Quality of Life After Childhood Cancer 1

Quality of Life after Childhood Cancer 1

Supplemental Table 1: Data quality, reliability and internal validity ofthe SF-36 in the Swiss Childhood Cancer Survivor Study (N=1593)

Missingsa / Floor
Effectsb / Ceiling
Effectsc / Internal Consistency / PCS
Correlations / Aimed PCS Correlationsd / MCS
Correlations / Aimed MCS Correlationsd
n / % / n / % / n / % / re / r / r / r / r
Physical health scores
Physical Functioning / 12 / 0.75 / 4 / 0.25 / 972 / 61.0 / 0.91 / 0.86 / ≥0.70 / 0.08 / ≤0.30
Role Limitation Physical / 27 / 1.69 / 11 / 0.69 / 1017 / 64.0 / 0.91 / 0.71 / ≥0.70 / 0.35 / ≤0.30
Bodily Pain / 8 / 0.50 / 4 / 0.25 / 1087 / 68.0 / 0.91 / 0.67 / ≥0.70 / 0.34 / ≤0.30
Energy & Vitality / 17 / 1.07 / 3 / 0.19 / 65 / 4.10 / 0.82 / 0.35 / ≥0.30 / 0.77 / ≥0.30
Mental health scores
General Health Perception / 16 / 1.00 / 1 / 0.07 / 258 / 16.0 / 0.81 / 0.63 / ≥0.30 / 0.46 / ≥0.30
Role Limitation Emotional / 24 / 1.51 / 8 / 0.51 / 978 / 61.0 / 0.88 / 0.24 / ≤0.30 / 0.78 / ≥0.70
Social Functioning / 9 / 0.57 / 8 / 0.51 / 966 / 60.0 / 0.83 / 0.39 / 0.30-0.70 / 0.77 / ≥0.70
Mental Health / 17 / 1.07 / 0 / 0 / 86 / 6.00 / 0.82 / 0.14 / ≤0.30 / 0.91 / ≥0.70

Abbreviations: PCS, Physical Component Summary; MCS, Mental Component Summary.

aParticipants with more than 50% missing items per scale.

bParticipants with a scale score of 0 (minimum).

cParticipants with a scale score of 100 (maximum).

d Aimed correlations of scaling assumption in order to support the factor structure of the PCS and MCS [1].

eCronbach’s alpha for the inter-item-correlation of each scale.

Quality of Life after Childhood Cancer 1

Supplemental Table 2: Classification of chronic health problems

Classified healthconditionsa / Symptoms (present at time of study) within each problem
Overweight / ▪ / Body mass index ≥ 25 kg/m2
Vision impairment / ▪ / Severe visual impairment or blindness in one or both eyes
▪ / Glaucoma
▪ / Problems with the retina (for example retinal detachment)
▪ / Very dry eyes needing treatment with eye drops
Hearing problem / ▪ / Mild problem not needing hearing aid or fixable with a hearing aid (in one or both ears)
▪ / Moderate problem only partially fixable with a hearing aid (in one or both ears)
▪ / Severe problem or deaf not fixable with a hearing aid (in one or both ears)
▪ / Tinnitus
Memory problem / ▪ / Patient reports regular memory failure
Digestive problem / ▪ / Gallstones
▪ / Acute or chronic hepatitis
▪ / Ulcer
▪ / Liver cirrhosis
▪ / Chronic constipation or diarrhea
▪ / Regular acid regurgitation, heartburn, reflux
▪ / Esophageal problems (for example difficulties swallowing)
▪ / Chronic pancreatitis
▪ / Chronic nausea
Musculoskeletal and neurological problem / ▪ / Any kind of paralysis
▪ / Weakness of the arms or legs
▪ / Reduced sensitivity of the arms or legs
▪ / Uncontrolled movements
▪ / Balance disorders
▪ / Reduced range of motion of joints
▪ / Chronic pain in bones or joints
▪ / Scoliosis
▪ / Shortening of the arms or legs
Thyroid problem / ▪ / Hyperthyroidism
▪ / Hypothyroidism
▪ / Struma
▪ / Thyroid tumor

aSurvivors were classified as having a health problem, if they reportedto have at least one of the symptoms listed within a condition.

