Lung cancer currently represents a leading cause of cancer death. Substantial progress achieved in the medical therapy of lung cancer during the last decade has been associated with the advent of targeted therapy, including immunotherapy. The targeted therapy has gradually shifted from drugs suppressing general mechanisms of tumor growth and progression to agents aiming at transforming mechanisms like driver mutations in a particular tumor. Knowledge of the molecular characteristics of a tumor has become an essential component of the more targeted therapeutic approach. There are specific challenges for biomarker determination in lung cancer, in particular a commonly limited size of tumor sample. Liquid biopsy is therefore of particular importance in the management of lung cancer. Laboratory medicine is an indispensable part of multidisciplinary management of lung cancer. Clinical Chemistry and Laboratory Medicine (CCLM) has played and will continue playing a major role in updating and spreading the knowledge in the field.

Department of Oncology and Radiotherapy and 4th Department of Medicine Charles University Medical School and Teaching Hospital Hradec Králové Czech Republic

Department of Oncology Palacký University Medical School and Teaching Hospital Olomouc Czech Republic

Zobrazit více v PubMed

Melichar, B. Laboratory medicine and medical oncology: the tale of two Cinderellas. Clin Chem Lab Med 2013;51:99–112. https://doi.org/10.1515/cclm-2012-0496 . DOI

Jemal, A, Bray, F, Center, MM, Ferlay, J, Ward, E, Forman, D. Global cancer statistics. CA Cancer J Clin 2011;61:69–90. https://doi.org/10.3322/caac.20107 . DOI

Thai, AA, Solomon, BJ, Sequist, LV, Gainor, JF, Heist, RS. Lung cancer. Lancet 2021;398:535–54. https://doi.org/10.1016/s0140-6736(21)00312-3 . DOI

Thun, MJ, Carter, BD, Feskanich, D, Freedman, ND, Prentice, R, Lopez, AD, et al.. 50-year trends in smoking-related mortality in the United States. N Engl J Med 2013;368:351–64. https://doi.org/10.1056/nejmsa1211127 . DOI

Howlader, N, Forjaz, G, Mooradian, MJ, Meza, R, Kong, CY, Cronin, KA, et al.. The effect of advances in lung-cancer treatment on population mortality. N Engl J Med 2020;383:640–9. https://doi.org/10.1056/nejmoa1916623 . DOI

van Meerbeeck, JP, Fennell, DA, De Ruysscher, DKM. Small-cell lung cancer. Lancet 2011;378:1741–55. https://doi.org/10.1016/s0140-6736(11)60165-7 . DOI

Goldstraw, P, Ball, D, Jett, JR, Le Chevalier, T, Lim, E, Nicholson, AG, et al.. Non-small-cell lung cancer. Lancet 2011;378:1727–40. https://doi.org/10.1016/s0140-6736(10)62101-0 . DOI

Decramer, M, Janssens, W, Miravitlles, M. Chronic obstructive pulmonary disease. Lancet 2012;379:1341–51. https://doi.org/10.1016/s0140-6736(11)60968-9 . DOI

Jamal-Hanjani, M, Wilson, GA, McGranahan, N, Birkbak, NJ, Watkins, TBK, Veeriah, S, et al.. Tracking the evolution of non-small-cell lung cancer. N Engl J Med 2017;376:2109–21.

Hirsch, FR, Scagliotti, GV, Mulshine, JL, Kwon, R, Curran, WJ, Wu, Y-L, et al.. Lung cancer: current therapies and new targeted treatments. Lancet 2017;389:299–311. https://doi.org/10.1016/s0140-6736(16)30958-8 . DOI

Sands, J, Tammemägi, MC, Couraud, S, Baldwin, DR, Borondy-Kitts, A, Yankelevitz, D, et al.. Lung screening benefits and challenges: a review of the data and outline for implementation. J Thorac Oncol 2021;16:37–53. https://doi.org/10.1016/j.jtho.2020.10.127 . DOI

van der Linden, N, Smit, EF, Uyl-de Groot, CA. Real-world costs of laboratory tests for non-small cell lung cancer. Clin Chem Lab Med 2015;53:e187–9. https://doi.org/10.1515/cclm-2014-1262 . DOI

Kossowska, B, Ferens-Sieczkowska, M, Gancarz, R, Passowicz-Muszyńska, E, Jankowska, R. Fucosylation of serum glycoproteins in lung cancer patients. Clin Chem Lab Med 2005;43:361–9. https://doi.org/10.1515/cclm.2005.066 . DOI

Filippou, PS, Ren, AH, Korbakis, D, Dimitrakopoulos, L, Soosaipillai, A, Barak, V, et al.. Exploring the potential of mucin 13 (MUC13) as a biomarker for carcinomas and other diseases. Clin Chem Lab Med 2018;56:1945–53. https://doi.org/10.1515/cclm-2018-0139 . DOI

Debeljak, Ž, Dundović, S, Badovinac, S, Mandić, S, Samaržija, M, Dmitrović, B, et al.. Serum carbohydrate sulfotransferase 7 in lung cancer and non-malignant pulmonary inflammations. Clin Chem Lab Med 2018;56:1328–35. https://doi.org/10.1515/cclm-2017-1157 . DOI

Hertlein, L, Stieber, P, Kirschenhofer, A, Krocker, K, Nagel, D, Lenhard, M, et al.. Human epididymis protein 4 (HE4) in benign and malignant diseases. Clin Chem Lab Med 2012;50:2181–8. https://doi.org/10.1515/cclm-2012-0097 . DOI

Nagy, B, Bhattoa, HP, Steiber, Z, Csobán, M, Szilasi, M, Méhes, G, et al.. Serum human epididymis protein 4 (HE4) as a tumor marker in men with lung cancer. Clin Chem Lab Med 2014;52:1639–48. https://doi.org/10.1515/cclm-2014-0041 . DOI

