Clinical insights into small cell lung cancer: Tumor heterogeneity, diagnosis, therapy, and future directions

Zsolt Megyesfalvi, Carl M Gay, Helmut Popper, Robert Pirker, Gyula Ostoros, Simon Heeke, Christian Lang, Konrad Hoetzenecker, Anna Schwendenwein, Kristiina Boettiger, Paul A Bunn Jr, Ferenc Renyi-Vamos, Karin Schelch, Helmut Prosch, Lauren A Byers, Fred R Hirsch, Balazs Dome, Zsolt Megyesfalvi, Carl M Gay, Helmut Popper, Robert Pirker, Gyula Ostoros, Simon Heeke, Christian Lang, Konrad Hoetzenecker, Anna Schwendenwein, Kristiina Boettiger, Paul A Bunn Jr, Ferenc Renyi-Vamos, Karin Schelch, Helmut Prosch, Lauren A Byers, Fred R Hirsch, Balazs Dome

Abstract

Small cell lung cancer (SCLC) is characterized by rapid growth and high metastatic capacity. It has strong epidemiologic and biologic links to tobacco carcinogens. Although the majority of SCLCs exhibit neuroendocrine features, an important subset of tumors lacks these properties. Genomic profiling of SCLC reveals genetic instability, almost universal inactivation of the tumor suppressor genes TP53 and RB1, and a high mutation burden. Because of early metastasis, only a small fraction of patients are amenable to curative-intent lung resection, and these individuals require adjuvant platinum-etoposide chemotherapy. Therefore, the vast majority of patients are currently being treated with chemoradiation with or without immunotherapy. In patients with disease confined to the chest, standard therapy includes thoracic radiotherapy and concurrent platinum-etoposide chemotherapy. Patients with metastatic (extensive-stage) disease are treated with a combination of platinum-etoposide chemotherapy plus immunotherapy with an anti-programmed death-ligand 1 monoclonal antibody. Although SCLC is initially very responsive to platinum-based chemotherapy, these responses are transient because of the development of drug resistance. In recent years, the authors have witnessed an accelerating pace of biologic insights into the disease, leading to the redefinition of the SCLC classification scheme. This emerging knowledge of SCLC molecular subtypes has the potential to define unique therapeutic vulnerabilities. Synthesizing these new discoveries with the current knowledge of SCLC biology and clinical management may lead to unprecedented advances in SCLC patient care. Here, the authors present an overview of multimodal clinical approaches in SCLC, with a special focus on illuminating how recent advancements in SCLC research could accelerate clinical development.

Keywords: chemotherapy; diagnosis; immunotherapy; molecular subtypes; small cell lung cancer.

© 2023 The Authors. CA: A Cancer Journal for Clinicians published by Wiley Periodicals LLC on behalf of American Cancer Society.

References

REFERENCES

    1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72(1):7-33. doi:10.3322/caac.21708
    1. Gazdar AF, Bunn PA, Minna JD. Small-cell lung cancer: what we know, what we need to know and the path forward. Nat Rev Cancer. 2017;17(12):725-737. doi:10.1038/nrc.2017.87
    1. George J, Lim JS, Jang SJ, et al. Comprehensive genomic profiles of small cell lung cancer. Nature. 2015;524(7563):47-53. doi:10.1038/nature14664
    1. Rudin CM, Brambilla E, Faivre-Finn C, Sage J. Small-cell lung cancer. Nat Rev Dis Primers. 2021;7(1):3. doi:10.1038/s41572-020-00235-0
    1. Jordan EJ, Kim HR, Arcila ME, et al. Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies. Cancer Discov. 2017;7(6):596-609. doi:10.1158/-16-1337
    1. Rudin CM, Poirier JT, Byers LA, et al. Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data. Nat Rev Cancer. 2019;19(5):289-297. doi:10.1038/s41568-019-0133-9
    1. Drapkin BJ, Rudin CM. Advances in small-cell lung cancer (SCLC) translational research. Cold Spring Harb Perspect Med. 2021;11(4):a038240. doi:10.1101/cshperspect.a038240
    1. Barnard WG. The nature of the “oat-celled sarcoma” of the mediastinum. J Pathol Bacteriol. 1926;29(3):241-244. doi:10.1002/path.1700290304
    1. Azzopardi JG. Oat-cell carcinoma of the bronchus. J Pathol Bacteriol. 1959;78(2):513-519. doi:10.1002/path.1700780218
    1. Haddadin S, Perry MC. History of small-cell lung cancer. Clin Lung Cancer. 2011;12(2):87-93. doi:10.1016/j.cllc.2011.03.002
    1. Matthews MJ, Kanhouwa S, Pickren J, Robinette D. Frequency of residual and metastatic tumor in patients undergoing curative surgical resection for lung cancer. Cancer Chemother Rep 3. 1973;4:63-67.
    1. Skarlos DV, Samantas E, Kosmidis P, et al. Randomized comparison of etoposide-cisplatin vs. etoposide-carboplatin and irradiation in small-cell lung cancer. A Hellenic Co-operative Oncology Group study. Ann Oncol. 1994;5(7):601-607. doi:10.1093/oxfordjournals.annonc.a058931
    1. Karim SM, Zekri J. Chemotherapy for small cell lung cancer: a comprehensive review. Oncol Rev. 2012;6(1):e4. doi:10.4081/oncol.2012.e4
    1. Rudin CM, Poirier JT. Small-cell lung cancer in 2016: shining light on novel targets and therapies. Nat Rev Clin Oncol. 2017;14(2):75-76. doi:10.1038/nrclinonc.2016.203
    1. Evans WK, Shepherd FA, Feld R, Osoba D, Dang P, Deboer G. VP-16 and cisplatin as first-line therapy for small-cell lung cancer. J Clin Oncol. 1985;3(11):1471-1477. doi:10.1200/jco.1985.3.11.1471
    1. Hirsch FR, Hansen HH, Hansen M, et al. The superiority of combination chemotherapy including etoposide based on in vivo cell cycle analysis in the treatment of extensive small-cell lung cancer: a randomized trial of 288 consecutive patients. J Clin Oncol. 1987;5(4):585-591. doi:10.1200/jco.1987.5.4.585
    1. Paul A.Bunn Jr, Greco FA, Einhorn L. Cyclophosphamide, doxorubicin, and etoposide as first-line therapy in the treatment of small-cell lung cancer. Semin Oncol. 1986;13:45-53.
    1. Ragavan M, Das M. Systemic therapy of extensive stage small cell lung cancer in the era of immunotherapy. Curr Treat Options Oncol. 2020;21(8):64. doi:10.1007/s11864-020-00762-8
    1. Horn L, Mansfield AS, Szczęsna A, et al. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018;379(23):2220-2229. doi:10.1056/nejmoa1809064
    1. Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019;394(10212):1929-1939. doi:10.1016/s0140-6736(19)32222-6
    1. Bray F, Ferlay J, Laversanne M, et al. Cancer Incidence in Five Continents: inclusion criteria, highlights from volume X and the global status of cancer registration. Int J Cancer. 2015;137(9):2060-2071. doi:10.1002/ijc.29670
    1. Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73(1):17-48. doi:10.3322/caac.21763
    1. Huang R, Wei Y, Hung RJ, et al. Associated links among smoking, chronic obstructive pulmonary disease, and small cell lung cancer: a pooled analysis in the International Lung Cancer Consortium. EBioMedicine. 2015;2(11):1677-1685. doi:10.1016/j.ebiom.2015.09.031
    1. Basumallik N, Agarwal M. Small Cell Lung Cancer. StatPearls Publishing LLC; 2022.
    1. Ragavan M, Patel MI. The evolving landscape of sex-based differences in lung cancer: a distinct disease in women. Eur Respir Rev. 2022;31(163):210100. doi:10.1183/16000617.0100-2021
    1. Torre LA, Siegel RL, Jemal A. Lung cancer statistics. Adv Exp Med Biol. 2016;893:1-19.
    1. Zhou K, Shi H, Chen R, et al. Association of race, socioeconomic factors, and treatment characteristics with overall survival in patients with limited-stage small cell lung cancer. JAMA Netw Open. 2021;4(1):e2032276. doi:10.1001/jamanetworkopen.2020.32276
    1. American Lung Association. Tobacco Use in Racial and Ethnic Populations. American Lung Association; 2022. <zaq;12>Accessed December 7, 2022.
    1. Stram DO, Park SL, Haiman CA, et al. Racial/ethnic differences in lung cancer incidence in the Multiethnic Cohort Study: an update. J Natl Cancer Inst. 2019;111(8):811-819. doi:10.1093/jnci/djy206
    1. Schwendenwein A, Megyesfalvi Z, Barany N, et al. Molecular profiles of small cell lung cancer subtypes: therapeutic implications. Mol Ther Oncolytics. 2021;20:470-483. doi:10.1016/j.omto.2021.02.004
    1. Wang S, Tang J, Sun T, et al. Survival changes in patients with small cell lung cancer and disparities between different sexes, socioeconomic statuses and ages. Sci Rep. 2017;7(1):1339. doi:10.1038/s41598-017-01571-0
    1. Siegel DA, Fedewa SA, Henley SJ, Pollack LA, Jemal A. Proportion of never smokers among men and women with lung cancer in 7 US states. JAMA Oncol. 2021;7(2):302-304. doi:10.1001/jamaoncol.2020.6362
    1. Khuder SA. Effect of cigarette smoking on major histological types of lung cancer: a meta-analysis. Lung Cancer. 2001;31(2-3):139-148. doi:10.1016/s0169-5002(00)00181-1
    1. Kim CH, Lee YC, Hung RJ, et al. Exposure to secondhand tobacco smoke and lung cancer by histological type: a pooled analysis of the International Lung Cancer Consortium (ILCCO). Int J Cancer. 2014;135(8):1918-1930. doi:10.1002/ijc.28835
    1. Sun JM, Choi YL, Ji JH, et al. Small-cell lung cancer detection in never-smokers: clinical characteristics and multigene mutation profiling using targeted next-generation sequencing. Ann Oncol. 2015;26(1):161-166. doi:10.1093/annonc/mdu504
    1. Liu X, Jiang T, Li W, et al. Characterization of never-smoking and its association with clinical outcomes in Chinese patients with small-cell lung cancer. Lung Cancer. 2018;115:109-115. doi:10.1016/j.lungcan.2017.11.022
    1. Hecht SS. Lung carcinogenesis by tobacco smoke. Int J Cancer. 2012;131(12):2724-2732. doi:10.1002/ijc.27816
    1. Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease: A Report of the Surgeon General. Centers for Disease Control and Prevention (US); 2010.
