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Definitive Liver Radiotherapy for Intrahepatic Cholangiocarcinoma with Extrahepatic Metastases. 肝内胆管癌肝外转移的明确肝放射治疗。
IF 11.6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2023-03-16 eCollection Date: 2023-08-01 DOI: 10.1159/000530134
Brian De, Rituraj Upadhyay, Kaiping Liao, Tiffany Kumala, Christopher Shi, Grace Dodoo, Joseph Abi Jaoude, Kelsey L Corrigan, Gohar S Manzar, Kathryn E Marqueen, Vincent Bernard, Sunyoung S Lee, Kanwal P S Raghav, Jean-Nicolas Vauthey, Ching-Wei D Tzeng, Hop S Tran Cao, Grace Lee, Jennifer Y Wo, Theodore S Hong, Christopher H Crane, Bruce D Minsky, Grace L Smith, Emma B Holliday, Cullen M Taniguchi, Albert C Koong, Prajnan Das, Milind Javle, Ethan B Ludmir, Eugene J Koay

Introduction: Tumor-related liver failure (TRLF) is the most common cause of death in patients with intrahepatic cholangiocarcinoma (ICC). Though we previously showed that liver radiotherapy (L-RT) for locally advanced ICC is associated with less frequent TRLF and longer overall survival (OS), the role of L-RT for patients with extrahepatic metastatic disease (M1) remains undefined. We sought to compare outcomes for M1 ICC patients treated with and without L-RT.

Methods: We reviewed ICC patients that found to have M1 disease at initial diagnosis at a single institution between 2010 and 2021 who received L-RT, matching them with an institutional cohort by propensity score and a National Cancer Database (NCDB) cohort by frequency technique. The median biologically effective dose was 97.5 Gy (interquartile range 80.5-97.9 Gy) for L-RT. Patients treated with other local therapies or supportive care alone were excluded. We analyzed survival with Cox proportional hazard modeling.

Results: We identified 61 patients who received L-RT and 220 who received chemotherapy alone. At median follow-up of 11 months after diagnosis, median OS was 9 months (95% confidence interval [CI] 8-11) and 21 months (CI: 17-26) for patients receiving chemotherapy alone and L-RT, respectively. TRLF was the cause of death more often in the patients who received chemotherapy alone compared to those who received L-RT (82% vs. 47%; p = 0.001). On multivariable propensity score-matched analysis, associations with lower risk of death included duration of upfront chemotherapy (hazard ratio [HR] 0.82; p = 0.005) and receipt of L-RT (HR: 0.40; p = 0.002). The median OS from diagnosis for NCDB chemotherapy alone cohort was shorter than that of the institutional L-RT cohort (9 vs. 22 months; p < 0.001).

Conclusion: For M1 ICC, L-RT associated with a lower rate of death due to TRLF and longer OS versus those treated with chemotherapy alone. Prospective studies of L-RT in this setting are warranted.

引言:肿瘤相关肝功能衰竭(TRLF)是肝内胆管癌(ICC)患者最常见的死亡原因。尽管我们之前表明,局部晚期ICC的肝脏放射治疗(L-RT)与TRLF频率较低和总生存期(OS)较长有关,但L-RT在肝外转移性疾病(M1)患者中的作用仍不明确。我们试图比较接受L-RT和不接受L-RT治疗的M1 ICC患者的结果。方法:我们回顾了2010年至2021年间在一家机构接受L-RT的初步诊断时发现患有M1疾病的ICC患者,通过倾向评分将其与一个机构队列和一个国家癌症数据库(NCDB)队列进行匹配。L-RT的中位生物有效剂量为97.5Gy(四分位间距80.5-97.9Gy)。仅接受其他局部治疗或支持性护理的患者被排除在外。我们用Cox比例风险模型分析生存率。结果:我们确定了61名接受L-RT的患者和220名单独接受化疗的患者。在诊断后11个月的中位随访中,单独接受化疗和L-RT的患者的中位OS分别为9个月(95%置信区间[CI]8-11)和21个月(CI:17-26)。与接受L-RT的患者相比,单独接受化疗的患者中TRLF是更常见的死亡原因(82%对47%;p=0.001)。在多变量倾向评分匹配分析中,与较低死亡风险相关的因素包括前期化疗的持续时间(危险比[HR]0.82;p=0.005)和接受L-RT(HR:0.40;p=0.002)。仅NCDB化疗队列的中位OS诊断时间短于机构L-RT队列(9个月对22个月;p<0.001)。结论:对于M1 ICC,与单独化疗相比,L-RT与TRLF和较长OS导致的死亡率较低有关。在这种情况下对L-RT进行前瞻性研究是有必要的。
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引用次数: 0
Surveillance, Diagnosis, and Treatment Outcome of Hepatocellular Carcinoma in Japan: 2023 Update. 日本肝细胞癌的监测、诊断和治疗结果:2023 年更新。
IF 11.6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2023-03-09 eCollection Date: 2023-06-01 DOI: 10.1159/000530079
Masatoshi Kudo
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引用次数: 0
Albumin-Bilirubin Grade Analyses of Atezolizumab plus Bevacizumab versus Sorafenib in Patients with Unresectable Hepatocellular Carcinoma: A Post Hoc Analysis of the Phase III IMbrave150 Study. 阿替珠单抗联合贝伐单抗与索拉非尼治疗不可切除肝细胞癌患者的白蛋白-胆红素分级分析:IMbrave150 III期研究的事后分析。
IF 13.8 1区 医学 Q1 Medicine Pub Date : 2023-03-04 eCollection Date: 2023-10-01 DOI: 10.1159/000529996
Masatoshi Kudo, Richard S Finn, Ann-Lii Cheng, Andrew X Zhu, Michel Ducreux, Peter R Galle, Naoya Sakamoto, Naoya Kato, Michitaka Nakano, Jing Jia, Arndt Vogel

Introduction: Atezolizumab + bevacizumab showed survival benefit in patients with unresectable hepatocellular carcinoma (HCC) versus sorafenib in the Phase III IMbrave150 study. This exploratory analysis examined the prognostic impact of a baseline albumin-bilirubin (ALBI) score.

