Introduction: Lenvatinib is indicated for the forefront treatment of advanced hepatocellular carcinoma (aHCC), but its use may be limited by the risk of esophagogastric varices (EGV) bleeding. This study assessed the prevalence, predictors, and complications of EGV in aHCC patients treated with lenvatinib. Methods: In this multicenter international retrospective study, cirrhotic patients treated with lenvatinib for aHCC, were enrolled if upper-gastrointestinal endoscopy was available within 6 months before treatment. Primary endpoint was the incidence of EGV bleeding during lenvatinib therapy; secondary endpoints were predictors for EGV bleeding, prevalence, and risk factors for the presence of EGV and high-risk EGV at baseline, as well as impact of EGV bleeding on patients’ survival. Results: 535 patients were enrolled in the study (median age: 72 years, 78% male, 63% viral etiology, 89% Child-Pugh A, 16% neoplastic portal vein thrombosis [nPVT], 56% Barcelona Clinic Liver Cancer-C): 234 had EGV (44%), 70 (30%) were at high risk and 59 were on primary prophylaxis. During lenvatinib treatment, 17 patients bled from EGV (3 grade 5), the 12-month cumulative incidence being 3%. The only baseline independent predictor of EGV bleeding was the presence of baseline high-risk EGV (hazard ratio: 6.94, 95% confidence interval [CI]: 2.23–21.57, p = 0.001). In these patients the 12-month risk was 17%. High-risk varices were independently associated with Child-Pugh B score (odds ratio [OR]: 2.12; 95% CI: 1.08–4.17, p = 0.03), nPVT (OR: 2.54; 95% CI: 1.40–4.61, p = 0.002), and platelets <150,000/μL (OR: 2.47; 95% CI: 1.35–4.50, p = 0.003). Conclusion: In hepatocellular carcinoma patients treated with lenvatinib, the risk of EGV bleeding was mostly low but significant only in patients with high-risk EGV at baseline.
{"title":"Incidence and predictors of esophagogastric varices bleeding in patients with hepatocellular carcinoma in lenvatinib","authors":"Massimo Iavarone, Eleonora Alimenti, Toshifumi Tada, Shigeo Shimose, Goki Suda, Changhoon Yoo, Caterina Soldà, Fabio Piscaglia, Giulia Tosetti, Fabio Marra, Caterina Vivaldi, Fabio Conti, Marta Schirripa, Hideki Iwamoto, Takuya Sho, So Heun Lee, Mario Domenico Rizzato, Matteo Tonnini, Margherita Rimini, Claudia Campani, Gianluca Masi, Francesco Foschi, Mariangela Bruccoleri, Takumi Kawaguchi, Takashi Kumada, Atsushi Hiraoka, Masanori Atsukawa, Shinya Fukunishi, Toru Ishikawa, Kazuto Tajiri, Hironori Ochi, Satoshi Yasuda, Hidenori Toyoda, Takeshi Hatanaka, Satoru Kakizaki, Kazuhito Kawata, Fujimasa Tada, Hideko Ohama, Norio Itokawa, Tomomi Okubo, Taeang Arai, Michitaka Imai, Atsushi Naganuma, Andrea Casadei-Gardini, Pietro Lampertico","doi":"10.1159/000534127","DOIUrl":"https://doi.org/10.1159/000534127","url":null,"abstract":"<b><i>Introduction:</i></b> Lenvatinib is indicated for the forefront treatment of advanced hepatocellular carcinoma (aHCC), but its use may be limited by the risk of esophagogastric varices (EGV) bleeding. This study assessed the prevalence, predictors, and complications of EGV in aHCC patients treated with lenvatinib. <b><i>Methods:</i></b> In this multicenter international retrospective study, cirrhotic patients treated with lenvatinib for aHCC, were enrolled if upper-gastrointestinal endoscopy was available within 6 months before treatment. Primary endpoint was the incidence of EGV bleeding during lenvatinib therapy; secondary endpoints were predictors for EGV bleeding, prevalence, and risk factors for the presence of EGV and high-risk EGV at baseline, as well as impact of EGV bleeding on patients’ survival. <b><i>Results:</i></b> 535 patients were enrolled in the study (median age: 72 years, 78% male, 63% viral etiology, 89% Child-Pugh A, 16% neoplastic portal vein thrombosis [nPVT], 56% Barcelona Clinic Liver Cancer-C): 234 had EGV (44%), 70 (30%) were at high risk and 59 were on primary prophylaxis. During lenvatinib treatment, 17 patients bled from EGV (3 grade 5), the 12-month cumulative incidence being 3%. The only baseline independent predictor of EGV bleeding was the presence of baseline high-risk EGV (hazard ratio: 6.94, 95% confidence interval [CI]: 2.23–21.57, <i>p</i> = 0.001). In these patients the 12-month risk was 17%. High-risk varices were independently associated with Child-Pugh B score (odds ratio [OR]: 2.12; 95% CI: 1.08–4.17, <i>p</i> = 0.03), nPVT (OR: 2.54; 95% CI: 1.40–4.61, <i>p</i> = 0.002), and platelets &lt;150,000/μL (OR: 2.47; 95% CI: 1.35–4.50, <i>p</i> = 0.003). <b><i>Conclusion:</i></b> In hepatocellular carcinoma patients treated with lenvatinib, the risk of EGV bleeding was mostly low but significant only in patients with high-risk EGV at baseline.","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134973088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Angeles García-Criado, Jordi Rimola, Susana Seijo, Anna Darnell, Ernest Belmonte, Victor Sapena, Julián Moreno-Rojas, Valeria Pérez, Virginia Hernández-Gea, Carmen Ayuso, Maria Reig, Juan Carlos García-Pagán, Jordi Bruix
Introduction: The incidence of hepatocellular carcinoma (HCC) in Budd-Chiari syndrome (BCS) is unknown and there is no validated diagnostic work-up to define the liver nodules with arterial phase hyperenhancement (APHE), suggesting malignancy. This prospective study evaluates HCC incidence in a Western cohort of patients with BCS and assesses the performance of MRI with hepatobiliary contrast (HB-MRI) for nodule characterization. Methods: Patients with BCS followed in our hospital were prospectively evaluated by MRI with extracellular contrast (EC-MRI). Nodules with APHE categorized as non-conclusively benign by 2 radiologists were studied by HB-MRI and reviewed by 2 radiologists blinded to the EC-MRI results. A new EC-MRI 1 year later and clinical, analytical, and sonographic follow-up every 6 months for a median of 10 years was performed. Results: A total of 55 non-conclusively benign nodules with APHE were detected at EC-MRI in 41 patients. While 32 of them were suggestive of HCC by EC-MRI, all the 55 nodules showed increased uptake of hepatobiliary contrast. An unequivocal central scar was seen in 12/55 nodules at HB-MRI regardless of it was not detected on the EC-MRI. None of the nodules was hypointense in the hepatobiliary phase (HBP). HCC was not detected during a median of 10 years of follow-up. Conclusions: Detection of nodules with APHE is frequent in patients with BCS, but HCC is rare in Western patients with BCS. While EC-MRI may detect nodules suggesting malignancy, the identification of contrast uptake in the HBP at HB-MRI may help categorize them as benign.
{"title":"MRI Using Gadoxetic Acid in the Work-Up of Liver Nodules Not Conclusively Benign in Budd-Chiari Syndrome: A Prospective Long-Term Follow-Up","authors":"Angeles García-Criado, Jordi Rimola, Susana Seijo, Anna Darnell, Ernest Belmonte, Victor Sapena, Julián Moreno-Rojas, Valeria Pérez, Virginia Hernández-Gea, Carmen Ayuso, Maria Reig, Juan Carlos García-Pagán, Jordi Bruix","doi":"10.1159/000533598","DOIUrl":"https://doi.org/10.1159/000533598","url":null,"abstract":"<b><i>Introduction:</i></b> The incidence of hepatocellular carcinoma (HCC) in Budd-Chiari syndrome (BCS) is unknown and there is no validated diagnostic work-up to define the liver nodules with arterial phase hyperenhancement (APHE), suggesting malignancy. This prospective study evaluates HCC incidence in a Western cohort of patients with BCS and assesses the performance of MRI with hepatobiliary contrast (HB-MRI) for nodule characterization. <b><i>Methods:</i></b> Patients with BCS followed in our hospital were prospectively evaluated by MRI with extracellular contrast (EC-MRI). Nodules with APHE