Search

Background: Patients with advanced non-small-cell lung cancer (NSCLC) with activating mutations in the epidermal growth factor receptor ( EGFR ) gene are a heterogeneous population who often develop brain metastases (BM). The optimal management of patients with asymptomatic brain metastases is unclear given the activity of newer-generation targeted therapies in the central nervous system. We present a protocol for an individual patient data (IPD) prospective meta-analysis to evaluate whether the addition of stereotactic radiosurgery (SRS) before osimertinib treatment will lead to better control of intracranial metastatic disease. This is a clinically relevant question that will inform practice., Methods: Randomised controlled trials will be eligible if they include participants with BM arising from EGFR- mutant NSCLC and suitable to receive osimertinib both in the first-line and second-line settings (P); comparisons of SRS followed by osimertinib versus osimertinib alone (I, C) and intracranial disease control included as an endpoint (O). Systematic searches of Medline (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL (EBSCO), PsychInfo, ClinicalTrials.gov and the WHO's International Clinical Trials Registry Platform's Search Portal will be undertaken. An IPD meta-analysis will be performed using methodologies recommended by the Cochrane Collaboration. The primary outcome is intracranial progression-free survival, as determined by response assessment in neuro-oncology-BM criteria. Secondary outcomes include overall survival, time to whole brain radiotherapy, quality of life, and adverse events of special interest. Effect differences will be explored among prespecified subgroups., Ethics and Dissemination: Approved by each trial's ethics committee. Results will be relevant to clinicians, researchers, policymakers and patients, and will be disseminated via publications, presentations and media releases., Prospero Registration: CRD42022330532., Competing Interests: Competing interests: SL: research funding and honoraria from AstraZeneca. YYS: honoraria from AstraZeneca and Janssen. AGS: research grants (institution) from Elekta AB, Varian, Seagen and BrainLAB; consulting fees from Varian, Elekta (Gamma Knife Icon), BrainLAB, Merck, Abbvie and Roche; honoraria from AstraZeneca, Elekta AB, Varian, BrainLAB, Accuray and Seagen. MBP: speaker fees from AZ, BMS, MSD and Roche. AN: research grants from Varian Medical Systems. RAS: advisory board with Amgen, Astra-Zeneca, Bayer, BMS, Boehringer Ingelheim, Janssen, Lily, Merck, Merck Serono, Novartis, Pfizer, Puma Biotechnology, Roche, Taiho, Takeda, Thermo Fisher and Yuhan Corporation; research grant from Astra-Zeneca and Boehringer Ingelheim. FHJ: clinical trial funding, received honoraria and participated in advisory boards for Astra Zeneca; received payments and honoraria from BeiGene and MSD for lectures and presentations; supported by the Peter Mac Foundation and the Victorian Cancer Agency. BJS: advisory board/honoraria from AstraZeneca, Pfizer, Novartis, Roche, Takeda, Merck, Bristol Mysers Squibb, Janssen, Amgen and Eli Lilly. IWKT: honorarium from Elekta and MSD. CH: advisory boards with Abbvie, Amgen, AstraZeneca, Bayer, BMS, Eisai, EMD Serono, Janssen, Jazz, Merck, Novartis, Pfizer, Roche, Sanofi and Takeda; research grants from AstraZeneca, EMD Serono and Roche. CKL: advisory board with Amgen, Astra Zeneca, GSK, Merck KGA, Norvatis, Pfizer, Roche, Takeda, Boehringer-Ingelheim and Yuhan; research funding (institution) from Astra Zeneca, Roche, Merck KGA and Amgen. KPR, AP, MD, DBS, AGS, JT, CNL, WYK, YH, YLEA, JL, CY, MCL and APT have no competing interests. CH, SL, FHJ, CKL, YYS, RAS and IWKT are study chairs on the included trials., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Stereotactic ablative radiotherapy (SABR) is used for treating lung tumors but can cause toxic effects, including life-threatening damage to central structures. Retrospective data suggested that small tumors up to 10 cm3 in volume can be well controlled with a biologically effective dose less than 100 Gy., Objective: To assess whether individualizing lung SABR