Role of Real-World Data in Assessing Cardiac Toxicity After Lung Cancer Radiotherapy

Abstract

Radiation-induced heart disease (RIHD) is a recent concern in patients with lung cancer after being treated with radiotherapy. Most of information we have in the field of cardiac toxicity comes from studies utilizing real-world data (RWD) as randomized controlled trials (RCTs) are generally not practical in this field. This article is a narrative review of the literature using RWD to study RIHD in patients with lung cancer following radiotherapy, summarizing heart dosimetric factors associated with outcome, strength, and limitations of the RWD studies, and how RWD can be used to assess a change to cardiac dose constraints.

Keywords: cardiac toxicity; heart dose constraints; lung cancer; radiation induced heart disease; real-world data.

Figure 1

Evidence leading to the development of the RAPID-RT programme of research. In 2013, Darby et al. reported a linear relationship between mean heart dose and major coronary events in patients with breast cancer treated with radiotherapy (36). Mcwilliam et al, in 2017, showed there is a strong correlation between dose received by the base of the heart and overall survival in patients with lung cancer (3). These findings were externally validated using data from RTOG 0617 trial (88). A pre-clinical study further validated that the base of the heart is a sensitive region (reverse translation) (89). A feasibility planning study demonstrated that it is possible to spare cardiac avoidance region (located at the base of the heart) on previous Manchester studies (90). The RAPID-RT programme, funded by the National institute for health research (NIHR), will evaluate the impact of the introduction of a dose limit to the cardiac avoidance region in all patients with stage II-III lung cancer treated with curative-intent radiotherapy at The Christie NHS Foundation Trust in Manchester, UK (27).