|
1
|
Liu JJ, Zhou M, Yuan T, Huang ZY, Zhang ZY. Conversion treatment for advanced intrahepatic cholangiocarcinoma: Opportunities and challenges. World J Gastroenterol 2025; 31:104901. [PMID: 40309227 PMCID: PMC12038554 DOI: 10.3748/wjg.v31.i15.104901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2025] [Revised: 02/22/2025] [Accepted: 03/26/2025] [Indexed: 04/18/2025] Open
Abstract
The prevalence of intrahepatic cholangiocarcinoma (ICC) is increasing globally. Despite advancements in comprehending this intricate malignancy and formulating novel therapeutic approaches over the past few decades, the prognosis for ICC remains poor. Owing to the high degree of malignancy and insidious onset of ICC, numerous cases are detected at intermediate or advanced stages of the disease, hence eliminating the chance for surgical intervention. Moreover, because of the highly invasive characteristics of ICC, recurrence and metastasis postresection are prevalent, leading to a 5-year survival rate of only 20%-35% following surgery. In the past decade, different methods of treatment have been investigated, including transarterial chemoembolization, transarterial radioembolization, radiotherapy, systemic therapy, and combination therapies. For certain patients with advanced ICC, conversion treatment may be utilized to facilitate surgical resection and manage disease progression. This review summarizes the definition of downstaging conversion treatment and presents the clinical experience and evidence concerning conversion treatment for advanced ICC.
Collapse
Affiliation(s)
- Jun-Jie Liu
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Mi Zhou
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Tong Yuan
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Zhi-Yong Huang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Zun-Yi Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| |
Collapse
|
|
2
|
O’Donnell CDJ, Majeed U, Rutenberg MS, Croome KP, Poruk KE, Toskich B, Jin Z. Advancements in Locoregional Therapies for Unresectable Intrahepatic Cholangiocarcinoma. Curr Oncol 2025; 32:82. [PMID: 39996882 PMCID: PMC11854535 DOI: 10.3390/curroncol32020082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2025] [Revised: 01/25/2025] [Accepted: 01/30/2025] [Indexed: 02/26/2025] Open
Abstract
Intrahepatic cholangiocarcinoma is an aggressive malignancy with rising incidence and poor outcomes. This review examines recent advancements in locoregional therapies for unresectable intrahepatic cholangiocarcinoma, focusing on external beam radiotherapy, transarterial radioembolization (TARE), hepatic artery infusion pump (HAIP) chemotherapy, and liver transplantation. Stereotactic body radiation therapy and proton beam therapy have shown promise in achieving local control and improving survival. TARE, with personalized dosimetry, has demonstrated encouraging results in select patient populations. HAIP chemotherapy, primarily studied using floxuridine, has yielded impressive survival outcomes in phase II trials. Liver transplantation, once contraindicated, is now being reconsidered for carefully selected patients with localized disease. While these locoregional approaches show potential, randomized controlled trials comparing them to standard systemic therapy are lacking. Patient selection remains crucial, with factors such as liver function, tumor burden, and molecular profile influencing treatment decisions. Ongoing research aims to optimize treatment sequencing, explore combination strategies with systemic therapies, and refine phenotype identification and patient selection criteria. As the landscape of intrahepatic cholangiocarcinoma management evolves, a multidisciplinary approach is essential to tailor treatment strategies and improve outcomes for patients with this challenging disease.
Collapse
Affiliation(s)
- Conor D. J. O’Donnell
- Department of Medicine, Division of Hematology-Oncology, Mayo Clinic Florida, Jacksonville, FL 32224, USA
| | - Umair Majeed
- Department of Medicine, Division of Hematology-Oncology, Mayo Clinic Florida, Jacksonville, FL 32224, USA
| | - Michael S. Rutenberg
- Department of Radiation Oncology, Mayo Clinic Florida, Jacksonville, FL 32224, USA
| | | | - Katherine E. Poruk
- Department of Surgical Oncology, Mayo Clinic Florida, Jacksonville, FL 32224, USA
| | - Beau Toskich
- Department of Interventional Radiology, Mayo Clinic Florida, Jacksonville, FL 32224, USA
| | - Zhaohui Jin
- Division of Medical Oncology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
| |
Collapse
|
|
3
|
Maspero M, Sposito C, Bongini MA, Cascella T, Flores M, Maccauro M, Chiesa C, Niger M, Pietrantonio F, Leoncini G, Bellia V, Bhoori S, Mazzaferro V. Liver Transplantation for Intrahepatic Cholangiocarcinoma After Chemotherapy and Radioembolization: An Intention-To-Treat Study. Transpl Int 2024; 37:13641. [PMID: 39544321 PMCID: PMC11560448 DOI: 10.3389/ti.2024.13641] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Accepted: 10/18/2024] [Indexed: 11/17/2024]
Abstract
Liver transplantation (LT) is a potentially curative experimental treatment for unresectable intrahepatic cholangiocarcinoma (iCC). Pre-transplant downstaging may help defining tumor aggressiveness and drive patient selection. We report the preliminary results of LT for liver-limited unresectable iCC after sequential downstaging with systemic chemotherapy and radioembolization (SYS-TARE). In case of sustained disease stability after SYS-TARE, patients underwent surgical nodal sampling and, if negative, were listed for LT. In this study, 13 patients with unresectable iCC underwent downstaging with SYS-TARE. The median age was 70 years and 77% were female. All had single bulky lesions at diagnosis. After SYS-TARE, 9 (69%) dropped out: 3 due to progressive disease after TARE with no response to second-line, 4 due to extrahepatic disease development and 2 due to positive nodal disease at pre-listing abdominal exploration. The median OS after dropout was 11.5 months. Four (31%) were successfully listed and transplanted. At pathology, viable tumor ranged from 30% to less than 5%. All four patients are alive and disease-free at 73, 40, 12, and 8 months from LT. LT for unresectable iCC after downstaging with SYS-TARE appears to select suitable patients for LT, achieving optimal oncological outcomes in case of response to therapy and no lymphnodal spread.
Collapse
Affiliation(s)
- Marianna Maspero
- HPB Surgery, Hepatology and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
| | - Carlo Sposito
- HPB Surgery, Hepatology and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
| | - Marco A. Bongini
- HPB Surgery, Hepatology and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Tommaso Cascella
- Interventional Radiology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Maria Flores
- HPB Surgery, Hepatology and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Marco Maccauro
- Nuclear Medicine and Physics, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Carlo Chiesa
- Nuclear Medicine and Physics, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Monica Niger
- Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | | | | | - Valentina Bellia
- HPB Surgery, Hepatology and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Sherrie Bhoori
- HPB Surgery, Hepatology and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - Vincenzo Mazzaferro
- HPB Surgery, Hepatology and Liver Transplantation Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
| |
Collapse
|
|
4
|
Cocozza MA, Dajti E, Braccischi L, Modestino F, Reimer P, Cucchetti A, Barbara G, Mosconi C. Survival After Transarterial Radioembolization in Patients with Unresectable Intrahepatic Cholangiocarcinoma: An Updated Meta-analysis and Meta-regression. Cardiovasc Intervent Radiol 2024; 47:1313-1324. [PMID: 39187651 PMCID: PMC11486776 DOI: 10.1007/s00270-024-03825-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Accepted: 07/25/2024] [Indexed: 08/28/2024]
Abstract
PURPOSE Transarterial radioembolization (TARE) has emerged as a promising therapeutic approach for unresectable intrahepatic cholangiocarcinoma (ICCA). We updated our previous meta-analysis with meta-regression to explore the efficacy of TARE in the context of ICCA. METHODS We searched PubMed and Scopus for studies published up to September 1, 2023. The primary outcome was overall survival. Secondary outcomes were tumor overall response rate, severe adverse events, and downstaging to surgery. Meta-analysis employed a random-effects model, and meta-regression was utilized to explore sources of heterogeneity. RESULTS We included 27 studies, involving 1365 patients. Pooled survival estimates at 1, 2, and 3 years were 52.6%, 27%, and 16.8%, respectively. Meta-regression revealed that the proportion of patients naïve to treatment was the only pre-TARE predictor of survival (1-, 2-, and 3-year survival of 70%, 45%, and 36% for treatment-naïve patients, mean survival 19.7 months vs. 44%, 18%, and 7% for non-naïve patients, mean survival 12.2 months). Overall response according to RECIST 1.1 and mRECIST was 19.6% and 67%, respectively. Effective downstaging to surgery was possible in varying rates (3-54%); the mean survival in these patients was 34.8 months (1-, 2-, and 3-year survival of 100%, 87%, and 64%). About 45.7% of patients experienced adverse events, but only 5.9% were severe. CONCLUSIONS Our study benchmarked the survival rates of patients undergoing TARE for unresectable ICCA and showed that this is a valid option in these patients, especially if naïve to previous treatments. Downstaging to surgery is feasible in selected patients with promising results.
Collapse
Affiliation(s)
- Maria Adriana Cocozza
- Division of Interventional Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Elton Dajti
- Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.
| | - Lorenzo Braccischi
- Division of Interventional Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Francesco Modestino
- Division of Interventional Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Peter Reimer
- Department of General and Oncologic Surgery, Morgagni-Pierantoni Hospital, AUSL Romagna, Forlì, Italy
| | - Alessandro Cucchetti
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
- Städtisches Klinikum Karlsruhe, Institute for Diagnostic and Interventional Radiology, Academic Teaching Hospital the University of Freiburg, Moltkestraße 90, 76133, Karlsruhe, Germany
| | - Giovanni Barbara
- Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Cristina Mosconi
- Division of Interventional Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| |
Collapse
|
|
5
|
Piñero F, Mauro E, Casciato P, Forner A. From evidence to clinical practice: Bridging the gap of new liver cancer therapies in Latin America. Ann Hepatol 2024; 29:101185. [PMID: 38042481 DOI: 10.1016/j.aohep.2023.101185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2023] [Accepted: 10/26/2023] [Indexed: 12/04/2023]
Abstract
The most common primary liver tumors are hepatocellular carcinoma and cholangiocarcinoma. They constitute the sixth most common neoplasia and the third cause of cancer-related deaths worldwide. Although both tumors may share etiologic factors, diagnosis, prognostic factors, and treatments, they differ substantially in determining distinctive clinical management. In recent years, significant advances have been made in the management of these neoplasms, particularly in advanced stages. In this review, we focus on the most relevant diagnostic, prognostic, and treatment aspects of both, hepatocellular carcinoma and cholangiocarcinoma, underlying their applicability in Latin America.
Collapse
Affiliation(s)
- Federico Piñero
- Hospital Universitario Austral, Austral University, School of Medicine, Buenos Aires, Argentina.
| | - Ezequiel Mauro
- Barcelona Clinic Liver Cancer (BCLC) group. IDIBAPS. Barcelona. Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Liver Unit. Liver Oncology Unit. ICMDM. Hospital Clinic Barcelona. Barcelona, Spain
| | | | - Alejandro Forner
- Barcelona Clinic Liver Cancer (BCLC) group. IDIBAPS. Barcelona. Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Liver Unit. Liver Oncology Unit. ICMDM. Hospital Clinic Barcelona. Barcelona, Spain; University of Barcelona, Barcelona, Spain.
| |
Collapse
|
|
6
|
Yu Q, Ungchusri E, Pillai A, Liao CY, Baker T, Fung J, DiSabato D, Zhang M, Liao C, Van Ha T, Ahmed O. Selective internal radiation therapy using yttrium-90 microspheres for treatment of localized and locally advanced intrahepatic cholangiocarcinoma. Eur Radiol 2024; 34:2374-2383. [PMID: 37812295 DOI: 10.1007/s00330-023-10203-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Revised: 06/01/2023] [Accepted: 06/25/2023] [Indexed: 10/10/2023]
Abstract
OBJECTIVES To evaluate safety and effectiveness of selective internal radiation therapy (SIRT) using yttrium-90 for localized and locally advanced intrahepatic cholangiocarcinoma (iCCA). METHODS A retrospective review was performed of patients with localized iCCA treated with SIRT at a single institution. Overall survival (OS), local tumor response, progression-free survival (PFS), and toxicity were collected. Stratified analysis was performed based on surgical resection. Predictor analysis of OS was performed using the Fine-Grey regression analysis model with patients bridged to surgery regarded as competing events. RESULTS A total of 28 consecutive patients with localized iCCA were treated with a total of 38 sessions of SIRT (17 segmental, 13 lobar, and 8 combined deliveries) and a mean dominant target dose per session of 238.4 ± 130.0 Gy. The cumulative radiologic response rate was 16/28 (57.1%) with a median PFS of 265 days. Median survival time (MST) was 22.9 months for the entire cohort with 1-year and 3-year survival of 78.4% and 45.1%, respectively. Ten patients (34.5%) were downstaged to surgical intervention (7 resection, 3 transplant) and showed longer OS (p = 0.027). The 1-year and 3-year OS for patients who received surgery were 100% and 62.5% (95% CI: 14.2-89.3%), respectively. Age (p = 0.028), Eastern Cooperative Oncology Group performance status (p = 0.030), and objective radiologic response (p=0.014) are associated with OS. Two ≥grade 3 hyperbilirubinemia, anemia, and one pleuro-biliary fistula occurred post-SIRT. CONCLUSIONS SIRT for localized iCCA is safe and effective in achieving radiological response, downstaging to surgery and transplant, and resulting in pathologic necrosis. CLINICAL RELEVANCE STATEMENT Selective internal radiation therapy should be considered for patients with localized and locally advanced intrahepatic cholangiocarcinoma. KEY POINTS • The effectiveness of radioembolization for intrahepatic cholangiocarcinoma (iCCA) can be underestimated given the inclusion of extrahepatic disease. • Radioembolization is safe and effective for local and locally advanced iCCA. Age, Eastern Cooperative Oncology Group performance status, and radiologic response are associated with survival. • Radioembolization should be considered for patients with localized and locally advanced iCCA.
