Stereotactic Body Radiation Therapy Treatment Research Articles

SBRT for the Treatment of Isolated Local Recurrence of Resected Pancreatic Cancer

<h3>Purpose/Objective(s)</h3> Following curative resection for pancreatic ductal adenocarcinoma (PDAC), there are high rates of local recurrence. The optimal treatment of patients with isolated local recurrence (ILR) – recurrence in the abdomen without distant metastases – is not known. This study evaluated stereotactic body radiation therapy (SBRT) as a treatment option for ILR. <h3>Materials/Methods</h3> A multi-institutional retrospective analysis was performed on patients with ILR of PDAC following oncologic surgical resection treated with SBRT. Patient demographics, tumor and prior treatment characteristics, details of recurrence, SBRT treatment design and dosimetry, and patient follow-up and toxicity data were recorded from the medical record. Progression and overall survival estimates were calculated using cumulative incidence and Kaplan-Meier models, respectively. <h3>Results</h3> Between January 2010 and December 2020, 34 patients (17 males and 17 females, median age 69 years) were treated at five institutions in the United States. At the time of initial resection, most patients had T3 tumors (71%) and involved lymph nodes (71%). 31 of 34 (91%) patients underwent a Whipple procedure and 3 (9%) had a distal pancreatectomy. The R0 resection rate was 68%. 29% and 85% received neoadjuvant or adjuvant chemotherapy, respectively; and 12% and 27% had prior neoadjuvant or adjuvant radiation courses around the time of initial surgical resection. Median time to ILR was 18.7mos. The most common location of recurrence was in the pancreatic remnant or near the superior mesenteric artery. All patients underwent 5-fraction photon (28 patients) or proton (6 patients) SBRT to a median dose of 3500cGy (range 3000-4000cGy) with a median BED of 5950cGy (α/β = 10). Median follow-up after SBRT was 3.05 years. The 1-year and 2-year cumulative incidence of cancer progression were 72% (95% CI 56-93%) and 92% (95% CI 76-100%). Distant metastasis was the most common site of first recurrence (15 of 23 recurrences, 65%). 6 patients (25%) had local failure as site of first recurrence. Prior radiation was not associated with increased risk of progression after SBRT (HR 1.31 95% CI 0.56-3.07, <i>P</i> = 0.54). 1-year and 2-year overall survival was 64% (95% CI 49-84%) and 40% (95% CI 25-64%), with a median survival of 1.2 years from time of SBRT. Four patients (12%) developed grade 3 toxicities within one year after completion of SBRT. There were no grade 4-5 toxicities. <h3>Conclusion</h3> For treatment of PDAC ILR after surgical resection, SBRT was well tolerated and offered high rates of local tumor control with low treatment-related toxicity.

The Utility of Stereotactic Body Radiotherapy for Pelvic Recurrences After Prior Radiation Therapy

Patients with locally recurrent colorectal cancer represent a particular clinical challenge as these patients often present with unresectable disease and a history of prior pelvic radiotherapy. While options are therefore limited, radiation is usually the only local therapy available. The purpose of this study was to analyze the efficacy and outcomes associated with treating recurrent colorectal cancer using stereotactic body radiation therapy (SBRT) in patients who have been previously irradiated to the pelvis.We identified 23 patients with recurrent rectal (n = 20, 87%) or colon (n = 3, 13%) adenocarcinoma who were treated with SBRT in the Department of Radiation Oncology at Stanford University from June 2009 to November 2019. In total, 11 males and 12 females were included in this study with a median age of 53 years old (range: 25-76). All 23 patients had a history of surgical resection and at least one course of radiation therapy to disease in the pelvis before SBRT treatment to the pelvis for recurrent cancer, of which 8 patients (35%) received two prior radiotherapy courses and 1 patient (4%) received three prior courses. Data collection included tumor staging and grading, radiation treatment details, and follow up information to determine toxicities and survival outcomes. Time to events were calculated from the completion of SBRT. Toxicities were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v.5.0.Median time to follow up was 91 months (range: 36-237). Median GTV and PTV volumes for tumor treated using SBRT were 79.9 and 136.5 cm3, respectively. Median SBRT dose was 40 Gy (range: 30 - 50). Median PTV mean dose was 41.8Gy. The median cumulative biological effective dose (BED) was 145 Gy (range: 72.0-254.4). Overall, 22 patients received 5 fractions of treatment and one patient received 4 of the 5 planned fractions due to deteriorating condition related to disease. Median time to overall survival (OS) was 125 months (range: 61-194) and median progression free survival (PFS) was 82 months (range: 57-142). The 3- and 5-year rate of local failure was 4.4% and 17.4%, respectively. Of the 23 patients in this cohort, there were 6 patients (26%) with grade 2 acute toxicities, including 3 patients (13%) with increased pain, and 6 patients (26%) with late grade 2 or 3 toxicities, including 3 patients (13%) with grade 3 neuropathy. There was no grade 3 or 4 acute, or grade 4 late toxicities reported. On univariate analysis, no factors were significantly predictive of OS, PFS, or toxicity.SBRT to previously irradiated areas of the pelvis was effective in controlling unresectable pelvic recurrences of colorectal cancer following previous radiation. While treatment was generally well-tolerated, pelvic pain was the most common acute toxicity, and neuropathy was the most common late toxicity. Further investigation is needed to improve the toxicity profile and optimize the therapeutic ratio.

