Reactive oxide species and ultrasound dual-responsive bilayer microneedle array for in-situ sequential therapy of acute myocardial infarction.

Acute myocardial infarction (AMI) resulting from coronary artery occlusion stands as the predominant cause of cardiovascular disability and mortality worldwide. An all-encompassing treatment strategy targeting pathological processes of oxidative stress, inflammation, proliferation and fibrotic remodeling post-AMI is anticipated to enhance therapeutic outcomes. Herein, an up-down-structured bilayer microneedle (Ce-CLMs-BMN) with reactive oxygen species (ROS) and ultrasound (US) dual-responsiveness is proposed for AMI in-situ sequential therapy. The upper-layer microneedle is formulated by crosslinking ROS-sensitive linker with polyvinyl alcohol loaded with cerium dioxide nanoparticles (CeNPs) featuring versatile enzyme-mimetic activities. During AMI acute phase, prompted by ischemia-induced microenvironmental redox imbalance, this layer swiftly releases CeNPs, which aid in eliminating excessive ROS and catalyzing oxygen gas (O2) production through multiple enzymatic pathways, thereby alleviating oxidative stress-induced damage and modulating inflammation. In AMI chronic repair phase, micro-nano reactors (CLMs) situated in the lower-layer microneedle undergo cascade reactions with the assistance of US irradiation to generate nitric oxide (NO). As a bioactive molecule with pro-angiogenic and anti-fibrotic effects, NO expedites cardiac repair while attenuating adverse remodeling. Additionally, its antiplatelet-aggregating properties contribute to thromboprophylaxis. In-vitro and in-vivo results substantiate the efficacy of this integrated healing approach in AMI management, showcasing promising prospects for advancing infarcted heart repair.

Curcumin Equipped Nanozyme-Like Metal-Organic Framework Platform for the Targeted Atherosclerosis Treatment with Lipid Regulation and Enhanced Magnetic Resonance Imaging Capability.

Atherosclerotic cardiovascular disease (ASCVD) has become the leading cause of death worldwide, and early diagnosis and treatment of atherosclerosis (AS) are crucial for reducing the occurrence of acute cardiovascular events. However, early diagnosis of AS is challenging, and oral anti-AS drugs suffer from limitations like imprecise targeting and low bioavailability. To overcome the aforementioned shortcomings, Cur/MOF@DS is developed, a nanoplatform integrating diagnosis and treatment by loading curcumin (Cur) into metal-organic frameworks with nanozymes and magnetic resonance imaging (MRI) properties. In addition, the surface-modification of dextran sulfate (DS) enables PCN-222(Mn) effectively target scavenger receptor class A in macrophages or foam cells within the plaque region. This nanoplatform employs mechanisms that effectively scavenge excessive reactive oxygen species in the plaque microenvironment, promote macrophage autophagy and regulate macrophage polarization to realize lipid regulation. In vivo and in vitro experiments confirm that this nanoplatform has outstanding MRI performance and anti-AS effects, which may provide a new option for early diagnosis and treatment of AS.

Digenic Inheritance of PROC and SERPINC1 Mutations Contributes to Multiple Sites Venous Thrombosis.

Venous thromboembolism (VTE) represents a worldwide health challenge, impacting millions of people each year. The genesis of venous thrombosis is influenced in part by genetic components. Hereditary thrombosis is described as a genetically determined susceptibility to VTE. In the present study, a male patient was referred to our department presenting with multiple venous thrombosis events in different locations. Given a lack of identifiable risk factors, we aimed to investigate the possible genetic factor underlying venous thrombosis. Whole-exome sequencing was employed to examine genes linked to inherited thrombophilia in the proband. Putative variants were subsequently confirmed through Sanger sequencing within the family. The proband was identified as carrying two genetic mutations. One is the novel c.400G > C (p.E134Q) mutation affecting the final nucleotide of exon 5 in the PROC gene, potentially impacting splicing. The other is a previously reported heterozygous nonsense variant c.1016G > A (p.W339X) in the SERPINC1 gene. The proband inherited the former from her mother and the latter from her father. The presence of digenic inheritance in the patient reflects the complex phenotype of venous thrombosis and demonstrates the significance of an unbiased approach to detect pathogenic variants, especially in patients with a high risk of hereditary thrombosis.

Bioinformatics Approach to Identify the Influences of COVID-19 on Ischemic Stroke.

As severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) is becoming more infectious and less virulent, symptoms beyond the lungs of the Coronavirus Disease 2019 (COVID-19) patients are a growing concern. Studies have found that the severity of COVID-19 patients is associated with an increased risk of ischemic stroke (IS); however, the underlying pathogenic mechanisms remain unknown. In this study, bioinformatics approaches were utilized to explore potential pathogenic mechanisms and predict potential drugs that may be useful in the treatment of COVID-19 and IS. The GSE152418 and GSE122709 datasets were downloaded from the GEO website to obtain the common differentially expressed genes (DEGs) of the two datasets for further functional enrichment, pathway analysis, and drug candidate prediction. A total of 80 common DEGs were identified in COVID-19 and IS datasets for GO and KEGG analysis. Next, the protein-protein interaction (PPI) network was constructed and hub genes were identified. Further, transcription factor-gene interactions and DEGs-miRNAs coregulatory network were investigated to explore their regulatory roles in disease. Finally, protein-drug interactions with common DEGs were analyzed to predict potential drugs. We successfully identified the top 10 hub genes that could serve as novel targeted therapies for COVID-19 and screened out some potential drugs for the treatment of COVID-19 and IS.

Drug-loaded balloon with built-in NIR controlled tip-separable microneedles for long-effective arteriosclerosis treatment.

Drug-eluting balloon (DEB) angioplasty has emerged as an effective treatment for cardiovascular and cerebrovascular diseases. However, distal embolism and late lumen restenosis could be caused by drug loss during DEB handling and rapid drug metabolization. Here, a drug-loaded balloon equipped with tip-separable microneedles on the balloon surface (MNDLB) was developed. Inbuilt near-infrared (NIR) ring laser inside the catheter inner shaft was introduced to activate the biodegradable microneedle tips for the first time. The drug-loaded tips thus could be embedded in the vasculature and then released antiproliferative drug - paclitaxel slowly via polymer degradation for more than half a year. A significant increase in drug delivery efficiency and superior therapeutic effectiveness compared with the standard DEB were demonstrated using an atherosclerosis rabbit model.

Case Report: Combined transcatheter arterial embolization and aortic stent-graft have better efficacy for bronchial artery aneurysms.

Bronchial artery aneurysm (BAA) is a rare and fatal condition that requires immediate treatment. However, conventional surgical and transcatheter arterial embolization treatments are less effective. In the present case, a 76-year-old hypertensive woman was admitted with dizziness and diagnosed with an unruptured bronchial artery aneurysm, which was treated by transcatheter arterial embolization and aortic stent-graft. The patient's clinical status was stable during the 4-year follow-up. Simultaneously, we reviewed 79 research papers, analyzing past BAA cases for their etiology, symptoms, and treatment outcomes. We found that catheter arterial embolization and aortic stent-graft implantation, especially for BAA of short-necked and arterial tortuosity, demonstrate superior efficacy compared to other methods. Therefore, we consider this approach to be the preferred choice in clinical BAA treatment.

A Survey of Survival Outcomes for Targeted Cancer Drugs Approved by the US Food and Drug Administration.

