Is Radiotherapy Warranted Following Intrahepatic Cholangiocarcinoma Resection? The Impact of Surgical Margins and Lymph Node Status on Survival

Hammad, Ahmed Mohammed Ali; Berger, Nick G.; Eastwood, Dan; Tsai, Susan; Turaga, Kiran K.; Christian, Kathleen K.; Johnston, Fabian M.; Pawlik, Timothy M.; Gamblin, T. Clark

doi:10.1245/s10434-016-5560-1

Cited by 29 publications

(27 citation statements)

References 21 publications

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“…For patients with resected cholangiocarcinoma, data from retrospective studies indicate a benefit from postoperative EBRT with concurrent chemotherapy, especially in patients with lymph-node-positive or resection-margin-positive disease 83–85 . Results of a multi-institutional, single-arm phase II study 86 demonstrated the safety and promising efficacy of adjuvant therapy consisting of gemcitabine plus capecitabine followed by conformal EBRT with concurrent capecitabine for patients with resected pCCA/dCCA and gallbladder cancer.…”

Section: The Evolving Role Of Radiation Therapymentioning

confidence: 99%

Cholangiocarcinoma — evolving concepts and therapeutic strategies

et al. 2017

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Cholangiocarcinoma is a disease entity comprising diverse epithelial tumours with features of cholangiocyte differentiation: cholangiocarcinomas are categorized according to anatomical location as intrahepatic (iCCA), perihilar (pCCA), or distal (dCCA). Each subtype has a distinct epidemiology, biology, prognosis, and strategy for clinical management. The incidence of cholangiocarcinoma, particularly iCCA, has increased globally over the past few decades. Surgical resection remains the mainstay of potentially curative treatment for all three disease subtypes, whereas liver transplantation after neoadjuvant chemoradiation is restricted to a subset of patients with early stage pCCA. For patients with advanced-stage or unresectable disease, locoregional and systemic chemotherapeutics are the primary treatment options. Improvements in external-beam radiation therapy have facilitated the treatment of cholangiocarcinoma. Moreover, advances in comprehensive whole-exome and transcriptome sequencing have defined the genetic landscape of each cholangiocarcinoma subtype. Accordingly, promising molecular targets for precision medicine have been identified, and are being evaluated in clinical trials, including those exploring immunotherapy. Biomarker-driven trials, in which patients are stratified according to anatomical cholangiocarcinoma subtype and genetic aberrations, will be essential in the development of targeted therapies. Targeting the rich tumour stroma of cholangiocarcinoma in conjunction with targeted therapies might also be useful. Herein, we review the evolving developments in the epidemiology, pathogenesis, and management of cholangiocarcinoma.

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Section: The Evolving Role Of Radiation Therapymentioning

confidence: 99%

Cholangiocarcinoma — evolving concepts and therapeutic strategies

et al. 2017

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“…When compared with the LR group, patients who underwent LT were younger (59 versus 63 [48-80] years; P = 0.03) and had a lower BMI (27 versus 29 [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] kg/m 2 ; P = 0.046; Table 1). A significantly higher rate of diabetes was seen in transplanted patients (23 [47%] versus 6 [23%]; P = 0.04), and they had a significantly higher MELD score (12 versus 7 [6][7][8][9][10][11][12][13][14]; P < 0.001).…”

Section: Lr Compared With Ltmentioning

confidence: 99%

“…Lymph nodes metastases are associated with poorer 5-year OS, as was demonstrated by a population-based study from the Mayo Clinic (33) and confirmed recently by another group. (34) Moreover, positron emission tomography/computed tomography with ( 18 F)fludeoxyglucose has high sensitivity for CCA, (35) but its role in determining tumor extension has not yet been described and needs to be evaluated.…”

Section: Context Of the Published Literaturementioning

confidence: 99%

Analysis of Liver Resection Versus Liver Transplantation on Outcome of Small Intrahepatic Cholangiocarcinoma and Combined Hepatocellular‐Cholangiocarcinoma in the Setting of Cirrhosis

