), and decreased blood counts (1.8%). Late toxicities included fracture (1.8%) at 1.5 years and 2 patients with radiation-induced osteonecrosis (3.6%) from dose of 40 Gy in 5F and 30 Gy in 5F (after prior 30 Gy/10F). One patient (n = 2%) required fixation post-radiation due to progression of disease or symptoms. With median follow up 19.4 months, 1 and 2-year rates of local control were 84% and 69%, progression-free survival were 55% and 27%, and overall survival were 91% and 74%. There was no significant association between patient or treatment characteristics and local control outcomes. Femur SBRT for oligometastatic disease control in well-selected patients was associated with good outcomes with minimal rates of acute and late toxicity. Further prospective study is warranted.

Clinical Efficacy and Safety of Once-Weekly Fractionation in Stereotactic Body Radiotherapy for Pulmonary Oligometastatic Lesions

As the oligometastatic disease paradigm has become more widely accepted, further investigation is needed to risk-stratify patients within this spectrum of disease and define optimal treatment methods. Stereotactic Body Radiotherapy (SBRT) has emerged as an efficacious and safe modality to control individual lesions and improve clinical outcomes in the setting of oligometastatic disease. There is scant literature describing ideal SBRT inter-fraction time intervals or their impact on clinical outcomes, especially for treating pulmonary oligometastases. Most institutions appear to offer treatments on consecutive days or every other day. In this abstract, we sought to evaluate the efficacy and safety of delivering SBRT treatments in a once-weekly fractionation scheme. The study was undertaken via retrospective review at a single institution. We included patients with pulmonary metastatic lesions treated with SBRT at our institution between 2015 and 2019. Patients with oligometastatic disease were included, defined as patients with 5 or fewer total metastatic lesions. Treatments were delivered between 3 and 5 fractions and using at least 5 Gy per fraction. Per institutional protocol, all treatments were delivered 7 days apart. From a single institution, 204 lesions from 111 patients were included. Median follow-up was 16.5 months [IQR 7 - 36.3]. Median dose was 40 Gy [IQR 30 - 50], median BED was 80 Gy [IQR 60-100], median dose per fraction was 10 Gy [IQR 8-11]. Median internal target volume (ITV) was 18.5 cc [IQR 9.3 - 45.8]. The most common tumor histologies were lung adenocarcinoma (38.2%), colorectal adenocarcinoma (15.6%), lung squamous cell carcinoma (12.7%), renal cell carcinoma (5.9%), breast invasive ductal carcinoma (5.4%), small cell lung cancer (3.9%), and melanoma (2.9%). 2-year local control (LC) rate was 85.7% and 5-year LC rate was 84.3%. 2-year regional control (RC) rate was 53.9% and 5-year RC was 49%. Median overall survival (OS) was 20 months [IQR 9 - 37.3]. Cox regression analysis revealed biologically effective dose (BED) (HR 0.99 [0.98 - 0.99] p = 0.001) as well as dose per fraction (HR 0.92 [0.86 - 0.97] p = 0.003) were both associated with improved OS. Longest tumor dimension was associated with worse OS independent of BED and dose per fraction (HR 1.26 [1.1 - 1.4] p = 0.001). Total toxicity incidence was 7.3%, which consisted only of G1-G2 cough, dyspnea, and fatigue. Treatment of pulmonary oligometastatic lesions with SBRT delivered via once-weekly fractionation is associated with excellent local control and minimal toxicity. Larger studies are warranted to directly compare clinical outcomes of weekly SBRT fractionation to other conventional SBRT treatment schedules.

Exploring the Efficacy and Molecular Mechanism of Systemic Therapy-Based Split-Course Stereotactic Body Radiation Therapy for Solid Tumors

Considering the therapeutic toxicity, the question of how to administer adequate chemotherapy to synchronize Stereotactic body radiation therapy (SBRT) treatment strategy for maximizing the benefits of neoadjuvant therapy to improve prognosis is a challenging and debatable issue. This study explores the feasibility and theoretical advantages of the simultaneous implementation of split-course SBRT with systemic treatment. We evaluated the effect of three irradiation regimens (conventional radiotherapy (C-R, 15×2 Gy, (D1-5, D8-12, D15-19)), continuous SBRT (C-S, 3×7 Gy, (D1-3)), split SBRT (S-S, 3×7 Gy, (D1, D10, D19)) in combination with systemic therapy (chemotherapy (gemcitabine), PD-1 inhibitor (Anti-mouse PD-1 antibody) and angiogenesis-targeting agent (Anlotinib)) on tumor growth and survival by using the immunologically active C57BL/6 bilateral subcutaneous model with different cancer cells. At different time points after treatment, we monitored changes in the tumor microenvironment and explored the possible mechanisms. In the case of radiotherapy alone, we found similar tumor control in all groups but the best survival in the S-S group. When combined with systemic therapy, the S-S group has shown advantages in tumor control and survival. And the S-S combination group induced more CD4+ and CD8+ T lymphocyte infiltration in the tumor, which had the highest number of tumor vessels and the smallest area of hypoxia. Tumor cell PD-L1 expression was increased after radiotherapy in all but the most elevated and persistent S-S combination treatment group. CD3+ T cells, CD4+ T cells and CD8+ T cells peaked at weeks 2-3 after treatment, and all remained at the highest level for 6 weeks in the S-S combination group. Meanwhile, PD-L1 expression was significantly higher in all tumors in the third week than in other groups. The most significant reduction in the hypoxic area and increase in perfusion level was observed in the S-S group in the third week. RNA sequencing analysis revealed that immune response-related pathways were upregulated on the irradiated and non-irradiated side, tumor proliferation and invasion on the non-irradiated side, and angiogenesis-related pathways were down-regulated in the fractionated SBRT combination treatment group. In both irradiated side and non-irradiated side tumor tissues where the abscopal effect was observed, immune response-related pathways were upregulated in the S-S group relative to the C-R group, and tumor proliferation and invasion and angiogenesis-related pathways were found to be downregulated in the non-irradiated side. In preclinical models, the combination of split SBRT with systemic therapy has been shown to be more advantageous than conventional segmentation, possibly by affecting immune cell infiltration in the tumor microenvironment and reducing tumor hypoxia.

