Delivering stereotactic body radiation therapy (SBRT also called stereotactic ablative radiotherapy) in one or four treatment sessions led to similar outcomes in patients with up to three lung metastases (ie, oligometastatic disease) in the phase II randomized SAFRON II trial. The study, conducted across 13 sites in Australia and New Zealand, was reported at the virtual 2020 American Society for Radiation Oncology (ASTRO) Annual Meeting and bolsters the case for stereotactic radiation therapy for oligometastatic cancer.¹

“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 lead author ­Shankar Siva, PhD, MBBS, FRANZCR, Associate Professor of Radiation Oncology and Head of the SBRT Program at Peter MacCallum Cancer Centre, Melbourne.

“The safe delivery of SBRT, particularly in a single session, requires a multifaceted system of quality assurance, peer review, and treatment planning.”

— Shankar Siva, PhD, MBBS, FRANZCR

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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 lungs. “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 lungs 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.

“These studies … used a wide variety of SBRT regimens, so we designed our trial to test the safety and effectiveness of SBRT in a more robust fashion,” he said.

Study Details

The phase II SAFRON II 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 and 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 did not differ 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 tumor control, as measured by freedom from local failure at 1 year, was 95% in the multifraction arm vs 93% in the single-fraction arm. The rate of disease-free survival at 1 year was 60% vs 59%, respectively; overall survival was 93% and 95%, respectively.

“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,” Dr. Siva said.

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 resource-stretched environments 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 up for the long term, but these early results indicate that single-fraction radiation could be carried out equally effectively across multiple institutions.”

Sue S. Yom, MD, PhD

Press conference moderator Sue S. Yom, MD, PhD, Professor in the Department of Radiation Oncology at University of California, San Francisco, said that Dr. Siva’s trial addresses whether the efficiency of SBRT can be further improved using a single-fraction approach. The study has the potential to change practice if these results hold up.

“In this trial of patients with one to three metastatic lung tumors, half of whom had colorectal cancer as the primary, side effects were low when delivering all radiotherapy in a single fraction. This approach may be as effective as treatment given in four fractions. Results will be confirmed at 3 years. If the findings presented today are maintained at 3 years, then patients with up to three lung metastases will be able to have radiation delivered in an extremely efficient manner in terms of time, resources, and quality of life,” Dr. Yom commented. 

DISCLOSURE: Dr. Siva has received honoraria from AstraZeneca; has received institutional honoraria from Bristol Myers Squibb, Roche, and Varian Medical Systems; has served as a consultant or advisor to AstraZeneca; has served as an institutional consultant or advisor to Janssen; has received institutional research funding from Varian Medical Systems; and has been reimbursed for institutional travel, accommodations, or other expenses by AstraZeneca. Dr. Yom has received institutional research funding from BioMimetix, Bristol Myers Squibb, Genentech, and Merck and holds patents or other intellectual property in Springer and UpToDate.

REFERENCE

1. Siva S, Bressel M, Kron T, et al: Stereotactic ablative fractionated radiotherapy versus radiosurgery for oligometastatic neoplasia to the lung: A randomized phase II trial. 2020 ASTRO Annual Meeting. Abstract 5. Presented October 28, 2020.