Browsing by Author "Hurria, Arti"
Now showing 1 - 10 of 10
Results Per Page
Sort Options
Item Assessing brain volume changes in older women with breast cancer receiving adjuvant chemotherapy: a brain magnetic resonance imaging pilot study(BMC, 2018-05-02) Chen, Bihong T.; Sethi, Sean K.; Jin, Taihao; Patel, Sunita K.; Ye, Ningrong; Sun, Can-Lan; Rockne, Russell C.; Haacke, E. Mark; Root, James C.; Saykin, Andrew J.; Ahles, Tim A.; Holodny, Andrei I.; Prakash, Neal; Mortimer, Joanne; Waisman, James; Yuan, Yuan; Somlo, George; Li, Daneng; Yang, Richard; Tan, Heidi; Katheria, Vani; Morrison, Rachel; Hurria, Arti; Medicine, School of MedicineBACKGROUND: Cognitive decline is among the most feared treatment-related outcomes of older adults with cancer. The majority of older patients with breast cancer self-report cognitive problems during and after chemotherapy. Prior neuroimaging research has been performed mostly in younger patients with cancer. The purpose of this study was to evaluate longitudinal changes in brain volumes and cognition in older women with breast cancer receiving adjuvant chemotherapy. METHODS: Women aged ≥ 60 years with stage I-III breast cancer receiving adjuvant chemotherapy and age-matched and sex-matched healthy controls were enrolled. All participants underwent neuropsychological testing with the US National Institutes of Health (NIH) Toolbox for Cognition and brain magnetic resonance imaging (MRI) prior to chemotherapy, and again around one month after the last infusion of chemotherapy. Brain volumes were measured using Neuroreader™ software. Longitudinal changes in brain volumes and neuropsychological scores were analyzed utilizing linear mixed models. RESULTS: A total of 16 patients with breast cancer (mean age 67.0, SD 5.39 years) and 14 age-matched and sex-matched healthy controls (mean age 67.8, SD 5.24 years) were included: 7 patients received docetaxel and cyclophosphamide (TC) and 9 received chemotherapy regimens other than TC (non-TC). There were no significant differences in segmented brain volumes between the healthy control group and the chemotherapy group pre-chemotherapy (p > 0.05). Exploratory hypothesis generating analyses focusing on the effect of the chemotherapy regimen demonstrated that the TC group had greater volume reduction in the temporal lobe (change = - 0.26) compared to the non-TC group (change = 0.04, p for interaction = 0.02) and healthy controls (change = 0.08, p for interaction = 0.004). Similarly, the TC group had a decrease in oral reading recognition scores (change = - 6.94) compared to the non-TC group (change = - 1.21, p for interaction = 0.07) and healthy controls (change = 0.09, p for interaction = 0.02). CONCLUSIONS: There were no significant differences in segmented brain volumes between the healthy control group and the chemotherapy group; however, exploratory analyses demonstrated a reduction in both temporal lobe volume and oral reading recognition scores among patients on the TC regimen. These results suggest that different chemotherapy regimens may have differential effects on brain volume and cognition. Future, larger studies focusing on older adults with cancer on different treatment regimens are needed to confirm these findings.Item Cancer-Related Cognitive Outcomes Among Older Breast Cancer Survivors in the Thinking and Living With Cancer Study(ASCO, 2018-11) Mandelblatt, Jeanne S.; Small, Brent J.; Luta, Gheorghe; Hurria, Arti; Jim, Heather; McDonald, Brenna C.; Graham, Deena; Zhou, Xingtao; Clapp, Jonathan; Zhai, Wanting; Breen, Elizabeth; Carroll, Judith E.; Denduluri, Neelima; Dilawari, Asma; Extermann, Martine; Isaacs, Claudine; Jacobsen, Paul B.; Kobayashi, Lindsay C.; Holohan Nudelman, Kelly; Root, James; Stern, Robert A.; Tometich, Danielle; Turner, Raymond; VanMeter, John W.; Saykin, Andrew J.; Ahles, Tim; Radiology and Imaging Sciences, School of MedicinePurpose To determine treatment and aging-related effects on longitudinal cognitive function in older breast cancer survivors. Methods Newly diagnosed nonmetastatic breast cancer survivors (n = 344) and matched controls without cancer (n = 347) 60 years of age and older without dementia or neurologic disease were recruited between August 2010 and December 2015. Data collection occurred during presystemic