Clinical Outcomes of Synchronous Lung Stereotactic Body Radiation Therapy Lesions via Single-Isocenter/Multi-Lesion Treatments

Lung cancer patients with synchronous primary or oligometastatic (< 5 lesions) with associated co-morbidities may not retain their treatment position for the extended stereotactic body radiotherapy (SBRT) treatment times with individual isocenter plans for each lesion due to discomfort or shortness of breath. SBRT using a single-isocenter/multi-lesion (SIML) volumetric arc therapy (VMAT) plan with flattening filter free (FFF) beam could significantly shorten overall treatment time, improve patient comfort and compliance and clinic efficiency. We report clinical results of treating multiple lung metastases or synchronous primary lung cancers with SIML lung SBRT. Eighty patients with synchronous primary lung cancers or oligometastatic lung tumors (two, n = 61; three, n = 10; four, n = 4; five n = 5; total treated lesions, n = 193) were simulated with abdominal compression and/or 4D-CT MIP images and treated with a highly-conformal SIML VMAT lung SBRT plans via 3-4 non-coplanar arcs. Common prescriptions were 50-55 Gy/5 fractions and 54 Gy/3 fractions prescribed 70-80% isodose line to the each PTV. Acuros dose calculation for 6MV-FFF beam was used for tissue heterogeneity corrections. RTOG-0618/0813 criteria were used to dose constraints to organs at risk (OAR) and target conformality. Treatment was delivered every other day or twice weekly with CBCT-guidance, adjustments made with 6DOF couch corrections on a medical linear accelerator, and treatment delivery time within 15 minutes. Local control rates and toxicity profile was evaluated using CTCAE v. 5.0 grading for pneumonitis, rib fracture and chest wall pain. All plans met RTOG-0618/0813 requirements for each tumor coverage, dose to OAR including normal lung and ribs. Mean follow up after last fraction of treatment was 16.9 months (range, 1.0-54.2 months). PTV volume ranged from 2.17 to 167.8 cc with mean volume of 16.1 cc. Of the 80 patients treated, 71 had adequate post-treatment thoracic CT imaging to assess local control. Local control was achieved in 167/175 (95.4%) of treated and followed lesions. CTCAE grade 1 asymptomatic pneumonitis was noted on thoracic CT scans in 42/71 (59.2%) of patients and occurred, on average 4.8 months after SBRT. Symptomatic pneumonitis and rib fracture did not occur in any patient. CTCAE grade 2 chest wall pain occurred in 4/80 (5.0%) treated patients and was managed conservatively with over-the-counter NSAIDS or acetaminophen. SIML lung SBRT for synchronous primary lung cancers or multiple lung metastases can be used as a variant to traditional multiple isocenter SBRT or chronologically separate treatment courses, and has excellent local control rates and low toxicity profile in our patient population. It can help improve comfort and compliance of the patients who have difficulty lying still for an extended treatment course, and significantly reduces treatment time via isocenter shifts/repeated CBCTs for image guidance, thus improving clinic efficiency.

Longitudinal Radiomics-Based Prediction of Local Recurrence after Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer

Computed tomography (CT)-based radiomic analysis is an emerging tool that can help predict recurrence after radiation in non-small cell lung cancer (NSCLC). Most studies have focused on using radiomic features obtained from pre-treatment CT scans but not on post-treatment CTs. Our goal was to determine if radiomic features derived from post-treatment CTs perform better than those from pre-treatment CTs in predicting local recurrence after stereotactic body radiation therapy (SBRT) in patients with early-stage NSCLC. Patients with T1/T2 N0 early-stage NSCLC were retrospectively reviewed. Criteria for selection included patients with biopsy-proven NSCLC, non-ground glass solid lesions, 4-5 fraction SBRT treatments, and non-contrast thin-slice CTs available at pre-treatment baseline and at 3 and 6 months post-SBRT. Clinical and tumor characteristics were compared using Chi-square and Student's t-tests. CT image pre-processing was performed and 107 radiomic features were extracted using 3D Slicer and open-source software. Univariate analysis for local recurrence was determined by Cox regression with death as a competing risk. The Benjamini-Hochberg Procedure was applied to control the false discovery rate. Pearson correlation analysis was used to exclude redundant features (r > 0.8), and multivariate analysis was conducted with Random Forest on the top-performing features found on univariate logistic regression. Models were trained on a class-balanced loss to account for class imbalance. Twenty iterations of stratified 3 k-fold cross-validation were used to select the best model by the area under the receiver operating characteristic curve (AUC). We identified and analyzed 86 patient tumors, including 76 non-local recurrences and 10 local recurrences (49 males, 37 females; age, median 72, range 52-91 years). No differences in age, histology, standardized uptake values on positron emission tomography scans, gross tumor volume, and radiation dose were found between patients with and without local recurrence (all p >0.05). The median time to local recurrence was 18.9 months (range 5.5-45.6 months). At the baseline, 3-month, and 6-month timepoints, 2, 10, and 10 radiomic features predicted local recurrence on Cox regression univariate analysis, respectively (all q <0.01). On multivariate analysis of top-performing radiomic features, the 3-month timepoint performed the best with a mean (±standard deviation) AUC score of 0.82 (±0.13) compared to a mean AUC of 0.73 (±0.086) at baseline and a mean AUC of 0.74 (±0.10) at 6 months. Post-treatment radiomic features at 3 months outperformed pre-treatment radiomic features in predicting local recurrence after SBRT for NSCLC. These results suggest radiomic data from follow-up CTs may be helpful when developing radiomic models to predict local recurrence in patients with NSCLC.

Frequent Friers: Outcomes in Patients Who Receive Multiple Courses of Lung SBRT

Stereotactic body radiation therapy (SBRT) is a definitive therapy for early-stage non-small cell lung cancer and solitary pulmonary metastases with high tolerability and excellent survival rates. With longer survival and patients developing subsequent primaries or oligometastatic disease, patients are receiving multiple repeat lung SBRT courses. This study aims to assess safety and efficacy of high-frequency SBRT (HF-SBRT) to the lung, defined as >3 courses. A retrospective review was performed of patients who received >3 courses of lung SBRT. Logistic regression was performed to identify predictors of radiation pneumonitis (RP) and worsening pulmonary function (WPF). Local control (LC) and overall survival (OS) were evaluated using the Kaplan-Meier method. Ninety-four courses of HF-SBRT to the lung were identified among 28 patients. 78% of patients received 3 SBRT courses, 12% received 4 courses, and 7.1% received >5 courses. Median follow-up was 4.4 years. Median age at time of treatment was 73 years-old; 58% males; 42% had an underlying pulmonary comorbidity; 39% prior lung surgery; 52% history of cardiac disease; 52% prior tobacco use; median ECOG 0. Median SBRT dose was 48 Gy. Median interval between courses was 5.6 months. Zero patients experienced greater than grade 2 acute CTCAE v5 toxicity. 7.2% (7) of patients developed RP at median time of 2.6 months [IQR: 1.4,7.4]; grade 1: 3 patients, grade 2: 1 patient, grade 3: 2 patients. Of patients who developed RP, 42% (3) went on to receive further SBRT without experiencing significant adverse events (AEs). History of pulmonary disease, prior lung surgery, and history of tobacco use strongly correlated with WPF but not RP (WPF p-values: <0.001, 0.003, <0.001, respectively). History of cardiac disease did not correlate with WPF or RP. Receiving bilateral lung SBRT treatment (vs unilateral) trended towards correlation with WPF (p = 0.06) and RP (p = 0.08). Time between SBRT courses did not significantly differ for those who developed RP (p = 0.62) or WPF (p = 0.42). No individual or plan sum dosimetric constraint (GTV, PTV, unilateral lung V5, lung V10, lung V20, unilateral mean lung dose, or total lung V20) significantly differed in those who experienced RP. WPF correlated with the plan sum unilateral lung V10 (p = 0.05). LC at 1-year was 100%, 1 local failure occurred at 13 months; 2-year OS was 91.7%, median OS 5.4 years. Overall, HF-SBRT was well tolerated. Development of RP did not correlate with a specific individual or plan sum dosimetric parameter, with patients receiving subsequent courses of SBRT without increased AEs. WPF increasingly occurred with subsequent SBRT courses and correlated with unilateral plan sum V10. This study suggests that in appropriately selected patients, SBRT after RP can still be provided as definitive care, while further studies should validate this and focus attention on mitigating long-term WPF in patients who receive HF-SBRT.

Assessment of Minimum Dose as a Strong Predictor of Local Failure after Spine SBRT

