No Survival Boost With Hypofractionated Image-Guided RT for NSCLC

Hypofractionated image-guided radiotherapy (IGRT) did not improve survival compared with conventionally fractionated radiotherapy (CFRT) in patients with advanced non-small cell lung cancer (NSCLC), who were unable to undergo concurrent chemoradiotherapy, according to results from a randomized phase III trial.

The 1-year overall survival (OS) rate — the study’s primary endpoint — was 37.7% for the IGRT group and 44.6% for the CFRT group, a difference that was not statistically significant, reported Robert Timmerman, MD, of the University of Texas Southwestern Medical Center in Dallas, and colleagues in JAMA Oncology.

There was also no statistically significant differences between the two groups in median OS (8.2 months with IGRT vs 10.6 months with CFRT), progression-free survival (6.4 months vs 7.3 months, respectively), probability of local relapse-free survival at 24 months (85.8% in the IGRT group and 66.1% in the CFRT group), and time to distant metastasis (median not reached vs 18 months, respectively).

Despite advances in radiotherapy over the last 10 years, “we do not yet have level 1 evidence that these advances have translated into improved patient outcomes,” wrote Melin Khandekar, MD, PhD, and Florence Keane, MD, both of Harvard Medical School and Massachusetts General Hospital in Boston, in an accompanying commentary.

Though this study was negative, it still had important lessons for thoracic radiation oncologists, they noted.

Specifically, Timmerman and team demonstrated the feasibility of conducting a multi-institutional trial to examine the effects of radiation dose and fractionation in lung cancer, they said. “This trial opens the door to studies of other radiation techniques that might improve our treatment of locally advanced lung cancer.”

Concurrent chemotherapy and CFRT followed by immunotherapy is the most effective treatment option for inoperable, locally advanced NSCLC, Timmerman and team said. However, due to comorbidities or cancer-associated decline, some patients are not candidates for concurrent chemoradiotherapy because of increased toxic effects.

Hypofractionated radiotherapy is an alternative for these patients, since it is given over a shorter period of time. In addition, advances in IGRT have improved treatment accuracy, allowing radiation oncologists to increase the prescribed dose.

This study included 103 patients with stage II/III NSCLC who were ineligible for standard concurrent chemoradiotherapy because of poor performance status; 96 patients (65.6% men, mean age 71) were randomized to receive hypofractionated IGRT (50 patients; 60 Gy in 15 fractions delivered over 3 weeks) or CFRT (46 patients; 60 Gy in 30 fractions delivered over 6 weeks).

A planned interim analysis indicated futility in reaching the trial’s primary endpoint, and the study was closed to further accrual.

While there were no differences in toxic effects ≥grade 3 between the two groups, there were substantially more grade 2 toxic effects in the IGRT group compared with the CFRT group (52% vs 23.9%).

“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,” Timmerman and team wrote.

“[F]or well-selected patients with NSCLC (i.e., peripheral primary tumors and limited mediastinal/hilar adenopathy), the convenience of hypofractionated radiotherapy regimens may offer an appropriate treatment option,” they noted.

“Additional trials will need to be powered for assessing equivalence between hypofractionated IGRT and CFRT for patients with stage II/III NSCLC who cannot receive concurrent therapies,” they concluded.