Xu-Feng Zhang1,2, Eliza W Beal2, Jeffery Chakedis2, Qinyu Chen2, Yi Lv1, Cecilia G Ethun3, Ahmed Salem4, Sharon M Weber4, Thuy Tran5, George Poultsides5, Andre Y Son6, Ioannis Hatzaras6, Linda Jin7, Ryan C Fields7, Stefan Buettner8, Charles Scoggins9, Robert C G Martin9, Chelsea A Isom10, Kamron Idrees10, Harveshp D Mogal11, Perry Shen11, Shishir K Maithel3, Carl R Schmidt2, Timothy M Pawlik12,13. 1. Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. 2. Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, The Ohio State University Wexner Medical Center, Columbus, OH, USA. 3. Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA. 4. Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. 5. Department of Surgery, Stanford University Medical Center, Stanford, CA, USA. 6. Department of Surgery, New York University, New York, NY, USA. 7. Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA. 8. Division of Surgical Oncology, Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA. 9. Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, KY, USA. 10. Division of Surgical Oncology, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA. 11. Department of Surgery, Wake Forest University, Winston-Salem, NC, USA. 12. Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, The Ohio State University Wexner Medical Center, Columbus, OH, USA. tim.pawlik@osumc.edu. 13. Surgery, Oncology, Health Services Management and Policy, The Ohio State University Wexner Medical Center, 395 W. 12th Ave., Suite 670, Columbus, OH, USA. tim.pawlik@osumc.edu.
Abstract
BACKGROUND: Time to tumor recurrence may be associated with outcomes following resection of hepatobiliary cancers. The objective of the current study was to investigate risk factors and prognosis among patients with early versus late recurrence of hilar cholangiocarcinoma (HCCA) after curative-intent resection. METHODS: A total of 225 patients who underwent curative-intent resection for HCCA were identified from 10 academic centers in the USA. Data on clinicopathologic characteristics, pre-, intra-, and postoperative details and overall survival (OS) were analyzed. The slope of the curves identified by linear regression was used to categorize recurrences as early versus late. RESULTS: With a median follow-up of 18.0 months, 99 (44.0%) patients experienced a tumor recurrence. According to the slope of the curves identified by linear regression, the functions of the two straight lines were y = -0.465x + 16.99 and y = -0.12x + 7.16. The intercept value of the two lines was 28.5 months, and therefore, 30 months (2.5 years) was defined as the cutoff to differentiate early from late recurrence. Among 99 patients who experienced recurrence, the majority (n = 80, 80.8%) occurred within the first 2.5 years (early recurrence), while 19.2% of recurrences occurred beyond 2.5 years (late recurrence). Early recurrence was more likely present as distant disease (75.1% vs. 31.6%, p = 0.001) and was associated with a worse OS (Median OS, early 21.5 vs. late 50.4 months, p < 0.001). On multivariable analysis, poor tumor differentiation (HR 10.3, p = 0.021), microvascular invasion (HR 3.3, p = 0.037), perineural invasion (HR 3.9, p = 0.029), lymph node metastases (HR 5.0, p = 0.004), and microscopic positive margin (HR 3.5, p = 0.046) were independent risk factors associated with early recurrence. CONCLUSIONS: Early recurrence of HCCA after curative resection was common (~35.6%). Early recurrence was strongly associated with aggressive tumor characteristics, increased risk of distant metastatic recurrence and a worse long-term survival.
BACKGROUND: Time to tumor recurrence may be associated with outcomes following resection of hepatobiliary cancers. The objective of the current study was to investigate risk factors and prognosis among patients with early versus late recurrence of hilar cholangiocarcinoma (HCCA) after curative-intent resection. METHODS: A total of 225 patients who underwent curative-intent resection for HCCA were identified from 10 academic centers in the USA. Data on clinicopathologic characteristics, pre-, intra-, and postoperative details and overall survival (OS) were analyzed. The slope of the curves identified by linear regression was used to categorize recurrences as early versus late. RESULTS: With a median follow-up of 18.0 months, 99 (44.0%) patients experienced a tumor recurrence. According to the slope of the curves identified by linear regression, the functions of the two straight lines were y = -0.465x + 16.99 and y = -0.12x + 7.16. The intercept value of the two lines was 28.5 months, and therefore, 30 months (2.5 years) was defined as the cutoff to differentiate early from late recurrence. Among 99 patients who experienced recurrence, the majority (n = 80, 80.8%) occurred within the first 2.5 years (early recurrence), while 19.2% of recurrences occurred beyond 2.5 years (late recurrence). Early recurrence was more likely present as distant disease (75.1% vs. 31.6%, p = 0.001) and was associated with a worse OS (Median OS, early 21.5 vs. late 50.4 months, p < 0.001). On multivariable analysis, poor tumor differentiation (HR 10.3, p = 0.021), microvascular invasion (HR 3.3, p = 0.037), perineural invasion (HR 3.9, p = 0.029), lymph node metastases (HR 5.0, p = 0.004), and microscopic positive margin (HR 3.5, p = 0.046) were independent risk factors associated with early recurrence. CONCLUSIONS: Early recurrence of HCCA after curative resection was common (~35.6%). Early recurrence was strongly associated with aggressive tumor characteristics, increased risk of distant metastatic recurrence and a worse long-term survival.
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