1. ASNR 2015 Poster# EP-19 Effect of Chemotherapy on Brain Structure and Cognition in Older Women with Breast Cancer: a Brain MRI Study 1 Bihong T. Chen MD. Ph.D., 2 Sunita K. Patel Ph.D., 3 David Utriainen MS., 3 Yongquan Ye Ph.D., 3 Mark Haacke Ph.D., 4 Arti Hurria MD. 1 Department of Diagnostic Radiology, City of Hope Medical Center, Duarte, CA 91010. 2 Department of Population Science, City of Hope Medical Center, Duarte, CA 91010. 3 Department of Radiology, MR Research Facility, Wayne State University, Detroit, MI. 4 Department of Medical Oncology, City of Hope Medical Center, Duarte, CA 91010.

2. Some patients with breast cancer suffer from subjective and objective cognitive deficits during and after chemotherapy, colloquially termed “chemobrain”. 1, 2 12 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 34 Background

3. 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.

4. 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 Toolbox 5 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.

5. Patient Group: Age > 60 Breast Cancer Stage I-III To receive adjuvant or neoadjuvant chemotherapy Geriatric Assessment Cognitive testing Brain fMRI brain Pre-treatment Adjuvant or Neoadjuvant Chemotherapy Toxicity Grading (NCI CTCAE version 4.0) Post-treatment Healthy Controls*: Age ≥ 60 No history of cancer Time point 1Time point 2 Geriatric Assessment Cognitive testing Brain fMRI brain Materials & Methods: Study Design

6. 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.

7. 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.

8. Results Part – 2: Cognitive testing 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 post- treatment changes between patients and healthy controls were not significant. Neuropsychological testing with NIH toolbox for cognition:

9. Results – Part 3: CMB data Two (25%) patients had 1 CMB (example arrow) each in both pre- and post-imaging while no healthy control had CMB. SWIM MIP over 5 slices SWI mIP over 5 slices T1WIT2 FLAIR SWIM = susceptibility weighted imaging and mapping, SWI = susceptibility weighted imaging, m/MIP= maximum /minimum intensity projection

10. Results Part – 4: WMH data White matter hyper-intensity (WMH) was more prevalent in the control group (TP1=3.0+/-4cm 3, TP2=2.7+/-3cm 3 ) compared to the patients (TP1=2.7+/-3cm 3, TP2=1.3+/-1cm 3 ), however 3 of the 4 subjects with greater than 3cm 3 of WMH were older than 71 years (2 controls and 1 patient). Healthy Control#1Healthy Control#2Patient 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.

11. 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+/-75cm 3 Controls TP2=1080+/-78cm 3 Patients TP1=1091+/-61cm 3 Patients TP2=1097+/-67cm 3

12. 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.

13. 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

14. 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