New Approaches in Hepatocellular Carcinoma

Assessing response in hepatocellular carcinoma (HCC) can be very challenging, with RECIST criteria representing the only accepted method for assessing response, states Jeff Geschwind, MD. However, after local/regional therapy, tumors do not shrink, making RECIST assessment difficult. As a result, surrogate markers of tumor response are needed.

Another option for assessing response is through contrast enhanced imaging, which led to the development of the European Association for the Study of Liver (EASL) criteria, which calls for a bi-dimensional measurement of the residual enhancing portion of the tumor using contrast-enhanced CT or MRI. However, this strategy is complicated, and perpetuated the creation of the modified RECIST (mRECIST), Geschwind notes. The mRECIST system uni-dimensionally measures the longest axis of the residual enhancing portion of the tumor.

In addition to novel approaches for measuring response, new treatment options are also under exploration. Small studies have demonstrated efficacy with anti-CTLA-4 inhibitors in patients with HCC. Although promising, one concern is the reactivation that has been seen with other agents that have immunosuppressive or immunomodulating properties, notes Robert G. Gish, MD.

In addition to CTLA-4, PD-1 and PD-L1 agents are being explored to remove immune exhaustion concerns and allow the immune system to revitalize and potentially attack the virus and the liver cancer at the same time. In an early phase I/II, the PD-1 inhibitor nivolumab demonstrated an objective response rate of 19% in patients with advanced HCC.

Along with immunotherapy, the ability to deliver very small microspheres, 40 microns in size, loaded with chemotherapy is another major breakthrough in HCC, according to Geschwind. These microspheres are imageable, allowing the amount of chemotherapy delivered to the tumor to be calculated.

In conclusion, Gish stresses the importance of screening, surveillance, detecting liver disease, and detecting liver cancer early. In the next 20 years, states Adam C. Yopp, MD, there will be incredible new technologies and drugs that will make a definite impact in HCC. Richard Finn, MD, and Geschwind agree that patients are best served by having a multidisciplinary team. Finally, the panelists stress the importance of community oncologists continuing to engage with the research community, by enrolling appropriate patients into clinical trials, to improve outcomes for all patients.