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TOPLINE:

Adding an intermediate-dose stereotactic ablative radiotherapy (SABR) boost of TKGy to hypofractionated concurrent chemoradiation appears safe and improves outcomes in patients with unresectable, locally advanced non–small-cell lung cancer (NSCLC).

METHODOLOGY:

• In advanced NSCLC, radiation dose-escalation treatment, based on the biologic effective dose, may identify and target residual disease and enhance locoregional control.
• This early-phase dose-escalation trial was conducted at University of California, Los Angeles, and included 28 patients with unresectable stage II or III NSCLC who received hypofractionated concurrent chemoradiation.
• All patients received a base radiation dose of 4 Gy in 10 fractions (40 Gy total), followed by an adaptive SABR boost to residual, metabolically active disease based on interim 18F-fludeoxyglucose PET/CT scan without a treatment break.
• Depending on the dose-limiting toxic effects within 90 days, 10 patients received a low-dose SABR boost (5 fractions of 5 Gy or 25 Gy total), 9 received an intermediate-dose boost (5 fractions of 6 Gy or 30 Gy total), and 9 received a high-dose SABR boost (5 fractions of 7 Gy or 35 Gy total).
• Researchers aimed to identify the maximum tolerated dose, defined as the highest total dose where less than 33% of patients experienced dose-limiting toxic effects within the 90-day risk-assessment period.

TAKEAWAY:

• The study did not reach the maximum tolerated dose.
• The median overall survival for all patients was 25.9 months during a median follow-up of 18.2 months.
• At 2 years, overall survival rates were 30.0% in the low-dose cohort, 76.2% in the intermediate-dose group, and 55.6% in the high-dose cohort, whereas local control rates were 74.1%, 85.7%, and 100.0%, respectively. Patients in the intermediate-dose cohort displayed the most favorable toxic effects profile and a trend toward improved locoregional control.
• The high-dose cohort experienced three grade ≥ 3 toxic effects, including two grade 5 events. The low-dose cohort encountered two grade 3 toxic events, whereas the intermediate-dose cohort had none.

IN PRACTICE:

Patients in the intermediate cohort "exhibited the most promising therapeutic ratio, indicated by a favorable toxic effects profile and a trend toward improved [locoregional control]," researchers wrote, adding that the high-dose boost came with a risk for grade 5 toxic effects.

SOURCE:

This study was led by Trudy C. Wu from the University of California, Los Angeles, and published online on December 11, 2024, in JAMA Oncology.

LIMITATIONS:

The study's limitations included a nonrandomized design, a limited sample size, and the need for longer follow-up to assess late toxic effects, especially in the high-dose cohort. It is also unclear how this regimen will apply with immunotherapy as only one patient in the trial received consolidative immunotherapy.

DISCLOSURES:

This work was supported by University of California, Los Angeles. The study author reported receiving research support, personal, consulting, or advisory fees from various sources outside this work.