dose and fractionation by tumor size, location, and histological characteristics may be associated with local tumor control., Design, Setting, and Participants: This nonrandomized controlled trial (the iSABR trial, so named for individualized SABR) was a phase 2 multicenter trial enrolling participants from November 15, 2011, to December 5, 2018, at academic medical centers in the US and Japan. Data were analyzed from December 9, 2020, to May 10, 2023. Patients were enrolled in 3 groups according to cancer type: initial diagnosis of non-small cell lung cancer (NSCLC) with an American Joint Committee on Cancer 7th edition T1-3N0M0 tumor (group 1), a T1-3N0M0 new primary NSCLC with a history of prior NSCLC or multiple NSCLCs (group 2), or lung metastases from NSCLC or another solid tumor (group 3)., Intervention: Up to 4 tumors were treated with once-daily SABR. The dose ranged from 25 Gy in 1 fraction for peripheral tumors with a volume of 0 to 10 cm3 to 60 Gy in 8 fractions for central tumors with a volume greater than 30 cm3., Main Outcome: Per-group freedom from local recurrence (same-lobe recurrence) at 1 year, with censoring at time of distant recurrence, death, or loss to follow-up., Results: In total, 217 unique patients (median [IQR] age, 72 [64-80] years; 129 [59%] male; 150 [69%] current or former smokers) were enrolled (some multiple times). There were 240 treatment courses: 79 in group 1, 82 in group 2, and 79 in group 3. A total of 285 tumors (211 [74%] peripheral and 74 [26%] central) were treated. The most common dose was 25 Gy in 1 fraction (158 tumors). The median (range) follow-up period was 33 (2-109) months, and the median overall survival was 59 (95% CI, 49-82) months. Freedom from local recurrence at 1 year was 97% (90% CI, 91%-99%) for group 1, 94% (90% CI, 87%-97%) for group 2, and 96% (90% CI, 89%-98%) for group 3. Freedom from local recurrence at 5 years ranged from 83% to 93% in the 3 groups. The proportion of patients with grade 3 to 5 toxic effects was low, at 5% (including a single patient [1%] with grade 5 toxic effects)., Conclusions and Relevance: The results of this nonrandomized controlled trial suggest that individualized SABR (iSABR) used to treat lung tumors may allow minimization of treatment dose and is associated with excellent local control. Individualized dosing should be considered for use in future trials., Trial Registration: ClinicalTrials.gov Identifier: NCT01463423.

Introduction: Patients with EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC) are at particularly high risk of developing brain metastases (BrM). In addition to EGFR targeting tyrosine kinase inhibitors (TKI), radiosurgery (SRS) has an important role in the management of EGFRm BrM. However, data specific to the response and toxicity of EGFRm BrM to SRS are sparse. We evaluated the incidence of local failure (LF) and toxicity of EGFRm and EGFR-wild-type (EGFRwt) BrM treated with SRS., Methods: We analyzed a prospective registry of BrM patients treated at our centre between 2008 and 2017 and identified EGFRm and EGFRwt NSCLC patients treated with SRS ± systemic therapy for BrM. Incidences of local failure (LF) and radionecrosis (RN) were determined, and Cox regression was performed for univariate and multivariate analyses (MVAs)., Results: We analyzed data from 218 patients (615 lesions - 225 EGFRm and 390 EGFRwt). Median imaging follow-up per patient was 14.5 months (0.5-96.3). Prior to or concomitant with SRS, 62 % of EGFRm patients received TKI and 93 % received TKI post SRS. The 24-month incidence of LF was 6% and 16 % for EGFRm BrM and EGFRwt, respectively (0.43(0.19-0.95); p = 0.037). The 24-month incidence of RN was 4% and 6% for EGFRm and EGFRwt BrM, respectively (0.8(0.32-1.98) p = 0.63). On MVA, BrM size and prescription dose (PD) significantly correlated with a higher risk of LF and BrM size correlated with a higher risk of RN., Conclusion: We observed excellent rates of response and toxicity following SRS in EGFRm compared to EGFRwt NSCLC, suggesting that EGFRm BrM have a favourable risk benefit ratio compared to EGFRwt NSCLC., (Copyright © 2021 Elsevier B.V. All rights reserved.)

