scholarly journals Establishment of a Pretreatment Nomogram to Predict the 6-Month Mortality Rate of Patients with Advanced Biliary Tract Cancers Undergoing Gemcitabine-Based Chemotherapy

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3139
Author(s):  
Chiao-En Wu ◽  
Wen-Kuan Huang ◽  
Wen-Chi Chou ◽  
Chia-Hsun Hsieh ◽  
John Wen-Cheng Chang ◽  
...  
Keyword(s):  
Liver Metastasis ◽  
Mortality Rate ◽  
Biliary Tract ◽  
Mortality Risk ◽  
Treatment Options ◽  
Univariate Analysis ◽  
Cytotoxic Agents ◽  
Response To Treatment ◽  
Tract Cancer ◽  
Additional Information

Background: The estimation of mortality risk among patients diagnosed with advanced cancer provides important information for clinicians and patients in clinical practice. Currently, gemcitabine-based chemotherapy regimens are the standard treatment for patients with advanced biliary tract cancer (BTC). We aimed to develop a nomogram to predict the 6-month mortality rate among patients with advanced BTC to help physicians evaluate treatment options and outcomes. Patients: We conducted a retrospective analysis to evaluate the 6-month mortality rate among patients with advanced BTC who underwent gemcitabine-based chemotherapy from 2012 to 2018. Data regarding pretreatment factors and the clinical response to treatment were collected. Univariate and multivariate analyses were performed to identify independent factors for nomogram creation. Results: A total of 202 advanced BTC patients who were treated with gemcitabine-based chemotherapy were included in this analysis. No difference in survival was identified between patients undergoing gemcitabine monotherapy and those treated with gemcitabine combined with other cytotoxic agents. The univariate analysis revealed 10 significant factors, while the multivariate analysis identified four independent factors, including gender, monocyte to lymphocyte ratio (MLR), alkaline phosphatase (ALP), and liver metastasis, which were used to establish the nomogram. The performance of this nomogram for the prediction of 6-month mortality risk was found to be promising and feasible based on logistic regression. Conclusion: A nomogram based on four independent pretreatment factors, including gender, MLR, ALP, and liver metastasis, was established to predict the 6-month mortality risk in patients with advanced BTC; it can provide clinicians and patients with additional information when evaluating treatment outcomes.

scholarly journals Contemporary Tailored Oncology Treatment of Biliary Tract Cancers

2019 ◽  
Vol 2019 ◽  
pp. 1-15
Author(s):  
Fiona Turkes ◽  
Juliet Carmichael ◽  
David Cunningham ◽  
Naureen Starling
Keyword(s):  
Clinical Trials ◽  
Biliary Tract ◽  
Treatment Options ◽  
Prognostic Significance ◽  
Response To Treatment ◽  
Genomic Profiling ◽  
Biliary Tract Cancers ◽  
Comprehensive Genomic Profiling ◽  
Genomic Aberrations ◽  
Oncology Treatment

Biliary tract cancers (BTCs) are poor prognosis malignancies with limited treatment options. Capecitabine has recently emerged as an effective agent in the adjuvant setting; however, treatment of advanced disease is still limited to first-line cisplatin and gemcitabine chemotherapy. Recent global efforts in genomic profiling and molecular subtyping of BTCs have uncovered a wealth of genomic aberrations which may carry prognostic significance and/or predict response to treatment, and several targeted agents have shown promising results in clinical trials. As such, the uptake of comprehensive genomic profiling for patients with BTCs and the expansion of basket trials to include these patients are growing. This review describes the currently approved systemic therapies for BTCs and provides insight into the emerging targeted and immunotherapeutic agents, as well as conventional chemotherapeutic regimes, currently being investigated in clinical trials.

scholarly journals Biliary Tract Cancers: Molecular Heterogeneity and New Treatment Options

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3370
Author(s):  
Nicola Personeni ◽  
Ana Lleo ◽  
Tiziana Pressiani ◽  
Francesca Colapietro ◽  
Mark Robert Openshaw ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Advanced Disease ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Standard Of Care ◽  
Resistance Mechanisms ◽  
Anatomical Location ◽  
Molecular Heterogeneity ◽  
Isocitrate Dehydrogenase 1 ◽  
Tract Cancer