categorized as non-conclusively benign by 2 radiologists were studied by HB-MRI and reviewed by 2 radiologists blinded to the EC-MRI results. A new EC-MRI 1 year later and clinical, analytical, and sonographic follow-up every 6 months for a median of 10 years was performed. <b><i>Results:</i></b> A total of 55 non-conclusively benign nodules with APHE were detected at EC-MRI in 41 patients. While 32 of them were suggestive of HCC by EC-MRI, all the 55 nodules showed increased uptake of hepatobiliary contrast. An unequivocal central scar was seen in 12/55 nodules at HB-MRI regardless of it was not detected on the EC-MRI. None of the nodules was hypointense in the hepatobiliary phase (HBP). HCC was not detected during a median of 10 years of follow-up. <b><i>Conclusions:</i></b> Detection of nodules with APHE is frequent in patients with BCS, but HCC is rare in Western patients with BCS. While EC-MRI may detect nodules suggesting malignancy, the identification of contrast uptake in the HBP at HB-MRI may help categorize them as benign.","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"26 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136214853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Proteinuria is one of the adverse events of atezolizumab plus bevacizumab combination therapy (Atezo + Bev) and can cause interruption in the use of Bev. However, the risk factors for proteinuria in patients with hepatocellular carcinoma (HCC) who are receiving Atezo + Bev have not yet been investigated. The aim of this study was to identify the risk factors for early onset of proteinuria in Atezo + Bev for patients with unresectable HCC.
Methods: Sixty-four patients with Child-Pugh scores of 5-7, an Eastern Cooperative Oncology Group performance status of 0 or 1, and low level of proteinuria (1+ or less on a dipstick test and urine protein-to-creatinine ratio (UPCR) less than 2.0 g/g Cr) at the initiation of therapy were analyzed. The level of proteinuria was evaluated based on the Common Terminology Criteria for Adverse Events version 5.0. We adopted the UPCR for the quantitative test instead of a 24-h urine collection. The incidence of proteinuria and changes in liver function were retrospectively investigated.
Results: The cumulative incidence of proteinuria over a 24-week period was 34.4%. Multivariate analysis showed that a low estimated glomerular filtration rate (hazard ratio [HR], 3.807; 95% confidence interval [CI], 1.579-9.180; p = 0.003), treatment for hypertension (HR, 6.224; 95% CI, 1.614-24.010; p = 0.008), and high systolic blood pressure (SBP) (HR, 2.649; 95% CI, 1.133-6.194; p = 0.025) were risk factors for proteinuria. Serum albumin levels and albumin-bilirubin scores in patients with proteinuria worsened. In addition, a mean SBP ≥135 mm Hg during treatment was the only risk factor for the development of severe proteinuria (UPCR >2 g/g Cr).
Conclusion: Our study found that controlling blood pressure is extremely important for the management of proteinuria in patients with HCC who are receiving Atezo + Bev.
{"title":"Risk Factors for Early Onset of Proteinuria in Patients Receiving Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma.","authors":"Yuwa Ando, Tomokazu Kawaoka, Masanari Kosaka, Yuki Shirane, Yusuke Johira, Ryoichi Miura, Serami Murakami, Shigeki Yano, Kei Amioka, Kensuke Naruto, Yumi Kosaka, Shinsuke Uchikawa, Kenichiro Kodama, Hatsue Fujino, Takashi Nakahara, Atushi Ono, Eisuke Murakami, Masami Yamauchi, Wataru Okamoto, Shoichi Takahashi, Michio Imamura, Hiroshi Aikata","doi":"10.1159/000528145","DOIUrl":"https://doi.org/10.1159/000528145","url":null,"abstract":"<p><strong>Introduction: </strong>Proteinuria is one of the adverse events of atezolizumab plus bevacizumab combination therapy (Atezo + Bev) and can cause interruption in the use of Bev. However, the risk factors for proteinuria in patients with hepatocellular carcinoma (HCC) who are receiving Atezo + Bev have not yet been investigated. The aim of this study was to identify the risk factors for early onset of proteinuria in Atezo + Bev for patients with unresectable HCC.