Abstract GS6-04: Development and validation of a chemotherapy toxicity (Chemo Tox) risk score for older patients (Pts) with breast cancer (BC) receiving adjuvant/neoadjuvant treatment (Adjuvant Tx): A R01 and BCRF funded prospective multicenter study
Authors: Hurria A , Magnuson A , Gross CP , Tew WP , Klepin HD , Wildes TM , Muss HB , Dotan E , Freedman R , O'Connor T , Dale W , Cohen HJ , Katheria V , Arsenyan A , Levi A , Kim H , Sun C-L 
Published: May 2019

Abstract
Background: Older pts with BC receiving adjuvant tx are at increased risk of chemo tox; however, no BC-specific tool exists to quantify this risk. The Cancer and Aging Research Group (CARG) developed/validated a chemo tox score for older pts with all stages of solid tumor. The goals of this study were to: 1) build upon the CARG score by developing/validating CARG-BC (a BC specific adjuvant chemo tox score for older pts) and 2) evaluate its association with dose modifications, reduced relative dose intensity (RDI) and hospitalizations.
Methods: 501 pts age ≥65 with stage I-III BC from 16 sites were accrued (300 development; 201 validation cohort). A pre-chemo assessment captured: CARG chemo tox score, BC tumor/tx variables, and additional geriatric assessment (GA) items. Grade 3-5 chemo tox by NCI CTCAE v 4.0 was captured. Univariate analysis identified chemo tox risk factors (p&lt;0.10) in addition to the CARG score which were used to develop a predictive model by best subset method; each risk factor was assigned a score, and summed to yield a total score (CARG-BC). Model performance was assessed by area under the ROC curves (AUC) of the development cohort, 10-fold internal validation, external validation, and goodness of fit.
Results: Among 501 pts, 28 received non-standard regimens and were excluded, leaving 473 evaluable pts: 283 development and 190 validation cohort. The development cohort (median age 70; range 65-85) had Stage I (39%), II (41%), & III (20%) BC with 65% hormone positive, 24% triple negative, 27% Her2 positive; and 37% received an anthracycline. Grade 3-5 tox occurred in 46% (36% grade 3, 10% grade 4, 0.4% grade 5). The CARG score was significantly associated with grade 3-5 tox (p&lt;0.001; AUC 0.64). The addition of BC tumor/tx & GA variables (CARG-BC: see table) improved the AUC to 0.76 (95% CI, 0.70-0.82; goodness of fit p=0.28). The score ranged from 0-19, (low risk 0-5, mid risk 6-9, high risk 10+) and was significantly associated with grade 3-5 tox (p&lt;0.001) while KPS was not (p=0.20). The 10-fold internal validation AUC was 0.78. The external validation AUC (0.69) was not statistically different (p=0.15) from the development AUC. A higher CARG-BC score was associated with dose delay/reduction, chemo discontinuation, hospitalization, and RDI&lt;85% (all p-value &lt;0.001).
Conclusions: We developed and validated a risk score (CARG-BC) which identifies an older pt's risk for adjuvant BC chemo tox and is associated with dose reduction, delay, reduced RDI, and hospitalization. This tool could be considered as a part of adjuvant tx decision-making.
Chemo Tox Risk Score for BC (CARG-BC) Grade 3-5 Tox (%)ScoreCARG-Score: age, # of chemo drugs, dose, hemoglobin, creatinine clearance, hearing, falls, ability to walk 1 block and take meds, decreased social activitiesLow360Middle573High613StageI330II/III552Planned Tx Duration≤ 3 mo.330&gt; 3 mo.584AnthracyclineNo380Yes591Liver FunctionNormal450Abnormal623Ability to Walk a MileNot limited370Limited613Someone to Provide AdviceMost of Time440None to Some of Time613 CARG-BC Risk ScoreLow210-5Middle456-9High7910+
Citation Format: Hurria A, Magnuson A, Gross CP, Tew WP, Klepin HD, Wildes TM, Muss HB, Dotan E, Freedman R, O'Connor T, Dale W, Cohen HJ, Katheria V, Arsenyan A, Levi A, Kim H, Sun C-L. Development and validation of a chemotherapy toxicity (Chemo Tox) risk score for older patients (Pts) with breast cancer (BC) receiving adjuvant/neoadjuvant treatment (Adjuvant Tx): A R01 and BCRF funded prospective multicenter study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS6-04.