Yang, HJ, Gu, Y, Chen, C, Xu, C, Bao, YX. Diagnostic value of pro-gastrin-releasing peptide for small cell lung cancer: a meta-analysis. Clin Chem Lab Med 2011;49:1039–46. https://doi.org/10.1515/cclm.2011.161 . DOI

Mroczko, B, Szmitkowski, M, Niklinski, J. Stem cell factor and granulocyte-macrophage-colony stimulating factor as candidates for tumour markers for non-small-cell lung cancer. Clin Chem Lab Med 1999;37:959–62. https://doi.org/10.1515/cclm.1999.141 . DOI

Calişkan-Can, E, Firat, H, Ardiç, S, Simşek, B, Torun, M, Yardim-Akaydin, S. Increased levels of 8-hydroxydeoxyguanosine and its relationship with lipid peroxidation and antioxidant vitamins in lung cancer. Clin Chem Lab Med 2008;46:107–12. https://doi.org/10.1515/cclm.2008.010 . DOI

Pei, Q, Luo, Y, Chen, Y, Li, J, Xie, D, Ye, T. Artificial intelligence in clinical applications for lung cancer: diagnosis, treatment and prognosis. Clin Chem Lab Med 2022;60:1974–83. https://doi.org/10.1515/cclm.2022.0291 . DOI

Gurioli, G, Martignano, F, Salvi, S, Costantini, M, Gunelli, R, Casadio, V. GSTP1 methylation in cancer: a liquid biopsy biomarker? Clin Chem Lab Med 2018;56:702–17. https://doi.org/10.1515/cclm-2017-0703 . DOI

Son, SM, Woo, CG, Han, HS, Lee, KH, Lim, YH, Lee, OJ. Analysis of EGFR mutation status in malignant pleural effusion and plasma from patients with advanced lung adenocarcinoma. Clin Chem Lab Med 2020;58:1547–55. https://doi.org/10.1515/cclm-2019-1139 . DOI

Buyru, N, Tigli, H, Duranyildiz, D, Dalay, N. Molecular detection of squamous cell carcinoma antigen transcripts in peripheral blood of cancer patients. Clin Chem Lab Med 2006;44:538–41. https://doi.org/10.1515/cclm.2006.104 . DOI

Markou, A, Liang, Y, Lianidou, E. Prognostic, therapeutic and diagnostic potential of microRNAs in non-small cell lung cancer. Clin Chem Lab Med 2011;49:1591–603. https://doi.org/10.1515/cclm.2011.661 . DOI

Wang, N, Guo, W, Song, X, Liu, L, Niu, L, Song, X, et al.. Tumor-associated exosomal miRNA biomarkers to differentiate metastatic vs. nonmetastatic non-small cell lung cancer. Clin Chem Lab Med 2020;58:1535–45. https://doi.org/10.1515/cclm-2019-1329 . DOI

Markopoulou, S, Nikolaidis, G, Liloglou, T. DNA methylation biomarkers in biological fluids for early detection of respiratory tract cancer. Clin Chem Lab Med 2012;50:1723–31. https://doi.org/10.1515/cclm-2012-0124 . DOI

Wolrab, D, Jirásko, R, Cífková, E, Höring, M, Mei, D, Chocholoušková, M, et al.. Lipidomic profiling of human serum enables detection of pancreatic cancer. Nat Commun 2022;13:124. https://doi.org/10.1038/s41467-021-27765-9 . DOI

Buszewski, B, Ulanowska, A, Kowalkowski, T, Cieśliński, K. Investigation of lung cancer biomarkers by hyphenated separation techniques and chemometrics. Clin Chem Lab Med 2011;50:573–81. https://doi.org/10.1515/cclm.2011.769 . DOI

Ligor, M, Ligor, T, Bajtarevic, A, Ager, C, Pienz, M, Klieber, M, et al.. Determination of volatile organic compounds in exhaled breath of patients with lung cancer using solid phase microextraction and gas chromatography mass spectrometry. Clin Chem Lab Med 2009;47:550–60. https://doi.org/10.1515/cclm.2009.133 . DOI

Lippi, G, Cervellin, G. Canine olfactory detection of cancer versus laboratory testing: myth or opportunity? Clin Chem Lab Med 2012;50:435–9. https://doi.org/10.1515/cclm.2011.672 . DOI

Melichar, B, Plebani, M. Cancer diagnosis: from dogs to DNA or from DNA to dogs? Clin Chem Lab Med 2012;50:415–8. https://doi.org/10.1515/cclm.2011.786 . DOI

Fischer, B, Lassen, U, Mortensen, J, Larsen, S, Loft, A, Bertelsen, A, et al.. Preoperative staging of lung cancer with combined PET-CT. N Engl J Med 2009;361:32–9. https://doi.org/10.1056/nejmoa0900043 . DOI

Donington, J, Schumacher, L, Yanagawa, J. Surgical issues for operable early-stage non–small-cell lung cancer. J Clin Oncol 2022;40:530–8. https://doi.org/10.1200/jco.21.01592 . DOI

Watine, J. Laboratory variables as additional staging parameters in patients with small-cell lung carcinoma. A systematic review. Clin Chem Lab Med 1999;37:931–8. https://doi.org/10.1515/cclm.1999.138 . DOI

Daly, ME. Inoperable early-stage non–small-cell lung cancer: stereotactic ablative radiotherapy and rationale for systemic therapy. J Clin Oncol 2022;40:539–45. https://doi.org/10.1200/jco.21.01611 . DOI

Daly, ME, Singh, N, Ismaila, N, Antonoff, MB, Arenberg, DA, Bradley, J, et al.. Management of stage III non–small-cell lung cancer: ASCO guideline. J Clin Oncol 2022;40:1356–84. https://doi.org/10.1200/jco.21.02528 . DOI

