INTRODUCTION:The American Society of Clinical Oncology guidelines recommend geriatric assessment (GA)-guided interventions to inform care for older adults with cancer. GA-guided intervention delivery to lower-resourced settings has been limited. We assessed the feasibility of implementing GA-guided supportive care (GAIN-S) via telehealth in a lower-resourced setting. MATERIALS AND METHODS:A quality improvement study was conducted in a low-resourced community oncology practice in the Mojave Desert. Eligible participants were 65+ years with a diagnosis of cancer, newly initiating care at the clinic. At baseline, patients completed: GA, SupportScreen, and the Fulmer SPICES assessment. A geriatric oncology nurse practitioner (GNP) reviewed GA results and implemented GAIN-S via telehealth between April 2020 and January 2023. Key outputs measured included: number of patients who completed GAIN-S; number of referrals to supportive care services and completion rate; and patient satisfaction with telehealth visits. Participants' demographics, distance traveled for care, type of cancer, stage, treatment, and telehealth satisfaction items were summarized using descriptive statistics. To evaluate the implementation process, run charts were utilized. RESULTS:A total of 253 patients (median age 72, 62% non-Hispanic White, 22% lived 60+ miles from the clinic, 40% had stage III or greater, 30% received chemotherapy) completed assessments. Two hundred forty-two had initial visits with the GNP, 197 via tele-video, and 45 via telephone for a total telehealth encounter participation rate of 96%. The GNP reviewed vulnerabilities with 231 patients and generated 483 accepted referrals for supportive care services, of which over 88% of services were completed. The highest numbers of accepted referrals were to pharmacy (177), social work (154), occupational therapy (79), and physical therapy (55). Over 92% of patients were satisfied with telehealth-based GAIN-S for ease of visit, access to care with their provider, and telehealth use. DISCUSSION:Telehealth-based GAIN-S is feasible and acceptable, providing accessible healthcare to older patients with cancer in a lower-resourced community setting. This approach highlights telehealth delivery of GAIN-S in our clinical enterprise and has implications for other such settings.

1582 Background: The ASCO Global Guideline recommends routine geriatric assessment (GA) for adults aged ≥65 years with cancer to identify vulnerabilities beyond standard oncology evaluation and guide tailored management. However, real-world implementation of GA-guided interventions in low-resource settings remains limited. Building on prior feasibility work in private (PRI) oncology settings, we evaluated the feasibility and implementation of a remote, multidisciplinary GA-guided intervention in public (PUB) oncology settings in Brazil. Methods: We conducted a prospective feasibility and implementation study in PUB settings, with contextual reference to prior PRI experience. Patients aged ≥65 years initiating chemotherapy underwent baseline GA assessing functional status, depressive symptoms (GDS), cognitive screening (Mini-Cog), chemotherapy toxicity risk (CARG), nutritional status, and quality of life (FACT-G), with repeat assessment at 12 weeks. Identified impairments prompted referral to telehealth interventions (geriatrics, nutrition, psychology/psychiatry, exercise). Feasibility outcomes included recruitment, GA completion, referral recommendations, and follow-up retention. Implementation barriers in PUB settings were prospectively documented. Results: A total of 109 patients were included (PRI n=61; PUB n=48). The PUB cohort was younger (mean age 72 vs 76), included a higher proportion of Black participants (58% vs 44%), had lower education (no/limited 19% and elementary school 50% vs college degree 47%), and more advanced disease (92% stage III-IV vs 54% stage IV). Baseline geriatric vulnerability was similar (median CARG 6 vs 7, GDS 2); weight loss was more frequent in PUB (54% vs 36%). Quality of life was lower in PUB (FACT-G -5 points). GA identified actionable vulnerabilities, with 21% referred to ≥1 specialist (vs 33% in PRI) and 44% to ≥2 specialists (vs 28% in PRI). Key challenges included delayed recruitment, limited digital literacy (63%), restricted videoconferencing (73%), delays in nutritional supplements (38%), and exercise adaptation (50%), prompting ongoing, context-specific adaptations. Conclusions: Remote GA delivery and identification of actionable vulnerabilities were feasible in PUB settings in Brazil. Similar geriatric vulnerability profiles and characterization of implementation barriers support the scalability of GA-guided care in low-resource settings. Clinical trial information: NCT07084454 .

