Locally advanced inoperable primary or recurrent non-small cell lung cancer treated with 4-week hypofractionated radiation therapy (3 Gy/fraction).

Background: The prognosis of locally advanced non-small cell lung cancer (NSCLC) treated with conventional radiotherapy remains poor. Hypofractionation reduces overall treatment time increasing biological effect in patients not suitable for concurrent chemo-radiotherapy.

Method: From January 2009 to October 2016, 76 inoperable locally advanced primary or recurrent NSCLC patients were treated with 60 Gy in 20 fractions of 3 Gy/each for 4 weeks as exclusive or post-chemotherapy treatment. Fifty-eight patients (76.3%) had stage III and 18 (23.7%) stage IV (≤ 2 metastases) disease: 63 primary (82.9%) and 13 recurrent (17.1%).

Results: Median and 2-year overall survival were 17 months and 38.9%, respectively. Median and 2-year loco-regional progression free survival were 27 months and 55.3%, respectively. Univariate and multivariate analyses demonstrated that patients with complete response presented better outcomes, whereas no statistically relevant difference was evidenced in terms of previous chemotherapy, recurrent vs primary disease, volume and stage. Thirty patients (39.5%) presented acute esophagitis (1-grade 3) and 19 (25.0%) acute pneumonitis (2-grade 3). Six patients (7.9%) developed grade 2-3 late pneumonitis and 3 patients (3.9%) grade 1 late esophagitis.

Conclusion: In patients not suitable of concurrent radio-chemotherapy, exclusive or sequential hypofractionated schedule using 60 Gy in 20 fractions was well tolerated and presented promising results. Complete local response was a predictor of better outcomes, and any efforts will be made to perform prospective clinical trials to further evaluate hypofractionated regimens with increased lesional BED.