Radioembolization Plus Chemotherapy for First-line Treatment of Locally Advanced Intrahepatic Cholangiocarcinoma

Edeline, Julien; Touchefeu, Yann; Guiu, Boris; Farge, Olivier; Tougeron, David; Baumgaertner, Isabelle; Ayav, Ahmet; Campillo‐Gimenez, Boris; Beuzit, Luc; Pracht, Marc; Lièvre, Astrid; Sourd, Samuel Le; Boudjéma, Karim; Rolland, Yan; Boucher, Éveline; Garin, Étienne

doi:10.1001/jamaoncol.2019.3702

Cited by 218 publications

(220 citation statements)

References 43 publications

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“…Of note, only a minority of patients had impaired liver function in our cohort reflected by normal bilirubin levels in most patients. Interestingly, Edeline et al found carcinoembryogenic antigen (CEA) to be a prognostic factor in advanced ICC undergoing combined radioembolization and chemotherapy [25].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the advent of new chemotherapy regimens with improved survival rates [6], immunotherapies, as well as improved patient selection, promise novel multimodal treatment options when combined with 90 Y TARE for the treatment of ICC [27][28][29]. The first prospective trial combining radioembolization and chemotherapy (again with cisplatin and gemcitabine), which was recently published, reported a median overall survival of 22 months following combined treatment [25]. The improved survival rates in this study compared to our cohort is attributed again to the much-advanced tumor stages and similarly increased morbidity in our cohort, having undergone already multiple therapies, while the study cohort of Edeline et al were all therapy-naïve when included in the protocol.…”

Section: Discussionmentioning

confidence: 99%

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Prognostic Factors for Overall Survival in Advanced Intrahepatic Cholangiocarcinoma Treated with Yttrium-90 Radioembolization

Köhler

Harders

Lohöfer

et al. 2019

JCM

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Purpose: To evaluate factors associated with survival following transarterial 90Y (yttrium) radioembolization (TARE) in patients with advanced intrahepatic cholangiocarcinoma (ICC). Methods: This retrospective multicenter study analyzed the outcome of three tertiary care cancer centers in patients with advanced ICC following resin microsphere TARE. Patients were included either after failed previous anticancer therapy, including relapse after surgical resection, or for having a minimum of 25% of total liver volume affected by ICC. Patients were stratified and response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria at 3 months. Kaplan–Meier analysis was performed to analyze survival followed by cox regression to determine independent prognostic factors for survival. Results: 46 patients were included (19 male, 27 female), median age 62.5 years (range 29–88 years). A total of 65% of patients had undergone previous therapy, while 63% had a tumor volume > 25% of the entire liver volume. Median survival was 9.5 months (95% CI: 6.1–12.9 months). Due to loss in follow-up, n = 37 patients were included in the survival analysis. Cox regression revealed the extent of liver disease to one or both liver lobes being associated with survival, irrespective of tumor volume (p = 0.041). Patients with previous surgical resection of ICC had significantly decreased survival (3.9 vs. 12.8 months, p = 0.002). No case of radiation-induced liver disease was observed. Discussion: Survival after 90Y TARE in patients with advanced ICC primarily depends on disease extent. Only limited prognostic factors are associated with a general poor overall survival.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Prognostic Factors for Overall Survival in Advanced Intrahepatic Cholangiocarcinoma Treated with Yttrium-90 Radioembolization

Köhler

Harders

Lohöfer

et al. 2019

JCM

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“…Alternative agents such as bintrafusp alfa (M7824), a bifunctional monoclonal antibody targeting transforming growth factor-beta trap and anti-PD-L1, have been explored in pre-treated biliary tract cancers and granted orphan drug designation by the FDA, based on promising phase I findings (ORR of 20% in unselected biliary tract cancer population). 42 Other therapeutic options: liver-directed therapies and immunotherapy For selected patients with liver-predominant or locally advanced disease, strategies involving liverdirected therapies [43][44][45][46] and external beam radiotherapy 47 are being explored, respectively. Ongoing clinical trials are likely to elucidate the role of such approaches (for example: ABC-07, EudraCT 2014-003656-31 and SIRCCA, NCT02807181).…”