Collapse
Affiliation(s)
- Qian Yu
- Vascular and Interventional Radiology, Department of Radiology, Medical Center, University of Chicago, University of Chicago, 5841 S Maryland Ave, Chicago, IL, 60637, USA.
| | - Ethan Ungchusri
- Vascular and Interventional Radiology, Department of Radiology, Medical Center, University of Chicago, University of Chicago, 5841 S Maryland Ave, Chicago, IL, 60637, USA
| | - Anjana Pillai
- Division of Gastroenterology, Hepatology, and Nutrition, Medical Center, University of Chicago, University of Chicago, Chicago, IL, 60637, USA
| | - Chih-Yi Liao
- Section of Hematology/Oncology, Department of Medicine, University of Chicago Medicine, Chicago, IL, 60637, USA
| | - Talia Baker
- Liver Tumor Center, University of Chicago Medicine, Chicago, IL, 60637, USA
| | - John Fung
- Liver Tumor Center, University of Chicago Medicine, Chicago, IL, 60637, USA
| | - Diego DiSabato
- Liver Tumor Center, University of Chicago Medicine, Chicago, IL, 60637, USA
| | - Mengxue Zhang
- Department of Pathology, University of Chicago Medicine, Chicago, IL, 60637, USA
| | - Chuanhong Liao
- Department of Public Health Sciences, University of Chicago, Chicago, IL, 60637, USA
| | - Thuong Van Ha
- Vascular and Interventional Radiology, Department of Radiology, Medical Center, University of Chicago, University of Chicago, 5841 S Maryland Ave, Chicago, IL, 60637, USA
| | - Osman Ahmed
- Vascular and Interventional Radiology, Department of Radiology, Medical Center, University of Chicago, University of Chicago, 5841 S Maryland Ave, Chicago, IL, 60637, USA
| |
Collapse
|
|
7
|
Bragazzi MC, Venere R, Ribichini E, Covotta F, Cardinale V, Alvaro D. Intrahepatic cholangiocarcinoma: Evolving strategies in management and treatment. Dig Liver Dis 2024; 56:383-393. [PMID: 37722960 DOI: 10.1016/j.dld.2023.08.052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 08/07/2023] [Accepted: 08/21/2023] [Indexed: 09/20/2023]
Abstract
Intrahepatic cholangiocarcinoma is the second most frequent primary liver cancer after hepatocellular carcinoma. According to International Classification of Diseases-11 (ICD-11), intrahepatic cholangiocarcinoma is identified by a specific diagnostic code, different with respect to perihilar-CCA or distal-CCA. Intrahepatic cholangiocarcinoma originates from intrahepatic small or large bile ducts including the second-order bile ducts and has a silent presentation that combined with the highly aggressive nature and refractoriness to chemotherapy contributes to the alarming increasing incidence and mortality. Indeed, at the moment of the diagnosis, less than 40% of intrahepatic cholangiocarcinoma are suitable of curative surgical therapy, that is so far the only effective treatment. The main goals of clinicians and researchers are to make an early diagnosis, and to carry out molecular characterization to provide the patient with personalized treatment. Unfortunately, these goals are not easily achievable because of the heterogeneity of this tumor from anatomical, molecular, biological, and clinical perspectives. However, recent progress has been made in molecular characterization, surgical treatment, and management of intrahepatic cholangiocarcinoma and, this article deals with these advances.
Collapse
Affiliation(s)
- Maria Consiglia Bragazzi
- Department of Medical-Surgical Sciences and Biotechnology, Sapienza University of Rome Polo Pontino, Italy.
| | - Rosanna Venere
- Department of Medical-Surgical Sciences and Biotechnology, Sapienza University of Rome Polo Pontino, Italy
| | - Emanuela Ribichini
- Department Translational and Precision, Sapienza University of Rome, Italy
| | - Francesco Covotta
- Department Translational and Precision, Sapienza University of Rome, Italy
| | - Vincenzo Cardinale
- Department Translational and Precision, Sapienza University of Rome, Italy
| | - Domenico Alvaro
- Department Translational and Precision, Sapienza University of Rome, Italy
| |
Collapse
|
|
8
|
Woodhead G, Lee S, Struycken L, Goldberg D, Hannallah J, Young S. Interventional Radiology Locoregional Therapies for Intrahepatic Cholangiocarcinoma. Life (Basel) 2024; 14:217. [PMID: 38398726 PMCID: PMC10890186 DOI: 10.3390/life14020217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Revised: 12/22/2023] [Accepted: 01/12/2024] [Indexed: 02/25/2024] Open
Abstract
Surgical resection remains the cornerstone of curative treatment for intrahepatic cholangiocarcinoma (iCCA), but this option is only available to a small percentage of patients. For patients with unresectable iCCA, systemic therapy with gemcitabine and platinum-based agents represents the mainstay of treatment; however, the armamentarium has grown to include targeted molecular therapies (e.g., FGFR2 inhibitors), use of adjuvant therapy, liver transplantation in select cases, immunotherapy, and locoregional liver-directed therapies. Despite advances, iCCA remains a challenge due to the advanced stage of many patients at diagnosis. Furthermore, given the improving options for systemic therapy and the fact that the majority of iCCA patients succumb to disease progression in the liver, the role of locoregional therapies has increased. This review will focus on the expanding role of interventional radiology and liver-directed therapies in the treatment of iCCA.
Collapse
Affiliation(s)
- Gregory Woodhead
- Department of Medical Imaging, Division of Interventional Radiology, University of Arizona Medical Center, Tucson, AZ 85712, USA; (L.S.); (D.G.); (J.H.); (S.Y.)
| | - Sean Lee
- Department of Basic Biomedical Sciences, Touro College of Osteopathic Medicine, Middletown, NY 10027, USA;
| | - Lucas Struycken
- Department of Medical Imaging, Division of Interventional Radiology, University of Arizona Medical Center, Tucson, AZ 85712, USA; (L.S.); (D.G.); (J.H.); (S.Y.)
| | - Daniel Goldberg
- Department of Medical Imaging, Division of Interventional Radiology, University of Arizona Medical Center, Tucson, AZ 85712, USA; (L.S.); (D.G.); (J.H.); (S.Y.)
| | - Jack Hannallah
- Department of Medical Imaging, Division of Interventional Radiology, University of Arizona Medical Center, Tucson, AZ 85712, USA; (L.S.); (D.G.); (J.H.); (S.Y.)
| | - Shamar Young
- Department of Medical Imaging, Division of Interventional Radiology, University of Arizona Medical Center, Tucson, AZ 85712, USA; (L.S.); (D.G.); (J.H.); (S.Y.)
| |
Collapse
|
|
9
|
Wagemans MEHM, Kunnen B, Stella M, van Rooij R, Smits M, Bruijnen R, Lam MGEH, de Jong HWAM, Braat AJAT. Comparison of 3 Different Therapeutic Particles in Radioembolization of Locally Advanced Intrahepatic Cholangiocarcinoma. J Nucl Med 2024; 65:272-278. [PMID: 38176716 DOI: 10.2967/jnumed.123.265597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 11/07/2023] [Indexed: 01/06/2024] Open
Abstract
Our objective was to compare 3 different therapeutic particles used for radioembolization in locally advanced intrahepatic cholangiocarcinoma. Methods: 90Y-glass, 90Y-resin, and 166Ho-labeled poly(l-lactic acid) microsphere prescribed activity was calculated as per manufacturer recommendations. Posttreatment quantitative 90Y PET/CT and quantitative 166Ho SPECT/CT were used to determine tumor-absorbed dose, whole-normal-liver-absorbed dose, treated-normal-liver-absorbed dose, tumor-to-nontumor ratio, lung-absorbed dose, and lung shunt fraction. Response was assessed using RECIST 1.1 and the [18F]FDG PET-based change in total lesion glycolysis. Hepatotoxicity was assessed using the radioembolization-induced liver disease classification. Results: Six 90Y-glass, 8 90Y-resin, and 7 166Ho microsphere patients were included for analysis. The mean administered activity was 2.6 GBq for 90Y-glass, 1.5 GBq for 90Y-resin, and 7.0 GBq for 166Ho microspheres. Tumor-absorbed dose and treated-normal-liver-absorbed dose were significantly higher for 90Y-glass than for 90Y-resin and 166Ho microspheres (mean tumor-absorbed dose, 197 Gy for 90Y-glass vs. 73 Gy for 90Y-resin and 50 Gy for 166Ho; mean treated-normal-liver-absorbed dose, 79 Gy for 90Y-glass vs. 37 Gy for 90Y-resin and 31 Gy for 166Ho). The whole-normal-liver-absorbed dose and tumor-to-nontumor ratio did not significantly differ between the particles. All patients had a lung-absorbed dose under 30 Gy and a lung shunt fraction under 20%. The 3 groups showed similar toxicity and response according to RECIST 1.1 and [18F]FDG PET-based total lesion glycolysis changes. Conclusion: The therapeutic particles used for radioembolization differed from each other and showed significant differences in absorbed dose, whereas toxicity and response were similar for all groups. This finding emphasizes the need for separate dose constraints and dose targets for each particle.
Collapse
Affiliation(s)
- Martijn E H M Wagemans
- Department of Radiology and Nuclear Medicine, UMC Utrecht, Utrecht, The Netherlands; and
| | - Britt Kunnen
- Department of Radiology and Nuclear Medicine, UMC Utrecht, Utrecht, The Netherlands; and
- Image Sciences Institute, UMC Utrecht and University Utrecht, Utrecht, The Netherlands
| | - Martina Stella
- Department of Radiology and Nuclear Medicine, UMC Utrecht, Utrecht, The Netherlands; and
| | - Rob van Rooij
- Department of Radiology and Nuclear Medicine, UMC Utrecht, Utrecht, The Netherlands; and
| | - Maarten Smits
- Department of Radiology and Nuclear Medicine, UMC Utrecht, Utrecht, The Netherlands; and
| | - Rutger Bruijnen
- Department of Radiology and Nuclear Medicine, UMC Utrecht, Utrecht, The Netherlands; and
| | - Marnix G E H Lam
- Department of Radiology and Nuclear Medicine, UMC Utrecht, Utrecht, The Netherlands; and
| | - Hugo W A M de Jong
- Department of Radiology and Nuclear Medicine, UMC Utrecht, Utrecht, The Netherlands; and
| | - Arthur J A T Braat
- Department of Radiology and Nuclear Medicine, UMC Utrecht, Utrecht, The Netherlands; and
| |
Collapse
|
|
10
|
Young S, Hannallah J, Goldberg D, Khreiss M, Shroff R, Arshad J, Scott A, Woodhead G. Liver-Directed Therapy Combined with Systemic Therapy: Current Status and Future Directions. Semin Intervent Radiol 2023; 40:515-523. [PMID: 38274222 PMCID: PMC10807971 DOI: 10.1055/s-0043-1777711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2024]
Abstract
In the past several decades, major advances in both systemic and locoregional therapies have been made for many cancer patients. This has led to modern cancer treatment algorithms frequently calling for active interventions by multiple subspecialists at the same time. One of the areas where this can be clearly seen is the concomitant use of locoregional and systemic therapies in patients with primary or secondary cancers of the liver. These combined algorithms have gained favor over the last decade and are largely focused on the allure of the combined ability to control systemic disease while at the same time addressing refractory/resistant clonal populations. While the general concept has gained favor and is likely to only increase in popularity with the continued establishment of viable immunotherapy treatments, for many patients questions remain. Lingering concerns over the increase in toxicity when combining treatment methods, patient selection, and sequencing remain for multiple cancer patient populations. While further work remains, some of these questions have been addressed in the literature. This article reviews the available data on three commonly treated primary and secondary cancers of the liver, namely, hepatocellular carcinoma, cholangiocarcinoma, and metastatic colorectal cancer. Furthermore, strengths and weaknesses are reviewed and future directions are discussed.
