Stereotactic Body Radiation Therapy (SBRT) for NSCLC

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December 23, 2007 - 10:54 pm email to a friend printer friendly view / write comments

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Dr. West

One emerging alternative to standard radiation therapy for medically inoperable patients with early stage NSCLC is stereotactic body radiation therapy (SBRT). This technique requires fixation and very precise treatment planning for a brief course of radiation that targets a more limited radiation field. One key issue with SBRT is that it presumes you don’t need to do extensive radiation to lymph node areas around the primary tumor — this is a big topic, but the evidence generally suggests this to be true, that we really need to focus more on treating the disease we see with stronger and more precise radiation, rather than get too distracted by the potential presence of microscopic regional disease in lymph nodes that appear normal on scans (abstract here, for example).

Our standard radiation dose of 60-66 Gray (the unit of radiation administration) for NSCLC is based on remarkably little evidence and goes back several decades. In fact, we know that similar or lower doses of RT are very effective in eradicating microscopic disease and laryngeal cancers that measure just a few millimeters, but radiation that is routinely administered in the 70 Gray and higher range are fair to good at treating smaller tumors like prostate and cervical cancers, both of which generally falling in the range of a few cm. In contrast, radiation for NSCLC lung lesions are often in the 5-10 cm range, and radiation in the 60 Gy range just isn’t that effective for such large and not especially radiosensitive tumors.

Newer techniques allow us to potentially deliver one or just a few fractions of very high dose radiation to a precisely limited area, thus reducing the risk of damage to surrounding areas and the need to administer radiation over many fractions over several weeks (radiation at low doses over many weeks takes advantages of the fact that normal non-cancer cells can recover better from radiation-induced DNA damage, leading to our routines of small doses accumulating over many weeks). By giving very high doses to a very defined area, stereotactic radiation becomes similar to a non-invasive form of surgery, leading to it being marketed as “gamma knife” or “cyber knife” (if you actually see any knives during these procedures, you should be concerned). This line of study was pioneered in the field of treating brain lesions, where the skull can serve as a reference system and the entire area can be immobilized with a fixed frame screwed into the skull (temporarily). These strategies are now very widely used for primary brain tumors or metastases to the brain from other sites.

But there are new techniques that allow introduction of the previously brain-based approach to body lesions as well. One of the less technical ones is to have a device that compresses the abdomen to minimize the ability of the diaphragm to move up and down and change the shape of the lungs:

(Click on image to enlarge)

That white arc is where a patient’s abdomen is, and the vertical screw clamps down on the abdomen to limit motion. You may also note the presence of a metal frame on either side of the chest to hold it in place as well. It may seem medieval, but this is a potential step forward in treating cancer.

Other developments include more precise “image-guided radiation therapy” (in which the radiation is adjusted based on ongoing feedback from scans) and approaches such as “respiratory gating”, in which the radiation beam is on only during the same point in a patient’s respiratory cycle, such as at the end of expiration, in order to keep the chest structures as precisely in their expected place as possible. New lung SBRT systems may employ a gold fiducial (or fiduciary marker) that is placed in or near the lesion as a fixed reference point that can be continuously monitored during treatment. only administering RT when the marker is in a particular place or narrow range.

There have been a growing number of single-institution studies of SBRT for early stage NSCLC in medically inoperable patients or those who refused surgery (example abstracts here and here). However, a much larger retrospective experience has been published by Onishi and colleagues from Japan. A full report of 245 patients with stage I NSCLC treated in Japan between 1995 and 2003 were treated with varying doses and schedules, anywhere from a single large dose up to 22 fractions (abstract here). The local recurrence rate was 14.5%, and superior results were noted among recipients of a higher biological equivalent dose (or BED, a product of both total dose and the time it took to give it — the same total dose is equal to a lower BED if given over more fractions) of 100 Gray or higher compared with those who received a lower dose (local recurrence rate 8.1% vs. 26.4%, respectively, p < 0.05):

In addition, survival was significantly better for the approximately 40% of patients who underwent SBRT but were considered medically operable, presumably overall healthier than the other 60% who were medically inoperable (p < 0.01):

Importantly, side effects were quite modest overall, primarily with low grade pneumonitis and very low rates of esophagitis or skin reactions. These data were all updated with 300 patients at ASCO 2006, with the same overall findings (abstract here).

SBRT isn’t yet widely available, but it’s becoming an increasingly used tool, one that we’ll need to study in carefully designed clinical trials to better determine where its role should be. It certainly appears to be an option to deliver higher doses of radiation with potentially less collateral damage to surrounding tissues, along with a much shorter duration of treatment.

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