Hepatobiliary Cancers, Version 2.2014

Benson, Al B.; D’Angelica, Michael I.; Abrams, Thomas A.; Are, Chandrakanth; Bloomston, P. Mark; Chang, Daniel T.; Clary, Bryan M.; Covey, Anne M.; Ensminger, William D.; Iyer, Renuka; Kelley, Robin Kate; Linehan, David C.; Malafa, Mokenge P.; Meranze, Steven G.; Park, James O.; Pawlik, Timothy M.; Posey, James; Scaife, Courtney L.; Schefter, Tracey E.; Sigurdson, Elin R.; Tian, G. Gary; Vauthey, Jean Nicolas; Venook, Alan P.; Yen, Yun; Zhu, Andrew X.; Hoffmann, K; McMillian, Nicole R.; Sundar, Hema

doi:10.6004/jnccn.2014.0112

Cited by 91 publications

(74 citation statements)

References 166 publications

(219 reference statements)

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“…However, biliary cancers are often diagnosed via ductal brushings obtained during endoscopic retrograde cholangiopancreatography (ERCP), which often yields insufficient material for molecular testing. Therefore, neither molecular profiling nor targeted therapy are standard practice(13), despite the presence of many molecular targets(14), (10). …”

Section: Introductionmentioning

confidence: 99%

Cell-Free DNA Next-Generation Sequencing in Pancreatobiliary Carcinomas

et al. 2015

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Patients with pancreatic and biliary carcinomas lack personalized treatment options, in part because biopsies are often inadequate for molecular characterization. Cell-free DNA (cfDNA) sequencing may enable a precision oncology approach in this setting. We attempted to prospectively analyze 54 genes in tumor and cfDNA for 26 patients. Tumor sequencing failed in nine patients (35%). In the remaining 17, 90.3% (95% CI: 73.1–97.5%) of mutations detected in tumor biopsies were also detected in cfDNA. The diagnostic accuracy of cfDNA sequencing was 97.7%, with 92.3% average sensitivity and 100% specificity across five informative genes. Changes in cfDNA correlated well with tumor marker dynamics in serial sampling (r=0.93). We demonstrate that cfDNA sequencing is feasible, accurate, and sensitive in identifying tumor-derived mutations without prior knowledge of tumor genotype or the abundance of circulating tumor DNA. cfDNA sequencing should be considered in pancreatobiliary cancer trials where tissue sampling is unsafe, infeasible, or otherwise unsuccessful.

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Section: Introductionmentioning

confidence: 99%

Cell-Free DNA Next-Generation Sequencing in Pancreatobiliary Carcinomas

et al. 2015

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“…Although TACE is regarded by some as the superior method of embolization, recently published randomized clinical trial data have demonstrated no significant survival difference between TACE, DEB TACE and bland HAE [11–13]. Consequently, the most recently published National Comprehensive Cancer Network consensus guidelines for the treatment of HCC suggest embolization, either bland HAE or TACE, as the standard of care for patients with intermediate/advanced HCC without extra hepatic spread or main portal vein involvement [14]…”

Section: Introductionmentioning

confidence: 99%

Locoregional Therapy for Hepatocellular Carcinoma with and without Extrahepatic Spread