Methods: Patients with treatment-naïve unresectable HCC, ≥1 measurable untreated lesion, and Child-Pugh class A liver function were randomized 2:1 to receive atezolizumab 1,200 mg + bevacizumab 15 mg/kg every 3 weeks or sorafenib 400 mg twice daily. Overall survival (OS) and progression-free survival (PFS) were assessed in the intention-to-treat population by ALBI/modified (m)ALBI grade. Time to deterioration (TTD; defined as time to 0.5-point increase from the baseline ALBI score over 2 visits or death) of liver function and safety were investigated.

Results: Of 501 enrolled patients, 336 were randomized to receive atezolizumab + bevacizumab (ALBI grade [G] 1: n = 191; G2: n = 144 [mALBI G2a: n = 72, G2b: n = 72]; missing ALBI grade: n = 1) and 165 to sorafenib (ALBI G1: n = 87; G2: n = 78 [mALBI G2a: n = 37; G2b: n = 41]). Median follow-up was 15.6 months. OS and PFS improved with atezolizumab + bevacizumab versus sorafenib in patients with ALBI G1 (OS HR: 0.50 [95% CI: 0.35, 0.72]; PFS HR: 0.61 [95% CI: 0.45, 0.82]). In patients with ALBI G2 or mALBI G2a or G2b, PFS was numerically longer with atezolizumab + bevacizumab versus sorafenib, but no OS benefit was seen. Median TTD in the intention-to-treat population was 10.2 months (95% CI: 8.0, 11.0) with atezolizumab + bevacizumab versus 8.6 months (95% CI: 6.2, 11.8) with sorafenib (HR: 0.82 [95% CI: 0.65, 1.03]). Safety profiles of atezolizumab and bevacizumab were consistent with previous analyses, regardless of ALBI grade.

Conclusion: ALBI grade appeared to be prognostic for outcomes with both atezolizumab + bevacizumab and sorafenib treatment in patients with HCC. Atezolizumab + bevacizumab preserved liver function for a numerically longer duration than sorafenib.

引言:在IMbrave150 III期研究中,与索拉非尼相比,阿替佐利单抗+贝伐单抗在不可切除肝细胞癌(HCC)患者中显示出生存益处。这项探索性分析检查了基线白蛋白-胆红素(ALBI)评分对预后的影响。方法:将接受治疗的幼稚不可切除HCC、≥1个可测量的未经治疗的病变和Child-Pugh A级肝功能的患者以2:1随机分组,接受atezolizumab 1200 mg+贝伐单抗15 mg/kg,每3周一次或索拉非尼400 mg,每日两次。通过ALBI/改良(m)ALBI分级评估意向治疗人群的总生存率(OS)和无进展生存率(PFS)。研究了肝功能和安全性的恶化时间(TTD;定义为2次就诊或死亡后从基线ALBI评分增加0.5分的时间)。结果:在501名入选患者中,336名患者随机接受atezolizumab+bevacizumab治疗(ALBI分级[G]1:n=191;G2:n=144[mALBI G2a:n=72,G2b:n=72];缺失ALBI分级:n=1),165名患者接受索拉非尼治疗(ALBI G1:n=87;G2:n=78[mALBI G2a:n=37;G2b:n=41])。中位随访时间为15.6个月。在ALBI G1患者中,atezolizumab+bevacizumab与索拉非尼相比OS和PFS得到改善(OS HR:0.50[95%CI:0.35,0.72];PFS HR:0.61[95%CI:445,0.82])。在ALBI G2或mALBI G2a或G2b患者中,与索拉非尼相比,atezolazumab+贝伐单抗的PFS在数值上更长,但没有观察到OS益处。意向治疗人群中,atezolizumab+贝伐单抗的中位TTD为10.2个月(95%CI:8.0,11.0),而索拉非尼的中位TTP为8.6个月(95%CI:6.2,11.8)(HR:0.82[95%CI:0.65,1.03])。无论ALBI分级如何,atezolazumab和贝伐珠单抗的安全性与先前的分析一致。结论:ALBI分级似乎是atezolizumab+贝伐单抗和索拉非尼治疗HCC患者的预后。阿替佐利单抗+贝伐单抗比索拉非尼在数值上更长的时间内保持肝功能。
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引用次数: 1
Computed Tomography-Defined Sarcopenia in Outcomes of Patients with Unresectable Hepatocellular Carcinoma Undergoing Radioembolization: Assessment with Total Abdominal, Psoas, and Paraspinal Muscles. 计算机断层扫描确定的不可切除肝细胞癌患者接受放射栓塞治疗的结果中的肌肉减少:用腹部、腰肌和棘旁肌进行评估。
IF 13.8 1区 医学 Q1 Medicine Pub Date : 2023-02-23 eCollection Date: 2023-12-01 DOI: 10.1159/000529676
Chih-Horng Wu, Ming-Chih Ho, Chien-Hung Chen, Ja-Der Liang, Kai-Wen Huang, Mei-Fang Cheng, Chih-Kai Chang, Chia-Hung Chang, Po-Chin Liang

Introduction: Sarcopenia is an adverse prognostic factor in patients with liver cirrhosis and hepatocellular carcinoma (HCC). Image-based sarcopenia assessment allows a standardized method to assess abdominal skeletal muscle. However, which is an index muscle for sarcopenia remains unclear. Therefore, we investigated whether sarcopenia defined according to different muscle groups with computed tomography (CT) scans can predict the prognosis of HCC after radioembolization.

