• Albumin-bilirubin grade
• Biliary tract cancers
• CA19-9
• Radiation therapy
• Survival

• Humans
• Female
• Male
• Retrospective Studies
• Biliary Tract Neoplasms/radiotherapy
• Biliary Tract Neoplasms/mortality
• Biliary Tract Neoplasms/pathology
• Middle Aged
• Aged
• Prognosis
• Adult
• Aged, 80 and over
• Survival Rate
• Risk Assessment

• chemotherapy
• cholangiocarcinoma
• gallbladder
• radiotherapy
• surgery
• systemic therapy
• targeted treatment

• biliary disease
• cholangiocarcinoma
• multidisciplinary
• primary liver malignancy
• radiotherapy

• Cholangiocarcinoma (CCA)
• extrahepatic cholangiocarcinoma (extrahepatic CCA)
• hilar cholangiocarcinoma (hilar CCA)
• liver transplant
• neoadjuvant chemoradiation

• Chemotherapy
• gallbladder cancer
• intensity modulated radiotherapy techniques
• radiation therapy
• unresectable

• Antineoplastic Combined Chemotherapy Protocols/adverse effects
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Chemoradiotherapy/adverse effects
• Chemoradiotherapy/methods
• Cohort Studies
• Gallbladder Neoplasms/drug therapy
• Gallbladder Neoplasms/radiotherapy
• Humans

Surgical resection is a treatment of choice for gallbladder cancer (GBC) patients but only 10% of patients have a resectable disease at presentation. Even after surgical resection, overall survival (OS) has been poor due to high rates of recurrence. Combination of surgery and systemic therapy can improve outcomes in this aggressive disease.

To summarize our single-center experience with multimodality management of resectable GBC patients.

Data of all patients undergoing surgery for suspected GBC from January 2012 to December 2018 was retrieved from a prospectively maintained electronic database. Information extracted included demographics, operative and perioperative details, histopathology, neoadjuvant/adjuvant therapy, follow-up, and recurrence. To know the factors associated with recurrence and OS, univariate and multivariate analysis was done using log rank test and cox proportional hazard analysis for categorical and continuous variables, respectively. Multivariate analysis was done using multiple regression analysis.

Of 274 patients with GBC taken up for surgical resection, 172 (62.7%) were female and the median age was 56 years. On exploration, 102 patients were found to have a metastatic or unresectable disease (distant metastasis in 66 and locally unresectable in 34). Of 172 patients who finally underwent surgery, 93 (54%) underwent wedge resection followed by anatomical segment IVb/V resection in 66 (38.4%) and modified extended right hepatectomy in 12 (7%) patients. The postoperative mortality at 90 d was 4.6%. During a median follow-up period of 20 mo, 71 (41.2%) patients developed recurrence. Estimated 1-, 3-, and 5-years OS rates were 86.5%, 56%, and 43.5%, respectively. Estimated 1- and 3-year disease free survival (DFS) rates were 75% and 49.2%, respectively. On multivariate analysis, inferior OS was seen with pT3/T4 tumor (P = 0.0001), perineural invasion (P = 0.0096), and R+ resection (P = 0.0125). However, only pT3/T4 tumors were associated with a poor DFS (P < 0.0001).

Multimodality treatment significantly improves the 5-year survival rate of patients with GBC up to 43%. R+ resection, higher T stage, and perineural invasion adversely affect the outcome and should be considered for systemic therapy in addition to surgery to optimize the outcomes. Multimodality treatment of GBC has potential to improve the survival of GBC patients.