Purpose: This study aimed to investigate alterations in brain white matter fiber bundle integrity among older long-term breast cancer survivors treated with chemotherapy, with a focus on identifying potential neural correlates of cancer-related cognitive impairment (CRCI). Methods: Women aged 65 years and older were prospectively enrolled and divided into three groups: breast cancer survivors 5 to 15 years after chemotherapy treatment (C+), breast cancer survivors without chemotherapy (C-), and age-sex-matched healthy controls (HC). Participants underwent brain MRI with diffusion tensor imaging and cognitive testing at time point 1 (TP1) upon enrollment and again after two years at time point 2 (TP2). White matter fiber tract integrity was assessed using fractional anisotropy-based (FA) tractography across 80 major fiber bundles in the brain. Results: Over the two-year period, both C+ and C- groups exhibited significant reductions in white matter integrity with FA reductions noted in several fiber tracts, including the left inferior fronto-occipital fasciculus (C+ group: p < 0.01; C- group: p = 0.01), right inferior fronto-occipital fasciculus (p < 0.01), left inferior longitudinal fasciculus (C+ group: p < 0.01; C- group: p = 0.04), right inferior longitudinal fasciculus (C+ group: p = 0.04; C- group: p = 0.02), right vertical occipital fasciculus (C+ group: p < 0.02; C- group: p = 0.01), left anterior corticostriatal tracts (C+ group: p < 0.01; C- group: p = 0.02), right anterior corticostriatal tracts (C+ group: p = 0.01; C- group: p = 0.02), anterior commissure (C+ group: p = 0.01; C- group: p = 0.03), and forceps minor (C+ group: p = 0.03; C- group: p = 0.01). In addition, FA reductions were noted in the left superior longitudinal fasciculus (p < 0.01), uncinate fasciculus (p = 0.01), thalamic radiation (p = 0.04), left optic radiations (p = 0.04) and right optic radiations (p = 0.03) in the C+ group only. No significant changes over time were detected in the HC group (p > 0.05). The fiber tract changes were considered statistically significant at a threshold of p < 0.05, with family-wise error (FWE) correction. Significant positive correlation was found between the longitudinal changes in the right inferior fronto-occipital fasciculus and the fluid composite cognition score in the C+ group (R = 0.65 and p = 0.03; Pearson's correlation). Conclusions: This study showed continued white matter fiber tract alterations in the older long-term breast cancer survivors who may have cognitive difficulties years after chemotherapy. Diffusion tensor imaging may provide valuable insights into the white matter microstructural correlates of CRCI in older cancer survivors.

Among older adults with early breast cancer, the risk of chemotoxicity can vary widely despite similar chronological age. Here, we evaluated whether epigenetic indicators of biological age can stratify the risk of chemotoxicity in this population. In a prospective study of 394 women age > 65 with stage I–III breast cancer treated with neo/adjuvant chemotherapy, we analyzed peripheral blood DNA methylation patterns to estimate epigenetic age acceleration (EAA) before chemotherapy. We tested five epigenetic clocks. The primary endpoint was grade 2+ chemotoxicity (yes/no, yes defined as any grade 2+ toxicity attributed to chemotherapy). Using multivariable logistic regression, we examined the association between EAA and grade 2+ chemotoxicity, adjusting for demographic, clinical, and geriatric covariates. We also evaluated the relationship between EAA and individual grade 2+ toxicities. The median (range) pre-treatment chronological age was 70 years (65–85); 65

PURPOSE:Older adults with early-stage breast cancer (EBC) receiving neo/adjuvant chemotherapy frequently discontinue treatment early. However, the incidence, risk factors, and survival implications of early discontinuation remain poorly understood. METHODS:This is a post-hoc analysis of 501 older adults (aged≥65) with EBC treated with neo/adjuvant chemotherapy from the Hurria Older PatiEnts (HOPE) Study. Prior to chemotherapy, we collected sociodemographic, clinical, and geriatric assessment characteristics. The primary outcome was early discontinuation (yes/no), defined as not completing all planned chemotherapy. We used multivariable logistic regression with stepwise selection to identify pretreatment risk factors and the Kaplan-Meier method to evaluate the impact of discontinuation on survival. RESULTS:Of 501 participants (median [range] age, 70 [65-86] years), 113 (23%) had early discontinuation. After multivariable analysis, ≥1 fall within 6 months (odds ratio [OR] = 2.06, 95% CI: 1.11-3.81, p = 0.02) and an activity of daily living score <85 (OR = 2.00, 95% CI: 1.26-3.18, p = 0.003) were identified as risk factors for early discontinuation. Participants with both risk factors were at highest risk (OR = 4.61, 95% CI: 2.18-9.79, p < 0.001). With a median follow up of 4.3 years, early discontinuation was not associated with worse overall or breast cancer-specific survival but was associated with higher non-breast cancer-specific mortality (Hazard Ratio = 2.94, 95% CI 1.22-7.07, p = 0.02). CONCLUSION:In this cohort of older adults with EBC, nearly one-quarter discontinued chemotherapy early. Early discontinuation was associated with increased non-cancer related mortality but not cancer-related mortality, emphasizing the importance of identifying high-risk older adults and optimizing treatment delivery.

