Which factor offers the highest risk for developing doxorubicin-related cardiotoxicity?

• A. 300 mg/m2 cumulative dose
• B. Mediastinal radiotherapy exposure
• C. 350 mg/m2
• D. Age under 60

Answer: (B)

Mediastinal radiotherapy exposure markedly raises the heart’s vulnerability to anthracycline damage. Doxorubicin causes cardiotoxicity in a dose-dependent way, but when the heart has already been exposed to radiation, there is additional injury to the myocardium and coronary vessels. This combination has a synergistic effect, making cardiotoxicity more likely than from the drug dose alone.

Chest radiation can cause fibrosis, microvascular damage, and pericardial disease, all of which lower the heart’s reserve. Even if the cumulative doxorubicin dose isn’t at the highest thresholds, the added radiation injury pushes the risk higher compared with the other options listed. Lower cumulative doses, like 300 or 350 mg/m2, are still risky, but not as impactful as chest radiotherapy exposure in this context. Age under 60 is not a stronger risk factor here than chest radiotherapy exposure.