Evaluating the metabolic effects of neoadjuvant treatment in clear cell renal cell carcinoma using hyperpolarised pyruvate MRI

Despite recent advances, [~]50% of people developing renal cell carcinoma (RCC) will die of the disease. The development of new neoadjuvant therapeutic strategies requires reliable companion biomarkers to measure early and successful response to treatment. Tumour size changes are often late markers of response, but novel imaging-based biomarkers may be more accurate for treatment response prediction. Here we evaluated the potential of hyperpolarised carbon-13 MRI (HP 13C-MRI) as an emerging clinical imaging technique for assessing response to neoadjuvant treatment in RCC, as part of the WIndow of opportunity in REnal cancer (WIRE) trial. The change in LAC/PYR ratio following treatment was variable across the four patients (mean{+/-}S.D. %change = +6{+/-}27%). LAC/PYR decreased in the patient treated with cediranib monotherapy (-21%), and in one of the patients receiving combination treatment (-14%). A higher LAC/PYR ratio post-treatment was observed in the second patient receiving combination treatment (+21%) and in the patient receiving olaparib monotherapy (+35%). This is the first study to evaluate the potential of clinical HP 13C-MRI in assessing early treatment response in renal cancer, which detected metabolic changes following treatment in the absence of significant changes in tumour size. Future studies should assess this finding in larger patient cohorts. Patient summaryIn this study we used an emerging clinical imaging technique, called hyperpolarised carbon-13 MRI, to visualise how kidney cancer changes with drug treatment before surgery. The method visualised rapid changes in cancer metabolism before substantial changes were seen in tumour size, the latter being the conventional method for detecting response to treatment. Hyperpolarised carbon-13 MRI holds promise in informing clinicians which cancers have successfully responded, and which may benefit from a change in treatment.