{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:09:33Z","timestamp":1792706973784,"version":"4.5.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Lung cancer during pregnancy is exceedingly rare and poses unique diagnostic and therapeutic challenges. Clinical decisions must balance urgent, potentially lifesaving maternal treatment with fetal safety, often in the absence of evidence-based guidelines. This systematic review aimed to characterize clinical features, treatment patterns, and maternal\u2013fetal outcomes among reported cases of primary lung cancer diagnosed during pregnancy, focusing on case reports and case series.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We systematically searched PubMed, Embase, Scopus, and Google Scholar from 1948 through March 2024 for articles reporting primary lung cancer diagnosed during pregnancy. Eligible studies included case reports, case series, or observational reports providing individual-level data. We extracted demographics, tumor characteristics, staging, molecular profile, treatment type and timing (during pregnancy and postpartum), and maternal\u2013fetal outcomes. Descriptive statistics were performed, and exploratory analyses were conducted to assess associations between selected variables and outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 4,411 records were identified, and 88 publications contributing 96 unique cases met the inclusion criteria. The mean maternal age at diagnosis was 32.9 \u00b1 5.0 years (range 18\u201342). Most patients (65%) presented with stage III\u2013IV disease at diagnosis. Tobacco use was reported in 33% of cases and was significantly associated with advanced stage at presentation (p = 0.0006). Among tumors with reported molecular testing, 58.9% harbored actionable driver alterations, most commonly ALK rearrangements (32.9%) and EGFR mutations (21.4%). Chemotherapy during pregnancy was administered in 22.8% of cases, most commonly platinum-based doublets, with a mean gestational age at initiation of 21.8 weeks (SD \u00b1 10.4). Targeted therapies, including EGFR and ALK tyrosine kinase inhibitors, were typically initiated in the postpartum period in 30 patients (31.6% of the overall cohort). Among reported pregnancies, 69 (71.9%) resulted in live births. Term delivery occurred in 46.9% of cases, while preterm delivery occurred in 25.0%. Pregnancy termination was reported in 17.7% of cases and fetal demise in 1.0%. Advanced maternal disease stage was significantly associated with adverse fetal outcomes, including preterm delivery, pregnancy termination, or fetal demise (p &amp;lt; 0.0001).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Lung cancer during pregnancy most often presents at advanced stages, with a high prevalence of actionable molecular alterations. Multidisciplinary management and routine molecular profiling are essential. In the limited case-based literature, chemotherapy administered during the second and third trimesters has not demonstrated a clear signal of major congenital toxicity; however, these findings should be interpreted with caution, given the small sample size, heterogeneity of reporting, and lack of long-term follow-up. Targeted therapies are generally deferred until the postpartum period. Early diagnosis, optimized imaging protocols, and coordinated maternal\u2013fetal care are critical. International registries and consensus guidelines are urgently needed to guide treatment decisions and improve maternal and fetal outcomes in this rare clinical scenario.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1780320","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T04:49:14Z","timestamp":1778647754000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Treating without guidelines: management and outcomes of lung cancer diagnosed during pregnancy \u2014 a systematic review"],"prefix":"10.3389","volume":"16","author":[{"given":"Nehemias","family":"Guevara Rodriguez","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology, Oncology, and Bone Marrow Transplantation, SSM Health\u2013Saint Louis University School of Medicine","place":["St. Louis, MO, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noemy","family":"Coreas","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Gynecologic Oncology, Universidad de El Salvador (UES); Instituto Salvadore\u00f1o del Seguro Social (ISSS)","place":["San Salvador, El Salvador"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coral","family":"Olazagasti","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology and Oncology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine","place":["Miami, FL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Imbimbo","sequence":"additional","affiliation":[{"name":"Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Ospedale Regionale Bellinzona e Valli","place":["Bellinzona, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narjust","family":"Florez","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School","place":["Boston, MA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2002-0279","article-title":"Coexistence