Yasemin SÖYLER, Pınar AKIN KABALAK, Suna KAVURGACI, Funda DEMİRAĞ, Ülkü YILMAZ

Sınıflandırılamayan akciğer yüksek dereceli nöroendokrin karsinomaların klinik özellikleri ve sağ kalım sonuçları

Amaç: Bu çalışmanın amacı patolojik olarak tiplendirilemeyen yüksek dereceli nöroendokrin karsinomların (uYDNEK) klinik özelliklerini ve sağ kalım sonuçlarını değerlendirmek ve küçük hücreli akciğer kanseri (KHAK) ile karşılaştırmaktır. Yöntem ve Gereçler: Bu retrospektif ve gözlemsel çalışmada YDNEK hastalarının klinik özellikleri değerlendirildi. Progresyonsuz sağkalım (PFS) ve genel sağkalım (OS) Kaplan-Meier yöntemi kullanılarak hesaplandı. PFS ve OS ile ilişkili bağımsız risk faktörlerini belirlemek için Cox-regresyon analizleri yapıldı. Bulgular: Çalışmaya 121 hasta [uYDNEK (n=35), KHAK (n=86)] dahil edildi. Primer tümör çoğunlukla sağ tarafta ve santral yerleşimliydi. Tanı anındaki evre 43 (%35,5) hastada lokal ileri, 78 (%64,5) hastada ileri idi. uYDNEK ve KHAK grupların klinik özellikleri benzerdi. Çalışma popülasyonunun medyan PFS ve OS'si sırasıyla 8,8 (%95 Cl 7,29 – 10,30) ve 10,9 (%95 Cl 9,9 – 11,8) ay olarak hesaplandı. uYDNEK ve KHAK grupları arasında PFS (9.4 ve 8.6 ay, p = 0.99) ve OS (12 ve 10.7 ay, p = 0.51) istastistiksel olarak benzer bulundu. 6-aylık, 1-yıllık, 2-yıllık PFS ve OS hesaplandı, 2 grup arasında istatistiksel fark bulunmadı. Cox regresyon analizinde primer tümörün sağ tarafta yerleşimi (HR: 1.558, 95%Cl 1.044 – 2.325, p = 0.03) ve ileri evre hastalık (HR: 1.928, 95%Cl 1.292 – 2.877, p = 0.001) OS için kötü prognostik faktör olarak bulundu. Cox regresyon analizinin sonuçları, histopatolojik alt tiplerin PFS ve OS üzerinde bir etkisinin olmadığını gösterdi. Sonuç: Patolojik olarak sınıflandırılamayan YDNEK hastaları KHAK hastaları ile benzer klinik ve sağ kalım özellikleri göstermektedir.

Anahtar Kelimeler:

yüksek dereceli nöroendokrin karsinoma, küçük hücreli akciğer kanseri, nöroendokrin tümörler

Clinical features and survival outcomes of unclassified high-grade neuroendocrine carcinoma of the lung

Background: Differentiating high-grade neuroendocrine carcinomas (HGNEC) is difficult. We aimed to assess the clinical features and survival outcomes of unclassified HGNEC (uHGNEC) and to compare it with small-cell lung cancer (SCLC). Material and Methods: This was a retrospective and observational study of HGNEC patients. Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS). Cox-regression analyses were used to determine the risk factors independently associated with PFS and OS. Results: One hundred twenty-one patients [uHGNEC (n = 35), SCLC (n = 86)] were analysed. The primary tumour was mostly right-sided, located in the centre of the lungs. The IASLC stage at diagnosis was locally advanced in 43 (35.5%) patients and advanced in 78 (64.5%) patients. uHGNEC and SCLC groups shared similar clinical features. The study population's median PFS and OS were 8.8 (95%Cl 7.29 – 10.30) and 10.9 (95%Cl 9.9 – 11.8) months, respectively. uHGNEC- and SCLC groups had a similar PFS (9.4 vs 8.6 months, p = 0.99) and OS (12 vs 10.7 months, p = 0.51). The six-month, one- and two-year PFS and OS of two groups were also similar. Among all patients, a right-sided tumour (HR: 1.558, 95%Cl 1.044 – 2.325, p = 0.03) and advanced-stage disease (HR: 1.928, 95%Cl 1.292 – 2.877, p = 0.001) were prognostic factors for poor OS. Cox-regression analysis indicated that histopathology did not have an impact on PFS and OS. Conclusion: HGNEC patients who cannot be classified pathologically behave like SCLC.

