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

• Published in: International journal of radiation oncology, biology, physics Vol. 83; no. 4; pp. e487 - e493
• Main Authors: Gondi, Vinai, M.D, Hermann, Bruce P., Ph.D, Mehta, Minesh P., M.D., FASTRO, Tomé, Wolfgang A., Ph.D., FAAPM
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.07.2012
• Subjects: Adult; ADULTS; Aged; Aged, 80 and over; Brain Neoplasms - pathology; Brain Neoplasms - secondary; Brain Neoplasms - surgery; Brain tumors; Case-Control Studies; CLINICAL TRIALS; Conformal radiotherapy; DOSE EQUIVALENTS; Dose Fractionation; Dose-Response Relationship, Radiation; DOSIMETRY; Female; Glioma - pathology; Glioma - surgery; Hematology, Oncology and Palliative Medicine; HIPPOCAMPUS; Hippocampus - radiation effects; Humans; IRRADIATION; Male; Memory Disorders - etiology; Memory Disorders - prevention & control; Meningeal Neoplasms - surgery; Meningioma - surgery; Mental Recall - radiation effects; Middle Aged; MULTIVARIATE ANALYSIS; NEOPLASMS; Neurilemmoma - pathology; Neurilemmoma - surgery; Neurocognitive function; Organ Sparing Treatments - methods; PATIENTS; Prospective Studies; RADIATION DOSES; Radiation Therapy Oncology Group 0933; Radiology; RADIOLOGY AND NUCLEAR MEDICINE; Radiosurgery - adverse effects; Radiosurgery - methods; RADIOTHERAPY; Regression Analysis; Young Adult; Conformal radiotherapy; Radiation Therapy Oncology Group 0933; Brain tumors; Neurocognitive function; Hippocampus
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2011.10.021

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 ≤−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 α/β ratio of 2 Gy were computed. Fisher’s 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.