Table 1.
Factors affect the risk of RACVD.
| Factors | Description | References |
|---|---|---|
| PATIENT FACTOR | ||
| Pre-existing cardiovascular risk factors | Patients with pre-existing cardiovascular risk factors, such as prior cardiovascular disease, diabetes, COPD, smoking history, and high BMI (obesity), increase the risk of RACVD. | (21, 56–59) |
| BRCA1/2 mutation carriers | Patients with BRCA1/2 mutation demonstrate a higher risk of CVD than that of control patients. | (60) |
| Vulnerable populations | Pediatric and elderly cancer patients are vulnerable to RTCVD. | (40–43) |
| CANCER FACTOR | ||
| Lung cancer | RT to lung cancers increases the risk of RTCVD. | (13, 61, 62) |
| Esophagus cancer | RT to esophagus cancers, especially the middle/lower third tumors, has a high risk of RTCVD. | (63) |
| Breast cancer | RT to breast cancers, especially the left side breast, burdens a substantial risk of RTCVD that may develop in decades. | (12, 21, 64, 65) |
| Head and neck cancers | RT to head and neck cancers increases the risk of RTCVD, mainly carotid stenosis and subsequent ischemic stroke. | (10, 45) |
| Lymphoma | RT to lymphomas that involved the thorax or head and neck regions demonstrates a high risk of RTCVD. | (8, 44, 66) |
| RT HEART DOSE CONSTRAINS | ||
| *Lung SABR |
1. 50 Gy in 4 fractions: V40 ≤ 1c.c.; V20 ≤ 5c.c.; Dmax ≤ 45 Gy. 2. 70 Gy in 10 fractions: V45 ≤ 1c.c.; Dmax ≤ 60 Gy. |
(67–69) |
| *Lung RT | V30 ≤ 45%; MHD < 26 Gy. | (67, 70) |
| *Breast RT | V5 < 10%; V25 < 5%; MHD <4 Gy. | (67) |
| *Esophagus RT | Dmax (0.03 cc) ≤ 52 Gy; V40 < 50%; MHD < 26 Gy. | (67) |
| *Lymphoma RT | MHD < 5 Gy ideal, no higher than 15 Gy. | (67) |
| COMBINED THERAPY | ||
| **Chemotherapy | Some regimens demonstrate cardiotoxicities, e.g., anthracycline agents. | (26–29, 65) |
| **Targeted therapy | Some targeted therapy has cardiotoxicities, e.g., anti-Her2 and anti-VEGF agents. | (30–33) |
| **Immunotherapy | Some immunotherapeutic drugs have cardiotoxicities, e.g., anti-PD1/PDL1 agents. | (34–36) |
| OTHER FACTORS | ||
| ***Statins | Statins use may decrease the risk of RACVD in irradiated cancer patients. | (71) |
| ****ACEI and angiotensin II receptor antagonist | These agents may decrease the risk of RACVD in irradiated cancer patients. | (72, 73) |
The dose to OARs is different according to the irradiated sites and cancer disease extension. Radiation oncologists always judge the pros and cons of RT to achieve better tumor control and fewer toxicities, i.e., judging for maximum tolerated dose (MTD) or as low as reasonably achievable (ALARA) (67, 74).
Multimodality treatment is the cornerstone in managing cancer patients. However, combined treatments irreversibly enhance the risk of RTCVD.
Statin used in irradiated cancer patients with hypercholesterolemia may demonstrate double benefits of decreasing the blood level of cholesterol and the risk of RACVD.
ACEIs and angiotensin II receptor antagonists used in irradiated patients with hypertension may have double benefits of controlling blood pressure and decreasing the risk of RACVD.
“V5” represents the percent volume of organ at risk (i.e., the heart) that is irradiated with an IR dose of ≥ 5 Gy. V25, V30, V40, and V45 are similar representations.
ACEI, angiotensin-converting enzyme inhibitor; ALARA, as low as reasonably achievable; BMI, body mass index; COPD, chronic obstructive pulmonary disease; Dmax, maximal dose; Gy, gray; MHD, mean heart dose; MTD, maximum tolerated dose; OAR, organ at risk; RACVD, radiation-associated cardiovascular dysfunction; RT, radiotherapy; SABR, stereotactic ablative body radiotherapy; VEGF, vascular endothelial growth factor.