Keywords:

high-grade neuroendocrine carcinoma, pulmonary neuroendocrine carcinomas, small-cell lung cancer,

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Kaynakça 1. Wang Y, Qian F, Chen Y, Yang Z, Hu M, Lu J, et al. Comparative Study of Pulmonary Combined Large-Cell Neuroendocrine Carcinoma and Combined Small-Cell Carcinoma in Surgically Resected High-Grade Neuroendocrine Tumors of the Lung. Front Oncol. 2021;11:714549. doi:10.3389/fonc.2021.714549
2. Travis WD, Brambilla E, Nicholson AG, Yatabe Y, Austin JHA, Beasley MB, 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.0000000000000630
3. Travis WD, Al-Dayel FH, Bubendorf L, Chung JH. Rekhtman N, Scagliotti G. Thoracic Tumours: WHO Classification of Tumours; 2021.
4. Borczuk AC. Pulmonary Neuroendocrine Tumors. Surg Pathol Clin. 2020;13(1):35-55. doi:10.1016/j.path.2019.10.002
5. Lantuejoul S, Fernandez-Cuesta L, Damiola F, Girard N, McLeer A. New molecular classification of large cell neuroendocrine carcinoma and small cell lung carcinoma with potential therapeutic impacts. Transl Lung Cancer Res. 2020;9:2233-2244. doi:10.21037/tlcr-20-269
6. La Salvia A, Persano I, Siciliani A, Verrico M, Bassi M, Modica R, et al. Prognostic significance of laterality in lung neuroendocrine tumors. Endocrine. 2022;76: 733-746 doi:10.1007/s12020-022-03015-w
7. Moon JY, Choi SH, Kim TH, Lee J, Pyo JH, Kim YT, et al. Clinical features and treatment outcomes of resected large cell neuroendocrine carcinoma of the lung. Radiat Oncol J. 2021;39:288-296. doi:10.3857/roj.2021.00423
8. Andrini E, Marchese PV, De Biase D, Mosconi C, Siepe G, Panzuto F, et al. Large Cell Neuroendocrine Carcinoma of the Lung: Current Understanding and Challenges. J Clin Med. 2022;11:1461 doi:10.3390/jcm11051461
9. Savu C, Melinte A, Diaconu C, Stiru O, Gherhgiceanu F, Tudorica SDO, et al. Lung neuroendocrine tumors: A systematic literature review (Review). Exp Ther Med. 2021;23:176. doi:10.3892/etm.2021.11099
10. Goldstraw P, Chansky K, Crowley J, Rami-Porta R, Asamura H, Eberhardt W, et al. The IASLC Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer. J Thorac Oncol. 2016;11:39-51. doi:10.1016/ j.jtho.2015.09.009
11. Zhang Y, Wang W, Hu Q, Liang Z, Zhou P, Tang Y, et al. Clinic and genetic similarity assessments of atypical carcinoid, neuroendocrine neoplasm with atypical carcinoid morphology and elevated mitotic count and large cell neuroendocrine carcinoma. BMC Cancer. 2022;22:321. doi:10.1186/s12885-022-09391-w
12. Waqar SN, Morgensztern D. Treatment advances in small cell lung cancer (SCLC). Pharmacol Ther. 2017;180:16-23. doi:10.1016/j.pharmthera.2017.06.002
13. Franco F, Carcereny E, Guirado M, Ortega AL, Lopez-Castro R, Rodriguez-Abreu D, et al. Epidemiology, treatment, and survival in small cell lung cancer in Spain: Data from the thoracic tumor registry. PLoS One. 2021;16:e0251761. doi:10.1371/journal.pone.0251761
14. Rudin CM, Brambilla E, Faivre-Finn C, Sage J. Small-cell lung cancer. Nat Rev Dis Prim. 2021;7(1):3. doi:10.1038/s41572-020-00235-0
15. Seigneurin A, Delafosse P, Trétarre B, Woronoff AS, Velten M, Grosclaude P, et al. Are comorbidities associated with long-term survival of lung cancer? A population-based cohort study from French cancer registries. BMC Cancer. 2018;18(1):1091. doi:10.1186/s12885-018-5000-7
16. Jones GS, Khakwani A, Pascoe A, Foweraker K, McKeever TM, Hubbard RB, et al. Factors associated with survival in small cell lung cancer: an analysis of real-world national audit, chemotherapy and radiotherapy data. Ann Palliat Med. 2021;10:4055-4068. doi:10.21037/apm-20-1824
17. Rich AL, Tata LJ, Free CM, Stanley RA, Peake MD, Baldwin DR, et al. How do patient and hospital features influence outcomes in small-cell lung cancer in England. Br J Cancer. 2011;105:746-752. doi:10.1038/bjc.2011.310
18. Handa Y, Tsutani Y, Ito M, Miyata Y, Mukaida H, Kaneko M, et al. Clinical Behavior of Combined Versus Pure High-Grade Neuroendocrine Carcinoma. Clin Lung Cancer. 2022;23:e9-e16.e1. doi:10.1016/j.cllc.2021.06.010
19. Sonkin D, Thomas A, Teicher BA. Are neuroendocrine negative small cell lung cancer and large cell neuroendocrine carcinoma with WT RB1 two faces of the same entity? Lung Cancer Manag. 2019;8:LMT13. doi:10.2217/lmt-2019-0005
20. Isaka M, Nakagawa K, Ohde Y, Okumura T, Watanabe R, Ito I, et al. A clinicopathological study of peripheral, small-sized high-grade neuroendocrine tumours of the lung: Differences between small-cell lung carcinoma and large-cell neuroendocrine carcinoma. Eur J Cardiothoracic Surg. 2012;41:841-846. doi:10.1093/ejcts/ezr132