Esophagus-Sparing Radiation Fails QOL Test in Lung Cancer

Esophageal-sparing intensity-modulated radiotherapy (ES-IMRT) failed to improve esophageal quality of life, but did significantly reduce the incidence of symptomatic esophagitis, in patients with advanced non-small cell lung cancer (NSCLC), according to the phase III PROACTIVE trial.

Among 90 patients, there was no statistically significant difference in esophageal quality of life between those who received ES-IMRT and those who received standard radiotherapy (RT), with mean 2-week Functional Assessment of Cancer Therapy esophageal cancer subscale (ECS) scores of 54.3 and 50.5, respectively (P=0.06), reported Alexander V. Louie, MD, PhD, of Sunnybrook Health Sciences Centre at the University of Toronto, and colleagues.

However, symptomatic RT-associated esophagitis occurred in only 2% of the ES-IMRT arm compared with 24% of the control arm (P=0.002), with this benefit being most evident in patients receiving 30 Gy in 10 fractions, they noted in JAMA Oncology.

“These findings suggest that ES-IMRT may be an option for patients in whom reduction of esophageal toxic events is important,” Louie and team wrote.

In a commentary accompanying the study, Ashley A. Weiner, MD, PhD, and Joel E. Tepper, MD, both of the University of North Carolina School of Medicine in Chapel Hill, observed that while decreasing radiation dose to a portion of the esophagus reduced esophageal-related toxic effects, “in the absence of meeting the primary QOL [quality of life] endpoint and without demonstration of adequate symptom palliation, one cannot recommend ES-IMRT as a standard therapy for palliation of thoracic symptoms due to NSCLC.”

“But the important concept behind this trial — decreasing the dose to a portion of the tumor to reduce treatment-associated toxic effects — should be investigated with further studies,” they wrote.

The PROACTIVE (Palliative Radiation for Advanced Central Lung Tumors With Intentional Avoidance of the Esophagus) study enrolled 90 patients (median age at randomization 72, 56% women) with stage III/IV NSCLC who were eligible for palliative thoracic RT (20 Gy in 5 fractions or 30 Gy in 10 fractions) from June 2016 to March 2019.

The study’s primary outcome was esophageal quality of life 2 weeks post-RT, as measured by ECS scores (higher scores corresponded with improved quality of life). Secondary outcomes included overall survival, toxic events, and other quality-of-life metrics.

In a post-hoc subgroup analysis, Louie and colleagues noted that the nonsignificant improvement demonstrated with ES-IMRT was mainly observed in patients receiving 30 Gy (ESC scores 56.4 vs 51.1 for the control group, P=0.06) compared with those receiving 20 Gy (50.9 vs 49.7, respectively, P=0.68).

Over the 1-year follow-up, 56 deaths occurred, 27 in the control arm and 29 in the ES-IMRT arm. Overall survival was similar between arms, with a median of 8.6 months in the control arm versus 8.7 months in the ES-IMRT arm.

Louie and colleagues pointed out that the use of ES-IMRT had several limitations compared with standard palliative RT. For example, ES-IMRT takes more time to design and thus may be inappropriate in a situation in which more urgent RT is needed. They also noted that ES-IMRT is more costly and that cost-effectiveness is likely to be a subject of future research.

Finally, the ES-IMRT technique “requires a paradigm shift in palliative RT planning,” they wrote. “Typically, the entire tumor target is treated with the full RT prescription doses in these scenarios; reduction of dose along the organ at risk and target interface is more commonly performed with curative and/or ablative doses. Therefore, there is still uncertainty as to whether using ES-IMRT produced equivalent results on the tumor, but that would require a much larger noninferiority study.”