Department of Psychiatry, The University of Texas MD Anderson Cancer Center, Unit 1454, 1515 Holcombe Blvd, Houston, TX 77030-4009, USA.
Neuroimmunology Laboratories, Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Unit 1055, 1515 Holcombe Blvd, Houston, TX 77030-4009, USA.
Psychoneuroendocrinology. 2022 Oct;144:105866. doi: 10.1016/j.psyneuen.2022.105866. Epub 2022 Jul 11.
Fatigue is frequently experienced during treatment for cancer and persists for months to years after treatment completion in a subset of patients. The underlying mechanisms remain poorly understood. We postulated that reduced cellular energy metabolism may underlie fatigue in cancer patients and survivors and tested this hypothesis in a sample of patients newly diagnosed with early-stage breast cancer (n = 49) followed for approximately 1 year from before the start of neoadjuvant chemotherapy (NACT) till after treatment completion.
Patient-reported fatigue was assessed with the Checklist Individual Strength, and blood samples were obtained before, during, and shortly after NACT. A final assessment was completed after surgery and radiation therapy, 4-6 months after NACT. At each study time point, mitochondrial oxygen consumption and glycolytic activity were measured in peripheral blood mononuclear cells (PBMC). Associations of these measures of PBMC energy metabolism with fatigue were assessed in multilevel models.
Before NACT, higher mitochondrial oxygen consumption and glycolytic activity were associated with higher fatigue, whereas after completion of all primary treatment, these assessments were associated with lower fatigue.
These findings suggest that lower cellular energy metabolism after treatment may be a novel target for interventions aimed at preventing or reducing persistent fatigue. Earlier studies investigated the use of supplements for maintaining mitochondrial health during treatment, with mixed results; when proven to be safe, such interventions may be more effective after treatment and in individuals with reduced mitochondrial oxygen consumption rates.
癌症治疗过程中患者常经历疲劳，并且在一部分患者中，这种疲劳会在治疗结束后持续数月至数年。其潜在机制仍知之甚少。我们推测，细胞能量代谢减少可能是癌症患者和幸存者疲劳的原因，并在一组新诊断为早期乳腺癌的患者中对此假设进行了测试（n=49），这些患者从新辅助化疗（NACT）开始前大约随访 1 年，直到治疗结束后。
采用个体力量检查表评估患者报告的疲劳情况，并在 NACT 前、期间和结束后不久采集血样。在手术和放疗后、NACT 结束后 4-6 个月完成最终评估。在每个研究时间点，测量外周血单核细胞（PBMC）中的线粒体耗氧量和糖酵解活性。使用多层次模型评估这些 PBMC 能量代谢指标与疲劳的相关性。
在 NACT 之前，较高的线粒体耗氧量和糖酵解活性与较高的疲劳程度相关，而在所有主要治疗完成后，这些评估与较低的疲劳程度相关。
这些发现表明，治疗后细胞能量代谢降低可能是预防或减轻持续性疲劳的新靶点。早期研究调查了在治疗期间使用补充剂来维持线粒体健康的效果，结果喜忧参半；当被证明安全时，此类干预措施在治疗后和线粒体耗氧率降低的个体中可能更有效。
