2. 复旦大学附属中山医院介入治疗科,上海 200032
2. Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
近年来胰腺癌的发病率呈不断上升趋势,国内以上海市发病率最高,为7.2/10万。而且,胰腺癌可能将成为发达国家癌症死亡的第二大原因[1-2]。胰腺导管腺癌是最常见的胰腺癌病理类型,占75%~90%[3]。胰腺癌早期发病隐匿,约80%的患者就诊时已处于晚期,无法接受外科手术切除治疗,其5年生存率约为9%[4-5]。此外,约1/3的局部进展期胰腺癌患者在手术切除前就已经存在隐匿性肝转移,即使接受了根治性切除术,仍面临50%~80%的局部复发和25%~50%的远处转移风险[6]。肝转移是影响晚期胰腺癌患者术后生存的主要因素之一[7]。
静脉化疗和放射治疗对晚期胰腺癌的疗效不甚理想[6, 8-9]。胰腺导管腺癌多为乏血供,瘤体周围存在致密的纤维间质,使化疗药物很难渗入肿瘤内部,导致静脉化疗的疗效不佳,且不良反应多见[9]。近年来尝试的靶向治疗和免疫治疗尚未获得成功。经动脉灌注化疗(transcatheter arterial infusion, TAI)及经动脉灌注化疗栓塞术(transarterial chemoembolization, TACE)可以提高肿瘤局部化疗药物浓度,增强药物对肿瘤细胞的杀伤力,能控制或延缓胰腺肿瘤及肝内转移灶的进展,是目前延长晚期不可切除胰腺癌患者生存期的主要治疗手段之一[10-11]。
1 经动脉介入治疗的理论基础胰腺主要由腹腔干分支供血,其中胃十二指肠动脉和肠系膜上动脉的分支供应胰头部,脾动脉分支供应胰体尾部[12]。肝转移癌主要由肝动脉分支供血。动脉造影可以清晰显示胰腺原发肿瘤及肝转移肿瘤的供血动脉[13]。通常按照肿瘤部位的不同选择相应的供血动脉进行TAI,使药物能够覆盖全部胰腺肿瘤。针对肝脏转移肿瘤,可进行TACE。
相对于静脉化疗,TAI的优势主要包括:(1)TAI明显提高肿瘤组织药物浓度,增强药物抗肿瘤效应,降低循环血液药物浓度,从而减少药物对全身脏器的损伤。化疗药物通过动脉灌注肿瘤组织后仍会进入循环系统,因此对于循环系统中的肿瘤细胞及微转移灶也有杀伤作用,能有效减少复发和转移。(2)肿瘤靶器官内局部高浓度的化疗药物形成的细胞毒作用可有效克服肿瘤耐药性,并能抑制肿瘤坏死因子α(tumor necrosis factor-α, TNF-α)、白介素-1(interleukin-1, IL-1)、白介素-6(interleukin-6, IL-6)的产生和释放,从而进一步抑制肿瘤组织的生长和转移。(3)TACE可以使肿瘤细胞处于低氧环境中,增强化疗药物的抗肿瘤作用。对于部分局部进展期胰腺癌患者,行TAI降期后可进行外科手术治疗。
2 经导管动脉内介入治疗胰腺癌的有效性与安全性TAI由于首过效应,可提高肿瘤组织药物浓度,产生较强的细胞毒性作用,导致肿瘤细胞凋亡、坏死,克服耐药性,抑制肿瘤的发展和转移。同时降低循环血液中药物浓度,减少全身不良反应。孙建等[14]对术前介入化疗的胰腺癌患者手术切除标本进行组织病理学分析,发现TAI可以导致患者胰腺癌组织细胞坏死,缩小肿瘤组织。Rezaee等[15]在裸鼠原位胰腺癌模型中对比了TAI与全身静脉化疗的治疗效果,发现与静脉使用吉西他滨相比,动脉内灌注吉西他滨的裸鼠肿瘤细胞坏死及凋亡明显增加;同时发现,静脉内吉西他滨的浓度为动脉灌注药物浓度的300倍才能达到与TAI同等的抗肿瘤效果。Shamseddine等[16]对7例胰腺癌患者行TAI,4例行静脉化疗,采用药物代谢动力学分析发现介入治疗组进入肿瘤组织的药物浓度较静脉化疗组高,血浆药物浓度较静脉化疗组低,血液系统不良反应的发生率降低,抗肿瘤效应增强。这些研究分别从基础和临床方面验证了经动脉内介入治疗胰腺癌的有效性。
