Advances in clinical molecular diagnosis and treatment of pulmonary large cell neuroendocrine carcinoma

doi:10.3760/cma.j.cn371439-20231130-00077

Abstract

Abstract:

Pulmonary large cell neuroendocrine carcinoma （LCNEC） is a rare type of malignant neuroendocrine tumor with poor prognosis， with the median overall survival being around one year in advanced diseases. The prognosis of patients with non-small cell lung cancer has been greatly improved with the application of molecular detecting techniques， targeted therapy and immunotherapy. However， little progress has been made in the diagnosis and treatment of LCNEC with no unified standard of diagnosis and treatment protocol. The clinical molecular diagnosis and treatment of LCNEC is of great significance. Exploring the research progress related to the diagnosis and treatment of LCNEC can provide reference for improving the existing clinical diagnosis and treatment difficulties of LCNEC.

Key words: Lung neoplasms, Carcinoma, neuroendocrine, Pathology, molecular, Antineoplastic protocols, Immune checkpoint inhibitors

Han Yi, Zhang Tongmei, Qi Fei, Zhang Yong. Advances in clinical molecular diagnosis and treatment of pulmonary large cell neuroendocrine carcinoma[J]. Journal of International Oncology, 2024, 51(7): 468-473.

References 44

[1]	Minami Y. Ⅲ. The notable topics of the 5th Edition of WHO Classification for the Thoracic Tumours(2021)[J]. Gan To Kagaku Ryoho, 2022, 49(8): 847-852. pmid: 36046969
[2]	Rekhtman N. Lung neuroendocrine neoplasms: recent progress and persistent challenges[J]. Mod Pathol, 2022, 35(Suppl 1): 36-50. DOI: 10.1038/s41379-021-00943-2.
[3]	Metovic J, Barella M, Bianchi F, et al. Morphologic and molecular classification of lung neuroendocrine neoplasms[J]. Virchows Arch, 2021, 478(1): 5-19. DOI: 10.1007/s00428-020-03015-z.
[4]	Shah S, Gosain R, Groman A, et al. Incidence and survival outcomes in patients with lung neuroendocrine neoplasms in the United States[J]. Cancers (Basel), 2021, 13(8): 1753. DOI:10.3390/cancers13081753.
[5]	孟宇, 练延帮, 许跃, 等. 支气管肺大细胞神经内分泌癌的临床和分子病理特点[J]. 中华医学杂志, 2022, 102(14): 1020-1027. DOI: 10.3760/cma.j.cn112137-20210814-01816.
[6]	Krpina K, Vranić S, Tomić K, et al. Small cell lung carcinoma: current diagnosis, biomarkers, and treatment options with future perspectives[J]. Biomedicines, 2023, 11(7): 1982. DOI:10.3390/biomedicines11071982.
[7]	Rekhtman N, Pietanza MC, Hellmann MD, et al. Next-generation sequencing of pulmonary large cell neuroendocrine carcinoma reveals small cell carcinoma-like and non-small cell carcinoma-like subsets[J]. Clin Cancer Res, 2016, 22(14): 3618-3629. DOI: 10.1158/1078-0432.CCR-15-2946. pmid: 26960398
[8]	George J, Walter V, Peifer M, et al. Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors[J]. Nat Commun, 2018, 9(1): 1048. DOI:10.1038/s41467-018-03099-x. pmid: 29535388
[9]	Miyoshi T, Umemura S, Matsumura Y, et al. Genomic profiling of large-cell neuroendocrine carcinoma of the lung[J]. Clin Cancer Res, 2017, 23(3): 757-765. DOI: 10.1158/1078-0432.CCR-16-0355. pmid: 27507618
[10]	Cao L, Li ZW, Wang M, et al. Clinicopathological characteristics, treatment and survival of pulmonary large cell neuroendocrine carcinoma: a SEER population-based study[J]. PeerJ, 2019, 7: e6539. DOI: 10.7717/peerj.6539.
[11]	Peng KW, Cao HJ, You YF, et al. Optimal surgery type and adjuvant therapy for T₁N₀M₀ lung large cell neuroendocrine carcinoma[J]. Front Oncol, 2021, 11: 591823. DOI: 10.3389/fonc.2021.591823.
[12]	Lowczak A, Kolasinska-Cwikla A, Ćwikła JB, et al. Outcomes of patients with clinical stage Ⅰ-ⅢA large-cell neuroendocrine lung cancer treated with resection[J]. J Clin Med, 2020, 9(5): 1370. DOI:10.3390/jcm9051370.
[13]	Raman V, Jawitz OK, Yang CJ, et al. Outcomes for surgery in large cell lung neuroendocrine cancer[J]. J Thorac Oncol, 2019, 14(12): 2143-2151. DOI: 10.1016/j.jtho.2019.09.005. pmid: 31557535
