Radical Resection in Entero-Pancreatic Neuroendocrine Tumors: Recurrence-Free Survival Rate and Definition of a Risk Score for Recurrence.
Journal
Annals of surgical oncology
ISSN: 1534-4681
Titre abrégé: Ann Surg Oncol
Pays: United States
ID NLM: 9420840
Informations de publication
Date de publication:
Sep 2022
Sep 2022
Historique:
received:
01
03
2022
accepted:
11
04
2022
pubmed:
19
5
2022
medline:
11
8
2022
entrez:
18
5
2022
Statut:
ppublish
Résumé
Surgery with radical intent is the only potentially curative option for entero-pancreatic neuroendocrine tumors (EP-NETs) but many patients develop recurrence even after many years. The subset of patients at high risk of disease recurrence has not been clearly defined to date. The aim of this retrospective study was to define, in a series of completely resected EP-NETs, the recurrence-free survival (RFS) rate and a risk score for disease recurrence. This was a multicenter retrospective analysis of sporadic pancreatic NETs (PanNETs) or small intestine NETs (SiNETs) [G1/G2] that underwent R0/R1 surgery (years 2000-2016) with at least a 24-month follow-up. Survival analysis was performed using the Kaplan-Meier method and risk factor analysis was performed using the Cox regression model. Overall, 441 patients (224 PanNETs and 217 SiNETs) were included, with a median Ki67 of 2% in tumor tissue and 8.2% stage IV disease. Median RFS was 101 months (5-year rate 67.9%). The derived prognostic score defined by multivariable analysis included prognostic parameters, such as TNM stage, lymph node ratio, margin status, and grading. The score distinguished three risk categories with a significantly different RFS (p < 0.01). Approximately 30% of patients with EP-NETs recurred within 5 years after radical surgery. Risk factors for recurrence were disease stage, lymph node ratio, margin status, and grading. The definition of risk categories may help in selecting patients who might benefit from adjuvant treatments and more intensive follow-up programs.
Sections du résumé
BACKGROUND
BACKGROUND
Surgery with radical intent is the only potentially curative option for entero-pancreatic neuroendocrine tumors (EP-NETs) but many patients develop recurrence even after many years. The subset of patients at high risk of disease recurrence has not been clearly defined to date.
OBJECTIVE
OBJECTIVE
The aim of this retrospective study was to define, in a series of completely resected EP-NETs, the recurrence-free survival (RFS) rate and a risk score for disease recurrence.
PATIENTS AND METHODS
METHODS
This was a multicenter retrospective analysis of sporadic pancreatic NETs (PanNETs) or small intestine NETs (SiNETs) [G1/G2] that underwent R0/R1 surgery (years 2000-2016) with at least a 24-month follow-up. Survival analysis was performed using the Kaplan-Meier method and risk factor analysis was performed using the Cox regression model.
RESULTS
RESULTS
Overall, 441 patients (224 PanNETs and 217 SiNETs) were included, with a median Ki67 of 2% in tumor tissue and 8.2% stage IV disease. Median RFS was 101 months (5-year rate 67.9%). The derived prognostic score defined by multivariable analysis included prognostic parameters, such as TNM stage, lymph node ratio, margin status, and grading. The score distinguished three risk categories with a significantly different RFS (p < 0.01).
CONCLUSIONS
CONCLUSIONS
Approximately 30% of patients with EP-NETs recurred within 5 years after radical surgery. Risk factors for recurrence were disease stage, lymph node ratio, margin status, and grading. The definition of risk categories may help in selecting patients who might benefit from adjuvant treatments and more intensive follow-up programs.
Identifiants
pubmed: 35583694
doi: 10.1245/s10434-022-11837-1
pii: 10.1245/s10434-022-11837-1
doi:
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
5568-5577Subventions
Organisme : european neuroendocrine tumor society
ID : ENETS Excellence Academy Fellowship Grant 2017
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022. Society of Surgical Oncology.
