Multiparametric MRI of Early Tumor Response to Immune Checkpoint Blockade in Metastatic Melanoma

Abstract

Background: Immune checkpoint inhibitors are now standard of care treatment for many cancers. Treatment failure in metastatic melanoma is often due to tumor heterogeneity not easily captured by conventional CT or tumor biopsy. The aim of this prospective study was to investigate early microstructural and functional changes within melanoma metastases following immune checkpoint blockade using multiparametric MRI. Methods: Fifteen treatment-naive metastatic melanoma patients (total 27 measurable target lesions) were imaged at baseline, and following three weeks and twelve weeks of treatment on immune checkpoint inhibitors using T2-weighted imaging, diffusion kurtosis imaging and dynamic contrast-enhanced MRI. Treatment timepoint changes in tumor cellularity, vascularity and heterogeneity within individual metastases were evaluated and correlated to the clinical outcome within each patient. Results: Differential tumor growth kinetics in response to immune checkpoint blockade were measured in individual metastases within the same patient. Early detection of tumor cell death or cell loss measured by a significant increase in the apparent diffusivity Dapp (p < 0.05) was observed in both responding and pseudoprogressive lesions after three week of treatment. Tumor heterogeneity (apparent kurtosis Kapp) was consistently higher in the pseudoprogressive and true progressive lesions, compared to the responding lesions throughout the first twelve weeks of treatment. These preceded tumor regression and significant tumor vascularity changes (Ktrans, ve and vp) detected after twelve weeks of immunotherapy (p < 0.05). Conclusions: Multiparametric MRI demonstrated potential for early detection of successful response to immunotherapy in metastatic melanoma.