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Diagnostic yield of endobronchial ultrasound-guided transbronchial needle aspiration to assess tumor-programmed cell death ligand-1 expression in mediastinal lymph nodes metastasized from non-small cell lung cancer

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Abstract

Purpose

We investigated the utility of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) to evaluate programmed cell death ligand-1 (PD-L1) expression in patients with advanced non-small cell lung cancer (NSCLC).

Methods

A retrospective chart review of patients who underwent EBUS-TBNA between April 2017 and April 2019 was conducted. Among patients diagnosed with NSCLC, we investigated the rate of successful evaluation of tumor PD-L1 expression, compared the relevant factors between patients with evaluable and those with unevaluable PD-L1 expression, and examined the response to immune checkpoint inhibitors (ICIs) after EBUS-TBNA.

Results

Of the 40 patients assessed, 32 (80%) had evaluable PD-L1 expression. Patients with evaluable PD-L1 expression were older than those with unevaluable PD-L1 expression (p = 0.017), and we noted a tendency for a larger diameter of the biopsied lymph node (p = 0.12). The response rate to ICIs was 100% in patients with a tumor proportion score (TPS) ≥ 50%, 33% in those with a TPS 1–49%, and 0% in those with a TPS < 1%.

Conclusion

The diagnostic yield of EBUS-TBNA to evaluate PD-L1 expression in advanced NSCLC appeared acceptable in association with relevant clinical outcomes after treatment with ICIs. A further prospective study with a larger sample size is required to confirm our findings.

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References

  1. Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387(10027):1540–50.

    Article  CAS  PubMed  Google Scholar 

  2. Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016;375(19):1823–33.

    Article  CAS  PubMed  Google Scholar 

  3. 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(2):123–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. 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(17):1627–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J, et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017;389(10066):255–65.

    Article  PubMed  Google Scholar 

  6. Gandhi L, Rodríguez-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(22):2078–92.

    Article  CAS  PubMed  Google Scholar 

  7. Paz-Ares L, Luft A, Vicente D, Tafreshi A, Gümüş M, Mazières J, et al. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N Engl J Med. 2018;379(21):2040–51.

    Article  CAS  PubMed  Google Scholar 

  8. Higashi T, Nakamura F, Shibata A, Emgori Y, Nishimoto H. The national database of hospital-based cancer registries: a nationwide infrastructure to support evidence-based cancer care and cancer control policy in Japan. Jpn J Clin Oncol. 2014;44(1):2–8.

    Article  PubMed  Google Scholar 

  9. Usman Ali M, Miller J, Peirson L, Fitzpatrick-Lewis D, Kenny M, Sherifali D, et al. Screening for lung cancer: a systematic review and meta-analysis. Prev Med. 2016;89:301–14.

    Article  PubMed  Google Scholar 

  10. Um SW, Kim HK, Jung SH, Han J, Lee KJ, Park HY, et al. Endobronchial ultrasound versus mediastinoscopy for mediastinal nodal staging of non-small-cell lung cancer. J Thorac Oncol. 2015;10(2):331–7.

    Article  PubMed  Google Scholar 

  11. Czarnecka-Kujawa K, Rochau U, Siebert U, Atenafu E, Darling G, Waddell TK, et al. Cost-effectiveness of mediastinal lymph node staging in non-small cell lung cancer. J Thorac Cardiovasc Surg. 2017;153(6):1567–78.

    Article  PubMed  Google Scholar 

  12. Roach C, Zhang N, Corigliano E, Jansson M, Toland G, Ponto G, et al. Development of a companion diagnostic PD-L1 immunohistochemistry assay for pembrolizumab therapy in non-small-cell lung cancer. Appl Immunohistochem Mol Morphol. 2016;24(6):392–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Sakata KK, Midthun DE, Mullon JJ, Kern RM, Nelson DR, Edell ES, et al. Comparison of programmed death ligand-1 immunohistochemical staining between endobronchial ultrasound transbronchial needle aspiration and resected lung cancer specimens. Chest. 2018;154(4):827–37.

    Article  PubMed  Google Scholar 

  14. Sakakibara R, Inamura K, Tambo Y, Ninomiya H, Kitazono S, Yanagitani N, et al. EBUS-TBNA as a promising method for the evaluation of tumor PD-L1 expression in lung cancer. Clin Lung Cancer. 2017;18(5):527–34.

    Article  CAS  PubMed  Google Scholar 

  15. Tsunoda A, Morikawa K, Inoue T, Miyazawa T, Hoshikawa M, Takagi M, et al. A prospective observational study to assess PD-L1 expression in small biopsy samples for non-small-cell lung cancer. BMC Cancer. 2019;19(1):546.

    Article  PubMed  PubMed Central  Google Scholar 

  16. 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(12):896–907.

    Article  CAS  PubMed  Google Scholar 

  17. Wang G, Ionescu DN, Lee CH, Hiruki T, Myers R, Shaipanich T, et al. PD-L1 testing on the EBUS-FNA cytology specimens of non-small cell lung cancer. Lung Cancer. 2019;136:1–5.

    Article  PubMed  Google Scholar 

  18. Labarca G, Folch E, Jantz M, Mehta HJ, Majid A, Fernandez-Bussy S. Adequacy of samples obtained by endobronchial ultrasound with transbronchial needle aspiration for molecular analysis in patients with non-small cell lung cancer: systematic review and meta-analysis. Ann Am Thorac Soc. 2018;15(10):1205–16.

