Avoiding Specific Region of Brain During Whole-Brain Radiotherapy Prevents Memory Loss

Avoiding Specific Region of Brain During Whole-Brain Radiotherapy Prevents 
Memory Loss 
ATLANTA, GA  -- (Marketwired) -- 09/23/13 --  Limiting the amount of
radiation absorbed in the hippocampal portion of the brain during
whole-brain radiotherapy (WBRT) for brain metastases preserves memory
function in patients for up to six months after treatment, according
to research presented today at the American Society for Radiation
Oncology's (ASTRO's) 55th Annual Meeting. 
The single-arm, phase II study was a multi-institutional,
international clinical trial in the U.S. and Canada, conducted
through the Radiation Therapy Oncology Group (RTOG). Researchers
compared the study group to a historical control group of patients
who had received WBRT without hippocampal avoidance in the
PCI-P-120-9801 phase III trial (Li 2007). 
This study enrolled 113 adult patients from 2011 through 2013 who had
a measurable brain metastasis outside a 5-mm margin around the
hippocampus. Of those patients, 100 were analyzable and 76 percent
were categorized as recursive partitioning analysis (RPA) class II.
All patients received hippocampal avoidance whole-brain radiotherapy
(HA-WBRT) to 30 Gy in 10 fractions. In all analyzable patients, the
dose received by the entirety of the hippocampus did not exceed 10
Gy, and the maximum dose did not exceed 17 Gy. Patients were assessed
using the Hopkins Verbal Learning Test - Delayed Recall (HVLT-DR),
the HVLT - Recall (HVLT-R) and the HVLT - Immediate Recognition
(HVLT-IR) at baseline and post-treatment at two-, four- and six-month
intervals. The primary endpoint of the trial was the HVLT-DR at four
Results showed that the 42 patients who were analyzable at four
months post-RT had a seven percent decline in HVLT-DR from baseline
to four months (95 percent confidence interval (CI): -4.7 percent to
18.7 percent). This is statistically significant when compared to the
historical control group (p=0.0003), which demonstrated a 30 percent
decline in HVLT-DR at four months. Six months after treatment, the 29
analyzable patients had a two percent decline in HVLT-DR from
baseline (95 percent CI: -9.2 percent to 13.1 percent). 
"Radiotherapy to the brain is known to impact the memory function of
cancer survivors," said Vinai Gondi, MD, lead author of the study,
Co-Director of the Cadence Brain Tumor Center and Associate Director
of Research at the Cadence Proton Center in Warrenville, Ill, and
Clinical Assistant Professor at the University of Wisconsin School of
Medicine and Public Health in Madison, Wis. "A compartment of neural
stem cells located in the hippocampus, sensitive to radiotherapy and
important for memory function, is thought to be central to these
effects. Our research group developed advanced radiotherapy
techniques that spare this hippocampal neural stem cell compartment
from significant radiation doses. The study results were
statistically better than historical data of whole-brain radiotherapy
without hippocampal sparing and present a number of opportunities to
introduce hippocampal sparing in other contexts of radiotherapy to
the brain. The RTOG is currently developing phase III trials to
explore these other contexts and to validate these results."  
The abstract, "Memory Preservation with Conformal Avoidance of the
Hippocampus during Whole-Brain Radiotherapy (WBRT) for Patients with
Brain Metastases: Primary Endpoint Results of RTOG 0933," will be
presented in detail during the Plenary session at ASTRO's Annual
Meeting at 2:00 p.m. Eastern time, on Monday, September 23, 2013. To
speak with Dr. Gondi, call Michelle Kirkwood on September 22 - 25,
2013, in the ASTRO Press Office at the Georgia World Congress Center
in Atlanta at 404-222-5303 or 404-222-5304, or email
ASTRO's 55th Annual Meeting, held in Atlanta, September 22-25, 2013,
is the premier scientific meeting in radiation oncology and brings
together more than 11,000 attendees including oncologists from all
disciplines, medical physicists, dosimetrists, radiation therapists,
radiation oncology nurses and nurse practitioners, biologists,
physician assistants, practice administrators, industry
representatives and other health care professionals from around the
world. The theme of the 2013 meeting is "Patients: Hope -- Guide --
Heal" and focuses on patient-centered care and the importance of the
physician's role in improving patient-reported outcomes and the
quality and safety of patient care. The four-day scientific meeting
includes presentation of four plenary papers, 363 oral presentations,
1,460 posters and 144 digital posters in 70 educational sessions and
scientific panels for 19 disease sites/tracks. Keynote and featured
speakers include: William B. Munier, director of the Center for
Quality Improvement and Patient Safety at the Agency for Healthcare
Research and Quality; Darrell G. Kirch, MD, president and CEO of the
Association of American Medical Colleges; James Cosgrove, PhD,
director of the U.S. Government Accountability Office; Otis W.
Brawley, MD, chief medical officer of the American Cancer Society;
and Peter Friedl, MD, PhD, of St. Radboud University Nijmegen Medical
Centre at the University of Nijmegen and MD Anderson Cancer Center. 
ASTRO is the premier radiation oncology society in the world, with
more than 10,000 members who are physicians, nurses, biologists,
physicists, radiation therapists, dosimetrists and other health care
professionals that specialize in treating patients with radiation
therapies. As the leading organization in radiation oncology, the
Society is dedicated to improving patient care through professional
education and training, support for clinical practice and health
policy standards, advancement of science and research, and advocacy.
