Background: Functional decline during NSCLC treatment is critically important to older adults. Yet, data on functional decline—particularly during chemoIO, IO, and targeted therapy—remain limited. Additionally, the best measures to capture functional decline from the patient’s perspective remain unknown.

Methods: We conducted a multisite, mixed methods prospective cohort study to characterize function during systemic NSCLC treatment and compare quantitative measures with gold standard qualitative descriptions of patients’ lived experience. Prior to and at 2 months after treatment initiation, 69 adults age >65 with advanced NSCLC starting chemo, IO, and/or targeted therapy underwent geriatric assessments including instrumental activities of daily living (IADL), EORTC QLQ-C30 Physical Functioning (PF), and Life-Space Assessment (LSA). LSA measures where a person goes in their environment, how frequently, and how independently. Pretreatment functional impairment and decline at 2 months were assessed. In a qualitative substudy, 16 purposively sampled patients with diverse pretreatment function completed two semi-structured interviews (pretreatment, 2 months) to explore treatment effects on daily functioning. Grounded theory was used to code for functional decline. Using the qualitative patient experience as the gold standard, sensitivity and specificity were calculated for each functional measure.

Results: Mean age was 75 (range 65-94). NSCLC treatment included IO (36%), targeted therapy (28%), chemoIO (23%), and chemo (13%). Pretreatment functional impairment was common and ~25% of patients experienced functional decline on quantitative measures at 2 months (Table). Qualitatively, 50% described functional decline at 2 months. LSA had the highest sensitivity (71%) and similar specificity (88%) as IADL and PF.

	Pretreatment impairment (%, N = 69)	Functional Decline at 2 Months (%, N = 69)	Sensitivity (%, n = 16)	Specificity (%, n = 16)
IADL	67	23	50	88
PF	67	20	43	88
LSA	41	24	71	88

Conclusions: Functional decline during NSCLC treatment is common. LSA provides a sensitive and specific patient-centered measure of function.