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Imaging Diagnosis of Various Hepatocellular Carcinoma Subtypes and Its Hypervascular Mimics: Differential Diagnosis Based on Conventional Interpretation and Artificial Intelligence. 各种肝细胞癌亚型及其高血管模拟的影像学诊断:基于传统解释和人工智能的鉴别诊断。
IF 13.8 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2023-06-01 DOI: 10.1159/000528538
Yasunori Minami, Naoshi Nishida, Masatoshi Kudo

Background: Hepatocellular carcinoma (HCC) is unique among malignancies, and its characteristics on contrast imaging modalities allow for a highly accurate diagnosis. The radiological differentiation of focal liver lesions is playing an increasingly important role, and the Liver Imaging Reporting and Data System adopts a combination of major features including arterial phase hyper-enhancement (APHE) and the washout pattern.

Summary: Specific HCCs such as well or poorly differentiated type, subtypes including fibrolamellar or sarcomatoid and combined hepatocellular-cholangiocarcinoma do not often demonstrate APHE and washout appearance. Meanwhile, hypervascular liver metastases and hypervascular intrahepatic cholangiocarcinoma can demonstrate APHE and washout. There are still other hypervascular malignant liver tumors (i.e., angiosarcoma, epithelioid hemangioendothelioma) and hypervascular benign liver lesions (i.e., adenoma, focal nodular hyperplasia, angiomyolipoma, flash filling hemangioma, reactive lymphoid hyperplasia, inflammatory lesion, arterioportal shunt), which need to be distinguished from HCC. When a patient has chronic liver disease, differential diagnosis of hypervascular liver lesions can be even more complicated. Meanwhile, artificial intelligence (AI) in medicine has been widely explored, and recent advancement in the field of deep learning has provided promising performance for the analysis of medical images, especially radiological imaging data contain diagnostic, prognostic, and predictive information which AI can extract. The AI research studies have demonstrated high accuracy (over 90% accuracy) for classifying lesions with typical imaging features from some hepatic lesions. The AI system has a potential to be implemented in clinical routine as decision support tools. However, for the differential diagnosis of many types of hypervascular liver lesions, further large-scale clinical validation is still required.

Key messages: Clinicians should be aware of the histopathological features, imaging characteristics, and differential diagnoses of hypervascular liver lesions to a precise diagnosis and more valuable treatment plan. We need to be familiar with such atypical cases to prevent a diagnostic delay, but AI-based tools also need to learn a large number of typical and atypical cases.

背景:肝细胞癌(HCC)在恶性肿瘤中是独特的,其在对比成像模式上的特点允许高度准确的诊断。肝局灶性病变的影像学鉴别越来越重要,肝脏影像学报告和数据系统采用动脉期超增强(APHE)和洗脱模式等主要特征相结合。摘要:特异性hcc,如高分化型或低分化型,亚型包括纤维板层或肉瘤样和合并肝细胞-胆管癌,通常不表现出APHE和冲洗样表现。同时,高血管性肝转移和高血管性肝内胆管癌可表现为APHE和冲洗。还有其他高血管恶性肝肿瘤(如血管肉瘤、上皮样血管内皮瘤)和肝脏高血管良性病变(如腺瘤、局灶性结节增生、血管平滑肌脂肪瘤、闪充性血管瘤、反应性淋巴样增生、炎性病变、动脉门静脉分流),需要与HCC区分。当患者患有慢性肝病时,对高血管性肝脏病变的鉴别诊断可能更加复杂。与此同时,人工智能(AI)在医学领域得到了广泛的探索,深度学习领域的最新进展为医学图像的分析提供了很好的表现,特别是放射成像数据中包含AI可以提取的诊断、预后和预测信息。人工智能研究表明,对某些肝脏病变具有典型影像学特征的病变进行分类,准确率高达90%以上。人工智能系统有可能作为决策支持工具在临床常规中实施。然而,对于许多类型的肝高血管病变的鉴别诊断,仍需要进一步的大规模临床验证。关键信息:临床医生应了解肝脏高血管病变的组织病理特征、影像学特征和鉴别诊断,以便准确诊断和制定更有价值的治疗方案。我们需要熟悉这些非典型病例,以防止诊断延误,但基于人工智能的工具也需要学习大量的典型和非典型病例。
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引用次数: 2
Phase 2 Study of the PD-1 Inhibitor Serplulimab plus the Bevacizumab Biosimilar HLX04 in Patients with Previously Treated Advanced Hepatocellular Carcinoma. PD-1抑制剂Serplulimab和贝伐单抗生物类似药HLX04在既往治疗的晚期肝细胞癌患者中的2期研究
IF 13.8 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2023-06-01 DOI: 10.1159/000526638
Zhenggang Ren, Guoliang Shao, Jie Shen, Li Zhang, Xu Zhu, Weijia Fang, Guoping Sun, Yuxian Bai, Jianbing Wu, Lianxin Liu, Yuan Yuan, Jingdong Zhang, Zhen Li, Ling Zhang, Tao Yin, Jincai Wu, Xiaoli Hou, Qingyu Wang, Jun Zhu, Jia Fan

Introduction: Current treatments for patients with previously treated advanced hepatocellular carcinoma (HCC) provide modest survival benefits. We evaluated the safety and antitumor activity of serplulimab, an anti-PD-1 antibody, plus the bevacizumab biosimilar HLX04 in this patient population.

Methods: In this open-label, multicenter, phase 2 study in China, patients with advanced HCC who failed prior systemic therapy received serplulimab 3 mg/kg plus HLX04 5 mg/kg (group A) or 10 mg/kg (group B) intravenously every 2 weeks. The primary endpoint was safety.

Results: As of April 8, 2021, 20 and 21 patients were enrolled into groups A and B, and they had received a median of 7 and 11 treatment cycles, respectively. Grade ≥3 treatment-emergent adverse events were reported by 14 (70.0%) patients in group A and 12 (57.1%) in group B. Most immune-related adverse events were grade ≤3. The objective response rate was 30.0% (95% confidence interval [CI], 11.9-54.3) in group A and 14.3% (95% CI, 3.0-36.3) in group B. Median duration of response was not reached (95% CI, 3.3-not evaluable [NE]) in group A and was 9.0 months (95% CI, 7.9-NE) in group B. Median progression-free survival was 2.2 months (95% CI, 1.4-5.5) and 4.1 months (95% CI, 1.5-NE), and median overall survival was 11.6 months (95% CI, 6.4-NE) and 14.3 months (95% CI, 8.2-NE) in groups A and B, respectively.

