Is the morphological subtype of Extra-Pulmonary Neuroendocrine Carcinoma clinically relevant?

Melissa Frizziero, Alice Durand, Rodrigo G. Taboada, Elisa Zaninotto, Claudio Luchini, Bipasha Chakrabarty, Valérie Hervieu, Laura C. L. Claro, Cong Zhou, Sara Cingarlini, Michele Milella, Thomas Walter, Rachel S. Riechelmann, Angela Lamarca, Richard Hubner, Wasat Mansoor, Juan Valle, Mairead Mcnamara

Research output: Contribution to journalArticlepeer-review

Abstract

Extra-pulmonary neuroendocrine carcinomas (EP-NECs) are lethal cancers with limited treatment options. Identification of contributing factors to the observed heterogeneity of clinical outcomes within the EP-NEC family is warranted, to enable identification of effective treatments. A multicentre retrospective study investigated potential differences in ‘real-world’ treatment/survival outcomes between small cell (SC) versus (vs.) non-SC EP-NECs. One-hundred-seventy patients were included; 77 (45.3%) had SC and 93 (54.7%) had non-SC EP-NEC. Compared to the SC subgroup, the non-SC subgroup had; 1) a lower mean Ki-67 (69.3% vs. 78.7%, p=0.002); 2) a lower proportion of cases with a Ki-67≥55% (73.9% vs. 88.7%, p=0.025); 3) reduced sensitivity to first-line platinum/etoposide (objective response rate; 31.6% vs. 55.1%, p=0.015, and disease control rate; 59.7% vs. 79.6%, p=0.027); 4) worse progression-free survival (PFS) (adjusted-HR=1.615, p=0.016) and overall survival (OS) (adjusted-HR=1.640, p=0.015) in the advanced setting. Within the advanced EP-NEC cohort, subgroups according to morphological subtype and Ki-67 (< vs. ≥55%) had significantly different PFS (adjusted-p=0.021) and OS (adjusted-p=0.051), with the non-SC/Ki-67<55% and non-SC/Ki-67≥55% subgroups showing the best and worst outcomes, respectively. To conclude, the morphological subtype of EP-NEC provides complementary information to Ki-67 and may aid identification of patients who could benefit from alternative first-line treatment strategies to platinum/etoposide.
Original languageEnglish
JournalCancers
Publication statusAccepted/In press - 13 Aug 2021

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