    1. Van Duuren BL, Goldschmidt BM. Cocarcinogenic and tumor-promoting agents in tobacco carcinogenesis. J Natl Cancer Inst. 1976;56(6):1237-1242. doi:10.1093/jnci/56.6.1237
    1. Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation. Signal Transduct Targeted Ther. 2017;2(1):17023. doi:10.1038/sigtrans.2017.23
    1. Smith CJ, Perfetti TA, King JA. Perspectives on pulmonary inflammation and lung cancer risk in cigarette smokers. Inhal Toxicol. 2006;18(9):667-677. doi:10.1080/08958370600742821
    1. Wong KK, Jacks T, Dranoff G. NF-κB fans the flames of lung carcinogenesis. Cancer Prev Res. 2010;3(4):403-405. doi:10.1158/1940-6207.capr-10-0042
    1. Liu J, Chen SJ, Hsu SW, et al. MARCKS cooperates with NKAP to activate NF-kB signaling in smoke-related lung cancer. Theranostics. 2021;11(9):4122-4136. doi:10.7150/thno.53558
    1. Thomas A, Mian I, Tlemsani C, et al. Clinical and genomic characteristics of small cell lung cancer in never smokers: results from a retrospective multicenter cohort study. Chest. 2020;158(4):1723-1733. doi:10.1016/j.chest.2020.04.068
    1. Torres-Durán M, Curiel-García MT, Ruano-Ravina A, et al. Small-cell lung cancer in never-smokers. ESMO Open. 2021;6(2):100059. doi:10.1016/j.esmoop.2021.100059
    1. Rodríguez-Martínez Á, Torres-Durán M, Barros-Dios JM, Ruano-Ravina A. Residential radon and small cell lung cancer. a systematic review. Cancer Lett. 2018;426:57-62. doi:10.1016/j.canlet.2018.04.003
    1. Hystad P, Demers PA, Johnson KC, Carpiano RM, Brauer M. Long-term residential exposure to air pollution and lung cancer risk. Epidemiology. 2013;24(5):762-772. doi:10.1097/ede.0b013e3182949ae7
    1. Lamichhane DK, Kim HC, Choi CM, et al. Lung cancer risk and residential exposure to air pollution: a Korean population-based case-control study. Yonsei Med J. 2017;58(6):1111-1118. doi:10.3349/ymj.2017.58.6.1111
    1. Wang J, Liu Q, Yuan S, et al. Genetic predisposition to lung cancer: comprehensive literature integration, meta-analysis, and multiple evidence assessment of candidate-gene association studies. Sci Rep. 2017;7(1):8371. doi:10.1038/s41598-017-07737-0
    1. Harbour JW, Lai SL, Whang-Peng J, Gazdar AF, Minna JD, Kaye FJ. Abnormalities in structure and expression of the human retinoblastoma gene in SCLC. Science. 1988;241(4863):353-357. doi:10.1126/science.2838909
    1. Takahashi T, Nau MM, Chiba I, et al. p53: a frequent target for genetic abnormalities in lung cancer. Science. 1989;246(4929):491-494. doi:10.1126/science.2554494
    1. Sutherland KD, Proost N, Brouns I, Adriaensen D, Song JY, Berns A. Cell of origin of small cell lung cancer: inactivation of Trp53 and Rb1 in distinct cell types of adult mouse lung. Cancer Cell. 2011;19(6):754-764. doi:10.1016/j.ccr.2011.04.019
    1. Huang YH, Klingbeil O, He XY, et al. POU2F3 is a master regulator of a tuft cell-like variant of small cell lung cancer. Genes Dev. 2018;32(13-14):915-928. doi:10.1101/gad.314815.118
    1. Chen HJ, Poran A, Unni AM, et al. Generation of pulmonary neuroendocrine cells and SCLC-like tumors from human embryonic stem cells. J Exp Med. 2019;216(3):674-687. doi:10.1084/jem.20181155
    1. Quintanal-Villalonga Á, Chan JM, Yu HA, et al. Lineage plasticity in cancer: a shared pathway of therapeutic resistance. Nat Rev Clin Oncol. 2020;17(6):360-371. doi:10.1038/s41571-020-0340-z
    1. Niederst MJ, Sequist LV, Poirier JT, et al. RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer. Nat Commun. 2015;6(1):6377. doi:10.1038/ncomms7377
    1. Gazeu A, Aubert M, Pissaloux D, et al. Small-cell lung cancer transformation as a mechanism of resistance to pralsetinib in RET-rearranged lung adenocarcinoma: a case report. Clin Lung Cancer. 2023;24(1):72-75. doi:10.1016/j.cllc.2022.10.005
    1. Offin M, Chan JM, Tenet M, et al. Concurrent RB1 and TP53 alterations define a subset of EGFR-mutant lung cancers at risk for histologic transformation and inferior clinical outcomes. J Thorac Oncol. 2019;14(10):1784-1793. doi:10.1016/j.jtho.2019.06.002
    1. Oser MG, Niederst MJ, Sequist LV, Engelman JA. Transformation from non-small-cell lung cancer to small-cell lung cancer: molecular drivers and cells of origin. Lancet Oncol. 2015;16(4):e165-e172. doi:10.1016/s1470-2045(14)71180-5
    1. Piper-Vallillo AJ, Sequist LV, Piotrowska Z. Emerging treatment paradigms for EGFR-mutant lung cancers progressing on osimertinib: a review. J Clin Oncol. 2020;38(25):2926-2936. doi:10.1200/jco.19.03123
    1. Marcoux N, Gettinger SN, O'Kane G, et al. EGFR-mutant adenocarcinomas that transform to small-cell lung cancer and other neuroendocrine carcinomas: clinical outcomes. J Clin Oncol. 2019;37(4):278-285. doi:10.1200/jco.18.01585
    1. Ferrer L, Giaj Levra M, Brevet M, et al. A brief report of transformation from NSCLC to SCLC: molecular and therapeutic characteristics. J Thorac Oncol. 2019;14(1):130-134. doi:10.1016/j.jtho.2018.08.2028
    1. Balla A, Khan F, Hampel KJ, Aisner DL, Sidiropoulos N. Small-cell transformation of ALK-rearranged non-small-cell adenocarcinoma of the lung. Cold Spring Harb Mol Case Stud. 2018;4(2):a002394. doi:10.1101/mcs.a002394
    1. Ahmed T, Vial MR, Ost D, Stewart J, Hasan MA, Grosu HB. Non-small cell lung cancer transdifferentiation into small cell lung cancer: a case series. Lung Cancer. 2018;122:220-223. doi:10.1016/j.lungcan.2018.06.024
    1. Puca L, Vlachostergios PJ, Beltran H. Neuroendocrine differentiation in prostate cancer: emerging biology, models, and therapies. Cold Spring Harb Perspect Med. 2019;9(2):a030593. doi:10.1101/cshperspect.a030593
    1. Peifer M, Fernández-Cuesta L, Sos ML, et al. Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer. Nat Genet. 2012;44(10):1104-1110. doi:10.1038/ng.2396
    1. Rudin CM, Durinck S, Stawiski EW, et al. Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer. Nat Genet. 2012;44(10):1111-1116. doi:10.1038/ng.2405
    1. Romero OA, Torres-Diz M, Pros E, et al. MAX inactivation in small cell lung cancer disrupts MYC-SWI/SNF programs and is synthetic lethal with BRG1. Cancer Discov. 2014;4(3):292-303. doi:10.1158/-13-0799
    1. Mollaoglu G, Guthrie MR, Böhm S, et al. MYC drives progression of small cell lung cancer to a variant neuroendocrine subtype with vulnerability to aurora kinase inhibition. Cancer Cell. 2017;31(2):270-285. doi:10.1016/j.ccell.2016.12.005
    1. Patel AS, Yoo S, Kong R, et al. Prototypical oncogene family Myc defines unappreciated distinct lineage states of small cell lung cancer. Sci Adv. 2021;7(5). doi:10.1126/sciadv.abc2578
    1. Augustyn A, Borromeo M, Wang T, et al. ASCL1 is a lineage oncogene providing therapeutic targets for high-grade neuroendocrine lung cancers. Proc Natl Acad Sci U S A. 2014;111(41):14788-14793. doi:10.1073/pnas.1410419111
    1. Meder L, König K, Ozretić L, et al. NOTCH, ASCL1, p53 and RB alterations define an alternative pathway driving neuroendocrine and small cell lung carcinomas. Int J Cancer. 2016;138(4):927-938. doi:10.1002/ijc.29835
    1. Lim JS, Ibaseta A, Fischer MM, et al. Intratumoural heterogeneity generated by Notch signalling promotes small-cell lung cancer. Nature. 2017;545(7654):360-364. doi:10.1038/nature22323
    1. Bensch KG, Corrin B, Pariente R, Spencer H. Oat-cell carcinoma of the lung. Its origin and relationship to bronchial carcinoid. Cancer. 1968;22(6):1163-1172. doi:10.1002/1097-0142(196811)22:6<1163::aid-cncr2820220612>;2-l
    1. Carney DN, Gazdar AF, Bepler G, et al. Establishment and identification of small cell lung cancer cell lines having classic and variant features. Cancer Res. 1985;45:2913-2923.
    1. Berniker AV, Abdulrahman AA, Teytelboym OM, Galindo LM, Mackey JE. Extrapulmonary small cell carcinoma: imaging features with radiologic-pathologic correlation. Radiographics. 2015;35(1):152-163. doi:10.1148/rg.351140050
    1. Gazdar AF, Carney DN, Nau MM, Minna JD. Characterization of variant subclasses of cell lines derived from small cell lung cancer having distinctive biochemical, morphological, and growth properties. Cancer Res. 1985;45:2924-2930.
