Large Cell Neuroendocrine Carcinoma of the Lung: Clinico-Pathologic Features, Treatment, and Outcomes

Abstract

Clinical features and management of large cell neuroendocrine lung carcinoma of the lung are poorly described. We report a series of 49 patients with stage IV large cell neuroendocrine lung carcinomas; 47% had brain metastases. In 17 patients with molecular testing, 24% of tumors harbored KRAS mutations. Response to platinum/etoposide in these patients was poorer than historic data for small-cell lung cancer, however prognosis was similar. Background Large cell neuroendocrine carcinoma (LCNEC) accounts for approximately 3% of lung cancers. Pathologic classification and optimal therapies are debated. We report the clinicopathologic features, treatment and survival of a series of patients with stage IV LCNEC. Materials and Methods Cases of pathologically-confirmed stage IV LCNEC evaluated at Memorial Sloan Kettering Cancer Center from 2006 to 2013 were identified. We collected demographic, treatment, and survival data. Available radiology was evaluated by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria. Results Forty-nine patients with stage IV LCNEC were identified. The median age was 64 years, 63% of patients were male, and 88% were smokers. Twenty-three patients (n = 23/49; 47%) had brain metastases, 17 at diagnosis and 6 during the disease course. Seventeen LCNEC patients (35%) had molecular testing, of which 24% had KRAS mutations (n = 4/17). Treatment data for first-line metastatic disease was available on 37 patients: 70% (n = 26) received platinum/etoposide and 30% (n = 11) received other regimens. RECIST was completed on 23 patients with available imaging; objective response rate was 37% (95% confidence interval, 16%–62%) with platinum/etoposide, while those treated with other first-line regimens did not achieve a response. Median overall survival was 10.2 months (95% confidence interval, 8.6–16.4 months) for the entire cohort. Conclusion Patients with stage IV LCNEC have a high incidence of brain metastases. KRAS mutations are common. Patients with stage IV LCNEC do not respond as well to platinum/etoposide compared with historic data for extensive stage small-cell lung cancer; however, the prognosis is similar. Prospective studies are needed to define optimum therapy for stage IV LCNEC.

Rovalpituzumab tesirine, a DLL3-targeted antibody-drug conjugate, in recurrent small-cell lung cancer: a first-in-human, first-in-class, open-label, phase 1 study

“…The entire study cohort received a median of two doses (IQR 1–3; range 1–14) of rovalpituzumab tesirine. Because patients with large-cell neuroendocrine tumours comprised a small proportion of the study population (10%), and outcomes can differ from those of patients with small-cell lung cancer, 9 they were excluded from endpoint analyses. Clinical characteristics of the 74 participants (age range 38–81 years) with small-cell lung cancer were typical of patients with advanced recurrent disease (table 1).…”

Ki-67 labeling index of neuroendocrine tumors of the lung has a high level of correspondence between biopsy samples and surgical specimens when strict counting guidelines are applied

“…In metastatic lung NET, the importance of the Ki-67 LI on biopsy samples is not so much the diagnosis as such (which paradoxically matters less once high-grade NET has been excluded) but rather to guide subsequent therapy choice [33]. This molecular, morphological, and clinical heterogeneity of lung NET [20,39,[46][47][48][49][50] is similar to that of G3 GEP NET for which the Ki-67 LI is of equal diagnostic importance [26,[51][52][53][54][55][56]. Of note, LCNECs of the lung show a wide range of histological and molecular features, as some cases are morphologically close to SCCs [13, 14,16,47], while others are closer to conventional non-small cell carcinoma [47,[57][58][59]] and yet others to AC [3,8,47].…”

Next-Generation Sequencing of Pulmonary Large Cell Neuroendocrine Carcinoma Reveals Small Cell Carcinoma–like and Non–Small Cell Carcinoma–like Subsets

“…Clinically, LCNEC are generally associated with high rate of metastases and poor patient survival, but remarkably broad survival ranges have been reported (7). In addition, highly variable results have been reported regarding the chemosensitivity of LCNEC to platinum/etoposide–based regimens utilized for SCLC (8–10), resulting in the lack of consensus on whether LCNEC should be clinically managed as SCLC versus non-SCLC (NSCLC).…”