Progesterone receptor expression and prediction of benefits of adjuvant radiotherapy in de novo atypical meningiomas after gross-total resection

Abstract

OBJECTIVE Benefits of adjuvant radiotherapy (ART) after gross-total resection (GTR) of de novo atypical meningiomas (AMs) are controversial, and factors predictive of radiotherapy benefits in patients with de novo AMs after GTR are unknown. The authors aimed to evaluate the benefits of ART and explore potential factors sensitizing AMs to ART. METHODS A total of 231 consecutive patients who were pathologically diagnosed with de novo AMs and treated with GTR (Simpson class I–III resections) from 2010 to 2018 were enrolled in the study. Clinicopathological and prognostic information was collected and analyzed. Univariate and multivariate Cox analyses were used to evaluate prognostic predictors and compare the response to radiotherapy. Propensity score matching (PSM) was used to balance the confounding bias in subgroups. RESULTS A total of 138 patients (59.74%) received ART. Progesterone receptor (PR) expression was positive in 157 patients (67.97%). During the mean follow-up period of 76.25 months, 65 patients (28.14%) experienced recurrence and 38 (16.45%) died of tumor progression. For disease-specific survival (DSS), ART was a better prognostic factor via univariate (p = 0.003) and multivariate (p = 0.025) analyses. For progression-free survival (PFS), univariate Cox analysis showed that ART improved PFS (p = 0.013), but multivariate analysis did not (p = 0.068). Positive PR expression (p = 0.019), age 53.5 years or younger (p = 0.012), and Ki-67 7.5% or lower (p = 0.025) were independent prognostic predictors for better PFS. In the subcohort analysis, the beneficial impact of ART was observed in the PR-negative cohort (p = 0.002) but not in the PR-positive cohort (p = 0.86). The heterogeneity analysis demonstrated that the PR-negative cohort was more sensitive to ART than the PR-positive cohort (p = 0.036). ART was not found to be associated with better PFS in younger patients (≤ 53.5 years, p = 0.14), older patients (> 53.5 years, p = 0.085), those with a Ki-67 index ≤ 7.5% (p = 0.068), or those with a Ki-67 > 7.5% (p = 0.13). The contrasting effects of ART in the PR-negative versus PR-positive cohorts remained true even after PSM, confirming that PR-negative, but not PR-positive, de novo AMs benefited from ART after GTR. CONCLUSIONS ART was an independent prognostic factor for DSS of patients with de novo AMs treated with GTR (p = 0.025), but not for PFS (p = 0.068). Negative PR expression was a radiosensitive biomarker on PFS for de novo AM patients after GTR.

Ki-67 labeling index predicts tumor progression patterns and survival in patients with atypical meningiomas following stereotactic radiosurgery

“…However, limited studies have focused on the recurrence patterns according to intrinsic tumor characteristics, which is clinically signi cant as atypical meningiomas often exhibit marginal recurrences outside the radiation eld [25]. Ki-67 LI provides insight into the proliferative nature of tumors, and while it has been used as a prognostic factor for postoperative recurrence in atypical meningiomas [13,27,28,30,31], few studies have evaluated Ki-67 LI as a prognosticator for atypical meningioma SRS outcomes. Shepard et al reported that a higher LI was associated with shorter PFS after SRS in a cohort including atypical and anaplastic meningiomas classi ed as a Ki-67 LI of > 15% and ≤ 15% [13].…”

“…The Ki-67 labeling index (LI) is a valuable tool that re ects tumor proliferation capability and has been shown to correlate with progression after surgery for benign and high-grade meningiomas [27][28][29][30][31].…”

Biomarkers for prognosis of meningioma patients: A systematic review and meta-analysis

“…Prognostic value of progesterone receptor (PR) expression. Two studies [54,96] with a total of 318 participants reported the association between PR expression and PFS of high grade (grade II and grade III) meningioma patients. The forest plot showed no significant association between PR expression and PFS (HR = 0.81, 95%CI 0.40 to 1.62, I 2 = 80%), Fig 3A . On the other hand, 3 studies [14,23,99] with a total of 460 participants indicated the statistically significant association between positive PR expression and good prognosis of RFS of meningioma patients (HR = 0.60, 95%CI 0.41 to 0.88, I 2 = 22%), Fig 3B . Apart from our meta-analysis, Guadagno et al [48] reported that high PR expression was associated with good prognosis of OS and RFS of meningioma patients using a Log rank test (p<0.05).…”