title: Survival outcome of stage I ovarian clear cell carcinoma with lympho-vascular space invasion.
abstract: BACKGROUND
  The clinical impact of lympho-vascular space invasion (LVSI) in early-stage ovarian clear cell carcinoma (OCCC) is not well understood. Given the distinct tumor biology and survival patterns of OCCC, the significance of LVSI on survival outcome and treatment response was examined in OCCC.
  
  
  METHODS
  A multicenter study was conducted to examine stage IA-IC3 OCCC cases that underwent primary surgical staging including lymphadenectomy. LVSI status was determined from archived histopathology slides, correlated with clinico-pathological results, chemotherapy patterns, and survival outcomes.
  
  
  RESULTS
  LVSI was observed in 47 (20.3%) among 232 cases. In univariate analysis, LVSI was associated with older age (p=0.042), large tumor size (p=0.048), and stage IC (p=0.035). In survival analysis, LVSI was associated with decreased disease-free survival (DFS, 5-year rate, 70.6% versus 92.1%, p=0.0004) and overall survival (OS, 78.8% versus 93.3%, p=0.008) on univariate analysis. After controlling for age, tumor size, stage, and chemotherapy use, LVSI remained an independent prognostic factor for decreased survival outcomes (DFS, hazard ratio [HR] 4.35, 95% confidence interval [CI] 1.73-10.9, p=0.002; and OS, HR 4.73, 95%CI 1.60-14.0, p=0.015). Among 210 cases who received postoperative chemotherapy, while regimen type did not impact survival outcome regardless of LVSI status (DFS, p=0.63), the number of administered cycles showed a survival benefit towards ≥6cycles for patients with LVSI-positive tumors (DFS, p=0.009; and OS, p=0.016).
  
  
  CONCLUSIONS
  LVSI is an important marker to predict survival outcome of stage I OCCC. Regardless of chemotherapy type, patients with stage I OCCC showing LVSI may benefit from receiving postoperative chemotherapy.
authors.affiliation: Gynecologic Oncology, Obstetrics and Gynecology, Los Angeles County Medical Center, University of Southern California, Los Angeles, CA, USA; Norris Comprehensive Cancer Center, Los Angeles, CA, USA. Electronic address: koji.matsuo@gmail.com.
authors.forename: Koji
authors.initials: K
authors.lastname: Matsuo
authors.affiliation: Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yoshino
authors.affiliation: Gynecologic Oncology, Saitama Medical University International Medical Center, Japan.
authors.forename: Kosei
authors.initials: K
authors.lastname: Hasegawa
authors.affiliation: Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Japan.
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Murakami
authors.affiliation: Gynecologic Oncology, Saitama Medical University International Medical Center, Japan; Obstetrics and Gynecology, The University of Tokyo Faculty of Medicine, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ikeda
authors.affiliation: Obstetrics and Gynecology, Niigata University Graduate School of Medicine, Niigata, Japan.
authors.forename: Sosuke
authors.initials: S
authors.lastname: Adachi
authors.affiliation: Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Hiramatsu
authors.affiliation: Obstetrics and Gynecology, Osaka Rosai Hospital, Japan.
authors.forename: Takuhei
authors.initials: T
authors.lastname: Yokoyama
authors.affiliation: Obstetrics and Gynecology, Tokushima University Graduate School of Medicine, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Nishimura
authors.affiliation: Pathology, Mercy Medical Center Baltimore, MD, USA.
authors.forename: Todd B
authors.initials: TB
authors.lastname: Sheridan
authors.affiliation: Obstetrics and Gynecology, Niigata University Graduate School of Medicine, Niigata, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Enomoto
authors.affiliation: Gynecologic Oncology, Saitama Medical University International Medical Center, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fujiwara
authors.affiliation: Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Japan.
authors.forename: Noriomi
authors.initials: N
authors.lastname: Matsumura
authors.affiliation: Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Konishi
authors.affiliation: Obstetrics and Gynecology, Imperial College of London, London, UK.
authors.forename: Christina
authors.initials: C
authors.lastname: Fotopoulou
authors.affiliation: Gynecologic Oncology, Obstetrics and Gynecology, Los Angeles County Medical Center, University of Southern California, Los Angeles, CA, USA; Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
authors.forename: Lynda D
authors.initials: LD
authors.lastname: Roman
authors.affiliation: Gynecologic Oncology, MD-Anderson Cancer Center, University of Texas, Houston, TX, USA; Center for RNA Interference and Non-Coding RNA, University of Texas, Houston, TX, USA.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
mesh_terms: D018262:Adenocarcinoma, Clear Cell; D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D006801:Humans; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000473:pathology* / Q000601:surgery; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000473:pathology* / Q000601:surgery; D010051:Ovarian Neoplasms / Q000473:pathology* / Q000601:surgery; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome
keywords: Clear cell carcinoma; Lymphovascular space invasion; Ovarian cancer; Postoperative chemotherapy