For patients with operable early-stage non-small cell lung cancer (NSCLC), noninvasive stereotactic radiation appears to be as safe and effective as surgery, according to a new prospective multicenter clinical trial by researchers in Japan, reported at the ASTRO Annual Meeting.
“Stereotactic radiation is a standard treatment for patients with inoperable disease, but it can be an alternative for operable patients,” lead author Yasushi Nagata, MD, Professor and Radiation Oncologist at Hiroshima University, said at a news briefing.
Dr. Nagata presented data from a Phase II trial involving 64 patients with operable early-stage NSCLC who were treated with stereotactic body radiation therapy (SBRT) at 15 medical centers and followed for an average of four years.
After three years, 76% remained cancer free, comparable to survival rates reported for such patients who undergo surgery, Dr. Nagata said.
In the Japanese study, each patient underwent four radiation treatments over the course of four to eight days. He explained that the stereotactic body technique is a specialized form of external-beam radiation that delivers high doses of radiation to small and very precisely defined tumors over a short period. Patients are placed in special braces to prevent any movement during treatment, and they first undergo special CT scans to precisely identify tumor characteristics before each treatment.
SBRT has become increasingly popular for inoperable Stage I non-small cell lung cancer, and is used selectively in patients who are candidates for surgery, but this is the first study to evaluate risks and benefits in such patients.
“We can now confirm with more confidence that SBRT is an effective treatment alternative for aged patients with early non-small cell lung cancer,” Dr. Nagata said. “In the future, there is a possibility that radiation will be a substitute for surgery in selected patients with Stage I NSCLC. I encourage patients with early lung cancer to talk to their doctors about all possible treatment options.”
In the study, patients of both genders were included, with a median tumor size of 21 mm, ranging from 10 to 30 mm. These included 40 patients with adenocarcinomas, 21 with squamous cell carcinomas, and four with other forms of the disease. They received doses of 48 Gy at the isocenter of just the primary tumor in four fractions over four to eight days.
In all, cancer progressed in 25 patients, and the three-year progression-free, local progression-free survival, and event-free survival rates were 54.5%, 68.5%, and 51.4%, respectively.
Regarding side effects from treatment, Grade 3 toxicity was observed in 9% of the patients as follows: chest pain in 1.5%, dyspnea in 3.1%, hypoxia in 1.5%, and pneumonitis in 3.1%; there was, however, no Grade 4 or 5 toxicity observed.
Lynn D. Wilson, MD, Professor and Vice Chairman of Therapeutic Radiology at Yale University School of Medicine, who moderated the news briefing, explained that surgery remains the primary treatment in the United States for patients with early lung cancer: “Stereotactic radiation is used in the US, but generally not as an alternative for a patient who has an operable tumor.”
Favorable Toxicity Profile
At last year's ASTRO meeting, Robert Timmerman, MD, Professor and Vice-Chair of Radiation Oncology at the University of Texas Southwestern Medical Center in Dallas, presented similar findings. In that paper, he and his colleagues reported that stereotactic body radiation contained early-stage, medically inoperable lung cancer at its site of origin in a clinical trial involving 55 patients. The local control rate was 98% and more than half of the patients were alive and cancer free at three years.
Asked about the new study, he told OT that the new data demonstrated that radiotherapy had a very favorable toxicity profile and an “impressive” three-year overall survival rate. Moreover, the researchers were able to complete the trial very quickly, follow the patients carefully, and the study also included patients with borderline operational status, unlike earlier studies.
“In my opinion, this data is encouraging and supports ongoing investigation in the use of SBRT in operable patients, preferably on controlled trials,” he said.
The American College of Surgeons Oncology Group (ACOSOG) and Radiation Therapy Oncology Group (RTOG) are about to open a joint Phase III randomized trial in more than 400 patients comparing surgical resection to stereotactic ablative radiation.
“Enrollment to this trial should be prioritized as it should provide the highest level evidence to guide therapy,” Dr. Timmerman said.
With regard to the study by Dr. Nagata and his team, Dr. Timmerman noted that the trial was completed very quickly, with good accrual, and the patients were tracked very carefully. Moreover, they included patients with borderline status who are not typically included in surgical series.
“These are positives, but the most significant finding was that there was a very favorable toxicity profile associated with treatment, and overall survival rate were impressive,” he said.
Less positive features of the study's design, said Dr. Timmerman, included the fact that it included a “highly select” patient population with small tumors (a smaller subset of Stage I patients).
“This clouds the applicability to the broader population of operable Stage I patients,” he commented. Also, in this subpopulation, some smaller surgical series from Japan have reported even better survival rates.
“For a group of patients exclusively with small tumors of under 3 cm, primary tumor progression, i.e., failure to control the targeted tumor, was higher than in the RTOG 0236 study, which included tumors up to 5 cm,” he noted.
Moreover, the RTOG study used a considerably more potent dose.
“As such, the dose used in the JCOG trial may be inadequate specifically for operable patients.”