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Open Access Special Issue

Molecular Markers in Guiding Lung Cancer Diagnosis and Treatment

  • Vivian Li1
  • Wickii T. Vigneswaran1,2,*,

1Department of Thoracic and Cardiovascular Surgery, Stritch School of Medicine, Loyola University, Chicago, IL 60153, USA

2Loyola University Health System, Maywood, IL 60153, USA

DOI: 10.31083/j.jomh1808164 Vol.18,Issue 8,August 2022 pp.1-12

Published: 31 August 2022

(This article belongs to the Special Issue Lung Cancer: The Changing Paradigm)

*Corresponding Author(s): Wickii T. Vigneswaran E-mail:


Background: Lung cancer has the highest mortality rates and one of the lowest 5-year survival rates amongst cancer types in the world. Although there are constant advancements in treatment, the overall prognosis for lung cancer continues to be poor. In order to achieve early detection and personalized targeted treatment, an effective method is needed to make prognostic and treatment decisions. Methods: A thorough literature search was conducted to identify tumor tissue, blood, and expired breath markers that have been discovered in lung cancer. Articles were chosen by determining main markers holding promise for future clinical use. Results: Data suggests significance in using tumor tissue markers as promising diagnostic, prognostic and predictive of treatment response and outcome. Epidermal Growth Factor Receptor (EGFR) and Anaplastic Lymphoma Kinase (ALK) and ROS-1 biomarkers can be used to decide to treat with EGFR-TKI and ALK-TKI, respectively. KRAS and p53 mutations suggest a likelihood of developing EGFR-TKI resistance. And c-MET is showing pertinence in predicting disease recurrence. Blood and expired breath markers are two more novel sources for biomarkers that is gaining more ground in lung cancer research. Circulating tumor cells (CTC) and DNA (ctDNA) were shown to be important markers in lung cancer prognosis and treatment response prediction. Circulating tumor cells suggest negative prognosis and increased likelihood of recurrence, while ctDNA data indicates use in treatment monitoring to help make decisions without keeping patients on disagreeable therapies. Volatile organic compounds (VOC) are the least studied, but investigators have noticed changes in VOC profiles between healthy and lung cancer patients. Blood and expired breath markers continue to be studied as these would be a welcome alternative to invasive biopsies. Recently there had been interest in using specific tumor biomarkers for imaging to localize tumors and determine disease progression. Conclusions: Years of research have elucidated multiple candidates as biomarkers found in tumor tissues, circulation, and even in exhaled air. Although more studies need to be performed on some markers mentioned in this review, such as EGFR, KRAS, ALK, and ROS-1, there is enough evidence for some use of these biomarkers to guide decisions in clinic, as well as evidence for promising future developments.


lung cancer; biomarkers; predictive biomarker; prognostic biomarker

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Vivian Li,Wickii T. Vigneswaran. Molecular Markers in Guiding Lung Cancer Diagnosis and Treatment. Journal of Men's Health. 2022. 18(8);1-12.


[1] Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Es-timates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians. 2021; 71: 209–249.

[2] Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA: A Cancer Journal for Clinicians. 2021; 71: 7–33.

[3] American Cancer Society (ACS). Cancer Facts and Figures– 2021. Atlanta: American Cancer Society. 2021. Available at: ancer-facts-figures/cancer-facts-figures-2021.html (Accessed: 13 January 2022).

[4] Marcu LG. Imaging Biomarkers of Tumour Proliferation and In-vasion for Personalised Lung Cancer Therapy. Journal of Per-sonalized Medicine. 2020; 10: 222.

[5] Mendoza DP, Piotrowska Z, Lennerz JK, Digumarthy SR. Role of imaging biomarkers in mutation-driven non-small cell lung cancer. World Journal of Clinical Oncology. 2020; 11: 412–427.

[6] Fang S, Wang Z. EGFR mutations as a prognostic and predic-tive marker in non-small-cell lung cancer. Drug Design, Devel-opment and Therapy. 2014; 8: 1595–1611.

[7] Vincent MD, Kuruvilla MS, Leighl NB, Kamel-Reid S. Biomarkers that currently affect clinical practice: EGFR, ALK, MET, KRAS. Current Oncology. 2012; 19: S33–S44.

[8] Korpanty GJ, Graham DM, Vincent MD, Leighl NB. Biomark-ers That Currently Affect Clinical Practice in Lung Cancer: EGFR, ALK, MET, ROS-1, and KRAS. Frontiers in Oncology. 2014; 4: 204.