Older adults with early breast cancer can have very different risks of chemotoxicity despite similar chronological age. This heterogeneity may be due to differences in biological age. However, few studies have evaluated whether epigenetic indicators of biological age can stratify the risk of chemotoxicity in older adults with early breast cancer. In a prospective multicenter study of 394 adults age >65 with stage I-III breast cancer treated with neo/adjuvant chemo, we analyzed DNA methylation patterns from peripheral blood to estimate epigenetic age acceleration (EAA) prior to chemo. We tested three generations of epigenetic age algorithms (1st gen: Horvath and Hannum; 2nd gen: PhenoAge and GrimAge; 3rd gen: DunedinPACE). We calculated EAA as the residual that results from regressing epigenetic age on chronological age. The primary endpoint was grade 2+ chemotoxicity (yes/no, yes defined as any grade 2+ toxicity attributed to chemo). Using multivariable logistic regression, we examined the association between EAA (analyzed as continuous and categorical [quartiles] variables) and grade 2+ chemotoxicity, adjusting for demographic, geriatric, and clinical covariates. The median (range) pre-treatment chronological age was 70 (65-85), 65% had stage II/III disease, 38% had anthracycline, and 75% received G-CSF prophylaxis. A total of 334 (84.8%) participants experienced a grade 2+ toxicity. After adjusting for age, cell composition, stage, race/ethnicity, education, regimen, organ function, and geriatric assessment variables, there was no significant association between the measures of EAA and grade 2+ chemotoxicity (Table). In this cohort of older adults with early breast cancer, there was no significant association between pre-treatment EAA and grade 2+ chemotoxicity. Further research is needed to examine how measures of biological age can be translated to the clinical care of older patients with breast cancer. Jingran Ji, Canlan Sun, Marla Lipsyc-Sharf, Nikita V. Baclig, Yulia A. Zektser, Ali Al Saleem, Joseph D. Olivera, Kelly S. Synold, Lauren R. Zelman, Alexandra M. Binder, Mina S. Sedrak. Epigenetic age acceleration measures and chemotoxicity in older adults with early breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 623.

Our group previously showed that p16INK4a (p16) expression, a biomarker of senescence (a fundamental process of aging), increases after adjuvant breast cancer chemo. However, no study has examined whether this increase in p16 is driven by cancer, chemo, or both. Here, we compare the change in p16 between older adults with early breast cancer who receive chemo, those who do not, and those without cancer. We prospectively recruited 701 adults age ≥65 with stage I-III breast cancer (composed of three age-matched cohorts: 501 treated with chemo [BC chemo], 100 treated without chemo [BC control]), and 100 without cancer (NC control). Sociodemographic, functional, and clinical characteristics were collected at baseline. The p16 level in peripheral blood CD3+ T lymphocytes was obtained at two time points: ≤14 days pre-chemo (T1) and ≤30 days post-chemo (or at matched time points in the BC and NC control groups, T2). The primary endpoint was the mean ∆p16 level from T1 to T2. Data was analyzed using descriptive statistics, t-tests, and analysis of variance (ANOVA). There were no differences in T1 age, race/ethnicity, education, comorbidities, or functional status across the three groups. At T1, there was no difference in mean p16 levels across the three groups (p=0.06) (Table). At T2, the BC chemo group had a significantly higher mean p16 level compared to the BC and NC control groups (p<0.01). The mean ∆p16 levels from T1 to T2 were significantly different among the three groups (p=0.04). The BC chemo group had a 15% increase in mean ∆p16 from T1 to T2 (p<0.01), while the BC and NC control groups had no significant change. In a cohort of older adults with early breast cancer, the combination of breast cancer and chemo led to increases in p16 levels. Further independent validation of these findings is needed to understand the role of senescence in older adults with early breast cancer treated with chemo. Chaiyaporn C. Vatanatham, Jingran Ji, Canlan Sun, Marla D. Lipsyc-Sharf, Nikita V. Baclig, Yuliya A. Zektser, Ali Al Saleem, Joseph D. Olivera, Kelly S. Synold, Lauren R. Zelman, Hyman B. Muss, Mina S. Sedrak. Changes in the senescence biomarker p16INK4a among older adults with early breast cancer treated with and without chemotherapy and non-cancer controls [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 621.

