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20-08-2021 | Non-small-cell lung cancer | News

Hypofractionated image-guided RT not the answer for chemoradiotherapy-ineligible NSCLC

Laura Cowen

medwireNews: Hypofractionated image-guided radiotherapy (IGRT) does not improve survival relative to conventional radiotherapy in patients with stage II or III non-small-cell lung cancer (NSCLC) ineligible for concurrent chemoradiotherapy, research shows.

The phase 3 trial included 96 patients (mean age 71.0 years, 65.6% men) with poor performance status who were randomly assigned to receive hypofractionated IGRT (60 Gy in 15 fractions; n=50) or conventionally fractionated radiotherapy (CFRT; 60 Gy in 30 fractions; n=46). It was closed early due to futility at the interim analysis.

Robert Timmerman (University of Texas Southwestern Medical Center, Dallas, USA) and co-investigators report that, at study closure, after a median 8.7 months of follow-up, there was no significant difference in the 1-year overall survival (OS) rate between the patients who received hypofractionated IGRT and those who received CFRT, at 37.7% versus 44.6%.

There were also no significant differences between the two groups in median OS (8.2 vs 10.6 months) or progression-free survival (6.4 vs 7.3 months).

An exploratory analysis of data for 77 patients treated at the main study site revealed that the probability of local relapse-free survival was numerically higher with hypofractionated IGRT than with CFRT (85.8 vs 66.1%), while the median time to distant metastasis was not reached in the former group but was 18.0 months in the latter.

The team found that there was no difference in grade 3–5 radiation-related adverse events (AEs) between the two arms, with 18 and 19 events recorded in the hypofractionated IGRT and CFRT groups, respectively.

The rate of grade 2 AEs, however, was significantly higher with hypofractionated IGRT than with CFRT, at 52.0% versus 23.9%. The most common grade 2 toxicity was esophagitis, which occurred in 22.0% of the hypofractionated IGRT group and 8.7% of the CFRT group.

In addition, 40.0% of individuals who received hypofractionated IGRT experienced grade 2 respiratory toxicity compared with 15.2% of those who received CFRT.

Writing in JAMA Oncology, Timmerman and co-authors say: “Although there were no differences in grades 3 to 5 toxic effects, the increase in grade 2 toxic effects may have been critical in this patient population with poor performance status, highlighting the importance of selecting patients who would tolerate fewer toxic effects such as esophagitis and dyspnea owing to factors such as age, tumor location, or comorbidities.”

They conclude that while hypofractionated IGRT was not associated with improved survival, “the convenience of hypofractionated radiotherapy regimens may offer an appropriate treatment option” for certain patients with NSCLC, such as those with peripheral primary tumors and limited mediastinal/hilar adenopathy.

The team adds: “Further studies are needed to verify equivalence between these radiotherapy regimens.”

In an accompanying comment Melin Khandekar and Florence Keane, both from Harvard Medical School in Boston, Massachusetts, USA, say that there have been significant improvements in lung cancer care over the past 10 years, in part due to the introduction of targeted therapies and immunotherapies.

But they point out that “[a]lthough advances in radiotherapy have accompanied these improvements, we do not yet have level 1 evidence that these advances have translated into improved patient outcomes.”

The commentators conclude: “This study, despite its negative outcome, is an initial foray into exploring the effect of radiation technique on lung cancer outcomes, and we hope it will be the first of many to add to our understanding of modern radiotherapy in lung cancer.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group

JAMA Oncol 2021; doi:10.1001/jamaoncol.2021.3186
JAMA Oncol 2021; doi:10.1001/jamaoncol.2021.3180