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肾细胞癌(renal cell carcinoma,RCC)是肾脏最常见的恶性肿瘤,占全部恶性肿瘤的3%~5%。在美国,RCC分别位居男性和女性恶性肿瘤的第6位和第10位,估计到2020年新增病例73 750例,病死病例14 830例[1]。RCC早期易经血源性传播,高达17%的患者在确诊时存在远处转移[2]。转移性肾癌(metastatic renal cell carcinoma,mRCC)无手术指征,主要以保守治疗为主,约35%的mRCC患者或局部手术治疗后复发的患者通常需要全身治疗[3]。但mRCC对放疗和化疗均不敏感,患者预后差,中位生存时间仅为12个月左右[4]。近年来随着对RCC发病机制的了解愈发深入,多种靶向低氧诱导因子(hypoxia inducible factor,HIF)信号通路的药物已被研发并应用于临床[3]。目前用于mRCC的药物主要分为两类:血管内皮生长因子抑制剂(抑制HIF下游基因功能)和mTOR抑制剂(抑制HIF翻译)[5]。前者包括舒尼替尼、索拉非尼、阿西替尼、帕唑帕尼、卡博替尼和乐伐替尼;后者包括替西罗莫司和依维莫司(everolimus,EVL)。有研究报道,靶向药物明显延长了mRCC患者的无进展生存期(progression-free-survival,PFS)和总生存期(overall survival,OS)[6-7]。
美国食品和药物管理局已批准了11种治疗mRCC的一线和二线靶向药物[3]。在有多种靶向治疗方案可供选择的情况下,如何在疾病的自然病程中为每位患者选择最佳治疗方法是目前该领域面临的一个巨大挑战,因此需要寻找有效的生物标志物,准确和客观地评估靶向药物疗效并预测不良反应,这对于避免无效治疗、提高患者的生存质量也是至关重要的。
18F-FDG PET/CT评估转移性肾癌靶向治疗疗效及预后的应用
Application of 18F-FDG PET/CT in evaluating the efficacy and prognosis of targeted therapy for metastatic renal cell carcinoma
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摘要: 转移性肾癌(mRCC)对放疗和化疗均不敏感,患者预后差。随着分子靶向治疗的发展,舒尼替尼和索拉非尼等多种靶向药物极大地改善了mRCC的预后,但靶向治疗对部分患者的疗效不佳,靶向药物还可能引起相关的不良反应。因此,早期无创性评估肿瘤对靶向药物的反应,从而为患者选择最佳治疗方案尤为重要。然而国内外的研究者至今尚未找到理想的生物标志物。作为一种功能影像,PET/CT在许多肿瘤中的临床价值已被认可,近年来其在mRCC中的应用也逐渐增多。笔者就PET/CT在评估mRCC靶向治疗疗效及预后中的价值及局限性作一综述。
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关键词:
- 转移性肾癌 /
- 氟脱氧葡萄糖F18 /
- 正电子发射断层显像术 /
- 体层摄影术,X线计算机 /
- 疗效 /
- 预后
Abstract: Metastatic renal cell carcinoma (mRCC) is insensitive to both radiotherapy and chemotherapy; hence, the prognosis of patients with mRCC is poor. With the development of molecular targeted therapy, various targeted drugs, such as sunitinib and sorafenib, have greatly improved the prognosis of mRCC. However, targeted therapy is not effective for some patients, and targeted drugs may also cause related adverse reactions. Therefore, early non-invasive assessment of tumor response to targeted drugs is particularly important to allow patients and physicians to decide on the best course of treatment. However, researchers worldwide have not yet found an ideal biomarker for mRCC. As a functional imaging technology, the clinical value of PET/CT has been recognized in diagnosing numerous tumors. In recent years, the application of PET/CT in mRCC has gradually increased. This review focuses on the application of PET/CT in patients with mRCC. In particular, this review discusses the value and limitations of the application of PET/CT in evaluating targeted treatment response and prognosis. -
[1] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020[J]. CA Cancer J Clin, 2020, 70(1): 7−30. DOI: 10.3322/caac.21590. [2] Capitanio U, Montorsi F. Renal cancer[J]. Lancet, 2016, 387(10021): 894−906. DOI: 10.1016/S0140−6736(15)00046−X. [3] Posadas EM, Limvorasak S, Figlin RA. Targeted therapies for renal cell carcinoma[J]. Nat Rev Nephrol, 2017, 13(8): 496−511. DOI: 10.1038/nrneph.2017.82. [4] 董培, 刘洋, 张志凌, 等. 靶向治疗时代转移性肾癌多学科综合治疗的单中心经验总结[J]. 中华泌尿外科杂志, 2020, 41(1): 1−7. DOI: 10.3760/cma.j.issn.1000−6702.2020.01.001.