</p><p><strong>Methods: </strong>Sixty-four patients with Child-Pugh scores of 5-7, an Eastern Cooperative Oncology Group performance status of 0 or 1, and low level of proteinuria (1+ or less on a dipstick test and urine protein-to-creatinine ratio (UPCR) less than 2.0 g/g Cr) at the initiation of therapy were analyzed. The level of proteinuria was evaluated based on the Common Terminology Criteria for Adverse Events version 5.0. We adopted the UPCR for the quantitative test instead of a 24-h urine collection. The incidence of proteinuria and changes in liver function were retrospectively investigated.</p><p><strong>Results: </strong>The cumulative incidence of proteinuria over a 24-week period was 34.4%. Multivariate analysis showed that a low estimated glomerular filtration rate (hazard ratio [HR], 3.807; 95% confidence interval [CI], 1.579-9.180; <i>p</i> = 0.003), treatment for hypertension (HR, 6.224; 95% CI, 1.614-24.010; <i>p</i> = 0.008), and high systolic blood pressure (SBP) (HR, 2.649; 95% CI, 1.133-6.194; <i>p</i> = 0.025) were risk factors for proteinuria. Serum albumin levels and albumin-bilirubin scores in patients with proteinuria worsened. In addition, a mean SBP ≥135 mm Hg during treatment was the only risk factor for the development of severe proteinuria (UPCR >2 g/g Cr).</p><p><strong>Conclusion: </strong>Our study found that controlling blood pressure is extremely important for the management of proteinuria in patients with HCC who are receiving Atezo + Bev.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"12 3","pages":"251-261"},"PeriodicalIF":13.8,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1f/7b/lic-0012-0251.PMC10433089.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10049724","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}
Background/aim: There is no known report regarding the relationship of atezolizumab plus bevacizumab (Atez/Bev) treatment with muscle volume loss (MVL) in unresectable hepatocellular carcinoma (u-HCC) patients. This study aimed to elucidate the clinical relationship between MVL and Atez/Bev.
Materials/methods: From September 2020 to December 2021, 229 u-HCC patients treated with Atez/Bev and with muscle volume data obtained by computed tomography at the baseline available were analyzed (median age, 74 years; males, 186 (81.2%); ECOG PS 0/1, 221 (96.5%); HCV:HBV:alcohol:others = 81:33:40:75; Child-Pugh A, 212 (92.6%); modified albumin-bilirubin (mALBI) grade 1:2a:2b = 79:60:90; BCLC 0:A:B:C = 1:24:87:117; median observation period, 6.8 months). Japan Society of Hepatology criteria were used for definition of MVL and prognostic factors were retrospectively evaluated.
Results: Multivariate Cox-hazard analysis of prognostic factors for progression-free survival (PFS) showed elevated alpha-fetoprotein (AFP) (≥100 ng/mL) (HR 1.848, 95% CI 1.264-2.702, p = 0.002), mALBI grade (≥2a) (HR 1.563, 95% CI 1.035-2.359, p = 0.034), and MVL (HR 1.479, 95% CI 1.020-2.144, p = 0.039) as significant factors. For overall survival (OS), significant factors included elevated AFP (≥100 ng/mL) (HR 3.564, 95% CI 1.856-6.844, p < 0.001), mALBI grade (≥2a) (HR 3.451, 95% CI 1.580-7.538, p = 0.002), and MVL (HR 2.119, 95% CI 1.150-3.904, p = 0.016). Patients with MVL (MVL group, n = 91) showed worse PFS than those without (non-MVL group, n = 138) (median PFS 5.3 vs. 7.6 months, p = 0.025), while the MVL group showed worse OS (p = 0.038), though neither reached the median survival time.
Conclusion: MVL may be a clinical factor related to poor prognosis in patients receiving Atez/Bev treatment for u-HCC.