Stereotactic body radiation therapy (SBRT) has demonstrated robust clinical benefits in carefully selected patients, improving local control and even overall survival (OS). Even so, a wide range of dose-fractionation schemes are used in clinical practice. We seek to assess a large database to determine clinical and dosimetric predictors of local failure after spine SBRT. From a large institutional database, spine SBRT treatments with subsequent imaging follow-up to assess local control were identified. Patients were treated with a simultaneous integrated boost technique using 1 or 3 fractions, generally delivering 20-24 Gy in 1 fraction to the high dose volume and 16 Gy to the low dose volume (or 30-36 Gy and 24 Gy for 3 fraction treatments). Exclusions included: lack of imaging follow-up, proton therapy, and benign primary histologies. Statistical analyses included Cox proportional hazards analyses and the robust log-rank statistic for cut-point analysis. The cumulative incidence of local failure with death as a competing risk was considered as the primary endpoint. A total of 522 eligible spine SBRT treatments (68% single fraction) were identified in 377 unique patients. Patients had a median OS of 43.7 months (95% confidence interval: 34.3-54.4). The cumulative incidence of local failure was 19.3% (15.3-23.2) at 1 year and 25.6% (21.1-29.9) at 2 years. Univariate analysis identified that the minimum dose (normalized for the prescription dose) was a strong predictor of local failure (p = 0.0093). Among patients treated with a single fraction, statistical significance was maintained (p = 0.024). No other dosimetric factors were predictive of local failure. In a cut point analysis, the log-rank statistic was maximized at 15.8 Gy minimum dose for single-fraction treatment (HR = 0.51, 95% CI: 0.34 - 0.75, p = 0.0009). Cumulative incidence of local failure was 15.1% (9.8-20.2) vs. 24.7% (17.2-31.5) at 1 year using this cut-off. Comparable local control was demonstrated with a minimum dose of 14 Gy (HR = 0.57, 95%: 0.37 - 0.87, p = 0.009), with reduced local control with lower minimum doses. Among a range of clinical factors assessed, only epidural and soft tissue involvement were predictive of local failure (HR = 1.80 and 1.98, respectively). Multivariable analyses incorporating soft tissue involvement, epidural extension, and multilevel disease confirmed the 15.8 Gy cutoff for single fraction cases (HR = 0.58, 95% CI: 0.38-0.88, p = 0.011). Spine SBRT offers favorable local control using a range of dose-fractionation schemes; however, minimum dose has a strong association with local control, unlike any other dosimetric factors tested. Furthermore, statistical significance was maintained even when considering epidural extension and potential limitations from dose to the spinal cord. Our data suggests that the minimum dose should be prioritized during treatment planning, ideally to at least 14 - 15.8 Gy for single fraction.

Dosimetric Impact of Radiolucent Carbon Fiber Hardware for Post-Operative Spine Stereotactic Body Radiation Therapy

The spine is the most common site of osseous metastases. In the non-operative setting, there is growing support for stereotactic body radiation therapy (SBRT) over conventional radiation therapy for improved pain relief and local control. Hybrid therapy consisting of separation surgery and post-operative SBRT is considered in patients with biomechanical instability and epidural cord compression. Surgery traditionally requires titanium (Ti) implants, which introduce artifacts on post-operative imaging in addition to increased uncertainty and beam attenuation. Use of radiolucent carbon fiber reinforced polyetheretherketone (CFR-PEEK) hardware has been shown to provide safe and comparable surgical outcomes as compared to Ti. Our primary objective is to assess the dosimetric impact of Ti versus carbon fiber implants in spine SBRT. Single institution retrospective series of post-operative spine SBRT from 2019-2020. Re-irradiation cases were excluded. The electronic medical record and treatment planning systems (TPS) were queried. Dosimetric analyses compared original Ti plans with reoptimized plans, replacing Ti hardware electronic density with carbon fiber. Maintaining clinical goals, dose calculations were performed in a treatment planning system using a collapsed cone algorithm. All treatments used step and shoot intensity modulated radiation therapy to avoid beam angles with significant metal along the beam path. Metallic artifacts were contoured and assigned the appropriate tissue density. A D'Agostino-Pearson test was used to assess data for normality. We used paired Student's t-tests to compare three dosimetric outcomes in the setting of Ti and carbon fiber implants. Planning target volume (PTV) coverage was represented by the volume receiving at least the prescribed dose (%), the maximum point dose (dmax, cGy) to the spinal cord planning risk volume (PRV, 2 mm margin), and the overall hot spot intensity (plan dmax). A series of 14 consecutive SBRT cases were evaluated (dose 27-30 Gy in 3-5 fractions). All dosimetric outcomes were normally distributed (p>0.05). We found a statistically significant difference in PTV coverage between the original SBRT treatment plans with Ti hardware (mean 85.1 ± 7.9%) and reoptimized carbon fiber hardware (87.3 ± 6.6%; p = 0.002). There was no significant difference in mean spinal cord PRV dmax between Ti and carbon fiber plans (1846 ± 483 cGy vs. 1842 ± 495 cGy; p>0.05). We observed a nonsignificant increase in mean overall dmax from 3932 ± 416 cGy in the Ti cohort to 4111 ± 906 cGy in the carbon fiber cohort (p>0.05). Carbon fiber implants provide a significant increase in SBRT target coverage, without impacting the overall plan and spinal cord PRV dmax in this retrospective series. In addition to improved post-operative imaging and reduced uncertainty, carbon fiber hardware may offer dosimetric advantages as compared to traditional Ti spinal implants, and warrants further investigation in a larger cohort.