Cardiac Motion and its Impact on Target Coverage During SBRT for Refractory Ventricular Tachycardia

<h3>Purpose/Objective(s)</h3> Refractory ventricular tachycardia (VT) is a common cause of death and morbidity in the heart failure population. Stereotactic body radiation therapy (SBRT) is a new and promising approach to treating VT, but there are practical concerns about SBRT delivery to the heart, which undergoes motion from both cardiac and respiratory cycles. In this study, we investigate motion magnitudes from both cycles and their impact on treatment margins and target coverage for VT SBRT. <h3>Materials/Methods</h3> Twenty-one patients were treated with SBRT for VT at our institution between April 2018 and December 2020 under an IRB-approved registry protocol. All patients had respiratory-correlated 4DCT for treatment planning and 7 patients had diagnostic cardiac-gated CT scans taken less than two weeks prior to treatment. Target structures were delineated on free-breathing CT and transferred to respiratory average (RAVG) CT via rigid registration. Dose was initially calculated on the RAVG per current institutional standard of care. For this retrospective study, deformable image registration (DIR) was applied between RAVG and the cardiac average CT (CAVG), systolic, and diastolic CTs from the cardiac dataset. Target contours were transferred to the registration target image. Motion magnitudes and distributions from the deformation vector fields were analyzed. Internal target volumes (ITVs) were created on the respiratory average images for quantitative analysis of target motion and coverage changes. From these 7 patients, 11 distinct target volumes were treated, with 8 being epicardial and 3 endocardial. Motion and dosimetry for all 11 targets were analyzed separately. <h3>Results</h3> The average (SD) target shift magnitudes (in mm) from the RAVG to CAVG CTs were 2.0 ± 1.0, 2.0 ± 1.3, and 4.0 ± 2.0 in the left-right (LR), anterior/posterior (AP), and superior/inferior (SI) directions. Endocardial targets had greater motion magnitude than epicardial targets, with mean shifts of 2.2 ± 1.0, 2.3 ± 1.9, and 4.2 ± 2.4 in the LR, AP, and SI directions versus 1.4 ± 0.9, 1.3 ± 0.8, and 3.6 ± 0.5. Cardiac cycle motion showed more variability for epicardial targets with shifts of 1.4 ± 2.5, 2.4 ± 3.0, and 2.5 ± 3.7 in the LR, AP and SI directions, versus 2.0 ± 0.6, 2.1 ± 0.8, and 1.6 ± 0.7 for endocardial targets. Creation of motion encompassing ITVs led to an average target size increase of 100% (25 cm³). V95 for initial target volumes was 99.9 ± 0.4% while the average V95 for ITVs was 84.1 ± 15.6%. Similarly, D95 for the target dropped from 108.2 ± 5.7% to 75.3 ± 28.4%. <h3>Conclusion</h3> In this cohort of patients undergoing SBRT for VT, cardiac shifts were location-dependent and were largest in the SI direction. These shifts typically exceeded the 1-5 mm margins used for SBRT treatment planning and ITV generation to encompass all target motion led to a doubling in target size. Our data suggest that cardiac-gated delivery may be helpful to minimize treatment volumes and spare cardiac tissue.

Role of Stereotactic Body Radiotherapy (SBRT) in the Treatment of Oligo Metastatic Colorectal Cancer: Analysis of a Large Multi-Institutional Database

In recent years, stereotactic body radiotherapy (SBRT) has emerged as an effective local treatment for oligometastatic cancers. However, it has been suggested that colorectal cancers may represent a more radioresistant histology, even to the high doses used in SBRT. Here, we report local recurrence rates, progression free-survival, and overall survival of patients with oligometastatic CRC treated with SBRT using a large multi-institutional data-base.We collected data retrospectively from six cancer centers with a high volume of SBRT treatments from Jan 1 2008 to December 31, 2016. Our primary outcome was local recurrence while secondary outcomes included overall survival (OS), local recurrence free survival, progression free survival, oligo-progression, and widespread progression. Time-to event outcomes were estimated using the Kaplan-Meier method. Univariable regression analysis was performed to determine the relationship between patient, tumor and treatment variables and outcomes. Variables significant on univariable screen were entered into a multivariable model. All analysis was performed in R (R Foundation for Statistical Computing, version 4.0.2) RESULTS: We identified 235 patients with a total of 381 oligometastatic CRC lesions that were treated with SBRT. The mean age was 70.7 ± 12.2 years, 58% of patients were male with a median follow-up of 25.5 months. The most common site of metastasis was the lung (n = 133, 56.6%) with a total of 239 (62.7%) lesions. The median time to local recurrence was not reached with the 1- and 5-year local recurrence rate was 13.6% and 44.3% respectively. The median OS was 49 months with a 2-and 5-year probability of 76.1% and 35.9% respectively. On multivariable analysis, a BED10 of ≥100 Gy (HR 0.67, 95% CI 0.45-0.99) and the presence of lung (HR 0.53, 95% CI 0.34-0.82) or lymph node metastasis as opposed to liver metastasis (HR 0.31, 95% CI 0.13-0.74) were associated with improved local control. Larger total PTV size (≥17.5cc) was associated with worse overall survival (HR 2.62, 95% CI 1.45-4.72), progression free survival (HR 2.01, 95% CI 1.39-2.90) and widespread progression (HR = 2.82, 95% CI: 1.63-4.88). Use of prior systemic therapy before SBRT was also adversely associated with widespread progression (HR = 1.90, 95% CI: 1.22-2.95).This large multi-institutional analysis found that the use of SBRT for oligometastatic colorectal cancer resulted in favorable overall survival. However, local recurrence is appreciably lower than what has historically been demonstrated in other cancer primary sites. These results suggest that an increase in BED should be considered if feasible and safe, in order to optimize local control. Increased overall PTV size may also be an indicator for the need for systemic therapy in addition to SBRT.

