Hepatobiliary Malignancies: Recent Advancements and Future Directions

A special issue of Current Oncology (ISSN 1718-7729). This special issue belongs to the section "Gastrointestinal Oncology".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 62330

Special Issue Editor


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Guest Editor
1. Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawaharacho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
2. Department of Gastroenterological Surgery and Oncology, Kitano Hospital Medical Research Institute, 2-4-20 Ogimachi, Kita-ku, Osaka 530-8480, Japan
Interests: liver surgery; liver tumor; liver fibrosis; biliary surgery; biliary disease; liver transplantation; pancreatic surgery; laparoscopic surgery

Special Issue Information

Dear Colleagues,

Hepatobiliary malignancies includes a variety of cancers such as hepatocellular carcinoma and cholangiocarcinoma and represent one of the most challenging human neoplasms to be treated. Compared to cancers of the gastrointestinal tracts, the development of therapeutic means is lagging behind due to the rarity of the diseases. The aggressive nature of the disease itself and the difficulty of early detection limit the number of patients eligible for curative treatment. In addition, surgery is often highly invasive and associated with high risk. Due to these complex factors, the therapeutic outcome of hepatobiliary malignancies is suboptimal, leaving much room for improvement.

There have been many highlights in recent years regarding the treatment of hepatobiliary malignancies. The development of molecular targeted agents and immunotherapies for hepatocellular carcinoma has revolutionized the treatment of advanced hepatocellular carcinoma. The introduction of minimally invasive laparoscopic surgery has increased the number of patients who benefit from surgery and may contribute to further expanding the indications for liver surgery. The indications for liver transplantation for hepatobiliary malignancies has gradually expanded and may be the last hope for patients who were otherwise incurable.

In the present Special Issue “Hepatobiliary Malignancies: Recent Advancements and Future Directions”, we would like to gather submissions that cover significant contributions in the following issues:

A. Surgical therapies

1) Resection: laparoscopic and robotic hepatobiliary surgeries, recent advancement and the future

2) Liver transplantation: expanding indications for hepatocellular carcinoma liver transplantation for hepatobiliary malignancies other than hepatocellular carcinoma (intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma, colorectal liver metastasis, and liver metastasis from endocrine tumors)

B. Pharmacological therapies

1) Molecular targeted therapies and immunotherapies for hepatocellular carcinoma

2) Pharmacological therapies for cholangiocarcinoma: recent advances and future directions

3) Genomic medicine for hepatobiliary malignancies

C. Non-surgical and non-pharmacological therapies for hepatobiliary malignancies

1) Ablation therapies for hepatocellular carcinoma

2) Transarterial therapies for hepatocellular carcinoma

3) Radiation therapies for hepatobiliary malignancies

Dr. Kojiro Taura
Guest Editor

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Keywords

  • liver cancer
  • hepatocellular carcinoma
  • cholangiocarcinoma
  • resection

Published Papers (21 papers)

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Editorial

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3 pages, 157 KiB  
Editorial
Advances and Future Directions in Hepatobiliary Malignancies
by Kojiro Taura
Curr. Oncol. 2023, 30(11), 9786-9788; https://doi.org/10.3390/curroncol30110710 - 07 Nov 2023
Viewed by 731
Abstract
I am delighted to present this Special Issue of our journal, focusing on “Hepatobiliary Malignancies: Recent Advancements and Future Directions” [...] Full article
(This article belongs to the Special Issue Hepatobiliary Malignancies: Recent Advancements and Future Directions)

