title: Operability and chemotherapy responsiveness in advanced low-grade serous ovarian cancer. An analysis of the AGO Study Group metadatabase.
abstract: OBJECTIVE
  Since almost two decades standard 1st-line chemotherapy for advanced ovarian cancer (AOC) has been a platinum/taxane combination. More recently, this general strategy has been challenged because different types of AOC may not benefit homogenously. Low-grade serous ovarian cancer (LGSOC) is one of the candidates in whom efficacy of standard chemotherapy should be revised.
  
  
  METHODS
  This study is an exploratory case control study of the AGO-metadatabase of 4 randomized phase III trials with first-line platinum combination chemotherapy without any targeted therapy. Patients with advanced FIGO IIIBIV low-grade serous ovarian cancer were included and compared with control cases having high-grade serous AOC.
  
  
  RESULTS
  Out of 5114 patients in this AGO database 145 (2.8%) had LGSOC and of those thirty-nine (24.1%) had suboptimal debulking with post-operative residual tumor >1cm, thus being eligible for response evaluation. An objective response was observed in only 10 patients and this 23.1% response rate (RR) was significantly lower compared to 90.1% RR in the control cohort of high-grade serous ovarian cancer (HGSOC) (p<0.001). Both, LGSOC and HGSOC patients who underwent complete cytoreduction had significantly better progression free survival (PFS) and overall survival (OS) in comparison to those with residuals after primary surgery, accordingly (p<0.001).
  
  
  CONCLUSIONS
  Our observation indicates that low-grade serous cancer is not as responsive to platinum-taxane-based chemotherapy as high-grade serous AOC. In contrast, surgical debulking showed a similar impact on outcome in both types of AOC thus indicating different roles for both standard treatment modalities. Systemic treatment of low grade serous AOC urgently warrants further investigations.
authors.affiliation: Department of Gynecology and Gynecological Oncology, Kliniken Essen Mitte, Henricistrasse 92, 45136 Essen, Germany; Department of Gynecology, European Competence Center for Ovarian Cancer, Charite-University Medicine of Berlin, Augustenberger Platz 1, 13353 Berlin, Germany. Electronic address: jacgrab@yahoo.com.
authors.forename: Jacek P
authors.initials: JP
authors.lastname: Grabowski
authors.affiliation: Department of Gynecology and Gynecological Oncology, Kliniken Essen Mitte, Henricistrasse 92, 45136 Essen, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Harter
authors.affiliation: Department of Gynecology and Gynecological Oncology, Kliniken Essen Mitte, Henricistrasse 92, 45136 Essen, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Heitz
authors.affiliation: Group d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO), Oncology Department, Universite Paris Descartes, AP-HP, Hopitaux Universitaires Paris Centre, Site Hotel Dieu, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Pujade-Lauraine
authors.affiliation: Koordinierungszentrum fuer Klinische Studien, Philipps-Universitaet Marburg, Karl-von-Frisch-Str. 4, 35043 Marburg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Reuss
authors.affiliation: Nordic Society of Gynaecological Oncology Group (NSGO), Department of Gynecologic Oncology, Norwegian Radium Hospital, Oslo University Hospital, PB4953 Nydalen, 0424 Oslo, Norway.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Kristensen
authors.affiliation: Group d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO), Université de Lyon-Centre Léon Bérard, Department of Medical Oncology and EA SIS, 4128 Lyon, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ray-Coquard
authors.affiliation: Department of Gynecology and Obstetrics, Klinikum Duisburg, Zu den Rehwiesen 9-11, 47055 Duisburg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Heitz
authors.affiliation: Department of Gynecology and Gynecological Oncology, Kliniken Essen Mitte, Henricistrasse 92, 45136 Essen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Traut
authors.affiliation: Gynecologic Oncology Center, Kiel, Herzog-Friedrich-Str. 21, 24103 Kiel, Germany.
authors.forename: Jacobus
authors.initials: J
authors.lastname: Pfisterer
authors.affiliation: Department of Gynecology and Gynecological Oncology, Kliniken Essen Mitte, Henricistrasse 92, 45136 Essen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: du Bois
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D016022:Case-Control Studies; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D017326:Clinical Trials, Phase III as Topic; D065426:Cytoreduction Surgical Procedures; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D018365:Neoplasm, Residual; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000473:pathology* / Q000628:therapy*; D010051:Ovarian Neoplasms / Q000473:pathology* / Q000628:therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D015996:Survival Rate; D019772:Topotecan / Q000008:administration & dosage; D016896:Treatment Outcome; D055815:Young Adult; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D015251:Epirubicin; D019772:Topotecan; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin; D000093542:Gemcitabine
keywords: High-grade serous ovarian cancer; Low-grade serous ovarian cancer; Objective response; Platinum chemotherapy