Radiation technique reduces symptomatic esophagitis in patients with advanced lung cancer
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Esophageal-sparing intensity-modulated radiotherapy did not significantly improve esophageal quality of life but reduced incidence of symptomatic esophagitis among patients with advanced non-small cell lung cancer.
The results of the multicenter randomized, phase 3 PROACTIVE trial, published in JAMA Oncology, suggest esophageal-sparing intensity-modulated radiotherapy (ES-IMRT) may be most beneficial in reducing symptomatic esophagitis when the prescription dose is higher (30 Gy), researchers reported.
"Patients with advanced lung cancer can often have symptoms from their cancer, which palliative radiotherapy can help improve. However, radiotherapy can result in side effects such as temporary esophagitis or trouble with swallowing,” Alexander V. Louie, MD, PhD, MSc, FRCPC, clinician scientist, associate professor and radiation oncologist at University of Toronto Sunnybrook Health Sciences Centre, told Healio. “As these patients are often unwell, our motivation was to determine if using a modern radiation technique could improve symptoms from lung cancer with fewer swallowing side effects.”
Methodology
The analysis included 90 patients (56% women; median age at randomization, 72 years) with stage III or stage IV NSCLC eligible for palliative thoracic radiotherapy (20 Gy in five fractions or 30 Gy in 10 fractions) at six tertiary academic centers. Louie and colleagues randomly assigned them 1:1 to standard radiation therapy (control group) or ES-IMRT between June 16, 2016, and March 6, 2019.
Researchers compromised target coverage so the maximum esophagus dose was no more than 80% of the radiation prescription dose; 36 patients (40%) received 20 Gy and 54 (60%) received 30 Gy.
Louie and colleagues used the esophageal cancer subscale of the Functional Assessment of Cancer Therapy: Esophagus questionnaire to measure esophageal quality of life 2 weeks after radiation therapy, which served as the primary outcome. Higher subscale scores indicated improved quality of life, with a change of 2 to 3 points deemed clinically meaningful. Secondary outcomes included OS, toxic events and other quality-of-life measures.
Key findings
Results showed a mean 2-week esophageal cancer subscale score of 50.5 (95% CI, 47.2-53.8) in the control arm vs. 54.3 (95% CI, 51.9-56.7) in the ES-IMRT arm, a difference that fell short of statistical significance.
“We were very hopeful that we would demonstrate improvement in esophageal quality of life,” Louie said. “A P value of .06 suggests that we were either underpowered (ie, would require a larger study sample size to demonstrate statistical significance) or that esophageal-sparing IMRT indeed does not improve quality of life to a high degree as we had hypothesized.”
However, researchers reported symptomatic radiation therapy-associated esophagitis in 24% (n = 11) of patients in the control arm vs. only 2% (n = 1) in the ES-IMRT arm (P = .002). Results of a post hoc subgroup analysis based on the stratification factor showed a reduction in esophagitis in more patients who received 30 Gy (30% [n = 8] vs. 0%) compared with 20 Gy (17% [n = 3] vs. 6% [n = 1]).
Louie and colleagues reported similar OS with standard radiotherapy (median, 8.6 months; 95% CI, 5.7-15.6) and ES-IMRT (median, 8.7 months; 95% CI, 5.1-10.2).
Implications
The results suggest ES-IMRT may be an option for patients in whom reduction of esophageal toxic events is important, researchers wrote.
The trial could also pave the way to research in other disease sites, Louie said.
“This was a randomized controlled trial of a modern vs. standard radiotherapy technique for patients with incurable lung cancer. I think the same concept can be applied in other disease sites and anatomic regions to help guide value-based radiotherapy cancer care that is rooted in high-quality evidence,” Louie told Healio.
As Louie and colleagues noted, a large noninferiority study would be required to evaluate palliation, Ashley A. Weiner, MD, PhD, assistant professor and director of the radiation oncology residency training program at UNC Health, and Joel E. Tepper, MD, FASTRO, Hector MacLean Distinguished Professor of Cancer Research at UNC School of Medicine, wrote in a corresponding editorial.
“In the absence of meeting the primary 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,” Weiner and Tepper wrote. “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.”
References:
Louie AV, et al. JAMA Oncol. 2022:doi:10.1001/jamaoncol.2021.7664.
Weiner AA, et al. JAMA Oncol. 2022;doi:10.1001/jamaoncol.2021.7604.
For more information:
Alexander V. Louie, MD, PhD, MSc, FRCPC, can be reached at Odette Cancer Centre, Sunnybrook Health Sciences Centre, 2075 Bayview Ave., Toronto, Ontario, Canada, M4N 3M5; email: alexander.louie@sunnybrook.ca.
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