BACKGROUND: The last two decades have witnessed the vigorous development of targeted cancer drugs and the potent therapeutic effects of these drugs have been validated by various true and surrogate end points. Overall survival (OS) and progression-free survival (PFS) outcomes were two important end points used in targeted cancer drugs clinical trials but investigation on which was rare as a consequence of inherent heterogeneity and complexity. Here, we present the review and analysis of OS and PFS outcomes of all targeted cancer drugs approved by the U.S. Food and Drug Administration (FDA) through December 31, 2019, in the setting of clinical studies. METHODS: The targeted cancer drug directory was accessed via NCI website. The survival outcomes of those drugs in the setting of clinical trials were collected from publicly available Package Inserts and ClinicalTrials.gov. Median overall (OS) and progression-free survival (PFS) outcomes were summarized for targeted cancer drugs that were evaluated as monotherapies in clinical trials, contributions of targeted drugs to combination therapies in terms of survival benefit were analyzed, survival outcomes of FDA-approved first-line targeted therapies in different cancers were investigated, and the correlation between the absolute OS gain (ΔOS) and PFS gain (ΔPFS) as well as the hazard ratios for PFS (HRPFS) and OS (HROS) between comparative arms of available randomized clinical trials was evaluated. RESULTS: A total of 223 indications for 126 targeted cancer drugs have been approved by the FDA through December 31, 2019, among which 28 indications of 23 drugs have been approved for first-line therapies. Eighty indications for leukemia, lymphoma, and rare cancer types without survival data were excluded in the investigation of survival outcomes. For the remaining 143 indications, 99 were approved as monotherapies and 72 were approved as combination therapies. Among monotherapy subset, 18 of 72 (25%) indications with available OS outcomes have maximum median OS less than 12 months, 55 of 72 (76%) drug indications have maximum median OS less than 24 months, and 67 of 72 (93%) have maximum median OS less than 36 months. Regarding PFS, 38 of 88 (43%) drug indications have maximum median PFS less than 6 months, 69 of 88 (78%) drug indications have maximum median PFS less than 12 months, and 84 of 88 (95%) drug indications have maximum median PFS less than 24 months. The addition of targeted drugs to combination regimens under FDA's approval provided notable survival benefit, but the median value of OS gain rate of the available combination regimens was lower than that of PFS. The univariate Spearman Rank correlation coefficient suggested a significant positive correlation between ΔOS and ΔPFS (R = 0.62) but a weak correlation between HROS and HRPFS (R = 0.11) in 46 randomized clinical trials that investigated contributions of targeted cancer drugs to combination therapies with available data. A moderate correlation between ΔOS and ΔPFS (R = 0.43) and a rather weak correlation between HROS and HRPFS (R = 0.07) were also found in other randomized clinical trials that included in our study with available data. CONCLUSIONS: The survival benefit provided by targeted cancer drugs varied a lot among cancer types. Though targeted cancer drugs showed improvements in both OS and PFS in approved combination regimens, the median value of OS gain rate was lower than that of PFS. As only weak correlation was found between HRPFS and HROS, the evidence supporting the use of PFS as a surrogate to OS in the setting of targeted cancer drugs might also be limited.

Robotic-assisted thoracic surgery reduces perioperative complications and achieves a similar long-term survival profile as posterolateral thoracotomy in clinical N2 stage non-small cell lung cancer patients: a multicenter, randomized, controlled trial.

BACKGROUND: Our previous study demonstrated the safety and short-term efficacy of robotic-assisted thoracic surgery (RATS) in clinical N2 (c-N2) stage non-small cell lung cancer (NSCLC) patients. From this, the present study was devised, in which the follow-up time and sample size were both extended to explore the long-term efficacy and potential benefit in survival of RATS compared with lobectomy in c-N2 stage NSCLC patients. METHODS: Patients with c-N2 NSCLS were randomly assigned in a 1:1 ratio to accept operation through thoracotomy or RATS. The da Vinci Surgical System (Si/Xi) was applied in the RATS group, while conventional lobectomy with a rib-spreading incision was applied in the posterolateral thoracotomy group. Primary endpoint was defined as disease free survival and overall survival (OS) of all recruited patients. RESULTS: Compared with posterolateral thoracotomy group (N=72), the RATS group (N=76) had a reduced blood loss (P<0.001), decreased drainage duration (P=0.002), and decreased postoperative pain visual analog score (all P<0.001), but increased overall cost (P<0.001). Meanwhile, no difference in the other postoperative complications (such as air leakage, subcutaneous emphysema, atrial fibrillation etc.) was found between the RATS group and the posterolateral thoracotomy group (all P>0.05). Regarding long-term outcome, no difference in disease-free survival (DFS; P=0.925) or OS (P=0.853) was observed between the RATS group and posterolateral thoracotomy group. Subgroup analyses and multivariable Cox regression analyses also found no difference in DFS or OS between the RATS group and posterolateral thoracotomy groups. CONCLUSIONS: RATS reduced intraoperative bleeding, drainage duration, postoperative pain, and achieved similar long-term survival outcomes compared with posterolateral thoracotomy in c-N2 stage NSCLC patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-INR-17012777.

IL-33 promotes the progression of vascular restenosis after carotid artery balloon injury by promoting carotid artery intimal hyperplasia and inflammatory response.