Toxicity of Patients with Ultra-Central Thoracic Tumors Treated with Stereotactic Body Radiotherapy (SBRT) with Dose of 50 Gy in 5 Fractions

The ideal regimen for stereotactic body radiotherapy (SBRT) in ultra-central lung tumors is still to be defined, mostly due to the risk of unacceptable or fatal toxicity. There is not much information on outcomes after SBRT for this group of patients. We summarize here our experience with ultra-central lung cancer patients treated with the dose of 50 Gy delivered in 5 fractions. This study is a retrospective review of all cases of ultra-central thoracic tumors treated with SBRT with the dose of 50 Gy in 5 fractions, delivered every other day, at our institution. In all cases, as we defined ultra-central lung tumor, the PTV overlapped or touched one or more of the following structures: bronchial tree, trachea, great vessels, heart, and esophagus. Metastatic and primary lung lesions were included. The volumes of treatment were defined by 4D-CT to consider breathing motion. Normal organs constraints followed the recommendations of the RTO 0813 trial as follows: Spinal cord: max 30 Gy. Lung right or lung left: V13 Gy[cc] < 1500. Esophagus: max 52 Gy and nonadjacent esophagus: V27.5 Gy[cc] < 5. Heart: V32 Gy[cc] < 15; max 52 Gy. Great vessels: max 52 Gy and non-adjacent great vessels V47 Gy[cc] < 10. Trachea plus bronchus: max 52 Gy and non-adjacent V18 Gy[cc] < 4. Follow-up, at the discretion of the treating MD, included periodic CT scans of the thorax after SBRT and assessment of radiation-induced toxicity scored with CTCv3.0. Between December 2015 and February 2022, 86 patients were eligible for this review. Median follow-up was 17 months (range: 1-76 months); the median age was 74 years (range: 37-98 years). Histology was as follows: 50 patients had biopsy proved NSCLC, 16 had no biopsy, and 20 had metastatic non-lung primaries. Overlapped structures were as follows: with great vessels in 46 cases, heart in 20 cases, trachea/branchial tree in 18 cases, and esophagus in 2 cases. In 16 patients the overlap was present in more than one structure. Overall, 68.6% did not report acute toxicity. The most common acute side effects were fatigue (15.1%), coughing (8.1%), shortness of breath (6.9%), esophagitis (2.3%), and dysphagia (1.1%). No grade 3 or more significant toxicity was described. As acute side effects, many patients had exacerbations of the previous condition, such as shortness of breath (16 pts) or coughing (4 pts) during follow-up. Pneumonitis was found as a late side effect in four cases. One patient had empyema associated with a fistula in the non-irradiated lung, where the patient had previous surgery, but in the irradiated lung no severe complication was detected. There were no deaths attributed to the SBRT treatment. 67.5% of 86 patients were alive at the time of the review; 87.2% had local control, and 65.1% had metastases-free survival. In this cohort of patients, no death or even severe acute or chronic toxicity was attributed to SBRT. SBRT seems safe for ultra-central lesions using the regimen of 50 Gy in 5 fractions with the constraints of the RTOG 0813 trial.

Optimized Target Delineation Procedure for the Radiosurgery Treatment of Ventricular Tachycardia: Observer-Independent Accuracy

Stereotactic body radiotherapy (SBRT) has shown promising results for patients with recurrent ventricular tachycardia that failed catheter ablation. The simplest method of target delineation based on manual transfer of CTV from several 3D visualizations (electroanatomic mapping system) to planning CT slices (2D) was subjective and very time consuming. Advanced methods are based on merging of electroanatomic maps (EAM) with CT. To date, 2 types of EAM-CT merge were proposed: manual alignment of EAM structures with segmented CT structures [1,2] and use of semi-automatic algorithm [3]. The goal of this work was to modify current method [2] with the use of robust automatic algorithms to assure reasonably short learning curve. This work is based on data of 10 patients who had previously undergone SBRT treatment for ventricular tachycardia (VT). Two observers participated in this study: (1) an electrophysiologist technician (cardiology) with substantial experience in EAM-CT merge, and (2) a clinical engineer (radiotherapy) with minimum experience with EAM-CT merge. Observer (1) performed EAM-CT merge three times for each case with an interval of at least 8h. Observer (2) did EAM-CT merge once for each patient following instructions written by observer 1. EAM-CT merge consist of 3 main steps: segmentation of left ventricle from CT (CT LV), registration of the CT LV and EAM, CTV delineation from EAM specific points. Mean Hausdorff distance (MHD), Dice Similarity Coefficient (DSC) and absolute difference in Center of Gravity (CoG) were used to assess intra/interobserver variability. All quantitative data was expressed as the mean and SD. Intraobserver variability Three segmented CT LVs were compared with each other. The mean DSC was 0,92±0,01 for all cases. The MHD was 1,49 ± 0,23 mm and the mean absolute difference in CoG coordinates was <1.5mm for all cases. The mean DSC and MHD for 3 CTVs altogether was 0,82±0,06 and 0,71 ±0,22 mm. The mean absolute difference in CoG was 0,64mm, 0,95mm and 0,78mm for X, Y, and Z coordinates, respectively. Interobserver variability Segmented CT LVs showed great similarity (mean DSC of 0,91±0,01, MHD of 1,86±0,47 mm) for all cases. The mean DSC comparing CTVs from both observers was 0,81±0,11 and MHD was 0,87±0,45 mm. The difference in CT LV volumes correlates with DSC of compared CTVs (Pearson´s correlation coefficient R = 0,8, p = 0,005) indicating that accurate segmentation of CT LV is crucial for successful precise CTV delineation. Modification of the current method based on incorporating automatic algorithms created a robust and fast method for CTV delineation. High similarity of both, the segmented CT LVs and delineated CTVs between observers confirmed robustness of the proposed method and steep learning curve.

