American Association for Cancer Research
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Figure S2 from Molecular Subtypes of Pulmonary Large-cell Neuroendocrine Carcinoma Predict Chemotherapy Treatment Outcome

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posted on 2023-03-31, 19:21 authored by Jules L. Derks, Noémie Leblay, Erik Thunnissen, Robert Jan van Suylen, Michael den Bakker, Harry J.M. Groen, Egbert F. Smit, Ronald Damhuis, Esther C. van den Broek, Amélie Charbrier, Matthieu Foll, James D. McKay, Lynnette Fernandez-Cuesta, Ernst-Jan M. Speel, Anne-Marie C. Dingemans

Progression-free survival for subtypes of chemotherapy in panel-consensus LCNEC with A) RB1 wild-type*; B) RB1 mutation; C) H-score {greater than or equal to}50 for RB1* IHC; D) H-score <50 for RB1 IHC; E) H-score <50 for P16 IHC; F) H-score {greater than or equal to}50 for RB1* or <50 for P16 on IHC analysis. Abbreviations: No, number of. *Case 162 excluded from analyses.


Dutch Cancer Society




Purpose: Previous genomic studies have identified two mutually exclusive molecular subtypes of large-cell neuroendocrine carcinoma (LCNEC): the RB1 mutated (mostly comutated with TP53) and the RB1 wild-type groups. We assessed whether these subtypes have a predictive value on chemotherapy outcome.Experimental Design: Clinical data and tumor specimens were retrospectively obtained from the Netherlands Cancer Registry and Pathology Registry. Panel-consensus pathology revision confirmed the diagnosis of LCNEC in 148 of 232 cases. Next-generation sequencing (NGS) for TP53, RB1, STK11, and KEAP1 genes, as well as IHC for RB1 and P16 was performed on 79 and 109 cases, respectively, and correlated with overall survival (OS) and progression-free survival (PFS), stratifying for non–small cell lung cancer type chemotherapy including platinum + gemcitabine or taxanes (NSCLC-GEM/TAX) and platinum-etoposide (SCLC-PE).Results: RB1 mutation and protein loss were detected in 47% (n = 37) and 72% (n = 78) of the cases, respectively. Patients with RB1 wild-type LCNEC treated with NSCLC-GEM/TAX had a significantly longer OS [9.6; 95% confidence interval (CI), 7.7–11.6 months] than those treated with SCLC-PE [5.8 (5.5–6.1); P = 0.026]. Similar results were obtained for patients expressing RB1 in their tumors (P = 0.001). RB1 staining or P16 loss showed similar results. The same outcome for chemotherapy treatment was observed in LCNEC tumors harboring an RB1 mutation or lost RB1 protein.Conclusions: Patients with LCNEC tumors that carry a wild-type RB1 gene or express the RB1 protein do better with NSCLC-GEM/TAX treatment than with SCLC-PE chemotherapy. However, no difference was observed for RB1 mutated or with lost protein expression. Clin Cancer Res; 24(1); 33–42. ©2017 AACR.