Collapse
Affiliation(s)
- Shamar Young
- Division of Interventional Radiology, Department of Medical Imaging, University of Arizona, Tucson, Arizona
| | - Jack Hannallah
- Division of Interventional Radiology, Department of Medical Imaging, University of Arizona, Tucson, Arizona
| | - Dan Goldberg
- Division of Interventional Radiology, Department of Medical Imaging, University of Arizona, Tucson, Arizona
| | - Mohammad Khreiss
- Division of Surgical Oncology, Department of Surgery, University of Arizona, Tucson, Arizona
| | - Rachna Shroff
- Division of Hematology and Oncology, Department of Medicine, University of Arizona, Tucson, Arizona
| | - Junaid Arshad
- Division of Hematology and Oncology, Department of Medicine, University of Arizona, Tucson, Arizona
| | - Aaron Scott
- Division of Hematology and Oncology, Department of Medicine, University of Arizona, Tucson, Arizona
| | - Gregory Woodhead
- Division of Interventional Radiology, Department of Medical Imaging, University of Arizona, Tucson, Arizona
| |
Collapse
|
|
11
|
Gorji L, Aoun H, Critchfield J, Al Hallak N, Beal EW. Locoregional Therapy for Intrahepatic Cholangiocarcinoma: The Role of Intra-Arterial Therapies. Cancers (Basel) 2023; 15:4727. [PMID: 37835420 PMCID: PMC10571998 DOI: 10.3390/cancers15194727] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2023] [Revised: 09/18/2023] [Accepted: 09/22/2023] [Indexed: 10/15/2023] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) is a rare disease with a rising incidence. While surgical resection is the only curative option, the disease process is often identified in advanced stages, as this malignancy often remains clinically silent in early development. Only one-third of patients are eligible for resection at the time of diagnosis. For patients who cannot undergo resection, intra-arterial therapies are reasonable palliative treatment options; in rare occasions, these may be bridging therapies, as well. The premise of bland embolization and most chemoembolization intra-arterial therapies is that the arterial supply of the tumor is occluded to induce tumor necrosis, while radioembolization utilizes the arterial flow of the tumor to deliver radiation therapy. In this review, we discuss the use of transarterial embolization, transarterial chemoembolization, and selective internal radiation therapy for the treatment of ICC. Phase III randomized controlled clinical trials are difficult to tailor to this extremely rare and aggressive disease, but ultimately, further investigation should be pursued to define the patient population that will derive the greatest benefit from each modality.
Collapse
Affiliation(s)
- Leva Gorji
- Department of Surgery, Kettering Health, Dayton, OH 45402, USA;
| | - Hussein Aoun
- Department of Interventional Radiology, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA; (H.A.); (J.C.)
| | - Jeffrey Critchfield
- Department of Interventional Radiology, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA; (H.A.); (J.C.)
| | - Najeeb Al Hallak
- Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA;
| | - Eliza W. Beal
- Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA;
- Department of Surgery, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA
| |
Collapse
|
|
12
|
Kis B, Shridhar R, Mhaskar R, Gyano M, Frakes JM, El-Haddad G, Choi J, Kim RD, Hoffe SE. Radioembolization with Yttrium-90 Glass Microspheres as a First-Line Treatment for Unresectable Intrahepatic Cholangiocarcinoma-A Prospective Feasibility Study. J Vasc Interv Radiol 2023; 34:1547-1555. [PMID: 37210030 DOI: 10.1016/j.jvir.2023.05.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 04/22/2023] [Accepted: 05/10/2023] [Indexed: 05/22/2023] Open
Abstract
PURPOSE To evaluate the safety and effectiveness of yttrium-90 (90Y) radioembolization as first-line treatment for unresectable intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS This prospective study enrolled patients who had never received chemotherapy, liver embolization, and radiation therapy. The tumors were solitary in 16 patients, multiple in 8 patients, unilobar in 14 patients, and bilobar in 10 patients. Patients underwent transarterial radioembolization with 90Y-labeled glass microspheres. The primary end point was hepatic progression-free survival (HPFS). Secondary end points were overall survival (OS), tumor response, and toxicity. RESULTS Twenty-four patients (age, 72.3 years ± 9.3; 12 women) were included in the study. The median delivered radiation dose was 135.5 Gy (interquartile range, 77.6 Gy). The median HPFS was 5.5 months (95% CI, 3.9-7.0 months). Analysis failed to identify any prognostic factor associated with HPFS. Imaging response at 3 months showed 56% disease control, and the best radiographic response was 71% disease control. The median OS from the radioembolization treatment was 19.4 months (95% CI, 5.0-33.7). Patients with solitary ICC had significantly longer median OS than patients with multifocal ICC: 25.9 months (95% CI, 20.8-31.0 months) versus 10.7 months (95% CI, 8.0-13.4 months) (P = .02). Patients with progression on the 3-month imaging follow-up had significantly shorter median OS than patients who had stable disease at 3 months: 10.7 months (95% CI, 0.7-20.7 months) versus 37.3 months (95% CI, 16.5-58.1 months) (P = .003). Two (8%) Grade 3 toxicities were reported. CONCLUSIONS First-line treatment of ICC with radioembolization showed promising OS and minimal toxicity, especially in patients with solitary tumor. Radioembolization may be considered as a first-line treatment option for unresectable ICC.
Collapse
Affiliation(s)
- Bela Kis
- Department of Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center, Tampa, Florida.
| | - Ravi Shridhar
- Radiation Oncology, AdventHealth Cancer Institute, Orlando, Florida
| | - Rahul Mhaskar
- Department of Internal Medicine, University of South Florida Morsani College of Medicine, Tampa, Florida
| | - Marcell Gyano
- Department of Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center, Tampa, Florida
| | - Jessica M Frakes
- Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida
| | - Ghassan El-Haddad
- Department of Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center, Tampa, Florida
| | - Junsung Choi
- Department of Diagnostic Imaging and Interventional Radiology, Moffitt Cancer Center, Tampa, Florida
| | - Richard D Kim
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, Florida
| | - Sarah E Hoffe
- Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida
| |
Collapse
|
|
13
|
Bourien H, Pircher CC, Guiu B, Lamarca A, Valle JW, Niger M, Edeline J. Locoregional Treatment in Intrahepatic Cholangiocarcinoma: Which Treatment for Which Patient? Cancers (Basel) 2023; 15:4217. [PMID: 37686493 PMCID: PMC10486617 DOI: 10.3390/cancers15174217] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Revised: 08/08/2023] [Accepted: 08/14/2023] [Indexed: 09/10/2023] Open
Abstract
For unresectable intrahepatic cholangiocarcinoma (iCC), different locoregional treatments (LRT) could be proposed to patients, including radiofrequency ablation (RFA) and microwave ablation (MWA), external beam radiotherapy (EBRT) or transarterial treatments, depending on patient and tumor characteristics and local expertise. These different techniques of LRT have not been compared in a randomized clinical trial; most of the relevant studies are retrospective and not comparative. The aim of this narrative review is to help clinicians in their everyday practice discuss the pros and cons of each LRT, depending on the individual characteristics of their patients.
Collapse
Affiliation(s)
- Héloïse Bourien
- Medical Oncology Department, Centre Eugène Marquis, 35000 Rennes, France;
| | - Chiara Carlotta Pircher
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Tumori, 20133 Milano, Italy; (C.C.P.); (M.N.)
| | - Boris Guiu
- Interventional Radiology Department, CHU de Montpellier, 34090 Montpellier, France;
| | - Angela Lamarca
- Oncology Department, Fundación Jiménez Díaz University Hospital, 28022 Madrid, Spain;
- Medical Oncology Department, Division of Cancer Sciences, University of Manchester, Manchester M13 9PL, UK;
- The Christie NHS Foundation Trust, Manchester M20 4BX, UK
| | - Juan W Valle
- Medical Oncology Department, Division of Cancer Sciences, University of Manchester, Manchester M13 9PL, UK;
- The Christie NHS Foundation Trust, Manchester M20 4BX, UK
| | - Monica Niger
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Tumori, 20133 Milano, Italy; (C.C.P.); (M.N.)
| | - Julien Edeline
- Medical Oncology Department, Centre Eugène Marquis, 35000 Rennes, France;
| |
Collapse
|
|
14
|
Zhao K, Erinjeri JP, Sotirchos VS, Alexander ES, Moussa AM, Marinelli B, Ziv E, Sofocleous CT, Abou-Alfa GK, Jarnagin WR, Karimi A, Yarmohammadi H. Factors affecting outcomes of Yttrium-90 radioembolization in heavily pretreated patients with intrahepatic cholangiocarcinoma. Abdom Radiol (NY) 2023; 48:2434-2442. [PMID: 37145313 DOI: 10.1007/s00261-023-03930-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 04/13/2023] [Accepted: 04/18/2023] [Indexed: 05/06/2023]
Abstract
PURPOSE Transarterial radioembolization (TARE) is a liver-directed treatment for unresectable intrahepatic cholangiocarcinoma (ICC). The aim of this study is to evaluate factors affecting outcomes of TARE in heavily pretreated ICC patients. METHODS We evaluated pretreated ICC patients who received TARE from January 2013 to December 2021. Prior treatments included systemic therapy, hepatic resection, and liver-directed therapies, including hepatic arterial infusion chemotherapy, external beam radiation, transarterial embolization, and thermal ablation. Patients were classified based on history of hepatic resection and genomic status based on next-generation sequencing (NGS). The primary endpoint was overall survival (OS) after TARE. RESULTS Fourteen patients with median age 66.1 years (range, 52.4-87.5), 11 females and 3 males, were included. Prior therapies included systemic in 13/14 patients (93%), liver resection in 6/14 (43%), and liver-directed therapy in 6/14 (43%). Median OS was 11.9 months (range, 2.8-81.0). Resected patients had significantly longer median OS compared to unresected patients (16.6 versus 7.9 months; p = 0.038). Prior liver-directed therapy (p = 0.043), largest tumor diameter > 4 cm (p = 0.014), and > 2 hepatic segments involvement (p = 0.001) were associated with worse OS. Nine patients underwent NGS; 3/9 (33.3%) and had a high-risk gene signature (HRGS), defined as alterations in TP53, KRAS, or CDKN2A. Patients with a HRGS had worse median OS (10.0 versus 17.8 months; p = 0.024). CONCLUSIONS TARE may be used as salvage therapy in heavily treated ICC patients. Presence of a HRGS may predict worse OS after TARE. Further investigation with more patients is recommended to validate these results.
Collapse
Affiliation(s)
- Ken Zhao
- Department of Interventional Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
| | - Joseph P Erinjeri
- Department of Interventional Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Vlasios S Sotirchos
- Department of Interventional Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Erica S Alexander
- Department of Interventional Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Amgad M Moussa
- Department of Interventional Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Brett Marinelli
- Department of Interventional Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Etay Ziv
- Department of Interventional Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | | | - Ghassan K Abou-Alfa
- Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Department of Medicine, Weill Medical College at Cornell University, New York, NY, USA
| | - William R Jarnagin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Anita Karimi
- Department of Interventional Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Hooman Yarmohammadi
- Department of Interventional Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| |
Collapse
|
|
15
|
Alvaro D, Gores GJ, Walicki J, Hassan C, Sapisochin G, Komuta M, Forner A, Valle JW, Laghi A, Ilyas SI, Park JW, Kelley RK, Reig M, Sangro B. EASL-ILCA Clinical Practice Guidelines on the management of intrahepatic cholangiocarcinoma. J Hepatol 2023; 79:181-208. [PMID: 37084797 DOI: 10.1016/j.jhep.2023.03.010] [Citation(s) in RCA: 109] [Impact Index Per Article: 54.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Accepted: 03/10/2023] [Indexed: 04/23/2023]
Abstract
Intrahepatic cholangiocarcinoma (iCCA) develops inside the liver, between bile ductules and the second-order bile ducts. It is the second most frequent primary liver cancer after hepatocellular carcinoma, and its global incidence is increasing. It is associated with an alarming mortality rate owing to its silent presentation (often leading to late diagnosis), highly aggressive nature and resistance to treatment. Early diagnosis, molecular characterisation, accurate staging and personalised multidisciplinary treatments represent current challenges for researchers and physicians. Unfortunately, these challenges are beset by the high heterogeneity of iCCA at the clinical, genomic, epigenetic and molecular levels, very often precluding successful management. Nonetheless, in the last few years, progress has been made in molecular characterisation, surgical management, and targeted therapy. Recent advances together with the awareness that iCCA represents a distinct entity amongst the CCA family, led the ILCA and EASL governing boards to commission international experts to draft dedicated evidence-based guidelines for physicians involved in the diagnostic, prognostic, and therapeutic management of iCCA.
Collapse
|
|
16
|
Casáns-Tormo I, Guijarro-Rosaleny J, Lluch-García P, Rodríguez-Parra H, Roselló-Keränen S, Asensio-Valero L. Evaluation of results after 112 radioembolizations with 90Y-microspheres. Rev Esp Med Nucl Imagen Mol 2023:S2253-8089(23)00053-8. [PMID: 37269983 DOI: 10.1016/j.remnie.2023.05.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 05/07/2023] [Accepted: 05/09/2023] [Indexed: 06/05/2023]
Abstract
AIM To determine the results of radioembolization transarterial (TARE), in the treatment of liver tumors, a retrospective evaluation was performed after 112 TARE with 90Y-microspheres administered in 82 patients in a single hospital, analyzing efficacy and safety, after a follow-up greater than or equal to 1 year post-TARE in all patients, and evaluating the possible relationship between treatment response and patient survival. MATERIAL AND METHODS We have administered 57 single TARE and 55 multiple TARE in patients with hepatocellular carcinoma (53), liver metastases (25) and cholangiocarcinoma (4), with prior multidisciplinary evaluation, clinical, angiographic and gammagraphic (planar/SPECT/SPECT-CT with 99mTc-MAA), multicompartment model (MIRD equations), post-TARE screening (planar/SPECT/SPECT-CT), clinical and radiological follow-up, tumor response evaluation (mRECIST criteria) and Kaplan-Meier analysis to determine progression-free survival and overall survival (OS). RESULTS Therapeutic intention was palliative (82%) and as bridge to liver transplantation/surgical resection (17%). We obtained response (R), complete or partial, in 65.9% of cases. One year after TARE 34.7% of patients with R and 19.2% of non-R were progression-free (p: 0.003), with OS of 80% for R and 37.5% for non-R (p: 0.001). Survival analysis showed median OS of 18 months (95% CI 15.7-20.3) for R and 9 months (95% CI 6.1-11.8) for non-R (p: 0.03). We found mild (27.6%) and severe (5.3%) side effects, all of them resolved, without higher incidence after multiple TARE. CONCLUSION TARE with 90Y-microspheres, in appropriately selected patients with liver tumors, provides therapeutic efficacy and low rate of toxicity, with higher progression-free survival and OS in patients with TARE response compared to those who did not respond.
