Multi-institutional Development and External Validation of a Nomogram to Predict Recurrence After Curative Resection of Pancreatic Neuroendocrine Tumors

Abstract

Objective: To develop a nomogram estimating the probability of recurrence free at 5 years after resection for localized G1/G2 pancreatic neuroendocrine tumors (PanNETs). Background: Among patients undergoing resection of PanNETs, approximately 17% experience recurrence. It is not established which patients are at risk, with no consensus on optimal followup. Method: A multi-institutional database of patients with G1/G2 PanNETs treated at two institutions was used to develop a nomogram estimating the rate of freedom from recurrence at 5-years after curative resection. A second cohort of patients from three additional institutions was used to validate the nomogram. Prognostic factors were assessed by univariate analysis using Cox regression model. The nomogram was internally validated using bootstrap resampling method and on the external cohort. Performance was assessed by concordance-index (c-index) and a calibration curve. Results: The nomogram was constructed using a cohort of 632 patients. Overall, 68% of PanNETs were G1, the median follow-up was 51 months and we observed 74 recurrences. Variables included in the nomogram were the number of positive nodes, tumor diameter, Ki-67 and vascular/perineural invasion. The model bias-corrected c-index from the internal validation was 0.85 which was higher than ENETS/AJCC 8th staging scheme (c-index 0.76, p=<0.001). On the external cohort of 328 patients, the nomogram c-index was 0.84 (95% CI: 0.79-0.88). Conclusion: Our externally validated nomogram predicts the probability of recurrence free survival at 5 years after PanNETs curative resection, with improved accuracy over current staging systems. Estimating individual recurrence risk will guide the development of personalized surveillance programs following surgery.

Infiltrating pattern and prognostic value of tertiary lymphoid structures in resected non-functional pancreatic neuroendocrine tumors

“…Memorial Sloan-Kettering Cancer Center (MSKCC) constructed a nomogram using four variables: number of positive lymph nodes, Ki67 index, tumor diameter, and presence of vascular or perineural invasion. 6 For comparison, we constructed a MSKCC-based nomogram using these same variables and applied the nomogram to the Fudan cohort and external validation set (figure 4D). 6…”

Clinical and Molecular Risk Factors for Recurrence Following Radical Surgery of Well-Differentiated Pancreatic Neuroendocrine Tumors

“…It follows that F-PanNETs present with a clinical hormone syndrome that favors diagnosis at early stages. Furthermore, it has been observed that F-PanNETs have a lower median proliferative index and are less likely to have vascular or perineural invasion compared to NF-PanNETs (9). Those features, as discussed later in this review, have a relevant impact on prognosis.…”

“…While previously it was suspected that the majority of resected PanNETs were functioning, with insulinomas being the most frequent type, recent data show that between 60 and 90% of PanNETs are non-functional (1,19). The functioning status has been reported as a favorable characteristic of PanNET, as recurrence occurs in this group in ∼4% of cases (9). However, although some F-PanNETs including insulinoma are commonly reported to be benign (20), the prognosis of F-PanNETs is still predominately driven by the tumor stage and pathological features, regardless of hormone secretion (1).…”

“…Several retrospective studies have validated the prognostic value of PanNET grading, showing that higher grade is associated with an increased risk of recurrence and shorter overall survival, and to date, it is considered the most significant prognostic factor for disease relapse (9,14,17,25,26). When evaluating the risk of recurrence, G3 PanNETs have a worse prognosis than G1/G2, whereas G2 PanNETs exhibit up to 11-folded risk to recur compared to G1 neoplasms (4,9). Patients with G3 PanNET need to be strictly surveilled following curative surgery, whereas the outcomes of G1 and G2 neoplasms are more heterogeneous, and their stratification based solely on grade can be inaccurate.…”

A neotype nomogram based on accessible clinical indicators to predict the overall survival of esophageal cancer patients underwent radical resection

“…Therefore, a type of model called nomogram that can incorporate multiple prognostic factors is maturing. Recently, nomograms are popularly investigated in cancer-related survival, recurrence and metastasis with considerable potential (21)(22)(23)(24). Overall survival (OS) is regarded as a most commonly used outcome for cancer-related survival prognosis with confounding factors while the nomogram studies on EC-related OS prediction are less of quantity.…”