Section: Current State Of Playmentioning

confidence: 99%

Molecular targeted therapies: Ready for “prime time” in biliary tract cancer

Lamarca

Barriuso

McNamara

et al. 2020

Journal of Hepatology

274

221

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The prognosis for patients with biliary tract cancers (cholangiocarcinoma and gallbladder cancer) is poor, while the incidence of these cancers is increasing. Most patients are diagnosed with advanced disease when treatment options are limited to palliative approaches, mainly focused on chemotherapy. In recent years, novel treatment targets of relevance to biliary tract cancers, mainly present in patients with intrahepatic cholangiocarcinoma, have been identified and are rapidly changing the field. These include fibroblast growth factor receptor (FGFR) fusions and isocitrate dehydrogenase (IDH)-1 and-2 mutations which are each present in around 10-20% of patients with intrahepatic cholangiocarcinoma. In addition, inhibition of other pathways/molecules is currently being explored, including human epidermal growth factor receptor (HER) family members, the Wnt pathway, neurotropic tyrosine kinase receptor (NTRK) fusions and BRAF mutations. The IDH1 inhibitor ivosidenib has already been tested in a phase III clinical trial in pretreated cholangiocarcinoma and showed benefit in terms of progression-free survival. Multiple FGFR inhibitors have consistently shown high response rates in phase II/III trials, especially for patients harbouring FGFR2 fusions. Herein, we provide an overview of the status of targeted therapies in biliary tract cancers, discussing the current clinical development of IDH and FGFR inhibitors in detail, as well as reviewing current caveats and future steps.

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“…60 Pre-surgical selective internal radiation therapy (SIRT) in iCCA has shown promising preliminary results in terms of safety and effectiveness, 61,62 even in association with chemotherapy, in the treatment of advanced iCCA. 63 In a study on 45 patients with unresectable iCCA, Yttrium 90 (Y 90 ) SIRT combined with gemcitabine and/or platinum chemotherapy achieved an 18% rate of conversion to free-margin surgery with no significant toxicity. 62 An example of efficacy of such combination treatment is presented in Fig.…”

Section: Role Of Neoadjuvant Therapies From a Surgical Perspectivementioning

confidence: 99%

Liver resection and transplantation for intrahepatic cholangiocarcinoma

Mazzaferro

Gorgen

Roayaie

et al. 2020

Journal of Hepatology

250

182

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The incidence of intrahepatic cholangiocarcinoma (iCCA) is increasing worldwide. Although several advances have been made in the past decades to better understand this complex malignancy and to develop new treatment strategies, the prognosis of iCCA remains dismal. Liver resection (LR) is the mainstay of treatment but only a minority of patients are amenable to surgery. In most cases, patients with iCCA will require a major hepatectomy for complete resection of the tumour. This may be contraindicated or increase the surgical burden in patients with chronic liver disease and small remnant liver volume. Lymphadenectomy with a minimal harvest of 6 lymph nodes is considered adequate, as microscopic nodal metastases have been shown in more than 40% of patients. Current 5-year overall survival following LR is in the range of 25%-40%. For locally advanced disease not amenable to upfront LR, neoadjuvant locoregional therapies may be used with the aim of converting these patients to resectability or even to transplantation in well-selected cases. Recent studies have shown that liver transplantation (LT) might be a treatment option for patients with unresectable very-early iCCA (i.e. < − 2 cm), with survival outcomes comparable to those of hepatocellular carcinoma. In patients with unresectable, advanced tumours, confined to the liver who achieve sustained response to neoadjuvant treatment, LT may be considered an option within prospective protocols. The role of adjuvant therapies in iCCA is still under debate. Herein, we review the recent advances in the surgical treatment of iCCA and examine its correlation with locoregional therapies, adjuvant and neo-adjuvant strategies.

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Radioembolization Plus Chemotherapy for First-line Treatment of Locally Advanced Intrahepatic Cholangiocarcinoma

Abstract: Radioembolization plus chemotherapy as first-line treatment of locally-advanced intrahepatic cholangiocarcinoma. The multi-center single-arm phase 2 MISPHEC study (14) Radiology,

Cited by 218 publications

References 43 publications

Prognostic Factors for Overall Survival in Advanced Intrahepatic Cholangiocarcinoma Treated with Yttrium-90 Radioembolization

Prognostic Factors for Overall Survival in Advanced Intrahepatic Cholangiocarcinoma Treated with Yttrium-90 Radioembolization

Molecular targeted therapies: Ready for “prime time” in biliary tract cancer

Liver resection and transplantation for intrahepatic cholangiocarcinoma

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