{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:09:29Z","timestamp":1791925769717,"version":"4.3.4"},"reference-count":34,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"Importance<\/jats:title>Despite recent breakthroughs in therapy, advanced lung cancer still poses a therapeutic challenge. The survival profile of patients with metastatic lung cancer remains poorly understood by metastatic disease type (ie, de novo stage IV vs distant recurrence).<\/jats:p><\/jats:sec>Objective<\/jats:title>To evaluate the association of metastatic disease type on overall survival (OS) among patients with non\u2013small cell lung cancer (NSCLC) and to identify potential mechanisms underlying any survival difference.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>Cohort study of a national US population based at a tertiary referral center in the San Francisco Bay Area using participant data from the National Lung Screening Trial (NLST) who were enrolled between 2002 and 2004 and followed up for up to 7 years as the primary cohort and patient data from Stanford Healthcare (SHC) for diagnoses between 2009 and 2019 and followed up for up to 13 years as the validation cohort. Participants from NLST with de novo metastatic or distant recurrent NSCLC diagnoses were included. Data were analyzed from January 2021 to March 2023.<\/jats:p><\/jats:sec>Exposures<\/jats:title>De novo stage IV vs distant recurrent metastatic disease.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>OS after diagnosis of metastatic disease.<\/jats:p><\/jats:sec>Results<\/jats:title>The NLST and SHC cohort consisted of 660 and 180 participants, respectively (411 men [62.3%] vs 109 men [60.6%], 602 White participants [91.2%] vs 111 White participants [61.7%], and mean [SD] age of 66.8 [5.5] vs 71.4 [7.9] years at metastasis, respectively). Patients with distant recurrence showed significantly better OS than patients with de novo metastasis (adjusted hazard ratio [aHR], 0.72; 95% CI, 0.60-0.87; P<\/jats:italic>\u2009&amp;lt;\u2009.001) in NLST, which was replicated in SHC (aHR, 0.64; 95% CI, 0.43-0.96; P<\/jats:italic>\u2009=\u2009.03). In SHC, patients with de novo metastasis more frequently progressed to the bone (63 patients with de novo metastasis [52.5%] vs 19 patients with distant recurrence [31.7%]) or pleura (40 patients with de novo metastasis [33.3%] vs 8 patients with distant recurrence [13.3%]) than patients with distant recurrence and were primarily detected through symptoms (102 patients [85.0%]) as compared with posttreatment surveillance (47 patients [78.3%]) in the latter. The main finding remained consistent after further adjusting for metastasis sites and detection methods.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In this cohort study, patients with distant recurrent NSCLC had significantly better OS than those with de novo disease, and the latter group was associated with characteristics that may affect overall survival. This finding can help inform future clinical trial designs to ensure a balance for baseline patient characteristics.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2023.35813","type":"journal-article","created":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T15:01:05Z","timestamp":1695740465000},"page":"e2335813","source":"Crossref","is-referenced-by-count":17,"title":["Overall Survival Among Patients With De Novo Stage IV Metastatic and Distant Metastatic Recurrent Non\u2013Small Cell Lung Cancer"],"prefix":"10.1001","volume":"6","author":[{"given":"Chloe C.","family":"Su","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, California"},{"name":"Quantitative Sciences Unit, Department of Medicine, Stanford University School of Medicine, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie T.","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, California"},{"name":"Veterans Affairs Palo Alto Healthcare System, Palo Alto, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunji","family":"Choi","sequence":"additional","affiliation":[{"name":"Quantitative Sciences Unit, Department of Medicine, Stanford University School of Medicine, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathaniel J.","family":"Myall","sequence":"additional","affiliation":[{"name":"Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel W.","family":"Neal","sequence":"additional","affiliation":[{"name":"Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, California"},{"name":"Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison W.","family":"Kurian","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, California"},{"name":"Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, California"},{"name":"Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henning","family":"Stehr","sequence":"additional","affiliation":[{"name":"Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Wood","sequence":"additional","affiliation":[{"name":"Research Informatics Center, Department of Medicine, Stanford University School of Medicine, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solomon M.","family":"Henry","sequence":"additional","affiliation":[{"name":"Research Informatics Center, Department of Medicine, Stanford University School of Medicine, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah M.","family":"Backhus","sequence":"additional","affiliation":[{"name":"Veterans Affairs Palo Alto Healthcare System, Palo Alto, California"},{"name":"Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California"},{"name":"Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann N.","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Radiology, Stanford University School of Medicine, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather A.","family":"Wakelee","sequence":"additional","affiliation":[{"name":"Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, California"},{"name":"Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Summer