• Gallbladder cancer
• Multimodality
• Surgical resection
• Adjuvant
• Chemotherapy
• Chemoradiotherapy

• Female
• Gallbladder Neoplasms/pathology
• Gallbladder Neoplasms/surgery
• Hepatectomy
• Humans
• Middle Aged
• Neoadjuvant Therapy
• Neoplasm Staging
• Retrospective Studies
• Survival Rate
• Tertiary Healthcare

• Radiotherapy (RT)
• biliary cancer
• cholangiocarcinoma

• Biliary duct cancer
• Cholangiocarcinome
• Cholangiocarcnoma
• Radiation oncology
• Radiotherapy
• Radiothérapie
• Revue

Biliary tract cancers (BTC) are a disease entity comprising diverse epithelial tumors, which are categorized according to their anatomical location as intrahepatic (iCCA), perihilar (pCCA), distal (dCCA) cholangiocarcinomas, and gallbladder carcinomas (GBC), with distinct epidemiology, biology, and prognosis. Complete surgical resection is the mainstay in operable BTC as it is the only potentially curative treatment option. Nevertheless, even after curative (R0) resection, the 5-year survival rate ranges between 20 and 40% and the disease free survival rates (DFS) is approximately 48–65% after one year and 23–35% after three years without adjuvant treatment. Improvements in adjuvant chemotherapy have improved the DFS, but the role of adjuvant radiotherapy is unclear. On the other hand, more than 50% of the patients present with unresectable disease at the time of diagnosis, which limits the prognosis to a few months without treatment. Herein, we review the role of radiotherapy in the treatment of cholangiocarcinoma in the curative and palliative setting.

• biliary tract cancer
• brachytherapy
• chemoradiation
• cholangiocarcinoma
• stereotactic body radiotherapy

• cholangiocarcinoma
• dose-volume histogram
• postoperative-radiation therapy
• radiation-induced liver disease
• remnant liver

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols
• Cholangiocarcinoma/drug therapy
• Cholangiocarcinoma/pathology
• Cholangiocarcinoma/radiotherapy
• Cholangiocarcinoma/surgery
• Cisplatin/therapeutic use
• Combined Modality Therapy
• Deoxycytidine/analogs & derivatives
• Deoxycytidine/therapeutic use
• Drug Combinations
• Hepatectomy
• Humans
• Kaplan-Meier Estimate
• Liver Diseases/prevention & control
• Liver Neoplasms/drug therapy
• Liver Neoplasms/pathology
• Liver Neoplasms/radiotherapy
• Liver Neoplasms/surgery
• Middle Aged
• Neoplasm Staging
• Oxonic Acid/therapeutic use
• Pyridines/therapeutic use
• Radiation Injuries/prevention & control
• Radiation-Sensitizing Agents/therapeutic use
• Radiotherapy Dosage
• Radiotherapy, Adjuvant
• Tegafur/therapeutic use
• Tomography, X-Ray Computed
• Gemcitabine

Extrahepatic bile duct cancer (EBDC) is a rare malignancy that involves neoplastic changes extending from both hepatic ducts to the common bile duct. The treatment of choice is surgical resection, but the predominant pattern of initial treatment failure is locoregional recurrence. Accordingly, adjuvant radiotherapy has been administered after surgical resection based on these rationales. At this time, there is minimal evidence supporting adjuvant radiotherapy, because there have been no phase III trials evaluating its benefit. Relatively small retrospective studies have tried to compare outcomes associated with EBDC treated with or without radiotherapy. We aimed to review studies investigating adjuvant radiotherapy for resected EBDC. Because less than one-third of EBDC cases are amenable to curative resection at diagnosis, other locoregional treatment modalities need to be considered, including radiotherapy. The next aim of this review was to summarize reports of definitive radiotherapy for unresectable EBDC. Patients with advanced EBDC often experience biliary obstruction, which can lead to jaundice and progress to death. Biliary stent insertion is an important palliative procedure, but stents are prone to occlusion after subsequent ingrowth of the EBDC. Radiotherapy can be effective for maintaining the patency of inserted stents. We also reviewed the benefit of palliative radiotherapy combined with the biliary stent insertion. Lastly, we discuss the existing gaps in the evidence supporting radiotherapy in the management of EBDC.

