Purpose

A metric for measuring the efficacy of concurrent chemoradiotherapy (cCRT) for stage III non-small cell lung cancer (NSCLC) is in-field tumor control. However, evaluating in-field control rates from published studies is challenging, as many report progression-free survival rates that consider disease progression events occurring outside the RT treatment field. This hampers an understanding of the interactions between RT and consolidation immune checkpoint inhibitor (ICI) therapy, as well measurements of the benefit of surgical resection in lieu of cCRT for locally advanced NSCLC treated with similar systemic therapies. To address this issue, we examined how in-field progression rates are reported in the literature evaluating outcomes for stage III NSCLC treated with cCRT.

Methods

A systematic review was conducted using PubMed, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search included all interventional, observational, prospective, or retrospective studies reporting outcomes in patients with stage III NSCLC who received cCRT ± ICI, published January 2000 to November 2024. Reference lists from retrieved articles were reviewed to identify missed studies. Statistical comparisons between published progression rates were deemed inappropriate for cross-study comparisons.

Results

Sixty articles met inclusion criteria, reporting outcomes from 63% prospective and 37% retrospective studies. Cohort sizes ranged from 10 to 713, totaling 7,350 patients. Median follow-up ranged from 14 to 132 months. Post-cCRT response assessments used criteria established by RECIST (46%), WHO (12%), and ECOG (2%), while 40% did not specify evaluation parameters. Of 60 publications, only 18 had sufficient information to evaluate in-field progression. This included 16 studies evaluating cCRT-alone and 2 studies with cCRT + ICI. Of these 18 studies, four included evaluations of progression within regional lymph nodes or the thorax (see Table). Median in-field progression rates were 30.8% [95% CI 23.1-37.9%] for cCRT, and 17.5% [95% CI 4.0-30.9%] for cCRT + ICI. Only one retrospective study (n=120) reported “in-field only” progression rates at 41% with cCRT and 11% with cCRT + ICI.

Conclusions

Most publications reporting outcomes following cCRT ± ICI do not specify in-field progression rates. Limited data exist to determine whether the benefits of ICI arise from improved tumor control in-field, out-of-field, or both. Future studies will have a greater impact if they clarify what the in-field progression rates are following cCRT ± systemic therapies.