Limited health literacy is associated with frailty and poor outcomes among older adults, but data linking cancer health literacy to frailty in older adults with cancer are limited, especially in low-resource settings. We conducted a preliminary analysis using interim data from the ongoing geriatric assessment-guided intervention and supportive care trial via the multi-institutional Geriatric Oncology Therapy Optimization program (GAIN-S GOTO) to examine this association. GAIN-S is a single institution randomized controlled trial (RCT) within the Cancer and Aging Research Group (CARG)- GOTO initiative, delivering geriatric assessment (GA)–guided intervention via telehealth to support oncology decision-making in low-resource community practices. Eligible participants were ≥65 years with a new cancer diagnosis initiating therapy. Before treatment, patients completed a GA and the 6-item Cancer Health Literacy Test (CHLT-6). Participants with fewer than 5 correct answers were classified as limited. Frailty was measured using the Deficit Accumulation Index (DAI; range 0-1) based on the GA and categorized as robust (<0.2), prefrail (0.2–0.34), or frail (≥0.35). We used multinomial and ordinal logistic regression to examine the association between cancer health literacy and frailty. Analyses were performed in SAS 9.4, with two-sided p-values <0.05 considered significant. Among 91 participants (median age 71, range 65–88), 65% were female. The most common cancers were lung (n=17), breast (n=13), endometrial (n=11), and colorectal (n=10). Forty-three (47%) had stage I–III disease and 48 (53%) had stage IV. Thirty-nine (43%) had a high school education or less, 62 (68%) were White, and 50 (55%) were married. Overall, 21 (23%) were classified as having limited cancer health literacy. Limited cancer health literacy was more common among those with lower education (39% vs. 12%, p=0.003). Based on DAI, 33 (36%) were robust, 40 (44%) prefrail, and 18 (20%) frail. In multivariable multinomial logistic regression, limited cancer health literacy was associated with significantly higher odds of frailty (OR=4.7, 95% CI: 1.06–21.2, p=0.04) and non-significantly higher odds of prefrailty (OR=2.16, 95% CI: 0.58–8.10, p=0.17) after adjusting for age and education. Ordinal logistic regression showed a significant trend toward greater frailty severity associated with limited cancer health literacy (p=0.04). Limited cancer health literacy was associated with higher frailty among older adults with cancer in low-resource settings participating in a clinical trial. Incorporating cancer health literacy evaluation into geriatric assessment may help identify vulnerable patients with cancer and guide supportive interventions. These findings have implications for patient centered equitable cancer care and clinical trial engagement among older adults. Future directions include identifying whether adding cancer health literacy assessment enhances the effectiveness of geriatric assessment to improve cancer treatment outcomes. Tanyanika Phillips, Can-Lan Sun, Heeyoung Kim, Leana Cabrera Chien, Africa Robison, Su Su Soe San, Ty Lee, Vani Katheria, William Dale. Preliminary findings on cancer health literacy and frailty in older adults with cancer: Insights from the ongoing GAIN-S GOTO trial [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr B044.

11040 Background: Older adults with early breast cancer are a heterogenous population with varying physiologic and functional age. Pretreatment frailty may help better characterize this heterogenous population compared to chronological age. We investigated the association between pretreatment frailty and clinical outcomes in older adults with early breast cancer treated with chemo. Methods: We leveraged a prospective cohort of 499 adults age ≥65 with stage I-III breast cancer undergoing treatment with neo/adjuvant chemo (R01AG037037). Pretreatment frailty status was determined using a Deficit Accumulation Index, which categorized patients as robust vs. prefrail/frail. Clinical outcomes included grade 3+ toxicity, dose reduction, treatment delay, early chemo discontinuation, hospitalization, and survival (overall, breast cancer related, and non-breast cancer related). We conducted a multivariable analysis evaluating the association between baseline frailty status (robust vs. prefrail/frail) and these outcomes, adjusting for age, race/ethnicity, stage, and regimen. Results: The median (range) age was 70 (65-86) years, 65% had stage II/III disease, and 38% received anthracycline. At baseline, 21% were prefrail/frail and 79% were robust. In total, 46% had a grade 3+ toxicity, 24% had a dose reduction, 26% had a treatment delay, 22% had early chemo discontinuation, and 23% were hospitalized. After multivariable analysis, prefrail/frail participants had greater odds of having grade 3+ toxicity (odds ratio [OR]=2.70, 95% CI, 1.66-4.40), dose reduction (OR=1.87, 95% CI 1.12-3.15), treatment delay (OR=1.85, 95% CI 1.10-3.13), and early chemo discontinuation (OR=1.76, 95% CI 1.05-2.95) compared to robust participants. Prefrail/frail participants had a higher likelihood of non-breast cancer related death (hazard ratio=2.56, 95% CI 1.08-6.05) compared to robust participants. There were no associations between frailty and hospitalizations, overall survival, and breast cancer related mortality. Conclusions: In this cohort of older adults with early breast cancer, participants who were prefrail/frail pretreatment had an increased risk of grade 3+ toxicity, dose reduction, treatment delay, early chemo discontinuation, and non-breast cancer related death. Pretreatment frailty assessments may improve risk stratification of older adults with early breast cancer and guide treatment decision-making. Clinical trial information: NCT01472094 . Clinical outcomes in older adults with early breast cancer, odds ratio (95% CI).* Frailty Status Grade 3+ Tox (n=229) Dose Reduction (n=120) Treatment Delay (n=132) Early Discontinuation (n=111) Hospitalization (n=115) Robust 1.00 1.00 1.00 1.00 1.00 Prefrail/Frail 2.70 (1.66-4.40) 1.87 (1.12-3.15) 1.85 (1.10-3.13) 1.76 (1.05-2.95) 1.61 (0.96-2.69) *Adjusted for age, race/ethnicity, stage, and regimen.