• Extrahepatic bile duct cancer
• Patterns of failure
• Adjuvant radiotherapy
• Definitive radiotherapy
• Palliative radiotherapy
• Biliary stent

To evaluate the effect of escalated dose radiation therapy (EDR, defined as doses >50.4 Gy in 28 fractions [59.5 Gy BED]) on overall survival (OS), freedom from local progression (FFLP), and freedom from distant progression (FFDP) of patients with unresectable extrahepatic cholangiocarcinoma (EHCC).

A consecutive cohort of 80 patients who underwent radiotherapy for unresectable EHCC from 2001 to 2015 was identified. Demographic, tumor, treatment, toxicity, and laboratory variables were collected. The maximal RT doses ranged from 30 to 75 Gy (median 50.4 Gy, at 1.8‐4.5 Gy/fraction). Gross tumor volume (GTV) coverage by maximal dose in EDR group ranged from 38% to 100%. Kaplan–Meier method was used to estimate OS, FFLP, and FFDP. Univariate and multivariate Cox regression models were analyzed.

After radiotherapy, median OS, FFLP, and FFDP were 18.7, 22.6, and 24.3 months, respectively. There was no significant difference in OS or FFLP between patients who received EDR to portions of the GTV and patients who did not. On multivariate analysis, bigger GTV, age, and ECOG performance status were independently associated with shorter OS. Local progression on chemotherapy prior to RT was independently associated with shorter FFLP. High baseline neutrophil/lymphocyte ratio (>5.3) was independently associated with shorter FFDP. Toxicity grades were similar in EDR and lower doses except lymphopenia which was higher in EDR (P = 0.053).

EDR to selective portions of the GTV may not benefit patients with unresectable EHCC despite having acceptable toxicity. New methods to improve local control and survival for unresectable EHCC are needed.

• dose escalation
• extrahepatic cholangiocarcinoma
• radiation therapy
• toxicity
• unresectable extrahepatic cholangiocarcinoma

• adjuvant therapy
• cholangiocarcinoma
• prognostic factor
• radiotherapy
• survival

We report single-institution clinical efficacy and safety outcomes for patients with unresectable locally advanced cholangiocarcinoma who were treated with stereotactic body radiation therapy (SBRT) and a subset of patients who received neoadjuvant SBRT and chemotherapy as part of an orthotopic liver transplantation (OLT) protocol.

From October 2008 to June 2015, 31 consecutive patients with unresectable extrahepatic (n = 25) or intrahepatic (n = 6) cholangiocarcinoma were treated with SBRT and retrospectively analyzed. Four patients underwent liver transplantation, and 1 underwent resection. SBRT was delivered in 5 fractions with a median dose of 40 Gy. Toxicity was scored using the Common Terminology Criteria for Adverse Events Version 4.0. Overall survival (OS), time to progression, and local control were estimated using the Kaplan-Meier method.

The median follow-up time was 11.5 months. The 1- and 2-year OS rates were 59% and 33%, respectively, with a median survival of 15.7 months. The 1- and 2-year freedom from progression was 67% and 34%, respectively. Median time to progression was 16.8 months. Nine patients had local failure. The actuarial 1- and 2-year local control rates were 78% and 47%, respectively. Among patients who also had OLT, the median OS was 31.3 months. Twenty-four patients (77%) experienced some form of acute grade 1-2 toxicity, most commonly fatigue or pain. Five patients (16%) experienced grade ≥3 toxicity.

SBRT is a promising option for patients with unresectable or recurrent cholangiocarcinoma either as a component of neoadjuvant therapy prior to OLT or as part of definitive therapy for patients who are unresectable and not eligible for transplantation.

There is no specific quality of life (QoL) measurement tool to quantify QoL in patients with biliary tract cancer. Quality of life measurement is an increasingly crucial trial end point and is now being incorporated into clinical practice.

This International Multicentre Phase IV Validation Study assessed the QLQ-BIL21 module in 172 patients with cholangiocarcinoma and 91 patients with cancer of the gallbladder. Patients completed the questionnaire at baseline pretherapy and subsequently at 2 months. Following this, the psychometric properties of reliability, validity, scale structure and responsiveness to change were analysed.

