183
Views
18
CrossRef citations to date
0
Altmetric
Review

Multiple Primary Lung Cancers: A New Challenge in the Era of Precision Medicine

ORCID Icon, , , ORCID Icon & ORCID Icon
Pages 10361-10374 | Published online: 20 Oct 2020

References

  • Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7–30. doi:10.3322/caac.2159031912902
  • Chang Y-L, Wu C-T, Lin S-C, Hsiao C-F, Jou Y-S, Lee Y-C. Clonality and prognostic implications of p53 and epidermal growth factor receptor somatic aberrations in multiple primary lung cancers. Clin Cancer Res. 2007;13(1):52–58. doi:10.1158/1078-0432.CCR-06-174317200338
  • Battafarano RJ, Meyers BF, Guthrie TJ, Cooper JD, Patterson GA. Surgical resection of multifocal non-small cell lung cancer is associated with prolonged survival. Ann Thorac Surg. 2002;74(4):988–994. doi:10.1016/S0003-4975(02)03878-X12400733
  • Zuin A, Andriolo LG, Marulli G, et al. Is lobectomy really more effective than sublobar resection in the surgical treatment of second primary lung cancer? Eur J Cardiothorac Surg. 2013;44(2):e120–e125; discussion e125. doi:10.1093/ejcts/ezt219
  • Stella F, Luciano G, Dell’Amore A, et al. Pulmonary metastases from NSCLC and MPLC (Multiple Primary Lung Cancers): management and outcome in a single centre experience. Heart Lung Circ. 2016;25(2):191–195. doi:10.1016/j.hlc.2015.07.01626525847
  • Mascalchi M, Comin CE, Bertelli E, et al. Screen-detected multiple primary lung cancers in the ITALUNG trial. J Thorac Dis. 2018;10(2):1058–1066. doi:10.21037/jtd.2018.01.9529607181
  • Boyle JM, Tandberg DJ, Chino JP, D’Amico TA, Ready NE, Kelsey CR. Smoking history predicts for increased risk of second primary lung cancer: a comprehensive analysis. Cancer. 2015;121(4):598–604. doi:10.1002/cncr.2909525283893
  • Yang H, Sun Y, Yao F, et al. Surgical therapy for bilateral multiple primary lung cancer. Ann Thorac Surg. 2016;101(3):1145–1152. doi:10.1016/j.athoracsur.2015.09.02826602007
  • Chang YL, Wu CT, Lee YC. Surgical treatment of synchronous multiple primary lung cancers: experience of 92 patients. J Thorac Cardiovasc Surg. 2007;134(3):630–637. doi:10.1016/j.jtcvs.2007.06.00117723810
  • Martini N, Melamed MR. Multiple primary lung cancers. J Thorac Cardiovasc Surg. 1975;70(4):606–612. doi:10.1016/S0022-5223(19)40289-4170482
  • Benjamin DK, James ML, Frank CD, David RJ. Special treatment issues in non-small cell lung cancer-diagnosis and management of lung cancer, 3rd ed: American College of Chest physicians evidence-based clinical practice guidelines. Chest. 2013;143(5):e369S–e399S.23649447
  • Rami-Porta RAH, Travis WD, Rusch VW. AJCC Cancer Staging Manual. 8 ed. France: Springer International Publishing; 2017.