Conclusion: Serplulimab plus HLX04 showed a manageable safety profile and promising antitumor activity in patients with previously treated advanced HCC.

目前的治疗方法对先前治疗过的晚期肝细胞癌(HCC)患者提供了适度的生存益处。我们在该患者群体中评估了serplulimab(一种抗pd -1抗体)和贝伐单抗生物类似药HLX04的安全性和抗肿瘤活性。方法:在中国进行的这项开放标签、多中心、2期研究中,既往全身治疗失败的晚期HCC患者每2周静脉注射serpluliumab 3mg /kg + HLX04 5mg /kg (A组)或10mg /kg (B组)。主要终点是安全性。结果:截至2021年4月8日,A组20例,B组21例,中位治疗周期分别为7个和11个。A组14例(70.0%)和b组12例(57.1%)报告了≥3级治疗后出现的不良事件。大多数免疫相关不良事件≤3级。客观反应率为30.0%(95%可信区间(CI), 11.9 - -54.3)在A组和14.3%(95%可信区间,3.0 - -36.3)在B组平均响应时间没有达到(95% CI, 3.3——可评价的[不])在A组为9.0个月(95% CI, 7.9 - NE)在B组中位无进展生存期是2.2个月(95% CI, 1.4 - -5.5)和4.1个月(95% CI, 1.5 - NE),中位总生存期是11.6个月和14.3个月(95% CI, 6.4 - NE)和(95% CI, 8.2 - NE)在A和B组,分别。结论:Serplulimab联合HLX04在先前治疗过的晚期HCC患者中显示出可控的安全性和有希望的抗肿瘤活性。
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引用次数: 2
Low Baseline CXCL9 Predicts Early Progressive Disease in Unresectable HCC with Atezolizumab Plus Bevacizumab Treatment. 低基线CXCL9预测阿特唑单抗加贝伐单抗治疗不可切除HCC的早期进展性疾病
IF 13.8 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2023-06-01 DOI: 10.1159/000527759
Shunichi Hosoda, Goki Suda, Takuya Sho, Koji Ogawa, Megumi Kimura, Zijian Yang, Sonoe Yoshida, Akinori Kubo, Yoshimasa Tokuchi, Takashi Kitagataya, Osamu Maehara, Shunsuke Ohnishi, Akihisa Nakamura, Ren Yamada, Masatsugu Ohara, Naoki Kawagishi, Mitsuteru Natsuizaka, Masato Nakai, Kenichi Morikawa, Ken Furuya, Masaru Baba, Yoshiya Yamamoto, Kazuharu Suzuki, Takaaki Izumi, Takashi Meguro, Katsumi Terashita, Jun Ito, Takuto Miyagishima, Naoya Sakamoto

Introduction: Atezolizumab plus bevacizumab treatment is highly effective in patients with unresectable hepatocellular carcinoma (HCC). However, progressive disease (PD) occurs in approximately 20% of HCC patients treated with atezolizumab plus bevacizumab, resulting in a poor prognosis. Thus, the prediction and early detection of HCC is crucial.

Methods: Patients with unresectable HCC treated with atezolizumab plus bevacizumab and had baseline preserved serum (n = 68) were screened and classified according to their PD, 6 weeks after treatment initiation (early PD; n = 13). Of these, 4 patients each with and without early PD were selected for cytokine array and genetic analyses. The identified factors were validated in the validated cohort (n = 60) and evaluated in patients treated with lenvatinib.

Results: No significant differences were observed in the genetic alterations in circulating tumor DNA. Cytokine array data revealed that baseline MIG (CXCL9), ENA-78, and RANTES differed substantially between patients with and without early PD. Subsequent analysis in the validation cohort revealed that baseline CXCL9 was significantly lower in patients with early PD than that in patients without early PD, and the best cut-off value of serum CXCL9 to predict early PD was 333 pg/mL (sensitivity: 0.600, specificity: 0.923, AUC = 0.75). In patients with lower serum CXCL9 (<333 pg/mL), 35.3% (12/34) experienced early PD with atezolizumab plus bevacizumab, while progression-free survival (PFS) was significantly shorter relative to that in patients without (median PFS, 126 days vs. 227 days; HR: 2.41, 95% CI: 1.22-4.80, p = 0.0084). While patients with objective response to lenvatinib had significantly lower CXCL9 levels compared with those of patients without.

Conclusion: Baseline low serum CXCL9 (<333 pg/mL) levels may predict early PD in patients with unresectable HCC treated with atezolizumab plus bevacizumab.

简介:Atezolizumab联合贝伐单抗治疗对不可切除的肝细胞癌(HCC)患者非常有效。然而,在阿特唑单抗加贝伐单抗治疗的HCC患者中,大约20%的患者会出现进行性疾病(PD),导致预后不良。因此,HCC的预测和早期发现是至关重要的。方法:用阿特唑单抗联合贝伐单抗治疗的不可切除HCC患者,基线保存血清(n = 68),在治疗开始后6周(早期PD;N = 13)。选取4例早期PD患者(不论有无早期PD)进行细胞因子测序和基因分析。在已验证的队列(n = 60)中验证了确定的因素,并在lenvatinib治疗的患者中进行了评估。结果:循环肿瘤DNA的遗传改变无显著性差异。细胞因子阵列数据显示,基线MIG (CXCL9)、ENA-78和RANTES在早期PD患者和非早期PD患者之间存在显著差异。验证队列的后续分析显示,早期PD患者的基线CXCL9明显低于无早期PD患者,血清CXCL9预测早期PD的最佳临界值为333 pg/mL(敏感性:0.600,特异性:0.923,AUC = 0.75)。血清CXCL9较低的患者(p = 0.0084)。而对lenvatinib有客观反应的患者与无客观反应的患者相比,CXCL9水平显著降低。结论:基线低血清CXCL9 (
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引用次数: 4
Long-Term Regression after Discontinuation of Regorafenib Administered for Sorafenib-Refractory Hepatocellular Carcinoma. 停止瑞非尼治疗索拉非尼难治性肝细胞癌后的长期回归。
IF 13.8 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2023-06-01 DOI: 10.1159/000529139
Heewon Bae, Je Ryung Gil, Moon Hyung Lee, Taekyu Lim
A patient with hepatocellular carcinoma(HCC) staged Barcelona Clinic for Liver Cancer stage B started chemotherapy because of intrahepatic recurrence after hepatic segmentectomy. Regorafenib was started as a second-line treatment due to refractory to sorafenib treatment, but was discontinued after 26 months due to side effects. After two years of follow-up, the patients achieved unexpected long-term regression. We present the potential of regorafenib effect for anti-tumor immunity through possible pharmacological mechanisms.
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引用次数: 1
Regorafenib versus Cabozantinib as a Second-Line Treatment for Advanced Hepatocellular Carcinoma: An Anchored Matching-Adjusted Indirect Comparison of Efficacy and Safety. 瑞非尼与卡博赞替尼作为晚期肝细胞癌的二线治疗:锚定匹配调整后的疗效和安全性的间接比较
IF 13.8 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2023-06-01 DOI: 10.1159/000527403
Philippe Merle, Masatoshi Kudo, Stanimira Krotneva, Kirhan Ozgurdal, Yun Su, Irina Proskorovsky

