Somatostatin Receptor Theranostics for Refractory Meningiomas

Abstract

Somatostatin receptor (SSTR)-targeted peptide receptor radionuclide therapy (PRRT) represents a promising approach for treatment-refractory meningiomas progressing after surgery and radiotherapy. The aim of this study was to provide outcomes of patients harboring refractory meningiomas treated by 177Lu-DOTATATE and an overall analysis of progression-free survival at 6 months (PFS-6) of the same relevant studies in the literature. Eight patients with recurrent and progressive WHO grade II meningiomas were treated after multimodal pretreatment with 177Lu-DOTATATE between 2019 and 2022. Primary and secondarily endpoints were progression-free survival at 6-months (PFS-6) and toxicity, respectively. PFS-6 analysis of our case series was compared with other similar relevant studies that included 86 patients treated with either 177Lu-DOTATATE or 90Y-DOTATOC. Our retrospective study showed a PFS-6 of 85.7% for WHO grade II progressive refractory meningiomas. Treatment was clinically and biologically well tolerated. The overall analysis of the previous relevant studies showed a PFS-6 of 89.7% for WHO grade I meningiomas (n = 29); 57.1% for WHO grade II (n = 21); and 0 % for WHO grade III (n = 12). For all grades (n = 86), including unknown grades, PFS-6 was 58.1%. SSTR-targeted PRRT allowed us to achieve prolonged PFS-6 in patients with WHO grade I and II progressive refractory meningiomas, except the most aggressive WHO grade II tumors. Large scale randomized trials are warranted for the better integration of PRRT in the treatment of refractory meningioma into clinical practice guidelines.

Lutathera® Orphans: State of the Art and Future Application of Radioligand Therapy with 177Lu-DOTATATE

“…In a study by Seystahl et al [70] RLT, offered mainly with [ 177 Lu]Lu-DOTATATE (85% of patients), obtained 6-month PFS rates of 100%, 57%, and 0% for grade I, II, and III refractory meningiomas, respectively. In a recent study [68] on a small group of selected patients affected by WHO grade II refractory meningiomas, 6-month PFS was 85.7% and 1-year PFS was 66.7%. The treatment was safe and well tolerated.…”

“…Unlike the NETTER-2, COMPOSE trial requires 2-deoxy-2-[ 18 F]fluoro-d-glucose ([ 18 F]FDG) PET/CT imaging as inclusion criteria, following several reports in literature highlighting its growing importance [22][23][24][25]. Indeed, a deep discordance between [ 18 F]FDG and [ 68 Ga]Ga-DOTA-SSTR imaging might limit RLT efficacy, allowing the consideration of other treatments. As a matter of fact, a recent EANM Focus 3 consensus suggests the routine employment of [ 18 F]FDG PET/CT for all G3 NET candidates for RLT, as high-proliferation tumors are most likely to show mismatched [ 18 F]FDG positive and [ 68 Ga]Ga-DOTA-SSTR negative lesions [26].…”

“…However, this theranostic model presents several drawbacks, including dosimetric issues and consequent high risk of therapy-related myelosuppression [46]. In recent years, growing evidence of the overexpression of SSTR type 2 and 3 in PPGLs determined an increased use of [ 68 Ga]Ga-DOTA-SSA PET/CT [48][49][50]. Overall, a lesion-based sensitivity of 92% was reported across a wide range of mutations, outperforming any other functional imaging investigation, in particular for SDHx mutated metastatic PPGLs and in non-metastatic head and neck PGL [49].…”

“…A few studies evaluated the efficacy of RLT in meningiomas, administrating 2-5 cycles of [ 90 Y]Y-DOTATATE/-DOTATOC or [ 177 Lu]Lu-DOTATATE/-DOTATOC [67,68]. In a metaanalysis performed by Mirian et al [69], RLT-offered as mono-therapy or in combination with other oncological treatments-allowed a comprehensive DCR of 63% in refractory meningiomas.…”

Meningiomas and Somatostatin Analogs: A Systematic Scoping Review on Current Insights and Future Perspectives

“…By using peptide receptor radionuclide therapy (PRRP) with 177Lu-DOTATATE or 90Y-DOTATOC, imaging and therapy is combined, as one radionuclide emits positrons or photons suitable for imaging, while the other emits particles for anti-tumoral effect [55]. Although there are promising preliminary reports for treatment-refractory meningiomas, the efficacy of PRRP is still much unexplored [55][56][57][58][59][60][61]. Furthermore, several issues need resolving, such as the number of cycles, intervals between the cycles and the optimal activity to be administered [55].…”