Large cell neuroendocrine carcinoma of the lung: Prognostic factors to predict clinical outcomes.

Abstract

e20515 Background: Large cell neuroendocrine carcinoma of the lung (LCNEC) is a rare tumor, with clinical and molecular features between non-small cell and small-cell lung cancer (NSCLC and SCLC, respectively). To date, little is known about factors able to predict clinical outcome of these patients. We sought to identify prognostic factors in LCNEC. Methods: We retrospectively collected pathologically-confirmed LCNEC patients treated at the S. Orsola Malpighi Hospital of Bologna between 01/01/2009 and 31/12/2020. LCNEC was defined as tumor with neuroendocrine morphology, expression of ≥2 neuroendocrine markers (including chromogranin A, synaptophysin, or CD56) at immunohistochemistry and high tumor grade (defined as necrosis and high Ki67 ≥ 50% or high mitotic rate, ≥ 10 mitoses per 2 mm2). Clinical features, pathological features, and blood test values (including neuron-specific enolase [NSE], carcinoembryonic antigen [CEA], cytokeratin 19 fragment [cyfra 21-1]) were correlated with progression-free survival to first-line chemotherapy (PFS) and overall survival from the diagnosis of extensive disease (OS). Results: Eighty-one LCNEC patients (median age 69 years, range 63-76) were identified. Twenty-seven (33.3%) had limited-stage disease and 52 patients (67.5%) had Eastern cooperative oncology group performance status (ECOG PS) ≥ 1 at diagnosis. When extensive disease was found (ED-LCNEC, N = 67), 23 patients (34.3%) had liver metastases, 10 (14.9%) had brain metastases and 24 (35.8%) had bone metastases. Treatment in ED-LCNEC was platinum plus etoposide in 45 patients (81.9%) and platinum plus paclitaxel in 10 patients (18.1%). Among 55 patients treated with platinum-based chemotherapy, 5 patients (9.1%) received cisplatin, while 50 (90.9%) received carboplatin. Overall, OS was 9.17 months (95% confidence interval [95%CI]7.17-13.87), PFS was 4.87 months (95%CI 4.21-6.02) and ORR was 38.2% (95%CI 25.4-42.3, N = 21/56). At univariate analysis, ECOG PS ≥ 1 (P = 0.049), presence of liver (P = 0.004) and bone metastases (P = 0.009), ≥ 2 non-nodal metastatic sites (P < 0.001), elevated NSE (P = 0.009) and CEA level at diagnosis (P = 0.011) were associated with increased risk of death. At multivariate analysis, ECOG PS ≥ 1 (P = 0.020), ≥ 2 metastatic sites (P = 0.002), and elevated NSE level at diagnosis (P = 0.009) were independently associated with the risk of death. At univariate analysis brain metastases (P = 0.017), ≥2 metastatic sites (P = 0.006) and elevated value of CEA at baseline (P = 0.026) were associated with increased risk of progression. At multivariate analysis, only the presence of brain metastases (P = 0.043) retained its association with the risk of progression. Conclusions: In ED-LCNEC of the lung, ECOG PS, number of non-nodal sites of metastases and NSE at baseline are associated with worse survival, while the presence of brain metastases is associated with shorter PFS.