TPS8124 Background: Immune checkpoint inhibitor (ICI)–based regimens are standard first-line therapy for metastatic non–small-cell lung cancer (NSCLC) without actionable driver mutations; however, most patients experience disease progression within 12 months. A subset develop oligoprogression, defined by progression at a limited number of metastatic sites with otherwise controlled disease. Oligoprogression represents a therapeutic window in which local ablative therapy could be used to prolong disease control. In the prior phase II CURB trial, SBRT was shown to significantly prolong progression-free survival (PFS) in patients with oligoprogressive NSCLC. Methods: CCTG-BR38 is an international, multicenter, open-label, randomized phase III trial conducted through the NCI National Clinical Trials Network. Adults with stage IV NSCLC receiving first-line ICI ± chemotherapy who develop ≤5 extracranial oligoprogressive lesions are randomized 1:1 to: (1) switch to second-line standard systemic therapy or (2) SBRT (30 Gy in 3 fractions) to all oligoprogressive sites followed by continuation of the same first-line systemic therapy. Randomization is stratified by type of first-line systemic therapy (ICI alone vs ICI + chemotherapy), number of oligoprogressive lesions (1–2 vs 3–5), and ECOG performance status (0-1 vs 2). Patients with treated, stable brain metastases are eligible. Primary Endpoints: Dual primary endpoints are PFS and overall survival (OS). Secondary endpoints include safety (CTCAE v5.0), patient-reported adverse events (PRO-CTCAE), quality of life (EORTC QLQ-C30/LC13), and cost-effectiveness (EQ-5D-5L; Canadian sites). Optional blood and tissue collection for exploratory biomarker analyses are planned. Statistical Considerations: A total of 320 patients (160 per arm) will be enrolled. The sample size is based on detecting a HR of 0.7 for OS (an improvement in median OS from 10 to 14.3 months) with 80% power using a 1-sided 2% level test (the overall 1-sided 2.5% type I error will be assigned 2% to OS and 0.5% to PFS). Interim analyses for futility and efficacy are planned. Current Status: The trial was centrally activated on April 3, 2025. Accrual is ongoing across Canadian and US NCTN sites. Clinical trial information: NCT06686771 .

BACKGROUND AND PURPOSE:SABR-5 was a provincially coordinated, single-arm phase II trial of SABR for patients with up to five extracranial metastases across all six BC Cancer centres. The primary objective was to prospectively quantify treatment-related toxicity in a population-based setting. This analysis reports extended follow-up and long-term toxicity outcomes. MATERIALS AND METHODS:Adults with oligometastatic or oligoprogressive disease (≤5 extracranial metastases) were enrolled between 2016 and 2020, when SABR for these indications in BC was available only through this trial. All grade ≥ 3 events underwent central review by a provincial toxicity committee. Toxicity was evaluated using crude per-patient rates, cumulative incidence methods, annual landmark analyses to year 5, and assessment of toxicity duration. Median follow-up for this update was 54.2 months. RESULTS:A total of 380 patients were treated (median age 69 years; 32% female). Most patients (91%) had one or two lesions treated. Crude per-patient rates of treatment-related toxicity were 18.9% for grade 2, 5.8% for grade 3, 0.0% for grade 4, and 0.3% for grade 5. There were no additional treatment-related deaths beyond the single previously reported case. The most frequent grade ≥ 3 toxicities were fracture (2.9%) and pain (1.8%). The cumulative incidence of grade 2 and grade ≥ 3 toxicity at 5 years was 24% and 7%, respectively. Annual landmark analyses demonstrated that most evaluable patients remained grade 0-1 at each timepoint. Analysis of toxicity duration demonstrated that most grade 3 events resolved within a year (median durations typically < 12 months), and persistent long-term toxicity was uncommon and predominantly low-grade. CONCLUSION:SABR delivered within a population-based, quality-assured program is associated with a low incidence of late high-grade toxicity and no new treatment-related deaths. These findings provide durable reassurance regarding the long-term safety of SABR for patients with limited extracranial metastatic disease. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT02933242.