We report a previously undescribed pattern of brain metastases in patients with e pidermal growth factor receptor -mutated non-small-cell lung cancer treated with tyrosine kinase inhibitors and radiation therapy. These highly distinct lesions appear to spread focally within the leptomeninges, with invasion along the perivascular spaces (FLIP). The survival of patients with FLIP was significantly better compared with patients with classic leptomeningeal disease (median survival, 21 versus 3 months; P  = .003). It is unclear whether this pattern of growth is unique to epidermal growth factor receptor -mutated non-small-cell lung cancer., (© 2020 by American Journal of Neuroradiology.)

Context: Death anxiety is common in patients with metastatic cancer, but its relationship to brain metastases and cognitive decline is unknown. Early identification of death anxiety and its determinants allows proactive interventions to be offered to those in need., Objectives: To identify psychological, physical, and disease-related (including brain metastases and cognitive impairment) factors associated with death anxiety in metastatic non-small cell lung cancer (mNSCLC) patients., Methods: A cross-sectional pilot study with mNSCLC outpatients completing standardized neuropsychological tests and validated questionnaires measuring death anxiety, cognitive concerns, illness intrusiveness, depression, demoralization, self-esteem, and common cancer symptoms. We constructed a composite for objective cognitive function (mean neuropsychological tests z-scores)., Results: Study measures were completed by 78 patients (50% females; median age 62 years [range 37-82]). Median time since mNSCLC diagnosis was 11 months (range 0-89); 53% had brain metastases. At least moderate death anxiety was reported by 43% (n = 33). Objective cognitive impairment was present in 41% (n = 32) and perceived cognitive impairment in 27% (n = 21). Death anxiety, objective, and perceived cognitive impairment did not significantly differ between patients with and without brain metastases. In univariate analysis, death anxiety was associated with demoralization, depression, self-esteem, illness intrusiveness, common physical cancer symptoms, and perceived cognitive impairment. In multivariate analysis, demoralization (P < 0.001) and illness intrusiveness (P = 0.001) were associated with death anxiety., Conclusion: Death anxiety and brain metastases are common in patients with mNSCLC but not necessarily linked. The association of death anxiety with both demoralization and illness intrusiveness highlights the importance of integrated psychological and symptom management. Further research is needed on the psychological impact of brain metastases., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

Objective:: Stereotactic ablative radiotherapy (SABR) is being increasingly used as a non-invasive treatment for early-stage non-small cell lung cancer (NSCLC). A non-invasive method to estimate treatment outcomes in these patients would be valuable, especially since access to tissue specimens is often difficult in these cases., Methods:: We developed a method to predict survival following SABR in NSCLC patients using analysis of quantitative image features on pre-treatment CT images. We developed a Cox Lasso model based on two-dimensional Riesz wavelet quantitative texture features on CT scans with the goal of separating patients based on survival., Results:: The median log-rank p-value for 1000 cross-validations was 0.030. Our model was able to separate patients based upon predicted survival. When we added tumor size into the model, the p-value lost its significance, demonstrating that tumor size is not a key feature in the model but rather decreases significance likely due to the relatively small number of events in the dataset. Furthermore, running the model using Riesz features extracted either from the solid component of the tumor or from the ground glass opacity (GGO) component of the tumor maintained statistical significance. However, the p-value improved when combining features from the solid and the GGO components, demonstrating that there are important data that can be extracted from the entire tumor., Conclusions:: The model predicting patient survival following SABR in NSCLC may be useful in future studies by enabling prediction of survival-based outcomes using radiomics features in CT images., Advances in Knowledge:: Quantitative image features from NSCLC nodules on CT images have been found to significantly separate patient populations based on overall survival (p = 0.04). In the long term, a non-invasive method to estimate treatment outcomes in patients undergoing SABR would be valuable, especially since access to tissue specimens is often difficult in these cases.