Methods: In this retrospective study, we analyzed patients who underwent radioembolization for unresectable HCC between January 2010 and December 2019. Before treatment, the total abdominal muscle (TAM), psoas muscle (PM), and paraspinal muscle (PS) areas were evaluated using a single CT slice at the third lumbar vertebra. In previous studies, sarcopenia was determined using the TAM, PM, and PS after stratifying by sex. Finally, we investigated each muscle-defined sarcopenia to decide whether or not it can serve as a prognostic factor for overall survival (OS).

Results: We included 92 patients (74 men and 18 women). TAM, PM, and PS areas were significantly higher in the men than in the women (all p < 0.05). The patients with sarcopenia defined using PM, but not TAM and PS, exhibited significantly poorer OS than those without sarcopenia (median 15.3 vs. 23.8 months, p = 0.034, 0.821, and 0.341, respectively). After adjustment for clinical variables, such as body mass index, liver function, alpha-fetoprotein level, clinical staging, treatment response, and posttreatment curative therapy, PM-defined sarcopenia (hazard ratio: 1.899, 95% confidence interval: 1.087-3.315) remained an independent predictor for the poor OS.

Conclusion: CT-assessed sarcopenia defined using PM was an independent prognostic factor for the poorer prognosis of unresectable HCC after radioembolization.

肌少症是肝硬化和肝细胞癌(HCC)患者的一个不良预后因素。基于图像的肌肉减少症评估允许一种标准化的方法来评估腹部骨骼肌。然而,哪块肌肉是肌肉减少症的指标仍不清楚。因此,我们研究了计算机断层扫描(CT)根据不同肌肉群定义的肌肉减少是否可以预测HCC放射栓塞后的预后。方法:在这项回顾性研究中,我们分析了2010年1月至2019年12月期间接受放射栓塞治疗不可切除HCC的患者。治疗前,在第三腰椎用单片CT评估总腹肌(TAM)、腰肌(PM)和棘旁肌(PS)区域。在以往的研究中,按性别分层后,使用TAM、PM和PS来确定肌肉减少症。最后,我们调查了每个肌肉定义的肌肉减少症,以确定它是否可以作为总生存期(OS)的预后因素。结果:纳入92例患者(男性74例,女性18例)。男性TAM、PM、PS区明显高于女性(均p < 0.05)。以PM而非TAM和PS定义的肌少症患者的OS明显低于无肌少症患者(中位15.3个月vs. 23.8个月,p分别= 0.034、0.821和0.341)。在调整了体重指数、肝功能、甲胎蛋白水平、临床分期、治疗反应和治疗后治疗等临床变量后,pm定义的肌肉减少症(风险比:1.899,95%可信区间:1.087-3.315)仍然是不良OS的独立预测因子。结论:ct评估肌少症是放射栓塞后不可切除HCC预后较差的独立预后因素。
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引用次数: 1
APPLE News 苹果公司的新闻
IF 13.8 1区 医学 Q1 Medicine Pub Date : 2023-02-17 DOI: 10.1159/000529383

Liver Cancer 2023;12:93–93
肝癌2023;12:93-93
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引用次数: 0
Pembrolizumab as Second-Line Therapy for Advanced Hepatocellular Carcinoma: Longer Term Follow-Up from the Phase 3 KEYNOTE-240 Trial. Pembrolizumab作为晚期肝癌的二线治疗:KEYNOTE-240 3期试验的长期随访。
IF 11.6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2023-02-14 eCollection Date: 2023-09-01 DOI: 10.1159/000529636
Philippe Merle, Masatoshi Kudo, Julien Edeline, Mohamed Bouattour, Ann-Lii Cheng, Stephen L Chan, Thomas Yau, Marcelo Garrido, Jennifer Knox, Bruno Daniele, Valeriy Breder, Ho Yeong Lim, Sadahisa Ogasawara, Stéphane Cattan, Yee Chao, Abby B Siegel, Iván Martinez-Forero, Ziwen Wei, Chih-Chin Liu, Richard S Finn

Introduction: KEYNOTE-240 showed a favorable benefit/risk profile for pembrolizumab versus placebo in patients with sorafenib-treated advanced hepatocellular carcinoma (HCC); however, prespecified statistical significance criteria for overall survival (OS) and progression-free survival (PFS) superiority were not met at the final analysis. Outcomes based on an additional 18 months of follow-up are reported.

Methods: Adults with sorafenib-treated advanced HCC were randomized 2:1 to pembrolizumab 200 mg intravenously every 3 weeks or placebo. Dual primary endpoints were OS and PFS assessed per RECIST v1.1 by blinded independent central review (BICR). Secondary endpoints included objective response rate (ORR), assessed per RECIST v1.1 by BICR, and safety.

Results: 413 patients were randomized (pembrolizumab, n = 278; placebo, n = 135). As of July 13, 2020, median (range) time from randomization to data cutoff was 39.6 (31.7-48.8) months for pembrolizumab and 39.8 (31.7-47.8) months for placebo. Estimated OS rates (95% CI) were 17.7% (13.4-22.5%) for pembrolizumab and 11.7% (6.8-17.9%) for placebo at 36 months. The estimated PFS rate (95% CI) for pembrolizumab was 8.9% (5.3-13.6%) and 0% for placebo at 36 months. ORR (95% CI) was 18.3% (14.0-23.4%) for pembrolizumab and 4.4% (1.6-9.4%) for placebo. Immune-mediated hepatitis events did not increase with follow-up. No viral hepatitis flare events were reported.

Conclusion: With extended follow-up, pembrolizumab continued to maintain improvement in OS and PFS and was associated with a consistent adverse event profile compared with placebo in patients with sorafenib-treated advanced HCC. Although KEYNOTE-240 did not meet prespecified statistical significance criteria at the final analysis, these results together with the antitumor activity of second-line pembrolizumab observed in KEYNOTE-224 and the statistically significant and clinically meaningful OS and PFS benefits of second-line pembrolizumab in patients from Asia observed in KEYNOTE-394 reinforce the clinical activity of pembrolizumab in previously treated patients with advanced HCC.

