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      Comparison of Long-term Survival of Patients With Early-Stage Non–Small Cell Lung Cancer After Surgery vs Stereotactic Body Radiotherapy

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      , MD 1 , , , PhD 2 , , MD 1 , , PhD 3
      JAMA Network Open
      American Medical Association

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          Key Points

          Question

          How does the long-term survival after curative-intent surgery with regional lymph node examination of various extents compare with long-term survival after stereotactic body radiotherapy for early-stage non–small cell lung cancer?

          Findings

          In this cohort study of 104 709 patients in the US National Cancer Database with early-stage non–small cell lung cancer, those who received surgery coupled with regional lymph node examination of an appropriate extent had significantly better long-term survival than those who received stereotactic body radiotherapy.

          Meaning

          These findings suggest that curative-intent surgery, when coupled with regional lymph node examination, is generally associated with the best long-term overall survival in patients with early-stage non–small cell lung cancer.

          Abstract

          This cohort study compares long-term overall survival of patients with early-stage non–small cell lung cancer treated with stereotactic body radiotherapy vs surgery including various degrees of lymph node examination.

          Abstract

          Importance

          Previous comparisons of surgery and stereotactic body radiotherapy (SBRT) for early-stage (ES) non–small cell lung cancer (NSCLC) did not account for the extent of regional lymph node examination (LNE) during surgery.

          Objective

          To compare long-term overall survival (OS) of patients with ES NSCLC after surgery vs SBRT when the extent of regional LNE in patients undergoing surgery is thoroughly considered.

          Design, Setting, and Participants

          Cohort study with survival comparisons using the multivariable Cox proportional hazards model and after propensity score matching. Data from the National Cancer Database were analyzed from October 28, 2018, through April 18, 2019. Patients with ES NSCLC diagnosed between January 1, 2004, and December 31, 2015, who underwent any curative-intent surgery or SBRT were included.

          Main Outcomes and Measures

          Long-term OS.

          Results

          Of 104 709 total patients, 91 330 underwent surgery (42 508 [46.5%] male; median [interquartile range] age, 68 [61-75] years) and 13 379 received SBRT (6065 [45.3%] male; median [interquartile range] age, 75 [68-81] years). Surgery, especially lobectomy (hazard ratio [HR], 0.53; 95% CI, 0.50-0.56), and regional LNE, especially when more than 10 lymph nodes were examined (HR, 0.73; 95% CI, 0.69-0.77), were associated with better long-term OS ( P < .001). Pneumonectomy was not associated with reduced mortality risk when 0 nodes were examined (HR for stage T1, 1.43; 95% CI, 0.67-3.06; P = .35; HR for stage T2-T3, 0.62; 95% CI, 0.34-1.13; P = .12) or when more than 15 nodes were examined for stage T1 disease in patients younger than 80 years (HR, 0.77; 95% CI, 0.54-1.09; P = .14) or when patients aged 80 years or older received regional LNE of any extent (>15 nodes examined: HR for stage T1, 0.65; 95% CI, 0.16-2.64; P = .54; HR for stage T2-T3, 0.90; 95% CI, 0.50-1.60; P = .71). Less extensive surgery was not associated with improved OS when 0 nodes were examined in patients aged 80 years or older with stage T2 to T3 tumors (HR for lobectomy, 0.90; 95% CI, 0.65-1.25; P = .53) and in selected operable patients older than 75 years with stage T1 tumors (HR for lobectomy, 1.07; 95% CI, 0.57-2.00; P = .84).

          Conclusions and Relevance

          This study found that, overall, surgery coupled with regional LNE of appropriate extent was associated with the best long-term OS in patients with ES NSCLC.

          Related collections

          Most cited references24

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          Impact of Examined Lymph Node Count on Precise Staging and Long-Term Survival of Resected Non–Small-Cell Lung Cancer: A Population Study of the US SEER Database and a Chinese Multi-Institutional Registry