12135 Background: Epigenetic clocks are blood-based biomarkers developed to predict biological age and mortality risk from DNA methylation data. Here, we investigated the association between epigenetic clocks and grade 2+ chemotoxicities, given that low grade toxicity has significant clinical impact in older adults with breast cancer. Methods: This was a secondary analysis of a prospective cohort of 394 adults age ≥65 with stage I-III breast cancer who completed treatment with neo/adjuvant chemo. We analyzed peripheral blood DNA methylation to estimate epigenetic age acceleration (EAA) prior to chemo. We estimated EAA using three generations of epigenetic clocks (1st gen: Horvath and Hannum; 2nd gen: PhenoAge and GrimAge; 3rd gen: DunedinPACE). Our outcomes of interest were the five most frequently reported grade 2+ chemotoxicities. Using multivariable logistic regression, we examined the association between EAA (as continuous variables) and the chemotoxicities of interest, adjusting for age, stage, race/ethnicity, education, regimen, organ function, cell composition, and geriatric assessment variables. Results: The median (range) chronological age of the participants was 70 (65-85). Most (65%) had stage II/III disease, 38% received anthracycline, and 75% received G-CSF prophylaxis. A total of 334 (84.8%) participants experienced a grade 2+ toxicity. The five most common grade 2+ toxicities were fatigue (34%), anemia (31%), infection (30%), neuropathy (20%), and diarrhea (13%). On multivariable analysis, we observed an association between pretreatment GrimAge and infection (OR=1.35, 95% CI 1.03-1.77, p=0.03) as well as DunedinPACE and diarrhea (OR=1.43, 95% CI 1.01-2.03, p=0.04). Conclusions: In this study of older adults with early breast cancer, we saw an association between some measures of EAA and select grade 2+ toxicities. Further research is needed to examine how measures of biological age can guide the care of older adults with early breast cancer. Clinical trial information: NCT01472094 . Grade 2+ chemotoxicity in older adults with early breast cancer, odds ratio (95% CI). Measures of EAA* Fatigue(n=134) Anemia(n=121) Infection(n=120) Neuropathy(n=77) Diarrhea(n=53) First gen Horvath 0.86 (0.67-1.10) 0.97 (0.75-1.26) 0.95 (0.75-1.22) 1.22 (0.91-1.65) 1.02 (0.74 -1.41) Hannum 0.90 (0.69-1.16) 1.14 (0.86-1.50) 1.03 (0.79-1.33) 1.15 (0.84-1.56) 0.81 (0.56-1.17) Second gen PhenoAge 1.13 (0.86-1.48) 1.10 (0.81-1.48) 1.02 (0.77-1.35) 1.22 (0.88-1.69) 1.10 (0.76-1.60) GrimAge 1.11 (0.86-1.44) 1.17 (0.88-1.56) 1.35 (1.03-1.77) 1.04 (0.76-1.43) 1.39 (0.98-1.96) Third gen DunedinPACE 1.24 (0.96-1.61) 1.09 (0.82-1.44) 1.06 (0.81-1.38) 1.14 (0.83-1.56) 1.43 (1.01-2.03) *The first and second gen clocks are in chronologic years and DunedinPACE is in biological year per chronologic year. OR adjusted for age, stage, race/ethnicity, education, regimen, organ function, cell composition, and geriatric assessment variables.