引言:KEYNOTE-240显示,在索拉非尼治疗的晚期肝细胞癌(HCC)患者中,pembrolizumab与安慰剂相比具有良好的获益/风险状况;然而,在最终分析中,未达到预先指定的总生存率(OS)和无进展生存率(PFS)优势的统计学显著性标准。报告了基于额外18个月随访的结果。方法:索拉非尼治疗晚期HCC的成年人以2:1的比例随机接受每3周静脉注射200 mg pembrolizumab或安慰剂。双主要终点是根据RECIST v1.1通过盲法独立中心评审(BICR)评估OS和PFS。次要终点包括BICR根据RECIST v1.1评估的客观有效率(ORR)和安全性。结果:413名患者被随机分组(pembrolizumab,n=278;安慰剂,n=135)。截至2020年7月13日,pembrolizumab从随机化到数据截止的中位(范围)时间为39.6(31.7-48.8)个月,安慰剂为39.8(31.7-47.8)个月。36个月时,pembrolizumab和安慰剂的估计OS发生率(95%CI)分别为17.7%(13.4-2.5%)和11.7%(6.8-17.9%)。36个月时,pembrolizumab的估计PFS率(95%CI)为8.9%(5.3-13.6%),安慰剂为0%。pembrolizumab的ORR(95%CI)为18.3%(14.0-23.4%),安慰剂为4.4%(1.6-9.4%)。免疫介导的肝炎事件没有随着随访而增加。未报告病毒性肝炎突发事件。结论:在索拉非尼治疗的晚期HCC患者中,随着随访时间的延长,pembrolizumab在OS和PFS方面继续保持改善,并且与安慰剂相比,不良事件发生率一致。尽管KEYNOTE-240在最终分析时不满足预先指定的统计学显著性标准,这些结果与KEYNOTE-224中观察到的二线pembrolizumab的抗肿瘤活性以及KEYNOTE-394中观察到在亚洲患者中二线pembrulizumab具有统计学意义和临床意义的OS和PFS益处一起,加强了pembrolizhumab在先前治疗的晚期HCC患者中的临床活性。
{"title":"Pembrolizumab as Second-Line Therapy for Advanced Hepatocellular Carcinoma: Longer Term Follow-Up from the Phase 3 KEYNOTE-240 Trial.","authors":"Philippe Merle, Masatoshi Kudo, Julien Edeline, Mohamed Bouattour, Ann-Lii Cheng, Stephen L Chan, Thomas Yau, Marcelo Garrido, Jennifer Knox, Bruno Daniele, Valeriy Breder, Ho Yeong Lim, Sadahisa Ogasawara, Stéphane Cattan, Yee Chao, Abby B Siegel, Iván Martinez-Forero, Ziwen Wei, Chih-Chin Liu, Richard S Finn","doi":"10.1159/000529636","DOIUrl":"10.1159/000529636","url":null,"abstract":"<p><strong>Introduction: </strong>KEYNOTE-240 showed a favorable benefit/risk profile for pembrolizumab versus placebo in patients with sorafenib-treated advanced hepatocellular carcinoma (HCC); however, prespecified statistical significance criteria for overall survival (OS) and progression-free survival (PFS) superiority were not met at the final analysis. Outcomes based on an additional 18 months of follow-up are reported.</p><p><strong>Methods: </strong>Adults with sorafenib-treated advanced HCC were randomized 2:1 to pembrolizumab 200 mg intravenously every 3 weeks or placebo. Dual primary endpoints were OS and PFS assessed per RECIST v1.1 by blinded independent central review (BICR). Secondary endpoints included objective response rate (ORR), assessed per RECIST v1.1 by BICR, and safety.</p><p><strong>Results: </strong>413 patients were randomized (pembrolizumab, <i>n</i> = 278; placebo, <i>n</i> = 135). As of July 13, 2020, median (range) time from randomization to data cutoff was 39.6 (31.7-48.8) months for pembrolizumab and 39.8 (31.7-47.8) months for placebo. Estimated OS rates (95% CI) were 17.7% (13.4-22.5%) for pembrolizumab and 11.7% (6.8-17.9%) for placebo at 36 months. The estimated PFS rate (95% CI) for pembrolizumab was 8.9% (5.3-13.6%) and 0% for placebo at 36 months. ORR (95% CI) was 18.3% (14.0-23.4%) for pembrolizumab and 4.4% (1.6-9.4%) for placebo. Immune-mediated hepatitis events did not increase with follow-up. No viral hepatitis flare events were reported.</p><p><strong>Conclusion: </strong>With extended follow-up, pembrolizumab continued to maintain improvement in OS and PFS and was associated with a consistent adverse event profile compared with placebo in patients with sorafenib-treated advanced HCC. Although KEYNOTE-240 did not meet prespecified statistical significance criteria at the final analysis, these results together with the antitumor activity of second-line pembrolizumab observed in KEYNOTE-224 and the statistically significant and clinically meaningful OS and PFS benefits of second-line pembrolizumab in patients from Asia observed in KEYNOTE-394 reinforce the clinical activity of pembrolizumab in previously treated patients with advanced HCC.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":null,"pages":null},"PeriodicalIF":11.6,"publicationDate":"2023-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10601873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71412863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impact of Intrahepatic External Beam Radiotherapy in Advanced Hepatocellular Carcinoma Patients Treated with Tyrosine Kinase Inhibitors. 肝内外束放射治疗对酪氨酸激酶抑制剂治疗的晚期肝癌患者的影响。
IF 13.8 1区 医学 Q1 Medicine Pub Date : 2023-02-10 eCollection Date: 2023-10-01 DOI: 10.1159/000529635
Myung Ji Goh, Hee Chul Park, Jeong Il Yu, Wonseok Kang, Geum-Youn Gwak, Yong-Han Paik, Joon Hyeok Lee, Kwang Cheol Koh, Seung Woon Paik, Dong Hyun Sinn, Moon Seok Choi

Introduction: We aimed to investigate whether concurrent use of intrahepatic external beam radiotherapy (EBRT) is a viable option for patients with advanced hepatocellular carcinoma (HCC) undergoing tyrosine kinase inhibitor (TKI) therapy.

