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. 2024 Mar 19;110(10):726–734. doi: 10.1136/heartjnl-2023-323474

Table 1.

Characteristics of the analysed survivors and siblings

Survivors Siblings
All survivors
n=1381*
Only anthracyclines/mitoxantrone
n=809
Only heart RT
n=158
Heart RT and anthracyclines/mitoxantrone
n=253
Potentially cardiotoxic therapy
n=155
n=272
Demographics, diagnosis and treatment history
Sex, n (%)
Female 719 (52) 379 (47) 83 (53) 116 (46) 83 (54) 162 (60)
Age at diagnosis, years, median (IQR) 6.2 (3.2–11.3) 6.3 (3.1–11.4) 6.9 (2.9–9.8) 6.9 (3.8–12.2) 4.1 (2.6–8.3)
0–<5 572 (41) 322 (40) 66 (42) 95 (38) 87 (56)
5–<10 397 (29) 236 (29) 54 (34) 68 (27) 36 (23)
10–<15 322 (23) 194 (24) 31 (20) 69 (27) 27 (17)
15–18 90 (7) 57 (7) 7 (4) 21 (8) 5 (3)
Primary cancer diagnosis, n (%)
Leukaemias 559 (41) 358 (44) 18 (11) 88 (35) 92 (59)
Lymphomas/reticuloendothelial 334 (24) 228 (28) 25 (16) 63 (25) 16 (10)
CNS, intracranial and intraspinal neoplasms 46 (3) 3 (0.4) 35 (22) 1 (0.4) 6 (4)
Neuroblastoma and other peripheral nervous cell tumours 43 (3) 19 (2) 16 (10) 8 (3) 1 (1)
Retinoblastoma 1 (0.1) 0 (0) 0 (0) 0 (0) 1 (1)
Renal tumours 165 (12) 41 (5) 44 (28) 61 (24) 19 (12)
Hepatic tumours 11 (1) 11 (1) 0 (0) 0 (0) 0 (0)
Bone tumours 118 (9) 92 (11) 5 (3) 20 (8) 1 (1)
Soft tissue and other extraosseous sarcomas 69 (5) 52 (6) 4 (3) 11 (4) 2 (1)
Germ cell tumours 28 (2) 4 (1) 7 (4) 1 (0.4) 16 (10)
Others 7 (1) 1 (0.1) 5 (3) 0 (0) 1 (1)
Age at follow-up, years, median (IQR) 34.7 (28.5–42.1) 32.9 (27.5–39.8) 45.8 (38.0–50.3) 35.5 (30.9–41.0) 34.3 (25.7–43.5) 36.8 (29.2–43.7)
15–<25, n (%) 187 (14) 129 (16) 3 (2) 18 (7) 37 (24) 36 (13)
25–<35 521 (38) 347 (43) 25 (16) 102 (40) 43 (28) 90 (33)
35–<45 432 (31) 239 (30) 45 (29) 99 (39) 48 (31) 88 (32)
≥45 241 (18) 94 (12) 85 (54) 34 (13) 27 (17) 58 (21)
Time since cancer diagnosis, years, median (IQR) 26.9 (21.5–34.4) 25.6 (21.0–31.0) 40.1 (29.2–44.0) 27.3 (22.2–33.7) 30.7 (19.6–35.8)
10–<20, n (%) 264 (19) 169 (21) 11 (7) 38 (15) 45 (29)
20–<30 580 (42) 404 (50) 29 (18) 115 (46) 29 (19)
30–<40 402 (29) 213 (26) 38 (24) 90 (36) 58 (38)
≥40 135 (10) 23 (3) 80 (51) 9 (4) 22 (14)
Cumulative anthracycline dose†, mg/m2, median (IQR) 180 (120–288) 180 (120–288) 200 (150–299)
No anthracyclines, n (%) 336 (24) 20 (3) 158 (100) 3 (1) 155 (100)
1–100 174 (13) 138 (17) 36 (14)
100.1–250 551 (40) 425 (53) 125 (49)
>250 314 (23) 222 (28) 89 (35)
Missing 6 4 0
Mitoxantrone dose, mg/m2, median (IQR) 40 (20–72) 44 (20–93) 20 (20–50)
