1. Cardiotoxicity of radiotherapy for malignancy
RTOW
Saturday, March 5, 2016
Erika Swanson, MD
Radiation Oncologist
Columbia St. Mary’s

2. Objectives Understand cardiac anatomy
Learn pathophysiology of cardiotoxicity
Discuss different malignancies associated with high risk of RT related cardiotoxicity
Review dosimetry and DVH data
Learn strategies to limit cardiac dose
Brief introduction to Cardio-oncology program/Survivorship

3. Why should we care?
Cancer and heart disease are the leading causes of morbidity and morality in US
Modern treatment has improved survival for cancer patients
Long-term cancer survivors are expected to increase by 30% in the next decade
18 million by 2022 in US alone
Curigliano CA Cancer J Clin 2016

4. Cardiac anatomy

5. Cardiac anatomy

6. Pulmonary trunk
Right auricle
Aorta
Left atrium
Descending
aorta

7. Conus arteriosus
Right atrium
Aortic bulb
Left ventricle
Left atrium
Esophagus

8. Conus arteriosus
Right atrium
Left ventricle
Left atrium

9. Right ventricle
Left ventricle
Right atrium
Esophagus
Left atrium

10. LAD

11. How’re you doing??

12. Cardiac Physiology
Dr. Nand will be covering this next lecture

13. Pathophysiology
Endothelial dysfunction is felt to be the precipitating factor in most cardiac sequelae
Impaired function
Stimulation of growth factors
Fibrosis
Small vessel occlusion and eventual cell death
Oxidative stress causes direct DNA damage, which activates inflammatory response. Endothelial cells recruit fibroblasts, resulting in collagen deposition and fibrosis. Thickening of the artery.
Jaworski JACC, 2013

14. Overview of RT cardiotoxicity
Acute effects (<6 mos)
Late effects (3 – 30 years)
Pericarditis
Chronic pericarditis
Coronary artery disease
Valvular disease
Cardiomyopathy
Conduction abnormalities

15. Acute Pericarditis Symptoms
Chest pain
Fever (+/-)
sharp, worse with coughing or inspiration
May be reduced by standing up or sitting forward
Usually worsened by lying flat

16. Pathology 58 y/o with breast cancer with constrictive pericarditis
Tricuspid and mitral valve thickening and fusion (breast ca)
CAD in 26 y/o!! With HL.

17. Risk factors for developing RT cardiotoxicity
Radiation dose
Dose per fraction
Volume of heart irradiated
Concominant administration of cardiotoxic drugs
Younger age
CV risk factors (smoking, hypertension, high chol)

18. Radiation therapy in breast cancer
Stage I long term overall survival ~95%
1 in 8 women diagnosed with breast cancer
RT is standard of care after breast conserving surgery
Reduces LR by ~60%  improve OS
PMRT indicated for N+, T3, positive margins
Reduces LRR by ~50-60%  improve OS (4-5%)

19. EBCTCG meta-analysis
Lancet 2000

20. EBCTCG
Lancet 2000

21. Left breast tangents

22. Left breast tangent DVH
Mean dose: 329 cGy
Max dose: 5088 cGy
V5: 17%

23. Dose Limitations Whole heart dose V16Gy < 5% V8Gy < 100%
Mean < 320 cGy

24. Want to hear more?

25. Radiotherapy for early stage Hodgkin Lymphoma
Long term survival approaches 90-95%
RT is often used in combination with 2-4 cycles of ABVD
Some may give more chemo and omit RT
RT always indicated for bulky disease
Table is showing increase in cardiac mortality (not morbidity) in survivors, 25% die cardiac related death.

26. Hodgkin Lymphoma Aleman, Blood 2007
Cardiac mortality is number one cause of non-cancer death.
Aleman, Blood 2007

27. Hodgkin Lymphoma Jaworski, JACC 2013
Table is showing increase in cardiac mortality (not morbidity) in survivors, increases as time goes on, 25% die cardiac related death.
Jaworski, JACC 2013

33. Stage IIB Unfavorable HL IMRT

34. Stage II HL DVH
Mean dose: 2326 cGy
Max dose: 3968 cGy
V5: 98%

35. Esophageal Cancer and RT
Survival is ~30% at 3 years
Radiation is used with concurrent chemotherapy
Definitive for squamous cell carcinoma
Neo-adjuvant for adenocarcinoma
Most common cardiotoxicities seen are pericarditis and decreased left ventricular ejection fraction

36. Esophageal Cancer

37. IMRT DVH Esophageal Cancer
Mean dose: 2669 cGy
Max dose: 5316 cGy
V5: 100%

38. Lung cancer Survival for stage III NSCLC is ~20% at 5 yrs
RTOG 0617 (74 Gy vs 60Gy)
OS worse in the high dose arm
MVA: Volume of heart receiving >5Gy and >30Gy were independent predictors of overall survival

39. Stage IIIA NSCLC

40. Stage IIIA NSCLC DVH
Mean dose: 1084 cGy
Max dose: 6711 cGy
V5: 54%

41. Strategies to limit the dose to heart
Patient set up
Prone position (insert prone dosimetry)
Breath hold
Respiratory gating
Treatment strategy
Omit RT when possible
Reduce RT dose
Limit RT field
Don’t deliver RT with concurrent cardiotoxic drugs
Technique
IMRT
Block the heart
Protons
Dr. Nand will discuss controversies regarding the data here

42. Prone breast tangents

43. Prone breast tangent DVH
Mean dose: 148cGy
Max dose: 2543 cGy
V5: 2%

44. Protons for HL
Hoppe, IJROBP 2011

45. Survivorship
There are no formal guidelines for following patients after thoracic radiation
Consider cardiac perfusion and/or calcium scoring by CT for those with doses >35 Gy to the coronary arteries, starting 5 years after RT or after age 30-35
Cardio-oncology program
Discipline developed in response to combined decision making necessary to optimize care for cancer patients

46. You made it!