Research

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8 pages, 1886 KiB  
Communication
Fiducial Markers Allow Accurate and Reproducible Delivery of Liver Stereotactic Body Radiation Therapy
by Marina Moskalenko, Bernard L. Jones, Adam Mueller, Shirley Lewis, Jay C. Shiao, Sara J. Zakem, Tyler P. Robin and Karyn A. Goodman
Curr. Oncol. 2023, 30(5), 5054-5061; https://doi.org/10.3390/curroncol30050382 - 16 May 2023
Cited by 1 | Viewed by 1757
Abstract
Fiducial markers are utilized for image guided radiotherapy (IGRT) alignment during the delivery of liver stereotactic body radiosurgery (SBRT). There are limited data demonstrating the impact of matching fiducials on the accuracy of liver SBRT. This study quantifies the benefit of fiducial-based alignment [...] Read more.
Fiducial markers are utilized for image guided radiotherapy (IGRT) alignment during the delivery of liver stereotactic body radiosurgery (SBRT). There are limited data demonstrating the impact of matching fiducials on the accuracy of liver SBRT. This study quantifies the benefit of fiducial-based alignment and improvements in inter-observer reliability. Nineteen patients with 24 liver lesions were treated with SBRT. Target localization was performed using fiducial markers on cone-beam computed tomography (CBCT). Each CBCT procedure was retrospectively realigned to match both the liver edge and fiducial markers. The shifts were recorded by seven independent observers. Inter-observer variability was analyzed by calculating the mean error and uncertainty for the set-up. The mean absolute Cartesian error observed from fiducial and liver edge-based alignment was 1.5 mm and 5.3 mm, respectively. The mean uncertainty from fiducial and liver edge-based alignment was 1.8 mm and 4.5 mm, respectively. An error of 5 mm or greater was observed 50% of the time when aligning to the liver surface versus 5% of the time when aligning to fiducial markers. Aligning to the liver edge significantly increased the error, resulting in increased shifts when compared to alignment to fiducials. Tumors of 3 cm or farther from the liver dome had higher mean errors when aligned without fiducials (4.8 cm vs. 4.4 cm, p = 0.003). Our data support the use of fiducial markers for safer and more accurate liver SBRT. Full article
(This article belongs to the Special Issue Hepatobiliary Malignancies: Recent Advancements and Future Directions)
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9 pages, 569 KiB  
Article
Osteopenia Is Associated with Shorter Survival in Patients with Intrahepatic Cholangiocarcinoma
by Atsushi Miki, Yasunaru Sakuma, Jun Watanabe, Kazuhiro Endo, Hideki Sasanuma, Takumi Teratani, Alan Kawarai Lefor, Joji Kitayama and Naohiro Sata
Curr. Oncol. 2023, 30(2), 1860-1868; https://doi.org/10.3390/curroncol30020144 - 02 Feb 2023
Cited by 3 | Viewed by 1640
Abstract
Background: The prognostic importance of osteopenia in patients with intrahepatic cholangiocarcinoma (ICC) undergoing hepatectomy is unclear. The aim of this study was to evaluate the impact of osteopenia on survival in patients with ICC. Methods: A total of 71 patients who underwent hepatectomy [...] Read more.
Background: The prognostic importance of osteopenia in patients with intrahepatic cholangiocarcinoma (ICC) undergoing hepatectomy is unclear. The aim of this study was to evaluate the impact of osteopenia on survival in patients with ICC. Methods: A total of 71 patients who underwent hepatectomy at Jichi Medical University between July 2008 and June 2022 were included in this study. Non-contrast computed tomography scan images at the eleventh thoracic vertebra were used to assess bone mineral density. The cutoff value was calculated using a threshold value of 160 Hounsfield units. Overall survival curves were made using the Kaplan–Meier method and the log-rank test was used to evaluate survival. The hazard ratio (HR) and 95% confidence interval (CI) for overall survival were calculated using Cox’s proportional hazard model. Results: In multivariable analysis, osteopenia (HR 3.66, 95%CI 1.16–14.1, p = 0.0258) and the platelet–lymphocyte ratio (HR 6.26, 95%CI 2.27–15.9, p = 0.0008) were significant independent factors associated with overall survival. There were no significant independent prognostic factors for recurrence-free survival. Conclusions: Preoperative osteopenia is significantly associated with postoperative survival in patients with ICC undergoing hepatectomy. Full article
(This article belongs to the Special Issue Hepatobiliary Malignancies: Recent Advancements and Future Directions)
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11 pages, 1589 KiB  
Article
Temporary Reversal of Hepatoenteric Collaterals during 90Y Radioembolization Planning and Administration
by Peiman Habibollahi, Bruno C. Odisio, Varshana Gurusamy, Joshua D. Kuban, Rony Avritscher, Mohamed E. Abdelsalam, Beth A. Chasen, Ravi Murthy and Armeen Mahvash
Curr. Oncol. 2022, 29(12), 9582-9592; https://doi.org/10.3390/curroncol29120753 - 06 Dec 2022
Cited by 1 | Viewed by 1495
Abstract
Purpose: This paper aims to evaluate the safety and efficacy of the temporary redirection of blood flow of hepatoenteric collaterals using a balloon catheter in the common hepatic artery (CHA) to prevent the nontarget deposition of 90Y microspheres. Materials and Methods: In [...] Read more.