Introduction: The tyrosine kinase inhibitors regorafenib and cabozantinib remain the mainstay in second-line treatment of advanced hepatocellular carcinoma (HCC). There is currently no clear evidence of superiority in efficacy or safety to guide choice between the two treatments.

Methods: We conducted an anchored matching-adjusted indirect comparison using individual patient data from the RESORCE trial of regorafenib and published aggregate data from the CELESTIAL trial of cabozantinib. Second-line HCC patients with prior sorafenib exposure of ≥3 months were included in the analyses. Hazard ratios (HRs) and restricted mean survival time (RMST) were estimated to quantify differences in overall survival (OS) and progression-free survival (PFS). Safety outcomes compared were rates of grade 3 or 4 adverse events (AEs), occurring in >10% of patients, and discontinuation or dose reduction due to treatment-related AEs.

Results: After matching adjustment for differences in baseline patient characteristics, regorafenib showed a favorable OS (HR, 0.80; 95% CI: 0.54, 1.20) and ∼3-month-longer RMST over cabozantinib (RMST difference, 2.76 months; 95% CI: -1.03, 6.54), although not statistically significant. For PFS, there was no numerical difference in HR (HR, 1.00; 95% CI: 0.68, 1.49) and no clinically meaningful difference based on RMST analyses (RMST difference, -0.59 months; 95% CI: -1.83, 0.65). Regorafenib showed a significantly lower incidence of discontinuation (risk difference, -9.2%; 95% CI: -17.7%, -0.6%) and dose reductions (-15.2%; 95% CI: -29.0%, -1.5%) due to treatment-related AEs (any grade). Regorafenib was also associated with a lower incidence (not statistically significant) of grade 3 or 4 diarrhea (risk difference, -7.1%; 95% CI: -14.7%, 0.4%) and fatigue (-6.3%; 95% CI: -14.6%, 2.0%).

Conclusion: This indirect treatment comparison suggests, relative to cabozantinib, that regorafenib could be associated with favorable OS (not statistically significant), lower rates of dose reductions and discontinuation due to treatment-related AEs, and lower rates of severe diarrhea and fatigue.

简介:酪氨酸激酶抑制剂瑞戈非尼和卡博赞替尼仍然是晚期肝细胞癌(HCC)二线治疗的主要药物。目前还没有明确的证据表明这两种治疗方法在疗效或安全性上有优势。方法:我们使用来自reorafenib的resce试验的个体患者数据和来自cabozantinib的CELESTIAL试验的汇总数据进行了锚定匹配调整的间接比较。先前索拉非尼暴露≥3个月的二线HCC患者被纳入分析。评估风险比(hr)和限制平均生存时间(RMST)以量化总生存期(OS)和无进展生存期(PFS)的差异。比较的安全性结果是3级或4级不良事件(ae)的发生率,发生在>10%的患者中,以及由于治疗相关的ae而停药或减少剂量。结果:在对基线患者特征差异进行匹配调整后,瑞非尼显示出良好的OS (HR, 0.80;95% CI: 0.54, 1.20)和比卡博赞替尼更长3个月的RMST (RMST差异,2.76个月;95% CI: -1.03, 6.54),但无统计学意义。对于PFS, HR没有数值差异(HR, 1.00;95% CI: 0.68, 1.49),基于RMST分析无临床意义差异(RMST差异,-0.59个月;95% ci: -1.83, 0.65)。瑞非尼的停药发生率显著降低(风险差-9.2%;95% CI: -17.7%, -0.6%)和剂量减少(-15.2%;95% CI: -29.0%, -1.5%),原因是与治疗相关的ae(任何级别)。瑞非尼还与3级或4级腹泻发生率较低相关(无统计学意义)(风险差异为-7.1%;95% CI: -14.7%, 0.4%)和疲劳(-6.3%;95% ci: -14.6%, 2.0%)。结论:这一间接治疗比较表明,相对于卡博赞替尼,瑞戈非尼可能与良好的OS(无统计学意义)、较低的剂量减少率和因治疗相关不良反应而停药率以及较低的严重腹泻和疲劳率相关。
{"title":"Regorafenib versus Cabozantinib as a Second-Line Treatment for Advanced Hepatocellular Carcinoma: An Anchored Matching-Adjusted Indirect Comparison of Efficacy and Safety.","authors":"Philippe Merle,&nbsp;Masatoshi Kudo,&nbsp;Stanimira Krotneva,&nbsp;Kirhan Ozgurdal,&nbsp;Yun Su,&nbsp;Irina Proskorovsky","doi":"10.1159/000527403","DOIUrl":"https://doi.org/10.1159/000527403","url":null,"abstract":"<p><strong>Introduction: </strong>The tyrosine kinase inhibitors regorafenib and cabozantinib remain the mainstay in second-line treatment of advanced hepatocellular carcinoma (HCC). There is currently no clear evidence of superiority in efficacy or safety to guide choice between the two treatments.</p><p><strong>Methods: </strong>We conducted an anchored matching-adjusted indirect comparison using individual patient data from the RESORCE trial of regorafenib and published aggregate data from the CELESTIAL trial of cabozantinib. Second-line HCC patients with prior sorafenib exposure of ≥3 months were included in the analyses. Hazard ratios (HRs) and restricted mean survival time (RMST) were estimated to quantify differences in overall survival (OS) and progression-free survival (PFS). Safety outcomes compared were rates of grade 3 or 4 adverse events (AEs), occurring in >10% of patients, and discontinuation or dose reduction due to treatment-related AEs.</p><p><strong>Results: </strong>After matching adjustment for differences in baseline patient characteristics, regorafenib showed a favorable OS (HR, 0.80; 95% CI: 0.54, 1.20) and ∼3-month-longer RMST over cabozantinib (RMST difference, 2.76 months; 95% CI: -1.03, 6.54), although not statistically significant. For PFS, there was no numerical difference in HR (HR, 1.00; 95% CI: 0.68, 1.49) and no clinically meaningful difference based on RMST analyses (RMST difference, -0.59 months; 95% CI: -1.83, 0.65). Regorafenib showed a significantly lower incidence of discontinuation (risk difference, -9.2%; 95% CI: -17.7%, -0.6%) and dose reductions (-15.2%; 95% CI: -29.0%, -1.5%) due to treatment-related AEs (any grade). Regorafenib was also associated with a lower incidence (not statistically significant) of grade 3 or 4 diarrhea (risk difference, -7.1%; 95% CI: -14.7%, 0.4%) and fatigue (-6.3%; 95% CI: -14.6%, 2.0%).</p><p><strong>Conclusion: </strong>This indirect treatment comparison suggests, relative to cabozantinib, that regorafenib could be associated with favorable OS (not statistically significant), lower rates of dose reductions and discontinuation due to treatment-related AEs, and lower rates of severe diarrhea and fatigue.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"12 2","pages":"145-155"},"PeriodicalIF":13.8,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/14/24/lic-0012-0145.PMC10267565.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9661031","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: 2
PD-1/CTLA-4 Blockade Leads to Expansion of CD8+PD-1int TILs and Results in Tumor Remission in Experimental Liver Cancer. PD-1/CTLA-4阻断导致实验性肝癌中CD8+PD-1int TILs的扩增和肿瘤缓解结果
IF 13.8 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2023-06-01 DOI: 10.1159/000526899
Sandra Bufe, Artur Zimmermann, Sarina Ravens, Immo Prinz, Laura Elisa Buitrago-Molina, Robert Geffers, Norman Woller, Florian Kühnel, Steven R Talbot, Fatih Noyan, Michael Peter Manns, Heiner Wedemeyer, Matthias Hardtke-Wolenski, Elmar Jaeckel, Ana C Davalos-Misslitz