Background: Alternative treatment regimens are needed for patients with non-small cell lung cancer (NSCLC) who cannot receive definitive treatment with concurrent chemoradiotherapy, surgery, or stereotactic ablative radiotherapy (SABR)., Patients and Methods: We report survival, patterns of failure and toxicity outcomes for patients with NSCLC who were not eligible for surgical resection, concurrent chemoradiotherapy, or SABR and underwent hypofractionated intensity-modulated radiotherapy (IMRT). Kaplan-Meier survival analysis was used to evaluate the progression-free and overall survival. Competing risk analysis was used to evaluate in-field, locoregional, and distant failure., Results: A total of 42 patients treated to 52.5 to 60 Gy in 15 fractions were included. Most of the patients had metastatic or recurrent disease (64%) and a relatively large, centrally located tumor burden (74%). The median follow-up period was 13 months (interquartile range, 6-18 months). All patients received the total prescribed dose. The median survival was 15.1 months. The overall and progression-free survival rates at 1 year were 63% and 22.5%, respectively. The pattern of failure was predominantly distant, with only 2% of patients experiencing isolated in-field recurrence. The cumulative incidence of in-field failure at 6 and 12 months was 2.5% (95% confidence interval, 0.4%-15.6%) and 16.1% (95% confidence interval, 7.5%-34.7%), respectively. The risk of esophageal toxicity was associated with the esophageal mean dose, maximal point dose, and dose to the 5 cm 3 volume. The risk of pneumonitis was associated with the lung mean dose and volume receiving 18 Gy., Conclusion: Hypofractionated IMRT without concurrent chemotherapy provides favorable rates of local control and survival for well-selected patients with NSCLC who cannot tolerate standard definitive therapy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: We determined cumulative dose to critical structures, rates of toxicity, and outcomes following thoracic reirradiation., Methods and Materials: We retrospectively reviewed our institutional database for patients treated between 2008 and 2014, who received thoracic reirradiation with overlap of 25% prescribed isodose lines. Patients received courses of hyperfractionated (n=5), hypofractionated (n=5), conventionally fractionated (n=21), or stereotactic ablative radiation therapy (n=51). Doses to critical structures were converted to biologically effective dose, expressed as 2 Gy per fraction equivalent dose (EQD2; α/β = 2 for spinal cord; α/β = 3 for other critical structures)., Results: We identified 82 courses (44 for retreatment) in 38 patients reirradiated at a median 16 months (range: 1-71 months) following initial RT. Median follow-up was 17 months (range: 3-57 months). Twelve- and 24-month overall survival rates were 79.6% and 57.3%, respectively. Eighteen patients received reirradiation for locoregionally recurrent non-small cell lung cancer with 12-month rates of local failure and regional recurrence and distant metastases rates of 13.5%, 8.1%, and 15.6%, respectively. Critical structures receiving ≥75 Gy EQD2 included spinal cord (1 cm(3); n=1), esophagus (1 cm(3); n=10), trachea (1 cm(3); n=11), heart (1 cm(3); n=9), aorta (1 cm(3); n=16), superior vena cava (1 cm(3); n=12), brachial plexus (0.2 cm(3); n=2), vagus nerve (0.2 cm(3); n=7), sympathetic trunk (0.2 cm(3); n=4), chest wall (30 cm(3); n=12), and proximal bronchial tree (1 cm(3); n=17). Cumulative dose-volume (D cm(3)) toxicity following reirradiation data included esophagitis grade ≥2 (n=3, D1 cm(3) range: 41.0-100.6 Gy), chest wall grade ≥2 (n=4; D30 cm(3) range: 35.0-117.2 Gy), lung grade 2 (n=7; V20combined-lung range: 4.7%-21.7%), vocal cord paralysis (n=2; vagus nerve D0.2 cm(3) range: 207.5-302.2 Gy), brachial plexopathy (n=1; D0.2 cm(3) = 242.5 Gy), and Horner's syndrome (n=1; sympathetic trunk D0.2 cm(3) = 130.8 Gy). No grade ≥4 toxicity was observed., Conclusions: Overlapping courses of reirradiation can be safely delivered with acceptable toxicity. Some toxicities occurred acutely at doses considered safe for a single course of therapy (esophagus). We observed rib fracture, brachial plexopathy, and Horner's syndrome for patients receiving high cumulative doses to corresponding critical structures., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to demonstrate that anatomic optimization through selection of the degree of breath hold that yields the largest separation between the target and nearby organ at risk could result in dosimetrically superior treatment plans., Methods and Materials: Thirty patients with 41 plans were included in this planned secondary analysis of a prospective trial. Fifteen plans were created for treatment with use of natural end exhale (NEE), and 26 plans used deep inspiration breath hold (DIBH). To evaluate whether the original plan was dosimetrically optimal, we replanned treatment using the opposite respiratory state with the same beam configuration as the original plan. A treatment plan was deemed superior if it met protocol constraints when the other did not. If both plans met or violated the constraints, the plans were deemed equivalent., Results: Of the 26 plans originally planned with DIBH and replanned with NEE, 3 plans were dosimetrically superior with NEE, 1 plan was dosimetrically superior with DIBH, and 22 plans were dosimetrically equivalent. Of the 15 plans originally planned with NEE, 4 plans were dosimetrically superior with NEE, 2 plans were dosimetrically superior with DIBH, and 9 plans were dosimetrically equivalent., Conclusions: For 10 of 41 plans, planning with 1 respiratory state was superior. To obtain uniformly optimal plans, individual anatomic optimization would be needed., (Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: Accurate survival stratification in early-stage non-small cell lung cancer (NSCLC) could inform the use of adjuvant therapy. We developed a clinically implementable mortality risk score incorporating distinct tumor microenvironmental gene expression signatures and clinical variables., Methods: Gene expression profiles from 1106 nonsquamous NSCLCs were used for generation and internal validation of a nine-gene molecular prognostic index (MPI). A quantitative polymerase chain reaction (qPCR) assay was developed and validated on an independent cohort of formalin-fixed paraffin-embedded (FFPE) tissues (n = 98). A prognostic score using clinical variables was generated using Surveillance, Epidemiology, and End Results data and combined with the MPI. All statistical tests for survival were two-sided., Results: The MPI stratified stage I patients into prognostic categories in three microarray and one FFPE qPCR validation cohorts (HR = 2.99, 95% CI = 1.55 to 5.76, P < .001 in stage IA patients of the largest microarray validation cohort; HR = 3.95, 95% CI = 1.24 to 12.64, P = .01 in stage IA of the qPCR cohort). Prognostic genes were expressed in distinct tumor cell subpopulations, and genes implicated in proliferation and stem cells portended poor outcomes, while genes involved in normal lung differentiation and immune infiltration were associated with superior survival. Integrating the MPI with clinical variables conferred greatest prognostic power (HR = 3.43, 95% CI = 2.18 to 5.39, P < .001 in stage I patients of the largest microarray cohort; HR = 3.99, 95% CI = 1.67 to 9.56, P < .001 in stage I patients of the qPCR cohort). Finally, the MPI was prognostic irrespective of somatic alterations in EGFR, KRAS, TP53, and ALK., Conclusion: The MPI incorporates genes expressed in the tumor and its microenvironment and can be implemented clinically using qPCR assays on FFPE tissues. A composite model integrating the MPI with clinical variables provides the most accurate risk stratification., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Stereotactic ablative radiotherapy (SABR) is a highly effective treatment for early-stage non-small cell lung cancer. Although direct comparisons from randomized trials are not available, rates of both primary tumor control and distant metastasis are similar between SABR and surgery. Overall survival is lower after SABR compared with surgery, largely reflecting that a primary selection criterion for SABR has been medical inoperability because of decreased cardiopulmonary function and other comorbidities that lead to decreased survival independent of non-small cell lung cancer. Survival outcomes between SABR and surgery are much more similar in propensity-matched cohorts. Newer potential indications for SABR include treatment of operable patients; of oligometastatic lung cancer, in which SABR has emerged as an alternative to metastasectomy; and of oligoprogressive lung cancer, an attractive concept especially as improved personalized systemic therapies emerge, and prospective trials are currently being conducted in these settings. Although toxicity in modern series is low, SABR is clearly capable of producing fatal complications, and understanding the risk factors and approaches for mitigating them has been emerging in recent years. Thus, appropriate patient selection is a vital, evolving, and controversial topic., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: Radiotherapy can result in lymphopenia, which has been linked to poorer survival. Here, we test the hypothesis that radiotherapy-induced lymphopenia is mediated by a tumor-secreted factor, Galectin-1 (Gal-1), which possesses T-cell proapoptotic activities., Experimental Design: Matched Gal-1 wild-type (WT) or null mice were implanted with Lewis lung carcinoma (LLC-1) that either expressed Gal-1 or had Gal-1 stably downregulated. Tumors were irradiated locally and circulating Gal-1 and T cells were measured. Tumor growth, lung metastasis, intratumoral T-cell apoptosis, and microvessel density count were quantified. Thiodigalactoside (TDG), a Gal-1 inhibitor, was used to inhibit Gal-1 function in another group of mice to validate the observations noted with Gal-1 downregulation. Lymphocyte counts, survival, and plasma Gal-1 were analyzed in cohorts of radiotherapy-treated lung [non-small cell lung cancer (NSCLC)] and head and neck cancer patients., Results: LLC irradiation increased Gal-1 secretion and decreased circulating T cells in mice, regardless of host Gal-1 expression. Inhibition of tumor Gal-1 with either shRNA or thiodigalactoside ablated radiotherapy-induced lymphopenia. Irradiated shGal-1 tumors showed significantly less intratumoral CD8(+) T-cell apoptosis and microvessel density, which led to marked tumor growth delay and reduced lung metastasis compared with controls. Similar observations were made after thiodigalactoside treatment. Radiotherapy-induced lymphopenia was associated with poorer overall survival in patients with NSCLC treated with hypofractionated radiotherapy. Plasma Gal-1 increased whereas T-cell decreased after radiation in another group of patients., Conclusions: Radiotherapy-related systemic lymphopenia appeared to be mediated by radiotherapy-induced tumor Gal-1 secretion that could lead to tumor progression through intratumoral immune suppression and enhanced angiogenesis., (©2014 American Association for Cancer Research.)

