Don’t Go Breaking My Heart: Cardiac Toxicity Prevention in Lung Cancer and Management Through Multidisciplinary Care

Cardiovascular complications from thoracic radiation are increasingly common for multiple reasons. Historically, most patients diagnosed with thoracic malignancies, such as non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), thymic carcinomas, and mesothelioma, have had a poor prognosis and inevitably did not live long enough to experience late cardiac side effects from radiation.

With improvements in systemic therapy such as checkpoint inhibitors, emerging targeted drugs, and advanced local ablative therapies with surgery and radiation, prognosis has improved, with patients living longer—including those with advanced and/or metastatic disease. In radiation oncology, better treatment techniques, including intensity modulated radiation therapy (IMRT), stereotactic body radiation therapy (SBRT), respiratory gating to account for tumor movement, and particle therapy, have enabled us to treat all stages of disease, limiting dose to the surrounding lung, which at one point was the limiting factor. These improved outcomes now place more emphasis on survivorship and the long-term management of late side effects, including cardiac toxicity.

Given the importance of cardiac toxicity, the field of radiation oncology has developed better planning guidelines to reduce cardiac toxicity following radiation treatment. The focus, as we have learned, cannot be solely on reducing radiation pneumonitis; heart dose must also be considered, as we are now seeing more cardiac toxicity with various therapies patients are on, including immune checkpoint inhibitors and tyrosine kinase inhibitors.

We now have suggested dose constraints for the entire heart, including mean heart dose and V30, for example, but we also have identified potential dose constraints for specific cardiac substructures. These dose constraints are nicely summarized in a review by Banfill et al.1 Importantly, our field can now auto-contour cardiac substructures during planning, allowing us to be more deliberate about where we deposit radiation dose—not simply think of the dose to the heart as a whole.2

There have been multiple studies demonstrating a significant correlation between the dose delivered to the heart and overall survival, to the extent that radiation-induced heart disease (RIHD) in these studies actually negated the potential benefit from radiation.3 For example, the use of postoperative radiation therapy (PORT) in stage III-N2 NSCLC has always been somewhat controversial. In the two most recent randomized trials, PORT was found to have no significant impact on disease-free survival, which may have been influenced by higher rates of cardiovascular toxicities leading to death.4,5

As we have improved our radiation techniques and established clear dose constraints during radiation planning to prevent cardiac toxicity, I feel we still lack consensus on proper baseline screening for cardiac risk factors, as well as on the appropriate follow-up surveillance and management of cardiac toxicity in radiation oncology.

Additionally, while many radiation oncologists have standardized protocols to manage the more common side effects, including esophagitis and pneumonitis, many practices do not have a standardized approach to monitor high-risk cardiovascular cases. Therefore, I have highlighted several guidelines, including the following:

1. European Society of Cardiology/International Cardio-Oncology Society:6 Provides guidance for risk stratifying based on baseline cardiac comorbidities. This includes risk categorization based on mean radiation dose to the heart and designated pathways based on risk stratification, including referral to cardiology and cardiovascular disease assessments such as electrocardiogram (ECG), echocardiogram, and cardiac biomarker testing.
2. American Society of Clinical Oncology:7 Categorizes high-risk patients by radiation dose ≥ 30 Gy, < 30 Gy with anthracycline-based systemic therapies, or < 30 Gy where the heart is in the treatment field. If deemed high risk, patients should undergo an echocardiogram, along with possible cardiac magnetic resonance imaging, cardiac biomarker testing, and referral to cardiology based on findings. An echocardiogram may be performed within 6 to 12 months after treatment is completed.
3. European Society of Medical Oncology:8 Based on the American Society of Echocardiography (ASE) and the European Association of Cardiovascular Imaging (EACVI), symptomatic patients with a history of mediastinal radiation should undergo annual focused history and physical exams with echocardiograms. Asymptomatic patients should undergo a screening echocardiogram 10 years after radiation therapy and every 5 years thereafter.