of pregnancy and Malignancy","volume":"7","author":"Pavlidis","year":"2002","journal-title":"Oncologist"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(04)01466-4","article-title":"Use of chemotherapy during human pregnancy","volume":"5","author":"Cardonick","year":"2004","journal-title":"Lancet Oncol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2005.10.014","article-title":"Cancer and pregnancy: poena magna, not anymore","volume":"42","author":"Pentheroudakis","year":"2006","journal-title":"Eur J Cancer"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1916623","article-title":"The effect of advances in lung-cancer treatment on population mortality","volume":"383","author":"Howlader","year":"2020","journal-title":"N Engl J Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1080\/714052775","article-title":"Lung cancer in pregnancy: case reports and review of the literature","volume":"10","author":"Mujaibel","year":"2001","journal-title":"J Matern Fetal Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.4065\/70.4.384","article-title":"Lung cancer complicating pregnancy: case report and review of the literature","volume":"70","author":"Van Winter","year":"1995","journal-title":"Mayo Clin Proc"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2007.10.010","article-title":"Lung cancer during pregnancy: an emerging issue","volume":"59","author":"Pavlidis","year":"2008","journal-title":"Lung Cancer"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2015.12.004","article-title":"Lung cancer during pregnancy: a narrative review","volume":"7","author":"Mitrou","year":"2016","journal-title":"J Adv Res"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1089\/whr.2023.0085","article-title":"Clinical features and management of lung cancer during pregnancy: a narrative review based on reported cases","volume":"4","author":"Zhou","year":"2023","journal-title":"Womens Health Rep (New Rochelle)"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.21037\/apm-20-999","article-title":"Three cases of lung cancer in pregnancy and literature review","volume":"9","author":"Han","year":"2020","journal-title":"Ann Palliat Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2024.02.005","article-title":"From approximation to precision: fertility and pregnancy questions in young patients with lung cancer","volume":"19","author":"Peccatori","year":"2024","journal-title":"J Thorac Oncol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000002355","article-title":"Guidelines for diagnostic imaging during pregnancy and lactation","volume":"130","year":"2017","journal-title":"Obstet Gynecol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60829-5","article-title":"Gynaecological cancers in pregnancy","volume":"379","author":"Morice","year":"2012","journal-title":"Lancet"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2015.2413","article-title":"Breast cancer during pregnancy","volume":"1","author":"Loibl","year":"2015","journal-title":"JAMA Oncol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1136\/ijgc-2018-000061","article-title":"Management of cancer during pregnancy and current evidence of obstetric, neonatal, and pediatric outcome: a review article","volume":"29","author":"Maggen","year":"2019","journal-title":"Int J Gynecol Cancer"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.suronc.2011.06.002","article-title":"Cancer and pregnancy: a comprehensive review","volume":"20","author":"Voulgaris","year":"2011","journal-title":"Surg Oncol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdt199","article-title":"Cancer, pregnancy and fertility: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"24","author":"Peccatori","year":"2013","journal-title":"Ann Oncol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3109\/00016349.2010.512070","article-title":"Pharmacokinetics of chemotherapeutic agents in pregnancy: a preclinical and clinical study","volume":"89","author":"Van Calsteren","year":"2010","journal-title":"Acta Obstet Gynecol Scand"},{"key":"B19","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1200\/JCO.2008.17.4110","article-title":"Cause-specific survival for women diagnosed with cancer during pregnancy: a registry-based cohort study","volume":"27","author":"Stensheim","year":"2009","journal-title":"J Clin Oncol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(11)70363-1","article-title":"Long-term cognitive and cardiac outcomes after prenatal exposure to chemotherapy in children aged 18 months or older: an observational study","volume":"13","author":"Amant","year":"2012","journal-title":"Lancet Oncol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpobgyn.2015.02.002","article-title":"Management of cancer in pregnancy","volume":"29","author":"Amant","year":"2015","journal-title":"Best Pract Res Clin Obstet Gynaecol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1097\/IGC.0b013e31821e73b2","article-title":"Management of cancer during pregnancy: obstetric and neonatal outcomes","volume":"21","author":"Lataifeh","year":"2011","journal-title":"Int