Abstract BACKGROUND There are examples of incongruence between the WHO grade and clinical course in meningioma patients. This incongruence between WHO grade and recurrence has led to search for other prognostic histological markers. OBJECTIVE To study the correlation between the Ki-67 proliferative index (PI), risk of recurrence, and recurrence rates in meningioma patients. METHODS We prospectively collected pathological diagnosis of de novo consecutive meningiomas. In total, we followed 159 patients with clinical controls until recurrence, death, or emigration. We estimated the correlation between risk of recurrence and Ki-67 PI when adjusted for age at diagnosis, sex, WHO grade, extent of surgical resection, and tumor location. We estimated the cumulative incidence of recurrence when considering death without recurrence a competing risk. We report recurrence rates per 100 person-years. RESULTS A 1%-point increase of Ki-67 PI yielded a hazard ratio of 1.12 (95% CI: 1.01-1.24) in a multivariate analysis. The cumulative incidence of recurrence was 3% for Ki-67 0% to 4% vs 19% for Ki-67 > 4% meningiomas after 1 yr, but 24% vs 35%, respectively, after 10 yr. There was no significant difference in mean Ki-67 PI between nonrecurrent and recurrent meningioma in a 2-sample t-test (P = .08). The strongest relationship was detected between Ki-67 PI and time to recurrence: Ki-67 < 4% meningiomas recurred after median 4.8 yr, compared to 0.60 to 0.75 yr for patients with higher Ki-67 PI. CONCLUSION Ki-67 PI was a marker for time to recurrence rather than a predictor of recurrence. Ki-67 PI may be utilized for patient tailored follow-up.

Background: Somatostatin receptor (SSTR)-targeted peptide receptor radionuclide therapy (PRRT) represents a promising approach for treatment-refractory meningiomas. Methods: We performed an individual patient data (IPD) meta-analysis including all published meningioma patients treated with SSTR-targeted PRRT. Main outcomes were toxicity, response to treatment, progression-free survival (PFS), and overall survival (OS). We applied the Kaplan-Meier method to estimate survival probabilities and report incidence rates per 100 person-years. We applied Cox proportional hazards models to determine the effect of covariates. Results: We screened 537 papers, and identified six eligible cohort studies. We included a total of 111 patients with treatment-refractory meningioma who received SSTR-targeted PRRT. Disease control was achieved in 63% of patients. Six-month PFS was 94%, 48% and 0% for WHO (World Health Organization)-I,-II, &-III, respectively. The risk of disease progression decreased by 13% per 1000 MBq increase in the total applied activity. One-year OS was 88%, 71%, and 52% for WHO-I,-II &-III, respectively. The risk of death decreased by 17% per 1000-MBq increase of the total applied activity. Main side effects comprised transient hematotoxicities such as anemia in 22%, leukopenia in 13%, lymphocytopenia in 24%, and thrombocytopenia in 17% of patients. Conclusion: This IPD meta-analysis represents the most comprehensive analysis of benefits and adverse events of SSTR-targeted PRRT for treatment-refractory meningioma. The treatment was well tolerated, achieved disease control in most cases, and showed promising PFS and OS.

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