Risk Factors for Distant Metastasis in Extrahepatic Bile Duct Cancer after Curative Resection (KROG 1814)
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Purpose Risk factors predicting distant metastasis (DM) in extrahepatic bile duct cancer (EHBDC) patients treated with curative resection were investigated.Materials and Methods Medical records of 1,418 EHBDC patients undergoing curative resection between Jan 2000 and Dec 2015 from 14 institutions were reviewed. After resection, 924 patients (67.6%) were surveilled without adjuvant therapy, 297 (21.7%) were treated with concurrent chemoradiotherapy (CCRT) and 148 (10.8%) with CCRT followed by chemotherapy. To exclude the treatment effect from innate confounders, patients not treated with adjuvant therapy were evaluated.Results After a median follow-up of 36.7 months (range, 2.7 to 213.2 months), the 5-year distant metastasis-free survival (DMFS) rate was 57.7%. On multivariate analysis, perihilar or diffuse tumor (hazard ratio [HR], 1.391; p=0.004), poorly differentiated histology (HR, 2.014; p < 0.001), presence of perineural invasion (HR, 1.768; p < 0.001), positive nodal metastasis (HR, 2.670; p < 0.001) and preoperative carbohydrate antigen (CA) 19-9 ≥ 37 U/mL (HR, 1.353; p < 0.001) were significantly associated with inferior DMFS. The DMFS rates significantly differed according to the number of these risk factors. For validation, patients who underwent adjuvant therapy were evaluated. In patients with ≥ 3 factors, additional chemotherapy after CCRT resulted in a superior DMFS compared with CCRT alone (5-year rate, 47.6% vs. 27.7%; p=0.001), but the benefit of additional chemotherapy was not observed in patients with 0-2 risk factors.Conclusion Tumor location, histologic differentiation, perineural invasion, lymph node metastasis, and preoperative CA 19-9 level predicted DM risk in resected EHBDC. These risk factors might help identifying a subset of patients who could benefit from additional chemotherapy after resection.
Abstract
Purpose Risk factors predicting distant metastasis (DM) in extrahepatic bile duct cancer (EHBDC) patients treated with curative resection were investigated.Materials and Methods Medical records of 1,418 EHBDC patients undergoing curative resection between Jan 2000 and Dec 2015 from 14 institutions were reviewed. After resection, 924 patients (67.6%) were surveilled without adjuvant therapy, 297 (21.7%) were treated with concurrent chemoradiotherapy (CCRT) and 148 (10.8%) with CCRT followed by chemotherapy. To exclude the treatment effect from innate confounders, patients not treated with adjuvant therapy were evaluated.Results After a median follow-up of 36.7 months (range, 2.7 to 213.2 months), the 5-year distant metastasis-free survival (DMFS) rate was 57.7%. On multivariate analysis, perihilar or diffuse tumor (hazard ratio [HR], 1.391; p=0.004), poorly differentiated histology (HR, 2.014; p < 0.001), presence of perineural invasion (HR, 1.768; p < 0.001), positive nodal metastasis (HR, 2.670; p < 0.001) and preoperative carbohydrate antigen (CA) 19-9 ≥ 37 U/mL (HR, 1.353; p < 0.001) were significantly associated with inferior DMFS. The DMFS rates significantly differed according to the number of these risk factors. For validation, patients who underwent adjuvant therapy were evaluated. In patients with ≥ 3 factors, additional chemotherapy after CCRT resulted in a superior DMFS compared with CCRT alone (5-year rate, 47.6% vs. 27.7%; p=0.001), but the benefit of additional chemotherapy was not observed in patients with 0-2 risk factors.Conclusion Tumor location, histologic differentiation, perineural invasion, lymph node metastasis, and preoperative CA 19-9 level predicted DM risk in resected EHBDC. These risk factors might help identifying a subset of patients who could benefit from additional chemotherapy after resection.
