Dirk De Ruysscher, MD, PhD: There are different types of radiation we can use and this depends, of course, on the aim of the treatment and also what the patient can bear. The aim of the treatment is broadly speaking, palliation or curative intent. When it comes to palliation, most of the time it’s 5 times 4 gray, sometimes 10 times 3 gray, just aiming to reduce cough, for instance, sometimes pain, but more dyspnea and cough. And because stage IIII non—small cell lung cancer is a disease where the patient has a median age of something like 70, and most patients have smoked, let’s say, 30 to 60 packs a year, a lot of patients have so many comorbidities that we only can offer them palliative treatment. In the Netherlands, for instance, it’s about 20% to 25% of those patients who can only be offered palliative treatment, and so that’s a very important part of the whole spectrum of stage III disease.

In patients who are amenable to curative treatment, the first choice in most of the patients is concurrent chemotherapy and radiation. In that case, we deliver radiation, 60 gray. So 5 times a week to a total dose of 60 gray. That’s the classical one because there’s been randomized studies, mostly coming from the United States, showing that there’s no use to increase the radiation dose that has no benefit for the patients. We did a lot of studies on hyperfractionated radiation and X-ray radiation where you give a whole bunch of the treatment in a short overall treatment time. If you give this together with chemotherapy, you don’t have an improved overall survival rate. So that’s not to be given.

If you give sequential chemoradiation, that means you give first chemotherapy and then radiation. This is better for patients whose general condition is not so good, so for instance, performance status 2 or for patients who are elderly, and the cutoff is more difficult to define, but something like 74, 75 years old. Then it’s probably better to offer them chemotherapy and radiation, and then we give the radiation accelerated because we have shown that in that circumstance, you indeed have a better overall survival, even after 5 years without increasing toxicity. And then it is better to give something like 60 to 66 gray in 20 to 24 fractions, so a really hyperfractionated regimen. Probably this is better for the frail and for the elderly patient because if you give them concurrent chemoradiation, because of the excessive mortality, because of toxicity, the overall survival may be worse even if you give them the so-called first choice treatment. So you should be aware of that.

Then you have a smaller group that is really elderly patients, patients of about 80 years old, or who have a lot of comorbidities. They can be given radiation alone, and in that case, it’s still curative. However, the 5-year overall survival is only between 15% and 20%. But the toxicity of that treatment is quite low as well. So it’s always a balance, of course, between toxicity and the overall survival on one hand and on the other hand, the comorbidity of the patient. Because most of those patients have lung emphysema, have cardiac disease, have already had a stroke because of their smoking history.

The type of radiation is external beam radiation. Brachytherapy has been used a lot in the past for palliation, but nowadays because of the better techniques, we can do it computerized and with the external beam. So there’s no use except for some very special cases to use brachytherapy anymore, which is good for the patients because you don’t need an endoscopy. For the rest, most patients are treated with photon beams, using some kind of intensity modulated radiation treatment. It may be with tomotherapy, it may be VMAT [volumetric modulated arc radiotherapy], it may be automated techniques, but all of those techniques are about the same if you look at the overall results.

What is important though is to stick to some standard protocols. For instance, we have published protocols of the EORTC [European Organization for Research and Treatment of Cancer], which specify the technique, the type of calculation of the dose, which constraints should be used for the normal tissues to avoid excessive toxicity, and so on and so forth. Very detailed technical papers are available, and it’s important to really stick to them and not to use something out of the box because then you may run into excessive toxicity or less local tumor control. That’s obvious. Proton therapy may be used as well, but that’s in a lot of countries, not in the Netherlands. That’s an experimental treatment because we don’t have too much data about it, but we expect less toxicity because by using protons you have a lower dose to the organs like the heart and the lungs. However, I should stress that it’s not the case that you should treat all patients with proton therapy. It’s only a very small group who may benefit from this more expensive treatment.

Transcript Edited for Clarity