近年来,关于动脉内介入治疗晚期胰腺癌的临床研究不断被报道[17-21]。Azizi等[22]采用丝裂霉素、顺铂、吉西他滨联合碘油行TACE治疗32例胰腺腺癌肝转移患者,3例部分缓解(partial response,PR)、23例疾病稳定(stable disease,SD),患者总生存期(overall survival, OS)为16个月。Vogl等[23]采用同样的方案对112例胰腺导管腺癌伴肝转移患者实施TACE,其中11.59%的患者达到PR、78.26%患者达到SD,患者的OS为19个月。国内一项回顾性临床研究[21]对354例晚期不可切除胰腺癌患者采取以吉西他滨为主药的TAI联合其他治疗后,患者的OS为7个月,同时发现患者的年龄、肿瘤部位、介入前CA199水平是患者预后的独立影响因素。这些临床研究进一步验证了TAI治疗晚期胰腺癌的有效性。但这些研究多为单中心回顾性临床研究,且不同研究之间存在较大异质性。因此,有待于未来开展多中心、前瞻性研究进一步评估动脉内介入治疗的临床疗效。
一项荟萃分析[24]纳入包括298例患者的6个随机对照临床试验,结果显示,8例患者通过TAI获得完全缓解(complete response,CR),与静脉化疗组相比,TAI组有更多的患者获得PR (58.06% vs 29.37%)、临床疗效更好(78.06% vs 29.37%)、并发症发生率更低(49.03% vs 71.33%)、血液系统不良反应更少(60.87% vs 85.71%),OS更长(5~21个月vs 2.7~14个月),1年生存率更高(28.6%~41.2% vs 0~12.9%)。有研究[17, 19]报道,TAI及TACE导致的并发症通常比较轻微,且多具有自限性;介入后常见的不良反应包括恶心呕吐、腹痛、发热、血细胞减少等,经对症处理后均可在短期内缓解;极少数患者在TACE术后发生肝脓肿,其可能由各种原因导致的胆道逆行感染所引起。总之,TAI治疗晚期胰腺癌较静脉化疗对全身脏器的毒性小。此外,接受TAI患者的生活质量也优于接受静脉化疗者[25]。
3 动脉内介入化疗药物中国胰腺癌诊疗规范指出,TAI常用的药物包括吉西他滨、氟尿嘧啶、阿霉素类(表阿霉素)、铂类药物(顺铂、洛铂)等[26]。既往将吉西他滨作为治疗晚期胰腺癌的一线药物[27]。近年来,多项研究尝试以其他化疗药物与吉西他滨联合治疗胰腺癌。Ueno等[28]关于白蛋白紫杉醇联合吉西他滨治疗转移性胰腺癌患者的Ⅱ期临床研究中,患者无进展生存期(progression-free survival, PFS)和OS分别为6.5和13.5个月。一项Ⅲ期临床研究(MPACT)[29]对比了吉西他滨联合白蛋白紫杉醇与吉西他滨单药对胰腺癌患者生存期的影响,发现联合用药能显著延长晚期胰腺癌患者的OS(8.5个月vs 6.7个月)。Postlewait等[30]将吉西他滨与顺铂联合应用于吉西他滨一线治疗失败后的胰腺癌切除术后复发患者,联合治疗后患者中位OS为35.5个月。PRODIGE研究[31]结果显示,FOLFIRINOX(氟尿嘧啶+亚叶酸钙+伊立替康+奥沙利铂)较吉西他滨显著改善了患者的OS和PFS,但FOLFIRINOX方案毒性较大。近年来,研究者们对FOLFIRINOX方案进行了改良(mFOLFIRINOX),保证了药物疗效,同时降低了药物不良反应[32-34]。目前mFOLFIRINOX方案已被推荐为转移性胰腺癌的一线治疗方案[35-36]。