Liver stereotactic body radiation therapy without fiducial or retained ethiodized oil guidance warrants greater than 5 mm planning target volumes.

For liver stereotactic body radiation therapy (SBRT), the placement of fiducial markers or retained ethiodized oil by transarterial chemoembolisation (TACE) provides a landmark for consistent target localisation. TACE and fiducial markers are invasive procedures that harbour additional risks. We hypothesise that liver SBRT can be accurately delivered without the use of these invasive surrogate markers. We retrospectively identified 50 consecutive patients who underwent liver SBRT with respiratory motion management to a single lesion which exhibited retained ethiodized oil per prior TACE delivery. For each SBRT fraction, two manual rigid image registrations were performed by the treating physician. One using the liver contour as a surrogate for the target and second aligning only to the radio-opaque retained ethiodized oil of the treated lesion. The magnitude of the displacement vector between the two registration methods was used to assess the accuracy of target localisation if ethiodized oil was not present. For the 50 patients, a total of 244 analysable cone-beam CTs (CBCTs) were included (six CBCTs excluded due to poor ethiodized oil visualisation). Respiratory motion management techniques consisted of active breathing control for 13 and abdominal compression for 37 patients. Forty-two patients had peripheral lesions and eight had central lesions (<2 cm from left and right portal veins). The average target localisation offset between the two registration methods (i.e. liver contour vs. retained ethiodized oil alignment) for patients with a single peripheral or central liver lesion was 5.8 and 5.3 mm, respectively. Across all patients, the average change in target position exceeded 5 mm for image registration methods based on the liver contour alone versus the retained ethiodized oil region. This suggests that margins greater than 5 mm may be required for respiratory motion-managed liver SBRT treatments in patients who do not undergo prior TACE or fiducial placement.

Hypoxia dose painting in SBRT – the virtual clinical trial approach

Background Treating hypoxic tumours remains a challenge in radiotherapy as hypoxia leads to enhanced tumour aggressiveness and resistance to radiation. As escalating the doses is rarely feasible within the healthy tissue constraints, dose-painting strategies have been explored. Consensus about the best of care for hypoxic tumours has however not been reached because, among other reasons, the limits of current functional in-vivo imaging systems in resolving the details and dynamics of oxygen transport in tissue. Computational modelling of the tumour microenvironment enables the design and conduction of virtual clinical trials by providing relationships between biological features and treatment outcomes. This study presents a framework for assessing the therapeutic influence of the individual characteristics of the vasculature and the resulting oxygenation of hypoxic tumours in a virtual clinical trial on dose painting in stereotactic body radiotherapy (SBRT) circumventing the limitations of the imaging systems. Material and methods The homogeneous doses required to overcome hypoxia in simulated SBRT treatments of 1, 3 or 5 fractions were calculated for tumours with heterogeneous oxygenation derived from virtual vascular networks. The tumour control probability (TCP) was calculated for different scenarios for oxygenation dynamics resulting on cellular reoxygenation. Results A three-fractions SBRT treatment delivering 41.9 Gy (SD 2.8) and 26.5 Gy (SD 0.1) achieved only 21% (SD 12) and 48% (SD 17) control in the hypoxic and normoxic subvolumes, respectively whereas fast reoxygenation improved the control by 30% to 50%. TCP values for the individual tumours with similar characteristics, however, might differ substantially, highlighting the crucial role of the magnitude and time evolution of hypoxia at the microscale. Conclusion The results show that local microvascular heterogeneities may affect the predicted outcome in the hypoxic core despite escalated doses, emphasizing the role of theoretical modelling in understanding of and accounting for the dominant factors of the tumour microenvironment.

Comparison of two optimization algorithms (VOLOTM , SEQU) for CyberKnife® treatment of acoustic neuromas, lung metastases, and liver metastases.

Two optimization algorithms VOLO™ and sequential optimization algorithm (SEQU) are compared in the Precision® treatment planning system from Accuray® for stereotactic radiosurgery and stereotactic body radiotherapy (SBRT) treatment plans. The aim is to compare the two algorithms to assess if VOLO™ is better of SEQU in certain treatment site. Sixty clinical treatment cases were compared. Entities include Acoustic neuroma (AN), lung metastases, and liver metastases. In each entity, 10 SEQU and 10 VOLO™ treatment plans were optimized. The Ray-Tracing calculation algorithm was used for all treatment plans and the treatments were planned exclusively with fixed cones (5-50mm). The number of nodes, beams, total MU, and treatment time were compared. Conformity index (CI), new conformity index (nCI), homogeneity index (HI), gradient index (GI), and target coverage were examined for agreement. Dmin , Dmean , Dmax , D100%, D98%, and D2% dose in the target volume as well as exposure to organs at risk was checked. To determine peripheral doses, the isodose volumes from V10% to V98% were evaluated. AN treatment plans showed significant differences for the number of nodes, beams, total MU, treatment time, D98%, D100% for the target volume, and the doses for all organs at risk. VOLO™ achieved better results on average. Total MU, treatment time, coverage, and D98% are significantly better for VOLO™ for lung metastases. For liver metastases, a significant reduction in number of nodes, total MU, and treatment time was observed for VOLO™ plans. The mean target coverage increased slightly with VOLO™, while the mean CI deteriorated slightly. The averages of Dmin , Dmean , D98%, D100%, and V80% resulted in a significant increase for VOLO™. The results of the present study indicate that VOLO™ should be used in place of SEQU as a standard for AN cases moving forward. Despite the lack of significance in the lung and liver cases, VOLO™ optimization is recommended because OAR sparing was similar, but coverage, Dmin , and Dmean were increased, and thus better tumor control can be expected.