Analysis of the QLQ-BIL21 scales showed appropriate reliability with Cronbach's α-coefficients >0.70 for all scales overall. Intraclass correlations exceeded 0.80 for all scales. Convergent validity >0.40 was demonstrated for all items within scales, and discriminant validity was confirmed with values <0.70 for all scales compared with each other. Scale scores changed in accordance with Karnofsky performance status and in response to clinical change.

The QLQ-BIL21 is a valid tool for the assessment of QoL in patients with cholangiocarcinoma and cancer of the gallbladder.

• Brachytherapy
• cholangiocarcinoma
• extrahepatic
• radiation

• Adjuvant
• Chemoradiothearpy
• Chemotherapy
• Cholangiocarcinoma
• Definitive

• Chemotherapy
• Hilar cholangiocarcinoma
• Radiation

• Biliary Tract Neoplasms/epidemiology
• Biliary Tract Neoplasms/genetics
• Biliary Tract Neoplasms/radiotherapy
• Cholangiocarcinoma/epidemiology
• Cholangiocarcinoma/genetics
• Cholangiocarcinoma/radiotherapy
• Gallbladder Neoplasms/epidemiology
• Gallbladder Neoplasms/genetics
• Gallbladder Neoplasms/radiotherapy
• Humans
• Molecular Targeted Therapy
• Neoplasm Proteins/genetics
• Signal Transduction

Gallbladder cancer (GBC) is an uncommon disease in the majority of the world despite being the most common and aggressive malignancy of the biliary tree. Early diagnosis is essential for improved prognosis; however, indolent and nonspecific clinical presentations with a paucity of pathognomonic/predictive radiological features often preclude accurate identification of GBC at an early stage. As such, GBC remains a highly lethal disease, with only 10% of all patients presenting at a stage amenable to surgical resection. Among this select population, continued improvements in survival during the 21st century are attributable to aggressive radical surgery with improved surgical techniques. This paper reviews the current available literature of the 21st century on PubMed and Medline to provide a detailed summary of the epidemiology and risk factors, pathogenesis, clinical presentation, radiology, pathology, management, and prognosis of GBC.

To report the results of stereotactic body radiotherapy (SBRT) for unresectable primary or recurrent cholangiocarcinoma.

From January 2005 through August 2013, 58 patients with unresectable primary (n = 28) or recurrent (n = 30) cholangiocarcinoma treated by SBRT were retrospectively analyzed. The median prescribed dose was 45 Gy in 3 fractions (range, 15 to 60 Gy in 1-5 fractions). Patients were treated by SBRT only (n = 53) or EBRT + SBRT boost (n = 5). The median tumor volume was 40 mL (range, 5 to 1,287 mL).

The median follow-up duration was 10 months (range, 1 to 97 months). The 1-year, 2-year overall survival rates, and median survival were 45%, 20%, and 10 months, respectively. The median survival for primary group and recurrent group were 5 and 13 months, respectively. Local control rate at 1-year and 2-year were 85% and 72%, respectively. Disease progression-free survival rates at 1-year and 2-year were 26% and 23%, respectively. In univariate analysis, ECOG performance score (0-1 vs. 2-3), treatment volume (<50 vs. ≥50 mL), and pre-SBRT CEA level (<5 vs. ≥5 ng/mL) were significant in overall survival rate. In multivariate analysis, ECOG score (p = 0.037) and tumor volume (p = 0.030) were statistically significant. In the recurrent tumor group, patients with >12 months interval from surgery to recurrence showed statistically significant higher overall survival rate than those with ≤12 months (p = 0.026). Six patients (10%) experienced ≥grade 3 complications.

SBRT can be considered as an effective local modality for unresectable primary or recurrent cholangiocarcinoma.

