Table 2.

Representative Selection of Panelists’ Rationales for Echocardiographic Screening Childhood Cancer Survivors at Risk for Cardiomyopathy

	Scenario	Panelist Recommendation	Agree, n (%)	Comments (+)	Disagree, n (%)	Comments (−)
Timing	Childhood cancer survivor at risk of cardiomyopathy	Initiation within 1 y off therapy	31/40 (78)	Patients may develop dysfunction depending on exposure acutely, subacutely or delayed; all of these are time points of risk. Late identification of dysfunction in adult data has a significantly decreased response rate to medications. Establishing a baseline to serve as comparison is crucial, as some patients remain asymptomatic until there has been a significant decline in cardiac function.	9/40 (22)	Screening within the first 10 y has very low yield unless acute cardiac complications occurred during treatment with anthracyclines. Delay screening until entry into survivorship care (2-5 y).
		Duration indefinitely	36/40 (90)	Patients may be at risk, and in fact risk may continue to increase, up to about 40 y after receipt of chemotherapy/radiation. Cardiac late effects may occur many years (decades) after exposure. Risk for CVD and heart failure increases with aging.	4/40 (10)	For low-risk patients with no cardiac history, we stop screening if there is prolonged stability on echocardiography and only screen in presence of clinical symptoms thereafter. For high-risk patients, if start at every 1-2 y, would change to every 5 y if echocardiographic results stable over 5-10 y. Take into account what other comorbidities may affect the risk/benefit ratio of screening (ie, recurrent cancer, stroke, dementia, etc).
Treatment factors	Chest radiation, any dose (no anthracyclines)	Screening required	22/39 (56)	Although higher doses do increase risk, risk is seen even at the lowest doses. Studies have shown even lower doses (<15 Gy) are associated with some risk (for both heart disease and cardiac mortality). There is no “safe dose” of radiation. There is no clear dose threshold for CVD risk from extension of adult breast cancer literature. Cutoffs are imperfect and can miss disease.	17/39 (44)	Radiation is most commonly associated with coronary artery disease, which is not screen detectable with echo….RT doses <15 Gy are likely to have a very low absolute risk for screen-detectable echocardiographic abnormality. For asymptomatic patients with normal examination results, would not recommend serial screens.
	Chest radiation threshold dose (≥15 Gy, no anthracyclines)	Screening required	13/39 (33)	Aligns with COG long-term follow-up guidelines. >15 Gy appears to be the cutoff for moderate risk for developing cardiomyopathy.	26/39 (67)	Highest risk is >35 Gy; in absence of other risk factors would limit screening to this higher risk group (repeat testing is not without harms). If other risk factors (eg, smoking, HTN, hyperlipidemia), would lower threshold to screen.
	Thoracic spinal radiation 15-36 Gy (no anthracyclines)	Screening required	37/40 (93)	Unless using proton radiation, there is exit-dose or low-dose exposure to the heart when treating the thoracic spine. Radiation exposure to the thorax is associated with substantial risk for the subsequent development of CVD.	3/40 (7)	If proton RT was used, the heart dose is likely negligible.
	Fractionated TBI (no anthracyclines)	Screening required	30/39 (77)	TBI is associated with cardiovascular complications, including cardiomyopathy. Evidence is quite limited, but once cardiomyopathy does develop, prognosis can be quite poor, and interventions do exist to possibly improve outcomes. So until more evidence becomes available, I would err on the side of including any radiation including TBI as a risk factor.	9/39 (33)	Insufficient data to support screening. There are harms of overmedicalizing these patients’ lives. TBI doses are <15 Gy. This recommendation would otherwise be inconsistent with the [COG LTFU] recommendation not to screen patients treated with <15 Gy and no anthracyclines.
Recommended change to frequency if…	Proton rather than photon radiation	No change to screening frequency	32/40 (80)	I don’t feel we have enough long-term data on proton therapy to feel safe in changing the screening recommendations. Dosimetry information may not be available.	8/40 (20)	[Screening frequency is] based on heart dose, and often protons can decrease heart dose compared with photons.
	Patient received dexrazoxane	No change to screening frequency	38/40 (95)	There are not enough data to determine if the short-term cardioprotective benefits of dexrazoxane translate into long-term protection.	2/40 (5)	Dexrazoxane has been shown to be cardioprotective…based on what we do know I think 5-y screening intervals are reasonable.
	Age <1 y at treatment	Increase screening frequency	22/40 (55)	In [a] registry risk model, young age at treatment (<1 y old) increased the risk of myocardial dysfunction and cardiac mortality. Younger age and developing tissues are generally at higher risk for toxicity.	18/40 (45)	Higher risk, but no evidence that more frequent screening has an advantage. [Our group] no longer does this since publication of new [COG LTFU] guidelines.

COG = Children’s Oncology Group; CVD = cardiovascular disease; HTN = hypertension; LTFU = long-term follow-up; RT = radiation therapy; TBI = total body irradiation.