Delivering stereotactic body radiation therapy (SBRT, also called stereotactic ablative radiotherapy) in either one or four treatment sessions led to similar outcomes in patients with up to three lung metastases in the randomized SAFRON II trial. The study, reported by Shankar Siva, PhD, and colleagues at the virtual 2020 American Society for Radiation Oncology (ASTRO) Annual Meeting, was conducted across 13 sites in Australia and New Zealand, and bolsters the case for stereotactic radiation therapy for oligometastatic cancer (Abstract 5).
“I think the future of radiation oncology should be these ultrashort treatments. Our results indicate that SBRT can be safe and effective for patients whose cancer has spread to the lungs, even when it is delivered in a single session,” stated first author Dr. Siva, Associate Professor of Radiation Oncology and Head of the SBRT Program at Peter MacCallum Cancer Center, Melbourne, Australia.
Shankar Siva, PhD
The lung is the second most common site of metastatic cancer. Up to half of all cancers with primary sites elsewhere in the body spread to the lung.
“Most patients [with lung metastases] are treated with lifelong anticancer therapy, with little prospect for long-term cancer control,” Dr. Siva explained.
Recent smaller, single-center studies have shown that some patients with limited spread to the lung may be suitable for surgery or SBRT. The studies, with many limitations, suggest that these patients can be long-term survivors if treated with SBRT.
"For patients with a limited number of metastases, recent studies have shown that there can be long-term survivors with the use of SBRT," said Dr. Siva. "These studies tend to be smaller institutional series with a wide variety of SBRT regimens, so we designed our trial to test the safety and effectiveness of SBRT in a more robust fashion."
Study Details
The phase II TROG Cancer Research trial randomly assigned 90 patients in a 1:1 ratio to two treatment arms. Half received a single fraction of 28 Gy, and the other half received a biologically equivalent regimen of four fractions of 12 Gy each. All patients had up to three lung metastases from other primary tumor sites (excluding hematologic malignancies), most commonly colorectal cancer (47%). All metastases were ≤ 5 cm, located in the peripheral lung, and all primary and extrathoracic disease was treated.
The study was conducted over a 3-year period from 2015 to 2018. The primary endpoint was the rate of severe side effects at 1 year.
Multisession SBRT led to a slight preponderance of swallowing symptoms compared with the single-fraction approach. Other side effects were no different between the two treatment arms.
High-grade side effects within the first year following treatment were as follows:
- In the four-fraction arm, there was one patient with a grade 5 event (pneumonitis within 3 months of SBRT, with undiagnosed underlying interstitial lung disease), with no grade 3 or 4 events.
- In the single-fraction arm, two patients had grade 3 events, both under 3 months in duration, with no grade 4 or 5 events. The grade 3 events—including fatigue, loss of breath, and chest pain—were managed with medical intervention.
- Within 1 year of treatment, the rate of grade 3 or higher toxicities was 3% in the four-fraction arm vs 5% in the single-fraction arm.
The rate of local control, as measured by freedom from local failure at 1 year, was 95% for the multifraction arm vs 93% for the single-fraction arm. The rate of disease-free survival at 1 year was 60% vs 59%, respectively; overall survival was 93% vs 95%.
“Both arms met the prespecified limits for toxicity. Both single-fraction and four-fraction SBRT have acceptable toxicity for patients with one to three secondary cancer sites in the lung. Oncologic outcomes are similar with both approaches,” said Dr. Siva.
"Both arms met the prespecified limits for toxicity. Both single-fraction and four-fraction SBRT have acceptable toxicity for patients with one to three secondary cancer sites in the lung. Oncologic outcomes are similar with both approaches."— Shankar Siva, PhD
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Study Implications
Although the outcomes were similar with both approaches, “Single-session SBRT is a one-stop knockout punch for patients with one to three metastases to the lung. This might have implications for treatment selection in a resource-stretched environment and widespread application,” stated Dr. Siva.
Single-fraction SBRT requires one visit to the clinic and is an outpatient treatment that does not require anesthesia. “This is appealing in the era of COVID-19, since it reduces patient time and transmission risk in the clinic,” Dr. Siva noted.
Dr. Siva emphasized the importance of quality assurance with SBRT. “The safe delivery of SBRT, particularly in a single session, requires a multifaceted system of quality assurance, peer review, and treatment planning. You need to be absolutely certain of the accuracy of your treatment delivery, and I think it’s very important that treatment teams achieve the same high levels of quality control, to make sure we are achieving the best in cancer care.”
He also noted that single-fraction SBRT is used less often due to concerns about comparable efficacy with multifraction SBRT. “Thankfully, in this study, at least a year out we are seeing similar efficacy, where 93% to 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.”
Disclosure: For full disclosures of the study authors, visit myastroapp2020.com.