    1. Denny SK, Yang D, Chuang CH, et al. Nfib promotes metastasis through a widespread increase in chromatin accessibility. Cell. 2016;166(2):328-342. doi:10.1016/j.cell.2016.05.052
    1. Semenova EA, Kwon MC, Monkhorst K, et al. Transcription factor NFIB is a driver of small cell lung cancer progression in mice and marks metastatic disease in patients. Cell Rep. 2016;16(3):631-643. doi:10.1016/j.celrep.2016.06.020
    1. Ko J, Winslow MM, Sage J. Mechanisms of small cell lung cancer metastasis. EMBO Mol Med. 2021;13(1):e13122. doi:10.15252/emmm.202013122
    1. Wu Q, Guo J, Liu Y, et al. YAP drives fate conversion and chemoresistance of small cell lung cancer. Sci Adv. 2021;7(40):eabg1850. doi:10.1126/sciadv.abg1850
    1. Yang D, Qu F, Cai H, et al. Axon-like protrusions promote small cell lung cancer migration and metastasis. Elife. 2019;8:e50616. doi:10.7554/elife.50616
    1. Zhang W, Girard L, Zhang YA, et al. Small cell lung cancer tumors and preclinical models display heterogeneity of neuroendocrine phenotypes. Transl Lung Cancer Res. 2018;7(1):32-49. doi:10.21037/tlcr.2018.02.02
    1. Lohinai Z, Megyesfalvi Z, Suda K, et al. Comparative expression analysis in small cell lung carcinoma reveals neuroendocrine pattern change in primary tumor versus lymph node metastases. Transl Lung Cancer Res. 2019;8(6):938-950. doi:10.21037/tlcr.2019.11.30
    1. Dora D, Rivard C, Yu H, et al. Neuroendocrine subtypes of small cell lung cancer differ in terms of immune microenvironment and checkpoint molecule distribution. Mol Oncol. 2020;14(9):1947-1965. doi:10.1002/1878-0261.12741
    1. Park H, Tseng SC, Sholl LM, Hatabu H, Awad MM, Nishino M. Molecular characterization and therapeutic approaches to small cell lung cancer: imaging implications. Radiology. 2022;305(3):512-525. doi:10.1148/radiol.220585
    1. Poirier JT, George J, Owonikoko TK, et al. New approaches to SCLC therapy: from the laboratory to the clinic. J Thorac Oncol. 2020;15(4):520-540. doi:10.1016/j.jtho.2020.01.016
    1. Baine MK, Hsieh MS, Lai WV, et al. SCLC subtypes defined by ASCL1, NEUROD1, POU2F3, and YAP1: a comprehensive immunohistochemical and histopathologic characterization. J Thorac Oncol. 2020;15(12):1823-1835. doi:10.1016/j.jtho.2020.09.009
    1. Megyesfalvi Z, Barany N, Lantos A, et al. Expression patterns and prognostic relevance of subtype-specific transcription factors in surgically resected small-cell lung cancer: an international multicenter study. J Pathol. 2022;257(5):674-686. doi:10.1002/path.5922
    1. Handa T, Hayashi T, Ura A, et al. Comparison of ASCL1, NEUROD1, and POU2F3 expression in surgically resected specimens, paired tissue microarrays, and lymph node metastases in small cell lung carcinoma. Histopathology. 2023;82(6):860-869. doi:10.1111/his.14872
    1. Qi J, Zhang J, Liu N, Zhao L, Xu B. Prognostic implications of molecular subtypes in primary small cell lung cancer and their correlation with cancer immunity. Front Oncol. 2022;12:779276. doi:10.3389/fonc.2022.779276
    1. Furuta M, Sakakibara-Konishi J, Kikuchi H, et al. Analysis of DLL3 and ASCL1 in surgically resected small cell lung cancer (HOT1702). Oncologist. 2019;24(11):e1172-e1179. doi:10.1634/theoncologist.2018-0676
    1. Kosari F, Ida CM, Aubry MC, et al. ASCL1 and RET expression defines a clinically relevant subgroup of lung adenocarcinoma characterized by neuroendocrine differentiation. Oncogene. 2014;33(29):3776-3783. doi:10.1038/onc.2013.359
    1. Wooten DJ, Groves SM, Tyson DR, et al. Systems-level network modeling of small cell lung cancer subtypes identifies master regulators and destabilizers. PLoS Comput Biol. 2019;15(10):e1007343. doi:10.1371/journal.pcbi.1007343
    1. Poirier JT, Dobromilskaya I, Moriarty WF, Peacock CD, Hann CL, Rudin CM. Selective tropism of Seneca Valley virus for variant subtype small cell lung cancer. J Natl Cancer Inst. 2013;105(14):1059-1065. doi:10.1093/jnci/djt130
    1. Baine MK, Febres-Aldana CA, Chang JC, et al. POU2F3 in SCLC: clinicopathologic and genomic analysis with a focus on its diagnostic utility in neuroendocrine-low SCLC. J Thorac Oncol. 2022;17(9):1109-1121. doi:10.1016/j.jtho.2022.06.004
    1. Gay CM, Stewart CA, Park EM, et al. Patterns of transcription factor programs and immune pathway activation define four major subtypes of SCLC with distinct therapeutic vulnerabilities. Cancer Cell. 2021;39(3):346-360.e7. doi:10.1016/j.ccell.2020.12.014
    1. Caeser R, Egger JV, Chavan S, et al. Genomic and transcriptomic analysis of a library of small cell lung cancer patient-derived xenografts. Nat Commun. 2022;13(1):2144. doi:10.1038/s41467-022-29794-4
    1. Simpson KL, Stoney R, Frese KK, et al. A biobank of small cell lung cancer CDX models elucidates inter- and intratumoral phenotypic heterogeneity. Nat Cancer. 2020;1(4):437-451. doi:10.1038/s43018-020-0046-2
    1. Borromeo MD, Savage TK, Kollipara RK, et al. ASCL1 and NEUROD1 reveal heterogeneity in pulmonary neuroendocrine tumors and regulate distinct genetic programs. Cell Rep. 2016;16(5):1259-1272. doi:10.1016/j.celrep.2016.06.081
    1. Owonikoko TK, Dwivedi B, Chen Z, et al. YAP1 expression in SCLC defines a distinct subtype with T-cell-inflamed phenotype. J Thorac Oncol. 2021;16(3):464-476. doi:10.1016/j.jtho.2020.11.006
    1. Stewart CA, Gay CM, Xi Y, et al. Single-cell analyses reveal increased intratumoral heterogeneity after the onset of therapy resistance in small-cell lung cancer. Nat Cancer. 2020;1(4):423-436. doi:10.1038/s43018-019-0020-z
    1. Szeitz B, Megyesfalvi Z, Woldmar N, et al. In-depth proteomic analysis reveals unique subtype-specific signatures in human small-cell lung cancer. Clin Transl Med. 2022;12(9):e1060. doi:10.1002/ctm2.1060
    1. Poirier JT, Gardner EE, Connis N, et al. DNA methylation in small cell lung cancer defines distinct disease subtypes and correlates with high expression of EZH2. Oncogene. 2015;34(48):5869-5878. doi:10.1038/onc.2015.38
    1. Valko Z, Megyesfalvi Z, Schwendenwein A, et al. Dual targeting of BCL-2 and MCL-1 in the presence of BAX breaks venetoclax resistance in human small cell lung cancer. Br J Cancer. Published online March 14, 2023. doi:10.1038/s41416-023-02219-9
    1. Takagi S, Ishikawa Y, Mizutani A, et al. LSD1 inhibitor T-3775440 inhibits SCLC cell proliferation by disrupting LSD1 interactions with SNAG domain proteins INSM1 and GFI1B. Cancer Res. 2017;77(17):4652-4662. doi:10.1158/0008-5472.can-16-3502
    1. Chalishazar MD, Wait SJ, Huang F, et al. MYC-driven small-cell lung cancer is metabolically distinct and vulnerable to arginine depletion. Clin Cancer Res. 2019;25(16):5107-5121. doi:10.1158/1078-0432.ccr-18-4140
    1. McColl K, Wildey G, Sakre N, et al. Reciprocal expression of INSM1 and YAP1 defines subgroups in small cell lung cancer. Oncotarget. 2017;8(43):73745-73756. doi:10.18632/oncotarget.20572
    1. Horie M, Saito A, Ohshima M, Suzuki HI, Nagase T. YAP and TAZ modulate cell phenotype in a subset of small cell lung cancer. Cancer Sci. 2016;107(12):1755-1766. doi:10.1111/cas.13078
    1. Oboshi S, Tsugawa S, Seido T, Shimosato Y, Koide T. A new floating cell line derived from human pulmonary carcinoma of oat cell type. Gan. 1971;62:505-514.
    1. Ohara H, Okamoto T. A new in vitro cell line established from human oat cell carcinoma of the lung. Cancer Res. 1977;37:3088-3095.
