Cập nhật hướng dẫn về xét nghiệm biomarker dự đoán trong ung thư phổi không tiểu biến tiến triển: Một sự đồng thuận quốc gia của Hiệp hội Bệnh lý Tây Ban Nha và Hiệp hội Ung thư Y tế Tây Ban Nha

Clinical and Translational Oncology - Tập 22 Số 7 - Trang 989-1003 - 2020
Pilar Garrido1, Esther Conde2, Javier de Castro3, Javier Gómez-Román4, Enriqueta Felip5, Lara Pijuán6, Dolores Isla7, Julián Sanz8, Luís Paz-Ares9, Fernando López‐Ríos2
1Department of Medical Oncology, Hospital Universitario Ramón y Cajal, Universidad Alcalá, IRYCIS, CIBERONC, Ctra. de Colmenar Viejo, km. 9100, 28034, Madrid, Spain
2Department of Pathology-Laboratorio de Dianas Terapéuticas, Hospital Universitario HM Sanchinarro, CIBERONC, Madrid, Spain
3Department of Medical Oncology, Hospital Universitario La Paz, Madrid, Spain
4Department of Pathology, Hospital Universitario Marqués de Valdecilla, Universidad de Cantabria, IDIVAL, Santander, Spain
5Department of Medical Oncology, Hospital Universitari Vall d'Hebron, Barcelona, Spain
6Department of Pathology, Hospital del Mar, Barcelona, Spain
7Department of Medical Oncology, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain
8Department of Pathology, Facultad de Medicina, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Universidad Complutense de Madrid, Madrid, Spain
9Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain

Tóm tắt

Tóm tắt

Năm 2011, Hiệp hội Ung thư Y tế Tây Ban Nha (SEOM) và Hiệp hội Bệnh lý Tây Ban Nha (SEAP) đã khởi động một dự án hợp tác nhằm thiết lập các hướng dẫn về xét nghiệm biomarker cho bệnh nhân ung thư phổi không tiểu biến tiến triển (NSCLC) dựa trên bằng chứng hiện có. Vì lĩnh vực này đang phát triển không ngừng, các hướng dẫn này đã được cập nhật, trước đây vào năm 2012 và 2015 và hiện tại vào năm 2019. Bằng chứng hiện tại cho thấy các xét nghiệm bắt buộc cần thực hiện trên tất cả bệnh nhân bị NSCLC tiến triển là xét nghiệm các đột biến EGFRBRAF, các biến dạng ALKROS1, cũng như sự biểu hiện PD-L1. Nhu cầu ngày càng tăng trong việc nghiên cứu các biomarker mới nổi đã thúc đẩy việc sử dụng quy trình giải mã quy mô lớn (xin định thế hệ tiếp theo, NGS) một cách thường xuyên. Việc điều phối giữa tất cả các chuyên gia liên quan và ưu tiên các xét nghiệm và công nghệ phù hợp nhất cho từng trường hợp vẫn là một thách thức.

Từ khóa


Tài liệu tham khảo

Felip E, Concha A, de Castro J, Gomez-Roman J, Garrido P, Ramirez J, et al. Biomarker testing in advanced non-small-cell lung cancer: a National Consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology. Clin Transl Oncol. 2015;17:103–12.

Garrido P, de Castro J, Concha A, Felip E, Isla D, Lopez-Rios F, et al. Guidelines for biomarker testing in advanced non-small-cell lung cancer. A National Consensus of the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathology (SEAP). Clin Transl Oncol. 2012;14:338–49.

Eberhard DA, Giaccone G, Johnson BE, Non-Small-Cell Lung Cancer Working G. Biomarkers of response to epidermal growth factor receptor inhibitors in non-small-cell lung cancer working group: standardization for use in the clinical trial setting. J Clin Oncol. 2008;26:983–94.