Leal

Gönen

Covey

et al. 2015

Journal of Vascular and Interventional Radiology

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Objective This study evaluates the use of locoregional therapy in patients with hepatocellular carcinoma (HCC) with and without extrahepatic disease (EHD). Methods Patients who underwent locoregional therapy for HCC were identified from institutional databases. Clinicopathologic and treatment characteristics were compared between patients with and without EHD. Survival and progression were assessed using the Kaplan-Meier method and multivariate analysis was completed. Results Of 224 included patients, 39(17%) had radiologic evidence of EHD. Patients without EHD were older than those with EHD (68.8+/−10.1 vs. 65.0+/−11.7 years, p=0.04), however, underlying liver disease/function and tumor characteristics were not different. Type of locoregional therapy (HAE vs.DEB TACE, p=0.12; RFA+embolization, p=0.07) was similar. Progression occurred in 75% (169/224) of patients. Progression free survival did not differ between the two groups (13[10.3–15.7] months EHD vs.18 [14.6–21.4] months no EHD, p=0.13). Overall survival (OS) was 13(4.1–21.9) months and 25(20.4–29.6) months in the EHD and no EHD groups, respectively (p=0.02). On multivariate analysis, systemic therapy following locoregional treatment was the only variable independently associated with PFS (HR 0.70(0.49–1.00), p=0.04) while EHD (HR 1.60(1.02–2.50), p=0.04) and tumor size (HR 1.77(1.21–2.58), p=0.003) were independently associated with worse OS. Conclusions Patients with HCC and limited EHD treated with locoregional therapy have worse OS than patients without EHD; however, PFS was not different. Use of systemic therapy following locoregional therapy was independently associated with improved PFS in this cohort and suggests further prospective studies of locoregional, systemic and combination therapies are necessary to improve outcome in this high risk population of patients.

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“…Cytotoxic chemo-therapy remains the mainstay of treatment for advanced disease (Table 1) [4–7]. The National Comprehensive Cancer Network (NCCN) guidelines [8] consider gemcitabine combined with cisplatin to be standard of care first-line chemotherapy for patients with biliary tract cancers based upon results of the largest randomized controlled phase III ABC-02 trial to date, which showed improved median overall survival with combination therapy versus gemcitabine alone (11.7 versus 9 months) [6]. Other active chemotherapy regimens include (1) gemcitabine with oxaliplatin or capecitabine, (2) capecitabine with cisplatin or oxaliplatin, (3) fluorouracil with cisplatin or oxaliplatin, (4) single-agent fluorouracil, (5) single-agent capecitabine, or (6) single-agent gemcitabine [9–11].…”

Section: Traditional Therapy For Biliary Tract Carcinomasmentioning

confidence: 99%

“…As previously described, biliary tract tumors have often been grouped together in clinical trials and treatment algorithms, such as the NCCN guidelines [8]. However, they are distinct biologically and genomically.…”

Section: Traditional Therapy For Biliary Tract Carcinomasmentioning

confidence: 99%

Genomics of gallbladder cancer: the case for biomarker-driven clinical trial design

Sicklick

Fanta

Shimabukuro

et al. 2016

Cancer Metastasis Rev

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Background and aims Gallbladder carcinoma is a rare, aggressive malignancy of the biliary tract associated with a poor prognosis. Despite the deployment of targeted therapies that have demonstrated marked survival benefits in many tumor types, traditional cytotoxic chemotherapy has remained the mainstay of treatment for unresectable and metastatic gall-bladder cancer. Methods Systematic review of ongoing and prior clinical studies shows a paucity of biomarker-driven therapeutic trials using targeted agents in gallbladder cancer. In fact, over the past 6 years, of the 38 therapeutic biliary tract protocols listed on clinicaltrials.gov, only 6 (21 %) utilized targeted therapies based upon tumor biomarkers or genomics. Now that we have entered the era of next-generation sequencing and precision medicine, we are beginning to identify common and specific genetic alterations in gallbladder carcinomas. Results A review of the literature reveals alterations in ARID1A, BRAF, CDKN2A/B, EGFR, ERBB2-4, HKN-RAS, PIK3CA, PBRM1, and TP53. Given the widespread use of tumor genomic profiling and the fact that most of the aforementioned alterations are pharmacologically tractable, these observations suggest the potential for new therapeutic strategies in this aggressive malignancy. Conclusions Taken together, further understanding of the genomic landscape of gallbladder cancer coupled with biomarker-driven clinical trials that match therapies to targets are urgently needed.

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Hepatobiliary Cancers, Version 2.2014

Cited by 91 publications

References 166 publications

Cell-Free DNA Next-Generation Sequencing in Pancreatobiliary Carcinomas

Cell-Free DNA Next-Generation Sequencing in Pancreatobiliary Carcinomas

Locoregional Therapy for Hepatocellular Carcinoma with and without Extrahepatic Spread

Genomics of gallbladder cancer: the case for biomarker-driven clinical trial design

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