Selecting Appropriate Clinical Trial Endpoints for Geroscience Trials: A Path Towards Consensus.

Using a modified Delphi process, we engaged 28 experts in clinical trials, geriatrics, and research translation to determine if there were consensus around what clinical endpoints should be used for trials evaluating the efficacy of interventions to prevent or treat multiple age-related conditions. Four focus groups developed themes. Statements related to those themes were circulated back to participants in a survey.

Gerotherapeutics: aging mechanism-based pharmaceutical and behavioral interventions to reduce cancer racial and ethnic disparities.

The central premise of this article is that a portion of the established relationships between social determinants of health and racial and ethnic disparities in cancer morbidity and mortality is mediated through differences in rates of biological aging processes. We further posit that using knowledge about aging could enable discovery and testing of new mechanism-based pharmaceutical and behavioral interventions ("gerotherapeutics") to differentially improve the health of cancer survivors from minority populations and reduce cancer disparities. These hypotheses are based on evidence that lifelong differences in adverse social determinants of health contribute to disparities in rates of biological aging ("social determinants of aging"), with individuals from minoritized groups experiencing accelerated aging (ie, a steeper slope or trajectory of biological aging over time relative to chronological age) more often than individuals from nonminoritized groups.

UGT1A1*28 polymorphism and the risk of toxicity and disease progression in patients with breast cancer receiving sacituzumab govitecan.

Background: Sacituzumab govitecan (sacituzumab) emerged as an important agent in metastatic and locally recurrent HER2-negative breast cancer treatment. UGT1A1 polymorphisms have also been shown to predict sacituzumab toxicity.

Methods: In this retrospective study, we sought to evaluate the associations between UGT1A1 status, toxicity, and therapeutic outcomes in sacituzumab recipients with advanced breast cancer who underwent genotype testing for UGT1A1 alleles (N = 68).

Functional decline in older breast cancer survivors treated with and without chemotherapy and non-cancer controls: results from the Hurria Older PatiEnts (HOPE) prospective study.

Purpose: 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.

Methods: 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.

Outcome prioritization and preferences among older adults with cancer starting chemotherapy in a randomized clinical trial.

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.

Randomized placebo-controlled, double-blind clinical trial of nanoemulsion curcumin in women with aromatase inhibitor-induced arthropathy: an Alliance/NCORP pilot trial.

Purpose: Aromatase inhibitor (AI) therapy reduces risk of recurrence and death for postmenopausal women with breast cancer (BC); however, AI-induced arthralgia (AIIA) can lead to discontinuation of treatment. Curcumin, a bioactive polyphenolic substance, may help ameliorate inflammation-related conditions including osteoarthritis and pain.

Methods: We conducted a multisite randomized placebo-controlled, double-blind pilot trial (Alliance A22_Pilot9) to evaluate the effects of nanoemulsion curcumin (NEC, 200 mg/day) in postmenopausal women experiencing AIIA for ≥ 3 months.

Brain white matter microstructural changes in chemotherapy-treated older long-term breast cancer survivors.

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.

Falls prechemotherapy and toxicity-related hospitalization during adjuvant chemotherapy for breast cancer in older women: Results from the prospective multicenter HOPE trial.

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.

HER2-targeted antibody-drug conjugates for breast cancer: ancestry and dose adjustment for thrombocytopenia.

Background: Thrombocytopenia is a common adverse event on HER2-targeted therapies, fam-trastuzumab deruxtecan (T-DXd) and ado-trastuzumab emtansine (T-DM1). A reported association of Asian ancestry with this event merits investigation to rule out potential confounding.

Methods: Subjects in this retrospective cohort were female patients with HER2 positive breast cancer, of Asian or non-Hispanic White ancestry, who initiated T-DM1 or T-DXd from January 2017 through October 2021.

Predicting All-Cause Mortality in Women With and Without Breast Cancer Using the Schonberg Index: A Women's Health Initiative Study.

Background: When treating older women with breast cancer, life expectancy is an important consideration. ASCO recommends calculating 10-year mortality probabilities to inform treatment decisions. One useful tool is the Schonberg index, which predicts risk-based all-cause 10-year mortality.

Altered gyrification in chemotherapy-treated older long-term breast cancer survivors.

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 to 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 & 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.

Facilitators and Barriers to Older Adult Participation in Cancer Trials: A Qualitative Study Exploring Patient-Caregiver Dyad Congruence.

Purpose: Family caregivers play an integral role in caring for older adults with cancer. Few studies have examined older adults with cancer and their family caregivers as a unit in a relationship or a dyad. Dyad congruence, or consistency in perspective, is relevant to numerous aspects of living with cancer, including the decision to enroll in a cancer clinical trial.

Clonal hematopoiesis in older patients with breast cancer receiving chemotherapy.

Background: The expansion of hematopoietic stem cells carrying recurrent somatic mutations, termed clonal hematopoiesis (CH), is common in elderly individuals and is associated with increased risk of myeloid malignancy and all-cause mortality. Though chemotherapy is a known risk factor for developing CH, how myelosuppressive therapies affect the short-term dynamics of CH remains incompletely understood. Most studies have been limited by retrospective design, heterogeneous patient populations, varied techniques to identifying CH, and analysis of single timepoints.

Predicting Hyperglycemia Among Patients Receiving Alpelisib Plus Fulvestrant for Metastatic Breast Cancer.

Background: Hyperglycemia is recognized as a common adverse event for patients receiving alpelisib but has been little studied outside of clinical trials. We report the frequency of alpelisib-associated hyperglycemia in a real-world setting and evaluate proposed risk factors.

Patients And Methods: We retrospectively identified patients with PIK3CA-mutated, hormone receptor-positive, metastatic breast cancer who initiated treatment with alpelisib plus fulvestrant between August 2019 and December 2021.

Toxicity risk score and clinical decline after adjuvant chemotherapy in older breast cancer survivors.

Background: Chemotoxicity risk scores were developed to predict grade 3-5 chemotherapy toxicity in older women with early breast cancer. However, whether these toxicity risk scores are associated with clinically meaningful decline in patient health remains unknown.

Methods: In a prospective study of women aged 65 years and older with stage I-III breast cancer treated with chemotherapy, we assessed chemotoxicity risk using the Cancer and Aging Research Group-Breast Cancer (CARG-BC) score (categorized as low, intermediate, and high).

The role of self-perceived age in older adults considering adjuvant chemotherapy.

Introduction: Aging-related concerns can increase the risk of treatment toxicities among older adults considering adjuvant chemotherapy. We previously demonstrated that older adults with cancer who reported feeling older than their chronological age (i.e.