    1. Ramirez RD, Sheridan S, Girard L, et al. Immortalization of human bronchial epithelial cells in the absence of viral oncoproteins. Cancer Res. 2004;64(24):9027-9034. doi:10.1158/0008-5472.can-04-3703
    1. Gazdar AF, Girard L, Lockwood WW, Lam WL, Minna JD. Lung cancer cell lines as tools for biomedical discovery and research. J Natl Cancer Inst. 2010;102(17):1310-1321. doi:10.1093/jnci/djq279
    1. Sato T, Stange DE, Ferrante M, et al. Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett's epithelium. Gastroenterology. 2011;141(5):1762-1772. doi:10.1053/j.gastro.2011.07.050
    1. Rossi R, De Angelis ML, Xhelili E, et al. Lung cancer organoids: the rough path to personalized medicine. Cancers (Basel). 2022;14(15):3703. doi:10.3390/cancers14153703
    1. Berns A, Barbacid M. Mouse models of cancer. Mol Oncol. 2013;7(2):143-145. doi:10.1016/j.molonc.2013.02.014
    1. Gazdar AF, Savage TK, Johnson JE, et al. The comparative pathology of genetically engineered mouse models for neuroendocrine carcinomas of the lung. J Thorac Oncol. 2015;10(4):553-564. doi:10.1097/jto.0000000000000459
    1. Schaffer BE, Park KS, Yiu G, et al. Loss of p130 accelerates tumor development in a mouse model for human small-cell lung carcinoma. Cancer Res. 2010;70(10):3877-3883. doi:10.1158/0008-5472.can-09-4228
    1. McFadden DG, Papagiannakopoulos T, Taylor-Weiner A, et al. Genetic and clonal dissection of murine small cell lung carcinoma progression by genome sequencing. Cell. 2014;156(6):1298-1311. doi:10.1016/j.cell.2014.02.031
    1. Meuwissen R, Linn SC, Linnoila RI, Zevenhoven J, Mooi WJ, Berns A. Induction of small cell lung cancer by somatic inactivation of both Trp53 and Rb1 in a conditional mouse model. Cancer Cell. 2003;4(3):181-189. doi:10.1016/s1535-6108(03)00220-4
    1. Nguyen EM, Taniguchi H, Chan JM, et al. Targeting lysine-specific demethylase 1 rescues major histocompatibility complex class I antigen presentation and overcomes programmed death-ligand 1 blockade resistance in SCLC. J Thorac Oncol. 2022;17(8):1014-1031. doi:10.1016/j.jtho.2022.05.014
    1. Daniel VC, Marchionni L, Hierman JS, et al. A primary xenograft model of small-cell lung cancer reveals irreversible changes in gene expression imposed by culture in vitro. Cancer Res. 2009;69(8):3364-3373. doi:10.1158/0008-5472.can-08-4210
    1. Frese KK, Tuveson DA. Maximizing mouse cancer models. Nat Rev Cancer. 2007;7(9):645-658. doi:10.1038/nrc2192
    1. Drapkin BJ, George J, Christensen CL, et al. Genomic and Functional fidelity of small cell lung cancer patient-derived xenografts. Cancer Discov. 2018;8(5):600-615. doi:10.1158/-17-0935
    1. Fujiwara S. Humanized mice: a brief overview on their diverse applications in biomedical research. J Cell Physiol. 2018;233(4):2889-2901. doi:10.1002/jcp.26022
    1. Megyesfalvi Z, Tallosy B, Pipek O, et al. The landscape of small cell lung cancer metastases: organ specificity and timing. Thorac Cancer. 2021;12(6):914-923. doi:10.1111/1759-7714.13854
    1. Gandhi L, Johnson BE. Paraneoplastic syndromes associated with small cell lung cancer. J Natl Compr Cancer Netw. 2006;4(6):631-638. doi:10.6004/jnccn.2006.0052
    1. Iams WT, Shiuan E, Meador CB, et al. Improved prognosis and increased tumor-infiltrating lymphocytes in patients who have SCLC with neurologic paraneoplastic syndromes. J Thorac Oncol. 2019;14(11):1970-1981. doi:10.1016/j.jtho.2019.05.042
    1. Soomro Z, Youssef M, Yust-Katz S, Jalali A, Patel AJ, Mandel J. Paraneoplastic syndromes in small cell lung cancer. J Thorac Dis. 2020;12(10):6253-6263. doi:10.21037/jtd.2020.03.88
    1. Anwar A, Jafri F, Ashraf S, Jafri MAS, Fanucchi M. Paraneoplastic syndromes in lung cancer and their management. Ann Transl Med. 2019;7(15):359. doi:10.21037/atm.2019.04.86
    1. Binks S, Uy C, Honnorat J, Irani SR. Paraneoplastic neurological syndromes: a practical approach to diagnosis and management. Pract Neurol. 2022;22(1):19-31. doi:10.1136/practneurol-2021-003073
    1. Lennon VA, Kryzer TJ, Griesmann GE, et al. Calcium-channel antibodies in the Lambert-Eaton syndrome and other paraneoplastic syndromes. N Engl J Med. 1995;332(22):1467-1474. doi:10.1056/nejm199506013322203
    1. Winkler AS, Dean A, Hu M, Gregson N, Chaudhuri KR. Phenotypic and neuropathologic heterogeneity of anti-Hu antibody-related paraneoplastic syndrome presenting with progressive dysautonomia: report of two cases. Clin Auton Res. 2001;11(2):115-118. doi:10.1007/bf02322055
    1. Dalmau J, Furneaux HM, Cordon-Cardo C, Posner JB. The expression of the Hu (paraneoplastic encephalomyelitis/sensory neuronopathy) antigen in human normal and tumor tissues. Am J Pathol. 1992;141:881-886.
    1. Mutoh T, Tachi M, Yano S, Mihara T, Yamamoto H. Impairment of Trk-neurotrophin receptor by the serum of a patient with subacute sensory neuropathy. Arch Neurol. 2005;62(10):1612-1615. doi:10.1001/archneur.62.10.1612
    1. Panunzio A, Sartori P. Lung cancer and radiological imaging. Curr Radiopharm. 2020;13(3):238-242. doi:10.2174/1874471013666200523161849
    1. Gridelli C, Rossi A, Carbone DP, et al. Non-small-cell lung cancer. Nat Rev Dis Primers. 2015;1:15009. doi:10.1038/nrdp.2015.9
    1. Danaher L, Niknejad M, El-Feky M. Small cell lung cancer. Accessed December 7, 2022. <zaq;13>
    1. Purandare NC, Rangarajan V. Imaging of lung cancer: implications on staging and management. Indian J Radiol Imaging. 2015;25(02):109-120. doi:10.4103/0971-3026.155831
    1. Kalemkerian GP. Staging and imaging of small cell lung cancer. Cancer Imaging. 2012;11(1):253-258. doi:10.1102/1470-7330.2011.0036
    1. Martucci F, Pascale M, Valli MC, et al. Impact of (18)F-FDG PET/CT in staging patients with small cell lung cancer: a systematic review and meta-analysis. Front Med. 2019;6:336. doi:10.3389/fmed.2019.00336
    1. van der Leest C, Smit EF, Baas J, et al. SUVmax during 18FDG-PET scanning in small cell lung cancer: similar information as in non-small cell lung cancer? Lung Cancer. 2012;76(1):67-71. doi:10.1016/j.lungcan.2011.09.007
    1. Zer A, Domachevsky L, Rapson Y, et al. The role of 18F-FDG PET/CT on staging and prognosis in patients with small cell lung cancer. Eur Radiol. 2016;26(9):3155-3161. doi:10.1007/s00330-015-4132-2
    1. Lapa C, Hänscheid H, Wild V, et al. Somatostatin receptor expression in small cell lung cancer as a prognostic marker and a target for peptide receptor radionuclide therapy. Oncotarget. 2016;7(15):20033-20040. doi:10.18632/oncotarget.7706
    1. Yung RC. Tissue diagnosis of suspected lung cancer: selecting between bronchoscopy, transthoracic needle aspiration, and resectional biopsy. Respir Care Clin. 2003;9(1):51-76. doi:10.1016/s1078-5337(02)00083-7
    1. Rivera MP, Mehta AC, Wahidi MM. Establishing the diagnosis of lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143(5 suppl):e142S-e165S. doi:10.1378/chest.12-2353
    1. van Overhagen H, Brakel K, Heijenbrok MW, et al. Metastases in supraclavicular lymph nodes in lung cancer: assessment with palpation, US, and CT. Radiology. 2004;232(1):75-80. doi:10.1148/radiol.2321030663
    1. El-Bayoumi E, Silvestri GA. Bronchoscopy for the diagnosis and staging of lung cancer. Semin Respir Crit Care Med. 2008;29(3):261-270. doi:10.1055/s-2008-1076746
    1. Prosch H, Strasser G, Sonka C, et al. Cervical ultrasound (US) and US-guided lymph node biopsy as a routine procedure for staging of lung cancer. Ultraschall Med. 2007;28(06):598-603. doi:10.1055/s-2007-963215
    1. Chen CC, Bai CH, Lee KY, Chou YT, Pan ST, Wang YH. Evaluation of the diagnostic accuracy of bronchial brushing cytology in lung cancer: a meta-analysis. Cancer Cytopathol. 2021;129(9):739-749. doi:10.1002/cncy.22436
    1. Chandrika S, Yarmus L. Recent developments in advanced diagnostic bronchoscopy. Eur Respir Rev. 2020;29(157):190184. doi:10.1183/16000617.0184-2019
    1. Sehgal IS, Agarwal R, Dhooria S, Prasad KT, Aggarwal AN. Role of EBUS TBNA in staging of lung cancer: a clinician's perspective. J Cytol. 2019;36(1):61-64. doi:10.4103/joc.joc_172_18
    1. Um SW, Kim HK, Jung SH, et al. Endobronchial ultrasound versus mediastinoscopy for mediastinal nodal staging of non-small-cell lung cancer. J Thorac Oncol. 2015;10(2):331-337. doi:10.1097/jto.0000000000000388
    1. Detterbeck FC, Lewis SZ, Diekemper R, Addrizzo-Harris D, Alberts WM. Executive summary: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143(5 suppl):7S-37S. doi:10.1378/chest.12-2377
    1. Rivera MP, Mehta AC. Initial diagnosis of lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest. 2007;132(3 suppl):131S-148S. doi:10.1378/chest.07-1357
    1. Lee KH, Lim KY, Suh YJ, et al. Diagnostic accuracy of percutaneous transthoracic needle lung biopsies: a multicenter study. Korean J Radiol. 2019;20(8):1300-1310. doi:10.3348/kjr.2019.0189
    1. Borelli C, Vergara D, Simeone A, et al. CT-guided transthoracic biopsy of pulmonary lesions: diagnostic versus nondiagnostic results. Diagnostics (Basel). 2022;12(2):359. doi:10.3390/diagnostics12020359
    1. Sihoe ADL, Hiranandani R, Wong H, Yeung ESL. Operating on a suspicious lung mass without a preoperative tissue diagnosis: pros and cons. Eur J Cardiothorac Surg. 2013;44(2):231-237. doi:10.1093/ejcts/ezs671
    1. Pizzutilo EG, Pedrani M, Amatu A, et al. Liquid biopsy for small cell lung cancer either de novo or transformed: systematic review of different applications and meta-analysis. Cancers (Basel). 2021;13(9):2265. doi:10.3390/cancers13092265
    1. Mohan S, Foy V, Ayub M, et al. Profiling of circulating free DNA using targeted and genome-wide sequencing in patients with SCLC. J Thorac Oncol. 2020;15(2):216-230. doi:10.1016/j.jtho.2019.10.007
    1. Farsad M. FDG PET/CT in the staging of lung cancer. Curr Radiopharm. 2020;13(3):195-203. doi:10.2174/1874471013666191223153755
    1. Treadwell JR, Mitchell MD, Tsou A, Torigian D, Aggarwal C, Schoelles KM. AHRQ Comparative Effectiveness Reviews. Imaging for the Pretreatment Staging of Small Cell Lung Cancer. Agency for Healthcare Research and Quality (US); 2016.