Purpose: This paper aims to evaluate the safety and efficacy of the temporary redirection of blood flow of hepatoenteric collaterals using a balloon catheter in the common hepatic artery (CHA) to prevent the nontarget deposition of 90Y microspheres. Materials and Methods: In this retrospective single-center study of patients who received 90Y radioembolization (RE) from September 2010 to September 2015, diagnostic (67 patients) or treatment (72 patients) angiograms with the attempted use of a balloon catheter in the CHA to temporarily direct blood flow away from the hepatoenteric arteries were analyzed. SPECT/CT nuclear scintigraphy was performed after both diagnosis and treatment. Results: Overall, only 12 hepatoenteric arteries in 11 patients required embolization due to persistent hepatoenteric flow despite the use of the balloon occlusion technique in a total of 86 patients. Physicians performed the 90Y RE using balloon occlusion with glass (n = 22) or resin (n = 50) microspheres. Over 80% administration of the prescribed 90Y dose was accomplished in 34 (67%) resin and 20 (95%) glass microsphere patients. Post-treatment 90Y RE scintigraphy confirmed the absence of extrahepatic activity in all patients. One grade 2 gastrointestinal ulcer was present after 90 days of follow-up. Conclusion: Temporary CHA occlusion with a balloon catheter is a reliable and reproducible alternative to the conventional coil embolization of hepatoenteric arteries during diagnostic Tc-99m macroaggregated albumin and therapeutic 90Y RE delivery. Full article
(This article belongs to the Special Issue Hepatobiliary Malignancies: Recent Advancements and Future Directions)
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12 pages, 1244 KiB  
Article
Stereotactic Radiotherapy after Incomplete Transarterial (Chemo-) Embolization (TAE\TACE) versus Exclusive TAE or TACE for Treatment of Inoperable HCC: A Phase III Trial (NCT02323360)
by Tiziana Comito, Mauro Loi, Ciro Franzese, Elena Clerici, Davide Franceschini, Marco Badalamenti, Maria Ausilia Teriaca, Lorenza Rimassa, Vittorio Pedicini, Dario Poretti, Luigi Alessandro Solbiati, Guido Torzilli, Roberto Ceriani, Ana Lleo, Alessio Aghemo, Armando Santoro and Marta Scorsetti
Curr. Oncol. 2022, 29(11), 8802-8813; https://doi.org/10.3390/curroncol29110692 - 16 Nov 2022
Cited by 11 | Viewed by 3652
Abstract
Background: Hepatocellular carcinoma (HCC) is the most frequent liver malignancy and a leading cause of cancer death in the world. In unresectable HCC patients, transcatheter arterial (chemo-) embolization (TAE/TACE) has shown a disease response in 15–55% of cases. Though multiple TAE/TACE courses can [...] Read more.
Background: Hepatocellular carcinoma (HCC) is the most frequent liver malignancy and a leading cause of cancer death in the world. In unresectable HCC patients, transcatheter arterial (chemo-) embolization (TAE/TACE) has shown a disease response in 15–55% of cases. Though multiple TAE/TACE courses can be administered in principle, Stereotactic Body Radiotherapy (SBRT) has emerged as an alternative option in the case of local relapse following multiple TAE/TACE courses. Methods: This is a single-center, prospective, randomized, controlled, parallel-group superiority trial of SBRT versus standard TAE/TACE for the curative treatment of the intermediate stage of HCC after an incomplete response following TAE/TACE (NCT02323360). The primary endpoint is 1-year local control (LC): 18 events were needed to assess a 45% difference (HR: 0.18) in favor of SBRT. The secondary endpoints are 1-year Progression-Free Survival (PFS), Distant Recurrence-Free Survival (DRFS), Overall Survival (OS) and the incidence of acute and late complications. Results: At the time of the final analysis, 40 patients were enrolled, 19 (49%) in the TAE/TACE arm and 21 (51%) in the SBRT arm. The trial was prematurely closed due to slow accrual. The 1- and 2-year LC rates were 57% and 36%. The use of SBRT resulted in superior LC as compared to TAE/TACE rechallenge (median not reached versus 8 months, p = 0.0002). PFS was 29% and 16% at 1 and 2 years, respectively. OS was 86% and 62% at 1 year and 2 years, respectively. In the TAE arm, PFS was 13% and 6% at 1 and 2 years, respectively. In the SBRT arm, at 1 and 2 years, PFS was 37% and 21%, respectively. OS at 1 and 2 years was 75% and 64% in the SBRT arm and 95% and 57% in the TACE arm, respectively. No grade >3 toxicity was recorded. Conclusions: SBRT is an effective treatment option in patients affected by inoperable HCC experiencing an incomplete response following ≥1 cycle of TAE/TAC. Full article
(This article belongs to the Special Issue Hepatobiliary Malignancies: Recent Advancements and Future Directions)
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8 pages, 1741 KiB  
Article
Is Laparoscopic Hepatectomy Safe for Giant Liver Tumors? Proposal from a Single Institution for Totally Laparoscopic Hemihepatectomy Using an Anterior Approach for Giant Liver Tumors Larger Than 10 cm in Diameter
by Hiroyuki Nitta, Akira Sasaki, Hirokatsu Katagiri, Shoji Kanno and Akira Umemura
Curr. Oncol. 2022, 29(11), 8261-8268; https://doi.org/10.3390/curroncol29110652 - 31 Oct 2022
Cited by 4 | Viewed by 1525
Abstract
Background: The efficacy and safety of laparoscopic liver resections for liver tumors that are larger than 10 cm remain unclear. We developed a safe laparoscopic right hemihepatectomy for giant liver tumors using an anterior approach. Methods: Eighty patients who underwent laparoscopic hemihepatectomy between [...] Read more.
Background: The efficacy and safety of laparoscopic liver resections for liver tumors that are larger than 10 cm remain unclear. We developed a safe laparoscopic right hemihepatectomy for giant liver tumors using an anterior approach. Methods: Eighty patients who underwent laparoscopic hemihepatectomy between January 2011 and December 2021 were divided into a nongiant tumor group (n = 65) and a giant tumor group (n = 15) for comparison. Results: The median operating time, amount of blood loss, and length of postoperative hospital stay did not differ significantly between the nongiant and giant tumor groups. The sizes of the tumors and weights of the resected liver were significantly larger in the giant tumor group. A comparison between a nongiant group (n = 23) and a giant group (n = 12) treated with laparoscopic right hemihepatectomy showed similar results. Conclusions: Laparoscopic hemihepatectomy, especially that performed on the right side, for giant tumors larger than 10 cm can be performed safely. Surgical techniques for giant liver tumors have been standardized, and their application is expected to spread widely in the future. Full article