Interleukin (IL)-33 is associated with vascular restenosis after carotid artery balloon injury. This work aims to investigate the involvement of IL-33 in carotid artery balloon injury. We first constructed carotid artery balloon injury model in male Wistar rats. Then, we found that IL-33 was highly expressed in the rats with carotid artery balloon injury 3, 14 and 21 days after surgery. Furthermore, IL-33 treatment promoted inflammatory response and carotid artery intimal hyperplasia in the rats with carotid artery balloon injury, which was effectively improved by anti-IL-33 treatment. In addition, IL-33 treatment enhanced proliferation, migration, inflammatory response and tube formation of human umbilical vein endothelial cells in a concentration-dependent way. In summary, our study demonstrates that IL-33 treatment promotes the progression of vascular restenosis after carotid artery balloon injury by enhancing carotid artery intimal hyperplasia and inflammatory response. Thus, our findings suggest that IL-33 maybe a valuable target for carotid artery balloon injury therapies.

miR-1301-3p promotes the proliferation and migration of lung cancer cells via direct repression of polymerase I and transcript release factor.

Aberrant expression of microRNAs (miRNAs or miRs) is associated with a number of human diseases, including lung cancer. Although numerous differentially expressed miRNAs have been identified in lung cancer via microarray and sequencing methods, to the best of our knowledge, only a small portion of these miRNAs have been experimentally verified. In the present study, miR-1301-3p expression levels in lung tumor tissues and lung cancer cells were measured by reverse transcription-quantitative PCR (RT-qPCR) and by analyzing previously published data. Cell Counting Kit-8 and Transwell assays were used to analyze the function of miR-1301-3p in lung cancer tissues and cells. Bioinformatics analysis, RT-qPCR, western blotting and a dual-luciferase reporter assay were performed to investigate the mechanism of miR-1301-3p in lung cancer cells. It was identified that miR-1301-3p is an upregulated miRNA in lung cancer via analyzing previously published microarray and The Cancer Genome Atlas-lung squamous cell carcinoma project data, and the upregulation of miR-1301-3p was confirmed in collected clinical samples and cells. Inhibition of miR-1301-3p suppressed lung cancer cell proliferation and migration. In addition, miR-1301-3p inhibition upregulated E-cadherin, an epithelial cell maker, and downregulated vimentin, a mesenchymal cell marker. Using bioinformatics analysis, it was revealed that polymerase I and transcript release factor (PTRF) is a target of miR-1301-3p. RT-qPCR, western blotting and dual-luciferase reporter assays demonstrated that PTRF is targeted by miR-1301-3p in lung cancer cells. The rescue experiments indicated that silencing PTRF could attenuate the inhibition of cell proliferation and migration induced by miR-1301-3p inhibitor in lung cancer cells. Furthermore, a strong negative correlation between miR-1301-3p and PTRF mRNA was identified in clinical samples. In summary, the present data highlight the involvement of miR-1301-3p in the proliferation and migration of lung cancer cells, indicating that miR-1301-3p may be a promising biomarker for lung cancer.

Immunohistochemistry biomarker TP53 expression predicts the survival of thymomas.

BACKGROUND: Thymomas are rare malignancies. Thymectomy is the optimal therapy which could prolong the survival of patients. However, prognostic factors of thymomas are not clear. METHODS: Thymomas patients were enrolled from 2001 to 2016. Clinical and pathological prognostic factors of thymomas were evaluated by univariate and multivariate analyses. RESULTS: A total number of 98 patients was eligible for this study. All patients were received complete resection (CR). Diagnostic age [elder than the median 60 vs. younger than 60, hazard ratio (HR) =2.325, P=0.027], Masaoka stage (III vs. I, HR =10.756, P<0.001; IV vs. I, HR =6.558, P=0.014), and diabetes mellitus (DM) (with vs. without, HR =0.142, P=0.004) were independent prognostic factors for overall survival (OS). Immunohistochemistry (IHC) biomarker TP53 expression also influenced OS significantly (positive vs. negative, HR =5.157, P=0.018). Furthermore, age (elder than 60 vs. younger than 60, HR =2.980, P=0.022) was independent prognostic factors for recurrence free survival (RFS). CONCLUSIONS: We found that diagnostic age, clinical stages, DM, TP53 expression in IHC, and quality perioperative nursing are prognostic factors in thymomas.

Robot-assisted thoracoscopic surgery versus thoracotomy for c-N2 stage NSCLC: short-term outcomes of a randomized trial.

