Finding the Appropriate Therapeutic Strategy in Patients with Neuroendocrine Tumors of the Pancreas: Guideline Recommendations Meet the Clinical Reality

Abstract

The systemic treatment of patients with pancreatic neuroendocrine tumors is based on placebo-controlled trials and long-established chemotherapy approaches. In addition, peptide receptor radionuclide therapy (PRRT) was approved as a parallel approach for pancreatic neuroendocrine tumors (NET), in addition to small bowel NET, after the NETTER-1 trial. The current ESMO and NCCN guidelines attempted to describe treatment algorithms for pancreatic NET based on the current data. In our survey, we recorded therapy decisions for the first- until the third-line of therapy in German-speaking countries (Germany, Austria, and Switzerland) using fictional case reports and discussed these in the context of the current ESMO guidelines. Compared with the recommendations of the guidelines, PRRT was used more frequently and earlier. In patients with NET G1/G2 Ki-67 < 10%, the therapy algorithm consisting of somatostatin analogs (SSA)-PRRT-targeted therapy is a relevant approach. In clinical situations where chemotherapy is primarily used (remission pressure, Ki-67 > 10%), second-line PRRT was found acceptance and was often considered prior to targeted therapies. Despite the lack of prospective controlled trials, our study demonstrated the pivotal impact of PRRT. Therefore, further studies should compare PRRT with chemotherapy in pancreatic NETs in different clinical settings in first- and second-line approaches.

Role of Somatostatin Signalling in Neuroendocrine Tumours

“…After six cycles of STZ/5-FU (over nine months), the patient progressed four months later without treatment. The majority of participants preferred PRRT (38.6%, n = 32) over STZ/5-FU reinduction (26.5%, n = 22) [136]. In patients with GEP-NET G1 and G2, 177Lu-PRRT was compared to the mTOR inhibitor everolimus.…”

Orchestrating Treatment Modalities in Metastatic Pancreatic Neuroendocrine Tumors—Need for a Conductor

“…Some patients may not qualify for or may not be willing to undergo any kind of surgery. In this situation, control of liver metastasis by PRRT or SIRT should be considered an option in addition to or within a sequential approach to the installed systemic treatment [75]. In contrast to SIRT, the SSTR-2 density of the tumor cells is essential for performing a PRRT in advanced pNETs.…”

Hemorrhagic Colitis Caused by Everolimus in a Patient with Nonfunctional Pancreatic Neuroendocrine Neoplasms: A Case Report

“…A fine-needle aspiration biopsy was performed under endoscopic ultrasound and revealed a pancreatic neuroendocrine tumor upon histologic examination (equivalent to G2). We decided that surgical resection was contraindicated for this patient, and she was treated with the molecular-targeted drug everolimus [ 2 , 3 ]. Because the patient was diagnosed with hypertension on admission, she was also started on amlodipine besylate (5 mg/day).…”