美国国家综合癌症网络(NCCN)、美国临床肿瘤学会(ASCO)和欧洲肿瘤内科学会(ESMO)及中国国家卫生健康委员会均推荐FOLFIRINOX方案为体能状态好[美国东部肿瘤协作组(ECOG)评分为0分或1分]晚期胰腺癌患者的标准方案;而对于体能状态不佳(ECOG评分>1分)的患者,首选吉西他滨或mFOLFIRINOX作为一线治疗。晚期胰腺癌患者在一线化疗后出现病情进展,其中有40%~50%能够接受二线化疗[37]。对于吉西他滨或mFOLFIRINOX一线化疗后出现进展的胰腺癌患者,可选择联合用药(吉西他滨与顺铂)或其他药物(5-FU)进行二线化疗[26]。TAI药物的选择与用量需根据患者的年龄、体质量、肝肾功能决定。有待开展前瞻性临床研究进一步比较不同药物方案TAI治疗胰腺癌的安全性与有效性,为临床介入治疗方案的制定提供指导。
4 动脉内介入栓塞治疗晚期胰腺癌的动脉内介入治疗包括胰腺供血动脉TAI以及对肝转移癌行TACE。对于是否可以栓塞胰腺供血动脉,目前尚不明确。胰腺对缺血高度敏感,如行胰腺动脉栓塞,可能导致急性胰腺炎的发生,但目前未见相关文献报道。因此,临床上对于胰腺癌病灶仅采用灌注化疗,极少进行栓塞。对于晚期胰腺癌伴肝转移,临床上多采用TACE治疗肝转移灶;而对于多数乏血供的肝转移癌,造影时供血动脉显示不明显,仅采取TAI。目前TACE的栓塞剂主要包括碘油、明胶海绵、聚乙烯醇(polyvinylalcohol, PVA)颗粒、空白微球、载药微球及放射性微球等。明胶海绵由于被降解吸收后会造成血管再通,并不单独用于肿瘤血管的栓塞,通常用于永久性栓塞剂栓塞动脉后的巩固栓塞。对于胰腺癌肝转移灶的栓塞通常使用碘油与化疗药的混合乳剂、PVA颗粒、微球。目前关于栓塞剂的选择和使用缺乏统一规范,有待开展更多的前瞻性临床研究,进一步探讨不同栓塞剂对TACE疗效及患者预后的影响。
载药微球已广泛应用于原发性肝癌及结直肠癌肝转移TACE治疗[38-39]。载药微球可缓慢释放化疗药物,维持肿瘤组织内的药物浓度,延长药物对肿瘤细胞的杀伤时间,提高药物抗肿瘤作用。相对于传统碘油化疗栓塞及空白微球栓塞, 载药微球能降低静脉系统的血药浓度、减轻患者的术后反应,对肿瘤的抑制具有明显的优势[40]。但载药微球能否提高患者生存期获益目前存在争议。De Baere等[41]的研究纳入20例高分化神经内分泌肿瘤肝转移患者,对其采用载阿霉素微球(500~700 μm)的TACE治疗,16例获得PR、3例获得SD,OS为15个月,不良反应主要是腹痛、恶心呕吐等,未见严重并发症发生。因此,载药微球TACE是一种有效、安全的介入治疗手段,但目前在胰腺癌肝转移中的临床应用仍较少,且费用昂贵,临床疗效及经济学效益有待开展大样本前瞻性临床研究确定。
经动脉放射栓塞治疗(transcatheter arterial radioembolization,TARE)是指在动脉内注射放射性钇90微球选择性内照射治疗,能够有效抑制肿瘤组织的生长。国外越来越多将放射性微球栓塞应用于胰腺癌肝转移的治疗[42-43]。Michl等[44]对17例胰腺腺癌肝转移患者进行钇90放射性栓塞治疗,并经PET/CT评估疗效,结果显示6例获得CR、1例获得PR、10例获得SD,患者中位OS为8.8个月。Kim等[45]对33例胰腺癌肝转移患者(其中32例为既往接受过化疗等其他治疗后进展)进行TARE治疗,结果显示,8例获得PR、7例获得SD、4例为PD,治疗后OS为8.1个月;患者未出现严重的肝脏毒性,常见疲劳、腹痛、恶心、体质量下降、腹胀等3级以下不良反应。此外,2例患者出现3级不良反应(1例腹胀和腹水,1例腹痛和疲劳)。该研究表明,TARE治疗胰腺癌肝转移能够有效抑制患者肝内转移癌的生长,明显提高患者临床生存获益。另有研究[46-47]报道,其可能会引起放射性胃炎和胃肠道溃疡、胆囊炎、放射性肺炎和肝脏损伤等,但发生率均低。目前报道的TARE临床研究均为小样本,缺乏更高级别的循证医学证据,因此需要大样本临床研究进一步评估TARE的安全性和有效性。