BACKGROUND: Safety and short-term efficacy of robot-assisted thoracoscopic surgery (RATS) for early-stage non-small cell lung cancer (NSCLC) have been previously proven; however, RATS for N2 stage NSCLC was barely evaluated. The aim of this randomized controlled trial (RCT) was to explore the short-term outcome of RATS for cN2 stage NSCLC. METHODS: Total of 113 patients who were diagnosed with clinically single cN2 stage NSCLC were enrolled and randomly assigned to RATS and thoracotomy groups. The patients in RATS group were treated by lobectomy and mediastinal lymph node dissection using the da Vinci Surgical System, while the patients in thoracotomy group underwent lobectomy and mediastinal lymph node dissection from. And, short-term outcomes were analyzed statistically. RESULTS: The data from 108 subjects (58 in RATS and 55 in thoracotomy groups) were eligible for analyses. Five patients who received robot-assisted lobectomy initially was converted intraoperatively to open operation due to extensive pleural adhesion and equipment issues. And, one subject underwent robot-assisted surgery was died preoperatively due to pulmonary embolism. Compared with thoracotomy, RATS was associated with less intraoperative blood loss (86.3±41.1 vs. 165.7±46.4 mL, P<0.001), median chest duration (4 vs. 5, P<0.01), visual analog scores at postoperative day one to five (P<0.001), and slightly fewer incidence of postoperative complications. Also, both surgical approaches revealed comparable drainages and nodal harvest. The cancer residual margins occurred in one subject in RATS group and three patients in thoracotomy group (P=0.56). However, overall cost of subjects underwent RATS was higher than those received thoracotomy (100,367±19,251 vs. 82,002±20,434, P<0.001). CONCLUSIONS: Present study proves that the feasibility and safety of RATS lobectomy to treat patients with cN2 stage NSCLC, and it should be superior to thoracotomy due to lesser intraoperative blood loss.

Loss of asparagine synthetase suppresses the growth of human lung cancer cells by arresting cell cycle at G0/G1 phase.

The aim of this research is to determine the role of human asparagine synthetase (ASNS) in human lung cancer. In the present study, immunohistochemical staining and the Oncomine database mining showed that the expression of ASNS gene was higher in lung cancer tissues than that in the normal tissues by. In addition, western blot assay showed that ASNS was elevated in lung cancer A549 and 95D cell lines as compared with that in H1299 and H460 cells. Therefore, A549 and 95D cells were chosen for subsequent MTT and colony formation assay. It was found that knockdown of ASNS inhibited the growth and colony formation abilities of A549 and 95D cells. Flow cytometry showed that ASNS silencing arrested cell cycle progression at G0/G1 phase in A549 cells, probably through regulating the expression of cell cycle molecules such as CDK2 and Cyclin E1 as shown by quantitative real-time PCR. Taken together, our study indicates that ASNS may be an important target for lung cancer diagnosis and treatment.

The predictive and prognostic values of factors associated with visceral pleural involvement in resected lung adenocarcinomas.

BACKGROUND: The predictive and prognostic impact of factors associated with visceral pleural invasion (VPI) on survival and recurrence in patients with resected lung adenocarcinomas is not clearly defined. PATIENTS AND METHODS: A total of 505 consecutive patients with stage Ia-IIIa lung adenocarcinomas treated with radical resection were included. The predominant growth pattern was classified according to the new classification system for lung adenocarcinoma proposed by the International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society. The correlations of VPI with clinical and pathologic parameters were analyzed. RESULTS: The incidence of VPI was significantly lower in lepidic predominant group (15.5% vs 4.5%, P<0.001) and higher in solid and micropapillary predominant group (28.6% vs 17.6%, P=0.004 and 14.7% vs 4.2%, P<0.001, respectively). VPI correlated with higher risk in regional postoperative recurrence (hazard ratio, 2.341; 95% confidence interval, 1.564-3.504) and distant recurrence (hazard ratio, 2.193; 95% confidence interval, 1.665-2.89) in surgically resected lung adenocarcinomas. However, when growth patterns of adenocarcinoma were lumped into multivariate analysis, VPI was not a significant independent predictive factor for survival (P=0.854 for overall survival [OS] and P=0.575 for disease-free survival [DFS]) and recurrence (P=0.38 for regional recurrence and P=0.089 for distant recurrence). Of the 95 patients with stage Ib, those who received adjuvant chemotherapy had longer DFS and OS than the patients who received no chemotherapy after surgery. However, these differences in DFS and OS did not reach statistical significance (P=0.063 for DFS, P=0.85 for OS). CONCLUSION: VPI was associated with solid and micropapillary histology. In addition, stage Ib patients with solid histologic subtype tumor showed longer DFS and OS, highlighting a potential benefit in this subgroup of patients and necessitating the need for larger clinical trials.

