Do CT perfusion measures differ in primary renal tumors versus metastatic lesions in patients receiving treatment for advanced renal cell carcinoma?

Perfusion CT allows for the visualization and quantification of tumor vascularity by measuring blood perfusion in tissues. Due to its highly vascularized nature, renal cell carcinoma (RCC) is especially amenable to visualization with perfusion CT. It has been suggested that measurements of perfusion in metastatic RCC lesions may predict the efficacy of anti-angiogenesis agents. We have previously reported that CT perfusion measurements after only 8 days of treatment can correlate with the efficacy of targeted therapy in patients with advanced RCC. We hypothesize that perfusion imaging early during treatment with targeted therapy can detect changes in vascularity in both primary RCC renal lesions and metastatic RCC lesions. We aim to determine if there is a difference in early CT perfusion measures comparing renal lesions with metastatic lesions during therapy.

In this IRB-approved prospective study, patients with advanced RCC received a perfusion CT scan prior to treatment (baseline), and 7-10 days after initiating treatment (day 8). Perfusion measurements of tumor vascularity included blood volume (BV), blood flow (BF), mean transit time (MTT), and flow extraction product (FEP). The longest dimension was measured in each lesion. Clinical response was defined based on RECIST 1.1 after 12 weeks of treatment. Univariable logistic regression analysis was used to determine the association of clinical response and tumor location. We evaluated the relationship between tumor location and change in each measure from baseline to day 8. Association between clinical response and each individual measure for each tumor location was evaluated separately (renal lesion or metastatic lesion). Significance testing was assessed at a two-sided alpha level of 0.10.

11 patients with advanced RCC who required treatment with anti-angiogenesis agents or immune checkpoint inhibitor were enrolled. 5 patients had primary renal masses imaged with perfusion CT, one patient had both a primary renal mass and a metastatic lesion, and 5 patients had metastatic RCC lesions (in single or multiple sites, including adrenal, pancreas, lung, liver and soft tissue).

At 12 weeks, 67% of the renal masses had stable RECIST measurements and 33% had RECIST measurements consistent with progressive disease. Among the metastatic lesions, 25% had stable measurements and 75% progressed at 12 weeks. There was no statistically significant association between tumor location (kidney or metastasis) and clinical response (stable or progressive disease) (OR: 6.0 (90% CI: 0.85-42.5); p=0.13).

At the early imaging time point, we were able to quantify changes from baseline to day 8 in tumor vascularity measures, whereas tumor size did not significantly change during this short interval. Changes at Day 8, in BF, BV and FEP measures in metastatic lesions had greater variation compared to renal lesions (Figure 1). Pts with stable disease had greater decreases in BV and BF for both renal and metastatic lesions compared to patients with progressive lesions. Further, in patients with stable disease, changes in vascularity were more pronounced in metastatic lesions compared to renal lesions (Figure 2). Our results are consistent with the notion that stabilization of tumor growth by targeted therapy can be associated with decreases in tumor vascularity measurements.

We found that early changes in BF and BV in advanced RCC patients were of greater magnitude in patients with stable disease compared to progressive disease. In addition, changes were more pronounced in metastatic tumor sites compared to primary renal tumors. This work suggests that early perfusion changes, especially in metastatic lesions, might be helpful to determine if patients are benefiting from targeted therapy. Further studies are needed to see if CT perfusion measures can be developed as a biomarker to measure early therapeutic response.