Stereotactic body radiation therapy borrows the best elements of other forms of radiotherapy. Like intracranial stereotactic radiosurgery, stereotactic body radiation therapy uses multiple beams to spread out entrance dose and achieve dose fall-off to normal tissues. It also uses advanced imaging techniques to target and relocate the tumor for each treatment and employs 4D imaging for motion control technology.
By combining all these factors, SBRT delivers a potent radiation dose in five or fewer fractions and offers unique results that are different from conventionally fractionated radiotherapy, according to Robert D. Timmerman, MD, professor of radiation oncology and neurosurgery at the University of Texas Southwestern Medical Center in Dallas. This puts SBRT in position to be the standard of care for frail patients with stage I non-small-cell lung cancer (NSCLC).
It's true that SBRT has a lot of bells and whistles, but are proponents guilty of worshiping technology for technology's sake? Quite possibly, said David Ball, MD, deputy director of the division of radiation oncology at Peter MacCallum Cancer Centre in Melbourne. While SBRT offers no shortage of razzle-dazzle, it lacks the clinical and scientific evidence to support its routine use in stage I, inoperable NSCLC, he said.
Dr. Timmerman and Dr. Ball debated the pros and cons of SBRT as the standard of care in stage I NSCLC at the 2009 World Conference on Lung Cancer in San Francisco.
Dramatic improvement in local control
The first clinical models for SBRT were in patients with early-stage NSCLC who had multiple comorbidities and whose tumors were medically inoperable, said Dr. Timmerman. "The intent originally was to improve the rather poor tumor control these patients experienced after conventionally fractionated radiotherapy," he explained. "And most investigators using [SBRT] early on assumed that this would probably be at some expense at least in terms of increased toxicity compared with conventionally fractionated radiotherapy.
"But honestly that experience has not borne out. Tumor control has been dramatically improved [with SBRT] and the treatment is surprisingly well tolerated even with long-term follow up," he added.
The benefits of SBRT in early-stage NSCLC include:
|•||The tumor is significantly debulked and/or eradicated for a local control rate ranging from 60% to 90%.|
|•||Local immune function is, on the whole, preserved, especially in comparison with conventional radiotherapy.|
|•||Necrosis is avoided.|
There are a number of multicenter trials to support the use of SBRT. In the phase II RTOG 0236 trial, SBRT achieved a 98% local control rate. SBRT delivered a dose of 60 Gy to the tumor in three fractions over one week. The three-year overall survival (OS) was 56% in NSCLC patients with documented comorbidities, such as emphysema, heart disease, and stroke (ASTRO 2009 abstract 5).
Also, Pia Baumann, MD, and colleagues at institutions in Sweden, Norway, and Denmark reported a three-year local tumor control rate of more than 90%, with limited toxicity, in fifty-seven patients with NSCLC stages T1N0M0 and T2N0M0. SBRT was delivered three times at a dose of 15 Gy, 67% isodose of the planning target volume (J Clin Oncol 27:3290-3296, 2009).
The Japan Clinical Oncology Group is currently analyzing data from a trial of SBRT in patients with operable tumors (trial 0403), but in their previous research, the Japanese trial leaders have described excellent outcomes, including good long-term survival, for patients who have had SBRT, and favorable comparisons with patients treated with standard surgery have been made. However, Dr. Timmerman stressed that these studies were retrospective and not controlled (J Clin Oncol online, January 11, 2010).
"So the level of evidence shows SBRT for the frail patients is showing very good results, consistent results in mature phase II trials over many continents," Dr. Timmerman said. "The Scandinavian group is considering a study to randomize [patients] to SBRT or to conventional radiotherapy. The question is: Is that trial feasible? Is it necessary?" Historically, phase III data are required before a treatment method can become the standard of care, he said, but is it a must-have? Not necessarily. "Admittedly, in the modern era we generally require newer therapies to be proven by such high level evidence, especially if the standard and experimental therapy are similar. My position, however, in this case is that the evidence is so overwhelming that a phase III trial is unnecessary," he said.