Daly, ME, Ismaila, N, Decker, RH, Higgins, K, Owen, D, Saxena, A, et al.. Radiation therapy for small-cell lung cancer: ASCO guideline endorsement of an ASTRO guideline. J Clin Oncol 2021;39:931–9. https://doi.org/10.1200/jco.20.03364 . DOI

Antonia, SJ, Villegas, A, Daniel, D, Vicente, D, Murakami, S, Hui, R, et al.. Durvalumab after chemoradiotherapy in stage III non–small-cell lung cancer. N Engl J Med 2017;377:1919–29. https://doi.org/10.1056/nejmoa1709937 . DOI

Tsui, DCC, Camidge, DR, Rusthoven, CG. Managing central nervous system spread of lung cancer: the state of the art. J Clin Oncol 2022;40:642–60. https://doi.org/10.1200/jco.21.01715 . DOI

Jasper, K, Stiles, B, McDonald, F, Palma, DA. Practical management of oligometastatic non-small-cell lung cancer. J Clin Oncol 2022;40:635–41. https://doi.org/10.1200/jco.21.01719 . DOI

Reck, M, Rabe, KF. Precision diagnosis and treatment for advanced non-small-cell lung cancer. N Engl J Med 2017;377:849–61. https://doi.org/10.1056/nejmra1703413 . DOI

Chaft, JE, Shyr, Y, Sepesi, B, Forde, PM. Preoperative and postoperative systemic therapy for operable non-small-cell lung cancer. J Clin Oncol 2022;40:546–55. https://doi.org/10.1200/jco.21.01589 . DOI

Zugazagoitia, J, Paz-Ares, L. Extensive-stage small-cell lung cancer: first-line and second-line treatment options. J Clin Oncol 2022;40:671–80. https://doi.org/10.1200/jco.21.01881 . DOI

Winton, T, Livingston, R, Johnson, D, Rigas, J, Johnston, M, Butts, C, et al.. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med 2005;352:2589–97. https://doi.org/10.1056/nejmoa043623 . DOI

Arriagada, R, Bergman, B, Dunant, A, Le Chevalier, T, Pignon, JP, Vansteenkiste, J, et al.. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med 2004;350:351–60.

Schiller, JH, Harrington, D, Belani, CP, Langer, C, Sandler, A, Krook, J, et al.. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 2002;346:92–8. https://doi.org/10.1056/nejmoa011954 . DOI

Azzoli, CG, Baker, S, Temin, S, Pao, W, Aliff, T, Brahmer, J, et al.. American Society of Clinical Oncology Clinical Practice Guideline update on chemotherapy for stage IV non-small-cell lung cancer. J Clin Oncol 2009;27:6251–66. https://doi.org/10.1200/jco.2009.23.5622 . DOI

Sundstrom, S, Bremnes, RM, Kaasa, S, Aasebo, U, Hatlevoll, R, Dahle, R, et al.. Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results form a randomized phase III trial with 5 years’ follow-up. J Clin Oncol 2002;20:4665–72. https://doi.org/10.1200/jco.2002.12.111 . DOI

Bogart, JA, Waqar, SN, Mix, MD. Radiation and systemic therapy for limited-stage small-cell lung cancer. J Clin Oncol 2022;40:661–70. https://doi.org/10.1200/jco.21.01639 . DOI

Schiller, JH, Adak, S, Cella, D, deVore, RF, Johnson, DH. Topotecan versus observation after cisplatin plus etoposide in extensive-stage small-cell lung cancer: E7593 a a phase III trial of the Eastern Cooperative Oncology Group. J Clin Oncol 2001;19:2114–22. https://doi.org/10.1200/jco.2001.19.8.2114 . DOI

von Pawel, J, Schiller, JH, Shepherd, FA, Fields, SZ, Kleisbauer, JP, Chrysson, NG, et al.. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol 1999;17:658–67. https://doi.org/10.1200/jco.1999.17.2.658 . DOI

Giaccone, G, Herbst, RS, Manegold, C, Scagliotti, G, Rosell, R, Miller, V, et al.. Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial – INTACT 1. J Clin Oncol 2004;22:777–84. https://doi.org/10.1200/jco.2004.08.001 . DOI

Kelly, K, Crowley, J, Bunn, PA, Presant, CA, Grevstad, PK, Moinpour, CM, et al.. Randomized phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in the treatment of patients with advanced non-small-cell lung cancer: a Southwest Oncology Group trial. J Clin Oncol 2001;19:3210–8. https://doi.org/10.1200/jco.2001.19.13.3210 . DOI

Fossella, F, Pereira, JR, von Pawel, J, Pluzanska, A, Gorbounova, V, Kaukel, E, et al.. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbin plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol 2003;21:3016–24. https://doi.org/10.1200/jco.2003.12.046 . DOI

Scagliotti, GV, Parikh, P, von Pawel, J, Biesma, B, Vansteenkiste, J, Manegold, C, et al.. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol 2008;26:3543–51. https://doi.org/10.1200/jco.2007.15.0375 . DOI

Rudd, RM, Gower, NH, Spiro, SG, Eisen, TG, Harper, PG, Littler, JAH, et al.. Gemcitabine plus carboplatin versus mitomycin, ifosfamide, and cisplatin in patients with stage IIIB or IV non-small-cell lung cancer: a phase III randomized study of the London Lung Cancer Group. J Clin Oncol 2005;23:142–53. https://doi.org/10.1200/jco.2005.03.037 . DOI

Alberola, V, Camps, C, Provencio, M, Isla, D, Rosell, R, Vadell, C, et al.. Cisplatin plus gemcitabine versus a cisplatin-based triplet versus nonplatinum sequential doublets in advanced non-small-cell lung cancer: a Spanish Lung Cancer Group phase III randomized trial. J Clin Oncol 2003;21:3207–13. https://doi.org/10.1200/jco.2003.12.038 . DOI