SupplementalTable 3: Comparison of participants and non-participants in the Swiss Childhood Cancer Survivor Study

Survivor participants
(n=1593) / Survivor non-participantsa
(n=933)
n / %b / n / %b / p-valuec
Sex / <0.001
Male / 847 / 53 / 577 / 62
Female / 746 / 47 / 356 / 38
Diagnosis (ICCC-3) / <0.001
I Leukemia / 573 / 36 / 279 / 30
II Lymphoma / 290 / 18 / 192 / 21
III CNS tumor / 210 / 13 / 143 / 15
IV Neuroblastoma / 67 / 4 / 43 / 5
V Retinoblastoma / 37 / 2 / 25 / 3
VI Renal tumor / 107 / 7 / 44 / 4
VII Hepatic tumor / 10 / 1 / 4 / 1
VIII Bone tumor / 77 / 4 / 36 / 4
IX Soft tissue sarcoma / 89 / 6 / 58 / 6
X Germ cell tumor / 45 / 3 / 37 / 4
XI & XII Other tumord / 19 / 1 / 20 / 1
Langerhans Cell Histiocytosis / 69 / 4 / 52 / 6
Surgery of tumor resection / 0.335
No / 909 / 57 / 514 / 55
Yes / 684 / 43 / 419 / 45
Chemotherapy / <0.001
No / 253 / 16 / 203 / 22
Yes / 1340 / 84 / 730 / 78
Radiotherapy / 0.741
No radiotherapy / 982 / 62 / 587 / 63
Body & limb irradiation / 314 / 20 / 183 / 20
Cranial & spinal irradiation / 297 / 18 / 163 / 17
Bone marrow transplantation / 0.975
No / 1526 / 96 / 894 / 96
Yes / 67 / 4 / 39 / 4
Relapse / 0.250
No / 1398 / 88 / 804 / 86
Yes / 195 / 12 / 129 / 14
mean / SD / mean / SD / p-valuee
Age at study / 25.1 / 6.9 / 25.2 / 7.5 / 0.560
Age at diagnosis / 7.6 / 4.7 / 7.6 / 4.6 / 0.448
Time since diagnosis / 17.4 / 6.9 / 17.6 / 7.8 / 0.743

NOTE: Percentages are based upon available data for each variable.

Abbreviations: CNS, Central Nervous System; ICCC-3, International Classification of Childhood Cancer - Third Edition; n, number.

aNon-participants include: 222 without current address, 448 who did not respond, 135 who refused to participate, 122 who answered an abridged questionnaire and 6 with all items missing on the SF-36(Figure 1).

bColumn percentages are given.

cP-value calculated from chi-square statistics.

dOther malignant epithelial neoplasms, malignant melanomas and other or unspecified malignant neoplasms.

e P-value calculated on two-sample mean-comparison test (t-test).

Supplemental Table 4: Factors associated with the SF-36 Physical Component Summary in survivors (mean differences by characteristics from linear regression models)