  • Chen T-F, Xie C-Y, Rao B-Y, et al. Surgical treatment to multiple primary lung cancer patients: a systematic review and meta-analysis. BMC Surg. 2019;19(1):185. doi:10.1186/s12893-019-0643-031795997
  • Li R, Li X, Xue R, et al. Early metastasis detected in patients with multifocal pulmonary ground-glass opacities (GGOs). Thorax. 2018;73(3):290–292. doi:10.1136/thoraxjnl-2017-21016929056599
  • Su K, Gao S, Ying J, Zou S, He J. Sequencing a super multiple synchronous lung cancer reveals a novel variant in driver gene ARID1B. J Thorac Cardiovasc Surg. 2018;155(6):e185–e191. doi:10.1016/j.jtcvs.2018.01.01029576263
  • Nikitas J, DeWees T, Rehman S, et al. Stereotactic body radiotherapy for early-stage multiple primary lung cancers. Clin Lung Cancer. 2019;20(2):107–116. doi:10.1016/j.cllc.2018.10.01030477740
  • Detterbeck FC, Jones DR, Kernstine KH, Naunheim KS. Special treatment issues. Chest. 2003;123(1):244S–258S. doi:10.1378/chest.123.1_suppl.244S12527583
  • Shen KR, Meyers BF, Larner JM, Jones DR. Special treatment issues in lung cancer - ACCP evidence-based clinical practice guidelines (2nd edition). Chest. 2007;132(3):290S–305S. doi:10.1378/chest.07-138217873175
  • Groome PA, Bolejack V, Crowley JJ, et al. The IASLC lung cancer staging project: validation of the proposals for revision of the T, N, and M descriptors and consequent stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours. J Thorac Oncol. 2007;2(8):694–705. doi:10.1097/JTO.0b013e31812d05d517762335
  • Detterbeck FC, Franklin WA, Nicholson AG, et al. The IASLC lung cancer staging project: background data and proposed criteria to distinguish separate primary lung cancers from metastatic foci in patients with two lung tumors in the forthcoming eighth edition of the TNM classification for lung cancer. J Thorac Oncol. 2016;11(5):651–665. doi:10.1016/j.jtho.2016.01.02526944304
  • Detterbeck FC, Boffa DJ, Kim AW, Tanoue LT. The eighth edition lung cancer stage classification. Chest. 2017;151(1):193–203. doi:10.1016/j.chest.2016.10.01027780786
  • Detterbeck FC, Nicholson AG, Franklin WA, et al. The IASLC lung cancer staging project: summary of proposals for revisions of the classification of lung cancers with multiple pulmonary sites of involvement in the forthcoming eighth edition of the TNM classification. J Thorac Oncol. 2016;11(5):639–650.26940528
  • Park E, Ahn S, Kim H, et al. Targeted sequencing analysis of pulmonary adenocarcinoma with multiple synchronous ground-glass/lepidic nodules. J Thorac Oncol. 2018;13(11):1776–1783. doi:10.1016/j.jtho.2018.07.09730121391
  • Ren YJ, Huang SJ, Dai CY, et al. Germline predisposition and copy number alteration in pre-stage lung adenocarcinomas presenting as ground-glass nodules. Front Oncol. 2019;9:288. doi:10.3389/fonc.2019.0028831058088
  • Zhang Y, Li G, Li Y, et al. Imaging features suggestive of multiple primary lung adenocarcinomas. Ann Surg Oncol. 2019;27(6):2061–2070.31863415
  • Matsunaga T, Suzuki K, Takamochi K, Oh S. New simple radiological criteria proposed for multiple primary lung cancers. Jpn J Clin Oncol. 2017;47(11):1073–1077. doi:10.1093/jjco/hyx11328973259
  • Yu F, Tang J, Liu W, et al. Genetic profiling of synchronous multiple primary lung carcinomas presenting as ground-glass opacities. J Clin Oncol. 2019;37(15_suppl):e20034–e20034. doi:10.1200/JCO.2019.37.15_suppl.e20034
  • Travis WD, Brambilla E, Nicholson AG, et al. The 2015 World Health Organization classification of lung tumors: impact of genetic, clinical and radiologic advances since the 2004 classification. J Thorac Oncol. 2015;10(9):1243–1260. doi:10.1097/JTO.000000000000063026291008
