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.