Approaches in Radiation for Locally Advanced NSCLC

At the 2019 Perspectives in Thoracic Oncology meeting, Abigail Berman, MD, MSCE, Assistant Professor of Radiation Oncology, University of Pennsylvania, and Associate Director, Medical, Penn Center for Precision Medicine, Philadelphia, presented on radiation therapy approaches for patients with locally advanced non–small-cell lung cancer (NSCLC).

In an interview with Oncology Learning Network, Dr Berman summarized the details of her presentation.

Dr Berman: I spoke about radiation approaches for locally advanced NSCLC. Specifically, I focused on the role of proton therapy in locally advanced NSCLC.

I started off by talking about how, now more than ever, it's really important to consider what radiation approaches you're using, because in the era of the PACIFIC trial and immunotherapy being an important component of treatment, patients are not only living longer, but we're giving them more treatment, which makes them more exposed to the risk of various toxicities, most notably pneumonitis or other organ damage near the target.

In general, when considering the role of radiation, you not only have to consider toxicity, but also the importance of local control. We saw from our most recent conference this past year in 2019 that out of all patients who progress, intra thoracic progression is still the most common place of progression, so local control is still critically important.

We know from RTOG 0617 that 60 Gy is superior to a higher dose. However, there may be select circumstances where, if we can achieve a higher dose safely, then we may be able to achieve better local control; therefore, that may be the best outcome for the patient.

We have increasingly had an appreciation of what we call our organs at risk in the radiation world, which means the doses that go to various organs nearby the target. In the case of locally advanced lung cancer, that is the lung, the esophagus, and the heart.

In the case of the lung, we're worried about pneumonitis. As many are aware, immunotherapy itself— which is now a backbone of the locally advanced treatment paradigm—poses a risk for pneumonitis as well. We have to think about the risk of not only radiation induced pneumonitis, but also immunotherapy induced pneumonitis.

Fortunately, studies have shown that, in general, the risk only goes between, say, 3% to 11% of grade ≥3 pneumonitis. I really think that that is a testament to radiation oncologists being very vigilant about keeping the total lung dose down nicely.

In terms of proton therapy, there have been conflicting studies, some that demonstrate excellent outcomes and some that demonstrate that there may not be much superiority above that of intensity modulated radiation.

However, the studies that have compared them, or the 1 large study, does have significant flaws in the sense that it had a heterogeneous population. It used an older type of proton therapy than is typically used nowadays, and also demonstrated that there was some significant heterogeneity in the planning approaches with proton therapy. Therefore, the approach for whether or not proton therapy is appropriate for a patient should be on a case by case basis.

One appreciation that we have recently is of the heart dose. For a long time, radiation oncologists felt that the heart was an organ that was not damaged in the short term, but rather would only really be at risk in the long term.

Now, we have an appreciation that, in the short term, we can see cardiac damage, and therefore we strive to keep the heart dose below at least 20 Gy, if not the dose <20 Gy, if not <10 Gy, ideally. When we keep that heart dose low, proton therapy is just one way we often are able to lower the dose very nicely.

We don't have clear consensus in our literature as to exactly which dosimetric parameters or which cardiac substructures are the most critical when it comes to heart dose. However, if we just look at an overall heart dose, the mean, that seems to be one of our best approximates right now.

In addition, when we think about heart dose, we have to always remember that the lung dose, for which we have excellent data to prevent pneumonitis, and our target coverage, are really the most important tenets of radiation for locally advanced non small cell lung cancer, whether you're treating with protons or photons.

Lowering heart dose is excellent as well, but to keep all of these aspects in our minds. Therefore, we really strongly consider proton therapy for patients particularly with large tumors, with preexisting comorbidities, particularly cardiac comorbidities, of young patients, or patients with very centrally located disease that are particularly close to the heart.