J Gynecol Cancer"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1508913","article-title":"Pediatric outcome after maternal cancer diagnosed during pregnancy","volume":"373","author":"Amant","year":"2015","journal-title":"N Engl J Med"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2014.00157","article-title":"Treatment paradigms for patients with metastatic non-small cell lung cancer, squamous lung cancer: first, second, and third-line","volume":"4","author":"Al-Farsi","year":"2014","journal-title":"Front Oncol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1612674","article-title":"Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer","volume":"376","author":"Mok","year":"2017","journal-title":"N Engl J Med"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1801005","article-title":"Pembrolizumab plus chemotherapy in metastatic non\u2013small-cell lung cancer","volume":"378","author":"Gandhi","year":"2018","journal-title":"N Engl J Med"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(11)70232-7","article-title":"Effect of crizotinib on overall survival in ALK-positive non\u2013small-cell lung cancer","volume":"12","author":"Shaw","year":"2011","journal-title":"Lancet Oncol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0405220101","article-title":"EGF receptor gene mutations are common in lung cancers from \u201cnever smokers\u201d and are associated with sensitivity of tumors to gefitinib and erlotinib","volume":"101","author":"Pao","year":"2004","journal-title":"Proc Natl Acad Sci USA"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa040938","article-title":"Activating mutations in the epidermal growth factor receptor underlying responsiveness of non\u2013small-cell lung cancer to gefitinib","volume":"350","author":"Lynch","year":"2004","journal-title":"N Engl J Med"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2016.05.021","article-title":"Clinicopathologic features of non\u2013small-cell lung cancer diagnosed during pregnancy or the peripartum period","volume":"11","author":"Tansir","year":"2016","journal-title":"J\u00a0Thorac Oncol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2016.06.003","article-title":"Lung cancer in pregnancy\u2014A forgotten disease entity","volume":"11","author":"Rothschild","year":"2016","journal-title":"J Thorac Oncol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2021.02.005","article-title":"First case report of pregnancy on alectinib in a woman with metastatic ALK-rearranged lung cancer","volume":"16","author":"Weidenbaum","year":"2021","journal-title":"J\u00a0Thorac Oncol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2017.03.059","article-title":"Racial and ethnic disparities in early-stage lung cancer survival","volume":"145","author":"Soneji","year":"2014","journal-title":"Chest"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.02.1758","article-title":"The effect of race on invasive staging and surgery in non\u2013small-cell lung cancer","volume":"24","author":"Lathan","year":"2006","journal-title":"J Clin Oncol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1007\/s40615-023-01625-2","article-title":"Disparities in lung cancer: a targeted literature review examining lung cancer screening, diagnosis, treatment, and survival outcomes in the United States","volume":"11","author":"Dwyer","year":"2024","journal-title":"J Racial Ethn Health Disparities"},{"key":"B36","doi-asserted-by":"publisher","first-page":"78","DOI":"10.3322\/canjclin.54.2.78","article-title":"Cancer disparities by race\/ethnicity and socioeconomic status","volume":"54","author":"Ward","year":"2004","journal-title":"CA Cancer J Clin"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.2217\/fon-2022-0992","article-title":"Intersectionality in patients with cancer: who should care and why","volume":"18","author":"Chen","year":"2022","journal-title":"Future Oncol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1200\/EDBK_100037","article-title":"Patient-centered care in the management of cancer during pregnancy","volume":"43","author":"Sorouri","year":"2023","journal-title":"Am Soc Clin Oncol Educ Book"},{"key":"B39","doi-asserted-by":"publisher","first-page":"17","DOI":"10.3322\/caac.21763","article-title":"Cancer statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA Cancer J Clin"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2010.793","article-title":"Factors associated with decisions to undergo surgery among patients with newly diagnosed early-stage lung cancer","volume":"303","author":"Cykert","year":"2010","journal-title":"JAMA"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1780320\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T04:49:20Z","timestamp":1778647760000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1780320\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,13]]},"references-count":40,"alternative-id":["10.3389\/fonc.2026.1780320"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1780320","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,13]]},"article-number":"1780320"}}