treatment/control enrollment and at 12 and 24 months through biospecimens; surveys; self-reported Functional Assessment of Cancer Therapy-Cognitive Function; and neuropsychological tests that measured attention, processing speed, and executive function (APE) and learning and memory (LM). Linear mixed-effects models tested two-way interactions of treatment group (control, chemotherapy with or without hormonal therapy, and hormonal therapy) and time and explored three-way interactions of ApoE (ε4+ v not) by group by time; covariates included baseline age, frailty, race, and cognitive reserve. Results Survivors and controls were 60 to 98 years of age, were well educated, and had similar baseline cognitive scores. Treatment was related to longitudinal cognition scores, with survivors who received chemotherapy having increasingly worse APE scores (P = .05) and those initiating hormonal therapy having lower LM scores at 12 months (P = .03) than other groups. These group-by-time differences varied by ApoE genotype, where only ε4+ survivors receiving hormone therapy had short-term decreases in adjusted LM scores (three-way interaction P = .03). For APE, the three-way interaction was not significant (P = .14), but scores were significantly lower for ε4+ survivors exposed to chemotherapy (−0.40; 95% CI, −0.79 to −0.01) at 24 months than ε4+ controls (0.01; 95% CI, 0.16 to 0.18; P < .05). Increasing age was associated with lower baseline scores on all cognitive measures (P < .001); frailty was associated with baseline APE and self-reported decline (P < .001). Conclusion Breast cancer systemic treatment and aging-related phenotypes and genotypes are associated with longitudinal decreases in cognitive function scores in older survivors. These data could inform treatment decision making and survivorship care planning.Item Cognitive effects of cancer and its treatments at the intersection of aging: what do we know; what do we need to know?(Elsevier, 2013-12) Mandelblatt, Jeanne S.; Hurria, Arti; McDonald, Brenna C.; Saykin, Andrew J.; Stern, Robert A.; VanMeter, John W.; McGuckin, Meghan; Traina, Tiffani; Denduluri, Neelima; Turner, Scott; Howard, Darlene; Jacobsen, Paul B.; Ahles, Tim; Department of Radiology and Imaging Sciences, IU School of MedicineThere is a fairly consistent, albeit non-universal body of research documenting cognitive declines after cancer and its treatments. While few of these studies have included subjects aged 65 years and older, it is logical to expect that older patients are at risk of cognitive decline. Here, we use breast cancer as an exemplar disease for inquiry into the intersection of aging and cognitive effects of cancer and its therapies. There are a striking number of common underlying potential biological risks and pathways for the development of cancer, cancer-related cognitive declines, and aging processes, including the development of a frail phenotype. Candidate shared pathways include changes in hormonal milieu, inflammation, oxidative stress, DNA damage and compromised DNA repair, genetic susceptibility, decreased brain blood flow or disruption of the blood-brain barrier, direct neurotoxicity, decreased telomere length, and cell senescence. There also are similar structure and functional changes seen in brain imaging studies of cancer patients and those seen with "normal" aging and Alzheimer's disease. Disentangling the role of these overlapping processes is difficult since they require aged animal models and large samples of older human subjects. From what we do know, frailty and its low cognitive reserve seem to be a clinically useful marker of risk for cognitive decline after cancer and its treatments. This and other results from this review suggest the value of geriatric assessments to identify older patients at the highest risk of cognitive decline. Further research is needed to understand the interactions between aging, genetic predisposition, lifestyle factors, and frailty phenotypes to best identify the subgroups of older patients at greatest risk for decline and to develop behavioral and pharmacological interventions targeting this group. We recommend that basic science and population trials be developed specifically for older hosts with intermediate endpoints of relevance to this group, including cognitive