Jennifer J. Hu and Cristiane Takita, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL; James J. Urbanic, University of California, San Diego, Encinitas, CA; L. Doug Case, Doris R. Brown, Carl D. Langefeld, Mark O. Lively, Glenn J. Lesser, and Edward G. Shaw, Wake Forest University School of Medicine, Winston-Salem; Sandra E. Mitchell, Randolph Cancer Center Southeast Cancer Control Consortium, Asheboro, NC; Jean L. Wright, Johns Hopkins University, Baltimore, MD; Anu Thakrar, John H Stroger, Jr Hospital of Cook County Minority-Based Community Clinical Oncology Program (MBCCOP), Chicago, IL; David Bryant, Cancer Center of Kansas/Wichita CCOP, Wichita, KS; Kathy Baglan, St Louis-Cape Girardeau CCOP, St Louis, MO; Jon Strasser, Delaware/Christiana Care Health Services CCOP, Newark, DE; and Luis Baez-Diaz, San Juan MBCCOP, San Juan, Puerto Rico.
J Clin Oncol. 2018 Aug 20;36(24):2473-2482. doi: 10.1200/JCO.2017.77.1790. Epub 2018 Jul 10.
Purpose This study examined an inflammatory biomarker, high-sensitivity C-reactive protein (hsCRP), in radiotherapy (RT)-induced early adverse skin reactions or toxicities in breast cancer. Patients and Methods Between 2011 and 2013, 1,000 patients with breast cancer who underwent RT were evaluated prospectively for skin toxicities through the National Cancer Institute-funded Wake Forest University Community Clinical Oncology Program Research Base. Pre- and post-RT plasma hsCRP levels and Oncology Nursing Society skin toxicity criteria (0 to 6) were used to assess RT-induced skin toxicities. Multivariable logistic regression analyses were applied to ascertain the associations between hsCRP and RT-induced skin toxicities after adjusting for potential confounders. Results The study comprised 623 white, 280 African American, 64 Asian/Pacific Islander, and 33 other race patients; 24% of the patients were Hispanic, and 47% were obese. Approximately 42% and 15% of patients developed RT-induced grade 3+ and 4+ skin toxicities, respectively. The hsCRP levels differed significantly by race and body mass index but not by ethnicity. In multivariable analysis, grade 4+ skin toxicity was significantly associated with obesity (odds ratio [OR], 2.17; 95% CI, 1.41 to 3.34], post-RT hsCRP ≥ 4.11 mg/L (OR, 1.61; 95% CI, 1.07 to 2.44), and both factors combined (OR, 3.65; 95% CI, 2.18 to 6.14). Above-median post-RT hsCRP (OR, 1.93; 95% CI, 1.03 to 3.63), and change in hsCRP (OR, 2.80; 95% CI, 1.42 to 5.54) were significantly associated with grade 4+ skin toxicity in nonobese patients. Conclusion This large prospective study is the first to our knowledge of hsCRP as an inflammatory biomarker in RT-induced skin toxicities in breast cancer. We demonstrate that nonobese patients with elevated RT-related change in hsCRP levels have a significantly increased risk of grade 4+ skin toxicity. The outcomes may help to predict RT responses and guide decision making.
目的 本研究旨在探讨炎症生物标志物高敏 C 反应蛋白(hsCRP)在乳腺癌放疗(RT)引起的早期皮肤不良反应或毒性中的作用。
方法 2011 年至 2013 年间,通过美国国家癌症研究所资助的维克森林大学社区临床肿瘤学研究基地,前瞻性评估了 1000 例接受 RT 的乳腺癌患者的皮肤毒性。使用 hsCRP 水平和肿瘤护理学会皮肤毒性标准(0 至 6 级)来评估 RT 引起的皮肤毒性。采用多变量逻辑回归分析来确定 hsCRP 与 RT 诱导的皮肤毒性之间的关联,同时调整潜在混杂因素。
结果 研究纳入了 623 名白人、280 名非裔美国人、64 名亚裔/太平洋岛民和 33 名其他种族患者;24%的患者为西班牙裔,47%的患者为肥胖患者。约 42%和 15%的患者分别发生了 RT 诱导的 3+级和 4+级皮肤毒性。hsCRP 水平在种族和体重指数上有显著差异,但在族裔上没有差异。多变量分析显示,4+级皮肤毒性与肥胖(比值比[OR],2.17;95%置信区间[CI],1.41 至 3.34])、RT 后 hsCRP≥4.11mg/L(OR,1.61;95%CI,1.07 至 2.44)以及两者的联合(OR,3.65;95%CI,2.18 至 6.14)显著相关。高于中位值的 RT 后 hsCRP(OR,1.93;95%CI,1.03 至 3.63)和 hsCRP 变化(OR,2.80;95%CI,1.42 至 5.54)与非肥胖患者的 4+级皮肤毒性显著相关。
结论 本大规模前瞻性研究首次证实 hsCRP 是乳腺癌 RT 诱导皮肤毒性的炎症生物标志物。我们发现,hsCRP 水平与 RT 相关的升高且变化较大的非肥胖患者发生 4+级皮肤毒性的风险显著增加。这些结果可能有助于预测 RT 反应并指导决策。