medwireNews: Esophageal-sparing intensity-modulated radiotherapy (ES-IMRT) reduces the incidence of esophagitis but not does not improve esophageal quality of life (QoL) versus standard palliative thoracic RT in people with advanced lung cancer, research shows.
The multicenter, phase 3 PROACTIVE trial included 90 patients (median age 72 years, 56% women) with stage III/IV incurable non-small-cell lung cancer (NSCLC) who were randomly assigned to receive ES-IMRT (n=45) or standard RT (n=45) between 2016 and 2019. Of these, 40% in each group received 20 Gy in 5 fractions and 60% received 30 Gy in 10 fractions, as decided by the treating radiation oncologist.
Alexander Louie (Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada) and co-authors report in JAMA Oncology that the mean esophagus dose was 9.8 Gy in the ES-IMRT arm and 10.2 Gy in the standard RT arm, with maximum esophagus doses of 23.8 Gy and 25.3 Gy, respectively.
At 2 weeks after RT, the researchers found that there was no significant difference in esophageal quality of life between the two groups. Specifically, the mean score on the esophageal cancer subscale of the Functional Assessment of Cancer Therapy: Esophagus questionnaire was 54.3 points in the ES-IMRT arm versus 50.5 points in the control arm.
There was, however, a significant difference in the incidence of grade 2 or worse symptomatic RT-associated esophagitis, at 2% among the participants who received ES-IMRT compared with 24% in those given standard RT.
Furthermore, a post-hoc subgroup analysis based on the intended radiotherapy dose revealed that reduction in esophagitis was only significant among the patients who received 30 Gy. In this case, there were no cases of grade 2 or worse esophagitis in the ES-IMRT group compared with an incidence of 30% in the standard RT group. The corresponding rates among people who received 20 Gy were 6% and 17%, a nonsignificant difference.
“[T]hese findings suggest that ES-IMRT may be most beneficial when the prescription dose is higher (30 Gy),” Louie et al remark.
The authors also note that there was no significant difference in median overall survival between the two arms, at 8.7 months with ES-IMRT and 8.6 months with standard RT. In total, there were 56 deaths during the 1-year follow-up period, 29 in the ES-IMRT arm and 27 in the control arm.
The researchers say that “mitigating the QOL detriment from any palliative treatments is paramount” because the patients “have a limited life expectancy.”
They suggest that “ES-IMRT may be an option for patients in whom reduction of esophageal toxic events is important.”
In an accompanying comment Ashley Weiner and Joel Tepper, both from the University of North Carolina, in Chapel Hill, USA, say: “Louie et al have conducted a well-designed trial that has demonstrated a decrease in esophageal treatment-related toxic effects by decreasing the dose to a portion of the esophagus.”
However, they stress that “one cannot recommend ES-IMRT as a standard therapy for palliation of thoracic symptoms due to NSCLC” because the primary QoL endpoint was not met and the study did not measure NSCLC symptom palliation.
Nonetheless the commentators say “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.”
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JAMA Oncol 2022; doi:10.1001/jamaoncol.2021.7664
JAMA Oncol 2022; doi:10.1001/jamaoncol.2021.7604