Accelerated Hypofractionated Chemoradiation With Adaptive SABR Boost in Locally Advanced, Unresectable NSCLC

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In a U.S. single-center radiation dose-expansion study reported in JAMA Oncology, Wu et al found that chemoradiation with adaptively increased stereotactic ablative radiotherapy (SABR) boost doses was safe and effective in patients with locally advanced, unresectable non–small cell lung cancer (NSCLC). 

Study Details

The study included 28 patients with inoperable stage II or III disease enrolled at the University of California, Los Angeles, between May 2011 and May 2018. All patients received accelerated hypofractionated chemoradiation with 4 Gy × 10 fractions followed by an adaptive SABR boost to residual metabolically active disease consisting of an additional 25 Gy (low, 5 Gy × 5 fractions), 30 Gy (intermediate, 6 Gy × 5 fractions), or 35 Gy (high, 7 Gy × 5 fractions) with concurrent weekly carboplatin/paclitaxel. Patients advanced to a higher SABR boost dose if dose-limiting toxic effects (any grade ≥ 3 pulmonary, gastrointestinal, or cardiac toxicity or any nonhematologic grade ≥ 4 toxic effects) occurred in less than 33% of patients in the boost cohort within 90 days of follow-up. Patients received a total prescribed dose of 65, 70, or 75 Gy in 15 fractions, depending on the phase of the dose-escalation protocol in which the patient was enrolled.

The primary objective of the study was to determine the maximum tolerated dose, defined as the highest total dose in which up to 33% of patients experienced a dose-limiting toxic effect within the 90-day risk-assessment period. This was done by reaching the maximum tolerated dose or a total dose of 75 Gy by escalating the dose per fraction of the SABR boost.

Key Findings

The protocol-specified maximum tolerated dose was not exceeded. SABR boost dose cohorts evaluated included 10 patients in the low-dose, 9 in the intermediate-dose, and 9 in the high-dose cohorts.

Overall, the incidence rates of nonhematologic acute and late (> 90 days) grade ≥ 3 toxic effects were 11% and 7%, respectively. No grade 3 toxic effects were observed in the intermediate-dose cohort. Two patients in the high-dose cohort had grade 5 pulmonary toxic effects.  

Local control rates at 2 years were 74.1%, 85.7%, and 100.0% in the low-, intermediate-, and high-dose cohorts, respectively. Overall survival rates at 2 years were 30.0%, 76.2%, and 55.6% in the low-, intermediate-, and high-dose cohorts, respectively.

The investigators concluded: “This early-phase, dose-escalation nonrandomized controlled trial showed that concurrent chemoradiation with an adaptive SABR boost to 70 Gy in 15 fractions with concurrent chemotherapy is a safe and effective regimen for patients with locally advanced, unresectable NSCLC.”

Percy Lee, MD, of the Department of Radiation Oncology, City of Hope Orange County, Lennar Foundation Cancer Center, is the corresponding author of the JAMA Oncology article.

Disclosure: This work was supported in part by internal funds from the University of California, Los Angeles, and City of Hope Orange County. For full disclosures of the study authors, visit

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