[9] Planchard D, Loriot Y, Goubar A, Commo F, Soria J. Differen-tial expression of biomarkers in men and women. Seminars in Oncology. 2009; 36: 553–565.

[10] Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, et al. Activating mutations in the epider-mal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. The New England Journal of Medicine. 2004; 350: 2129–2139.

[11] Kosaka T, Yatabe Y, Onozato R, Kuwano H, Mitsudomi T. Prog-nostic implication of EGFR, KRAS, and TP53 gene mutations in a large cohort of Japanese patients with surgically treated lung adenocarcinoma. Journal of Thoracic Oncology. 2009; 4: 22–29.

[12] Jeon JH, Kang CH, Kim H, Seong YW, Park IK, Kim YT. Prog-nostic and predictive role of epidermal growth factor receptor mutation in recurrent pulmonary adenocarcinoma after curative resection. European Journal of Cardio-Thoracic Surgery. 2015; 47: 556–562.

[13] D’Angelo SP, Janjigian YY, Ahye N, Riely GJ, Chaft JE, Sima CS, et al. Distinct Clinical Course of EGFR -Mutant Resected Lung Cancers: Results of Testing of 1118 Surgical Specimens and Effects of Adjuvant Gefitinib and Erlotinib. Journal of Tho-racic Oncology. 2012; 7: 1815–1822.

[14] Liu W, Zhao L, Pang Q, Yuan Z, Li B, Wang P. Prognostic value of epidermal growth factor receptor mutations in resected lung adenocarcinomas. Medical Oncology. 2014; 31: 771.

[15] Pinto JA, Vallejos CS, Raez LE, Mas LA, Ruiz R, Torres-Roman JS, et al. Gender and outcomes in non-small cell lung cancer: an old prognostic variable comes back for targeted therapy and immunotherapy? ESMO Open. 2018; 3: e000344.

[16] Xiao J, Zhou L, He B, Chen Q. Impact of Sex and Smoking on the Efficacy of EGFR-TKIs in Terms of Overall Survival in Non-small-Cell Lung Cancer: A Meta-Analysis. Frontiers in Oncol-ogy. 2020; 10: 1531.

[17] Ragavan M, Patel MI. The evolving landscape of sex-based dif-ferences in lung cancer: a distinct disease in women. European Respiratory Review. 2022; 31: 210100.

[18] Salgia R, Pharaon R, Mambetsariev I, Nam A, Sattler M. The im-probable targeted therapy: KRAS as an emerging target in non-small cell lung cancer (NSCLC). Cell Reports Medicine. 2021; 2: 100186.

[19] Mascaux C, Iannino N, Martin B, Paesmans M, Berghmans T, Dusart M, et al. The role of RAS oncogene in survival of patients with lung cancer: a systematic review of the literature with meta-analysis. British Journal of Cancer. 2005; 92: 131–139.

[20] Renaud S, Falcoz P, Schaëffer M, Guenot D, Romain B, Ol-land A, et al. Prognostic value of the KRAS G12V mutation in 841 surgically resected Caucasian lung adenocarcinoma cases. British Journal of Cancer. 2015; 113: 1206–1215.

[21] Nadal E, Chen G, Prensner JR, Shiratsuchi H, Sam C, Zhao L, et al. KRAS-G12C mutation is associated with poor outcome in surgically resected lung adenocarcinoma. Journal of Thoracic Oncology. 2014; 9: 1513–1522.

[22] Massarelli E, Varella-Garcia M, Tang X, Xavier AC, Ozburn NC, Liu DD, et al. KRAS mutation is an important predictor of resistance to therapy with epidermal growth factor receptor ty-rosine kinase inhibitors in non-small-cell lung cancer. Clinical Cancer Research. 2007; 13: 2890–2896.

[23] Morris SW, Kirstein MN, Valentine MB, Dittmer K, Shapiro DN, Look AT, et al. Fusion of a kinase gene, ALK, to a nucle-olar protein gene, NPM, in non-Hodgkin’s lymphoma. Science. 1994; 267: 316–317.

[24] Patel JN, Ersek JL, Kim ES. Lung cancer biomarkers, targeted therapies and clinical assays. Translational Lung Cancer Re-search. 2015; 4: 503–514.

[25] Inamura K, Takeuchi K, Togashi Y, Hatano S, Ninomiya H, Mo-toi N, et al. EML4-ALK lung cancers are characterized by rare other mutations, a TTF-1 cell lineage, an acinar histology, and young onset. Modern Pathology. 2009; 22: 508–515.