背景/目的:在不可切除的肝细胞癌(u-HCC)患者中，atezolizumab加贝伐单抗(Atez/Bev)治疗与肌肉体积损失(MVL)的关系尚无已知的报道。本研究旨在阐明MVL与Atez/Bev的临床关系。材料/方法:从2020年9月至2021年12月，229例u-HCC患者接受Atez/Bev治疗，并在基线时通过计算机断层扫描获得肌肉体积数据(中位年龄，74岁;男性186人(81.2%);Ecog ps 0/ 1,221 (96.5%);HCV:HBV:酒精:其他= 81:33:40:75;Child-Pugh A, 212 (92.6%);改性白蛋白-胆红素(mALBI)分级1:2a:2b = 79:60:90;BCLC 0: a: b: c = 1:24:87:117;中位观察期为6.8个月)。采用日本肝病学会的标准定义MVL，并对预后因素进行回顾性评估。结果:多因素Cox-hazard分析无进展生存期(PFS)预后因素显示，甲胎蛋白(AFP)升高(≥100 ng/mL) (HR 1.848, 95% CI 1.264-2.702, p = 0.002)、mALBI分级(≥2a) (HR 1.563, 95% CI 1.035-2.359, p = 0.034)和MVL (HR 1.479, 95% CI 1.020-2.144, p = 0.039)为显著因素。对于总生存率(OS)，显著因素包括AFP升高(≥100 ng/mL) (HR 3.564, 95% CI 1.856-6.844, p < 0.001)、mALBI分级(≥2a) (HR 3.451, 95% CI 1.580-7.538, p = 0.002)和MVL (HR 2.119, 95% CI 1.150-3.904, p = 0.016)。MVL患者(MVL组，n = 91)的PFS较无MVL患者(非MVL组，n = 138)差(中位PFS 5.3 vs. 7.6个月，p = 0.025)，而MVL组的OS较差(p = 0.038)，但均未达到中位生存时间。结论:MVL可能是u-HCC患者接受Atez/Bev治疗预后不良的一个临床因素。
{"title":"Relationship of Atezolizumab plus Bevacizumab Treatment with Muscle Volume Loss in Unresectable Hepatocellular Carcinoma Patients: Multicenter Analysis.","authors":"Atsushi Hiraoka, Takashi Kumada, Toshifumi Tada, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Shinya Fukunishi, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Hironori Ochi, Satoshi Yasuda, Hidenori Toyoda, Chikara Ogawa, Takashi Nishimura, Takeshi Hatanaka, Satoru Kakizaki, Noritomo Shimada, Kazuhito Kawata, Atsushi Naganuma, Masaki Kaibori, Takaaki Tanaka, Hideko Ohama, Kazuhiro Nouso, Asahiro Morishita, Akemi Tsutsui, Takuya Nagano, Norio Itokawa, Tomomi Okubo, Taeang Arai, Michitaka Imai, Yohei Koizumi, Shinichiro Nakamura, Kouji Joko, Hiroko Iijima, Hisashi Kosaka, Yoichi Hiasa, Masatoshi Kudo","doi":"10.1159/000527402","DOIUrl":"https://doi.org/10.1159/000527402","url":null,"abstract":"<p><strong>Background/aim: </strong>There is no known report regarding the relationship of atezolizumab plus bevacizumab (Atez/Bev) treatment with muscle volume loss (MVL) in unresectable hepatocellular carcinoma (u-HCC) patients. This study aimed to elucidate the clinical relationship between MVL and Atez/Bev.</p><p><strong>Materials/methods: </strong>From September 2020 to December 2021, 229 u-HCC patients treated with Atez/Bev and with muscle volume data obtained by computed tomography at the baseline available were analyzed (median age, 74 years; males, 186 (81.2%); ECOG PS 0/1, 221 (96.5%); HCV:HBV:alcohol:others = 81:33:40:75; Child-Pugh A, 212 (92.6%); modified albumin-bilirubin (mALBI) grade 1:2a:2b = 79:60:90; BCLC 0:A:B:C = 1:24:87:117; median observation period, 6.8 months). Japan Society of Hepatology criteria were used for definition of MVL and prognostic factors were retrospectively evaluated.</p><p><strong>Results: </strong>Multivariate Cox-hazard analysis of prognostic factors for progression-free survival (PFS) showed elevated alpha-fetoprotein (AFP) (≥100 ng/mL) (HR 1.848, 95% CI 1.264-2.702, <i>p</i> = 0.002), mALBI grade (≥2a) (HR 1.563, 95% CI 1.035-2.359, <i>p</i> = 0.034), and MVL (HR 1.479, 95% CI 1.020-2.144, <i>p</i> = 0.039) as significant factors. For overall survival (OS), significant factors included elevated AFP (≥100 ng/mL) (HR 3.564, 95% CI 1.856-6.844, <i>p</i> < 0.001), mALBI grade (≥2a) (HR 3.451, 95% CI 1.580-7.538, <i>p</i> = 0.002), and MVL (HR 2.119, 95% CI 1.150-3.904, <i>p</i> = 0.016). Patients with MVL (MVL group, <i>n</i> = 91) showed worse PFS than those without (non-MVL group, <i>n</i> = 138) (median PFS 5.3 vs. 7.6 months, <i>p</i> = 0.025), while the MVL group showed worse OS (<i>p</i> = 0.038), though neither reached the median survival time.</p><p><strong>Conclusion: </strong>MVL may be a clinical factor related to poor prognosis in patients receiving Atez/Bev treatment for u-HCC.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"12 3","pages":"209-217"},"PeriodicalIF":13.8,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3a/91/lic-0012-0209.PMC10433099.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10406206","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}
