Biomarkers of Response to Etoposide-Platinum Chemotherapy in Patients with Grade 3 Neuroendocrine Neoplasms
| Autor: | Ophélie De Rycke, Olivia Hentic, Louis de Mestier, Jérôme Cros, Gérard Zalcman, Philippe Ruszniewski, Anthony Turpin, Anne Couvelard, Caroline Lacombe, Aurélie Cazes, Valérie Gounant |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research medicine.medical_specialty medicine.medical_treatment chemotherapy lcsh:RC254-282 Gastroenterology Article 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Clinical endpoint Etoposide Chemotherapy Lung tumor response neuroendocrine neoplasms business.industry biomarkers Cell cycle lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Staining 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Immunohistochemistry business Immunostaining medicine.drug |
| Zdroj: | Cancers Volume 13 Issue 4 Cancers, Vol 13, Iss 643, p 643 (2021) |
| ISSN: | 2072-6694 |
| DOI: | 10.3390/cancers13040643 |
| Popis: | Etoposide-platinum (EP) chemotherapy has long been the reference treatment for grade 3 neuroendocrine neoplasms (G3 NEN). However, G3 NEN are heterogeneous, including well-differentiated tumors (NET) and poorly differentiated large (LCNEC) or small (SCNEC) cell carcinomas, whose response to EP chemotherapy varies considerably. Our aim was to evaluate predictive biomarkers for the response to EP chemotherapy in G3 NEN. We retrospectively studied 89 patients with lung (42%) and digestive (58%) G3 NEN treated by EP chemotherapy between 2006 and 2020. All cases were centrally reviewed for cytomorphology/Ki-67 and immunohistochemistry of retinoblastoma protein (Rb)/p53/p16, analyzed using a semi-quantitative score. The absence of Rb staining (Rbinap) or the absence of very intense p53 staining (p53inap) were considered inappropriate. Rb staining was also studied as a quantitative marker, the best threshold being determined by ROC curve. Intense p16 staining (p16high) also suggested cell cycle dysregulation. Our primary endpoint was the objective response rate (ORR). We included 10 G3 NET, 31 LCNEC and 48 SCNEC, which showed ORR of 20%, 32% and 75%, respectively (NET vs. NEC, p = 0.040 LCNEC vs. SCNEC, p < 0.001). The ORR was significantly higher in NEN presenting with Rbinap (63% vs. 42%, p = 0.025) and p16high (66% vs. 35%, p = 0.006). Rb < 150 optimally identified responders (AUC = 0.657, p < 0.001). The ORR was 67% in Rb < 150 (vs. 25%, p = 0.005). On multivariate analysis, only Rb < 150 was independently associated with ORR (OR 4.16, 95% CI 1.11–15.53, p = 0.034). We confirm the heterogeneity of the response to EP treatment in G3 NEN. Rb < 150 was the best predictive biomarker for the response to EP, and p53 immunostaining had no additional value. |
| Databáze: | OpenAIRE |
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