    1. Santos JC, Abreu MH, Santos MS, et al. Bone scintigraphy and PET-CT: a necessary alliance for bone metastasis detection in breast cancer [abstract]? J Clin Oncol. 2020;38(15 suppl):e13070. doi:10.1200/jco.2020.38.15_suppl.e13070
    1. Tong E, McCullagh KL, Iv M. Advanced imaging of brain metastases: from augmenting visualization and improving diagnosis to evaluating treatment response. Front Neurol. 2020;11:270. doi:10.3389/fneur.2020.00270
    1. Raso MG, Bota-Rabassedas N, Wistuba II. Pathology and classification of SCLC. Cancers (Basel). 2021;13(4):820. doi:10.3390/cancers13040820
    1. Sturgis CD, Nassar DL, D'Antonio JA, Raab SS. Cytologic features useful for distinguishing small cell from non-small cell carcinoma in bronchial brush and wash specimens. Am J Clin Pathol. 2000;114(2):197-202. doi:10.1309/8mqg-6xek-3x9l-a9xu
    1. Nicholson SA, Beasley MB, Brambilla E, et al. Small cell lung carcinoma (SCLC): a clinicopathologic study of 100 cases with surgical specimens. Am J Surg Pathol. 2002;26(9):1184-1197. doi:10.1097/00000478-200209000-00009
    1. Fisseler-Eckhoff A, Demes M. Neuroendocrine tumors of the lung. Cancers (Basel). 2012;4(3):777-798. doi:10.3390/cancers4030777
    1. Kaltsas G, Androulakis II, de Herder WW, Grossman AB. Paraneoplastic syndromes secondary to neuroendocrine tumours. Endocr Relat Cancer. 2010;17(3):R173-R193. doi:10.1677/erc-10-0024
    1. National Lung Screening Trial Research Team; Aberle DR, Adams AM, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011:365:395-409. doi:10.1056/NEJMoa1102873
    1. Thomas A, Pattanayak P, Szabo E, Pinsky P. Characteristics and outcomes of small cell lung cancer detected by CT screening. Chest. 2018;154(6):1284-1290. doi:10.1016/j.chest.2018.07.029
    1. Silva M, Galeone C, Sverzellati N, et al. Screening with low-dose computed tomography does not improve survival of small cell lung cancer. J Thorac Oncol. 2016;11(2):187-193. doi:10.1016/j.jtho.2015.10.014
    1. Wender R, Fontham ET, Barrera E Jr, et al. American Cancer Society lung cancer screening guidelines. CA Cancer J Clin. 2013;63(2):107-117. doi:10.3322/caac.21172
    1. Mathios D, Johansen JS, Cristiano S, et al. Detection and characterization of lung cancer using cell-free DNA fragmentomes. Nat Commun. 2021;12(1):5060. doi:10.1038/s41467-021-24994-w
    1. Delfi Diagnostics. Delfi Diagnostics Initiates 15,000-Patient Prospective Lung Cancer Screening Trial. Delfi Diagnostics; 2022. Accessed December 7, 2022.
    1. Grail. Grail Announces Final Results From the PATHFINDER Multi-Cancer Early Detection Screening Study at ESMO Congress 2022. Grail; 2022. Accessed December 7, 2022.
    1. Parsons A, Daley A, Begh R, Aveyard P. Influence of smoking cessation after diagnosis of early stage lung cancer on prognosis: systematic review of observational studies with meta-analysis. BMJ. 2010;340(1):b5569. doi:10.1136/bmj.b5569
    1. US Environmental Protection Agency (EPA). A Citizen's Guide to Radon. The Guide to Protecting Yourself and Your Family from Radon. EPA; 2016.
    1. Mc Laughlin JP, Gutierrez-Villanueva JL, Perko T. Suggestions for improvements in national radon control strategies of member states which were developed as a requirement of EU Directive 2013/59 EURATOM. Int J Environ Res Publ Health. 2022;19(7):3805. doi:10.3390/ijerph19073805
    1. Amin MB, Greene FL, Edge SB, et al. The eighth edition AJCC Cancer Staging Manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin. 2017;67(2):93-99. doi:10.3322/caac.21388
    1. Lim W, Ridge CA, Nicholson AG, Mirsadraee S. The 8th lung cancer TNM classification and clinical staging system: review of the changes and clinical implications. Quant Imaging Med Surg. 2018;8(7):709-718. doi:10.21037/qims.2018.08.02
    1. Nicholson AG, Chansky K, Crowley J, et al. The International Association for the Study of Lung Cancer Lung Cancer Staging Project: proposals for the revision of the clinical and pathologic staging of small cell lung cancer in the forthcoming eighth edition of the TNM classification for lung cancer. J Thorac Oncol. 2016;11(3):300-311. doi:10.1016/j.jtho.2015.10.008
    1. Micke P, Faldum A, Metz T, et al. Staging small cell lung cancer: Veterans Administration Lung Study Group versus International Association for the Study of Lung Cancer-what limits limited disease? Lung Cancer. 2002;37(3):271-276. doi:10.1016/s0169-5002(02)00072-7
    1. Ganti AKP, Loo BW, Bassetti M, et al. Small Cell Lung Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Cancer Netw. 2021;19(12):1441-1464. doi:10.6004/jnccn.2021.0058
    1. Williams R, Eskandari N, Kendall A. Staging of small cell lung cancer (SCLC): comparison of two criteria by survival analysis [abstract]. J Clin Oncol. 2006;24(18 suppl):17030. doi:10.1200/jco.2006.24.18_suppl.17030
    1. Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5(6):649-655. doi:10.1097/00000421-198212000-00014
    1. Fox W, Scadding JG. Medical Research Council comparative trial of surgery and radiotherapy for primary treatment of small-celled or oat-celled carcinoma of bronchus. Ten-year follow-up. Lancet. 1973;2(7820):63-65. doi:10.1016/s0140-6736(73)93260-1
    1. Lad T, Piantadosi S, Thomas P, Payne D, Ruckdeschel J, Giaccone G. A prospective randomized trial to determine the benefit of surgical resection of residual disease following response of small cell lung cancer to combination chemotherapy. Chest. 1994;106(6 suppl):320S-323S. doi:10.1378/chest.106.6.320s
    1. Shepherd FA, Ginsberg RJ, Feld R, Evans WK, Johansen E. Surgical treatment for limited small-cell lung cancer. The University of Toronto Lung Oncology Group experience. J Thorac Cardiovasc Surg. 1991;101(3):385-393. doi:10.1016/s0022-5223(19)36720-0
    1. Tsuchiya R, Suzuki K, Ichinose Y, et al. Phase II trial of postoperative adjuvant cisplatin and etoposide in patients with completely resected stage I-IIIa small cell lung cancer: the Japan Clinical Oncology Lung Cancer Study Group Trial (JCOG9101). J Thorac Cardiovasc Surg. 2005;129(5):977-983. doi:10.1016/j.jtcvs.2004.05.030
    1. Liu T, Chen Z, Dang J, Li G. The role of surgery in stage I to III small cell lung cancer: a systematic review and meta-analysis. PLoS One. 2018;13(12):e0210001. doi:10.1371/journal.pone.0210001
    1. Combs SE, Hancock JG, Boffa DJ, Decker RH, Detterbeck FC, Kim AW. Bolstering the case for lobectomy in stages I, II, and IIIA small-cell lung cancer using the National Cancer Data Base. J Thorac Oncol. 2015;10(2):316-323. doi:10.1097/jto.0000000000000402
    1. Yang CFJ, Chan DY, Speicher PJ, et al. Role of adjuvant therapy in a population-based cohort of patients with early-stage small-cell lung cancer. J Clin Oncol. 2016;34(10):1057-1064. doi:10.1200/jco.2015.63.8171
    1. Pignon JP, Tribodet H, Scagliotti GV, et al. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group. J Clin Oncol. 2008;26(21):3552-3559. doi:10.1200/jco.2007.13.9030
    1. Rami-Porta R, Wittekind C, Goldstraw P. Complete resection in lung cancer surgery: proposed definition. Lung Cancer. 2005;49(1):25-33. doi:10.1016/j.lungcan.2005.01.001
    1. Edwards JG, Chansky K, Van Schil P, et al. The IASLC Lung Cancer Staging Project: analysis of resection margin status and proposals for residual tumor descriptors for non-small cell lung cancer. J Thorac Oncol. 2020;15(3):344-359. doi:10.1016/j.jtho.2019.10.019
    1. Varlotto JM, Recht A, Flickinger JC, Medford-Davis LN, Dyer AM, DeCamp MM. Lobectomy leads to optimal survival in early-stage small cell lung cancer: a retrospective analysis. J Thorac Cardiovasc Surg. 2011;142(3):538-546. doi:10.1016/j.jtcvs.2010.11.062
    1. Rami-Porta R, Wittekind C, Goldstraw P. Complete resection in lung cancer surgery: from definition to validation and beyond. J Thorac Oncol. 2020;15(12):1815-1818. doi:10.1016/j.jtho.2020.09.006