(This article belongs to the Special Issue Hepatobiliary Malignancies: Recent Advancements and Future Directions)
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8 pages, 492 KiB  
Article
Hepatic Abscess following Yttrium-90 Radioembolization in Patients with Surgical Bilioenteric Anastomosis or Compromised Sphincter of Oddi: A Tertiary Cancer Center Experience
by Kevin N. Agahi, Armeen Mahvash and Mohamed E. Abdelsalam
Curr. Oncol. 2022, 29(10), 7051-7058; https://doi.org/10.3390/curroncol29100553 - 28 Sep 2022
Cited by 1 | Viewed by 1628
Abstract
Purpose: We describe our experience with the development of hepatobiliary infection in patients with prior surgical, percutaneous, or endoscopic biliary interventions who are receiving transarterial radioembolization (TARE) with yttrium-90 (90Y) for primary or metastatic hepatobiliary lesions. Methods: Records of [...] Read more.
Purpose: We describe our experience with the development of hepatobiliary infection in patients with prior surgical, percutaneous, or endoscopic biliary interventions who are receiving transarterial radioembolization (TARE) with yttrium-90 (90Y) for primary or metastatic hepatobiliary lesions. Methods: Records of 15 patients with a history of prior biliary intervention and liver malignancy subsequently treated with TARE at the participating medical center from November 2009 to September 2015 were reviewed. The primary endpoint was the development of a hepatic abscess or cholangitis in a patient after radioembolization. Results: A total of 15 patients comprising 9 men and 6 women, with a median age of 49 years (range 30–73), underwent 17 TARE with 90Y procedures. Of the 15 patients, 2 (13.3%) of them developed a hepatobiliary infection. A single patient (6.6%) developed a hepatobiliary abscess. Conclusion: Our study shows a low incidence rate of hepatic abscess following TARE in patients with prior biliary intervention. Full article
(This article belongs to the Special Issue Hepatobiliary Malignancies: Recent Advancements and Future Directions)
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7 pages, 815 KiB  
Article
Intensive Follow-Up Program and Oncological Outcomes of Biliary Tract Cancer Patients after Curative-Intent Surgery: A Twenty-Year Experience in a Single Tertiary Medical Center
by Alessandro Rizzo, Riccardo Carloni, Giorgio Frega, Andrea Palloni, Alessandro Di Federico, Angela Dalia Ricci, Raffaele De Luca, Simona Tavolari and Giovanni Brandi
Curr. Oncol. 2022, 29(7), 5084-5090; https://doi.org/10.3390/curroncol29070402 - 19 Jul 2022
Cited by 3 | Viewed by 2228
Abstract
Aim. The aim of this research was to assess the impact of an intensive follow-up program on BTC patients who had received surgery with curative intent at a tertiary referral hospital. Methods. BTC patients were followed-up every three months during the first two [...] Read more.
Aim. The aim of this research was to assess the impact of an intensive follow-up program on BTC patients who had received surgery with curative intent at a tertiary referral hospital. Methods. BTC patients were followed-up every three months during the first two years after their first surgery and every six months from the third to the fifth post-operative year. Results. A total of 278 BTC patients who received R0/R1 surgery were included. A total of 17.7% of patients underwent a second surgery following disease relapse, and none of these patients experienced additional disease relapse. Conclusions. An intensive follow-up after surgical resection may help in the early identification of disease relapse, leading to early treatment and prolonged survival in selected cases. Full article
(This article belongs to the Special Issue Hepatobiliary Malignancies: Recent Advancements and Future Directions)
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12 pages, 1820 KiB  
Article
Endobiliary Radiofrequency Ablation Combined with Gemcitabine and Cisplatin in Patients with Unresectable Extrahepatic Cholangiocarcinoma
by Tadahisa Inoue, Itaru Naitoh, Rena Kitano, Mayu Ibusuki, Yuji Kobayashi, Yoshio Sumida, Yukiomi Nakade, Kiyoaki Ito and Masashi Yoneda
Curr. Oncol. 2022, 29(4), 2240-2251; https://doi.org/10.3390/curroncol29040182 - 23 Mar 2022
Cited by 13 | Viewed by 2416
Abstract
Background: Endobiliary radiofrequency ablation (RFA) is a promising treatment modality for patients with extrahepatic cholangiocarcinoma (eCCA). However, no study has investigated the combined use of endobiliary RFA and gemcitabine plus cisplatin (GC) chemotherapy. This study aimed to examine the feasibility and efficacy of [...] Read more.