Collapse
Affiliation(s)
- I Casáns-Tormo
- Servicio de Medicina Nuclear, Hospital Clínico Universitario, Valencia, Spain.
| | - J Guijarro-Rosaleny
- Servicio de Radiodiagnóstico, Hospital Clínico Universitario, Valencia, Spain
| | - P Lluch-García
- Servicio de Medicina Digestiva, Hospital Clínico Universitario, Valencia, Spain
| | - H Rodríguez-Parra
- Servicio de Medicina Nuclear, Hospital Clínico Universitario, Valencia, Spain
| | - S Roselló-Keränen
- Servicio de Oncología Médica, Hospital Clínico Universitario, Valencia, Spain
| | - L Asensio-Valero
- Servicio de Medicina Nuclear, Hospital Clínico Universitario, Valencia, Spain
| |
Collapse
|
|
17
|
Moroney J, Trivella J, George B, White SB. A Paradigm Shift in Primary Liver Cancer Therapy Utilizing Genomics, Molecular Biomarkers, and Artificial Intelligence. Cancers (Basel) 2023; 15:2791. [PMID: 37345129 PMCID: PMC10216313 DOI: 10.3390/cancers15102791] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Revised: 05/02/2023] [Accepted: 05/10/2023] [Indexed: 06/23/2023] Open
Abstract
Primary liver cancer is the sixth most common cancer worldwide and the third leading cause of cancer-related death. Conventional therapies offer limited survival benefit despite improvements in locoregional liver-directed therapies, which highlights the underlying complexity of liver cancers. This review explores the latest research in primary liver cancer therapies, focusing on developments in genomics, molecular biomarkers, and artificial intelligence. Attention is also given to ongoing research and future directions of immunotherapy and locoregional therapies of primary liver cancers.
Collapse
Affiliation(s)
- James Moroney
- Division of Vascular and Interventional Radiology, Department of Radiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
| | - Juan Trivella
- Division of Gastroenterology and Hepatology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA
| | - Ben George
- Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA
| | - Sarah B. White
- Division of Vascular and Interventional Radiology, Department of Radiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
| |
Collapse
|
|
18
|
Auer TA, Collettini F, Segger L, Pelzer U, Mohr R, Krenzien F, Gebauer B, Geisel D, Hosse C, Schöning W, Fehrenbach U. Interventional Treatment Strategies in Intrahepatic Cholangiocarcinoma and Perspectives for Combined Hepatocellular-Cholangiocarcinoma. Cancers (Basel) 2023; 15:cancers15092655. [PMID: 37174120 PMCID: PMC10177209 DOI: 10.3390/cancers15092655] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2023] [Revised: 05/01/2023] [Accepted: 05/03/2023] [Indexed: 05/15/2023] Open
Abstract
cHCC-CCA is an uncommon type of liver cancer that exhibits clinical and pathological characteristics of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), which are the two main forms of primary liver cancer. The similarity to HCC and CCA makes therapeutical strategies challenging. The poor prognosis of CCA in general, as well as for cHCC-CCA, is mainly attributable to the fact that diagnosis is often at an advanced stage of disease. During the last decade, locoregional therapies usually performed by interventional radiologists and its established role in HCC treatment have gained an increasing role in CCA treatment as well. These comprise a wide range of options from tumor ablation procedures such as radiofrequency ablation (RFA), microwave ablation (MWA), computed tomography high-dose rate brachytherapy (CT-HDRBT), and cryoablation to transarterial chemoembolization (TACE), including the option of intra-arterial administration of radioactive spheres (transarterial radioembolization-TARE), and much attention has focused on the potential of individual concepts in recent years. The purpose of this review is to provide an overview of current radiologic interventions for CCA (excluding options for eCCA), to review and appraise the existing literature on the topic, and to provide an outlook on whether such interventions may have a role as treatment for cHCC-CCA in the future.
Collapse
Affiliation(s)
- Timo Alexander Auer
- Department of Radiology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
- Berlin Institute of Health (BIH), Anna-Louisa-Karsch-Straße 2, 10178 Berlin, Germany
| | - Federico Collettini
- Department of Radiology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
- Berlin Institute of Health (BIH), Anna-Louisa-Karsch-Straße 2, 10178 Berlin, Germany
| | - Laura Segger
- Department of Radiology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Uwe Pelzer
- Department of Hematology, Oncology and Cancer Immunology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Raphael Mohr
- Department of Hepatology and Gastroenterology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Felix Krenzien
- Department of Surgery-CVK/CCM, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Bernhard Gebauer
- Department of Radiology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Dominik Geisel
- Department of Radiology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Clarissa Hosse
- Department of Radiology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Wenzel Schöning
- Department of Surgery-CVK/CCM, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| | - Uli Fehrenbach
- Department of Radiology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
| |
Collapse
|
|
19
|
Müller C, Omari J, Mohnike K, Bär C, Pech M, Keitel V, Venerito M. Multidisciplinary Treatment of Patients with Progressive Biliary Tract Cancer after First-Line Gemcitabine and Cisplatin: A Single-Center Experience. Cancers (Basel) 2023; 15:2598. [PMID: 37174064 PMCID: PMC10177261 DOI: 10.3390/cancers15092598] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2023] [Revised: 04/07/2023] [Accepted: 04/30/2023] [Indexed: 05/15/2023] Open
Abstract
BACKGROUND Patients with unresectable biliary tract cancer (uBTC) who progress despite first-line gemcitabine plus cisplatin (GC) treatment have limited systemic options with a modest survival benefit. Data are lacking on the clinical effectiveness and safety of personalized treatment based on multidisciplinary discussion for patients with progressing uBTC. METHODS This retrospective single-center study included patients with progressive uBTC who received either best supportive care or personalized treatment based on multidisciplinary discussion, including minimally invasive, image-guided procedures (MIT); FOLFIRI; or both (MIT and FOLFIRI), between 2011 and 2021. RESULTS Ninety-seven patients with progressive uBTC were identified. Patients received best supportive care (n = 50, 52%), MIT (n = 14, 14%), FOLFIRI (n = 19, 20%), or both (n = 14, 14%). Survival after disease progression was better in patients who received MIT (8.8 months; 95% CI: 2.60-15.08), FOLFIRI (6 months; 95% CI: 3.30-8.72), or both (15.1 months; 95% CI: 3.66-26.50) than in patients receiving BSC (0.36 months; 95% CI: 0.00-1.24, p < 0.001). The most common (>10%) grade 3-5 adverse events were anemia (25%) and thrombocytopenia (11%). CONCLUSION Multidisciplinary discussion is critical for identifying patients with progressive uBTC who might benefit the most from MIT, FOLFIRI, or both. The safety profile was consistent with previous reports.
Collapse
Affiliation(s)
- Christian Müller
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, 39120 Magdeburg, Germany
| | - Jazan Omari
- Department of Radiology and Nuclear Medicine, Otto-von-Guericke University Hospital, 39120 Magdeburg, Germany
| | - Konrad Mohnike
- DTZ Diagnostic and Therapeutic Center, 10243 Berlin, Germany
| | - Caroline Bär
- Department of Radiology and Nuclear Medicine, Otto-von-Guericke University Hospital, 39120 Magdeburg, Germany
| | - Maciej Pech
- Department of Radiology and Nuclear Medicine, Otto-von-Guericke University Hospital, 39120 Magdeburg, Germany
| | - Verena Keitel
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, 39120 Magdeburg, Germany
| | - Marino Venerito
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, 39120 Magdeburg, Germany
| |
Collapse
|
|
20
|
Owen M, Makary MS, Beal EW. Locoregional Therapy for Intrahepatic Cholangiocarcinoma. Cancers (Basel) 2023; 15:2384. [PMID: 37190311 PMCID: PMC10137284 DOI: 10.3390/cancers15082384] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 04/08/2023] [Accepted: 04/18/2023] [Indexed: 05/17/2023] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis, and surgical resection (SR) offers the only potential for cure. Unfortunately, only a small proportion of patients are eligible for resection due to locally advanced or metastatic disease. Locoregional therapies (LRT) are often used in unresectable liver-only or liver-dominant ICC. This review explores the role of these therapies in the treatment of ICC, including radiofrequency ablation (RFA), microwave ablation (MWA), transarterial chemoembolization (TACE), transarterial radioembolization (TARE), external beam radiotherapy (EBRT), stereotactic body radiotherapy (SBRT), hepatic arterial infusion (HAI) of chemotherapy, irreversible electroporation (IE), and brachytherapy. A search of the current literature was performed to examine types of LRT currently used in the treatment of ICC. We examined patient selection, technique, and outcomes of each type. Overall, LRTs are well-tolerated in the treatment of ICC and are effective in improving overall survival (OS) in this patient population. Further studies are needed to reduce bias from heterogenous patient populations and small sample sizes, as well as to determine whether certain LRTs are superior to others and to examine optimal treatment selection.
Collapse
Affiliation(s)
- Mackenzie Owen
- The Ohio State University College of Medicine, Columbus, OH 43210, USA
| | - Mina S. Makary
- Division of Vascular and Interventional Radiology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
| | - Eliza W. Beal
- Departments of Surgery and Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA
| |
Collapse
|
|
21
|
Moris D, Palta M, Kim C, Allen PJ, Morse MA, Lidsky ME. Advances in the treatment of intrahepatic cholangiocarcinoma: An overview of the current and future therapeutic landscape for clinicians. CA Cancer J Clin 2023; 73:198-222. [PMID: 36260350 DOI: 10.3322/caac.21759] [Citation(s) in RCA: 224] [Impact Index Per Article: 112.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Revised: 08/25/2022] [Accepted: 08/29/2022] [Indexed: 01/27/2023] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver tumor and remains a fatal malignancy in the majority of patients. Approximately 20%-30% of patients are eligible for resection, which is considered the only potentially curative treatment; and, after resection, a median survival of 53 months has been reported when sequenced with adjuvant capecitabine. For the 70%-80% of patients who present with locally unresectable or distant metastatic disease, systemic therapy may delay progression, but survival remains limited to approximately 1 year. For the past decade, doublet chemotherapy with gemcitabine and cisplatin has been considered the most effective first-line regimen, but results from the recent use of triplet regimens and even immunotherapy may shift the paradigm. More effective treatment strategies, including those that combine systemic therapy with locoregional therapies like radioembolization or hepatic artery infusion, have also been developed. Molecular therapies, including those that target fibroblast growth factor receptor and isocitrate dehydrogenase, have recently received US Food and Drug Administration approval for a defined role as second-line treatment for up to 40% of patients harboring these actionable genomic alterations, and whether they should be considered in the first-line setting is under investigation. Furthermore, as the oncology field seeks to expand indications for immunotherapy, recent data demonstrated that combining durvalumab with standard cytotoxic therapy improved survival in patients with ICC. This review focuses on the current and future strategies for ICC treatment, including a summary of the primary literature for each treatment modality and an algorithm that can be used to drive a personalized and multidisciplinary approach for patients with this challenging malignancy.
Collapse
Affiliation(s)
- Dimitrios Moris
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA
| | - Manisha Palta
- Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, USA
| | - Charles Kim
- Department of Radiology, Duke University Medical Center, Durham, North Carolina, USA
| | - Peter J Allen
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA
| | - Michael A Morse
- Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
| | - Michael E Lidsky
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA
| |
Collapse
|
|
22
|
Mauro E, Ferrer-Fàbrega J, Sauri T, Soler A, Cobo A, Burrel M, Iserte G, Forner A. New Challenges in the Management of Cholangiocarcinoma: The Role of Liver Transplantation, Locoregional Therapies, and Systemic Therapy. Cancers (Basel) 2023; 15:1244. [PMID: 36831586 PMCID: PMC9953927 DOI: 10.3390/cancers15041244] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Revised: 02/03/2023] [Accepted: 02/11/2023] [Indexed: 02/18/2023] Open
Abstract
Cholangiocarcinoma (CCA) is a neoplasm with high mortality that represents 15% of all primary liver tumors. Its worldwide incidence is on the rise, and despite important advances in the knowledge of molecular mechanisms, diagnosis, and treatment, overall survival has not substantially improved in the last decade. Surgical resection remains the cornerstone therapy for CCA. Unfortunately, complete resection is only possible in less than 15-35% of cases, with a risk of recurrence greater than 60%. Liver transplantation (LT) has been postulated as an effective therapeutic strategy in those intrahepatic CCA (iCCA) smaller than 3 cm. However, the low rate of early diagnosis in non-resectable patients justifies the low applicability in clinical practice. The evidence regarding LT in locally advanced iCCA is scarce and based on small, retrospective, and, in most cases, single-center case series. In this setting, the response to neoadjuvant chemotherapy could be useful in identifying a subgroup of patients with biologically less aggressive tumors in whom LT may be successful. The results of LT in pCCA are promising, however, we need a very careful selection of patients and adequate experience in the transplant center. Locoregional therapies may be relevant in unresectable, liver-only CCA. In iCCA smaller than 2 cm, particularly those arising in patients with advanced chronic liver disease in whom resection or LT may not be feasible, thermal ablation may become a reliable alternative. The greatest advances in the management of CCA occur in systemic treatment. Immunotherapy associated with chemotherapy has emerged as the gold standard in the first-line treatment. Likewise, the most encouraging results have been obtained with targeted therapies, where the use of personalized treatments has shown high rates of objective and durable tumor response, with clear signs of survival benefit. In conclusion, the future of CCA treatment seems to be marked by the development of new treatment strategies but high-quality, prospective studies that shed light on their use and applicability are mandatory.
