Peptide Receptor Radionuclide Therapy in Advanced Refractory Meningiomas: Efficacy and Toxicity in a Long Follow-up

Abstract

Recurrence of meningiomas after surgery and radiotherapy deserves specific attention because of the lack of active third-line therapies. Somatostatin receptors are usually overexpressed on the cell membrane of meningiomas, and this has led the way to a radionuclide theranostic approach. Diagnoses with ⁶⁸Ga-DOTA-octreotide and peptide receptor radionuclide therapy (PRRT) with ⁹⁰Y/¹⁷⁷Lu-DOTA-octreotide are currently possible options within experimental protocols or as compassionate use in small patient groups. Methods: From October 2009 to October 2021, 42 meningioma patients with radiologic recurrence after standard therapies were treated with ⁹⁰Y-DOTATOC (dosage of 1.1 or 5.5 GBq) or with ¹⁷⁷Lu-DOTATATE (dosage of 3.7 or 5.5 GBq) in a mean of 4 cycles. All patients showed intense uptake at diagnostic ⁶⁸Ga-DOTATOC PET/CT or in an ¹¹¹In-octreotide scan. Results: Of 42 patients treated, 5 patients received ⁹⁰Y-DOTATOC with a cumulative activity of 11.1 GBq and 37 patients received ¹⁷⁷Lu-DOTATATE with a cumulative activity of 22 GBq. The disease control rate was 57%. With a median follow-up of 63 mo, median progression-free survival was 16 mo, and median overall survival was 36 mo. Retreatment ¹⁷⁷Lu-PRRT was performed in 6 patients with an administered median activity of 13 GBq in a mean of 5 cycles. With a 75.8-mo follow-up, median progression-free survival and overall survival were 6.5 and 17 mo, respectively. Only 1 patient discontinued the treatment because of grade 3 platelet toxicity. A rapidly transient grade 2 neutropenia was recorded in 1 retreated patient. Conclusion: PRRT in patients with advanced meningiomas overexpressing somatostatin receptor 2 was active and well tolerated, showing a 57% disease control rate. Furthermore, PRRT could represent a potential retreatment option. Further studies, also in combination with other treatments, are warranted.

Keywords: 177Lu; meningiomas; oncology; peptide receptor radionuclide therapy.

Graphical abstract

FIGURE 1.

Flow diagram of patients selection and treatment. R/R = recurrent or refractory.

FIGURE 2.

(A) ⁶⁸Ga-DOTATOC PET/CT–positive image of symptomatic patient who underwent 2 resections in 1990 and in 1992. (B) MRI from 2018 of same patient with recurrent and progressive meningioma, who also received radiotherapy (50 Gy/25 fractions) with neither disease nor symptom improvement. After multidisciplinary discussion, decision was made to include patient in our ¹⁷⁷Lu protocol, and after 5 cycles of ¹⁷⁷Lu-DOTATATE PRRT, patient obtained partial response with clinical improvement. ⁶⁸Ga-DOTATOC PET/CT performed in 2022 (C) showed persistent positivity and partial response that was confirmed at last MRI on June 3, 2023 (D).

FIGURE 3.

Kaplan–Meier curve of PFS (left) and OS (right) of cohort.