Cheung 2017.

Methods	Study design: cross‐sectional study Instrument used to assess fatigue: PedsQL Multidimensional Fatigue Scale Validated questionnaire: yes Cut‐off score or criterion for severe fatigue: NAa Time points at which outcome data were collected: NA, cross‐sectional study Inclusion criteria: active survivors who were receiving paediatric follow‐up care, at least 5 years from diagnosis, over 8 years of age, alive Exclusion criteria: previous treatment with cranial irradiation for CNS relapse or bone marrow transplantation or additional chemotherapy for a secondary cancer, pre‐existing non‐cancer‐related neurodevelopmental or genetic disorder associated with cognitive impairment or brain injury unrelated to cancer, lack of proficiency in English, not eligible for follow‐up
Participants	Sample characteristics: N of participants original cohort: 408; N of participants described study group: 70; N of participants study group of interest: 70; N of participants fatigue assessed: 70 Participant characteristics: Tumour type: ALL n = 70 Tumour stage: nm Age at diagnosis: female mean 6.8 years (SD 4.5; range 1.9 ‐ 17.7); male mean 7.0 years (SD 4.8; range 1.2 ‐ 16.5) Time since diagnosis: female mean 7.1 years (SD 1.7; range 5.1 ‐ 11.6); male mean 7.8 years (SD 2.0; range 5.1 ‐ 12.5) Age at assessment: female mean 13.9 years (SD 4.3; range 8.1 ‐ 25.4); male mean 14.8 years ( SD 5.1; range 8.5 ‐ 25.5) F/M: 35/35 BMI: female mean 22.2 kg/m2 (SD 5.0; range 14.1 ‐ 36.7); male mean 23.1 kg/m2 (SD 8.3; range 15.4 ‐ 46.4) Race: White n = 56, Black n = 12, other n = 2 Ethnicity: Hispanic n = 6, non‐Hispanic n = 64 Marital status: nm Highest completed education level: education in years, female mean 7.4 (SD 3.6; range 2 ‐ 14); male mean 7.6 (SD 3.9; range 2 ‐ 14) Employment: nm Physical activity level: nm Sleeping problems: sleep duration in hours, female mean 9.05 (SD 1.7); male mean 8.96 (SD 1.1) Psychosocial problems: nm Comorbidities: nm Genetic factors/mutations: nm
Interventions	N of participants chemotherapy: 70 N of participants radiotherapy: 0 N of participants surgery: 0 Chemotherapeutic agents, cumulative dose: Oral dexamethasone, mg/m2: female mean 1061.0 (SD 204.1; range 444.2 ‐ 1534.8); male mean 1148.0 (SD 326.2; range 412.3 ‐ 1690.1) IV Erwinia‐asparaginase, 1000 U/m2: female mean 375.2 (SD 227.8; range 146.0 ‐ 741.2); male mean 402.0 (SD 284.6; range 178.9 ‐ 871.9) IV L‐asparaginase, 1000 U/m2: female mean 215.5 (SD 147.0; range 85.9 ‐ 584.5); male mean 314.7 (SD 198.5; range 44.4 ‐ 539.9) IV Peg‐asparaginase, 1000 U/m2: female mean 7.8 (SD 3.8; range 2.5 ‐ 12.9); male mean 17.1 (SD 15.5; range 2.5 ‐ 44.7) IV cytarabine Standard dose, g/m2: female mean 1.4 (SD 1.6; range 0.3 ‐ 4.8); male mean 2.6 (SD 1.8; range 0.6 ‐ 4.9) IV cytarabine High dose, g/m2: female mean 7.4 (SD 1.6; range 3.9 ‐ 8.1); male mean 8.6 (SD 2.7; range 7.7 ‐ 19.6) IV cyclophosphamide, g/m2: female mean 1.9 (SD 1.6; range 1.0 ‐ 4.9); male mean 2.9 (SD 1.8; range 0.9 ‐ 6.2) IV daunorubicin, mg/m2: female mean 49.0 (SD 10.5; range 25.0 ‐ 91.9); male mean 48.8 (SD 9.1; range 24.6 ‐ 71.0) IV doxorubicin, mg/m2: female mean 90.4 (SD 51.2; range 58.9 ‐ 209.0); male mean 127.0 (SD58.6; range 58.4 ‐ 191.5) IV leucovorin, mg/m2: female mean 337.8 (SD 155.0; range 200.0 ‐ 655.0); male mean 379.1 (SD 269.6; range 75.0 ‐ 1645.0) IV methotrexate standard dose, g/m2: female mean 3.3 (SD 0.8; range 0.2 ‐ 5.1); male mean 5.2 (SD 4.4; range 2.7 ‐ 29.4) IV methotrexate high ‐ dose ‐ low ‐ risk arm, g/m2: female n=26, mean 11.6 (SD 1.8; range 0.9 ‐ 16.4); male n=15, mean 11.5 (SD 3.2; range 2.5 ‐ 17.1) IV methotrexate high ‐ dose ‐ standard ‐ risk arm, g/m2: female n=9, mean 20.8 (SD 4.8; range 15.6 ‐ 29.3); male n=20, mean 19.5 (SD 4.4; range 7.4 ‐ 26.3) IT methotrexate, mL: female mean 148.7 (SD 34.1; range 93.0 ‐ 276.0); male mean 180.1 (SD 52.5; range 60.0 ‐ 288.0) IV vincristine, mg/m2: female mean 59.1 (SD 11.4; range 31.1 ‐ 73.3); male mean 58.1 (SD 13.3; range 28.7 ‐ 74.6) IT chemotherapy, no of counts: female mean 13.1 (SD 3.1; range 9 ‐ 23); male mean 15.6 (SD 4.3; range 11 ‐ 24)
Outcomes	Severe fatigue: N of participants with severe fatigue: NDa Risk and associated factors: Dependent factor: fatigue (continuous)b Univariable: Non‐significant: gender (P = 0.19)
Notes	Funding sources: Supported by the National Institute of Mental Health (grant MH085849 to K.R.K.), the National Cancer Institute (grant CA195547 to M.M.H and L.L.R), and the American Lebanese Syrian Associated Charities. Support to St Jude Children’s Research Hospital was also provided by the Cancer Center Support (CORE) grant (CA21765, CharlesW. M. Roberts, Principal Investigator) Declaration of interest: Angela Panoskaltsis‐Mortari reports a family member employed by BioTechne, which owns the company from which some of the kits used for biomarker analysis were purchased (R&D Systems) aAuthors report fatigue on a continuous scale. Additional information on severe fatigue was requested and not available. bAnalysis was performed with the subscale score for general fatigue as outcome (T‐test). Effect estimate was not reported in the article.
Risk of bias
Bias	Authors' judgement	Support for judgement
Representative study group (selection bias)	High risk	The described study group consisted of < 90% of the original cohort of cancer survivors
Adequate follow‐up assessment (attrition bias)	Low risk	Outcome was assessed for > 95% of study group of interest
Blinded outcome assessor (detection bias) All outcomes	High risk	Outcome assessors were not blinded to the investigated determinant
Adjustment important confounders	High risk	No multivariable analyses
Well‐defined study group (reporting bias)	Low risk	Type of cancer and cancer treatment are mentioned, including specific chemotherapeutic agents and cumulative dose. Inclusion and exclusion criteria are described.
Well‐defined follow‐up (reporting bias)	Low risk	Length of follow‐up is mentioned
Well‐defined outcome fatigue (reporting bias)	Low risk	Authors reported which instrument they used to assess fatigue, and how they described fatigue (continuous scale)
Well‐defined risk estimation	High risk	None were calculated