Ethnic diversity in treatment response for colorectal cancer: proof of concept for radiomics-driven enrichment trials

BackgroundSeveral barriers hamper recruitment of diverse patient populations in multicenter clinical trials which determine efficacy of new systemic cancer therapies.PurposeWe assessed if quantitative analysis of computed tomography (CT) scans of metastatic colorectal cancer (mCRC) patients using imaging features that predict overall survival (OS) can unravel the association between ethnicity and efficacy.MethodsWe retrospectively analyzed CT images from 1584 mCRC patients in two phase III trials evaluating FOLFOX & PLUSMN; panitumumab (n = 331, 350) and FOLFIRI & PLUSMN; aflibercept (n = 437, 466) collected from August 2006 to March 2013. Primary and secondary endpoints compared RECIST1.1 response at month-2 and delta tumor volume at month-2, respectively. An ancillary study compared imaging phenotype using a peer-reviewed radiomics-signature combining 3 imaging features to predict OS landmarked from month-2. Analysis was stratified by ethnicity.ResultsIn total, 1584 patients were included (mean age, 60.25 & PLUSMN; 10.57 years; 969 men). Ethnicity was as follows: African (n = 50, 3.2%), Asian (n = 66, 4.2%), Caucasian (n = 1413, 89.2%), Latino (n = 27, 1.7%), Other (n = 28, 1.8%). Overall baseline tumor volume demonstrated Africans and Caucasians had more advanced disease (p < 0.001). Ethnicity was associated with treatment response. Response per RECIST1.1 at month-2 was distinct between ethnicities (p = 0.048) with higher response rate (55.6%) in Latinos. Overall delta tumor volume at month-2 demonstrated that Latino patients more likely experienced response to treatment (p = 0.021). Radiomics phenotype was also distinct in terms of tumor radiomics heterogeneity (p = 0.023).ConclusionThis study highlights how clinical trials that inadequately represent minority groups may impact associated translational work. In appropriately powered studies, radiomics features may allow us to unravel associations between ethnicity and treatment efficacy, better elucidate mechanisms of resistance, and promote diversity in trials through predictive enrichment.

Automated summary

This study assessed the association between ethnicity and efficacy by using quantitative analysis of computed tomography (CT) scans of metastatic colorectal cancer (mCRC) patients. The results showed significant differences in treatment response, tumor volume change, and tumor imaging features among different ethnicities. The study highlights the impact of inadequate representation of minority groups in clinical trials on associated translational work.