Methods: A total of 453 patients with Barcelona Clinic Liver Cancer stage C (BCLC C) HCC, who started first-line treatment with TKI with intrahepatic EBRT (TKI + RT, n = 97) or TKI without intrahepatic EBRT (TKI, n = 356) were analyzed. The overall survival (OS) and progression-free survival (PFS) were compared in the overall cohort, patients who received at least 8 weeks of TKI treatment and a propensity score-matched cohort.

Results: OS and PFS were better in those treated with TKI + RT than TKI (8.6 vs. 4.4 months and 4.5 vs. 2.3 months, respectively, with p < 0.001). Of note, the TKI + RT group demonstrated significantly longer time to intrahepatic tumor progression. In subgroup analysis, TKI + RT led to better OS than TKI in all subgroups and PFS was significantly improved in patients without extrahepatic metastasis and those with portal vein invasion. There was no significant difference in treatment discontinuation due to adverse events between the TKI + RT and TKI groups (32.0% vs. 37.9%, p = 0.34). Furthermore, patients treated with TKI + RT showed better liver function preservation over time compared to TKI without intrahepatic EBRT. Comparable treatment outcomes were observed between patients who received at least 8 weeks of TKI treatment and the propensity score-matched cohort.

Conclusion: Concurrent intrahepatic EBRT targeting the liver and/or macrovascular invasion can be a viable option to improve outcomes of BCLC stage C patients receiving TKI therapy with an aim to control intrahepatic progression and preserving the liver function.

引言:我们旨在研究同时使用肝内外束放射治疗(EBRT)是否是接受酪氨酸激酶抑制剂(TKI)治疗的晚期肝细胞癌(HCC)患者的可行选择。方法:对453例巴塞罗那临床癌症C期(BCLC C)HCC患者进行分析,这些患者开始采用TKI加肝内EBRT(TKI+RT,n=97)或TKI不加肝内EBRT(TKI,n=356)的一线治疗。在整个队列、接受至少8周TKI治疗的患者和倾向评分匹配的队列中比较了总生存期(OS)和无进展生存期(PFS)。结果:TKI+RT组的OS和PFS优于TKI组(分别为8.6个月和4.4个月,4.5个月和2.3个月,p<0.001)。值得注意的是,TKI+RT组肝内肿瘤进展的时间明显更长。在亚组分析中,TKI+RT在所有亚组中的OS均优于TKI,并且在没有肝外转移和有门静脉浸润的患者中PFS显著改善。TKI+RT组和TKI组因不良事件而中断治疗的情况没有显著差异(32.0%对37.9%,p=0.34)。此外,与未进行肝内EBRT的TKI相比,TKI+RT治疗的患者随着时间的推移表现出更好的肝功能保存。在接受了至少8周TKI治疗的患者和倾向评分匹配的队列之间观察到了可比较的治疗结果。结论:同时靶向肝脏和/或大血管侵犯的肝内EBRT是改善接受TKI治疗的BCLC C期患者预后的可行选择,目的是控制肝内进展并保护肝功能。
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引用次数: 0
Association between Smoking Cessation and the Risk of Cholangiocarcinoma and Ampulla of Vater Cancer: A Nationwide Cohort Study. 戒烟与癌症胆管癌和壶腹部风险的相关性:一项全国性队列研究。
IF 13.8 1区 医学 Q1 Medicine Pub Date : 2023-02-09 eCollection Date: 2023-10-01 DOI: 10.1159/000529609
Joo-Hyun Park, Jung Yong Hong, Kyungdo Han

Introduction: The association between smoking cessation and intrahepatic and extrahepatic cholangiocarcinoma (iCCA and eCCA) risk is unclear. Furthermore, the association in individuals with preexisting risk factors is unknown. We aimed to investigate the association between smoking status (especially smoking cessation) and CCA risk according to individuals' glycemic status.

Methods: In this nationwide cohort study, 9,520,629 adults without cancer who underwent national health screening by the Korean National Health Insurance Service in 2009 were followed up through 2018. The hazard ratios (HRs) and 95% confidence intervals (CIs) for CCA were estimated after adjusting for potential confounders.

Results: During the 78.3 person-years of follow-up, 16,236 individuals were newly diagnosed with CCA. Quitters had a significantly lower risk of iCCA and eCCA compared to current smokers in all glycemic status groups (all p < 0.01). The HRs (95% CIs) for iCCA in current smokers and quitters were 1.33 (1.24-1.43) versus 0.98 (0.90-1.06) in individuals with normoglycemia, 1.49 (1.37-1.63) versus 1.17 (1.06-1.28) in individuals with prediabetes, and 2.15 (1.96-2.37) versus 1.58 (1.42-1.75) in individuals with diabetes, compared to never-smokers with normoglycemia. Current smokers with diabetes or prediabetes had a synergistically increased risk of iCCA (all p < 0.01). However, quitters with diabetes and prediabetes had an iCCA risk comparable to that of never-smokers. Analysis of eCCA yielded similar results. Smoking was not independently associated with the risk of the ampulla of Vater cancer. However, smoking combined with diabetes or prediabetes was associated with an increased risk of the ampulla of Vater cancer (all p < 0.05).

Conclusion: Smoking cessation was associated with a reduced risk of CCA, despite the synergistically increased risk in current smokers with diabetes and prediabetes. Our findings suggest a crucial opportunity to reduce the risk of CCA. More individualized and intensive cancer prevention education is needed against CCA.