Collapse
Affiliation(s)
- Ezequiel Mauro
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Av. Monforte de Lemos, 3-5. Pabellón 11, Planta 0, 28029 Madrid, Spain
| | - Joana Ferrer-Fàbrega
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Av. Monforte de Lemos, 3-5. Pabellón 11, Planta 0, 28029 Madrid, Spain
- Hepatobiliopancreatic Surgery and Liver and Pancreatic Transplantation Unit, Department of Surgery, ICMDM, Hospital Clinic Barcelona, 08036 Barcelona, Spain
- Faculty of Medicine, University of Barcelona, C/ de Casanova, 143, 08036 Barcelona, Spain
| | - Tamara Sauri
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Faculty of Medicine, University of Barcelona, C/ de Casanova, 143, 08036 Barcelona, Spain
- Medical Oncology Department, ICMHO, Hospital Clinic Barcelona, 08036 Barcelona, Spain
| | - Alexandre Soler
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Radiology Department, CDI, Hospital Clinic Barcelona, 08036 Barcelona, Spain
| | - Amparo Cobo
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Nuclear Medicine Department, CDI, Hospital Clinic Barcelona, 08036 Barcelona, Spain
| | - Marta Burrel
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Department of Interventional Radiology, CDI, Hospital Clinic Barcelona, 08036 Barcelona, Spain
| | - Gemma Iserte
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Av. Monforte de Lemos, 3-5. Pabellón 11, Planta 0, 28029 Madrid, Spain
- Liver Unit, Liver Oncology Unit, ICMDM, Hospital Clinic Barcelona, 08036 Barcelona, Spain
| | - Alejandro Forner
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Av. Monforte de Lemos, 3-5. Pabellón 11, Planta 0, 28029 Madrid, Spain
- Faculty of Medicine, University of Barcelona, C/ de Casanova, 143, 08036 Barcelona, Spain
- Liver Unit, Liver Oncology Unit, ICMDM, Hospital Clinic Barcelona, 08036 Barcelona, Spain
| |
Collapse
|
|
23
|
Ohaegbulam KC, Koethe Y, Fung A, Mayo SC, Grossberg AJ, Chen EY, Sharzehi K, Kardosh A, Farsad K, Rocha FG, Thomas CR, Nabavizadeh N. The multidisciplinary management of cholangiocarcinoma. Cancer 2023; 129:184-214. [PMID: 36382577 DOI: 10.1002/cncr.34541] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 10/11/2022] [Accepted: 10/14/2022] [Indexed: 11/17/2022]
Abstract
Cholangiocarcinoma is a lethal malignancy of the biliary epithelium that can arise anywhere along the biliary tract. Surgical resection confers the greatest likelihood of long-term survivability. However, its insidious onset, difficult diagnostics, and resultant advanced presentation render the majority of patients unresectable, highlighting the importance of early detection with novel biomarkers. Developing liver-directed therapies and emerging targeted therapeutics may offer improved survivability for patients with unresectable or advanced disease. In this article, the authors review the current multidisciplinary standards of care in resectable and unresectable cholangiocarcinoma, with an emphasis on novel biomarkers for early detection and nonsurgical locoregional therapy options.
Collapse
Affiliation(s)
- Kim C Ohaegbulam
- Department of Radiation Medicine, Oregon Health & Science University, Portland, Oregon, USA
| | - Yilun Koethe
- Department of Interventional Radiology, Oregon Health & Science University, Portland, Oregon, USA
| | - Alice Fung
- Department of Diagnostic Radiology, Oregon Health & Science University, Portland, Oregon, USA
| | - Skye C Mayo
- Department of Surgical Oncology, Oregon Health & Science University, Portland, Oregon, USA
| | - Aaron J Grossberg
- Department of Radiation Medicine, Oregon Health & Science University, Portland, Oregon, USA
| | - Emerson Y Chen
- Division of Hematology/Medical Oncology, Oregon Health & Science University, Portland, Oregon, USA
| | - Kaveh Sharzehi
- Division of Gastroenterology and Hepatology, Oregon Health & Science University, Portland, Oregon, USA
| | - Adel Kardosh
- Division of Hematology/Medical Oncology, Oregon Health & Science University, Portland, Oregon, USA
| | - Khashayar Farsad
- Department of Interventional Radiology, Oregon Health & Science University, Portland, Oregon, USA
| | - Flavio G Rocha
- Department of Surgical Oncology, Oregon Health & Science University, Portland, Oregon, USA
| | - Charles R Thomas
- Department of Radiation Medicine, Oregon Health & Science University, Portland, Oregon, USA.,Department of Radiation Oncology, Dartmouth School of Medicine, Hanover, New Hampshire, USA
| | - Nima Nabavizadeh
- Department of Radiation Medicine, Oregon Health & Science University, Portland, Oregon, USA
| |
Collapse
|
|
24
|
Mosconi C, Cacioppa LM, Cappelli A, Gramenzi AG, Vara G, Modestino F, Renzulli M, Golfieri R. Update of the Bologna Experience in Radioembolization of Intrahepatic cholangiocarcinoma. Technol Cancer Res Treat 2023; 22:15330338231155690. [PMID: 36927302 PMCID: PMC10026142 DOI: 10.1177/15330338231155690] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/18/2023] Open
Abstract
BACKGROUND Intrahepatic cholangiocarcinoma (ICC) is the second most common primitive liver cancer and is rising in incidence worldwide. Given its low survival and resectability rates, locoregional therapies such as Yttrium-90 transarterial radioembolization (Y-TARE) are increasingly being employed. This retrospective study aim was to confirm and update our previous results about overall survival (OR), safety, and efficacy of Y-TARE in patients with unresectable/recurrent ICC. MATERIALS AND METHODS OS was evaluated as primary endpoint while radiological tumor response at 3 months, based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, was considered as secondary endpoint. RESULTS Over a total of 49 patients, the overall median survival was 16 months (27-41 months, 95% confidence interval [CI]) from Y-TARE procedure. A significantly longer survival was recorded in naive patients compared to patients previously submitted to any type of liver-directed treatment and radical surgery (18 vs 14 months, P=.015 and 28 vs 14 months, P=.001, respectively). Target lesion and overall objective response for RECIST 1.1 criteria were 64.6% and 52.1%, respectively. Low rates of postprocedural and late complications were recorded. CONCLUSIONS In unresectable and recurrent ICC, Y-TARE confirms its safety and its potential in increasing OS, especially in naive patients.
Collapse
Affiliation(s)
- Cristina Mosconi
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Laura Maria Cacioppa
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Alberta Cappelli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Anna Giulia Gramenzi
- Division of Semeiotic, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Giulio Vara
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Francesco Modestino
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Matteo Renzulli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Rita Golfieri
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| |
Collapse
|
|
25
|
Ahmed O, Yu Q, Patel M, Hwang G, Pillai A, Liao CY, Fung J, Baker T. Yttrium-90 Radioembolization and Concomitant Systemic Gemcitabine, Cisplatin, and Capecitabine as the First-Line Therapy for Locally Advanced Intrahepatic Cholangiocarcinoma. J Vasc Interv Radiol 2022; 34:702-709. [PMID: 36521794 DOI: 10.1016/j.jvir.2022.12.017] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 11/20/2022] [Accepted: 12/05/2022] [Indexed: 12/14/2022] Open
Abstract
PURPOSE To determine the safety and effectiveness of yttrium-90 transarterial radioembolization (TARE) combined with systemic gemcitabine, cisplatin, and capecitabine for the first-line treatment of locally advanced intrahepatic cholangiocarcinoma (iCCA). MATERIALS AND METHODS Data of 13 patients with treatment-naïve, locally advanced iCCA treated with a downstaging protocol using gemcitabine, cisplatin, TARE, and capecitabine were retrospectively reviewed. Overall survival (OS), local tumor response (modified Response Evaluation Criteria in Solid Tumors), progression-free survival (PFS), technical adverse events, and toxicity were measured. RESULTS Calculated from the time of diagnosis, the median OS was 29 months (95% confidence interval [CI], 15 to not reached), with a 1-year OS of 84.6% (95% CI, 52.2%-95.9%) and 2-year OS of 52.9% (95% CI, 20.3%-77.5%). The median OS values were 24 months (95% CI, 8 to not reached) and 21 months (95% CI, 5 to not reached) from the time of initial cycle of chemotherapy and TARE, respectively. Patients who were downstaged to surgery (n = 7, 53.8%) had a more favorable OS (median OS, not reached vs 15 months; P = .0221). Complete and partial radiologic responses were achieved in 5 (38.5%) and 6 (46.2%) patients, respectively. The median PFS was 13 months (95% CI, 12 to not reached). Although no serum toxicity with Grade >2 occurred within 3 months after TARE, 1 patient was no longer a surgical candidate given suboptimal nutrition status despite successful downstage on imaging studies. Two patients required a reduced dose or delay of post-TARE chemotherapy. CONCLUSIONS First-line combination therapy with TARE and systemic gemcitabine, cisplatin, and capecitabine is an effective treatment with an acceptable safety profile for iCCA with a high rate of downstaging to resection.
Collapse
Affiliation(s)
- Osman Ahmed
- Department of Radiology, University of Chicago Medical Center, University of Chicago, Chicago, Illinois
| | - Qian Yu
- Department of Radiology, University of Chicago Medical Center, University of Chicago, Chicago, Illinois.
| | - Mikin Patel
- Department of Radiology, University of Chicago Medical Center, University of Chicago, Chicago, Illinois
| | - Gloria Hwang
- Department of Radiology, University of Chicago Medical Center, University of Chicago, Chicago, Illinois
| | - Anjana Pillai
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Chicago Medical Center, University of Chicago, Chicago, Illinois
| | - Chih-Yi Liao
- Hematology and Oncology, Department of Medicine, University of Chicago Medical Center, University of Chicago, Chicago, Illinois
| | - John Fung
- Transplantation Institute, Department of Surgery, University of Chicago Medical Center, University of Chicago, Chicago, Illinois
| | - Talia Baker
- Transplantation Institute, Department of Surgery, University of Chicago Medical Center, University of Chicago, Chicago, Illinois; Division of Transplantation and Advanced Hepatobiliary Surgery, University of Utah, Salt Lake City, Utah
| |
Collapse
|
|
26
|
Robinson TJ, Du L, Matsuoka L, Sze DY, Kennedy AS, Gandhi RT, Kouri BE, Collins ZS, Kokabi N, Grilli CJ, Wang EA, Lee JS, Brown DB. Survival and Toxicities after Yttrium-90 Transarterial Radioembolization of Cholangiocarcinoma in the RESiN Registry. J Vasc Interv Radiol 2022; 34:694-701.e3. [PMID: 36509236 DOI: 10.1016/j.jvir.2022.10.042] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 10/28/2022] [Accepted: 10/30/2022] [Indexed: 12/13/2022] Open
Abstract
PURPOSE To report outcomes in patients with intrahepatic cholangiocarcinoma treated with yttrium-90 resin microspheres (transarterial radioembolization [TARE]) from a multicenter, prospective observational registry. MATERIALS AND METHODS Ninety-five patients (median age, 67 years [interquartile range {IQR}, 59-74]; 50 men) were treated in 27 centers between July 2015 and August 2020. Baseline demographic characteristics included imaging findings, performance status, and previous systemic or locoregional treatments. Dosimetry method was tracked. Overall survival (OS) and progression-free survival were calculated using the Kaplan-Meier method. The best imaging response was calculated using the Response Evaluation Criteria in Solid Tumors v1.1. Grade ≥3 toxicities were assessed using Common Terminology Criteria for Adverse Events v5. Cox regression analysis was performed. RESULTS Fifty-two of 86 (60%) patients had multifocal tumors, and 24/89 (27%) had extrahepatic tumors. The median index tumor diameter was 7.0 cm (IQR, 4.9-10 cm). The activity calculation method was reported in 59/95 (62%) patients, with body surface area being the most frequently used method (45/59, 76%). Median OS for the cohort was 14 months (95% confidence interval, 12-22). OS at 3, 6, 12, and 24 months was 94%, 80%, 63%, and 34%, respectively. Median OS was longer in patients without cirrhosis (19.1 vs 12.2 months, P = .05). Cirrhosis, previous chemotherapy (OS, 19.1 vs 10.6 months for treatment-naïve; P = .07), and imaging response at 6 months (OS, 16.4 vs 9.5 months for no response; P = .06) underwent regression analysis. Imaging response predicted OS at regression (hazard ratio, 0.39; P = .008). Grade 3-4 bilirubin toxicities were noted in 5 of 72 (7%) patients. Grade 3 albumin toxicity was noted in 1 of 72 (1.4%) patients. CONCLUSIONS Objective response at 6 months predicted longer OS after TARE for intrahepatic cholangiocarcinoma. The incidence of liver function toxicity was <10%.