Malapelle U, Mayo-de-Las-Casas C, Molina-Vila MA, Rosell R, Savic S, Bihl M, et al. Consistency and reproducibility of next-generation sequencing and other multigene mutational assays: a worldwide ring trial study on quantitative cytological molecular reference specimens. Cancer Cytopathol. 2017;125:615–26.

Dietel M, Bubendorf L, Dingemans AM, Dooms C, Elmberger G, Garcia RC, et al. Diagnostic procedures for non-small-cell lung cancer (NSCLC): recommendations of the European expert group. Thorax. 2016;71:177–84.

Angulo B, Conde E, Suarez-Gauthier A, Plaza C, Martinez R, Redondo P, et al. A comparison of EGFR mutation testing methods in lung carcinoma: direct sequencing, real-time PCR and immunohistochemistry. PLoS One. 2012;7:e43842.

Jennings LJ, Arcila ME, Corless C, Kamel-Reid S, Lubin IM, Pfeifer J, et al. Guidelines for validation of next-generation sequencing-based oncology panels: a joint consensus recommendation of the Association for Molecular Pathology and College of American Pathologists. J Mol Diagn. 2017;19:341–65.

Doxtader EE, Cheng YW, Zhang Y. Molecular testing of non-small cell lung carcinoma diagnosed by endobronchial ultrasound-guided transbronchial fine-needle aspiration. Arch Pathol Lab Med. 2018;143:670–6.

Jain D, Roy-Chowdhuri S. Molecular pathology of lung cancer cytology specimens: a concise review. Arch Pathol Lab Med. 2018;142:1127–33.

Roy-Chowdhuri S, Stewart J. Preanalytic variables in cytology: lessons learned from next-generation sequencing—the MD Anderson experience. Arch Pathol Lab Med. 2016;140:1191–9.

Noll B, Wang WL, Gong Y, Zhao J, Kalhor N, Prieto V, et al. Programmed death ligand 1 testing in non-small cell lung carcinoma cytology cell block and aspirate smear preparations. Cancer Cytopathol. 2018;126:342–52.

Auger M, Brimo F, Kanber Y, Fiset PO, Camilleri-Broet S. A practical guide for ancillary studies in pulmonary cytologic specimens. Cancer Cytopathol. 2018;126(Suppl 8):599–614.

Conde E, Angulo B, Izquierdo E, Paz-Ares L, Belda-Iniesta C, Hidalgo M, et al. Lung adenocarcinoma in the era of targeted therapies: histological classification, sample prioritization, and predictive biomarkers. Clin Transl Oncol. 2013;15:503–8.

Rolfo C, Mack PC, Scagliotti GV, Baas P, Barlesi F, Bivona TG, et al. Liquid biopsy for advanced non-small cell lung cancer (NSCLC): a statement paper from the IASLC. J Thorac Oncol. 2018;13:1248–68.

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.

Yu HA, Suzawa K, Jordan E, Zehir A, Ni A, Kim R, et al. Concurrent alterations in EGFR-mutant lung cancers associated with resistance to EGFR kinase inhibitors and characterization of MTOR as a mediator of resistance. Clin Cancer Res. 2018;24:3108–18.

Planchard D, Popat S, Kerr K, Novello S, Smit EF, Faivre-Finn C, et al. Metastatic non-small cell lung cancer: esmo clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2019;129:iv192–237.

Westover D, Zugazagoitia J, Cho BC, Lovly CM, Paz-Ares L. Mechanisms of acquired resistance to first- and second-generation EGFR tyrosine kinase inhibitors. Ann Oncol. 2018;29:i10–9.

Mok TS, Wu YL, Ahn MJ, Garassino MC, Kim HR, Ramalingam SS, et al. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med. 2017;376:629–40.

Oxnard GR, Hu Y, Mileham KF, Husain H, Costa DB, Tracy P, et al. Assessment of resistance mechanisms and clinical implications in patients with EGFR T790M-positive lung cancer and acquired resistance to osimertinib. JAMA Oncol. 2018;4:1527–34.