引言:戒烟与肝内和肝外胆管癌(iCCA和eCCA)风险之间的关系尚不清楚。此外,与先前存在的风险因素相关的个体尚不清楚。我们旨在根据个体的血糖状况,调查吸烟状况(尤其是戒烟)与CCA风险之间的关系。方法:在这项全国性队列研究中,对2009年接受韩国国家健康保险服务局全国健康筛查的9520629名无癌症成年人进行了随访,直至2018年。CCA的危险比(HR)和95%置信区间(CI)是在调整潜在混杂因素后估计的。结果:在78.3人年的随访中,16236人被新诊断为CCA。在所有血糖状态组中,戒烟者患iCCA和eCCA的风险均显著低于当前吸烟者(均p<0.01)。当前吸烟者和戒烟者的iCCA的HR(95%CI)分别为1.33(1.24-1.43)和0.98(0.90-1.06),糖尿病前期患者为1.49(1.37-1.63)和1.17(1.06-1.28),糖尿病患者为2.15(1.96-2.37),而血糖正常的从不吸烟者为1.58(1.42-1.75)。目前患有糖尿病或糖尿病前期的吸烟者患iCCA的风险协同增加(均p<0.01)。然而,患有糖尿病和糖尿病前期的戒烟者患iCCA风险与从不吸烟者相当。eCCA的分析得出了类似的结果。吸烟与癌症壶腹部的风险并没有独立的相关性。然而,吸烟合并糖尿病或糖尿病前期与Vater癌症壶腹部风险增加相关(均p<0.05)。结论:尽管目前糖尿病和糖尿病前期吸烟者的风险协同增加,但戒烟与CCA风险降低相关。我们的研究结果为降低CCA风险提供了一个重要的机会。需要针对CCA进行更个性化和强化的癌症预防教育。
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引用次数: 0
Achievement of Complete Response and Drug-Free Status by Atezolizumab plus Bevacizumab Combined with or without Curative Conversion in Patients with Transarterial Chemoembolization-Unsuitable, Intermediate-Stage Hepatocellular Carcinoma: A Multicenter Proof-Of-Concept Study. Atezolizumab联合贝伐单抗联合或不联合治疗动脉化疗栓塞不合适的中晚期肝癌患者实现完全缓解和无药物状态:一项多中心概念验证研究。
IF 13.8 1区 医学 Q1 Medicine Pub Date : 2023-02-07 eCollection Date: 2023-09-01 DOI: 10.1159/000529574
Masatoshi Kudo, Tomoko Aoki, Kazuomi Ueshima, Kaoru Tsuchiya, Masahiro Morita, Hirokazu Chishina, Masahiro Takita, Satoru Hagiwara, Yasunori Minami, Hiroshi Ida, Naoshi Nishida, Chikara Ogawa, Tetsu Tomonari, Noriaki Nakamura, Hidekatsu Kuroda, Atsushi Takebe, Yoshifumi Takeyama, Masaaki Hidaka, Susumu Eguchi, Stephen L Chan, Masayuki Kurosaki, Namiki Izumi

Introduction: Atezolizumab plus bevacizumab therapy is extremely effective in the treatment of intermediate-stage hepatocellular carcinoma (HCC), with a response rate of 44%, as reported in the IMbrave150 trial. When tumor shrinkage is obtained, achieving complete response (CR) is possible in many cases using curative conversion with resection, ablation, or superselective transarterial chemoembolization (TACE) with curative intent. This concept, i.e., curative conversion by combining systemic therapy and locoregional therapy, has not been reported before. This multicenter proof-of-concept study was conducted to show the value of curative conversion in immunotherapy-treated intermediate-stage HCC meeting TACE-unsuitable criteria.

Methods: This study included 110 consecutive Child-Pugh A patients who received atezolizumab plus bevacizumab as first-line treatment for unresectable and TACE-unsuitable intermediate-stage HCC at seven centers in Japan. CR rate, drug-free rate, time to CR, change in liver function, efficacy in positron emission tomography (PET)-positive HCC, progression-free survival (PFS), and overall survival (OS) were assessed in patients who achieved CR using resection, ablation, superselective TACE with curative intent following atezolizumab plus bevacizumab or atezolizumab plus bevacizumab alone.

Results: Clinical or pathological CR was achieved in 38 patients (35%) (median observation period: 21.2 months). The modalities of curative conversion in 35 patients were as follows: resection, 7; ablation, 13; and superselective TACE, 15. Three patients achieved clinical CR with atezolizumab plus bevacizumab therapy alone. Among the 38 CR patients, 25 achieved drug-free status. PFS was not reached, and 3 patients experienced recurrence after reaching CR. Regarding OS, there were no deaths in any of the CR patients. The albumin-bilirubin score did not deteriorate after locoregional therapy or resection. Of seven PET-positive patients who achieved CR with atezolizumab plus bevacizumab followed by curative conversion, five achieved drug-free status.

Conclusion: The achievement of CR rate by curative conversion in patients treated with atezolizumab plus bevacizumab as the preceding therapy for unresectable and TACE-unsuitable intermediate-stage HCC was 35%. Overall, 23% of patients achieved drug-free status and no recurrence was observed from this patient subgroup with CR and drug-free status. Thus, achieving CR and/or drug-free status should be a therapeutic goal for patients with intermediate-stage HCC without vascular invasion or extrahepatic spread.