Background: Checkpoint inhibitors act on exhausted CD8+ T cells and restore their effector function in chronic infections and cancer. The underlying mechanisms of action appear to differ between different types of cancer and are not yet fully understood.

Methods: Here, we established a new orthotopic HCC model to study the effects of checkpoint blockade on exhausted CD8+ tumor-infiltrating lymphocytes (TILs). The tumors expressed endogenous levels of HA, which allowed the study of tumor-specific T cells.

Results: The induced tumors developed an immune-resistant TME in which few T cells were found. The few recovered CD8+ TILs were mostly terminally exhausted and expressed high levels of PD-1. PD-1/CTLA-4 blockade resulted in a strong increase in the number of CD8+ TILs expressing intermediate amounts of PD-1, also called progenitor-exhausted CD8+ TILs, while terminally exhausted CD8+ TILs were almost absent in the tumors of treated mice. Although transferred naïve tumor-specific T cells did not expand in the tumors of untreated mice, they expanded strongly after treatment and generated progenitor-exhausted but not terminally exhausted CD8+ TILs. Unexpectedly, progenitor-exhausted CD8+ TILs mediated the antitumor response after treatment with minimal changes in their transcriptional profile.

Conclusion: In our model, few doses of checkpoint inhibitors during the priming of transferred CD8+ tumor-specific T cells were sufficient to induce tumor remission. Therefore, PD-1/CTLA-4 blockade has an ameliorative effect on the expansion of recently primed CD8+ T cells while preventing their development into terminally exhausted CD8+ TILs in the TME. This finding could have important implications for future T-cell therapies.

