ASTRO 2015

Is 3D-conformational or intensity-modulated radiation therapy better for NSCLC?

Dr Stephen Chun - MD Anderson Cancer Centre, Houston, USA

We looked at one of the largest studies ever to look at chemoradiotherapy for locally advanced lung cancer. To begin with, lung cancer is the leading cause of cancer mortality in the United States. There are about 200,000 cases per year and about a third of those cases are what we’d call locally advanced or unresectable, they cannot be removed by surgery. So in those cases the standard of care is chemotherapy with radiation therapy. In one of the largest trials called RTOG-0617 the radiation technique, either 3D-conformal technique or IMRT, intensity modulated radiation, was left to the discretion of the treating physician. 3D-conformal technique is an older technique that sculpts radiation doses in straight lines directed at tumours whereas IMRT, by using highly conformal and modulated beam arrangements, sculpts and moulds the radiation dose to tumours in a much more sophisticated way such that you can spare normal tissues to a much greater degree than you can with 3D-conformal technique. Because of that, we had the idea that by looking at these two populations we might be able to tell whether there were differences in outcomes by different radiation technique in this trial.

What was the main hypothesis of the analysis?

Our main hypothesis was that by using highly complex and modulated beam arrangements we would improve oncologic outcomes. Whether this be toxicity or tumour control, we looked at all sorts of outcomes including the ability to tolerate chemotherapy as well.

What were the main findings?

One of the main findings that we found to be associated with IMRT was a significant two-fold reduction in the rate of severe pneumonitis. We defined severe or grade 3 pneumonitis as requiring high dose steroids, requiring oxygen, requiring a hospital admission, a ventilator or death. So we were really dealing with the most serious types of pneumonitis. There was a significant reduction associated with IMRT and in multivariant analysis IMRT continued to be associated with reduced pneumonitis risk and this effect was most pronounced in the largest tumours that are the most difficult to treat.

What about the tumour control?

We saw similar control between IMRT and 3D conformal, although the tumours were much larger with the IMRT group.

What are the clinical implications?

The potential ramifications of the pneumonitis finding are such that a hospital admission for pneumonitis or for any serious toxicity can run upwards of tens of thousands of dollars for admission. By reducing serious toxicity, when multiplied over the 70,000 or so patients with lung cancer per year, there are incredible potentials for cost savings, in the order of billions of dollars from this study.

What are some of the future research aims?

I think once the outcomes of this study are reported we would then want to look at long-term outcomes of 3D and IMRT. Presently we are not seeing a survival benefit associated with IMRT, however, patients with IMRT had less severe pneumonitis, they also received more chemotherapy and they also received lower doses to the heart. All of these things give us some idea that with more follow-up there might be a survival advantage associated with IMRT but we don’t have that data yet.

What is the main take home message from these data?

Our main take home message from the data is that right now in this country in this trial about 50% were treated with 3D-conformal technique, 50% were treated with IMRT. Our main take-home message is that, because of the benefits associated with IMRT, IMRT might be routinely considered for patients with locally advanced lung cancer. For the past decade IMRT has been accepted for disease sites like the head and neck, the prostate, the brain and other sites because of toxicity benefits. What we are seeing here is a toxicity benefit and we believe that these findings support more routine use of IMRT for this population.

So should clinicians now be using IMRT over 3DSRT in NSLC?

For the past two, almost three, decades the standard of care for lung cancer with concurrent chemoradiation was 3D-conformal technique. This is really a practice changing study. We are advocating changing from 3D-technique which will frequently treat from in front, from behind, maybe both sides, whereas IMRT has maybe a dozen beam arrangements, highly modulated, highly sculpted to the tumour and able to provide a much greater degree of sparing of normal tissue. So we’ve made that transition for prostate, for head and neck, for brain some time ago. This study, I believe, provides justification for making a similar leap in lung cancer.