Loss Of Hemoglobin Mass Is Associated With Decreased Aerobic Capacity After Chemotherapy For Gastroesophageal Cancer

BACKGROUND: Chemotherapy can cause marked impairments in aerobic capacity which is problematic as low aerobic capacity is associated with lower treatment tolerance and increased risk of mortality in patients with cancer; however, the mechanisms underlying the impaired aerobic capacity are largely unknown. PURPOSE: To investigate if changes in blood volume or hemoglobin mass (Hbmass) are associated with changes in aerobic capacity after chemotherapy. METHODS: This study is part of an RCT (NCT03490565) that tests the effect of exercise in patients with gastroesophageal cancer undergoing neoadjuvant chemotherapy. In a subgroup of participants, blood volume (BV), red blood cell volume (RBCV), plasma volume (PV) and Hb mass were measured before and after chemotherapy using 10-min carbon monoxide rebreathing. Aerobic capacity was assessed as the peak power output in a maximal incremental exercise test on an electronically braked bicycle ergometer. The exercise and control group were pooled and analyzed together with no information on group allocation. Comparisons were made using student’s t-test and correlation analyses were performed using Pearson’s product-moment correlation. RESULTS: We included 98 patients (20 females and 78 males, age: 65 ± 7 years, BMI: 27.0 ± 4.9 kg/m2). The females had lower BV (4.7 ± 0.9 vs. 6.0 ± 0.9 L, P < 0.01), RBCV (1.9 ± 0.4 vs. 2.6 ± 0.5 L, P < 0.01), PV (2.8 ± 0.5 vs. 3.5 ± 0.5 L, P < 0.01), Hbmass (602 ± 141 vs. 836 ± 168 g, P < 0.01), and aerobic capacity (125 ± 35 vs. 185 ± 51 watt, P < 0.01) compared with the males. At baseline, aerobic capacity was correlated with Hbmass (r = 0.67, P < 0.01), BV (r = 0.63, P < 0.01), RBCV (r = 0.64, P < 0.01), and PV (r = 0.50, P < 0.01). After chemotherapy, Hbmass (-10.4 ± 13.2%, P < 0.01), RBCV (-8.3 ± 16.7%, P < 0.01), and aerobic capacity (-8.5 ± 18.6%, P < 0.01) were decreased while PV was increased (+9.1 ± 18.0%, P < 0.01) and BV was unchanged (+1.4 ± 12.8%, P = 0.44). Changes in Hb mass were associated with changes aerobic capacity (r = 0.32, P = 0.02, N = 54), whereas changes in BV, RBCV, and PV were not. CONCLUSION: In patients with gastroesophageal cancer, aerobic capacity is correlated with Hbmass, BV, RBCV, and PV. After chemotherapy, the change in aerobic capacity is associated with change in Hbmass. Supported by TrygFonden, Lundbeckfonden, Beckett Fonden, and World Cancer Research Fund.