体素内不相干运动成像评估局部晚期宫颈癌同步放化疗疗效的价值

Value of introvoxel incoherent motion imaging on evaluating concurrent chemoradiotherapy response in patients with advanced uterine cervix cancer

目的 探讨体素内不相干运动（IVIM）评估局部晚期宫颈癌同步放化疗疗效的价值。方法 前瞻性纳入2015年7月至2016年12月河南省肿瘤医院，经临床和影像检查诊断为中晚期（≥ⅡB）宫颈癌，完成同步放化疗计划的63例患者。63例患者均于治疗前、治疗中（治疗3周，总剂量30 Gy），治疗结束（治疗8周，总剂量90 Gy）行常规盆腔MRI平扫、IVIM和动态增强扫描。记录肿瘤治疗前、治疗中和治疗后的ADC、纯扩散系数（D）、伪扩散系数（D＊）和灌注分数（f）值，并计算治疗中、治疗后各参数的变化率。依据实体瘤疗效评价标准，将患者分为治疗敏感组和不敏感组，并于治疗结束1个月内行MRI复查，计算肿瘤消退率。采用Mann-Whitney U检验比较治疗敏感组和不敏感组间各参数和参数变化率的差异，采用Spearman法评价各参数和参数变化率与肿瘤消退率的相关性，采用logistic回归模型筛选出可能预测疗效的ADC值，采用ROC分析各参数评价宫颈癌同步放化疗疗效的效能。结果 治疗前和治疗后1个月肿瘤最大径分别为（47.5±12.9）、（12.8±10.0）mm，肿瘤消退率为（66.7±33.6）%。治疗敏感组48例，不敏感组15例。治疗前ADC、D、D＊、f值分别为0.74（0.43，1.14）×10-3、0.58（0.33，0.91）×10-3、12.12（2.30，21.4）×10-3mm2/s和9.65%（4.45%，13.89%），其中，ADC、D值与肿瘤退缩率呈正相关（r值分别为0.773、0.840，P均〈0.05）。治疗敏感组ADC、D值均高于不敏感组，差异有统计学意义（P均〈0.05）。治疗中敏感组ADC、D、f值均高于不敏感组，差异有统计学意义（P均〈0.05），与肿瘤消退率呈正相关（r值分别为0.808、0.834、0.563，P均〈0.05）。治疗后敏感组ADC、D、f值均高于不敏感组，差异有统计学意义（P均〈0.05），其中治疗后ADC、D值与肿瘤消退率呈正相关（r值分别为0.799、0.829，P均〈0.05）。治疗中ADC、D、f值变化率与肿瘤消退率呈正相关（r值分别为0.526、0.573、0.454，P均〈0.05）；治疗后ADC、D、f值变化率与肿瘤消退率也呈正相关（r值分别为0.541、0.555、0.388，P均〈0.05）。治疗中、治疗后治疗敏感组ADC、D、f值变化率均高于不敏感组，差异有统计学意义（P均〈0.05）。logistic回归分析结果显示，仅治疗前ADC值和治疗后D值可作为预测宫颈癌同步放化疗疗效的独立指标，B、Wald、优势比和P值分别为22.488、8.431、1.429、0.004和16.542、8.517、1.779、0.004。治疗前ADC值、治疗前D值、治疗中ADC值变化率、治疗中D值变化率、治疗中f值变化率、治疗后ADC值变化率、治疗后D值变化率、治疗后f值变化率预测宫颈癌放化疗疗效的ROC下面积分别为0.890、0.926、0.942、0.851、0.803、0.929、0.951和0.906。结论 局部中晚期宫颈癌治疗前、治疗中IVIM参数值及其变化率可以较好地预测和评估同步放化疗效果，具有较高的临床价值。