Dong P, Liu Y, Zhang ZL, et al. Disciplinary management for metastatic renal cell carcinoma in the ear of targeted therapy: a single center exp[J]. Chin J Urol, 2020, 41(1): 1−7. DOI: 10.3760/cma.j.issn.1000−6702.2020.01.001.[5] 邹俊遐, 陈科. 缺氧诱导因子(HIFs)在肾癌发生中的作用及其分子机制[J]. 遗传, 2018, 40(5): 341−356. DOI: 10.16288/j.yczz.17−406.
Zou JX, Chen K. Roles and molecular mechanisms of hypoxia-inducible factors in renal cell carcinoma[J]. Hereditas, 2018, 40(5): 341−356. DOI: 10.16288/j.yczz.17−406.[6] Choueiri TK, Hessel C, Halabi S, et al. Cabozantinib versus sunitinib as initial therapy for metastatic renal cell carcinoma of intermediate or poor risk (Alliance A031203 CABOSUN randomised trial): Progression-free survival by independent review and overall survival update[J]. Eur J Cancer, 2018, 94: 115−125. DOI: 10.1016/j.ejca.2018.02.012. [7] Ruiz-Morales JM, Swierkowski M, Wells JC, et al. First-line sunitinib versus pazopanib in metastatic renal cell carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium[J]. Eur J Cancer, 2016, 65: 102−108. DOI: 10.1016/j.ejca.2016.06.016. [8] Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada[J]. J Natl Cancer Inst, 2000, 92(3): 205−216. DOI: 10.1093/jnci/92.3.205. [9] van Persijn van Meerten EL, Gelderblom H, Bloem JL. RECIST revised: implications for the radiologist. A review article on the modified RECIST guideline[J]. Eur Radiol, 2010, 20(6): 1456−1467. DOI: 10.1007/s00330−009−1685−y. [10] Ueno D, Yao M, Tateishi U, et al. Early assessment by FDG-PET/CT of patients with advanced renal cell carcinoma treated with tyrosine kinase inhibitors is predictive of disease course[J/OL]. BMC Cancer, 2012, 12: 162[2019-03-10]. https://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-12-162. DOI: 10.1186/1471-2407-12-162. [11] Smith AD, Shah SN, Rini BI, et al. Morphology, Attenuation, Size, and Structure (MASS) Criteria: Assessing Response and Predicting Clinical Outcome in Metastatic Renal Cell Carcinoma on Antiangiogenic Targeted Therapy[J]. AJR Am J Roentgenol, 2010, 194(6): 1470−1478. DOI: 10.2214/AJR.09.3456. [12] Flaherty KT. Sorafenib in Renal Cell Carcinoma[J]. Clin Cancer Res, 2007, 13(2Suppl): 747s−752s. DOI: 10.1158/1078−0432.CCR−06−2063. [13] Rixe O, Bukowski RM, Michaelson MD, et al. Axitinib treatment in patients with cytokine-refractory metastatic krenal-cell cancer: a phase Ⅱ study[J]. Lancet Oncol, 2007, 8(11): 975−984. DOI: 10.1016/s1470−2045(07)70285−1. [14] van der Veldt AAM, Meijerink MR, van den Eertwegh AJM, et al. Sunitinib for Treatment of Advanced Renal Cell Cancer: Primary Tumor Response[J]. Clin Cancer Res, 2008, 14(8): 2431−2436. DOI: 10.1158/1078−0432.CCR−07−4089. [15] 王琳. 靶向时代肿瘤疗效评价标准的探索 [J].中国肿瘤临床, 2015, 42(6): 366−370. DOI: 10.3969/j.issn.1000−8179.20142149.
