For patients with stage II/III non small-cell lung cancer who are ineligible for concurrent chemoradiotherapy, the use of hypofractionated image-guided radiotherapy offers no benefit over conventionally fractionated radiotherapy, a new study has concluded.
The authors of the phase 3 randomized clinical trial (NCT01459497) found that although more research is needed to needed to verify the equivalence of the two radiotherapy regimens, hypofractionated radiotherapy may still represent a viable treatment option in a subset of well-selected NSCLC patients.
Reporting online in JAMA Oncology, the multicenter team of researchers behind the study explained that a notable portion of individuals with stage II/III NSCLC are unable to undergo standard concurrent chemoradiotherapy because the risk of toxic effects outweighs the therapy’s potential benefits.
“Without concurrent chemotherapy, however, the efficacy of conventional radiotherapy is reduced,” they wrote. As such, they set out to determine if the use of hypofractionated image-guided radiotherapy (IGRT) improves overall survival relative to conventionally fractionated radiotherapy in these patients.
A total of 103 patients were enrolled in the trial between November 13, 2012 and August 28, 2018; all had stage II/III NSCLC and Zubrod performance status of at least 2. The participants had also lost at least 10% of their body weight in the previous six months, and/or were ineligible for concurrent chemoradiotherapy after an oncology consultation.
Eligible patients were randomized to undergo either hypofractionated IGRT (60 Gy in 15 fractions) or conventionally fractionated radiotherapy (60 Gy in 30 fractions). The trial’s primary endpoint was one-year overall survival.
According to lead author Puneeth Iyengar, MD, PhD, of the Simmons Comprehensive Cancer Center at the University of Texas Southwestern Medical Center in Dallas, 96 patients from the original cohort were analyzed (63 men; mean age 71.0 years). Among these, 50 received hypofractionated IGRT and 46 underwent conventionally fractionated radiotherapy. At that point, a planned interim analysis suggested futility in reaching the primary endpoint, closing the trial to further patient accrual.
It was found that over a median follow-up of 8.7 months, one-year overall survival was 37.7% among individuals who received hypofractionated IGRT, compared with 44.6% among their counterparts who underwent treatment with conventionally fractionated radiotherapy (P =0.29). Similarly, no differences were found between groups with respect to median overall survival (8.2 months and 10.6 months, respectively; P =0.17) and progression-free survival (6.4 months and 7.3 months, respectively; P =0.77).
The two groups also proved statistically comparable in terms of time to local failure, time to distant metastasis, and toxic treatment effects of at least grade three. Five individuals in the hypofractionated IGRT group died during treatment. Of these, four died after receiving fewer than four fractions; one patient died from a traumatic fall that was deemed to be the product of altered mental status following eight fractions.
The investigators also performed univariate and multivariate regression analyses of factors associated with overall survival outcomes. These analyses confirmed that the type of treatment was not significantly associated with overall survival.
Despite these findings, the researchers believe that hypofractionated radiotherapy may still play a role in certain patients with NSCLC, such as those with peripheral primary tumors and limited mediastinal/hilar adenopathy.
“I think perhaps in a larger setting with more patients and perhaps not as ambitious a primary endpoint you may be able to tease out in which patients can we safely administer the hypofractionation and in which patients we cannot, based on multivariate analyses,” Iyengar said in a recorded interview with JAMA Oncology.
“So I’m not necessarily ready to close the book on this area.”
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