Most patients with biliary tract cancer (BTC) are diagnosed with advanced disease, relapse rates are high in those undergoing surgery and prognosis remains poor, while the incidence is increasing. Treatment options are limited, and chemotherapy is still the standard of care in both adjuvant and advanced disease setting. In recent years, different subtypes of BTC have been defined depending on the anatomical location and genetic and/or epigenetic aberrations. Especially for intrahepatic cholangiocarcinoma (iCCA) novel therapeutic targets have been identified, including fibroblast growth factor receptor 2 gene fusions and isocitrate dehydrogenase 1 and 2 mutations, with molecularly targeted agents having shown evidence of activity in this subgroup of patients. Additionally, other pathways are being evaluated in both iCCA and other subtypes of BTC, alongside targeting of the immune microenvironment. The growing knowledge of BTC biology and molecular heterogeneity has paved the way for the development of new therapeutic approaches that will completely change the treatment paradigm for this disease in the near future. This review provides an overview of the molecular heterogeneity of BTC and summarizes new targets and emerging therapies in development. We also discuss resistance mechanisms, open issues, and future perspectives in the management of BTC.

A phase II trial of regorafenib as a single agent in patients with advanced and metastatic biliary tract carcinoma and first-line chemotherapy failure.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. TPS498-TPS498
Author(s):  
Anuj Kishor Patel ◽  
Ronald G. Stoller ◽  
John C. Rhee ◽  
Barry C. Lembersky ◽  
James Ohr ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Phase Ii ◽  
Biliary Tract Cancer ◽  
Systemic Chemotherapy ◽  
Single Agent ◽  
Response To Treatment ◽  
Mri Imaging ◽  
First Line ◽  
Tract Cancer ◽  
Line Chemotherapy

TPS498 Background: Biliary tract cancers (including cholangiocarcinomas) are rare but aggressive malignancies with limited options for treatment. Currently, the combination of gemcitabine and cisplatin is considered the upfront systemic chemotherapy for patients with advanced and metastatic diseases. There is no ‘standard’ for second-line treatment. Several signaling pathways have been identified that might play a role in the development of biliary tract cancer and that may represent targets for directed therapies. Overexpression of VEGF and alterations of the Ras/Raf pathway have been identified in the majority of cholangiocarcinoma; some studies have shown these mutations to be associated with metastasis and poorer prognosis. Regorafenib is an oral multikinase inhibitor of multiple angiogenic and oncogenic kinases (VEGFR1-3, TIE2, PDGFR-β, FGFR1, KIT, RET, RAF) which has shown efficacy as a single agent in multiple solid tumors. This study evaluates the efficacy of regorafenib in patients with advanced/metastatic biliary tract cancer following the failure of first-line chemotherapy. Methods: Enrollment in this phase II, single-arm trial is ongoing. Eligible patients have unresectable advanced or metastatic biliary tract adenocarcinoma, and have failed first-line systemic chemotherapy. Patients receive regorafenib 120 mg orally daily in a 21 days on, 7 days off cycle. Tumor measurements take place every 3 cycles by CT or MRI imaging. Patients continue on therapy until disease progression or unacceptable toxicities. The primary end point of this study is median progression-free survival (PFS). To evaluate for evidence of activity, defined as a median PFS of 3.5 months or greater, with 83% power (one-sided test, α=0.10), target enrollment is 37 patients. Secondary endpoints include safety, overall response rate, disease control rate, median overall survival, and changes in biomarker levels. The correlation of these biomarkers and of tumor mutations with response to treatment is built into the study as well. As of September 2014, 9 patients had been enrolled. ClinicalTrials.gov Identifier: NCT02053376. Clinical trial information: NCT02053376.

PD-L1 expression as a prognostic marker in patients with advanced biliary tract cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16679-e16679
Author(s):  
Hyera Kim ◽  
Jung Yong Hong ◽  
Jeeyun Lee ◽  
Se Hoon Park ◽  
Joon Oh Park ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Checkpoint Inhibitors ◽  
Univariate Analysis ◽  
Group Analysis ◽  
Progression Free Survival ◽  
Tumor Location ◽  
Tract Cancer ◽  
Positive Score ◽  
Combined Positive Score