          Purpose We investigated the correlation between the number of examined lymph nodes (ELNs) and correct staging and long-term survival in non–small-cell lung cancer (NSCLC) by using large databases and determined the minimal threshold for the ELN count. Methods Data from a Chinese multi-institutional registry and the US SEER database on stage I to IIIA resected NSCLC (2001 to 2008) were analyzed for the relationship between the ELN count and stage migration and overall survival (OS) by using multivariable models. The series of the mean positive LNs, odds ratios (ORs), and hazard ratios (HRs) were fitted with a LOWESS smoother, and the structural break points were determined by Chow test. The selected cut point was validated with the SEER 2009 cohort. Results Although the distribution of ELN count differed between the Chinese registry (n = 5,706) and the SEER database (n = 38,806; median, 15 versus seven, respectively), both cohorts exhibited significantly proportional increases from N0 to N1 and N2 disease (SEER OR, 1.038; China OR, 1.012; both P < .001) and serial improvements in OS (N0 disease: SEER HR, 0.986; China HR, 0.981; both P < .001; N1 and N2 disease: SEER HR, 0.989; China HR, 0.984; both P < .001) as the ELN count increased after controlling for confounders. Cut point analysis showed a threshold ELN count of 16 in patients with declared node-negative disease, which were examined in the derivation cohorts (SEER 2001 to 2008 HR, 0.830; China HR, 0.738) and validated in the SEER 2009 cohort (HR, 0.837). Conclusion A greater number of ELNs is associated with more-accurate node staging and better long-term survival of resected NSCLC. We recommend 16 ELNs as the cut point for evaluating the quality of LN examination or prognostic stratification postoperatively for patients with declared node-negative disease.
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            Stereotactic Body Radiation Therapy for Operable Early-Stage Lung Cancer

            Stereotactic body radiation therapy (SBRT) has become a standard treatment for patients with medically inoperable early-stage lung cancer. However, its effectiveness in patients medically suitable for surgery is unclear.
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              Complete resection in lung cancer surgery: proposed definition.

              To propose an internationally accepted definition of complete resection in lung cancer surgery. The International Association for the Study of Lung Cancer (IASLC) Staging Committee created the Complete Resection Subcommittee in 2001 to work on an international definition of complete resection in lung cancer surgery. The previous definitions of complete resection and the rules of the International Union Against Cancer regarding the TNM residual tumor classification, together with a thorough review of the pertinent literature, and the input of the members of the IASLC Staging Committee were considered in order to get an international consensus on the definition of complete resection in lung cancer surgery. Complete resection requires all of the following: free resection margins proved microscopically; systematic nodal dissection or lobe-specific systematic nodal dissection; no extracapsular nodal extension of the tumor; and the highest mediastinal node removed must be negative. Whenever there is involvement of resection margins, extracapsular nodal extension, unremoved positive lymph nodes or positive pleural or pericardial effusions, the resection is defined as incomplete. When the resection margins are free and no residual tumor is left, but the resection does not fulfill the criteria for complete resection, there is carcinoma in situ at the bronchial margin or positive pleural lavage cytology, the term uncertain resection is proposed. The proposed definitions of complete, incomplete and uncertain resections are clear and reproducible in an international setting to study their prognostic impact prospectively.
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                Author and article information

                Journal
                JAMA Netw Open
                JAMA Netw Open
                JAMA Netw Open
                JAMA Network Open
                American Medical Association
                2574-3805
                20 November 2019
                November 2019
                20 November 2019
                : 2
                : 11
                : e1915724
                Affiliations
                [1 ]Marshfield Clinic, Marshfield, Wisconsin
                [2 ]West Virginia Clinical and Translational Science Institute, Erma Byrd Biomedical Research Center, West Virginia University Health Sciences Center, Morgantown
                [3 ]Department of Biostatistics, West Virginia University Health Sciences Center, Morgantown
                Author notes
                Article Information
                Accepted for Publication: October 1, 2019.
                Published: November 20, 2019. doi:10.1001/jamanetworkopen.2019.15724
                Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2019 Chi A et al. JAMA Network Open.
                Corresponding Author: Alexander Chi, MD, Department of Oncology, Marshfield Clinic, 1000 N Oak Ave, Marshfield, WI 54449 ( achiaz2010@ 123456gmail.com ).
                Author Contributions: Dr Chi had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
                Concept and design: Chi, Fang, Wen.
                Acquisition, analysis, or interpretation of data: All authors.
                Drafting of the manuscript: Chi, Fang, Wen.
                Critical revision of the manuscript for important intellectual content: All authors.
                Statistical analysis: Fang, Wen.
                Administrative, technical, or material support: Chi, Fang.
                Supervision: Chi.
                Conflict of Interest Disclosures: None reported.
                Article
                zoi190596
                10.1001/jamanetworkopen.2019.15724
                6902813
                31747032
                a3d1b041-3740-4a18-908a-6102eef7e2fe
                Copyright 2019 Chi A et al. JAMA Network Open.

                This is an open access article distributed under the terms of the CC-BY License.

                History
                : 4 August 2019
                : 1 October 2019
                Categories
                Research
                Original Investigation
                Online Only
                Oncology

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