Chengcheng Gui1, Tracy D Vannorsdall2, Lawrence R Kleinberg1, Ryan Assadi1, Joseph A Moore1, Chen Hu1,3, Alfredo Quiñones-Hinojosa4, Kristin J Redmond1. 1. Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, Maryland. 2. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, Maryland. 3. Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland. 4. Department of Neurosurgery, Mayo Clinic, Jacksonville, Florida.
Abstract
BACKGROUND: In treating glioblastoma, irradiation of the neural progenitor cell (NPC) niches is controversial. Lower hippocampal doses may limit neurocognitive toxicity, but higher doses to the subventricular zones (SVZ) may improve survival. OBJECTIVE: To prospectively evaluate the impact of limiting radiation dose to the NPC niches on tumor progression, survival, and cognition in patients with glioblastoma. METHODS: Patients with glioblastoma received resection followed by standard chemoradiation. Radiation dose to the NPC niches, including the bilateral hippocampi and SVZ, was minimized without compromising tumor coverage. The primary outcome was tumor progression in the spared NPC niches. Follow-up magnetic resonance imaging was obtained bimonthly. Neurocognitive testing was performed before treatment and at 6- and 12-mo follow-up. Cox regression evaluated predictors of overall and progression-free survival. Linear regression evaluated predictors of neurocognitive decline. RESULTS: A total of 30 patients enrolled prospectively. The median age was 58 yr. Median mean doses to the hippocampi and SVZ were 49.1 and 41.8 gray (Gy) ipsilaterally, and 16.5 and 19.9 Gy contralaterally. Median times to death and tumor progression were 16.0 and 7.6 mo, and were not significantly different compared to a matched historical control. No patients experienced tumor progression in the spared NPC-containing regions. Overall survival was associated with neurocognitive function (P ≤ .03) but not dose to the NPC niches. Higher doses to the hippocampi and SVZ predicted greater decline in verbal memory (P ≤ .01). CONCLUSION: In treating glioblastoma, limiting dose to the NPC niches may reduce cognitive toxicity while maintaining clinical outcomes. Further studies are needed to confirm these results.
BACKGROUND: In treating glioblastoma, irradiation of the neural progenitor cell (NPC) niches is controversial. Lower hippocampal doses may limit neurocognitive toxicity, but higher doses to the subventricular zones (SVZ) may improve survival. OBJECTIVE: To prospectively evaluate the impact of limiting radiation dose to the NPC niches on tumor progression, survival, and cognition in patients with glioblastoma. METHODS:Patients with glioblastoma received resection followed by standard chemoradiation. Radiation dose to the NPC niches, including the bilateral hippocampi and SVZ, was minimized without compromising tumor coverage. The primary outcome was tumor progression in the spared NPC niches. Follow-up magnetic resonance imaging was obtained bimonthly. Neurocognitive testing was performed before treatment and at 6- and 12-mo follow-up. Cox regression evaluated predictors of overall and progression-free survival. Linear regression evaluated predictors of neurocognitive decline. RESULTS: A total of 30 patients enrolled prospectively. The median age was 58 yr. Median mean doses to the hippocampi and SVZ were 49.1 and 41.8 gray (Gy) ipsilaterally, and 16.5 and 19.9 Gy contralaterally. Median times to death and tumor progression were 16.0 and 7.6 mo, and were not significantly different compared to a matched historical control. No patients experienced tumor progression in the spared NPC-containing regions. Overall survival was associated with neurocognitive function (P ≤ .03) but not dose to the NPC niches. Higher doses to the hippocampi and SVZ predicted greater decline in verbal memory (P ≤ .01). CONCLUSION: In treating glioblastoma, limiting dose to the NPC niches may reduce cognitive toxicity while maintaining clinical outcomes. Further studies are needed to confirm these results.
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