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 ( 90 Y) and Lutetium-177 ( 177 Lu) peptides in pheochromocytomas (PCCs) and paragangliomas (PGLs). Methods We retrospectively analyzed more than 1500 patients with histologically proven neuroendocrine tumors treated with 177 Lu- or 90 Y-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 90 Y, sixteen (53%) with 177 Lu and ten (33%) with 90 Y + 177 Lu respectively. The median total cumulative activity from treatment with 90 Y- alone was 9.45 GBq (range 5.11–14.02 GBq), from 177 Lu- alone was 21.9 GBq (7.55–32.12 GBq) and from the combination treatment was 4.94 GBq from 90 Y- and 6.83 GBq from 177 Lu- (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 177 Lu- or 90 Y-DOTA-TATE or –TOC is feasible and well tolerated in advanced PGLs and PCCs.