LAUSR

TO THE EDITOR: We read with great interest the article by Wang et al.6 (Wang Y, Wang Y, Fan X, et al: Putamen involvement and survival outcomes in patients with insular low-grade gliomas. J Neurosurg [epub ahead of print August 26, 2016. DOI: 10.3171/2016.5.JNS1685]). The authors classified 211 low-grade insular gliomas according to whether or not the tumors involved the putamen on MR images. They found putaminal involvement to be a significant predictor of both progression-free survival (PFS) and overall survival (OS) on multivariate analysis, in addition to extent of resection and IDH1 mutation. We commend the authors for performing a study of a large number of Grade II insular gliomas. However, we have several concerns. First, using T2-weighted images to determine putaminal involvement, albeit the best sequence available, can introduce ambiguities.4 It is well known that tumors vary in the amount of edema that is captured by T2 hyperintensity, and that the actual tumor cells can extend far beyond the T2 hyperintense region. We believe that T1-weighted images should also be examined along with the T2-weighted images to increase the diagnostic confidence of putaminal involvement. Second, the authors did not take into account the involvement of other brain regions surrounding the tumor besides the putamen, such as the frontal and temporal lobes. We would like to know how the authors classified the Grade II gliomas as primarily insular in the first place, and how they distinguished between purely insular Grade II gliomas and paralimbic Grade II gliomas, because previous studies have demonstrated distinct IDH1/IDH2 mutation profiles between these two types of tumor.2 In a study by Tang et al. comparing 20 purely insular Grade II gliomas and 22 paralimbic Grade II gliomas that involved the frontal and/or temporal lobe, the authors showed that purely insular Grade II gliomas displayed a higher frequency of IDH1 mutations with a favorable outcome compared with IDH1 wild-type paralimbic gliomas.5 However, IDH1 mutated paralimbic gliomas shared many parameters with the purely insular gliomas with respect to growth patterns, survival, and microRNA profile.5 This suggests that the survival benefit of insular gliomas is mainly determined by molecular characteristics instead of involvement in other regions of the brain, including the putamen. Even though the current paper demonstrated the significance of putaminal involvement on the multivariate analysis, the analysis did not account for the effects of chemoradiation. Radiotherapy and chemotherapy are frequently administered in patients with Grade II gliomas and have been shown to affect survival, especially in patients after a subtotal resection or biopsy.1,3 Similarly, it is unclear if 1p19q co-deletion status was included in the multivariate analysis. Because follow-up was only available for 150 of 211 patients, loss to follow-up could have introduced patient selection bias and affected validity of the survival analysis as well. In conclusion, putaminal involvement is likely a nonspecific finding of Grade II tumors that also involve other regions of the brain. Its significance on the multivariate analysis is cast in doubt by using only T2 hyperintensity to estimate putaminal involvement, the lack of information on chemoradiation, and patient selection bias due to loss to follow-up.