참고문헌 (23)
- Henson DE, "Carcinoma of the extrahepatic bile ducts. Histologic types, stage of disease, grade, and survival rates", Cancer, 70, pp.1498~1501 (1992)
- Kopelson G, "Pat terns of failure after curative surgery for extra-hepatic bil iary tract carcinoma : implications for adjuvant therapy", Int J Radiat Oncol Biol Phys, 7, pp.413~417 (1981)
- Launois B, "Surgery for hilar cholangiocarcinoma : French experience in a collective survey of 552 extrahepatic bile duct cancers", J Hepatobiliary Pancreat Surg, 7, pp.128~134 (2000)
- Spolverato G, "Defining the chance of statistical cure among patients with extrahepatic biliary tract cancer", World J Surg, 41, pp.224~231 (2017)
- Jang JY, "Actual long-term outcome of extrahepatic bile duct cancer after surgical resection", Ann Surg, 241, pp.77~84 (2005)
- Koo TR, "Patterns of failure and prognostic factors in resected extrahe patic bile duct cancer : implication for adjuvant radiotherapy", Radiat Oncol J, 32, pp.63~69 (2014)
- Kim TH, "Role of adjuvant chemoradiotherapy for resected extrahepatic biliary tract cancer", Int J Radiat Oncol Biol Phys, 81, pp.e8539~ (2011)
- Kim K, "Adjuvant chemoradiotherapy after curative resection for extrahepatic bile duct cancer : a long-term single center expe rience", Am J Clin Oncol, 35, pp.136~140 (2012)
- Rizzo A, "Pitfalls, challenges, and updates in adju vant systemic treatment for resected biliary tract cancer", Expert Rev Gastroenterol Hepatol, 15, pp.547~554 (2021)
- Anderson C, "Adjuvant therapy for resected extra hepatic cholangiocarcinoma : a review of the literature and future directions", Cancer Treat Rev, 35, pp.322~327 (2009)
- Kim K, "Role of adjuvant radiotherapy in extrahepatic bile duct cancer : a multicenter retrospective study(Korean Radiation Oncology Group 18-14)", Eur J Cancer, 157, pp.31~39 (2021)
- McNamara MG, "Outcome of adjuvant therapy in biliary tract cancers", Am J Clin Oncol, 38, pp.382~387 (2015)
- Krasnick BA, "Adjuvant therapy is associated with impro ved survival after curative resection for hilar cholangiocarci noma : A multi-institution analysis from the U. S. extrahepatic biliary malignancy consortium", J Surg Oncol, 117, pp.363~371 (2018)
- Glazer ES, "Neither neoadjuvant nor adjuvant therapy increases survival after biliary tract cancer resection with wide negative margins", J Gastrointest Surg, 16, pp.1666~1671 (2012)
- Ebata T, "Randomized clinical trial of adjuvant gemcitabine chemotherapy versus observation in resected bile duct can cer", Br J Surg, 105, pp.192~202 (2018)
- Primrose JN, "Capecitabine compared with observation in resected biliary tract cancer(BILCAP) : a randomised, controlled, mul ticentre, phase 3 study", Lancet Oncol, 20, pp.663~673 (2019)
- Shroff RT, "Adjuvant therapy for resected biliary tract cancer : ASCO clinical practice guideline", J Clin Oncol, 37, pp.1015~1027 (2019)
- Bridgewater J, "Long-term outcomes and exploratory analy ses of the randomized phase III BILCAP study", J Clin Oncol, 40, pp.2048~2057 (2022)
- Kim K, "Distant metastasis risk stratification for patients undergoing curative resection followed by adjuvant chemoradiation for extrahepatic bile duct cancer", Int J Radiat Oncol Biol Phys, 84, pp.81~87 (2012)
- Lim KH, "Adju vant concurrent chemoradiation therapy(CCRT)alone versus CCRT followed by adjuvant chemotherapy : which is better in patients with radically resected extrahepatic biliary tract cancer? : a non-randomized, single center study", BMC Cancer, 9, pp.345~ (2009)
- Im JH, "Surgery alone versus surgery followed by chemotherapy and radio therapy in resected extrahepatic bile duct cancer : treatment outcome analysis of 336 patients", Cancer Res Treat, 48, pp.583~595 (2016)
- Ecker BL, "Identification of patients for adjuvant therapy after resection of carcinoma of the extrahepatic bile ducts : a propen sity score-matched analysis", Ann Surg Oncol, 24, pp.3926~3933 (2017)
- Choi SH, "Adju-vant radiotherapy for extrahepatic cholangiocarcinoma : a quality assessment-based meta-analysis", Liver Cancer, 10, pp.419~432 (2021)