Wang L. Exploration of tumor response evaluation criteria in the era of tar-geted therapy[J]. Chin J Clin Oncol, 2015, 42(6): 366−370. DOI: 10.3969/j.issn.1000−8179.20142149.[16] Choi H, Charnsangavej C, Faria SC, et al. Correlation of Computed Tomography and Positron Emission Tomography in Patients With Metastatic Gastrointestinal Stromal Tumor Treated at a Single Institution With Imatinib Mesylate: Proposal of New Computed Tomography Response Criteria[J]. J Clin Oncol, 2007, 25(13): 1753−1759. DOI: 10.1200/JCO.2006.07.3049. [17] Schmidt N, Hess V, Zumbrunn T, et al. Choi response criteria for prediction of survival in patients with metastatic renal cell carcinoma treated with anti-angiogenic therapies[J]. Eur Radiol, 2013, 23(3): 632−639. DOI: 10.1007/s00330−012−2640−x. [18] van der Veldt AAM, Meijerink MR, van den Eertwegh AJM, et al. Choi response criteria for early prediction of clinical outcome in patients with metastatic renal cell cancer treated with sunitinib[J]. Br J Cancer, 2010, 102(5): 803−809. DOI: 10.1038/sj.bjc.6605567. [19] 张百红, 岳红云. 实体瘤疗效评价标准简介[J]. 国际肿瘤学杂志, 2016, 43(11): 845−847. DOI: 10.3760/cma.j.issn.1673−422X.2016.11.011.
Zhang BH, Yue HY. Brief introduction of response evaluation criteria in solid tumors[J]. J Int Oncol, 2016, 43(11): 845−847. DOI: 10.3760/cma.j.issn.1673−422X.2016.11.011.[20] Revheim ME, Winge-Main AK, Hagen G, et al. Combined Positron Emission Tomography/Computed Tomography in Sunitinib Therapy Assessment of Patients with Metastatic Renal Cell Carcinoma[J]. Clin Oncol (R Coll Radiol), 2011, 23(5): 339−343. DOI: 10.1016/j.clon.2010.11.006. [21] Lin J, Xie GZ, Liao GX, et al. Prognostic value of 18F-FDG-PET/CT in patients with nasopharyngeal carcinoma: a systematic review and meta-analysis[J/OL]. Oncotarget, 2017, 8(20): 33884−33896[2019-03-10]. https://www.oncotarget.com/article/13934/text/. DOI: 10.18632/oncotarget.13934. [22] Ravina M, Saboury B, Chauhan MS, et al. Utility of <sup>18</sup>F-FDG PET/CT in Pre-Surgical Risk Stratification of Patients with Breast Cancer[J]. Hell J Nucl Med, 2019, 22(3): 165−171. DOI: 10.1967/s002449911051. [23] van Uden DJP, Prins MW, Siesling S, et al. [18F]FDG PET/CT in the staging of inflammatory breast cancer: A systematic review[J/OL]. Crit Rev Oncol Hematol, 2020, 151: 102943[2019-03-10]. http://doi.org/10.1016/j.critrevonc.2020.102943. DOI: 10.1016/j.critrevonc.2020.102943 [24] Soydal C, Koksoy EB, Yasar A, et al. Prognostic Importance of Bone Marrow Uptake on Baseline <sup>18</sup>F-FDG Positron Emission Tomography in Diffuse Large B Cell Lymphoma[J]. Cancer Biother Radiopharm, 2016, 31(10): 361−365. DOI: 10.1089/cbr.2016.2132. [25] Ding QY, Cheng X, Yang L, et al. PET/CT evaluation of response to chemotherapy in non-small cell lung cancer: PET response criteria in solid tumors (PERCIST) versus response evaluation criteria in solid tumors (RECIST)[J]. J Thorac Dis, 2014, 6(6): 677−683. DOI: 10.3978/j.issn.2072−1439.2014.05.10. [26] van Weehaeghe D, Gheysens O, Vandecaveye V, et al. Mixed response on regorafenib treatment for GIST (gastro-intestinal stromal