BACKGROUND:Research on cardiac radioablation (CR) has highlighted the importance of accounting for respiratory-induced motion during treatment, promoting investigation into methods to reduce its impact. PURPOSE:To investigate the efficacy of abdominal compression (AC) to reduce respiratory-induced motion for CR patients by quantifying their respiratory-induced motion under AC and free breathing (FB) conditions. METHODS AND MATERIALS:Nine patients were imaged with 5 Hz bi-planar fluoroscopy on the Vero4DRT linear accelerator for 15-20 seconds under both AC and FB conditions in preparation for CR. As the soft tissue target is not visible on bi-planar X-ray images, the implantable cardioverter defibrillator (ICD) lead tip was used as a motion surrogate. The position of the ICD lead tip was tracked and triangulated in each bi-planar image frame, with the respiratory component of motion extracted using a lowpass filter. Properties of respiratory-induced motion were quantified including the average (across patient breaths) peak-to-peak motion extent, the mean total 3D magnitude of displacement, and the standard deviation of motion for each patient. RESULTS:The average (95% CI) extent of RV lead respiratory-induced motion was [3.0 (1.1, 5.0), 2.8 (1.6, 4.1), 7.0 (4.2, 9.7)] mm under FB and [2.1 (1.4, 2.8), 2.7 (1.7, 3.8), 4.7 (3.5, 5.9)] mm under AC in the [right-left, anterior-posterior, inferior-superior] directions. Eight out of nine patients had a reduction in the mean respiratory-induced total 3D displacement under AC, with an average ( ± $ \pm $ STD) across patients of (3.2 ± $\pm $ 1.7) mm under FB and (2.2 ± $ \pm $ 0.8) mm under AC. Averaged across patients, the standard deviation (95% CI) of respiratory-induced motion was [1.3 (0.5, 2.0), 1.2 (0.7, 1.6), 3.1 (1.7, 4.5)] mm under FB and [0.9 (0.6, 1.3), 1.2 (0.6, 1.8), 2.0 (1.3, 2.7)] mm under AC. CONCLUSIONS:For eight out of nine CR patients investigated, the respiratory-induced RV lead motion was reduced when using AC compared to FB conditions.

PURPOSE:The use of SABR for oligometastatic cancer is expanding, but prospective long-term survival data are limited. This study reports long-term secondary outcomes of overall survival (OS), progression-free survival (PFS), local control, and prognostic factors from the population-based phase 2 SABR-5 trial. METHODS AND MATERIALS:The SABR-5 trial was a single-arm phase 2 study with the primary endpoint of toxicity, conducted across 6 regional cancer centers in British Columbia, Canada. Eligible patients had ≤5 oligometastases (new or uncontrolled by prior therapy, including induced oligometastatic disease), were ≥18 years of age with ECOG performance status 0-2, and had a life expectancy ≥6 months. All lesions were treated with SABR. RESULTS:From November 2016 to July 2020, 380 patients were treated. The most common histologies were prostate (32.1%), colorectal (16.6%), and breast (11.1%). Most patients (90.5%) had 1-2 lesions. Median follow-up was 54.2 months. Median OS was 64.6 months (95% CI, 61.0-68.1) and median PFS was 14.6 months (95% CI, 11.6-17.6). Five-year OS, PFS, and local control were 58.6% (95% CI, 53.5-63.7), 20.3% (95% CI, 16.2-24.4), and 85.1% (95% CI, 82.0-88.1), respectively. On multivariable analysis, worse OS was independently associated with ECOG ≥1, larger tumor diameter, colorectal or lung histology, 1-2 lesions, no upfront systemic therapy, and absence of synchronous oligometastatic disease. Predictors of worse PFS included ECOG ≥1, larger tumor diameter, no upfront systemic therapy, oligoprogression, and metachronous disease. CONCLUSIONS:In this large population-based cohort consisting of genuine oligometastatic, oligoprogressive, and induced oligometastatic disease, the median OS and PFS were 64.6 months and 14.6 months, respectively. The favorable OS and PFS may suggest a role for SABR beyond the genuine oligometastatic paradigm, highlighting the potential benefit of durable local tumor control in this patient population.

