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Pilot study of DCE-MRI to predict progression-free survival with sorafenib therapy in renal cell carcinoma
Keith T Flaherty1, Mark A Rosen, Daniel F Heitjan
1Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ktflaherty@aol.com
Background:
The investigation of angiogenesis inhibitors is of particular interest in renal cell carcinoma (RCC), in which dysregulated blood vessel formation has been correlated with shortened survival. Sorafenib is a novel RAF and VEGF receptor tyrosine kinase inhibitor. We conducted this study to (a) determine if sorafenib is anti-angiogenic, and (b) to relate anti-angiogenic effect to outcome.
Results:
Four patients achieved partial response by WHO criteria (ORR 24%). Median time to progression (TTP) was 12.9 months. K(trans) decreased significantly during treatment with sorafenib (60.3% decline, 95% CI 46.1-74.6%). The percent decline in K(trans) and change in tumor size by CT scan were significantly associated with progression-free survival (p = 0.01 and 0.05, respectively). In addition, K(trans) at baseline was also significantly associated with progress-free survival (p = 0.02).
Patients And Methods:
Seventeen patients with metastatic RCC underwent dynamic-contrast enhanced magnetic resonance imaging (DCE-MRI). DCE-MRI was used to calculate the gadolinium exchange constant between blood and tumor interstitial tissue, K(trans).
Conclusions:
In patients with RCC, inhibition of tumor vascular permeability by sorafenib was associated with improved outcome. Moreover, baseline tumor vascular permeability, expected to be a poor prognosis factor, was a predictive marker of favorable response to therapy.
Insights
Sorafenib, a novel tyrosine kinase inhibitor, demonstrated anti-angiogenic effects in renal cell carcinoma (RCC) patients. Reduced tumor vascular permeability correlated with improved outcomes and predicted favorable response to therapy.
Area of Science:
- Oncology
- Pharmacology
- Medical Imaging
Background:
- Angiogenesis inhibitors are crucial for renal cell carcinoma (RCC) due to the link between aberrant blood vessel formation and poor prognosis.
- Sorafenib, a dual RAF and VEGF receptor tyrosine kinase inhibitor, is investigated for its anti-angiogenic potential.
- The study aims to assess sorafenib's anti-angiogenic capacity and its correlation with patient outcomes in RCC.
Purpose of the Study:
- To evaluate the anti-angiogenic effect of sorafenib in patients with metastatic renal cell carcinoma (RCC).
- To determine the relationship between the anti-angiogenic effect of sorafenib and patient outcomes, including response and survival.
- To explore the predictive value of baseline tumor vascular permeability for treatment response.
Main Methods:
- Seventeen patients with metastatic RCC were included in the study.
- Dynamic-contrast enhanced magnetic resonance imaging (DCE-MRI) was utilized to measure K(trans), a marker of tumor vascular permeability.
- K(trans) was calculated before and during sorafenib treatment.
Main Results:
- Sorafenib treatment led to a significant decrease in K(trans), indicating an anti-angiogenic effect (60.3% decline).
- Four patients (24%) achieved partial response according to WHO criteria.
- Both the percentage decline in K(trans) and changes in tumor size were significantly associated with progression-free survival. Baseline K(trans) also predicted progression-free survival.
Conclusions:
- Sorafenib's inhibition of tumor vascular permeability in RCC patients is linked to improved clinical outcomes.
- Baseline tumor vascular permeability serves as a predictive marker for a favorable response to sorafenib therapy in RCC.