A Practical Method to Prolong Expiratory Breath Holds for Abdominal Stereotactic Body Radiotherapy

Motion management is crucial to safe and efficacious treatment for abdominal stereotactic body radiotherapy (SBRT). Expiratory breath hold (EBH) treatment is attractive as it does not require sophisticated gating technologies and minimizes abdominal target motion compared to inspiratory breath hold and abdominal compression; however, few patients can perform prolonged EBH to allow efficient treatment. We hypothesized that providing patients supplemental oxygen and controlling respiratory rate (RR) at the upper limit of normal would improve EBH times, increase the percentage of patients eligible for EBH treatment and decrease EBH treatment time.Starting in 2020, we provided patients supplemental oxygen (50% O2 via Venturi mask) with synchronization to a RR of 18 breaths/min with a metronome at the time of CT simulation. Patients were eligible for EBH treatment if they were able to complete two consecutive 20 second EBH. Eligible patients were treated per standard institutional guidelines for abdominal SBRT with EBH. We retrospectively identified all completed EBH treatments with this new supplemented procedure (EBHsupp) from our departmental database. Historical controls treated with EBH prior to this new procedure (EBHRA, where RA = room air) were identified and matched 1:1 based on patient age, sex, RT prescription, number of treatment arcs, and comorbidities via individual matching. Individual patient EBH times, total treatment time, cone beam CT (CBCT) time, and treatment arc time were extracted from the treatment planning software. Statistical comparisons were made with chi-squared test for categorical variables and student's t-test for continuous variables.We identified 8 patients that received 10 abdominal SBRT treatment plans with EBHsupp (two patients had two lesions requiring two separate treatment plans). There was no statistical difference between the EBHsupp and EBHRA groups with respect to patient characteristics. Eight of 11 (73%) screened EBHsupp patients were able to undergo EBH treatment compared to historical department standard of ∼30% with EBHRA. The EBHsupp group had a significant improvement in maximum (50.5 vs 30.9 s, P = 0.002) and median (24.0 vs 17.8 s, P = 0.016) EBH times compared to the EBHRA group and required less breath holds to complete their treatment (9.1 vs 13.9, P = 0.029). Time for CBCT was reduced with EBHsupp (6.5 vs 8.6 min, P = 0.004) and there was a trend towards decreased time for treatment arc completion (3.1 vs 4.0 min, P = 0,10) and overall treatment time (18.6 vs 21.7 min, P = 0.12).Providing supplemental oxygen and controlling respiratory rate at 18 breaths/min significantly improves EBH time. This intervention is simple, inexpensive, safe, and may allow more patients to be treated with EBH while decreasing overall treatment time.C.S. Schneider: None. S. Shen: None. J.B.Fiveash: None. R. Jacob: None.

Multisequence MRI With Functional Imaging May Improve Pseudoprogression vs. Viable Tumor Determination Following High Dose Adaptive MRgRT in Patients With Pancreatic Adenocarcinoma

<h3>Purpose/Objective(s)</h3> For patients with Borderline Resectable (BR) and Locally Advanced (LA) pancreatic adenocarcinoma, multi-fraction ablative stereotactic body radiotherapy (SBRT) by MRgRT provides a highly effective approach for locoregional therapy. Traditionally, the first post treatment scan is performed with multi-phase CT, but a multiparametric and multisequence MRI may offer a better approach to evaluate post-treatment response using a reproducible exam with functional imaging and quantifiable biomarkers. The objective of this study is to develop MR biomarkers to more accurately and reproducibly evaluate treatment response and to differentiate between post-treatment inflammatory response resulting in pseudoprogression from background post-treatment fibrosis and residual disease. <h3>Materials/Methods</h3> With institutional review board approval, patients with BR and LA pancreatic adenocarcinoma who were imaged with MRI 3-5 months following MRgRT with pre- and post-SBRT pancreas protocol CT scans were included. Primary endpoints were to assess for treatment response, to identify residual foci of disease, and to identify pseudoprogression caused by inflammation, fibroinflammatory change, post-treatment fibrosis, and necrotic change. A specific diagnostic MRI protocol was developed at our institution to evaluate for post treatment changes. <h3>Results</h3> Ten patients satisfied the above inclusion criteria. Employing a morphologic approach with traditional RECIST criteria, all patients demonstrated an increase in the size of the primary tumor between pre-treatment and post treatment CT scans (an average increase of 24 % +/- 13.4%). On MRI these post-treatments beds demonstrated functional imaging signs of response with an average apparent diffusion coefficient (ADC) above a threshold level of 1500 µm²/sec (average of 1993.9 µm²/sec +/- 437), consistent for necrotic change or cystic debris. Additionally, the normalized tumor contrast ratio measured below 0.5 (average of 0.194 +/- 0.13), consistent for no appreciable internal enhancement with kinetic profiles showing no rapid wash in or contrast persistence. Functional T2 map values were greater than 150 ms (average of 217 ms +/- 81.2), highlighting residual inflammation, while functional T1 map values were obscured by this same inflammatory signal (range, 1036 -3966 ms; average of 1930 +/- 1143). <h3>Conclusion</h3> Specialized post-SBRT multisequence MRI protocols with functional imaging detail pseudoprogression that is frequently characterized by CT as stable or worsening disease. These findings have important implications for assessment of post SBRT treatment response and further therapy options. Further data is needed to clarify the kinetics of response to determine the most appropriate post treatment imaging acquisition time point. Future validation with prospective post SBRT MRI imaging with specific sequencing protocols to assess response is warranted.

