The implementation of a multidisciplinary team, which has demonstrated a marked survival advantage compared with single-provider care, is critical in hepatocellular carcinoma (HCC), particularly as it relates to the evolving role of radiation, surgical resection, liver transplantation, and systemic treatment, explained Neehar Parikh, MD.
"HCC is a unique malignancy in that multidisciplinary care has been shown to improve outcomes," said Parikh. "Every patient diagnosed with HCC deserves to know whether they are a candidate for transplant, so they can proceed with [their] treatment."
Moreover, the HCC community is also anticipating the approval of the frontline combination of atezolizumab (Tecentriq) and bevacizumab (Avastin) in the advanced setting.
In an interview with OncLive, Parikh, an assistant professor, transplant hepatologist, and medical director of the Multidisciplinary Liver Tumor Clinic and Living Donor Liver Transplantation Program at Michigan Medicine, University of Michigan, shed light on the role of multidisciplinary care in HCC, other therapeutic modalities on the horizon, and anticipated sequencing challenges in the paradigm.
OncLive: What is the role of multidisciplinary care in HCC?
Parikh: Most university [centers] have a multidisciplinary group of physicians that take care of patients with HCC. This group includes hepatologists, interventional radiologists, medical oncologists, diagnostic radiologists, and palliative care physicians. These physicians work together to come up with treatment plans and handle any complications their patients with HCC may develop over time.
A few analyses have shown that multidisciplinary care versus single-provider care can improve the overall survival and cure [rates] of patients with HCC.
Should all patients with HCC be evaluated for transplant?
Every patient with liver cancer should be evaluated to determine whether they are eligible for a liver transplant because transplant is associated with the best outcome, regardless of which patient population you look at.
Once [a patient has access] to a center that does liver transplant, they usually have access to the multidisciplinary care team. Of course, not every patient is going to be eligible [for transplant], but it is difficult to determine whether a patient is eligible without understanding the nuances behind transplant and liver cancer.
What factors influence whether a patient is eligible for transplant?
It is complicated, and it varies by center to some degree. Traditionally, we have used tumor size and the number [of lesions] as the criteria for liver transplant, [according to] the national Milan criteria. Of course, patients have to have other qualifications [to be eligible for transplant]. They have to have a social support [system], as well as not have any major psychosocial issues or substance abuse [problems]. If a patient passes those bars, they may be eligible for liver transplant.
Additionally, there are some patients who [fall outside of those parameters] who receive transplant through a living donor, or [after being de-staged] with treatment. It is not a "cut and dry" answer, so it is good for the patient to be evaluated in an expert center.
How will novel combinations impact the treatment paradigm of HCC?
We are expecting the approval of atezolizumab plus bevacizumab for the first-line treatment of patients with advanced HCC. The paradigm is changing, at least in the United States. That regimen will likely become our standard of care, and everything in the second-line and subsequent settings will shift.
The question ultimately becomes, "How do you sequence therapies?" There is no clear paradigm for that at this point, so that is an area of ongoing research.
What other therapeutic modalities are available for patients with HCC?
Liver transplantation is an evolving field in HCC. We are going to see more living donation for these patients who tend to be disadvantaged with the current system.
We also have to think about the role of surgical resection. Should we be doing surgery on more patients or more aggressive surgical interventions? The outcomes are important in this patient population.
Locoregional therapies are also effective therapies for experienced centers to have in their toolbox. They may offer somewhat equivalent outcomes [to systemic therapies], but it is important to ensure the patient receives the therapy that is right for them.
What is the role of radiation in HCC?
Radiotherapy is still an evolving field as most of the data are retrospective. There are some deficiencies in the literature, but there are several ongoing trials. We hope to have better data regarding the role of stereotactic body radiotherapy (SBRT) in HCC. For the most part, people agree that SBRT is effective and safe.
These are patients who may not otherwise be amenable to thermal ablation or some other therapy, such as surgical resection. SBRT seems to have reasonable outcomes in some patients. However, the question of how patients with larger tumors [respond to SBRT] remains unanswered. Additionally, if a patient is eligible for chemoembolization and radiation, we don't know whether one is better than the other.
There are some retrospective data that suggest SBRT can be effective in this patient population, but we don't know. There are a lot of open questions, but thankfully, there are a lot of ongoing trials that will give us some answers.
Where do you see the field headed in the next 5 to 10 years?
There are multiple agents and combinations that are being evaluated in phase 3 clinical trials. We will see more positive trials, given the way they are designed.
However, again, the question will become, "How do we choose which regimen is right for which patient?" The atezolizumab/bevacizumab regimen has certain advantages since it will likely be the first to market, and both agents are given via infusion. Additionally, the combination does not require a TKI like some of the other combinations do, which increases the toxicity.
It will be interesting to see superior response rates with other regimens that are under evaluation, but in a selected population of patients with HCC. I don't know if we are going to see much better results than the IMbrave150 trial. We are likely going to be left with several different options in the frontline setting.
In the future, I hope that we will identify biomarkers to determine who is going to respond to what therapy. Those could be blood-based biomarkers, radiographic biomarkers, or biomarkers based upon the tumor mutational burden. We're moving toward a more personalized way of treating patients with intermediate to advanced HCC, which I hope will improve patient outcomes.
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