5 动脉内介入治疗联合其他治疗由于胰腺癌独特的解剖位置和复杂的病理类型,单一治疗往往疗效欠佳。综合多种治疗手段联合治疗,能够弥补各治疗手段的局限,增强抗肿瘤效果,延长患者的生存时间。回顾性临床研究[48]显示45%和21%的转移性胰腺癌患者在吉西他滨治疗失败后分别接受了2种或2种以上的治疗。目前越来越多的临床研究[49-50]表明,对于胰腺癌,多种治疗手段联合治疗较单一治疗方式更有优势。联合治疗需要严格制定治疗策略,控制化疗药物用量,减轻联合治疗引起的叠加不良效应。国内一项临床回顾性研究[51]纳入61例胰腺癌患者,其中55例患者接受化疗联合放疗(43例采取TAI),6例单纯接受放疗,患者OS和无病生存期(disease-free survival, DFS)分别为27.4和16.7个月,3级以上不良反应发生率为29.5% (18/61),无治疗相关死亡。
晚期胰腺癌的非血管介入治疗包括射频消融术、微波消融术、冷冻消融术、高强度聚焦超声治疗、125I粒子植入术、不可逆电穿孔治疗等。不同介入技术的联合应用可明显提高抗肿瘤效应,延长患者生存期。王忠敏等[52]在早期研究中采用CT引导下125I放射性粒子植入联合吉西他滨和氟尿嘧啶TAI治疗晚期不可切除胰腺癌患者,其中CR 2例、PR 9例、SD 3例,总有效率为68.8%,患者中位OS为11个月。Giardino等[53]采用TAI联合静脉化疗、射频消融术综合治疗168例胰腺癌患者,其中位OS为34.0个月。国内一项多中心临床研究[11]纳入610例胰腺癌患者,分为静脉化疗组、TAI组、TAI联合物理消融组,结果显示,联合治疗组明显优于单纯静脉化疗组和TAI组。中山大学肿瘤中心的一项研究[54]对比了不可逆电穿孔联合化疗与单独化疗治疗局部晚期胰腺癌患者的临床疗效,结果显示接受联合治疗的患者获得了更长的PFS及OS。因此,建议多种介入手段联合或与其他治疗联合,以提高晚期胰腺癌患者的生存获益。但目前仍缺乏多种介入治疗、以及联合治疗与动脉内介入治疗的前瞻性临床对照研究,有待进一步开展。
目前,分子靶向治疗、免疫治疗在晚期胰腺癌中的应用虽有初步进展,但能够获益的患者人群有待确定。此外,5%~7%的胰腺癌患者携带BRCA1和BRCA2突变;聚ADP核糖聚合酶(poly ADP-ribose polymerase,PARP)抑制剂对于这类患者具有较好的临床疗效[55]。1%的胰腺癌患者存在错配修复基因功能缺陷(deficient mismatch repair,dMMR);PD-1抗体免疫治疗对该类患者显示出良好的疗效[56]。随着基础研究的不断深入,期待动脉内介入治疗与分子靶向治疗、免疫治疗联合以给更多的患者带来获益。
6 小结经动脉介入治疗已成为晚期胰腺癌重要的治疗手段,其有效性及安全性已得到大量临床及基础研究的证实,但仍缺乏大样本的前瞻性临床随机对照研究,其临床应用有待进一步推广。随着对胰腺癌基础及临床研究的不断深入,将经动脉介入治疗与其他治疗手段联合,在减少患者全身不良反应的前提下,不断提高临床疗效。多学科联合,综合多种治疗手段,基于分子分型和生物标志物选择药物,制定个体化的治疗方案,进行精准治疗,才能不断提高患者的生存获益和生活质量。
利益冲突:所有作者声明不存在利益冲突。
[1] |
RAHIB L, SMITH B D, AIZENBERG R, et al. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States[J]. Cancer Res, 2014, 74(11): 2913-2921.
