{"paper_id":"082ff6b8-c49f-4437-b452-ef76b54660ab","body_text":"Utility of Molecular Markers in Predicting Local Control Specific to Lung Cancer Spine Metastases Treated with Stereotactic Body Radiotherapy | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Utility of Molecular Markers in Predicting Local Control Specific to Lung Cancer Spine Metastases Treated with Stereotactic Body Radiotherapy Dana Shor, Alexander V. Louie, Kang Liang Zeng, Ines Menjak, Eshetu G. Atenafu, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3840775/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 25 Mar, 2024 Read the published version in Journal of Neuro-Oncology → Version 1 posted 8 You are reading this latest preprint version Abstract Background and purpose: We report outcomes following spine stereotactic body radiotherapy (SBRT) in metastatic non-small cell lung cancer (NSCLC) and the significance of programmed death-ligand 1 (PD-L1) status, epidermal growth factor receptor (EGFR) mutation and timing of immune check point inhibitors (ICI) on local failure (LF). Materials and methods: 165 patients and 389 spinal segments were retrospectively reviewed from 2009 to 2021. Baseline patient characteristics, treatment and outcomes were abstracted. Primary endpoint was local failure (LF) and secondary, overall survival (OS) and vertebral compression fracture (VCF). Multivariable analysis (MVA) evaluated factors predictive of LF and VCF. Results: The median follow-up and OS were: 13.0 months (range, 0.5–95.3 months) and 18.4 months (95% CI 11.4–24.6). 52.1% were male and 76.4% had adenocarcinoma. Of the 389 segments, 30.3% harboured an EGFR mutation and 17.0% were PD-L1 ≥ 50%. The 24 months LF rate in PD-L1 ≥ 50% vs PD-L1 < 50% was 10.7% vs. 38.0%, and in EGFR-positive vs. negative was 18.1% vs. 30.0%. On MVA, PD-L1 status of ≥ 50% (HR 0.32, 95% CI 0.15–0.69, p = 0.004) significantly predicted for lower LF compared to PD-L1 < 50%. Lower LF trend was seen with ICI administration peri and post SBRT (HR 0.41, 95% CI 0.16–1.05, p = 0.062). On MVA, polymetastatic disease (HR 3.28, 95% CI 1.84–5.85, p < 0.0001) and ECOG ≥ 2 (HR 1.87, 95% CI 1.16–3.02, p = 0.011) significantly predicted for worse OS and absence of baseline VCF predicted for lower VCF rate (HR 0.20, 95% CI 0.10–0.39, p < 0.0001). Conclusion: We report a significant association of PD-L1 ≥ 50% status on improved LC rates from spine SBRT in NSCLC patients. Figures Figure 1 Figure 2 Figure 3 INTRODUCTION Over the past decade, the survival from metastatic non-small cell lung carcinoma (NSCLC) has improved due to targeted therapies against oncogenic driver mutations and the use of immune check point inhibitors (ICI) 1–5 . The third generation Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitor (TKI), Osimertinib, has significantly enhanced the overall survival (OS) for patients with an activating EGFR mutation, particularly those with exon 19 deletion and exon 21 (L858R) point mutation 6 . Immunotherapy using ICI either as monotherapy 7 or combined with chemotherapy 5,8 , depending on programmed death-ligand 1(PD-L1) status, is the now the standard of care. With increasing survival, there is growing demand to optimize local control (LC) to sites of visible metastases for patients with limited number of targetable sites (oligometastases) or those progressing despite systemic therapy. Phase II trials have demonstrated improved survival with directed stereotactic body radiotherapy (SBRT) in oligometastatic lung cancer 9–12 . As an early adopter of SBRT for oligometastases, we described outcomes in a large patient cohort with various histologies including 260 lung cancer patients, that compare favorably to prospective data with limited sample sizes 13 . Approximately 30–55% of metastases from lung cancer occur within the spine 14 , which can cause debilitating pain and progress to neurologic impairment. The Canadian Cancer Trials Group Symptom Control Protocol 24 (CCTG SC24) randomized controlled trial, compared 24 Gy in 2 SBRT fractions to 20 Gy in 5 fractions palliative external beam radiotherapy (cEBRT) in patients presenting with painful spinal metastases. Higher rates of complete pain response were reported at 3 and 6 months post-SBRT 15 . An institutional CCTG SC24 sub-group analysis, with mature follow-up, reported reduced local failure (LF) rates and less frequent re-irradiation rates following SBRT as compared to cEBRT 16 . The trial included mixed histology and there is an urgent need to understand histology specific outcomes for spine SBRT, in particular the prognostic value of molecular markers and modern systemic therapies. The aim of the present study was to report our experience with spine SBRT in NSCLC patients with spinal metastases and determine the prognostic impact of targetable mutations and PD-L1 status. MATERIALS AND METHODS We retrospectively reviewed NSCLC patients with spine metastases treated with spine SBRT at our institution between 2009 and 2021. Post-operative cases were excluded. We categorized the NSCLC subtypes as adenocarcinoma, squamous cell carcinoma and adeno-squamous carcinoma, and excluded neuroendocrine lung cancers (small cell, large cell and carcinoid tumors). Oncogenic driver alterations were recorded, principally EGFR mutations and anaplastic lymphoma kinase (ALK) fusions. Beginning in 2021, other drivers such as human epidermal growth factor receptor (HER2) and mesenchymal epithelial transition factor receptor (MET) were recorded. PD-L1 status was stratified into < 1%, 1–49% and ≥ 50% positivity. Mutational and PD-L1 status that were not available nor reported were designated as unknown. PD-L1 immunohistochemistry (IHC) was performed using the Dako/Agilent 22C3 PharmDX CDx Assay (prior to 2019) or a validated laboratory developed test (LDT) using the 22C3 antibody (after 2019). EGFR mutations were tested via quantitative polymerase chain reaction using the Entrogen EGFR Mutation Analysis Kit EGFR-RT52 (2009–2021) or the Biocartis Idylla EGFR Mutation Test (2020-21), or by next generation sequencing (NGS) using the Oncomine Focus Assay (OFA) (from June 2021 onwards) (Thermo Fisher Scientific). ALK fusions were tested by IHC using an LDT with the ALK 5A4 antibody (2015–2019) and with ALK 1A4 antibody (July 2019–2021), using protocols optimized for the detection of ALK gene rearrangements. Other molecular markers (e.g. MET) was done by NGS using OFA (from June 2021). Metastatic burden was classified as solitary spinal metastases, oligometastatic (2–5 metastases) or polymetastatic (> 5 metastases), when at least one treated metastasis was within the spine. Systemic therapies from metastatic diagnosis to last follow up were reviewed. The last systemic agent to be administered > 1 month prior to SBRT was categorized as ‘pre-SBRT’, agents delivered 1-month prior to or following SBRT were classified as ‘peri-SBRT’, and those > 1-month after SBRT as ‘post-SBRT’. Patients followed institutional protocol with full spine MRI and clinical assessment every 2–3 months. Our SBRT treatment technique has been previously described 17,18 . Our target delineation approach adhere to International Spine Radiosurgery Consortium guidelines 19,20 , and Dunne et al. for the sacrum 19 . Treatment planning approach is based on isotoxic principles respecting spinal cord tolerance 21,22 . This study was approved by the local institutional research ethics board (IRB approval number SUN-5062). The primary outcome was LF, defined according to SPINO as a gross unequivocal increase in tumor volume or linear dimension, any new or progressive tumor within the epidural space and/or neurological deterioration attributable to pre-existing epidural disease with equivocal increased epidural disease on serial MRI (two or three consecutive MRI scans) 23 . Secondary outcomes included OS and adverse events, mainly new or progressive vertebral compression fracture (VCF). The adverse events were reported according to common terminology criteria for adverse events version 5 (CTCAEv5) 24 . Statistical analysis Descriptive statistics summarized baseline clinical and tumor factors. LF and VCF were assessed per spinal segment, and OS on a per patient. Cumulative LF and VCF rates were calculated with competing risk analysis method, using death as a competing risk. OS was calculated using the Kaplan-Meier method. Univariate comparisons between cohorts employed the log-rank test for OS and Gray’s test for LF and VCF. Multivariable Cox proportional hazards models assessed the joint impact of covariates of interest on the primary and secondary outcomes. Predictors for LF included: baseline epidural and paraspinal disease, adenocarcinoma versus other NSCLC histology, spine SBRT dose and fractionation, SINS classification, dosimetric factors, prior radiation to the same segment, smoking history, PD-L1 and EGFR status and systemic therapy use (TKI, IO and chemotherapy). Predictors for OS included: age, ECOG (Eastern Cooperative Oncology Group) performance status, metastatic burden (presence of liver, lung and brain metastases), adenocarcinoma versus other NSCLC histology, baseline epidural and paraspinal disease, spine SBRT dose and fractionation, SINS classification, dosimetric factors, prior radiation to the same segment, smoking history, PD-L1 and EGFR status and systemic therapy use. Potential predictors for VCF included: baseline VCF, baseline epidural and paraspinal disease, prior radiation to same segment, SINS classification, spine SBRT dose and fractionation, age, gender, and systemic therapy use. ALK, HER2, MET target mutations were not used due to limited patient numbers. P-values were 2-sided with a 0.05 threshold for statistical significance. Multivariable models used a univariable screening p-value threshold of 0.15 and backward selection to identify the most predictive factors. Statistical analysis used SAS version 9.4 (2002–2012 SAS Institute, Inc., Cary, NC). RESULTS Patient Demographics A total of 389 metastatic spinal segments in 165 patients were treated with SBRT. Baseline characteristics are summarized in Tables 1 and 2 . Median patient follow-up was 13.0 months (range: 0.5–95.3), median spinal segment follow-up was 8.8 months (range: 0.03–73.5), and median time from diagnosis to SBRT was 11.2 months (range: 0.03–159.2). 52.1% were male and most were ECOG 0–1 (83.6%). 87.9% had an American Spinal Injury Association impairment scale (ASIA) of E, 76.4% were adenocarcinoma and 61.0% had a smoking history. 74 (44.8%) were polymetastatic, 63 (38.2%) oligometastatic and 28 (17.0%) had solitary treated spinal metastasis. Table 1 Baseline demographic factors Patient factors N = 165 Median age (years) 66.5 (IQR: 59.8–74.4) Time from diagnosis to treatment (months) Median (inter-quartile) 11.2 (2.4–22.7) Gender Female 79 (47.9%) Male 86 (52.1%) ECOG * 0–1 138 (83.6%) ≥2 27 (16.4%) ASIA > E 145 (87.9%) Other 20 (12.1%) Metastatic burden Solitary > 28 (17.0%) Oligometastatic $ 63 (38.2%) Polymetastatic # 74 (44.8%) Visceral metastases Lung and liver 15 (9.1%) Liver 8 (4.8%) Lung 42 (25.5%) Neither lung nor liver 100 (60.6%) Brain metastases 46 (27.9%) Histology Adenocarcinoma 126 (76.4%) Others % 39 (23.6%) Previous smoking history 100 (61.0%) Driver mutation status No driver mutation 105 (65.2%) EGFR positive 49 (30.4%) Non EGFR driver mutation 7 (4.3%) Missing 4 PD-L1 PD-L1 ≥ 50% 29 (17.6%) PD-L1 1–49% 26 (15.8%) PD-L1 < 1% 45 (27.3%) PD-L1 Unknown 65 (39.4%) Immunotherapy use Pre SBRT x ICI $ 4 (2.4%) Pre and peri and post SBRT ! ICI 12 (7.3%) Peri and post SBRT ICI 15 (9.1%) Post SBRT ICI 29 (17.6%) No ICI used 105 (63.6%) TKI @ use Pre SBRT TKI 40 (12.0%) Peri SBRT TKI 38 (23%) Post SBRT TKI 46 (28%) *ECOG : Eastern Co-operative Oncology Group, > ASIA : American Spinal Injury Association, > Solitary (1 metastasis); $ Oligometastatic (2–5 metastases); # Polymetastases (> 5 metastases), % Other histology (squamous cell carcinoma or adenosquamous) $ ICI : immune check point inhibitors. @ TKI : tyrosine kinase inhibitor Table 2 Baseline Tumor/Treatment factors Segment factors (N = 389) Treatment indication De novo 308 (79.2%) Retreatment 81 (20.8%) Spinal level treated Cervical 52 (13.4%) Thoracic 226 (58.1%) Lumbar 86 (22.1%) Sacrum 25 (6.4%) Dose and fractionation 24-28Gy/2fractions 239 (61.4%) 30Gy/4fractions 106 (27.2%) Other 44 (11.3%) Paraspinal extension 108 (27.8%) Epidural extension Low grade (1a-c) 89 (22.9%) High grade (2–3) 35 (9.0%) No Epidural Disease 265 (68.1%) SINS classification Stable 189 (48.6%) Potentially unstable 180 (46.3%) Unstable 20 (5.1%) Baseline VCF ! present 65 (16.7%) Driver Mutation Status No driver mutation 249 (64.0%) EGFR Positive 118 (30.3%) Exon 19 deletion 50 (42.0%) Exon 21 point mutation 48 (41.0%) Exon 20 T790M 8 (7.0%) Unknown mutation 12 (10%) Non EGFR driver mutation ** 22 (5.7%) PD-L1 PD-L1 ≥ 50% 66 (17.0%) PD-L1 1–49% 88 (22.6%) PD-L1 @ <1% 98 (25.2%) PD-L1 Unknown 137 (35.2%) Dosimetric factors Median (range) Cord PRV/Thecal Sac ^ (EQD2 2 ) ? 