Piotrowska Z, Isozaki H, Lennerz JK, Gainor JF, Lennes IT, Zhu VW, et al. Landscape of acquired resistance to osimertinib in EGFR-mutant NSCLC and clinical validation of combined EGFR and RET inhibition with osimertinib and BLU-667 for acquired RET fusion. Cancer Discov. 2018;8:1529–39.

Lindeman NI, Cagle PT, Aisner DL, Arcila ME, Beasley MB, Bernicker EH, et al. Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors: guideline from the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology. Arch Pathol Lab Med. 2018;142:321–46.

Solomon BJ, Kim DW, Wu YL, Nakagawa K, Mekhail T, Felip E, et al. Final overall survival analysis from a study comparing first-line crizotinib versus chemotherapy in ALK-mutation-positive non-small-cell lung cancer. J Clin Oncol. 2018;36:2251–8.

Kalemkerian GP, Narula N, Kennedy EB, Biermann WA, Donington J, Leighl NB, et al. Molecular testing guideline for the selection of patients with lung cancer for treatment with targeted tyrosine kinase inhibitors: American Society of Clinical Oncology Endorsement of the College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology Clinical Practice Guideline Update. J Clin Oncol. 2018;36:911–9.

Nakamura H, Tsuta K, Yoshida A, Shibata T, Wakai S, Asamura H, et al. Aberrant anaplastic lymphoma kinase expression in high-grade pulmonary neuroendocrine carcinoma. J Clin Pathol. 2013;66:705–7.

Conde E, Hernandez S, Prieto M, Martinez R, Lopez-Rios F. Profile of Ventana ALK (D5F3) companion diagnostic assay for non-small-cell lung carcinomas. Expert Rev Mol Diagn. 2016;16:707–13.

Thunnissen E, Allen TC, Adam J, Aisner DL, Beasley MB, Borczuk AC, et al. Immunohistochemistry of pulmonary biomarkers: a perspective from members of the pulmonary pathology society. Arch Pathol Lab Med. 2018;142:408–19.

Lozano MD, Echeveste JI, Abengozar M, Mejias LD, Idoate MA, Calvo A, et al. Cytology smears in the era of molecular biomarkers in non-small cell lung cancer: doing more with less. Arch Pathol Lab Med. 2018;142:291–8.

Conde E, Suarez-Gauthier A, Benito A, Garrido P, Garcia-Campelo R, Biscuola M, et al. Accurate identification of ALK positive lung carcinoma patients: novel FDA-cleared automated fluorescence in situ hybridization scanning system and ultrasensitive immunohistochemistry. PLoS One. 2014;9:e107200.

Wistuba I, Sholl N, Lindeman N. ALK and ROS1 testing with NGS. In: Tsao MS, Hirsch FR, Yatabe Y, editors. IASLC atlas of ALK and ROS1 testing in lung cáncer. 2nd ed. FL: Editorial Rx Press; 2016.

Kerr KM, Lopez-Rios F. Precision medicine in NSCLC and pathology: how does ALK fit in the pathway? Ann Oncol. 2016;27(Suppl 3):iii16–24.

Ali SM, Hensing T, Schrock AB, Allen J, Sanford E, Gowen K, et al. Comprehensive genomic profiling identifies a subset of crizotinib-responsive ALK-rearranged non-small cell lung cancer not detected by fluorescence in situ hybridization. Oncologist. 2016;21:762–70.

Reguart N, Teixido C, Gimenez-Capitan A, Pare L, Galvan P, Viteri S, et al. Identification of ALK, ROS1, and RET fusions by a multiplexed mRNA-based assay in formalin-fixed, paraffin-embedded samples from advanced non-small-cell lung cancer patients. Clin Chem. 2017;63:751–60.

Lin JJ, Riely GJ, Shaw AT. Targeting ALK: precision medicine takes on drug resistance. Cancer Discov. 2017;7:137–55.

