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转移性肾细胞癌的系统治疗:扩散加权 MRI 的表观扩散系数在预测早期治疗反应中的作用。

Systemic treatment of the metastatic renal cell carcinoma: usefulness of the apparent diffusion coefficient of diffusion-weighted MRI in prediction of early therapeutic response.

机构信息

Department of Urology, Lviv National Medical University n.a. Danylo Halytsky, Pekarska Str. 69, Lviv, Ukraine.

Medical center "Euroclinic", Lviv, Ukraine.

出版信息

Clin Exp Med. 2020 May;20(2):277-287. doi: 10.1007/s10238-020-00612-9. Epub 2020 Feb 5.

Abstract

Accurate prediction of early treatment response to systemic therapy (ST) with tyrosine kinase inhibitors (TKI) in patients with metastatic renal cell carcinoma (mRCC) could help avoid ineffective and expensive treatment with serious side effects. Neither RECIST v.1.1 nor Choi criteria successfully discriminate between patients with mRCC who received ST having a short or long time to progression (TTP). There is no biomarker, which is able to predict early therapeutic response to TKIs application in patients with mRCC. The goal of our study was to investigate the potential of apparent diffusion coefficient (ADC) of diffusion-weighted imaging (DWI) of MRI in prediction of early therapeutic response to ST with pazopanib in patients with mRCC. The retrospective study enrolled 32 adult patients with conventional mRCC who received pazopanib (mean duration-7.5 ± 3.45). The mean duration of follow-up was 11.85 ± 4.34 months. In all patients as baseline examination and 1 month after treatment, 1.5T MRI including DWI sequence was performed followed by ADC measurement of the main renal lesion. For assessment of the therapeutic response, RECIST 1.1 is used. Partial response (PR), stable disease (SD) and progressive disease (PD) were observed in 12 (37.50%), 10 (31.25%) and 10 (31.25%) cases with mean TTP of 10.33 ± 2.06 months (95% confidence interval, CI = 9.05-11.61), 7.40 ± 2.50 months (95% CI = 5.61-9.19) and 4.20 ± 1.99 months (95% CI = 2.78-5.62) accordingly (p < 0.05). There was no difference in change of main lesions' longest size 1 month after ST in patients with PR, SD and PD. Comparison of mean ADC values before and 1 month after systemic treatment showed significant decrease by 19.11 ± 10.64% (95% CI = 12.35-25.87) and by 7.66 ± 6.72% (95% CI = 2.86-12.47) in subgroups with PR and SD, respectively (p < 0.05). There was shorter TTP in patients with mRCC if ADC of the main renal lesion 1 month after the ST increased from the baseline less than 1.73% compared to patients with ADC levels above this threshold: 5.29 ± 3.45 versus 9.50 ± 2.04 months accordingly (p < 0.001). Overall, our findings highlighted the use of ADC as a predictive biomarker for early therapeutic response assessment. Use of ADC will be effective and useful for reliable prediction of responders and non-responders to systemic treatment with pazopanib.

摘要

准确预测转移性肾细胞癌 (mRCC) 患者接受系统治疗 (ST) 的早期治疗反应,可以帮助避免因严重副作用而无效和昂贵的治疗。RECIST v.1.1 和 Choi 标准均不能区分接受 ST 的 mRCC 患者的无进展生存期 (TTP) 是长还是短。目前尚无生物标志物能够预测 mRCC 患者接受酪氨酸激酶抑制剂 (TKI) 治疗的早期治疗反应。我们的研究目的是探讨 MRI 扩散加权成像 (DWI) 的表观扩散系数 (ADC) 在预测 mRCC 患者接受 pazopanib 治疗的早期治疗反应中的潜在价值。这项回顾性研究纳入了 32 名接受 pazopanib 治疗的常规 mRCC 成年患者(平均治疗持续时间为 7.5±3.45 个月)。中位随访时间为 11.85±4.34 个月。在所有患者中,基线检查和治疗后 1 个月均进行了 1.5T MRI 检查,包括 DWI 序列,并随后测量了主要肾脏病变的 ADC 值。采用 RECIST 1.1 进行治疗反应评估。观察到 12 例(37.50%)患者部分缓解(PR)、10 例(31.25%)患者疾病稳定(SD)和 10 例(31.25%)患者疾病进展(PD),中位 TTP 分别为 10.33±2.06 个月(95%置信区间,CI=9.05-11.61)、7.40±2.50 个月(95% CI=5.61-9.19)和 4.20±1.99 个月(95% CI=2.78-5.62)(p<0.05)。PR、SD 和 PD 患者治疗后 1 个月时主要病变最长径的变化无差异。系统治疗后 1 个月时,PR 和 SD 亚组的 ADC 值分别较基线值下降了 19.11±10.64%(95% CI=12.35-25.87)和 7.66±6.72%(95% CI=2.86-12.47)(p<0.05)。如果 ST 后 1 个月的主要肾脏病变 ADC 值增加幅度小于 1.73%(与 ADC 值超过该阈值的患者相比),mRCC 患者的 TTP 会更短:分别为 5.29±3.45 个月和 9.50±2.04 个月(p<0.001)。总的来说,我们的研究结果强调了 ADC 作为预测早期治疗反应的生物标志物的应用。ADC 的使用将对可靠地预测 pazopanib 系统治疗的应答者和无应答者具有有效性和实用性。

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