e16679 Background: Biliary tract cancer (BTC) is associated with poor prognosis because of its aggressive and heterogeneous nature. Programmed death ligand 1 (PD-L1) has been considered as a novel biomarker for prognosis and response of immune checkpoint inhibitors in various tumors. However, there are limited data reporting on the role of PD-L1 in advanced BTC patients. Methods: We analyzed 186 patients with advanced BTC who received palliative gemcitabine and platinum between May 2010 and December 2019. All patients were evaluated for PD-L1 expression by combined positive score (CPS) positivity. Results: In all 186 patients, the median age was 62 years (range 38-82), and the primary tumor location was intrahepatic cholangiocarcinoma (IH-CCC) in 72 patients (38.7%), extrahepatic (EH)-CCC in 90 (48.4%), and gallbladder (GB) cancer in 24 (12.9%). There were 158 (84.9%) patients with recurrent disease and 28 (15.1%) with metastatic disease. Among the 186 patients, 53 (28.5%) had PD-L1 CPS positivity, and 133 were CPS negative. The median overall survival (OS) of patients with PD-L1 CPS positivity or negativity was 12.1 and 15.4 months, respectively. The median progression-free survival (PFS) in patients with PD-L1 positivity or negativity was 5.7 and 7.1 months, respectively. The OS and PFS were not statistically different between groups. In sub-group analysis, EH-CCC patients with PD-L1 negativity had more favorable OS (17.2 vs. 11.6 months, p= 0.002) and PFS (7.8 vs. 5.4 months, p= 0.005) than those that were PD-L1 negative. However, this finding was not reproduced in patients with IH-CCC or GB cancer. Univariate analysis of the association between PD-L1 expression and OS in patients with advanced BTC indicated that PD-L1 CPS positivity has a prognostic role in sub-populations older than 60 years (HR 1.743, CI 1.001-3.034, p = 0.050), those with EH-CCC (HR 2.449, CI 1.355-4.426, p = 0.003), and those with liver metastasis (HR 2.511, CI 1.362-4.626, p = 0.003). Conclusions: This study demonstrated that PD-L1 expression might be a novel prognostic biomarker in patients with EH-CCC but not for patients with IH-CCC or GB cancer.

Analysis of 94 patients with advanced biliary tract cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15172-15172
Author(s):  
B. Andritzky ◽  
S. Adler ◽  
I. Burkholder ◽  
I. Thöm ◽  
G. Schuch ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bile Duct ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Primary Tumor ◽  
Median Overall Survival ◽  
Response Rate ◽  
Cytotoxic Agents ◽  
Tract Cancer ◽  
Line Chemotherapy

15172 Background: Cholangiocarcinoma or gallbladder cancer are often diagnosed at an advanced stage with limited treatment options. Methods: Between 1994 and 2004, 94 patients (pts) (47 male, 47 female) with advanced biliary tract cancer were treated at the Department of Oncology and Hematology, University Hospital Hamburg-Eppendorf. Clinical and histopathological characteristics, response to chemotherapy, and survival were investigated in a retrospective analysis. Median age was 59 years (range 30–80) and median Karnofsky performance status was 90%. Predominant histologic type was adenocarcinoma (94.7%). Primary tumor sites were extrahepatic bile duct (29.9%), gallbladder (28.7%), intrahepatic bile duct (10.6%), ampulla of Vater (2.1%), not specified (28.7%). Predominant localizations of metastases were liver (73 pts (77.7%)), lymph nodes (49 pts (52.1%)) and the peritoneum (14 pts (14.9%)). 33 pts (35.1%) underwent surgery of the primary tumor at time of diagnosis. Results: 72 of 94 pts (76.6%) received a first-line chemotherapy, all together 10 different chemotherapy regimens were used. The median number of cycles was 2.5 (range 1 - 12). A single agent chemotherapy with gemcitabine was the most often adminstered regimen (23 pts (31.9%)), followed by carboplatin and etoposide plus whole body hyperthermia (12 pts (16.7%)) and 5- fluorouracil and folic acid (10 pts (13.9%)). The overall response rate was 8.3% (95% CI 3.1 - 17.3) (34.7% SD, 47.2% PD, 9.7% not evaluable). Second-line chemotherapy was given in 27 patients, which induced no tumor response, but a stable disease rate of 22.2%. Median time to follow- up was 44.8 months. Survival was calculated for all 94 pts since time of diagnosis. Median overall survival was 12.2 months and median progression-free survival 9.2 months. The median overall survival time for the 72 pts who were treated with chemotherapy was 14.0 months, and for the 22 pts who did not receive chemotherapy 10.7 months (p=0.2). Conclusions: Our analysis showed a poor prognosis for patients with advanced biliary tract cancer. Response rate to chemotherapy was low. Therefore, well tolerated cytotoxic agents should be used and new treatment strategies (including molecular targeted therapy) should be further investigated. No significant financial relationships to disclose.

