Dynamic Nuclear Polarization-MR Spectroscopic Imaging of Hepatocellular Carcinoma Metabolism to Predict Response Following Locoregional or Systemic Therapy

Hepatocellular carcinoma (HCC) is the most rapidly increasing cause of cancer mortality in the United States (US)1. HCC is a notoriously chemo-resistant malignancy. Surgical resection or liver transplantation remain the therapies of choice; however, fewer than 20% of HCC patients are candidates for resection, and transplantation rates are limited both by a static donor pool and HCC progression which precludes eligibility. Locoregional therapies for HCC include (i) trans-arterial chemoembolization (TACE), an endovascular locoregional embolotherapy that involves hepatic artery embolization with intra-arterial infusion of a chemotherapeutic agent, (ii) trans-arterial radioembolization (TARE), an endovascular locoregional embolotherapy that involves hepatic artery embolization with intra-arterial infusion of a non-absorbable microspheres containing the radioactive material yttrium-90 (Y90) and (iii) microwave ablation, a percutaneous therapy that targets tumor cells using thermal energy. Together with systemic therapies (ST), these approaches represent the most commonly used treatments for HCC in the United States.

While these therapies have a proven survival benefit, local recurrence and progressive disease are common, and long-term survival rates are poor even following a complete radiographic response (49% over median follow-up of 72 months), due at least in part, to suboptimal measures of response. Conventional imaging approaches have been unsuccessful in providing representative measures of response that are essential for guiding locoregional and systemic therapies for HCC. These approaches apply established guidelines for measurements provided by anatomic imaging, such as tumor size, and were originally intended to allow a uniform response assessment following conventional chemotherapeutics. The general inability of these guidelines to characterize the response to LRT or systemic therapy underscores fundamental limitations in the applied imaging paradigms which fail to provide functional measures of the intended therapeutic effect or the associated tumor response. This challenge requires the development of new imaging paradigms applying knowledge of the underlying tumor biology to enable the detection of treatment refractory, viable tumor domains.