44.6 (13.3-127.50) V100 (%) 80 (49.0–97.0) PTV & Volume (cm3) 116.2 (12.4–612.0) Mean dose (EQD2 10 ) 48 (29.0–67.0) CTV @ Volume (cm3) 74.8 (5.9–456.0) Mean dose (EQD2 10 ) 49 (12.0–77.0) # SINS : spine instability neoplastic score; ! VCF : vertebral compression fracture; ? EQD2 : equivalent dose in 2Gy fractions, subscript represents α/β; ^ PRV : planning risk volume; & PTV : planning target volume; @ CTV : clinical target volume; x SBRT : stereotactic body radiotherapy; $$ EGFR : epidermal growth factor receptor; ## PD-L1 = programmed death ligand 1; **Non EGFR driver mutation: anaplastic lymphoma kinase mutation (ALK), human epidermal growth factor receptor 2 (HER 2) mutation or Mesenchymal epithelial transition proto-oncoge (MET) mutation. Tumor and treatment Characteristics Thoracic spine was the most common metastatic site (58.1%), prescription dose was 24Gy or 28Gy in 2 fractions (61.4%), and 79.2% were de novo (not previously irradiated). 27.8% segments had paraspinal disease, 31.8% had epidural disease, 16.7% had an existing VCF and 48.6% of segments were Spine Instability Neoplastic Score (SINS) stable. 30.3% of the treated segments were EGFR mutation positive, 5.7% had a non-EGFR mutation such as ALK, HER2 or MET, and 64.0% had no driver mutations (Table 2 ). Of the 118 EGFR positive segments, 42.0% had an EGFR exon 19 deletion, 41.0% had an exon 21 L858R point mutation, 7.0% had an exon 20 T790M mutation and 10.0% had an unknown mutation. Of the 389 treated segments, 47.8% were PD-L1 < 50%, 17.0% PD-L1 ≥ 50% and 35.2% PD-L1 unknown. 22 of the 118 (18.6%) segments with EGFR mutation were also PD-L1 ≥ 50%. Of 165 patients, 4 (2.4%) received ICI pre SBRT, 27 (16.4%) peri-SBRT and 29 (17.6%) post SBRT. Of the 56 patients with a driver mutation (49 with EGFR and 7 with non-EGFR), all treated with a TKI at some point during their disease course with 40 (12.0%) receiving TKI pre SBRT, 38 (23.0%) peri-SBRT and 46 (28.0%) post SBRT (Table 1 ). Local failure The median time to LF among those who failed locally was 7.1 months (range: 0.4–35.4), with cumulative LF rates at 6, 12 and 24 months of 11.4% (95% CI 8.5–14.8), 16.4% (95% CI 12.8–20.3) and 26.3% (95% CI 21.7–31.1), respectively. LF rates based on PD-L1 status at 6, 12, and 24 months were 15.2% (95% CI 10.4–20.7), 19.8% (95% CI 14.4–26.0) and 38.0% (95% 30.0–46.0%) in those PD-L1 < 50%, respectively, vs 9.2% (95% CI 3.7–17.7), 10.7% (95% CI 4.7–19.7) and 10.7% (95% CI 4.7–19.7) in those PD-L1 ≥ 50% (p = 0.001), respectively (Fig. 1 ). The LF rates based on EGFR status at 6, 12, and 24 months rate were 11.3% (95% CI 7.8–15.7), 16.6% (95% CI 12.2–21.6) and 30% (95% CI 23.9–36.4) in those EGFR negative, vs 7.6% (95% CI 3.7–13.4), 12.9% (95% CI 7.6–19.8) and 18.1% (95% CI 11.5–25.9) in those EGFR positive (p = 0.032), respectively (Fig. 2 ). Univariable analysis (UVA) identified EGFR positive status (HR 0.61, 95% CI 0.37–0.99, p = 0.046), ICI administration (HR 0.48, 95% CI 0.2–0.9, p = 0.021), TKI pre SBRT (HR 0.57, 95% CI 0.34–0.95, p = 0.0314), PD-L1 > 50% (HR 0.33, 95% CI 0.16–0.71, p = 0.0048), and absence of paraspinal disease (HR 0.52, 95% CI 0.35–0.77, p = 0.0013) predicted for lower LF. Multivariable analysis (MVA) showed PD-L1 status of ≥ 50% (HR 0.32, 95% CI 0.15–0.69, p = 0.004) and PD-L1 unknown (HR 0.54, 95% CI 0.34–0.84, p = 0.007) as significant predictors for lower LF compared to PD-L1 < 50% (Table 3 ). There was a trend towards a lower risk of LF when ICI was administered peri- and post-SBRT (HR 0.41, 95% CI 0.16–1.05, p = 0.062) as compared to other time periods of ICI administration (no ICI use at any point, ICI pre-SBRT only and ICI post-SBRT only). Table 3 Multivariable analysis for local failure, overall survival and vertebral compression fracture Parameter P-value HR 95% CI Local failure PD-L1 ≥ 50% 0.004 0.32 0.15–0.69 Unknown 0.007 0.54 0.34–0.84 PD-L1 < 50% Reference ICI use Peri and post SBRT ICI 0.062 0.41 0.16–1.05 Pre and Peri and Post SBRT ICI 0.429 0.69 0.28–1.73 No ICI at any point, pre SBRT ICI only and post SBRT ICI only Reference Overall survival Metastatic burden Polymetastatic < .0001 3.28 1.84–5.85 Oligometastatic 0.466 1.24 0.69–2.22 Solitary metastasis Reference ECOG ≥ 2 0.011 1.87 1.16–3.02 0–1 Reference Vertebral compression fracture Baseline VCF No < .0001 0.20 0.10–0.39 Yes Reference Baseline paraspinal disease No 0.098 0.57 0.29–1.11 Yes Reference Overall survival The median OS was 18.4 months (95% CI 11.4–24.6), with a 12 and 24 month rate of 56.1% (95% CI 48.0-63.4) and 43.1% (95% CI 35-50.1), respectively. On UVA, ECOG 0 or 1 (HR 0.41, 95% CI 0.26–0.66, p = 0.0002), presence of oligometastases (HR 0.34, 95% CI 0.23–0.53, p < 0.0001) and treatment to a solitary spinal metastasis (HR 0.29, 95% CI 0.16–0.51, p < 0.0001, Fig. 3 ) were associated with improved OS. Metastatic disease in the lung (HR 1.68, 95% CI 1.10–2.58, p = 0.017), lung and liver both (HR 3.62, 95% CI 1.99–6.56, p < 0.0001) were prognostic for worse OS. No significant differences in OS were found based on molecular subtypes, specifically in those EGFR positive vs. EGFR negative patients (median of 19.4 months vs 14.3 months, p = 0.586) and those PD-L1 < 50% vs. PD-L1 ≥ 50% segments (19.4 months vs 19.9 months, p = 0.534). On MVA, polymetastatic disease (HR 3.28, 95% CI 1.84–5.85, p < 0.0001) and ECOG ≥ 2 (HR 1.87, 95% CI 1.16–3.02, p = 0.011) significantly predicted for worse OS (Table 3 ). Toxicity The overall rate of new or progressive VCF was 10.03%; 22 segments (5.7%) developed a new VCF and 17 (4.4%) had progression of an existing VCF. The median time to new or progressive VCF was 5.2 months (range: 0.6–51.4). The cumulative incidence of new or progressive VCF at 12 and 24 months was 6.6% (95% CI 4.4–9.4%) and 8.8% (95% CI 6.1–12.0%), respectively. On UVA, baseline VCF (HR 5.14, 95% CI 2.63–10.06, p < .0001), SINS VBC < 50% collapse (HR 5.11, 95% CI 2.38–10.95, p < 0.0001), SINS VBC ≥ 50% collapse (HR 3.33, 95% CI 0.94–11.79, p = 0.0619), SINS potentially unstable (HR 1.73, 95% CI 0.82–3.68, p = 0.1522), SINS unstable (HR 6.11, 95% CI 2.26–16.52, p = 0.0004), presence of epidural disease (HR 2.57, 95% CI 1.31–5.02, p = 0.006) and combination of paraspinal and epidural disease (HR 2.2, 95% CI 1.02–4.84, p = 0.0459) were associated with increased rate of VCF. On MVA, only absence of a baseline VCF retained significance (HR 0.20, 95% CI 0.10–0.39, p < 0.0001). Radiation-induced radiculopathy was reported in 1 cervical, 6 thoracic, 6 lumbar and 5 sacral segments [18/389 (4.6%)] segments. The median time to radiculopathy was 13.5 months (range: 3.3–35.1). 15/18 (83.3%) were grade 2 and 3/18 (16.7%) were grade 3 in severity. There were no radiation myelopathy events. DISCUSSION We report robust outcomes specific to NSCLC spinal metastases treated with SBRT and the prognostic significance of molecular markers. At 2 years, LF and VCF rates were as expected at 25.4% and 8.8%, respectively. UVA identified lower risk of LF in those with an EGFR mutation and those with a PD-L1 status of ≥ 50%; however, only PD-L1 status of ≥ 50% retained significance on MVA. There was a trend towards lower LF risk when ICI was administered peri- and post-SBRT. Favorable LC rates in EGFR positive and PDL1 ≥ 50% as shown in Figs. 1 and 2 may have therapeutic implications. In particular, as the 2-year rates of LF in those EGFR negative versus positive were 30.0% vs 18.1%, respectively, and 38.0% vs 10.7% in those PD-L1 < 50% vs ≥ 50%, respectively. Zeng et al., report that 28 Gy vs. 24 Gy in 2 fractions spine SBRT results in better rates of LC without increasing the risk of VCF. Dose-escalation may be more appropriate for the EGFR negative and PD-L1 < 50% patients and our data serves to personalize treatment based on mutational status. On MVA, only PD-L1 ≥ 50% retained significance for LC. The question remains as to why the EGFR status lost significance on MVA. In this study, 17.6% of patients exhibited high PD-L1 status and 30.4% were EGFR positive. A significant statistical interaction between those EGFR positive and those PD-L1 positive was observed, with PD-L1 retaining significance as a contributing factor for LF. NSCLC patients with EGFR mutation treated with single anti PD-1 (programmed death 1) or PD-L1 ICI have not benefited from IO 25,26 . Additionally, PD-L1 expression is down regulated by EGFR TKI inhibitors in NSCLC cell lines with mutated EGFR 27 and it is hypothesized that weaker immunogenicity in EGFR mutated NSCLC (due to low mutational burden and lack of CD8 + tumor-infiltrating lymphocytes) results in a suboptimal response to ICI 28 . A complex relationship exists between EGFR and PD-L1 signaling pathways and much remains to be discovered regarding their interplay in the context of treatment response. We observed a trend towards a lower risk of LF when ICI was administered peri- and post-SBRT (HR 0.41, 95% CI 0.16–1.05, p = 0.062). It has been proposed that combining ICI with SBRT leads to enhanced immunogenic tumor cell eradication via activation of innate and adaptive immune system and up regulation of cytotoxic T-cells 29,30 . This synergistic interaction between the two treatment modalities 31 may be further enhanced in patients with high PD-L1 status, and potentially contributed to our observed trend of lower LF rates. Clinical data supports the therapeutic impact of ICI and SBRT in lung cancer. In early-stage NSCLC, Chang et al., demonstrated that the addition of Nivolumab to SBRT improved the 4-year event free survival from 53% with SBRT alone to 77% 32 . Altorki et al. showed that sub-ablative SBRT dose of 24 Gy in 3 fractions with durvalumab improves major pathologic response compared to durvalumab alone prior to surgery in early NSCLC 33 . In locally advanced unresectable NSCLC, the PACIFIC study concluded that the addition of ICI to conventionally fractionated chemoradiotherapy improves both progression free survival (PFS) and OS 34 . In advanced NSCLC, the PEMBRO-RT trial demonstrated that SBRT followed by pembrolizumab in any PD-L1 status doubled the objective response (36% vs 18%) and OS (15.9 vs 7.6 months) rates compared with pembrolizumab alone 35 . ICI sequencing alongside SBRT studies, report an impact on OS but not LF when ICI is administered post-SBRT 35–38 . Eckstein et al. report that sequencing of ICI with SBRT was not associated with LF or toxicity difference but delivering ICI after SBRT was associated with longer OS (31.8 months) vs. pre-SBRT (6.6 months) 36 . A pooled analysis metastatic NSCLC patients in the PEMBRO-RT and MDACC clinical trials 37 , showed no impact on LF but improved abscopal effect (65% vs 43%), PFS (9.0 months vs. 4.4 months) and OS (19.2 months vs. 8.7 months) when pembrolizumab was administered 1-week post SBRT vs pembrolizumab alone 37 . Lee et al. analyzed the timing of ICI with spinal SBRT in mixed histology patients; no significant impact of ICI timing with SBRT on OS (p = 0.6), LC (p = 0.3) or toxicity was found, however, numerically, OS improved in patients who received ICI concurrently (14.8 months) or post SBRT (27.2 months) compared to ICI alone (10 months) 38 . SBRT timing with ICI was explored in metastatic NSCLC in the SABRseq phase I trial (NCT03307759), the study was closed early due to poor accrual. In the 13 patients evaluated there was no significant toxicity found when SABR was delivered before or after pembrolizumab 39 . We speculate our result of a trend towards better LC when ICI was given concurrently with or close to the time of SBRT, may enhance the synergy between the two therapies. Why we did not observe any impact on OS with ICI, or with TKI in the mutant positive cohort, in the MVA reflects the heterogeneity of the population with respect timing of administrations, performance status, metastatic burden (including presence or absence of brain metastases), and prior lines of systemic therapy delivered. This study needs to be considered in the context of both its strengths and limitations. Despite its retrospective nature, this is the largest study evaluating spine SBRT specifically in metastatic NSCLC, and with a large proportion of patients analyzed for relevant biomarkers. Missing biomarker data was most notable for PD-L1 status in an earlier time period, as this was only routinely analyzed at our institution beginning in 2014. Finally, we did not collect comprehensive information regarding neurological status, pain assessment, and changes in quality-of-life following SBRT. In conclusion, we identified a significant association of PD-L1 ≥ 50% status on improved LC rates in NSCLC patients with spinal metastases treated with spine SBRT and submit that additional research is warranted to determine the most effective sequencing of spine SBRT and ICI in PD-L1 positive patients. DECLARATIONS Author Contribution Dana Shor: Conceptualization, Investigation, writing original draft, writing-review and editing, visualizationAlexander V. Louie: Conceptualization, methodology, validation, writing-review and editing, supervision K. Liang Zeng: Conceptualization, methodology, validation, writing-review and editing, supervisionInes Menjak: Conceptualization, methodology, validation, writing-review and editingEshetu G. Atenafu: Formal analysisChia-Lin Tseng: writing-review and editingJay Detsky: writing-review and editingJeremie Larouche: writing-review and editingBeibei Zhang: writing-review and editingHany Soliman: writing-review and editingSten Myrehaug: writing-review and editingPejman Jabehdar Maralani: writing-review and editingDavid M. Hwang: writing-review and editingArjun Sahgal: Conceptualization, methodology, validation, writing-review and editing, supervisionHanbo Chen: Conceptualization, methodology, validation, writing-review and editing, supervision REFERENCES Soria JC, Ohe Y, Vansteenkiste J, et al. Osimertinib in Untreated EGFR -Mutated Advanced Non–Small-Cell Lung Cancer. N Engl J Med . 