Background: Endobiliary radiofrequency ablation (RFA) is a promising treatment modality for patients with extrahepatic cholangiocarcinoma (eCCA). However, no study has investigated the combined use of endobiliary RFA and gemcitabine plus cisplatin (GC) chemotherapy. This study aimed to examine the feasibility and efficacy of endobiliary RFA with GC therapy for patients with unresectable eCCA. Methods: The study outcomes included overall survival (OS), progression-free survival (PFS), time to recurrent biliary obstruction (RBO), and adverse events associated with the treatment. These parameters were retrospectively compared between 25 patients who underwent RFA with self-expandable metal stent (SEMS) placement followed by GC therapy (with-RFA group) and a control cohort of 25 patients who underwent SEMS placement alone and GC therapy (without-RFA group). Results: The median time to RBO was significantly longer in the with-RFA group (10.7 versus 5.2 months, p = 0.048). The median OS was significantly higher in patients with locally advanced tumors in the with-RFA group (23.1 versus 16.6 months, p = 0.032), but did not differ significantly in patients with metastasis (11.4 versus 8.5 months, p = 0.180). Similarly, the median PFS was significantly higher in the with-RFA group in patients with locally advanced disease (10.1 versus 7.3 months, p = 0.015), while there was no significant difference in patients with metastasis (5.4 versus 4.4 months, p = 0.529). The rates of various toxicities did not differ significantly between the groups. Conclusions: Endobiliary RFA prolonged the patency period of uncovered SEMS combined with GC therapy in patients with eCCA. Although RFA also yielded survival benefits, its effect was restricted to locally advanced tumors. Full article
(This article belongs to the Special Issue Hepatobiliary Malignancies: Recent Advancements and Future Directions)
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13 pages, 1414 KiB  
Article
Low Platelet Count Predicts Reduced Survival in Potentially Resectable Hepatocellular Carcinoma
by Christopher Schrecker, Oliver Waidmann, Hanan El Youzouri, Jörg Trojan, Andreas Anton Schnitzbauer, Wolf Otto Bechstein, Stefan Zeuzem and Christine Koch
Curr. Oncol. 2022, 29(3), 1475-1487; https://doi.org/10.3390/curroncol29030124 - 28 Feb 2022
Cited by 7 | Viewed by 3254
Abstract
The prognostic role of platelet count in hepatocellular carcinoma (HCC) remains unclear, and in fact both thrombocytopenia and thrombocytosis are reported as predictors of unfavourable outcomes. This study aimed to clarify the prognostic value of preoperative platelet count in potentially resectable HCC. We [...] Read more.
The prognostic role of platelet count in hepatocellular carcinoma (HCC) remains unclear, and in fact both thrombocytopenia and thrombocytosis are reported as predictors of unfavourable outcomes. This study aimed to clarify the prognostic value of preoperative platelet count in potentially resectable HCC. We retrospectively reviewed 128 patients who underwent hepatic resection for HCC at a tertiary academic centre (2007–2019). Patient data were modelled by regression analysis, and platelet count was treated as a continuous variable. 89 patients had BCLC 0/A tumours and 39 had BCLC B tumours. Platelet count was higher in patients with larger tumours and lower in patients with higher MELD scores, advanced fibrosis, and portal hypertension (p < 0.001 for all listed variables). After adjusting for BCLC stage and tumour diameter, low platelet count associated with reduced overall survival (hazard ratio 1.25 per 50/nL decrease in platelet count, 95% confidence interval (CI) 1.02–1.53, p = 0.034) and increased perioperative mortality (odds ratio 1.96 per 50/nL decrease in platelet count, 95% CI 1.19–3.53, p = 0.014). Overall, low platelet count correlates with increased liver disease severity, inferior survival, and excess perioperative mortality in resectable HCC. These insights might be applied in clinical practice to better select patients for resection. Full article
(This article belongs to the Special Issue Hepatobiliary Malignancies: Recent Advancements and Future Directions)
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10 pages, 2153 KiB  
Article
Pretreatment Neutrophil-to-Lymphocyte Ratio as a Predictive Marker of Response to Atezolizumab Plus Bevacizumab for Hepatocellular Carcinoma
by Yuji Eso, Haruhiko Takeda, Kojiro Taura, Atsushi Takai, Ken Takahashi and Hiroshi Seno
Curr. Oncol. 2021, 28(5), 4157-4166; https://doi.org/10.3390/curroncol28050352 - 14 Oct 2021
Cited by 32 | Viewed by 3041
Abstract
Background: Combination therapy with anti-programmed death-ligand 1 monoclonal antibody atezolizumab plus anti-vascular endothelial growth factor agent bevacizumab (Atezo/Bev) was approved in 2020 as a first-line treatment for unresectable hepatocellular carcinoma (HCC). Atezo/Bev therapy is relatively well tolerated; however, factors that can predict its [...] Read more.
Background: Combination therapy with anti-programmed death-ligand 1 monoclonal antibody atezolizumab plus anti-vascular endothelial growth factor agent bevacizumab (Atezo/Bev) was approved in 2020 as a first-line treatment for unresectable hepatocellular carcinoma (HCC). Atezo/Bev therapy is relatively well tolerated; however, factors that can predict its response have not yet been reported. Thus, we aimed to investigate whether the pretreatment neutrophil-to-lymphocyte ratio (NLR) could predict the therapeutic response in patients with HCC treated with Atezo/Bev therapy. Methods: We analyzed the course of 40 patients with HCC who received Atezo/Bev therapy at our hospital and attempted to identify pretreatment factors that could predict response by comparing those who achieved disease control with those who did not. Results: The pretreatment NLR value in patients who achieved disease control was significantly lower than that in patients with disease progression (2.47 vs. 4.48, p = 0.013). Using the optimal NLR cut-off value for predicting response (3.21) determined by receiver operating characteristic curve analysis, patients with NLR ≤ 3.21 had significantly better progression-free survival than those with NLR > 3.21 (p < 0.0001), although there were no significant differences in liver function or tumor-related background factors between the two groups. Conclusions: The pretreatment NLR value may be a useful predictor of response to Atezo/Bev therapy for HCC. Full article
(This article belongs to the Special Issue Hepatobiliary Malignancies: Recent Advancements and Future Directions)
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Review