背景:检查点抑制剂作用于耗尽的CD8+ T细胞,并恢复其在慢性感染和癌症中的效应功能。潜在的作用机制似乎在不同类型的癌症之间有所不同,目前还没有完全了解。方法:建立原位肝癌模型,研究检查点阻断对耗尽CD8+肿瘤浸润淋巴细胞(TILs)的影响。肿瘤表达内源性HA水平,这使得研究肿瘤特异性T细胞成为可能。结果:诱导肿瘤发生免疫抵抗性TME, T细胞较少。少数恢复的CD8+ til大多终末耗尽,表达高水平的PD-1。PD-1/CTLA-4阻断导致表达中量PD-1的CD8+ TILs(也称为祖细胞耗尽的CD8+ TILs)数量显著增加,而在治疗小鼠的肿瘤中几乎不存在终端耗尽的CD8+ TILs。虽然转移的naïve肿瘤特异性T细胞在未治疗小鼠的肿瘤中不扩增,但它们在治疗后扩增强烈,并产生祖细胞耗尽但未最终耗尽的CD8+ TILs。出乎意料的是,祖细胞耗尽的CD8+ TILs介导了治疗后的抗肿瘤反应,其转录谱的变化很小。结论:在我们的模型中,在转移的CD8+肿瘤特异性T细胞启动过程中,很少剂量的检查点抑制剂足以诱导肿瘤缓解。因此,PD-1/CTLA-4阻断对新近启动的CD8+ T细胞的扩增有改善作用,同时阻止它们在TME中发育为终末耗尽的CD8+ til。这一发现可能对未来的t细胞治疗具有重要意义。
{"title":"PD-1/CTLA-4 Blockade Leads to Expansion of CD8<sup>+</sup>PD-1<sup>int</sup> TILs and Results in Tumor Remission in Experimental Liver Cancer.","authors":"Sandra Bufe,&nbsp;Artur Zimmermann,&nbsp;Sarina Ravens,&nbsp;Immo Prinz,&nbsp;Laura Elisa Buitrago-Molina,&nbsp;Robert Geffers,&nbsp;Norman Woller,&nbsp;Florian Kühnel,&nbsp;Steven R Talbot,&nbsp;Fatih Noyan,&nbsp;Michael Peter Manns,&nbsp;Heiner Wedemeyer,&nbsp;Matthias Hardtke-Wolenski,&nbsp;Elmar Jaeckel,&nbsp;Ana C Davalos-Misslitz","doi":"10.1159/000526899","DOIUrl":"https://doi.org/10.1159/000526899","url":null,"abstract":"<p><strong>Background: </strong>Checkpoint inhibitors act on exhausted CD8<sup>+</sup> T cells and restore their effector function in chronic infections and cancer. The underlying mechanisms of action appear to differ between different types of cancer and are not yet fully understood.</p><p><strong>Methods: </strong>Here, we established a new orthotopic HCC model to study the effects of checkpoint blockade on exhausted CD8<sup>+</sup> tumor-infiltrating lymphocytes (TILs). The tumors expressed endogenous levels of HA, which allowed the study of tumor-specific T cells.</p><p><strong>Results: </strong>The induced tumors developed an immune-resistant TME in which few T cells were found. The few recovered CD8<sup>+</sup> TILs were mostly terminally exhausted and expressed high levels of PD-1. PD-1/CTLA-4 blockade resulted in a strong increase in the number of CD8<sup>+</sup> TILs expressing intermediate amounts of PD-1, also called progenitor-exhausted CD8<sup>+</sup> TILs, while terminally exhausted CD8<sup>+</sup> TILs were almost absent in the tumors of treated mice. Although transferred naïve tumor-specific T cells did not expand in the tumors of untreated mice, they expanded strongly after treatment and generated progenitor-exhausted but not terminally exhausted CD8<sup>+</sup> TILs. Unexpectedly, progenitor-exhausted CD8<sup>+</sup> TILs mediated the antitumor response after treatment with minimal changes in their transcriptional profile.</p><p><strong>Conclusion: </strong>In our model, few doses of checkpoint inhibitors during the priming of transferred CD8<sup>+</sup> tumor-specific T cells were sufficient to induce tumor remission. Therefore, PD-1/CTLA-4 blockade has an ameliorative effect on the expansion of recently primed CD8<sup>+</sup> T cells while preventing their development into terminally exhausted CD8<sup>+</sup> TILs in the TME. This finding could have important implications for future T-cell therapies.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"12 2","pages":"129-144"},"PeriodicalIF":13.8,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/08/c4/lic-0012-0129.PMC10267567.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9648640","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: 2
Elderly Patients with Hepatocellular Carcinoma Benefit from Liver Transplantation as Much as Younger Ones. 老年肝细胞癌患者从肝移植中获益与年轻人一样多。
IF 13.8 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2023-06-01 DOI: 10.1159/000528830
Jens Mittler, Stefan Heinrich, Martina Koch, Maria Hoppe-Lotichius, Ali Hadian, Arndt Weinmann, Roman Kloeckner, Peter Robert Galle, Hauke Lang

Introduction: The literature on liver transplantation (LT) for cirrhosis-associated hepatocellular carcinoma (cirr-HCC) in elderly patients (≥65 years of age) is scarce. The aim of this study was therefore to analyze the outcome after LT for cirr-HCC in elderly patients in our single-center experience.

Methods: All consecutive patients who underwent LT for cirr-HCC at our center were identified from our prospectively collected LT database and stratified into an elderly (≥65 years) and a younger (<65 years) cohort. Perioperative mortality as well as Kaplan-Meier estimations of overall (OS) and recurrence-free survival (RFS) were compared between age strata. A subgroup analysis was performed for patients with HCC only inside Milan criteria. For further oncological comparison, outcome in the subgroup of elderly LT recipients with HCC inside Milan was also compared to a group of elderly patients undergoing liver resection for cirr-HCC inside Milan extracted from our institutional liver resection database.

Results: Out of 369 consecutive patients with cirr-HCC who underwent LT between 1998 and 2022 at our center, we identified 97 elderly (with a subgroup of 14 septuagenarians) and 272 younger LT patients. 5- and 10-year OS in elderly compared to younger LT patients was 63% and 52% versus 63% and 46% (p = 0.67), respectively, while 5- and 10-year RFS was 58% and 49% versus 58% and 44% (p = 0.69). 5-/10-year OS and RFS in 50 elderly LT recipients with HCC inside Milan were 68%/55% and 62%/54%, respectively, which compared to 46%/38% (p = 0.07) and 26%/14% (p < 0.0001) in elderly patients after liver resection for cirr-HCC inside Milan.

Conclusion: Our results in almost 100 elderly patients after LT for cirr-HCC show that older age per se should not be considered a contraindication to LT and that selected elderly patients older than 65 and even 70 years benefit from LT as much as younger ones.