• Cholangiocarcinoma
• Radiosurgery

• Foie
• Liver
• Metastases
• Métastases
• Primary tumours
• Radiothérapie stéréotaxique
• Stereotactic radiotherapy
• Tumeurs primitives

• Carcinoma/radiotherapy
• Carcinoma/secondary
• Carcinoma/surgery
• Carcinoma, Hepatocellular/radiotherapy
• Carcinoma, Hepatocellular/surgery
• Hepatitis/etiology
• Humans
• Liver/radiation effects
• Liver Neoplasms/radiotherapy
• Liver Neoplasms/secondary
• Liver Neoplasms/surgery
• Multimodal Imaging
• Organ Sparing Treatments
• Organs at Risk
• Radiation Injuries/etiology
• Radiosurgery/methods
• Radiotherapy Dosage
• Radiotherapy Planning, Computer-Assisted
• Radiotherapy, Intensity-Modulated
• Surgery, Computer-Assisted

• Bile Duct Neoplasms/therapy
• Chemoradiotherapy/methods
• Cholangiocarcinoma/therapy
• Evidence-Based Medicine
• Humans
• Meta-Analysis as Topic
• PubMed
• Radiotherapy Dosage
• Treatment Outcome

• Chemotherapy
• Gall bladder cancer
• Targeted therapy

• biliary tract
• malignancies
• ct
• mri
• ultrasound
• cholangiocarcinoma
• gall bladder carcinoma
• ampullary carcinoma

• Biliary Tract Neoplasms/diagnosis
• Biliary Tract Neoplasms/pathology
• Biliary Tract Neoplasms/therapy
• Cholangiocarcinoma/diagnosis
• Cholangiopancreatography, Endoscopic Retrograde
• Cholangiopancreatography, Magnetic Resonance
• Endosonography
• Humans
• Magnetic Resonance Imaging
• Neoplasm Staging
• Positron-Emission Tomography

• Adjuvant therapy
• Cholangiocarcinoma
• Extrahepatic
• Palliative surgery
• Survival

We examined the efficacy and toxicity of proton beam therapy (PBT) for treating advanced cholangiocarcinoma.

The clinical data and outcomes of 28 cholangiocarcinoma patients treated with PBT between January 2009 and August 2011 were retrospectively examined. The Kaplan–Meier method was used to estimate overall survival (OS), progression-free survival (PFS), and local control (LC) rates, and the log-rank test to analyze the effects of different clinical and treatment variables on survival. Acute and late toxicities were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.

The median age of the 17 male and 11 female patients was 71 years (range, 41 to 84 years; intrahepatic/peripheral cholangiocarcinoma, n = 6; hilar cholangiocarcinoma/Klatskin tumor, n = 6; distal extrahepatic cholangiocarcinoma, n = 3; gallbladder cancer, n = 3; local or lymph node recurrence, n = 10; size, 20–175 mm; median 52 mm). The median radiation dose was 68.2 Gy (relative biological effectiveness [RBE]) (range, 50.6 to 80 Gy (RBE)), with delivery of fractions of 2.0 to 3.2 Gy (RBE) daily. The median follow-up duration was 12 months (range, 3 to 29 months). Fifteen patients underwent chemotherapy and 8 patients, palliative biliary stent placement prior to PBT. OS, PFS, and LC rates at 1 year were 49.0%, 29.5%, and 67.7%, respectively. LC was achieved in 6 patients, and was better in patients administered a biologically equivalent dose of 10 (BED10) > 70 Gy compared to those administered < 70 Gy (83.1% vs. 22.2%, respectively, at 1 year). The variables of tumor size and performance status were associated with survival. Late gastrointestinal toxicities grade 2 or greater were observed in 7 patients <12 months after PBT. Cholangitis was observed in 11 patients and 3 patients required stent replacement.

Relatively high LC rates after PBT for advanced cholangiocarcinoma can be achieved by delivery of a BED10 > 70 Gy. Gastrointestinal toxicities, especially those of the duodenum, are dose-limiting toxicities associated with PBT, and early metastatic progression remains a treatment obstacle.

