PDF(Pubmed)
Abstract：
UNASSIGNED: Whether stereotactic body radiotherapy (SBRT) as a bridge to liver transplant for hepatocellular carcinoma (HCC) is effective and safe is still unknown.
UNASSIGNED: To investigate the feasibility of SBRT before deceased donor liver transplant (DDLT) for previously untreated unresectable HCC.
UNASSIGNED: In this phase 2 nonrandomized controlled trial conducted between June 1, 2015, and October 18, 2019, 32 eligible patients within UCSF (University of California, San Francisco) criteria underwent dual-tracer (18F-fluorodeoxyglucose and 11C-acetate [ACC]) positron emission tomography with computed tomography (PET-CT) and magnetic resonance imaging (MRI) with gadoxetate followed by SBRT of 35 to 50 Gy in 5 fractions, and the same imaging afterward while awaiting DDLT. Statistical analysis was performed on an intention-to-treat basis between October 1 and 31, 2023.
UNASSIGNED: Patients received SBRT followed by DDLT when matched deceased donor grafts were available.
UNASSIGNED: Coprimary end points were progression-free survival (PFS) and objective response rates (ORRs) by the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), modified RECIST (mRECIST), and PET Response Criteria in Solid Tumors (PERCIST). Secondary end points were local control rate, overall survival (OS), and safety.
UNASSIGNED: A total of 32 patients (median age, 59 years [IQR, 54-63 years]; 22 men [68.8%]) with 56 lesions received SBRT. After a median follow-up of 74.6 months (IQR, 40.1-102.9 months), the median PFS was 17.6 months (95% CI, 6.6-28.6 months), and the median OS was 60.5 months (95% CI, 29.7-91.2 months). The 5-year PFS was 39.9% (95% CI, 19.9%-59.9%), and the 5-year OS was 51.3% (95% CI, 31.7%-70.9%). In terms of number of patients, ORRs were 62.5% ([n = 20] 95% CI, 54.2%-68.7%) by RECIST 1.1, 71.9% ([n = 23] 95% CI, 63.7%-79.0%) by mRECIST, and 78.1% ([n = 25] 95% CI, 73.2%-86.7%) by PERCIST. In terms of number of lesions, ORRs were 75.0% ([n = 42] 95% CI, 61.6%-80.8%) by RECIST 1.1, 83.9% ([n = 47] 95% CI, 74.7%-90.6%) by mRECIST, and 87.5% ([n = 49] 95% CI, 81.3%-98.6%) by PERCIST. Twenty patients with 36 lesions received DDLT, of whom 15 patients (75.0%) with 21 lesions (58.3%) exhibited pathologic complete response. Multivariable analyses revealed that pretreatment metabolic tumor volume (MTV) based on ACC (hazard ratio [HR], 1.06 [95% CI, 1.01-1.10]; P = .01) and complete metabolic response (CMR) by PERCIST (HR, 0.31 [95% CI, 0.10-0.96]; P = .04) were associated with PFS, while pretreatment MTV based on ACC (HR, 1.07 [95% CI, 1.03-1.16]; P = .01), total lesion activity based on ACC (HR, 1.01 [95% CI, 1.00-1.02]; P = .02), and CMR by PERCIST (HR, 0.21 [95% CI, 0.07-0.73]; P = .01) were associated with OS. Toxic effects associated with SBRT were reported for 9 patients (28.1%), with 1 grade 3 event.
UNASSIGNED: This phase 2 nonrandomized controlled trial demonstrated promising survival and safety outcomes of SBRT before DDLT for unresectable HCC. Future randomized clinical trials are warranted.
UNASSIGNED: To investigate the feasibility of SBRT before deceased donor liver transplant (DDLT) for previously untreated unresectable HCC.
UNASSIGNED: In this phase 2 nonrandomized controlled trial conducted between June 1, 2015, and October 18, 2019, 32 eligible patients within UCSF (University of California, San Francisco) criteria underwent dual-tracer (18F-fluorodeoxyglucose and 11C-acetate [ACC]) positron emission tomography with computed tomography (PET-CT) and magnetic resonance imaging (MRI) with gadoxetate followed by SBRT of 35 to 50 Gy in 5 fractions, and the same imaging afterward while awaiting DDLT. Statistical analysis was performed on an intention-to-treat basis between October 1 and 31, 2023.
UNASSIGNED: Patients received SBRT followed by DDLT when matched deceased donor grafts were available.
