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      Adjuvant therapy is associated with improved survival after curative resection for hilar cholangiocarcinoma: A multi-institution analysis from the U.S. extrahepatic biliary malignancy consortium

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          Abstract

          <div class="section"> <a class="named-anchor" id="S1"> <!-- named anchor --> </a> <h5 class="section-title" id="d13795441e420">Background</h5> <p id="P1">Curative-intent treatment for localized hilar cholangiocarcinoma (HC) requires surgical resection. However, the effect of adjuvant therapy (AT) on survival is unclear. We analyzed the impact of AT on overall (OS) and recurrence free survival (RFS) in patients undergoing curative resection. </p> </div><div class="section"> <a class="named-anchor" id="S2"> <!-- named anchor --> </a> <h5 class="section-title" id="d13795441e425">Methods</h5> <p id="P2">We reviewed patients with resected HC between 2000 and 2015 from the ten institutions participating in the U.S. Extrahepatic Biliary Malignancy Consortium. We analyzed the impact of AT on RFS and OS. The probability of RFS and OS were calculated in the method of Kaplan and Meier and analyzed using multivariate Cox regression analysis. </p> </div><div class="section"> <a class="named-anchor" id="S3"> <!-- named anchor --> </a> <h5 class="section-title" id="d13795441e430">Results</h5> <p id="P3">A total of 249 patients underwent curative resection for HC. Patients who received AT and those who did not had similar demographic and preoperative features. In a multivariate Cox regression analysis, AT conferred a significant protective effect on OS (HR 0.58, p=0.013), and this was maintained in a propensity matched analysis (HR 0.66, p=0.033). The protective effect of AT remained significant when node negative patients were excluded (HR 0.28, p=0.001), while it disappeared (HR 0.76, p=0.260) when node positive patients were excluded. </p> </div><div class="section"> <a class="named-anchor" id="S4"> <!-- named anchor --> </a> <h5 class="section-title" id="d13795441e435">Conclusions</h5> <p id="P4">Adjuvant therapy should be strongly considered after curative-intent resection for hilar cholangiocarcinoma, particularly in patients with node positive disease. </p> </div>

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          Cholangiocarcinoma.

          Shahid Khan, Howard C Thomas, Brian Davidson … (2005)
          Cholangiocarcinoma is a devastating malignancy that presents late, is notoriously difficult to diagnose, and is associated with a high mortality. The incidence of intrahepatic cholangiocarcinoma is increasing worldwide. The cause for this rise is unclear, although it could be related to an interplay between predisposing genetic factors and environmental triggers. MRI and CT with endoscopic ultrasound and PET provide useful diagnostic information in certain patients. Surgical resection is the only chance for cure, with results depending on careful technique and patient selection. Data suggest that liver transplantation could offer long-term survival in selected patients when combined with neoadjuvant chemoradiotherapy. Chemotherapy and radiotherapy have been ineffective for patients with inoperable tumours. For most of these patients biliary drainage is the mainstay of palliation. However, controversy exists over the type and positioning of biliary stents. Photodynamic treatment is a new palliative technique that might improve quality of life.
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            Staging, resectability, and outcome in 225 patients with hilar cholangiocarcinoma.

