(P 200) FRAILTY ASSESSMENT IN OLDER PATIENTS RECEIVING SARCOMA THERAPY

Objective: Treatment (tx) for advanced/metastatic sarcoma can have significant toxicities in older patients (pts). Although geriatric screening tools and lab tests can be useful to predict adverse outcomes in older patients receiving tx, they have not been widely evaluated or used for patients with sarcoma. Here, we used a patient-completed survey (VES-13) and a provider-completed survey (G8) to study associations between risk for poor outcomes and prevalence of treatment-associated toxicities in older pts with sarcoma. Moreover, we examined whether plasma concentrations of biomarkers of senescence, a biological mediator of frailty, differed between patients identified as lower versus higher risk by the VES-13 and G8.

Methods: This prospective pilot study included pts age 65 years and above with advanced or metastatic sarcoma, on observation or therapy. Validated geriatric screens were used to identify at-risk or frail pts, including VES-13 survey (for patients) and G8 survey (for providers). Pts had SASP lab collection at two timepoints with clinic follow up, prior to treatment and after at least 2 months of therapy. SASP included: Activin A, ADAMTS13, Eotaxin, Fas, GDF-15, GRO alpha, ICAM-1, IFNg, IL-15, IL-6, IL-7, IL-8, MCP-1, MDC, MMP-1, MMP-2, MMP-7, MMP-9, MPO, Osteoactivin, Osteopontin, PAI-1, PARC, PDGF-AA, PDGF-AB, PLA2G7, RAGE, RANTES, SOST, SPARC, TNF RI, TNF RII, TNF-a, TRAIL, uPAR, VEGF. Descriptive analysis was performed for demographics. SASP proteins were analyzed using Wilcoxon Signed Rank test and Benjamini-Hochberg adjustment with α = 0.1 as the chosen type-1 error rate.

Results: Seventeen pts completed the survey and lab collection. The pt demographics, sarcoma subtypes and systemic therapies received are summarized in Table 1 and 2. The median age was 78 years old (range 66 to 92) and the majority of pts were male (65%). Most pts received doxorubicin (7) or a tyrosine kinase inhibitor (7).

Ten pts (59%) reported an at-risk score of 3 or greater on VES-13 (median 3, range 0 to 7). By comparison, the provider survey G8 showed that 14 pts (82%) had an at-risk score of 13 or lower (median score 13, range 9 to 17). One pt was hospitalized for tumor related symptoms and pursued hospice instead of tx. For the remaining 16 pts on tx, 5 pts (31%) discontinued due to toxicity including 2 pts who were hospitalized with sepsis (all 5 pts scored at-risk on G8 whereas only 2 pts had at-risk score on VES-13). Four pts (25%) had tx held due to lab abnormalities (1 pt resumed at lower dose, remainder continued at full dose).

In unadjusted analysis of SASP proteins for 13 pts with follow up, MMP-7, IFNg, uPAR, Activin A, TNF RII, TNFa showed significant increase while MMP-9 showed significant decrease in value over time (p< 0.1). When adjusted for multiple comparisons, no SASP protein showed significant difference. Pts with at-risk G8 score had trend of higher SASP values for all proteins except ADAMTS13 and Activin A, compared to pts without at-risk score. This was not observed with VES-13 score. There was variability in SASP trend of pts who discontinued tx for toxicity.

Conclusion: This pilot study showed a trend of select SASP proteins increasing in older pts receiving sarcoma treatment, potentially reflecting effect of senescence with cancer directed therapy. Providers are more likely to identify frailty compared to pts. The G8 survey is a useful screening tool for older pts in which systemic therapy for sarcoma is being considered. A larger sample size is needed to confirm our findings.