    1. Zhang S, Sun X, Sun L, Xiong Z, Ma J, Han C. Benefits of postoperative thoracic radiotherapy for small cell lung cancer subdivided by lymph node stage: a systematic review and meta-analysis. J Thorac Dis. 2017;9(5):1257-1264. doi:10.21037/jtd.2017.03.174
    1. Schreiber D, Rineer J, Weedon J, et al. Survival outcomes with the use of surgery in limited-stage small cell lung cancer: should its role be re-evaluated? Cancer. 2010;116(5):1350-1357. doi:10.1002/cncr.24853
    1. Xu J, Yang H, Fu X, et al. Prophylactic cranial irradiation for patients with surgically resected small cell lung cancer. J Thorac Oncol. 2017;12(2):347-353. doi:10.1016/j.jtho.2016.09.133
    1. Bischof M, Debus J, Herfarth K, et al. Surgery and chemotherapy for small cell lung cancer in stages I-II with or without radiotherapy. Strahlenther Onkol. 2007;183(12):679-684. doi:10.1007/s00066-007-1740-z
    1. Yang Y, Zhang D, Zhou X, et al. Prophylactic cranial irradiation in resected small cell lung cancer: a systematic review with meta-analysis. J Cancer. 2018;9(2):433-439. doi:10.7150/jca.21465
    1. Rusthoven CG, Kavanagh BD. Prophylactic cranial irradiation (PCI) versus active MRI surveillance for small cell lung cancer: the case for equipoise. J Thorac Oncol. 2017;12:1746-1754. doi:10.1016/j.jtho.2017.08.016
    1. Hoda MA, Klikovits T, Klepetko W. Controversies in oncology: surgery for small cell lung cancer? It's time to rethink the case. ESMO Open. 2018;3:e000366. doi:10.1136/esmoopen-2018-000366
    1. Zhang C, Li C, Shang X, Lin J, Wang H. Surgery as a potential treatment option for patients with stage III small-cell lung cancer: a propensity score matching analysis. Front Oncol. 2019;9:1339. doi:10.3389/fonc.2019.01339
    1. Mascaux C, Paesmans M, Berghmans T, et al. A systematic review of the role of etoposide and cisplatin in the chemotherapy of small cell lung cancer with methodology assessment and meta-analysis. Lung Cancer. 2000;30(1):23-36. doi:10.1016/s0169-5002(00)00127-6
    1. Fink TH, Huber RM, Heigener DF, et al. Topotecan/cisplatin compared with cisplatin/etoposide as first-line treatment for patients with extensive disease small-cell lung cancer: final results of a randomized phase III trial. J Thorac Oncol. 2012;7(9):1432-1439. doi:10.1097/jto.0b013e318260de75
    1. Hatfield LA, Huskamp HA, Lamont EB. Survival and toxicity after cisplatin plus etoposide versus carboplatin plus etoposide for extensive-stage small-cell lung cancer in elderly patients. J Oncol Pract. 2016;12(7):666-673. doi:10.1200/jop.2016.012492
    1. Bishop JF, Raghavan D, Stuart-Harris R, et al. Carboplatin (CBDCA, JM-8) and VP-16-213 in previously untreated patients with small-cell lung cancer. J Clin Oncol. 1987;5(10):1574-1578. doi:10.1200/jco.1987.5.10.1574
    1. Rossi A, Di Maio M, Chiodini P, et al. Carboplatin- or cisplatin-based chemotherapy in first-line treatment of small-cell lung cancer: the COCIS meta-analysis of individual patient data. J Clin Oncol. 2012;30(14):1692-1698. doi:10.1200/jco.2011.40.4905
    1. Daly ME, Ismaila N, Decker RH, et al. Radiation therapy for small-cell lung cancer: ASCO guideline endorsement of an ASTRO guideline. J Clin Oncol. 2021;39(8):931-939. doi:10.1200/jco.20.03364
    1. Bunn PA Jr, Lichter AS, Makuch RW, et al. Chemotherapy alone or chemotherapy with chest radiation therapy in limited stage small cell lung cancer. A prospective, randomized trial. Ann Intern Med. 1987;106(5):655-662. doi:10.7326/0003-4819-106-5-655
    1. Corso CD, Rutter CE, Park HS, et al. Role of chemoradiotherapy in elderly patients with limited-stage small-cell lung Cancer. J Clin Oncol. 2015;33(36):4240-4246. doi:10.1200/jco.2015.62.4270
    1. Christodoulou M, Blackhall F, Mistry H, et al. Compliance and outcome of elderly patients treated in the concurrent once-daily versus twice-daily radiotherapy (CONVERT) trial. J Thorac Oncol. 2019;14(1):63-71. doi:10.1016/j.jtho.2018.09.027
    1. Turrisi AT 3rd, Kim K, Blum R, et al. Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med. 1999;340(4):265-271. doi:10.1056/nejm199901283400403
    1. Faivre-Finn C, Snee M, Ashcroft L, et al. Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial. Lancet Oncol. 2017;18(8):1116-1125. doi:10.1016/s1470-2045(17)30318-2
    1. Glatzer M, Schmid S, Radovic M, Früh M, Putora PM. The role of radiation therapy in the management of small cell lung cancer. Breathe (Sheff). 2017;13(4):e87-e94. doi:10.1183/20734735.009617
    1. Levy A, Le Péchoux C, Faivre-Finn C. Twice-daily chemoradiotherapy in limited-stage small-cell lung cancer. Lancet Oncol. 2021;22(6):e220. doi:10.1016/s1470-2045(21)00255-2
    1. Murray N, Coy P, Pater JL, et al. Importance of timing for thoracic irradiation in the combined modality treatment of limited-stage small-cell lung cancer. The National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 1993;11(2):336-344. doi:10.1200/jco.1993.11.2.336
    1. Spiro SG, James LE, Rudd RM, et al. Early compared with late radiotherapy in combined modality treatment for limited disease small-cell lung cancer: a London Lung Cancer Group multicenter randomized clinical trial and meta-analysis. J Clin Oncol. 2006;24:3823-3830. doi:10.1200/jco.2005.05.3181
    1. Pujol JL, Carestia L, Daurès JP. Is there a case for cisplatin in the treatment of small-cell lung cancer? A meta-analysis of randomized trials of a cisplatin-containing regimen versus a regimen without this alkylating agent. Br J Cancer. 2000;83(1):8-15. doi:10.1054/bjoc.2000.1164
    1. Sundstrøm S, Bremnes RM, Kaasa S, et al. Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years' follow-up. J Clin Oncol. 2002;20(24):4665-4672. doi:10.1200/jco.2002.12.111
    1. Aupérin A, Arriagada R, Pignon JP, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group. N Engl J Med. 1999;341(7):476-484. doi:10.1056/nejm199908123410703
    1. Scotti V, Meattini I, Franzese C, et al. Radiotherapy timing in the treatment of limited-stage small cell lung cancer: the impact of thoracic and brain irradiation on survival. Tumori. 2014;100(3):289-295. doi:10.1177/1578.17206
    1. Farris MK, Wheless WH, Hughes RT, et al. Limited-stage small cell lung cancer: is prophylactic cranial irradiation necessary? Pract Radiat Oncol. 2019;9(6):e599-e607. doi:10.1016/j.prro.2019.06.014
    1. Rodríguez de Dios N, Couñago F, Murcia-Mejía M, et al. Randomized phase III trial of prophylactic cranial irradiation with or without hippocampal avoidance for small-cell lung cancer (PREMER): a GICOR-GOECP-SEOR study. J Clin Oncol. 2021;39(28):3118-3127. doi:10.1200/jco.21.00639
    1. Brown PD, Pugh S, Laack NN, et al. Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial. Neuro Oncol. 2013;15(10):1429-1437. doi:10.1093/neuonc/not114
    1. Rapp SR, Case LD, Peiffer A, et al. Donepezil for irradiated brain tumor survivors: a phase III randomized placebo-controlled clinical trial. J Clin Oncol. 2015;33(15):1653-1659. doi:10.1200/jco.2014.58.4508
    1. Berta J, Rózsás A, Megyesfalvi Z, Ostoros G, Döme B. Thoracic irradiation as consolidation therapy in patients with extensive-stage small cell lung cancer. Curr Opin Oncol. 2023;35(1):54-60. doi:10.1097/cco.0000000000000911
    1. Slotman BJ, van Tinteren H, Praag JO, et al. Use of thoracic radiotherapy for extensive stage small-cell lung cancer: a phase 3 randomised controlled trial. Lancet. 2015;385(9962):36-42. doi:10.1016/s0140-6736(14)61085-0
    1. Slotman BJ, van Tinteren H, Praag JO, et al. Radiotherapy for extensive stage small-cell lung cancer-authors' reply. Lancet. 2015;385(9975):1292-1293. doi:10.1016/s0140-6736(15)60679-1
    1. Jeremic B, Shibamoto Y, Nikolic N, et al. Role of radiation therapy in the combined-modality treatment of patients with extensive disease small-cell lung cancer: a randomized study. J Clin Oncol. 1999;17(7):2092-2099. doi:10.1200/jco.1999.17.7.2092