Références
Niederle B, Pape UF, Costa F, et al. ENETS consensus guidelines update for neuroendocrine neoplasms of the Jejunum and Ileum. Neuroendocrinology. 2016;103(2):125-138.
doi: 10.1159/000443170
Falconi M, Eriksson B, Kaltsas G, et al. ENETS consensus guidelines update for the management of patients with functional pancreatic neuroendocrine tumors and non-functional pancreatic neuroendocrine tumors. Neuroendocrinology. 2016;103(2):153-171.
doi: 10.1159/000443171
Partelli S, Bartsch DK, Capdevila J, et al. ENETS consensus guidelines for standard of care in neuroendocrine tumours: surgery for small intestinal and pancreatic neuroendocrine tumours. Neuroendocrinology. 2017;105(3):255-265.
doi: 10.1159/000464292
Rindi G, Kloppel G, Alhman H, et al. TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Arch. 2006;449(4):395-401.
doi: 10.1007/s00428-006-0250-1
Rindi G, Kloppel G, Couvelard A, et al. TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system. Virchows Arch. 2007;451(4):757-762.
doi: 10.1007/s00428-007-0452-1
Genc CG, Jilesen AP, Partelli S, et al. A new scoring system to predict recurrent disease in grade 1 and 2 nonfunctional pancreatic neuroendocrine tumors. Ann Surg. 2018;267(6):1148-1154.
doi: 10.1097/SLA.0000000000002123
Viudez A, Carvalho FL, Maleki Z, et al. A new immunohistochemistry prognostic score (IPS) for recurrence and survival in resected pancreatic neuroendocrine tumors (PanNET). Oncotarget. 2016;7(18):24950-24961.
doi: 10.18632/oncotarget.7436
Primavesi F, Andreasi V, Hoogwater FJH, et al. A preoperative clinical risk score including C-reactive protein predicts histological tumor characteristics and patient survival after surgery for sporadic non-functional pancreatic neuroendocrine neoplasms: an international multicenter cohort study. Cancers (Basel). 2020;12(5):1235.
doi: 10.3390/cancers12051235
Zou S, Jiang Y, Wang W, Zhan Q, Deng X, Shen B. Novel scoring system for recurrence risk classification of surgically resected G1/2 pancreatic neuroendocrine tumors - Retrospective cohort study. Int J Surg. 2020;74:86-91.
doi: 10.1016/j.ijsu.2019.12.034
Pulvirenti A, Javed AA, Landoni L, et al. Multi-institutional development and external validation of a nomogram to predict recurrence after curative resection of pancreatic neuroendocrine tumors. Ann Surg. 2021;274(6):1051–1057.
doi: 10.1097/SLA.0000000000003579
Xiang JX, Zhang XF, Weiss M, et al. Early recurrence of well-differentiated (G1) neuroendocrine liver metastasis after curative-intent surgery: risk factors and outcome. J Surg Oncol. 2018;118(7):1096-1104.
doi: 10.1002/jso.25246
Zaidi MY, Lopez-Aguiar AG, Switchenko JM, et al. A novel validated recurrence risk score to guide a pragmatic surveillance strategy after resection of pancreatic neuroendocrine tumors: an international study of 1006 patients. Ann Surg. 2019;270(3):422-433.
doi: 10.1097/SLA.0000000000003461
Ausania F, Senra Del Rio P, Gomez-Bravo MA, et al. Can we predict recurrence in WHO G1-G2 pancreatic neuroendocrine neoplasms? Results from a multi-institutional Spanish study. Pancreatology. 2019;19(2):367-371.
doi: 10.1016/j.pan.2019.01.007
Fisher AV, Lopez-Aguiar AG, Rendell VR, et al. Predictive value of chromogranin A and a pre-operative risk score to predict recurrence after resection of pancreatic neuroendocrine tumors. J Gastrointest Surg. 2019;23(4):651-658.
doi: 10.1007/s11605-018-04080-1
Sun HT, Zhang SL, Liu K, et al. MRI-based nomogram estimates the risk of recurrence of primary nonmetastatic pancreatic neuroendocrine tumors after curative resection. J Magn Reson Imaging. 2019;50(2):397-409.
doi: 10.1002/jmri.26603
Sho S, Court CM, Winograd P, et al. A prognostic scoring system for the prediction of metastatic recurrence following curative resection of pancreatic neuroendocrine tumors. J Gastrointest Surg. 2019;23(7):1392-1400.
doi: 10.1007/s11605-018-4011-7
Merath K, Bagante F, Beal EW, et al. Nomogram predicting the risk of recurrence after curative-intent resection of primary non-metastatic gastrointestinal neuroendocrine tumors: an analysis of the U.S. Neuroendocrine Tumor Study Group. J Surg Oncol. 2018;117(5):868-878.
doi: 10.1002/jso.24985
Gao H, Liu L, Wang W, et al. Novel recurrence risk stratification of resected pancreatic neuroendocrine tumor. Cancer Lett. 2018;412:188-193.
