Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933): A phase II multi-institutional trial

Vinai Gondi, Stephanie L. Pugh, Wolfgang A. Tome, Chip Caine, Ben Corn, Andrew Kanner, Howard Rowley, Vijayananda Kundapur, Albert DeNittis, Jeffrey N. Greenspoon, Andre A. Konski, Glenn S. Bauman, Sunjay Shah, Wenyin Shi, Merideth Wendland, Lisa Kachnic, Minesh P. Mehta

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Abstract

Purpose: Hippocampal neural stem-cell injury during whole-brain radiotherapy (WBRT) may play a role in memory decline. Intensity-modulated radiotherapy can be used to avoid conformally the hippocampal neural stem-cell compartment during WBRT (HA-WBRT). RTOG 0933 was a single-arm phase II study of HA-WBRT for brain metastases with prespecified comparison with a historical control of patients treated with WBRT without hippocampal avoidance. Patients and Methods: Eligible adult patients with brain metastases received HA-WBRT to 30 Gy in 10 fractions. Standardized cognitive function and quality-of-life (QOL) assessments were performed at baseline and 2, 4, and 6 months. The primary end point was the Hopkins Verbal Learning Test-Revised Delayed Recall (HVLT-R DR) at 4 months. The historical control demonstrated a 30% mean relative decline in HVLT-R DR from baseline to 4 months. To detect a mean relative decline ≤ 15% in HVLT-R DR after HA-WBRT, 51 analyzable patients were required to ensure 80% statistical power with α = 0.05. Results: Of 113 patients accrued from March 2011 through November 2012, 42 patients were analyzable at 4 months. Mean relative decline in HVLT-R DR from baseline to 4 months was 7.0% (95% CI, -4.7% to 18.7%), significantly lower in comparison with the historical control (P < .001). No decline in QOL scores was observed. Two grade 3 toxicities and no grade 4 to 5 toxicities were reported. Median survival was 6.8 months. Conclusion: Conformal avoidance of the hippocampus during WBRT is associated with preservation of memory and QOL as compared with historical series.

Original languageEnglish (US)
Pages (from-to)3810-3816
Number of pages7
JournalJournal of Clinical Oncology
Volume32
Issue number34
DOIs
StatePublished - Dec 1 2014

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Gondi, V., Pugh, S. L., Tome, W. A., Caine, C., Corn, B., Kanner, A., Rowley, H., Kundapur, V., DeNittis, A., Greenspoon, J. N., Konski, A. A., Bauman, G. S., Shah, S., Shi, W., Wendland, M., Kachnic, L., & Mehta, M. P. (2014). Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933): A phase II multi-institutional trial. Journal of Clinical Oncology, 32(34), 3810-3816. https://doi.org/10.1200/JCO.2014.57.2909