Development and Internal Validation of an RPA-Based Model Predictive of Pain Flare Incidence After Spine SBRT

Radiotherapy is a standard palliative treatment for spine metastasis, but pain flares (PF) are a common acute toxicity. Prophylactic corticosteroids can reduce the rate of PF in patients receiving traditional palliative regimens, but less is known about prophylaxis for stereotactic body radiotherapy (SBRT). We aim to identify a subset of patients treated with spine SBRT with the highest rate of PF to optimize the use of prophylactic steroids.From December 2007-August 2019, 469 patients received 680 spine SBRT treatments. After exclusion of benign histology, particle therapy, and patients with missing data, the final cohort included 424 patients with 610 treatments. We defined PF as acute worsening of pain at the treatment site requiring initiation of or higher-dose corticosteroids, opiates, and/or hospitalization. First, data was split into 70% training and 30% validation sets with comparable patient characteristics using a random number generator. Feature importance testing was conducted, and a correlation heatmap helped exclude correlated variables. Feature extraction involved selecting the variables used in the highest-fidelity recursive partitioning analysis (RPA) models. Each RPA model was trained, validated, and tested using only the training dataset. Selected variables were verified using the Fisher exact test and univariate t-test.We identified 125 total PF (20%), treated with steroids (14%), opioids (40%), both (39%), or hospitalization (6%). Six variables were identified by RPA. Of these, 5 met significance on Fisher exact test with P < 0.02: renal primary (OR 2.23), soft tissue involvement (OR 1.96), Bilsky > 0 (OR 2.17), SINS > 6 (OR 2.98), and gross tumor volume > 8 cc (OR 2.80). One point was assigned for each variable. The low-risk (LR) group (score = 0, n = 159) had PF rates of 7.0% and 13.6% in the training and validation sets, respectively; the intermediate-risk (IR) group (score = 1, n = 150) had rates of 14.0% and 16.3%; and the high-risk (HR) group (score > 1, n = 301) had rates of 28.8% and 31.3%. A logistic model confirmed the increased pain flare rate in the HR group compared to LR and IR treatments combined (OR = 3.50, 95% CI: 2.06-5.92) or considered separately (OR = 5.41, 2.48-11.78). The concordance index was 0.66 (0.60-0.73) and 0.62 (0.52-0.71) in the training and internal validation sets. Notably, patients with PF after prior spine SBRT had a 61% rate of PF with subsequent spine SBRT, compared to only 5% for patients without PF after prior spine SBRT.Our internally-validated model identifies a high-risk group of patients more likely to develop PF after spine SBRT, for whom prophylactic steroids may confer the greatest benefit. Evaluation in a clinical trial is warranted.

Determining Radiation Doses of Critical Normal Tissues for Stereotactic Body Radiotherapy (SBRT) of Central Lung Tumors

While respiratory motion is included in the definition of target volumes for lung SBRT, delineation of organs at risk (OARs) and dose calculation are typically performed on average intensity projection images (AIP). This approach often misses structural detail during contouring due to motion blurring on AIP. Including respiratory motion in the dose calculation for OARs will result in more accurate dose assessment, which is necessary to establish reliable dose-effect relationships, particularly for SBRT of central lung tumors with a high risk of critical side effects.For 17 centrally-located lung tumors, clinical 4DCT-based SBRT treatment plans (BED≥100 Gy in 76%) were created for both AIP and mid ventilation image (MidV, 30% breathing phase) and contour sets. Internal GTVs were produced via GTV propagation over all breathing phases. OARs were outlined on both AIP and MidV images according to RTOG 0813. Both plans were also recalculated on all 10 breathing phases and registered back deformably to the MidV to assess differences in the accumulated OAR doses over the full breathing cycle. MidV was selected over the AIP as the reference image for comparison as it does not suffer from motion blurring.Volumes were, on average, larger on AIP than MidV image sets for all OARs by 3-15% (P < 0.05 for heart, lungs, great vessels (GV)), except the esophagus. Mean differences ± SDs in the max doses (Gy) between respiration-averaged MidV and AIP plans were for proximal bronchial tree (PBT) 2.26 ± 2.11, heart 2.24 ± 2.89, GV 1.71 ± 1.12, esophagus 1.38 ± 1.1, spinal cord 1.11 ± 0.67, and trachea 0.71 ± 1.16. Doses were significantly different for heart Dmean/10cc/15cc (P = 0.03/0.03/0.04). Relative to MidV plans, AIP plans resulted in higher max doses for PBT in 11/17 (65%) plans, 9/17 (53%) for esophagus, GV and spinal cord, and 5/17 (29%) for heart and trachea. Max dose differences > 5 Gy were observed for GV and PBT in 2/17 (12%) and for heart in 3/17 (18%) of individual plans. Superior-inferior carina motion ranged from 0.32 to 0.73 cm. No significant correlations between dose differences and carina motion were identified.Though limited by a small sample size, this study represents a comprehensive assessment of OAR doses for SBRT planning of centrally located lung tumors including the effects of respiratory motion. We often observed only small differences in dose delivered to central OARs. However, clinically relevant differences ≥ 5 Gy were observed in individual patients for PBT, GV and heart, resulting in over- or underestimation of the actual OAR dose over the full breathing cycle when using AIP-based planning. We therefore recommend MidV image-based OAR dose assessment to develop reliable dose-effect relationships for central lung OARs.D.A. Cooper: None. L. Padilla: None. A. Watson: None. K. Neiderer: None. B. Smith: None. E. Weiss: Research Grant; NIH. royalties; UpToDate.

