Neoadjuvant Treatment of Nonfunctioning Pancreatic Neuroendocrine Tumors with [¹⁷⁷Lu-DOTA⁰,Tyr³]Octreotate

Abstract

Pancreatic neuroendocrine tumors (NETs) are rare neoplasms for which surgery has almost the only potential for cure. When surgery is not possible because of tumor size and vascular involvement, neoadjuvant treatment with [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate ( 177 Luoctreotate) may be an option. Methods: We studied 29 Dutch patients with a pathology-proven nonfunctioning pancreatic NET treated with 177 Lu-octreotate. All patients had a borderline or unresectable pancreatic tumor (group 1) or oligometastatic disease (defined as #3 liver metastases) (group 2). Progression-free survival (PFS) was analyzed using the Kaplan-Meier method and Cox proportional hazards modeling. Results: After the treatment with 177 Luoctreotate, successful surgery was performed in 9 of 29 patients (31%). Six patients had a Whipple procedure, 2 patients had a pylorus-preserving pancreaticoduodenectomy, and 1 patient had a distal pancreatectomy and splenectomy. The median PFS was 69 mo for patients with successful surgery and 49 mo for the other patients. For comparison, the median PFS in 90 other patients with a nonfunctioning pancreatic NET with more than 3 liver metastases or other metastases was 25 mo. Conclusion: Neoadjuvant treatment with 177 Lu-octreotate is a valuable option for patients with initially unresectable pancreatic NETs.

Successful neoadjuvant peptide receptor radionuclide therapy for an inoperable pancreatic neuroendocrine tumour

“…These include biological agents (sunitinib or everolimus), systemic chemotherapy, arterial embolization, chemoembolization, radiofrequency ablative therapy, cytoreductive surgery and PPRT. Recently, a retrospective positive experience has been reported on neoadjuvant PPRT-induced tumour down-staging (successful surgical R0/R1 surgery in 31% of cases without major adverse effects) (5). On the other hand, a sequential approach of surgery followed by PPRT has been proposed as having a radiobiological rationale (surgical debulking would reduce the tumour burden allowing higher radiation concentrations to smaller lesions).…”

“…3C). These histological results have only been documented in a few cases of successful PPRT-induced tumour regression (5). Although symptomatic relive occurred shortly after 177 Lu-octreotate PRRT, progressive tumour regression, due to radiation damage, was observed 6 months after the last treatment cycle compared to the 2-month evaluation.…”

“…Neoadjuvant treatments for advanced NET patients are considered experimental, but in a few selected cases, they have been shown to be successful for stabilizing the disease or even allowing down-staging of both the primary tumour and its metastasis (3). Although PPRT is considered a second- or third-line therapy for progressive somatostatin receptor (SSTR)-positive pancreatic NETs (1), it has been recently shown to be an effective and safe neoadjuvant treatment option in a few case reports and small case series of advanced inoperable pancreatic NET patients (4, 5). …”

ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Neoplasms: Peptide Receptor Radionuclide Therapy with Radiolabelled Somatostatin Analogues

“…Nevertheless, retrospective analyses of outcome in pancreatic NET suggest similarly impressive survival [35,37]. The neoadjuvant use of PRRT in patients with unresectable or borderline resectable primary pancreatic tumours has also been suggested [38,39]. …”

Unmet Needs in Functional and Nonfunctional Pancreatic Neuroendocrine Neoplasms

“…The recent approval of PRRT and its increasing availability may be particularly useful for this approach. In a recent study [88] involving patients with advanced PanNENs, PRRT with 177 Lu-octreotate resulted in 9 patients downsized to the extent that successful surgery could be performed. In a future study of such patients the various pathologic, radiologic, liquid tumor markers, and demographic features that have been reported in numerous studies to have prognostic significant in PanNENs could be incorporated (Table 2).…”