title: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for the treatment of advanced epithelial ovarian carcinoma: upfront therapy, at first recurrence, or later?
abstract: OBJECTIVE
  Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) has been proposed as treatment for advanced epithelial ovarian carcinoma (EOC). No consensus exists on when to administer CRS+HIPEC during the natural history of the disease, namely, as upfront therapy, at first recurrence, or at second or subsequent recurrence.
  
  
  METHODS
  We analyzed a series of patients with advanced EOC collected prospectively in an institution with a peritoneal malignant disease treatment program. Patients were treated with CRS+HIPEC upfront, at first recurrence, and at second or subsequent recurrence.
  
  
  RESULTS
  We treated 42 patients: 15 upfront, 19 at first recurrence, and 8 at second or subsequent recurrence. Cytoreduction was complete (CC0) in 75% of cases; residual disease was <2.5 mm (CC1) in 25%. Severe morbidity (CTCAE v.3.0, grade 3-4) was 26%, and hospital mortality was 7%. After a median follow-up of 24 months, median overall survival was 77.8 months for patients treated upfront, 62.8 months for patients treated at first recurrence, and 35.7 months for patients treated at second or subsequent recurrence. Disease-free survival was 21.1 months, 18 months, and 5.7 months, respectively. Overall survival in the upfront and first recurrence groups was similar, and statistically significant differences with the second recurrence group were identified (p<0.03).
  
  
  CONCLUSIONS
  Treatment of advanced EOC using CRS+HIPEC is promising in terms of overall survival and disease-free survival when administered as upfront and at first recurrence therapy. These results warrant further evaluation in a randomized trial.
authors.affiliation: Peritoneal Carcinomatosis Program, General Surgery Unit III, Hospital General Universitario Gregorio Marañón, C/Doctor Esquerdo 46, 28007 Madrid, Spain. Electronic address: lgonzalezb.hgugm@salud.madrid.org.
authors.forename: L
authors.initials: L
authors.lastname: Gonzalez Bayon
authors.forename: M A
authors.initials: MA
authors.lastname: Steiner
authors.forename: W
authors.initials: W
authors.lastname: Vasquez Jimenez
authors.forename: J M
authors.initials: JM
authors.lastname: Asencio
authors.forename: P
authors.initials: P
authors.lastname: Alvarez de Sierra
authors.forename: F
authors.initials: F
authors.lastname: Atahualpa Arenas
authors.forename: J
authors.initials: J
authors.lastname: Rodriguez del Campo
authors.forename: J L
authors.initials: JL
authors.lastname: Garcia Sabrido
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000077216:Carcinoma, Ovarian Epithelial; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D007274:Injections, Intraperitoneal; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D011446:Prospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
keywords: Advanced epithelial ovarian carcinoma; Cytoreductive surgery; First recurrence therapy; Hyperthermic intraperitoneal chemotherapy; Second or subsequent recurrence therapy; Upfront therapy