PURPOSE:To investigate the time-resolved translations and rotations of the heart through respiration and their impact on target localization accuracy in cardiac radioablation (CR). METHODS AND MATERIALS:Twelve patient data sets, from 6 patients, were acquired with 5 Hz, biplanar kV, fluoroscopy for 15 to 20 seconds in preparation for CR. Each patient was imaged twice, with and without abdominal compression. Included patients undergoing CR had implanted cardiac leads in the right ventricle (RV), right atrium (RA), and left ventricle (LV). Time-resolved respiratory motion for each cardiac lead was determined by monitoring the lead tip in biplanar images, triangulating its 3D position, and low-pass filtering its motion. The following 3 motion compensation strategies to model the target's position were simulated: (1) no respiratory motion compensation; (2) RV lead respiratory compensation; and (3) 6-degree-of-freedom (6DoF) respiratory motion modeling using all 3 cardiac leads. The 6DoF model also enabled quantification of the time-resolved translation and rotations of the cardiac lead cluster due to respiration. Each scenario was evaluated on its ability to predict the position of an independent pseudotarget, represented by the most proximal LV lead electrode, on the lateral wall of the LV. RESULTS:The average rotational amplitude of the cardiac lead cluster through respiration was 2.4∘±0.6° (right-left), 1.3° ± 0.4° (superior-inferior), and 1.7° ± 0.7° (anterior-posterior). For each patient, 6DoF respiratory motion compensation significantly (P≤.001) reduced respiratory motion localization errors compared with no motion compensation and RV lead only compensation. The average magnitude of 3D localization errors in respiratory motion compensation was 2.8 ± 1.1 mm without motion compensation, 2.0 ± 1.0 mm with RV lead compensation, and 0.8 ± 0.4 mm with 6DoF motion modeling. CONCLUSIONS:The rotation of the heart through respiration in CR, and its importance for real-time motion monitoring, is presented for the first time. For each patient data set, 6DoF modeling significantly improved the accuracy of respiratory motion localization for pseudotargets on the lateral wall of the LV.

Purpose: The optimal SABR treatment delivery schedule in stage I non-small cell lung cancer (NSCLC) remains unclear. This population-based study investigated grade >= 2 toxicity rates, local failure (LF), and overall survival (OS) in patients treated with 48 Gy in 4 fractions scheduled every other day versus daily with weekends and consecutive daily without weekends. Methods and Materials: Between January 2019 and June 2022, treatment records using 48 Gy in 4 fractions were extracted from a provincial cancer registry and grouped by delivery as every other day, daily with weekends, or consecutive daily without weekends. Toxicity events were recorded using National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. The KaplanMeier method was used to compute OS and LF was calculated using cumulative incidence methods with death as a competing risk. Cox regression analyses and Fine-Gray modeling was used to assess for variables associated with OS and LF, respectively. Results: Of 404 patients meeting study criteria, 190, 111, and 103 received SABR every other day, daily with weekends, and consecutive daily without weekends, respectively. More patients receiving SABR daily with weekends were medically inoperable and more patients receiving SABR consecutive daily without weekends had tumors abutting the chest wall. Median follow-up time was 29.5 months (IQR, 19.2-38.4 months). Overall toxicity was low, with crude rates of acute and late grade >= 2 toxicity not being statistically different among the groups. No grade 4 or 5 toxicities were recorded. LF rates at 24 months were not different at 7.5% (95% CI, 3.7-11.3), 9.5% (95% CI, 3.9-15.1), and 11.0% (95% CI, 4.9-17.2) for the every other day, daily with weekends, and consecutive daily without weekends groups, respectively (P = .60). Schedules of daily with weekends and consecutive daily without weekends were not associated with LF. Similarly, no significant differences in median OS were found among the every other day, daily with weekends, and consecutive daily without weekends groups at 47.5 months (95% CI, 39.26-55.74), 52.7 months (95% CI, 34.7-70.7), and 49.0 months (95% CI, 31.6-66.4), respectively. Schedules of daily with weekends and consecutive daily without weekends were not associated with OS. Conclusions: This population-based study demonstrated no statistically significant differences in grade >= 2 toxicity rates, LF, and OS for patients with stage I NSCLC treated with lung SABR using 48 Gy in 4 fractions delivered every other day, daily with weekends, and consecutive daily without weekends. Patient convenience and optimization of resources may be considered when choosing a lung SABR treatment delivery schedule. (c) 2024 American Society for Radiation Oncology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