[14]	Chen H, Ishihara M, Horita N, et al. Effect of adjuvant and palliative chemotherapy in large cell neuroendocrine carcinoma of the lung: a systematic review and meta-analysis[J]. Cancers (Basel), 2021, 13(23): 5948. DOI:10.3390/cancers13235948.
[15]	Gu JJ, Gong DH, Wang YX, et al. The demographic and treatment options for patients with large cell neuroendocrine carcinoma of the lung[J]. Cancer Med, 2019, 8(6): 2979-2993. DOI: 10.1002/cam4.2188.
[16]	Wakeam E, Adibfar A, Stokes S, et al. Defining the role of adjuvant therapy for early-stage large cell neuroendocrine carcinoma[J]. J Thorac Cardiovasc Surg, 2020, 159(5): 2043-2054.e9. DOI: 10.1016/j.jtcvs.2019.09.077. pmid: 31759623
[17]	Andreetti C, Ibrahim M, Gagliardi A, et al. Adjuvant chemotherapy, extent of resection, and immunoistochemical neuroendocrine markers as prognostic factors of early-stage large-cell neu-roendocrine carcinoma[J]. Thorac Cancer, 2022, 13(7): 900-912. DOI: 10.1111/1759-7714.14287. pmid: 35170859
[18]	Raman V, Jawitz OK, Yang CJ, et al. Adjuvant therapy for patients with early large cell lung neuroendocrine cancer: a national analysis[J]. Ann Thorac Surg, 2019, 108(2): 377-383. DOI: 10.1016/j.athoracsur.2019.03.053.
[19]	Haruki T, Matsui S, Oshima Y, et al. Prognostic impact of surgical treatment for high-grade neuroendocrine carcinoma of the lung: a multi-institutional retrospective study[J]. J Thorac Dis, 2022, 14(4): 1070-1078. DOI: 10.21037/jtd-21-1938. pmid: 35572862
[20]	Kenmotsu H, Niho S, Tsuboi M, et al. Randomized phase Ⅲ study of irinotecan plus cisplatin versus etoposide plus cisplatin for completely resected high-grade neuroendocrine carcinoma of the lung: JCOG1205/1206[J]. J Clin Oncol, 2020, 38(36): 4292-4301. DOI: 10.1200/JCO.20.01806.
[21]	Gang J, Xue L, Xiang S. The role of postoperative radiotherapy (PORT) in pulmonary large cell neuroendocrine carcinoma (PLCNEC)[J]. Cancer Radiothérapie, 2020, 24(3): 215-221. DOI: 10.1016/j.canrad.2020.02.004.
[22]	Jiang YZ, Lei C, Zhang XF, et al. Double-edged role of radiotherapy in patients with pulmonary large-cell neuroendocrine carcinoma[J]. J Cancer, 2019, 10(25): 6422-6430. DOI: 10.7150/jca.32446. pmid: 31772675
[23]	Limonnik V, Abel S, Finley GG, et al. Factors associated with treatment receipt and overall survival for patients with locally advanced large cell neuroendocrine carcinoma of the lung: a national cancer database analysis[J]. Lung Cancer, 2020, 150: 107-113. DOI: 10.1016/j.lungcan.2020.10.001. pmid: 33126090
[24]	Le Treut J, Sault MC, Lena H, et al. Multicentre phase Ⅱ study of cisplatin-etoposide chemotherapy for advanced large-cell neu-roendocrine lung carcinoma: the GFPC 0302 study[J]. Ann Oncol, 2013, 24(6): 1548-1552. DOI: 10.1093/annonc/mdt009. pmid: 23406729
[25]	Niho S, Kenmotsu H, Sekine I, et al. Combination chemotherapy with irinotecan and cisplatin for large-cell neuroendocrine carcinoma of the lung: a multicenter phase Ⅱ study[J]. J Thorac Oncol, 2013, 8(7): 980-984. DOI: 10.1097/JTO.0b013e31828f6989.
[26]	Derks JL, van Suylen RJ, Thunnissen E, et al. Chemotherapy for pulmonary large cell neuroendocrine carcinomas: does the regimen matter?[J]. Eur Respir J, 2017, 49(6): 1601838. DOI:10.1183/13993003.01838-2016.
[27]	Ogikubo M, Isaka T, Ishikawa Y, et al. Postoperative relapse of combined large-cell neuroendocrine carcinoma of the lung with a remarkable transient response to amrubicin monotherapy in an elderly patient—a case report[J]. Gan to kagaku ryoho, 2021, 48(5): 681-683. pmid: 34006713
[28]	Ørting AM, Clausen MM, Soldath P, et al. Treatment of inoperable large cell neuroendocrine lung cancer with single agent temozolomide[J]. Acta Oncol, 2023, 62(12): 1952-1955. DOI: 10.1080/0284186X.2023.2258444.
[29]	Dudnik E, Kareff S, Moskovitz M, et al. Real-world survival outcomes with immune checkpoint inhibitors in large-cell neuroendocrine tumors of lung[J]. J Immunother Cancer, 2021, 9(2): e001999. DOI: 10.1136/jitc-2020-001999.