293 Prostate Stereotactic Body Radiotherapy Treatment Planning and Image Guidance: Initial Experience from Two Institutions

293 Prostate Stereotactic Body Radiotherapy Treatment Planning and Image Guidance: Initial Experience from Two Institutions

Exploring the Use of Contour-Based Intrafraction Motion Review for Spine Stereotactic Body Radiation Therapy Treatments

Patient motion during radiation therapy treatment is a concern, especially for spine stereotactic body radiation therapy cases where the sharper dose gradient presents a toxicity threat to the spinal cord. Intrafraction motion review (IMR) is an application used to monitor patient position during treatment. The presence of spinal fixation hardware presents an opportunity for motion tracking to manually pause the beam. A cohort of 17 clinicians were shown a video of the imaging console during a simulated treatment. Participants decided after each triggered image if they would pause the treatment beam, indicating that they believed the phantom to have moved outside of clinical tolerance. A spine phantom with hardware intact was positioned on a motion platform, which was programmed to make shifts ranging in size from 0.5 to 1.5 mm. A 1-mm isotropic expansion contour from the hardware was overlayed on the triggered planar x-ray images using the IMR application. User perception sensitivity did not exceed 0.5 until there was a physical shift of 1.4 mm, indicating that most users will not be able to reliably discriminate submillimeter shifts using contour-based shift identification. If adaptations to standard of care are implemented clinically, the proposed method should be evaluated and the role of training and education should be examined before implementation. However, contour-based IMR could still provide beneficial information for larger intrafraction motion during treatment and could be valuable for identifying gross anatomic motion during treatment.

A Cancer Care Ontario Consensus-Based Organizational Guideline for the Planning and Delivery of Spine Stereotactic Body Radiation Therapy Treatment in Ontario

The proposed recommendations are primarily based on the consensus opinion and in-field experience of the Ontario Health/Cancer Care Ontario stereotactic body radiation therapy (SBRT) for Spine Metastasis Guideline Development Group and published literature when available. Primary consideration was given to the perceived benefits for patients and the small likelihood of harm arising from recommendation implementation. Apart from the magnetic resonance imaging (MRI) follow-up strategy, all evidence was considered indirect and was provided by the working group in conjunction with their collective expertise in the field of SBRT.The application of an SBRT program requires a multidisciplinary team consisting of a radiation oncologist, spine surgeon, neuroradiologist, medical physicist, medical dosimetrist, and radiation therapist. In Canada, linear accelerators are the most used treatment delivery units and should follow technology-specific quality assurance procedures. Immobilization technique is location dependant. Treatment planning MRI sequences should be acquired no more than 14 days from the date of treatment. In the case of epidural disease, simulation MRI should be completed no more than 7 days from the date of treatment. After treatment, patients should be followed with routine clinical visits every 3 months for the first year, every 3 to 6 months during years 2 and 3, and every 4 to 6 months thereafter.The recommendations enclosed provide a framework for the minimum requirements for a cancer center in Ontario, Canada to offer SBRT for spine metastases.

Predictive Power of the Albumin-Bilirubin Score for Hepatotoxicity in Stereotactic Ablative Radiation Therapy for Hepatocellular Carcinoma.

Assessment of liver function is crucial in predicting treatment outcomes for hepatocellular carcinoma (HCC). This study aimed to evaluate the prognostic performance of the albumin-bilirubin (ALBI) score for predicting hepatotoxicity following stereotactic body radiation therapy (SBRT) in HCC patients. A retrospective analysis was conducted on 123 HCC cases treated between 2018 and 2020. ALBI and Child-Turcotte-Pugh (CTP) scores were calculated, and hepatotoxicity was defined as a post-SBRT CTP score increase ≥2. Receiver operating characteristic (ROC) curves were used for comparison. The optimal cutoff value of the ALBI score was determined. Among the 121 patients analyzed, hepatotoxicity occurred in 5%. The ALBI score showed better predictive accuracy (area under the ROC curve: 0.77) than the CTP score. The optimal cutoff value of the ALBI score was -2.47, with a sensitivity of 85.7% and a specificity of 71.1%. Multivariable analysis revealed that ALBI score and PTV were significant factors for hepatotoxicity. In conclusion, the ALBI score demonstrated prognostic value for hepatotoxicity prediction after SBRT in HCC patients. Considering the ALBI score and PTV provides valuable insights for assessing hepatotoxicity risk during SBRT treatment for HCC.