Univariable regression / Multivariable regressiona
Mean diff.b / 95% CI / p-value / Mean diff.b / 95% CI / p-valuec
Age at study (years) / 0.002 / 0.029
<20 / ref / ref
20-29 / 1.91 / 0.69 / - / 3.12 / 1.62 / 0.36 / - / 2.88
≥30 / 2.35 / 0.91 / - / 3.79 / 2.15 / 0.17 / - / 4.13
Sex / <0.001 / <0.001
Male / ref / ref
Female / 2.90 / 1.89 / - / 3.92 / 2.99 / 2.01 / - / 3.97
Migration background / 0.110
Native Swiss / ref
Immigrant / -1.50 / -3.33 / - / 0.34
Parents’ education / 0.040 / 0.056
Primary / 0.48 / -1.33 / - / 2.29 / 0.70 / -1.03 / - / 2.43
Secondary / ref / ref
Tertiary / 0.27 / -1.08 / - / 1.62 / 0.61 / -0.68 / - / 1.91
Unknown / -2.90 / -5.01 / - / -0.79 / -2.32 / -4.33 / - / -0.30
Diagnosis / <0.001 / <0.001
Leukemia / ref / ref
Lymphoma / 0.05 / -1.37 / - / 1.48 / -0.93 / -2.49 / - / 0.62
CNS tumor / -5.72 / -7.33 / - / -4.11 / -7.53 / -9.88 / - / -5.18
Neuroblastoma / -2.63 / -5.19 / - / -0.08 / -4.89 / -7.76 / - / -2.02
Retinoblastoma / -3.80 / -7.24 / - / -0.35 / -6.24 / -10.03 / - / -2.46
Renal & Hepatic tumor / -1.41 / -3.40 / - / 0.59 / -3.31 / -5.82 / - / -0.81
Bone tumor / -9.30 / -11.68 / - / -6.92 / -11.39 / -14.14 / - / -8.65
Soft tissue sarcoma / -2.43 / -4.66 / - / -0.19 / -3.65 / -6.19 / - / -1.10
Germ cell tumor / -1.99 / -5.07 / - / 1.10 / -3.43 / -6.75 / - / -0.12
Other tumord / -1.81 / -6.48 / - / 2.86 / -3.88 / -8.75 / - / 0.98
LCH / -0.50 / -2.99 / - / 1.99 / -3.00 / -5.72 / - / -0.28
Age at diagnosis (years) / 0.570
0-4 / 0.46 / -0.84 / - / 1.75
5-9 / ref
10-15 / -0.24 / -1.44 / - / 0.96
Surgery of tumor resection / <0.001 / 0.032
No / ref / ref
Yes / -2.32 / -3.34 / - / -1.29 / 1.69 / 0.14 / - / 3.25
Chemotherapy / 0.064 / 0.181
No / ref / ref
Yes / 1.33 / -0.08 / - / 2.73 / -1.25 / -3.08 / - / 0.58
Radiotherapy / 0.002 / 0.013
No radiotherapy / ref / ref
Body & limbirradiation / -1.63 / -2.95 / - / -0.31 / -0.73 / -2.12 / - / 0.66
Cranial & spinal irradiation / -2.16 / -3.52 / - / -0.80 / -2.09 / -3.49 / - / -0.69
BMT / <0.001 / 0.003
No / ref / ref
Yes / -4.83 / -7.40 / - / -2.25 / -3.92 / -6.54 / - / -1.30
Time since diagnosis (years) / 0.001 / 0.398
<10 / ref / ref
10-19 / -2.08 / -3.54 / - / -0.62 / -1.02 / -2.47 / - / 0.43
20-29 / 1.18 / -0.01 / - / 2.37 / -0.07 / -1.48 / - / 1.33
≥30 / 0.14 / -2.28 / - / 2.55 / -1.29 / -4.06 / - / 1.47
Relapse / <0.001 / <0.001
No relapse / ref / ref
Yes, relapse / -4.07 / -5.64 / - / -2.49 / -2.88 / -4.49 / - / -1.27

Abbreviations: BMT, Bone Marrow Transplantation; CNS; Central Nervous System; CI, Confidence Interval; diff., difference; LCH, Langerhans Cell Histiocytosis; ref, reference.

aIn the multivariable model we included all variables that were significantly associated (p≤0.05) with either the PCS or the MCS in the univariable linear regression models. Additionally we included a priori age, sex, parents’ education, diagnosis, treatment and time since diagnosis independent of their level of association.

b Mean differences for different charactersitics from univariable and multivariable regression models, representing the average increased (positive value) or decreased (negative value) HRQoL summary score compared to the reference category.

cGlobal p-value calculated with likelihood ratio test.

dOther malignant epithelial neoplasms, malignant melanomas and other or unspecified malignant neoplasms.

Supplemental Table 5: Factors associated with the SF-36 Mental Component Summary in survivors (mean differences by characteristics from linear regression models)