2018;378(2):113-125. doi:10.1056/NEJMoa1713137 Shaw AT, Bauer TM, de Marinis F, et al. First-Line Lorlatinib or Crizotinib in Advanced ALK -Positive Lung Cancer. N Engl J Med . 2020;383(21):2018-2029. doi:10.1056/NEJMoa2027187 Mok TSK, Wu YL, Kudaba I, et al. 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J Clin Oncol . 2020;38(25):2830-2838. doi:10.1200/JCO.20.00818 Chen H, Louie AV, Higginson DS, Palma DA, Colaco R, Sahgal A. Stereotactic Radiosurgery and Stereotactic Body Radiotherapy in the Management of Oligometastatic Disease. Clin Oncol . 2020;32(11):713-727. doi:10.1016/j.clon.2020.06.018 Iyengar P, Wardak Z, Gerber DE, et al. Consolidative Radiotherapy for Limited Metastatic Non–Small-Cell Lung Cancer: A Phase 2 Randomized Clinical Trial. JAMA Oncol . 2018;4(1):e173501. doi:10.1001/jamaoncol.2017.3501 Poon I, Erler D, Dagan R, et al. Evaluation of Definitive Stereotactic Body Radiotherapy and Outcomes in Adults With Extracranial Oligometastasis. JAMA Netw Open . 2020;3(11):e2026312. doi:10.1001/jamanetworkopen.2020.26312 Maccauro G, Spinelli MS, Mauro S, Perisano C, Graci C, Rosa MA. Physiopathology of Spine Metastasis. Int J Surg Oncol . 2011;2011:1-8. doi:10.1155/2011/107969 Sahgal A, Myrehaug SD, Siva S, et al. CCTG SC.24/TROG 17.06: A Randomized Phase II/III Study Comparing 24Gy in 2 Stereotactic Body Radiotherapy (SBRT) Fractions Versus 20Gy in 5 Conventional Palliative Radiotherapy (CRT) Fractions for Patients with Painful Spinal Metastases. Int J Radiat Oncol . 2020;108(5):1397-1398. doi:10.1016/j.ijrobp.2020.09.019 Zeng KL, Myrehaug S, Soliman H, et al. Mature Local Control and Reirradiation Rates Comparing Spine Stereotactic Body Radiation Therapy With Conventional Palliative External Beam Radiation Therapy. Int J Radiat Oncol . 2022;114(2):293-300. doi:10.1016/j.ijrobp.2022.05.043 Hyde D, Lochray F, Korol R, et al. Spine Stereotactic Body Radiotherapy Utilizing Cone-Beam CT Image-Guidance With a Robotic Couch: Intrafraction Motion Analysis Accounting for all Six Degrees of Freedom. Int J Radiat Oncol . 2012;82(3):e555-e562. doi:10.1016/j.ijrobp.2011.06.1980 Sangha A, Korol R, Sahgal A. Stereotactic Body Radiotherapy for the Treatment of Spinal Metastases: An Overview of the University of Toronto, Sunnybrook Health Sciences Odette Cancer Centre, Technique. J Med Imaging Radiat Sci . 2013;44(3):126-133. doi:10.1016/j.jmir.2013.04.002 Cox BW, Spratt DE, Lovelock M, et al. International Spine Radiosurgery Consortium Consensus Guidelines for Target Volume Definition in Spinal Stereotactic Radiosurgery. Int J Radiat Oncol . 2012;83(5):e597-e605. doi:10.1016/j.ijrobp.2012.03.009 Burgess L, Zeng KL, Myrehaug S, et al. Stereotactic Body Radiation Therapy for Posterior Element-Only Spinal Metastases: A First Report on Outcomes and Validation of Recommended Clinical Target Volume Delineation Practice. Pract Radiat Oncol . Published online March 2023:S1879850023000632. doi:10.1016/j.prro.2023.03.009 Sahgal A, Weinberg V, Ma L, et al. Probabilities of Radiation Myelopathy Specific to Stereotactic Body Radiation Therapy to Guide Safe Practice. Int J Radiat Oncol . 2013;85(2):341-347. doi:10.1016/j.ijrobp.2012.05.007 Sahgal A, Chang JH, Ma L, et al. Spinal Cord Dose Tolerance to Stereotactic Body Radiation Therapy. Int J Radiat Oncol . 2021;110(1):124-136. doi:10.1016/j.ijrobp.2019.09.038 Thibault I, Chang EL, Sheehan J, et al. Response assessment after stereotactic body radiotherapy for spinal metastasis: a report from the SPIne response assessment in Neuro-Oncology (SPINO) group. Lancet Oncol . 2015;16(16):e595-e603. doi:10.1016/S1470-2045(15)00166-7 Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Published online November 27, 2017. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_5x7.pdf Huang Q, Zhang H, Hai J, et al. Impact of PD-L1 expression, driver mutations and clinical characteristics on survival after anti-PD-1/PD-L1 immunotherapy versus chemotherapy in non-small-cell lung cancer: A meta-analysis of randomized trials. OncoImmunology . 2018;7(12):e1396403. doi:10.1080/2162402X.2017.1396403 Lee CK, Man J, Lord S, et al. Checkpoint Inhibitors in Metastatic EGFR- Mutated Non–Small Cell Lung Cancer—A Meta-Analysis. J Thorac Oncol . 2017;12(2):403-407. doi:10.1016/j.jtho.2016.10.007 Azuma K, Ota K, Kawahara A, et al. Association of PD-L1 overexpression with activating EGFR mutations in surgically resected nonsmall-cell lung cancer. Ann Oncol . 2014;25(10):1935-1940. doi:10.1093/annonc/mdu242 Anagnostou V, Niknafs N, Marrone K, et al. Multimodal genomic features predict outcome of immune checkpoint blockade in non-small-cell lung cancer. Nat Cancer . 2020;1(1):99-111. doi:10.1038/s43018-019-0008-8 Luke JJ, Lemons JM, Karrison TG, et al. Safety and Clinical Activity of Pembrolizumab and Multisite Stereotactic Body Radiotherapy in Patients With Advanced Solid Tumors. J Clin Oncol . 2018;36(16):1611-1618. doi:10.1200/JCO.2017.76.2229 Luke JJ, Onderdonk BE, Bhave SR, et al. Improved Survival Associated with Local Tumor Response Following Multisite Radiotherapy and Pembrolizumab: Secondary Analysis of a Phase I Trial. Clin Cancer Res . 2020;26(24):6437-6444. doi:10.1158/1078-0432.CCR-20-1790 Turgeon G, Weickhardt A, Azad AA, Solomon B, Siva S. Radiotherapy and immunotherapy: a synergistic effect in cancer care. Med J Aust . 2019;210(1):47-53. doi:10.5694/mja2.12046 Chang JY, Lin SH, Dong W, et al. Stereotactic ablative radiotherapy with or without immunotherapy for early-stage or isolated lung parenchymal recurrent node-negative non-small-cell lung cancer: an open-label, randomised, phase 2 trial. The Lancet . Published online July 2023:S0140673623013843. doi:10.1016/S0140-6736(23)01384-3 Altorki NK, McGraw TE, Borczuk AC, et al. Neoadjuvant durvalumab with or without stereotactic body radiotherapy in patients with early-stage non-small-cell lung cancer: a single-centre, randomised phase 2 trial. Lancet Oncol . 2021;22(6):824-835. doi:10.1016/S1470-2045(21)00149-2 Spigel DR, Faivre-Finn C, Gray JE, et al. Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non–Small-Cell Lung Cancer. J Clin Oncol . 2022;40(12):1301-1311. doi:10.1200/JCO.21.01308 Theelen WSME, Peulen HMU, Lalezari F, et al. Effect of Pembrolizumab After Stereotactic Body Radiotherapy vs Pembrolizumab Alone on Tumor Response in Patients With Advanced Non–Small Cell Lung Cancer: Results of the PEMBRO-RT Phase 2 Randomized Clinical Trial. JAMA Oncol . 2019;5(9):1276. doi:10.1001/jamaoncol.2019.1478 Eckstein J, Gogineni E, Sidiqi B, Lisser N, Parashar B. Effect of Immunotherapy and Stereotactic Body Radiation Therapy Sequencing on Local Control and Survival in Patients With Spine Metastases. Adv Radiat Oncol . 2023;8(3):101179. doi:10.1016/j.adro.2023.101179 Theelen WSME, Chen D, Verma V, et al. Pembrolizumab with or without radiotherapy for metastatic non-small-cell lung cancer: a pooled analysis of two randomised trials. Lancet Respir Med . 2021;9(5):467-475. doi:10.1016/S2213-2600(20)30391-X Lee E, Chen X, LeCompte MC, et al. Safety and clinical efficacy of immune checkpoint inhibition and stereotactic body radiotherapy in patients with spine metastasis. J Neurosurg Spine . Published online May 1, 2023:1-9. doi:10.3171/2023.3.SPINE221086 Siva S, McMahon R, Bressel M, et al. SABRSeq: A Randomized Phase Ib Trial of SABR Sequencing with Pembrolizumab in Metastatic Non-Small Cell Lung Cancer (NSCLC). Int J Radiat Oncol . 2023;117(2):e58. doi:10.1016/j.ijrobp.2023.06.774 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 25 Mar, 2024 Read the published version in Journal of Neuro-Oncology → Version 1 posted Editorial decision: Revision requested 23 Jan, 2024 Reviews received at journal 18 Jan, 2024 Reviewers agreed at journal 11 Jan, 2024 Reviewers agreed at journal 10 Jan, 2024 Reviewers invited by journal 10 Jan, 2024 Editor assigned by journal 08 Jan, 2024 Submission checks completed at journal 08 Jan, 2024 First submitted to journal 06 Jan, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-3840775\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":265812250,\"identity\":\"e1243a58-dcd9-42f1-b57c-a648f49f4099\",\"order_by\":0,\"name\":\"Dana Shor\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Sunnybrook Health Science Centre\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Dana\",\"middleName\":\"\",\"lastName\":\"Shor\",\"suffix\":\"\"},{\"id\":265812252,\"identity\":\"4d182b19-facc-49d2-addb-6b3602896d43\",\"order_by\":1,\"name\":\"Alexander V. 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The third generation Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitor (TKI), Osimertinib, has significantly enhanced the overall survival (OS) for patients with an activating EGFR mutation, particularly those with exon 19 deletion and exon 21 (L858R) point mutation \\u003csup\\u003e6\\u003c/sup\\u003e. Immunotherapy using ICI either as monotherapy \\u003csup\\u003e7\\u003c/sup\\u003e or combined with chemotherapy \\u003csup\\u003e5,8\\u003c/sup\\u003e, depending on programmed death-ligand 1(PD-L1) status, is the now the standard of care. With increasing survival, there is growing demand to optimize local control (LC) to sites of visible metastases for patients with limited number of targetable sites (oligometastases) or those progressing despite systemic therapy. Phase II trials have demonstrated improved survival with directed stereotactic body radiotherapy (SBRT) in oligometastatic lung cancer \\u003csup\\u003e9\\u0026ndash;12\\u003c/sup\\u003e. As an early adopter of SBRT for oligometastases, we described outcomes in a large patient cohort with various histologies including 260 lung cancer patients, that compare favorably to prospective data with limited sample sizes \\u003csup\\u003e13\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eApproximately 30\\u0026ndash;55% of metastases from lung cancer occur within the spine \\u003csup\\u003e14\\u003c/sup\\u003e, which can cause debilitating pain and progress to neurologic impairment. The Canadian Cancer Trials Group Symptom Control Protocol 24 (CCTG SC24) randomized controlled trial, compared 24 Gy in 2 SBRT fractions to 20 Gy in 5 fractions palliative external beam radiotherapy (cEBRT) in patients presenting with painful spinal metastases. Higher rates of complete pain response were reported at 3 and 6 months post-SBRT \\u003csup\\u003e15\\u003c/sup\\u003e. An institutional CCTG SC24 sub-group analysis, with mature follow-up, reported reduced local failure (LF) rates and less frequent re-irradiation rates following SBRT as compared to cEBRT \\u003csup\\u003e16\\u003c/sup\\u003e. The trial included mixed histology and there is an urgent need to understand histology specific outcomes for spine SBRT, in particular the prognostic value of molecular markers and modern systemic therapies.