Purpose: To identify clinical and dosimetric factors associated with vagus nerve (VN) and recurrent laryngeal nerve (RecLN) injury following stereotactic ablative radiation therapy (SABR) in the chest., Methods and Materials: We examined the clinical courses and SABR plans of 67 patients treated for T1 or T2 non-small cell lung cancer of the upper right or left lung, including 2 who developed vocal cord paresis (VCP) following treatment. After developing a contouring atlas for the VN and RecLN in the thorax, dose to those structures was retrospectively determined for each patient, and we identified 12 patients whose treatment imparted significant dose to either nerve and who were assessable for more than 12 months follow-up. Biologically effective doses using linear-quadratic (LQ) and linear quadratic-linear (LQ-L) modeling were correlated with VN and RecLN toxicity., Results: Of 12 patients, 2 developed VCP. The first underwent repeat SABR and received a cumulative single fraction equivalent dose (alpha/beta = 3; SFED3) of 37.4 or 64.5 Gy to the VN and 13.7 or 15.3 Gy to the RecLN (by LQ or LQ-L modeling, respectively). This was the highest VN dose and fifth highest RecLN dose in the cohort. The second had rheumatoid arthritis and connective tissue disease and received a SFED3 of 16 Gy to the VN and 19.5 Gy to the RecLN (by both LQ and LQ-L modeling). This was in the upper tertile of VN and RecLN doses for the cohort., Conclusions: Following SABR for non-small cell lung cancer, VCP was associated with high cumulative dose to the VN in 1 patient and a moderately high dose to the VN and RecLN in another patient with rheumatoid arthritis and connective tissue disease. Particularly in the setting of reirradiation or connective tissue disease, potential toxicity to the VN or RecLN should be considered., (© 2014. Published by Elsevier Inc. All rights reserved.)

Introduction/background: The aim of this study was to identify imaging-based predictors of progression in patients treated with SABR for stage I NSCLC., Patients and Methods: Between March 2003 and December 2012, 117 patients with stage I NSCLC meeting our study criteria were treated with SABR at Stanford University. Median follow-up was 17 months (range, 3-74 months) for all patients and 19 months for living patients (range, 3-74 months). Tumors were classified according to whether or not they contacted the pleura adjacent to the chest wall or mediastinum (MP), according to their maximum dimension based on computed tomography scans, and, for 102 patients who had archived pretreatment fluorine-18 fluorodeoxyglucose positron-emission tomography scans, according to SUVmax., Results: Ten patients (9%) developed local progression, 17 (15%) developed regional progression, and 19 (16%) developed distant metastasis. Two-year freedom from local progression, freedom from regional progression, and freedom from distant metastasis (FFDM) were 88%, 83%, and 83%, respectively. Overall survival was 70% at 2 years. FFDM was significantly associated with MP contact, maximum tumor dimension, and SUVmax, and these variables could be combined into an exploratory prognostic index that identified patients at highest risk for developing metastases., Conclusion: In our cohort, noninvasive, imaging-based features were associated with distant progression after SABR for early stage NSCLC. If validated, our prognostic index could allow identification of patients who might benefit from systemic therapy after SABR., (Published by Elsevier Inc.)