Establishment and evaluation of neoadjuvant radiotherapy and chemotherapy efficacy evaluation model for advanced rectal cancer based on MRI and RTN-1C
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摘要:
目的建立基于MRI和网状蛋白1C（RTN-1C）的进展期直肠癌新辅助放化疗疗效评估模型并评价该模型的效能。 方法选取2018年8月~2020年11月在开滦总医院林西医院就诊的134例进展期直肠癌患者作为研究对象，并根据是否达到病理学完全缓解将其分为2组：完全缓解组（n=39）和未完全缓解组（n=95）。用Ficoll密度梯度分离法获取外周血中单个核细胞，用蛋白质免疫印迹法检测单个核细胞中RTN-1C表达量。用Logistic回归分析进展期直肠癌新辅助放化疗疗效的风险因素，并构建上述风险因素的列线图回归模型；用ROC曲线、校准曲线和决策曲线分析评价预测模型的价值。 结果完全缓解组的容积转运常数（Ktrans）、血管外细胞外间隙容积比（Ve）、回流速率常数（Kep）和RTN-1C相对表达量均高于未完全缓解组（P < 0.05）；表观弥散系数（ADC）低于未完全缓解组（[0.88±0.05）×10-3 mm2/s vs（0.92±0.05）×10-3 mm2/s, P < 0.05]。Logistic回归分析结果显示T4期和高ADC值是进展期直肠癌新辅助放化疗疗效独立危险因素（P < 0.05），高Ktrans值、高Ve值和高RTN-1C相对表达量是进展期直肠癌新辅助放化疗疗效的独立保护因素（P < 0.05）。当阈值概率在0.39%~0.42%，0.75%~0.80%和0.86%~0.88%时，模型B评价进展期直肠癌新辅助放化疗疗效的净收益高于模型A；当阈值概率在其他范围时，模型A评价进展期直肠癌新辅助放化疗疗效的净收益高于模型B。 结论基于MRI和RTN-1C构建的模型A对进展期直肠癌新辅助放化疗疗效有较高的区分度、校准度和临床应用价值，可辅助临床做出更好决策。 Abstract:ObjectiveTo establish a model for evaluating the efficacy of neoadjuvant radiotherapy and chemotherapy for advanced rectal cancer based on MRI and reticulin 1C (RTN-1C) and evaluate the efficacy of the model. MethodsA total of 134 patients with advanced rectal cancer treated in Linxi Hospital of Kailuan General Hospital from August 2018 to November 2020 were selected as subjects. According to whether they achieved pathological complete response, they were divided into two groups : complete remission group (n=39) and incomplete remission group (n=95). The mononuclear cells in peripheral blood were obtained by Ficoll density gradient separation method, and the expression of RTN-1C in mononuclear cells was detected by Western blot. Logistic regression was used to analyze the risk factors of neoadjuvant radiotherapy and chemotherapy efficacy in advanced rectal cancer, and the nomogram regression model of these risk factors was established. Receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis were used to evaluate the value of the prediction model. ResultsThe volume transfer constant (Ktrans), extravascular extracellular space volume ratio (Ve), reflux rate constant (Kep) and relative expression of RTN-1C in the complete remission group were all higher than those in the incomplete remission group; apparent diffusion coefficient (ADC) in the complete remission group was lower than that in the incomplete remission group (P < 0.05). The results of logistic regression analysis showed that T4 stage and high ADC value were independent risk factors for the efficacy of neoadjuvant radiotherapy and chemotherapy in advanced rectal cancer (P < 0.05). High Ktrans, high Ve value and high relative expression of RTN-1C were independent protective factors for the efficacy of neoadjuvant radiotherapy and chemotherapy in advanced rectal cancer (P < 0.05). When the threshold probability was 0.39%-0.42%, 0.75%-0.80% and 0.86%-0.88%, the net benefit of model B evaluating the efficacy of neoadjuvant radiotherapy and chemotherapy in advanced rectal cancer was higher than that of model A. When the threshold probability was in other ranges, the net benefit of model A evaluating the efficacy of neoadjuvant radiotherapy and chemotherapy in advanced rectal cancer was higher than that of model B. ConclusionModel A based on MRI and RTN-1C have a high degree of discrimination, calibration and clinical application value for the efficacy of neoadjuvant radiotherapy and chemotherapy in advanced rectal cancer, which can assist clinical decision-making. -
图 1 两组的RTN-1C相对表达量比较
A、C、D、E为未完全缓解组中患者；B、F为完全缓解组中患者
Figure 1. Comparison of the relative expression levels of RTN-1C in the two groups.