\\u003c/p\\u003e \\u003cp\\u003eThe aim of the present study was to report our experience with spine SBRT in NSCLC patients with spinal metastases and determine the prognostic impact of targetable mutations and PD-L1 status.\\u003c/p\\u003e\"},{\"header\":\"MATERIALS AND METHODS\",\"content\":\"\\u003cp\\u003eWe retrospectively reviewed NSCLC patients with spine metastases treated with spine SBRT at our institution between 2009 and 2021. Post-operative cases were excluded. We categorized the NSCLC subtypes as adenocarcinoma, squamous cell carcinoma and adeno-squamous carcinoma, and excluded neuroendocrine lung cancers (small cell, large cell and carcinoid tumors). Oncogenic driver alterations were recorded, principally EGFR mutations and anaplastic lymphoma kinase (ALK) fusions. Beginning in 2021, other drivers such as human epidermal growth factor receptor (HER2) and mesenchymal epithelial transition factor receptor (MET) were recorded. PD-L1 status was stratified into \\u0026lt;\\u0026thinsp;1%, 1\\u0026ndash;49% and \\u0026ge;\\u0026thinsp;50% positivity. Mutational and PD-L1 status that were not available nor reported were designated as unknown.\\u003c/p\\u003e \\u003cp\\u003ePD-L1 immunohistochemistry (IHC) was performed using the Dako/Agilent 22C3 PharmDX CDx Assay (prior to 2019) or a validated laboratory developed test (LDT) using the 22C3 antibody (after 2019). EGFR mutations were tested via quantitative polymerase chain reaction using the Entrogen EGFR Mutation Analysis Kit EGFR-RT52 (2009\\u0026ndash;2021) or the Biocartis Idylla EGFR Mutation Test (2020-21), or by next generation sequencing (NGS) using the Oncomine Focus Assay (OFA) (from June 2021 onwards) (Thermo Fisher Scientific). ALK fusions were tested by IHC using an LDT with the ALK 5A4 antibody (2015\\u0026ndash;2019) and with ALK 1A4 antibody (July 2019\\u0026ndash;2021), using protocols optimized for the detection of ALK gene rearrangements. Other molecular markers (e.g. MET) was done by NGS using OFA (from June 2021).\\u003c/p\\u003e \\u003cp\\u003eMetastatic burden was classified as solitary spinal metastases, oligometastatic (2\\u0026ndash;5 metastases) or polymetastatic (\\u0026gt;\\u0026thinsp;5 metastases), when at least one treated metastasis was within the spine. Systemic therapies from metastatic diagnosis to last follow up were reviewed. The last systemic agent to be administered\\u0026thinsp;\\u0026gt;\\u0026thinsp;1 month prior to SBRT was categorized as \\u0026lsquo;pre-SBRT\\u0026rsquo;, agents delivered 1-month prior to or following SBRT were classified as \\u0026lsquo;peri-SBRT\\u0026rsquo;, and those\\u0026thinsp;\\u0026gt;\\u0026thinsp;1-month after SBRT as \\u0026lsquo;post-SBRT\\u0026rsquo;.\\u003c/p\\u003e \\u003cp\\u003ePatients followed institutional protocol with full spine MRI and clinical assessment every 2\\u0026ndash;3 months. Our SBRT treatment technique has been previously described \\u003csup\\u003e17,18\\u003c/sup\\u003e. Our target delineation approach adhere to International Spine Radiosurgery Consortium guidelines \\u003csup\\u003e19,20\\u003c/sup\\u003e, and Dunne et al. for the sacrum \\u003csup\\u003e19\\u003c/sup\\u003e. Treatment planning approach is based on isotoxic principles respecting spinal cord tolerance \\u003csup\\u003e21,22\\u003c/sup\\u003e. This study was approved by the local institutional research ethics board (IRB approval number SUN-5062).\\u003c/p\\u003e \\u003cp\\u003eThe primary outcome was LF, defined according to SPINO as a gross unequivocal increase in tumor volume or linear dimension, any new or progressive tumor within the epidural space and/or neurological deterioration attributable to pre-existing epidural disease with equivocal increased epidural disease on serial MRI (two or three consecutive MRI scans) \\u003csup\\u003e23\\u003c/sup\\u003e. Secondary outcomes included OS and adverse events, mainly new or progressive vertebral compression fracture (VCF). The adverse events were reported according to common terminology criteria for adverse events version 5 (CTCAEv5) \\u003csup\\u003e24\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eStatistical analysis\\u003c/h2\\u003e \\u003cp\\u003eDescriptive statistics summarized baseline clinical and tumor factors. LF and VCF were assessed per spinal segment, and OS on a per patient. Cumulative LF and VCF rates were calculated with competing risk analysis method, using death as a competing risk. OS was calculated using the Kaplan-Meier method. Univariate comparisons between cohorts employed the log-rank test for OS and Gray\\u0026rsquo;s test for LF and VCF. Multivariable Cox proportional hazards models assessed the joint impact of covariates of interest on the primary and secondary outcomes. Predictors for LF included: baseline epidural and paraspinal disease, adenocarcinoma versus other NSCLC histology, spine SBRT dose and fractionation, SINS classification, dosimetric factors, prior radiation to the same segment, smoking history, PD-L1 and EGFR status and systemic therapy use (TKI, IO and chemotherapy). Predictors for OS included: age, ECOG (Eastern Cooperative Oncology Group) performance status, metastatic burden (presence of liver, lung and brain metastases), adenocarcinoma versus other NSCLC histology, baseline epidural and paraspinal disease, spine SBRT dose and fractionation, SINS classification, dosimetric factors, prior radiation to the same segment, smoking history, PD-L1 and EGFR status and systemic therapy use. Potential predictors for VCF included: baseline VCF, baseline epidural and paraspinal disease, prior radiation to same segment, SINS classification, spine SBRT dose and fractionation, age, gender, and systemic therapy use. ALK, HER2, MET target mutations were not used due to limited patient numbers. P-values were 2-sided with a 0.05 threshold for statistical significance. Multivariable models used a univariable screening p-value threshold of 0.15 and backward selection to identify the most predictive factors. Statistical analysis used SAS version 9.4 (2002\\u0026ndash;2012 SAS Institute, Inc., Cary, NC).\\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"RESULTS\",\"content\":\"\\u003cdiv id=\\\"Sec5\\\" class=\\\"Section2\\\"\\u003e\\n\\u003ch2\\u003ePatient Demographics\\u003c/h2\\u003e\\n\\u003cp\\u003eA total of 389 metastatic spinal segments in 165 patients were treated with SBRT. Baseline characteristics are summarized in Tables\\u0026nbsp;\\u003cspan class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e and \\u003cspan class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e. Median patient follow-up was 13.0 months (range: 0.5\\u0026ndash;95.3), median spinal segment follow-up was 8.8 months (range: 0.03\\u0026ndash;73.5), and median time from diagnosis to SBRT was 11.2 months (range: 0.03\\u0026ndash;159.2). 52.1% were male and most were ECOG 0\\u0026ndash;1 (83.6%). 87.9% had an American Spinal Injury Association impairment scale (ASIA) of E, 76.4% were adenocarcinoma and 61.0% had a smoking history. 74 (44.8%) were polymetastatic, 63 (38.2%) oligometastatic and 28 (17.0%) had solitary treated spinal metastasis.\\u003c/p\\u003e\\n\\u003cdiv class=\\\"gridtable\\\"\\u003e\\n\\u003ctable id=\\\"Tab1\\\" border=\\\"1\\\"\\u003e\\u003ccaption\\u003e\\n\\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 1\\u003c/div\\u003e\\n\\u003cdiv class=\\\"CaptionContent\\\"\\u003e\\n\\u003cp\\u003eBaseline demographic factors\\u003c/p\\u003e\\n\\u003c/div\\u003e\\n\\u003c/caption\\u003e\\n\\u003cthead\\u003e\\n\\u003ctr\\u003e\\n\\u003cth align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cspan class=\\\"Underline\\\"\\u003ePatient factors\\u003c/span\\u003e\\u003c/p\\u003e\\n\\u003c/th\\u003e\\n\\u003cth align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eN\\u0026thinsp;=\\u0026thinsp;165\\u003c/p\\u003e\\n\\u003c/th\\u003e\\n\\u003c/tr\\u003e\\n\\u003c/thead\\u003e\\n\\u003ctbody\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eMedian age (years)\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e66.5 (IQR: 59.8\\u0026ndash;74.4)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eTime from diagnosis to treatment (months)\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eMedian (inter-quartile)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e11.2 (2.4\\u0026ndash;22.7)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eGender\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eFemale\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e79 (47.9%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eMale\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e86 (52.1%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eECOG\\u003c/strong\\u003e*\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e0\\u0026ndash;1\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e138 (83.6%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u0026ge;2\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e27 (16.4%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eASIA\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003e\\u0026gt;\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eE\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e145 (87.9%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eOther\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e20 (12.1%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eMetastatic burden\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eSolitary\\u003csup\\u003e\\u0026gt;\\u003c/sup\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e28 (17.0%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eOligometastatic\\u003csup\\u003e$\\u003c/sup\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e63 (38.2%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003ePolymetastatic\\u003csup\\u003e#\\u003c/sup\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e74 (44.8%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eVisceral metastases\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eLung and liver\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e15 (9.1%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eLiver\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e8 (4.8%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eLung\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e42 (25.5%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eNeither lung nor liver\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e100 (60.6%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eBrain metastases\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e46 (27.9%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eHistology\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eAdenocarcinoma\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e126 (76.4%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eOthers\\u003csup\\u003e%\\u003c/sup\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e39 (23.6%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003ePrevious smoking history\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e100 (61.0%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eDriver mutation status\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eNo driver mutation\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e105 (65.2%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eEGFR positive\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e49 (30.4%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eNon EGFR driver mutation\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e7 (4.3%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eMissing\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e4\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003ePD-L1\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003ePD-L1\\u0026thinsp;\\u0026ge;\\u0026thinsp;50%\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e29 (17.6%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003ePD-L1 1\\u0026ndash;49%\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e26 (15.8%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003ePD-L1\\u0026thinsp;\\u0026lt;\\u0026thinsp;1%\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e45 (27.3%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003ePD-L1 Unknown\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e65 (39.4%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eImmunotherapy use\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003ePre SBRT\\u003csup\\u003ex\\u003c/sup\\u003e ICI\\u003csup\\u003e$\\u003c/sup\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e4 (2.4%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003ePre and peri and post SBRT\\u003csup\\u003e!