    Article  PubMed  Google Scholar 

  19. van der Heijden EH, Casal RF, Trisolini R, Steinfort DP, Hwangbo B, Nakajima T, et al. Guideline for the acquisition and preparation of conventional and endobronchial ultrasound-guided transbronchial needle aspiration specimens for the diagnosis and molecular testing of patients with known or suspected lung cancer. Respiration. 2014;88(6):500–17.

    Article  PubMed  Google Scholar 

  20. Cicek T, Ozturk A, Yılmaz A, Aktas Z, Demirag F, Akyurek N. Adequacy of EBUS-TBNA specimen for mutation analysis of lung cancer. Clin Respir J. 2019;13(2):92–7.

    Article  CAS  PubMed  Google Scholar 

  21. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47.

    Article  CAS  PubMed  Google Scholar 

  22. Kanda Y. Investigation of the freely available easy-to-use software 'EZR' for medical statistics. Bone Marrow Transpl. 2013;48(3):452–8.

    Article  CAS  Google Scholar 

  23. Matthew E, Philip AJC, Julie M, Paul B, Helen D, Leena J, et al. EBUS-TBNA in elderly patients with lung cancer: safety and performance outcomes. J Thorac Oncol. 2014;9(3):370–6.

    Article  Google Scholar 

  24. Wahidi MM, Herth F, Yasufuku K, Shepherd RW, Yarmus L, Chawla M, et al. Technical aspects of endobronchial ultrasound-guided transbronchial needle aspiration: CHEST guideline and expert panel report. Chest. 2016;149(3):816–35.

    Article  PubMed  Google Scholar 

  25. Davenport RD. Rapid on-site evaluation of transbronchial aspirates. Chest. 1990;98(1):59–61.

    Article  CAS  PubMed  Google Scholar 

  26. Sehgal IS, Dhooria S, Aggarwal AN, Agarwal R. Impact of rapid on-site cytological evaluation (ROSE) on the diagnostic yield of transbronchial needle aspiration during mediastinal lymph node sampling: systematic review and meta-analysis. Chest. 2018;153(4):929–38.

    Article  PubMed  Google Scholar 

  27. Mondoni M, Carlucci P, Di Marco F, Rossi S, Santus P, D'Adda A, et al. Rapid on-site evaluation improves needle aspiration sensitivity in the diagnosis of central lung cancers: a randomized trial. Respiration. 2013;86(1):52–8.

    Article  PubMed  Google Scholar 

  28. Diacon AH, Schuurmans MM, Theron J, Louw M, Wright CA, Brundyn K, et al. Utility of rapid on-site evaluation of transbronchial needle aspirates. Respiration. 2005;72(2):182–8.

    Article  PubMed  Google Scholar 

  29. Trisolini R, Cancellieri A, Tinelli C, de Biase D, Valentini I, Casadei G, et al. Randomized trial of endobronchial ultrasound-guided transbronchial needle aspiration with and without rapid on-site evaluation for lung cancer genotyping. Chest. 2015;148(6):1430–7.

    Article  PubMed  Google Scholar 

  30. Kitazono S, Fujikawa Y, Tsuta K, Utsumi H, Kanda S, Horinouchi H, et al. Reliability of small biopsy samples compared with resected specimens for the determination of programmed death-ligand 1 expression in non-small-cell lung cancer. Clin Lung Cancer. 2015;16(5):385–90.

    Article  CAS  PubMed  Google Scholar 

  31. Ilie M, Long-Mira E, Bence C, Butori C, Lassalle S, Bouhlel L, et al. Comparative study of the PD-L1 status between surgically resected specimens and matched biopsies of NSCLC patients reveal major discordances: a potential issue for anti-PD-L1 therapeutic strategies. Ann Oncol. 2016;27(1):147–53.

    Article  CAS  PubMed  Google Scholar 

  32. Elfving H, Mattsson JSM, Lindskog C, Backman M, Menzel U, Micke P. Programmed Cell Death Ligand 1 Immunohistochemistry: a concordance study between surgical specimen, biopsy, and tissue microarray. Clin Lung Cancer. 2019;20(4):258–62.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Thoracic Surgery, Kyoto University Hospital, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan

    Katsutaka Mineura, Masatsugu Hamaji, Hidenao Kayawake, Satona Tanaka, Yoshito Yamada, Yojiro Yutaka, Daisuke Nakajima, Akihiro Ohsumi, Toshi Menju, Toyofumi F. Chen-Yoshikawa & Hiroshi Date

  2. Department of Diagnostic Pathology, Kyoto University Hospital, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan

    Akihiko Yoshizawa & Naoki Nakajima

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  1. Katsutaka Mineura
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  2. Masatsugu Hamaji
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Correspondence to Masatsugu Hamaji.

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Katsutaka Mineura and his co-authors have no conflicts of interest. Authors have nothing to disclose with regard to commercial support.

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Mineura, K., Hamaji, M., Yoshizawa, A. et al. Diagnostic yield of endobronchial ultrasound-guided transbronchial needle aspiration to assess tumor-programmed cell death ligand-1 expression in mediastinal lymph nodes metastasized from non-small cell lung cancer. Surg Today 50, 1049–1055 (2020). https://doi.org/10.1007/s00595-020-01989-6

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