  • Kadota K, Nitadori J, Sima CS, et al. Tumor spread through air spaces is an important pattern of invasion and impacts the frequency and location of recurrences after limited resection for small stage I lung adenocarcinomas. J Thorac Oncol. 2015;10(5):806–814. doi:10.1097/JTO.000000000000048625629637
  • Hara K, Mizuguchi S, Okada S, et al. Intensity of SLX predicts distance of tumor spread through alveolar spaces in stage I lung adenocarcinoma. Thorac Cancer. 2019;10(4):832–838. doi:10.1111/1759-7714.1300830821130
  • Kadota K, Kushida Y, Kagawa S, et al. Limited resection Is associated with a higher risk of locoregional recurrence than lobectomy in stage I lung adenocarcinoma with tumor spread through air spaces. Am J Surg Pathol. 2019;43(8):1033–1041. doi:10.1097/PAS.000000000000128531107717
  • Eguchi T, Kameda K, Lu S, et al. Lobectomy is associated with better outcomes than sublobar resection in Spread through Air Spaces (STAS)-positive T1 lung adenocarcinoma: a propensity score-matched analysis. J Thorac Oncol. 2019;14(1):87–98. doi:10.1016/j.jtho.2018.09.00530244070
  • Shiono S, Endo M, Suzuki K, Yarimizu K, Hayasaka K, Yanagawa N. Spread through air spaces is a prognostic factor in sublobar resection of non-small cell lung cancer. Ann Thorac Surg. 2018;106(2):354–360. doi:10.1016/j.athoracsur.2018.02.07629625101
  • Dijkman BG, Schuurbiers OCJ, Vriens D, et al. The role of 18F-FDG PET in the differentiation between lung metastases and synchronous second primary lung tumours. Eur J Nucl Med Mol Imaging. 2010;37(11):2037–2047. doi:10.1007/s00259-010-1505-220533031
  • Liu Y, Tang Y, Xue Z, et al. SUVmax ratio on PET/CT may differentiate between lung metastases and synchronous multiple primary lung cancer. Acad Radiol. 2020;27(5):618–623. doi:10.1016/j.acra.2019.07.00131787567
  • Suh YJ, Lee HJ, Sung P, et al. A novel algorithm to differentiate between multiple primary lung cancers and intrapulmonary metastasis in multiple lung cancers with multiple pulmonary sites of involvement. J Thorac Oncol. 2020;15(2):203–215. doi:10.1016/j.jtho.2019.09.22131634666
  • Hosny A, Parmar C, Quackenbush J, Schwartz LH, Aerts H. Artificial intelligence in radiology. Nat Rev Cancer. 2018;18(8):500–510. doi:10.1038/s41568-018-0016-529777175
  • Topol EJ. High-performance medicine: the convergence of human and artificial intelligence. Nat Med. 2019;25(1):44–56. doi:10.1038/s41591-018-0300-730617339
  • Bera K, Schalper KA, Rimm DL, Velcheti V, Madabhushi A. Artificial intelligence in digital pathology - new tools for diagnosis and precision oncology. Nat Rev Clin Oncol. 2019;16(11):703–715. doi:10.1038/s41571-019-0252-y31399699
  • Nishio M, Sugiyama O, Yakami M, et al. Computer-aided diagnosis of lung nodule classification between benign nodule, primary lung cancer, and metastatic lung cancer at different image size using deep convolutional neural network with transfer learning. PLoS One. 2018;13(7):e0200721.30052644
  • Nasrullah N, Sang J, Alam MS, Mateen M, Cai B, Hu H. Automated lung nodule detection and classification using deep learning combined with multiple strategies. Sensors (Basel). 2019;19(17):3722.
  • Travis WD, Elizabeth B, Konrad M-H, Harris CC. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart. Lyon, France: IARC Press; 2004.
  • Girard N, Deshpande C, Lau C, et al. Comprehensive histologic assessment helps to differentiate multiple lung primary nonsmall cell carcinomas from metastases. Am J Surg Pathol. 2009;33(12):1752–1764. doi:10.1097/PAS.0b013e3181b8cf0319773638
  • Travis WD, Brambilla E, Burke A, Marx A, Nicholson AG. WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart. 4th ed., Vol. 7 Lyon, France: International Agency for Research on Cancer; 2015.
