Surgery after sunitinib administration to improve survival of patients with advanced pancreatic neuroendocrine neoplasms

Abstract

Background Little research is available regarding the treatments combining surgical resection with systemic chemotherapy for advanced pancreatic neuroendocrine neoplasm patients. We retrospectively elucidated whether sunitinib administration before surgery in advanced pancreatic neuroendocrine neoplasm (Pan‐NEN) patients increases survival. Methods This study included 106 of 326 Pan‐NEN patients with distant metastases and/or unresectable locally advanced tumors who visited our department to receive sunitinib for more than 1 mo during April 2002 to December 2019. Risk factors for overall survival (OS) and disease‐free survival (DFS) were analyzed. Results The median duration of preoperative sunitinib administration and observation time after sunitinib were 6 and 26.5 mo, respectively. Of 106 patients, 31 (29.2%) underwent surgery following sunitinib administration. Hepatectomy, synchronous hepatopancreatectomy, pancreatectomy, and lymphadenectomy were performed for 13, 12, 5, and 1 patient, respectively. The 5‐y OS rates in the resected and nonresected groups were 88.9% and 14.1%, respectively (P < .001). In the multivariate analysis, the absence of surgical resection following sunitinib (hazard ratio [HR], 13.1; P = .001), poor differentiation (HR, 5.5; P = .007), and bilateral liver metastases (HR, 3.7; P = .048) were independent risk factors for OS, although large liver tumor volumes were more evident in the nonresected group, as patient characteristics. The median DFS was 16.1 mo in 22 patients who underwent R0/1 resections, and risk factors for postoperative recurrence were Ki‐67 index >7.8% (HR, 7.4; P = .02) and R1 resection (HR, 4.4; P = .04). Conclusion Surgical resection after sunitinib administration improved OS in advanced Pan‐NENs.

Neoadjuvant therapy in pancreatic neuroendocrine neoplasms: A systematic review and meta-analysis

“…In the remaining 34 studies, there were 7 conference records, 8 case reports and 5 review excluded and 5 literatures excluded for other reasons [letter to editor (n=2), perioperative systematic treatment (n=1), replication of the study patients (n=1) and missing key information (n=1)]. Finally, we selected a total of 9 studies for meta-analysis ( 9 , 12 , 15 , 23 – 28 ) ( Figure 1 ).…”

“…Finally, there was a study using sunitinib as the target therapy regimen with a dose of 525mg/28d and the median treatment duration was 6 months ( 28 ).…”

“…However, studies on the role of targeted drugs in neoadjuvant therapy of pNENs are very rare. And there was only 1 study about sunitinib as the neoadjuvant therapy regimen included in our study, and the side effects of targeted therapy were not detailed description in this study (28).…”

“…However, studies on the role of targeted drugs in neoadjuvant therapy of pNENs are very rare. And there was only 1 study about sunitinib as the neoadjuvant therapy regimen included in our study, and the side effects of targeted therapy were not detailed description in this study ( 28 ). Unfortunately, in this study, 29.25% (31/106) of patients successfully completed “down-staging” therapy and underwent surgery after sunitinib, but the objective response rate of sunitinib was not described in this study.…”

Role of surgical treatments in high-grade or advanced gastroenteropancreatic neuroendocrine neoplasms

“…However, whether neoadjuvant treatments can improve the surgical prognoses in GEP-NEN LM remains unclear. Murase et al [ 68 ] analyzed 106 pNEN cases with LM or locally advanced tumors[ 68 ]. All patients received sunitinib, among which 31 underwent surgery after sunitinib treatment.…”