doi: 10.1016/j.canlet.2017.10.036
Cao LL, Lu J, Lin JX, et al. A novel predictive model based on preoperative blood neutrophil-to-lymphocyte ratio for survival prognosis in patients with gastric neuroendocrine neoplasms. Oncotarget. 2016;7(27):42045-42058.
doi: 10.18632/oncotarget.9805
Evers M, Rinke A, Rutz J, Ramaswamy A, Maurer E, Bartsch DK. Prognostic factors in curative resected locoregional small intestine neuroendocrine neoplasms. World J Surg. 2021;45(4):1109–1117.
doi: 10.1007/s00268-020-05884-6
Bosman FT. WHO classification of tumours of the digestive system. Lyon: IARC Press; 2010.
Knigge U, Capdevila J, Bartsch DK, et al. ENETS consensus recommendations for the standards of care in neuroendocrine neoplasms: follow-up and documentation. Neuroendocrinology. 2017;105(3):310-319.
doi: 10.1159/000458155
Boninsegna L, Panzuto F, Partelli S, et al. Malignant pancreatic neuroendocrine tumour: lymph node ratio and Ki67 are predictors of recurrence after curative resections. Eur J Cancer. 2012;48(11):1608-1615.
doi: 10.1016/j.ejca.2011.10.030
Wu L, Chen F, Chen S, Wang L. The lymph node ratio optimizes staging in patients with small intestinal neuroendocrine tumors. Neuroendocrinology. 2018;107(3):209-217.
doi: 10.1159/000491017
Zaidi MY, Lopez-Aguiar AG, Dillhoff M, et al. Prognostic role of lymph node positivity and number of lymph nodes needed for accurately staging small bowel neuroendocrine tumors. JAMA Surg. 2019;154(2):134–140.
doi: 10.1001/jamasurg.2018.3865
Zhang XF, Wu Z, Cloyd J, et al. Margin status and long-term prognosis of primary pancreatic neuroendocrine tumor after curative resection: results from the US Neuroendocrine Tumor Study Group. Surgery. 2019;165(3):548–556.
doi: 10.1016/j.surg.2018.08.015
Partelli S, Javed AA, Andreasi V, et al. The number of positive nodes accurately predicts recurrence after pancreaticoduodenectomy for nonfunctioning neuroendocrine neoplasms. Eur J Surg Oncol. 2018;44(6):778-783.
doi: 10.1016/j.ejso.2018.03.005
Shen C, Dasari A, Chu Y, et al. Clinical, pathological, and demographic factors associated with development of recurrences after surgical resection in elderly patients with neuroendocrine tumors. Ann Oncol. 2017;28(7):1582-1589.
doi: 10.1093/annonc/mdx164
Slagter AE, Ryder D, Chakrabarty B, et al. Prognostic factors for disease relapse in patients with neuroendocrine tumours who underwent curative surgery. Surg Oncol. 2016;25(3):223-228.
doi: 10.1016/j.suronc.2016.05.019
Cives M, Anaya DA, Soares H, Coppola D, Strosberg J. Analysis of postoperative recurrence in stage I-III midgut neuroendocrine tumors. J Natl Cancer Inst. 2018;110(3):282-289.
doi: 10.1093/jnci/djx174
Genc CG, Falconi M, Partelli S, et al. Recurrence of pancreatic neuroendocrine tumors and survival predicted by Ki67. Ann Surg Oncol. 2018;25(8):2467-2474.
doi: 10.1245/s10434-018-6518-2
Titan AL, Norton JA, Fisher AT, et al. Evaluation of outcomes following surgery for locally advanced pancreatic neuroendocrine tumors. JAMA Netw Open. 2020;3(11):e2024318.
doi: 10.1001/jamanetworkopen.2020.24318
Zhang C, Wu Y, Zhuang H, et al. Establishment and validation of an AJCC stage- and histologic grade-based nomogram for pancreatic neuroendocrine tumors after surgical resection. Cancer Manag Res. 2019;11:7345-7352.
doi: 10.2147/CMAR.S200340
Merola E, Pavel ME, Panzuto F, et al. Functional imaging in the follow-up of enteropancreatic neuroendocrine tumors: clinical usefulness and indications. J Clin Endocrinol Metab. 2017;102(5):1486-1494.
doi: 10.1210/jc.2016-3732