Comella, P, Frasci, G, Panza, N, Manzione, L, De Cataldis, G, Cioffi, R, et al.. Randomized trial comparing cisplatin, gemcitabine, and vinorelbine with either cisplatin and gemcitabine or cisplatin and vinorelbin in advanced non-small-cell lung cancer: interim analysis of a phase III trial of the Southern Italy Cooperative Oncology Group. J Clin Oncol 2000;18:1451–7. https://doi.org/10.1200/jco.2000.18.7.1451 . DOI

Shepherd, FA, Dancey, J, Ramlau, R, Mattson, K, Gralla, R, O’Rourke, M, et al.. Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol 2000;18:2095–103. https://doi.org/10.1200/jco.2000.18.10.2095 . DOI

van de Vijver, MJ, He, YF, van’t Veer, LJ, Dai, H, Hart, AAM, Voskuil, DW, et al.. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 2002;347:1999–2009. https://doi.org/10.1056/nejmoa021967 . DOI

Chen, HY, Yu, SL, Chen, CH, Chang, GC, Chen, CY, Yuan, A, et al.. A five-gene signature and clinical outcome in non-small-cell lung cancer. N Engl J Med 2007;356:11–20. https://doi.org/10.1056/nejmoa060096 . DOI

Olaussen, KA, Dunant, A, Fouret, P, Brambilla, E, André, F, Haddad, V, et al.. DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med 2006;355:983–91. https://doi.org/10.1056/nejmoa060570 . DOI

Friboulet, L, Olaussen, KA, Pignon, JP, Shepherd, FA, Tsao, MS, Graziano, S, et al.. ERCC1 isoform expression and DNA repair in non-small-cell lung cancer. N Engl J Med 2013;368:1101–10. https://doi.org/10.1056/nejmoa1214271 . DOI

Burris, HA. Overcoming acquired resistance to anticancer therapy: focus on the PI3K/AKT/mTOR pathway. Cancer Chemother Pharmacol 2013;71:829–42. https://doi.org/10.1007/s00280-012-2043-3 . DOI

Sandler, A, Gray, R, Perry, MC, Brahmer, J, Schiller, JH, Dowlati, A, et al.. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 2006;355:2542–50. https://doi.org/10.1056/nejmoa061884 . DOI

Garon, EB, Ciuleanu, T-E, Arrieta, O, Prabhash, K, Syrigos, KN, Goksel, T, et al.. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet 2014;384:665–73. https://doi.org/10.1016/s0140-6736(14)60845-x . DOI

Reck, M, Kaiser, R, Mellemgaard, A, Douillard, JY, Orlov, S, Krzakowski, M, et al.. Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial. Lancet Oncol 2014;15:143–55. https://doi.org/10.1016/s1470-2045(13)70586-2 . DOI

Kim, ES, Hirsh, V, Mok, T, Socinski, MA, Gervais, R, Wu, YL, et al.. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial. Lancet 2008;372:1809–18. https://doi.org/10.1016/s0140-6736(08)61758-4 . DOI

Shepherd, FA, Pereira, JR, Ciuleanu, T, Tan, EH, Hirsh, V, Thongprasert, S, et al.. Erlotinib in previously treated non-small-cell-lung cancer. N Engl J Med 2005;353:123–32. https://doi.org/10.1056/nejmoa050753 . DOI

Yang, JC, Wu, YL, Schuler, M, Sebastian, M, Popat, S, Yamamoto, N, et al.. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol 2015;16:141–51. https://doi.org/10.1016/s1470-2045(14)71173-8 . DOI

Wu, YL, Cheng, Y, Zhou, X, Lee, KH, Nakagawa, K, Niho, S, et al.. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol 2017;18:1454–66. https://doi.org/10.1016/s1470-2045(17)30608-3 . DOI

Wu, YL, Tsuboi, M, He, J, John, T, Grohe, C, Majem, M, et al.. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med 2020;383:1711–23. https://doi.org/10.1056/nejmoa2027071 . DOI

Solomon, BJ, Mok, T, Kim, DW, Wu, YL, Nakagawa, K, Mekhail, T, et al.. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med 2014;371:2167–77. https://doi.org/10.1056/nejmoa1408440 . DOI

Shaw, AT, Kim, DW, Mehra, R, Tan, DS, Felip, E, Chow, LQ, et al.. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med 2014;370:1189–97. https://doi.org/10.1056/nejmoa1311107 . DOI

Peters, S, Camidge, DR, Shaw, AT, Gadgeel, S, Ahn, JS, Kim, DW, et al.. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med 2017;377:829–38. https://doi.org/10.1056/nejmoa1704795 . DOI

Camidge, DR, Kim, HR, Ahn, MJ, Yang, JC, Han, JY, Lee, JS, et al.. Brigatinib versus crizotinib in ALK-positive non-small-cell lung cancer. N Engl J Med 2018;379:2027–39. https://doi.org/10.1056/nejmoa1810171 . DOI

Horn, L, Wang, Z, Wu, G, Poddubskaya, E, Mok, T, Reck, M, et al.. Ensartinib vs crizotinib for patients with anaplastic lymphoma kinase-positive non-small cell lung cancer: a randomized clinical trial. JAMA Oncol 2021;7:1617–25. https://doi.org/10.1001/jamaoncol.2021.3523 . DOI

Shaw, AT, Bauer, TM, de Marinis, F, Felip, E, Goto, Y, Liu, G, et al.. First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer. N Engl J Med 2020;383:2018–29. https://doi.org/10.1056/nejmoa2027187 . DOI

Planchard, D, Besse, B, Groen, HJM, Souquet, PJ, Quoix, E, Baik, CS, et al.. Dabrafenib plus trametinib in patients with previously treated BRAF(V600E)-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial. Lancet Oncol 2016;17:984–93. https://doi.org/10.1016/s1470-2045(16)30146-2 . DOI

Hyman, DM, Puzanov, I, Subbiah, V, Faris, JE, Chau, I, Blay, JY, et al.. Vemurafenib in multiple nonmelanoma cancers with BRAF V600 mutations. N Engl J Med 2015;373:726–36. https://doi.org/10.1056/nejmoa1502309 . DOI

