SBRT FOR STAGE I NSCLC

SAN FRANCISCO ― There was no significant increase in late toxicity when stereotactic body radiation therapy (SBRT) was used in the treatment of early-stage ― but inoperable ― non–small-cell lung cancers (NSCLCs), according to new 5-year results from RTOG 0236.

The findings are important because they address a past concern of study critics, who worried that SBRT, which is delivered in higher doses than standard radiation, would produce more toxicities over the long term, said lead author Robert Timmerman, MD, of University of Texas Southwestern Medical Center in Dallas.

The new 5-year results are "practice changing," Dr. Timmerman told reporters at a press conference here at the American Society for Radiation Oncology (ASTRO) 56th Annual Meeting.

"They were practice changing in 2010," he added, referring to 3-year results published a few years ago (JAMA. 2010;303:1070-1076).

"This is the first significant change in these patients in 50 years," Dr. Timmerman has said in the past about the trial results and SBRT for lung cancer.

Now, Dr. Timmerman explained that at 5 years, the single-arm, phase 2 trial of 59 patients had a "very impressive" overall survival rate of 40% and a primary tumor recurrence rate of 7%, which is "very low" and "on par with surgery."

The overall survival rate at 5 years is "good" but "declining" from 3 years (55%), partly because of the baseline medical problems of these frail patients, he added.

Notably, severe toxicity ― a potential bugaboo of the trial ― remained relatively unchanged at 5 years, he said.

There were 2 grade 4 toxicities, which was the same number reported at 3 years. And there were 15 grade 3 toxicities, which was only 2 more than the initial report.

"We did not see those horrible long-term toxicities," said Dr. Timmerman.

However, there was a downside to the new data — local-regional failure increased (38% at 5 years vs 13% at 3 years). These late failures were mostly in the involved lobe but also in the hilum and mediastinum.

Dr. Timmerman explained that the failures were likely due to micrometastases in the involved lobe that were outside the treatment area.

He also told the ASCO audience that, like late toxicities, late failures were an earlier concern and a cause for hesitation about SBRT as a treatment for lung cancer. Better staging or effective adjuvant therapy is needed, he added.

With the 5-year data now tabulated, SBRT can continue to change practice in early-stage but inoperable NSCLC, suggested Dr. Timmerman.

As many as 10,000 cases of NSCLC are diagnosed every year in patients who are too frail for surgery because of conditions such as emphysema, heart disease, and stroke. An estimated 40% to 50% of US cancer centers now perform SBRT on such patients.

But a survey has indicated that another 30% of centers are "poised" to perform it, meaning they have the technology, he said. "These results will change that dynamic," said Dr. Timmerman, referring to a potential jump in usage in this setting.

SBRT for lung cancer is "extremely well tolerated" by patients treated at his center, said Benjamin Movsas, MD, of the Henry Ford Hospital in Detroit, Michigan.

The RTOG 0236 is a "landmark trial," inasmuch as it is the first cooperative group trial of SBRT, which is still a relatively new technology, said Dr. Movsas, who moderated the press conference. "SBRT has made a big difference in practice," he told Medscape Medical News. But he also credited other single-center studies of SBRT in this setting for helping evolve practice.

In his oral presentation at an ASTRO session yesterday, Dr. Timmerman said the earlier results published in 2010 lead to a "significant transition in routine care" for inoperable lung cancers.

More Study Details

The study enrolled 59 patients with early-stage (T1 to T2N0M0) NSCLC between May 2004 and October 2006.

The diagnosis of lung cancer was based on a biopsy, but all further staging was done using noninvasive tests. Patients were included only if they had concomitant medical conditions that prevented them from undergoing surgery, which is the first-line treatment for early-stage lung cancer. These are patients who are "typically not allowed in clinical trials," said Dr. Timmerman.

Of the 59 patients, 55 were evaluable for the analysis, with a median follow-up time of 4 years overall and 7.2 years for survivors. Forty-four patients had T1 tumors, and 11 patients had T2 tumors. The median age of the patients enrolled in the study was 72 years; the patients were predominantly white (93%) and female (62%). Of the patients, 88% had a performance score of 0 or 1.

A treatment-plan reanalysis showed that study dose was approximately 18 Gy delivered in 3 fractions (54 Gy total). This is considered a "more potent form of SBRT," said Dr. Timmerman.

SBRT is a type of external beam therapy that uses focused radiation beams at a tumor via detailed imaging. Compared with standard radiation therapy, SBRT delivers high doses of radiation to the tumor in a decreased amount of treatment time, according to ASCO press materials.

The study was funded by the National Institutes of Health. Dr. Timmerman has financial ties to Varian Medical Systems.

American Society for Radiation Oncology (ASTRO) 56th Annual Meeting: Abstract 3682. Presented September 14, 2014.