function and trajectories of frailty. Clinicians and their older patients can advance the field by active encouragement of and participation in research designed to improve the care and outcomes of the growing population of older cancer patients.Item Cognitive function prior to systemic therapy and subsequent well-being in older breast cancer survivors: longitudinal findings from the Thinking and Living with Cancer Study(Wiley, 2020-06) Kobayashi, Lindsay C.; Cohen, Harvey Jay; Zhai, Wanting; Zhou, Xingtao; Small, Brent J.; Luta, George; Hurria, Arti; Carroll, Judith; Tometich, Danielle; McDonald, Brenna C.; Graham, Deena; Jim, Heather S.L.; Jacobsen, Paul; Root, James C.; Saykin, Andrew J.; Ahles, Tim A.; Mandelblatt, Jeanne; Radiology and Imaging Sciences, School of MedicineObjective: To investigate the relationships between self-reported and objectively measured cognitive function prior to systemic therapy and subsequent well-being outcomes over 24 months in older breast cancer survivors. Methods: Data were from 397 women aged 60 to 98 diagnosed with non-metastatic breast cancer in the Thinking and Living with Cancer Study recruited from 2010-2016. Cognitive function was measured at baseline (following surgery, prior to systemic therapy) using neuropsychological assessments of attention, processing speed, and executive function (APE), learning and memory (LM), and the self-reported FACT-Cog scale. Well-being was measured using the FACT-G functional, physical, social, and emotional well-being domain scales at baseline and 12 and 24 months later, scaled from 0 (low) to 100 (high). Linear mixed-effects models assessed the relationships between each of baseline APE, LM, and FACT-Cog quartiles with well-being scores over 24 months, adjusted for confounding variables. Results: At baseline, older survivors in the lowest APE, LM, and FACT-Cog score quartiles experienced poorer global well-being than those in the highest quartiles. At 24 months, older survivors tended to improve in well-being, and there were no differences according to baseline APE or LM scores. At 24 months, mean global well-being was 80.3 (95% CI: 76.2-84.3) among those in the lowest vs 86.6 (95% CI: 83.1-90.1) in the highest FACT-cog quartile, a clinically meaningful difference of 6.3 points (95% CI: 1.5-11.1). Conclusions: Among older breast cancer survivors, self-reported, but not objective cognitive impairments, were associated with lower global well-being over the first 2 years of survivorship.Item Cognitive impairment in older patients with breast cancer before systemic therapy: is there an interaction between cancer and comorbidity?(American Society of Clinical Oncology, 2014-06-20) Mandelblatt, Jeanne S.; Stern, Robert A.; Luta, Gheorghe; McGuckin, Meghan; Clapp, Jonathan D.; Hurria, Arti; Jacobsen, Paul B.; Faul, Leigh Anne; Isaacs, Claudine; Denduluri, Neelima; Gavett, Brandon; Traina, Tiffany A.; Johnson, Patricia; Silliman, Rebecca A.; Turner, R. Scott; Howard, Darlene; Van Meter, John W.; Saykin, Andrew J.; Ahles, Tim; Department of Medicine, IU School of MedicinePURPOSE: To determine if older patients with breast cancer have cognitive impairment before systemic therapy. PATIENTS AND METHODS: Participants were patients with newly diagnosed nonmetastatic breast cancer and matched friend or community controls age > 60 years without prior systemic treatment, dementia, or neurologic disease. Participants completed surveys and a 55-minute battery of 17 neuropsychological tests. Biospecimens were obtained for APOE genotyping, and clinical data were abstracted. Neuropsychological test scores were standardized using control means and standard deviations (SDs) and grouped into five domain z scores. Cognitive impairment was defined as any domain z score two SDs below or ≥ two z scores 1.5 SDs below the control mean. Multivariable analyses evaluated pretreatment differences considering age, race, education, and site; comparisons between patient cases also controlled for surgery. RESULTS: The 164 patient cases and 182 controls had similar neuropsychological domain scores. However, among patient cases, those with stage II to III cancers had lower executive function compared with those with stage 0 to I disease, after adjustment (P = .05). The odds of impairment were