Transcript J Cancer Res Ther

ASNR 2015 Poster# EP-19
Effect of Chemotherapy on Brain Structure and
Cognition in Older Women with Breast Cancer:
a Brain MRI Study
1Bihong
T. Chen MD. Ph.D., 2Sunita K. Patel Ph.D., 3David Utriainen MS., 3Yongquan Ye Ph.D., 3Mark Haacke Ph.D., 4Arti Hurria MD.
1Department
of Diagnostic Radiology, City of Hope Medical Center, Duarte, CA 91010.
of Population Science, City of Hope Medical Center, Duarte, CA 91010.
3Department of Radiology, MR Research Facility, Wayne State University, Detroit, MI.
4Department of Medical Oncology, City of Hope Medical Center, Duarte, CA 91010.
2Department
Background
• Some patients with breast cancer suffer from subjective and
objective cognitive deficits during and after chemotherapy,
colloquially termed “chemobrain”.1, 2
• Cancer and its treatment affect cognition. Older patients are
especially concerned about cognitive impairment affecting quality
of life.
• Brain structural changes including cerebral microbleeds (CMB)
detected on brain MRI scans are associated with cognitive
dysfunction.3, 4
Purpose
•
To evaluate the effect of chemotherapy on brain structure and
cognition in older women with breast cancer receiving adjuvant
chemotherapy. Specifically,
– To evaluate alteration in brain structure such as cerebral
microbleeds (CMB), white matter lesions and brain volumes.
– To correlate brain structural changes with neuropsychological
performance in older women with breast cancer receiving
adjuvant chemotherapy.
Materials & Methods: Summary
• This is an on-going prospective longitudinal study of women age ≥ 60
with stage I-III breast cancers receiving adjuvant chemotherapy.
• Patients with breast cancer underwent neuropsychological
assessment with the NIH Toolbox5 and brain fMRI prior to
chemotherapy (pre-treatment) and again1 month after chemotherapy
(post-treatment).
• Age-matched Healthy controls (HC) underwent the same assessments
at the same time points.
Materials & Methods: Study Design
Pre-treatment
Patient Group:
•Age > 60
•Breast Cancer
•Stage I-III
•To receive adjuvant or neoadjuvant
chemotherapy
Healthy Controls*:
•Age ≥ 60
•No history of cancer
Geriatric
Assessment
Cognitive testing
Brain fMRI brain
Time point 1
Adjuvant or Neoadjuvant Chemotherapy
Toxicity Grading (NCI CTCAE version 4.0)
Post-treatment
Geriatric
Assessment
Cognitive testing
Brain fMRI brain
Time point 2
Materials & Methods: MRI Protocol
• The MRI scan protocol includes T1WI, T2 FLAIR and
Susceptibility weighted imaging (SWI).
• SPIN software (Detroit, MI) was used for post-process.
SWI,
Sequence
1.0mm1.5mm
Orientation
Axial
Sagital
Axial
TR(ms)
1900
6000
27
TE(ms)
2.94
397
18
Flip Angle(º)
9
120
15
No. of partitions
160
120
144
FOV (mm x mm) 201 x 230256 x 256 168 x 224
Matrix size(Nx x
440 x 512516 x 512 336 x 448
Ny)
Resolution (mm
0.449 x 0.449
0.5 X 0.5 0.5 X 0.5
x mm)
Slice Thickness
1.5
1
1
(mm)
Reconstructed
120
160
128
no. of images
T1 w/o
T2 Flair
contrast
Results – Part 1: Demographic Data
• Eight patients (age 66.4+/-5
years) and 9 age-matched
healthy controls (aged 66.2+/6 years) have completed two
assessments.
Results Part – 2: Cognitive testing
Neuropsychological testing with NIH toolbox for cognition:
•
Neurocognitive testing with NIH
toolbox shows practice effect
where time point 2 scores
improve in both groups (Table
1).
•
There is functional decrease
from time point 1 to time point
2 in the chemotherapy-treated
patient group for the SF-36
Physical health QOL measure.
•
Neurocognitive testing results
from repeated measures
analyses of variance
(RANOVA) to examine
differences in pre- and posttreatment changes between
patients and healthy controls
were not significant.
Results – Part 3: CMB data
• Two (25%) patients had 1 CMB (example arrow) each in both preand post-imaging while no healthy control had CMB.
SWIM MIP over 5 slices
SWI mIP over 5 slices
SWIM = susceptibility weighted imaging and mapping,
SWI = susceptibility weighted imaging,
m/MIP= maximum /minimum intensity projection
T1WI
T2 FLAIR
Results Part – 4: WMH data
•
White matter hyper-intensity (WMH) was more prevalent in the control group
(TP1=3.0+/-4cm3, TP2=2.7+/-3cm3) compared to the patients (TP1=2.7+/-3cm3,
TP2=1.3+/-1cm3), however 3 of the 4 subjects with greater than 3cm3 of WMH
were older than 71 years (2 controls and 1 patient).
Healthy Control#1
Healthy Control#2
Patient
Note the appearance in the WMH distribution in the Healthy Control#1 on the left. This may indicate the
presence of vascular disease. The other WMH examples do not show this pattern but are similar in their
appearance to each other.
Results part – 5: Brain Volume Data
• Parenchymal brain volumes were consistent between scans for
both healthy controls and chemotherapy patients with the removal
of 1 patient TP2 scan due to data quality.
•
•
•
•
Controls TP1=1086+/-75cm3
Controls TP2=1080+/-78cm3
Patients TP1=1091+/-61cm3
Patients TP2=1097+/-67cm3
Conclusion
•
The patient group on chemotherapy shows a higher incidence of
cerebral microbleeds (CMB) than the healthy control group;
•
The total brain volume and white matter hyperintense (WMH) lesion
volumes do not differ between the patient chemotherapy group and the
healthy control group.
•
SWI scan sequence shows potential to evaluate brain structural
changes in older cancer patients receiving chemotherapy.
•
Brain volume, white matter lesion volume, and CMB count can
potentially be used as neuroimaging biomarkers for evaluation of
cognitive effects of chemotherapy older patients with cancer.
Acknowledgement
•
This study is funded by NIH/NIA grants:
– GEMSSTAR R03 AG045090-02 (CHEN)
– R01 AG037037-01A1 (Hurria)
•
This study is registered in ClinicalTrials.gov as: NCT01992432
•
Key words:
– cerebral microbleed (CMB)
– brain volume
– chemotherapy
– cognition
References
1. Hurria A, Somlo G, Ahles T. Renaming "chemobrain". Cancer Invest 2007;25:373-377
2. Dutta V. Chemotherapy, neurotoxicity, and cognitive changes in breast cancer. J Cancer
Res Ther 2011;7:264-269
3. Lei C, Lin S, Tao W, et al. Association between cerebral microbleeds and cognitive
function: a systematic review. J Neurol Neurosurg Psychiatry 2013;84:693-697
4. Haacke EM, Ye Y. The role of susceptibility weighted imaging in functional MRI.
Neuroimage 2012;62:923-929
5. Gershon RC, Wagster MV, Hendrie HC, et al. NIH toolbox for assessment of neurological
and behavioral function. Neurology 2013;80:S2-6