关于肝移植(LT)治疗老年患者(≥65岁)肝硬化相关肝细胞癌(cirr-HCC)的文献很少。因此,本研究的目的是在我们的单中心经验中分析老年患者肝细胞癌肝移植后的结果。方法:从我们前瞻性收集的肝移植数据库中确定所有在我们中心连续接受肝移植的cirr-HCC患者,并将其分为老年人(≥65岁)和年轻人(结果:在我们中心1998年至2022年期间连续接受肝移植的369名cirr-HCC患者中,我们确定了97名老年人(其中14名70岁以上)和272名年轻的肝移植患者。与年轻LT患者相比,老年人5年和10年的OS分别为63%和52%,而5年和10年的RFS分别为58%和49%,58%和44% (p = 0.67)。米兰市50例老年肝癌肝移植患者的5- 10年OS和RFS分别为68%/55%和62%/54%,而米兰市老年肝癌肝切除术后患者的5- 10年OS和RFS分别为46%/38% (p = 0.07)和26%/14% (p < 0.0001)。结论:我们对近100例老年肝细胞癌肝移植后患者的研究结果表明,年龄本身不应被视为肝移植的禁忌症,65岁甚至70岁以上的老年患者与年轻患者一样受益于肝移植。
{"title":"Elderly Patients with Hepatocellular Carcinoma Benefit from Liver Transplantation as Much as Younger Ones.","authors":"Jens Mittler,&nbsp;Stefan Heinrich,&nbsp;Martina Koch,&nbsp;Maria Hoppe-Lotichius,&nbsp;Ali Hadian,&nbsp;Arndt Weinmann,&nbsp;Roman Kloeckner,&nbsp;Peter Robert Galle,&nbsp;Hauke Lang","doi":"10.1159/000528830","DOIUrl":"https://doi.org/10.1159/000528830","url":null,"abstract":"<p><strong>Introduction: </strong>The literature on liver transplantation (LT) for cirrhosis-associated hepatocellular carcinoma (cirr-HCC) in elderly patients (≥65 years of age) is scarce. The aim of this study was therefore to analyze the outcome after LT for cirr-HCC in elderly patients in our single-center experience.</p><p><strong>Methods: </strong>All consecutive patients who underwent LT for cirr-HCC at our center were identified from our prospectively collected LT database and stratified into an elderly (≥65 years) and a younger (<65 years) cohort. Perioperative mortality as well as Kaplan-Meier estimations of overall (OS) and recurrence-free survival (RFS) were compared between age strata. A subgroup analysis was performed for patients with HCC only inside Milan criteria. For further oncological comparison, outcome in the subgroup of elderly LT recipients with HCC inside Milan was also compared to a group of elderly patients undergoing liver resection for cirr-HCC inside Milan extracted from our institutional liver resection database.</p><p><strong>Results: </strong>Out of 369 consecutive patients with cirr-HCC who underwent LT between 1998 and 2022 at our center, we identified 97 elderly (with a subgroup of 14 septuagenarians) and 272 younger LT patients. 5- and 10-year OS in elderly compared to younger LT patients was 63% and 52% versus 63% and 46% (<i>p</i> = 0.67), respectively, while 5- and 10-year RFS was 58% and 49% versus 58% and 44% (<i>p</i> = 0.69). 5-/10-year OS and RFS in 50 elderly LT recipients with HCC inside Milan were 68%/55% and 62%/54%, respectively, which compared to 46%/38% (<i>p</i> = 0.07) and 26%/14% (<i>p</i> < 0.0001) in elderly patients after liver resection for cirr-HCC inside Milan.</p><p><strong>Conclusion: </strong>Our results in almost 100 elderly patients after LT for cirr-HCC show that older age per se should not be considered a contraindication to LT and that selected elderly patients older than 65 and even 70 years benefit from LT as much as younger ones.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"12 2","pages":"171-177"},"PeriodicalIF":13.8,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10267523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9654521","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: 2
Deficient Immune Response following SARS-CoV-2 Vaccination in Patients with Hepatobiliary Carcinoma: A Forgotten, Vulnerable Group of Patients. 肝胆癌患者接种严重急性呼吸系统综合征冠状病毒2型疫苗后免疫反应不足:被遗忘的弱势患者群体。
IF 13.8 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2023-05-10 eCollection Date: 2023-09-01 DOI: 10.1159/000529608
Malte B Monin, Leona I Baier, Jens G Gorny, Moritz Berger, Taotao Zhou, Robert Mahn, Farsaneh Sadeghlar, Christian Möhring, Christoph Boesecke, Kathrin van Bremen, Jürgen K Rockstroh, Christian P Strassburg, Anna-Maria Eis-Hübinger, Matthias Schmid, Maria A Gonzalez-Carmona

Introduction: Data on immune response rates following vaccination for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in patients with hepatobiliary carcinoma (HBC) are rare. However, impaired immunogenicity must be expected due to the combination of chronic liver diseases (CLDs) with malignancy and anticancer treatment.

Methods: In this prospective, longitudinal study, 101 patients were included, of whom 59 were patients with HBC under anticancer treatment. A cohort of patients with a past medical history of gastrointestinal cancer, of whom 28.6% had HBC without detectable active tumor disease having been off therapy for at least 12 months, served as control. Levels of SARS-CoV-2 anti-spike IgG, surrogate neutralization antibodies (sNABs), and cellular immune responses were compared. In uni- and multivariable subgroup analyses, risk factors for impaired immunogenicity were regarded. Data on rates and clinical courses of SARS-CoV-2 infections were documented.

Results: In patients with HBC under active treatment, levels of SARS-CoV-2 anti-spike IgG were significantly lower (2.55 log10 BAU/mL; 95% CI: 2.33-2.76; p < 0.01) than in patients in follow-up care (3.02 log10 BAU/mL; 95% CI: 2.80-3.25) 4 weeks after two vaccinations. Antibody levels decreased over time, and differences between the groups diminished. However, titers of SARS-CoV-2 sNAB were for a longer time significantly lower in patients with HBC under treatment (64.19%; 95% CI: 55.90-72.48; p < 0.01) than in patients in follow-up care (84.13%; 95% CI: 76.95-91.31). Underlying CLD and/or liver cirrhosis Child-Pugh A or B (less than 8 points) did not seem to further impair immunogenicity. Conversely, chemotherapy and additional immunosuppression were found to significantly reduce antibody levels. After a third booster vaccination for SARS-CoV-2, levels of total and neutralization antibodies were equalized between the groups. Moreover, cellular response rates were balanced. Clinically, infection rates with SARS-CoV-2 were low, and no severe courses were observed.

Conclusion: Patients with active HBC showed significantly impaired immune response rates to basic vaccinations for SARS-CoV-2, especially under chemotherapy, independent of underlying cirrhotic or non-cirrhotic CLD. Although booster vaccinations balanced differences, waning immunity was observed over time and should be monitored for further recommendations. Our data help clinicians decide on individual additional booster vaccinations and/or passive immunization or antiviral treatment in patients with HBC getting infected with SARS-CoV-2.