PURPOSE/OBJECTIVES:There are limited data on outcomes in patients with ultracentral pulmonary oligometastases treated with SABR. The purpose of this study was to determine whether ultracentral location was prognostic for toxicity and survival. MATERIAL AND METHODS:Oligometastatic lung lesions treated on the single-arm phase 2 SABR-5 trial were retrospectively stratified into 2 cohorts: ultracentral tumors (UC), defined as planning target volume overlap or direct tumor abutment to the proximal bronchial tree, esophagus, great vessels, or heart, and nonultracentral tumors. Cohorts were compared with respect to grade ≥ 2 toxicity, progression-free survival (PFS), and overall survival (OS). RESULTS:In total, 41 patients with 45 ultracentral metastases and 93 patients with 172 nonultracentral metastases underwent SABR. The most common primary histologies were colorectal (30%), lung (13%), and renal (13%), and these did not differ between groups. Patients with UC had a lower median PFS of 5.8 months compared with 15.8 months in patients with non ultracentral tumors (P < .001). OS was also worse in the UC cohort: median 29.0 months versus not yet reached (P < .001). On multivariable regression, UC remained prognostic for worse PFS (hazard ratio 2.18, P = .004) and OS (hazard ratio 3.45, P < .001). Groups had similar rates of local tumor control. Patients with UC had higher 2-year cumulative incidence of polymetastatic progression: 69.2% versus 31.4% (P < .001). The 2-year cumulative incidence of grade ≥ 2 toxicity was 14.6% for patients with UC and 9.8% for patients with nonultracentral tumors (P = .74). There were no grade 4 or 5 toxicities. CONCLUSIONS:In this prospective patient cohort, SABR for ultracentral tumor had low toxicity rates and good local control. However, ultracentral location was an adverse prognostic feature for survival. This finding should be validated with larger studies and may be a factor when weighing the benefit versus risk of SABR in patients with pulmonary oligometastases.

Background/Objectives: Stereotactic body radiation therapy (SBRT) is a therapeutic option for hepatocellular carcinoma (HCC). This study reviewed outcomes and toxicities of SBRT for HCC using a gimbal-mounted linear accelerator and real-time monitoring system. Methods: A single-institution, retrospective review of SBRT for HCC using DTT between January 2018 and December 2020 was undertaken. Endpoints included local control (LC) and overall survival (OS). Results: A total of 74 patients with 82 tumors treated were identified. Median follow-up was 40.8 months. LC at 1, 3, and 5 years was 89.6%, 71.0%, and 59.9%, respectively. Median time to local failure was not reached. Median OS was 41.3 months (95% CI 30.7–51.8 months). OS at 1, 3, and 5 years was 89.2%, 60.6%, and 33.9%, respectively. On UVA, GTV ≥ 30 cm3 (p = 0.038), and PTV ≥ 150 cm3 (p = 0.010) were associated with an absolute drop in platelet count by ≥50,000/mm3 within six weeks of SBRT, while prior focal liver treatment (p = 0.097) showed a trend toward significance. Underlying viral cirrhosis (p = 0.033), A6 or higher pre-SBRT Child–Pugh score (p = 0.010), and pre-SBRT platelet count <100,000/mm3 (p = 0.017) were significant for a rise in Child–Pugh score of 2 points or more, and the volume of liver-GTV <1000 cm3 (p = 0.093) approached significance. Conclusions: SBRT using DTT is an effective therapeutic option for selected patients with HCC, providing acceptable local control and toxicity.

BACKGROUND:Distant progression is the predominant failure pattern after metastasis-directed stereotactic body radiotherapy (SBRT) for oligometastatic disease, but prognostic tools to guide post-progression management are lacking. We aimed to validate the prognostic value of distant metastasis velocity (DMV) for overall survival (OS) and widespread failure-free survival (WFFS) after distant progression. METHODS:Two independent international cohorts of patients with extracranial oligometastatic disease (≤5 lesions) who developed distant progression after SBRT were analyzed. The primary outcome was OS; secondary outcome was WFFS in the subgroup of patients with repeat oligometastasis at distant progression. DMV was defined as the number of new or progressing metastases per month after initial metastasis-directed SBRT. RESULTS:Among 563 patients (median age 68 years, 56 % male), DMV stratified prognosis in both cohorts. In the prospective cohort (n = 221), median OS was 35.7 months for patients with DMV ≤ 0.5 metastases/month versus 20.6 months for DMV > 0.5 (P = 0.0001). In the retrospective cohort (n = 342), OS was 32.8 vs. 12.1 months (P < 0.0001). Similar trends were observed for WFFS (prospective cohort, n = 91: 6.8 vs. 3.0 months, p = 0.42; retrospective cohort, n = 341: 18.8 vs. 6.1 months, p < 0.0001). CONCLUSION:Higher DMV was consistently associated with worse outcomes after progression in oligometastatic disease. Its reproducibility across tumor types and independent cohorts supports DMV as a simple, dynamic, and clinically relevant prognostic marker. DMV should be further explored as a component of multimodal prognostic models to refine patient selection and guide post-progression treatment strategies.