Drilon, A, Oxnard, GR, Tan, DSW, Loong, HHF, Johnson, M, Gainor, J, et al.. Efficacy of selpercatinib in RET fusion-positive non-small-cell lung cancer. N Engl J Med 2020;383:813–24. https://doi.org/10.1056/nejmoa2005653 . DOI

Gainor, JF, Curigliano, G, Kim, DW, Lee, DH, Besse, B, Baik, CS, et al.. Pralsetinib for RET fusion-positive non-small-cell lung cancer (ARROW): a multi-cohort, open-label, phase 1/2 study. Lancet Oncol 2021;22:959–69. https://doi.org/10.1016/s1470-2045(21)00247-3 . DOI

Wolf, J, Seto, T, Han, JY, Reguart, N, Garon, EB, Groen, HJM, et al.. Capmatinib in MET exon 14-mutated or MET-amplified non-small-cell lung cancer. N Engl J Med 2020;383:944–57. https://doi.org/10.1056/nejmoa2002787 . DOI

Paik, PK, Felip, E, Veillon, R, Sakai, H, Cortot, AB, Garassino, MC, et al.. Tepotinib in non-small-cell lung cancer with MET exon 14 skipping mutations. N Engl J Med 2020;383:931–43.

Drilon, A, Siena, S, Dziadziuszko, R, Barlesi, F, Krebs, MG, Shaw, AT, et al.. Entrectinib in ROS1 fusion-positive non-small-cell lung cancer: integrated analysis of three phase 1-2 trials. Lancet Oncol 2020;21:261–70. https://doi.org/10.1016/s1470-2045(19)30690-4 . DOI

Drilon, A, Laetsch, TW, Kummar, S, DuBois, SG, Lassen, UN, Demetri, GD, et al.. Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children. N Engl J Med 2018;378:731–9. https://doi.org/10.1056/nejmoa1714448 . DOI

Skoulidis, F, Li, BT, Dy, GK, Price, TJ, Falchook, GS, Wolf, J, et al.. Sotorasib for lung cancers with KRAS p.G12C mutation. N Engl J Med 2021;384:2371–81. https://doi.org/10.1056/nejmoa2103695 . DOI

Jänne, PA, Riely, GJ, Gadgeel, SM, Heist, RS, Ou, SI, Pacheco, JM, et al.. Adagrasib in non-small-cell lung cancer harboring a KRAS(G12C) mutation. N Engl J Med 2022;387:120–31. https://doi.org/10.1056/nejmoa2204619 . DOI

Park, K, Haura, EB, Leighl, NB, Mitchell, P, Shu, CA, Girard, N, et al.. Amivantamab in EGFR exon 20 insertion–mutated non–small-cell lung cancer progressing on platinum chemotherapy: initial results from the CHRYSALIS phase I study. J Clin Oncol 2021;39:3391–402. https://doi.org/10.1200/jco.21.00662 . DOI

Li, BT, Smit, EF, Goto, Y, Nakagawa, K, Udagawa, H, Mazières, J, et al.. Trastuzumab deruxtecan in HER2-mutant non-small-cell lung cancer. N Engl J Med 2022;386:241–51. https://doi.org/10.1056/nejmoa2112431 . DOI

Cataldo, VD, Gibbons, DL, Perez-Soler, R, Quintas-Cardama, A. Treatment of non-small-cell lung cancer with erlotinib or gefitinib. N Engl J Med 2011;364:947–55. https://doi.org/10.1056/nejmct0807960 . DOI

Bartoušková, M, Melichar, B. Precision medicine in medical oncology: hope, disappointment and reality. Clin Chem Lab Med 2020;58:1427–31. https://doi.org/10.1515/cclm-2020-0231 . DOI

Robert, C, Grob, JJ, Stroyakovskiy, D, Karaszewska, B, Hauschild, A, Levchenko, E, et al.. Five-year outcomes with dabrafenib plus trametinib in metastatic melanoma. N Engl J Med 2019;381:626–36. https://doi.org/10.1056/nejmoa1904059 . DOI

Riudavets, M, Sullivan, I, Abdayem, P, Planchard, D. Targeting HER2 in non-small-cell lung cancer (NSCLC): a glimpse of hope? An updated review on therapeutic strategies in NSCLC harbouring HER2 alterations. ESMO Open 2021;6:100260. https://doi.org/10.1016/j.esmoop.2021.100260 . DOI

Melichar, B, Adenis, A, Lockhart, AC, Bennouna, J, Dees, EC, Kayaleh, O, et al.. Safety and activity of alisertib, an investigational aurora kinase A inhibitor, in patients with breast cancer, small-cell lung cancer, non-small-cell lung cancer, head and neck squamous-cell carcinoma, and gastro-oesophageal adenocarcinoma: a five-arm phase 2 study. Lancet Oncol 2015;16:395–405. https://doi.org/10.1016/s1470-2045(15)70051-3 . DOI

Garon, EB, Rizvi, NA, Hui, RN, Leighl, N, Balmanoukian, AS, Eder, JP, et al.. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med 2015;372:2018–28. https://doi.org/10.1056/nejmoa1501824 . DOI

Reck, M, Rodriguez-Abreu, D, Robinson, AG, Hui, RN, Csoszi, T, Fulop, A, et al.. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 2016;375:1823–33. https://doi.org/10.1056/nejmoa1606774 . DOI

Borghaei, H, Paz-Ares, L, Horn, L, Spigel, DR, Steins, M, Ready, NE, et al.. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 2015;373:1627–39. https://doi.org/10.1056/nejmoa1507643 . DOI

Brahmer, J, Reckamp, KL, Baas, P, Crinò, L, Eberhardt, WE, Poddubskaya, E, et al.. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 2015;373:123–35. https://doi.org/10.1056/nejmoa1504627 . DOI

