To the Heart of the Matter: Cardiac Safety & Lung Radiation Treatment

The April Global Radiation Oncology Twitter Journal Club (#RadOnc #JC) will be taking safety to heart by focusing on the cardiac toxicity of lung irradiation!

Consider joining anytime Saturday April 17^th 8am CST to Sunday April 18^th.
 Live Hour tweetchat with study authors & guests Sunday April 18th 1-2pm CST.

Lung radiation treatment is at the unique intersection of the two leading causes of death: cardiovascular disease and cancer.¹ While advanced lung cancer carries a poor prognosis, recent data shows improvement with the 2-year relative lung-cancer specific survival increasing from 26% in 2001 to 35% in 2014.² This improvement is usually attributed to newer targeted therapies to cancer driver mutations.²  However, some question if it may also be due to better cardiac sparing with more modernized radiation treatment techniques.³ While we have usually prioritized cancer control over late toxicity for patients, these improvements in survival rates renews a concern for the late effects of thoracic treatments, especially cardiac toxicity.

Radiation-induced heart disease (RIHD) has usually been studied after mediastinal irradiation for another cancer also affecting adolescents and young adults – Hodgkin’s disease. There is a wide range of side effects thought to reflect the distinct functional properties of the different cardiac substructures, including the pericardium, myocardium, cardiac valves, conduction system, and coronary arteries.⁴ The coronary arteries are usually of great concern, where radiation may accelerate inflammation and the long-term development of atherosclerotic plaques that can cause stroke and myocardial infarction.⁵ This potential toxicity is thought to be an even bigger concern for patients with pre-existing coronary artery disease (CAD) risk factors. CADs are known to be strongly associated with age and smoking risk factors, which are also common considerations in patients with lung cancer.

The importance of radiation dose delivery to the heart was first suggested by of RTOG 0617, a landmark trial for radiation oncology. Secondary analyses and long-term follow-up suggested overall survival (OS) may be associated with radiation treatment plan parameters such as the heart V40,⁶ V30,⁷ and V5.⁷ This spurred new debate, more analyses showing the importance of heart dose, ¹ and with better technology efforts to further characterize cardiac substructures in the present era.

These changes to our understanding brought on by new technology and care raise many questions. Seeking to help answer them with enabling technologies and passionate hearts and minds, this month’s #RadOnc #JC will feature a study by Atkins et al:⁸

Atkins KM et al. Association of Left Anterior Descending (LAD) Coronary Artery Radiation Dose With Major Adverse Cardiac Events (MACE) and Mortality in Patients With Non–Small Cell Lung Cancer. JAMA Oncol. 2021;7(2):206–219.

Thanks to JAMA Oncology, this article is free to access for the duration of the chat to encourage more inclusive participation. We will also be joined by the study’s authors Dr. Katelyn Atkins (@_katelynatkins) and Dr. Ray Mak (@Dr_RayMak) along with special guests of diverse expertise.

Guiding Topics:

T1 Background: What is the incidence of radiation-induced heart disease (RIHD) in advanced lung cancer treatment? Which major adverse cardiac events (MACEs) are most common or of greatest concern?

T2 Methods: How were different radiation dose parameters selected in this study? Why were Receiver Operating Curves (ROCs) and cut-point analyses used? What was done to account for bias?

T3 Results: Which radiation treatment dose parameters were found to be significant in the study and why? What is the bottom line?

T4 Discussion: What is the current practice in treating locally advanced lung cancer in your region? Do you consider cardiac toxicity when managing lung cancer and if so, how? Which dosimetric parameters do you utilize when evaluating a plan for heart dose?Do you consider cardiac substructures in radiation treatment and if so, how? What are the study strengths and weaknesses? Are any populations not covered? How could these study results help your local practice?

T5 #ChartRounds & Next Steps: How can we further decrease the risk of cardiac disease in lung cancer patients treated with radiation? How could cardiac risk stratification be incorporated into future studies or clinical practice? Can practices from other disease sites (i.e. breast cancer or lymphoma) help?

T6 #PatientsIncluded: What lung cancer treatment goals and side effects are important for patients? What is involved with heart health assessments and cardiac follow-up for patients with lung cancer? How can clinicians, patients, and others work together to improve outcomes for heart health and lung cancer?

Some tips to participate:

• Guidelines on how to sign up & participate
• Disclaimer for ways to keep #RadOnc #JC rewarding and professional. If you’re not ready, just lurk & tune in to the conversation.

Free to Access References:

1. Banfill K, Giuliani M, Aznar M, et al. Cardiac Toxicity of Thoracic Radiotherapy: Existing Evidence and Future Directions. J Thorac Oncol. 2021;16(2):216-227.

2. Howlader N, Forjaz G, Mooradian MJ, Meza R, Kong CY, Cronin KA, Mariotto AB, Lowy DR, Feuer EJ. The Effect of Advances in Lung-Cancer Treatment on Population Mortality. N Engl J Med. 2020 Aug 13;383(7):640-649.

3. Bradley JD, Hu C, Komaki RR, Masters GA, Blumenschein GR, Schild SE, Bogart JA, Forster KM, Magliocco AM, Kavadi VS, Narayan S, Iyengar P, Robinson CG, Wynn RB, Koprowski CD, Olson MR, Meng J, Paulus R, Curran WJ Jr, Choy H. Long-Term Results of NRG Oncology RTOG 0617: Standard- Versus High-Dose Chemoradiotherapy With or Without Cetuximab for Unresectable Stage III Non-Small-Cell Lung Cancer. J Clin Oncol. 2020 Mar 1;38(7):706-714.

4. Heidenreich PA, Kapoor JR Radiation induced heart disease. Heart 2009;95:252-258.

5. Weintraub  NL, Jones  WK, Manka  D.  Understanding radiation-induced vascular disease.   J Am Coll Cardiol. 2010;55(12):1237-1239.

6. Chun S.G., Hu C., Choy H. 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. 2017;35:56–62

7. Bradley J.D., Paulus R., Komaki R. Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. Lancet Oncol. 2015;16:187–199.8. Atkins KM, Chaunzwa TL, Lamba N, et al. Association of Left Anterior Descending Coronary Artery Radiation Dose With Major Adverse Cardiac Events and Mortality in Patients With Non–Small Cell Lung Cancer. JAMA Oncol. 2021;7(2):206–219.