[26] Camidge DR, Bang Y, Kwak EL, Iafrate AJ, Varella-Garcia M, Fox SB, et al. Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study. The Lancet. Oncology. 2012; 13: 1011–1019.

[27] Shaw AT, Kim DW, Nakagawa K, Seto T, Crinó L, Ahn MJ, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. The New England Journal of Medicine. 2013; 368: 2385–2394.

[28] Shaw AT, Kim D, Mehra R, Tan DSW, Felip E, Chow LQM, et al. Ceritinib in ALK-rearranged non-small-cell lung cancer. The New England Journal of Medicine. 2014; 370: 1189–1197.

[29] Shaw AT, Kim TM, Crinò L, Gridelli C, Kiura K, Liu G, et al. Ceritinib versus chemotherapy in patients with ALK-rearranged non-small-cell lung cancer previously given chemotherapy and crizotinib (ASCEND-5): a randomised, controlled, open-label, phase 3 trial. The Lancet. Oncology. 2017; 18: 874–886.

[30] Kim HR, Lim SM, Kim HJ, Hwang SK, Park JK, Shin E, et al. The frequency and impact of ROS1 rearrangement on clinical outcomes in never smokers with lung adenocarcinoma. Annals of Oncology. 2013; 24: 2364–2370.

[31] Lin JJ, Shaw AT. Recent Advances in Targeting ROS1 in Lung Cancer. Journal of Thoracic Oncology. 2017; 12: 1611–1625.

[32] Shaw AT, Riely GJ, Bang Y-, Kim D-, Camidge DR, Solomon BJ, et al. Crizotinib in ROS1-rearranged advanced non-small-cell lung cancer (NSCLC): updated results, including overall survival, from PROFILE 1001. Annals of Oncology. 2019; 30: 1121–1126.

[33] Liu C, Yu H, Chang J, Chen H, Li Y, Zhao W, et al. Crizotinib in Chinese Patients with ROS1-Rearranged Advanced Non‒Small-Cell Lung Cancer in Routine Clinical Practice. Targeted Oncol-ogy. 2019; 14: 315–323.

[34] Zhu Q, Zhan P, Zhang X, Lv T, Song Y. Clinicopathologic char-acteristics of patients with ROS1 fusion gene in non-small cell lung cancer: a meta-analysis. Translational Lung Cancer Re-search. 2015; 4: 300–309.

[35] Salgia R. Role of c-Met in cancer: emphasis on lung cancer. Seminars in Oncology. 2009; 36: S52–S58.

[36] Jeffers M, Fiscella M, Webb CP, Anver M, Koochekpour S, Vande Woude GF. The mutationally activated Met receptor mediates motility and metastasis. Proceedings of the National Academy of Sciences of the United States of America. 1998; 95: 14417–14422.

[37] Tsao MS, Liu N, Chen JR, Pappas J, Ho J, To C, et al. Differential expression of Met/hepatocyte growth factor receptor in subtypes of non-small cell lung cancers. Lung Cancer. 1998; 20: 1–16.

[38] Park S, Choi Y, Sung CO, An J, Seo J, Ahn M, et al. High MET copy number and MET overexpression: poor outcome in non-small cell lung cancer patients. Histology and Histopathology. 2012; 27: 197–207.

[39] Cappuzzo F, Marchetti A, Skokan M, Rossi E, Gajapathy S, Fe-licioni L, et al. Increased MET gene copy number negatively af-fects survival of surgically resected non-small-cell lung cancer patients. Journal of Clinical Oncology. 2009; 27: 1667–1674.

[40] Cheng T, Chang M, Huang S, Sheu C, Kao E, Cheng Y, et al. Overexpression of circulating c-met messenger RNA is signifi-cantly correlated with nodal stage and early recurrence in non-small cell lung cancer. Chest. 2005; 128: 1453–1460.

[41] Zucali PA, Ruiz MG, Giovannetti E, Destro A, Varella-Garcia M, Floor K, et al. Role of cMET expression in non-small-cell lung cancer patients treated with EGFR tyrosine kinase in-hibitors. Annals of Oncology. 2008; 19: 1605–1612.

[42] Lee YJ, Han J, Lee GK, Shin J, Yun SA, Oh JY, et al. C-MET overexpression as a resistance biomarker to epidermal growth factor receptor tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer. Journal of Clinical Oncology. 2016; 34: e20660–e20660.