Reduction of inter-observer differences in the delineation of the target in spinal metastases SBRT using an automatic contouring dedicated system

BackgroundApproximately one third of cancer patients will develop spinal metastases, that can be associated with back pain, neurological symptoms and deterioration in performance status. Stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT) have been offered in clinical practice mainly for the management of oligometastatic and oligoprogressive patients, allowing the prescription of high total dose delivered in one or few sessions to small target volumes, minimizing the dose exposure of normal tissues. Due to the high delivered doses and the proximity of critical organs at risk (OAR) such as the spinal cord, the correct definition of the treatment volume becomes even more important in SBRT treatment, thus making it necessary to standardize the method of target definition and contouring, through the adoption of specific guidelines and specific automatic contouring tools. An automatic target contouring system for spine SBRT is useful to reduce inter-observer differences in target definition. In this study, an automatic contouring tool was evaluated.MethodsSimulation CT scans and MRI data of 20 patients with spinal metastases were evaluated. To evaluate the advantage of the automatic target contouring tool (Elements SmartBrush Spine), which uses the identification of different densities within the target vertebra, we evaluated the agreement of the contours of 20 spinal target (2 cervical, 9 dorsal and 9 lumbar column), outlined by three independent observers using the automatic tool compared to the contours obtained manually, and measured by DICE similarity coefficient.ResultsThe agreement of GTV contours outlined by independent operators was superior with the use of the automatic contour tool compared to manually outlined contours (mean DICE coefficient 0.75 vs 0.57, p = 0.048).ConclusionsThe dedicated contouring tool allows greater precision and reduction of inter-observer differences in the delineation of the target in SBRT spines. Thus, the evaluated system could be useful in the setting of spinal SBRT to reduce uncertainties of contouring increasing the level of precision on target delivered doses.

Implementing stereotactic accelerated partial breast irradiation using magnetic resonance guided radiation therapy

IntroductionAccelerated partial breast irradiation (APBI) seeks to reduce irradiated volumes and radiation exposure for patients while maintaining acceptable clinical outcomes. Magnetic resonance image-guided radiotherapy (MRgRT) provides excellent soft-tissue contrast for treatment localization, which can reduce setup uncertainty, thus reducing margins in the external beam setting. Additionally, stereotactic body radiotherapy (SBRT)-style regimens with high gradients can also be executed. This MR-guided stereotactic APBI (MRgS-APBI) approach can be utilized for a lower number of fractions and spare a greater volume of healthy tissues compared to conventional 3D external beam APBI. MethodsOur MRgS-APBI program was developed for two prospective non-randomized phase I/II clinical trials (20Gyx1 and 8.5Gyx3). Both breast SBRT treatment planning and MRgRT delivery techniques were described in this study. Simulation included both CT and MRI with specialized immobilization to accommodate MR-guided setup and cine-MRI treatment gating. Dosimetry data from 48 single-fraction and 19 three-fraction patients were collected and evaluated. This included planning objectives and SBRT-specific indices. During treatment, setup errors were calculated to evaluate setup reproducibility and duty cycle was calculated using cine-MRI data during gated delivery. ResultsIn both the single- and three- fraction trials combined, 88.5% of the possible dosimetric objectives across all patients were met during planning. The majority of the planning objectives were easily achievable indicating the potential for stricter objectives for subsequent S-APBI treatments. The average magnitude of setup uncertainties was 1.0 cm ± 0.6 cm across all treatments. In the three-fraction trial, the average beam-on duty-cycle for the MRI-gated delivery was 83.0 ± 13.0%. There were no technical MRgS-APBI related issues that resulted in discontinuation of treatment across all patients. ConclusionSBRT-style dosimetry and delivery for APBI is feasible using MR-guidance. The program development and dosimetric outcomes reported here can serve as a guide for other institutions considering the clinical implementation of MR-guided stereotactic APBI.

Characterisation of a synthetic diamond detector for end-to-end dosimetry in stereotactic body radiotherapy and radiosurgery.

Background and purposeSynthetic diamond detectors offer real time measurement of dose in radiotherapy applications which require high spatial resolution. Additional considerations and corrections are required for measurements where the diamond detector is orientated at various angles to the incident beam. This study investigated diamond detectors for end-to-end testing of Stereotactic Body Radiotherapy (SBRT) and Stereotactic Radiosurgery (SRS) in the context of dosimetry audits.Material and methodsSeven individual diamond detectors were investigated and compared with respect to warm up stability, dose-rate dependence, linearity, detector shadowing, energy response, cross-calibration, angular dependence and positional sensitivity in SBRT and SRS.ResultsLarge variation in the cross calibration factors was found between the seven individual detectors. For each detector, the energy dependence in the cross calibration factor was on average <0.6% across the beam qualities investigated (Co-60 Gamma Knife, and MV beams with TPR20,10 0.684–0.733). The angular corrections for individual fields were up to 5%, and varied with field size. However, the average angular dependence for all fields in a typical SRS treatment delivery was <1%. The overall measurement uncertainty was 3.6% and 3.1% (2σ) for an SRS and SBRT treatment plan respectively.ConclusionSynthetic diamond detectors were found to be reliable and robust for end-to-end dosimetry in SBRT and SRS applications. Orientation of the detector relative to the beam axis is an important consideration, as significant corrections are required for angular dependence.