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15 pages, 1022 KiB  
Review
Hepatocellular Carcinoma, Alpha Fetoprotein, and Liver Allocation for Transplantation: Past, Present and Future
by Brianna Ruch, Josiah Wagler, Kayla Kumm, Chi Zhang, Nitin N. Katariya, Mauricio Garcia-Saenz-de-Sicilia, Emmanouil Giorgakis and Amit K. Mathur
Curr. Oncol. 2022, 29(10), 7537-7551; https://doi.org/10.3390/curroncol29100593 - 08 Oct 2022
Cited by 5 | Viewed by 2301
Abstract
Hepatocellular carcinoma (HCC) is one of the leading indications for liver transplantation and has been the treatment of choice due to the oncologic benefit for patients with advanced chronic liver disease (AdvCLD) and small tumors for the last 25 years. For HCC patients [...] Read more.
Hepatocellular carcinoma (HCC) is one of the leading indications for liver transplantation and has been the treatment of choice due to the oncologic benefit for patients with advanced chronic liver disease (AdvCLD) and small tumors for the last 25 years. For HCC patients undergoing liver transplantation, alpha fetoprotein (AFP) has increasingly been applied as an independent predictor for overall survival, disease free recurrence, and waitlist drop out. In addition to static AFP, newer studies evaluating the AFP dynamic response to downstaging therapy show enhanced prognostication compared to static AFP alone. While AFP has been utilized to select HCC patients for transplant, despite years of allocation policy changes, the US allocation system continues to take a uniform approach to HCC patients, without discriminating between those with favorable or unfavorable tumor biology. We aim to review the history of liver allocation for HCC in the US, the utility of AFP in liver transplantation, the implications of weaving AFP as a biomarker into policy. Based on this review, we encourage the US transplant community to revisit its HCC organ allocation model, to incorporate more precise oncologic principles for patient selection, and to adopt AFP dynamics to better stratify waitlist dropout risk. Full article
(This article belongs to the Special Issue Hepatobiliary Malignancies: Recent Advancements and Future Directions)
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13 pages, 623 KiB  
Review
Current Clinical Practice of Precision Medicine Using Comprehensive Genomic Profiling Tests in Biliary Tract Cancer in Japan
by Masashi Kanai
Curr. Oncol. 2022, 29(10), 7272-7284; https://doi.org/10.3390/curroncol29100573 - 30 Sep 2022
Cited by 5 | Viewed by 2390
Abstract
With the recent advances of next generation sequencing technologies, comprehensive genomic profiling (CGP) tests, which are designed to measure more than hundreds of cancer-related genes at a time, have now been widely introduced into daily clinical practice. For the patients whose tumor samples [...] Read more.
With the recent advances of next generation sequencing technologies, comprehensive genomic profiling (CGP) tests, which are designed to measure more than hundreds of cancer-related genes at a time, have now been widely introduced into daily clinical practice. For the patients whose tumor samples are not fit for tissue-based CGP tests, a blood-based CGP test (liquid biopsy) is available as an alternative option. Three CGP tests, “OncoGuide NCC™Oncopanel System (124 genes)”, “FoundationOne®CDx (324 genes)”, and “Founda-tionOne®CDx Liquid (324 genes)”, are now reimbursed by public insurance in 233 hospitals designated for cancer genomic medicine in Japan. In biliary tract cancer, the prevalence of druggable variants is relatively higher compared to other cancer types and the European Society for Medical Oncology recommends routine use of CGP tests for advanced biliary tract cancer to guide treatment options. The latest National Cancer Center Network guideline lists eight druggable markers (NTRK fusion, MSI-H, TMB-H, BRAF V600E, FGFR2 fusions/rearrangement, IDH1 mutations, RET fusion, and HER2 overexpression) and matched therapies. In Japan, matched therapies for four markers (NTRK, MSI-H, TMB-H, and FGFR2) are reimbursed by public insurance (as of September 2022). The progress of genomic profiling technology will contribute to the improvement of the dismal clinical outcomes of this disease in the future. Full article
(This article belongs to the Special Issue Hepatobiliary Malignancies: Recent Advancements and Future Directions)
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13 pages, 594 KiB  
Review
Optimization of the Clinical Effectiveness of Radioembolization in Hepatocellular Carcinoma with Dosimetry and Patient-Selection Criteria
by Philippe d’Abadie, Stephan Walrand, Renaud Lhommel, Michel Hesse, Ivan Borbath and François Jamar
Curr. Oncol. 2022, 29(4), 2422-2434; https://doi.org/10.3390/curroncol29040196 - 29 Mar 2022
Cited by 3 | Viewed by 2540
Abstract
Selective internal radiation therapy (SIRT) is part of the treatment strategy for hepatocellular carcinoma (HCC). Strong clinical data demonstrated the effectiveness of this therapy in HCC with a significant improvement in patient outcomes. Recent studies demonstrated a strong correlation between the tumor response [...] Read more.
Selective internal radiation therapy (SIRT) is part of the treatment strategy for hepatocellular carcinoma (HCC). Strong clinical data demonstrated the effectiveness of this therapy in HCC with a significant improvement in patient outcomes. Recent studies demonstrated a strong correlation between the tumor response and the patient outcome when the tumor-absorbed dose was assessed by nuclear medicine imaging. Dosimetry plays a key role in predicting the clinical response and can be optimized using a personalized method of activity planning (multi-compartmental dosimetry). This paper reviews the main clinical results of SIRT in HCC and emphasizes the central role of dosimetry for improving it effectiveness. Moreover, some patient and tumor characteristics predict a worse outcome, and toxicity related to SIRT treatment of advanced HCC patient selection based on the performance status, liver function, tumor characteristics, and tumor targeting using technetium-99m macro-aggregated albumin scintigraphy can significantly improve the clinical performance of SIRT. Full article
