Study Strengthens Case for SBRT Use in Oligometastatic Neoplasia to the Lung

Findings from a randomized phase 2 trial, presented at the American Society for Radiation Oncology (ASTRO) Annual Meeting, strengthened the case for radiation therapy as a treatment for cancer that has begun to spread throughout the body.¹

The study, conducted across 11 medical centers in Australia and New Zealand, indicated that patients with up to 3 lung metastases who were treated with stereotactic body radiation therapy (SBRT) fared comparably well whether their radiation was delivered in 1 or 4 treatment sessions.

“I think the future of radiation oncology could be these ultra-short treatments,” lead investigator Shankar Siva, PhD, an associate professor of radiation oncology and head of the SBRT program at the Peter MacCallum Cancer Centre in Melbourne, Australia, said in a press release.² “Our results indicate that SBRT can be a safe and effective treatment for patients whose cancer has spread to their lungs, even when it’s delivered in a single session.”

The Trans Tasman Radiation Oncology Group (TROG) 13.01/Australasian Lung Cancer Trials Group SAFRON II (NCT01965223) was a multicenter, randomized, screening phase 2 trial which randomized 90 patients into 2 treatment arms. Half of the study participants received a single fraction of 28Gy and the other half received a biologically-equivalent regimen of 4 fractions of 12Gy each. Each patient had up to 3 lung metastases from primary tumors in other sites, the most common being colorectal cancer (47%), followed by lung (11%) and kidney (10%).

The primary end point was to compare outcomes between the 2 treatment arms, defined as treatment related toxicity CTCAE V4.0 grade 3 within 1 year of treatment. If either arm was considered safe (if the maximum observed significant toxicity rate was 5% with upper limit of the 80% confidence <17% [one-sided 10% alpha]), then the trial would progress to assess secondary end points of quality of life, local control (LC), overall survival (OS), time to distant failure, disease free survival (DFS), quality of life (QoL), and cost effectiveness.

In total, 37 patients in each treatment arm were deemed eligible for safety analyses at 1 year after treatment. In the cohort who received a single treatment, 2 patients had grade 3 side effects, including fatigue, loss of breath and chest pain (5%; 80% CI, 1-14); however, no patients experienced grade 4 or 5 side effects. Moreover, in the cohort who received 4 SBRT treatments, 1 patient died after experiencing pneumonitis within 3 months of treatment (3%; 80% CI, 0.3%-10%); there were no grade 3 or 4 events.

Importantly though, the events on the single-fraction arm lasted less than 3 months and the investigators found undiagnosed interstitial lung disease in the patient who died on the 4-fraction arm.

Additionally, the researchers compared survival rates between the groups a year after treatment and found them to be almost identical across both regimens. LC at 1-year between ARM 1 and ARM 2 was 93% (95% CI, 79-98%) versus 95% (95% CI, 81-99%), OS was 95% (95% CI, 83-99%) and 93% (95% CI, 80-98%), and DFS was 59% (95% CI, 43-72%) and 60% (44-73%), respectively. However, researchers will continue to analyze these secondary end points up to 3 years after treatment, as well as QoL and cost effectiveness.

Should single-fraction SBRT continue to prove safe and effective over the long-term, single-fraction SBRT may become an appealing treatment option for patients with oligometastatic cancer to the lungs. In addition, SBRT offers practical benefits for patients, such as fewer trips to a clinic, less time off work, and lower treatment costs.

“When we compress a multi-treatment course into a single treatment, there is a potential risk of higher toxicity,” explained Siva. “Based on our own anecdotal experience, we are quite comfortable using the single treatment approach, but globally, it's used less often.”

"There also are concerns that a single treatment might not have the same kind of effectiveness as multiple treatments,” Siva added. “Thankfully, in this study, at least a year out we are seeing similar efficacy, where 93-95% of the tumors were controlled in both arms. Our final analysis will show if this holds for the long-term, but these early results indicate that single fraction radiation could be carried out equally effectively across multiple institutions.”

References:

1. Siva S, Bressel M, Kron T, et al. Stereotactic Ablative Fractionated Radiotherapy versus Radiosurgery for Oligometastatic Neoplasia to the Lung: A Randomised Phase II Trial. Presented at the American Society for Radiation Oncology (ASTRO) Annual Meeting. Abstract #: 5.

2. Group trial bolsters case for stereotactic radiation therapy for tumors that travel to the lungs [news release]. Arlington, Virginia. Published October 26, 2020. Accessed October 30, 2020. https://www.newswise.com/articles/group-trial-bolsters-case-for-stereotactic-radiation-therapy-for-tumors-that-travel-to-the-lungs?sc=sphr&xy=10021790