Vivian Rosery1,2, Stephan Mika1, Kurt Werner Schmid3, Henning Reis3,4, Martin Stuschke5, Jürgen Treckmann6, Peter Markus7, Brigitte Schumacher8, David Albers8, Bastian Mende9, Harald Lahner10, Marcel Wiesweg1,11, Martin Schuler1,11, Jens T Siveke1,2,12,11, Stefan Kasper13,14. 1. Department of Medical Oncology, West German Cancer Center, University Hospital Essen (AöR), Essen, Germany. 2. Bridge Institute of Experimental Tumor Therapy, West German Cancer Center, University Hospital Essen (AöR), Essen, Germany. 3. Institute of Pathology, West German Cancer Center, University Hospital Essen (AöR), Essen, Germany. 4. Institute of Pathology, University Hospital Frankfurt, Frankfurt, Germany. 5. Department of Radiotherapy, West German Cancer Center, University Hospital Essen (AöR), Essen, Germany. 6. General, Visceral and Transplantation Surgery, University Hospital Essen (AöR), Essen, Germany. 7. Department of General Surgery and Traumatology, Elisabeth Hospital Essen, Essen, Germany. 8. Department of Gastroenterology, Elisabeth Hospital Essen, Essen, Germany. 9. Central Pharmacy, University Hospital Essen (AöR), Essen, Germany. 10. Department of Endocrinology and Metabolism, University Hospital Essen (AöR), Essen, Germany. 11. German Cancer Consortium (DKTK), Partner Site University Hospital Essen (AöR), Essen, Germany. 12. Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK), Partner site University Hospital Essen, and German Cancer Research Center (DKFZ), Heidelberg, Germany. 13. Department of Medical Oncology, West German Cancer Center, University Hospital Essen (AöR), Essen, Germany. stefan.kasper-virchow@uk-essen.de. 14. German Cancer Consortium (DKTK), Partner Site University Hospital Essen (AöR), Essen, Germany. stefan.kasper-virchow@uk-essen.de.
Abstract
PURPOSE: High-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN G3) are rare and heterogeneous malignancies with poor prognosis. Aim of this study was to develop prognosticators identifying those patients that derive the most benefit from currently available systemic therapies. METHODS: This retrospective analysis included 78 patients with metastatic GEP-NEN G3. For patients with imaging data available (n = 52), the overall response rate (ORR) and disease control rate (DCR) were evaluated according to the Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1). A Cox proportional hazard model was used to analyze the prognostic value of selected clinical and blood-based biomarkers. The impact of palliative chemotherapy regimens on time-to-treatment-failure (TTF) and overall survival (OS) was assessed. RESULTS: Median OS of the study cohort was 9.0 months (95% CI 7.0-11.1). The majority of patients received first-line treatment with platinum plus etoposide (83.3%). The ORR and DCR of the RECIST-evaluable subgroup were 34.6% and 76.9%. Median TTF upon first-line treatment was 4.9 months (95% CI 3.4-6.4). Multivariate analysis identified the Eastern Cooperative Oncology Group performance status (ECOG PS), lactate dehydrogenase (LDH) and absolute lymphocyte count as independent prognostic factors. A prognostic score based on these parameters discriminated patients with favorable and unfavorable outcomes. CONCLUSION: Outcomes of patients with GEP-NEN G3 are still limited. A new prognostic score identifying those patients benefitting from current platinum/etoposide-based chemotherapy protocols may help as stratification factor in future trial design.
PURPOSE: High-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN G3) are rare and heterogeneous malignancies with poor prognosis. Aim of this study was to develop prognosticators identifying those patients that derive the most benefit from currently available systemic therapies. METHODS: This retrospective analysis included 78 patients with metastatic GEP-NEN G3. For patients with imaging data available (n = 52), the overall response rate (ORR) and disease control rate (DCR) were evaluated according to the Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1). A Cox proportional hazard model was used to analyze the prognostic value of selected clinical and blood-based biomarkers. The impact of palliative chemotherapy regimens on time-to-treatment-failure (TTF) and overall survival (OS) was assessed. RESULTS: Median OS of the study cohort was 9.0 months (95% CI 7.0-11.1). The majority of patients received first-line treatment with platinum plus etoposide (83.3%). The ORR and DCR of the RECIST-evaluable subgroup were 34.6% and 76.9%. Median TTF upon first-line treatment was 4.9 months (95% CI 3.4-6.4). Multivariate analysis identified the Eastern Cooperative Oncology Group performance status (ECOG PS), lactate dehydrogenase (LDH) and absolute lymphocyte count as independent prognostic factors. A prognostic score based on these parameters discriminated patients with favorable and unfavorable outcomes. CONCLUSION: Outcomes of patients with GEP-NEN G3 are still limited. A new prognostic score identifying those patients benefitting from current platinum/etoposide-based chemotherapy protocols may help as stratification factor in future trial design.
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