引言:据IMbrave150试验报道,阿替佐利单抗联合贝伐单抗治疗中期肝细胞癌(HCC)非常有效,有效率为44%。当肿瘤缩小时,在许多情况下,通过切除、消融或具有治疗目的的超选择性动脉化疗栓塞(TACE)进行治疗转换,可以实现完全缓解(CR)。这一概念,即通过联合全身治疗和局部治疗的治疗转化,以前没有报道过。这项多中心概念验证研究旨在显示符合TACE不合适标准的免疫疗法治疗中期HCC的疗效转化价值。方法:本研究纳入了110名连续的Child-Pugh A患者,他们在日本的7个中心接受atezolizumab联合贝伐单抗作为不可切除和TACE不适用的中期HCC的一线治疗。评估了在atezolizumab联合贝伐单抗或atezolizimab联合贝伐单抗单独治疗后,通过切除、消融、超选择性TACE达到CR的患者的CR率、无药率、CR时间、肝功能变化、正电子发射断层扫描(PET)阳性HCC的疗效、无进展生存期(PFS)和总生存期(OS)。结果:38例患者(35%)获得临床或病理CR(中位观察期21.2个月)。35例患者的疗效转换方式如下:切除7例;消融,13;和超选择性TACE,15。三名患者通过atezolizumab联合贝伐单抗单独治疗获得临床CR。在38名CR患者中,25名患者达到了无药物状态。未达到PFS,3名患者在达到CR后出现复发。关于OS,任何CR患者均未死亡。白蛋白-胆红素评分在局部治疗或切除后没有恶化。在7名PET阳性患者中,有5名患者在atezolizumab联合贝伐单抗治疗后获得CR,随后进行了治疗转换,其中5名患者获得了无药物状态。结论:atezolizumab联合贝伐单抗作为不可切除和TACE不适用的中期HCC的前一种治疗方法,通过疗效转化的患者CR率为35%。总体而言,23%的患者达到了无药物状态,在CR和无药物状态的患者亚组中没有观察到复发。因此,对于没有血管侵犯或肝外扩散的中期HCC患者,实现CR和/或无药物状态应该是一个治疗目标。
{"title":"Achievement of Complete Response and Drug-Free Status by Atezolizumab plus Bevacizumab Combined with or without Curative Conversion in Patients with Transarterial Chemoembolization-Unsuitable, Intermediate-Stage Hepatocellular Carcinoma: A Multicenter Proof-Of-Concept Study.","authors":"Masatoshi Kudo,&nbsp;Tomoko Aoki,&nbsp;Kazuomi Ueshima,&nbsp;Kaoru Tsuchiya,&nbsp;Masahiro Morita,&nbsp;Hirokazu Chishina,&nbsp;Masahiro Takita,&nbsp;Satoru Hagiwara,&nbsp;Yasunori Minami,&nbsp;Hiroshi Ida,&nbsp;Naoshi Nishida,&nbsp;Chikara Ogawa,&nbsp;Tetsu Tomonari,&nbsp;Noriaki Nakamura,&nbsp;Hidekatsu Kuroda,&nbsp;Atsushi Takebe,&nbsp;Yoshifumi Takeyama,&nbsp;Masaaki Hidaka,&nbsp;Susumu Eguchi,&nbsp;Stephen L Chan,&nbsp;Masayuki Kurosaki,&nbsp;Namiki Izumi","doi":"10.1159/000529574","DOIUrl":"https://doi.org/10.1159/000529574","url":null,"abstract":"<p><strong>Introduction: </strong>Atezolizumab plus bevacizumab therapy is extremely effective in the treatment of intermediate-stage hepatocellular carcinoma (HCC), with a response rate of 44%, as reported in the IMbrave150 trial. When tumor shrinkage is obtained, achieving complete response (CR) is possible in many cases using curative conversion with resection, ablation, or superselective transarterial chemoembolization (TACE) with curative intent. This concept, i.e., curative conversion by combining systemic therapy and locoregional therapy, has not been reported before. This multicenter proof-of-concept study was conducted to show the value of curative conversion in immunotherapy-treated intermediate-stage HCC meeting TACE-unsuitable criteria.</p><p><strong>Methods: </strong>This study included 110 consecutive Child-Pugh A patients who received atezolizumab plus bevacizumab as first-line treatment for unresectable and TACE-unsuitable intermediate-stage HCC at seven centers in Japan. CR rate, drug-free rate, time to CR, change in liver function, efficacy in positron emission tomography (PET)-positive HCC, progression-free survival (PFS), and overall survival (OS) were assessed in patients who achieved CR using resection, ablation, superselective TACE with curative intent following atezolizumab plus bevacizumab or atezolizumab plus bevacizumab alone.</p><p><strong>Results: </strong>Clinical or pathological CR was achieved in 38 patients (35%) (median observation period: 21.2 months). The modalities of curative conversion in 35 patients were as follows: resection, 7; ablation, 13; and superselective TACE, 15. Three patients achieved clinical CR with atezolizumab plus bevacizumab therapy alone. Among the 38 CR patients, 25 achieved drug-free status. PFS was not reached, and 3 patients experienced recurrence after reaching CR. Regarding OS, there were no deaths in any of the CR patients. The albumin-bilirubin score did not deteriorate after locoregional therapy or resection. Of seven PET-positive patients who achieved CR with atezolizumab plus bevacizumab followed by curative conversion, five achieved drug-free status.</p><p><strong>Conclusion: </strong>The achievement of CR rate by curative conversion in patients treated with atezolizumab plus bevacizumab as the preceding therapy for unresectable and TACE-unsuitable intermediate-stage HCC was 35%. Overall, 23% of patients achieved drug-free status and no recurrence was observed from this patient subgroup with CR and drug-free status. Thus, achieving CR and/or drug-free status should be a therapeutic goal for patients with intermediate-stage HCC without vascular invasion or extrahepatic spread.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2023-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10603621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71412860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 5
Surgical Outcomes of Laparoscopic versus Open Hepatectomy for Left Hepatocellular Carcinoma: Propensity Score Analyses Using Retrospective Japanese and Korean Individual Patient Data. 腹腔镜与开放式肝切除术治疗左肝细胞癌的手术结果:使用回顾性日本和韩国个体患者数据的倾向评分分析。
IF 13.8 1区 医学 Q1 Medicine Pub Date : 2023-02-01 DOI: 10.1159/000527294
Masaki Kaibori, Kengo Yoshii, Yuzo Umeda, Takahito Yagi, Takehiro Okabayashi, Kenta Sui, Akira Mori, Yuhei Hamaguchi, Kiyoshi Kajiyama, Daisuke Hokuto, Kazuteru Monden, Tomoharu Yoshizumi, Yoriko Nomura, Kan Toriguchi, Jong Man Kim, Gi Hong Choi, Je Ho Ryu, Yangseok Koh, Koo Jeong Kang, Young Kyoung You, Kwang-Sik Chun, Young Seok Han, Chan Woo Cho, Young Il Choi, Dong-Sik Kim, Jae Do Yang, Keita Mori, Atsushi Hiraoka, Hiroki Yamaue, Masafumi Nakamura, Masakazu Yamamoto, Itaru Endo

Introduction: This study aimed to compare the prognostic impact of laparoscopic left hepatectomy (LLH) with that of open left hepatectomy (OLH) on patient survival after resection of left hepatocellular carcinoma (HCC).

