Unresectable locally advanced NSCLC
Options and controversy around management options for unresectable stage IIIA and IIIB NSCLC
Like Charlie Brown always thinking that this time will be different when he tries to kick the football without Lucy pulling it away, we get lulled into thinking that we know the intuitive, obvious answer in medicine without really testing it, only to find that our assumption was wrong yet again. This time, the important new result comes from the annual meeting of the American Society for Therapeutic Radiation and Oncology (ASTRO), which is just ending in Miami. There, investigators from the Radiation Therapy Oncology Group (RTOG) released some important early results from a study, RTOG 0617, that will impact the way stage III (locally advanced) NSCLC is managed.
While in many older studies the dose of radiation was in the 60-61 Gray (Gy) range (Gy being the units of radiation dose) over 6-6.5 weeks, there has been a drift in routine practice to often higher doses, to 63-66 Gy pretty routinely and even up to 70-74 Gy in some places, and not just in clinical trials. This isn’t really based on the proven value of a higher dose over a lower dose, but rather based on the concept that the 60-61 Gy level wasn’t found to be the clear best dose in the past, but rather was what was considered to be more or less safe and feasible at the time, while there is really a dose-response effect beyond that. Then, over the past 10-15 years, certain centers have done research using more refined radiation techniques to deliver chest radiation up to doses in the range of 74 Gy or even higher, with concurrent chemotherapy. Since then, more and more radiation oncologists have followed, using conformal radiation techniques to routinely push what is perceived as a “standard dose” of chest radiation with concurrent chemotherapy, as many of us in the field came to view radiation to 60-61 Gy as potential under-dosing of treatment for concurrent chemoradiation today.
Here’s another case in the recording I did with Drs. Jyoti Patel from Northwestern and Bob Doebele from University of Colorado, discussing a series of perplexing cases in lung cancer management, then combining their comments with the responses from several other terrific experts (Drs. Suresh Ramalingam, Jonathan Goldman, Julie Brahmer, Heather Wakelee, and Karen Reckamp) about the same case. From each one, you can get a sense of the variability in how different lung cancer experts share the same set of data but have their own interpretation and style for cases where there are significant gaps in what the data tell us.
This particular case is one we struggle with all the time, and one for which many people have asked questions here. Once someone with unresectable stage III NSCLC has completed initial chemo/radiation, typically over an approximately seven week period, should we recommend any additional treatment after that. We are generally tempted to do so, in hopes of providing better results than what we might expect without it, but we don’t have evidence that it helps. I think you’ll get a clear sense of the uncertainty (at least mine), but several of the speakers also note their different mindset for those patients treated with weekly carbo/Taxol (paclitaxel) (which we believe doesn’t give meaningful systemic dosing to eradicate micrometastatic disease, but it can help make the radiation given concurrently more effective) versus “full dose” cisplatin/etoposide (which we feel does treat possible distant disease in addition to helping make the radiation more effective where it is directed).
So here’s the audio and video versions of the podcast, along with the transcript and figures from the presentation.
The answer is, “Usually pretty early”. I tell my patients that the risk is “front-loaded”, meaning that we typically see recurrences occur in the first couple of years after curative therapy for lung cancer, if they’re going to happen at all. That said, I haven’t seen a lot of data that actually illustrates the point, but there was a presentation at ASCO this past year that addressed how well recurrences/disease-free survival predict overall survival after surgery for resectable NSCLC. Not surprisingly, there was a very good correlation, though it wasn’t perfect (patients can die from side effects of the treatment, or from unrelated but competing medical problems).
In the process of reviewing the data from two “meta-analyses” of multiple smaller studies of chemotherapy after surgery, either with or without radiation also administered, a group led by Dr. Michiels from Institute Gustave-Roussy in Villejuif, France reported on the “lead time” that diseease-free survival gives in predicting overall survival. They found that, if recurrences were going to ever happen, about 50% occurred within the first year, at least two-thirds within two years, and about 80% or more within three years.