\\u003c/sup\\u003e ICI\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e12 (7.3%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003ePeri and post SBRT ICI\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e15 (9.1%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003ePost SBRT ICI\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e29 (17.6%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eNo ICI used\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e105 (63.6%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eTKI\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003e@\\u003c/strong\\u003e\\u003c/sup\\u003e \\u003cstrong\\u003euse\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003ePre SBRT TKI\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e40 (12.0%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003ePeri SBRT TKI\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e38 (23%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003ePost SBRT TKI\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e46 (28%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003c/tbody\\u003e\\n\\u003ctfoot\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd colspan=\\\"2\\\"\\u003e\\u003cstrong\\u003e*ECOG\\u003c/strong\\u003e: Eastern Co-operative Oncology Group, \\u003csup\\u003e\\u003cstrong\\u003e\\u0026gt;\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003eASIA\\u003c/strong\\u003e: American Spinal Injury Association, \\u003csup\\u003e\\u0026gt;\\u003c/sup\\u003eSolitary (1 metastasis);\\u003csup\\u003e\\u003cstrong\\u003e$\\u003c/strong\\u003e\\u003c/sup\\u003eOligometastatic (2\\u0026ndash;5 metastases); \\u003csup\\u003e\\u003cstrong\\u003e#\\u003c/strong\\u003e\\u003c/sup\\u003ePolymetastases (\\u0026gt;\\u0026thinsp;5 metastases), \\u003csup\\u003e\\u003cstrong\\u003e%\\u003c/strong\\u003e\\u003c/sup\\u003e Other histology (squamous cell carcinoma or adenosquamous) \\u003csup\\u003e\\u003cstrong\\u003e$\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003eICI\\u003c/strong\\u003e: immune check point inhibitors. \\u003csup\\u003e\\u003cstrong\\u003e@\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003eTKI\\u003c/strong\\u003e: tyrosine kinase inhibitor\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003c/tfoot\\u003e\\n\\u003c/table\\u003e\\n\\u003c/div\\u003e\\n\\u003cdiv class=\\\"gridtable\\\"\\u003e\\n\\u003cdiv class=\\\"colspec\\\" align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/div\\u003e\\n\\u003ctable id=\\\"Tab2\\\" border=\\\"1\\\"\\u003e\\u003ccaption\\u003e\\n\\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 2\\u003c/div\\u003e\\n\\u003cdiv class=\\\"CaptionContent\\\"\\u003e\\n\\u003cp\\u003eBaseline Tumor/Treatment factors\\u003c/p\\u003e\\n\\u003c/div\\u003e\\n\\u003c/caption\\u003e\\n\\u003cthead\\u003e\\n\\u003ctr\\u003e\\n\\u003cth align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cspan class=\\\"Underline\\\"\\u003eSegment factors\\u003c/span\\u003e\\u003c/p\\u003e\\n\\u003c/th\\u003e\\n\\u003cth align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cspan class=\\\"Underline\\\"\\u003e(N\\u0026thinsp;=\\u0026thinsp;389)\\u003c/span\\u003e\\u003c/p\\u003e\\n\\u003c/th\\u003e\\n\\u003c/tr\\u003e\\n\\u003c/thead\\u003e\\n\\u003ctbody\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eTreatment indication\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eDe novo\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e308 (79.2%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eRetreatment\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e81 (20.8%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eSpinal level treated\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eCervical\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e52 (13.4%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eThoracic\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e226 (58.1%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eLumbar\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e86 (22.1%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eSacrum\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e25 (6.4%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eDose and fractionation\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e24-28Gy/2fractions\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e239 (61.4%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e30Gy/4fractions\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e106 (27.2%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eOther\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e44 (11.3%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eParaspinal extension\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e108 (27.8%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eEpidural extension\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eLow grade (1a-c)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e89 (22.9%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eHigh grade (2\\u0026ndash;3)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e35 (9.0%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eNo Epidural Disease\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e265 (68.1%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eSINS classification\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eStable\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e189 (48.6%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003ePotentially unstable\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e180 (46.3%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eUnstable\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e20 (5.1%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eBaseline VCF\\u003c/strong\\u003e\\u003csup\\u003e!\\u003c/sup\\u003e \\u003cstrong\\u003epresent\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e65 (16.7%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eDriver Mutation Status\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eNo driver mutation\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e249 (64.0%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eEGFR Positive\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e118 (30.3%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eExon 19 deletion\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e50 (42.0%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eExon 21 point mutation\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e48 (41.0%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eExon 20 T790M\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e8 (7.0%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eUnknown mutation\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e12 (10%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eNon EGFR driver mutation\\u003csup\\u003e**\\u003c/sup\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e22 (5.7%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003ePD-L1\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003ePD-L1\\u0026thinsp;\\u0026ge;\\u0026thinsp;50%\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e66 (17.0%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003ePD-L1 1\\u0026ndash;49%\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e88 (22.6%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003ePD-L1\\u003csup\\u003e@\\u003c/sup\\u003e \\u0026lt;1%\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e98 (25.2%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003ePD-L1 Unknown\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e137 (35.2%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eDosimetric factors\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eMedian (range)\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eCord PRV/Thecal Sac\\u003csup\\u003e^\\u003c/sup\\u003e (EQD2\\u003csub\\u003e2\\u003c/sub\\u003e)\\u003csup\\u003e?\\u003c/sup\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e44.6 (13.3-127.50)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eV100 (%)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e80 (49.0\\u0026ndash;97.0)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003ePTV\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003e\\u0026amp;\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eVolume (cm3)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e116.2 (12.4\\u0026ndash;612.0)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eMean dose (EQD2\\u003csub\\u003e10\\u003c/sub\\u003e)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e48 (29.0\\u0026ndash;67.0)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCTV\\u003c/strong\\u003e\\u003csup\\u003e\\u003cstrong\\u003e@\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eVolume (cm3)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e74.8 (5.9\\u0026ndash;456.0)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eMean dose (EQD2\\u003csub\\u003e10\\u003c/sub\\u003e)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e49 (12.0\\u0026ndash;77.0)\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003c/tbody\\u003e\\n\\u003ctfoot\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd colspan=\\\"2\\\"\\u003e\\u003csup\\u003e\\u003cstrong\\u003e#\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003eSINS\\u003c/strong\\u003e: spine instability neoplastic score; \\u003csup\\u003e\\u003cstrong\\u003e!\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003eVCF\\u003c/strong\\u003e: vertebral compression fracture; \\u003csup\\u003e\\u003cstrong\\u003e?\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003eEQD2\\u003c/strong\\u003e: equivalent dose in 2Gy fractions, subscript represents \\u0026alpha;/\\u0026beta;; \\u003csup\\u003e\\u003cstrong\\u003e^\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003ePRV\\u003c/strong\\u003e: planning risk volume; \\u003csup\\u003e\\u003cstrong\\u003e\\u0026amp;\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003ePTV\\u003c/strong\\u003e: planning target volume; \\u003csup\\u003e\\u003cstrong\\u003e@\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003eCTV\\u003c/strong\\u003e: clinical target volume; \\u003csup\\u003e\\u003cstrong\\u003ex\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003eSBRT\\u003c/strong\\u003e: stereotactic body radiotherapy; \\u003csup\\u003e\\u003cstrong\\u003e$$\\u003c/strong\\u003e\\u003c/sup\\u003e\\u003cstrong\\u003eEGFR\\u003c/strong\\u003e: epidermal growth factor receptor; \\u003csup\\u003e\\u003cstrong\\u003e##\\u003c/strong\\u003e\\u003c/sup\\u003e \\u003cstrong\\u003ePD-L1\\u003c/strong\\u003e\\u0026thinsp;=\\u0026thinsp;programmed death ligand 1; **Non EGFR driver mutation: anaplastic lymphoma kinase mutation (ALK), human epidermal growth factor receptor 2 (HER 2) mutation or Mesenchymal epithelial transition proto-oncoge (MET) mutation.\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003c/tfoot\\u003e\\n\\u003c/table\\u003e\\n\\u003c/div\\u003e\\n\\u003cdiv id=\\\"Sec6\\\" class=\\\"Section3\\\"\\u003e\\n\\u003ch2\\u003eTumor and treatment Characteristics\\u003c/h2\\u003e\\n\\u003cp\\u003eThoracic spine was the most common metastatic site (58.1%), prescription dose was 24Gy or 28Gy in 2 fractions (61.4%), and 79.2% were de novo (not previously irradiated). 27.8% segments had paraspinal disease, 31.8% had epidural disease, 16.7% had an existing VCF and 48.6% of segments were Spine Instability Neoplastic Score (SINS) stable.\\u003c/p\\u003e\\n\\u003cp\\u003e30.3% of the treated segments were EGFR mutation positive, 5.7% had a non-EGFR mutation such as ALK, HER2 or MET, and 64.0% had no driver mutations (Table\\u0026nbsp;\\u003cspan class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e). Of the 118 EGFR positive segments, 42.0% had an EGFR exon 19 deletion, 41.0% had an exon 21 L858R point mutation, 7.0% had an exon 20 T790M mutation and 10.0% had an unknown mutation. Of the 389 treated segments, 47.8% were PD-L1\\u0026thinsp;\\u0026lt;\\u0026thinsp;50%, 17.0% PD-L1\\u0026thinsp;\\u0026ge;\\u0026thinsp;50% and 35.2% PD-L1 unknown. 22 of the 118 (18.6%) segments with EGFR mutation were also PD-L1\\u0026thinsp;\\u0026ge;\\u0026thinsp;50%.\\u003c/p\\u003e\\n\\u003cp\\u003eOf 165 patients, 4 (2.4%) received ICI pre SBRT, 27 (16.4%) peri-SBRT and 29 (17.6%) post SBRT. Of the 56 patients with a driver mutation (49 with EGFR and 7 with non-EGFR), all treated with a TKI at some point during their disease course with 40 (12.0%) receiving TKI pre SBRT, 38 (23.0%) peri-SBRT and 46 (28.0%) post SBRT (Table\\u0026nbsp;\\u003cspan class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e).