Abstract Body (Do not enter title and authors here): Background Childhood cancer survivors (CCS) frequently show poor exercise performance, but its pathophysiology and clinical significance are poorly understood.

Methods Poor exercise performers, defined as peak oxygen consumption (VO2)/kg < 80% of predicted maximum VO2/kg, were enrolled, including 40 CCS (20 males, 20 females) and 32 controls (15 males, 17 females) from 79 CCS and 147 age-matched controls, respectively. Peak and submaximal CPET parameters were compared between CCS and controls with poor exercise performance. Submaximal slope parameters represent a trend up to anaerobic threshold (AT).

Results Ages and anthropometric measurements (weight, height, and body mass index) were comparable between CCS and controls in both sexes (Table 1). Both resting and peak heart rate (HR) were significantly higher in CCS than in controls in males. There was no significant difference in peak VO2/kg, peak oxygen pulse (OP)/kg, peak respiratory exchange ratio, or VO2/kg at AT (VAT/kg) between CCS and controls in both sexes. Peak work rate (WR/kg) was significantly lower in CCS compared with that in controls in both sexes, suggesting reduced muscle strength in CCS. Figure 1 demonstrates decreased muscle mass/strength in CCS than in controls. In males, Δ[VO2/kg]/ ΔHR was significantly lower in CCS than in controls, indicating limited stroke volume reserve (SVR) in male CCS. In female, although there was no significant difference in Δ[VO2/kg]/ΔHR between CCS and controls, HR-dependency expressed by ΔHR/Δ[WR/kg] was significantly higher in CCS than in controls, suggesting impaired SVR. ΔVO2/ΔWR, a marker for physical conditioning, was comparable between CCS and controls in both sexes.

Conclusions Poor exercise performance in CCS is characterized mainly by decreased muscle mass/strength and impaired SVR for both sexs. Impaired SVR may be an early sign of subclinical cardiotoxicity. Poor exercise performance in CCS should be improved to prevent future cardiovascular complications.