Shi Wei, Misra Shagun, Li Madeline, Su Jie, Chong Lisa P, McCuske Megan, Williams Justin, Xu Wei, Ghoraie Laleh S, Sutherland D Robert, Han Kathy, Minden Mark D, Bratman Scott V, Yip Kenneth W, Liu Fei-Fei
Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
JNCI Cancer Spectr. 2020 May 8;4(5):pkaa037. doi: 10.1093/jncics/pkaa037. eCollection 2020 Oct.
Fatigue and insomnia are common symptoms experienced by breast cancer patients undergoing adjuvant radiation therapy (RT), yet the underlying mechanisms of these symptoms are unclear. In particular, the roles of hematopoietic stem cells (HSCs) and inflammatory cytokines remain to be elucidated.
Breast cancer patients (n = 147) completed questionnaires to longitudinally assess symptoms before, during, and after adjuvant RT. Phlebotomies were performed prior to RT, at the second and fifth treatment fractions, end of treatment (EOT), and 1 month after completing RT, assessing for CD34, CD45, full hematology, and 17 inflammatory cytokines. The associations between symptoms and all biomarkers were evaluated. All statistical tests were 2-sided.
General fatigue and insomnia worsened with RT, with peak levels observed at EOT, which remained statistically significant even after controlling for anxiety and depression ( < .05 for all). CD34, CD45, white blood cell, and lymphocyte counts decreased, with the lowest levels also observed at EOT ( < .001). Fatigue and insomnia were associated with changes in both interferon γ-induced protein 10 (IP-10) - ( = .03 and = .01, respectively) and tumor necrosis factor receptor II (TNF-RII) ( = .02 and = .006, respectively), while mental fatigue was associated with increased matrix metalloproteinases-2 (MMP-2) levels ( = .03). Patients who received prior chemotherapy demonstrated statistically significantly greater severity in all symptoms, with lower baseline HSC levels.
This is the first longitudinal study to examine linkages between symptoms, HSCs, and cytokines, demonstrating that fatigue and insomnia shared associations with increasing serum levels of IP-10 and TNF-RII, and mental fatigue was associated with increasing serum levels of MMP-2. Our findings highlight opportunities for further research into mechanisms and potential interventions for these symptoms.
疲劳和失眠是接受辅助放疗（RT）的乳腺癌患者常见的症状，然而这些症状的潜在机制尚不清楚。特别是，造血干细胞（HSC）和炎性细胞因子的作用仍有待阐明。
147例乳腺癌患者完成问卷调查，以纵向评估辅助放疗前、放疗期间和放疗后的症状。在放疗前、第二次和第五次治疗分次时、治疗结束时（EOT）以及完成放疗后1个月进行静脉穿刺，评估CD34、CD45、全血细胞分析和17种炎性细胞因子。评估症状与所有生物标志物之间的关联。所有统计检验均为双侧检验。
一般疲劳和失眠在放疗过程中加重，在EOT时达到峰值水平，即使在控制焦虑和抑郁后仍具有统计学意义（所有P值均<0.05）。CD34、CD45、白细胞和淋巴细胞计数下降，最低水平也出现在EOT时（所有P值均<0.001）。疲劳和失眠与干扰素γ诱导蛋白10（IP-10）（分别为P=0.03和P=0.01）和肿瘤坏死因子受体II（TNF-RII）（分别为P=0.02和P=0.006）水平的变化相关，而精神疲劳与基质金属蛋白酶-2（MMP-2）水平升高相关（P=0.03）。接受过化疗的患者在所有症状上的严重程度在统计学上显著更高，基线HSC水平更低。
这是第一项研究症状、HSC和细胞因子之间联系的纵向研究，表明疲劳和失眠与血清IP-10和TNF-RII水平升高相关，精神疲劳与血清MMP-2水平升高相关。我们的研究结果突出了对这些症状的机制和潜在干预措施进行进一步研究的机会。
