Prognostic factors for relapse in resected gastroenteropancreatic neuroendocrine neoplasms: A systematic review and meta-analysis
Hubner, Richard A
Valle, Juan W
McNamara, Mairead G
AffiliationUniversity of Manchester / The Christie NHS Foundation Trust, Manchester
MetadataShow full item record
AbstractBackground: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a rare, heterogeneous group of malignancies. Potential cure can be achieved through surgical resection, but only 42-57% achieve 5-year disease-free survival. Here, the factors associated with relapse following potentially-curative resection of GEP-NENs are investigated, using a systematic review and meta-analysis. Methods: A systematic search of MEDLINE, EMBASE, Web of Science, BIOSIS, CENTRAL, Cochrane Library, and abstracts from ESMO and ASCO was performed and last updated July 2020. Prospective and retrospective studies reporting factors associated with relapse in patients with GEP-NENs following resection of a primary tumour, including concurrent resection of a metastatic site were included. Papers not reporting the proportion of patients with tumour grades 1-3 were excluded. Only variables which were reported by at least 3 studies were included in the meta-analysis. Hazard Ratios (HR) for Relapse-Free Survival (RFS) or Overall Survival (OS) were weighted using generic inverse variance and pooled using random effects modelling. Results: Of 729 studies identified initially; 96 were eligible for inclusion in the meta-analysis (17,698 patients); 83 studies (14,801 patients) included pancreatic NENs only, the remaining 13 studies reported on mixed primary site or non-pancreatic NENs. For the entire cohort, on multivariable analysis, vascular resection performed [HR 2.25 (95% confidence interval (CI) 1.29-3.90), p¼0.004], M1 disease [HR 2.53 (95%CI 1.22- 5.23), p¼0.01], tumour size >20mm [HR 2.39 (95%CI 1.68-3.40), p 5% [HR 3.78 (95% CI 2.12-6.76), p 20mm [HR 5.32 (95%CI 1.64-17.25), p¼0.005], grade 2 [HR 4.48 (95% CI 2.89-6.94), p < 0.001], R1 resection [HR 2.97 (95%CI 1.47-6.02), p¼0.002], microvascular invasion [HR 2.60 (95%CI 1.01-6.75), p¼0.049], perineural invasion [HR 2.48 (95%CI 1.17-5.25), p¼0.02] and any lymph node positivity [HR 3.67 (95%CI 2.44- 5.52), p < 0.001]. When studies reporting on mixed primary site or non-pancreatic NENs were analysed independently, lymph node positivity [HR 2.21 (95%CI 1.58-3.08), p < 0.001], grade 2 [HR 5.80 (95% CI 3.35-10.04), p < 0.001] lymphovascular invasion [HR 4.90 (95% CI 1.39-17.26), p¼0.01], R1 resection [HR 2.40 (95% CI 1.36-4.22), p¼0.002] were prognostic for worse RFS in the univariable analysis. For these studies, pooling of multivariable data was possible only for lymph node positivity [HR 3.54 (95% CI 1.07-11.77), p¼0.04]. Few OS data were available for pooling; in univariable analysis (entire cohort), grade 2 disease [HR 5.17 (95%CI 1.58-16.93), p¼0.007] was prognostic for worse OS, while R1 resection was not [HR 1.89 (95%CI 0.82-4.39), p¼0.14). Conclusions: This is one of the largest meta-analyses to identify pathological tumour characteristics which are prognostic for RFS and OS following resection of GEP-NENs. The majority of included studies reported on pancreatic NENs, which may introduce bias; however, the results will inform selection and stratification criteria for future adjuvant trials.
CitationBroadbent R, Wheatley R, Stajer S, Jacobs T, Lamarca A, Hubner R, et al. P-53 Prognostic factors for relapse in resected gastroenteropancreatic neuroendocrine neoplasms: A systematic review and meta-analysis. Annals of Oncology. 2021 Jul;32:S114.
JournalAnnals of Oncology
TypeMeetings and Proceedings