  • Sun W, Feng L, Yang X, et al. Clonality assessment of multifocal lung adenocarcinoma by pathology evaluation and molecular analysis. Hum Pathol. 2018;81:261–271. doi:10.1016/j.humpath.2018.01.03030420048
  • Sun W, Liu Y, Liu XY, Lin DM, Lv N. Significance of nonmucinous lepidic component with mild nuclear atypia in the discrimination of multiple primary lung cancers from intrapulmonary metastases. Int J Clin Exp Pathol. 2014;7(11):7583–7596.25550795
  • Matsuzoe D, Hideshima T, Ohshima K, Kawahara K, Shirakusa T, Kimura A. Discrimination of double primary lung cancer from intrapulmonary metastasis by p53 gene mutation. Br J Cancer. 1999;79(9–10):1549–1552. doi:10.1038/sj.bjc.669024710188905
  • Iwata T, Sugio K, Uramoto H, et al. Detection of EGFR and K-ras mutations for diagnosis of multiple lung adenocarcinomas. Front Biosci (Landmark Ed). 2011;16:2961–2969. doi:10.2741/389121622214
  • Ikeda K, Nomori H, Ohba Y, et al. Epidermal growth factor receptor mutations in multicentric lung adenocarcinomas and atypical adenomatous hyperplasias. J Thorac Oncol. 2008;3(5):467–471. doi:10.1097/JTO.0b013e31816b4b1418448997
  • Chung J-H, Choe G, Jheon S, et al. Epidermal growth factor receptor mutation and pathologic-radiologic correlation between multiple lung nodules with ground-glass opacity differentiates multicentric origin from intrapulmonary spread. J Thorac Oncol. 2009;4(12):1490–1495. doi:10.1097/JTO.0b013e3181bc973119844187
  • Takamochi K, Oh S, Matsuoka J, Suzuki K. Clonality status of multifocal lung adenocarcinomas based on the mutation patterns of EGFR and K-ras. Lung Cancer. 2012;75(3):313–320. doi:10.1016/j.lungcan.2011.08.00722209037
  • Patel SB, Kadi W, Walts AE, et al. Next-generation sequencing: a novel approach to distinguish multifocal primary lung adenocarcinomas from intrapulmonary metastases. J Mol Diagn. 2017;19(6):870–880. doi:10.1016/j.jmoldx.2017.07.00628866070
  • Saab J, Zia H, Mathew S, Kluk M, Narula N, Fernandes H. Utility of genomic analysis in differentiating synchronous and metachronous lung adenocarcinomas from primary adenocarcinomas with intrapulmonary metastasis. Transl Oncol. 2017;10(3):442–449. doi:10.1016/j.tranon.2017.02.00928448960
  • Roepman P, Ten Heuvel A, Scheidel KC, et al. Added value of 50-gene panel sequencing to distinguish multiple primary lung cancers from pulmonary metastases: a systematic investigation. J Mol Diagn. 2018;20(4):436–445. doi:10.1016/j.jmoldx.2018.02.00729625247
  • Takahashi Y, Shien K, Tomida S, et al. Comparative mutational evaluation of multiple lung cancers by multiplex oncogene mutation analysis. Cancer Sci. 2018;109(11):3634–3642. doi:10.1111/cas.1379730216592
  • Chang JC, Alex D, Bott M, et al. Comprehensive next-generation sequencing unambiguously distinguishes separate primary lung carcinomas from intrapulmonary metastases: comparison with standard histopathologic approach. Clin Cancer Res. 2019;25(23):7113–7125. doi:10.1158/1078-0432.CCR-19-170031471310
  • Donfrancesco E, Yvorel V, Casteillo F, et al. Histopathological and molecular study for synchronous lung adenocarcinoma staging. Virchows Arch. 2020;476(6):835–842. doi:10.1007/s00428-019-02736-031900636
  • Higuchi R, Nakagomi T, Goto T, et al. Identification of clonality through genomic profile analysis in multiple lung cancers. J Clin Med. 2020;9(2):573. doi:10.3390/jcm9020573
  • Yap TA, Gerlinger M, Futreal PA, Pusztai L, Swanton C. Intratumor heterogeneity: seeing the wood for the trees. Sci Transl Med. 2012;4(127):127ps110. doi:10.1126/scitranslmed.3003854