Univariable regression / Multivariable regressiona
Mean diff.b / 95% CI / p-value / Mean diff.b / 95% CI / p-valuec
Age at study (years) / <0.001 / <0.001
<20 / ref / ref
20-29 / -3.45 / -4.90 / - / -2.00 / -4.24 / -5.78 / - / -2.70
≥30 / -2.95 / -4.67 / - / -1.23 / -5.24 / -7.66 / - / -2.82
Sex / <0.001 / <0.001
Male / ref / ref
Female / 5.83 / 4.64 / - / 7.02 / 5.71 / 4.51 / - / 6.90
Migration background / 0.124
Native Swiss / ref
Immigrant / -1.73 / -3.93 / - / 0.47
Parents’ education / 0.343 / 0.130
Primary / -1.68 / -3.86 / - / 0.49 / -1.28 / -3.39 / - / 0.84
Secondary / ref / ref
Tertiary / -0.59 / -2.21 / - / 1.03 / -1.34 / -2.92 / - / 0.25
Unknown / -1.42 / -3.96 / - / 1.11 / -2.13 / -4.60 / - / 0.34
Diagnosis / 0.386 / 0.687
Leukemia / ref / ref
Lymphoma / 1.71 / -0.05 / - / 3.47 / 1.13 / -0.77 / - / 3.03
CNS tumor / -0.43 / -2.42 / - / 1.56 / -0.39 / -3.26 / - / 2.48
Neuroblastoma / -1.44 / -4.60 / - / 1.71 / -2.76 / -6.26 / - / 0.74
Retinoblastoma / -1.14 / -5.40 / - / 3.11 / -1.03 / -5.66 / - / 3.59
Renal & Hepatic tumor / -0.01 / -2.48 / - / 2.46 / -1.17 / -4.24 / - / 1.89
Bone tumor / 2.21 / -0.74 / - / 5.15 / 1.38 / -1.98 / - / 4.73
Soft tissue sarcoma / 1.29 / -1.47 / - / 4.05 / 0.34 / -2.77 / - / 3.45
Germ cell tumor / -1.00 / -4.81 / - / 2.81 / -0.75 / -4.80 / - / 3.30
Other tumord / -2.44 / -8.21 / - / 3.32 / -1.64 / -7.58 / - / 4.30
LCH / -0.43 / -3.50 / - / 2.65 / -1.13 / -4.46 / - / 2.19
Age at diagnosis (years) / 0.848
0-4 / ref
5-9 / -0.33 / -1.89 / - / 1.22
10-15 / -0.40 / -1.84 / - / 1.04
Surgery of tumor resection / 0.901 / 0.226
No / ref / ref
Yes / 0.08 / -1.16 / - / 1.32 / 1.17 / -0.73 / - / 3.07
Chemotherapy / <0.001 / 0.017
No / ref / ref
Yes / 2.64 / 0.97 / - / 4.32 / 2.73 / 0.48 / - / 4.97
Radiotherapy / 0.675 / 0.778
No radiotherapy / ref / ref
Body & limbirradiation / 0.65 / -0.93 / - / 2.23 / 0.23 / -1.47 / - / 1.93
Cranial & spinal irradiation / -0.14 / -1.78 / - / 1.49 / -0.49 / -2.21 / - / 1.22
BMT / 0.767 / 0.705
No / ref / ref
Yes / 0.47 / -2.63 / - / 3.57 / -0.62 / -3.82 / - / 2.58
Time since diagnosis (years) / 0.035 / 0.014
<10 / ref / ref
10-19 / 2.48 / 0.72 / - / 4.23 / 1.70 / -0.07 / - / 3.47
20-29 / 0.73 / -0.70 / - / 2.16 / 2.43 / 0.72 / - / 4.15
≥30 / -0.76 / -3.67 / - / 2.14 / 1.47 / -1.91 / - / 4.85
Relapse / 0.393 / 0.369
No relapse / ref / ref
Yes, relapse / 0.83 / -1.07 / - / 2.73 / 0.90 / -1.07 / - / 2.87

Abbreviations: BMT, Bone Marrow Transplantation;CNS; Central Nervous System; CI, Confidence Interval; diff., difference; LCH, Langerhans Cell Histiocytosis; ref, reference.

cGlobal p-value calculated with likelihood ratio test.

dOther malignant epithelial neoplasms, malignant melanomas and other or unspecified malignant neoplasms.

