Aizer Ayal A, Abedalthagafi Malak, Bi Wenya Linda, Horvath Margaret C, Arvold Nils D, Al-Mefty Ossama, Lee Eudocia Q, Nayak Lakshmi, Rinne Mikael L, Norden Andrew D, Reardon David A, Wen Patrick Y, Ligon Keith L, Ligon Azra H, Beroukhim Rameen, Dunn Ian F, Santagata Sandro, Alexander Brian M
Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (A.A.A., M.C.H., N.D.A., B.M.A.); Department of Pathology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (M.A., K.L.L., A.H.L., S.S.); Department of Neurosurgery, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (W.L.B., O.A-M., I.F.D.); Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts (E.Q.L., L.N., M.L.R., A.D.N., D.A.R., P.Y.W., R.B.).
Neuro Oncol. 2016 Feb;18(2):269-74. doi: 10.1093/neuonc/nov177. Epub 2015 Aug 30.
The appropriate use of adjuvant therapy in patients with gross totally resected atypical meningioma requires an accurate assessment of recurrence risk. We sought to determine whether cytogenetic/genetic characterization may facilitate better estimation of the probability of recurrence.
We first analyzed our clinical database, including high-resolution DNA copy number data, to identify 11 common copy number aberrations in a pilot cohort of meningiomas of all grades. We summed these aberrations to devise a cytogenetic abnormality score (CAS) and determined the CAS from archived tissue of a separate cohort of 32 patients with gross totally resected atypical meningioma managed with surgery alone. Propensity score adjusted Cox regression was used to determine whether the CAS was predictive of recurrence.
An association between higher CAS and higher grade was noted in our pilot cohort with heterogeneity among atypical tumors. Among the 32 patients who underwent gross total resection of an atypical meningioma, the CAS was not significantly associated with age, gender, performance status, or tumor size/location but was associated with the risk of recurrence on univariable analysis (hazard ratio per aberration = 1.52; 95% CI = 1.08-2.14; P = .02). After adjustment, the impact of the dichotomized number of copy aberrations remained significantly associated with recurrence risk (hazard ratio = 4.47; 95% CI = 1.01-19.87; P = .05).
The number of copy number aberrations is strongly associated with recurrence risk in patients with atypical meningioma following gross total resection and may inform the appropriate use of adjuvant radiation therapy in these patients or be useful for stratification in clinical trials.
对于接受大体全切的非典型脑膜瘤患者,辅助治疗的合理应用需要准确评估复发风险。我们试图确定细胞遗传学/基因特征是否有助于更好地估计复发概率。
我们首先分析了我们的临床数据库,包括高分辨率DNA拷贝数数据,以在一个所有级别的脑膜瘤试点队列中识别11种常见的拷贝数畸变。我们将这些畸变相加,设计了一个细胞遗传学异常评分(CAS),并从另一组仅接受手术治疗的32例接受大体全切的非典型脑膜瘤患者的存档组织中确定了CAS。使用倾向评分调整的Cox回归来确定CAS是否可预测复发。
在我们的试点队列中,观察到较高的CAS与较高的分级之间存在关联,非典型肿瘤之间存在异质性。在32例接受非典型脑膜瘤大体全切的患者中,CAS与年龄、性别、体能状态或肿瘤大小/位置无显著关联,但在单变量分析中与复发风险相关(每畸变的风险比=1.52;95%CI=1.08-2.14;P=.02)。调整后,拷贝数畸变二分法数量的影响仍与复发风险显著相关(风险比=4.47;95%CI=1.01-19.87;P=.05)。
拷贝数畸变的数量与非典型脑膜瘤患者在大体全切后的复发风险密切相关,可能有助于指导这些患者辅助放疗的合理应用,或在临床试验中用于分层。