CAJ | 학술논문

目的：探讨低剂量白介素-2（IL-2）联合肝动脉化疗栓塞术（TACE）在 CT 引导下行射频消融术（RFA）（RFA）在≥5cm 的原发性肝癌的疗效和安全性。方法：2010年10月至2013年9月入组初治的原发性肝癌患者，随机分入低剂量 IL-2联合 RFA+TACE 组（A 组）或单纯RFA+TACE 组（B 组）；患者至少有1个肿瘤最大径≥5cm。D1行 TACE 术。D5±2行 RFA 术。A 组患者自 D10连续皮下注射重组人白介素-250万单位 QOD，共8周。主要观察终点为至疾病进展时间（TTP）；次要观察终点为客观有效率（ORR）、总生存期（OS）和安全性。结果：共50例患者入组，A、B 组均25例。患者中位年龄为55岁。中位随访期为518d（91~1227d）。IL-2相关的不良事件主要为注射部位硬结（64%）、低热（48%）和乏力（36%）。TACE 联合 RFA 治疗相关的不良事件多为轻至中度或一过性，最常见的包括发热（88.0%）、ALT 及 AST 升高（均为80.0%），疼痛（76.0%）和胆红素升高（66.0%）。其中 III 度疼痛10例，III 度 ALT 和 AST 升高各5例。两组之间在微创治疗的安全性方面无显著差异。总 ORR 均为74.0%，其中 CR 11例，PR 26例。1年和2年生存率分别为67.8%和52.9%。两组之间在 ORR 和 OS 方面无差异。但是，A组较 B 组 TTP 显著延长(301d 比153d，P =0.047)。在多因素分析中，IL-2并未改变患者预后或疗效。结论：低剂量 IL-2可能会进一步提高 RFA+TACE 在≥5cm 的原发性肝癌的疗效，且耐受性良好。需要进一步扩大样本量、探讨更高剂量或更长疗程 IL-2在此类患者的作用。
목적：탐토저제량백개소-2（IL-2）연합간동맥화료전새술（TACE）재 CT 인도하행사빈소융술（RFA）（RFA）재≥5cm 적원발성간암적료효화안전성。방법：2010년10월지2013년9월입조초치적원발성간암환자，수궤분입저제량 IL-2연합 RFA+TACE 조（A 조）혹단순RFA+TACE 조（B 조）；환자지소유1개종류최대경≥5cm。D1행 TACE 술。D5±2행 RFA 술。A 조환자자 D10련속피하주사중조인백개소-250만단위 QOD，공8주。주요관찰종점위지질병진전시간（TTP）；차요관찰종점위객관유효솔（ORR）、총생존기（OS）화안전성。결과：공50례환자입조，A、B 조균25례。환자중위년령위55세。중위수방기위518d（91~1227d）。IL-2상관적불량사건주요위주사부위경결（64%）、저열（48%）화핍력（36%）。TACE 연합 RFA 치료상관적불량사건다위경지중도혹일과성，최상견적포괄발열（88.0%）、ALT 급 AST 승고（균위80.0%），동통（76.0%）화담홍소승고（66.0%）。기중 III 도동통10례，III 도 ALT 화 AST 승고각5례。량조지간재미창치료적안전성방면무현저차이。총 ORR 균위74.0%，기중 CR 11례，PR 26례。1년화2년생존솔분별위67.8%화52.9%。량조지간재 ORR 화 OS 방면무차이。단시，A조교 B 조 TTP 현저연장(301d 비153d，P =0.047)。재다인소분석중，IL-2병미개변환자예후혹료효。결론：저제량 IL-2가능회진일보제고 RFA+TACE 재≥5cm 적원발성간암적료효，차내수성량호。수요진일보확대양본량、탐토경고제량혹경장료정 IL-2재차류환자적작용。
Objective: To explore the safety and efficacy of low-dose interleukin 2 (IL-2) combined with transcatheter arterial chemoembolization (TACE) fol owed by immediate CT-guided radiofrequency ablation (RFA) for large primary liver cancer (PLC) (maximum diameter ≥ 5 cm). Methods: From January 2009 to September 2013, treatment-na?ve patients with PLC ≥ 5 cm were randomly assigned to receive either low-dose IL-2 plus RFA combined with TACE (Group A) or RFA combined with TACE (Group B). All patients underwent lipiodol-based TACE on D1, and then received CT-guided RFA on D5±2. After that, for the patients in Group A, IL-2 was administered subcutaneously QOD at a dose of 500,000 u, for 8 consecutive weeks since D10. The primary endpoint was time to progression (TTP). The secondary endpoints included objective response rate (ORR), overal survival (OS) and safety. Results:A total of 50 patients (25 in each group) were recruited in this study. The median age of the cohort was 55 (range: 39-80). The median fol ow-up time was 518 days (range: 91-1227 days). IL-2 treatment-related adverse events (AEs) included reaction at injection site (64%, 16 cases), mild fever (48%, 12 cases) and hypodynamia (36%, 9cases). TACE combined with RFA treatment-emergent AEs were mainly mild or moderate, including 44 cases of fever (88.0%), 40 cases of ALT elevation (80.0%), 40 cases of AST elevation (80.0%), 38 cases of abdominal pain (76.0%) and 33 cases of TBIL elevation (66.0%). Grade 3 AEs comprised pain (10 cases), ALT elevation (5 cases) and AST elevation (5 cases). Moreover, al patients recovered from these AEs within 2 weeks without sequelae. Overal , the invasive treatment was associated with similar safety profiles in both two groups. The total ORR was 74.0% ( 11/50 CR and 26/50 PR). The 1-year and 2-year OS rates were 67.8% and 52.9%, respectively. No difference was found between the two groups in either ORR or OS. However, the results demonstrated that IL-2 significantly prolonged TTP (301d vs 153d, P=0.047). Multivariate Cox-regression model shown IL-2 administration was not significantly associated with outcome endpoints (OR, TTP or OS). Conclusion: Low-dose IL-2 may improve the efficacy of RFA combined with TACE for large hepatocellular carcinomas with well tolerability. The effect of IL-2 for the treatment of PLC would be identified by further investigations with higher doses or longer regimen period of IL-2.