    1. Yee D, Butts C, Reiman A, et al. Clinical trial of post-chemotherapy consolidation thoracic radiotherapy for extensive-stage small cell lung cancer. Radiother Oncol. 2012;102(2):234-238. doi:10.1016/j.radonc.2011.08.042
    1. Tian Y, Ma J, Jing X, et al. Radiation therapy for extensive-stage small-cell lung cancer in the era of immunotherapy. Cancer Lett. 2022;541:215719. doi:10.1016/j.canlet.2022.215719
    1. Meert AP, Paesmans M, Berghmans T, et al. Prophylactic cranial irradiation in small cell lung cancer: a systematic review of the literature with meta-analysis. BMC Cancer. 2001;1:5. doi:10.1186/1471-2407-1-5
    1. Arriagada R, Le Chevalier T, Rivière A, et al. Patterns of failure after prophylactic cranial irradiation in small-cell lung cancer: analysis of 505 randomized patients. Ann Oncol. 2002;13(5):748-754. doi:10.1093/annonc/mdf123
    1. Slotman B, Faivre-Finn C, Kramer G, et al. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med. 2007;357(7):664-672. doi:10.1056/nejmoa071780
    1. Eaton BR, Kim S, Marcus DM, et al. Effect of prophylactic cranial irradiation on survival in elderly patients with limited-stage small cell lung cancer. Cancer. 2013;119(21):3753-3760. doi:10.1002/cncr.28267
    1. Takahashi T, Yamanaka T, Seto T, et al. Prophylactic cranial irradiation versus observation in patients with extensive-disease small-cell lung cancer: a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18(5):663-671. doi:10.1016/s1470-2045(17)30230-9
    1. Yang CJ, Chan DY, Shah SA, et al. Long-term survival after surgery compared with concurrent chemoradiation for node-negative small cell lung cancer. Ann Surg. 2018;268(6):1105-1112. doi:10.1097/sla.0000000000002287
    1. Videtic GM, Stephans KL, Woody NM, et al. Stereotactic body radiation therapy-based treatment model for stage I medically inoperable small cell lung cancer. Pract Radiat Oncol. 2013;3(4):301-306. doi:10.1016/j.prro.2012.10.003
    1. Liu SV, Reck M, Mansfield AS, et al. Updated overall survival and PD-L1 subgroup analysis of patients with extensive-stage small-cell lung cancer treated with atezolizumab, carboplatin, and etoposide (IMpower133). J Clin Oncol. 2021;39(6):619-630. doi:10.1200/jco.20.01055
    1. Goldman JW, Dvorkin M, Chen Y, et al. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2021;22(1):51-65. doi:10.1016/s1470-2045(20)30539-8
    1. Mathieu L, Shah S, Pai-Scherf L, et al. FDA approval summary: atezolizumab and durvalumab in combination with platinum-based chemotherapy in extensive stage small cell lung cancer. Oncologist. 2021;26(5):433-438. doi:10.1002/onco.13752
    1. Paz-Ares L, Chen Y, Reinmuth N, et al. Durvalumab, with or without tremelimumab, plus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer: 3-year overall survival update from CASPIAN. ESMO Open. 2022;7(2):100408. doi:10.1016/j.esmoop.2022.100408
    1. Donlon NE, Power R, Hayes C, Reynolds JV, Lysaght J. Radiotherapy, immunotherapy, and the tumour microenvironment: turning an immunosuppressive milieu into a therapeutic opportunity. Cancer Lett. 2021;502:84-96. doi:10.1016/j.canlet.2020.12.045
    1. Diamond BH, Verma N, Shukla UC, Park HS, Koffer PP. Consolidative thoracic radiation therapy after first-line chemotherapy and immunotherapy in extensive-stage small cell lung cancer: a multi-institutional case series. Adv Radiat Oncol. 2022;7(2):100883. doi:10.1016/j.adro.2021.100883
    1. Welsh JW, Heymach JV, Guo C, et al. Phase 1/2 trial of pembrolizumab and concurrent chemoradiation therapy for limited-stage SCLC. J Thorac Oncol. 2020;15(12):1919-1927. doi:10.1016/j.jtho.2020.08.022
    1. Peters S, Pujol JL, Dafni U, et al. Consolidation nivolumab and ipilimumab versus observation in limited-disease small-cell lung cancer after chemo-radiotherapy-results from the randomised phase II ETOP/IFCT 4-12 STIMULI trial. Ann Oncol. 2022;33(1):67-79. doi:10.1016/j.annonc.2021.09.011
    1. Owonikoko TK, Behera M, Chen Z, et al. A systematic analysis of efficacy of second-line chemotherapy in sensitive and refractory small-cell lung cancer. J Thorac Oncol. 2012;7(5):866-872. doi:10.1097/jto.0b013e31824c7f4b
    1. Gardner EE, Lok BH, Schneeberger VE, et al. Chemosensitive relapse in small cell lung cancer proceeds through an EZH2-SLFN11 axis. Cancer Cell. 2017;31(2):286-299. doi:10.1016/j.ccell.2017.01.006
    1. Cañadas I, Rojo F, Taus Á, et al. Targeting epithelial-to-mesenchymal transition with Met inhibitors reverts chemoresistance in small cell lung cancer. Clin Cancer Res. 2014;20(4):938-950. doi:10.1158/1078-0432.ccr-13-1330
    1. Chen P, Kuang P, Wang L, et al. Mechanisms of drugs-resistance in small cell lung cancer: DNA-related, RNA-related, apoptosis-related, drug accumulation and metabolism procedure. Transl Lung Cancer Res. 2020;9(3):768-786. doi:10.21037/tlcr-19-547
    1. Song Y, Sun Y, Lei Y, Yang K, Tang R. YAP1 promotes multidrug resistance of small cell lung cancer by CD74-related signaling pathways. Cancer Med. 2020;9(1):259-268. doi:10.1002/cam4.2668
    1. Dingemans AC, Früh M, Ardizzoni A, et al. Small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up(☆). Ann Oncol. 2021;32(7):839-853. doi:10.1016/j.annonc.2021.03.207
    1. Eckardt JR, von Pawel J, Pujol J-L, et al. Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer. J Clin Oncol. 2007;25(15):2086-2092. doi:10.1200/jco.2006.08.3998
    1. von Pawel J, Schiller JH, Shepherd FA, et al. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol. 1999;17(2):658-667. doi:10.1200/jco.1999.17.2.658
    1. Das M, Padda SK, Weiss J, Owonikoko TK. Advances in treatment of recurrent small cell lung cancer (SCLC): insights for optimizing patient outcomes from an expert roundtable discussion. Adv Ther. 2021;38(11):5431-5451. doi:10.1007/s12325-021-01909-1
    1. Kondo R, Watanabe S, Shoji S, et al. A phase II study of irinotecan for patients with previously treated small-cell lung cancer. Oncology. 2018;94(4):223-232. doi:10.1159/000486622
    1. Trigo J, Subbiah V, Besse B, et al. Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial. Lancet Oncol. 2020;21(5):645-654. doi:10.1016/s1470-2045(20)30068-1
    1. Aix SP, Ciuleanu TE, Navarro A, et al. Combination lurbinectedin and doxorubicin versus physician's choice of chemotherapy in patients with relapsed small-cell lung cancer (ATLANTIS): a multicentre, randomised, open-label, phase 3 trial. Lancet Respir Med. 2023;11(1):74-86. doi:10.1016/s2213-2600(22)00309-5
    1. Ready NE, Ott PA, Hellmann MD, et al. Nivolumab monotherapy and nivolumab plus ipilimumab in recurrent small cell lung cancer: results from the CheckMate 032 randomized cohort. J Thorac Oncol. 2020;15(3):426-435. doi:10.1016/j.jtho.2019.10.004
    1. Chung HC, Piha-Paul SA, Lopez-Martin J, et al. Pembrolizumab after two or more lines of previous therapy in patients with recurrent or metastatic SCLC: results from the KEYNOTE-028 and KEYNOTE-158 studies. J Thorac Oncol. 2020;15(4):618-627. doi:10.1016/j.jtho.2019.12.109
    1. Owonikoko TK, Park K, Govindan R, et al. Nivolumab and ipilimumab as maintenance therapy in extensive-disease small-cell lung cancer: CheckMate 451. J Clin Oncol. 2021;39(12):1349-1359. doi:10.1200/jco.20.02212
    1. Spigel DR, Vicente D, Ciuleanu TE, et al. Second-line nivolumab in relapsed small-cell lung cancer: CheckMate 331(☆). Ann Oncol. 2021;32(5):631-641. doi:10.1016/j.annonc.2021.01.071
    1. Rudin CM, Awad MM, Navarro A, et al. Pembrolizumab or placebo plus etoposide and platinum as first-line therapy for extensive-stage small-cell lung cancer: randomized, double-blind, phase III KEYNOTE-604 study. J Clin Oncol. 2020;38(21):2369-2379. doi:10.1200/jco.20.00793
    1. American Society of Clinical Oncology (ASCO). Nivolumab Indication in Small Cell Lung Cancer Withdrawn in U.S. Market. ASCO; 2021.
    1. American Society of Clinical Oncology (ASCO). Pembrolizumab's Indication in Small Cell Lung Cancer Is Withdrawn. ASCO; 2021.