Herbst, RS, Giaccone, G, de Marinis, F, Reinmuth, N, Vergnenegre, A, Barrios, CH, et al.. Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC. N Engl J Med 2020;383:1328–39. https://doi.org/10.1056/nejmoa1917346 . DOI

Socinski, MA, Jotte, RM, Cappuzzo, F, Orlandi, F, Stroyakovskiy, D, Nogami, N, et al.. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N Engl J Med 2018;378:2288–301. https://doi.org/10.1056/nejmoa1716948 . DOI

Hellmann, MD, Paz-Ares, L, Bernabe Caro, R, Zurawski, B, Kim, SW, Carcereny Costa, E, et al.. Nivolumab plus ipilimumab in advanced non-small-cell lung cancer. N Engl J Med 2019;381:2020–31. https://doi.org/10.1056/nejmoa1910231 . DOI

Horn, L, Mansfield, AS, Szczęsna, A, Havel, L, Krzakowski, M, Hochmair, MJ, et al.. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med 2018;379:2220–9. https://doi.org/10.1056/nejmoa1809064 . DOI

Carbone, DP, Reck, M, Paz-Ares, L, Creelan, B, Horn, L, Steins, M, et al.. First-line nivolumab in stage IV or recurrent non-small-cell lung cancer. N Engl J Med 2017;376:2415–26. https://doi.org/10.1056/nejmoa1613493 . DOI

Forde, PM, Spicer, J, Lu, S, Provencio, M, Mitsudomi, T, Awad, MM, et al.. Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer. N Engl J Med 2022;386:1973–85. https://doi.org/10.1056/nejmoa2202170 . DOI

Felip, E, Altorki, N, Zhou, C, Csőszi, T, Vynnychenko, I, Goloborodko, O, et al.. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Lancet 2021;398:1344–57. https://doi.org/10.1016/s0140-6736(21)02098-5 . DOI

Sezer, A, Kilickap, S, Gümüş, M, Bondarenko, I, Özgüroğlu, M, Gogishvili, M, et al.. Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. Lancet 2021;397:592–604. https://doi.org/10.1016/s0140-6736(21)00228-2 . DOI

Prommegger, R, Widner, B, Murr, C, Unger, A, Fuchs, D, Salzer, GM. Neopterin: a prognostic variable in operations for lung cancer. Ann Thorac Surg 2000;70:1861–4. https://doi.org/10.1016/s0003-4975(00)01840-3 . DOI

Kerr, KM, Bibeau, F, Thunnissen, E, Botling, J, Ryška, A, Wolf, J, et al.. The evolving landscape of biomarker testing for non-small cell lung cancer in Europe. Lung Cancer 2021;154:161–75. https://doi.org/10.1016/j.lungcan.2021.02.026 . DOI

Han, Y, Li, J. Sample types applied for molecular diagnosis of therapeutic management of advanced non-small cell lung cancer in the precision medicine. Clin Chem Lab Med 2017;55:1817–33. https://doi.org/10.1515/cclm-2017-0112 . DOI

Frankel, D, Nanni-Metellus, I, Robaglia-Schlupp, A, Tomasini, P, Guinde, J, Barlesi, F, et al.. Detection of EGFR, KRAS and BRAF mutations in metastatic cells from cerebrospinal fluid. Clin Chem Lab Med 2018;56:851–6. https://doi.org/10.1515/cclm-2017-0527 . DOI

Buszewski, B, Ulanowska, A, Kowalkowski, T, Cieslinski, K. Lung cancer biomarkers by hyphenated separation techniques and chemometrics. Clin Chem Lab Med 2012;50:573–81.

Park, S, Hur, JY, Lee, KY, Lee, JC, Rho, JK, Shin, SH, et al.. Assessment of EGFR mutation status using cell-free DNA from bronchoalveolar lavage fluid. Clin Chem Lab Med 2017;55:1489–95. https://doi.org/10.1515/cclm-2016-0302 . DOI

Hwang, SH, Kim, KU, Kim, JE, Kim, HH, Lee, MK, Lee, CH, et al.. Detection of HOXA9 gene methylation in tumor tissues and induced sputum samples from primary lung cancer patients. Clin Chem Lab Med 2011;49:699–704. https://doi.org/10.1515/cclm.2011.108 . DOI

Pinzani, P, D’Argenio, V, Del Re, M, Pellegrini, C, Cucchiara, F, Salvianti, F, et al.. Updates on liquid biopsy: current trends and future perspectives for clinical application in solid tumors. Clin Chem Lab Med 2021;59:1181–200. https://doi.org/10.1515/cclm-2020-1685 . DOI

Ilie, M, Hofman, V, Leroy, S, Cohen, C, Heeke, S, Cattet, F, et al.. Use of circulating tumor cells in prospective clinical trials for NSCLC patients – standardization of the pre-analytical conditions. Clin Chem Lab Med 2018;56:980–9. https://doi.org/10.1515/cclm-2017-0764 . DOI

Pachmann, K, Clement, JH, Schneider, CP, Willen, B, Camara, O, Pachmann, U, et al.. Standardized quantification of circulating peripheral tumor cells from lung and breast cancer. Clin Chem Lab Med 2005;43:617–27. https://doi.org/10.1515/cclm.2005.107 . DOI

Wu, S, Liu, Z, Liu, S, Lin, L, Yang, W, Xu, J. Enrichment and enumeration of circulating tumor cells by efficient depletion of leukocyte fractions. Clin Chem Lab Med 2014;52:243–51. https://doi.org/10.1515/cclm-2013-0558 . DOI

Leers, MPG. Circulating tumor DNA and their added value in molecular oncology. Clin Chem Lab Med 2020;58:152–61. https://doi.org/10.1515/cclm-2019-0436 . DOI

Vinci, S, Gelmini, S, Pratesi, N, Conti, S, Malentacchi, F, Simi, L, et al.. Genetic variants in miR-146a, miR-149, miR-196a2, miR-499 and their influence on relative expression in lung cancers. Clin Chem Lab Med 2011;49:2073–80. https://doi.org/10.1515/cclm.2011.708 . DOI

