Introduction 177 Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) represents a possible therapeutic option for patients with metastatic inoperable phaeochromocytomas (PCC) and paragangliomas (PGL) who demonstrate adequate somatostatin analogue binding on molecular imaging. We describe treatment outcomes in our cohort of patients stratified according to germline pathogenic variants (PV) in Succinate Dehydrogenase ( SDHx ) subunit-encoding genes. Methods In this retrospective analysis, we evaluated 20 patients with metastatic PCC/PGL who underwent two or more cycles of 177 Lu-DOTATATE therapy. Clinical, radiological, and biochemical responses were assessed 8-12 weeks after the final PRRT cycle. We describe overall treatment efficacy at follow-up after stratifying according to the presence of germline SDHx PV. Radiological progression was quantified based on the sum of the longest diameter (SLD) of the target lesion. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier survival analysis. We also aimed to investigate the impact of PRRT on health-related quality of life (HRQoL), as assessed using the EORTC QLQ-GINET21 questionnaire. Results After a median follow-up of 29 months, we confirmed stable disease in 12 patients (60%), a partial response in one (5%), and progressive disease in 7 patients (35%). The absolute mean difference in SLD was +5±12 mm for bone lesions, -4±6 mm for peritoneal, +8±14mm for liver lesions and -1± 5 mm for lymph nodes (paired t-test p-value 0.273, 0.741, 0.208 and 0.826, respectively). Thirteen patients (65%) had received two or more previous lines of treatment. The overall median PFS for the entire cohort, PGL patients, SDHx positive and negative groups, was 24 months (95% CI, 9.9-38.1), 18 months (95% CI, 8.4-27.6), 24 months (95% CI, 11.9-36.0) and 18 months (95% CI, 0-48) respectively. No grade 3/4 cytopenia or nephrotoxicity was observed. Overall, HRQoL improved after PRRT, as evidenced by the progressive decline in overall symptom scores in the QLQ-GINET21. Conclusion 177 Lu-PRRT appears to be an effective therapy with a good safety profile for patients with metastatic PPGL. It also appears to improve HRQoL in patients with metastatic PPGL. Further studies are needed to explore the most effective treatment modalities in this group of patients and their sequencing.
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