[DOI]
|
[2] |
FERLAY J, COLOMBET M, SOERJOMATARAM I, et al. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods[J]. Int J Cancer, 2019, 144(8): 1941-1953.
[DOI]
|
[3] |
COLLISSON E A, SADANANDAM A, OLSON P, et al. Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy[J]. Nat Med, 2011, 17(4): 500-503.
[DOI]
|
[4] |
SIEGEL R L, MILLER K D, JEMAL A. Cancer Statistics, 2019[J]. CA Cancer J Clin, 2019, 69(1): 7-34.
[DOI]
|
[5] |
HUANG L, JANSEN L, BALAVARCA Y, et al. Stratified survival of resected and overall pancreatic cancer patients in Europe and the USA in the early twenty-first century: a large, international population-based study[J]. BMC Med, 2018, 16(1): 125.
[DOI]
|
[6] |
TEMPERO M A, MALAFA M P, CHIOREAN E G. NCCN Guidelines insights_ pancreatic adenocarcinoma, version 1.2019[J]. J Natl Compr Cancer Netw, 2019, 17(3): 202-210.
[DOI]
|
[7] |
VAN VELDHUISEN E, VAN DEN OORD C, BRADA L J, et al. Locally advanced pancreatic cancer: work-up, staging, and local intervention strategies[J]. Cancers(Basel), 2019, 11(7): 976.
|
[8] |
CHANDANA S, BABIKER H M, MAHADEVAN D. Therapeutic trends in pancreatic ductal adenocarcinoma (PDAC)[J]. Expert Opin on Investig Drugs, 2018, 28(2): 161-177.
[URI]
|
[9] |
HAJATDOOST L, SEDAGHAT K, WALKER E J, et al. Chemotherapy in pancreatic cancer: a systematic review[J]. Medicina(Kaunas), 2018, 54(3): 48.
[URI]
|
[10] |
GORDON A C, UDDIN O M, RIAZ A, et al. Making the case: intra-arterial therapy for less common metastases[J]. Semin Intervent Radiol, 2017, 34(2): 132-139.
[DOI]
|
[11] |
中国癌症研究基金会介入医学委员会, 中国介入医师分会介入医学材料与工程委员会. 晚期胰腺癌介入治疗临床操作指南(试行) (第三版)[J]. 临床放射学杂志, 2019, 38(1): 6-17. Interventional Medicine Committee of China Cancer Research Foundation, Committee of Interventional Medical Materials and Engineering. Clinical guidelines for interventional therapy of advanced pancreatic cancer (trial) (3rd edition)[J]. Journal of Clinical Radiology, 2019, 38(1): 6-17. [CNKI] |
[12] |
HENRY B M, SKINNINGSRUD B, SAGANIAK K, et al. Development of the human pancreas and its vasculature-An integrated review covering anatomical, embryological, histological, and molecular aspects[J]. Ann Anat, 2019, 221: 115-124.
[DOI]
|
[13] |
施惠斌, 杨敏捷, 王小林, 等. 晚期胰腺癌患者的肿瘤血供来源: 218例患者的DSA评价[J]. 中国临床医学, 2014, 21(1): 61-62. SHI H B, YANG M J, WANG X L, et al. Feeding arteries of advanced pancreatic cancer: evaluation of 218 patients by digital subtract angiography[J]. Chinese Journal of Clinical Medicine, 2014, 21(1): 61-62. [CNKI] |
[14] |
孙建, 倪泉兴, 傅德良, 等. 胰腺癌介入化疗后组织病理学改变及其意义[J]. 腹部外科, 2003, 16(4): 207-208. SUN J, NI Q X, FU D L, et al. Histopathological change of pancreatic carcinoma after interventional chemotherapy and its significance[J]. Journal of Abdominal Surgery, 2003, 16(4): 207-208. [DOI] |
[15] |
REZAEE M, WANG J, RAZAVI M, et al. A study comparing the effects of targeted intra-arterial and systemic chemotherapy in an orthotopic mouse model of pancreatic cancer[J]. Sci Rep, 2019, 9(1): 15929.
