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.

Keywords: meningioma; peptide receptor radionuclide therapy; somatostatin receptor; treatment-refractory meningioma.

Figure 1

Maximum intensity projection (MIP) of 68Ga-DOTATOC before treatment of each patient. (1–8) correspond to patients treated in accordance with the rest of the article.The red arrows in patient 1 show intense uptake in all intra-cranial multifocal meningiomas and mediastinal lymph node metastases, greater than the uptake in the liver (green arrow). The remaining patients (patients 2–8) have multifocal intracranial meninigiomas also showing higher or equal uptake of Ga-DOTATOC in tumor tissue than in healthy liver tissue.

Figure 2

Contrast-enhanced T1-weighted axial MRI after the second cycle of PRRT (a) and after the fourth cycle of PRRT (c) was merged with 68GA-DOTATOC PET (respectively, panels (b) and (d)). Two frontal lesions (white arrows) with high 68GA-DOTATOC uptake necrotized after 4 cycles (red arrows). The question remains as to the origin of this necrosis, which may be a direct effect of PRRT or a natural necrotic tumor progression. Patient 2 was the only patient to progress with this necrotic appearance. Unequivocal progression of the other lesions was assessed according to RANO criteria on the MRI performed 4 months later.

Figure 3

T2-weighted axial slice MRI. MRI before therapy (panels (a) and (b)) and after the second cycle of PRRT (panels (c) and (d)). White arrows show brain edema on baseline MRI which increases after the second cycle (red arrows). An increase in kinetic movements at the time of the second MRI (panels (c) and (d)) were due to the patient’s clinical deterioration in parallel with the radiological progression.