Impact of center case volume on cardiotoxicity during adjuvant trastuzumab in breast cancer.

Abstract

6625 Background: A recent study suggested that cardiotoxicity from trastuzumab (T) was associated with regional variation and insufficient cardiac monitoring (Ng et al.SABCS 2012). Few studies have examined the impact of centre or physician (MD) case volume (vol) on outcomes in systemic therapy. Methods: All breast cancer patients who were diagnosed in 2003-2009 in Ontario and treated with adjuvant T were identified through a provincial drug funding program, and linked to administrative databases to ascertain patient demographics, hospitalizations, cardiac risk factors, cardiac imaging, comorbidities, and treating centre and MD. For each year, we calculated case vol as the number of patients treated with adjuvant T by each MD and by each centre. Cardiotoxicity was defined as receiving less than 16 out of 18 doses of T because of heart failure (HF) admission, HF diagnosis by physician claims, or discontinuation after cardiac imaging. Insufficient cardiac monitoring was defined as per recent guideline and per Ng et al. Logistic regression and mixed models were constructed to examine factors associated with cardiotoxicity. Results: Our cohort consisted of 3,777 patients, 214 MDs and 68 centres. For patients, 16.5% were over age 65; 30.3%, 9.4%, and 1.2% had previous diagnoses of hypertension, diabetes, and HF, respectively; 16.9% had cardiotoxicity. Univariate analyses found that high centre vol, but not MD vol, was associated with lower cardiotoxicity. Cardiotoxicity rates by centre vol quintiles (Q) were 23.4% (Q1-3), 18.2% (Q4), and 15.2% (Q5). Multivariable analyses found that lower cardiotoxicity was associated with higher centre vol (OR=0.85 per Q, p=0.02) and diagnosis in recent years (2008-2009 vs. before 2008; OR=0.50, p<0.001), after adjusting for age, previous HF, comorbidities, regional variation, and cardiac monitoring. Accounting for clustering within centres, there remained a strong trend of lower cardiotoxicity with higher centre vol (OR=0.77 per Q, p=0.06) and recent diagnosis (OR=0.50, p<0.001). Conclusions: Our findings suggest a reduction in cardiotoxicity with experience and over time, and support the notion of centralization of systemic therapy in high vol centres to optimize outcomes.