Endoscopic Ultrasound-Guided Radiofrequency Ablation: A new Therapeutic Approach for Pancreatic Neuroendocrine Tumors

Kira Oleinikov; Alain Dancour; Julia Epshtein; Ariel Benson; Haggi Mazeh; Ilanit Tal; Shay Matalon; Carlos A. Benbassat; Dan M. Livovsky; Eran Goldin; David J. Gross; Harold Jacob; Simona Grozinsky-Glasberg

Disclosures

J Clin Endocrinol Metab. 2019;104(7):2637-2647. 

In This Article

Abstract and Introduction

Abstract

Context: Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is rapidly emerging as feasible therapy for patients with pancreatic neuroendocrine tumors (pNETs) in selected cases, as a result of its favorable safety profile.

Objective: To assess the feasibility, safety, and efficacy of EUS-RFA in a cohort of patients with functional and nonfunctional pNETs (NF-pNETs).

Design: Data on pNET patients treated with EUS-RFA between March 2017 and October 2018 at two tertiary centers was retrospectively analyzed.

Results: The cohort included 18 adults (eight women, 10 men), aged 60.4 ± 14.4 years (mean ± SD), seven insulinoma patients, and 11 patients with NF-pNETs. Twenty-seven lesions with a mean diameter of 14.3 ± 7.3 mm (range 4.5 to 30) were treated. Technical success defined as typical postablative changes on a surveillance imaging was achieved in 26 out of 27 lesions. Clinical response with normalization of glucose levels was observed in all (seven of seven) insulinoma cases within 24 hours of treatment. Overall, there were no major complications 48 hours postprocedure. No clinically significant recurrences were observed during mean follow-up of 8.7 ± 4.6 months (range 2 to 21 months).

Conclusions: EUS-guided RFA of pNETs is a minimally invasive, safe, and technically feasible procedure for selected patients.

Introduction

Pancreatic neuroendocrine neoplasms (pNENs) represent a group of wide-ranging biological variability tumors that comprise <3% of all primary pancreatic malignancies.[1,2] With the application of the World Health Organization 2017 classification, two groups of pNENs are morphologically distinguished: well-differentiated tumors, so-called pancreatic neuroendocrine tumors (pNETs), and poorly differentiated neoplasms, so-called small or large cell pancreatic neuroendocrine carcinomas. The importance of the distinction of pNETs from pancreatic neuroendocrine carcinomas was further emphasized by the introduction of a new tier of Grade 3 (G3) pNETs, based on the new insights of pNEN genetics and clinical observation of different responses to therapy.[3]

Although pNETs represent a relatively rare entity, their diagnosis has increased four- to sixfold over the last decades as a result of the availability of cross-sectional imaging.[4,5] Two trends became apparent in the course of the pNET growing incidence: a higher frequency of incidental findings and a smaller size of the detected lesion at diagnosis.[6–11] This tendency narrows the gap between annual clinical detection rate (0.8:100,000) and autopsy series prevalence (0.5% to 1.5%), thereby altering a standpoint regarding mortality rates in patients with asymptomatic neoplasms and consequently, an adequate treatment approach.[5,12–15]

The optimal management of pNETs involves a multimodal approach, reflective of their heterogeneity, namely, tumor size, grade, stage, functional status, rate of progression, association with genetic syndromes, etc..[16,17] In addition, patients' performance status and comorbidities have a profound impact on the therapeutic choice. These approaches are still evolving in pursuit of maximization of disease control and patient survival with the maintenance of quality of life.

With the assumption that all pNETs may be potentially malignant, surgical excision of localized disease appears, in principle, to be the only curative option.[17] In practice, as >70% of the tumors are nonfunctioning and up to 50% are incidentally discovered as asymptomatic lesions, the question may be raised whether morbidity and mortality rates of the surgical approach are justifiable in all cases. Therefore, for small (<1.5 to 2 cm), well-differentiated, asymptomatic, and nonfunctioning pNETs (NF-pNETs), the option of active surveillance was proposed, although it still entails the possibility of metastatic disease development.[17–22] For a sizable group of patients in whom the cytoreductive approach is indicated, as a result of either worrisome tumor features or functional status, but who are not considered as candidates for surgery, as a result of high perioperative risk or personal preferences, an alternative therapeutic approach is essential.

Thus, in recent years, there has been a growing interest in endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA), a technique that induces tumor mass thermal necrosis as a potentially curative technique that seems to carry a low periprocedural complications risk. However, data regarding the effectiveness and safety of EUS-RFA in patients with pNETs are scarce. In the current study, we retrospectively analyzed the initial experience in regard to procedural feasibility, safety, as well as clinical outcome of EUS-RFA treatment in a group of both functional (insulinomas) and NF-pNET patients. We have also reviewed the literature to compare our experience with the limited series previously reported.

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