Efficacy and safety of curative-intent intensity modulated radiotherapy (IMRT) for inoperable, locally-advanced non-small cell lung cancer: A systematic review

ABSTRACT

Intensity-modulated radiotherapy (IMRT), including volumetric modulated arc therapy (VMAT) is widely used for the treatment of non-small cell lung cancer (NSCLC) despite the lack of prospective, randomized evidence over three-dimensional conformal radiotherapy (3D-CRT). IMRT has been shown to reduce doses to normal tissue and organs at risk (OAR) in planning and retrospective studies. The protocol for this review was registered in the International Prospective Register of Systematic Reviews (PROSPERO ID: CRD42021239551). Systematic searches of MEDLINE and EMBASE databases were conducted using predefined criteria in 2020–2021 and repeated in October 2024. Eligible studies were screened and identified by two authors. Ten articles based on five randomized controlled trials (RCT) encompassing 936 patients and 19 articles (19 non-randomized trials) encompassing 1,093 patients were included. None of the trials compared IMRT with 3D-CRT for locally-advanced NSCLC. Meta-analysis was not feasible due to the heterogeneity of evidence base. The publications were assessed for risk of bias and summarized in tabular form before a narrative synthesis was carried out. At standard dose-fractionation, IMRT seems safe for inoperable, locally-advanced NSCLC. However, caution should be exercised when intensifying treatment, particularly with large planning target volume (PTV), major vascular abutment, or the presence of significant hemoptysis. IMRT is associated with lower rates of severe pneumonitis and lower cardiac doses. There is a need to establish dose-constraints for the heart. Greater improvements in survival have been seen using multi-modality treatment by combining novel systemic therapy with modern radiotherapy approaches.