  • Swanton C. Intratumor heterogeneity: evolution through space and time. Cancer Res. 2012;72(19):4875–4882. doi:10.1158/0008-5472.CAN-12-221723002210
  • Mansuet-Lupo A, Barritault M, Alifano M, et al. Proposal for a combined histomolecular algorithm to distinguish multiple primary adenocarcinomas from intrapulmonary metastasis in patients with multiple lung tumors. J Thorac Oncol. 2019;14(5):844–856. doi:10.1016/j.jtho.2019.01.01730721797
  • Liu Y, Zhang JJ, Li L, et al. Genomic heterogeneity of multiple synchronous lung cancer. Nat Commun. 2016;7:13200. doi:10.1038/ncomms1320027767028
  • Ma P, Fu Y, Cai MC, et al. Simultaneous evolutionary expansion and constraint of genomic heterogeneity in multifocal lung cancer. Nat Commun. 2017;8(1):823. doi:10.1038/s41467-017-00963-029018192
  • Abbosh C, Birkbak NJ, Swanton C. Early stage NSCLC - challenges to implementing ctDNA-based screening and MRD detection. Nat Rev Clin Oncol. 2018;15(9):577–586.29968853
  • Murphy SJ, Harris FR, Kosari F, et al. Using genomics to differentiate multiple primaries from metastatic lung cancer. J Thorac Oncol. 2019;14(7):1567–1582. doi:10.1016/j.jtho.2019.05.00831103780
  • Murphy SJ, Aubry MC, Harris FR, et al. Identification of independent primary tumors and intrapulmonary metastases using DNA rearrangements in non-small-cell lung cancer. J Clin Oncol. 2014;32(36):4050–4058. doi:10.1200/JCO.2014.56.764425385739
  • Shen C, Wang X, Tian L, et al. “Different trend” in multiple primary lung cancer and intrapulmonary metastasis. Eur J Med Res. 2015;20(1):17. doi:10.1186/s40001-015-0109-525889108
  • Tian L, Wang X, Zeng RJ, et al. Microsatellite alteration in plasma DNA discriminates multiple primary lung cancer from metastatic lung cancer. Transl Cancer Res. 2017;6(4):720–731. doi:10.21037/tcr.2017.07.07
  • Wang X, Wang M, MacLennan GT, et al. Evidence for common clonal origin of multifocal lung cancers. J Natl Cancer Inst. 2009;101(8):560–570. doi:10.1093/jnci/djp05419351924
  • Skvortsova K, Stirzaker C, Taberlay P. The DNA methylation landscape in cancer. Essays Biochem. 2019;63(6):797–811.31845735
  • Dor Y, Cedar H. Principles of DNA methylation and their implications for biology and medicine. Lancet. 2018;392(10149):777–786. doi:10.1016/S0140-6736(18)31268-630100054
  • Sano A, Kage H, Sugimoto K, et al. A second-generation profiling system for quantitative methylation analysis of multiple gene promoters: application to lung cancer. Oncogene. 2007;26(45):6518–6525. doi:10.1038/sj.onc.121048317452971
  • Wu L, Kang P, Tao S, et al. Genomic profiles and transcriptomic microenvironments in 2 patients with synchronous lung adenocarcinoma and lung squamous cell carcinoma: a case report. BMC Med Genomics. 2020;13(1):15.32005243
  • Ono K, Sugio K, Uramoto H, et al. Discrimination of multiple primary lung cancers from intrapulmonary metastasis based on the expression of four cancer-related proteins. Cancer. 2009;115(15):3489–3500. doi:10.1002/cncr.2438219452548
  • Chen DL, Mei LY, Zhou YB, et al. A novel differential diagnostic model for multiple primary lung cancer: differentially-expressed gene analysis of multiple primary lung cancer and intrapulmonary metastasis. Oncol Lett. 2015;9(3):1081–1088. doi:10.3892/ol.2015.288025663860
  • Rea F, Zuin A, Callegaro D, Bortolotti L, Guanella G, Sartori F. Surgical results for multiple primary lung cancers. Eur J Cardiothorac Surg. 2001;20(3):489–495. doi:10.1016/S1010-7940(01)00858-211509268
