Tjalling Bosse1, Elke E M Peters1, Carien L Creutzberg2, Ina M Jürgenliemk-Schulz3, Jan J Jobsen4, Jan Willem M Mens5, Ludy C H W Lutgens6, Elzbieta M van der Steen-Banasik7, Vincent T H B M Smit1, Remi A Nout8. 1. Department of Pathology, Leiden University Medical Center, The Netherlands. 2. Department of Radiotherapy, Leiden University Medical Center, The Netherlands. 3. Department of Radiation Oncology, University Medical Center Utrecht, The Netherlands. 4. Department of Radiotherapy, Medisch Spectrum Twente, Enschede, The Netherlands. 5. Department of Radiation Oncology, Erasmus MC - Daniel den Hoed Cancer Center, Rotterdam, The Netherlands. 6. MAASTtricht Radiation Oncology Clinic, The Netherlands. 7. Arnhems Radiotherapeutisch Instituut, ARTI, Arnhem, The Netherlands. 8. Department of Radiotherapy, Leiden University Medical Center, The Netherlands. Electronic address: r.a.nout@lumc.nl.
Abstract
BACKGROUND: Lymph-vascular space invasion (LVSI) is an important adverse prognostic factor in endometrial cancer (EC). However, its role in relation to type of recurrence and adjuvant treatment is not well defined, and there is significant interobserver variation. This study aimed to quantify LVSI and correlate this to risk and type of recurrence. METHODS: In the post operative radiation therapy in endometrial carcinoma (PORTEC)-trials stage I EC patients were randomised to receive external beam radiotherapy (EBRT) versus no additional treatment after surgery (PORTEC-1, n=714), or to EBRT versus vaginal brachytherapy (PORTEC-2, n=427). In tumour samples of 926 (81.2%) patients with endometrioid tumours LVSI was quantified using 2-, 3- and 4-tiered scoring systems. Cox proportional hazard models were used for time-to-event analysis. RESULTS: Any degree of LVSI was identified in 129 cases (13.9%). Substantial LVSI (n=44, 4.8%) using the 3-tiered approach had the strongest impact on the risk of distant metastasis (hazard ratio (HR) 4.5 confidence interval (CI) 2.4-8.5). In multivariate analysis (including: age, depth of myometrial invasion, grade, treatment) substantial LVSI remained the strongest independent prognostic factor for pelvic regional recurrence (HR 6.2 CI 2.4-16), distant metastasis (HR 3.6 CI 1.9-6.8) and overall survival (HR 2.0 CI 1.3-3.1). Only EBRT (HR 0.3 CI 0.1-0.8) reduced the risk of pelvic regional recurrence. CONCLUSIONS: Substantial LVSI, in contrast to focal or no LVSI, was the strongest independent prognostic factor for pelvic regional recurrence, distant metastasis and overall survival. Therapeutic decisions should be based on the presence of substantial, not 'any' LVSI. Adjuvant EBRT and/or chemotherapy should be considered for stage I EC with substantial LVSI.
RCT Entities:
BACKGROUND: Lymph-vascular space invasion (LVSI) is an important adverse prognostic factor in endometrial cancer (EC). However, its role in relation to type of recurrence and adjuvant treatment is not well defined, and there is significant interobserver variation. This study aimed to quantify LVSI and correlate this to risk and type of recurrence. METHODS: In the post operative radiation therapy in endometrial carcinoma (PORTEC)-trials stage I EC patients were randomised to receive external beam radiotherapy (EBRT) versus no additional treatment after surgery (PORTEC-1, n=714), or to EBRT versus vaginal brachytherapy (PORTEC-2, n=427). In tumour samples of 926 (81.2%) patients with endometrioid tumours LVSI was quantified using 2-, 3- and 4-tiered scoring systems. Cox proportional hazard models were used for time-to-event analysis. RESULTS: Any degree of LVSI was identified in 129 cases (13.9%). Substantial LVSI (n=44, 4.8%) using the 3-tiered approach had the strongest impact on the risk of distant metastasis (hazard ratio (HR) 4.5 confidence interval (CI) 2.4-8.5). In multivariate analysis (including: age, depth of myometrial invasion, grade, treatment) substantial LVSI remained the strongest independent prognostic factor for pelvic regional recurrence (HR 6.2 CI 2.4-16), distant metastasis (HR 3.6 CI 1.9-6.8) and overall survival (HR 2.0 CI 1.3-3.1). Only EBRT (HR 0.3 CI 0.1-0.8) reduced the risk of pelvic regional recurrence. CONCLUSIONS: Substantial LVSI, in contrast to focal or no LVSI, was the strongest independent prognostic factor for pelvic regional recurrence, distant metastasis and overall survival. Therapeutic decisions should be based on the presence of substantial, not 'any' LVSI. Adjuvant EBRT and/or chemotherapy should be considered for stage I EC with substantial LVSI.
Authors: A Stiekema; Car Lok; C M Korse; W J van Driel; V van der Noort; G G Kenter; K K Van de Vijver Journal: Virchows Arch Date: 2017-04-11 Impact factor: 4.064
Authors: Yushen Qian; Erqi L Pollom; Chika Nwachukwu; Kira Seiger; Rie von Eyben; Ann K Folkins; Elizabeth A Kidd Journal: Gynecol Oncol Date: 2017-07-11 Impact factor: 5.482
Authors: Marina Frimer; Eirwen M Miller; Viswanathan Shankar; Eugenia Girda; Keyur Mehta; Harriet O Smith; Dennis Y S Kuo; Gary L Goldberg; Mark H Einstein Journal: Int J Gynecol Cancer Date: 2018-11 Impact factor: 3.437
Authors: Francesco Multinu; Simone Garzon; Amy L Weaver; Michaela E McGree; Enrico Sartori; Fabio Landoni; Paolo Zola; Giorgia Dinoi; Giovanni Aletti; Matthew S Block; Angiolo Gadducci; Andrea Mariani Journal: Int J Gynecol Cancer Date: 2021-02-19 Impact factor: 3.437
Authors: Anna L Beavis; Ting-Tai Yen; Rebecca L Stone; Stephanie L Wethington; Caitlin Carr; Ji Son; Laura Chambers; Chad M Michener; Stephanie Ricci; Wesley C Burkett; Debra L Richardson; Allison-Stuart Staley; Susie Ahn; Paola A Gehrig; Diogo Torres; Sean C Dowdy; Mackenzie W Sullivan; Susan C Modesitt; Catherine Watson; Ashely Veade; Jessie Ehrisman; Laura Havrilesky; Angeles Alvarez Secord; Amy Loreen; Kaitlyn Griffin; Amanda Jackson; Akila N Viswanathan; Leah R Jager; Amanda N Fader Journal: Gynecol Oncol Date: 2020-01-14 Impact factor: 5.482