12122 Background: Chemotherapy is thought to accelerate aging by disrupting fundamental processes of aging such as cellular senescence. Senescence is a state of terminal cell cycle arrest that is linked to increased inflammation, tissue damage, and impaired regeneration. In older adults with early breast cancer, treatment with neo/adjuvant chemotherapy is associated with persistent increases in circulating p16 INK4a (p16) expression, an established biomarker of senescence. However, it remains unknown whether higher levels of p16 correlate with clinically meaningful aging outcomes, such as physical function, in older adults with early breast cancer. Methods: We analyzed a prospective cohort of 501 adults age >65 with stage I-III breast cancer receiving neo/adjuvant chemotherapy. We assessed physical function using the timed up and go test (TUG), at two time points: pre-chemotherapy (T1) and post-chemotherapy (T2). The TUG score was measured as the time (in seconds) a participant takes to stand up from a standard armchair, walk 3 meters, turn around, walk back to the chair, and sit down. We collected blood at T1 and quantified p16 expression levels in circulating CD3+ T lymphocytes. Expression of p16 was determined using TaqMan quantitative reverse-transcription polymerase chain reaction. We calculated the Spearman correlations to examine the relationship between blood p16 levels at T1 with TUG score at T1, at T2, and change in individual TUG score from T1 to T2. Results: The median age of participants was 70 years (range 65-86). The majority (64.4%) had stage II/III disease and 58.1% received an anthracycline. Baseline TUG scores were available for 467 participants and baseline p16 data were available for 317 participants. The mean baseline p16 level was 10.2 log 2 p16 units (SD = 0.9). Mean TUG scores were 11.4 sec (SD = 4.6) at T1 and 11.5 sec (SD = 5.3) at T2. The mean change in TUG score from T1 to T2 was 0.3 (SD = 4.2). There was no significant correlation observed between p16 and TUG score at T1 (r = 0.11, p = 0.05), T2 (r = 0.06, p = 0.36), or the change in TUG score from T1 to T2 (r = 0, p = 0.99). Conclusions: In this cohort of older adults with early breast cancer treated with neo/adjuvant chemotherapy, we did not find a correlation between pretreatment p16 and physical function as measured by TUG. Future studies are needed to understand the role of biological aging markers in improving precision risk assessment of treatment toxicity in older adults with cancer. Clinical trial information: NCT01472094 .

BACKGROUND:Older women with breast cancer frequently experience toxicity-related hospitalizations during adjuvant chemotherapy. Although the geriatric assessment can identify those at risk, its use in clinic remains limited. One simple, low-cost marker of vulnerability in older persons is fall history. Here, the authors examined whether falls prechemotherapy can identify older women at risk for toxicity-related hospitalization during adjuvant chemotherapy for breast cancer.METHODS:In a prospective study of women >65 years old with stage I-III breast cancer treated with adjuvant chemotherapy, the authors assessed baseline falls in the past 6 months as a categorical variable: no fall, one fall, and more than one fall. The primary end point was incident hospitalization during chemotherapy attributable to toxicity. Multivariable logistic regression was used to examine the association between falls and toxicity-related hospitalization, adjusting for sociodemographic, disease, and geriatric covariates.RESULTS:Of the 497 participants, 60 (12.1%) reported falling before chemotherapy, and 114 (22.9%) had one or more toxicity-related hospitalizations. After adjusting for sociodemographic, disease, and geriatric characteristics, women who fell more than once within 6 months before chemotherapy had greater odds of being hospitalized from toxicity during chemotherapy compared to women who did not fall (50.0% vs. 20.8% experienced toxicity-related hospitalization, odds ratio, 4.38; 95% confidence interval, 1.66-11.54, p = .003).CONCLUSIONS:In this cohort of older women with early breast cancer, women who experienced more than one fall before chemotherapy had an over 4-fold increased risk of toxicity-related hospitalization during chemotherapy, independent of sociodemographic, disease, and geriatric factors.

BACKGROUND:Depression and anxiety are prevalent in older adults with cancer but are often undertreated. Older adults are also at increased risk of chemotherapy toxicity (CT). This study evaluated the impact of depression and anxiety symptoms on severe CT risk in older adults with cancer. METHODS:This is a secondary analysis of a randomized trial (2:1) evaluating geriatric assessment-driven intervention (GAIN) versus standard of care (SOC) to reduce grade 3+ CT in older adults with cancer. Mental health was assessed via the Mental Health Inventory 13. CT was graded by National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. RESULTS:A total of 605 patients enrolled (402 GAIN; 203 SOC). Overall, 35% were depressed and 47% were anxious. Patients with depression had increased CT in the SOC arm (70.7% vs. 54.3%; p = .02) but not in the GAIN arm (54.3% vs. 48.5%; p = .27). CT was more likely in SOC patients with depression (odds ratio [OR], 2.03; 95% CI, 1.10-3.72). This association persisted after adjusting for Cancer and Aging Research Group toxicity score (OR, 1.98; 95% CI, 1.07-3.65) and for demographic, disease, and treatment factors (OR, 2.00; 95% CI, 1.03-3.85). Depression and CT were not associated in the GAIN arm (OR, 1.26; 95% CI, 0.84-1.91). Anxiety and CT were not associated in either arm. CONCLUSIONS:Elevated depression symptoms are associated with increased risk of severe CT in older adults with cancer, which was mitigated with GAIN. This suggests that treating depression symptoms may lower toxicity risk. Future studies are needed to confirm and investigate the impact of depression-specific interventions on outcomes.