Absolute dose measurements for lung gated delivery stereotactic body radiation therapy

PurposeTo evaluate absolute dose between phase- and amplitude-gated modes for lung stereotactic body radiation therapy (SBRT), using the moving targets developed in-house. MethodsThe moving targets were developed in-house, allowing measurements of absolute dose using Semiflex ion chamber, Pinpoint ion chamber and microDiamond detector. 24 plans were generated in the Pinnacle 16.2 treatment planning system (TPS). 720 partial dynamic conformal arcs (DCA), 120 for phase- and 120 for amplitude-gated mode per detector, were performed to compare dose discrepancy (planned vs measured doses), for all detectors. Single fraction of 15 Gy was delivered with TrueBeam Novalis STx, triggered on the stable phases (phase-gated mode) or near the end-exhalation (amplitude-gated mode), for a breathing period ranging from 2 s to 7 s, using flattened filter free beams (FFF). ResultsThe lowest discrepancy between measured and planned dose was obtained using the microDiamond detector in the phase-gated −0.1 (−0.2 to 0) % and −0.3 (−0.4 to −0.1) % in amplitude-gated mode (p < 0.001). Using PinPoint ion chamber, greater discrepancy was obtained in phase-gated −0.5 (−0.7 to −0.3) %, comparing to the amplitude-gated mode −0.1 (−0.2 to 0) % (p < 0.001). The greatest discrepancy was observed using the Semiflex ion chamber, with lesser differences between the phase-gated 1.5 (1.2–1.7) % and amplitude-gated mode 1.4 (1.2–1.5) (p = 0.134). ConclusionDetectors with low discrepancy, PinPoint ion chamber and microDiamond detectors, can be used in routine quality assurance for lung gated delivery in SBRT treatment, for commercial phantom as for phantom developed in-house.

Long-term outcomes of spinal SBRT. Is it important to select the treatment time?

SBRT (stereotactic body radiation therapy) is widely used as a curative treatment in tumoral lesions and has become a fundamental tool for the treatment of spine metastasis. In this study, we present survival and toxicity outcomes of spine SBRT after a 2-year follow-up. Data from spine SBRT treatments performed at our institution between March 2012 and February 2020 was collected. Medical records, including demographic, primary tumor, and treatment characteristics were reviewed. Patient follow-up included clinical evaluation, imaging, and blood tests. Toxicity was recorded according to CTCAE v4.0. We analyzed 73 consecutive spine SBRT treatments in 60 patients. 39.7% of the cases had primary breast cancer and 23.3% had prostate cancer. Most cases (87.7%) were treated with a single SBRT fraction of 16Gy. Median follow-up was 26.1months (range 1.7-78.6), and 1- and 2-year overall survival (OS) rates were 96.9% and 84.2%, respectively. Local control (LC) rates at 1- and 2-years were 76.3% and 70.6%, respectively. Multivariate analysis identified histology as a prognostic factor for both OS and LC. Patients who underwent spine SBRT 6months after the spinal lesion diagnosis had LC at 2years of 88%, vs 61.7% for those who underwent SBRT before this period. No grade III or higher toxicity was reported. The vertebral compression fracture (VCF) rate was 4.1%. Spine SBRT at our institution showed a 2-year LC of 70.6%, without G3 toxicities. Delaying SBRT at least 6months to administer systemic treatment was related to an improvement in local control.

PO-1986 Early toxicity with stereotactic body radiation therapy for prostate cancer

Purpose or Objective: Stereotactic body radiotherapy (SBRT) has proven to be a new option for localized prostate cancer. SBRT specific indications has been transformed due to SARS-2-COVID19 scenario. This communication shows our data about acute toxicity in patients treated with SBRT during the last sixteen months. Materials and Methods: This retrospective and observational study was performed on prostate cancer patients admitted into our radiotherapy department for SBRT between October 2019 until January 2021. SBRT treatment at our institution has been standardized as an IGRT technique using VMAT radiation therapy due to deliver total doses of 36.25 or 40 Gy in 5 fractions. The following variables were recorded: age, past medical history, previous treatment with anticoagulant or antiplatelet drugs, Performance Status (PS), ACE-27 score, IPSS score, Gleason score, Prostate Volume, Tumor Stage, PSA levels, Risk group following NCCN, Hormonotherapy, Radiation Area, RT Doses as well as different toxicity types depending on Genitourinary (GU) or Gastrointestinal (GI) location. Toxicity review was recorded (after RT, six month and 12 months) according to Common Terminology Criteria for Adverse Events (CTCAE). For the descriptive analysis, analytical variables were represented using absolute and relative frequencies. All statistical analysis were conducted using software from SPSS (version 25.0, Chicago, IL). The hypothesis of our study is SBRT technique will reduce radiotherapy sessions with a low rate of toxicity. Results: A total of 47 patients were included, with a median age of 71 years, performance status 0-1, including high risk prostate cancer (25 patients with Gleason score 6, 17 with score 7, 4 with score 8 and 1 with score 9), all of them without seminal vesicles affected. Related to NCCN risk group, 57.4 % of the patient had very low risk, low risk and favorable intermediate risk and 42.6% were unfavorable intermediate, high and very high risk. Androgen deprivation was associated in 40.4% of the cases with a median of treatment in six months (RI:6-24). Image Guided Radiotherapy was performed by matching of fiducial markers on kvCBCT images that were acquired prior to treatment, for positioning, and during treatment, for intrafraction movement control in 74.5% of the patients. The remaining 25.5% were treated by means of a gating system guided by continuous transperineal ultrasound scanning (Clarity ®system). Acute toxicity grade 1 and 2 after RT was greater at GU (51.1%/21,3%) than GI (12.8%/4.3%) location. During subsequent follow-up no patient developed acute GU or GI toxicity greater than or equal to grade 2. At 6 and 12 months evaluation GU toxicity was greater than GI, 31.7% Vs. 17.1% and 12%Vs.4%, respectively. Conclusion: Evaluation of toxicity during the early phase SBRT has proven to be a well tolerated treatment for prostate cancer in our series.