(This article belongs to the Special Issue Hepatobiliary Malignancies: Recent Advancements and Future Directions)
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14 pages, 1160 KiB  
Review
Systemic Treatment for Metastatic Biliary Tract Cancer: State of the Art and a Glimpse to the Future
by Alessandro Rizzo, Angela Dalia Ricci, Antonio Cusmai, Silvana Acquafredda, Giuseppe De Palma, Giovanni Brandi and Gennaro Palmiotti
Curr. Oncol. 2022, 29(2), 551-564; https://doi.org/10.3390/curroncol29020050 - 27 Jan 2022
Cited by 5 | Viewed by 3911
Abstract
Recent years have seen some breakthroughs in the therapeutic landscape of advanced biliary tract cancer (BTC). Firstly, a better understanding of the molecular background of BTC has led to important improvements in the management of these hepatobiliary malignancies, with the advent of targeted [...] Read more.
Recent years have seen some breakthroughs in the therapeutic landscape of advanced biliary tract cancer (BTC). Firstly, a better understanding of the molecular background of BTC has led to important improvements in the management of these hepatobiliary malignancies, with the advent of targeted agents representing an unprecedented paradigm shift, as witnessed by the FDA approval of pemigatinib and infigratinib for FGFR2-rearranged and ivosidenib in IDH1-mutant cholangiocarcinoma. In addition, several novel treatments are under assessment, including immune checkpoint inhibitors and combination chemotherapies. In the current review, we provide an overview of systemic treatment for metastatic BTC, summarizing recent clinical data on chemotherapy as well as the main results of targeted therapies and immunotherapy. Full article
(This article belongs to the Special Issue Hepatobiliary Malignancies: Recent Advancements and Future Directions)
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13 pages, 2589 KiB  
Review
Recent Advances in Photodynamic Imaging and Therapy in Hepatobiliary Malignancies: Clinical and Experimental Aspects
by Atsushi Nanashima, Masahide Hiyoshi, Naoya Imamura, Koichi Yano, Takeomi Hamada and Kengo Kai
Curr. Oncol. 2021, 28(5), 4067-4079; https://doi.org/10.3390/curroncol28050345 - 11 Oct 2021
Cited by 7 | Viewed by 2805
Abstract
The therapeutic and diagnostic modalities of light are well known, and derivative photodynamic reactions with photosensitizers (PSs), specific wavelengths of light exposure and the existence of tissue oxygen have been developed since the 20th century. Photodynamic therapy (PDT) is an effective local treatment [...] Read more.
The therapeutic and diagnostic modalities of light are well known, and derivative photodynamic reactions with photosensitizers (PSs), specific wavelengths of light exposure and the existence of tissue oxygen have been developed since the 20th century. Photodynamic therapy (PDT) is an effective local treatment for cancer-specific laser ablation in malignancies of some organs, including the bile duct. Although curability for extrahepatic cholangiocarcinoma is expected with surgery alone, patients with unresectable or remnant biliary cancer need other effective palliative therapies, including PDT. The effectiveness of PDT for cholangiocarcinoma has been reported experimentally or clinically, but it is not the standard option now due to problems with accompanied photosensitivity, limited access routes of irradiation, tumor hypoxia, etc. Novel derivative treatments such as photoimmunotherapy have not been applied in the field hepatobiliary system. Photodynamic diagnosis (PDD) has been more widely applied in the clinical diagnoses of liver malignancies or liver vascularization. At present, 5-aminolevulinic acid (ALA) and indocyanine green (ICG) dyes are mainly used as PSs in PDD, and ICG has been applied for detecting liver malignancies or vascularization. However, no ideal tools for combining both PDD and PDT for solid tumors, including hepatobiliary malignancies, have been clinically developed. To proceed with experimental and clinical trials, it is necessary to clarify the effective photosensitive drugs that are feasible for photochemical diagnosis and local treatment. Full article
(This article belongs to the Special Issue Hepatobiliary Malignancies: Recent Advancements and Future Directions)
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10 pages, 479 KiB  
Review
Ampullary Carcinoma: An Overview of a Rare Entity and Discussion of Current and Future Therapeutic Challenges
by Alessandro Rizzo, Vincenzo Dadduzio, Lucia Lombardi, Angela Dalia Ricci and Gennaro Gadaleta-Caldarola
Curr. Oncol. 2021, 28(5), 3393-3402; https://doi.org/10.3390/curroncol28050293 - 01 Sep 2021
Cited by 27 | Viewed by 13361
Abstract
Ampullary carcinomas (ACs) represent a rare entity, accounting for approximately 0.2% of all gastrointestinal solid tumors and 20% of all periampullary cancers (PACs). Unfortunately, few data are available regarding the optimal therapeutic strategy for ACs due to their rarity, and physicians frequently encounter [...] Read more.
Ampullary carcinomas (ACs) represent a rare entity, accounting for approximately 0.2% of all gastrointestinal solid tumors and 20% of all periampullary cancers (PACs). Unfortunately, few data are available regarding the optimal therapeutic strategy for ACs due to their rarity, and physicians frequently encounter significant difficulties in the management of these malignancies. In this review, we will provide an overview of current evidence on AC, especially focusing on biological features, histological characteristics, and available data guiding present and future therapeutic strategies for these rare, and still barely known, tumors. Full article
(This article belongs to the Special Issue Hepatobiliary Malignancies: Recent Advancements and Future Directions)
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Other

