The PANEN nomogram: clinical decision support for patients with metastatic pancreatic neuroendocrine neoplasm referred for peptide receptor radionuclide therapy

Aviral Singh^1*Sebastian Sanduleanu^2*Harshad Kulkarni³Thomas Langbein⁴Philippe Lambin⁵Richard P Baum⁶

• ¹GenesisCare (Australia), Wembley, Western Australia, Australia
• ²GFO Clinics Troisdorf, Troisdorf, Germany
• ³BAMF Health, Michigan, United States
• ⁴Zentralklinik, Bad Berka, Germany
• ⁵Maastricht University, Maastricht, Netherlands
• ⁶CURANOSTICUM, Wiesbaden-Frankfurt, Germany

Patients with pancreatic neuroendocrine neoplasms (P-NEN) may benefit from peptide receptor radionuclide therapy (PRRT). Prediction of overall survival (OS) using statistical models has the potential to guide treatment decisions. In this study, we have generated a clinicopathological and imaging parameter-based internally validated nomogram of patients who received PRRT for metastatic P-NEN to facilitate treatment decision support for the clinical management of such patients.We reviewed 447 pancreatic NEN patients treated with PRRT. Clinical variables for the prediction of overall survival (OS) included age, gender, Karnofsky performance score (KPS), weight loss, hepatomegaly, time from diagnosis to first PRRT (days), tumor functionality, presence of Hedinger syndrome, presence of liver metastases, presence of bone metastases, presence of lung metastases, alkaline phosphatase, FDG 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET) scan positivity, erythrocytes, platelets, creatinine clearance, leucocytes, and histologic grade of tumor differentiation based on KI-67 staining. A random survival forests (RSF) method was used to construct a model with an optimal number of clinical variables. The model was developed on 80% of the data and tested on the remaining 20% of the data. Performance of prediction was calculated using the c-index, a generalization of the area under the ROC curve (AUC) for survival models.Median follow up time was 2045 days (min 136 days, max 10329 days). Time from diagnosis to 1 st PRRT, alkaline phosphatase, KPS Karnofsky performance score, hepatomegaly, weight loss, [18F]FDGFDG-PET scan positivity, Ki-67% derived histologic grade, lung metastases, age, presence of bone metastases, platelet count, erythrocyte count, creatinine clearance, hemoglobin, presence of functioning tumor, creatinine, and gender, were in order of importance, all independent predictors for overall survival. The development set c-index was 0.86, while the test set c-index was 0.82. A nomogram was constructed based on the optimal number of clinical parameters selected in the RSF model.This study proposes an internally validated nomogram (PANEN-N) to accurately predict overall survival for pancreatic neuroendocrine neoplasm (P-NEN) patients following PRRT, which could be used for patient counseling to facilitate informed and shared decision support in daily clinical practice as well as for generating new hypotheses.