Low-dose volume perfusion computed tomography (VPCT) for diagnosis of solitary pulmonary nodules.

OBJECTIVE: To characterize solitary pulmonary nodules (SPN) in terms of perfusion parameters using low-dose volume perfusion computed tomography (VPCT) and two different calculation methods, compare their results, look for interobserver agreement of measurements and investigate the feasibility of low-dose VPCT. MATERIALS AND METHODS: This study was approved by the local Institutional Review Board and all patients provided written informed consent. Seventy-one patients (mean age 60.8 years ±9.6) with solitary pulmonary nodules were enrolled. Low-dose VPCT was performed for 38.63s covering the involved lung (70kV, 120mAs, 22 consecutive volume measurements, 50mL iodinated contrast, flow rate 4mL/s). Mean blood flow (BF), blood volume (BV) and k-trans were determined both with the maximum slope+Patlak vs. deconvolution method. Additionally, the difference of VPCT parameters between different type lesions and normal tissue was analyzed. Interobserver agreement for all perfusion parameters was calculated using intraclass correlation coefficients (ICC). The effective radiation dose of the VPCT and the total CT scan protocol were recorded. All CT findings were histologically confirmed by surgical intervention. RESULTS: The mean lesion size was 18.6mm. Interobserver agreement measure with ICC shows high agreement between the measurements (κ=0.85). The effective radiation dose of the VPCT was 9.3mSv. The mean perfusion values for BF, BV and k-trans of 120.6mL/100g tissue/', 11.6mL/100g tissue/', and 18.5mL/100g tissue/' for the deconvolution method, and 50.1mL/100g tissue/', 11.6mL/100g tissue/' and 24.3mL/100g tissue/' for the maximum slope+Patlak method, which were significantly higher than those of normal muscle (20.7mL/100g tissue/', 2.6mL/100g tissue/', and 7.6mL/100g tissue/' for the deconvolution method and 10.9mL/100g tissue/', 3.1mL/100g tissue/' and 8.1mL/100g tissue/' for the maximum slope method). The best overall correlation between calculation methods was achieved for measurements of BF. CONCLUSION: The low-dose volume perfusion CT of the solitary pulmonary nodules can effectively reduce the radiation dose and non-invasively assess perfusion of SPN within the entire lesion volume.

Survival outcome after stereotactic body radiation therapy and surgery for stage I non-small cell lung cancer: a meta-analysis.

PURPOSE: This study compared treatment outcomes of stereotactic body radiation therapy (SBRT) with those of surgery in stage I non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: Eligible studies of SBRT and surgery were retrieved through extensive searches of the PubMed, Medline, Embase, and Cochrane library databases from 2000 to 2012. Original English publications of stage I NSCLC with adequate sample sizes and adequate SBRT doses were included. A multivariate random effects model was used to perform a meta-analysis to compare survival between treatments while adjusting for differences in patient characteristics. RESULTS: Forty SBRT studies (4850 patients) and 23 surgery studies (7071 patients) published in the same period were eligible. The median age and follow-up duration were 74 years and 28.0 months for SBRT patients and 66 years and 37 months for surgery patients, respectively. The mean unadjusted overall survival rates at 1, 3, and 5 years with SBRT were 83.4%, 56.6%, and 41.2% compared to 92.5%, 77.9%, and 66.1% with lobectomy and 93.2%, 80.7%, and 71.7% with limited lung resections. In SBRT studies, overall survival improved with increasing proportion of operable patients. After we adjusted for proportion of operable patients and age, SBRT and surgery had similar estimated overall and disease-free survival. CONCLUSIONS: Patients treated with SBRT differ substantially from patients treated with surgery in age and operability. After adjustment for these differences, OS and DFS do not differ significantly between SBRT and surgery in patients with operable stage I NSCLC. A randomized prospective trial is warranted to compare the efficacy of SBRT and surgery.