Mazieres J, Zalcman G, Crino L, Biondani P, Barlesi F, Filleron T, et al. Crizotinib therapy for advanced lung adenocarcinoma and a ROS1 rearrangement: results from the EUROS1 cohort. J Clin Oncol. 2015;33:992–9.

Moro-Sibilot D, Faivre L, Zalcman G, Pérol M, Barlesi F, Otto J, et al. Crizotinib in patients with advanced ROS1-rearranged non-small cell lung cancer (NSCLC). Preliminary results of the ACSé phase II trial. J Clin Oncol. 2015;33:8065.

Shaw AT, Ou SH, Bang YJ, Camidge DR, Solomon BJ, Salgia R, et al. Crizotinib in ROS1-rearranged non-small-cell lung cancer. N Engl J Med. 2014;371:1963–71.

Bubendorf L, Buttner R, Al-Dayel F, Dietel M, Elmberger G, Kerr K, et al. Testing for ROS1 in non-small cell lung cancer: a review with recommendations. Virchows Arch. 2016;469:489–503.

Conde E, Hernandez S, Martinez R, Angulo B, De Castro J, Collazo-Lorduy A, et al. Assessment of a new ROS1 immunohistochemistry clone (SP384) for the identification of ROS1 rearrangements in non-small cell lung carcinoma patients: the ROSING study. J Thorac Oncol. 2019. https://doi.org/10.1016/j.jtho.2019.07.005 .

NCCN. Non-small cell lung cancer. In: NCCN clinical practice guidelines in oncology. 2018. https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf . Accessed 14 Dec 2018.

Sholl LM, Sun H, Butaney M, Zhang C, Lee C, Janne PA, et al. ROS1 immunohistochemistry for detection of ROS1-rearranged lung adenocarcinomas. Am J Surg Pathol. 2013;37:1441–9.

Yoshida A, Tsuta K, Wakai S, Arai Y, Asamura H, Shibata T, et al. Immunohistochemical detection of ROS1 is useful for identifying ROS1 rearrangements in lung cancers. Mod Pathol. 2014;27:711–20.

Zhao J, Chen X, Zheng J, Kong M, Wang B, Ding W. A genomic and clinicopathological study of non-small-cell lung cancers with discordant ROS1 gene status by fluorescence in situ hybridisation and immunohistochemical analysis. Histopathology. 2018;73:19–28.

Davies KD, Le AT, Sheren J, Nijmeh H, Gowan K, Jones KL, et al. Comparison of molecular testing modalities for detection of ROS1 rearrangements in a cohort of positive patient samples. J Thorac Oncol. 2018;13:1474–82.

Wu YL, Yang JC, Kim DW, Lu S, Zhou J, Seto T, et al. Phase II study of crizotinib in east asian patients with ROS1-positive advanced non-small-cell lung cancer. J Clin Oncol. 2018;36:1405–11.

Planchard D, Johnson BE. BRAF adds an additional piece of the puzzle to precision oncology-based treatment strategies in lung cancer. Arch Pathol Lab Med. 2018;142:796–7.

Yousem SA, Nikiforova M, Nikiforov Y. The histopathology of BRAF-V600E-mutated lung adenocarcinoma. Am J Surg Pathol. 2008;32:1317–21.

Nguyen-Ngoc T, Bouchaab H, Adjei AA, Peters S. BRAF alterations as therapeutic targets in non-small-cell lung cancer. J Thorac Oncol. 2015;10:1396–403.

Gautschi O, Milia J, Cabarrou B, Bluthgen MV, Besse B, Smit EF, et al. Targeted therapy for patients with BRAF-mutant lung cancer: results from the European EURAF cohort. J Thorac Oncol. 2015;10:1451–7.

Li S, Li L, Zhu Y, Huang C, Qin Y, Liu H, et al. Coexistence of EGFR with KRAS, or BRAF, or PIK3CA somatic mutations in lung cancer: a comprehensive mutation profiling from 5125 Chinese cohorts. Br J Cancer. 2014;110:2812–20.

