Which Lung Cancer Groups Should Get Radiation?

THERE ARE SEVERAL QUESTIONS surrounding how radiation therapy — especially combined with other agents — fits into the treatment of patients with oligometastatic lung cancer, according to Kevin Stephans, M.D.

Oligometastatic lung cancer is disease that has spread, but only to a limited number of sites in the body. As such, it can have a better prognosis than disease that has spread widely, and can possibly be treated differently.

“As we get more phase 3 data, we will have a better understanding of where (radiation) fits,” explains Stephans, who discussed oligometastases during the 2016 State of the Science Summit on Metastatic Non—Small Cell Lung Cancer offered by OncLive®, an online sister publication to CURE®. “Does it fit in up front, or does it fit in later? Do we treat patients up front when they have the biggest burden of disease to get rid of resistant clones [cells that can linger and cause a recurrence], or do we go with simple treatment up front and hold radiation for the time of progression?”

What is new in oligometastatic lung cancer?

In an interview with OncLive® during the meeting, Stephans, an associate staff member in radiation oncology at Cleveland Clinic, gave a recap of the latest research in oligometastases for patients with lung cancer.Stephans: Most patients who have metastatic disease will present with multiple metastatic sites all over the body — though a small percentage will present with more isolated disease. Obviously, most of the therapies — such as the systemic chemotherapy or immunotherapy — are going to address disease anywhere. Stereotactic body radiation therapy is a particular technology that could address only localized disease. The advantage is that the side effects tend to be few because the treatment is localized, and the disadvantage is that it is only going to address disease at that site.

What do community oncologists not know about this type of disease?

There are different prognostic ways to pick patients who may be likely to progress at one or a few sites only. People who are younger with fewer sites are more likely to have a long response to chemotherapy. As long as those sites are not located somewhere that would be too toxic to deliver radiation, they could safely be treated. A very small set of patients may benefit from that therapy.We do not have randomized trials that look at randomizing “yes or no” to radiation. We have trials that suggest that patients who are radiated do well, but we do not really know what the benefit of radiation is because they may just be people who were well-selected who were going to receive that treatment anyway. It is important to be very careful in choosing which patients receive which treatments. If they strictly meet the criteria, and they are expected to tolerate therapy, then that is a good way to go.

Another thing that has surprised people in the past is that, when radiation is combined with some different systemic agents, that regimen is also well tolerated, though occasionally there are expected side effects.

Are there any ongoing clinical trials for these patients taking place?

Using radiation together with a VEGF-targeted agent, such as Avastin (bevacizumab), has associated toxicities that are much higher than what was expected. That is one thing to be really careful of in these patients who are doing well; they are probably going to get more therapy down the line because they are still going to be a good fit. We have to be careful on how we select those therapies and be aware that they have had radiation in the past.Most of the clinical trials have been phase 2 studies, so all of the patients receive the intervention. At the 2016 Annual Meeting of the American Society of Clinical Oncology, there were finally some phase 3 studies coming out in which people were randomized to consolidate a radiation, or consolidate a local therapy versus a more systemic therapy. It is too early to have data on survival, but the progression-free survival was pretty long. It was over one year for the radiated patients, and it was longer than it was for the patients on additional systemic therapy.

What are the biggest questions surrounding patients with oligometastases?

This was for those with one to three sites and stable disease on their prior chemotherapy regimen. It is a reasonable option for those patients; it allows the oncologist to hold back effective systemic therapy a little bit longer, and then have that agent available in the future.Again, one of the biggest questions concerns where this type of therapy fits in, and people often discuss cost-effectiveness, as well. All of that may change as agents are out for longer periods of time. It is a moving target, and it is the same thing with radiation. However, one advantage is that radiation is a one-time therapy, or it does not have to be continued and repaid-for every month, so it may be very cost-effective in that model. Again, that is a moving target.