A prospective evaluation of whole brain volume loss and neurocognitive decline following hippocampal-sparing prophylactic cranial irradiation for limited-stage small-cell lung cancer.

Introduction: This study evaluated an association between whole brain volume loss and neurocognitive decline following prophylactic cranial irradiation (PCI) for limited-stage small-cell lung cancer (SCLC).

Methods: This was a secondary analysis of a prospective clinical trial that accrued patients at a single institution from 2013 to 2016. Patients with limited-stage SCLC treated with standard chemo-radiation received PCI 25 Gy/10 fractions, with mean hippocampal dose limited to < 8 Gy. Whole brain volumes were measured using MR imaging obtained before and at 6, 12, 18, and 24 months after PCI. Verbal memory was measured by the Hopkins Verbal Learning Test-Revised (HVLT-R) before and at 6 and 12 months after PCI. Univariate and multivariate linear regression evaluated associations between changes in whole brain volume and verbal memory.

Results: Twenty-two patients enrolled. The median whole brain volume before PCI was 1301 mL. Subsequent reduction in whole brain volume was greatest at 18 months after PCI (median change - 23 mL, range - 142 to 20, p = 0.03). At 6 months after PCI, reduction in volume was independently associated with decline in verbal memory, measured by two components of the HVLT-R (Delayed Recall: 0.06/mL volume change, p = 0.046; Percent Retained: 0.66/mL volume change, p = 0.030), when controlling for education and global cognitive function at baseline.

Conclusion: This is the first study to correlate reduction in whole brain volume and decline in neurocognitive function following whole brain radiation therapy (WBRT). This suggests that loss of brain volume after WBRT may be clinically significant and subsequently impact cognition and quality of life.