Objective To investigate the value of introvoxel incoherent motion （IVIM） using 3.0 T MRI to evaluate response to concurrent chemoradiotherapy （CCRT） in patients with advanced uterine cervix cancer.Methods From July 2015 to December 2016, 63 patients with advanced （≥ⅡB） cervical cancer diagnosed by clinical and imaging study, who had completed CCRT plan in Henan Cancer Hospital, were prospectively enrolled. Pelvic MRI protocol including T1WI, T2WI, IVIM and dynamic contrasted enhanced scans were performed in each patient before CCRT and 3 weeks after starting therapy （total dose of 30 Gy）, and at the end of therapy （total dose of 90 Gy, 8 weeks after therapy）. The mean values of ADC, true molecular diffusion coefficient （D）, pseudodiffusion coefficient （D＊） and perfusion fraction （f） in each tumor at pre-therapy, in the middle of therapy and post-therapy were measured and recorded as ADC-pre, D-pre, D＊-pre, f-pre;ADC-mid, D-mid, D＊-mid, f-mid and ADC-post, D-post, D＊-post, f-post, respectively;the change rates of these parameters during and after therapy （recorded as ΔADC-mid, ΔD-mid, ΔD＊-mid, Δf-mid; ΔADC-post, ΔD-post, ΔD＊-post, Δf-post） were also calculated. Patients were classified into response group and non-response group, according to response evaluation criteria in solid tumors after CCRT. MRI imaging study was performed in each patient within 1 month after CCRT to follow up, and tumor regression rate was calculated. The Mann-Whitney U test was used to compare differences of parameters and their change rates between response group and non-response group. Spearman correlation analysis was performed to assess relationships between parameters, parameter change rates and tumor regression rate. Logistic regression model was applied to find potential ADC values for predicting therapeutic response. ROC was used to analyze efficacy of ADC values for evaluating therapeutic response in advanced uterine cervix cancer after CCRT.Results The mean value of tumor maximum diameter before and after therapy was （47.5 ± 12.9） and （12.8 ± 10.0） mm, tumor regression rate was （66.7 ± 33.6）%. Forty-eight patients were in the response group and 15 in the non-response group. The mean value of ADC-pre, D-pre, D＊-pre and f-pre was 0.74（0.43, 1.14）×10-3, 0.58（0.33, 0.91）×10-3, 12.12（2.30, 21.4）×10-3mm2/s, 9.65%（4.45%, 13.89%）, respectively. Tumor regression rate had positive correlation with ADC-pre and D-pre （r=0.773, 0.840;P〈0.05）. Responders had increased ADC-pre, D-pre values than non-responders, which had statistically significant difference （P〈0.05）. Responders had increased ADC-mid, D-mid and f-mid values than non-responders, which had statistically significant difference （P〈0.05）, tumor regression rate had positive correlation with ADC-mid, D-mid and f-mid （r=0.808, 0.834, 0.563;P〈0.05）. Responders had increased ADC-post, D-post and f-post values than non-responders, which had statistically significant difference （P〈0.05）, tumor regression rate had positive correlation with ADC-post and D-post （r=0.799, 0.829;P〈0.05）.Tumor regression rate had positive correlation with ΔADC-mid, ΔD-mid, Δf-mid（r=0.526, 0.573, 0.454;P〈0.05） and with ΔADC-post, ΔD-post, Δf-post （r=0.541, 0.555, 0.388;P〈0.05）. Responders had increased ΔADC-mid, ΔD-mid, Δf-mid and ΔADC-post, ΔD-post, Δf-post, which had statistically significant difference （P〈0.05）. Logistic regression analysis revealed only ADC-pre and D-post could be independent factors to predict therapeutic response in advanced uterine cervix cancer after CCRT, values of B, Wald, odds ratio and P was 22.488, 8.431, 1.429, 0.004 and 16.542, 8.517, 1.779, 0.004. ROC analysis showed the area under the curve （AUC） of ADC-pre, D-pre, ΔADC-mid, ΔD-mid, Δf-mid, ΔADC-post, ΔD-post and Δf-post for predicting therapeutic response in advanced uterine cervix cancer after CCRT were 0.890, 0.926, 0.942, 0.851, 0.803, 0.929, 0.951 and 0.906, respectively.Conclusion The IVIM parameters before and during CCRT process and their changes are valuable for predicting and evaluating therapeutic response in advanced uterine cervix cancer after CCRT, with high clinical practice value.