Abstract
3104
Introduction: Patients with surgery- and radiation-refractory meningiomas or not amenable to surgery or external radiotherapy may benefit from novel therapies such as hydroxyurea, interferon alpha, and somatostatin analogs. However, the outcome remains poor, with an average 6-month progression-free survival (PFS) rate of 26% for WHO grade II and III meningioma and 29% for grade I meningiomas who have failed surgery and radiotherapy. Therefore, novel and more effective treatment options are urgently needed. A high density of somatostatin receptors (SSTRs) overexpressed in meningiomas provide the basis for SSTR-targeted peptide receptor radionuclide therapy (PRRT). The objective of this study was to assess the long-term efficacy, survival, and toxicity of PRRT in patients with refractory meningioma.
Methods: A total of 17 patients (9 men; age 41-78 y, mean age 57.7 ± 8.3 y) with refractory meningioma, presenting with progression or recurrence despite surgery or radiotherapy, or having inoperable tumors and lack of other therapeutic options, received PRRT with 177Lu- or 90Y- labeled somatostatin analogs (DOTATATE or DOTATOC) between February 2006 and March 2019. Kaplan-Meier analysis was performed to calculate progression-free survival (PFS) and overall survival (OS), defined from the start of PRRT. Treatment response was evaluated according to the Response Assessment in Neuro-Oncology (RANO) criteria as well as molecular imaging criteria (European Organization for Research and Treatment of Cancer). Short- and long-term toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE), v 5.0.
Results: Six patients (35%) had WHO-I, 10 patients (59%) had WHO-II, and 1 patient (6%) had WHO-III meningioma. Primary treatment before PRRT included surgery in 14 patients (82%), stereotactic radiosurgery in 5 patients (29%) and external beam radiation therapy in 6 patients (35%). Most patients received two cycles of PRRT, and up to 4 cycles were applied. The mean total administered activity was 12.7 GBq (range, 8.5–28.5 GBq). Of 14 patients monitored after 2 cycles of PRRT, disease control could be reached in 12 patients (disease control rate, 85.7%), with a partial response in 3 (21.4%), and stable disease in 9 (64.3%), whereas 2 patients (14.3%) had progressive disease, and by RECIST, there was stable disease in 12 (85.7%), and progressive disease in 2 (14.2%) patients. The 6-month PFS for all patients was 76%. The median PFS was 32.3 months, and the median OS has yet to be reached with a median follow-up of 75.6 months. All patients tolerated the therapy without any serious acute adverse effects. CTC-1 anemia was present in two patients (11.8%) at baseline which were not worsened to grade 2 after therapy and during long-term follow up. Five patients (29.4%) developed CTC-1 anemia after PRRT. CTC-1 leucopenia was observed in 2 patients (11.8%) after the first cycle. CTC-1 thrombocytopenia was observed in two patients (11.8%) including one at presentation which persisted, one discovered two months after the first therapy, which was reversible subsequently. Two CTC-1 renal toxicity (11.8%) were determined. No CTCAE grade 2-4 anemia, leukopenia, thrombocytopenia or renal toxicities was observed in any of the patients during or after PRRT. No hepatotoxicity was observed.
Conclusions: PRRT showed promising outcomes in patients with refractory meningiomas, with high disease control and encouraging progression-free survival and overall survival, which appears to be a favorable therapeutic option in patients with refractory meningioma. With long-term follow up, PRRT demonstrated favorable safety profile, resulting in very few side effects in this cohort of patients with meningioma.