UNASSIGNED: Coprimary end points were progression-free survival (PFS) and objective response rates (ORRs) by the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), modified RECIST (mRECIST), and PET Response Criteria in Solid Tumors (PERCIST). Secondary end points were local control rate, overall survival (OS), and safety.
UNASSIGNED: A total of 32 patients (median age, 59 years [IQR, 54-63 years]; 22 men [68.8%]) with 56 lesions received SBRT. After a median follow-up of 74.6 months (IQR, 40.1-102.9 months), the median PFS was 17.6 months (95% CI, 6.6-28.6 months), and the median OS was 60.5 months (95% CI, 29.7-91.2 months). The 5-year PFS was 39.9% (95% CI, 19.9%-59.9%), and the 5-year OS was 51.3% (95% CI, 31.7%-70.9%). In terms of number of patients, ORRs were 62.5% ([n = 20] 95% CI, 54.2%-68.7%) by RECIST 1.1, 71.9% ([n = 23] 95% CI, 63.7%-79.0%) by mRECIST, and 78.1% ([n = 25] 95% CI, 73.2%-86.7%) by PERCIST. In terms of number of lesions, ORRs were 75.0% ([n = 42] 95% CI, 61.6%-80.8%) by RECIST 1.1, 83.9% ([n = 47] 95% CI, 74.7%-90.6%) by mRECIST, and 87.5% ([n = 49] 95% CI, 81.3%-98.6%) by PERCIST. Twenty patients with 36 lesions received DDLT, of whom 15 patients (75.0%) with 21 lesions (58.3%) exhibited pathologic complete response. Multivariable analyses revealed that pretreatment metabolic tumor volume (MTV) based on ACC (hazard ratio [HR], 1.06 [95% CI, 1.01-1.10]; P = .01) and complete metabolic response (CMR) by PERCIST (HR, 0.31 [95% CI, 0.10-0.96]; P = .04) were associated with PFS, while pretreatment MTV based on ACC (HR, 1.07 [95% CI, 1.03-1.16]; P = .01), total lesion activity based on ACC (HR, 1.01 [95% CI, 1.00-1.02]; P = .02), and CMR by PERCIST (HR, 0.21 [95% CI, 0.07-0.73]; P = .01) were associated with OS. Toxic effects associated with SBRT were reported for 9 patients (28.1%), with 1 grade 3 event.
UNASSIGNED: This phase 2 nonrandomized controlled trial demonstrated promising survival and safety outcomes of SBRT before DDLT for unresectable HCC. Future randomized clinical trials are warranted.
摘要：
■立体定向放射治疗（SBRT）作为肝细胞癌（HCC）肝移植的桥梁是否有效且安全仍未知。
■为了研究在以前未经治疗的不可切除的HCC的死亡供体肝移植（DDLT）前SBRT的可行性。
■在2015年6月1日至2019年10月18日之间进行的第2阶段非随机对照试验中，UCSF中有32名符合条件的患者（加州大学，旧金山）的标准进行了双示踪剂（18F-氟脱氧葡萄糖和11C-乙酸[ACC]）正电子发射断层扫描，计算机断层扫描（PET-CT）和磁共振成像（MRI）以及gadoxetate，然后将SBRT分为35至50Gy5个部分，然后在等待DDLT时进行相同的成像。在2023年10月1日至31日期间，在意向治疗的基础上进行了统计分析。
