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Tchelebi LT, Jethwa KR, Levy AT, Anker CJ, Kennedy T, Grodstein E, Hallemeier CL, Jabbour SK, Kim E, Kumar R, Lee P, Small W, Williams VM, Sharma N, Russo S. American Radium Society (ARS) Appropriate Use Criteria (AUC) for Extrahepatic Cholangiocarcinoma. Am J Clin Oncol 2023; 46:73-84. [PMID: 36534388 PMCID: PMC9855763 DOI: 10.1097/coc.0000000000000969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Although uncommon, extrahepatic cholangiocarcinoma (EHCC) is a deadly malignancy, and the treatment approaches remain controversial. While surgery remains the only cure, few patients are candidates for resection up front, and there are high rates of both local and distant failure following resection. Herein, we systematically review the available evidence regarding treatment approaches for patients with EHCC, including surgery, radiation, and chemotherapy. The evidence regarding treatment outcomes was assessed using the Population, Intervention, Comparator, Outcome, and Study design (PICOS) framework. A summary of recommendations based on the available literature is outlined for specific clinical scenarios encountered by providers in the clinic to guide the management of these patients.
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Affiliation(s)
| | - Krishan R. Jethwa
- Department of Radiation Oncology, Mayo Clinic College of Medicine, Rochester, MN
| | | | - Christopher J. Anker
- Division of Radiation Oncology, University of Vermont Larner College of Medicine, Burlington, VT
| | - Timothy Kennedy
- Department of Surgery, Rutgers Cancer Institute, New Brunswick, NJ
| | - Elliot Grodstein
- Surgery, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead
| | | | - Salma K. Jabbour
- Department of Radiation Oncology, Rutgers Cancer Institute, New Brunswick, NJ
| | - Ed Kim
- Department of Radiation Oncology, University of Washington, Seattle, WA
| | - Rachit Kumar
- Department of Radiation Oncology, Banner MD Anderson Cancer Center, Phoenix, AZ
| | - Percy Lee
- Department of Radiation Oncology, City of Hope National Medical Center, Los Angeles, CA
| | - William Small
- Department of Radiation Oncology, Loyola University Stritch School of Medicine, Maywood, IL
| | | | - Navesh Sharma
- Department of Radiation Oncology, WellSpan Cancer Center, York, PA
| | - Suzanne Russo
- Department of Radiation Oncology, University Hospitals Cleveland, Case Western Reserve University School of Medicine, Cleveland, OH
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Huang X, Niu X, You Z, Long Y, Luo F, Ye H. Comparison of Four Lymph Node Stage Methods for Predicting the Prognosis of Distal Cholangiocarcinoma Patients After Surgery. Front Oncol 2021; 11:779761. [PMID: 34926292 PMCID: PMC8678514 DOI: 10.3389/fonc.2021.779761] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2021] [Accepted: 11/16/2021] [Indexed: 02/05/2023] Open
Abstract
Background The metastatic status of regional lymph nodes is an effective risk factor for the prognosis of distal cholangiocarcinoma (dCCA). But existing lymph node staging is not accurate enough and is susceptible to interference. This study aims to explore the predictive ability of the log odds of positive lymph nodes (LODDS) staging system of dCCA compared with existing lymph node staging systems. Methods A total of 928 dCCA patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database as the training cohort, and 207 dCCA patients from West China Hospital who underwent surgery were reviewed as the validation cohort. The least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression were conducted to identify the most meaningful factors relevant to prognosis. The performance of four lymph node stage systems was compared by a model-based approach. Result Age at diagnosis, pathological grade, American Joint Committee on Cancer (AJCC) tumor 7th T stage, tumor size, radiotherapy, chemotherapy, and lymph node stage system were independent prognostic factors. The model with the LODDS system had a better model fit with the highest C-index (0.679) and 1-/3-/5- area under the receiver operating characteristic curve (AUC) (0.739/0.671/0.658) as well as the lowest Akaike information criterion (AIC) (5,020.52). External validation results from 207 dCCA patients showed a C-index of 0.647 and 1-/3-/5-AUC of 0.740/0.683/0.589. Compared with the lymph node ratio (LNR), AJCC 8th N system, and 7th N system, the 5-year net reclassification improvement (NRI) of the LODDS system was 0.030 (95% CI: -0.079 to 0.147), 0.042 (95% CI: -0.062 to 0.139), and 0.040 (95% CI: -0.057 to 0.146), respectively. The integrated discrimination improvement (IDI) of LODDS improved compared with the LNR model (0.016; 95% CI: -0.001 to 0.036), AJCC 8th N system (0.020; 95% CI: 0.003-0.037), and AJCC 7th N system (0.019; 95% CI: 0.002-0.036). Decision curve analysis (DCA) also shows a greater net benefit of LODDS. In lymph node-negative patients, LODDS reveals a positive linear relationship with the hazard ratio (HR). The stage capacity of LODDS in a subgroup analysis stratified by examined lymph node number (ELNN) was consistent. Conclusions The LODDS lymph node stage system has superior predictive performance as compared with the LNR, AJCC 7th, and 8th lymph node stage systems. Meanwhile, LODDS has a more detailed staging ability and good stability.