BACKGROUND:Cardiac radioablation (CR) is an emerging treatment for ventricular tachycardia, a rapid abnormal heart rhythm. Effectively delivering radiation to CR targets requires understanding and accounting for geometric uncertainties. One important uncertainty is motion induced by the cardiac and respiratory cycles, which can be accounted for by expanding the targeted region by a margin accounting for the motion's effect on dosimetry. PURPOSE:To investigate margins to account for cardiac and respiratory motions in CR and compare different methods of computing these margins. METHODS:Eighty four hundred cardiorespiratory motion traces were created by joining 1050 cardiac motions derived from 30 Hz magnetic resonance images with eight respiratory motions from 5 Hz bi-planar kV fluoroscopy. Cardiac motions for each of the 17 segments of the left ventricle were acquired for 50 heart failure patients with a reduced ejection fraction. Respiratory motions were derived from the implantable cardioverter defibrillator lead's tip for eight CR patients. The margins needed to account for random errors were found using the convolution method by blurring a dose penumbra (Gaussian fall-off σ p ${\sigma _p}\;$ = 3.2 mm) with the motion. The motion margin was computed as the shift in the 95% dose level after blurring. Since these dosimetric margins do not consider rotations and shape deformation, they are considered a lower limit to account for cardiorespiratory motions. These motion margins were compared to (i) a sum of cardiac and respiratory motion amplitudes, similar to using an internal target volume (ITV); (ii) the van Herk et al. margin formula (MF =  β ( σ - σ p ) $\beta ( {\sigma - {\sigma _p}} )$ ); and (iii) the amplitude of respiratory motion alone, similar to using a respiratory ITV. RESULTS:The sum of cardiac and respiratory motion amplitudes significantly overestimated the motion margins by [2.2±0.7 right-left, 2.6±0.9 ant-post, 2.7±0.7 inf-sup] mm. The margin formula accurately calculated the motion margins with average differences from the convolution method of [0.00±0.06, 0.0±0.1, 0.0±0.1] mm. Accounting for the amplitude of respiratory motion alone was on average sufficient but not robust, as it could underestimate the motion margin by up to 5 mm. CONCLUSIONS:Margins to account for cardiorespiratory motion in CR can be calculated using a margin formula. The conservative approach of accounting for the amplitude of cardiorespiratory motion can significantly overestimate the needed margin which may result in excess healthy tissue damage.

PURPOSE:To investigate the utility of implanted cardiac leads or the diaphragm for active respiratory motion management in stereotactic arrhythmia radioablation by quantifying the relationship between their motions. METHODS AND MATERIALS:Seven patients treated with stereotactic arrhythmia radioablation were imaged using 5-Hz biplanar, kV x-ray fluoroscopy for 15-20 seconds under both abdominal compression (AC) and free breathing (FB) conditions. Three-dimensional motion traces for different regions of the heart were acquired by tracking and triangulating the position of all implanted cardiac leads. The heart's respiratory motion was extracted from the total motion (respiratory + cardiac) using a low-pass filter and described in optimized coordinates using principal component analysis. The existence of a relationship between the respiratory motion of different cardiac leads or the diaphragm was quantified using the Spearman rank correlation coefficient. Polynomial correlation models relating PC1 cardiac lead motion to the diaphragm were created and evaluated on the resultant errors. RESULTS:Eighty-one respiratory motion correlations between different positions of the heart or diaphragm were calculated under both AC and FB. Consistently strong correlations between the respiratory motion of different positions in the heart and the diaphragm required accounting for phase shifts between motions. When accounting for phase shifts, the proportion of strong (>0.7) PC1 respiratory motion correlations was 100% under FB and 92.6% under AC. Linear fitting of cardiac lead motion with the diaphragm resulted in mean absolute PC1 tracking errors of (1.0 ± 0.6) mm under FB and (0.7 ± 0.4) mm under AC. CONCLUSIONS:The respiratory motion of all combinations of implanted cardiac leads and the diaphragm are moderately to strongly correlated after accounting for phase shifts between motion traces. These phase shifts should be carefully considered to ensure patient safety during respiratory tracking or gating during stereotactic arrhythmia radioablation using cardiac leads or the diaphragm as internal surrogates.

