Y-90 Treatment in Earlier-Stage Disease Shows Promise

Radioembolization with yttrium 90 (Y90) has typically been used for patients in the later stages of hepatocellular carcinoma (HCC), but new data have suggested that treating patients at earlier stages might be beneficial. In this Q&A, Robert Lewandowski, MD, FSIR, shares some of the treatment strategies at his own practice and comments on the data informing them. Dr. Lewandowski is an interventional radiologist at Northwestern University Feinberg School of Medicine in Chicago, Illinois, and he will be a faculty member at the 2018 Symposium on Clinical Interventional Oncology (CIO) on February 3-4, 2018 in Hollywood, Florida.

In the past year of practicing Y-90 therapy, are there any clinical pearls that you want to share with your colleagues?

From a Y-90 standpoint, the area that I’m currently most excited about is adopting the therapy to treat patients with earlier-stage HCC. We are converting patients to curative liver resection with radiation lobectomy, and we are delivering ablative, high-dose, radiation in a segmental fashion, termed radiation segmentectomy, as an alternative to ablation or as a bridge to liver transplant.

Radioembolization has historically been employed for patients who were not appropriate candidates for other therapies secondary to more advanced disease requiring lobar treatments or those patients failing other embolotherapies. We’re now using radioembolization for healthier patients earlier in their disease course, and we’re getting some very interesting outcomes.

What led to that change in treatment strategy?

There are a few drivers for this change in our treatment strategies for patients with unresectable HCC. The first is the impact of now having treated >1,000 HCC patients with radioembolization at our center. Our multidisciplinary approach, close clinical follow-up, and data analysis inform of the versatility of this therapy. The second is the completion of a prospective randomized trial, the PREMIERE trial, at our institution. For patients with unresectable, non-ablate-able HCC, we compared conventional transarterial chemoembolization (cTACE) versus radioembolization with glass microspheres.

Published in Gastroenterology in 2016, the PREMIERE trial demonstrated that Y90 radioembolization provided significantly longer time to progression (TTP) than cTACE in patients with Barcelona Clinic Liver Cancer stages A or B disease.1 A prior retrospective study comparing segmental cTACE vs lobar radioembolization revealed TTP results favoring radioembolization;2  in the PREMIERE trial, the TTP for Y-90 was > 26 months versus 6.8 months for cTACE. By comparing Y90 and cTACE prospectively in similar HCC patients, we’re seeing superior outcomes for Y90. Longer time to progression is particularly important when the goal is bridging patients to liver transplant; recent organ allocation changes mandate a 6-month waiting period. Longer TTP equates to fewer treatments, fewer hospital visits, and fewer times patients’ families are driving them back and forth, etc.

Has that change to using Y90 at an earlier stage spread to the majority of IO practices?

The change to using Y90 at an earlier HCC stage has spread to some other practices, and I think many practices are interested in treating earlier. I encourage more people to take this approach. Outcomes from studies published by Edward Kim at Mount Sinai and Siddharth Padia at UCLA help validate our approach. The message is pretty consistent.3,4

For any practice that is beginning to treat in this manner, are there any changes to technique that are important to remember?      

There is little technical barrier to implementing this technique. Most interventional radiologists are skilled at segmental microcatheter techniques, and the use of cone-beam CT has become very common. Dosimetry considerations are not challenging, as we target > 200 Gray for the treated segment based on our prior work.5

Can you kind of give an example of how a patient might benefit from this treatment approach?

The obvious example is the HCC patient being bridged to liver transplant. With TTP > 26 months, the vast majority of these patients can be maintained with Milan criteria during their waiting period on the transplant list with just one treatment. Alternatively, segmental Y90 can be beneficial for those HCC patients that need a liver transplant but are outside of the Milan transplant criteria (e.g., tumor > 5 cm). This approach has been shown to have the ability to decrease tumors to within Milan criteria, facilitating liver transplant.6

Is there something that you personally learned or improved on in the past year in your own technique that you think would be beneficial to share?

