In Metastatic RCC, 10% Tumor Shrinkage Valid Indicator of VEGF Response

CT coronal image showing 18-cm right kidney mass.

Tumor shrinkage defined as a 10% decrease in the sum of the longest unidimensional diameter of the target lesion is a valid indicator of response to VEGF inhibition among patients with metastatic renal cell carcinoma when evaluated by a single radiologist observer, according to the results of a study published recently in Cancer.

“Prior reports have found a 10% tumor shrinkage threshold to be indicative of a survival benefit in patients with metastatic renal cell carcinoma, using either a single radiologist observer or independent central review,” wrote researchers led by Katherine M. Krajewski, MD, of Dana-Farber Cancer Institute. “The results of the current study are concordant with these prior reports, as we have demonstrated that changes beyond 95% limits of agreement of –7.3% to 7.86% in tumor burden are true detectable changes in overall tumor size rather than a measurement error when baseline and follow-up measurements are performed by a single radiologist.”

VEGF inhibitors are among the standard treatments currently available for patients with metastatic renal cell carcinoma. CT is used to assess a patient’s response to therapy and to determine if the therapy is effective or should be discontinued. RECIST criterion for an objective response requires a 30% decrease in the sum of the longest unidimensional diameter of the target lesions; however, very few patients with renal cell carcinoma achieve this criterion. Therefore, alternatives are needed to define a response to VEGF inhibitors in patients with metastatic renal cell carcinoma.

In this study, Krajewski and colleagues analyzed the use of 10% tumor shrinkage as a valid indicator of tumor shrinkage. The researchers sought to determine intraobserver and interobserver measurement agreement of CT size and attenuation measurements.

They enrolled 71 patients with metastatic renal cell carcinoma with 179 target lesions. All patients were participants in either a phase II or phase III trial of VEGF-targeted therapies. Target lesion long axis diameter and mean attenuation were independently measured by two radiologists.

Results indicated that 10% tumor shrinkage represented a true change in tumor size when measured by a single radiologist, evidenced by the 95% limits of agreement for the percentage change of the sum longest diameter (–7.3% to 7.86%). However, for interobserver variability the 95% limits of agreement were –16.3% to 15.4%.

“It is known that interobserver variation in tumor measurements is greater than intraobserver variation, and multiple prior reports have advocated the use of a single observer or independent review committees to improve consistency in serial measurements in any one patient,” the researchers wrote.

Data indicated that target lesion location significantly affected interobserver variability. Compared with the lung as a reference, the liver significantly contributed to measurement variability and interobserver variability.

“The use of a single trained observer for both baseline and follow-up measurements is recommended when assigning radiologic response using the alternative 10% tumor shrinkage threshold to better predict clinical outcome,” the researchers wrote.