Hypofractionated Chemoradiation With Adaptive SABR Appeared Effective in NSCLC

A dose-escalation strategy involving hypofractionated concurrent chemoradiation with adaptive stereotactic ablative radiotherapy (SABR) appeared safe and effective for patients with locally advanced non-small cell lung cancer (NSCLC) not suitable for surgery, an early-phase nonrandomized trial suggested.

Among 28 patients, 2-year local control rates were 74.1% for the low-dose cohort (65 Gy in 15 fractions), 85.7% for the intermediate-dose cohort (70 Gy in 15 fractions), and 100% for the high-dose cohort (75 Gy in 15 fractions), reported Percy Lee, MD, of City of Hope Orange County and Lennar Foundation Cancer Center in Irvine, California, and colleagues.

Of note, while none of the patients in the intermediate-dose cohort experienced a grade 3 or higher toxic effect, two deaths occurred in the high-dose arm, Lee and team noted in JAMA Oncology.

Thus, at a median follow-up of 3.5 years, “patients treated with 70 Gy in 15 fractions exhibited the most promising therapeutic ratio, indicated by a favorable toxic effects profile and a trend toward improved [local control],” the authors concluded.

However, they also pointed out that these results “should be approached with caution” because of the study’s small sample size, adding that while the findings suggest that increasing the biologic effective dose (BED) through hypofractionation appeared to enhance local control, this approach was limited by the two grade 5 toxic effects seen in the high-dose cohort.

In a commentary accompanying the study, Nataniel H. Lester-Coll, MD, of the University of Vermont Larner College of Medicine in Burlington, and Henry S. Park, MD, MPH, of Yale University School of Medicine in New Haven, Connecticut, observed that radiation dose escalation with hypofractionation, SBRT, and adaptive planning “is unlikely to be the only answer for how to optimize outcomes in unresectable stage II or III NSCLC.”

They noted that emerging technology such as online adaptive radiotherapy can enable daily modifications to treatment plans, and allow for real-time adjustments throughout the course of therapy.

“Such adaptability may facilitate BED escalation above 100 while minimizing normal tissue exposure to the lungs, esophagus, heart, and cardiac substructures,” they wrote. “Together, dose escalation with careful dosimetric planning and adaptive technologies may optimize the precision and efficacy of lung cancer radiotherapy, bolstering the likelihood of successful oncologic outcomes while also mitigating adverse effects experienced by patients.”

The patients in this early-phase single-center trial had a median age of 70 years, 57% were men, and 86% had unresectable stage III NSCLC. They were enrolled in low-dose (n=10), intermediate-dose (n=9), and high-dose (n=9) cohorts from May 2011 to May 2018.

All patients first received an accelerated hypofractionated dose of 4 Gy in 10 fractions with concurrent carboplatin and paclitaxel, followed by an adaptive SABR boost to target any remaining metabolically active cancer. The first 10 patients received a boost dose of 25 Gy (low-dose, 5 Gy × 5 fractions). If this was considered safe, patients proceeded to receive a higher boost dose of 30 Gy (intermediate, 6 Gy × 5 fractions), followed by 35 Gy (high, 7 Gy × 5 fractions), all with concurrent weekly chemotherapy.

While there were no grade 3 or higher toxic effects observed in the intermediate-dose cohort, there were two in the low-dose cohort (an acute grade 3 bronchial stenosis and a late grade 3 esophageal stenosis with ulceration). The high-dose cohort had the greatest burden of grade ≥3 toxic effects, including the two events of grade 5 pulmonary toxic effects.

Most patients (89%) experienced some form of acute grade 1 or 2 toxic effect, with late grade 1 or 2 toxic effects seen in 17 patients, including fatigue and inflammation of the esophagus or lungs resulting in sore throat or cough.

The median overall survival (OS) for all patients was 25.9 months, with 1- and 2-year pooled OS rates of 78.6% and 52.5%, respectively. Two-year OS rates were 30%, 76.2%, and 55.6% for the low-, intermediate-, and high-dose cohorts, respectively.

The median progression-free survival (PFS) for all patients was 9.8 months, with 1- and 2-year pooled PFS rates of 35.1% and 22%, respectively. Two-year PFS rates were 0%, 37.5%, and 25.4%, in the low-, intermediate-, and high-dose cohorts, respectively.

Limitations to the study included the nonrandomized design, small sample size, and the need for longer follow-up to evaluate late toxic effects, especially in the high-dose cohort given their later trial enrollment, noted Lee and colleagues.

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