tumor) according to 18F-FDG-PET/CT[J/OL]. BMC Cancer, 2018, 18: 253[2019-03-10]. https://link.springer.com/article/10.1186/s12885-018-4154-7. DOI: 10.1186/s12885-018-4154-7. [27] Nakaigawa N, Kondo K, Tateishi U, et al. FDG PET/CT as a prognostic biomarker in the era of molecular-targeting therapies: max SUVmax predicts survival of patients with advanced renal cell carcinoma[J/OL]. BMC Cancer, 2016, 16: 67[2019-03-10]. https://bmccancer.biomedcentral.com/articles/10.1186/s12885-016-2097-4. DOI: 10.1186/s12885-016-2097-4. [28] Minamimoto R, Nakaigawa N, Tateishi U, et al. Evaluation of Response to Multikinase Inhibitor in Metastatic Renal Cell Carcinoma by FDG PET/Contrast-Enhanced CT[J]. Clin Nucl Med, 2010, 35(12): 918−923. DOI: 10.1097/rlu.0b013e3181f9ddd9. [29] Vercellino L, Bousquet G, Baillet G, et al. <sup>18</sup>F-FDG PET/CT Imaging for an Early Assessment of Response to Sunitinib in Metastatic Renal Carcinoma: Preliminary Study[J]. Cancer Biother Radiopharm, 2009, 24(1): 137−144. DOI: 10.1089/cbr.2008.0527. [30] Nakaigawa N, Kondo K, Ueno D, et al. The acceleration of glucose accumulation in renal cell carcinoma assessed by FDG PET/CT demonstrated acquisition of resistance to tyrosine kinase inhibitor therapy[J/OL]. BMC Cancer, 2017, 17(1): 39[2019-03-10]. https://bmccancer.biomedcentral.com/articles/10.1186/s12885−016−3044−0. DOI: 10.1186/s12885-016-3044-0. [31] Ito H, Kondo K, Kawahara T, et al. One-month assessment of renal cell carcinoma treated by everolimus using FDG PET/CT predicts progression-free and overall survival[J]. Cancer Chemother Pharmacol, 2017, 79(5): 855−861. DOI: 10.1007/s00280−017−3275−z. [32] Nakaigawa N, Kondo K, Kaneta T, et al. FDG PET/CT after first molecular targeted therapy predicts survival of patients with renal cell carcinoma[J]. Cancer Chemother Pharmacol, 2018, 81(4): 739−744. DOI: 10.1007/s00280−018−3542−7. [33] Polverari G, Ceci F, Bertaglia V, et al. 18F-FDG Pet Parameters and Radiomics Features Analysis in Advanced Nsclc Treated with Immunotherapy as Predictors of Therapy Response and Survival[J/OL]. Cancers, 2020, 12(5): 1163[2019-03-10]. https://www.mdpi.com/2072−6694/12/5/1163. DOI: 10.3390/cancers12051163. [34] Moskowitz AJ, Schöder H, Gavane S, et al. Prognostic significance of baseline metabolic tumor volume in relapsed and refractory Hodgkin lymphoma[J]. Blood, 2017, 130(20): 2196−2203. DOI: 10.1182/blood−2017−06−788877. [35] Yoon HJ, Paeng JC, Kwak C, et al. Prognostic implication of extrarenal metabolic tumor burden in advanced renal cell carcinoma treated with targeted therapy after nephrectomy[J]. Ann Nucl Med, 2013, 27(8): 748−755. DOI: 10.1007/s12149−013−0742−4. [36] Hwang SH, Cho A, Yun MJ, et al. Prognostic Value of Pretreatment Metabolic Tumor Volume and Total Lesion Glycolysis Using <sup>18</sup>F-FDG PET/CT in Patients With Metastatic Renal Cell Carcinoma Treated With Anti-Vascular Endothelial Growth Factor-Targeted Agents[J]. Clin Nucl Med, 2017, 42(5): e235−e241. DOI: 10.1097/RLU.0000000000001612. [37] 胡裕效, 朱虹. PET显像在原发性肾细胞癌中的研究进展[J]. 肿瘤学杂志, 2008, 14(10): 852−855.
