3 years ago

Is the Importance of Heart Dose Overstated in the Treatment of Non-Small Cell Lung Cancer? A Systematic Review of the Literature

Tina Wanting Zhang, Jonatan Snir, R. Gabriel Boldt, George B. Rodrigues, Alexander V. Louie, Stewart Gaede, Ronald C. Mcgarry, James J. Urbanic, Megan E. Daly, David Palma

Publication date: Available online 7 January 2019

Source: International Journal of Radiation Oncology*Biology*Physics

Author(s): Tina Wanting Zhang, Jonatan Snir, R. Gabriel Boldt, George B. Rodrigues, Alexander V. Louie, Stewart Gaede, Ronald C. McGarry, James J. Urbanic, Megan E. Daly, David Palma

Abstract
Purpose

Some recent studies have suggested a relationship between cardiac dose and mortality in non-small cell lung cancer (NSCLC), but others have reported conflicting data. The goal of this study was to conduct a systematic review and meta-analysis to provide an evidence-based estimate of the relationship between cardiac dose and mortality in these patients.

Methods and Materials

A systematic review of MEDLINE (PubMed) and Embase databases (inception to January 2018) according to PRISMA guidelines was performed. Studies that evaluated cardiac dosimetric factors in patients with NSCLC and included outcomes of cardiac events, cardiac mortality and/or overall survival were identified.

Results

From 5614 patients across 22 studies, a total of 214 cardiac dosimetric parameters (94 unique) were assessed as possible predictors of cardiac toxicity or death. Assessed predictors included general (e.g. mean heart dose (MHD)), threshold-based (e.g. heart V5), and anatomical-based (e.g. atria, ventricles) dosimetric factors. The most commonly analyzed parameters were MHD, heart V5, and V30. Most studies did not make corrections for multiplicity of testing. For overall survival, V5 was found to be significant on multivariable analysis (MVA) in 1 of 11 studies, V30 in 2 of 12 studies and MHD was not significant in any of 8 studies. For cardiac events, V5 was found to be significant on MVA in 1 of 2 studies, V30 in 1 of 3 studies, and MHD in 2 of 4 studies. A meta-analysis of the data could not be performed, as most negative studies did not report effect estimates.

Conclusions

Consistent heart dose-volume parameters associated with overall survival of NSCLC patients were not identified. Multiplicity of testing is a major issue and likely inflates the overall rate of type I error in the literature. Future studies should specify predictors a priori, correct for multiplicity of testing, and report effect estimates for non-significant variables.

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