[DOI]
|
[16] |
SHAMSEDDINE A I, KHALIFEH M J, MOURAD F H, et al. Comparative pharmacokinetics and metabolic pathway of gemcitabine during intravenous and intra-arterial delivery in unresectable pancreatic cancer patients[J]. Clin Pharmacokinet, 2005, 44(9): 957-967.
[DOI]
|
[17] |
QIU B, ZHANG X, TSAUO J, et al. Transcatheter arterial infusion for pancreatic cancer: a 10-year National Cancer Center experience in 115 patients and literature review[J]. Abdom Radiol (NY), 2019, 44(8): 2801-2808.
[DOI]
|
[18] |
赵启生, 张卫平, 刘明秀. 不可切除胰腺癌经动脉导管化疗栓塞术治疗后的生存分析[J]. 中华胰腺病杂志, 2019, 19(2): 132-134. ZHAO Q S, ZHANG W P, LIU M X. Survival analysis after transcatheter chemoembolization for unresectable pancreatic cancer[J]. Chinese Journal of Pancreatology, 2019, 19(2): 132-134. [DOI] |
[19] |
ROSEMURGY A S, ROSS S B, VITULLI P L, et al. Safety study of targeted and localized intra-arterial delivery of gemcitabine in patients with locally advanced pancreatic adenocarcinoma[J]. J Pancreat Cancer, 2017, 3(1): 58-65.
[DOI]
|
[20] |
SUN J H, ZHOU T Y, ZHANG Y L, et al. Efficacy of transcatheter arterial chemoembolization for liver metastases arising from pancreatic cancer[J]. Oncotarget, 2017, 8(24): 39746-39755.
[DOI]
|
[21] |
LIU X Y, YANG X R, ZHOU G F, et al. Gemcitabine-based regional intra-arterial infusion chemotherapy in patients with advanced pancreatic adenocarcinoma[J]. Medicine (Baltimore), 2016, 95(11): e3098.
[DOI]
|
[22] |
AZIZI A, NAGUIB N N N, EMMANUE M, et al. Liver metastases of pancreatic cancer: role of repetitive transarterial chemoembolization (TACE) on tumor response and survival[J]. Pancreas, 2011, 40(8): 1271-1275.
[DOI]
|
[23] |
VOGL T J, MOHAMED S A, ALBRECHT M H, et al. Transarterial chemoembolization in pancreatic adenocarcinoma with liver metastases: MR-based tumor response evaluation, apparent diffusion coefficient (ADC) patterns, and survival rates[J]. Pancreatology, 2018, 18(1): 94-99.
[DOI]
|
[24] |
LIU F, TANG Y, SUN J, et al. Regional intra-arterial vs. systemic chemotherapy for advanced pancreatic cancer: a systematic review and meta-analysis of randomized controlled trials[J]. PLoS One, 2012, 7(7): e40847.
[DOI]
|
[25] |
MORAK M J M, PEK C J, KOMPANJE E J O, et al. Quality of life after adjuvant intra-arterial chemotherapy and radiotherapy versus surgery alone in resectable pancreatic and periampullary cancer[J]. Cancer, 2010, 116(4): 830-836.
[DOI]
|
[26] |
中华人民共和国国家卫生健康委员会. 胰腺癌诊疗规范(2018年版)[J]. 中华普通外科学文献(电子版), 2019, 13(4): 253-262. National Health Commission of the People's Republic of China. Diagnosis, management, and treatment of pancreatic adenocarcinoma (V2018)[J]. Chinese Archives of General Surgery(Electronic Edition), 2019, 13(4): 253-262. [DOI] |
[27] |
BURRIS R H 3rd, MOORE M J, ANDERSEN J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial[J]. J Clin Oncol, 1997, 15(6): 2403-2413.
[DOI]
|
[28] |
UENO H, IKEDA M, UENO M, et al. Phase Ⅰ/Ⅱ study of nab-paclitaxel plus gemcitabine for chemotherapy-naive Japanese patients with metastatic pancreatic cancer[J]. Cancer Chemother Pharmacol, 2016, 77(3): 595-603.