PURPOSE:To compare local failure, marginal failure, and toxicity in non-spine bone metastases (NSBMs) treated with versus without a CTV for stereotactic ablative radiotherapy (SABR). METHODS:The study included all patients in British Columbia treated with SABR for NSBMs on the SABR-5 trial (November 2016 - July 2020) and on the BC Oligometastases Registry (August 2020- October 2022). NSBMs were stratified based on CTV use for treatment planning. RESULTS:148 patients with 183 NSBMs were included. 145 (79 %) NSBMs were treated with a CTV. Most lesions received 35 Gy in 5 fractions (80 %) or 24 Gy in 2 fractions (15 %). Local failure rates did not differ, with a 2-year local failure of 8.6 % (95 % confidence interval [CI] 3.9-13.2) with a CTV and 8.1 % (95 % CI 0-16.8) without a CTV (p = 0.53). Marginal failure did not differ (6.4 % [95 % CI 2.3-10.5] and 2.6 %, [95 % CI 0-7.7], respectively [p = 0.23]). 2-year cumulative incidence of grade ≥ 2 toxicity did not differ (15.8 %, 95 % CI 9.7-21.9 and 16.2 %, 95 % CI 4.2-28.2 respectively; p = 1.00). On multivariable regression, use of a CTV was not associated with the risk of local-marginal failure (hazard ratio [HR] 1.81, 95 % CI 0.62-5.31, p = 0.28). Extraosseous extension (HR 2.59, 95 % CI 1.2-5.7, p = 0.02) and lack of receipt of systemic therapy (HR 0.27, 95 % CI 0.1-0.5, p = 0.0002) were associated with higher risk. CONCLUSIONS:Use of a CTV was not associated with local or marginal failure or toxicity. Extraosseous extension and lack of receipt of systemic therapy were associated with higher risk of local-marginal failure.

Purpose Although stereotactic ablative radiation therapy (SABR) is known for low toxicity and safety, its combined use with specific systemic therapies requires further investigation. This study aims to evaluate the toxicity of SABR in combination with various systemic therapies. Materials and Methods A secondary analysis of the SABR-5 trial evaluated grade 2+ and 3+ toxicities post-SABR in patients who had received high-risk or non-high-risk systemic therapies before SABR at 4 predefined intervals: concurrent with SABR, 1 day to 1 week prior, 1 to 2 weeks prior, or 2 to 12 weeks prior. High-risk systemic therapy was a priori defined as drugs that may increase treatment toxicity when delivered in close proximity to SABR. This category encompasses cytotoxic chemotherapy, multitargeted tyrosine kinase inhibitors, CDK 4/6 inhibitors, EGFR inhibitors, anti-VEGF agents, and anti-CTLA-4 agents. Results Among 380 patients, grade 2+ toxicity rates were 17.3% (35/202) off systemic therapy, 19.2% (19/99) on non-high-risk therapy, and 42.9% (3/7) on high-risk therapy concurrent with SABR. Grade 3+ rates were 3.5% (7/202), 4.0% (4/99), and 28.6% (2/7), respectively. On multivariable analysis, concurrent use of high-risk systemic therapy was associated with a higher risk of grade 3+ toxic effects (OR, 14.88; P = .009). No significant risk was noted when high-risk drugs were used within 1 week, 2 weeks, or 2 to 12 weeks of SABR or with any non-high-risk drugs. Grade 2+ toxic effects associated with concurrent high-risk systemic therapy were primarily bone/pain related. Increased tumor diameter also elevated grade 2+ toxicity risk (per 1 cm increment; G2+ OR, 1.19; P < .001). Conclusion Concurrent use of high-risk drugs has demonstrated a potential of increased SABR-related toxicity, warranting caution in their concurrent use with SABR. In contrast, combining non-high-risk drugs (eg, hormonal therapy) with SABR did not increase risk. Further research is essential to identify risks associated with this therapeutic combination.