■患者接受SBRT，然后在有匹配的已故供体移植物时接受DDLT。
■共同主要终点是实体瘤的无进展生存期（PFS）和客观缓解率（ORR），版本1.1(RECIST1.1)，修改后的RECIST(mRECIST)，和实体瘤的PET反应标准（PERCIST）。次要终点为局部控制率,总生存期（OS），和安全。
■共有32名患者（中位年龄，59年[IQR，54-63岁]；22名男性[68.8％]），56个病变接受SBRT。经过74.6个月的中位随访（IQR，40.1-102.9个月），中位PFS为17.6个月（95%CI，6.6-28.6个月），中位OS为60.5个月（95%CI，29.7-91.2个月）。5年PFS为39.9%（95%CI，19.9%-59.9%），5年OS为51.3%(95%CI,31.7%-70.9%)。就患者数量而言，根据RECIST1.1，ORR为62.5％（[n=20]95％CI，54.2％-68.7％），根据mRECIST为71.9％（[n=23]95％CI，63.7％-79.0％），和78.1%（[n=25]95%CI，73.2%-86.7%）。就病变的数量而言，通过RECIST1.1，ORR为75.0％（[n=42]95％CI，61.6％-80.8％），通过mRECIST为83.9％（[n=47]95％CI，74.7％-90.6％），和87.5%（[n=49]95%CI，81.3%-98.6%）。有36个病灶的20例患者接受了DDLT，其中15例（75.0%），21个病灶（58.3%）表现出病理完全缓解。多变量分析表明，基于ACC的预处理代谢性肿瘤体积(MTV)(风险比[HR]，1.06[95%CI，1.01-1.10]；P=0.01）和PERCIST的完全代谢反应（CMR）（HR，0.31[95%CI，0.10-0.96]；P=.04)与PFS相关，而基于ACC的MTV预处理(HR，1.07[95%CI，1.03-1.16]；P=0.01），基于ACC的总病变活动(HR，1.01[95%CI，1.00-1.02]；P=.02)，和CMR由PERCIST(HR，0.21[95%CI，0.07-0.73]；P=0.01）与OS相关。9例患者（28.1%）报告了与SBRT相关的毒性作用，有1个3级事件。
■这项2期非随机对照试验证明了SBRT在DDLT治疗不可切除的HCC之前的有希望的生存和安全性结果。未来的随机临床试验是必要的。
■为了研究在以前未经治疗的不可切除的HCC的死亡供体肝移植（DDLT）前SBRT的可行性。
■在2015年6月1日至2019年10月18日之间进行的第2阶段非随机对照试验中，UCSF中有32名符合条件的患者（加州大学，旧金山）的标准进行了双示踪剂（18F-氟脱氧葡萄糖和11C-乙酸[ACC]）正电子发射断层扫描，计算机断层扫描（PET-CT）和磁共振成像（MRI）以及gadoxetate，然后将SBRT分为35至50Gy5个部分，然后在等待DDLT时进行相同的成像。在2023年10月1日至31日期间，在意向治疗的基础上进行了统计分析。
■患者接受SBRT，然后在有匹配的已故供体移植物时接受DDLT。
■共同主要终点是实体瘤的无进展生存期（PFS）和客观缓解率（ORR），版本1.1(RECIST1.1)，修改后的RECIST(mRECIST)，和实体瘤的PET反应标准（PERCIST）。次要终点为局部控制率,总生存期（OS），和安全。
■共有32名患者（中位年龄，59年[IQR，54-63岁]；22名男性[68.8％]），56个病变接受SBRT。经过74.6个月的中位随访（IQR，40.1-102.9个月），中位PFS为17.6个月（95%CI，6.6-28.6个月），中位OS为60.5个月（95%CI，29.7-91.2个月）。5年PFS为39.9%（95%CI，19.9%-59.9%），5年OS为51.3%(95%CI,31.7%-70.9%)。就患者数量而言，根据RECIST1.1，ORR为62.5％（[n=20]95％CI，54.2％-68.7％），根据mRECIST为71.9％（[n=23]95％CI，63.7％-79.0％），和78.1%（[n=25]95%CI，73.2%-86.7%）。就病变的数量而言，通过RECIST1.1，ORR为75.0％（[n=42]95％CI，61.6％-80.8％），通过mRECIST为83.9％（[n=47]95％CI，74.7％-90.6％），和87.5%（[n=49]95%CI，81.3%-98.6%）。有36个病灶的20例患者接受了DDLT，其中15例（75.0%），21个病灶（58.3%）表现出病理完全缓解。多变量分析表明，基于ACC的预处理代谢性肿瘤体积(MTV)(风险比[HR]，1.06[95%CI，1.01-1.10]；P=0.01）和PERCIST的完全代谢反应（CMR）（HR，0.31[95%CI，0.10-0.96]；P=.04)与PFS相关，而基于ACC的MTV预处理(HR，1.07[95%CI，1.03-1.16]；P=0.01），基于ACC的总病变活动(HR，1.01[95%CI，1.00-1.02]；P=.02)，和CMR由PERCIST(HR，0.21[95%CI，0.07-0.73]；P=0.01）与OS相关。9例患者（28.1%）报告了与SBRT相关的毒性作用，有1个3级事件。
■这项2期非随机对照试验证明了SBRT在DDLT治疗不可切除的HCC之前的有希望的生存和安全性结果。未来的随机临床试验是必要的。