[43] Tsuta K, Kozu Y, Mimae T, Yoshida A, Kohno T, Sekine I, et al. C- MET/phospho-MET protein expression and MET gene copy number in non-small cell lung carcinomas. Journal of Thoracic Oncology. 2012; 7: 331–339.

[44] Gibbons DL, Byers LA, Kurie JM. Smoking, p53 mutation, and lung cancer. Molecular Cancer Research. 2014; 12: 3–13.

[45] Baryshnikova E, Destro A, Infante MV, Cavuto S, Cariboni U, Alloisio M, et al. Molecular alterations in spontaneous sputum of cancer-free heavy smokers: results from a large screening pro-gram. Clinical Cancer Research. 2008; 14: 1913–1919.

[46] Tammemagi MC, McLaughlin JR, Bull SB. Meta-analyses of p53 tumor suppressor gene alterations and clinicopathologi-cal features in resected lung cancers. Cancer Epidemiology, Biomarkers & Prevention. 1999; 8: 625–634.

[47] Tan DF, Li Q, Rammath N, Beck A, Wiseman S, Anderson T, et al. Prognostic significance of expression of p53 oncoprotein in primary (stage I-IIIa) non-small cell lung cancer. Anticancer Research. 2003; 23: 1665–1672.

[48] Shih C, Chen K, Wang Y, Lee P, Wang Y. Elevated p53 and p21waf1 mRNA expression in blood lymphocytes from lung cancer patients with chemoresistance. Cancer Detection and Pre-vention. 2007; 31: 366–370.

[49] Tsao M, Aviel-Ronen S, Ding K, Lau D, Liu N, Sakurada A, et al. Prognostic and predictive importance of p53 and RAS for adjuvant chemotherapy in non small-cell lung cancer. Journal of Clinical Oncology. 2007; 25: 5240–5247.

[50] Jung S, Kim DH, Choi YJ, Kim SY, Park H, Lee H, et al. Contri-bution of p53 in sensitivity to EGFR tyrosine kinase inhibitors in non-small cell lung cancer. Scientific Reports. 2021; 11: 19667.

[51] Lin X, Wang L, Xie X, Qin Y, Xie Z, Ouyang M, et al. Prognos-tic Biomarker TP53 Mutations for Immune Checkpoint Block-ade Therapy and Its Association With Tumor Microenvironment of Lung Adenocarcinoma. Frontiers in Molecular Biosciences. 2020; 7: 602328.

[52] Qian H, Zhang Y, Xu J, He J, Gao W. Progress and application of circulating tumor cells in non-small cell lung cancer. Molecular Therapy - Oncolytics. 2021; 22: 72–84.

[53] Cheung KJ, Ewald AJ. A collective route to metastasis: Seeding by tumor cell clusters. Science. 2016; 352: 167–169.

[54] Kapeleris J, Kulasinghe A, Warkiani ME, Vela I, Kenny L, O’Byrne K, et al. The Prognostic Role of Circulating Tumor Cells (CTCs) in Lung Cancer. Frontiers in Oncology. 2018; 8: 311.

[55] Alix-Panabières C, Pantel K. Challenges in circulating tumour cell research. Nature Reviews. Cancer. 2014; 14: 623–631.

[56] Krebs MG, Hou J, Sloane R, Lancashire L, Priest L, Nonaka D, et al. Analysis of circulating tumor cells in patients with non-small cell lung cancer using epithelial marker-dependent and -independent approaches. Journal of Thoracic Oncology. 2012; 7: 306–315.

[57] Hong Y, Fang F, Zhang Q. Circulating tumor cell clusters: what we know and what we expect (Review). International Journal of Oncology. 2016; 49: 2206–2216.

[58] Mocellin S, Hoon D, Ambrosi A, Nitti D, Rossi CR. The prognostic value of circulating tumor cells in patients with melanoma: a systematic review and meta-analysis. Clinical Cancer Research. 2006; 12: 4605–4613.

[59] Li Z, Xu K, Tartarone A, Santarpia M, Zhu Y, Jiang G. Cir-culating tumor cells can predict the prognosis of patients with non-small cell lung cancer after resection: a retrospective study. Translational Lung Cancer Research. 2021; 10: 995–1006.

[60] Zhang Z, Xiao Y, Zhao J, Chen M, Xu Y, Zhong W, et al. Re-lationship between circulating tumour cell count and prognosis following chemotherapy in patients with advanced non-small-cell lung cancer. Respirology. 2016; 21: 519–525.

