Stereotactic body radiation therapy (SBRT) improved overall survival and local disease control over standard radiotherapy (RT) for stage I lung cancer patients with inoperable disease, the phase III CHISEL trial showed.
In the randomized study of 101 non-small cell lung cancer (NSCLC) patients, median overall survival was 5 years in the SBRT arm compared with 3 years in the conventional RT arm (HR 0.53, 95% CI 0.30-0.94, P=0.027), reported David Ball, MD, of Peter MacCallum Cancer Centre in Melbourne, Australia, and colleagues.
At 2 years, 77% of patients treated with SBRT were still alive, compared with 59% of those treated with standard RT, as shown in the Lancet Oncology.
And there was a 68% reduction in the study's primary endpoint of local treatment failure for the SBRT group (HR 0.32, 95% CI, 0.13-0.77, P=0.008). At 2 years, the cumulative incidence of local treatment failure was 26% with standard RT versus 10% with SBRT.
"To the best of our knowledge, this study is the first to make a direct comparison that indicates that SBRT is associated with improved survival," Ball's team wrote, noting that this finding, plus the observed improvement of local control, provides evidence supporting SBRT as the "standard of care for the treatment of inoperable peripherally located stage I NSCLC."
They noted that the rapid and widespread adoption of SBRT has been largely driven by "convenience, tolerability, and high primary tumor control."
But level 1 evidence supporting its use in this setting had been lacking, said Faiez AlShafa, MD, and David Palma, MD, both of the London Health Sciences Centre in Ontario, Canada, in an accompanying editorial. They noted that new technologies and approaches are often adopted into radiological clinical practice without any firm evidence that the advances are actually beneficial.
"Premature adoption of a technology that is later proven to be unhelpful leads to unnecessary cost and possibly harm," they wrote. "We should recognize that although we ourselves might believe that our new technologies are beneficial, if we do not complete randomized controlled trials, other important stakeholders might not believe in these benefits."
This in itself is what makes the completed phase III CHISEL trial "a major step forward," said AlShafa and Palma, and the findings establish SBRT as the "standard radiotherapy approach in patients with stage I NSCLC who are not undergoing surgery."
CHISEL recruited a total of 101 patients at 11 hospitals in Australia and three in New Zealand with peripherally localized stage I NSCLC who were either ineligible for or refused surgery, and randomized them 2:1 to either SBRT or conventional RT.
For tumors <2 cm from the chest wall, SBRT patients received four 12 Gy fractions for a total of 48 Gy. Otherwise, SBRT patients received three 18 Gy fractions for a total of 54 Gy. For those in the conventional RT arm, treatment consisted of daily 2 Gy fractions for a total of 66 Gy or daily 2.5 Gy fractions for a total of 50 Gy, depending on institutional preference.
A total of 61 patients randomized to SBRT were treated according to protocol, as were 33 patients in the standard RT group. At a slightly longer median follow-up for the SBRT group (2.6 vs 2.1 years), fewer patients (14%) had progressed locally compared with 31% of those in the conventional RT arm. At the same follow-up point, 39% of patients treated with SBRT had died compared with 62% of patients treated with conventional RT.
Treatment was generally well tolerated in both groups, the researchers reported, with only one grade 4 adverse event (AE) and seven grade 3 AEs in SBRT-treated patients. Only two grade 3 AEs were documented in the standard RT arm.
One study limitation, according to Ball's group, was the choice of time to local treatment failure as the primary endpoint. "Initially, we planned to use the widely accepted RECIST criteria to record local treatment failure, with confirmation by biopsy or FDG-PET imaging," the authors explained. However, they found that by following SBRT treatment, "many patients developed dense fibrosis within the irradiated volume that would erroneously satisfy the criteria for progressive disease using the RECIST criteria." This obstacle was overcome by providing a list of radiological features associated with a higher risk of recurrence to the panel of independent radiology reviewers so that they could compensate for this limitation.
The study was funded by the Radiation and Optometry Section of the Australian Government Department of Health with the assistance of Cancer Australia, the Cancer Society of New Zealand, and the Cancer Research Trust New Zealand.
Ball reported grant funding from Cancer Australia for the conduct of the study and personal fees from Pfizer; other co-authors reported relationships with the Cancer Society of New Zealand, the Cancer Research Trust New Zealand, Pfizer, Novartis, Roche/Genentech, AstraZeneca, Merck, Bristol-Myers Squibb, and Loxo Oncology.
Alshafa and Palma reported having no competing interests.
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