  • Aziz TM, Saad RA, Glasser J, Jilaihawi AN, Prakash D. The management of second primary lung cancers. A single centre experience in 15 years. Eur J Cardiothorac Surg. 2002;21(3):527–533. doi:10.1016/S1010-7940(02)00024-611888775
  • Trousse D, Barlesi F, Loundou A, et al. Synchronous multiple primary lung cancer: an increasing clinical occurrence requiring multidisciplinary management. J Thorac Cardiovasc Surg. 2007;133(5):1193–1200. doi:10.1016/j.jtcvs.2007.01.01217467428
  • De Leyn P, Moons J, Vansteenkiste J, et al. Survival after resection of synchronous bilateral lung cancer. Eur J Cardiothorac Surg. 2008;34(6):1215–1222.18829338
  • Rostad H, Strand TE, Naalsund A, Norstein J. Resected synchronous primary malignant lung tumors: a population-based study. Ann Thorac Surg. 2008;85(1):204–209. doi:10.1016/j.athoracsur.2007.07.09118154811
  • Finley DJ, Yoshizawa A, Travis W, et al. Predictors of outcomes after surgical treatment of synchronous primary lung cancers. J Thorac Oncol. 2010;5(2):197–205. doi:10.1097/JTO.0b013e3181c814c520101145
  • Yu Y-C, Hsu P-K, Yeh Y-C, et al. Surgical results of synchronous multiple primary lung cancers: similar to the stage-matched solitary primary lung cancers? Ann Thorac Surg. 2013;96(6):1966–1974. doi:10.1016/j.athoracsur.2013.04.14224021769
  • Ishikawa Y, Nakayama H, Ito H, et al. Surgical treatment for synchronous primary lung adenocarcinomas. Ann Thorac Surg. 2014;98(6):1983–1988. doi:10.1016/j.athoracsur.2014.07.00625443005
  • Shimada Y, Saji H, Otani K, et al. Survival of a surgical series of lung cancer patients with synchronous multiple ground-glass opacities, and the management of their residual lesions. Lung Cancer. 2015;88(2):174–180. doi:10.1016/j.lungcan.2015.02.01625758554
  • Dai L, Yang HL, Yan WP, et al. The equivalent efficacy of multiple operations for multiple primary lung cancer and a single operation for single primary lung cancer. J Thorac Dis. 2016;8(5):855–861. doi:10.21037/jtd.2016.03.4227162659
  • Zhang Z, Gao S, Mao Y, et al. Surgical outcomes of synchronous multiple primary non-small cell lung cancers. Sci Rep. 2016;6:23252. doi:10.1038/srep2325227254665
  • Cheng H, Lei BF, Peng PJ, Lin YJ, Wang XJ. Histologic lung cancer subtype differentiates synchronous multiple primary lung adenocarcinomas from intrapulmonary metastases. J Surg Res. 2017;211:215–222. doi:10.1016/j.jss.2016.11.05028501120
  • Peng Y, Ren W, Wang H, Li M, Feng Z, Peng Z. Surgical treatment is an effective approach for patients with synchronous multiple primary lung cancers. J Cancer Res Ther. 2017;13(4):702–706. doi:10.4103/jcrt.JCRT_140_1728901318
  • Xiao F, Liu D, Guo Y, et al. Survival rate and prognostic factors of surgically resected clinically synchronous multiple primary non-small cell lung cancer and further differentiation from intrapulmonary metastasis. J Thorac Dis. 2017;9(4):990–1001. doi:10.21037/jtd.2017.03.5928523154
  • Zhao H, Yang H, Han K, et al. Clinical outcomes of patients with metachronous second primary lung adenocarcinomas. Onco Targets Ther. 2017;10:295–302. doi:10.2147/OTT.S12290828138252
  • Chen H, Fu Q, Sun K. Efficacy and prognosis analysis of surgical treatment for bilateral synchronous multiple primary non-small cell lung cancer. J BUON. 2019;24(6):2245–2252.31983090
  • Kang X, Zhang C, Zhou H, et al. Multiple pulmonary resections for synchronous and metachronous lung cancer at two Chinese centers. Ann Thorac Surg. 2020;109(3):856–863. doi:10.1016/j.athoracsur.2019.09.08831765616
  • Fourdrain A, Bagan P, Georges O, et al. Outcomes after contralateral anatomic surgical resection in multiple lung cancer. Thorac Cardiovasc Surg. 2020.