INTRODUCTION:Older adults with cancer facing competing treatments must prioritize between various outcomes. This study assessed health outcome prioritization among older adults with cancer starting chemotherapy. METHODS:Secondary analysis of a randomized trial addressing vulnerabilities in older adults with cancer. Patients completed three validated outcome prioritization tools: 1) Health Outcomes Tool: prioritizes outcomes (survival, independence, symptoms) using a visual analog scale; 2) Now vs. Later Tool: rates the importance of quality of life at three times-today versus 1 or 5 years in the future; and 3) Attitude Scale: rates agreement with outcome-related statements. The authors measured the proportion of patients prioritizing various outcomes and evaluated their characteristics. RESULTS:A total of 219 patients (median [range] age 71 [65-88], 68% with metastatic disease) were included. On the Health Outcomes Tool, 60.7% prioritized survival over other outcomes. Having localized disease was associated with choosing survival as top priority. On the Now vs. Later Tool, 50% gave equal importance to current versus future quality of life. On the Attitude Scale, 53.4% disagreed with the statement "the most important thing to me is living as long as I can, no matter what my quality of life is"; and 82.2% agreed with the statement "it is more important to me to maintain my thinking ability than to live as long as possible". CONCLUSION:Although survival was the top priority for most participants, some older individuals with cancer prioritize other outcomes, such as cognition and function. Clinicians should elicit patient-defined priorities and include them in decision-making.

PurposeThe objective of this study was to assess changes in hippocampal volume and shape in older long-term breast cancer survivors who were exposed to chemotherapy 5–15 years prior.MethodsThis study recruited female long-term breast cancer survivors aged 65 years or older with a history of chemotherapy (C+), age-matched breast cancer survivors who did not receive chemotherapy (C−), and healthy controls (HC). The participants were recruited 5–15 years after chemotherapy at time point 1 (TP1) and were followed up for 2 years at time point 2 (TP2). Assessments included hippocampal volume and shape from brain MRI scans and neuropsychological (NP) tests.ResultsAt TP1, each of the three groups was comprised of 20 participants. The C+ group exhibited a hippocampal volume loss estimated in proportion with total intracranial volume (ICV) in both the left and right hemispheres from TP1 to TP2. Regarding the hippocampal shape at TP1, the C+ group displayed inward changes compared to the control groups. Within the C+ group, changes in right hippocampal volume adjusted with ICV were positively correlated with crystalized composite scores (R = 0.450, p = 0.044). Additionally, in C+ groups, chronological age was negatively correlated with right hippocampal volume adjusted with ICV (R = −0.585, p = 0.007).ConclusionThe observed hippocampal volume reduction and inward shape deformation within the C+ group may serve as neural basis for cognitive changes in older long-term breast cancer survivors with history of chemotherapy treatment.

Abstract Purpose The purpose of this prospective longitudinal study was to evaluate the changes in brain surface gyrification in older long‐term breast cancer survivors 5–15 years after chemotherapy treatment. Methods Older breast cancer survivors aged ≥ 65 years treated with chemotherapy (C+) or without chemotherapy (C‐) 5–15 years prior and age‐ and sex‐matched healthy controls (HC) were recruited (time point 1 (TP1)) and followed up for 2 years (time point 2 (TP2)). Study assessments for both time points included neuropsychological (NP) testing with the NIH Toolbox cognition battery and cortical gyrification analysis based on brain MRI. Results The study cohort with data for both TP1 and TP2 consisted of the following: 10 participants for the C+ group, 12 participants for the C‐ group, and 13 participants for the HC group. The C+ group had increased gyrification in six local gyral regions including the right fusiform, paracentral, precuneus, superior, middle temporal gyri and left pars opercularis gyrus, and it had decreased gyrification in two local gyral regions from TP1 to TP2 (p < .05, Bonferroni corrected). The C‐ and HC groups showed decreased gyrification only (p < .05, Bonferroni corrected). In the C+ group, changes in right paracentral gyrification and crystalized composite scores were negatively correlated (R = –0.76, p = .01). Conclusions Altered gyrification could be the neural correlate of cognitive changes in older chemotherapy‐treated long‐term breast cancer survivors.