• K12 CA090628 NCI NIH HHS

To analyze the outcomes of chemoradiotherapy for extrahepatic bile duct (EHBD) cancer patients who underwent R2 resection or bypass surgery and to identify prognostic factors affecting clinical outcomes, especially in terms of molecular biomarkers.

Medical records of 21 patients with EHBD cancer who underwent R2 resection or bypass surgery followed by chemoradiotherapy from May 2001 to June 2010 were retrospectively reviewed. All surgical specimens were re-evaluated by immunohistochemical staining using phosphorylated protein kinase B (pAKT), CD24, matrix metalloproteinase 9 (MMP9), survivin, and β-catenin antibodies. The relationship between clinical outcomes and immunohistochemical results was investigated.

At a median follow-up of 20 months, the actuarial 2-year locoregional progression-free, distant metastasis-free and overall survival were 37%, 56%, and 54%, respectively. On univariate analysis using clinicopathologic factors, there was no significant prognostic factor. In the immunohistochemical staining, cytoplasmic staining, and nuclear staining of pAKT was positive in 10 and 6 patients, respectively. There were positive CD24 in 7 patients, MMP9 in 16 patients, survivin in 8 patients, and β-catenin in 3 patients. On univariate analysis, there was no significant value of immunohistochemical results for clinical outcomes.

There was no significant association between clinical outcomes of patients with EHBD cancer who received chemoradiotherapy after R2 resection or bypass surgery and pAKT, CD24, MMP9, survivin, and β-catenin. Future research is needed on a larger data set or with other molecular biomarkers.

• Chemoradiotherapy
• Extrahepatic bile duct cancer
• Immunohistochemistry
• Molecular biomarker

• Adenocarcinoma/mortality
• Adenocarcinoma/secondary
• Adenocarcinoma/surgery
• Adenocarcinoma/therapy
• Adult
• Aged
• Aged, 80 and over
• Bile Duct Neoplasms/mortality
• Bile Duct Neoplasms/pathology
• Bile Duct Neoplasms/surgery
• Bile Duct Neoplasms/therapy
• Bile Ducts, Extrahepatic/surgery
• Chemoradiotherapy, Adjuvant/adverse effects
• Chemoradiotherapy, Adjuvant/methods
• Disease-Free Survival
• Female
• Follow-Up Studies
• Humans
• Liver Neoplasms/mortality
• Liver Neoplasms/secondary
• Maintenance Chemotherapy/methods
• Male
• Middle Aged
• Prognosis
• Pyrimidines/therapeutic use
• Radiation-Sensitizing Agents/therapeutic use
• Radiotherapy Dosage
• Retrospective Studies
• Risk Factors
• Survival Rate
• Treatment Failure
• Tumor Burden

• Bile Duct Neoplasms/therapy
• Bile Ducts, Intrahepatic
• Chemoradiotherapy
• Cholangiocarcinoma/therapy
• Female
• Humans
• Liver Transplantation
• Male
• Tumor Burden

• Aged
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Bile Duct Neoplasms/drug therapy
• Bile Duct Neoplasms/mortality
• Bile Duct Neoplasms/radiotherapy
• Bile Duct Neoplasms/surgery
• Bile Duct Neoplasms/therapy
• Bile Ducts, Extrahepatic/pathology
• Chemotherapy, Adjuvant
• Cholangiocarcinoma/drug therapy
• Cholangiocarcinoma/mortality
• Cholangiocarcinoma/radiotherapy
• Cholangiocarcinoma/surgery
• Cholangiocarcinoma/therapy
• Cisplatin/administration & dosage
• Combined Modality Therapy
• Digestive System Surgical Procedures
• Female
• Fluorouracil/administration & dosage
• Humans
• Kaplan-Meier Estimate
• Leucovorin/administration & dosage
• Lymphatic Irradiation
• Male
• Middle Aged
• Radiotherapy, Adjuvant
• Radiotherapy, Conformal
• Retrospective Studies