引言:肝胆癌(HBC)患者接种严重急性呼吸系统综合征冠状病毒2型疫苗后的免疫应答率数据很少。然而,由于慢性肝病(CLD)与恶性肿瘤和抗癌治疗的结合,免疫原性必须受损。方法:在这项前瞻性纵向研究中,纳入了101名患者,其中59名是正在接受抗癌治疗的HBC患者。一组既往有胃肠道癌症病史的患者作为对照,其中28.6%的患者患有HBC,但未检测到活动性肿瘤疾病,已停止治疗至少12个月。比较了严重急性呼吸系统综合征冠状病毒2型抗刺突IgG、替代中和抗体(sNABs)和细胞免疫反应的水平。在单因素和多因素亚组分析中,考虑了免疫原性受损的危险因素。记录了严重急性呼吸系统综合征冠状病毒2型感染率和临床病程的数据。结果:在接受积极治疗的HBC患者中,两次接种疫苗4周后,严重急性呼吸系统综合征冠状病毒2型抗刺突IgG水平(2.55 log10 BAU/mL;95%可信区间:2.33-2.76;p<0.01)显著低于接受随访的患者(3.02 log10 BAU/mL;95%置信区间:2.80-3.25)。抗体水平随着时间的推移而下降,两组之间的差异也减少了。然而,在更长的时间内,接受治疗的HBC患者的严重急性呼吸系统综合征冠状病毒2型sNAB滴度(64.19%;95%可信区间:55.90-72.48;p<0.01)显著低于接受后续护理的患者(84.13%;95%置信区间:76.95-91.31)。潜在的CLD和/或肝硬化Child-Pugh a或B(低于8分)似乎没有进一步损害免疫原性。相反,化疗和额外的免疫抑制被发现可以显著降低抗体水平。在第三次接种严重急性呼吸系统综合征冠状病毒2型加强针后,两组之间的总抗体和中和抗体水平持平。此外,细胞反应率是平衡的。临床上,严重急性呼吸系统综合征冠状病毒2型的感染率较低,没有观察到严重的病程。结论:活动性HBC患者对严重急性呼吸系统综合征冠状病毒2型基础疫苗的免疫应答率显著受损,尤其是在化疗期间,与潜在的肝硬化或非肝硬化CLD无关。尽管加强疫苗接种平衡了差异,但随着时间的推移,免疫力下降,应进行监测,以获得进一步的建议。我们的数据有助于临床医生决定对感染严重急性呼吸系统综合征冠状病毒2型的HBC患者进行个人额外的加强针接种和/或被动免疫或抗病毒治疗。
{"title":"Deficient Immune Response following SARS-CoV-2 Vaccination in Patients with Hepatobiliary Carcinoma: A Forgotten, Vulnerable Group of Patients.","authors":"Malte B Monin,&nbsp;Leona I Baier,&nbsp;Jens G Gorny,&nbsp;Moritz Berger,&nbsp;Taotao Zhou,&nbsp;Robert Mahn,&nbsp;Farsaneh Sadeghlar,&nbsp;Christian Möhring,&nbsp;Christoph Boesecke,&nbsp;Kathrin van Bremen,&nbsp;Jürgen K Rockstroh,&nbsp;Christian P Strassburg,&nbsp;Anna-Maria Eis-Hübinger,&nbsp;Matthias Schmid,&nbsp;Maria A Gonzalez-Carmona","doi":"10.1159/000529608","DOIUrl":"https://doi.org/10.1159/000529608","url":null,"abstract":"<p><strong>Introduction: </strong>Data on immune response rates following vaccination for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in patients with hepatobiliary carcinoma (HBC) are rare. However, impaired immunogenicity must be expected due to the combination of chronic liver diseases (CLDs) with malignancy and anticancer treatment.</p><p><strong>Methods: </strong>In this prospective, longitudinal study, 101 patients were included, of whom 59 were patients with HBC under anticancer treatment. A cohort of patients with a past medical history of gastrointestinal cancer, of whom 28.6% had HBC without detectable active tumor disease having been off therapy for at least 12 months, served as control. Levels of SARS-CoV-2 anti-spike IgG, surrogate neutralization antibodies (sNABs), and cellular immune responses were compared. In uni- and multivariable subgroup analyses, risk factors for impaired immunogenicity were regarded. Data on rates and clinical courses of SARS-CoV-2 infections were documented.</p><p><strong>Results: </strong>In patients with HBC under active treatment, levels of SARS-CoV-2 anti-spike IgG were significantly lower (2.55 log<sub>10</sub> BAU/mL; 95% CI: 2.33-2.76; <i>p</i> < 0.01) than in patients in follow-up care (3.02 log<sub>10</sub> BAU/mL; 95% CI: 2.80-3.25) 4 weeks after two vaccinations. Antibody levels decreased over time, and differences between the groups diminished. However, titers of SARS-CoV-2 sNAB were for a longer time significantly lower in patients with HBC under treatment (64.19%; 95% CI: 55.90-72.48; <i>p</i> < 0.01) than in patients in follow-up care (84.13%; 95% CI: 76.95-91.31). Underlying CLD and/or liver cirrhosis Child-Pugh A or B (less than 8 points) did not seem to further impair immunogenicity. Conversely, chemotherapy and additional immunosuppression were found to significantly reduce antibody levels. After a third booster vaccination for SARS-CoV-2, levels of total and neutralization antibodies were equalized between the groups. Moreover, cellular response rates were balanced. Clinically, infection rates with SARS-CoV-2 were low, and no severe courses were observed.</p><p><strong>Conclusion: </strong>Patients with active HBC showed significantly impaired immune response rates to basic vaccinations for SARS-CoV-2, especially under chemotherapy, independent of underlying cirrhotic or non-cirrhotic CLD. Although booster vaccinations balanced differences, waning immunity was observed over time and should be monitored for further recommendations. Our data help clinicians decide on individual additional booster vaccinations and/or passive immunization or antiviral treatment in patients with HBC getting infected with SARS-CoV-2.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"12 4","pages":"339-355"},"PeriodicalIF":13.8,"publicationDate":"2023-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10601882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71412861","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
Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2022 Edition). 原发性癌症诊断和治疗指南(2022年版)。
IF 13.8 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2023-04-05 eCollection Date: 2023-10-01 DOI: 10.1159/000530495
Jian Zhou, Huichuan Sun, Zheng Wang, Wenming Cong, Mengsu Zeng, Weiping Zhou, Ping Bie, Lianxin Liu, Tianfu Wen, Ming Kuang, Guohong Han, Zhiping Yan, Maoqiang Wang, Ruibao Liu, Ligong Lu, Zhenggang Ren, Zhaochong Zeng, Ping Liang, Changhong Liang, Min Chen, Fuhua Yan, Wenping Wang, Jinlin Hou, Yuan Ji, Jingping Yun, Xueli Bai, Dingfang Cai, Weixia Chen, Yongjun Chen, Wenwu Cheng, Shuqun Cheng, Chaoliu Dai, Wengzhi Guo, Yabing Guo, Baojin Hua, Xiaowu Huang, Weidong Jia, Qiu Li, Tao Li, Xun Li, Yaming Li, Yexiong Li, Jun Liang, Changquan Ling, Tianshu Liu, Xiufeng Liu, Shichun Lu, Guoyue Lv, Yilei Mao, Zhiqiang Meng, Tao Peng, Weixin Ren, Hongcheng Shi, Guoming Shi, Ming Shi, Tianqiang Song, Kaishan Tao, Jianhua Wang, Kui Wang, Lu Wang, Wentao Wang, Xiaoying Wang, Zhiming Wang, Bangde Xiang, Baocai Xing, Jianming Xu, Jiamei Yang, Jianyong Yang, Yefa Yang, Yunke Yang, Shenglong Ye, Zhenyu Yin, Yong Zeng, Bixiang Zhang, Boheng Zhang, Leida Zhang, Shuijun Zhang, Ti Zhang, Yanqiao Zhang, Ming Zhao, Yongfu Zhao, Honggang Zheng, Ledu Zhou, Jiye Zhu, Kangshun Zhu, Rong Liu, Yinghong Shi, Yongsheng Xiao, Lan Zhang, Chun Yang, Zhifeng Wu, Zhi Dai, Minshan Chen, Jianqiang Cai, Weilin Wang, Xiujun Cai, Qiang Li, Feng Shen, Shukui Qin, Gaojun Teng, Jiahong Dong, Jia Fan

Background: Primary liver cancer, of which around 75-85% is hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people.

