Value of Peptide Receptor Radionuclide Therapy as Neoadjuvant Treatment in the Management of Primary Inoperable Neuroendocrine Tumors

Abstract

IntroductionNeuroendocrine neoplasms including neuroendocrine tumors (NETs) are often diagnosed as primary disseminated or inoperable. In those cases, systemic extensive therapy is necessary, but radical treatment is unlikely. As described in the literature, in some selected cases, peptide receptor radionuclide therapy (PRRT) may be used as a first-line/neoadjuvant therapy that allows further successful surgery. Such treatment may enable a reduction of total tumor burden or allow a radical treatment which improves the final outcomes.AimThis study aims to assess whether neoadjuvant PRRT could be a treatment option for patients with initially unresectable NETs.MethodsAmong the group of 114 patients treated with PRRT between the years 2005 and 2020, in 32 cases, it was the first-line therapy, mainly due to massive disease burden at the time of diagnosis. Among them, nine patients received PRRT as the first-line treatment due to the primary inoperable tumors with the intention of preoperative reduction of the tumor size in order to allow for a surgical treatment.ResultsNeoadjuvant PRRT enabled surgery in four out of nine (45%) patients. Finally, in two out of four cases, the goal (radical surgery) has been achieved.ConclusionPRRT may be considered not only as a palliative but also as a neoadjuvant therapy in advanced, somatostatin-positive NETs that were initially inoperable.

Radioligand therapy (RLT) as neoadjuvant treatment for inoperable pancreatic neuroendocrine tumors: a literature review

“…In this subset of patients RLT might allow subsequent locoregional hepatic therapies with a potential curative outcome and a consequent increase in PFS, OS and time to recurrence [26,33]. This recommendation is supported by the positive results obtained with neoadjuvant RLT in reducing liver disease burden, as previously reported [26][27][28]34]. Moreover, RLT-induced biological modifications can cause liver metastases necrotic involution, avoiding the need of a subsequent therapeutic approach [31].…”

“…Overall 148 patients with locally advanced PanNETs undergoing neoadjuvant RLT are described in literature. Seventytwo became eligible for surgery [16,[21][22][23][24][25][26][27][28][29]. Of note, we found 2 cases of extremely large primary tumors who became eligible for surgery following a significant tumor shrinkage and reduction in vascular involvement [24,25].…”

“…Among available studies, only one reported that a single patient was withdraw from neoadjuvant RLT before completing the treatment, due to severe hematologic toxicity [16]. Mild and transient hematologic toxicity was reported in other studies [21,23,24,27,29], in line with the most updated clinical and dosimetric evidence [37][38][39]. The available results derive from studies with heterogeneous neoadjuvant RLT schemes.…”

“…The available results derive from studies with heterogeneous neoadjuvant RLT schemes. Indeed, different isotopes have been employed: 90 Y in 3 studies [21,25,34], 177 Lu in 6 [22-24, 26, 28, 29] and both radioisotopes in 2 [16,27], always as mono-therapy. It should be noted that, overall, most of the patients (141/148) were treated with [ 177 Lu]-labeled radiopeptides.…”

Predictive Factors for Resistant Disease with Medical/Radiologic/Liver-Directed Anti-Tumor Treatments in Patients with Advanced Pancreatic Neuroendocrine Neoplasms: Recent Advances and Controversies

“…In this regard, treatments with both high cytoreductive effect and low rate of disease progression are needed for neoadjuvant therapy to reduce tumor size (i.e., downstaging), as well as for adjuvant therapy to prevent disease recurrence in a high-risk group [ 7 ]. Recently, PRRT is receiving increasing attention as a possible neoadjuvant therapy in panNENs with its high rate of radiological response [ 181 , 368 , 369 , 370 , 371 ], while evidence to support its applicability in the real clinical practice still needs to be validated prospectively.…”