\\u003c/p\\u003e\\n\\u003c/div\\u003e\\n\\u003c/div\\u003e\\n\\u003cdiv id=\\\"Sec7\\\" class=\\\"Section2\\\"\\u003e\\n\\u003ch2\\u003eLocal failure\\u003c/h2\\u003e\\n\\u003cp\\u003eThe median time to LF among those who failed locally was 7.1 months (range: 0.4\\u0026ndash;35.4), with cumulative LF rates at 6, 12 and 24 months of 11.4% (95% CI 8.5\\u0026ndash;14.8), 16.4% (95% CI 12.8\\u0026ndash;20.3) and 26.3% (95% CI 21.7\\u0026ndash;31.1), respectively. LF rates based on PD-L1 status at 6, 12, and 24 months were 15.2% (95% CI 10.4\\u0026ndash;20.7), 19.8% (95% CI 14.4\\u0026ndash;26.0) and 38.0% (95% 30.0\\u0026ndash;46.0%) in those PD-L1\\u0026thinsp;\\u0026lt;\\u0026thinsp;50%, respectively, vs 9.2% (95% CI 3.7\\u0026ndash;17.7), 10.7% (95% CI 4.7\\u0026ndash;19.7) and 10.7% (95% CI 4.7\\u0026ndash;19.7) in those PD-L1\\u0026thinsp;\\u0026ge;\\u0026thinsp;50% (p\\u0026thinsp;=\\u0026thinsp;0.001), respectively (Fig.\\u0026nbsp;\\u003cspan class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e). The LF rates based on EGFR status at 6, 12, and 24 months rate were 11.3% (95% CI 7.8\\u0026ndash;15.7), 16.6% (95% CI 12.2\\u0026ndash;21.6) and 30% (95% CI 23.9\\u0026ndash;36.4) in those EGFR negative, vs 7.6% (95% CI 3.7\\u0026ndash;13.4), 12.9% (95% CI 7.6\\u0026ndash;19.8) and 18.1% (95% CI 11.5\\u0026ndash;25.9) in those EGFR positive (p\\u0026thinsp;=\\u0026thinsp;0.032), respectively (Fig.\\u0026nbsp;\\u003cspan class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e).\\u003c/p\\u003e\\n\\u003cp\\u003eUnivariable analysis (UVA) identified EGFR positive status (HR 0.61, 95% CI 0.37\\u0026ndash;0.99, p\\u0026thinsp;=\\u0026thinsp;0.046), ICI administration (HR 0.48, 95% CI 0.2\\u0026ndash;0.9, p\\u0026thinsp;=\\u0026thinsp;0.021), TKI pre SBRT (HR 0.57, 95% CI 0.34\\u0026ndash;0.95, p\\u0026thinsp;=\\u0026thinsp;0.0314), PD-L1\\u0026thinsp;\\u0026gt;\\u0026thinsp;50% (HR 0.33, 95% CI 0.16\\u0026ndash;0.71, p\\u0026thinsp;=\\u0026thinsp;0.0048), and absence of paraspinal disease (HR 0.52, 95% CI 0.35\\u0026ndash;0.77, p\\u0026thinsp;=\\u0026thinsp;0.0013) predicted for lower LF.\\u003c/p\\u003e\\n\\u003cp\\u003eMultivariable analysis (MVA) showed PD-L1 status of \\u0026ge;\\u0026thinsp;50% (HR 0.32, 95% CI 0.15\\u0026ndash;0.69, p\\u0026thinsp;=\\u0026thinsp;0.004) and PD-L1 unknown (HR 0.54, 95% CI 0.34\\u0026ndash;0.84, p\\u0026thinsp;=\\u0026thinsp;0.007) as significant predictors for lower LF compared to PD-L1\\u0026thinsp;\\u0026lt;\\u0026thinsp;50% (Table\\u0026nbsp;\\u003cspan class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e). There was a trend towards a lower risk of LF when ICI was administered peri- and post-SBRT (HR 0.41, 95% CI 0.16\\u0026ndash;1.05, p\\u0026thinsp;=\\u0026thinsp;0.062) as compared to other time periods of ICI administration (no ICI use at any point, ICI pre-SBRT only and ICI post-SBRT only).\\u003c/p\\u003e\\n\\u003cdiv class=\\\"gridtable\\\"\\u003e\\n\\u003ctable id=\\\"Tab3\\\" border=\\\"1\\\"\\u003e\\u003ccaption\\u003e\\n\\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 3\\u003c/div\\u003e\\n\\u003cdiv class=\\\"CaptionContent\\\"\\u003e\\n\\u003cp\\u003eMultivariable analysis for local failure, overall survival and vertebral compression fracture\\u003c/p\\u003e\\n\\u003c/div\\u003e\\n\\u003c/caption\\u003e\\n\\u003cthead\\u003e\\n\\u003ctr\\u003e\\n\\u003cth colspan=\\\"2\\\" align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eParameter\\u003c/p\\u003e\\n\\u003c/th\\u003e\\n\\u003cth align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eP-value\\u003c/p\\u003e\\n\\u003c/th\\u003e\\n\\u003cth align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eHR\\u003c/p\\u003e\\n\\u003c/th\\u003e\\n\\u003cth align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e95% CI\\u003c/p\\u003e\\n\\u003c/th\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003cth colspan=\\\"5\\\" align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eLocal failure\\u003c/p\\u003e\\n\\u003c/th\\u003e\\n\\u003c/tr\\u003e\\n\\u003c/thead\\u003e\\n\\u003ctbody\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd rowspan=\\\"2\\\" align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003ePD-L1\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u0026ge;\\u0026thinsp;50%\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e0.004\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e0.32\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e0.15\\u0026ndash;0.69\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eUnknown\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e0.007\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e0.54\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e0.34\\u0026ndash;0.84\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003ePD-L1\\u0026thinsp;\\u0026lt;\\u0026thinsp;50%\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd colspan=\\\"3\\\" align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eReference\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd rowspan=\\\"2\\\" align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eICI use\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003ePeri and post SBRT ICI\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e0.062\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e0.41\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e0.16\\u0026ndash;1.05\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003ePre and Peri and Post SBRT ICI\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e0.429\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e0.69\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e0.28\\u0026ndash;1.73\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eNo ICI at any point, pre SBRT ICI only and post SBRT ICI only\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd colspan=\\\"3\\\" align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eReference\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd colspan=\\\"5\\\" align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eOverall survival\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eMetastatic burden\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003ePolymetastatic\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u0026lt;\\u0026thinsp;.0001\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e3.28\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e1.84\\u0026ndash;5.85\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eOligometastatic\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e0.466\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e1.24\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e0.69\\u0026ndash;2.22\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eSolitary metastasis\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd colspan=\\\"3\\\" align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eReference\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eECOG\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u0026ge;\\u0026thinsp;2\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e0.011\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e1.87\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e1.16\\u0026ndash;3.02\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e0\\u0026ndash;1\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd colspan=\\\"3\\\" align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eReference\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd colspan=\\\"5\\\" align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eVertebral compression fracture\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eBaseline VCF\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eNo\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u0026lt;\\u0026thinsp;.0001\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e0.20\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e0.10\\u0026ndash;0.39\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eYes\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd colspan=\\\"3\\\" align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eReference\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eBaseline paraspinal disease\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eNo\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e0.098\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e0.57\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003e0.29\\u0026ndash;1.11\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003ctr\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\n\\u003ctd align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eYes\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003ctd colspan=\\\"3\\\" align=\\\"left\\\"\\u003e\\n\\u003cp\\u003eReference\\u003c/p\\u003e\\n\\u003c/td\\u003e\\n\\u003c/tr\\u003e\\n\\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003c/div\\u003e\\n\\u003c/div\\u003e\\n\\u003cdiv id=\\\"Sec8\\\" class=\\\"Section2\\\"\\u003e\\n\\u003ch2\\u003eOverall survival\\u003c/h2\\u003e\\n\\u003cp\\u003eThe median OS was 18.4 months (95% CI 11.4\\u0026ndash;24.6), with a 12 and 24 month rate of 56.1% (95% CI 48.0-63.4) and 43.1% (95% CI 35-50.1), respectively. On UVA, ECOG 0 or 1 (HR 0.41, 95% CI 0.26\\u0026ndash;0.66, p\\u0026thinsp;=\\u0026thinsp;0.0002), presence of oligometastases (HR 0.34, 95% CI 0.23\\u0026ndash;0.53, p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.0001) and treatment to a solitary spinal metastasis (HR 0.29, 95% CI 0.16\\u0026ndash;0.51, p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.0001, Fig.\\u0026nbsp;\\u003cspan class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e) were associated with improved OS. Metastatic disease in the lung (HR 1.68, 95% CI 1.10\\u0026ndash;2.58, p\\u0026thinsp;=\\u0026thinsp;0.017), lung and liver both (HR 3.62, 95% CI 1.99\\u0026ndash;6.56, p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.0001) were prognostic for worse OS. No significant differences in OS were found based on molecular subtypes, specifically in those EGFR positive vs. EGFR negative patients (median of 19.4 months vs 14.3 months, p\\u0026thinsp;=\\u0026thinsp;0.586) and those PD-L1\\u0026thinsp;\\u0026lt;\\u0026thinsp;50% vs. PD-L1\\u0026thinsp;\\u0026ge;\\u0026thinsp;50% segments (19.4 months vs 19.9 months, p\\u0026thinsp;=\\u0026thinsp;0.534). On MVA, polymetastatic disease (HR 3.28, 95% CI 1.84\\u0026ndash;5.85, p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.0001) and ECOG\\u0026thinsp;\\u0026ge;\\u0026thinsp;2 (HR 1.87, 95% CI 1.16\\u0026ndash;3.02, p\\u0026thinsp;=\\u0026thinsp;0.011) significantly predicted for worse OS (Table\\u0026nbsp;\\u003cspan class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e).\\u003c/p\\u003e\\n\\u003c/div\\u003e\\n\\u003cdiv id=\\\"Sec9\\\" class=\\\"Section2\\\"\\u003e\\n\\u003ch2\\u003eToxicity\\u003c/h2\\u003e\\n\\u003cp\\u003eThe overall rate of new or progressive VCF was 10.03%; 22 segments (5.7%) developed a new VCF and 17 (4.4%) had progression of an existing VCF. The median time to new or progressive VCF was 5.2 months (range: 0.6\\u0026ndash;51.4). The cumulative incidence of new or progressive VCF at 12 and 24 months was 6.6% (95% CI 4.4\\u0026ndash;9.4%) and 8.8% (95% CI 6.1\\u0026ndash;12.0%), respectively. On UVA, baseline VCF (HR 5.14, 95% CI 2.63\\u0026ndash;10.06, p\\u0026thinsp;\\u0026lt;\\u0026thinsp;.0001), SINS VBC\\u0026thinsp;\\u0026lt;\\u0026thinsp;50% collapse (HR 5.11, 95% CI 2.38\\u0026ndash;10.95, p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.0001), SINS VBC\\u0026thinsp;\\u0026ge;\\u0026thinsp;50% collapse (HR 3.33, 95% CI 0.94\\u0026ndash;11.79, p\\u0026thinsp;=\\u0026thinsp;0.0619), SINS potentially unstable (HR 1.73, 95% CI 0.82\\u0026ndash;3.68, p\\u0026thinsp;=\\u0026thinsp;0.1522), SINS unstable (HR 6.11, 95% CI 2.26\\u0026ndash;16.52, p\\u0026thinsp;=\\u0026thinsp;0.0004), presence of epidural disease (HR 2.57, 95% CI 1.31\\u0026ndash;5.02, p\\u0026thinsp;=\\u0026thinsp;0.006) and combination of paraspinal and epidural disease (HR 2.2, 95% CI 1.02\\u0026ndash;4.84, p\\u0026thinsp;=\\u0026thinsp;0.0459) were associated with increased rate of VCF. On MVA, only absence of a baseline VCF retained significance (HR 0.20, 95% CI 0.10\\u0026ndash;0.39, p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.0001). Radiation-induced radiculopathy was reported in 1 cervical, 6 thoracic, 6 lumbar and 5 sacral segments [18/389 (4.6%)] segments. The median time to radiculopathy was 13.5 months (range: 3.3\\u0026ndash;35.1). 