图 2 列线图模型及评价
A：列线图回归模型A；B：列线图回归模型B；C：模型A和模型B评价进展期直肠癌新辅助放化疗疗效的ROC曲线；D：模型A的校准曲线；E：模型B的校准曲线；F：模型A和模型B的决策曲线分析曲线
Figure 2. Nomogram model and evaluation.
表 1 2组的临床特征比较
Table 1. Comparison of clinical features between the two groups
项目 完全缓解组（n=39） 未完全缓解组（n=95） t/χ2 P 年龄（岁, Mean±SD） 51.74±10.60 51.61±9.65 0.070 0.944 性别(n) 0.016 0.898 男 25 62 女 14 33 T分期(n) 2.999 0.083 T3 31 61 T4 8 34 N分期(n) 2.778 0.249 N0 27 51 N1 8 28 N2 4 16 
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表 2 两组的Ktrans、Ve、Kep和ADC值比较
Table 2. Comparison of Ktrans, Ve, Kep and ADC values of the two groups (Mean±SD)
分组 Ktrans值（/min） Ve值（%） Kep值（/min） ADC值（×10-3 mm2/s） 完全缓解组（n=39） 0.38±0.04 0.62±0.06 0.59±0.07 0.88±0.05 未完全缓解组（n=95） 0.33±0.03 0.53±0.07 0.51±0.09 0.92±0.05 t 7.131 7.155 4.692 3.880 P < 0.001 < 0.001 < 0.001 < 0.001 Ktrans: 容积转运常数; Ve: 血管外细胞外间隙容积比; Kep: 回流速率常数; ADC: 表观弥散系数.
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表 3 进展期直肠癌新辅助放化疗疗效的Logistic回归分析
Table 3. Logistic regression analysis of neoadjuvant radiotherapy and chemotherapy efficacy in advanced rectal cancer
因素 β SE Wald P OR（95%CI） T分期 1.823 0.868 4.410 0.036 6.191（1.129~33.946） N分期 -0.094 0.492 0.036 0.849 0.911（0.347~2.390） Ktrans值 -2.262 0.758 8.904 0.003 0.104（0.024~0.460） Ve值 1.392 0.723 3.707 0.054 0.249（0.060~1.025） ADC值 2.411 0.833 8.368 0.004 11.145（2.176~57.082） RTN-1C -2.617 0.755 12.029 0.001 0.073（0.017~0.320） RTN-1C：网状蛋白1C.
