Evaluating the metabolic effects of neoadjuvant treatment in clear cell renal cell carcinoma using hyperpolarized...

Despite recent therapeutic advances, renal cell carcinoma (RCC) has a high mortality rate. The development of new neoadjuvant strategies requires reliable companion biomarkers of early and successful response to treatment. A change in tumor size is a late measure of response and novel targeted imaging-based biomarkers may be more accurate for treatment response prediction. Here we evaluated the potential of hyperpolarized carbon-13 MRI (HP ¹³C-MRI), following the injection of hyperpolarized ¹³C-pyruvate, to assess response to neoadjuvant treatment in four patients with clear cell RCC as an exploratory outcome within a prospective clinical trial. The change in the tumor lactate-to-pyruvate ratio (LAC/PYR) following treatment varied across the patients: mean percentage change ± S.D. = +6 ± 27%. The largest decrease in LAC/PYR ratio was in the patient treated with cediranib monotherapy (-21%), followed by a smaller reduction in a patient receiving the combination of cediranib and olaparib (-14%). An increase in the LAC/PYR ratio post-treatment was observed in the second patient receiving combination treatment (+ 21%), with the largest increase in the patient receiving olaparib monotherapy (+ 35%). Metabolic changes were observed following treatment in the absence of significant changes in tumor size. In summary, HP ¹³C-MRI successfully captured heterogeneous metabolic responses to cediranib and olaparib therapy, revealing both increases and decreases in tumor lactate labelling, independent of any morphologic change. Finally, this is the first study to evaluate the potential of clinical HP ¹³C-MRI to assess early treatment response in renal cancer by using a range of therapeutics. KEY TAKE HOME MESSAGE: The study provides preliminary evidence supporting HP ¹³C-MRI as a promising imaging biomarker for evaluating early metabolic changes in renal cell carcinoma following neoadjuvant therapy. CLINICAL TRIALS REGISTRY: NCT03741426, Registration date: 13 November 2018.