Collapse
Affiliation(s)
- Taylor J Robinson
- Vanderbilt University School of Medicine, Vanderbilt University, Nashville, Tennessee
| | - Liping Du
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Lea Matsuoka
- Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Daniel Y Sze
- Division of Interventional Radiology, Stanford University, Palo Alto, California
| | - Andrew S Kennedy
- Department of Radiation Oncology, Sarah Cannon Research Institute, Nashville, Tennessee
| | - Ripal T Gandhi
- Division of Interventional Radiology, Miami Cardiac and Vascular Institute/Miami Cancer Institute, Miami, Florida
| | - Brian E Kouri
- Division of Interventional Radiology, Atrium Wake Forest Baptist Health, Winston-Salem, North Carolina
| | - Zachary S Collins
- Division of Interventional Radiology, University of Kansas, Kansas City, Kansas
| | - Nima Kokabi
- Division of Interventional Radiology and Image-Guided Therapy, Emory University School of Medicine, Atlanta, Georgia
| | - Christopher J Grilli
- Division of Interventional Radiology, Christiana Medical Center, Newark, Delaware
| | - Eric A Wang
- Division of Interventional Radiology, Carolinas Medical Center, Charlotte, North Carolina
| | - Justin S Lee
- Division of Interventional Radiology, Radiology Associates of Florida, Tampa, Florida
| | - Daniel B Brown
- Division of Interventional Radiology, Vanderbilt University Medical Center, Nashville, Tennessee.
| |
Collapse
|
|
27
|
Hosseini Shabanan S, Nezami N, Abdelsalam ME, Sheth RA, Odisio BC, Mahvash A, Habibollahi P. Selective Internal Radiation Therapy with Yttrium-90 for Intrahepatic Cholangiocarcinoma: A Systematic Review on Post-Treatment Dosimetry and Concomitant Chemotherapy. Curr Oncol 2022; 29:3825-3848. [PMID: 35735415 PMCID: PMC9222092 DOI: 10.3390/curroncol29060306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Revised: 05/18/2022] [Accepted: 05/23/2022] [Indexed: 01/27/2023] Open
Abstract
Selective internal radiation therapy (SIRT) with yttrium-90 (90Y)-loaded microspheres is increasingly used for the treatment of Intrahepatic Cholangiocarcinoma (ICC). Dosimetry verifications post-treatment are required for a valid assessment of any dose-response relationship. We performed a systematic review of the literature to determine how often clinics conducted post-treatment dosimetry verification to measure the actual radiation doses delivered to the tumor and to the normal liver in patients who underwent SIRT for ICC, and also to explore the corresponding dose-response relationship. We also investigated other factors that potentially affect treatment outcomes, including the type of microspheres used and concomitant chemotherapy. Out of the final 47 studies that entered our study, only four papers included post-treatment dosimetry studies after SIRT to quantitatively assess the radiation doses delivered. No study showed that one microsphere type provided a benefit over another, one study demonstrated better imaging-based response rates associated with the use of glass-based TheraSpheres, and two studies found similar toxicity profiles for different types of microspheres. Gemcitabine and cisplatin were the most common chemotherapeutic drugs for concomitant administration with SIRT. Future studies of SIRT for ICC should include dosimetry to optimize treatment planning and post-treatment radiation dosage measurements in order to reliably predict patient responses and liver toxicity.
Collapse
Affiliation(s)
| | - Nariman Nezami
- Division of Vascular and Interventional Radiology, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA;
- Experimental Therapeutics Program, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD 21201, USA
| | - Mohamed E. Abdelsalam
- Department of Interventional Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (M.E.A.); (R.A.S.); (B.C.O.); (A.M.)
| | - Rahul Anil Sheth
- Department of Interventional Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (M.E.A.); (R.A.S.); (B.C.O.); (A.M.)
| | - Bruno C. Odisio
- Department of Interventional Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (M.E.A.); (R.A.S.); (B.C.O.); (A.M.)
| | - Armeen Mahvash
- Department of Interventional Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (M.E.A.); (R.A.S.); (B.C.O.); (A.M.)
| | - Peiman Habibollahi
- Department of Interventional Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (M.E.A.); (R.A.S.); (B.C.O.); (A.M.)
| |
Collapse
|
|
28
|
Holster JJ, El Hassnaoui M, Franssen S, IJzermans JNM, de Jonge J, Mostert B, Polak WG, de Wilde RF, Homs MYV, Groot Koerkamp B. Hepatic Arterial Infusion Pump Chemotherapy for Unresectable Intrahepatic Cholangiocarcinoma: A Systematic Review and Meta-Analysis. Ann Surg Oncol 2022; 29:5528-5538. [PMID: 35294656 PMCID: PMC9356931 DOI: 10.1245/s10434-022-11439-x] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 01/24/2022] [Indexed: 02/06/2023]
Abstract
Background Patients with unresectable intrahepatic cholangiocarcinoma (iCCA) have poor survival. This systematic review describes the survival outcomes of hepatic arterial infusion pump (HAIP) chemotherapy with floxuridine for patients with unresectable iCCA. Patients and Methods A literature search was conducted using the electronic databases PubMed, Medline (Ovid), Embase, Web of Science, Google Scholar, and Cochrane to find studies that reported data on the survival of patients with unresectable iCCA treated with HAIP chemotherapy using floxuridine. The quality of the studies was assessed using the Newcastle–Ottawa quality assessment Scale (NOS). Overall survival (OS) was the primary outcome measure, and progression-free survival (PFS), response rates, resection rates, and toxicity were defined as secondary outcome measures. Results After removing duplicates, 661 publications were assessed, of which nine studies, representing a total of 478 patients, met the inclusion criteria. Three out of nine studies were phase II clinical trials, one study was a prospective dose-escalation study, and the remaining five studies were retrospective cohort studies. After accounting for overlapping cohorts, 154 unique patients were included for pooled analysis. The weighted median OS of patients with unresectable iCCA treated with HAIP chemotherapy with floxuridine was 29.0 months (range 25.0–39 months). The pooled 1-, 2-, 3-, and 5-year OS were 86.4, 55.5, 39.5, and 9.7%, respectively. Conclusion HAIP chemotherapy with floxuridine for patients with unresectable iCCA was associated with a 3-year OS of 39.5%, which is favorable compared with systemic chemotherapy for which no 3-year survivors were reported in the Advanced Biliary Cancer (ABC) trials. Supplementary Information The online version contains supplementary material available at 10.1245/s10434-022-11439-x.
Collapse
Affiliation(s)
- Jessica J Holster
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | | | - Stijn Franssen
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Jan N M IJzermans
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Jeroen de Jonge
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Bianca Mostert
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Wojciech G Polak
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Roeland F de Wilde
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Marjolein Y V Homs
- Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
| |
Collapse
|
|
29
|
Schartz D, Porter M, Schartz E, Kallas J, Gupta A, Butani D, Cantos A. Transarterial yrittrium-90 radioembolization for unresectable intrahepatic cholangiocarcinoma: a systematic review and meta-analysis. J Vasc Interv Radiol 2022; 33:679-686. [PMID: 35219834 DOI: 10.1016/j.jvir.2022.02.016] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Revised: 01/06/2022] [Accepted: 02/13/2022] [Indexed: 12/01/2022] Open
Abstract
PURPOSE To investigate the overall efficacy and survival profile of Yrittrium-90 (Y-90) radioembolization for unresectable intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS A systematic literature review and meta-analysis was completed using a random effects model. Studies describing the use of Y-90 for unresectable ICC were included. Disease control rate (DCR), downstaged to resectable rate, CA19-9 response rate, pooled overall median survival (OS), pooled median progression free survival (PFS), and mean reported survival rates ranging from 3 to 36 months (mo) were evaluated. RESULTS Twenty-one studies detailing a total of 921 patients were included. The overall DCR was 82.3% [95% Confidence Interval (CI): 76.7% to 87.8%, I2 = 81%). In 11% of cases, patients were downstaged to being surgically resectable (CI: 6.1% to 15.9%, I2 = 78%). The CA19-9 response rate was 67.2% (CI: 54.5% to 79,8%, I2 = 60%). From point of radioembolization, PFS was 7.8 months (CI: 4.2 mo to 11.3 mo, I2 = 94%), and overall median survival was 12.7 months (CI: 10.6 mo to 14.8 mo, I2 = 62%). Lastly, the overall mean reported survival proportions were at 3 mo (84% survival, SD: 10%), 6 mo (69%, SD:16%), 12 mo (47%, SD: 19%), 18 mo (31%, SD: 21%), 24 mo (30%, SD 19%), 30 mo (21% (SD: 27%), and at 36 mo (5%, SD 7%). CONCLUSIONS Radioembolization with Y-90 for unresectable ICC remains beneficial for both disease control and survival. Data from ongoing projects will continue to help optimize treatment and patient selection resulting in improved patient outcomes.
Collapse
Affiliation(s)
- Derrek Schartz
- University of Rochester Medical Center, Department of Imaging Sciences, Rochester, NY, USA.
| | - Marc Porter
- University of Rochester Medical Center, Department of Imaging Sciences, Rochester, NY, USA
| | - Emily Schartz
- University of Rochester Medical Center, Department of Imaging Sciences, Rochester, NY, USA
| | - Jeffrey Kallas
- University of Rochester Medical Center, Department of Imaging Sciences, Rochester, NY, USA
| | - Akshya Gupta
- University of Rochester Medical Center, Department of Imaging Sciences, Rochester, NY, USA
| | - Devang Butani
- University of Rochester Medical Center, Department of Imaging Sciences, Rochester, NY, USA
| | - Andrew Cantos
- University of Rochester Medical Center, Department of Imaging Sciences, Rochester, NY, USA
| |
Collapse
|
|
30
|
Wacker F, Dewald C. [Local and locoregional treatment of intrahepatic cholangiocarcinoma]. Radiologe 2022; 62:247-252. [PMID: 34981129 DOI: 10.1007/s00117-021-00946-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/29/2021] [Indexed: 01/27/2023]
Abstract
CLINICAL/METHODICAL ISSUE In the new edition of the German S3-guideline published in June 2021, the diagnosis and treatment of cholangiocarcinoma (CCA) and gallbladder carcinoma are addressed for the first time. This article discusses the local and locoregional treatment options for intrahepatic CCA (iCCA). STANDARD RADIOLOGICAL METHODS Mortality is high in iCCA and the incidence is rising. In unresectable patients, treatment options include local and locoregional approaches. METHODICAL INNOVATIONS Besides recommendations regarding surgery, biliary drainage, intraductal locoregional therapy and radiation therapy, two recommendations regarding interventional radiologic therapies are included in the updated S3-guideline. Percutaneous thermal ablation via radiofrequency or microwave ablation (RFA/MWA) is suggested for unresectable tumors with up to 3 cm in diameter as primary therapy and for recurrent tumors. In advanced, liver dominant iCCA, intra-arterial therapies such as transarterial radioembolization (TARE), transarterial chemoembolization (TACE) or hepatic arterial infusion (HAI) are recommended as single therapy or in combination with other therapies. ACHIEVEMENTS Due to a lack of randomized controlled studies, the efficacy of locoregional therapies in iCCA is challenging to assess; however, various cohort studies, meta-analyses and review articles confirm their efficiency. PRACTICAL RECOMMENDATIONS Interventional radiological therapies alone or in combination with systemic therapies have the potential to improve the prognosis of patients with iCCA. Due to the various therapeutic options, patients with iCCA should be treated in centers which cover the entire therapeutic spectrum.
Collapse
Affiliation(s)
- Frank Wacker
- Department of Diagnostic and Interventional Radiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Deutschland.
| | - Cornelia Dewald
- Department of Diagnostic and Interventional Radiology, Hannover Medical School, Carl-Neuberg Str. 1, 30625, Hannover, Deutschland
| |
Collapse
|
|
31
|
Nuclear Medicine Therapy in primary liver cancers. Nucl Med Mol Imaging 2022. [DOI: 10.1016/b978-0-12-822960-6.00180-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
|
|
32
|
Fabritius MP, Ben Khaled N, Kunz WG, Ricke J, Seidensticker M. Image-Guided Local Treatment for Unresectable Intrahepatic Cholangiocarcinoma-Role of Interventional Radiology. J Clin Med 2021; 10:jcm10235574. [PMID: 34884275 PMCID: PMC8658286 DOI: 10.3390/jcm10235574] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Revised: 11/24/2021] [Accepted: 11/24/2021] [Indexed: 01/27/2023] Open
Abstract
Intrahepatic cholangiocarcinoma is a highly aggressive malignancy with an increasing incidence in recent years. Prognosis is poor and most patients are not eligible for resection at the time of initial diagnosis due to the anatomic location, inadequate hepatic reserve, limiting comorbidities or metastatic disease. Several locoregional therapies from the field of interventional radiology exist for patients who are not amenable for surgery, or in case of local recurrence as a single treatment modality or combined with systemic treatment. To date, evidence is limited, with most conclusions drawn from single-center studies with small patient cohorts, often treated in the salvage situation or for local recurrence after initial resection. Nevertheless, the results are promising and suggest a survival benefit in selected patients. This narrative review focuses on the use of different locoregional treatment options for intrahepatic cholangiocarcinoma.
Collapse
Affiliation(s)
- Matthias P. Fabritius
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany; (W.G.K.); (J.R.)
- Correspondence: (M.P.F); (M.S.)
| | - Najib Ben Khaled
- Department of Medicine II, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany;
- German Cancer Consortium (DKTK), Partner Site Munich, Marchioninistr. 15, 81377 Munich, Germany
| | - Wolfgang G. Kunz
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany; (W.G.K.); (J.R.)
| | - Jens Ricke
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany; (W.G.K.); (J.R.)
| | - Max Seidensticker
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany; (W.G.K.); (J.R.)