[61] Frick MA, Feigenberg SJ, Jean-Baptiste SR, Aguarin LA, Mendes A, Chinniah C, et al. Circulating Tumor Cells are Asso-ciated with Recurrent Disease in Patients with Early-Stage Non–Small Cell Lung Cancer Treated with Stereotactic Body Radio-therapy. Clinical Cancer Research. 2020; 26: 2372–2380.

[62] Wu CY, Lee CL, Wu CF, Fu JY, Yang CT, Wen CT, et al. Circu-lating Tumor Cells as a Tool of Minimal Residual Disease Can Predict Lung Cancer Recurrence: A longitudinal, Prospective Trial. Diagnostics. 2020; 10: 144.

[63] Tamminga M, de Wit S, Hiltermann TJN, Timens W, Schuur-ing E, Terstappen LWMM, et al. Circulating tumor cells in ad-vanced non-small cell lung cancer patients are associated with worse tumor response to checkpoint inhibitors. Journal for Im-munoTherapy of Cancer. 2019; 7: 173.

[64] He Y, Shi J, Schmidt B, Liu Q, Shi G, Xu X, et al. Circulating Tumor Cells as a Biomarker to Assist Molecular Diagnosis for Early Stage Non-Small Cell Lung Cancer. Cancer Management and Research. 2020; 12: 841–854.

[65] Wang X, Ma K, Yang Z, Cui J, He H, Hoffman AR, et al. Sys-tematic Correlation Analyses of Circulating Tumor Cells with Clinical Variables and Tumor Markers in Lung Cancer Patients. Journal of Cancer. 2017; 8: 3099–3104.

[66] Mamdani H, Ahmed S, Armstrong S, Mok T, Jalal SI. Blood-based tumor biomarkers in lung cancer for detection and treat-ment. Translational Lung Cancer Research. 2017; 6: 648–660.

[67] Zhang Y, Zheng H, Zhan Y, Long M, Liu S, Lu J, et al. De-tection and application of circulating tumor cell and circulating tumor DNA in the non-small cell lung cancer. American Journal of Cancer Research. 2018; 8: 2377–2386.

[68] Ma M, Zhu H, Zhang C, Sun X, Gao X, Chen G. ”Liquid biopsy”-ctDNA detection with great potential and challenges. Annals of Translational Medicine. 2015; 3: 235.

[69] Catarino R, Coelho A, Araújo A, Gomes M, Nogueira A, Lopes C, et al. Circulating DNA: diagnostic tool and predictive marker for overall survival of NSCLC patients. PLoS ONE. 2012; 7: e38559.

[70] Sozzi G, Conte D, Leon M, Ciricione R, Roz L, Ratcliffe C, et al. Quantification of free circulating DNA as a diagnostic marker in lung cancer. Journal of Clinical Oncology. 2003; 21: 3902–3908.

[71] Ulivi P, Mercatali L, Casoni G, Scarpi E, Bucchi L, Silvestrini R, et al. Multiple marker detection in peripheral blood for NSCLC diagnosis. PLoS ONE. 2013; 8: e57401.

[72] Jiang T, Ren S, Zhou C. Role of circulating-tumor DNA analysis in non-small cell lung cancer. Lung Cancer. 2015; 90: 128–134.

[73] Sirera R, Bremnes RM, Cabrera A, Jantus-Lewintre E, San-martín E, Blasco A, et al. Circulating DNA is a useful prognos-tic factor in patients with advanced non-small cell lung cancer. Journal of Thoracic Oncology. 2011; 6: 286–290.

[74] Zhang C, Wei B, Li P, Yang K, Wang Z, Ma J, et al. Prognostic value of plasma EGFR ctDNA in NSCLC patients treated with EGFR-TKIs. PLoS ONE. 2017; 12: e0173524.

[75] Song Y, Hu C, Xie Z, Wu L, Zhu Z, Rao C, et al. Circulating tumor DNA clearance predicts prognosis across treatment reg-imen in a large real-world longitudinally monitored advanced non-small cell lung cancer cohort. Translational Lung Cancer Research. 2020; 9: 269–279.

[76] Phillips M, Herrera J, Krishnan S, Zain M, Greenberg J, Cata-neo RN. Variation in volatile organic compounds in the breath of normal humans. Journal of Chromatography. B, Biomedical Sciences and Applications. 1999; 729: 75–88.

[77] Horvath I, Lazar Z, Gyulai N, Kollai M, Losonczy G. Exhaled biomarkers in lung cancer. European Respiratory Journal. 2009; 34: 261–275.