8 pages, 1845 KiB  
Opinion
Stereotactic Body Radiotherapy for Hepatocellular Carcinoma: A Brief Overview
by Yukinori Matsuo
Curr. Oncol. 2023, 30(2), 2493-2500; https://doi.org/10.3390/curroncol30020190 - 18 Feb 2023
Cited by 8 | Viewed by 2463
Abstract
Stereotactic body radiotherapy (SBRT), a type of external beam radiotherapy, yields local control of hepatocellular carcinoma (HCC) at rates as high as 90%. SBRT has been recognized as an alternative therapy for patients for whom standard modalities such as surgery (resection or transplantation) [...] Read more.
Stereotactic body radiotherapy (SBRT), a type of external beam radiotherapy, yields local control of hepatocellular carcinoma (HCC) at rates as high as 90%. SBRT has been recognized as an alternative therapy for patients for whom standard modalities such as surgery (resection or transplantation) or ablation are deemed unsuitable. SBRT has the potential to improve the prognosis of HCC, as it can be used as an adjunct to other treatment modalities. The assessment of post-SBRT images of the treated tumor and surrounding normal liver tissue requires special attention. Future research is warranted to determine how best to use SBRT versus other therapies and how to combine them. Full article
(This article belongs to the Special Issue Hepatobiliary Malignancies: Recent Advancements and Future Directions)
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10 pages, 247 KiB  
Opinion
Recent Updates on Local Ablative Therapy Combined with Chemotherapy for Extrahepatic Cholangiocarcinoma: Photodynamic Therapy and Radiofrequency Ablation
by Tadahisa Inoue and Masashi Yoneda
Curr. Oncol. 2023, 30(2), 2159-2168; https://doi.org/10.3390/curroncol30020166 - 09 Feb 2023
Cited by 4 | Viewed by 1693
Abstract
Although chemotherapy constitutes of the first-line standard therapy for unresectable extrahepatic cholangiocarcinoma, the treatment outcomes are unsatisfactory. In recent years, local ablative therapy, which is delivered to the cholangiocarcinoma lesion via the percutaneous or endoscopic approach, has garnered attention for the treatment of [...] Read more.
Although chemotherapy constitutes of the first-line standard therapy for unresectable extrahepatic cholangiocarcinoma, the treatment outcomes are unsatisfactory. In recent years, local ablative therapy, which is delivered to the cholangiocarcinoma lesion via the percutaneous or endoscopic approach, has garnered attention for the treatment of unresectable, extrahepatic cholangiocarcinoma. Local ablative therapy, such as photodynamic therapy and radiofrequency ablation, can achieve local tumor control. A synergistic effect may also be expected when local ablative therapy is combined with chemotherapy. However, it is a long way from being entrenched as an established therapeutic technique, and several unresolved problems persist, including the paucity of evidence comparing photodynamic therapy and radiofrequency ablation. Clinical application of photodynamic therapy and radiofrequency ablation requires sound comprehension and assimilation of the available evidence to truly benefit each individual patient. In this study, we reviewed the current status, issues, and future prospects of photodynamic therapy and radiofrequency ablation for extrahepatic cholangiocarcinoma, with a special focus on their combination with chemotherapy. Full article
(This article belongs to the Special Issue Hepatobiliary Malignancies: Recent Advancements and Future Directions)
9 pages, 2565 KiB  
Systematic Review
Immune-Based Combinations versus Sorafenib as First-Line Treatment for Advanced Hepatocellular Carcinoma: A Meta-Analysis
by Alessandro Rizzo, Angela Dalia Ricci, Annarita Fanizzi, Raffaella Massafra, Raffaele De Luca and Giovanni Brandi
Curr. Oncol. 2023, 30(1), 749-757; https://doi.org/10.3390/curroncol30010057 - 05 Jan 2023
Cited by 4 | Viewed by 2252
Abstract
Recent years have observed the emergence of novel therapeutic opportunities for advanced hepatocellular carcinoma (HCC), such as combination therapies including immune checkpoint inhibitors. We performed a meta-analysis with the aim to compare median overall survival (OS), median progression-free survival (PFS), complete response (CR) [...] Read more.
Recent years have observed the emergence of novel therapeutic opportunities for advanced hepatocellular carcinoma (HCC), such as combination therapies including immune checkpoint inhibitors. We performed a meta-analysis with the aim to compare median overall survival (OS), median progression-free survival (PFS), complete response (CR) rate, and partial response (PR) rate in advanced HCC patients receiving immune-based combinations versus sorafenib. A total of 2176 HCC patients were available for the meta-analysis (immune-based combinations = 1334; sorafenib = 842) and four trials were included. Immune-based combinations decreased the risk of death by 27% (HR, 0.73; 95% CI, 0.65–0.83; p < 0.001); similarly, a PFS benefit was observed (HR, 0.64; 95% CI, 0.5–0.84; p < 0.001). In addition, immune-based combinations showed better CR rate and PR rate, with ORs of 12.4 (95% CI, 3.02–50.85; p < 0.001) and 3.48 (95% CI, 2.52–4.8; p < 0.03), respectively. The current study further confirms that first-line immune-based combinations have a place in the management of HCC. The CR rate observed in HCC patients receiving immune-based combinations appears more than twelve times higher compared with sorafenib monotherapy, supporting the long-term benefit of these combinatorial strategies, with even the possibility to cure advanced disease. Full article
(This article belongs to the Special Issue Hepatobiliary Malignancies: Recent Advancements and Future Directions)
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14 pages, 654 KiB  
Perspective
Emerging Systemic Therapies in Advanced Unresectable Biliary Tract Cancer: Review and Canadian Perspective
by Vincent C. Tam, Ravi Ramjeesingh, Ronald Burkes, Eric M. Yoshida, Sarah Doucette and Howard J. Lim
Curr. Oncol. 2022, 29(10), 7072-7085; https://doi.org/10.3390/curroncol29100555 - 28 Sep 2022
Cited by 6 | Viewed by 3255
Abstract
Biliary tract cancer (BTC) is a group of rare and aggressive malignancies with a dismal prognosis. There is currently a significant lack in effective treatment options for BTC, with gemcitabine-cisplatin remaining the first-line standard of care treatment for over a decade. A wave [...] Read more.
Biliary tract cancer (BTC) is a group of rare and aggressive malignancies with a dismal prognosis. There is currently a significant lack in effective treatment options for BTC, with gemcitabine-cisplatin remaining the first-line standard of care treatment for over a decade. A wave of investigational therapies, including new chemotherapy combinations, immunotherapy, and biomarker-driven targeted therapy have demonstrated promising results in BTC, and there is hope for many of these therapies to be incorporated into the Canadian treatment landscape in the near future. This review discusses the emerging therapies under investigation for BTC and provides a perspective on how they may fit into Canadian practice, with a focus on the barriers to treatment access. Full article
(This article belongs to the Special Issue Hepatobiliary Malignancies: Recent Advancements and Future Directions)
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