de la Torre Andrew N, Contractor Sohail, Castaneda Ismael, Cathcart Charles S, Razdan Dolly, Klyde David, Kisza Piotr, Gonzales Sharon F, Salazar Andres M
Department of Surgery, St Joseph's Regional Medical Center, Paterson.
Department of Surgery, Rutgers New Jersey Medical School-University Hospital.
J Hepatocell Carcinoma. 2017 Aug 7;4:111-121. doi: 10.2147/JHC.S136652. eCollection 2017.
To determine the safety of an approach to immunologically enhance local treatment of hepatocellular cancer (HCC) by combining nonlethal radiation, local regional therapy with intratumoral injection, and systemic administration of a potent Toll-like receptor (TLR) immune adjuvant.
Patients with HCC not eligible for liver transplant or surgery were subject to: 1) 3 fractions of 2-Gy focal nonlethal radiation to increase tumor antigen expression, 2) intra-/peri-tumoral (IT) injection of the TLR3 agonist, polyinosinic-polycytidylic acid polylysine carboxymethylcellulose (poly-ICLC), to induce an immunologic "danger" response in the tumor microenvironment with local regional therapy, and 3) systemic boosting of immunity with intramuscular poly-ICLC. Primary end points were safety and tolerability; secondary end points were progression-free survival (PFS) and overall survival (OS) at 6 months, 1 year, and 2 years.
Eighteen patients with HCC not eligible for surgery or liver transplant were treated. Aside from 1 embolization-related severe adverse event, all events were ≤grade II. PFS was 66% at 6 months, 39% at 12 months, and 28% at 24 months. Overall 1-year survival was 69%, and 2-year survival 38%. In patients <60 years old, 2-year survival was 62.5% vs. 11.1% in patients aged >60 years (<0.05). Several patients had prolonged PFS and OS.
Intra-tumoral injection of the TLR3 agonist poly-ICLC in patients with HCC is safe and tolerable when combined with local nonlethal radiation and local regional treatment. Further work is in progress to evaluate if this approach improves survival compared to local regional treatment alone and characterize changes in anticancer immunity.
通过联合非致死性放疗、瘤内注射局部区域治疗以及全身给予强效Toll样受体（TLR）免疫佐剂，确定一种免疫增强肝细胞癌（HCC）局部治疗方法的安全性。
不符合肝移植或手术条件的HCC患者接受以下治疗：1）3次2 Gy的局部非致死性放疗，以增加肿瘤抗原表达；2）瘤内/瘤周注射TLR3激动剂聚肌苷酸-聚胞苷酸聚赖氨酸羧甲基纤维素（poly-ICLC），通过局部区域治疗在肿瘤微环境中诱导免疫“危险”反应；3）肌肉注射poly-ICLC进行全身免疫增强。主要终点是安全性和耐受性；次要终点是6个月、1年和2年时的无进展生存期（PFS）和总生存期（OS）。
18例不符合手术或肝移植条件的HCC患者接受了治疗。除1例与栓塞相关的严重不良事件外，所有事件均≤Ⅱ级。6个月时PFS为66%，12个月时为39%，24个月时为28%。1年总生存率为69%，2年生存率为38%。年龄<60岁的患者2年生存率为62.5%，而年龄>60岁的患者为11.1%（<0.05）。有几名患者的PFS和OS延长。
HCC患者瘤内注射TLR3激动剂poly-ICLC与局部非致死性放疗和局部区域治疗联合使用时是安全且可耐受