S.","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, California"},{"name":"Quantitative Sciences Unit, Department of Medicine, Stanford University School of Medicine, Stanford, California"},{"name":"Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California"},{"name":"Department of Neurosurgery, Stanford University School of Medicine, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2023,9,26]]},"reference":[{"key":"zoi231029r1","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1038\/s41571-023-00798-3","article-title":"The global burden of lung cancer: current status and future trends.","volume":"20","author":"Leiter","year":"2023","journal-title":"Nat Rev Clin Oncol"},{"issue":"22","key":"zoi231029r2","doi-asserted-by":"publisher","first-page":"5218","DOI":"10.1002\/cncr.24625","article-title":"Local recurrence after surgery for early stage lung cancer: an 11-year experience with 975 patients.","volume":"115","author":"Kelsey","year":"2009","journal-title":"Cancer"},{"issue":"2","key":"zoi231029r3","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1097\/JTO.0b013e3181c20080","article-title":"Timing of local and distant failure in resected lung cancer: implications for reported rates of local failure.","volume":"5","author":"Boyd","year":"2010","journal-title":"J Thorac Oncol"},{"issue":"10183","key":"zoi231029r4","doi-asserted-by":"publisher","first-page":"1819","DOI":"10.1016\/S0140-6736(18)32409-7","article-title":"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.","volume":"393","author":"Mok","year":"2019","journal-title":"Lancet"},{"issue":"22","key":"zoi231029r5","doi-asserted-by":"publisher","first-page":"2078","DOI":"10.1056\/NEJMoa1801005","article-title":"Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer.","volume":"378","author":"Gandhi","year":"2018","journal-title":"N Engl J Med"},{"issue":"7","key":"zoi231029r6","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1016\/S1470-2045(19)30167-6","article-title":"Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first-line treatment for metastatic non-squamous non-small-cell lung cancer (IMpower130): a multicentre, randomised, open-label, phase 3 trial.","volume":"20","author":"West","year":"2019","journal-title":"Lancet Oncol"},{"issue":"12","key":"zoi231029r7","doi-asserted-by":"publisher","first-page":"e88","DOI":"10.1097\/MLR.0000000000000404","article-title":"Detecting lung and colorectal cancer recurrence using structured clinical\/administrative data to enable outcomes research and population health management.","volume":"55","author":"Hassett","year":"2017","journal-title":"Med Care"},{"issue":"2","key":"zoi231029r8","doi-asserted-by":"publisher","DOI":"10.1093\/jncics\/pky024","article-title":"Comparing survival after recurrent vs de novo stage IV advanced breast, lung, and colorectal cancer.","volume":"2","author":"Hassett","year":"2018","journal-title":"J Natl Cancer Inst Cancer Spectr"},{"issue":"3","key":"zoi231029r9","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1097\/COC.0000000000000513","article-title":"Survival implications of de novo versus recurrent metastatic non-small cell lung cancer.","volume":"42","author":"Moore","year":"2019","journal-title":"Am J Clin Oncol"},{"issue":"11","key":"zoi231029r10","doi-asserted-by":"publisher","first-page":"2169","DOI":"10.1093\/annonc\/mdq220","article-title":"Survival differences among women with de novo stage IV and relapsed breast cancer.","volume":"21","author":"Dawood","year":"2010","journal-title":"Ann Oncol"},{"issue":"3","key":"zoi231029r11","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1007\/s10549-016-4080-9","article-title":"Survival with metastatic breast cancer based on initial presentation, de novo versus relapsed.","volume":"161","author":"den Brok","year":"2017","journal-title":"Breast Cancer Res Treat"},{"issue":"9","key":"zoi231029r12","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1038\/bjc.2015.127","article-title":"Prognosis of metastatic breast cancer: are there differences between patients with de novo and recurrent metastatic breast cancer?","volume":"112","author":"Lobbezoo","year":"2015","journal-title":"Br J Cancer"},{"issue":"11","key":"zoi231029r13","doi-asserted-by":"publisher","first-page":"1618","DOI":"10.1038\/s41416-020-0784-z","article-title":"Survival and disease characteristics of de novo versus recurrent metastatic breast cancer in a cohort of young patients.","volume":"122","author":"McKenzie","year":"2020","journal-title":"Br J Cancer"},{"issue":"6","key":"zoi231029r14","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djv059","article-title":"Lung cancer prognosis before and after recurrence in a population-based setting.","volume":"107","author":"Consonni","year":"2015","journal-title":"J Natl Cancer Inst"},{"issue":"5","key":"zoi231029r15","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1002\/cncr.v115:5","article-title":"Factors associated with local and distant recurrence and survival in patients with resected nonsmall cell lung cancer.","volume":"115","author":"Varlotto","year":"2009","journal-title":"Cancer"},{"issue":"2","key":"zoi231029r16","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1164\/rccm.201502-0259OC","article-title":"Racial differences in outcomes within the national lung screening trial. implications for widespread implementation.","volume":"192","author":"Tanner","year":"2015","journal-title":"Am J Respir Crit Care Med"},{"issue":"1","key":"zoi231029r17","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1177\/0049124115610345","article-title":"Obtaining predictions from models fit to multiply imputed data.","volume":"45","author":"Miles","year":"2016","journal-title":"Sociol Methods Res"},{"issue":"3","key":"zoi231029r18","doi-asserted-by":"publisher","first-page":"191","DOI":"10.4103\/atm.ATM_276_16","article-title":"Distribution patterns of the metastases