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Affiliation(s)
- Xiuyi Huang
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaoya Niu
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Zhen You
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Youlin Long
- Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu, China
| | - Fan Luo
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Hui Ye
- Department of Biliary Surgery, West China Hospital, Sichuan University, Chengdu, China
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Shi XQ, Zhang JY, Tian H, Tang LN, Li AL. Role of adjuvant (chemo)radiotherapy for resected extrahepatic cholangiocarcinoma: a meta-analysis. J Zhejiang Univ Sci B 2020; 21:549-559. [PMID: 32633109 DOI: 10.1631/jzus.b1900691] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Adjuvant (chemo)radiotherapy (A(C)RT) may be an important supplement to surgery for extrahepatic cholangiocarcinoma (EHCC). However, whether all patients would achieve benefits from A(C)RT and which adjuvant regimen, adjuvant radiotherapy (ART) or adjuvant chemoradiotherapy (ACRT), would be preferred, are still undetermined. The low incidence of EHCC makes it difficult to carry out randomized controlled trials (RCTs); therefore, almost all clinical studies on radiotherapy are retrospective. We have conducted a meta-analysis of these retrospective studies. METHODS We conducted a meta-analysis of current retrospective studies using PubMed, Embase, and ClinicalTrials databases. All studies published in English that were related to A(C)RT and which analyzed overall survival (OS), disease-free survival (DFS), or locoregional recurrence-free survival (LRFS) were included. Estimated hazard ratios (HRs) were calculated for OS, DFS, and LRFS. RESULTS Data from eight studies including 685 patients were included. Our analysis showed that A(C)RT significantly improved OS (HR 0.69, 95% confidence interval (CI) 0.48-0.97, P=0.03), DFS (HR 0.60, 95% CI 0.47-0.76, P<0.0001), and LRFS (HR 0.27, 95% CI 0.17-0.41, P<0.00001) of EHCC overall. In subgroups, patients with microscopically positive resection margin (R1) could achieve a benefit from A(C)RT (HR 0.44, 95% CI 0.27-0.72, P=0.001). No statistically OS difference was observed in negative resection margin (R0) subgroup (HR 0.98, 95% CI 0.30-3.19, P=0.98).Significant OS benefit was found in patients who received concurrent ACRT (HR 0.40, 95% CI 0.26-0.62, P<0.0001), while the result of ART without chemotherapy showed no significant benefit (HR 1.14, 95% CI 0.29-4.50, P=0.85). In the distal cholangiocarcinoma subgroup, no significant difference was seen when ACRT and ART were included (HR 0.61, 95% CI 0.14-2.72, P=0.52), but a significant difference was seen when analyzing the concurrent ACRT only (HR 0.29, 95% CI 0.13-0.64, P=0.002). CONCLUSIONS A(C)RT may improve OS, DFS, and LRFS in EHCC patients, especially in those with R1 resection margins. ACRT may be superior to ART especially in distal patients.
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Affiliation(s)
- Xin-Qi Shi
- Department of Radiation Oncology, the First Hospital of China Medical University, Shenyang 110001, China
| | - Jing-Yu Zhang
- Department of Radiation Oncology, the First Hospital of China Medical University, Shenyang 110001, China
| | - Hua Tian
- Department of Radiation Oncology, the First Hospital of China Medical University, Shenyang 110001, China
| | - Ling-Na Tang
- Department of Radiation Oncology, the First Hospital of China Medical University, Shenyang 110001, China
| | - Ai-Lin Li
- Department of Radiation Oncology, the First Hospital of China Medical University, Shenyang 110001, China
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Koo T, Park HJ, Kim K. Radiation therapy for extrahepatic bile duct cancer: Current evidences and future perspectives. World J Clin Cases 2019; 7:1242-1252. [PMID: 31236388 PMCID: PMC6580339 DOI: 10.12998/wjcc.v7.i11.1242] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Revised: 04/02/2019] [Accepted: 04/19/2019] [Indexed: 02/05/2023] Open
Abstract
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.
