Chemoradiotherapy reduces cardiorespiratory fitness and increases fatigue in patients with HPV-positive oropharyngeal cancer.

Purpose: Chemoradiotherapy (CRT) for human papillomavirus-related oropharyngeal cancer (HPV+ OPC) causes substantial treatment-related toxicity, with well-known adverse effects on quality of life (QoL), weight loss, and self-reported physical functioning. However, its impact on objectively measured cardiorespiratory fitness is unknown. This study examined changes in cardiorespiratory fitness, body composition, grip strength, and patient-reported outcomes in patients with HPV+ OPC undergoing CRT. Methods: We invited 20 patients with HPV+ OPC scheduled for CRT (age: 61.2 {+/-} 7.1 years, female: n=4) to complete assessments at three timepoints: pre-CRT (baseline), 2-weeks post-CRT, and 8-weeks post-CRT. Cardiorespiratory fitness was assessed using a maximal incremental cardiopulmonary exercise test (CPET). Body composition was estimated using segmental bioelectrical impedance analysis. QoL was assessed using the EORTC QLQ-C30 and QLQ-H&N43, and physical activity was self-reported using the International Physical Activity Questionnaire-Short Form. The primary outcome was change in oxygen consumption at the anaerobic threshold ([V]O2 at AT) measured during CPET; an objective, effort-independent marker of cardiorespiratory fitness. Results: Mean [V]O2 at AT declined from 16.0 {+/-} 3.8 ml/kg/min at baseline to 12.0 {+/-} 3.4 ml/kg/min at 2-weeks post-CRT (adjusted mean change: -4.2, 95% CI: -5.4 to -3.0 ml/kg/min) and remained low at 8-weeks post-CRT. Peak oxygen consumption ([V]O2peak: -7.4, -9.3 to -5.4 ml/kg/min), body mass (-8.5, -10.7 to -6.2 kg), fat-free mass (-6.4, -7.7 to -5.0 kg), grip strength (-4.1, -7.2 to -0.99 kg), global health status (-26.9, -39.2 to -14.6 points), fatigue (49.8, 33.7 to 65.8 points), and several disease-specific symptoms were also adversely affected at 2-weeks post-CRT and remained impaired at 8 weeks. Conclusion: This is the first study to estimate the impact of CRT on cardiopulmonary fitness in patients with HPV+ OPC. Cardiorespiratory fitness declined by ~25% following CRT and remained reduced at 8-weeks. Targeted interventions to mitigate these adverse physiological effects warrants further investigation.