Over the past few years, I have learned to be more aggressive in treating HCC with a segmental approach, even with radioembolization. We are learning that outcomes are better with cTACE when performed with super selective techniques; we need to start performing radioembolization in a similar fashion when possible.

Are there any tips you have with managing these patients? 

Y-90 radioembolization is an outpatient therapy that’s fairly well-tolerated. Patients do not often have significant side effects or side effects that require intensive management. However, it’s important for interventional radiologists practicing Y-90 therapy or any cancer therapy to take ownership of these patients, particularly during the peri-procedural period. We have to manage side effects and complications, and we need to have a process in place in our offices to do so. We can’t expect medical oncologists or other colleagues to manage side effects from our procedures. We need to understand the management of side effects and complications and integrate that into our practices.

Do you have any tips for optimizing radiation doses?

Dosimetry is fairly simplistic. The dosimetry models in general, while not perfect, have over the course of thousands of patients now demonstrated safety. There is a lot of interest in optimizing outcomes through better understanding of dosimetry, but there is more work to be done in this arena.

The FOXFIRE Global studies have been a hot topic this year. Were there any other recent studies that you want to highlight?

The SARAH and SorAfenib prospective randomized Y90 trials in HCC were, in essence, negative trials, similar to the FOXFIRE trial. However, to digest the information, we need to see the manuscripts and understand which patients were treated and in what fashion, and better understand the limitations and outcomes. The reality is that the investigators found no difference in overall survival between sorafenib and resin radioembolization in patients with advanced disease. In reality, that finding is not unexpected given that survival studies in HCC are difficult. I think a more interesting concept is how to best combine systemic and loco-regional therapies. Our approach to these patients since 2008 with the approval of sorafenib for HCC has been to perform radioembolization followed by sorafenib 2-4 weeks later. I do think an important endpoint for these patients is quality of life, and I expect Y90 to outperform systemic therapies. We’ll certainly learn more about these studies and the FOXFIRE Global studies as time goes on, and I believe they’re important to the field of interventional radiology.

Do you have any comments on the multidisciplinary nature of treating patients?

A multidisciplinary approach to patient care is critical. A truly collaborative approach, putting local politics aside, is the best way to achieve optimal patient outcomes. This approach is also rewarding as we can learn from our colleagues in other disciplines while we put the patients’ interests first.

What are you excited about learning at CIO?

I’ve always enjoyed attending CIO. At the end of the day, I believe CIO provides faculty and attendees with some really practical information. I think that’s what differentiates it from other meetings—the nuts and bolts of clinical practice are thoroughly covered at this meeting.

References

1. Salem R, Gordon AC, Mouli S, et al. Y90 radioembolization significantly prolongs time to progression compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology. 2016;151(6):1155-1163.e2

2. Salem R, Lewandowski RJ, Kulik L, et al. Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology. 2011;140(2):497-507.e2

3. Biederman DM, Titano JJ, Bishay VL, et al. Radiation segmentectomy versus TACE combined with microwave ablation for unresectable solitary hepatocellular carcinoma up to 3 cm: a propensity score matching study. Radiology. 2017;283(3):895-905.

4. Padia SA, Johnson GE, Horton KJ, et al. Segmental yttrium-90 radioembolization versus segmental chemoembolization for localized hepatocellular carcinoma: results of a single-center, retrospective, propensity score-matched study. J Vasc Interv Radiol. 2017;28(6):777-785.e1

5. Vouche M, Habib A, Ward TJ, et al. Unresectable solitary hepatocellular carcinoma not amenable to radiofrequency ablation: multicenter radiology-pathology correlation and survival of radiation segmentectomy. Hepatology. 2014;60(1):192-201.

6. Lewandowski RJ, Kulik LM, Riaz A, et al. A comparative analysis of transarterial downstaging for hepatocellular carcinoma: chemoembolization versus radioembolization. Am J Transplant. 2009;9(8):1920-1928