15/18 (83.3%) were grade 2 and 3/18 (16.7%) were grade 3 in severity. There were no radiation myelopathy events.\\u003c/p\\u003e\\n\\u003c/div\\u003e\"},{\"header\":\"DISCUSSION\",\"content\":\"\\u003cp\\u003eWe report robust outcomes specific to NSCLC spinal metastases treated with SBRT and the prognostic significance of molecular markers. At 2 years, LF and VCF rates were as expected at 25.4% and 8.8%, respectively. UVA identified lower risk of LF in those with an EGFR mutation and those with a PD-L1 status of \\u0026ge;\\u0026thinsp;50%; however, only PD-L1 status of \\u0026ge;\\u0026thinsp;50% retained significance on MVA. There was a trend towards lower LF risk when ICI was administered peri- and post-SBRT.\\u003c/p\\u003e \\u003cp\\u003eFavorable LC rates in EGFR positive and PDL1\\u0026thinsp;\\u0026ge;\\u0026thinsp;50% as shown in Figs.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e and \\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e may have therapeutic implications. In particular, as the 2-year rates of LF in those EGFR negative versus positive were 30.0% vs 18.1%, respectively, and 38.0% vs 10.7% in those PD-L1\\u0026thinsp;\\u0026lt;\\u0026thinsp;50% vs\\u0026thinsp;\\u0026ge;\\u0026thinsp;50%, respectively. Zeng et al., report that 28 Gy vs. 24 Gy in 2 fractions spine SBRT results in better rates of LC without increasing the risk of VCF. Dose-escalation may be more appropriate for the EGFR negative and PD-L1\\u0026thinsp;\\u0026lt;\\u0026thinsp;50% patients and our data serves to personalize treatment based on mutational status.\\u003c/p\\u003e \\u003cp\\u003eOn MVA, only PD-L1\\u0026thinsp;\\u0026ge;\\u0026thinsp;50% retained significance for LC. The question remains as to why the EGFR status lost significance on MVA. In this study, 17.6% of patients exhibited high PD-L1 status and 30.4% were EGFR positive. A significant statistical interaction between those EGFR positive and those PD-L1 positive was observed, with PD-L1 retaining significance as a contributing factor for LF. NSCLC patients with EGFR mutation treated with single anti PD-1 (programmed death 1) or PD-L1 ICI have not benefited from IO \\u003csup\\u003e25,26\\u003c/sup\\u003e. Additionally, PD-L1 expression is down regulated by EGFR TKI inhibitors in NSCLC cell lines with mutated EGFR \\u003csup\\u003e27\\u003c/sup\\u003e and it is hypothesized that weaker immunogenicity in EGFR mutated NSCLC (due to low mutational burden and lack of CD8\\u0026thinsp;+\\u0026thinsp;tumor-infiltrating lymphocytes) results in a suboptimal response to ICI \\u003csup\\u003e28\\u003c/sup\\u003e. A complex relationship exists between EGFR and PD-L1 signaling pathways and much remains to be discovered regarding their interplay in the context of treatment response.\\u003c/p\\u003e \\u003cp\\u003eWe observed a trend towards a lower risk of LF when ICI was administered peri- and post-SBRT (HR 0.41, 95% CI 0.16\\u0026ndash;1.05, p\\u0026thinsp;=\\u0026thinsp;0.062). It has been proposed that combining ICI with SBRT leads to enhanced immunogenic tumor cell eradication via activation of innate and adaptive immune system and up regulation of cytotoxic T-cells \\u003csup\\u003e29,30\\u003c/sup\\u003e. This synergistic interaction between the two treatment modalities \\u003csup\\u003e31\\u003c/sup\\u003e may be further enhanced in patients with high PD-L1 status, and potentially contributed to our observed trend of lower LF rates. Clinical data supports the therapeutic impact of ICI and SBRT in lung cancer. In early-stage NSCLC, Chang et al., demonstrated that the addition of Nivolumab to SBRT improved the 4-year event free survival from 53% with SBRT alone to 77% \\u003csup\\u003e32\\u003c/sup\\u003e. Altorki et al. showed that sub-ablative SBRT dose of 24 Gy in 3 fractions with durvalumab improves major pathologic response compared to durvalumab alone prior to surgery in early NSCLC \\u003csup\\u003e33\\u003c/sup\\u003e. In locally advanced unresectable NSCLC, the PACIFIC study concluded that the addition of ICI to conventionally fractionated chemoradiotherapy improves both progression free survival (PFS) and OS \\u003csup\\u003e34\\u003c/sup\\u003e. In advanced NSCLC, the PEMBRO-RT trial demonstrated that SBRT followed by pembrolizumab in any PD-L1 status doubled the objective response (36% vs 18%) and OS (15.9 vs 7.6 months) rates compared with pembrolizumab alone \\u003csup\\u003e35\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eICI sequencing alongside SBRT studies, report an impact on OS but not LF when ICI is administered post-SBRT \\u003csup\\u003e35\\u0026ndash;38\\u003c/sup\\u003e. Eckstein et al. report that sequencing of ICI with SBRT was not associated with LF or toxicity difference but delivering ICI after SBRT was associated with longer OS (31.8 months) vs. pre-SBRT (6.6 months) \\u003csup\\u003e36\\u003c/sup\\u003e. A pooled analysis metastatic NSCLC patients in the PEMBRO-RT and MDACC clinical trials \\u003csup\\u003e37\\u003c/sup\\u003e, showed no impact on LF but improved abscopal effect (65% vs 43%), PFS (9.0 months vs. 4.4 months) and OS (19.2 months vs. 8.7 months) when pembrolizumab was administered 1-week post SBRT vs pembrolizumab alone \\u003csup\\u003e37\\u003c/sup\\u003e. Lee et al. analyzed the timing of ICI with spinal SBRT in mixed histology patients; no significant impact of ICI timing with SBRT on OS (p\\u0026thinsp;=\\u0026thinsp;0.6), LC (p\\u0026thinsp;=\\u0026thinsp;0.3) or toxicity was found, however, numerically, OS improved in patients who received ICI concurrently (14.8 months) or post SBRT (27.2 months) compared to ICI alone (10 months) \\u003csup\\u003e38\\u003c/sup\\u003e. SBRT timing with ICI was explored in metastatic NSCLC in the SABRseq phase I trial (NCT03307759), the study was closed early due to poor accrual. In the 13 patients evaluated there was no significant toxicity found when SABR was delivered before or after pembrolizumab \\u003csup\\u003e39\\u003c/sup\\u003e. We speculate our result of a trend towards better LC when ICI was given concurrently with or close to the time of SBRT, may enhance the synergy between the two therapies. Why we did not observe any impact on OS with ICI, or with TKI in the mutant positive cohort, in the MVA reflects the heterogeneity of the population with respect timing of administrations, performance status, metastatic burden (including presence or absence of brain metastases), and prior lines of systemic therapy delivered.\\u003c/p\\u003e \\u003cp\\u003eThis study needs to be considered in the context of both its strengths and limitations. Despite its retrospective nature, this is the largest study evaluating spine SBRT specifically in metastatic NSCLC, and with a large proportion of patients analyzed for relevant biomarkers. Missing biomarker data was most notable for PD-L1 status in an earlier time period, as this was only routinely analyzed at our institution beginning in 2014. Finally, we did not collect comprehensive information regarding neurological status, pain assessment, and changes in quality-of-life following SBRT.\\u003c/p\\u003e \\u003cp\\u003eIn conclusion, we identified a significant association of PD-L1\\u0026thinsp;\\u0026ge;\\u0026thinsp;50% status on improved LC rates in NSCLC patients with spinal metastases treated with spine SBRT and submit that additional research is warranted to determine the most effective sequencing of spine SBRT and ICI in PD-L1 positive patients.\\u003c/p\\u003e\"},{\"header\":\"DECLARATIONS\",\"content\":\"\\u003ch2\\u003eAuthor Contribution\\u003c/h2\\u003e\\u003cp\\u003eDana Shor: Conceptualization, Investigation, writing original draft, writing-review and editing, visualizationAlexander V. Louie: Conceptualization, methodology, validation, writing-review and editing, supervision K. Liang Zeng: Conceptualization, methodology, validation, writing-review and editing, supervisionInes Menjak: Conceptualization, methodology, validation, writing-review and editingEshetu G. Atenafu: Formal analysisChia-Lin Tseng: writing-review and editingJay Detsky: writing-review and editingJeremie Larouche: writing-review and editingBeibei Zhang: writing-review and editingHany Soliman: writing-review and editingSten Myrehaug: writing-review and editingPejman Jabehdar Maralani: writing-review and editingDavid M. Hwang: writing-review and editingArjun Sahgal: Conceptualization, methodology, validation, writing-review and editing, supervisionHanbo Chen: Conceptualization, methodology, validation, writing-review and editing, supervision\\u003c/p\\u003e\"},{\"header\":\"REFERENCES\",\"content\":\"\\u003col\\u003e\\n\\u003cli\\u003eSoria JC, Ohe Y, Vansteenkiste J, et al. Osimertinib in Untreated \\u003cem\\u003eEGFR\\u003c/em\\u003e -Mutated Advanced Non\\u0026ndash;Small-Cell Lung Cancer. \\u003cem\\u003eN Engl J Med\\u003c/em\\u003e. 2018;378(2):113-125. doi:10.1056/NEJMoa1713137\\u003c/li\\u003e\\n\\u003cli\\u003eShaw AT, Bauer TM, de Marinis F, et al. First-Line Lorlatinib or Crizotinib in Advanced \\u003cem\\u003eALK\\u003c/em\\u003e -Positive Lung Cancer. \\u003cem\\u003eN Engl J Med\\u003c/em\\u003e. 2020;383(21):2018-2029. doi:10.1056/NEJMoa2027187\\u003c/li\\u003e\\n\\u003cli\\u003eMok TSK, Wu YL, Kudaba I, et al. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. \\u003cem\\u003eThe Lancet\\u003c/em\\u003e. 2019;393(10183):1819-1830. doi:10.1016/S0140-6736(18)32409-7\\u003c/li\\u003e\\n\\u003cli\\u003eGadgeel S, Rodr\\u0026iacute;guez-Abreu D, Speranza G, et al. Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non\\u0026ndash;Small-Cell Lung Cancer. \\u003cem\\u003eJ Clin Oncol\\u003c/em\\u003e. 2020;38(14):1505-1517. doi:10.1200/JCO.19.03136\\u003c/li\\u003e\\n\\u003cli\\u003ePaz-Ares L, Vicente D, Tafreshi A, et al. A Randomized, Placebo-Controlled Trial of Pembrolizumab Plus Chemotherapy in Patients With Metastatic Squamous NSCLC: Protocol-Specified Final Analysis of KEYNOTE-407. \\u003cem\\u003eJ Thorac Oncol\\u003c/em\\u003e. 2020;15(10):1657-1669. doi:10.1016/j.jtho.2020.06.015\\u003c/li\\u003e\\n\\u003cli\\u003eAlamgeer M, Ganju V, Watkins DN. Novel therapeutic targets in non-small cell lung cancer. \\u003cem\\u003eCurr Opin Pharmacol\\u003c/em\\u003e. 2013;13(3):394-401. doi:10.1016/j.coph.2013.03.010\\u003c/li\\u003e\\n\\u003cli\\u003eReck M, Rodr\\u0026iacute;guez-Abreu D, Robinson AG, et al. Pembrolizumab versus Chemotherapy for PD-L1\\u0026ndash;Positive Non\\u0026ndash;Small-Cell Lung Cancer. \\u003cem\\u003eN Engl J Med\\u003c/em\\u003e. 2016;375(19):1823-1833. doi:10.1056/NEJMoa1606774\\u003c/li\\u003e\\n\\u003cli\\u003eGandhi L, Rodr\\u0026iacute;guez-Abreu D, Gadgeel S, et al. Pembrolizumab plus Chemotherapy in Metastatic Non\\u0026ndash;Small-Cell Lung Cancer. \\u003cem\\u003eN Engl J Med\\u003c/em\\u003e. 2018;378(22):2078-2092. doi:10.1056/NEJMoa1801005\\u003c/li\\u003e\\n\\u003cli\\u003eGomez DR, Tang C, Zhang J, et al. Local Consolidative Therapy Vs. Maintenance Therapy or Observation for Patients With Oligometastatic Non\\u0026ndash;Small-Cell Lung Cancer: Long-Term Results of a Multi-Institutional, Phase II, Randomized Study. \\u003cem\\u003eJ Clin Oncol\\u003c/em\\u003e. 2019;37(18):1558-1565. doi:10.1200/JCO.19.00201\\u003c/li\\u003e\\n\\u003cli\\u003ePalma DA, Olson R, Harrow S, et al. 