[DOI]
|
[29] |
GOLDSTEIN D, EL-MARAGHI R H, HAMMEL P, et al. Nab-paclitaxel plus gemcitabine for metastatic pancreatic cancer: long-term survival from a phase Ⅲ trial[J]. J Natl Cancer Inst, 2015, 107(2): dju413.
[DOI]
|
[30] |
POSTLEWAIT L M, ETHUN C G, KOOBY D A, et al. Combination gemcitabine/cisplatin therapy and ERCC1 expression for resected pancreatic adenocarcinoma: results of a Phase Ⅱ prospective trial[J]. J Surg Oncol, 2016, 114(3): 336-341.
[DOI]
|
[31] |
CONROY T, DESSEIGNE F, YCHOU M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer[J]. N Engl J Med, 2011, 364(19): 1817-1825.
[DOI]
|
[32] |
农天文, 覃涛, 李文竹, 等. 改良FOLFIRINOX方案一线治疗晚期转移性胰腺癌[J]. 中山大学学报(医学版), 2018, 39(2): 233-237. NONG T W, QIN T, LI W Z, et al. A new modified FOLFIRINOX(mFOLFIRINOX)regimen as first-line chemotherapy for patient with metastatic pancreatic adenocarcinoma(MPC)[J]. Journal of Sun Yat-sen University (Medical Sciences), 2018, 39(02): 233-237. [CNKI] |
[33] |
SINGH R R, O REILLY E M. New Treatment strategies for metastatic pancreatic ductal adenocarcinoma[J]. Drugs, 2020, 80(7): 647-669.
[DOI]
|
[34] |
NEVALA-PLAGEMANN C, HIDALGO M, GARRIDO-LAGUNA I. From state-of-the-art treatments to novel therapies for advanced-stage pancreatic cancer[J]. Nat Rev Clin Oncol, 2020, 17(2): 108-123.
[DOI]
|
[35] |
GLATZER M, HORBER D, MONTEMURRO M, et al. Choice of first line systemic treatment in pancreatic cancer among national experts[J]. Pancreatology, 2020, 20(4): 686-690.
[DOI]
|
[36] |
SCHEITHAUER W, PUTORA P M, GRÜNBERGER B, et al. Patterns of care in metastatic pancreatic cancer: patient selection in clinical routine[J]. Therap Adv Gastroenterol, 2019, 12: 1756284819877635.
|
[37] |
WALKER E J. Beyond first-line chemotherapy for advanced pancreatic cancer: an expanding array of therapeutic options?[J]. World J Gastroenterol, 2014, 20(9): 2224.
[DOI]
|
[38] |
LEWIS A L. DC Bead: a major development in the toolbox for the interventional oncologist[J]. Expert Rev Med Devices, 2009, 6(4): 389-400.
[DOI]
|
[39] |
YOUNG S, D′SOUZA D, FLANAGAN S, et al. Review of the clinical evidence for the use of DEBIRI in the treatment of colorectal metastatic disease[J]. Cardiovasc Intervent Radiol, 2017, 40(4): 496-501.
[DOI]
|
[40] |
KARALLI A, TEILER J, HAJI M, et al. Comparison of lipiodol infusion and drug-eluting beads transarterial chemoembolization of hepatocellular carcinoma in a real-life setting[J]. Scand J Gastroenterol, 2019, 54(7): 905-912.
[DOI]
|
[41] |
DE BAERE T, DESCHAMPS F, TERⅡTHEAU C, et al. Transarterial chemoembolization of liver metastases from well differentiated gastroenteropancreatic endocrine tumors with doxorubicin-eluting beads: preliminary results[J]. J Vasc Interv Radiol, 2008, 19(6): 855-861.
[DOI]
|
[42] |
MICHL M, HAUG A R, JAKOBS T F, et al. Radioembolization with Yttrium-90 microspheres (SIRT) in pancreatic cancer patients with liver metastases: efficacy, safety and prognostic factors[J]. Oncology, 2014, 86(1): 24-32.
