KEY POINTS
- This single-centre retrospective cohort included 131 patients with unresectable locally advanced NSCLC treated between 2012 and 2019. Patients received conventional concurrent chemoradiotherapy (n=52), conventional sequential chemoradiotherapy (n=37), or sequential chemotherapy followed by hypofractionated RT (n=42).
- The concurrent and conventionally fractionated sequential groups received 60 Gy in 30 fractions. The hypofractionated sequential group received chemotherapy followed by 55 Gy in 20 fractions, reducing the RT course from approximately 6 to 4 weeks.
- Three-year locoregional control was 62.0% with hypofractionated sequential treatment versus 34.8% with conventional sequential treatment and 62.0% with concurrent treatment (p=0.009). After multivariable adjustment, conventional sequential treatment remained associated with more than twice the risk of locoregional failure versus hypofractionation (HR 2.26, 95% CI 1.05–4.87; p=0.038).
- Overall survival did not significantly differ. Three-year OS was 33.3% with hypofractionated sequential treatment, 27.8% with conventional sequential treatment, and 22.2% with concurrent treatment (p=0.676); median OS was 19.6, 14.1, and 24.9 months, respectively.
- Progression-free and distant failure-free survival were also statistically similar between groups. Three-year PFS was 15.6%, 18.4%, and 27.2% for hypofractionated sequential, conventional sequential, and concurrent treatment, respectively (p=0.131).
- The improved locoregional control did not come with a clear toxicity penalty. Grade ≥2 esophagitis occurred in 50.0% with hypofractionated sequential treatment, 37.8% with conventional sequential treatment, and 46.1% with concurrent treatment (p=0.554); grade ≥2 pneumonitis occurred in 0%, 2.7%, and 1.9%, respectively (p=0.490).
- Interpretation is limited by major era and treatment differences: this was a non-randomized historical cohort, approximately 60% lacked pretreatment PET-CT, daily CBCT/IGRT was unavailable, and no patient received consolidation immunotherapy, making direct extrapolation to the current PACIFIC era uncertain.
CLINICAL TAKEAWAY
For patients with locally advanced NSCLC who are not suitable for concurrent chemoradiotherapy, sequential 55 Gy in 20 fractions may offer better locoregional control than a conventional 60 Gy/30-fraction sequential schedule while shortening treatment and preserving toxicity. The signal is clinically attractive, especially where radiotherapy capacity is limited, but the retrospective design and pre-durvalumab treatment era prevent this from establishing a new standard.