- Correspondence: (M.P.F); (M.S.)
| |
Collapse
|
|
33
|
Outcome and Safety after 103 Radioembolizations with Yttrium-90 Resin Microspheres in 73 Patients with Unresectable Intrahepatic Cholangiocarcinoma-An Evaluation of Predictors. Cancers (Basel) 2021; 13:cancers13215399. [PMID: 34771563 PMCID: PMC8582544 DOI: 10.3390/cancers13215399] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 10/22/2021] [Accepted: 10/26/2021] [Indexed: 12/22/2022] Open
Abstract
Simple Summary TARE with yttrium-90 (90Y) resin microspheres is emerging in many countries as a treatment option for ICC. Identification of patients that will benefit from TARE is a clinically relevant problem with individual but also economical relevance. The aim of this study was to detect outcome predictors for patients with ICC after TARE with 90Y resin microspheres. We found TARE with 90Y resin microspheres to be a safe treatment option for unresectable ICC. Predictive factors for TARE in ICC are CA-19-9 response, tumor burden, and cholinesterase. Multiple TARE sessions might further improve overall survival. Abstract Trans-arterial radioembolization (TARE) is increasingly evaluated for unresectable intrahepatic cholangiocarcinoma (ICC). Not all ICC patients benefit equally well from TARE. Therefore, we sought to evaluate variables predicting progression-free survival (PFS) and overall survival (OS). Patients with non-resectable ICC underwent TARE and were treated with 90Y resin microspheres. Baseline characteristics, biochemical/clinical toxicities, and response were examined for impact on PFS and OS. A total of 103 treatments were administered to 73 patients without major complications or toxicity. Mean OS was 18.9 months (95% confidence intervals (CI); 13.9–23.9 months). Mean and median PFS were 10.1 months (95% CI; 7.9–12.2) and 6.4 months (95% CI; 5.20–7.61), respectively. Median OS and PFS were significantly prolonged in patients with baseline cholinesterase (CHE) ≥ 4.62 kU/L (OS: 14.0 vs. 5.5 months; PFS: 6.9 vs. 3.2 months; p < 0.001). Patients with a tumor burden ≤ 25% had a significantly longer OS (15.2 vs. 6.6 months; p = 0.036). Median PFS was significantly longer for patients with multiple TARE cycles (24.4 vs. 5.8 months; p = 0.04). TARE is a considerable and safe option for unresectable ICC. CA-19-9, CHE, and tumor burden have predictive value for survival in patients treated with TARE. Multiple TARE treatments might further improve survival; this has to be confirmed by further studies.
Collapse
|
|
34
|
Laidlaw GL, Johnson GE. Recognizing and Managing Adverse Events in Y-90 Radioembolization. Semin Intervent Radiol 2021; 38:453-459. [PMID: 34629713 DOI: 10.1055/s-0041-1735617] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Transarterial radioembolization using yttrium-90 (Y-90) microspheres is an important therapy in the management of unresectable primary liver tumors or hepatic metastases. While radioembolization is generally well-tolerated, it is not free from adverse events, and familiarity with the prevention and treatment of radioembolization-specific complications is an important component of patient care. This article aims to review radioembolization-specific toxicities stratified by hepatic, extrahepatic, and systemic effects, with a focus on preventing and mitigating radioembolization-induced morbidity.
Collapse
Affiliation(s)
- Grace L Laidlaw
- Section of Interventional Radiology, Department of Radiology, University of Washington, Seattle, Washington
| | - Guy E Johnson
- Section of Interventional Radiology, Department of Radiology, University of Washington, Seattle, Washington
| |
Collapse
|
|
35
|
Ness JR, Molvar C. Radioembolization of Intrahepatic Cholangiocarcinoma: Patient Selection, Outcomes, and Competing Therapies. Semin Intervent Radiol 2021; 38:438-444. [PMID: 34629711 DOI: 10.1055/s-0041-1735526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Intrahepatic cholangiocarcinoma is the second most common primary hepatic malignancy and poses a therapeutic challenge owing to its late-stage presentation and treatment-resistant outcomes. Most patients are diagnosed with locally advanced, unresectable disease and are treated with a combination of systemic and local regional therapies. Transarterial radioembolization offers a survival benefit and a favorable side effect profile, with a growing body of evidence to support its use. Herein, we review patient selection and detail outcomes of radioembolization for intrahepatic cholangiocarcinoma, together with mention of competing treatments.
Collapse
Affiliation(s)
- Joseph Ray Ness
- Division of Diagnostic Radiology, Department of Radiology, Loyola University Medical Center, Maywood, Illinois
| | - Christopher Molvar
- Division of Diagnostic Radiology, Department of Radiology, Loyola University Medical Center, Maywood, Illinois
| |
Collapse
|
|
36
|
Paz-Fumagalli R, Core J, Padula C, Montazeri S, McKinney J, Frey G, Devcic Z, Lewis A, Ritchie C, Mody K, Krishnan S, Toskich B. Safety and initial efficacy of ablative radioembolization for the treatment of unresectable intrahepatic cholangiocarcinoma. Oncotarget 2021; 12:2075-2088. [PMID: 34611481 PMCID: PMC8487720 DOI: 10.18632/oncotarget.28060] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 08/18/2021] [Indexed: 01/06/2023] Open
Abstract
PURPOSE To investigate safety, response, and survival after ablative glass microsphere 90Y radioembolization for unresectable intrahepatic cholangiocarcinoma. MATERIALS AND METHODS A retrospective review of 37 radioembolizations in 28 patients treated with single compartment dose of ≥190 Gy encompassing >75% of the largest tumor was performed. Tumors were assessed for stage, morphology, and arterial supply. Response per Modified Response Evaluation Criteria in Solid Tumors (mRECIST), freedom from progression (FFP), progression-free survival (PFS), overall survival (OS), biochemical hepatic function, performance status, and adverse events were investigated. RESULTS The median highest dose per patient was 256.8 Gy (195.7-807.8). Objective response at 3 months was 94.1% (complete 44.1% and partial 50%). Median OS was not reached and the 30-month OS rate was 59%, with a median follow-up of 13.4 months (5.4-39.4). FFP in the radiated field and overall FFP at 30 months were 67% and 40%, respectively. Favorable arterial supply was associated with improved OS (p = 0.018). Unfavorable arterial supply was associated with worse OS [HR 5.7 (95% CI 1.1-28.9, p = 0.034)], and PFS [HR 5.9 (95% CI 1.9-18.4, p = 0.002)]. Patients with mass-forming tumors had a survival benefit (p = 0.002). Laboratory values and performance status did not significantly change 3 months after radioembolization. Grade 3 and 4 adverse events occurred in 2 (7.1%) patients. CONCLUSIONS Radioembolization of unresectable intrahepatic cholangiocarcinoma with ablative intent has a high response rate, promising survival, and is well tolerated.
Collapse
Affiliation(s)
- Ricardo Paz-Fumagalli
- Department of Radiology, Division of Interventional Radiology, Mayo Clinic Florida, Jacksonville, FL 32224, USA
| | - Jacob Core
- Department of Radiology, Division of Interventional Radiology, Mayo Clinic Florida, Jacksonville, FL 32224, USA
| | - Carlos Padula
- Department of Radiology, Division of Interventional Radiology, Mayo Clinic Florida, Jacksonville, FL 32224, USA
| | - Seyed Montazeri
- Department of Radiology, Division of Interventional Radiology, Mayo Clinic Florida, Jacksonville, FL 32224, USA
| | - John McKinney
- Department of Radiology, Division of Interventional Radiology, Mayo Clinic Florida, Jacksonville, FL 32224, USA
| | - Gregory Frey
- Department of Radiology, Division of Interventional Radiology, Mayo Clinic Florida, Jacksonville, FL 32224, USA
| | - Zlatko Devcic
- Department of Radiology, Division of Interventional Radiology, Mayo Clinic Florida, Jacksonville, FL 32224, USA
| | - Andrew Lewis
- Department of Radiology, Division of Interventional Radiology, Mayo Clinic Florida, Jacksonville, FL 32224, USA
| | - Charles Ritchie
- Department of Radiology, Division of Interventional Radiology, Mayo Clinic Florida, Jacksonville, FL 32224, USA
| | - Kabir Mody
- Division of Medical Oncology, Mayo Clinic Florida, Jacksonville, FL 32224, USA
| | - Sunil Krishnan
- Department of Radiation Oncology, Mayo Clinic Florida, Jacksonville, FL 32224, USA
| | - Beau Toskich
- Department of Radiology, Division of Interventional Radiology, Mayo Clinic Florida, Jacksonville, FL 32224, USA
| |
Collapse
|
|
37
|
Zori AG, Yang D, Draganov PV, Cabrera R. Advances in the management of cholangiocarcinoma. World J Hepatol 2021; 13:1003-1018. [PMID: 34630871 PMCID: PMC8473501 DOI: 10.4254/wjh.v13.i9.1003] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 06/09/2021] [Accepted: 08/06/2021] [Indexed: 02/06/2023] Open
Abstract
Cholangiocarcinoma (CCA) is a primary malignancy of the bile ducts with three anatomically and molecularly distinct entities: Intrahepatic CCA (iCCA), perihilar CCA (pCCA), and distal CCA. As a result of phenotypic and anatomic differences they differ significantly with respect to management. For each type of CCA there have been significant changes in management over the last several years which will be discussed in this review. Although resection remains the standard of care for all types of CCA, liver transplantation has been established as curative treatment for selected patients with pCCA and is being evaluated for iCCA with early success. With respect to systemic therapy capecitabine is now first line adjuvant therapy for all biliary tract malignancies after curative intent resection. Progress in exploiting the pathologic mutations and molecular abnormalities has also yielded regulatory approval of targeted therapy for CCA in patients with acquired alterations in the fibroblast growth factor receptor. There is also increased consensus in managing malignant biliary obstruction associated with CCA where pre-operative biliary stenting is not beneficial while self-expanding metal stents have been shown to be superior to plastic stents in patients who are not surgical candidates.
Collapse
Affiliation(s)
- Andreas G Zori
- Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, FL 32608, United States
| | - Dennis Yang
- Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, FL 32608, United States
| | - Peter V Draganov
- Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, FL 32608, United States
| | - Roniel Cabrera
- Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, FL 32608, United States
| |
Collapse
|
|
38
|
Zane KE, Cloyd JM, Mumtaz KS, Wadhwa V, Makary MS. Metastatic disease to the liver: Locoregional therapy strategies and outcomes. World J Clin Oncol 2021; 12:725-745. [PMID: 34631439 PMCID: PMC8479345 DOI: 10.5306/wjco.v12.i9.725] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 06/14/2021] [Accepted: 08/31/2021] [Indexed: 02/06/2023] Open
Abstract
Secondary cancers of the liver are more than twenty times more common than primary tumors and are incurable in most cases. While surgical resection and systemic chemotherapy are often the first-line therapy for metastatic liver disease, a majority of patients present with bilobar disease not amenable to curative local resection. Furthermore, by the time metastasis to the liver has developed, many tumors demonstrate a degree of resistance to systemic chemotherapy. Fortunately, catheter-directed and percutaneous locoregional approaches have evolved as major treatment modalities for unresectable metastatic disease. These novel techniques can be used for diverse applications ranging from curative intent for small localized tumors, downstaging of large tumors for resection, or locoregional control and palliation of advanced disease. Their use has been associated with increased tumor response, increased disease-free and overall survival, and decreased morbidity and mortality in a broad range of metastatic disease. This review explores recent advances in liver-directed therapies for metastatic liver disease from primary colorectal, neuroendocrine, breast, and lung cancer, as well as uveal melanoma, cholangiocarcinoma, and sarcoma. Therapies discussed include bland transarterial embolization, chemoembolization, radioembolization, and ablative therapies, with a focus on current treatment approaches, outcomes of locoregional therapy, and future directions in each type of metastatic disease.
Collapse
Affiliation(s)
- Kylie E Zane
- Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Jordan M Cloyd
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Khalid S Mumtaz
- Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Vibhor Wadhwa
- Department of Radiology, Weill Cornell Medical Center, New York City, NY 10065, United States
| | - Mina S Makary
- Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| |
Collapse
|
|
39
|
Edeline J, Lamarca A, McNamara MG, Jacobs T, Hubner RA, Palmer D, Groot Koerkamp B, Johnson P, Guiu B, Valle JW. Locoregional therapies in patients with intrahepatic cholangiocarcinoma: A systematic review and pooled analysis. Cancer Treat Rev 2021; 99:102258. [PMID: 34252720 DOI: 10.1016/j.ctrv.2021.102258] [Citation(s) in RCA: 58] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 07/02/2021] [Indexed: 01/27/2023]
Abstract
BACKGROUND Locoregional treatments (LRT) including radioembolisation (SIRT), transarterial chemo-embolisation (TACE), hepatic arterial infusion (HAI) of chemotherapy, external beam radiotherapy (EBRT) and ablation have been studied for the management of intrahepatic cholangiocarcinoma (iCC). The aim of this systematic review was to provide outcome benchmarks for clinical trial design. METHODS Identification of studies reporting outcomes of patients treated with LRT for iCC was performed using PubMed and Embase. Pooled weighted means were calculated for progression-free survival (PFS) and overall survival (OS); meta-analysis of proportions was used for estimation of pooled response rate. RESULTS 6325 entries were reviewed; 93 studies were eligible, representing 101 cohorts and 3990 patients: 15 cohorts (645 patients) for ablation, 18 cohorts (541 patients) for EBRT, 27 cohorts (1232 patients) for SIRT, 22 cohorts (1145 patients) for TACE, 16 cohorts (331 patients) for HAI and 3 cohorts (96 patients) not pooled. 74% of the studies were retrospective, 99% non-randomised. The pooled mean weighted OS was 30.2 months (95% confidence interval (CI): 21.8-38.6) for ablation, 18.9 (14.2-23.5) for EBRT, 14.1 (12.1-16.0) for SIRT, 15.9 (12.9-19.0) for TACE and 21.3 (15.4-27.1) for HAI. The pooled complete response rate was 93.9% for ablation. When analysed together, SIRT, TACE and HAI had a pooled mean weighted OS of 15.7 months, and 25.2 months for patients treated in first-line with concomitant systemic chemotherapy. CONCLUSIONS Available literature on LRT for iCC was heterogeneous and of insufficient quality to make strong recommendations. Ablation achieved satisfactory outcomes, and may be recommended when surgery is not feasible.
