A Systems Approach to Radiation-Induced Cardiopulmonary Toxicity—A Narrative Literature Review Focusing on the Interdependence of the Heart and the Lung in Thoracic Radiotherapy

Figures

• 

  Figure A1. Mechanistic models describe physiological phenomena mathematically by modeling how the system works internally. On the other hand, data-driven response models map inputs to outputs empirically.

• 

  Figure 1. Annual publication counts in PubMed until the end of 2025. The phrases sought in title or abstract of the papers published on PubMed were 1—(cardiac toxicity or cardiotoxicity or cardio toxicity or cardiac side-effect or cardiac side effect) and (radiation therapy or radiotherapy); 2—(lung toxicity or pulmonary toxicity or lung side-effect or lung side effect or pulmonary side-effect or pulmonary side effect) and (radiation therapy or radiotherapy); and 3—cardiopulmonary and (toxicity or side-effect or side effect) and (radiation therapy or radiotherapy).

• 

  Figure 2. Associations between lung and heart dysfunctions based on this subsection’s literature review [32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51]. FEV1, forced expiratory volume in 1 s; FVC, forced vital capacity; CAD, coronary artery disease; PHD, pulmonary heart disease; CVD, cardiovascular disease; COPD, chronic obstructive pulmonary disease.

• 

  Figure 3. Schematic block diagram of the cardiovascular system of Karamolegkos et al.’s enhanced cardiopulmonary model. Required model parameters are as follows: Psa and Ppa, systemic and pulmonary arterial blood pressures; Pra and Pla, right and left atrial pressures; Prv and Plv right and left ventricular pressures; Ppal, pulmonary arteriolar pressure; Ppc pulmonary capillary pressure; Ppv, pulmonary venous pressure; Pperi, pericardial pressure; Ppl, pleural (intrathoracic) pressure; PA, alveolar pressure; Vra and Vla, right and left atrial volumes; Vrv and Vlv, right and left ventricular volumes; Vspt, septal volume; Vperi, pericardial volume; VA alveolar volume; Qrv,o, and Qlv,o, right and left ventricular output blood flows; Qpa, pulmonary arterial blood flow; Qpal, pulmonary arteriolar blood flow; Qpc, pulmonary capillary blood flow; Qps, pulmonary shunt blood flow; MV, mitral valve; AV, aortic valve; TV, tricuspid valve; PV, pulmonary valve; H, imaginary plane defining the volumes of the septum and of the right and left ventricular free walls. This figure is copied from Figure 2 in Karamolegkos et al.’s manuscript [75] and is licensed under a Creative Commons Attribution 4.0 License.

• 

  Figure 4. A visual summary of a potential workflow for performing the required clinical measurements (Table 4) for calculating three sample parameters in Karamolegkos et al.’s cardiopulmonary system model (Figure 3) [75]. The three sample parameters are right and left ventricular volumes and alveolar volume. The goal is to assess the changes from pre- to post-radiotherapy timepoints to predict clinical endpoints (Figure 2). The measurements will be patient-specific and under any existing competing risk (Section Competing Risks and Risk Modeling Difficulties).