et al. 2020

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This multicenter study compares the outcomes of patients with cirrhosis undergoing liver transplantation (LT) or liver resection (LR) between January 2002 and July 2015 who had intrahepatic cholangiocarcinoma (iCCA) or combined hepatocellularcholangiocarcinoma (cHCC-CCA) found incidentally in the native liver. A total of 49 (65%) LT and 26 (35%) LR patients with cirrhosis and histologically confirmed iCCA/cHCC-CCA ≤5 cm were retrospectively analyzed. LT patients had significantly lower tumor recurrence (18% versus 46%; P = 0.01), for which the median diameter of the largest nodule (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.02-1.12]; P = 0.006) and tumor differentiation (HR, 3.74; 95% CI 1.71-8.17; P = 0.001) were independently predictive. The LT group had significantly higher 5-year recurrence-free survival (RFS; 75% versus 36%; P = 0.004). In patients with tumors >2 cm but ≤5 cm, LT patients had a lower recurrence rate (21% versus 48%; P = 0.06) and a higher 5-year RFS (74% versus 40%; P = 0.06). Independent risk factors for recurrence were LT (protective; HR, 0.23; 95% CI, 0.07-0.82; P = 0.02), the median diameter of the largest nodule (HR, 1.10; 95% CI, 1.02-1.73; P = 0.007), and tumor differentiation (HR, 4.16; 95% CI, 1.37-12.66; P = 0.01). In the LT group, 5-year survival reached 69% and 65% (P = 0.40) in patients with tumors ≤2 cm and >2-5 cm, respectively, and survival was also comparable between iCCA and cHCC-CCA patients (P = 0.29). LT may offer a benefit for highly selected patients with cirrhosis and unresectable iCCA/cHCC-CCA having tumors ≤5 cm. Efforts should be made to evaluate tumor differentiation, and these results need to be confirmed prospectively in a larger population. Liver Transplantation 26 785-798 2020 AASLD. SEE EDITORIAL ON PAGE 748Intrahepatic cholangiocarcinoma (iCCA) accounts for 20%-25% of all cholangiocarcinoma (CCA) cases, and its incidence is rising at an average of 14% per year in Western countries. (1,2) Moreover, the mixed form of iCCA and hepatocellular carcinoma (HCC), referred to as combined hepatocellularcholangiocarcinoma (cHCC-CCA), is well recognized and increasingly reported. (3) Liver cirrhosis is a major risk factor for iCCA, with an odds ratio of 22.92 (95% confidence interval [CI], 18.24-28.79), De Martin et al. De Martin et al. liver transplantatiOn, June 2020

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“…The Brisbane 2000 nomenclature 9 for liver anatomy and surgery was used to describe the liver resections. Transection of the liver parenchyma was performed under low central venous pressure (2)(3)(4)(5).…”

Section: Perioperative Care and Surgical Techniquementioning

confidence: 99%

Outcome after liver resection for primary and recurrent intrahepatic cholangiocarcinoma

et al. 2019

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BackgroundLiver resection is the only curative therapeutic option for intrahepatic cholangiocarcinoma (ICC), but the approach to recurrent ICC is controversial. This study analysed the outcome of liver resection in patients with recurrent ICC.MethodsDemographic, radiological, clinical, operative, surgical pathological and follow‐up data for all patients with a final surgical pathological diagnosis of ICC treated in a tertiary referral centre between 2001 and 2015 were collected retrospectively and analysed.ResultsA total of 190 patients had liver resection for primary ICC. The 1‐, 3‐ and 5‐year overall survival (OS) rates were 74·8, 56·6 and 37·9 per cent respectively. Independent determinants of OS were age 65 years or above (hazard ratio (HR) 2·18, 95 per cent c.i. 1·18 to 4·0; P = 0·012), median tumour diameter 5 cm or greater (HR 2·87, 1·37 to 6·00; P = 0·005), preoperative biliary drainage (HR 2·65, 1·13 to 6·20; P = 0·025) and local R1–2 status (HR 1·90, 1·02 to 3·53; P = 0·043). Recurrence was documented in 87 patients (45·8 per cent). The mean(s.d.) survival time after recurrence was 16(17) months. Independent determinants of recurrence were median tumour diameter 5 cm or more (HR 1·71, 1·09 to 2·68; P = 0·020), high‐grade (G3–4) tumour (HR 1·63, 1·04 to 2·55; P = 0·034) and local R1 status (HR 1·70, 1·09 to 2·65; P = 0·020). Repeat resection with curative intent was performed in 25 patients for recurrent ICC, achieving a mean survival of 25 (95 per cent c.i. 16 to 34) months after the diagnosis of recurrence. Patients deemed to have unresectable disease after recurrence received chemotherapy or chemoradiotherapy alone, and had significantly poorer survival.ConclusionPatients with recurrent ICC may benefit from repeat surgical resection.

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Is Radiotherapy Warranted Following Intrahepatic Cholangiocarcinoma Resection? The Impact of Surgical Margins and Lymph Node Status on Survival

Cited by 29 publications

References 21 publications

Cholangiocarcinoma — evolving concepts and therapeutic strategies

Cholangiocarcinoma — evolving concepts and therapeutic strategies

Analysis of Liver Resection Versus Liver Transplantation on Outcome of Small Intrahepatic Cholangiocarcinoma and Combined Hepatocellular‐Cholangiocarcinoma in the Setting of Cirrhosis

Outcome after liver resection for primary and recurrent intrahepatic cholangiocarcinoma

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