Single Dose of SBRT Effective for Oligometastatic Lung Lesions

Single Dose of SBRT Effective for Oligometastatic Lung Lesions

A single fraction of stereotactic body radiotherapy (SBRT) appeared to be an effective alternative to a multi-fraction approach for control of limited lung metastases in patients with cancer.

For the primary endpoint of severe adverse events (AEs) at 1 year, 5% of patients in the single-fraction arm experienced a grade ≥3 AE versus 3% in the multi-fraction arm, with both meeting prespecified criteria for acceptability, reported Shankar Siva, PhD, MBBS, of Peter MacCallum Cancer Centre in Melbourne.

“Both a single fraction of 28 Gy and four fractions to a total dose of 48 Gy of SBRT have acceptable side effect profiles for patients with one to three secondary cancer deposits to the lung,” he said during a press briefing at the virtual American Society for Radiation Oncology (ASTRO) annual meeting.

Of 36 evaluable patients in the single-dose arm, two had grade 3 AEs — including fatigue, chest pain, and loss of breath — and there were no fatal events. Among 36 evaluable patients in the multi-fraction arm, one patient who had undiagnosed interstitial lung disease died of pneumonitis within 3 months of SBRT (the only severe AE in this arm).

Examining all-grade toxicities, esophagitis and dermatitis were significantly more frequent in the multi-fraction arm, while all other common toxicities were not significantly different between the two approaches.

“Oncological outcomes for both appear to be similar to 1 year at this point,” said Siva.

Local control rates reached 93% in the single-fraction arm (95% CI 79-98) and 95% (95% CI 81-99) in the multi-fraction arm, while disease-free survival rates were 59% (95% CI 44-73) and 60% (95% CI 44-73), respectively.

The overall survival rate at 1 year was 95% (95% CI 83-99) in the single-fraction arm and 93% (95% CI 80-98) in the multi-fraction arm.

ASTRO discussant Thomas Dilling, MD, of Moffitt Cancer Center in Tampa, Florida, drew attention to the death in the multi-fraction arm, a patient with three lesions involving both lungs.

“[This] would make the risk for pneumonitis high even in a patient with healthy lungs,” he said. “This reinforces the point that patients with pulmonary fibrosis perhaps should not be treated with SBRT at all. Or if they are, perhaps it should be limited to a single lesion.”

SAFRON II was a randomized phase II trial conducted at 13 centers in Australia and New Zealand. From 2013 to 2015, the researchers assigned 90 patients with metastatic solid cancer and no more than three lung metastases in a 1:1 ratio to either a single 28 Gy fraction or 48 Gy over four fractions (biologically equivalent). Maximum tumor size was 5 cm and metastases had to be located more than 2 cm from central airways. Patients with ECOG 0-1 performance status were eligible for enrollment and simultaneous systemic therapy was not allowed.

Baseline characteristics were similar between arms. Mean patient age was 66.9 years, and 63% were men. Patients were stratified by number of lesions (1 vs 2-3) and tumor histology (colorectal vs non-colorectal).

A majority of patients (59%) had a single metastatic lesion, 30% had two, and 11% had three. Colorectal cancer was the most common primary cancer (47%), followed by lung cancer in 11% and kidney cancer in 10%.

Dilling also raised questions about the dose of radiation. While the biological equivalence between treatment arms was nearly identical for early effects (106 Gy with the single-fraction approach vs 105 Gy with the multi-fraction approach), the late effects are greater with the single fraction (289 Gy vs 240 Gy, respectively), he said.

He also feared that a dose of 105/106 Gy might not be a strong enough dose to control lung metastases, and pointed to studies from Moffitt suggesting some patients treated with 100 Gy for lung metastases still have local failure.

“In the past, most of our decision-making around doses to prescribe to a given tumor depended upon the site of origin of the lesion and clinical experiences gathered from previous clinical trials,” said Dilling. “However, it would be important as a field to try to quantitate a relative radiation sensitivity.”

  • Ian Ingram joined MedPage Today in 2018 as Deputy Managing Editor, and covers oncology for the site.

Disclosures

Siva disclosed relationships with Varian Industries, Merck-Sharp-Dohme, AstraZeneca, Bayer Pharmaceuticals, Bristol Myers Squibb, and Reflexion.

Dilling reported consulting for AstraZeneca and the National Comprehensive Cancer Network.

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