Balgkouranidou, I, Chimonidou, M, Milaki, G, Tsaroucha, E, Kakolyris, S, Georgoulias, V, et al.. SOX17 promoter methylation in plasma circulating tumor DNA of patients with non-small cell lung cancer. Clin Chem Lab Med 2016;54:1385–93. https://doi.org/10.1515/cclm-2015-0776 . DOI

Pellini, B, Chaudhuri, AA. Circulating tumor DNA minimal residual disease detection of non-small-cell lung cancer treated with curative intent. J Clin Oncol 2022;40:567–75. https://doi.org/10.1200/jco.21.01929 . DOI

Tie, J, Cohen, JD, Lahouel, K, Lo, SN, Wang, Y, Kosmider, S, et al.. Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer. N Engl J Med 2022;386:2261–72. https://doi.org/10.1056/nejmoa2200075 . DOI

Hanahan, D, Weinberg, RA. Hallmarks of cancer: the next generation. Cell 2011;144:646–74. https://doi.org/10.1016/j.cell.2011.02.013 . DOI

Lynch, TJ, Bell, DW, Sordella, R, Gurubhagavatula, S, Okimata, RA, Brannigan, BW, et al.. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004;350:2129–39. https://doi.org/10.1056/nejmoa040938 . DOI

Maemondo, M, Inoue, A, Kobayashi, K, Sugawara, S, Oizumi, S, Isobe, H, et al.. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 2010;362:2380–8. https://doi.org/10.1056/nejmoa0909530 . DOI

Rosell, R, Moran, T, Queralt, C, Porta, R, Cardenal, F, Camps, C, et al.. Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med 2009;361:958–67. https://doi.org/10.1056/nejmoa0904554 . DOI

Tan, AC, Tan, DSW. Targeted therapies for lung cancer patients with oncogenic driver molecular alterations. J Clin Oncol 2022;40:611–25. https://doi.org/10.1200/jco.21.01626 . DOI

Neijssen, J, Cardoso, RMF, Chevalier, KM, Wiegman, L, Valerius, T, Anderson, GM, et al.. Discovery of amivantamab (JNJ-61186372), a bispecific antibody targeting EGFR and MET. J Biol Chem 2021;296:100641. https://doi.org/10.1016/j.jbc.2021.100641 . DOI

Martínez-Carretero, C, Pascual, FI, Rus, A, Bernardo, I. Detection of EGFR mutations in patients with non-small cell lung cancer by high resolution melting. Comparison with other methods. Clin Chem Lab Med 2017;55:1970–8. https://doi.org/10.1515/cclm-2016-0353 . DOI

Cho, MC, Choi, CM, Kim, S, Jang, S, Jang, S, Park, CJ, et al.. Direct sequencing in cytological specimens as a useful strategy for detecting EGFR mutations in non-small cell lung cancer patients. Clin Chem Lab Med 2011;50:565–72. https://doi.org/10.1515/cclm.2011.704 . DOI

Pérez-Barrios, C, Sánchez-Herrero, E, Garcia-Simón, N, Barquín, M, Clemente, MB, Provencio, M, et al.. ctDNA from body fluids is an adequate source for EGFR biomarker testing in advanced lung adenocarcinoma. Clin Chem Lab Med 2021;59:1221–9. https://doi.org/10.1515/cclm-2020-1465 . DOI

Shin, S, Kim, J, Kim, Y, Cho, SM, Lee, KA. Assessment of real-time PCR method for detection of EGFR mutation using both supernatant and cell pellet of malignant pleural effusion samples from non-small-cell lung cancer patients. Clin Chem Lab Med 2017;55:1962–9. https://doi.org/10.1515/cclm-2016-0851 . DOI

Wang, MC, Wang, CL, Chen, TL, Chang, JW, Lu, JJ, Chang, PY, et al.. Predicting outcomes of EGFR-targeted therapy in non-small cell lung cancer patients using pleural effusions samples and peptide nucleic acid probe assay. Clin Chem Lab Med 2017;55:1979–86. https://doi.org/10.1515/cclm-2016-0809 . DOI

Schneider, J, Presek, P, Braun, A, Löffler, S, Woitowitz, HJ. Serum ras (p21) as a marker for occupationally derived lung cancer? Clin Chem Lab Med 2000;38:301–5. https://doi.org/10.1515/cclm.2000.042 . DOI

Wu, S, Zhu, Z, He, J, Luo, X, Xu, J, Ren-Heidenreich, L. A novel mutant-enriched liquidchip technology for the qualitative detection of somatic mutations in KRAS gene from both serum and tissue samples. Clin Chem Lab Med 2010;48:1103–6. https://doi.org/10.1515/cclm.2010.227 . DOI

Rho, JK, Lee, H, Park, CS, Choi, CM, Lee, JC. Sensitive detection of EML4-ALK fusion oncoprotein of lung cancer by in situ proximity ligation assay. Clin Chem Lab Med 2013;51:1843–8. https://doi.org/10.1515/cclm-2013-0044 . DOI

de Abreu, FB, Peterson, JD, Amos, CI, Wells, WA, Tsongalis, GJ. Effective quality management practices in routine clinical next-generation sequencing. Clin Chem Lab Med 2016;54:761–71. https://doi.org/10.1515/cclm-2015-1190 . DOI

Provencio, M, Pérez-Barrios, C, Barquin, M, Calvo, V, Franco, F, Sánchez, E, et al.. Next-generation sequencing for tumor mutation quantification using liquid biopsies. Clin Chem Lab Med 2020;58:306–13. https://doi.org/10.1515/cclm-2019-0745 . DOI

