Alessandra Pulvirenti1,2, Ammar A Javed3, Luca Landoni2, Nigel B Jamieson4,5, Joanne F Chou6, Marco Miotto2, Jin He3, Mithat Gonen6, Antonio Pea2, Laura H Tang7, Chiara Nessi2, Sara Cingarlini8, Michael I D'Angelica1, Anthony J Gill9, T Peter Kingham1, Aldo Scarpa10, Matthew J Weiss3, Vinod P Balachandran1, Jaswinder S Samra5, John L Cameron3, William R Jarnagin1, Roberto Salvia2, Christopher L Wolfgang3, Peter J Allen11, Claudio Bassiy2. 1. Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY. 2. Unit of General and Pancreatic Surgery, University and Hospital Trust of Verona, Italy. 3. Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD. 4. Department of Surgery, Glasgow Royal Infirmary, Glasgow, Scotland. 5. Department of Surgery, Royal North Shore Hospital, Sydney, Australia. 6. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY. 7. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY. 8. Department of Oncology, University and Hospital Trust of Verona, Italy. 9. Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research Royal North Shore Hospital, Sydney, Australia and Sydney Medical School, University of Sydney, Sydney, Australia. 10. Department of Pathology, University and Hospital Trust of Verona, Italy. 11. Department of Surgery, Hepatopancreatobiliary Service, Duke, University School of Medicine, Durham, NC.
Abstract
OBJECTIVE: To develop a nomogram estimating the probability of recurrence free at 5 years after resection for localized grade 1 (G1)/ grade 2 (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 follow-up. METHOD: A multi-institutional database of patients with G1/G2 PanNETs treated at 2 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 3 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 European Neuroendocrine Tumors Society/ American Joint Committee on Cancer 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% confidence interval 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 after surgery.
OBJECTIVE: To develop a nomogram estimating the probability of recurrence free at 5 years after resection for localized grade 1 (G1)/ grade 2 (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 follow-up. METHOD: A multi-institutional database of patients with G1/G2 PanNETs treated at 2 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 3 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 European Neuroendocrine Tumors Society/ American Joint Committee on Cancer 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% confidence interval 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 after surgery.
Authors: Angela Lamarca; Hamish Clouston; Jorge Barriuso; Mairéad G McNamara; Melissa Frizziero; Was Mansoor; Richard A Hubner; Prakash Manoharan; Sarah O'Dwyer; Juan W Valle Journal: J Clin Med Date: 2019-10-05 Impact factor: 4.241
Authors: Alessandra Pulvirenti; Rikiya Yamashita; Jayasree Chakraborty; Natally Horvat; Kenneth Seier; Caitlin A McIntyre; Sharon A Lawrence; Abhishek Midya; Maura A Koszalka; Mithat Gonen; David S Klimstra; Diane L Reidy; Peter J Allen; Richard K G Do; Amber L Simpson Journal: JCO Clin Cancer Inform Date: 2021-06
Authors: Alessandra Pulvirenti; Nitya Raj; Sara Cingarlini; Antonio Pea; Laura H Tang; Claudio Luchini; Joanne F Chou; Elisabetta Grego; Ioana Marinova; Marinela Capanu; Luca Landoni; Aldo Scarpa; Peter J Allen; David S Klimstra; Diane L Reidy-Lagunes Journal: Pancreas Date: 2021-02-01 Impact factor: 3.243