Feasibility and potential benefits of second-line chemotherapy in patients with advanced biliary tract cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 338-338
Author(s):  
Thomas Walter ◽  
Anne M. Horgan ◽  
Elizabeth McKeever ◽  
Trisha Min ◽  
Mairead McNamara ◽  
...  
Keyword(s):  
Disease Control ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Univariate Analysis ◽  
Single Agent ◽  
Objective Response ◽  
Second Line ◽  
Second Line Chemotherapy ◽  
Tract Cancer ◽  
Line Chemotherapy

338 Background: Chemotherapy is effective in metastatic or unresectable biliary tract cancer (BTC). The benefits of second-line chemotherapy (CT2) are unclear. Methods: We retrospectively studied all patients (pts) receiving at least one cycle of chemotherapy for advanced BTC at our institution between 1991 and 2011. We analyzed pt and chemotherapy characteristics (type of regimen; tumor response; time to progression (TTP); and overall survival (OS)). The objectives were: 1) to characterize pts eligible for CT2; 2) to evaluate the efficacy of CT2. Results: 367, 89 (24%), and 24 (6%) pts received CT1, CT2, and CT3, respectively. Primary tumor location was the gallbladder (30%), intraphepatic (16%), perihilar (20%), distal common bile duct (20%), and ampulla of Vater (14%). 88% had a baseline performance status of 0-1 prior to CT1. The regimen and efficacy data of CT1 and CT2 are presented in the Table . On univariate analysis females (p=0.002) and pts with TTP >6 months on CT1 (p=0.016) were the only variables associated with receiving CT2. The only factor associated with disease control (objective response+ stable disease) on CT2 was the regimen type (75% with a doublet versus 46% with monotherapy, p=0.03). Conclusions: Among patients with advanced BTC treated with chemotherapy, less than 25% received CT2; but responses were seen and were surprisingly high even in this selected population. Pts with a longer TTP on CT1 were more likely to be offered CT2. Better disease control with CT2 occurs with a doublet than single agent, however clearly more effective therapies must be found. Updated data will be presented. [Table: see text]

Treatment efficacy in patients with advanced biliary tract cancer receiving gemcitabine and cisplatin and 21-h infusional 5-FU: An analysis of 17 cases.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15195-e15195
Author(s):  
Mozaffar Aznab ◽  
Kiumars Eslam pia ◽  
Khosro Setayeshi ◽  
Mansour Rezaei ◽  
Kaveh Kavianymoghadam
Keyword(s):  
Lymph Node ◽  
Liver Metastasis ◽  
Gallbladder Cancer ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Medical Sciences ◽  
Curative Surgery ◽  
Local Invasion ◽  
Tract Cancer ◽  
Age Range

e15195 Background:Biliary tract a group of tumors which only a minority of patients is eligible for curative surgery. The purpose of this study was to identify efficacy treatment of gemcitabine, cisplatin, and 21h infusional 5-FU in patients with advanced BTC receiving this therapy, and the median time to progression and OS time. Methods: The data of 17 patients with advanced biliary tract cancer who referred to clinic oncology of Kermanshah University of Medical Sciences, which received treatment from January 2009 to December 2012 were collected. Patients with gallbladder cancer with local invasion into near structures or metastatic to lymph node and or liver and or peritoneal seeding and also patients with cholangiocarcinom were randomized to recieveing chemotherapy consisting of cycles of continuous infusion of 5-FU for 21-hours (600 mg/m2) days 1, 2, 3, and 4. Gemcitabine was given at dose of 1,250 mg/m2 days 1 and 8 and cisplatin was given at dose of 60 mg/m2 day 1 with G-csf every support. Each cycle repeated every 21 days for 6-7 cycles. Results: A total of 17 patients with age range 41-61 years studied.58.8% female and 41.2% were male. The 11 patients were gallbladder cancer with only local invasion into surrounding structures in 7 pts and 2 pts with only lymph node and peritoneal involving and 2 pts with lymph node and peritoneal involving and liver metastasis, and 6 patients were cholangiocarcinoma with lymph node and peritoneal involving in 3 pts and one pts with lymph node involving and one pts with liver metastasis. Four out of the 11 patients with gallbladder cancer with local invasion survived above 29 months one pts above 20 months. Means and medians for TTP of 6 pts which disease progressed was 11.2 and 9.6 months, respectively. Means for OS Time of 17 pts was 32 months. The overall 75.5% of pts are alive. This regimen was well tolerated, with neutropenia and thrombocytopenia as the most significant toxicities. Conclusions: The triple therapy with Gemcitabine cisplatin, 5-FU showed efficacy with manageable toxicity in patients with advanced BTC and demonstrated that the addition infusional 5-FU to cisplatin and gemcitabine afforded significant PFS and OS benefits.

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