AIMS:Single-fraction stereotactic ablative radiotherapy (SF-SABR) was introduced in British Columbia (BC), Canada, during the COVID-19 pandemic. It persists as a standard treatment owing to its comparable outcomes with fractionated regimens in two randomised phase II trials and advantages in resource utilisation and patient convenience. This study evaluated the clinical outcomes and toxicities in patients treated with SF-SABR for early stage non-small lung cancer (NSCLC) in BC. MATERIALS AND METHODS:This multi-institution population-based retrospective study included all patients treated with SF-SABR for early stage NSCLC between March 2020 and August 2023 in BC. All lesions were peripheral T1-T2 tumours, less than 5 cm in diameter. All patients were medically inoperable or declined surgery. Prescription doses were either 30 Gy or 34 Gy in one fraction. Assessed clinical outcomes included 2-year local failure (LF), distant failure (DF), and overall survival (OS). Toxicity endpoints were graded according to Common Terminology Criteria for Adverse Events version 5.0. RESULTS:A total of 179 lesions in 166 patients were included. The median follow-up was 23.0 months. The median age was 75 years. The majority (95%) of tumours were T1. The median tumour diameter was 1.5 cm. Prescription doses of 30 Gy and 34 Gy were delivered to 103 (57.5%) and 76 (42.5%) lesions, respectively. The 2-year LF, DF, and OS rates were 7.1%, 14.1%, and 81.5%, respectively. No grade 4 or 5 toxicities were reported. Crude rates of grade 2 and 3 toxicities were 17.3% and 2.2%, respectively. Grade 2 and 3 chest wall toxicity (CWT) rates were 5.6% and 0.6%, respectively. Chest wall abutment, diabetes, and prior thoracic radiation were significant predictors for CWT on univariate analysis. CONCLUSIONS:This multi-institution population-based study demonstrated that SF-SABR for early stage NSCLC had favourable early clinical outcomes and low toxicity rates comparable to data from other SF-SABR and multi-fraction lung SABR studies. Long-term follow-up of outcomes and toxicity for SF-SABR are warranted.

PURPOSE:This trial examined if patients with ≤5 sites of oligoprogression benefit from the addition of SABR to standard of care (SOC) systemic therapy. METHODS AND MATERIALS:We enrolled patients with 1 to 5 metastases progressing on systemic therapy, and after stratifying by type of systemic therapy (cytotoxic vs noncytotoxic), randomized 1:2 between continued SOC treatment versus SABR to all progressing lesions plus SOC. The trial was initially limited to non-small cell lung cancer but was expanded to include all nonhematologic malignancies to meet accrual goals. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), lesional control, quality of life, adverse events, and duration of systemic therapy postrandomization. RESULTS:Ninety patients with 127 oligoprogressive metastases were enrolled across 8 Canadian institutions, with 59 randomized to SABR and 31 to SOC. The median age was 67 years, and 39 (43%) were women. The most common primary sites were lung (44%), genitourinary (23%), and breast (13%). Protocol adherence in the SOC arm was suboptimal, with 11 patients (35%) either receiving high-dose/ablative therapies (conflicting with trial protocol) or withdrawing from the study. The median follow-up was 31 months. There was no difference in PFS between arms (median PFS 8.4 months in the SABR arm vs 4.3 months in the SOC arm, but curves cross and 2-year PFS was 9% vs 24%, respectively; P = .91). The median OS was 31.2 months versus 27.4 months, respectively (P = .22). Lesional control was superior with SABR (70% vs 38%, respectively; P = .0015). There were 2 (3.4%) grade 3 and no grade 4/5 adverse events attributable to SABR. CONCLUSIONS:SABR was well-tolerated with superior lesional control but did not improve PFS or OS. Accrual to this study was difficult, and the results may have been impacted by an unwillingness to forgo ablative treatments on the SOC arm. (NCT02756793).