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

  • Computed Tomography
  • Published:
European Radiology Aims and scope Submit manuscript

Abstract

Background

Several barriers hamper recruitment of diverse patient populations in multicenter clinical trials which determine efficacy of new systemic cancer therapies.

Purpose

We 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.

Methods

We retrospectively analyzed CT images from 1584 mCRC patients in two phase III trials evaluating FOLFOX ± panitumumab (n = 331, 350) and FOLFIRI ± 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.

Results

In total, 1584 patients were included (mean age, 60.25 ± 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).

Conclusion

This 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.

Clinical relevance statement

Radiomics could promote clinical trial diversity through predictive enrichment, hence benefit to historically underrepresented racial/ethnic groups that may respond variably to treatment due to socioeconomic factors and built environment, collectively referred to as social determinants of health.

Key Points

•Findings indicate ethnicity was associated with treatment response across all 3 endpoints. First, response per RECIST1.1 at month-2 was distinct between ethnicities (p = 0.048) with higher response rate (55.6%) in Latinos.

•Second, the overall delta tumor volume at month-2 demonstrated that Latino patients were more likely to experience response to treatment (p = 0.021). Radiomics phenotype was also distinct in terms of tumor radiomics heterogeneity (p = 0.023).

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Abbreviations

CR:

Complete response

CT:

Computed tomography

mCRC:

Metastatic colorectal cancer

OS:

Overall survival

PD:

Progressive disease

PR:

Partial response

RECIST1.1:

Response Evaluation Criteria in Solid Tumors 1.1

SD:

Stable disease

SDOH:

Social determinants of health

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Acknowledgements

Geoffrey R. Oxnard, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave., Boston, MA 02215, USA. Those acknowledge submitted permission to be cited.

Funding

Scientific and financial support for the Foundation for the National Institutes of Health Biomarkers Consortium Vol-PACT project was provided by Amgen; Boehringer Ingelheim; Merck KGaA, Darmstadt, Germany; Genentech Inc.; Merck & Co., Inc.; Regeneron Pharmaceuticals; and Millennium Pharmaceuticals, Inc., Cambridge, MA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. In-kind donations of phase III trial data to support this specific study were provided to the Foundation for the National Institutes of Health by Amgen and Sanofi.

Author information

Authors and Affiliations

  1. Department of Radiology, Columbia University Irving Medical Center and New York Presbyterian Hospital, 710 West 168th St, New York, NY, 10032, USA

    Laurent Dercle, Melissa Yang, Hao Yang, Lin Lu, Binsheng Zhao & Lawrence H. Schwartz

  2. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA

    Mithat Gönen, Jessica Flynn & Chaya S. Moskowitz

  3. Foundation for the National Institutes of Health (FNIH), 11400 Rockville Pike, Suite 600, North Bethesda, MD, 20852, USA

    Dana E. Connors

  4. Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA

    Diane Reidy-Lagunes

  5. Columbia University Herbert Irving Comprehensive Cancer Center, 161 Fort Washington Ave, New York, NY, 10032, USA

    Tito Fojo & Brian S. Henick

  6. Inova Center for Personalized Health and Schar Cancer Institute, 8100 Innovation Park Dr, Fairfax, VA, 22031, USA

    Sanja Karovic

  7. University of Virginia Cancer Center, 1240 Lee St, Charlottesville, VA, 22903, USA

    Sanja Karovic

Authors
  1. Laurent Dercle
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  2. Melissa Yang
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  6. Dana E. Connors
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  7. Hao Yang
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  8. Lin Lu
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  10. Tito Fojo
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  11. Sanja Karovic
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  12. Binsheng Zhao
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  13. Lawrence H. Schwartz
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Corresponding author

Correspondence to Laurent Dercle.

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Guarantor

The scientific guarantor of this publication is Laurent Dercle.

Conflict of interest

The authors of this manuscript declare relationships with the following companies:

  • Laurent Dercle. No relationship to disclose.

  • Melissa Yang. No relationship to disclose.

  • Mithat Gönen. Consulting or advisory role: Tesaro.

  • Jessica Flynn. No relationship to disclose.

  • Chaya S. Moskowitz. Consulting or advisory role: BioClinica.

  • Dana E. Connors. No relationship to disclose.

  • Hao Yang. No relationship to disclose.

  • Lu Lin. No relationship to disclose.

  • Tito Fojo. No relationship to disclose.

  • Sanja Karovic. No relationship to disclose.

  • Binsheng Zhao. Patents, royalties, other intellectual property: Varian Medical Systems.

  • Lawrence H. Schwartz. Consulting or advisory role: Novartis, Regeneron. Research Funding: Merck Sharp & Dohme (Inst), Pfizer (Inst), BMS (Inst). Patents, royalties, other intellectual property: Varian Medical Systems.

  • Brian Henick. Consulting or advisory role: AstraZeneca, Ideaya, Jazz Pharmaceuticals, DAVA Oncology. Research funding: Neximmune, SU2C, BMSF.

Statistics and biometry

Mithat Gonen, Jessica Flynn, and Chaya Moskowitz kindly provided statistical advice for this manuscript.

Informed consent

Written informed consent was obtained from all subjects (patients) in this study.

Ethical approval

Institutional review board approval was obtained.

Study subjects or cohorts overlap

Some study subjects or cohorts have been previously reported. This paper utilizes a trained and validated radiomics-signature from our prior publication in 2022 in European Journal of Cancer, “An imaging signature to predict outcome in metastatic colorectal cancer using routine computed tomography scans” (Eur J Cancer. 2022 Jan;161:138-147), on a different topic, methodology, and endpoints.

Methodology

•retrospective

•randomized controlled trial

•multicenter study

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Dercle, L., Yang, M., Gönen, M. et al. Ethnic diversity in treatment response for colorectal cancer: proof of concept for radiomics-driven enrichment trials. Eur Radiol 33, 9254–9261 (2023). https://doi.org/10.1007/s00330-023-09862-z

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  • DOI: https://doi.org/10.1007/s00330-023-09862-z

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