  • Lee D-S, LaChapelle C, Taioli E, et al. Second primary lung cancers demonstrate similar survival with wedge resection and lobectomy. Ann Thorac Surg. 2019;108(6):1724–1728. doi:10.1016/j.athoracsur.2019.06.02331376378
  • Owen D, Olivier KR, Mayo CS, et al. Outcomes of stereotactic body radiotherapy (SBRT) treatment of multiple synchronous and recurrent lung nodules. Radiat Oncol. 2015;10:43. doi:10.1186/s13014-015-0340-925889747
  • Usuda J, Ichinose S, Ishizumi T, et al. Management of multiple primary lung cancer in patients with centrally located early cancer lesions. J Thorac Oncol. 2010;5(1):62–68. doi:10.1097/JTO.0b013e3181c4228719952800
  • Grills IS, Mangona VS, Welsh R, et al. Outcomes after stereotactic lung radiotherapy or wedge resection for stage I non-small-cell lung cancer. J Clin Oncol. 2010;28(6):928–935. doi:10.1200/JCO.2009.25.092820065181
  • Videtic GMM, Donington J, Giuliani M, et al. Stereotactic body radiation therapy for early-stage non-small cell lung cancer: executive summary of an ASTRO evidence-based guideline. Pract Radiat Oncol. 2017;7(5):295–301. doi:10.1016/j.prro.2017.04.01428596092
  • Howington JA, Blum MG, Chang AC, Balekian AA, Murthy SC. Treatment of stage I and II non-small cell lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143(5Suppl):e278S–e313S. doi:10.1378/chest.12-235923649443
  • Sinha B, McGarry RC. Stereotactic body radiotherapy for bilateral primary lung cancers: the Indiana University experience. Int J Radiat Oncol Biol Phys. 2006;66(4):1120–1124. doi:10.1016/j.ijrobp.2006.06.04217145532
  • Creach KM, Bradley JD, Mahasittiwat P, Robinson CG. Stereotactic body radiation therapy in the treatment of multiple primary lung cancers. Radiother Oncol. 2012;104(1):19–22. doi:10.1016/j.radonc.2011.12.00522248508
  • Matthiesen C, Thompson JS, De La Fuente Herman T, Ahmad S, Herman T. Use of stereotactic body radiation therapy for medically inoperable multiple primary lung cancer. J Med Imaging Radiat Oncol. 2012;56(5):561–566. doi:10.1111/j.1754-9485.2012.02393.x23043577
  • Chang JY, Liu YH, Zhu Z, et al. Stereotactic ablative radiotherapy: a potentially curable approach to early stage multiple primary lung cancer. Cancer. 2013;119(18):3402–3410. doi:10.1002/cncr.2821723798353
  • Griffioen GH, Lagerwaard FJ, Haasbeek CJ, Smit EF, Slotman BJ, Senan S. Treatment of multiple primary lung cancers using stereotactic radiotherapy, either with or without surgery. Radiother Oncol. 2013;107(3):403–408. doi:10.1016/j.radonc.2013.04.02623746675
  • Rahn DA 3rd, Thakur S, Makani S, Sandhu A. Stereotactic body radiation therapy (SBRT) for multiple primary lung cancers (MPLC): a review and case series. J Radiosurg SBRT. 2013;2(2):135–140.29296352
  • Nishiyama K, Kodama K, Teshima T, Tada H. Stereotactic body radiotherapy for second pulmonary nodules after operation for an initial lung cancer. Jpn J Clin Oncol. 2015;45(10):947–952. doi:10.1093/jjco/hyv11326238818
  • Shintani T, Masago K, Takayama K, et al. Stereotactic body radiotherapy for synchronous primary lung cancer: clinical outcome of 18 cases. Clin Lung Cancer. 2015;16(5):e91–e96. doi:10.1016/j.cllc.2014.12.01125659504
  • Miyazaki T, Yamazaki T, Sato S, et al. Surgery or stereotactic body radiotherapy for metachronous primary lung cancer? A propensity score matching analysis. Gen Thorac Cardiovasc Surg. 2020. doi:10.1007/s11748-020-01394-3
