Immunotherapy in Unresectable Locally Advanced NSCLC - Episode 1

Locally Advanced NSCLC: Workup and Treatment Approach

D. Ross Camidge, MD, PhD:When any patient with non—small cell lung cancer presents, the important thing to do is to stage them, and that really is to figure out how far the cancer has spread around their body. At least in our practice, and in many places in the United States and in the NCCN guidelines, that would include an MRI of the brain with contrast and a PET/CT scan. What you’re really looking for is, is it stage 1, 2, 3, 4? And you’re trying to use that information to determine how you’re going to treat the patient. If there are areas that are lighting up on the scan and you’re not certain, then you’d actually seek a tissue-based diagnosis to surgically stage someone.

For many years, the treatment of stage 3 disease—so that’s cancer that has spread to involve lymph nodes in the middle of the chest in the mediastinum, either on the same side as the cancer, an N2 disease, or on the opposite side, N3 disease—has involved some aspects of chemotherapy and radiotherapy that used to be given sequentially. So, you would start with radiotherapy and then add in chemotherapy at the end, or induction chemotherapy and then radiotherapy. But over the past 20 years or so, the concept of combination chemoradiotherapy has really been defined as the best approach in patients who can tolerate that. There’s no doubt that it increases the toxicity.

Given the concurrent chemoradiotherapy to date, it has the best outcome compared to sequential therapy. Unless the patient is really very frail, I would pursue a combination chemoradiotherapy approach. And I think what has improved over the past few years is the tolerability of the chemotherapy because of supportive medication, and their ability to target the radiation in a much more effective way such that the effects on normal tissues are reduced.

In some of the big guideline panels, you realize that if you get enough doctors in the room, you’ll get multiple different opinions. So, people have preferences they’d like to induce with chemotherapy, or go for chemoradiotherapy and then surgery, or just definitive chemoradiotherapy upfront. Nobody really knows. At least in our practice, we tend, if we’re not going for trimodality therapy, to just go for chemoradiotherapy from the get-go. The only advantage of doing induction chemotherapy is if you shrink the tumor, will you reduce the size of the radiotherapy field, and will that matter? The only reason it might matter is, for example, in a large tumor, do you have a particularly large dose to the lungs and could you lessen that and make it safer to give if you shrank it down with chemotherapy? But for most people, chemoradiotherapy from the get-go is usually what happens.

Transcript edited for clarity.