Hepatic resection and radiofrequency ablation (RFA)/ microwave ablation are well-established curative treatments for hepatocellular carcinoma (HCC); however, the disease often recurs [1, 2]. Pathological studies of resected HCC specimens reported that microscopic intrahepatic metastases are present in about 10% of patients with a solitary HCC measuring 2 cm or less. Microvascular invasion is also present in about 27% of patients [3]. Based on these facts, it is believed that there is a certain risk of recurrence of intrahepatic metastasis, even for a single nodule measuring 2 cm or less. Furthermore, the larger the tumor, or the presence of multiple HCCs larger than 2 cm, increases the risk of intrahepatic metastasis and microvascular invasion, and therefore the risk of intrahepatic metastatic recurrence [4, 5]. There are two patterns of recurrence after curative treatment: early and late. Early recurrence involves mainly intrahepatic metastasis via the portal vein, while late recurrence has a more multicentric etiology [2]. About 80% of HCCs recur 5 years after RFA or resection [6]. The main reason for the poor prognosis associated with HCC is frequent recurrence, even after curative treatment. Repeated TACE to treat recurrence worsens liver function in many cases, resulting in death from liver failure. Conversely, if HCC recurrence after curative treatment can be suppressed, the prognosis should improve dramatically. Several adjuvant trials have been conducted to inhibit recurrence, but all yielded negative results [7–9]. To date, representative clinical trials of adjuvants that help to prevent recurrence include a trial of Vitamin K [7], the NIK-333 trial that used retinoid [8], and the STORM trial
{"title":"Adjuvant Atezolizumab-Bevacizumab after Resection or Ablation for Hepatocellular Carcinoma.","authors":"Masatoshi Kudo","doi":"10.1159/000531225","DOIUrl":"https://doi.org/10.1159/000531225","url":null,"abstract":"Hepatic resection and radiofrequency ablation (RFA)/ microwave ablation are well-established curative treatments for hepatocellular carcinoma (HCC); however, the disease often recurs [1, 2]. Pathological studies of resected HCC specimens reported that microscopic intrahepatic metastases are present in about 10% of patients with a solitary HCC measuring 2 cm or less. Microvascular invasion is also present in about 27% of patients [3]. Based on these facts, it is believed that there is a certain risk of recurrence of intrahepatic metastasis, even for a single nodule measuring 2 cm or less. Furthermore, the larger the tumor, or the presence of multiple HCCs larger than 2 cm, increases the risk of intrahepatic metastasis and microvascular invasion, and therefore the risk of intrahepatic metastatic recurrence [4, 5]. There are two patterns of recurrence after curative treatment: early and late. Early recurrence involves mainly intrahepatic metastasis via the portal vein, while late recurrence has a more multicentric etiology [2]. About 80% of HCCs recur 5 years after RFA or resection [6]. The main reason for the poor prognosis associated with HCC is frequent recurrence, even after curative treatment. Repeated TACE to treat recurrence worsens liver function in many cases, resulting in death from liver failure. Conversely, if HCC recurrence after curative treatment can be suppressed, the prognosis should improve dramatically. Several adjuvant trials have been conducted to inhibit recurrence, but all yielded negative results [7–9]. To date, representative clinical trials of adjuvants that help to prevent recurrence include a trial of Vitamin K [7], the NIK-333 trial that used retinoid [8], and the STORM trial","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"12 3","pages":"189-197"},"PeriodicalIF":13.8,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f4/57/lic-2023-0012-0003-531225.PMC10360452.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10291505","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}
Introduction: Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive liver malignancy with poor prognosis. Recently, the development of immune checkpoint inhibitors (ICIs), such as programmed cell death 1 (PD-1) inhibitors, has emerged as a promising strategy in multiple tumor types, including ICC. Microsatellite instability-high (MSI-H) is an important biomarker for ICIs in solid tumors. The response rate in patients with MSI-H is significantly higher than in those with microsatellite stability/microsatellite instability-low. And approximately 80-90% of the patients with MSI-H could maintain sustained clinical benefits once they had an initial response. However, some patients could have primary resistance at the beginning, and some might have acquired resistance after long-term treatment.