Methods: Among the 953 patients who received initial treatment for primary HCC that was resectable by either LLH or OLH from 2013 to 2017 in Japan and Korea, 146 patients underwent LLH and 807 underwent OLH. The inverse probability of treatment weighting approach based on propensity scoring was used to address the potential selection bias inherent in the recurrence and survival outcomes between the LLH and OLH groups.

Results: The occurrence rate of postoperative complications and hepatic decompensation was significantly lower in the LLH group than in the OLH group. Recurrence-free survival (RFS) was better in the LLH group than in the OLH group (hazard ratio, 1.33; 95% confidence interval, 1.03-1.71; p = 0.029), whereas overall survival (OS) was not significantly different. Subgroup analyses of RFS and OS revealed an almost consistent trend in favor of LLH over OLH. In patients with tumor sizes of ≥4.0 cm or those with single tumors, both RFS and OS were significantly better in the LLH group than in the OLH group.

Conclusions: LLH decreases the risk of tumor recurrence and improves OS in patients with primary HCC located in the left liver.

前言:本研究旨在比较腹腔镜左肝切除术(LLH)与开放式左肝切除术(OLH)对左肝细胞癌(HCC)切除术后患者生存率的影响。方法:2013年至2017年,日本和韩国953例接受LLH或OLH可切除的原发性HCC初始治疗患者中,146例患者接受LLH, 807例患者接受OLH。基于倾向评分的治疗加权逆概率方法用于解决LLH组和OLH组之间复发和生存结果中固有的潜在选择偏倚。结果:LLH组术后并发症及肝功能失代偿发生率明显低于OLH组。LLH组无复发生存期(RFS)优于OLH组(风险比,1.33;95%置信区间为1.03-1.71;p = 0.029),而总生存期(OS)无显著差异。RFS和OS的亚组分析显示LLH优于OLH的趋势几乎一致。在肿瘤大小≥4.0 cm或单一肿瘤患者中,LLH组的RFS和OS均显著优于OLH组。结论:左肝原发性HCC患者行LLH可降低肿瘤复发风险,改善OS。
{"title":"Surgical Outcomes of Laparoscopic versus Open Hepatectomy for Left Hepatocellular Carcinoma: Propensity Score Analyses Using Retrospective Japanese and Korean Individual Patient Data.","authors":"Masaki Kaibori,&nbsp;Kengo Yoshii,&nbsp;Yuzo Umeda,&nbsp;Takahito Yagi,&nbsp;Takehiro Okabayashi,&nbsp;Kenta Sui,&nbsp;Akira Mori,&nbsp;Yuhei Hamaguchi,&nbsp;Kiyoshi Kajiyama,&nbsp;Daisuke Hokuto,&nbsp;Kazuteru Monden,&nbsp;Tomoharu Yoshizumi,&nbsp;Yoriko Nomura,&nbsp;Kan Toriguchi,&nbsp;Jong Man Kim,&nbsp;Gi Hong Choi,&nbsp;Je Ho Ryu,&nbsp;Yangseok Koh,&nbsp;Koo Jeong Kang,&nbsp;Young Kyoung You,&nbsp;Kwang-Sik Chun,&nbsp;Young Seok Han,&nbsp;Chan Woo Cho,&nbsp;Young Il Choi,&nbsp;Dong-Sik Kim,&nbsp;Jae Do Yang,&nbsp;Keita Mori,&nbsp;Atsushi Hiraoka,&nbsp;Hiroki Yamaue,&nbsp;Masafumi Nakamura,&nbsp;Masakazu Yamamoto,&nbsp;Itaru Endo","doi":"10.1159/000527294","DOIUrl":"https://doi.org/10.1159/000527294","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to compare the prognostic impact of laparoscopic left hepatectomy (LLH) with that of open left hepatectomy (OLH) on patient survival after resection of left hepatocellular carcinoma (HCC).</p><p><strong>Methods: </strong>Among the 953 patients who received initial treatment for primary HCC that was resectable by either LLH or OLH from 2013 to 2017 in Japan and Korea, 146 patients underwent LLH and 807 underwent OLH. The inverse probability of treatment weighting approach based on propensity scoring was used to address the potential selection bias inherent in the recurrence and survival outcomes between the LLH and OLH groups.</p><p><strong>Results: </strong>The occurrence rate of postoperative complications and hepatic decompensation was significantly lower in the LLH group than in the OLH group. Recurrence-free survival (RFS) was better in the LLH group than in the OLH group (hazard ratio, 1.33; 95% confidence interval, 1.03-1.71; <i>p</i> = 0.029), whereas overall survival (OS) was not significantly different. Subgroup analyses of RFS and OS revealed an almost consistent trend in favor of LLH over OLH. In patients with tumor sizes of ≥4.0 cm or those with single tumors, both RFS and OS were significantly better in the LLH group than in the OLH group.</p><p><strong>Conclusions: </strong>LLH decreases the risk of tumor recurrence and improves OS in patients with primary HCC located in the left liver.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/af/e1/lic-0012-0032.PMC9982339.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10847172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
期刊
Liver Cancer
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