Abstract Purpose To assess white matter microstructural changes in older long‐term breast cancer survivors 5–15 years post‐chemotherapy treatment. Methods Breast cancer survivors aged 65 years or older who underwent chemotherapy (C+) and who did not undergo chemotherapy (C−) and age‐ and sex‐matched healthy controls (HC) were enrolled at time point 1 (TP1) and followed for 2 years for time point 2 (TP2). All participants underwent brain MRI with diffusion tensor images and neuropsychological (NP) testing with the NIH Toolbox Cognition Battery. Tract‐based spatial statistics (TBSS) analysis was performed on the diffusion tensor images to assess white matter microstructural changes with the fractional anisotropy (FA) parameter. Results There were significant longitudinal alterations in FA within the C+ group over time. The C+ group showed diminished FA in the body and genu of corpus callosum, anterior corona radiate, and external capsule on both the whole brain and region of interest (ROI) based analyses after p < 0.05 family‐wise error (FWE) correction. However, there were no significant group differences between the groups at TP1. Additionally, at TP1, a positive correlation (R = 0.58, p = 0.04) was observed between the FA value of the anterior corona radiata and the crystallized composite score in the C+ group. Conclusions Brain white matter microstructural alterations may be the underlying neural correlates of cognitive changes in older breast cancer survivors who had chemotherapy treatment years ago.

1510 Background: Based on randomized controlled trials,ASCO guidelines recommend use of geriatric assessment (GA)-directed interventions for older adults with cancer. The translation of these models to lower resourced settings has been limited. We assessed the feasibility of implementing GA-directed supportive care (GAIN-S) via telehealth in a lower resourced community setting. Methods: A quality improvement study was conducted in a high poverty, limited access, and low resourced community oncology practice (City of Hope - Antelope Valley [COH-AV]). Eligible participants were 65+ years with a new diagnosis of a malignant neoplasm under evaluation for cancer therapy. Before starting therapy, patients completed: baseline GA, SupportScreen, and the Fulmer SPICES assessment. A geriatric nurse practitioner (GNP) reviewed GA results and implemented multidisciplinary supportive care interventions (GAIN-S) via telehealth between April 2020 and January 2023. Key evaluation measures included: number of patients who completed GAIN-S; number of referrals to multidisciplinary supportive care services and completion rate; advance directives (ADs); and patient satisfaction with telehealth visits. Participants’ demographics, including distance traveled for care, type of cancer, stage, treatment, and telehealth satisfaction items, were summarized using descriptive statistics. To analyze and visualize the implementation process, run charts were utilized. Results: 251 patients (mean age 74, 62% Non-Hispanic White, 22% live 60+ miles from COH-AV, 56% stage II or less, 30% received chemotherapy) completed baseline assessments. 242 had initial visits with GNP, 197 via televideo and 45 via telephone. GNP reviewed vulnerabilities with 209 patients and generated 460 referrals for supportive care services, with 85% of services implemented. Highest numbers of referrals were to pharmacy (177), social work (142), occupational therapy (76), and physical therapy (48). GNP discussed GA-guided care plans with all patients and 43 patients completed AD after discussion with GNP. Over 92% of patients were satisfied with telehealth-based GAIN-S in terms of both ease of visit and access to care with their provider and with telehealth. Conclusions: Telehealth-based GAIN-S has proven to be feasible in providing accessible healthcare to older patients with cancer in a lower resourced community setting. This approach, well-received by most patients, highlights the potential of telehealth in delivering GAIN-S effectively in such settings.

This study aimed to assess whether physical functional decline in older women with early-stage breast cancer is driven by cancer, chemotherapy, or a combination of both. We prospectively sampled three groups of women aged ≥ 65: 444 with early-stage breast cancer receiving chemotherapy (BC Chemo), 98 with early-stage breast cancer not receiving chemotherapy (BC Control), and 100 non-cancer controls (NC Control). Physical function was assessed at two timepoints (T1 [baseline] and T2 [3, 4, or 6 months]) using the Physical Functioning Subscale (PF-10) of the RAND 36-item Short Form. The primary endpoint was the change in PF-10 scores from T1 to T2, analyzed continuously and dichotomously (Yes/No, with "yes" indicating a PF-10 decline > 10 points, i.e., a substantial and clinically meaningful difference). Baseline PF-10 scores were similar across all groups. The BC Chemo group experienced a significant decline at T2, with a median change in PF-10 of -5 (interquartile range [IQR], -20, 0), while BC Control and NC Control groups showed a median change of 0 (IQR, -5, 5; p < 0.001). Over 30