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Affiliation(s)
- Taeryool Koo
- Department of Radiation Oncology, Hallym University Sacred Heart Hospital, Anyang 14068, South Korea
| | - Hae Jin Park
- Department of Radiation Oncology, Hanyang University College of Medicine, Seoul 04763, South Korea
| | - Kyubo Kim
- Department of Radiation Oncology, Ewha Womans University College of Medicine, Seoul 07985, South Korea
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Adjuvant concurrent chemoradiation therapy in patients with microscopic residual tumor after curative resection for extrahepatic cholangiocarcinoma. Clin Transl Oncol 2017; 20:1011-1017. [PMID: 29256155 DOI: 10.1007/s12094-017-1815-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2017] [Accepted: 11/27/2017] [Indexed: 02/08/2023]
Abstract
PURPOSE We investigated the role of adjuvant concurrent chemoradiation therapy (CCRT) in patients with a microscopically positive resection margin (R1) after curative resection for extrahepatic cholangiocarcinoma (EHCC). METHODS/PATIENTS A total of 84 patients treated with curative resection for EHCC were included. Fifty-two patients with negative resection margins did not receive any adjuvant treatments (R0 + S group). The remaining 32 patients with microscopically positive resection margins received either adjuvant CCRT (R1 + CCRT group, n = 19) or adjuvant radiation therapy (RT) alone (R1 + RT group, n = 13). RESULTS During the median follow-up period of 26 months, the 2-year locoregional recurrence-free survival (LRRFS), disease-free survival (DFS), and overall survival rates (OS) were: 81.8, 62.6, and 61.5% for R0 + S group; 71.8, 57.8, and 57.9% for R1 + CCRT group; and 16.8, 9.6, and 15.4% for R1 + RT group, respectively. Multivariate analysis revealed that the R1 + CCRT group did not show any significant difference in survival rates compared with the R0 + S group. The R1 + RT group had lower LRRFS [hazard ratio (HR) 3.008; p = 0.044], DFS (HR 2.364; p = 0.022), and OS (HR 2.417; p = 0.011) when compared with the R0 + S and R1 + CCRT group. CONCLUSIONS A lack of significant survival difference between R0 + S group and R1 + CCRT group suggests that adjuvant CCRT ameliorates the negative effect of microscopic positive resection margin. In contrast, adjuvant RT alone is appeared to be inadequate for controlling microscopically residual tumor.
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Kim BH, Chie EK, Kim K, Jang JY, Kim SW, Oh DY, Bang YJ, Ha SW. Impact of radiation dose in postoperative radiotherapy after R1 resection for extrahepatic bile duct cancer: long term results from a single institution. Oncotarget 2017; 8:78076-78085. [PMID: 29100449 PMCID: PMC5652838 DOI: 10.18632/oncotarget.17368] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2016] [Accepted: 04/10/2017] [Indexed: 12/26/2022] Open
Abstract
PURPOSE This study was conducted to evaluate the impact of radiation dose after margin involved resection in patients with extrahepatic bile duct cancer. METHODS Among the 251 patients who underwent curative resection followed by adjuvant chemoradiotherapy, 86 patients had either invasive carcinoma (n = 63) or carcinoma in situ (n = 23) at the resected margin. Among them, 54 patients received conventional radiation dose (40-50.4 Gy) and 32 patients received escalated radiation dose (54-56 Gy). RESULTS Escalated radiation dose was associated with improved locoregional control (5yr rate, 73.8% vs. 47.1%, p = 0.069), but not disease-free survival (5yr rate, 43.4% vs. 32.6%, p = 0.490) and overall survival (5yr rate, 40.6% vs. 29.6%, p = 0.348). In multivariate analysis for locoregional control, invasive carcinoma at the margin (HR 2.957, p = 0.032) and escalated radiation dose (HR 0.394, p = 0.047) were independent prognostic factors. No additional gastrointestinal toxicity was observed in escalated dose group. CONCLUSIONS Delivery of radiation dose ≥ 54 Gy was well tolerated and associated with improved locoregional control, but not with overall survival after margin involved resection. Further validation study is warranted.