[DOI]
|
[43] |
KIM A Y, UNGER K, WANG H K, et al. Incorporating Yttrium-90 trans-arterial radioembolization (TARE) in the treatment of metastatic pancreatic adenocarcioma: a single center experience[J]. BMC Cancer, 2016, 16: 492.
[DOI]
|
[44] |
MICHL M, LEHNER S, PAPROTTKA P M, et al. Use of PERCIST for prediction of progression-free and overall survival after radioembolization for liver metastases from pancreatic cancer[J]. J Nucl Med, 2016, 57(3): 355-360.
[DOI]
|
[45] |
KIM A Y, FRANTZ S, BROWER J, et al. Radioembolization with Yttrium-90 microspheres for the treatment of liver metastases of pancreatic adenocarcinoma: a multicenter analysis[J]. J Vasc Interv Radiol, 2019, 30(3): 298-304.
[DOI]
|
[46] |
BRAAT M N, VAN ERPECUM K J, ZONNENBERG B A, et al. Radioembolization-Induced liver disease: a systematic review[J]. Eur J Gastroenterol Hepatol, 2017, 29(2): 144-152.
[DOI]
|
[47] |
SANGRO B, MARTINEZ-URBISTONDO D, BESTER L, et al. Prevention and treatment of complications of selective internal radiation therapy: expert guidance and systematic review[J]. Hepatology, 2017, 66(3): 969-982.
[DOI]
|
[48] |
NAGRIAL A M, CHIN V T, SJOQUIST K M, et al. Second-line treatment in inoperable pancreatic adenocarcinoma: a systematic review and synthesis of all clinical trials[J]. Crit Rev Oncol Hematol, 2015, 96(3): 483-497.
[DOI]
|
[49] |
RUTTER C E, PARK H S, CORSO C D, et al. Addition of radiotherapy to adjuvant chemotherapy is associated with improved overall survival in resected pancreatic adenocarcinoma: an analysis of the National Cancer Data Base[J]. Cancer, 2015, 121(23): 4141-4149.
[DOI]
|
[50] |
VAN LAETHEM J, HAMMEL P, MORNEX F, et al. Adjuvant gemcitabine alone versus gemcitabine-based chemoradiotherapy after curative resection for pancreatic cancer: a randomized EORTC-40013-22012/FFCD-9203/GERCOR Phase Ⅱ Study[J]. J Clin Oncol, 2010, 28(29): 4450-4456.
[DOI]
|
[51] |
MA N Y, WANG Z, ZHAO J D, et al. Improved survival in patients with resected pancreatic carcinoma using postoperative intensity-modulated radiotherapy and regional intra-arterial infusion chemotherapy[J]. Med Sci Monit, 2017, 23: 2315-2323.
[DOI]
|
[52] |
王忠敏, 陈克敏, 金冶宁, 等. CT引导下植入125I放射性粒子联合吉西他滨和氟尿嘧啶动脉灌注治疗胰腺癌的疗效[J]. 肿瘤, 2008, 12(28): 1102-1105. WANG Z M, CHEN K M, JIN Y N, et al. Clinical efficacy of CT-guided implantation of iodine125 seeds combined with intra-arterial perfusion of gemcitabine plus 5-fluorouracil on pancreatic cancer[J]. Tumor, 2008, 12(28): 1102-1105. [CNKI] |
[53] |
GIARDINO A, GIRELLI R, FRIGERIO I, et al. Triple approach strategy for patients with locally advanced pancreatic carcinoma[J]. HPB, 2013, 15(8): 623-627.
[DOI]
|
[54] |
HE C B, HUANG X, ZHANG Y, et al. Comparison of survival between irreversible electroporation followed by chemotherapy and chemotherapy alone for locally advanced pancreatic cancer[J]. Front Oncol, 2020, 10: 6.
[DOI]
|
[55] |
GOLAN T, HAMMEL P, RENI M, et al. Maintenance olaparib for Germline BRCA-mutated metastatic pancreatic cancer[J]. N Engl J Med, 2019, 381(4): 317-327.
[DOI]
|
[56] |
HU Z I, SHIA J, STADLER Z K, et al. Evaluating mismatch repair deficiency in pancreatic adenocarcinoma: challenges and recommendations[J]. Clin Cancer Res, 2018, 24(6): 1326-1336.
[DOI]
|