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J Clin Oncol. 2014 Dec 1;32(34):3810-6. doi: 10.1200/JCO.2014.57.2909. Epub 2014 Oct 27.

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.

Author information

1
Vinai Gondi, Cadence Brain Tumor Center and CDH Proton Center, Warrenville, IL; Vinai Gondi and Howard Rowley, University of Wisconsin School of Medicine and Public Health, Madison, WI; Stephanie L. Pugh, Radiation Therapy Oncology Group Statistical Center; Wenyin Shi, Thomas Jefferson University Hospital, Philadelphia; Albert DeNittis, Lankenau Medical Center, Main Line Community Clinical Oncology Program (CCOP), Wynnewood; Andre A. Konski, Chester County Hospital, West Chester; Wolfgang A. Tome, Montefiore Medical Center and Albert Einstein College of Medicine, Yeshiva University, Bronx, NY; Chip Caine, Intermountain Medical Center and University of Phoenix, Salt Lake City, UT; Ben Corn and Andrew Kanner, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Vijayananda Kundapur, Saskatoon Cancer Centre, Saskatoon, Saskatchewan; Jeffrey N. Greenspoon, McMaster University-Hamilton, Hamilton; Glenn S. Bauman, London Regional Cancer Program, London, Ontario, Canada; Sunjay Shah, Christiana Care Health Services CCOP, Newark, DE; Merideth Wendland, US Oncology-Willamette Valley Cancer Institute, Eugene, OR; Lisa Kachnic, Boston Medical Center Minority-Based CCOP, Boston, MA; and Minesh P. Mehta, University of Maryland School of Medicine, Baltimore, MD. vgondi@chicagocancer.org.
2
Vinai Gondi, Cadence Brain Tumor Center and CDH Proton Center, Warrenville, IL; Vinai Gondi and Howard Rowley, University of Wisconsin School of Medicine and Public Health, Madison, WI; Stephanie L. Pugh, Radiation Therapy Oncology Group Statistical Center; Wenyin Shi, Thomas Jefferson University Hospital, Philadelphia; Albert DeNittis, Lankenau Medical Center, Main Line Community Clinical Oncology Program (CCOP), Wynnewood; Andre A. Konski, Chester County Hospital, West Chester; Wolfgang A. Tome, Montefiore Medical Center and Albert Einstein College of Medicine, Yeshiva University, Bronx, NY; Chip Caine, Intermountain Medical Center and University of Phoenix, Salt Lake City, UT; Ben Corn and Andrew Kanner, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Vijayananda Kundapur, Saskatoon Cancer Centre, Saskatoon, Saskatchewan; Jeffrey N. Greenspoon, McMaster University-Hamilton, Hamilton; Glenn S. Bauman, London Regional Cancer Program, London, Ontario, Canada; Sunjay Shah, Christiana Care Health Services CCOP, Newark, DE; Merideth Wendland, US Oncology-Willamette Valley Cancer Institute, Eugene, OR; Lisa Kachnic, Boston Medical Center Minority-Based CCOP, Boston, MA; and Minesh P. Mehta, University of Maryland School of Medicine, Baltimore, MD.

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01227954.

PMID:
25349290
PMCID:
PMC4239303
DOI:
10.1200/JCO.2014.57.2909
[Indexed for MEDLINE]
Free PMC Article

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