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[1] Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA: A Cancer J Clin, 2018, 68(6): 394-424. doi: 10.3322/caac.21492 [2] 彭俊杰, 朱骥, 刘方奇, 等. 中国局部进展期直肠癌诊疗专家共识[J]. 中国癌症杂志, 2017, 27(1): 41-80. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGAZ201701009.htm [3] Fokas E, Liersch T, Fietkau R, et al. Tumor regression grading after preoperative chemoradiotherapy for locally advanced rectal carcinoma revisited: updated results of the CAO/ARO/AIO-94 trial [J]. J Clin Oncol, 2014, 32(15): 1554-62. doi: 10.1200/JCO.2013.54.3769 [4] Molinari C, Matteucci F, Caroli P, et al. Biomarkers and molecular imaging as predictors of response to neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer[J]. Clin Colorectal Cancer, 2015, 14(4): 227-38. doi: 10.1016/j.clcc.2015.05.014 [5] Kim NK, Hur H. New perspectives on predictive biomarkers of tumor response and their clinical application in preoperative chemoradiation therapy for rectal cancer[J]. Yonsei Med J, 2015, 56 (6): 1461-77. doi: 10.3349/ymj.2015.56.6.1461 [6] De Nardi P, Carvello M. How reliable is current imaging in restaging rectal cancer after neoadjuvant therapy?[J]. World J Gastroenterol, 2013, 19(36): 5964-72. doi: 10.3748/wjg.v19.i36.5964 [7] 李帅祥, 张革化, 常利红. 自噬在肿瘤放化疗增敏中的作用和机制[J]. 国际耳鼻咽喉头颈外科杂志, 2019, 43(2): 107-11. [8] D' Eletto M, Risuglia A, Oliverio S, et al. Modulation of autophagy by RTN-1C: role in autophagosome biogenesis[J]. Cell Death Dis, 2019, 10(12): 868. doi: 10.1038/s41419-019-2099-7 [9] Michaud M, Sukkurwala AQ, Di Sano F, et al. Synthetic induction of immunogenic cell death by genetic stimulation of endoplasmic Reticulum stress[J]. Oncoimmunology, 2014, 3: e28276. doi: 10.4161/onci.28276 [10] 董健, 谢宗源, 李垣婕, 等. 磁共振功能成像在进展期直肠癌新辅助放化疗疗效评估中的应用[J]. 中国临床研究, 2020, 33(6): 759-63. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGCK202006008.htm [11] 中华人民共和国国家卫生健康委员会. 中国结直肠癌诊疗规范(2020年版[) J]. 中华外科杂志, 2020, 58(8): 561-85. doi: 10.3760/cma.j.cn112139-20200518-00390 [12] Benson AB, Venook AP, Al- Hawary MM, et al. Rectal cancer, version 2.2018, NCCN clinical practice guidelines in oncology[J]. J Natl Compr Canc Netw, 2018, 16(7): 874-901. doi: 10.6004/jnccn.2018.0061 [13] 孙霞, 张志鹏, 温煦, 等. 慢性阻塞性肺病患者外周血单个核细胞自噬与疾病状态的相关性研究[J]. 中国医师进修杂志, 2019, 42(3): 238-44. [14] Ye G, Qin Y, Wang S, et al. Lamc1 promotes the Warburg effect in hepatocellular carcinoma cells by regulating PKM2 expression through AKT pathway[J]. Cancer Biol Ther, 2019, 20(5): 711-9. doi: 10.1080/15384047.2018.1564558 [15] Fokas E, Ströbel P, Fietkau R, et al. Tumor regression grading after preoperative chemoradiotherapy as a prognostic factor and individual-level surrogate for disease-free survival in rectal cancer [J]. J Natl Cancer Inst, 2017, 109(12): djx095. http://www.ncbi.nlm.nih.gov/pubmed/29206996 [16] Nacion AJD, Park YY, Kim NK. Contemporary management of locally advanced rectal cancer: Resolving issues, controversies and shifting paradigms[J]. Chin J Cancer Res, 2018, 30(1): 131-46. doi: 10.21147/j.issn.1000-9604.2018.01.14 [17] Tong T, Sun Y, Gollub MJ, et al. Dynamic contrast-enhanced MRI: Use in predicting pathological complete response to neoadjuvant chemoradiation in locally advanced rectal cancer[J]. J Magn Reson Imaging, 2015, 42(3): 673-80. doi: 10.1002/jmri.24835 [18] 肖楠, 陆艳荣, 朱丽娜, 等. DWI在直肠癌术前同步放化疗疗效预测中的作用[J]. 肿瘤防治研究, 2019, 46(4): 333-7. doi: 10.3971/j.issn.1000-8578.2019.18.1385 [19] Nougaret S, Vargas HA, Lakhman Y, et al. Intravoxel incoherent motion-derived histogram metrics for assessment of response after combined chemotherapy and radiation therapy in rectal cancer: initial experience and comparison between single- section and volumetric analyses[J]. Radiology, 2016, 280(2): 446-54. doi: 10.1148/radiol.2016150702 [20] 黄瑜亮, 黄斌, 严俊. 结直肠癌的早期诊断技术进展[J]. 分子影像学杂志, 2019, 42(1): 77-80. doi: 10.12122/j.issn.1674-4500.2019.01.18 -
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