Establishing Correlations between Breast Tumor Response to Radio-Immunotherapy and Radiomics from Multi-Parametric Imaging: An Animal Study

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Abstract
Triple-negative breast cancer (TNBC), which is a type of invasive breast cancer, is characterized by severe disease progression, poor prognosis, high recurrence rate, and short survival. We sought to gain new insight into TNBC by applying computed tomography (CT) and magnetic resonance (MR) quantitative imaging (radiomics) approaches to predict the outcome of radio-immunotherapy treatments in a syngeneic subcutaneous murine breast tumor model. Five Athymic Nude mice were implanted with breast cancer cell lines (4T1) tumors on the right flank. The animals were CT- and MRI-imaged, tumors were contoured, and radiomics features were extracted. All animals were treated with radiotherapy (RT), followed by the administration of PD1 inhibitor. Approximately 10 days later, the animals were sacrificed, tumor volumes were measured, and histopathology evaluation was performed through Ki-67 staining. Linear regression modeling between radiomics and Ki-67 results was performed to establish a correlation between quantitative imaging and post-treatment histochemistry. There was no correlation between tumor volumes and Ki-67 values. Multiple CT- and MRI-derived features, however, correlated with histopathology with correlation coefficients greater than 0.8. MRI imaging helps in tumor delineation as well as an additional orthogonal imaging modality for quantitative imaging purposes. This is the first investigation correlating simultaneously CT- and MRI-derived radiomics to histopathology outcomes of combined radio-immunotherapy treatments in a preclinical setting applied to treatment naïve tumors. The findings indicate that imaging can guide discrimination between responding and non-responding tumors for the combined RT and ImT treatment regimen in TNBC.

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