Minici Roberto, Ammendola Michele, Manti Francesco, Siciliano Maria Anna, Giglio Enrica, Minici Marco, Melina Marica, Currò Giuseppe, Laganà Domenico
Radiology Unit, Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy.
Digestive Surgery Unit, Science of Health Department, Magna Graecia University, Catanzaro, Italy.
Front Pharmacol. 2021 Apr 9;12:634084. doi: 10.3389/fphar.2021.634084. eCollection 2021.
In patients with early-stage hepatocellular carcinoma, awaiting liver transplantation, current guidelines by AASLD and ESMO recommend a bridging therapy with a loco-regional treatment to prevent progression outside transplantation criteria. The standard of care in delaying disease progression has been recognized to be the transarterial chemoembolization. Permanent occlusion of tumor feeding vessels has effects on tumour stromal microenvironment by inducing intra- and intercellular signaling processes counteracting hypoxia, such as the release of vascular endothelial growth factor, a promoter of neoangiogenesis, tumour proliferation and metastatic growth. Among chemoembolization interventions, TACE with degradable starch microspheres represents an alternative to conventional cTACE and DEB-TACE and it minimizes detrimental effects on tumour stromal microenvironment, guaranteeing a transient occlusion of tumour feeding arteries and avoiding VEGF overexpression.Between January 2015 and September 2020, 54 consecutive patients with early-stage hepatocellular carcinoma and Child-Pugh stage B, who had undergone DSM-TACE as a bridging therapy while awaiting liver transplantation, were eligible for the study. A total of 154 DSM-TACE was performed, with a mean number of 2.85 procedures per patient. 18 patients (33.3%) succeeded in achieving liver transplantation, with a mean waiting time-to-transplantation of 11.7 months. The cumulative rates of patients still active on the WL at 6 months were about 91 and 93% when considering overall drop-out and tumour-specific drop-out respectively. Overall survival was about 96% at 6 months and 92% at 12 months. 17 patients experienced adverse events after the chemoembolizations. For patients with HCC in the transplant waiting list and within the Child-Pugh B stage, life expectancy may be dominated by the liver dysfunction, rather than by the tumour progression itself. In this population subset, the choice of LRT is critical because LRT itself could become a dangerous tool that is likely to precipitate liver dysfunction to an extent that survival is shortened rather than prolonged. Hence, the current study demonstrates that DSM-TACE is not far from being an ideal LRT, because it has an excellent safety profile, maintaining an efficacy that guarantees a clear advantage on the dropout rate with respect to the non-operative strategy, thus justifying its use.
在等待肝移植的早期肝细胞癌患者中,美国肝病研究学会(AASLD)和欧洲肿瘤内科学会(ESMO)的现行指南推荐采用局部区域治疗进行桥接治疗,以防止疾病进展超出移植标准。延迟疾病进展的标准治疗方法被认为是经动脉化疗栓塞术。肿瘤供血血管的永久性闭塞通过诱导细胞内和细胞间信号传导过程来对抗缺氧,从而对肿瘤基质微环境产生影响,例如释放血管内皮生长因子,这是一种促进新血管生成、肿瘤增殖和转移生长的因子。在化疗栓塞干预措施中,使用可降解淀粉微球的经动脉化疗栓塞术(TACE)是传统cTACE和载药微球栓塞化疗(DEB-TACE)的替代方法,它将对肿瘤基质微环境的有害影响降至最低,保证了肿瘤供血动脉的短暂闭塞并避免血管内皮生长因子(VEGF)过度表达。2015年1月至2020年9月期间,54例连续的Child-Pugh B级早期肝细胞癌患者在等待肝移植期间接受了可降解淀粉微球经动脉化疗栓塞术(DSM-TACE)作为桥接治疗,符合本研究条件。共进行了154次DSM-TACE,每位患者平均进行2.85次手术。18例患者(33.3%)成功接受了肝移植,平均等待移植时间为11.7个月。分别考虑总体退出和肿瘤特异性退出时,6个月时仍在等待名单上的患者累积率分别约为91%和93%。6个月时总生存率约为96%,12个月时为92%。17例患者在化疗栓塞术后出现不良事件。对于移植等待名单上且处于Child-Pugh B级的肝细胞癌患者,预期寿命可能主要受肝功能障碍影响,而非肿瘤进展本身。在这一人群亚组中,局部区域治疗(LRT)的选择至关重要,因为LRT本身可能成为一种危险工具,可能会使肝功能障碍恶化到缩短而非延长生存期的程度。因此,本研究表明DSM-TACE堪称理想的LRT,因为它具有出色的安全性,在降低退出率方面保持了相对于非手术策略的明显优势,从而证明了其应用价值。