Updated results from RTOG 0236, a phase II trial examining stereotactic body radiation therapy for inoperable early-stage non–small cell lung cancer, indicate that this treatment continues to yield a high rate of primary tumor control. Compared with conventional radiotherapy, overall survival is also significantly improved.

The prognosis for non–small cell lung cancer (NSCLC) is best for the 20% of patients whose disease is detected early: Surgery is standard, and 60% to 80% are cured. However, due to comorbidities such as emphysema and heart disease, some patients are ineligible for surgery and fare worse on the traditional alternative—conventional fractionated radiotherapy, with a 2-year survival rate below 40%.

Stereotactic body radiation therapy (SBRT) may be a better option for these patients, says Robert Timmerman, MD, vice chair of radiation oncology at The University of Texas Southwestern Medical Center in Dallas, and principal investigator of RTOG 0236, the first phase II multicenter trial examining SBRT in patients with NSCLC who cannot tolerate surgery. He recently presented updated results of this study—first published in 2010—at the 2014 annual meeting of the American Society for Radiation Oncology in San Francisco, CA.

Within 5 years of SBRT, Timmerman reported, only 7% of 55 evaluable patients had primary tumor recurrence (at the site of origin). Another 38% of patients experienced spread of their disease within the same lobe or to nearby lymph nodes. The 5-year overall survival rate was 40%.

“Potential cures for lung cancer must be judged at least partly on their ability to control primary disease,” Timmerman says. SBRT, he adds, delivers on this essential requirement, at a rate similar to surgery. With SBRT, a few large doses of radiation directed from multiple angles overlap atop the tumor, ensuring highly focused delivery and minimal damage to surrounding tissue. Treatment time, usually 1.5 to 2 weeks, is also shorter than the 6 weeks required for conventional radiotherapy.

“No other approach looks as promising,” agrees Walter Curran, MD, chair of radiation oncology and director of Emory University's Winship Cancer Institute in Atlanta, GA.

Figuring out how to apply SBRT to lung tumors close to the central airway is also critical, Curran notes. The patients on RTOG 0236 all had peripheral tumors, but patients with central lung tumors face a greater risk of life-threatening injuries and bleeding from aggressive radiotherapy. He is eagerly awaiting results from RTOG 0813, a trial exploring the best SBRT dose and treatment schedule for these tumors.

With the positive long-term data from RTOG 0236, most U.S. oncologists now consider SBRT the new standard for inoperable early-stage NSCLC, Timmerman says. Whether SBRT will prove surgery's equal for patients who are candidates for surgery remains to be seen; attempts to set up a randomized trial comparing both therapies have been unsuccessful thus far.

“It's psychologically difficult for patients to let a coin flip decide between such disparate therapies,” Timmerman explains. However, he thinks that the design of a planned phase III trial that will prerandomize patients to surgery or SBRT and then obtain their informed consent—a concept called Zelen's design—may overcome this barrier; more than 80% of patients accepted prerandomization in other studies.

Ultimately, “we do need at least one high-level comparison,” Timmerman says. “Otherwise, SBRT's penetration into the treatment arsenal will be much slower.”