SAN FRANCISCO – Stereotactic body radiation therapy has durable safety and efficacy when used to treat early lung cancer in patients who can’t undergo surgery for medical reasons, according to updated results of the Radiation Therapy Oncology Group’s 0236 trial (RTOG 0236), reported at the annual scientific meeting of the American Society for Radiation Oncology.
The trial was the first North American cooperative group trial to test this image-guided, highly focused form of radiation. The 59 patients studied all had stage 1 non–small cell lung cancer, but were frail and unable to undergo surgery because of comorbidities such as emphysema, heart disease, and stroke.
“Patients like this are typically not allowed into clinical trials because their prognosis is so bad. But these were exactly the patients that we selected,” lead investigator Dr. Robert Timmerman, professor and vice chair of the Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, commented in a press briefing.
Susan London/Frontline Medical News
Dr. Robert Timmerman
Initial findings, reported after a median follow-up of about 3 years, led to “a fairly significant transition of care. The results at that time were frankly astounding, with nearly perfect tumor control at the treated site,” he said (JAMA 2010;303:1070-6). “There was skepticism, however, that led to sort of incomplete market penetration throughout cancer centers due to a concern about late toxicity that might occur with longer follow-up, or additional recurrences.”
But the updated results, now after a median follow-up of 4 years (7.2 years for survivors), showed that the 5-year rate of primary tumor recurrence in the radiation field was just 7%. “This is on par with surgery,” Dr. Timmerman noted.
Five-year overall survival was 40% (down from the initial 3-year rate of 56%). “Survival continues to decline as we might expect for a very frail population with competing causes of death but is still very impressive,” he maintained.
In terms of recurrences outside of the radiation field, seven patients had a regional failure (up from two initially), leading to a locoregional failure rate of 38% (up from 13%). “This indicates that our staging at the time of diagnosis was probably incorrect in that there were micrometastases. It did take a long time for many of these to appear, and most of them were in the involved lobe outside of the treated area,” Dr. Timmerman elaborated. “So, in response to that, we’ll need to look carefully at better staging and more effective adjuvant therapy to address this problem.”
Additionally, 15 patients developed disseminated metastases (up from 11). Five-year disease-free survival was therefore 26% (down from 48%).
“The really exciting news though was that there really wasn’t any significant difference in the toxicity with longer follow-up. This was something that many thought was going to happen,” Dr. Timmerman commented. Specifically, there were no treatment-related deaths. Seventeen patients experienced high-grade toxicity, consisting mainly of pulmonary toxicity.
The trial’s findings are pertinent to the roughly 10,000 patients in the United States each year who receive a diagnosis of stage I lung cancer and are not surgical candidates, according to Dr. Timmerman.
A survey done after the initial report suggested that although 70%-80% of centers have stereotactic body radiation therapy (SBRT) capability, only 40%-50% are actually using it. “These results, though, I think will change that dynamic. There were people who were skeptical, and in fact, there were a lot of notable people in our field who told everybody, ‘Pull the horses back,’ because there could be these late terrible side effects that were observed 100 years ago when similar treatment was done with low-tech treatments,” he said. “So that’s probably the biggest message from this long-term report: We did not see those horrible late side effects that were predicted.”
Lack of training may also explain in part the limited use of SBRT, he added. “You can buy the equipment if you have the money, but that doesn’t mean you have the training to run the equipment. So the big challenge that we will have as a profession – and I think ASTRO is really going to have to address this – is facilitating the training so that people can get this treatment where they live. Not everybody can go to the big academic medical centers and get treatment.”
“We are about to embark on a phase III trial that will randomize centers to treat with either SBRT or surgery for high-risk operable patients in clusters of three to five patients,” noted Dr. Timmerman. “This is very innovative. There have been several randomized trials that failed to accrue when the operable patients were randomized on a per-patient basis because there is such a disparity between the two treatments that the patient just couldn’t accept the randomization.”