Quality of Life after Childhood Cancer 1

Supplemental Table 6: Mean differences comparing survivors with and without chronic health problemsa on the eight subscales of the SF-36 (adjusted for age, gender & parents’ education)

Overweight / Vision impairments / Hearing problems / Memory problems / Digestive problems / Musculoskeletal / neurological problems / Thyroid problems
Physical functioning
Mean differenceb / -2.92 / -7.15 / -6.59 / -7.19 / -5.70 / -9.40 / -6.92
CI / -4.62 to -1.23 / -9.41 to -4.90 / -8.85 to -4.32 / -9.33 to -5.06 / -7.70 to -3.70 / -10.9 to -7.90 / -9.26 to -4.59
p-value / <0.001 / <0.001 / <0.001 / <0.001 / <0.001 / <0.001 / <0.001
Role physical
Mean differenceb / -1.42 / -3.91 / -5.09 / -6.31 / -4.27 / -5.11 / -4.02
CI / -2.49 to -0.34 / -5.36 to -2.47 / -6.52 to -3.66 / -7.64 to -4.98 / -5.53 to -3.00 / -6.06 to -4.16 / -5.52 to -2.53
p-value / 0.010 / <0.001 / <0.001 / <0.001 / <0.001 / <0.001 / <0.001
Bodily pain
Mean differenceb / -1.15 / -1.33 / -3.91 / -5.15 / -4.73 / -5.70 / -4.12
CI / -2.15 to -0.15 / -2.68 to -0.02 / -5.24 to -2.57 / -6.40 to -3.90 / -5.90 to -3.57 / -6.60 to -4.83 / -5.49 to -2.74
p-value / 0.024 / 0.054 / <0.001 / <0.001 / <0.001 / <0.001 / <0.001
Energy & vitality
Mean differenceb / -1.70 / -2.65 / -6.81 / -10.6 / -7.36 / -5.86 / -5.71
CI / -3.33 to -0.74 / -4.86 to -0.44 / -8.99 to -4.63 / -12.6 to -8.57 / -9.27 to -5.46 / -7.32 to -4.40 / -7.96 to -3.46
p-value / 0.040 / 0.019 / <0.001 / <0.001 / <0.001 / <0.001 / <0.001
General health
Mean differenceb / -3.76 / -4.01 / -5.91 / -8.56 / -8.33 / -8.00 / -8.38
CI / -5.27 to -2.24 / -6.06 to -1.97 / -7.94 to -3.86 / -10.5 to -6.65 / -10.1 to -6.56 / -9.34 to -6.67 / -10.5 to -6.29
p-value / <0.001 / <0.001 / <0.001 / <0.001 / <0.001 / <0.001 / <0.001
Role emotional
Mean differenceb / -0.76 / -2.63 / -3.14 / -6.34 / -3.85 / -2.91 / -2.51
CI / -1.88 to 0.36 / -4.16 to -1.11 / -4.64 to -1.63 / -7.74 to -4.94 / -5.17 to -2.52 / -3.92 to -1.89 / -4.08 to -0.95
p-value / 0.184 / 0.001 / <0.001 / <0.001 / <0.001 / <0.001 / 0.002
Social functioning
Mean differenceb / -1.11 / -4.09 / -5.71 / -7.73 / -6.78 / -5.80 / -3.81
CI / -2.48 to 0.26 / -5.92 to -2.25 / -7.55 to -3.88 / -9.44 to -6.02 / -8.37 to -5.18 / -7.02 to -4.58 / -5.71 to -1.91
p-value / 0.112 / <0.001 / <0.001 / <0.001 / <0.001 / <0.001 / <0.001
Mental health
Mean differenceb / -1.28 / -1.02 / -3.45 / -7.72 / -5.25 / -3.88 / -3.59
CI / -2.64 to 0.08 / -2.87 to 0.83 / -5.30 to -1.61 / -9.43 to -6.02 / -6.85 to -3.64 / -5.11 to -2.64 / -5.48 to -1.69
p-value / 0.066 / 0.283 / <0.001 / <0.001 / <0.001 / <0.001 / <0.001

Abbreviations: CI, 95% Confidence Interval; Coeff., Coefficient from linear regression.

a Classification of chronic health problems is described in SupplementalTable 2.

b A negative mean difference means that survivors with chronic health conditions reported lower HRQoL in the respective scale.

Quality of Life after Childhood Cancer 1

References

1. Ware J, Kosinski M, Dewey J (2000) How to score Version 2 of the SF-36 Health Survey. QualyMetric Incorporated, Lincoln, RI