    1. Coleman N, Zhang B, Byers LA, Yap TA. The role of Schlafen 11 (SLFN11) as a predictive biomarker for targeting the DNA damage response. Br J Cancer. 2021;124(5):857-859. doi:10.1038/s41416-020-01202-y
    1. Kundu K, Cardnell RJ, Zhang B, et al. SLFN11 biomarker status predicts response to lurbinectedin as a single agent and in combination with ATR inhibition in small cell lung cancer. Transl Lung Cancer Res. 2021;10(11):4095-4105. doi:10.21037/tlcr-21-437
    1. Pietanza MC, Waqar SN, Krug LM, et al. Randomized, double-blind, phase II study of temozolomide in combination with either veliparib or placebo in patients with relapsed-sensitive or refractory small-cell lung cancer. J Clin Oncol. 2018;36(23):2386-2394. doi:10.1200/jco.2018.77.7672
    1. Goodman AM, Kato S, Bazhenova L, et al. Tumor mutational burden as an independent predictor of response to immunotherapy in diverse cancers. Mol Cancer Ther. 2017;16(11):2598-2608. doi:10.1158/1535-7163.mct-17-0386
    1. Hellmann MD, Callahan MK, Awad MM, et al. Tumor mutational burden and efficacy of nivolumab monotherapy and in combination with ipilimumab in small-cell lung cancer. Cancer Cell. 2018;33(5):853-861.e854. doi:10.1016/j.ccell.2018.04.001
    1. Yu H, Batenchuk C, Badzio A, et al. PD-L1 expression by two complementary diagnostic assays and mRNA in situ hybridization in small cell lung cancer. J Thorac Oncol. 2017;12(1):110-120. doi:10.1016/j.jtho.2016.09.002
    1. Byers LA, Wang J, Nilsson MB, et al. Proteomic profiling identifies dysregulated pathways in small cell lung cancer and novel therapeutic targets including PARP1. Cancer Discov. 2012;2(9):798-811. doi:10.1158/-12-0112
    1. Calabrese CR, Almassy R, Barton S, et al. Anticancer chemosensitization and radiosensitization by the novel poly(ADP-ribose) polymerase-1 inhibitor AG14361. J Natl Cancer Inst. 2004;96(1):56-67. doi:10.1093/jnci/djh005
    1. Owonikoko TK, Dahlberg SE, Sica GL, et al. Randomized phase II trial of cisplatin and etoposide in combination with veliparib or placebo for extensive-stage small-cell lung cancer: ECOG-ACRIN 2511 study. J Clin Oncol. 2019;37(3):222-229. doi:10.1200/jco.18.00264
    1. Owonikoko TK, Dahlberg SE, Khan SA, et al. A phase 1 safety study of veliparib combined with cisplatin and etoposide in extensive stage small cell lung cancer: a trial of the ECOG-ACRIN Cancer Research Group (E2511). Lung Cancer. 2015;89:66-70. doi:10.1016/j.lungcan.2015.04.015
    1. Owen DH, Giffin MJ, Bailis JM, Smit MAD, Carbone DP, He K. DLL3: an emerging target in small cell lung cancer. J Hematol Oncol. 2019;12(1):61. doi:10.1186/s13045-019-0745-2
    1. Rudin CM, Pietanza MC, Bauer TM, et al. Rovalpituzumab tesirine, a DLL3-targeted antibody-drug conjugate, in recurrent small-cell lung cancer: a first-in-human, first-in-class, open-label, phase 1 study. Lancet Oncol. 2017;18:42-51. doi:10.1016/s1470-2045(16)30565-4
    1. Morgensztern D, Besse B, Greillier L, et al. Efficacy and safety of rovalpituzumab tesirine in third-line and beyond patients with DLL3-expressing, relapsed/refractory small-cell lung cancer: results from the phase II TRINITY study. Clin Cancer Res. 2019;25(23):6958-6966. doi:10.1158/1078-0432.ccr-19-1133
    1. Blackhall F, Jao K, Greillier L, et al. Efficacy and safety of rovalpituzumab tesirine compared with topotecan as second-line therapy in DLL3-high SCLC: results from the phase 3 TAHOE study. J Thorac Oncol. 2021;16(9):1547-1558. doi:10.1016/j.jtho.2021.02.009
    1. Lochmann TL, Bouck YM, Faber AC. BCL-2 inhibition is a promising therapeutic strategy for small cell lung cancer. Oncoscience. 2018;5(7-8):218-219. doi:10.18632/oncoscience.455
    1. Rudin CM, Hann CL, Garon EB, et al. Phase II study of single-agent navitoclax (ABT-263) and biomarker correlates in patients with relapsed small cell lung cancer. Clin Cancer Res. 2012;18(11):3163-3169. doi:10.1158/1078-0432.ccr-11-3090
    1. Lochmann TL, Floros KV, Naseri M, et al. Venetoclax is effective in small-cell lung cancers with high BCL-2 expression. Clin Cancer Res. 2018;24(2):360-369. doi:10.1158/1078-0432.ccr-17-1606
    1. Taniguchi H, Sen T, Rudin CM. Targeted therapies and biomarkers in small cell lung cancer. Front Oncol. 2020;10:741. doi:10.3389/fonc.2020.00741
    1. Owonikoko TK, Niu H, Nackaerts K, et al. Randomized phase II study of paclitaxel plus alisertib versus paclitaxel plus placebo as second-line therapy for SCLC: primary and correlative biomarker analyses. J Thorac Oncol. 2020;15(2):274-287. doi:10.1016/j.jtho.2019.10.013
    1. Kawahara M, Ushijima S, Kamimori T, et al. Second primary tumours in more than 2-year disease-free survivors of small-cell lung cancer in Japan: the role of smoking cessation. Br J Cancer. 1998;78(3):409-412. doi:10.1038/bjc.1998.507
    1. Kono M, Allen PK, Lin SH, et al. Incidence of second malignancy after successful treatment of limited-stage small-cell lung cancer and its effects on survival. J Thorac Oncol. 2017;12(11):1696-1703. doi:10.1016/j.jtho.2017.07.030
    1. Richardson GE, Tucker MA, Venzon DJ, et al. Smoking cessation after successful treatment of small-cell lung cancer is associated with fewer smoking-related second primary cancers. Ann Intern Med. 1993;119(5):383-390. doi:10.7326/0003-4819-119-5-199309010-00006
    1. Shields PG, Bierut L, Arenberg D, et al. Smoking Cessation, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Cancer Netw. 2023;21(3):297-322. doi:10.6004/jnccn.2023.0013
    1. American Society of Clinical Oncology (ASCO). Surveillance for Recurrence and Second Cancers: Guidelines and Caveats; ASCO; 2016.
    1. Chauvin JM, Zarour HM. TIGIT in cancer immunotherapy. J Immunother Cancer. 2020;8(2):e000957. doi:10.1136/jitc-2020-000957
    1. Rudin CM, Liu SV, Lu S, et al. SKYSCRAPER-02: primary results of a phase III, randomized, double-blind, placebo-controlled study of atezolizumab (atezo) + carboplatin + etoposide (CE) with or without tiragolumab (tira) in patients (pts) with untreated extensive-stage small cell lung cancer (ES-SCLC) [abstract]. J Clin Oncol. 2022;40(17 suppl):LBA8507. doi:10.1200/jco.2022.40.17_suppl.lba8507
    1. Mulroy MC, Cummings AL, Mendenhall MA, et al. Circulating tumor DNA (ctDNA) mutations may predict treatment response in extensive-stage small cell lung cancer (ES-SCLC) treated with talazoparib and temozolomide (TMZ) [abstract]. J Clin Oncol. 2021;39(15 suppl):8564. doi:10.1200/jco.2021.39.15_suppl.8564
    1. Chauhan A, Kolesar J, Yan D, et al. OA07.03 A phase II study of frontline rucaparib + nivolumab in platinum sensitive ES SCLC: interim analysis [abstract]. J Thorac Oncol. 2021;16(10):S859. doi:10.1016/j.jtho.2021.08.056
    1. Borghaei H, Paz-Ares L, Johnson M, et al. OA12.05 Phase 1 updated exploration and first expansion data for DLL3-targeted T-cell engager tarlatamab in small cell lung cancer [abstract]. J Thorac Oncol. 2022;17(9 suppl):S33. doi:10.1016/j.jtho.2022.07.062
    1. Johnson ML, Dy GK, Mamdani H, et al. Interim results of an ongoing phase 1/2a study of HPN328, a tri-specific, half-life extended, DLL3-targeting, T-cell engager, in patients with small cell lung cancer and other neuroendocrine cancers [abstract]. J Clin Oncol. 2022;40(16 suppl):8566. doi:10.1200/jco.2022.40.16_suppl.8566
    1. Wermke M, Felip E, Gambardella V, et al. Phase I trial of the DLL3/CD3 bispecific T-cell engager BI 764532 in DLL3-positive small-cell lung cancer and neuroendocrine carcinomas. Future Oncol. 2022;18(24):2639-2649. doi:10.2217/fon-2022-0196
    1. Byers L, Heymach J, Gibbons D, et al. 697 A phase 1 study of AMG 119, a DLL3-targeting, chimeric antigen receptor (CAR) T cell therapy, in relapsed/refractory small cell lung cancer (SCLC) [abstract]. J Immunother Cancer. 2022;10:A728.
    1. Weiss JM, Csoszi T, Maglakelidze M, et al. Myelopreservation with the CDK4/6 inhibitor trilaciclib in patients with small-cell lung cancer receiving first-line chemotherapy: a phase Ib/randomized phase II trial. Ann Oncol. 2019;30(10):1613-1621. doi:10.1093/annonc/mdz278
    1. Spigel DR, Townley PM, Waterhouse DM, et al. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011;29(16):2215-2222. doi:10.1200/jco.2010.29.3423
    1. Andrini E, Lamberti G, Mazzoni F, et al. A phase II, open-label, single-arm trial of carboplatin plus etoposide with bevacizumab and atezolizumab in patients with extended-stage small-cell lung cancer (CeLEBrATE study): background, design and rationale. Future Oncol. 2022;18(7):771-779. doi:10.2217/fon-2021-1027
    1. Meijer JJ, Leonetti A, Airò G, et al. Small cell lung cancer: novel treatments beyond immunotherapy. Semin Cancer Biol. 2022;86:376-385. doi:10.1016/j.semcancer.2022.05.004
    1. Chemi F, Pearce SP, Clipson A, et al. cfDNA methylome profiling for detection and subtyping of small cell lung cancers. Nat Cancer. 2022;3(10):1260-1270. doi:10.1038/s43018-022-00415-9
    1. Heeke S, Gay CM, Estecio MR, et al. MA01.03 Exploiting DNA methylation for classification of SCLC subtypes from liquid biopsies using a robust machine learning approach [abstract]. J Thorac Oncol. 2022;17(9 suppl):S43. doi:10.1016/j.jtho.2022.07.076
    1. Kim DW, Kim KC, Kim KB, Dunn CT, Park KS. Transcriptional deregulation underlying the pathogenesis of small cell lung cancer. Transl Lung Cancer Res. 2018;7(1):4-20. doi:10.21037/tlcr.2017.10.07
    1. Jia D, Augert A, Kim DW, et al. Crebbp loss drives small cell lung cancer and increases sensitivity to HDAC inhibition. Cancer Discov. 2018;8(11):1422-1437. doi:10.1158/-18-0385
    1. Llombart V, Mansour MR. Therapeutic targeting of “undruggable” MYC. EBioMedicine. 2022;75:103756. doi:10.1016/j.ebiom.2021.103756
    1. Shibata M, Ham K, Hoque MO. A time for YAP1: tumorigenesis, immunosuppression and targeted therapy. Int J Cancer. 2018;143(9):2133-2144. doi:10.1002/ijc.31561
    1. Green RA, Humphrey E, Close H, Patno ME. Alkylating agents in bronchogenic carcinoma. Am J Med. 1969;46(4):516-525. doi:10.1016/0002-9343(69)90071-0
    1. Miller AB, Fox W, Tall R. Five-year follow-up of the Medical Research Council comparative trial of surgery and radiotherapy for the primary treatment of small-celled or oat-celled carcinoma of the bronchus. Lancet. 1969;2(7619):501-505. doi:10.1016/s0140-6736(69)90212-8
    1. Bishop JF. Carboplatin/etoposide in small cell lung cancer. Oncology. 1992;49(suppl 1):11-17. discussion 17-18. doi:10.1159/000227105
    1. Borges M, Linnoila RI, van de Velde HJ, et al. An achaete-scute homologue essential for neuroendocrine differentiation in the lung. Nature. 1997;386(6627):852-855. doi:10.1038/386852a0
    1. Kularatne BY, Lorigan P, Browne S, Suvarna SK, Smith MO, Lawry J. Monitoring tumour cells in the peripheral blood of small cell lung cancer patients. Cytometry. 2002;50(3):160-167. doi:10.1002/cyto.10071

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