Solassol, J, Quantin, X, Larrieux, M, Senal, R, Audran, P, Grand, D, et al.. Comparison of five cell-free DNA isolation methods to detect the EGFR T790M mutation in plasma samples of patients with lung cancer. Clin Chem Lab Med 2018;56:e243–46. https://doi.org/10.1515/cclm-2017-0967 . DOI

Bodor, JN, Boumber, Y, Borghaei, H. Biomarkers for immune checkpoint inhibition in non–small cell lung cancer (NSCLC). Cancer 2020;126:260–70. https://doi.org/10.1002/cncr.32468 . DOI

Rizvi, NA, Hellmann, MD, Snyder, A, Kvistborg, P, Makarov, V, Havel, JJ, et al.. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 2015;348:124–8. https://doi.org/10.1126/science.aaa1348 . DOI

Wells, DK, van Buuren, MM, Dang, KK, Hubbard-Lucey, VM, Sheehan, KCF, Campbell, KM, et al.. Key parameters of tumor epitope immunogenicity revealed through a consortium approach improve neoantigen prediction. Cell 2020;183:818–34 e13. https://doi.org/10.1016/j.cell.2020.09.015 . DOI

Hellmann, MD, Ciuleanu, TE, Pluzanski, A, Lee, JS, Otterson, GA, Audigier-Valette, C, et al.. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med 2018;378:2093–104. https://doi.org/10.1056/nejmoa1801946 . DOI

Svaton, M, Zemanova, M, Skrickova, J, Jakubikova, L, Kolek, V, Kultan, J, et al.. Chronic inflammation as a potential predictive factor of nivolumab therapy in non-small cell lung cancer. Anticancer Res 2018;38:6771–82. https://doi.org/10.21873/anticanres.13048 . DOI

Li, HX, Bullock, K, Gurjao, C, Braun, D, Shukla, SA, Bosse, D, et al.. Metabolomic adaptations and correlates of survival to immune checkpoint blockade. Nat Commun 2019;10:4346. https://doi.org/10.1038/s41467-019-12361-9 . DOI

Melichar, B, Touskova, M, Solichova, D, Kralickova, P, Kopecky, O. CD4+ T-lymphocytopenia and systemic immune activation in patients with primary and secondary liver tumours. Scand J Clin Lab Invest 2001;61:363–70. https://doi.org/10.1080/003655101316911404 . DOI

Melichar, B, Študentová, H, Vitásková, D, Šrámek, V, Kujovská Krčmová, L, Pešková, E, et al.. Association of urinary neopterin, neutrophil-to-lymphocyte ratios with long-term survival in patients with breast cancer. Pteridines 2016;27:59–65. https://doi.org/10.1515/pterid-2016-0001 . DOI

Grieshober, L, Graw, S, Barnett, MJ, Goodman, GE, Chen, C, Koestler, DC, et al.. Pre-diagnosis neutrophil-to-lymphocyte ratio and mortality in individuals who develop lung cancer. Cancer Causes Control 2021;32:1227–36. https://doi.org/10.1007/s10552-021-01469-3 . DOI

Alessi, JV, Ricciuti, B, Alden, SL, Bertram, AA, Lin, JJ, Sakhi, M, et al.. Low peripheral blood derived neutrophil-to-lymphocyte ratio (dNLR) is associated with increased tumor T-cell infiltration and favorable outcomes to first-line pembrolizumab in non-small cell lung cancer. J Immunother Cancer 2021;9:e003536. https://doi.org/10.1136/jitc-2021-003536 . DOI

Zezulova, M, Bartouskova, M, Hlidkova, E, Adam, T, Kujovska Krcmova, L, Cervinkova, B, et al.. Citrulline as a biomarker of gastrointestinal toxicity in patients with rectal carcinoma treated with chemoradiation. Clin Chem Lab Med 2016;54:305–14. https://doi.org/10.1515/cclm-2015-0326 . DOI

Melichar, B, Dvorak, J, Krcmova, L, Hyspler, R, Urbánek, L, Solichova, D. Intestinal permeability and vitamin A absoption in patients with chemotherapy-induced diarrhea. Am J Clin Oncol 2008;31:580–4. https://doi.org/10.1097/coc.0b013e318174dbb9 . DOI

Melichar, B, Dvorak, J, Kalabova, H, Hyspler, R, Krcmova, L, Kasparova, M, et al.. Intestinal permeability, vitamin A absorption and serum alpha-tocopherol during therapy with gefitinib. Scand J Clin Lab Invest 2010;70:180–7. https://doi.org/10.3109/00365511003653581 . DOI

Kim, ES, Moon, S, Han, JH, Kim, SA, Lee, EH, Beom, SH, et al.. Association between serum γ-glutamyltransferase and pulmonary dysfunction. Clin Chem Lab Med 2012;50:2053–5. https://doi.org/10.1515/cclm-2012-0145 . DOI

Huddart, RA, Norman, A, Shahidi, M, Horwich, A, Coward, D, Nicholls, J, et al.. Cardiovascular disease as a long-term complication of treatment for testicular cancer. J Clin Oncol 2003;21:1513–23. https://doi.org/10.1200/jco.2003.04.173 . DOI

Melichar, B, Kalábová, H, Ungerman, L, Krcmová, L, Hyspler, R, Kasparová, M, et al.. Carotid intima-media thickness and laboratory parameters of atherosclerosis risk in patients with breast cancer. Anticancer Res 2012;32:4077–84.

Yang, HH, Chen, XF, Hu, W, Lv, DQ, Ding, WJ, Tang, LJ, et al.. Lipoprotein(a) level and its association with tumor stage in male patients with primary lung cancer. Clin Chem Lab Med 2009;47:452–7. https://doi.org/10.1515/cclm.2009.094 . DOI

Schroecksnadel, K, Frick, B, Fiegl, M, Winkler, C, Denz, HA, Fuchs, D. Hyperhomocysteinamia and immune activation in patients with cancer. Clin Chem Lab Med 2007;45:47–53.

Circulating tumor DNA measurement: a new pillar of medical oncology?