A Clinical Efficacy of PRRT in Patients with Advanced, Nonresectable, Paraganglioma-Pheochromocytoma, Related to SDHx Gene Mutation

Abstract

Paragangliomas and pheochromytomas (PPGLs) exhibit variable malignancy, advanced/hormonally active/progressive need therapy. PRRT (Peptide Receptor Radionuclide Therapy) could be an option for these patients. To evaluate the effectiveness of PRRT (90Y DOTATATE), based on overall survival (OS) and progression-free survival (PFS), in patients with PPGLs, related to SDHx gene mutation, we conducted a prospective open-label, single-center, phase II study. Thirteen patients were observed, eight PGL1 and five PGL4, all with advanced, non-resectable tumors, and eight had metastases. All were treated with 90Y DOTATATE. Efficacy was based on OS and PFS, and radiological response was based on RECIST. Hormonal activity was evaluated using serum-fractionated free catecholamines. Eight subjects had a clinical response, three were stable, and two exhibited disease progression. Among four patients with hormonally-active PPGLs, three showed a reduction and one showed normalization. OS for all was 68.0 months; PFS was 35.0 months. OS in PGL4 = 25.0 vs. N.R. (not reached) in PGL1. PFS in PGL4 = 12.0 vs. N.R. in PGL1. A difference was seen in the OS and PFS in patients who did not respond clinically, compared to those who did, OS = 22.0 vs. N.R. PFS = 7.0 vs. N.R. A difference in the OS and PFS was noted in patients with liver and bone involvement compared to those without. PRRT is an effective therapy in selected population of patients with SDHx, in those with locally-advanced, non-resectable tumors. Furthermore, it is effective regardless of the secretory status.

Peptide receptor radionuclide therapy in patients with metastatic progressive pheochromocytoma and paraganglioma: long-term toxicity, efficacy and prognostic biomarker data of phase II clinical trials

“…A diagnostic approach with 68Ga Dota-peptide PET/CT 10 and the therapeutic use of 90Y-DOTATOC and 177Lu-DOTATATE 11 , 12 , 13 in GEP-NETs has paved the way for their use in other NET histologies, including paragangliomas. 14 , 15 , 16 …”

Prevention and Management of Hormonal Crisis during Theragnosis with LU-DOTA-TATE in Neuroendocrine Tumors. A Systematic Review and Approach Proposal

“…Other centers have reported, 24 h following 177-LUDOTATE infusion, severe tumoral lysis syndrome which led to severe hypertension, shortness of breath, tachycardia, hyperkalemia, hyperphosphatemia and hypocalcemia with necessary admission to ICU [ 22 ]. Other patients developed severe hypotension or severe tachycardia during treatment infusion [ 16 , 17 , 21 , 22 , 25 , 26 , 41 ].…”

“…The scientific community appears to be sensitized to the fact that pharmacological treatment of pheochromocytoma and functional paraganglioma before surgery is of vital importance in these patients. However, several authors agree that metastatic functional paraganglioma and pheochromocytoma, which are candidates for PRRT, need to be pretreated and certain protocols should be assessed during treatment infusion in order to avoid the hormonal crisis previously described [ 16 , 17 , 21 , 25 , 41 , 42 ].…”

Somatostatin Receptors and Analogs in Pheochromocytoma and Paraganglioma: Old Players in a New Precision Medicine World

“…In a prospective study from 2019 by Kolasinska-Cwikla et al, 13 patients with metastatic SDHB and SDHD (n=5 and 8, respectively) were treated with 90 Y-DOTATATE, with an 82% response of stable disease after 1 year. The median OS and PFS were 68 months and 35 months, respectively, with no difference in the endpoints in patients who were either secretory or nonsecretory (94). A retrospective study assessing 90 Y-DOTATATE and 131 I-MIBG concluded that mPGLs were best suited for treatment by SSA-based PRRT.…”