Improvements in beam’s eye view fiducial tracking using a novel multilayer imager

Purpose. Electronic portal image devices (EPIDs) have been investigated previously for beams-eye view (BEV) applications such as tumor tracking but are limited by low contrast-to-noise ratio and detective quantum efficiency. A novel multilayer imager (MLI), consisting of four stacked flat-panels was used to measure improvements in fiducial tracking during liver stereotactic body radiation therapy (SBRT) procedures compared to a single layer EPID. Methods. The prototype MLI was installed on a clinical TrueBeam linac in place of the conventional DMI single-layer EPID. The panel was extended during volumetric modulated arc therapy SBRT treatments in order to passively acquire data during therapy. Images were acquired for six patients receiving SBRT to liver metastases over two fractions each, one with the MLI using all 4 layers and one with the MLI using the top layer only, representing a standard EPID. The acquired frames were processed by a previously published tracking algorithm modified to identify implanted radiopaque fiducials. Truth data was determined using respiratory traces combined with partial manual tracking. Results for 4- and 1-layer mode were compared against truth data for tracking accuracy and efficiency. Tracking and noise improvements as a function of gantry angle were determined. Results. Tracking efficiency with 4-layers improved to 82.8% versus 58.4% for the 1-layer mode, a relative improvement of 41.7%. Fiducial tracking with 1-layer returned a root mean square error (RMSE) of 2.1 mm compared to 4-layer RMSE of 1.5 mm, a statistically significant (p < 0.001) improvement of 0.6 mm. The reduction in noise correlated with an increase in successfully tracked frames (r = 0.913) and with increased tracking accuracy (0.927). Conclusion. Increases in MV photon detection efficiency by utilization of a MLI results in improved fiducial tracking for liver SBRT treatments. Future clinical applications utilizing BEV imaging may be enhanced by including similar noise reduction strategies.

Studies of Intra-Fraction Prostate Motion During Stereotactic Irradiation in First Irradiation and Re-Irradiation.

BackgroundUnderstanding intra-fractional prostate motions is crucial for stereotactic body radiation therapy (SBRT). No studies have focused on the intra-fractional prostate motions during re-irradiation with SBRT. The objective was to evaluate these translational and rotational motions in primary treated patients and in the context of re-irradiation.MethodsFrom January 2011 to March 2020, 162 patients with histologically proven prostate cancer underwent prostate SBRT, including 58 as part of a re-irradiation treatment. We used the continuous coordinates of the fiducial markers collected by an orthogonal X-ray dual-image monitoring system. The translations and rotations of the prostate were calculated. Prostate deviations representing overall movement was defined as the length of the 3D-vectors.ResultsA total of 858 data files were analyzed. The deviations over time in the group of primary treated patients were significantly larger than that of the group of re-irradiation, leading to a mean deviation of 2.73 mm (SD =1.00) versus 1.90 mm (SD =0.79), P<0.001. In the re-irradiation group, we identified displacements of -0.05 mm (SD =1.53), 0.20 mm (SD =1.46); and 0.42 mm (SD =1.24) in the left-right, superior-inferior and anterior-posterior planes. Overall, we observed increasing deviations over the first 30 min followed by a stabilization related to movements in the three translational axes.ConclusionThis is the first study to focus on intrafraction prostate motions in the context of re-irradiation. We observed that intra-fraction prostate motions persisted in the setting of re-irradiation, although they showed a significant reduction when compared with the first irradiation. These results will help to better estimate random errors during SBRT treatment of intra-prostatic recurrence after irradiation.

Direct visualization and correlation of liver stereotactic body radiation therapy treatment delivery accuracy with interfractional motion.

