A Systems Approach to Radiation-Induced Cardiopulmonary Toxicity-A Narrative Literature Review Focusing on the...

Thoracic radiotherapy, widely used in the treatment of mediastinal tumors, frequently exposes both the heart and lungs to ionizing radiation. While physiological interactions and shared vulnerability of the two organs have been known, heart and lung toxicities are assessed separately due to the lack of systematic studies and computational models demonstrating their interactions. For instance, based on the most updated NCCN guidelines for esophageal cancer, radiation prescriptions for preoperative, postoperative, and definitive intents are 41.4-50.4 Gy. Cardiopulmonary toxicities are well-known treatment side-effects in this disease site. Therefore, an exhaustive multi-layered list of dose-limits for lung and heart protection are recommended by NCCN guidelines. However, no combined or conditional (on the other organ's status) dose-limits are considered. Furthermore, while recommendations for dosimetric consideration of substructures during planning are becoming more common, whole heart and whole lung doses stay the main references for cardiac and pulmonary toxicities. A growing body of pre-clinical and clinical studies has investigated the interaction between cardiac and pulmonary systems in the context of radiation-induced toxicity. However, an analysis of cardiopulmonary system's collective response to radiation-particularly in predictive modeling, toxicity assessment, and treatment planning-is currently lacking. Here, we review the harmful interdependent interactions between the heart and lungs, especially in cancer patients and in response to treatment. Then we study the existing cardiopulmonary system models and conclude with potential strategies to collect the required parameters for models applicable to radiotherapy.