Radiation Oncology/NSCLC/LCNEC

Large Cell Neuroendocrine Carcinoma Epidemiology Incidence: 2-3.5% in resected lung specimens; probably higher in inoperable patients due to its aggressive nature Etiology: Smoking probably causative; 85-95% of patients have history of heavy tobacco use Median age at diagnosis: 66 years Present predominately in lung periphery (cough, hemoptysis, or post-obstructive PNA are not common presenting symptoms) Histology Historically grouped under neuroendocrine tumors of the lung (small cell, atypical carcinoid (LCNEC), typical carcinoid) In 1999 reassigned by WHO to Large Cell Carcinoma group, which includes several other unrelated but large cell histologies Cell size is typically 3X larger than for small cell CA Mitotic index is high, approaching that of small cell CA Cells contain neurosecretory granules, and typically stain positive for either neural cell adhesion molecule, chromogranin A, or synaptophysin Molecular markers suggest similarity of LCNEC and SCC, and difference from other large cell histologies (Ki-67+, p53+, Rb-) Survival 5-year OS of resected patients: ~30-40% Stage-adjusted survival is significantly worse than NSCLC Treatment Overview Most series reported are surgical Currently no definitive survival advantage for adjuvant chemotherapy Octreotide may have activity, and appears to control metastatic disease Washington University, 2005 (1988-2002) 15999058 -- "Large cell neuroendocrine carcinoma: an aggressive form of non-small cell lung cancer." (Battafarano RJ, J Thorac Cardiovasc Surg. 2005 Jul;130(1):166-72.) Retrospective. 2099 resected patients in database, 82 (4%) had large cell histology. LCNEC 45 patients, 50% Stage IA 5-year OS: overall 47%; LCNEC 30%, mixed neuroendocrine 30%, large cell carcinoma 71% (SS). Stage I LCNEC 5-year OS 32% Conclusion: LCNEC significantly worse survival after resection, even in Stage I disease Review 2006 17075564 -- "Large-cell neuroendocrine carcinoma of the lung." (Fernandez FG, Cancer Control. 2006 Oct;13(4):270-5.) Recommend classifying separately from NSCLC as Grade III neuroendocrine carcinoma, large-cell type