Therapeutic index of lymphadenectomy among patients with pancreatic neuroendocrine tumors: A multi‐institutional analysis

Abstract

Background: The benefit derived from lymph node dissection (LND) in patients with pancreatic neuroendocrine tumors (pNETs) based on clinicopathological characteristics remains unclear.Methods: Patients undergoing surgery for pNET between 1997 and 2016 were identified using a multi-institutional dataset. The therapeutic index of LND relative to patient characteristics was calculated.Results: Among 647 patients, the median number of lymph nodes (LNs) evaluated was 10 (interquartile range: 4-16) and approximately one quarter of patients had lymph node metastasis (LNM) (N = 159, 24.6%). Among patients with LNM, 5-year recurrence-free survival was 56.0%, reflecting a therapeutic index value of 13.8. The therapeutic index was highest among patients with a moderately/poorly-differentiated pNET (21.5), Ki-67 ≥ 3% (20.1), tumor size ≥2.0 cm (20.0), and tumor location at the head of the pancreas (20.0). Patients with ≥8 LNs evaluated had a higher therapeutic index than patients who had 1 to 7 LNs evaluated (≥8: 17.9 vs 1-7: 7.5; difference of index: 11.4).Conclusion: LND was mostly beneficial among patients with pNETs >2 cm, Ki-67 ≥ 3%, and lesions located at the pancreatic head as identification of LNM was most common among individuals with these tumor characteristics. Evaluation of ≥8 LNs was associated with a higher likelihood of identifying LNM as well as a higher therapeutic index, and therefore this number of LNs should be considered the goal. K E Y W O R D S lymphadenectomy, pancreatic neuroendocrine tumor, therapeutic index Lu Wu, Kota Sahara, and Diamantis I. Tsilimigras contributed equally to this work.

Survival benefit of lymphadenectomy for gallbladder cancer based on the therapeutic index: An analysis of the US extrahepatic biliary malignancy consortium

“…While LND is performed to adequately stage the disease and limit the locoregional tumor spread, the therapeutic index focuses more on the latter and aids in the identification of patients who will benefit the most from LND. Although the therapeutic index was first proposed in the treatment of gastric cancer, investigators have recently applied this concept to different types of malignancies, including colorectal and pancreatic cancer as well as intrahepatic cholangiocarcinoma . Nevertheless, to date, the nodal therapeutic index has not been examined among patients undergoing resection for GBC.…”

“…The therapeutic index is based on the rationale that lymphadenectomy may be most important among patients with a high estimated frequency of LNM, as well as individuals who are most likely to gain a survival benefit from the ascertainment of nodal status information . Nodal therapeutic index was first applied to determine the survival benefit of lymphadenectomy for gastric cancer, and more recently has been applied to patients with colorectal and pancreatic malignancies . Furthermore, the therapeutic index has been employed to define optimal LND in the Japanese Classification of Gastric Carcinoma guidelines, indicating the increasing adoption of this concept .…”

“… 5 Nodal therapeutic index was first applied to determine the survival benefit of lymphadenectomy for gastric cancer, 6 , 7 , 8 and more recently has been applied to patients with colorectal and pancreatic malignancies. 9 , 10 , 11 Furthermore, the therapeutic index has been employed to define optimal LND in the Japanese Classification of Gastric Carcinoma guidelines, indicating the increasing adoption of this concept. 12 , 13 To date, the nodal therapeutic index has not been examined among patients undergoing curative‐intent resection for GBC.…”

Long-Term Outcomes after Spleen-Preserving Distal Pancreatectomy for Pancreatic Neuroendocrine Tumors: Results from the US Neuroendocrine Study Group

“…Interestingly, the comparable long-term outcomes were attained despite differences in TNLE among patients undergoing SPDP versus DPS. While LN involvement has been demonstrated to be prognostic in some studies [26,29,30], other data have suggested that TNLE and LNM may not be as prognostically important among patients with pNET that have other favorable features such as ≤2 cm, Ki-67 < 3% [31]. To this point, Mao et al [32] reported that lymphadenectomy had no additional therapeutic benefit among patients undergoing resection for pNETs of the pancreatic body or tail.…”

Indications and outcomes of enucleation versus formal pancreatectomy for pancreatic neuroendocrine tumors

“…EN does not, however, involve resection of the tumor with a wide resection margin and lymphadenectomy is generally not performed at the time of EN, which could potentially compromise oncological outcomes. 12,13 To date, no clear recommendations exist around the indications regarding EN for pNETs. In addition, the majority of available studies report data from single center experiences or describe patients with a pNET as part of a larger study population, and, thus, the safety and efficacy of EN have not been thoroughly examined.…”