            W Jarnagin, Y. Fong, R Dematteo … (2001)
            To analyze resectability and survival in patients with hilar cholangiocarcinoma according to a proposed preoperative staging scheme that fully integrates local, tumor-related factors. In patients with hilar cholangiocarcinoma, long-term survival depends critically on complete tumor resection. The current staging systems ignore factors related to local tumor extent, preclude accurate preoperative disease assessment, and correlate poorly with resectability and survival. Demographics, results of imaging studies, surgical findings, pathology, and survival were analyzed prospectively in consecutive patients. Using data from imaging studies, all patients were placed into one of three stages based on the extent of ductal involvement by tumor, the presence or absence of portal vein compromise, and the presence or absence of hepatic lobar atrophy. From March 1991 through December 2000, 225 patients were evaluated, 77% of whom were seen and treated within the last 6 years. Sixty-five patients had unresectable disease; 160 patients underwent exploration with curative intent. Eighty patients underwent resection: 62 (78%) had a concomitant hepatic resection and 62 (78%) had an R0 resection (negative histologic margins). Negative histologic margins, concomitant partial hepatectomy, and well-differentiated tumor histology were associated with improved outcome after all resections. However, in patients who underwent an R0 resection, concomitant partial hepatectomy was the only independent predictor of long-term survival. Of the 9 actual 5-year survivors (of 30 at risk), all had a concomitant hepatic resection and none had tumor-involved margins; 3 of these 9 patients remained free of disease at a median follow-up of 88 months. The rates of complications and death after resection were 64% and 10%, respectively. In the 219 patients whose disease could be staged, the proposed system predicted resectability and the likelihood of an R0 resection and correlated with metastatic disease and survival. By taking full account of local tumor extent, the proposed staging system for hilar cholangiocarcinoma accurately predicts resectability, the likelihood of metastatic disease, and survival. Complete resection remains the only therapy that offers the possibility of long-term survival, and hepatic resection is a critical component of the surgical approach.
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              Adjuvant therapy in the treatment of biliary tract cancer: a systematic review and meta-analysis.

              Anne Horgan, Eitan Amir, Thomas Walter … (2012)
              The benefit of adjuvant therapy (AT) for biliary tract cancer (BTC) is unclear, with conflicting results from nonrandomized studies. We report a systematic review and meta-analysis to determine the impact of AT on survival. Studies published between 1960 and November 2010, which evaluated adjuvant chemotherapy (CT), radiotherapy (RT), or both (CRT) compared with curative-intent surgery alone for resected BTC were included. Only tumors of the gallbladder and bile ducts were assessed. Published data were extracted and computed into odds ratios (ORs) for death at 5 years. Subgroup analyses of benefit based on lymph node (LN) or resection margin positivity (R1) were prespecified. Data were weighted by generic inverse variance and pooled using random-effect modeling. Twenty studies involving 6,712 patients were analyzed. There was a nonsignificant improvement in overall survival with any AT compared with surgery alone (pooled OR, 0.74; P = .06). There was no difference between gallbladder and bile duct tumors (P = .68). The association was significant when the two registry analyses were excluded. Those receiving CT or CRT derived statistically greater benefit than RT alone (OR, 0.39, 0.61, and 0.98, respectively; P = .02). The greatest benefit for AT was in those with LN-positive disease (OR, 0.49; P = .004) and R1 disease (OR, 0.36; P = .002). This analysis supports AT for BTC. Prospective randomized trials are needed to provide better rationale for this commonly used strategy. On the basis of our data, such trials could involve two active comparators rather than a no-treatment arm among patients with LN-positive or R1 disease.
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                Author and article information

                Journal
                Title: Journal of Surgical Oncology
                Abbreviated Title: J Surg Oncol
                Publisher: Wiley
                ISSN: 00224790
                Publication date Created: March 2018
                Publication date (Print): March 2018
                Publication date (Electronic): December 28 2017
                Volume: 117
                Issue: 3
                Pages: 363-371
                Affiliations
                [1 ]Department of Surgery; Washington University School of Medicine; St Louis Missouri
                [2 ]Winship Cancer Institute; Emory University; Atlanta Georgia
                [3 ]The Ohio State University Comprehensive Cancer Center; Columbus Ohio
                [4 ]Stanford University Medical Center; Palo Alto California
                [5 ]Vanderbilt University Medical Center; Nashville Tennessee
                [6 ]University of Wisconsin School of Medicine and Public Health; Madison Wisconsin
                [7 ]University of Louisville; Louisville Kentucky
                [8 ]Wake Forest University; Winston-Salem North Carolina
                [9 ]New York University; New York New York
                Article
                DOI: 10.1002/jso.24836
                PMC ID: 5924689
                PubMed ID: 29284072
                SO-VID: 03ebeb97-a0fc-4a7c-adfc-a85d5fe42c0b
                Copyright © © 2017
                License:

                http://doi.wiley.com/10.1002/tdm_license_1.1

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