Static couch non-coplanar arc selection optimization for lung SBRT treatment planning

Objective. Non-coplanar arc geometry optimizations that take advantage of beam’s eye view (BEV) geometric overlap information have been proven to reduce dose to healthy organs-at-risk (OARs). Recently, a metric called mean arc distance (MAD) has been developed that quantifies the arc geometry sampling of 4π space. The purpose of this research is to combine improved BEV overlap information with MAD to generate static couch lung stereotactic body radiotherapy (SBRT) treatment plans deliverable on a C-arm linear accelerator. Approach. An algorithm utilizing the Moller–Trumbore ray-triangle intersection method was employed to compute a cost surrogate for dose to overlapping OARs using distances interpolated onto a PDD. Cost was combined with MAD for 100 000 random combinations of arc trajectories. A pathfinding algorithm for arc selection was created, balancing the contributions of MAD and 4π cost for the final trajectory. This methodology was evaluated for 18 lung SBRT patients. Cases were also planned with arcs from a clinical treatment template protocol for dosimetric and plan quality comparison. Results were evaluated using dose constraints in the context of RTOG0915. Main results. Five of six OARs had maximum dose reductions when planned with the arc trajectory optimization algorithm. Significant maximum dose reductions were found for esophagus (7.41 ± 0.91 Gy, p = 0.00019), trachea (5.56 ± 1.55 Gy, p = 0.0025), spinal cord (2.87 ± 1.13 Gy, p = 0.039), large bronchus (3.47 ± 1.49 Gy, p = 0.0075), and aorta (3.13 ± 0.99 Gy, p = 0.012). Mean dose to contralateral lung was also significantly reduced (0.50 ± 0.06 Gy, p = 0.00019). There were two significant increases in OAR doses: mean dose to ipsilateral lung (0.40 ± 0.09, p = 0.00086) and V5Gy to ipsilateral lung (1.95 ± 0.70%, p = 0.011). Paddick conformity index increased by 0.03 ± 0.02 (p = 0.14), remaining below a limit of 1.2 for both techniques. Significance. Static couch non-coplanar optimization yielded maximum dose reductions to OARs while maintaining target conformity for lung SBRT.

Leaf-individual calibration for a double stack multileaf collimator in photon radiotherapy.

In online adaptive stereotactic body radiotherapy treatments, linear accelerator delivery accuracy is essential. Recently introduced double stack multileaf collimators (MLCs) have new facets in their calibration. We established a radiation-based leaf-individual calibration (LIMCA) method for double stack MLCs. MLC leaf positions were evaluated from four cardinal angles with test patterns at measurement positions throughout the radiation field on EBT3 radiochromic film for each single stack. The accuracy of the method and repeatability of the results were assessed. The effect of MLC positioning errors was characterized for a measured output factor curve and a clinical patient plan. All positions in the motor step - position calibration file were optimized in the established LIMCA method. The resulting double stack mean accuracy for all angles was 0.2±0.1 mm for X1 (left bank) and 0.2±0.2 mm for X2 (right bank). The accuracy of the leaf position evaluation was 0.2 mm (95% confidence level). The MLC calibration remained stable over four months. Small MLC leaf position errors (e.g. 1.2 mm field size reduction) resulted in important dose errors (-5.8 %) for small quadratic fields of 0.83×0.83 cm2. Single stack position accuracy was essential for highly modulated treatment plans. LIMCA is a new double stack MLC calibration method that increases treatment accuracy from four angles and for all moving leaves.

Stereotactic Body Radiotherapy for Lung Oligo-metastases: Systematic Review and International Stereotactic Radiosurgery Society Practice Guidelines

PurposeA systematic review of treatment characteristics, outcomes, and treatment-related toxicities of stereotactic body radiation therapy (SBRT) for pulmonary oligometastases served as the basis for development of this International Stereotactic Radiosurgery Society (ISRS) practice guideline. MethodsIn accordance with PRISMA guidelines, a systematic review was performed of retrospective series with ≥50 patients/lung metastases, prospective trials with ≥25 patients/lung metastases, analyses of specific high-risk situations, and all randomized trials published between 2012 and July 2022 in the MEDLINE or Embase database using the key words “lung oligometastases”, “lung metastases”, “pulmonary metastases”, “pulmonary oligometastases”, “stereotactic body radiation therapy (SBRT)” and “stereotactic ablative body radiotherapy (SBRT)”. Weighted random effects models were used to calculate pooled outcomes estimates. ResultsOf the 1884 articles screened, 35 analyses (27 retrospective-, 5 prospective, and 3 randomized trials) reporting on treatment of >3600 patients and >4650 metastases were included. The median local control was 90 % (Range: 57–100 %) at 1 year and 79 % (R: 70–96 %) at 5 years. Acute toxicity ≥3 was reported for 0.5 % and late toxicity ≥3 for 1.8 % of patients. A total of 21 practice recommendations covering the areas of staging & patient selection (n = 10), SBRT treatment (n = 10), and follow-up (n = 1) were developed, with agreements rates of 100 %, except for recommendation 13 (83 %). ConclusionSBRT represents an effective definitive local treatment modality combining high local control rates with low risk of radiation-induced toxicities.