Author/Editor		Kobal, Boris; Noventa, Marco; Cvjetičanin, Branko; Barbič, Matija; Meglič, Leon; Herzog, Maruša; Bordi, Giulia; Vitagliano, Amerigo; Saccardi, Carlo; Škof, Erik
Title		Primary debulking surgery versus primary neoadjuvant chemotherapy for high grade advanced stage ovarian cancer
Type		članek
Vol. and No.		Letnik 52, št. 3
Publication year		2018
Volume		str. 307-319
ISSN		1318-2099 - Radiology and oncology
Language		eng
Abstract		The aim of the study was to analyze the overall survival (OS) and progression free survival (PFS) of patients with high grade and advanced stage epithelial ovarian cancer (EOC) with at least 60 months of follow-up treated in a single gynecologic oncology institute. We compared primary debulking surgery (PDS) versus neoadjuvant chemotherapy plus interval debulking surgery (NACT + IDS) stratifying data based on residual disease with the intent to identify the rationale for therapeutic option decision and the role of laparoscopic evaluation of resectability for that intention. Patients and methods. This is observational retrospective study on consecutive patients with diagnosis of high grade and International Federation of Gynecology and Obstetrics (FIGO) stage III/IV EOC referred to our center between January 2008 and May 2012. We selected only patients with a follow-up of at least 60 months. Primary endpoint was to compare PDS versus NACT + IDS in term of progression free survival (PFS) and overall survival (OS). Secondary endpoints were PFS and OS stratifying data according to residual disease after surgery in patients receiving PDS versus NACT + IDS. Finally, through Cox hazards models, we tested the prognostic value of different variables (patient age at diagnosis, residual disease after debulking, American Society of Anesthesiologists (ASA) stage, number of adjuvantchemotherapy cycles) for predicting OS. Results. A total number of 157 patients were included in data analysis. Comparing PDS arm (108 patients) and NACT + IDS arm (49 patients) we found no significant differences in term of OS (41.3 versus 34.5 months, respectively) and PFS (17.3 versus 18.3 months, respectively). According to residual disease we found no significant differences in term of OS between NACT + IDS patients with residual disease = 0 and PDS patients with residual disease = 0 or residual disease = 1, as well as no significant differences in PFS were found comparing NACT + IDS patients with residual disease = 0 and PDS patients with residual disease = 0; contrarily, median PFS resulted significantly lower in PDS patients receiving optimal debulking (residual disease = 1) in comparison to NACT + IDS patients receiving complete debulking (residual disease = 0). PDS arm was affected by a significant higher rate of severe post-operative complications (grade 3 and 4). Diagnostic laparoscopy before surgery was significantly associated with complete debulking. Conclusions. We confirm previous findings concerning the non-superiority of NACT + IDS compared to PDS for the treatment of EOC, even if NACT + IDS treatment was associated with significant lower rate of post-operative complications. On the other hand, selecting patients for NACT + IDS, based on laparoscopic evaluation of resectabilty prolongs the PFS and does not worse the OS compared to the patients not completely debulked with PDS.Na odločitev o vrsti zdravljenja bolnikov z napredovalim melanomom lahko pomembno vpliva status mutacij v genih za BRAF, NRAS IN c-KIT. Pogostost mutacij in njihove medsebojne povezave s histološkimi značilnostmi tumorskih tkiv na slovenski populaciji do sedaj še niso bili raziskani. Bolniki in metode. Analizo smo izvedli retrospektivno. Mutacije BRAF, NRAS in c-KIT smo določili na 230 patoloških vzorcih bolnikov, ki smo jih nameravali zdraviti s sistemsko terapijo zaradi metastatskega melanoma na Onkološkem Inštitutu Ljubljana med leti 2013 in 2016. Zbrali smo histološke značilnosti primarnih tumorjev in klinične podatke bolnikov ter jih testirali na medsebojno povezanost z mutacijskim statusom. Rezultati. Povprečna starost 230 bolnikov je bila 59 let (razpon 25%85). Moških je bilo 141 (61,3 %) in žensk 89 (38,7 %). Ugotovili smo 129 (56,1 %) mutacij BRAF, 31 (13,5 %) NRAS in 3 (1,3 %) c-KIT mutacij v tkivnih vzorcih. Med 129 bolniki z mutacijami BRAF je imelo 114 (88,4 %) bolnikov mutacijo V600E in 15 (11,6 %) mutacijo V600K. Bolniki z BRAF mutacijami so bili ob diagnozi mlajši (52 v primerjavi s 59 let, p < 0,05), bolniki z NRAS mutacijami starejši (61 v primerjavi s 55 leti, p < 0,05). Število mutacij c-KIT je bilo prenizko za smiselno testiranje na medsebojne povezanosti, je pa bil eden izmed treh melanomov s c-KIT mutacijo melanom sluznice. Zaključki. Rezultati analize so v skupini slovenskih bolnikov z metastatskim melanomom odkrili visok delež mutacij BRAF ter nizek delež mutacij NRAS in c-KIT v primerjavi s predhodno objavljenimi raziskavami v Evropi in Severni Ameriki. Eden od glavnih vzrokov so specifične značilnosti naše študijske populacije, ki niso bile enake kot značilnosti celotne populacije bolnikov z melanomom.
Keywords		epitelijski rak jajčnikov napredovali rak primarna citoredukcijska operacija intervalna citoredukcijska operacija epithelial ovarian cancer advanced stage primary debulking surgery interval debulking surgery