Case presentation: We present the case of an ICC patient with MSI-H who suffered rapid progression after a short-term remission with camrelizumab, a kind of PD-1 inhibitor, as second-line treatment. The patient's genomic and immune features were analyzed by next-generation sequencing and multiplex immunofluorescence staining to explore the possible mechanisms of the rapidly acquired resistance of ICIs in this MSI-H case.
Conclusion: The genomic and immunohistochemical analysis showed that TGFBR2 mutation, loss of HLA B44 supertype, carrying B62 supertype, and increased PD-L1+ cells, macrophages, and Tregs in the tumor microenvironment might be related to the nonsustain benefit of ICIs in this MSI-H patient.
{"title":"Genomic and Immune Features in an Intrahepatic Cholangiocarcinoma Patient with Microsatellite Instability-High Suffered Rapid Acquired Resistance to PD-1 Inhibitor.","authors":"Zhuo Cheng, Tianmei Zeng, Guang Yang, Di Liu, Zhi Zheng, Zhengang Yuan","doi":"10.1159/000530273","DOIUrl":"https://doi.org/10.1159/000530273","url":null,"abstract":"<p><strong>Introduction: </strong>Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive liver malignancy with poor prognosis. Recently, the development of immune checkpoint inhibitors (ICIs), such as programmed cell death 1 (PD-1) inhibitors, has emerged as a promising strategy in multiple tumor types, including ICC. Microsatellite instability-high (MSI-H) is an important biomarker for ICIs in solid tumors. The response rate in patients with MSI-H is significantly higher than in those with microsatellite stability/microsatellite instability-low. And approximately 80-90% of the patients with MSI-H could maintain sustained clinical benefits once they had an initial response. However, some patients could have primary resistance at the beginning, and some might have acquired resistance after long-term treatment.</p><p><strong>Case presentation: </strong>We present the case of an ICC patient with MSI-H who suffered rapid progression after a short-term remission with camrelizumab, a kind of PD-1 inhibitor, as second-line treatment. The patient's genomic and immune features were analyzed by next-generation sequencing and multiplex immunofluorescence staining to explore the possible mechanisms of the rapidly acquired resistance of ICIs in this MSI-H case.</p><p><strong>Conclusion: </strong>The genomic and immunohistochemical analysis showed that TGFBR2 mutation, loss of HLA B44 supertype, carrying B62 supertype, and increased PD-L1<sup>+</sup> cells, macrophages, and Tregs in the tumor microenvironment might be related to the nonsustain benefit of ICIs in this MSI-H patient.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"12 3","pages":"281-288"},"PeriodicalIF":13.8,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a5/df/lic-2023-0012-0003-530273.PMC10427924.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10603731","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}
Pub Date : 2023-07-28eCollection Date: 2023-09-01DOI: 10.1159/000532023
Masatoshi Kudo
{"title":"Drug-Off Criteria in Patients with Hepatocellular Carcinoma Who Achieved Clinical Complete Response after Combination Immunotherapy Combined with Locoregional Therapy.","authors":"Masatoshi Kudo","doi":"10.1159/000532023","DOIUrl":"10.1159/000532023","url":null,"abstract":"","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"12 4","pages":"289-296"},"PeriodicalIF":11.6,"publicationDate":"2023-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10601881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71412862","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}
Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare a rare subtype of hepatocellular carcinoma. The IMbrave150 trial demonstrated that atezolizumab and bevacizumab therapy (ABT) has better treatment outcomes than sorafenib for advanced HCC. However, since patients with known FLHCC were excluded from this trial, the effects of ABT on FLHCC remain unknown. We report the first case of ABT for advanced FLHCC followed by hepatectomy presenting pseudoprogression of lymph node (LN) metastases which was pathologically proven after surgery. The patient was a 30-year-old man with advanced FLHCC and multiple LN metastases behind the pancreatic head, and ABT was introduced. After four courses of treatment, CT indicated a minor decrease in the intratumor vascularity of the liver tumor. However, the size of metastatic LNs increased. Subsequently, the patient