[30]	Meng L, Cao B, Ji R, et al. Enhanced efficacy of chemotherapy by addition of immune checkpoint inhibitors in stage Ⅳ large cell neuroendocrine carcinoma of the lung: a real-world analysis[J]. J Cancer, 2023, 14(17): 3169-3175. DOI: 10.7150/jca.87052.
[31]	Zhang X, Sun YB, Miao Y, et al. Immune checkpoint inhibitor therapy achieved complete response for drug-sensitive EGFR/ALK mutation-negative metastatic pulmonary large-cell neuroendocrine carcinoma with high tumor mutation burden: a case report[J]. Onco Targets Ther, 2020, 13: 8245-8250. DOI: 10.2147/OTT.S259893.
[32]	Takimoto Sato M, Ikezawa Y, Sato M, et al. Large cell neuroendocrine carcinoma of the lung that responded to nivolumab: a case report[J]. Mol Clin Oncol, 2020, 13(1): 43-47. DOI: 10.3892/mco.2020.2045. pmid: 32499913
[33]	Chen F, Hua HB, Huang HQ. Neoadjuvant chemotherapy combined with immunotherapy for pulmonary large-cell neuroendocrine carcinoma: a case report[J]. Ann Palliat Med, 2021, 10(7): 8479-8483. DOI: 10.21037/apm-20-2536. pmid: 34118833
[34]	Arpin D, Charpentier MC, Bernardi M, et al. PD-L1-expression patterns in large-cell neuroendocrine carcinoma of the lung: potential implications for use of immunotherapy in these patients: the GFPC 03-2017 "EPNEC" study[J]. Ther Adv Med Oncol, 2020, 12: 1758835920937972. DOI: 10.1177/1758835920937972.
[35]	Schoenfeld AJ, Bandlamudi C, Lavery JA, et al. The genomic landscape of SMARCA4 alterations and associations with outcomes in patients with lung cancer[J]. Clin Cancer Res, 2020, 26(21): 5701-5708. DOI: 10.1158/1078-0432.CCR-20-1825.
[36]	李杨仪, 龚龑, 谢丛华. SAMHD1抑制肺腺癌细胞中PD-L1表达的研究[J]. 国际肿瘤学杂志, 2022, 49(11): 658-664. DOI: 10.3760/cma.j.cn371439-20220427-00130.
[37]	Peng WY, Cao LM, Chen LK, et al. Comprehensive characterization of the genomic landscape in Chinese pulmonary neuroendocrine tumors reveals prognostic and therapeutic markers (CSWOG-1901)[J]. Oncologist, 2022, 27(2): e116-e125. DOI: 10.1093/oncolo/oyab044. pmid: 35641209
[38]	Zhuo ML, Guan YF, Yang X, et al. The prognostic and therapeutic role of genomic subtyping by sequencing tumor or cell-free DNA in pulmonary large-cell neuroendocrine carcinoma[J]. Clin Cancer Res, 2020, 26(4): 892-901. DOI: 10.1158/1078-0432.CCR-19-0556. pmid: 31694833
[39]	Jelli B, Brandão M, Mekinda Z, et al. Systemic treatment for neuroendocrine non-small cell lung carcinoma: a cases series and a systematic review of the literature[J]. Lung Cancer, 2023, 181: 107232. DOI: 10.1016/j.lungcan.2023.107232.
[40]	Christopoulos P, Engel-Riedel W, Grohé C, et al. Everolimus with paclitaxel and carboplatin as first-line treatment for metastatic large-cell neuroendocrine lung carcinoma: a multicenter phase Ⅱ trial[J]. Ann Oncol, 2017, 28(8): 1898-1902. DOI: 10.1093/annonc/mdx268. pmid: 28535181
[41]	Hermans BCM, Derks JL, Thunnissen E, et al. DLL3 expression in large cell neuroendocrine carcinoma (LCNEC) and association with molecular subtypes and neuroendocrine profile[J]. Lung Cancer, 2019, 138: 102-108. DOI: 10.1016/j.lungcan.2019.10.010. pmid: 31678831
[42]	Blackhall F, Jao K, Greillier L, et al. Efficacy and safety of rovalpituzumab tesirine compared with topotecan as second-line therapy in DLL3-high SCLC: results from the phase 3 TAHOE study[J]. J Thorac Oncol, 2021, 16(9): 1547-1558. DOI: 10.1016/j.jtho.2021.02.009. pmid: 33607312
[43]	Morgensztern D, Johnson M, Rudin CM, et al. SC-002 in patients with relapsed or refractory small cell lung cancer and large cell neuroendocrine carcinoma: phase 1 study[J]. Lung Cancer, 2020, 145: 126-131. DOI: 10.1016/j.lungcan.2020.04.017. pmid: 32438272
[44]	Derks JL, Leblay N, Thunnissen E, et al. Molecular subtypes of pulmonary large-cell neuroendocrine carcinoma predict chemotherapy treatment outcome[J]. Clin Cancer Res, 2018, 24(1): 33-42. DOI: 10.1158/1078-0432.CCR-17-1921. pmid: 29066508