Among these guidelines, those from the European Society of Cardiology6 are the most relevant for radiation oncology, as they risk-stratify based on mean heart dose—a well-known predictor of RIHD; however, they note their guidelines rely on mean dose to the heart and not cardiac substructures, which provides only a surface-level view of potential cardiac toxicity.9

In addition to these guidelines, the American Radium Society Appropriate Use Criteria committee recently published guidelines on cardiac toxicity screening and surveillance, based on recommendations from thoracic oncologists and cardio-oncologists.10 These guidelines are based on several clinical scenarios, which risk-stratify based on presenting cardiac comorbidities and cardiac toxicity risk based on radiation treatment dose to the heart. A number of recommendations emerged from these guidelines to guide appropriate follow-up for monitoring cardiac toxicities. These recommendations are summarized as follows:

1. Patients without cardiac comorbidities who are at low risk: Cardiac-focused history and physical exams at baseline and 5 years following completion of radiation, evaluating for potential cardiovascular symptoms.
2. Patients with cardiac comorbidities who are at low risk of RIHD: Focused history and physical exams at baseline and within 6 to 12 months after completion of radiation. Additional prescreening and post-screening tests may be appropriate based on history and physical exam findings.
3. Patients without cardiac comorbidities who are at high risk of RIHD: Focused history and physical exams at baseline and within 6 to 12 months after radiation. A prescreening EKG is also recommended.
4. Patients with cardiac comorbidities who are at high risk of RIHD: Focused history and physical exams at baseline and within 6 to 12 months after completion of radiation, and they should be evaluated by a cardiologist/cardio-oncologist or internist before and after completion of radiation. Additionally, they should undergo a prescreening ECG and echocardiogram prior to treatment.

In summary, several guidelines can inform cardiac surveillance care following radiation treatment. In addition to routine history and physical examinations, ECGs, and cardiac imaging when indicated, it is important to continue educating our patients on lifestyle interventions, including smoking cessation, dietary modifications, cholesterol and blood pressure management, and exercise.

As the radiation oncology field has, for the most part, standardized surveillance and treatment for certain toxicities such as radiation pneumonitis, it is imperative that we standardize our practices for surveying and managing long-term cardiac toxicity. Our patients are living longer, and the heart matters.

References

• 1. Banfill K, Giuliani M, Aznar M, et al: Cardiac Toxicity of Thoracic Radiotherapy: Existing Evidence and Future Directions. J Thorac Oncol 16:216-227, 2021
• 2. van der Pol LHG, Blanck O, Grehn M, et al: Auto-contouring of cardiac substructures for Stereotactic arrhythmia radioablation (STAR): A STOPSTORM.eu consortium study. Radiother Oncol 202:110610, 2025
• 3. Chun SG, Hu C, Choy H, et al: Impact of Intensity-Modulated Radiation Therapy Technique for Locally Advanced Non-Small-Cell Lung Cancer: A Secondary Analysis of the NRG Oncology RTOG 0617 Randomized Clinical Trial. J Clin Oncol 35:56-62, 2017
• 4. Hui Z, Men Y, Hu C, et al: Effect of Postoperative Radiotherapy for Patients With pIIIA-N2 Non-Small Cell Lung Cancer After Complete Resection and Adjuvant Chemotherapy: The Phase 3 PORT-C Randomized Clinical Trial. JAMA Oncol 7:1178-1185, 2021
• 5. Le Pechoux C, Pourel N, Barlesi F, et al: Postoperative radiotherapy versus no postoperative radiotherapy in patients with completely resected non-small-cell lung cancer and proven mediastinal N2 involvement (Lung ART): an open-label, randomised, phase 3 trial. Lancet Oncol 23:104-114, 2022
• 6. Lyon AR, López-Fernández T, Couch LS, et al: 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS): Developed by the task force on cardio-oncology of the European Society of Cardiology (ESC). European Heart Journal 43:4229-4361, 2022
• 7. Armenian SH, Lacchetti C, Barac A, et al: Prevention and Monitoring of Cardiac Dysfunction in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 35:893-911, 2017
• 8. Curigliano G, Lenihan D, Fradley M, et al: Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations. Ann Oncol 31:171-190, 2020
• 9. Marks LB, Yorke ED, Jackson A, et al: Use of Normal Tissue Complication Probability Models in the Clinic. International Journal of Radiation Oncology*Biology*Physics 76:S10-S19, 2010
• 10. Amini A, Zaha VG, Hamad E, et al: American Radium Society Appropriate Use Criteria on Cardiac Toxicity Prevention and Management After Thoracic Radiotherapy. J Thorac Oncol 19:1654-1667, 2024