Grant Number:	5R37CA306402-02 Interpret this number
Primary Investigator:	Wong, Melisa
Organization:	Kaiser Foundation Research Institute
Project Title:	Predicting Trajectories of Function, Cognition, and Quality of Life Among Older Adults with Advanced Lung Cancer
Fiscal Year:	2026

PROJECT SUMMARY/ABSTRACT Older adults with non-small cell lung cancer (NSCLC)—the leading cause of cancer mortality1—are at increased risk for treatment toxicity compared to younger adults,2, 3 which can lead to impairments in function, cognition, and quality of life (QOL). Maintaining QOL is critically important to older adults,4 especially as they are living longer with advanced cancer where toxicity is often cumulative.5, 6 Over 70% of older adults with cancer would not choose a treatment that severely impairs function or cognition, even if it improves survival.7 In addition, NSCLC therapeutic advances have led to widespread use of immunotherapy with or without chemotherapy (chemo). Because immunotherapy typically causes fewer adverse events than chemo,8-12 older adults who are too frail for chemo are now considering immunotherapy options. Furthermore, older patients are not well represented in cancer clinical trials, which rarely evaluate function or cognition as outcomes.13-15 Therefore, older adults with NSCLC lack vital information about treatment tolerability that they need to make informed decisions, contributing to overtreatment of frail older adults and undertreatment of fit older adults.16 Despite the importance of function, cognition, and QOL to older patients and the growing population of frail older adults receiving NSCLC treatment, oncologists lack evidence-based tools to predict an individual patient’s trajectory for these survivorship outcomes. To move from cancer-centered to patient-centered decision making, oncologists must both 1) identify which older adults are at highest risk for poor treatment tolerability outcomes (focus of this application) and 2) communicate complex information about benefits and harms to patients to align decisions with patient goals (focus of PI Wong’s broader research; see biosketch). To begin characterizing changes in function, cognition, and QOL during NSCLC treatment, we established an observational cohort study (R03AG056439, K76AG064431) of adults aged >65 with advanced NSCLC (aNSCLC) starting systemic therapy with non-curative intent (N=185; 130 received chemo and/or immunotherapy).17, 18 Through serial geriatric assessments pretreatment and at 1, 2, 4, and 6 months (or until treatment discontinuation, whichever occurred earlier), we found that 46% of older patients developed functional decline in instrumental activities of daily living19 (IADL), 72% in life-space mobility,20 and 51% on the Short Physical Performance Battery21 (SPPB). In addition, 45% developed clinically meaningful decline in cognition (Montreal Cognitive Assessment22 [MoCA]) and 42% in QOL.23 For each outcome, less than half of those who declined recovered to their pretreatment baseline by 6 months. To further assess memory and executive function, we piloted the addition of two tablet-based cognitive assessments—Favorites and Match—which are optimized for accurate detection of cognitive impairment and reliably measure change.24-26 Building directly upon our preliminary work suggesting distinct trajectories for these survivorship outcomes, we will now develop prediction models for 6-month trajectories of function, cognition, and QOL during chemo and/or immunotherapy among older adults with aNSCLC. Chemoimmunotherapy, chemo alone, and immunotherapy alone are the mainstays of aNSCLC treatment for patients without targetable molecular alterations. To increase cohort generalizability and the sample size, which is required to accomplish our aims, we developed a Cancer and Aging Research Group27 (CARG) collaboration between Kaiser Permanente Northern California (KPNC), Ohio State University (OSU), and University of Rochester (UR). We will recruit an additional 714 participants for a total sample of 844 (estimated 700 evaluable patients based on a 17% attrition rate: 400 for the development cohort, the last 300 for the validation cohort). CARG patient stakeholders28 selected our study outcomes based on what matters most to them. We will apply an innovative approach to group-based latent class analysis to both identify distinct groups of trajectories for each outcome and use pretreatment demographic, clinical oncology, and geriatric assessment characteristics to produce personalized class-based trajectories for an individual patient with predicted probabilities for each curve. This project supports the NIA’s goal to mitigate the impact of aging-related conditions and the NCI’s Special Focus Area on survivorship outcomes for patients with advanced cancer. Our overall hypothesis is that there are clinically distinct groups of trajectories for each outcome that will be predicted by geriatric assessment characteristics. For each outcome measure below, a separate trajectory prediction model will be developed that will include pretreatment demographic, clinical oncology, and geriatric assessment characteristics for older adults living with aNSCLC receiving chemo and/or immunotherapy: Aim 1: Develop and validate functional trajectory prediction models for IADL, life-space mobility, and SPPB Aim 2: Develop and validate cognitive trajectory prediction models for MoCA, Favorites, and Match Aim 3: Develop and validate a QOL trajectory prediction model for EORTC QLQ-C30 This study will produce generalizable prediction tools for individualized trajectories of important survivorship outcomes that oncologists can use to a) more comprehensively describe how aNSCLC treatment will likely impact an older adult’s function, cognition, and QOL and b) compare options during shared decision making. With this information, older patients and their families can better prepare for how treatment might affect their daily lives, and oncologists can further optimize supportive care for those at highest risk.





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