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Affiliation(s)
- Byoung Hyuck Kim
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Republic of Korea
- Division of Biological Warfare Preparedness and Response, Armed Forces Medical Research Institute, Daejeon, Republic of Korea
| | - Eui Kyu Chie
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Kyubo Kim
- Department of Radiation Oncology, Ewha Womans University School of Medicine, Seoul, Republic of Korea
| | - Jin-Young Jang
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Sun Whe Kim
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Do-Youn Oh
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yung-Jue Bang
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Sung W. Ha
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Republic of Korea
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Kim MY, Kim JH, Kim Y, Byun SJ. Postoperative radiotherapy appeared to improve the disease free survival rate of patients with extrahepatic bile duct cancer at high risk of loco-regional recurrence. Radiat Oncol J 2016; 34:297-304. [PMID: 27951624 PMCID: PMC5207366 DOI: 10.3857/roj.2016.01879] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2016] [Revised: 08/26/2016] [Accepted: 10/04/2016] [Indexed: 01/27/2023] Open
Abstract
Purpose To investigate the outcomes of postoperative radiotherapy (RT), in patients with extrahepatic bile duct (EHBD) cancer by comparing the survival rate between patients undergoing surgery alone or surgery plus postoperative RT, and to identify the prognostic factors affecting survival. Materials and Methods Between 2000 and 2013, 52 patients with EHBD cancer underwent surgical resection. Of these, 33 patients did not receive postoperative RT (group I), and 19 patients did (group II). R1 resection was significantly more frequent in group II. The median radiation dose was 5,040 cGy. Results The 3-year overall survival (OS) rate for group I and group II was 38% and 56%, respectively (p = 0.274). The 3-year disease free survival (DFS) rate for group I and group II was 20% and 31%, respectively (p = 0.049), and the 3-year loco-regional recurrence free survival (LRFS) rates were 19% and 58%, respectively (p = 0.002). Multivariate analyses showed that postoperative RT and lymphovascular invasion were independent prognostic factors for DFS and LRFS. Overall, 42 patients (80%) experienced treatment failure. Distant metastasis was the predominant pattern of failure in group II. Conclusion Postoperative RT after surgical resection appeared to improve the loco-regional control and DFS rate. More effort is needed to reduce distant metastasis, the major pattern of failure, in patients who receive postoperative RT.
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Affiliation(s)
- Mi Young Kim
- Department of Radiation Oncology, Keimyung University Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Korea
| | - Jin Hee Kim
- Department of Radiation Oncology, Keimyung University Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Korea
| | - Yonghoon Kim
- Department of Surgery, Keimyung University Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Korea
| | - Sang Jun Byun
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Im JH, Seong J, Lee J, Kim YB, Lee IJ, Park JS, Yoon DS, Kim KS, Lee WJ. Postoperative radiotherapy dose correlates with locoregional control in patients with extra-hepatic bile duct cancer. Radiat Oncol J 2014; 32:7-13. [PMID: 24724046 PMCID: PMC3977131 DOI: 10.3857/roj.2014.32.1.7] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2013] [Revised: 01/13/2014] [Accepted: 02/13/2014] [Indexed: 12/21/2022] Open
Abstract
PURPOSE To evaluate the results of postoperative radiotherapy in patients with extra-hepatic bile duct cancer (EHBDC) and identify the prognostic factors for local control and survival. MATERIALS AND METHODS Between January 2001 and December 2010, we retrospectively reviewed the cases of 70 patients with EHBDC who had undergone curative resection and received postoperative radiotherapy. The median radiation dose was 50.4 Gy (range, 41.4 to 54 Gy). The resection margin status was R0 in 30 patients (42.9%), R1 in 25 patients (35.7%), and R2 in 15 patients (21.4%). RESULTS The 5-year rates of overall survival (OS), event-free survival (EFS), and locoregional control (LRC) for all patients were 42.9%, 38.3%, and 61.2%, respectively. The major pattern of failure was distant relapses (33 patients, 47.1%). A multivariate analysis showed that the postradiotherapy CA19-9 level, radiation dose (≥50 Gy), R2 resection margins, perineural invasion, and T stage were the significant prognostic factors for OS, EFS, and LRC. OS was not significantly different between the patients receiving R0 and R1 resections, but was significantly lower among those receiving R2 resection (54.6%, 56.1%, and 7.1% for R0, R1, and R2 resections, respectively). CONCLUSION In patients with EHBDC who had undergone curative resection, a postoperative radiotherapy dose less than 50 Gy was suboptimal for OS and LRC. Higher radiation doses may be needed to obtain better LRC. Further investigation of novel therapy or palliative treatment should be considered for patients receiving R2 resection.
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Affiliation(s)
- Jung Ho Im
- Department of Radiation Oncology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jinsil Seong
- Department of Radiation Oncology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jeongshim Lee
- Department of Radiation Oncology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Yong Bae Kim
- Department of Radiation Oncology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Ik Jae Lee
- Department of Radiation Oncology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jun Sung Park
- Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Dong Sup Yoon
- Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Kyung Sik Kim
- Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Woo Jung Lee
- Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
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