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Evaluation of Definitive Stereotactic Body Radiotherapy and Outcomes in Adults With Extracranial Oligometastasis. \\u003cem\\u003eJAMA Netw Open\\u003c/em\\u003e. 2020;3(11):e2026312. doi:10.1001/jamanetworkopen.2020.26312\\u003c/li\\u003e\\n\\u003cli\\u003eMaccauro G, Spinelli MS, Mauro S, Perisano C, Graci C, Rosa MA. Physiopathology of Spine Metastasis. \\u003cem\\u003eInt J Surg Oncol\\u003c/em\\u003e. 2011;2011:1-8. doi:10.1155/2011/107969\\u003c/li\\u003e\\n\\u003cli\\u003eSahgal A, Myrehaug SD, Siva S, et al. CCTG SC.24/TROG 17.06: A Randomized Phase II/III Study Comparing 24Gy in 2 Stereotactic Body Radiotherapy (SBRT) Fractions Versus 20Gy in 5 Conventional Palliative Radiotherapy (CRT) Fractions for Patients with Painful Spinal Metastases. \\u003cem\\u003eInt J Radiat Oncol\\u003c/em\\u003e. 2020;108(5):1397-1398. doi:10.1016/j.ijrobp.2020.09.019\\u003c/li\\u003e\\n\\u003cli\\u003eZeng KL, Myrehaug S, Soliman H, et al. Mature Local Control and Reirradiation Rates Comparing Spine Stereotactic Body Radiation Therapy With Conventional Palliative External Beam Radiation Therapy. \\u003cem\\u003eInt J Radiat Oncol\\u003c/em\\u003e. 2022;114(2):293-300. doi:10.1016/j.ijrobp.2022.05.043\\u003c/li\\u003e\\n\\u003cli\\u003eHyde D, Lochray F, Korol R, et al. Spine Stereotactic Body Radiotherapy Utilizing Cone-Beam CT Image-Guidance With a Robotic Couch: Intrafraction Motion Analysis Accounting for all Six Degrees of Freedom. \\u003cem\\u003eInt J Radiat Oncol\\u003c/em\\u003e. 2012;82(3):e555-e562. doi:10.1016/j.ijrobp.2011.06.1980\\u003c/li\\u003e\\n\\u003cli\\u003eSangha A, Korol R, Sahgal A. Stereotactic Body Radiotherapy for the Treatment of Spinal Metastases: An Overview of the University of Toronto, Sunnybrook Health Sciences Odette Cancer Centre, Technique. \\u003cem\\u003eJ Med Imaging Radiat Sci\\u003c/em\\u003e. 2013;44(3):126-133. doi:10.1016/j.jmir.2013.04.002\\u003c/li\\u003e\\n\\u003cli\\u003eCox BW, Spratt DE, Lovelock M, et al. International Spine Radiosurgery Consortium Consensus Guidelines for Target Volume Definition in Spinal Stereotactic Radiosurgery. \\u003cem\\u003eInt J Radiat Oncol\\u003c/em\\u003e. 2012;83(5):e597-e605. doi:10.1016/j.ijrobp.2012.03.009\\u003c/li\\u003e\\n\\u003cli\\u003eBurgess L, Zeng KL, Myrehaug S, et al. Stereotactic Body Radiation Therapy for Posterior Element-Only Spinal Metastases: A First Report on Outcomes and Validation of Recommended Clinical Target Volume Delineation Practice. \\u003cem\\u003ePract Radiat Oncol\\u003c/em\\u003e. Published online March 2023:S1879850023000632. doi:10.1016/j.prro.2023.03.009\\u003c/li\\u003e\\n\\u003cli\\u003eSahgal A, Weinberg V, Ma L, et al. Probabilities of Radiation Myelopathy Specific to Stereotactic Body Radiation Therapy to Guide Safe Practice. \\u003cem\\u003eInt J Radiat Oncol\\u003c/em\\u003e. 2013;85(2):341-347. doi:10.1016/j.ijrobp.2012.05.007\\u003c/li\\u003e\\n\\u003cli\\u003eSahgal A, Chang JH, Ma L, et al. Spinal Cord Dose Tolerance to Stereotactic Body Radiation Therapy. \\u003cem\\u003eInt J Radiat Oncol\\u003c/em\\u003e. 2021;110(1):124-136. doi:10.1016/j.ijrobp.2019.09.038\\u003c/li\\u003e\\n\\u003cli\\u003eThibault I, Chang EL, Sheehan J, et al. Response assessment after stereotactic body radiotherapy for spinal metastasis: a report from the SPIne response assessment in Neuro-Oncology (SPINO) group. \\u003cem\\u003eLancet Oncol\\u003c/em\\u003e. 2015;16(16):e595-e603. doi:10.1016/S1470-2045(15)00166-7\\u003c/li\\u003e\\n\\u003cli\\u003eCommon Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Published online November 27, 2017. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_5x7.pdf\\u003c/li\\u003e\\n\\u003cli\\u003eHuang Q, Zhang H, Hai J, et al. Impact of PD-L1 expression, driver mutations and clinical characteristics on survival after anti-PD-1/PD-L1 immunotherapy versus chemotherapy in non-small-cell lung cancer: A meta-analysis of randomized trials. \\u003cem\\u003eOncoImmunology\\u003c/em\\u003e. 2018;7(12):e1396403. doi:10.1080/2162402X.2017.1396403\\u003c/li\\u003e\\n\\u003cli\\u003eLee CK, Man J, Lord S, et al. Checkpoint Inhibitors in Metastatic EGFR- Mutated Non\\u0026ndash;Small Cell Lung Cancer\\u0026mdash;A Meta-Analysis. \\u003cem\\u003eJ Thorac Oncol\\u003c/em\\u003e. 2017;12(2):403-407. doi:10.1016/j.jtho.2016.10.007\\u003c/li\\u003e\\n\\u003cli\\u003eAzuma K, Ota K, Kawahara A, et al. Association of PD-L1 overexpression with activating EGFR mutations in surgically resected nonsmall-cell lung cancer. \\u003cem\\u003eAnn Oncol\\u003c/em\\u003e. 2014;25(10):1935-1940. doi:10.1093/annonc/mdu242\\u003c/li\\u003e\\n\\u003cli\\u003eAnagnostou V, Niknafs N, Marrone K, et al. Multimodal genomic features predict outcome of immune checkpoint blockade in non-small-cell lung cancer. \\u003cem\\u003eNat Cancer\\u003c/em\\u003e. 2020;1(1):99-111. doi:10.1038/s43018-019-0008-8\\u003c/li\\u003e\\n\\u003cli\\u003eLuke JJ, Lemons JM, Karrison TG, et al. Safety and Clinical Activity of Pembrolizumab and Multisite Stereotactic Body Radiotherapy in Patients With Advanced Solid Tumors. \\u003cem\\u003eJ Clin Oncol\\u003c/em\\u003e. 2018;36(16):1611-1618. doi:10.1200/JCO.2017.76.2229\\u003c/li\\u003e\\n\\u003cli\\u003eLuke JJ, Onderdonk BE, Bhave SR, et al. Improved Survival Associated with Local Tumor Response Following Multisite Radiotherapy and Pembrolizumab: Secondary Analysis of a Phase I Trial. \\u003cem\\u003eClin Cancer Res\\u003c/em\\u003e. 2020;26(24):6437-6444. doi:10.1158/1078-0432.CCR-20-1790\\u003c/li\\u003e\\n\\u003cli\\u003eTurgeon G, Weickhardt A, Azad AA, Solomon B, Siva S. Radiotherapy and immunotherapy: a synergistic effect in cancer care. \\u003cem\\u003eMed J Aust\\u003c/em\\u003e. 2019;210(1):47-53. doi:10.5694/mja2.12046\\u003c/li\\u003e\\n\\u003cli\\u003eChang JY, Lin SH, Dong W, et al. 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Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non\\u0026ndash;Small-Cell Lung Cancer. \\u003cem\\u003eJ Clin Oncol\\u003c/em\\u003e. 2022;40(12):1301-1311. doi:10.1200/JCO.21.01308\\u003c/li\\u003e\\n\\u003cli\\u003eTheelen WSME, Peulen HMU, Lalezari F, et al. Effect of Pembrolizumab After Stereotactic Body Radiotherapy vs Pembrolizumab Alone on Tumor Response in Patients With Advanced Non\\u0026ndash;Small Cell Lung Cancer: Results of the PEMBRO-RT Phase 2 Randomized Clinical Trial. \\u003cem\\u003eJAMA Oncol\\u003c/em\\u003e. 2019;5(9):1276. doi:10.1001/jamaoncol.2019.1478\\u003c/li\\u003e\\n\\u003cli\\u003eEckstein J, Gogineni E, Sidiqi B, Lisser N, Parashar B. Effect of Immunotherapy and Stereotactic Body Radiation Therapy Sequencing on Local Control and Survival in Patients With Spine Metastases. \\u003cem\\u003eAdv Radiat Oncol\\u003c/em\\u003e. 2023;8(3):101179. doi:10.1016/j.adro.2023.101179\\u003c/li\\u003e\\n\\u003cli\\u003eTheelen WSME, Chen D, Verma V, et al. Pembrolizumab with or without radiotherapy for metastatic non-small-cell lung cancer: a pooled analysis of two randomised trials. \\u003cem\\u003eLancet Respir Med\\u003c/em\\u003e. 2021;9(5):467-475. doi:10.1016/S2213-2600(20)30391-X\\u003c/li\\u003e\\n\\u003cli\\u003eLee E, Chen X, LeCompte MC, et al. Safety and clinical efficacy of immune checkpoint inhibition and stereotactic body radiotherapy in patients with spine metastasis. \\u003cem\\u003eJ Neurosurg Spine\\u003c/em\\u003e. Published online May 1, 2023:1-9. doi:10.3171/2023.3.SPINE221086\\u003c/li\\u003e\\n\\u003cli\\u003eSiva S, McMahon R, Bressel M, et al. SABRSeq: A Randomized Phase Ib Trial of SABR Sequencing with Pembrolizumab in Metastatic Non-Small Cell Lung Cancer (NSCLC). \\u003cem\\u003eInt J Radiat Oncol\\u003c/em\\u003e. 2023;117(2):e58. doi:10.1016/j.ijrobp.2023.06.774\\u003c/li\\u003e\\n\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":false,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":true,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"journal-of-neuro-oncology\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"neon\",\"sideBox\":\"Learn more about [Journal of Neuro-Oncology](https://www.springer.com/journal/11060)\",\"snPcode\":\"11060\",\"submissionUrl\":\"https://submission.nature.com/new-submission/11060/3\",\"title\":\"Journal of Neuro-Oncology\",\"twitterHandle\":\"\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"Springer Hybrid\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":false},\"keywords\":\"\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-3840775/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-3840775/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003ch2\\u003eBackground and purpose:\\u003c/h2\\u003e \\u003cp\\u003eWe report outcomes following spine stereotactic body radiotherapy (SBRT) in metastatic non-small cell lung cancer (NSCLC) and the significance of programmed death-ligand 1 (PD-L1) status, epidermal growth factor receptor (EGFR) mutation and timing of immune check point inhibitors (ICI) on local failure (LF).\\u003c/p\\u003e\\u003ch2\\u003eMaterials and methods:\\u003c/h2\\u003e \\u003cp\\u003e165 patients and 389 spinal segments were retrospectively reviewed from 2009 to 2021. Baseline patient characteristics, treatment and outcomes were abstracted. Primary endpoint was local failure (LF) and secondary, overall survival (OS) and vertebral compression fracture (VCF). Multivariable analysis (MVA) evaluated factors predictive of LF and VCF.\\u003c/p\\u003e\\u003ch2\\u003eResults:\\u003c/h2\\u003e \\u003cp\\u003eThe median follow-up and OS were: 13.0 months (range, 0.5\\u0026ndash;95.3 months) and 18.4 months (95% CI 11.4\\u0026ndash;24.6). 52.1% were male and 76.4% had adenocarcinoma. Of the 389 segments, 30.3% harboured an EGFR mutation and 17.0% were PD-L1\\u0026thinsp;\\u0026ge;\\u0026thinsp;50%. The 24 months LF rate in PD-L1\\u0026thinsp;\\u0026ge;\\u0026thinsp;50% vs PD-L1\\u0026thinsp;\\u0026lt;\\u0026thinsp;50% was 10.7% vs. 38.0%, and in EGFR-positive vs. negative was 18.1% vs. 30.0%. On MVA, PD-L1 status of \\u0026ge;\\u0026thinsp;50% (HR 0.32, 95% CI 0.15\\u0026ndash;0.69, p\\u0026thinsp;=\\u0026thinsp;0.004) significantly predicted for lower LF compared to PD-L1\\u0026thinsp;\\u0026lt;\\u0026thinsp;50%. Lower LF trend was seen with ICI administration peri and post SBRT (HR 0.41, 95% CI 0.16\\u0026ndash;1.05, p\\u0026thinsp;=\\u0026thinsp;0.062). On MVA, polymetastatic disease (HR 3.28, 95% CI 1.84\\u0026ndash;5.85, p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.0001) and ECOG\\u0026thinsp;\\u0026ge;\\u0026thinsp;2 (HR 1.87, 95% CI 1.16\\u0026ndash;3.02, p\\u0026thinsp;=\\u0026thinsp;0.011) significantly predicted for worse OS and absence of baseline VCF predicted for lower VCF rate (HR 0.20, 95% CI 0.10\\u0026ndash;0.39, p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.0001).\\u003c/p\\u003e\\u003ch2\\u003eConclusion:\\u003c/h2\\u003e \\u003cp\\u003eWe report a significant association of PD-L1\\u0026thinsp;\\u0026ge;\\u0026thinsp;50% status on improved LC rates from spine SBRT in NSCLC patients.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Utility of Molecular Markers in Predicting Local Control Specific to Lung Cancer Spine Metastases Treated with Stereotactic Body Radiotherapy\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2024-01-09 19:47:07\",\"doi\":\"10.21203/rs.3.rs-3840775/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0},{\"type\":\"decision\",\"content\":\"Revision requested\",\"date\":\"2024-01-23T11:36:42+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2024-01-18T20:03:14+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"599e779a-06d7-41b6-a4b5-578f722549af\",\"date\":\"2024-01-11T18:18:48+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"46b604e2-8390-480f-b85e-d5bb76378ba6\",\"date\":\"2024-01-10T13:11:00+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewersInvited\",\"content\":\"\",\"date\":\"2024-01-10T12:39:16+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorAssigned\",\"content\":\"\",\"date\":\"2024-01-08T05:44:57+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"checksComplete\",\"content\":\"\",\"date\":\"2024-01-08T05:44:57+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"submitted\",\"content\":\"Journal of Neuro-Oncology\",\"date\":\"2024-01-06T21:58:32+00:00\",\"index\":\"\",\"fulltext\":\"\"}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"journal-of-neuro-oncology\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"neon\",\"sideBox\":\"Learn more about [Journal of Neuro-Oncology](https://www.springer.com/journal/11060)\",\"snPcode\":\"11060\",\"submissionUrl\":\"https://submission.nature.com/new-submission/11060/3\",\"title\":\"Journal of Neuro-Oncology\",\"twitterHandle\":\"\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"Springer Hybrid\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":false}}],\"origin\":\"\",\"ownerIdentity\":\"aa2e74d8-da7f-4006-9b34-423d221507f8\",\"owner\":[],\"postedDate\":\"January 9th, 2024\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"published-in-journal\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2024-04-01T15:04:57+00:00\",\"versionOfRecord\":{\"articleIdentity\":\"rs-3840775\",\"link\":\"https://doi.org/10.1007/s11060-024-04603-8\",\"journal\":{\"identity\":\"journal-of-neuro-oncology\",\"isVorOnly\":false,\"title\":\"Journal of Neuro-Oncology\"},\"publishedOn\":\"2024-03-25 15:01:16\",\"publishedOnDateReadable\":\"March 25th, 2024\"},\"versionCreatedAt\":\"2024-01-09 19:47:07\",\"video\":\"\",\"vorDoi\":\"10.1007/s11060-024-04603-8\",\"vorDoiUrl\":\"https://doi.org/10.1007/s11060-024-04603-8\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-3840775\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-3840775\",\"identity\":\"rs-3840775\",\"version\":[\"v1\"]},\"buildId\":\"qtupq5eGEP_6zYnWcrvyt\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}