Hippocampal Dosimetry Predicts Neurocognitive Function Impairment After Fractionated Stereotactic Radiotherapy for Benign or Low-Grade Adult Brain Tumors

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• 作者：Vinai Gondi ; M.D.^&lowast ; ; Bruce P. Hermann ; Ph.D.^&dagger ; ; Minesh P. Mehta ; M.D. ; FASTRO^¶ ; ; Wolfgang A. Tomé ; Ph.D. ; FAAPM^&lowast ; ; ^&Dagger ; ; ^§ ; ; ^{tome@humonc.wisc.edu}
• 关键词：Neurocognitive function ; Hippocampus ; Conformal radiotherapy ; Radiation Therapy Oncology Group 0933 ; Brain tumors
• 刊名：International Journal of Radiation Oncology*Biology*Physics
• 出版年：2012
• 期刊代码：136_03603016
• 类别：med
• 出版时间：15 July, 2012
• 卷：83
• 期：4
• 页码：e487-e493
• 文件大小：460 K

摘要

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Purpose

To prospectively evaluate the association between hippocampal dose and long-term neurocognitive function (NCF) impairment for benign or low-grade adult brain tumors treated with fractionated stereotactic radiotherapy (FSRT).

Methods and Materials

Adult patients with benign or low-grade adult brain tumors were treated with FSRT per institutional practice. No attempt was made to spare the hippocampus. NCF testing was conducted at baseline and 18 months follow-up, on a prospective clinical trial. Regression-based standardized z scores were calculated by using similar healthy control individuals evaluated at the same test-retest interval. NCF impairment was defined as a z score 鈮も垝1.5. After delineation of the bilateral hippocampi according to the Radiation Therapy Oncology Group contouring atlas, dose-volume histograms were generated for the left and right hippocampi and for the composite pair. Biologically equivalent doses in 2-Gy fractions (EQD₂) assuming an 伪/尾 ratio of 2 Gy were computed. Fisher鈥檚 exact test and binary logistic regression were used for univariate and multivariate analyses, respectively. Dose-response data were fit to a nonlinear model.

Results

Of 29 patients enrolled in this trial, 18 completed both baseline and 18-month NCF testing. An EQD₂ to 40%of the bilateral hippocampi >7.3 Gy was associated with impairment in Wechsler Memory Scale-III Word List (WMS-WL) delayed recall (odds ratio [OR] 19.3; p = 0.043). The association between WMS-WL delayed recall and EQD₂ to 100%of the bilateral hippocampi >0.0 Gy trended to significance (OR 14.8; p = 0.068).

Conclusion

EQD₂ to 40%of the bilateral hippocampi greater than 7.3 Gy is associated with long-term impairment in list-learning delayed recall after FSRT for benign or low-grade adult brain tumors. Given that modern intensity-modulated radiotherapy techniques can reduce the dose to the bilateral hippocampi below this dosimetric threshold, patients should be enrolled in ongoing prospective trials of hippocampal sparing during cranial irradiation to confirm these preliminary results.