Leonetti A, Facchinetti F, Rossi G, Minari R, Conti A, Friboulet L, et al. BRAF in non-small cell lung cancer (NSCLC): pickaxing another brick in the wall. Cancer Treat Rev. 2018;66:82–94.

Odogwu L, Mathieu L, Blumenthal G, Larkins E, Goldberg KB, Griffin N, et al. FDA approval summary: dabrafenib and trametinib for the treatment of metastatic non-small cell lung cancers harboring BRAF V600E mutations. Oncologist. 2018;23:740–5.

Yu H, Boyle TA, Zhou C, Rimm DL, Hirsch FR. PD-L1 expression in lung cancer. J Thorac Oncol. 2016;11:964–75.

Lopes G, Wu YL, Kudaba I, Kowalski D, Cho BC, Castro G, et al. Pembrolizumab (pembro) versus platinum-based chemotherapy (chemo) as first-line therapy for advanced/metastatic NSCLC with a PD-L1 tumor proportion score (TPS) ≥ 1%: open-label, phase 3 KEYNOTE-042 study. J Clin Oncol. 2018;36:LBA4.

Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, 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.

Gandhi L, Rodriguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. 2018;378:2078–92.

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.

Mehnert JM, Monjazeb AM, Beerthuijzen JMT, Collyar D, Rubinstein L, Harris LN. The challenge for development of valuable immuno-oncology biomarkers. Clin Cancer Res. 2017;23:4970–9.

Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, et al. Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med. 2018;379:2342–50.

Peters S, Dafni U, Boyer M, De Ruysscher D, Faivre-Finn C, Felip E, et al. Position of a panel of international lung cancer experts on the approval decision for use of durvalumab in stage III non-small-cell lung cancer (NSCLC) by the committee for medicinal products for human use (CHMP). Ann Oncol. 2019;30:161–5.

IASLC. IASLC atlas of PD-L1 testing in lung cancer. 2017. https://www.iaslc.org/publications/iaslc-atlas-pd-l1-testing-lung-cancer . Accessed 1 Feb 2019.

Buttner R, Gosney JR, Skov BG, Adam J, Motoi N, Bloom KJ, et al. Programmed death-ligand 1 immunohistochemistry testing: a review of analytical assays and clinical implementation in non-small-cell lung cancer. J Clin Oncol. 2017;35:3867–76.

Heymann JJ, Bulman WA, Swinarski D, Pagan CA, Crapanzano JP, Haghighi M, et al. PD-L1 expression in non-small cell lung carcinoma: comparison among cytology, small biopsy, and surgical resection specimens. Cancer Cytopathol. 2017;125:896–907.

Robichaux JP, Elamin YY, Tan Z, Carter BW, Zhang S, Liu S, et al. Mechanisms and clinical activity of an EGFR and HER2 exon 20-selective kinase inhibitor in non-small cell lung cancer. Nat Med. 2018;24:638–46.

Peters S, Curioni-Fontecedro A, Nechushtan H, Shih JY, Liao WY, Gautschi O, et al. Activity of afatinib in heavily pretreated patients with ERBB2 mutation-positive advanced NSCLC: findings from a global named patient use program. J Thorac Oncol. 2018;13:1897–905.

Goss GD, Felip E, Cobo M, Lu S, Syrigos K, Lee KH, et al. Association of ERBB mutations with clinical outcomes of afatinib- or erlotinib-treated patients with lung squamous cell carcinoma: secondary analysis of the LUX-lung 8 randomized clinical trial. JAMA Oncol. 2018;4:1189–97.

Li BT, Shen R, Buonocore D, Olah ZT, Ni A, Ginsberg MS, et al. Ado-trastuzumab emtansine for patients with HER2-mutant lung cancers: results from a phase II basket trial. J Clin Oncol. 2018;36:2532–7.

Peters S, Stahel R, Bubendorf L, Bonomi P, Villegas A, Kowalski DM, et al. Trastuzumab emtansine (T-DM1) in patients with previously treated HER2-overexpressing metastatic non-small cell lung cancer: efficacy, safety, and biomarkers. Clin Cancer Res. 2019;25:64–72.

