RESUMEN
BACKGROUND: Despite the low recurrence rate of resected nonfunctional pancreatic neuroendocrine tumors (NF-pNETs), nearly all patients undergo long-term surveillance. A prediction model for recurrence may help select patients for less intensive surveillance or identify patients for adjuvant therapy. The objective of this study was to assess the external validity of a recently published model predicting recurrence within 5 years after surgery for NF-pNET in an international cohort. This prediction model includes tumor grade, lymph node status and perineural invasion as predictors. METHODS: Retrospectively, data were collected from 7 international referral centers on patients who underwent resection for a grade 1-2 NF-pNET between 1992 and 2018. Model performance was evaluated by calibration statistics, Harrel's C-statistic, and area under the curve (AUC) of the receiver operating characteristic curve for 5-year recurrence-free survival (RFS). A sub-analysis was performed in pNETs >2 cm. The model was improved to stratify patients into 3 risk groups (low, medium, high) for recurrence. RESULTS: Overall, 342 patients were included in the validation cohort with a 5-year RFS of 83% (95% confidence interval [CI]: 78-88%). Fifty-eight patients (17%) developed a recurrence. Calibration showed an intercept of 0 and a slope of 0.74. The C-statistic was 0.77 (95% CI: 0.70-0.83), and the AUC for the prediction of 5-year RFS was 0.74. The prediction model had a better performance in tumors >2 cm (C-statistic 0.80). CONCLUSIONS: External validity of this prediction model for recurrence after curative surgery for grade 1-2 NF-pNET showed accurate overall performance using 3 easily accessible parameters. This model is available via www.pancreascalculator.com.
Asunto(s)
Tumores Neuroectodérmicos Primitivos , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Humanos , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/cirugía , Nomogramas , Neoplasias Pancreáticas/patología , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: Small nonfunctional pancreatic neuroendocrine tumors (NF-PNETs) ≤2 cm have variable biological features, and there is no gold standard treatment for their management. The present study aimed to evaluate the risk of malignancy of small NF-PNETs and their outcomes following curative resection. METHODS: Patients with NF-PNETs undergoing surgical resection at the First Affiliated Hospital, College of Medicine, Zhejiang University, between 2012 and 2017 were included. Clinicopathological characteristics, perioperative results, and prognosis were retrospectively analyzed. RESULTS: A total of 73 patients were identified, including 28 with small NF-PNETs and 45 large PNETs; 32.1% of NF-PNETs ≤2 cm underwent a parenchyma-sparing pancreas surgery, which was >6.7% in large NF-PNETs. No statistically significant differences in perioperative results, postoperative complications, and long-term outcomes were found between small tumors undergoing standard and parenchyma-sparing pancreatectomy. Eighteen small tumors (64.3%) developed a perioperative complication, with a clinically significant pancreatic fistula rate of 25%; however, only 2 patient needed reintervention. Small NF-PNETs in 3 patients were malignant. Multivariate logistic regression showed that grade ≥3 and lymphovascular invasion were independently related to malignancy in NF-PNETs. CONCLUSIONS: Small NF-PNETs (≤2 cm) are not immune from potential malignancy. Surgical resection may be considered for small tumors and can provide favorable postoperative and long-term outcomes. Parenchyma-sparing pancreatectomy may be an alternative surgery for selected small local NF-PNETs.
RESUMEN
OBJECTIVE: This study retrospectively characterized the immune infiltrating profile in nonfunctional pancreatic neuroendocrine tumors (NF-PanNETs). METHODS: Tumor tissues from the 109-patient Fudan cohort and a 73-patient external validation set were evaluated by immunohistochemistry for 9 immune cell types: tumor-infiltrating neutrophils (TINs), tumor-associated macrophages (TAMs), CD11c+ dendritic cells, anti-NCR1+ natural killer (NK) cells, CD4+ and CD8+ T cells, CD45RO+ memory T cells, FOXP3+ regulatory T cells (Tregs), and CD20+ B cells. RESULTS: TINs were primarily distributed in the intratumoral area, dendritic cells and NK cells were scattered evenly in intratumoral and stromal areas, and Tregs were rarely detected. The remaining 5 cell types were primarily present in peritumoral stroma. Total TINs (P < .001) and TAMs (P = .002) increased as NF-PanNET grade rose. Kaplan-Meier analyses showed that high intratumoral TINs, total TAMs, and stromal CD4+ T-cell infiltration correlated with shorter recurrence-free survival (RFS, P = .010, P = .027, and P = .035, respectively) and overall survival (OS, P = .017, P = .029, and P = .045, respectively). Additionally, high intratumoral CD8+ T cell infiltration correlated with prolonged RFS (P = .039). Multivariate Cox regression demonstrated that intratumoral TINs, World Health Organization (WHO) classification, and eighth edition of the American Joint Committee on Cancer tumor-node-metastasis staging system (AJCC8th TNM) were independent factors for RFS (P = .043, P = .023, and P = .029, respectively), whereas intratumoral TINs and WHO classification were independent factors for OS (P = .010 and P = .007, respectively). Furthermore, the combination of TINs, WHO classification, and AJCC8th TNM remarkably improved prognostic accuracy for RFS. These results have been verified in the external validation set. CONCLUSION: Intratumoral TINs are an independent and unfavorable predictor of postoperative NF-PanNETs. A combination of TINs, WHO classification, and AJCC8th TNM could improve prognostic accuracy for RFS.