[78] Dent AG, Sutedja TG, Zimmerman PV. Exhaled breath analysis for lung cancer. Journal of Thoracic Disease. 2013; 5: S540–S550.

[79] Stone BG, Besse TJ, Duane WC, Evans CD, DeMaster EG. Ef-fect of regulating cholesterol biosynthesis on breath isoprene ex-cretion in men. Lipids. 1993; 28: 705–708.

[80] Galassetti PR, Novak B, Nemet D, Rose-Gottron C, Cooper DM, Meinardi S, et al. Breath ethanol and acetone as indicators of serum glucose levels: an initial report. Diabetes Technology & Therapeutics. 2005; 7: 115–123.

[81] Frank Kneepkens CM, Lepage G, Roy CC. The potential of the hydrocarbon breath test as a measure of lipid peroxidation. Free Radical Biology and Medicine. 1994; 17: 127–160.

[82] Jia Z, Patra A, Kutty VK, Venkatesan T. Critical Review of Volatile Organic Compound Analysis in Breath and in Vitro Cell Culture for Detection of Lung Cancer. Metabolites. 2019; 9: 52.

[83] Machado RF, Laskowski D, Deffenderfer O, Burch T, Zheng S, Mazzone PJ, et al. Detection of lung cancer by sensor array analyses of exhaled breath. American Journal of Respiratory and Critical Care Medicine. 2005; 171: 1286–1291.

[84] McCulloch M, Jezierski T, Broffman M, Hubbard A, Turner K, Janecki T. Diagnostic accuracy of canine scent detection in early- and late-stage lung and breast cancers. Integrative Cancer Therapies. 2006; 5: 30–39.

[85] Poli D, Carbognani P, Corradi M, Goldoni M, Acampa O, Balbi B, et al. Exhaled volatile organic compounds in patients with non-small cell lung cancer: cross sectional and nested short-term follow-up study. Respiratory Research. 2005; 6: 71.

[86] Phillips M, Altorki N, Austin JHM, Cameron RB, Cataneo RN, Greenberg J, et al. Prediction of lung cancer using volatile biomarkers in breath. Cancer Biomarkers. 2007; 3: 95–109.

[87] Schallschmidt K, Becker R, Jung C, Bremser W, Walles T, Neudecker J, et al. Comparison of volatile organic compounds from lung cancer patients and healthy controls-challenges and limitations of an observational study. Journal of Breath Re-search. 2016; 10: 046007.

[88] Mazzone PJ, Wang X, Lim S, Jett J, Choi H, Zhang Q, et al. Progress in the development of volatile exhaled breath signa-tures of lung cancer. Annals of the American Thoracic Society. 2015; 12: 752–757.

[89] Lin Y, Leng Q, Jiang Z, Guarnera MA, Zhou Y, Chen X, et al. A classifier integrating plasma biomarkers and radiological char-acteristics for distinguishing malignant from benign pulmonary nodules. International Journal of Cancer. 2017; 141: 1240–1248.

[90] Rios Velazquez E, Parmar C, Liu Y, Coroller TP, Cruz G, String-field O, et al. Somatic Mutations Drive Distinct Imaging Pheno-types in Lung Cancer. Cancer Research. 2017; 77: 3922–3930.

[91] Sun R, Limkin EJ, Vakalopoulou M, Dercle L, Champiat S, Han SR, et al. A radiomics approach to assess tumour-infiltrating CD8 cells and response to anti-PD-1 or anti-PD-L1 immunother-apy: an imaging biomarker, retrospective multicohort study. The Lancet. Oncology. 2018; 19: 1180–1191.

[92] Haim O, Abramov S, Shofty B, Fanizzi C, DiMeco F, Avisdris N, et al. Predicting EGFR mutation status by a deep learning ap-proach in patients with non-small cell lung cancer brain metas-tases. Journal of Neuro-Oncology. 2022. (in press)

[93] Gangadharan S, Sarkaria IN, Rice D, Murthy S, Braun J, Kucharczuk J, et al. Multiinstitutional Phase 2 Clinical Trial of Intraoperative Molecular Imaging of Lung Cancer. The Annals of Thoracic Surgery. 2021; 112: 1150–1159.

[94] Sun X, Xiao Z, Chen G, Han Z, Liu Y, Zhang C, et al. A PET imaging approach for determining EGFR mutation status for im-proved lung cancer patient management. Science Translational Medicine. 2018; 10: eaan8840.

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