of the lung carcinoma in relation to histological type of the primary tumor: an autopsy study.","volume":"12","author":"Milovanovic","year":"2017","journal-title":"Ann Thorac Med"},{"issue":"1","key":"zoi231029r19","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.lungcan.2014.07.020","article-title":"Metastatic sites and survival in lung cancer.","volume":"86","author":"Riihim\u00e4ki","year":"2014","journal-title":"Lung Cancer"},{"issue":"10","key":"zoi231029r20","doi-asserted-by":"publisher","first-page":"1485","DOI":"10.1097\/JTO.0b013e318267223a","article-title":"Prognostic impact of malignant pleural effusion at presentation in patients with metastatic non-small-cell lung cancer.","volume":"7","author":"Morgensztern","year":"2012","journal-title":"J Thorac Oncol"},{"issue":"2","key":"zoi231029r21","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.lungcan.2012.08.004","article-title":"Impact of visceral pleural invasion on the survival of patients with non-small cell lung cancer.","volume":"78","author":"Kudo","year":"2012","journal-title":"Lung Cancer"},{"issue":"4","key":"zoi231029r22","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1111\/resp.12496","article-title":"Clinical features and survival of lung cancer patients with pleural effusions.","volume":"20","author":"Porcel","year":"2015","journal-title":"Respirology"},{"key":"zoi231029r23","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.lungcan.2021.03.015","article-title":"Pleural effusion is a negative prognostic factor for immunotherapy in patients with non-small cell lung cancer (NSCLC): the pluie study.","volume":"155","author":"Epaillard","year":"2021","journal-title":"Lung Cancer"},{"issue":"6","key":"zoi231029r24","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1016\/j.cell.2010.01.025","article-title":"Immunity, inflammation, and cancer.","volume":"140","author":"Grivennikov","year":"2010","journal-title":"Cell"},{"issue":"9329","key":"zoi231029r25","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/S0140-6736(02)09552-1","article-title":"Malignant effusions and immunogenic tumour-derived exosomes.","volume":"360","author":"Andre","year":"2002","journal-title":"Lancet"},{"key":"zoi231029r26","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.critrevonc.2017.05.004","article-title":"Overcoming immunosuppression in bone metastases.","volume":"117","author":"Reinstein","year":"2017","journal-title":"Crit Rev Oncol Hematol"},{"issue":"3","key":"zoi231029r27","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1007\/s12149-021-01694-5","article-title":"Prognostic value of total tumour volume, adding necrosis to metabolic tumour volume, in advanced or metastatic non-small cell lung cancer treated with first-line pembrolizumab.","volume":"36","author":"Eude","year":"2022","journal-title":"Ann Nucl Med"},{"issue":"13","key":"zoi231029r28","doi-asserted-by":"publisher","first-page":"CT074","DOI":"10.1158\/1538-7445.AM2019-CT074","article-title":"Abstract CT074: Tumor mutational burden (TMB) as a biomarker of survival in metastatic non-small cell lung cancer (mNSCLC): Blood and tissue TMB analysis from MYSTIC, a Phase III study of first-line durvalumab \u00b1 tremelimumab vs chemotherapy.","volume":"79","author":"Peters","year":"2019","journal-title":"Cancer Res"},{"issue":"4-5","key":"zoi231029r29","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1053\/j.seminoncol.2019.10.002","article-title":"Baseline tumor size and survival outcomes in lung cancer patients treated with immune checkpoint inhibitors.","volume":"46","author":"Hopkins","year":"2019","journal-title":"Semin Oncol"},{"issue":"4","key":"zoi231029r30","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1016\/S0360-3016(02)02814-6","article-title":"Influence of tumor volume on survival in patients irradiated for non-small-cell lung cancer.","volume":"53","author":"Etiz","year":"2002","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"2","key":"zoi231029r31","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1016\/j.ijrobp.2005.07.967","article-title":"Prognostic factors for survival in stage III non-small-cell lung cancer treated with definitive radiation therapy: impact of tumor volume.","volume":"64","author":"Basaki","year":"2006","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"1","key":"zoi231029r32","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1186\/s13014-014-0283-6","article-title":"The effect of tumor volume and its change on survival in stage III non-small cell lung cancer treated with definitive concurrent chemoradiotherapy.","volume":"9","author":"Koo","year":"2014","journal-title":"Radiat Oncol"},{"issue":"4","key":"zoi231029r33","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1097\/JTO.0000000000000456","article-title":"Relationship between tumor size and survival in non-small-cell lung cancer (NSCLC): an analysis of the surveillance, epidemiology, and end results (SEER) registry.","volume":"10","author":"Zhang","year":"2015","journal-title":"J Thorac Oncol"},{"issue":"8","key":"zoi231029r34","doi-asserted-by":"publisher","first-page":"915","DOI":"10.6004\/jnccn.2020.7668","article-title":"Bone metastases, skeletal-related events, and survival in patients with metastatic non-small cell lung cancer treated with immune checkpoint inhibitors.","volume":"19","author":"Qin","year":"2021","journal-title":"J Natl Compr Canc Netw"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2809927\/su_2023_oi_231029_1695236110.3471.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T15:01:08Z","timestamp":1695740468000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2809927"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,26]]},"references-count":34,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2023,9,5]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2023.35813","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,26]]}}}