  • Arbour KC, Riely GJ. Systemic therapy for locally advanced and metastatic non-small cell lung cancer: a review. JAMA. 2019;322(8):764–774. doi:10.1001/jama.2019.1105831454018
  • Wu CY, Zhao C, Yang Y, et al. High discrepancy of driver mutations in patients with NSCLC and synchronous multiple lung ground-glass nodules. J Thorac Oncol. 2015;10(5):778–783. doi:10.1097/JTO.000000000000048725629635
  • Liu M, He WX, Song N, Yang Y, Zhang P, Jiang GN. Discrepancy of epidermal growth factor receptor mutation in lung adenocarcinoma presenting as multiple ground-glass opacities. Eur J Cardiothorac Surg. 2016;50(5):909–913. doi:10.1093/ejcts/ezw11327032467
  • Yang Y, Yin W, He W, et al. Phenotype-genotype correlation in multiple primary lung cancer patients in China. Sci Rep. 2016;6(1):36177. doi:10.1038/srep3617727796337
  • Ye C, Wang J, Li W, Chai Y. Novel strategy for synchronous multiple primary lung cancer displaying unique molecular profiles. Ann Thorac Surg. 2016;101(2):e45–e47. doi:10.1016/j.athoracsur.2015.06.04226777970
  • Ryoo BY, Na II, Yang SH, Koh JS, Kim CH, Lee JC. Synchronous multiple primary lung cancers with different response to gefitinib. Lung Cancer. 2006;53(2):245–248. doi:10.1016/j.lungcan.2006.05.01016787685
  • Bao Y, Wu J, Zhang J, Yu Y. Diagnosis and treatment of synchronous multiple primary lung cancer - a case report. Onco Targets Ther. 2019;12:4281–4285. doi:10.2147/OTT.S18331931213845
  • Liu P, Wang Y, Li X. Targeting the untargetable KRAS in cancer therapy. Acta Pharm Sin B. 2019;9(5):871–879. doi:10.1016/j.apsb.2019.03.00231649840
  • Sun F, Xi J, Zhan C, et al. Ground glass opacities: imaging, pathology, and gene mutations. J Thorac Cardiovasc Surg. 2018;156(2):808–813. doi:10.1016/j.jtcvs.2018.02.11029753514
  • Proto C, Ferrara R, Signorelli D, et al. Choosing wisely first line immunotherapy in non-small cell lung cancer (NSCLC): what to add and what to leave out. Cancer Treat Rev. 2019;75:39–51. doi:10.1016/j.ctrv.2019.03.00430954906
  • Yi M, Jiao D, Xu H, et al. Biomarkers for predicting efficacy of PD-1/PD-L1 inhibitors. Mol Cancer. 2018;17(1):129. doi:10.1186/s12943-018-0864-330139382
  • Tokuyasu H, Horie M, Ishikawa S, Sakai H, Miura H, Yamasaki A. Multiple lung cancers including squamous cell carcinoma with strong PD-L1 expression and adenocarcinoma with EGFR exon 19 deletion: a case report. Respir Med Case Rep. 2020;29:100976.31886125
  • Haratake N, Toyokawa G, Takada K, et al. Programmed death-ligand 1 expression and EGFR mutations in multifocal lung cancer. Ann Thorac Surg. 2018;105(2):448–454. doi:10.1016/j.athoracsur.2017.09.02529254651
  • Mansfield AS, Murphy SJ, Peikert T, et al. Heterogeneity of programmed cell death ligand 1 expression in multifocal lung cancer. Clin Cancer Res. 2016;22(9):2177–2182. doi:10.1158/1078-0432.CCR-15-224626667490
  • Galon J, Bruni D. Approaches to treat immune hot, altered and cold tumours with combination immunotherapies. Nat Rev Drug Discov. 2019;18(3):197–218.30610226
  • Kobayashi Y, Ambrogio C, Mitsudomi T. Ground-glass nodules of the lung in never-smokers and smokers: clinical and genetic insights. Transl Lung Cancer Res. 2018;7(4):487–497. doi:10.21037/tlcr.2018.07.0430225212
  • Mazieres J, Drilon A, Lusque A, et al. Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry. Ann Oncol. 2019;30(8):1321–1328. doi:10.1093/annonc/mdz16731125062