131I-MIBG negative progressive symptomatic metastatic paraganglioma: response and outcome with 177Lu-DOTATATE peptide receptor radionuclide therapy

Abstract

Objective: The primary aim of this study was to evaluate the long-term outcome of ¹⁷⁷Lu-DOTATATE PRRT in terms of clinical, biochemical and imaging response rates, disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) in ¹³¹I-metaiodobenzylguanidine (MIBG) negative progressive/symptomatic locally advanced or metastatic paragangliomas (PGL). The secondary aims of this study were to determine clinical toxicity of ¹⁷⁷Lu-DOTATATE and association of PFS with various variables.

Materials and methods: ¹³¹I-MIBG negative PGL with progressive/symptomatic locally advanced or metastatic disease that underwent ¹⁷⁷Lu-DOTATATE PRRT from 2012 to 2019 in our institute were evaluated. Standard dose activity of 5.55-7.4 GBq per cycle of ¹⁷⁷Lu-DOTATATE was administered in somatostatin receptor (SSTR) positive PGL. Post-PRRT response was evaluated under three broad categories: (a) symptomatic, (b) biochemical, and (c) imaging (molecular and anatomic imaging). The PFS and OS since first ¹⁷⁷Lu-DOTATATE cycle were determined. Associations of PFS with various variables were also investigated. The clinical toxicities of ¹⁷⁷Lu-DOTATATE in PGL were determined.

Results: Amongst a total of 9 PGL patients, response to ¹⁷⁷Lu-DOTATATE was seen in six patients, two patients, four patients and three patients on symptomatic, biochemical, molecular and anatomical based imaging response evaluation categories respectively with DCR of 67%. The median PFS and OS were not reached at a median follow-up of 40 months. Estimated PFS rate of 63% (95% CI 30-96%) and OS rate of 65% (95% CI 32-97%) were noticed at 40 months. Significant association of PFS was found for site of PGL (non-HNPGL), total cumulative dose of PRRT (> 22.2 GBq), and number of PRRT cycles patient received (≥ 4cycles). ¹⁷⁷Lu-DOTATATE was well tolerated without acute catecholamine crisis, nephrotoxicity or bone marrow suppression of any grade or high-grade (grade ≥ 2) hematological toxicities.

Conclusion: Our study showed favorable results with minimal low-grade and easily manageable side effects of ¹⁷⁷Lu-DOTATATE in patients of PGL. Thus, ¹⁷⁷Lu-DOTATATE may be considered as promising therapeutic option in ¹³¹I-MIBG negative and SSTR positive subset of PGL cases. However, further prospective study in a large number of patients is required for validation of our study results.

Keywords: 131I-MIBG therapy; 177Lu-DOTATATE; Neuroendocrine tumors (NETs); Paraganglioma (PGL); Peptide receptor radionuclide therapy (PRRT).