Peptide receptor radionuclide therapy with 177Lu- or 90Y-SSTR peptides in malignant pheochromocytomas (PCCs) and paragangliomas (PGLs): results from a single institutional retrospective analysis

Background: Malignant pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare tumors and available systemic therapies are limited.

Aim: To explore the role of peptide receptor radionuclide therapy (PRRT) with Yttrium-90 (⁹⁰Y) and Lutetium-177 (¹⁷⁷Lu) peptides in pheochromocytomas (PCCs) and paragangliomas (PGLs).

Methods: We retrospectively analyzed more than 1500 patients with histologically proven neuroendocrine tumors treated with ¹⁷⁷Lu- or ⁹⁰Y-DOTA-TATE or -TOC between 1999 to 2017 at our Institute. Overall, 30 patients with confirmed malignant PCCs and PGLs matched inclusion/exclusion criteria and were considered eligible for this analysis.

Results: Thirty (n = 30) patients were treated: 22 with PGLs and 8 with PCCs (12 M and 18 F, median age 47 [IQR: 35-60 years]). Eighteen patients (n = 18) had head and neck PGLs, 3 patients thoracic PGLs and 1 patient abdominal PGL. Sixteen patients (53%) had locally advanced and fourteen (47%) had metastatic disease. Twenty-seven (90%) patients had disease progression at baseline. Four (13%) patients were treated with ⁹⁰Y, sixteen (53%) with ¹⁷⁷Lu and ten (33%) with ⁹⁰Y + ¹⁷⁷Lu respectively. The median total cumulative activity from treatment with ⁹⁰Y- alone was 9.45 GBq (range 5.11-14.02 GBq), from ¹⁷⁷Lu- alone was 21.9 GBq (7.55-32.12 GBq) and from the combination treatment was 4.94 GBq from ⁹⁰Y- and 6.83 GBq from ¹⁷⁷Lu- (ranges 1.04-10.1 and 2.66-20.13 GBq, respectively). Seven out of 30 (23%) patients had partial response and 19 (63%) stable disease. Median follow up was 8.9 years (IQR: 2.9-12). The 5-y and 10-y PFS was 68% (95% CI: 48-82) and 53% (95% CI: 33-69), respectively, whereas 5-y and 10-y OS was 75% (95% CI: 54-87) and 59% (95% CI: 38-75), respectively. Grade 3 or 4 acute hematological toxicity occurred in three patients, two with leucopenia and one with thrombocytopenia, respectively.

Conclusion: PRRT with ¹⁷⁷Lu- or ⁹⁰Y-DOTA-TATE or -TOC is feasible and well tolerated in advanced PGLs and PCCs.