Treatment options of metastatic and nonmetastatic VIPoma: a review

Abstract

Purpose VIPoma belongs to the group of neuroendocrine neoplasms. These tumours are located mostly in the pancreas and produce high levels of vasoactive intestinal peptide (VIP). In most cases, a metastatic state has already been reached at the initial diagnosis, with high levels of VIP leading to a wide spectrum of presenting symptoms. These symptoms include intense diarrhoea and subsequent hypopotassaemia but also cardiac complications, with life-threatening consequences. Treatment options include symptomatic therapy, systemic chemotherapy and targeted therapy, as well as radiation and surgery. Due to the low incidence of VIPoma, there are no prospective studies or evidence-based therapeutic standards to date. Methods To evaluate the possible impact of different therapy strategies, we performed literature research using PubMed. Results All possible treatment modalities for VIPoma have at least one of two therapy goals: antisecretory effects (symptom control) and antitumoural effects (tumour burden reduction). Symptomatic therapy is the most important in the emergency setting to rehydrate, balance electrolytes and stabilise the patient. Symptomatic therapy is also of great importance perioperatively. Somatostatin analogues play a major role in symptom control, although their efficiency is often limited. Chemotherapy may be effective in reaching stable disease for a certain time period, although its impact on symptom control is limited and often delayed. Among targeted therapy options, the usage of sunitinib appears to be the most effective in terms of symptom control and showing antitumoural effects at the same time. Experience with radiation is still limited; however, local ablative procedures seem to be promising options. Peptide receptor radiotherapy (PRRT) with radiolabelled somatostatin analogues (SSAs, 177Lu-DOTATATE) offers a targeted approach, especially in patients with high somatostatin receptor density. Surgery is the first-line therapy for nonmetastatic VIPoma. Additionally, if the resection of all visible tumour lesions is possible, the surgical approach seems preferable to other strategies in highly symptomatic patients. The role of surgery in very advanced stages where only tumour debulking is possible remains debatable. However, a high rate of immediate symptom control can be achieved by tumour debulking followed by somatostatin therapy, although the impact on survival remains unclear. Conclusion Surgery is the only curative option for nonmetastatic VIPoma. Additionally, surgery should be a first-line therapy option for highly symptomatic patients, especially if the resection of all tumour lesions (primary tumour and metastasis) is achievable. In frail patients, other modalities can be used.

A case of vasoactive intestinal peptide-secreting tumor (VIPoma) arising from <i>MEN1</i> inactivation which recurred 15 years after the initial resection

“…Here, we report the case of a female patient with VIPoma that recurred after a long-term diseasefree period following initial surgery. In general, most VIPomas are metastatic at diagnosis [3]; however, this case, fortunately, did not demonstrate metastasis either at the primary onset or at the time of recurrence, allowing curative surgeries. Nearly all recurrences in patients with p-NEN were detected within 10 years after surgery [5,6].…”

“…pancreatic VIPomas [3]. Recent whole-exome analysis of p-NENs has shown that a few somatic alterations are commonly identified in genes implicated in four main pathways in sporadic p-NEN cases: chromatin remodeling, DNA damage repair, telomere maintenance, and activation of mTOR signaling [12][13][14].…”

“…VIPoma is extremely rare, with an estimated incidence of less than 1 in 10 million individuals per year in the general population [2]. Most VIPomas are sporadic, whereas 5% are associated with multiple endocrine neoplasia type 1 (MEN1) syndrome [3]. Excessive VIP secretion causes clinical symptoms characterized by refractory watery diarrhea, often associated with electrolyte imbalance, such as hypokalemia and achlorhydria, known as WDHA syndrome.…”

“…Excessive VIP secretion causes clinical symptoms characterized by refractory watery diarrhea, often associated with electrolyte imbalance, such as hypokalemia and achlorhydria, known as WDHA syndrome. Sixty to eighty percent VIPomas are metastatic at diagnosis, with the liver being the most frequent site of metastasis [3]. VIPomas often exhibit slow growth despite malignant behavior, and their prognosis depends on pathological characteristics, tumor development, metastatic spread, and surgical resectability [4].…”

Longterm outcome of rare functioning pancreatic neuroendocrine neoplasms

“…The diagnosis of rf-pNEN cannot be based solely on positive immunohistochemical results of resected specimens [2,5]. As of 2022, approximately 600 glucagonomas [7,8,9,10], 100 Vipomas [11,12,13] and 60 calcitonin-producing pNEN [14,15] have been reported in case reports or small case series, whereas reports on other rf-pNENs do not exceed 10-25 cases per subtype [1,16,17,18,19,20].…”