The Loss of Radiographic Enhancement in Primary Renal Cell Carcinoma Tumors Following Multitargeted Receptor Tyrosine Kinase Therapy is an Additional Indicator of Response

Objectives

To characterize radiographic intratumoral contrast enhancement in the primary tumor of patients with renal cell carcinoma treated with either sorafenib or sunitinib, and to compare the relationship between primary tumor response and loss of enhancement. Use of the antiangiogenic multitargeted tyrosine kinase inhibitors sorafenib and sunitinib in renal cell carcinoma often results in stabilization of tumor size based on measurement of external tumor diameter; however, internal tumor changes in enhancement have been occasionally noted.

Methods

Thirty patients who received sunitinib or sorafenib therapy were evaluated for primary tumor response with contrast-enhanced computed tomography images before and after at least 1 cycle of treatment. Evaluation of intratumoral contrast enhancement was quantified using a workstation that allowed for three-dimensional renderings of the kidney and measurement of density in Hounsfield units (HU). The relationship between loss of intratumoral enhancement and other outcome variables was examined.

Results

A loss of enhancement within the primary tumor, following therapy with tyrosine kinase inhibitors, was positively associated with primary tumor response (P = .0053). Additionally, the degree of post-treatment tumor enhancement was positively associated with tumor response to tyrosine kinase inhibition (P = .045).

Conclusions

Intratumoral changes in computed tomography enhancement after receptor tyrosine kinase inhibition correlate with primary tumor response, and may be a useful adjunct to the standard response evaluation criteria in solid tumors (RECIST criteria) in assessing response to therapy. Prospective studies evaluating antiangiogenic agents should explore intratumoral changes in contrast enhancement as part of response criteria, and examine the effect of intratumoral changes on survival-based outcomes.