Cardiotoxicity following thoracic radiotherapy for lung cancer

Abstract

Radiotherapy is the standard of care treatment for unresectable NSCLC, combined with concurrent chemotherapy and adjuvant immunotherapy. Despite technological advances in radiotherapy planning and delivery, the risk of damage to surrounding thoracic tissues remains high. Cardiac problems, including arrhythmia, heart failure and ischaemic events, occur in 20% of patients with lung cancer who undergo radiotherapy. As survival rates improve incrementally for this cohort, minimising the cardiovascular morbidity of RT is increasingly important. Problematically, the reporting of cardiac endpoints has been poor in thoracic radiotherapy clinical trials, and retrospective studies have been limited by the lack of standardisation of nomenclature and endpoints. How baseline cardiovascular profile and cardiac substructure radiation dose distribution impact the risk of cardiotoxicity is incompletely understood. As Thoracic Oncology departments seek to expand the indications for radiotherapy, and as the patient cohort becomes older and more comorbid, there is a pressing need for cardiotoxicity to be comprehensively characterised with sophisticated oncology, physics and cardio-oncology evaluations. This review synthesises the evidence base for cardiotoxicity in conventional radiotherapy, focusing on lung cancer, including current data, unmet clinical needs, and future scientific directions.

Fig. 1. Categorisation of cardiovascular factors and study endpoints in radiation heart disease particularly in the setting of lung cancer.

a is a summary schema for how critical cardiovascular factors can be considered temporally. b displays the positive and negative characteristics of commonly employed study designs. (MI = myocardial infarction; IHD = ischaemic heart disease).

Fig. 2. Summary of published dosimetric relationships for cardiac endpoints in lung radiotherapy studies.

The three-dimensional reconstruction of autosegmented cardiac substructures from a lung cancer radiotherapy plan, annotated with the literature on post-radiotherapy cardiac event endpoints by substructure, and proposed dose constraints where available (*no dose threshold reported; Vxx = percentage volume receiving at least XX Gy; Dmax = maximum dose; Dmean = mean dose).

Fig. 3. Suggested priorities at each stage of the patient journey for both clinicians and researchers.

(CVRF = cardiovascular risk factor; ECD = established cardiac disease; ECG = electrocardiogram; RIHD = radiation-induced heart disease; PRV = planning organ at risk volume).