Response to Peptide Receptor Radionuclide Therapy in Pheocromocytomas and Paragangliomas: A Systematic Review and Meta-Analysis

Abstract

Introduction. Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE and 90Y-DOTATOC showed efficacy in the metastatic setting of pheocromocytomas (PCCs) and paragangliomas (PGLs) where no standard therapies have been established. Background. A search of peer-reviewed and English articles reporting on 177Lu-DOTATATE and 90Y-DOTATOC efficacy was performed through Medline and Scopus. A subsequent meta-analysis was performed to evaluate the pooled effect size on disease control rate (DCR) with PRRT. Secondary endpoints were description of patients’ genetic characteristics, hematologic toxicity, and time-to-outcome. The pooled effect was estimated with both a mixed-effects model and a random-effects model. Results. Twelve studies met the criteria for this meta-analysis: ten with 177Lu- and two with 90Y-PRRTs (213 patients). The largest one included 46 patients. Median ages ranged from 32.5 to 60.4 years. When reported, mutations of SDHB were the most frequent genetic alterations. The pooled DCRs were 0.83 (95% CI: 0.75–0.88) and 0.76 (95% CI: 0.56–0.89) for 177Lu- and 90Y-PRRT, respectively. The pooled DCR for PRRT was 0.81 (95% CI: 0.74–0.87). Conclusions. We report an updated and solid estimate of DCR achieved with 177Lu- and 90Y-PRRT in PCCs and PGLs, showing that these therapies can be considered in the multidisciplinary treatment of PCCs and PGLs as alternatives to I-131 MIBG and chemotherapy.

Succinate dehydrogenase mutations in head and neck paragangliomas: A systematic review and meta‐analysis of individual patients' data

“…83,84 Another treatment modality that has gained significance is peptide receptor radionuclide therapy (PRRT), which has been suggested to be effective in a multimodal treatment approach to metastatic pheochromocytomas and paragangliomas, where other treatment options have failed. 85 Similarly, tyrosine kinase inhibitors (TKIs) have also been shown to treat metastatic or locally unresectable paragangliomas and pheochromocytomas. 86 Given this evolving treatment paradigm and the prevalence of genetic mutations among patients with HNPs, understanding how mutations influence the clinical behavior and natural history of HNPs may lead to the development of a more standardized and individualized treatment approach to mutation-related HNPs.…”

“…The decision to treat with surgical resection, radiotherapy, or observation depends on the observed clinical behavior of the paraganglioma in question: surgery may be the first choice for large, symptomatic, or functioning tumors; radiotherapy can be utilized in cases of smaller, multiple tumors, or when surgical resection is not feasible; observation is suitable for indolent, slow‐growing tumors 83,84 . Another treatment modality that has gained significance is peptide receptor radionuclide therapy (PRRT), which has been suggested to be effective in a multimodal treatment approach to metastatic pheochromocytomas and paragangliomas, where other treatment options have failed 85 . Similarly, tyrosine kinase inhibitors (TKIs) have also been shown to treat metastatic or locally unresectable paragangliomas and pheochromocytomas 86 .…”

The Management of Phaeochromocytomas and Paragangliomas in the Era of Precision Medicine: Where Are We Now? Evidence-Based Systemic Treatment Options and Future Cluster Oriented Perspectives

“…Even though evidence for its use in metastatic PPGLs with high uptake of 68Ga-labeled SSA is limited (V,B according to 2021 ESMO guidelines), several small retrospective and few prospective studies suggest a high efficacy in metastatic PPGLs, especially in SDHB-mutated tumors [ 21 , 30 , 106 , 107 , 108 , 109 , 110 , 111 ].…”

“…In a recent meta-analysis published by our group in 2023, we assessed the efficacy of PRRT treatment based on 177Lu-DOTATATE and 90Y-DOTATOC in 213 patients affected by PPGLs. The primary endpoint was the correct quantification of DCR: a pooled DCR of 83% and 76% for 177Lu-DOTATATE and 90Y-DOTATOC treatments respectively was found, with a good toxicity profile [ 109 ].…”

Improving susceptibility of neuroendocrine tumors to radionuclide therapies: personalized approaches towards complementary treatments

“…Several clinical studies suggest that PRRT is one of the most effective therapies for metastatic PPGLs, especially for those with SDHx mutations 7 , 35 . A recently published meta-analysis estimated the disease control rate in PPGLs treated with PRRT at 81% 36 . PRRT is well tolerated with limited acute and medium-term toxicity profiles and only low rates of nephrotoxicity and therapy-related myeloid neoplasms.…”