significantly higher among older, nonwhite, less educated women and those with greater comorbidity, after adjustment. Patient case or control status, anxiety, depression, fatigue, and surgery were not associated with impairment. However, there was an interaction between comorbidity and patient case or control status; comorbidity was strongly associated with impairment among patient cases (adjusted odds ratio, 8.77; 95% CI, 2.06 to 37.4; P = .003) but not among controls (P = .97). Only diabetes and cardiovascular disease were associated with impairment among patient cases. CONCLUSION: There were no overall differences between patients with breast cancer and controls before systemic treatment, but there may be pretreatment cognitive impairment within subgroups of patient cases with greater tumor or comorbidity burden.Item Gray matter density reduction associated with adjuvant chemotherapy in older women with breast cancer(Springer, 2018-11) Chen, Bihong T.; Jin, Taihao; Patel, Sunita K.; Ye, Ningrong; Sun, Can‑Lan; Ma, Huiyan; Rockne, Russell C.; Root, James C.; Saykin, Andrew J.; Ahles, Tim A.; Holodny, Andrei I.; Prakash, Neal; Mortimer, Joanne; Waisman, James; Yuan, Yuan; Li, Daneng; Somlo, George; Vazquez, Jessica; Levi, Abrahm; Tan, Heidi; Yang, Richard; Katheria, Vani; Hurria, Arti; Medicine, School of MedicinePURPOSE: The purpose of this study was to evaluate longitudinal changes in brain gray matter density (GMD) before and after adjuvant chemotherapy in older women with breast cancer. METHODS: We recruited 16 women aged ≥ 60 years with stage I-III breast cancers receiving adjuvant chemotherapy (CT) and 15 age- and sex-matched healthy controls (HC). The CT group underwent brain MRI and the NIH Toolbox for Cognition testing prior to adjuvant chemotherapy (time point 1, TP1) and within 1 month after chemotherapy (time point 2, TP2). The HC group underwent the same assessments at matched intervals. GMD was evaluated with the voxel-based morphometry. RESULTS: The mean age was 67 years in the CT group and 68.5 years in the HC group. There was significant GMD reduction within the chemotherapy group from TP1 to TP2. Compared to the HC group, the CT group displayed statistically significantly greater GMD reductions from TP1 to TP2 in the brain regions involving the left anterior cingulate gyrus, right insula, and left middle temporal gyrus (pFWE(family-wise error)-corrected < 0.05). The baseline GMD in left insula was positively correlated with the baseline list-sorting working memory score in the HC group (pFWE-corrected < 0.05). No correlation was observed for the changes in GMD with the changes in cognitive testing scores from TP1 to TP2 (pFWE-corrected < 0.05). CONCLUSIONS: Our findings indicate that GMD reductions were associated with adjuvant chemotherapy in older women with breast cancer. Future studies are needed to understand the clinical significance of the neuroimaging findings. This study is registered on ClinicalTrials.gov (NCT01992432).Item Phase III Trial Evaluating Letrozole As First-Line Endocrine Therapy With or Without Bevacizumab for the Treatment of Postmenopausal Women With Hormone Receptor-Positive Advanced-Stage Breast Cancer: CALGB 40503 (Alliance)(American Society of Clinical Oncology, 2016-08-01) Dickler, Maura N.; Barry, William T.; Cirrincione, Constance T.; Ellis, Matthew J.; Moynahan, Mary Ellen; Innocenti, Federico; Hurria, Arti; Rugo, Hope S.; Lake, Diana E.; Hahn, Olwen; Schneider, Bryan P.; Tripathy, Debasish; Carey, Lisa A.; Winer, Eric P.; Hudis, Clifford A.; Medicine, School of MedicinePURPOSE: To investigate whether anti-vascular endothelial growth factor therapy with bevacizumab prolongs progression-free survival (PFS) when added to first-line letrozole as treatment of hormone receptor-positive metastatic breast cancer (MBC). PATIENTS AND METHODS: Women with hormone receptor-positive MBC were randomly assigned 1:1 in a multicenter, open-label, phase III trial of letrozole (2.5 mg orally per day) with or without bevacizumab (15 mg/kg intravenously once every 3 weeks) within strata defined by measurable disease and disease-free interval. This trial had 90% power to detect a 50% improvement in median PFS from 6 to 9 months. Using a one-sided α = .025, a target sample size of 352 patients was planned. RESULTS: From May 2008 to November 2011, 350 women were recruited; 343 received treatment and were observed for efficacy and safety. Median age was 58 years (range, 25 to 87 years). Sixty-two percent had measurable disease, and 45% had de novo MBC. At a median follow-up of 39 months, the addition of bevacizumab resulted in a significant reduction in the hazard of progression (hazard ratio, 0.75; 95% CI, 0.59 to 0.96; P = .016) and a prolongation in median PFS from 15.6 months with letrozole to 20.2 months with letrozole plus bevacizumab. There was no significant difference in overall survival (hazard ratio, 0.87; 95% CI, 0.65 to 1.18; P = .188), with median overall survival of 43.9 months with letrozole versus 47.2 months with letrozole plus bevacizumab. The largest increases in incidence of grade 3 to 4 treatment-related toxicities with the addition of bevacizumab were hypertension (24% v 2%) and proteinuria (11% v 0%). CONCLUSION: The addition of bevacizumab to letrozole improved PFS in hormone receptor-positive MBC, but this benefit was associated with a markedly increased risk of grade 3 to 4 toxicities. Research on predictive markers will be required to clarify the role of bevacizumab in this setting.Item Pre-treatment psychoneurological symptoms and their association with longitudinal cognitive function and quality of life in older breast cancer survivors(Elsevier, 2019-03) Tometich, Danielle; Small, Brent J.; Carroll, Judith E.; Zhai, Wanting; Luta, George; Zhou, Xingtao; Kobayashi, Lindsay C.; Ahles, Tim; Saykin, Andrew J.; Clapp, Jonathan D.; Jim, Heather S. L.; Jacobsen, Paul B.; Hurria, Arti; Graham, Deena; McDonald, Brenna C.; Denduluri, Neelima; Extermann, Martine; Isaacs, Claudine; Dilawari, Asma; Root, James; Rini, Christine; Mandelblatt, Jeanne S.; Radiology and Imaging Sciences, School of MedicineContext Symptoms affect quality of life (QOL), functional status, and cognitive function in cancer survivors, but older survivors are understudied. Objectives To identify prototypical pre-systemic therapy psychoneurological symptom clusters among older breast cancer survivors, and determine whether these symptom clusters predicted cognition and QOL over time. Methods Women with newly diagnosed non-metastatic breast cancer (n=319) and matched non-cancer controls (n=347) aged 60+ completed questionnaires and neuropsychological tests before systemic therapy and 12- and 24-months later. Latent class analysis identified clusters of survivors based upon their pre-therapy depression, anxiety, fatigue, sleep disturbance, and pain. Linear mixed-effects models examined changes in objective cognition, perceived cognition, and functional status (instrumental activities of daily living (IADL) disability, functional well-being, and breast cancer-specific QOL) by group, controlling for covariates. Results Nearly one-fifth of older survivors were classified as having a high pre-therapy symptoms (n=51; 16%); the remainder had a low symptoms (n=268; 84%); both groups improved over time on all outcomes. However, compared to the low symptom group and controls, survivors with high symptoms had lower baseline objective cognition and lower perceived cognition at baseline and 24-months, lower functional well-being at baseline and 12-months, greater IADL disability at baseline, and lower breast cancer-specific QOL at all time points (all p<0.05). Conclusion Nearly one-fifth of older breast cancer survivors had high psychoneurological symptoms at diagnosis, which, predict clinically meaningful decrements in perceived cognition and function in the first 24 months post-diagnosis. Pre-treatment psychoneurological symptom clusters could identify survivors for monitoring or intervention.Item Subcortical brain iron deposition and cognitive performance in older women with breast cancer receiving adjuvant chemotherapy: A pilot MRI study(Elsevier, 2018-12) Chen, Bihong T.; Ghassaban, Kiarash; Jin, Taihao; Patel, Sunita K.; Ye, Ningrong; Sun, Can-Lan; Kim, Heeyoung; Rockne, Russell C.; Haacke, E. Mark; Root, James C.; Saykin, Andrew J.; Ahles, Tim A.; Holodny, Andrei I.; Prakash, Neal; Mortimer, Joanne; Waisman, James; Yuan, Yuan; Somlo, George; Li, Daneng; Yang, Daneng; Yang, Richard; Tan, Heidi; Katheria, Vani; Morrison, Rachel; Hurria, Arti; Radiology and Imaging