Collapse
Affiliation(s)
- Julien Edeline
- Department of Medical Oncology, Centre Eugène Marquis, Rennes, France.
| | - Angela Lamarca
- Department of Medical Oncology, The Christie NHS Foundation, Manchester/Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom
| | - Mairéad G McNamara
- Division of Cancer Sciences, University of Manchester/Department of Medical Oncology, Manchester, United Kingdom
| | - Timothy Jacobs
- The Library, The Christie NHS Foundation Trust, Manchester, United Kingdom
| | - Richard A Hubner
- Department of Medical Oncology, The Christie NHS Foundation, Manchester/Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom
| | - Dan Palmer
- University of Liverpool, Liverpool, United Kingdom
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, Netherlands
| | | | - Boris Guiu
- Departement of Radiology, St-Eloi University Hospital, Montpellier, France
| | - Juan W Valle
- Division of Cancer Sciences, University of Manchester/Department of Medical Oncology, Manchester, United Kingdom
| |
Collapse
|
|
40
|
Sarwar A, Ali A, Ljuboja D, Weinstein JL, Shenoy-Bhangle AS, Nasser IA, Morrow MK, Faintuch S, Curry MP, Bullock AJ, Ahmed M. Neoadjuvant Yttrium-90 Transarterial Radioembolization with Resin Microspheres Prescribed Using the Medical Internal Radiation Dose Model for Intrahepatic Cholangiocarcinoma. J Vasc Interv Radiol 2021; 32:1560-1568. [PMID: 34454031 DOI: 10.1016/j.jvir.2021.08.009] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Revised: 08/09/2021] [Accepted: 08/14/2021] [Indexed: 01/06/2023] Open
Abstract
PURPOSE To evaluate outcomes of patients with intrahepatic cholangiocarcinoma (iCCA) undergoing neoadjuvant yttrium-90 (90Y) transarterial radioembolization (TARE) with resin microspheres prescribed using the Medical Internal Radiation Dose (MIRD) model. MATERIALS AND METHODS This retrospective institutional review board-approved study included 37 patients with iCCA treated with 90Y-TARE from October 2015 to September 2020. The primary outcome was overall survival (OS) from 90Y-TARE. The secondary outcomes were progression-free survival (PFS), Response Evaluation Criteria In Solid Tumors 1.1 imaging response, and downstaging to resection. Patients with tumor proximity to the middle hepatic vein (<1 cm) and/or insufficient future liver remnant were treated with neoadjuvant intent (n = 21). Patients were censored at the time of surgery or at the last follow-up for the Kaplan-Meier survival analysis. RESULTS For 31 patients (69 years; interquartile range, 64-74 years; 20 men [65%]) included in the study, the first-line therapy was 90Y-TARE for 23 (74%) patients. Imaging assessment at 6 months showed a disease control rate of 86%. The median PFS was 5.4 months (95% confidence interval [CI], 3-not reached). The PFS was higher after first-line 90Y-TARE (7.4 months [95% CI, 5.3-not reached]) than that after subsequent 90Y-TARE (2.7 months [95% CI, 2-not reached]) (P = .007). The median OS was 22 months (95% CI, 7.3-not reached). The 1- and 2-year OS rates were 60% (95% CI, 41%-86%) and 40% (95% CI, 19.5%-81%). In patients treated with neoadjuvant intent, 11 of 21 patients (52%) underwent resections. The resection margins were R0 and R1 in 8 (73%) and 3 (27%) of 11 patients, respectively. On histological review in 10 patients, necrosis of ≥90% tumor was achieved in 7 of 10 patients (70%). CONCLUSIONS First-line 90Y-TARE prescribed using the MIRD model as neoadjuvant therapy for iCCA results in good survival outcome and R0 resection for unresectable patients.
Collapse
Affiliation(s)
- Ammar Sarwar
- Division of Vascular and Interventional Radiology, Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
| | - Aamir Ali
- Division of Vascular and Interventional Radiology, Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Damir Ljuboja
- Division of Vascular and Interventional Radiology, Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Jeffrey L Weinstein
- Division of Vascular and Interventional Radiology, Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Anuradha S Shenoy-Bhangle
- Division of Abdominal Imaging, Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Imad A Nasser
- Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Matthew K Morrow
- Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Salomao Faintuch
- Division of Vascular and Interventional Radiology, Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Michael P Curry
- Division of Gastroenterology and Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Andrea J Bullock
- Division of Hematology and Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Muneeb Ahmed
- Division of Vascular and Interventional Radiology, Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| |
Collapse
|
|
41
|
Yu Q, Liu C, Pillai A, Ahmed O. Twenty Years of Radiation Therapy of Unresectable Intrahepatic Cholangiocarinoma: Internal or External? A Systematic Review and Meta-Analysis. Liver Cancer 2021; 10:433-450. [PMID: 34721506 PMCID: PMC8527917 DOI: 10.1159/000516880] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Accepted: 04/25/2021] [Indexed: 02/04/2023] Open
Abstract
PURPOSE Both external beam radiation therapy (EBRT) and selective-internal radiation therapy (SIRT) are implemented to treat unresectable intrahepatic cholangiocarcinoma (iCCA). The present study aimed to evaluate the efficacy of EBRT and SIRT in managing iCCA through a systematic review and meta-analysis. METHODS PubMed and Cochrane database were queried to search for studies published from January 2000 toJune 2020 without language restrictions. Median survival time, overall survival, and radiological response were extracted. Secondary outcomes such as complication rates, predictors of survival, and downstage to surgery were pooled. Patient-level survival data were obtained to generate Kaplan-Meier survival graph. Pooled outcomes were analyzed with a random-effect model. RESULTS Twenty-nine and 20 studies including 732 and 443 patients from the SIRT and EBRT groups were included in the present study. From initial radiation treatment, the median survival time for patients who underwent SIRT and EBRT were 12.0 (95% confidence interval [CI]: 10.8-14.6) and 13.6 (95% CI: 11.1-16.0) months, respectively. As first-line therapy, the median survival time was 36.1 (95% CI: 20.6-39.5) months for SIRT and 11.0 (95% CI: 9.3-13.6) months for EBRT. Both radiation modalities were effective in downstaging initially unresectable iCCA to surgery (SIRT: 30.5%; EBRT: 18.3%). Patients in the SIRT group encountered more post-embolization abdominal pain (6.9 vs. 2.2%), ulcer (1.0 vs. 0.5%), nausea (1.6 vs. 0.7%), anorexia (5.9 vs. 0%), thrombocytopenia (7.3 vs. 6.0%), hyperbilirubinemia (5.2 vs. 2.1%), and hypoalbuminemia (13.2 vs. 3.3%), whereas EBRT was associated with higher rates of anemia (0.6 vs. 7.5%) and neutropenia (6.5 vs. 11.0%). CONCLUSIONS Both EBRT and SIRT were safe and effective in treating unresectable iCCA. However, available evidence was highly heterogeneous regarding patient population, limiting fair comparison between 2 radiation modalities. Future high-quality comparative studies are warranted.
Collapse
Affiliation(s)
- Qian Yu
- Department of Surgery, Cleveland Clinic Florida, Weston, Florida, USA,*Qian Yu, yuqian1006*gmail.com
| | - Chenyu Liu
- Ben May Department of Cancer Research, University of Chicago, Chicago, Illinois, USA
| | - Anjana Pillai
- Division of Gastroenterology, Hepatology, and Nutrition, University of Chicago, Chicago, Illinois, USA
| | - Osman Ahmed
- Division of Interventional Radiology, Department of Radiology, University of Chicago, Chicago, Illinois, USA
| |
Collapse
|
|
42
|
Mosconi C, Solaini L, Vara G, Brandi N, Cappelli A, Modestino F, Cucchetti A, Golfieri R. Transarterial Chemoembolization and Radioembolization for Unresectable Intrahepatic Cholangiocarcinoma-a Systemic Review and Meta-Analysis. Cardiovasc Intervent Radiol 2021; 44:728-738. [PMID: 33709272 DOI: 10.1007/s00270-021-02800-w] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Accepted: 02/05/2021] [Indexed: 01/07/2023]
Abstract
PURPOSE Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis, when unresectable; therefore, intra-arterial therapies (IAT) such as trans-arterial chemoembolization (TACE) and trans-arterial radioembolization (TARE) have been employed. With the present systematic review and meta-analysis, we aimed to analyse published studies to understand if one IAT can be superior to the alternative. MATERIALS AND METHODS A systematic search of PubMed and Web of Science databases was performed for articles published until 1 March 2020 relevant to IAT for ICC. Overall survival was the primary end point. Occurrence of clinical adverse events and tumour overall response were secondary outcome measures. RESULTS A total of 31 articles (of 793, n.1695 patients) were selected for data extraction, 13 were on TACE (906 patients) and 18 were on TARE (789 patients). Clinical and tumour characteristics showed moderate heterogeneity between the two groups. The median survival after TACE was 14.2 months while after TARE was 13.5 months (95%C.I.: 11.4-16.1). The survival difference was small (d = 0.112) at 1 year and negligible at 2 years (d = 0.028) and at 3 years (d = 0.049). The radiological objective response after TACE was 20.6% and after TARE was 19.3% (d = 0.032). Clinical adverse events occurred in 58.5% after TACE, more frequently than after TARE (43.0%, d = 0.314). CONCLUSION In conclusion, IATs are promising treatments for improving outcomes for patients with unresectable ICC. To date, TACE and TARE provide similar good outcomes, except for adverse events. Therefore, the decision about techniques is determined by ability to utilize these resources and patient specific factors (liver function or lesion dimension).
Collapse
Affiliation(s)
- Cristina Mosconi
- Department of Radiology, IRCCS, Azienda Ospedaliero-Universitaria Di Bologna, Sant'Orsola-Malpighi Hospital, Via Albertoni 15, 40138, Bologna, Italy.
| | - Leonardo Solaini
- Department of Medical and Surgical Sciences-DIMEC, Alma Mater Studiorum - University of Bologna, Bologna, Italy
- Department of Surgery, Morgagni - Pierantoni Hospital, Forlì, Italy
| | - Giulio Vara
- Department of Radiology, IRCCS, Azienda Ospedaliero-Universitaria Di Bologna, Sant'Orsola-Malpighi Hospital, Via Albertoni 15, 40138, Bologna, Italy
| | - Nicolò Brandi
- Department of Radiology, IRCCS, Azienda Ospedaliero-Universitaria Di Bologna, Sant'Orsola-Malpighi Hospital, Via Albertoni 15, 40138, Bologna, Italy
| | - Alberta Cappelli
- Department of Radiology, IRCCS, Azienda Ospedaliero-Universitaria Di Bologna, Sant'Orsola-Malpighi Hospital, Via Albertoni 15, 40138, Bologna, Italy
| | - Francesco Modestino
- Department of Radiology, IRCCS, Azienda Ospedaliero-Universitaria Di Bologna, Sant'Orsola-Malpighi Hospital, Via Albertoni 15, 40138, Bologna, Italy
| | - Alessandro Cucchetti
- Department of Medical and Surgical Sciences-DIMEC, Alma Mater Studiorum - University of Bologna, Bologna, Italy
- Department of Surgery, Morgagni - Pierantoni Hospital, Forlì, Italy
| | - Rita Golfieri
- Department of Radiology, IRCCS, Azienda Ospedaliero-Universitaria Di Bologna, Sant'Orsola-Malpighi Hospital, Via Albertoni 15, 40138, Bologna, Italy
- Department of Specialized, Diagnostic and Experimental Medicine - DIMES, Alma Mater Studiorum - University of Bologna, Bologna, Italy
| |
Collapse
|
|
43
|
Abstract
Cholangiocarcinoma is the second most common primary malignancy of the liver. This review will focus on the mass-forming intrahepatic type of this disease and discuss the role of medical, surgical, and radiation oncology in managing this difficult disease. A global understanding to the management of intrahepatic cholangiocarcinoma (ICC) can help the interventional radiologist understand the role of locoregional therapies such as ablation, transarterial chemoembolization, and radioembolization in the management of ICC.
Collapse
Affiliation(s)
- Pouya Entezari
- Section of Interventional Radiology, Department of Radiology, Northwestern Memorial Hospital, Chicago, Illinois
| | - Ahsun Riaz
- Section of Interventional Radiology, Department of Radiology, Northwestern Memorial Hospital, Chicago, Illinois
| |
Collapse
|