ASTRO publishes two medical journals, International Journal of
Radiation Oncology -- Biology -- Physics (www.redjournal.org) and
Practical Radiation Oncology (www.practicalradonc.org); developed and
maintains an extensive patient website, www.rtanswers.org; and
created the Radiation Oncology Institute (www.roinstitute.org), a
non-profit foundation to support research and education efforts
around the world that enhance and confirm the critical role of
radiation therapy in improving cancer treatment. To learn more about
ASTRO, visit www.astro.org. 
2013 American Society for Radiation Oncology (ASTRO) 55th Annual
News Briefing, Monday, September 23, 2013, 8:30 a.m. Eastern time 
Scientific Session: Monday, September 23, 2013, 2:00 - 3:10 pm ET,
Georgia World Congress Center 
LBA1 Memory Preservation with Conformal Avoidance of the Hippocampus
during Whole-Brain Radiotherapy (WBRT) for Patients with Brain
Metastases: Primary Endpoint Results of RTOG 0933 
V. Gondi1,2, M. P. Mehta*3, S. Pugh*4, W. A. Tome*5, A. Kanner*6, C.
Caine*7, H. Rowley*8, V. Kundapur*9, J. N. Greenspoon*10, L.
Kachnic*11. 1Cadence Health Brain Tumor Center, Warrenville, IL, 2CDH
Proton Center, Warrenville, IL, 3University of Maryland School of
Medicine, Baltimore, MD, 4Radiation Therapy Oncology
Group-Statistical Center, Philadelphia, PA, 5Albert Einstein College
of Medicine, Bronx, NY, 6Tel Aviv Sourasky Medical Center, Tel Aviv,
Israel, 7Intermountain Medical Center, Salt Lake City, UT,
8University of Wisconsin School of Medicine & Public Health, Madison,
WI, 9Saskatoon Cancer Centre, Saskatoon, SK, Canada, 10McMaster
University-Hamilton, Hamilton, ON, Canada, 11Boston University
Medical Center, Boston, MA.  
Purpose/Objective(s): Hippocampal dose during WBRT has been
hypothesized to play a role in cognitive decline. This may be
preventable using intensity-modulated radiotherapy to conformally
avoid the hippocampus during WBRT (HA-WBRT). RTOG 0933 was a
single-arm phase II study of HA-WBRT for brain metastases with a
primary cognitive endpoint and pre-specified comparison to a
historical control of WBRT without hippocampal avoidance.
Materials/Methods: Eligible adult patients with brain metastases
received HA-WBRT to 30 Gy in 10 fractions. Hippocampal 100% dose and
maximum dose could not exceed 10 Gy and 17 Gy, respectively.
Standardized cognitive assessments were performed at baseline, 2, 4,
and 6 months (mos). The primary endpoint was the Hopkins Verbal
Learning Test Delayed Recall (HVLT-DR) at 4 mos. Secondary endpoints
included HVLT Recall (HVLT-R) and Immediate Recognition (HVLT-IR).
The historical control consisted of brain metastases patients treated
with WBRT on the PCI-P-120-9801 phase III trial, which demonstrated a
30% mean relative decline in HVLT-DR from baseline to 4 mos. To
detect a minimum relative 50% improvement, leading to an absolute 15%
or less mean relative decline in HVLT-DR following HA-WBRT, 51
analyzable patients were required to ensure 80% statistical power
with alpha=0.05.
Results: 113 patients were accrued from March 2011 through November
2013; 100 were eligible for analysis. 76% of patients were RPA class
II. Two treatment-related grade 3 adverse events were reported
(fatigue, headache); no treatment-related grade 4-5 events were
observed. Median survival was 6.8 mos (95% confidence interval
(95%CI) 4.8-10.9 mos). 3 patients (4.5%) had progression in the
hippocampal avoidance region, consistent with expected event-rate. 42
patients were analyzable at 4 mos. Mean relative decline in HVLT-DR
from baseline to 4 mos was 7.0% (95%CI: -4.7% to 18.7%), which was
significant in comparison to the historical control (p=0.0003). Mean
relative decline in HVLT-R and HVLT-IR from baseline to 4 mos was
3.6% (95%CI: -2.9% to 10.1%) and 1.6% (95%CI: -2.8% to 6.0%),
respectively. 29 patients were analyzable at 6 mos with a mean
relative decline in HVLT-DR, HVLT-R and HVLT-IR from baseline to 6
mos of 2.0% (95%CI: -9.2% to 13.1%), -3.0% (95%CI: -12.0% to 5.9%)
and 0.7% (95%CI: -3.1% to 4.4%), respectively.
Conclusions: Conformal avoidance of the hippocampus during WBRT is
associated with memory preservation at 4 and 6 mos follow-up. These
phase II results compare favorably to historical series and warrant
further validation in a phase III trial, currently under development
in the RTOG.
Acknowledgment: This project was supported by RTOG grant U10 CA21661,
and CCOP grant U10 CA37422 from the National Cancer Institute (NCI). 
V. Gondi: None. M.P. Mehta: E. Research Grant; NCI-NIH, RTOG. F.
Honoraria; Merck, Genentech. G. Consultant; AbbVie, Elekta, Novocure,
Viewray, Phillips. H. Travel Expenses; Merck, Genentech, Elekta,
Novocure, Phillips. L. Stock Options; Pharmacyclics, Accuray. N.
Royalty; DEMOS Publishers, Elsevier. Q. Leadership; RTOG. S. Pugh:
None. W.A. Tome: None. A. Kanner: None. C. Caine: None. H. Rowley: E.
Research Grant; Guerbet. G. Consultant; Bracco, Eli Lilly, GE
Healthcare, H. Lundbeck A/S. O. Patent/License Fee/Copyright; GE
Healthcare. V. Kundapur: None. J.N. Greenspoon: None. L. Kachnic:
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Nancy Mayes
Mayes Communications
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