Pahuja KB, Nguyen TT, Jaiswal BS, Prabhash K, Thaker TM, Senger K, et al. Actionable activating oncogenic ERBB2/HER2 transmembrane and juxtamembrane domain mutations. Cancer Cell. 2018;34(792–806):e5.

Cancer Genome Atlas Research N. Comprehensive molecular profiling of lung adenocarcinoma. Nature. 2014;511:543–50.

Awad MM, Oxnard GR, Jackman DM, Savukoski DO, Hall D, Shivdasani P, et al. MET exon 14 mutations in non-small-cell lung cancer are associated with advanced age and stage-dependent MET genomic amplification and c-met overexpression. J Clin Oncol. 2016;34:721–30.

Paik PK, Drilon A, Fan PD, Yu H, Rekhtman N, Ginsberg MS, et al. Response to MET inhibitors in patients with stage IV lung adenocarcinomas harboring MET mutations causing exon 14 skipping. Cancer Discov. 2015;5:842–9.

Felip E, Sakai H, Patel J, Horn L, Veillon R, Griesinger F, et al. OA12.01 phase II data for the MET inhibitor tepotinib in patients with advanced NSCLC and MET exon 14-skipping mutations. J Thorac Oncol. 2018;13:S347.

Drilon A, Hu ZI, Lai GGY, Tan DSW. Targeting RET-driven cancers: lessons from evolving preclinical and clinical landscapes. Nat Rev Clin Oncol. 2018;15:150.

Mukhopadhyay S, Pennell NA, Ali SM, Ross JS, Ma PC, Velcheti V. RET-rearranged lung adenocarcinomas with lymphangitic spread, psammoma bodies, and clinical responses to cabozantinib. J Thorac Oncol. 2014;9:1714–9.

Subbiah V, Velcheti V, Tuch BB, Ebata K, Busaidy NL, Cabanillas ME, et al. Selective RET kinase inhibition for patients with RET-altered cancers. Ann Oncol. 2018;29:1869–76.

Drilon A, Wang L, Arcila ME, Balasubramanian S, Greenbowe JR, Ross JS, et al. Broad, hybrid capture-based next-generation sequencing identifies actionable genomic alterations in lung adenocarcinomas otherwise negative for such alterations by other genomic testing approaches. Clin Cancer Res. 2015;21:3631–9.

Gatalica Z, Xiu J, Swensen J, Vranic S. Molecular characterization of cancers with NTRK gene fusions. Mod Pathol. 2019;32:147–53.

Farago AF, Taylor MS, Doebele RC, Zhu VW, Kummar S, Spira AI, et al. Clinicopathologic features of non-small-cell lung cancer harboring an NTRK gene fusion. JCO Precis Oncol. 2018;2:1–12.

Hechtman JF, Benayed R, Hyman DM, Drilon A, Zehir A, Frosina D, et al. Pan-Trk immunohistochemistry is an efficient and reliable screen for the detection of NTRK fusions. Am J Surg Pathol. 2017;41:1547–51.

Marchio C, Scaltriti M, Ladanyi M, Iafrate AJ, Bibeau F, Dietel M, et al. ESMO recommendations on the standard methods to detect NTRK fusions in daily practice and clinical research. Ann Oncol. 2019;30(9):1417–27. https://doi.org/10.1093/annonc/mdz204 .

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.

Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, et al. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348:124–8.

Büttner R, Longshore JW, López-Ríos F, Merkelbach-Bruse S, Normanno N, Rouleau E, et al. Implementing TMB measurement in clinical practice: considerations on assayrequirements. ESMO Open. 2019;4:e000442.

Ferrer I, Zugazagoitia J, Herbertz S, John W, Paz-Ares L, Schmid-Bindert G. KRAS-mutant non-small cell lung cancer: from biology to therapy. Lung Cancer. 2018;124:53–64.

