Lung Ablation Year in Review

Lung ablation is an active area of research in interventional oncology, and recently published studies have given clinicians more factors to consider when determining which patients are good candidates for the procedure. In this Q&A, Stephen Solomon, MD, reviews recently published trials, looks ahead to upcoming publications, and explains how genetic and histology factors may help predict response to ablation. Dr. Solomon is Chief of the Interventional Radiology Service at Memorial Sloan Kettering Cancer Center in New York City. He presented on lung ablation on Sunday, February 4 at the Symposium on Clinical Interventional Oncology (CIO).

Tell us about some of the most important research in lung ablation in the past year.

Dr. Solomon: Etay Ziv, MD, PhD, from our group published a paper in Radiology in 2017. It looked at the predictive value of KRAF mutation status in assessing local recurrence in patients undergoing image-guided primary lung cancer ablation. The study results showed that there is a relationship between having a KRAF mutation and a higher chance of local recurrence.

We also have several other ongoing studies looking at whether other markers indicate a good or bad response, and we are examining whether adding certain drugs and modifications to ablation could improve response. In the last year, we’ve also looked at whether the histology of lung cancer impacts response, and we found that patients with micropapillary lung cancer did worse than patients with other types of lung cancer.¹

These are two important studies for the field. They tell clinicians that patients with a KRAF mutation or micropapillary lung histology are less likely to do well. Maybe the margins need to be bigger for those patients, or maybe those patients are not good candidates for the procedure and should be referred to surgery or radiation. These studies are helpful to set expectations for both clinicians and patients.

What data are you expecting in 2018?

Dr. Solomon: Data from the SOLSTICE trial is highly anticipated. The trial is looking at cryoablation of lung metastases and assessing safety and efficacy. The study has closed to recruitment, and the data will be compiled and published soon.

The ECLIPSE trial, which was published in October 2015, was the prelude to the SOLSTICE trial. ECLIPSE was multicenter, but it had a smaller number of centers than SOLSTICE. ECLIPSE evaluated the safety, feasibility, and efficacy of cryoablation for treating metastatic pulmonary disease. In the ECLIPSE trial, the overall survival rate at 1 year was very high, nearly 98%. However, that number included a mix of tumors, so I’m not sure if the high overall survival rate is meaningful. The main takeaway was that it is safe to do lung cryoablation.

I especially like that SOLSTICE represents the interventional radiology community coming together for a prospective multicenter trial. These sorts of trials have been somewhat challenging for our specialty. There are lots of practitioners operating independently and with their own preferred methods, making it difficult to bring everyone together for a large study. SOLSTICE was very well organized, and I congratulate the team for the relatively fast accrual rate of a large number of patients. It’s encouraging to know that interventional radiology can conduct a trial such as SOLSTICE.

This trend of more trials is starting to happen in other areas as well, including radioembolization with the EPOCH and SIRFLOX trials. Oncology has a high bar of evidence and requires trials to move the needle on treatments. Thus, SOLSTICE and other trials of its nature are important because prospective, multicenter data provides a very high level of evidence. I think SOLSTICE will show that ablation can cause local control of metastatic disease, but we will have to wait until publication to see what the data says.

What is the next step for the field after the SOLSTICE trial?

Dr. Solomon: Other trials will look at energy sources beyond cryoablation, such as microwave ablation. Although SOLSTICE might show that cryoablation can locally control a tumor, other trials may focus on whether treatment helps to prolong overall survival. It might take a longer time to show there is an advantage in overall survival, but shorter endpoints such as chemotherapy holiday might also be possible.

Were there any studies that look at combining lung ablation with other modalities?

Dr. Solomon: I think an interesting area of the lung ablation field is the combination with immunotherapy and trying to understand how ablation can help to make the immunotherapies more effective. We know that immunotherapies might work better if you provide an antigen for the immune system to attack. Ablation is a good way to do that. Ablation causes a wound, and the wound releases signals that draw in the immune system to the area with the cancer. There have been several papers that have shown the beneficial effect of combining ablation with immunotherapy. That is something that has been coming out little by little, and hopefully we’ll have more information on that in the coming years.

On the other hand, some animal data has suggested that lesions that are not completely ablated may release signals that could potentially increase tumor growth. Better understanding that phenomenon biologically will help us figure out ways to control it.

What are some challenges with lung ablation?

Dr. Solomon: We do a lot of lung ablation at my institution, and that repetition makes us very comfortable performing the procedure. I think any challenges can be resolved by training and practice. As interventional radiologists, we have been focused mostly on the liver, but we need to have people dedicated to lung ablation. Practices should designate someone to focus on the lung just as they designate someone to be dedicated to liver interventions.

What are you expecting to see in the next 5 to 10 years?

Dr. Solomon: I think we’re still on a learning curve with lung ablation. We need to better understand the different technologies and modalities so that we can develop consistent, reproducible ablations. On the biological side, we need to understand what influences the results. During the past year, our group showed that there are certain genetic and histologic markers that indicate who would have a good response or not to lung ablation. Additionally, we need more physicians trained to offer lung ablation.

—Interview by Lauren LeBano

Reference

1. Gao S, Stein S, Petre EN, et al. Micropapillary and/or solid histologic subtype based on pre-treatment biopsy predicts local recurrence after thermal ablation of lung adenocarcinoma. Cardiovasc Intervent Radiol. 2017. doi: 10.1007/s00270-017-1760-8. [Epub ahead of print.]