No mitoxantrone, n (%) 1308 (95) 755 (94) 234 (93) 155 (100)
1–40 40 (3) 26 (3) 14 (6)
>40 31 (2) 26 (3) 5 (2)
Missing 2 (0.1) 2 0
RT including the heart region dose, Gy, median (IQR) 12 (3.5–20.5) 14 (3–20) 10 (5–21)
No RT including the heart region, n (%) 965 (70) 809 (100) 0 (0) 0 (0) 155 (100)
1–15 260 (19) 82 (54) 177 (70)
15.1–30 98 (7) 56 (37) 41 (16)
>30 50 (4) 15 (10) 35 (14)
Missing 8 (1) 5 0
Vincristine exposed, n (%) 1153 (70) 690 (85) 237 (94) 102 (65) 118 (76)
Ifosfamide exposed, n (%) 207 (15) 109 (14) 5 (3) 77 (30) 14 (9)
Cyclophosphamide exposed, n (%) 774 (57) 552 (68) 39 (30) 157 (62) 23 (15)
Outpatient clinic data, median (IQR)
Waist circumference, cm 86 (78–94) 85 (78–94) 88 (80–97) 83 (75–90) 88 (81–96) 86 (80–95)
Systolic blood pressure, mm Hg 121 (112–132) 120 (112–129) 130 (118–142) 119 (110–131) 122 (112–134) 119 (109–128)
Diastolic blood pressure, mm Hg 75 (68–81) 74 (68–81) 78 (72–84) 75 (68–81) 75 (67–82) 73 (66–79)
Impaired LVEF at evaluation‡ 294 (21) 160 (22) 31 (23) 84 (38) 16 (14) 13 (5)
Severe impaired LVEF at evaluation§ 57 (5) 36 (5) 4 (3) 17 (8) 0 (0) 0 (0)
Questionnaire data, n (%)
Ever smoked >1 year¶ 377 (27) 231 (31) 43 (28) 67 (29) 35 (24) 79 (37)
Hypertension** 82 (6) 32 (4) 27 (18) 14 (6) 9 (6) 2 (1)
Use of lipid-lowering medication 57 (4) 16 (2) 18 (11) 16 (6) 7 (5) 1 (0.4)
Diabetes** 26 (3) 8 (1) 9 (6) 7 (3) 2 (1) 0 (0)
Arrhythmia** 16 (1) 7 (1) 6 (4) 3 (1) 0 (0) 0 (0)
Myocardial infarction** 4 (0.3) 1 (0.1) 1 (1) 2 (1) 0 (0) 0 (0)
Heart failure** 48 (4) 27 (4) 4 (3) 17 (7) 0 (0) 0 (0)
Cardiac surgery 23 (2) 8 (1) 8 (5) 5 (2) 2 (1) 0 (0)
Congenital heart disease 26 (2) 18 (2) 2 (1) 2 (1) 4 (3) 2 (1)

*In six survivors, the cardiotoxic cancer treatment was unclear due to missing information on either anthracycline exposure or heart RT.

†Calculated as doxorubicin+daunorubicin×0.5+epirubicine×0.8+idarubicine×3.

‡Defined as LVEF below normal threshold <54% (females) or <52% (males). Missing in 198.

§Defined as LVEF <45%. Missing in 198.

¶Composite of DCCSS LATER Study parts 1 and 2. Missing in 164.

**Self-reported and validated against appropriate medication use. Questionnaire data missing in 111 for hypertension, in 106 for diabetes, in 114 for arrhythmia, in 106 for myocardial infraction.

CNS, central nervous system; DCCSS LATER, Dutch Childhood Cancer Survivor Study LATER cohort (1963–2001); LVEF, left ventricular ejection fraction; n, number; RT, radiotherapy.