Conde E, Caminoa A, Dominguez C, Calles A, Walter S, Angulo B, et al. Aligning digital CD8(+) scoring and targeted next-generation sequencing with programmed death ligand 1 expression: a pragmatic approach in early-stage squamous cell lung carcinoma. Histopathology. 2018;72:270–84.

Marcus L, Lemery SJ, Keegan P, Pazdur R. FDA approval summary: pembrolizumab for the treatment of microsatellite instability-high solid tumors. Clin Cancer Res. 2019;25:3753–8.

Yatabe Y, Dacic S, Borczuk AC, Warth A, Russell PA, Lantuejoul S, et al. Best practices recommendations for diagnostic immunohistochemistry in lung cancer. J Thorac Oncol. 2018;14:377–407.

Woo JS, Reddy OL, Koo M, Xiong Y, Li F, Xu H. Application of immunohistochemistry in the diagnosis of pulmonary and pleural neoplasms. Arch Pathol Lab Med. 2017;141:1195–213.

Layfield LJ, Hammer RD, White SK, Furtado LV, Schmidt RL. Molecular testing strategies for pulmonary adenocarcinoma: an optimal approach with cost analysis. Arch Pathol Lab Med. 2019;143:628–33.

Levy BP, Chioda MD, Herndon D, Longshore JW, Mohamed M, Ou SH, et al. Molecular testing for treatment of metastatic non-small cell lung cancer: how to implement evidence-based recommendations. Oncologist. 2015;20:1175–81.

Lim C, Sekhon HS, Cutz JC, Hwang DM, Kamel-Reid S, Carter RF, et al. Improving molecular testing and personalized medicine in non-small-cell lung cancer in Ontario. Curr Oncol. 2017;24:103–10.

van de Haar J, Hoes L, Voest E. Advancing molecular tumour boards: highly needed to maximise the impact of precision medicine. ESMO Open. 2019;4:e000516.

Rogers TM, Arnau GM, Ryland GL, Huang S, Lira ME, Emmanuel Y, et al. Multiplexed transcriptome analysis to detect ALK, ROS1 and RET rearrangements in lung cancer. Sci Rep. 2017;7:42259.

Benayed R, Offin M, Mullaney K, Sukhadia P, Rios K, Desmeules P, et al. High yield of RNA sequencing for targetable kinase fusions in lung adenocarcinomas with no mitogenic driver alteration detected by DNA sequencing and low tumor mutation burden. Clin Cancer Res. 2019;25:4712–22.

Santarpia M, Liguori A, D’Aveni A, Karachaliou N, Gonzalez-Cao M, Daffina MG, et al. Liquid biopsy for lung cancer early detection. J Thorac Dis. 2018;10:S882–97.

Taus A, Camacho L, Rocha P, Hardy-Werbin M, Pijuan L, Piquer G, et al. Dynamics of EGFR mutation load in plasma for prediction of treatment response and disease progression in patients with EGFR-mutant lung adenocarcinoma. Clin Lung Cancer. 2018;19(387–94):e2.

Sholl LM, Aisner DL, Allen TC, Beasley MB, Cagle PT, Capelozzi VL, et al. Liquid biopsy in lung cancer: a perspective from members of the pulmonary pathology society. Arch Pathol Lab Med. 2016;140:825–9.

SEAP. “Reglas y Consejos” sobre buenas prácticas profesionales en anatomía patológica. 2013. https://www.seap.es/c/document_library/get_file?uuid=c08d2461-7bac-46e1-8eee-f9db7ec5e95a&groupId=10157 . Accessed 14 Dec 2018.

Nakhleh RE, Nose V, Colasacco C, Fatheree LA, Lillemoe TJ, McCrory DC, et al. Interpretive diagnostic error reduction in surgical pathology and cytology: guideline from the College of American Pathologists Pathology and Laboratory Quality Center and the Association of Directors of Anatomic and Surgical Pathology. Arch Pathol Lab Med. 2016;140:29–40.