Sciences, School of MedicineAs the number of older adults in the U.S. increases, so too will the incidence of cancer and cancer-related cognitive impairment (CRCI). However, the exact underlying biological mechanism for CRCI is not yet well understood. We utilized susceptibility-weighted imaging with quantitative susceptibility mapping, a non-invasive MRI-based technique, to assess longitudinal iron deposition in subcortical gray matter structures and evaluate its association with cognitive performance in women age 60+ with breast cancer receiving adjuvant chemotherapy and age-matched women without breast cancer as controls. Brain MRI scans and neurocognitive scores from the NIH Toolbox for Cognition were obtained before chemotherapy (time point 1) and within one month after the last infusion of chemotherapy for the patients and at matched intervals for the controls (time point 2). There were 14 patients age 60+ with breast cancer (mean age 66.3 ± 5.3 years) and 13 controls (mean age 68.2 ± 6.1 years) included in this study. Brain iron increased as age increased. There were no significant between- or within- group differences in neurocognitive scores or iron deposition at time point 1 or between time points 1 and 2 (p > 0.01). However, there was a negative correlation between iron in the globus pallidus and the fluid cognition composite scores in the control group at time point 1 (r = −0.71; p < 0.01), but not in the chemotherapy group. Baseline iron in the putamen was negatively associated with changes in the oral reading recognition scores in the control group (r = 0.74, p < 0.01), but not in the chemotherapy group. Brain iron assessment did not indicate cancer or chemotherapy related short-term differences, yet some associations with cognition were observed. Studies with larger samples and longer follow-up intervals are warranted.Item Symptom burden among older breast cancer survivors: The Thinking and Living With Cancer (TLC) study(Wiley, 2020-03-15) Mandelblatt, Jeanne S.; Zhai, Wanting; Ahn, Jaeil; Small, Brent J.; Ahles, Tim A.; Carroll, Judith E.; Denduluri, Neelima; Dilawari, Asma; Extermann, Martine; Graham, Deena; Hurria, Arti; Isaacs, Claudine; Jacobsen, Paul B.; Jim, Heather S. L.; Luta, George; McDonald, Brenna C.; Patel, Sunita K.; Root, James C.; Saykin, Andrew J.; Tometich, Danielle B.; Zhou, Xingtao; Cohen, Harvey J.; Radiology and Imaging Sciences, School of MedicineBackground: Little is known about longitudinal symptom burden and its consequences for well-being, and if lifestyle moderates burden in older survivors. Methods: We report on 36-month data from survivors 60+ with newly diagnosed non-metastatic breast cancer and non-cancer controls recruited August 2010-June 2016. Symptom burden was a sum of self-reported symptoms/diseases: pain (yes/no), fatigue (FACT-fatigue), cognitive (FACT-cog), sleep problems (yes/no), depression (CES-D), anxiety (STAI), and cardiac problems and neuropathy (yes/no). Well-being was measured using the FACT-G, scaled from 0–100. Lifestyle included smoking, alcohol use, BMI, physical activity, and leisure activities. Mixed models assessed relationships between treatment group (chemotherapy +/− hormonal, hormonal only, control) and symptom burden, lifestyle, and covariates. Separate models tested the effects of fluctuations in symptom burden and lifestyle on function. Results: All groups reported high baseline symptoms, and levels remained high over time; survivor-control differences were most notable for cognitive and sleep problems, anxiety, and neuropathy. The adjusted burden score was highest among chemotherapy-exposed survivors, followed by hormonal therapy vs. controls (p<.001). Burden score was related to physical, emotional, and functional well-being (e.g., survivors with lower vs. higher burden scores had 12.4-point higher physical well-being score). The composite lifestyle score was not related to symptom burden or well-being, but physical activity was significantly associated with each outcome (<.005). Conclusions: Cancer and its treatments are associated with a higher level of actionable symptoms and greater loss of well-being over time in older breast cancer survivors than comparable non-cancer populations, suggesting the need for surveillance and opportunities for intervention.