Hu YX, Zhu H. Progress in PET Imaging in Renal Cell Carcinoma[J]. J Oncol, 2008, 14(10): 852−855.[38] 孟晓云, 陈跃. 肿瘤葡萄糖转运蛋白与脱氧葡萄糖显像剂摄取研究[J]. 实用放射学杂志, 2007, 23(4): 542−545. DOI: 10.3969/j.issn.1002−1671.2007.04.036.
Meng XY, Chen Y. Study on the Tumor GIut and the Uptake of DG Imaging Agent[J]. J Pract Radiol, 2007, 23(4): 542−545. DOI: 10.3969/j.issn.1002−1671.2007.04.036.[39] 宋建华, 赵晋华, 陈香, 等. <sup>18</sup>F-FDG PET/CT对肾脏肿瘤的诊断价值[J]. 中华核医学与分子影像杂志, 2013, 33(3): 184−187. DOI: 10.3760/cma.j.issn.2095−2848.2013.03.007.
Song JH, Zhao JH, Chen X, et al. The value of diagnosing kidney neoplasms with <sup>18</sup>F-FDG PET/CT[J]. Chin J Nucl Med Mol Imaging, 2013, 33(3): 184−187. DOI: 10.3760/cma.j.issn.2095−2848.2013.03.007.[40] 郭峰, 汪清, 倪泽称, 等. <sup>18</sup>F-FDG PET-CT显像在肾癌原发灶及转移灶诊断中的价值[J]. 医学临床研究, 2010, 27(10): 1827−1829, 1833. DOI: 10.3969/j.issn.1671−7171.2010.10.009.
Guo F, Wang Q, Ni ZC, et al. Comparison Study of <sup>18</sup>F-FDG PET-CT and Enhanced-CT in the Diagnosis of Primary Lesion and Metastatic Lesion of Renal Carcinoma[J]. J Clin Res, 2010, 27(10): 1827−1829, 1833. DOI: 10.3969/j.issn.1671−7171.2010.10.009.[41] 徐白萱, 姚树林, 关志伟, 等. <sup>18</sup>F-FDG PET(PET/CT)肾癌显像特点分析[J]. 军医进修学院学报, 2010, 31(7): 640−642.
Xu BX, Yao SL, Guan ZW, et al. Characteristics of <sup>18</sup>F-FDG PET for space occupying renal cancer[J]. J Chin PLA Postgrad Med Sch, 2010, 31(7): 640−642.[42] 朱艳芳, 谢新立, 于艳霞, 等. <sup>18</sup>F-FDG PET/CT显像SUV<sub>max</sub>对不同病理分型肾细胞癌的鉴别价值[J]. 郑州大学学报(医学版), 2018, 53(6): 807−811. DOI: 10.13705/j.issn.1671−6825.2018.04.086.
Zhu YF, Xie XL, Yu YX, et al. Clinical application value of different pathological classifications of renal cell carcinoma using the SUV<sub>max</sub> of <sup>18</sup>F-FDG PET/CT[J]. J Zhengzhou Univ (Med Sci), 2018, 53(6): 807−811. DOI: 10.13705/j.issn.1671−6825.2018.04.086.[43] Kayani I, Avril N, Bomanji J, et al. Sequential FDG-PET/CT as a Biomarker of Response to Sunitinib in Metastatic Clear Cell Renal Cancer[J]. Clin Cancer Res, 2011, 17(18): 6021−6028. DOI: 10.1158/1078−0432.CCR−10−3309. [44] 程远, 王振光. <sup>18</sup>F-FDG PET/CT全身显像辐射剂量估计及风险评价[J]. 中华核医学与分子影像杂志, 2017, 37(7): 430−433. DOI: 10.3760/cma.j.issn.2095−2848.2017.07.012.
Cheng Y, Wang ZG. Estimation of patient radiation dose and risk from whole body <sup>18</sup>F-FDG PET/CT examination[J]. Chin J Nucl Med Mol Imaging, 2017, 37(7): 430−433. DOI: 10.3760/cma.j.issn.2095−2848.2017.07.012.
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