presented with bloody stool, and colonoscopy revealed immune-related colitis caused by atezolizumab. Therefore, the fifth course was canceled. A right hemihepatectomy following percutaneous transhepatic portal vein embolization (PTPE) was performed to increase the future liver remnant volume. After PTPE, dynamic CT revealed an objective response to ABT; SD in RECIST 1.1 (7% increase in the LN size and no change of liver tumor), and PR in modified RECIST (47% decrease in the intratumor vascularity of the liver tumor and LNs). Three weeks after PTPE, right hemihepatectomy plus nodal dissection was successfully performed. Pathological findings revealed that approximately 60%–70% of the liver tumor and 70%–80% of the metastatic LNs were necrotic, indicating a good response to ABT. The increasing size of metastatic LNs that occurred during the treatment course was deemed pseudoprogression. Pseudoprogression can be found in patients with solid malignancies treated with immune checkpoint inhibitors, however, rarely occurs in HCC. The first response to metastatic LNs was observed 20 weeks after ABT initiation combined with an increase in nodal volume and a decrease in vascularity. In the updated data of the IMbrave150 trial, 19% of the first responses occurred after week 24. Physicians should consider that ABT may also be effective in FLHCC and may cause pseudoprogression before determining a treatment strategy.
{"title":"Atezolizumab and Bevacizumab Combination Therapy and Sequential Conversion Hepatectomy for Advanced Fibrolamellar Hepatocellular Carcinoma Presenting Pseudoprogression.","authors":"Ryota Matsuki, Naohiro Okano, Nobuhiro Hasui, Shohei Kawaguchi, Hirokazu Momose, Keiichiro Kitahama, Kiyotaka Nagahama, Masaharu Kogure, Yutaka Suzuki, Fumio Nagashima, Junji Shibahara, Hideaki Mori, Yoshihiro Sakamoto","doi":"10.1159/000527250","DOIUrl":"https://doi.org/10.1159/000527250","url":null,"abstract":"Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare a rare subtype of hepatocellular carcinoma. The IMbrave150 trial demonstrated that atezolizumab and bevacizumab therapy (ABT) has better treatment outcomes than sorafenib for advanced HCC. However, since patients with known FLHCC were excluded from this trial, the effects of ABT on FLHCC remain unknown. We report the first case of ABT for advanced FLHCC followed by hepatectomy presenting pseudoprogression of lymph node (LN) metastases which was pathologically proven after surgery.\u0000The patient was a 30-year-old man with advanced FLHCC and multiple LN metastases behind the pancreatic head, and ABT was introduced. After four courses of treatment, CT indicated a minor decrease in the intratumor vascularity of the liver tumor. However, the size of metastatic LNs increased. Subsequently, the patient presented with bloody stool, and colonoscopy revealed immune-related colitis caused by atezolizumab. Therefore, the fifth course was canceled. A right hemihepatectomy following percutaneous transhepatic portal vein embolization (PTPE) was performed to increase the future liver remnant volume. After PTPE, dynamic CT revealed an objective response to ABT; SD in RECIST 1.1 (7% increase in the LN size and no change of liver tumor), and PR in modified RECIST (47% decrease in the intratumor vascularity of the liver tumor and LNs). Three weeks after PTPE, right hemihepatectomy plus nodal dissection was successfully performed. Pathological findings revealed that approximately 60%–70% of the liver tumor and 70%–80% of the metastatic LNs were necrotic, indicating a good response to ABT. The increasing size of metastatic LNs that occurred during the treatment course was deemed pseudoprogression. Pseudoprogression can be found in patients with solid malignancies treated with immune checkpoint inhibitors, however, rarely occurs in HCC. The first response to metastatic LNs was observed 20 weeks after ABT initiation combined with an increase in nodal volume and a decrease in vascularity. In the updated data of the IMbrave150 trial, 19% of the first responses occurred after week 24. Physicians should consider that ABT may also be effective in FLHCC and may cause pseudoprogression before determining a treatment strategy.","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"12 2","pages":"180-183"},"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/48/7c/lic-0012-0180.PMC10267524.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9654525","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：