In patients with advanced non-small cell lung cancer (NSCLC), esophageal-sparing intensity-modulated radiotherapy (ES-IMRT) decreased the incidence of treatment-related esophagitis and demonstrated a trend toward improved esophageal quality of life compared with standard radiotherapy (RT), according to results recently presented at the American Society for Radiation Oncology (ASTRO) Annual Meeting.
While commonly used to alleviate local symptoms in patients with advanced NSCLC, palliative thoracic RT is associated with an increased risk of esophagitis, characterized by inflammation and irritation of the esophagus. In the phase 3 PROACTIVE trial, a team of researchers led by first author Alexander Louie, MD, PhD, MSc, Assistant Professor of Radiation Oncology at the University of Toronto, investigated the safety and efficacy of ES-IMRT as an alternative to standard RT.
The trial enrolled 90 patients with stage III or IV NSCLC who were planned to receive thoracic RT. Eligible patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 3 and a life expectancy of 3 months or less. Patients were stratified by RT dose of either 20 Gy in five fractions or 30 Gy in 10 fractions and were randomized to receive standard RT or ES-IMRT, defined as 80% or less of the standard RT dose. The primary end point was esophageal quality of life two weeks after RT. Quality of life was measured with the Functional Assessment of Cancer Therapy (FACT) Esophageal Cancer Subscale (ECS), with clinical significance defined as a two- to three-point change in total score. Secondary end points included overall survival, toxicity, and quality of life.
For patients receiving ES-IMRT, the two-week ECS score was 54.3 ± 7.6, compared with 50.5 ± 10.2 for those receiving standard RT (P=0.063). The change in ECS scores from baseline was 1.3 ± 9.7 for patients in the ES-IMRT group and -3.0 ± 10.8 for those in the standard RT group (P=0.065). The incidence of RT-related esophagitis was significantly lower in patients receiving ES-IMRT compared with the control group (2.2% vs 24.4%). Among patients in the ES-IMRT group compared with the standard RT group, the reduction in incidence of esophagitis was observed in patients receiving 30 Gy (29.6% vs 0%) and in RT fields with esophagus lengths of <10 cm (29.4% vs 0%). However, the benefit was not seen in patients receiving 20 Gy (16.7% vs 5.6%) or in RT fields with esophagus lengths of ≥10 cm (21.4% vs 6.3%). Overall survival was similar between patients in the ES-IMRT group receiving 20 Gy in 5 fractions and 30 Gy in 10 fractions (8.6 vs 8.7 months). Predictors of symptomatic esophagitis included prior chemotherapy (odds ratio of 9.3) and standard RT (odds ratio of 16.8).
"ES-IMRT demonstrated a trend toward improved esophageal quality of life and reduced the incidence of symptomatic esophagitis," conclude Dr. Louie and colleagues. "This benefit of ES-IMRT appears most prominent when the prescription dose is higher (30 Gy in 10 fractions) and for targets that encompass an esophageal length ≤10 cm."
For More Information
Louie AV, Granton PV, Bezjak A, et al (2020). A phase III randomized trial of palliative radiation for advanced central lung tomors with intentional avoidance of the esophagus (PROACTIVE). Int J Radiat Oncol Biol Phys, 108(suppl_3):S105-S106. DOI:10.1016/j.ijrobp.2020.07.2287
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