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Chemoradiotherapy reduces cardiorespiratory fitness and increases fatigue in patients with HPV-positive oropharyngeal cancerChemotherapy and radiation may reduce fitness in patients with HPV-related throat cancer

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Key Takeaway
Note that chemoradiotherapy is associated with significant declines in cardiorespiratory fitness and increases in fatigue among patients with HPV-positive oropharyngeal cancer.

This single-arm observational study evaluated the impact of chemoradiotherapy (CRT) on cardiorespiratory fitness and body composition in patients with human papillomavirus-related oropharyngeal cancer. The cohort consisted of 20 patients (four females) assessed at baseline, two weeks, and eight weeks post-CRT. No comparator group was included, limiting the ability to isolate treatment effects from natural disease progression or recovery.

Main results demonstrated significant declines across multiple physiological domains. Oxygen consumption at the anaerobic threshold decreased from 16.0 +/- 3.8 ml/kg/min at baseline to 12.0 +/- 3.4 ml/kg/min at two weeks post-CRT. Peak oxygen consumption, body mass, fat-free mass, and grip strength all showed adverse changes at two weeks that persisted through eight weeks. Specifically, body mass declined by 8.5 kg (95% CI: -10.7 to -6.2), and fatigue scores increased by 49.8 points (95% CI: 33.7 to 65.8).

Global health status also deteriorated, dropping by 26.9 points (95% CI: -39.2 to -14.6). The study did not report serious adverse events, discontinuations, or specific tolerability data beyond the listed adverse events such as weight loss and fatigue. These findings highlight the substantial physiological burden associated with CRT in this population.

Key limitations include the very small sample size of 20 patients and the absence of a control group, which precludes definitive causal conclusions. As the first study to estimate CRT impact on cardiopulmonary fitness in this specific cancer type, it warrants further investigation. Targeted interventions to mitigate these adverse effects are suggested, but generalizability remains uncertain due to the study design and size.

Researchers studied twenty patients with HPV-positive oropharyngeal cancer who underwent chemoradiotherapy. The team measured changes in physical fitness, body weight, and overall health status before treatment and at two and eight weeks after. They found that oxygen consumption at the anaerobic threshold dropped from 16.0 to 12.0 ml/kg/min by the two-week mark. This decline in peak oxygen use continued to be impaired at the eight-week follow-up. Alongside reduced fitness, patients also lost body mass and fat-free muscle mass, while grip strength decreased by an average of 4.1 kg.

Patients also reported worsening global health status and significantly higher levels of fatigue, which increased by nearly 50 points on average. These physical and functional changes were observed in both women and men within this small group. The study highlights that treatment-related side effects can persist for months after the initial therapy ends. Readers should understand that while these findings are concerning, they come from a single-arm design with very few participants.

This is the first study to estimate the impact of this treatment on cardiopulmonary fitness in this specific cancer group. However, the small sample size limits how widely these results can be applied to other patients. Further research is needed to confirm these effects and to develop targeted interventions that can help mitigate these adverse physiological changes. Until more data is available, these results should be viewed as an early signal rather than a definitive rule for all patients.

What this means for you:
Small study suggests chemoradiotherapy may reduce fitness and increase fatigue in HPV throat cancer patients for up to 8 weeks.

Study Details

Sample sizen = 4
EvidenceLevel 5
PublishedApr 2026
View Original Abstract ↓
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.
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