Table 1:

Summary of key clinical evaluations of muscle health and childhood cancer

Author Country	Year published	Population	Study design	N	Age	Muscle mass assessment method	Muscle function assessment method	Results
Children with cancer
Yang Korea	2019	Children newly diagnosed with cancer: 70% male Controls: 73 % male	Prospective	30 patients: 19 hematological malignancy,11 solid tumor 30 controls	Patient mean (SD): 10.9 (3.8) y Control mean (range):12.3 (6.3–17.2) y	FFM mass by DXA		Leg FFM differed between groups Patients’ median fat free mass ↓ during treatment
Brinksma The Netherlands	2015	Children newly diagnosed with cancer: 48.4% male	Prospective	133 patients: 39.8% hematological malignancy, 33.1% solid tumor, 27.1% brain tumor	Median (range) 8.1 (0.1–17.7) y	FFM via BIA		FFM was low at diagnosis, and remained low during treatment FFM was lowest in children with brain malignancies BMI ↑ during treatment
Rayar Canada	2013	Children with ALL: 63% male	Prospective	91 patients	Mean 6.1 y, median (range) 5.0 (1.2–17.6) y	SMM by DXA		SMM was low at diagnosis, ↓with treatment, and remained low 12 months after diagnosis
Ness United States Canada	2015	Children newly diagnosed with ALL: 65.1% male 63.3% white	Cross-sectional	109 patients	Median (range) 10 (4–18) y		Lower extremity isometric strength by HHD “break” test Hand grip strength by HHD Motor development by BOT2-SF	Patients had weaker knee extensors and hands at start of treatment Patients had worse motor abilities at diagnosis than expected
Gocha United States	2003	Children with ALL Controls	Prospective	16 patients 8 controls	Patient median (range): 9.6 (4–15) y Controls: age-and gender matched		Knee extension and ankle dorsiflexion strength by HHD Functional mobility by TUG	Patients were weaker in knee extensor and ankle dorsiflexor muscles, and had lower functional mobility than controls before start of treatment Patients’ ankle weakness worsened over 28 days of treatment Knee extensor strength was negatively correlated with functional mobility in patients
Akyay Turkey	2014	Children with ALL, on-therapy: 60% male Children with ALL, off therapy: 55.6% male On-therapy controls: 60% male Off-therapy controls: 55.6% male	Prospective	15 on-therapy patients 18 off-therapy patients 15 on-therapy controls 18 off-therapy controls	Children on-therapy mean (SD): 9.7(4.5) y Children off-therapy mean (SD): 12.5 (5.2) y On-therapy control mean (SD): 9.7 (4.5) y Off-therapy control mean (SD): 12.5 (5.2) y		Hand grip strength by HHD Functional mobility by TUG	On-therapy patients: Strength and functional mobility ↓ during treatment and was lower than off-therapy patients and controls Off-therapy patients had lower functional mobility than controls
Schoenmaker The Netherlands	2006	Children with cancer: 50% male	Prospective	18 patients: 17 ALL, 1 T-NHL	Range 0–18 y		Upper and lower extremity strength by MMT and HHD	Muscle weakness and mobility issues were most severe in the first two months of treatment All patients had muscle weakness in at least one muscle measured by MMT Lower extremity muscle weakness measured by HHD persisted 6 months after therapy in patients older than 5.5 y
Survivors of childhood cancer
Tonorezos United States	2013	Survivors of childhood ALL: 44.4% male 72% white	Cross-sectional	117 survivors	Median (range) 23 (18–37) y	Lean mass by DXA		Survivors who received cranial radiation had less lean body mass than survivors without cranial radiation
Boland United States	2016	Survivors of childhood ALL: 47.7% male 87% white Community controls: 47.7% male 87% white	Cross-sectional	365 survivors 365 controls	Survivor median (range): 28.5 (18.4–44.6) y Controls: 5-year age matched	Relative lean muscle mass by DXA		Survivors had lower absolute and relative lean mass than controls
Ness United States	2012	Survivors of childhood ALL: 48.9% male 93.7% white	Cross-sectional	415 survivors	Median (range): 35.6 (21.9–52.3) y		Lower extremity muscle strength by isokinetic dynamometry Functional mobility by TUG	Survivors had dorsiflexion weakness (16.9%), plantarflexion weakness (24.6%), knee extensor weakness (30.1%) and limited functional mobility (3.6%) Knee extensor weakness increased risk for limited physical performance
Hovi Finland	1993	Female survivors of childhood ALL Controls	Cross-sectional	43 survivors 37 controls	Survivor mean (range): 19 (14–30) y Control mean (range): 19.4 (14 – 30 ) y		Elbow, knee and hand grip isometric strength by custom-made dynamometer chair Abdominal muscular endurance by maximal sit-up test Upper body muscular endurance by maximal push-up test	Survivors had less abdominal and upper body endurance and weaker elbow and knee extensors than controls
Ness United States	2015	Survivors of childhood ALL: 47.7% male 12.1% black Community controls: 47.7% male 12.1% black	Cross-sectional	365 survivors 365 controls	Survivor mean (SD): 28.6 (5.9) y Control mean (SD): 28.9 (7.5) y	% FFM and relative lean mass by DXA	Hand grip strength by HHD Knee extensor and ankle dorsiflexion strength by isokinetic dynamometry	Compared to controls: Female survivors with a history of cranial radiation had lower % FFM and relative lean mass (g/m2) Male survivors had lower % FFM Survivors were weaker and had less endurance in their quadriceps muscles Survivors with a history of cranial radiation had hand-grip weakness
Van Brussel The Netherlands	2006	Survivors of childhood ALL: 46.2% male	Cross-sectional	13 survivors	Mean (SD): 15.5_(5.8) y		Grip strength by HHD “make” test Upper and lower extremity strength by HHD “break” test	Survivors had knee extensor weakness
Ness United States	2019	Survivors of childhood cancer: 51.1% male 84.1% non-Hispanic white Community controls: 48.8% male 90.2% non-Hispanic white	Cross-sectional	1260 survivors 285 controls	Survivor mean (SD): 36.4.6 (9.2) y	% lean mass and relative lean mass by DXA	Isokinetic quadriceps strength by isokinetic dynamometry	Survivors had lower % lean mass and lower relative lean mass z-scores that controls Cranial radiation exposure >20 Gy was associated with quadriceps weakness Quadriceps weakness (−1 SD) increased risk for exercise intolerance (OR, 1.49; 95% CI, 1.23 to 1.82

Abbreviations: ALL, Acute lymphoblastic leukemia; T-NHL, T-cell Non-Hodgkin lymphoma ;y, years; %, percent; TUG, Time Up and Go; DXA, dual-energy x-ray absorptiometry; BIA, bioelectrical impedance analysis; HHD, Hand-held dynamometer; MMT, manual muscle testing; PEDI, pediatric evaluation of disability inventory; FFM, fat free mass; SMM, skeletal muscle mass; BOT2-SF, Bruininks-Oseretsky Test of Motor Proficiency Version 2 Short Form; ROM, range of motion; ↑, increase; ↓, decrease; ≥, equal to or greater than; OR, odds ratio; CI, confidence interval;