Esophageal-Sparing Intensity-Modulated Radiotherapy Improves Symptomatic Esophagitis in Advanced NSCLC

While quality of life did not improve with esophageal-sparing intensity-modulated radiotherapy, patients with stage III/IV non–small cell lung cancer did experience a reduction in symptomatic esophagitis.

Patients with stage III/IV non–small cell lung cancer (NSCLC) treated with esophageal-sparing intensity-modulated radiotherapy (ES-IMRT) did not have an improvement in quality of life, but did see a significant reduction in symptomatic esophagitis, according to a phase 3 PROACTIVE trial (NCT02752126) published in JAMA Oncology.

Patients had an esophageal cancer subscale (ECS) score of 50.5 (95% CI, 47.2-53.8) in the standard radiotherapy arm compared with 54.3 (95% CI, 51.9-56.7) in the ES-IMRT arm (P = .06). Symptomatic radiotherapy-associated esophagitis was observed in 24.0% of patients in the control arm and 2.0% of patients in the ES-IMRT arm (P = .02).

A total of 90 patients with incurable stage III/IV NSCLC were randomized across 6 centers in Canada, 71% of whom had stage IV disease. Additionally, 72% had an ECOG status of 0 to 1. Treatment was administered to 40% of patients at 20 Gy in 5 fractions and 60% received 30 Gy in 10 fractions. In the control arm, the mean esophagus dose was 10.2 Gy with a maximum dose of 25.3 Gy. In the ES-IMRT arm, the mean dose was 9.8 Gy and the maximum dose was 23.8 Gy.

In the ES-IMRT arm, 22 of 45 patients had cancer in direct contact with the esophagus and required a 20% reduction in dosing in that area. In the control arm, the mean number of cycles received was 7.7 vs 5.1 in the ES-IMRT arm (P = .68).

Two weeks following radiotherapy, 80 patients completed the ECS quality of life form. The post-hoc analysis found when dividing patients by stratification factors, benefit was primarily observed in patients receiving 30 Gy with a score of 51.1 in the standard arm vs 56.4 in the ES-IMRT arm (P = .06) compared with 20 Gy at 49.7 vs 50.9, respectively (P = .68).

The incidence of grade 2 esophagitis was observed in 24% of patients in the radiotherapy arm and in 2% of those in the ES-IMRT arm. The benefit was primarily observed among those who received the 30 Gy dosage, including 30% patients vs 0% in each respective arm (P = .004) compared with the 20 Gy group at 15% vs 6%, respectively (P = .60).

In the exploratory multivariable analysis, investigators identified that treatment with prior chemotherapy (OR, 9.33; 95% CI, 1.53-56.82; P = .02) was predictive of symptomatic esophagitis, as well as randomization to the control arm, stratified by the intended dose, (OR, 16.83; 95% CI, 1.85-152.84; P = .01). However, the intended dose of 30 Gy or 20 Gy was not significantly predictive of symptomatic esophagitis (OR, 1.37; 95% CI, 0.38-5.00; P = .63), but randomization in the control arm was significantly predictive (OR, 9.74; 95% CI, 1.70-55.87; P = .01).

In the trial, 56 patients died during the 1-year follow-up period, 27 of whom were in the control arm and 29 were in the ES-IMRT arm. Between arms, the overall survival was 8.6 months (95% CI, 5.7-15.6) in the control arm compared with the ES-IMRT arm at 8.7 months (95% CI, 5.1-10.2).


Louie AV, Granton PV, Fairchild A, et al. Palliative radiation for advanced central lung tumors with intentional avoidance of the esophagus (PROACTIVE): a phase 3 randomized clinical trial. JAMA Oncol. Published Online February 24, 2022. doi:10.1001/jamaoncol.2021.7664

Related Videos
An expert from Yale School of Medicine discusses how the approval of adjuvant pembrolizumab expands treatment to include patients with IB, II, III, and IIIA resected, early-stage, non–small cell lung cancer regardless of PD-L1 expression.
Alexander Spira, MD, PhD, FACP, of the Virginia Cancer Specialists, discusses how the FDA approval of adagrasib for KRAS G12C–mutated non–small cell lung cancer can provide benefit for this patient population.
Pooling data with other radiation trials, looking more closely at central non-small cell lung cancer, and exploring secondary outcomes represent the next steps in terms of analyzing stereotactic body radiation (SBRT) vs conventional hypofractionated radiotherapy (CRT), according to Anand Swaminath, MD.
Anand Swaminath, MD, reviews the design of the phase 3 LUSTRE trial comparing a 3-week conventional radiotherapy regimen with stereotactic body radiotherapy among patients with stage I medically inoperable non-small cell lung cancer.
Stereotactic body radiation therapy yielded numerical improvements in terms of local control compared with conventional hypofractionated radiotherapy among patients with stage I medically inoperable non-small cell lung cancer, according to findings from the phase 3 LUSTRE trial.
Data from the phase 3 LUSTRE trial indicated that stereotactic body radiotherapy is a safe and effective alternative to conventional radiation for use in patients with stage I medically-inoperable non-small lung cancer, according to an expert from Juravinski Cancer Centre in Canada.
Hossein Borghaei, DO, MS, discussed where investigators may drive future research following the phase 2 Lung-MAP trial examining pembrolizumab and ramucirumab in previously treated advanced non–small cell lung cancer.
Hossein Borghaei, DO, MS, highlights data that read out of the phase 2 Lung-MAP trial, assessing ramucirumab/pembrolizumab in previously treated advanced non–small cell lung cancer.
Related Content