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

Article

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).

Reference

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
A panel of 3 experts on lung cancer
A panel of 3 experts on lung cancer
A panel of 3 experts on lung cancer
Byoung Chul Cho, MD, PhD, highlights ongoing trials assessing intravenous and subcutaneous amivantamab in EGFR-mutant non–small cell lung cancer.
A panel of 3 experts on lung cancer
A panel of 3 experts on lung cancer
The use of CT scans may help practices adaptively plan and adjust radiotherapy courses for patients with non–small cell lung cancer.
Patients with NSCLC who have comorbidities or frailty may also be able to receive treatment with fewer toxicities via proton beam radiotherapy.
Terrence T. Sio, MD, MS, emphasizes multidisciplinary collaboration for treating patients with NSCLC who may require more than 1 type of therapy.
Video 2 - "MARIPOSA-2 Phase 3 Study Design and Treatment Arms"
Related Content