This study used the visualization of hypo‐intense regions on liver‐specific MRI to directly quantify stereotactic body radiation therapy (SBRT) spatial delivery accuracy. Additionally, the interfractional motion of the liver region was determined and compared with the MRI‐based evaluation of liver SBRT spatial treatment delivery accuracy. Primovist®‐enhanced MRI scans were acquired from 17 patients, 8–12 weeks following the completion of liver SBRT treatment. Direct visualization of radiation‐induced focal liver reaction in the form of hypo‐intensity was determined. The auto‐delineation approach was used to localize these regions, and center‐of‐mass (COM) discrepancy was quantified between the MRI hypo‐intensity and the CT‐based treatment plan. To assess the interfractional motion of the liver region, a planning CT was registered to a Cone Beam CT obtained before each treatment fraction. The interfractional motion assessed from this approach was then compared against the localized hypo‐intense MRI regions. The mean ± SD COM discrepancy was 1.4 ± 1.3 mm in the left‐right direction, 2.6 ± 1.8 mm in an anteroposterior direction, and 1.9 ± 2.6 mm in the craniocaudal direction. A high correlation was observed between interfractional motion of visualized hypo‐intensity and interfractional motion of planning treatment volume (PTV); the quantified Pearson correlation coefficient was 0.96. The lack of correlation was observed between Primovist® MRI‐based spatial accuracy and interfractional motion of the liver, where Pearson correlation coefficients ranged from −0.01 to −0.26. The highest random and systematic errors quantified from interfractional motion were in the craniocaudal direction. This work demonstrates a novel framework for the direct evaluation of liver SBRT spatial delivery accuracy.

Abstract 677: Immune biomarkers of response to Ra223 dichloride and stereotactic body radiation therapy in patients with oligometastatic prostate cancers

Abstract Prostate cancer is the second leading cause of death in men in the developed countries. Androgen deprivation therapy (ADT) is commonly used to treat prostate tumors at earlier stages due to hormone-dependence of cancer cells. However, the onset of androgen-resistance with tumor progression and the negative impact of ADT on the quality of life are significant challenges. To address these issues, we have initiated a novel clinical trial combining radium Ra223 dichloride with stereotactic body radiation treatment (SBRT) and short course of ADT in patients with oligometastatic, castration-sensitive prostate cancer (NCT03351735). Patients with one to four oligometastatic prostate cancer lesions have been receiving ADT for nine months, together with SBRT to all metastatic sites and six cycles of Ra223 to target micrometastatic bone lesions. Eight out of the planned 24 patients have already completed the full treatment course, with five patients currently on surveillance (not requiring any further treatment) and three patients receiving next cycle of therapy. As part of this investigator-initiated study, we have performed a comprehensive immune characterization of peripheral immune cells and serum immune biomarkers in all treated patients. Based on flow cytometric analysis, we found a significant decrease in the percentage of CD4+ T cells befoe and after SBRT (cycle 1) but no changes in the elevated levels of programmed cell death-1 (PD-1), a marker of T-cell exhaustion, on the circulating CD4+ and CD8+ T cells. In addition, we observed high levels of the activated STAT3 (pSTAT3) in myeloid-derived suppressor cells (MDSCs), together with its downstream target Arginase-I. Finally, IL-8 stood out as a cytokine strongly elevated in plasma of patients who received the complete Ra223 treatment but not directly after SBRT. Overall, these preliminary results suggest that this combinatorial radiotherapy patients with oligometastatic prostate cancers impacts immune cell activity but rather than leading to T cell activation it may promote tolerogenic activity of MDSCs. Citation Format: Marice Alcantara, Tanya Dorff, Jessica Liu, Paul Frankel, Przemyslaw Twardowski, Savita Dandapani, Marcin Kortylewski. Immune biomarkers of response to Ra223 dichloride and stereotactic body radiation therapy in patients with oligometastatic prostate cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 677.

Efficacy and safety of stereotactic body radiotherapy (SBRT) in oligometastatic/persistent/recurrent ovarian cancer: a prospective, multicenter phase II study (MITO-RT3/RAD)

BackgroundStereotactic body radiotherapy (SBRT) has shown promising results in the clinical setting of oligometastatic, persistent, or recurrent disease in several malignancies including ovarian cancer.Primary ObjectiveThe MITO-RT3/RAD trial is a prospective,...

Prolonged overall treatment time negatively affects the outcomes of stereotactic body radiotherapy for early-stage non-small-cell lung cancer: A propensity score-weighted, single-center analysis.

Previous studies have reported conflicting results for the effect of overall treatment time with stereotactic body radiotherapy on tumor control in early-stage non-small-cell lung cancer. To examine this effect, we conducted a propensity score-weighted, retrospective, observational study at a single institution. We analyzed the data of 200 patients with early-stage non-small-cell lung cancer who underwent stereotactic body radiotherapy (48 Gy in 4 fractions) at our institution between January 2007 and October 2013. Patients were grouped into consecutive (overall treatment time = 4–5 days, n = 116) or non-consecutive treatment groups (overall treatment time = 6–10 days, n = 84). The outcomes of interest were local control and overall survival. The Cox regression model was used with propensity score and inverse probability of treatment weighting. The median overall treatment times in the consecutive and non-consecutive groups were 4 and 6 days, respectively. The 5-year local control and overall survival rates in the consecutive vs. the non-consecutive group were 86.3 vs. 77.2% and 55.5 vs. 51.8%, respectively. After propensity score weighting, consecutive stereotactic body radiotherapy was associated with positive local control (adjusted hazard ratio 0.30, 95% confidence interval 0.14–0.65; p = 0.002) and overall survival (adjusted hazard ratio 0.56, 95% confidence interval 0.34–0.91; p = 0.019) benefits. The prolonged overall treatment time of stereotactic body radiotherapy treatment negatively affected the outcomes of patients with early-stage non-small-cell lung cancer. To our knowledge, this is the first study to show that in patients with early-stage non-small-cell lung cancer treated with the same dose-fractionation regimen, consecutive stereotactic body radiotherapy has a more beneficial effect on tumor control than non-consecutive stereotactic body radiotherapy.