Summary: Since the publication of Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China in June 2017, which were updated by the National Health Commission in December 2019, additional high-quality evidence has emerged from researchers worldwide regarding the diagnosis, staging, and treatment of liver cancer, that requires the guidelines to be updated again. The new edition (2022 Edition) was written by more than 100 experts in the field of liver cancer in China, which not only reflects the real-world situation in China but also may reshape the nationwide diagnosis and treatment of liver cancer.

Key messages: The new guideline aims to encourage the implementation of evidence-based practice and improve the national average 5-year survival rate for patients with liver cancer, as proposed in the "Health China 2030 Blueprint."

背景:原发性癌症是我国第四大恶性肿瘤,也是肿瘤死亡的第二大原因,约占我国原发性肝癌的75-85%,对我国人民的生命健康构成重大威胁。摘要:自2017年6月国家卫生健康委员会于2019年12月更新的《中国原发性癌症诊断和治疗指南》发布以来,世界各地的研究人员在癌症的诊断、分期和治疗方面出现了更多高质量的证据,需要再次更新指南。新版(2022年版)由中国癌症领域的100多位专家撰写,不仅反映了中国的现实情况,也可能重塑癌症的全国诊疗。关键信息:新指南旨在鼓励实施循证实践,提高癌症患者的全国平均5年生存率,正如《健康中国2030蓝图》所提出的那样
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引用次数: 7
Survival Trends in Sorafenib for Advanced Hepatocellular Carcinoma: A Reconstructed Individual Patient Data Meta-Analysis of Randomized Trials. 索拉非尼治疗晚期肝癌的生存趋势:随机试验的重建个体患者数据荟萃分析。
IF 11.6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2023-03-28 eCollection Date: 2023-10-01 DOI: 10.1159/000529824
Darren Jun Hao Tan, Ansel Shao Pin Tang, Wen Hui Lim, Cheng Han Ng, Benjamin Nah, Clarissa Fu, Jieling Xiao, Benjamin Koh, Phoebe Wen Lin Tay, Eunice X Tan, Margaret Teng, Nicholas Syn, Mark D Muthiah, Nobuharu Tamaki, Sung Won Lee, Beom Kyung Kim, Thomas Yau, Arndt Vogel, Rohit Loomba, Daniel Q Huang

Background: Emerging data suggest that outcomes for advanced hepatocellular carcinoma (HCC) treated with sorafenib may have improved over time. We aimed to provide robust, time-to-event estimates of survival outcomes for sorafenib in advanced HCC.

Summary: In this systematic review and individual patient data meta-analysis of randomized-controlled trials (RCTs), we searched MEDLINE and Embase from inception till September 2022 for RCTs that provided data for overall survival (OS) and progression-free survival (PFS) for sorafenib monotherapy as first-line systemic therapy for advanced HCC. We performed a pooled analysis using reconstructed individual participant data from published Kaplan-Meier curves to obtain robust estimates for OS and PFS. Of 1,599 articles identified, 29 studies (5,525 patients) met the inclusion criteria. Overall, the median OS was 10.4 (95% CI: 9.6-11.4) months. Median OS increased over time, from 9.8 (95% CI: 8.8-10.7) months in studies before 2015 to 13.4 (95% CI: 11.03-15.24) months in studies from 2015 onwards (p < 0.001). OS did not differ by trial phase, geographical region, or study design. The overall median PFS was 4.4 (95% CI: 3.9-4.8) months, but PFS did not improve over time. Sensitivity analysis of studies from 2015 and onwards to account for the introduction of direct-acting antivirals determined that hepatitis C virus was associated with reduced mortality (p < 0.001). There was minimal heterogeneity in the estimates for OS (all I2 ≤ 33).

Key messages: Survival outcomes for sorafenib in advanced HCC have improved over time. These data have important implications for clinical trial design.

背景:新出现的数据表明,索拉非尼治疗晚期肝细胞癌(HCC)的疗效可能会随着时间的推移而改善。我们旨在为索拉非尼治疗晚期HCC的生存结果提供可靠的、及时的估计。总结:在这项随机对照试验(RCT)的系统综述和个体患者数据荟萃分析中,我们从开始到2022年9月搜索了MEDLINE和Embase的随机对照试验,这些试验提供了索拉非尼单药治疗作为晚期HCC一线系统治疗的总生存率(OS)和无进展生存率(PFS)数据。我们使用从已发表的Kaplan-Meier曲线重建的个体参与者数据进行了汇总分析,以获得OS和PFS的稳健估计。在确定的1599篇文章中,29项研究(5525名患者)符合纳入标准。总体而言,中位OS为10.4个月(95%CI:9.6-11.4)。中位OS随着时间的推移而增加,从2015年之前研究的9.8个月(95%CI:8.8-10.7)增加到2015年以后研究的13.4个月(95%CI:11.03-15.24)(p<0.001)。OS在试验阶段、地理区域或研究设计方面没有差异。总体中位PFS为4.4个月(95%CI:3.9-4.8),但PFS并没有随着时间的推移而改善。考虑到直接作用抗病毒药物的引入,对2015年及以后的研究进行了敏感性分析,确定丙型肝炎病毒与死亡率降低有关(p<0.001)。OS的估计值具有最小的异质性(所有I2≤33)。关键信息:索拉非尼治疗晚期HCC的生存结果随着时间的推移而改善。这些数据对临床试验设计具有重要意义。
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引用次数: 0
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Liver Cancer
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