title: Neoadjuvant radiotherapy with or without chemotherapy followed by extrafascial hysterectomy for locally advanced endometrial cancer clinically extending to the cervix or parametria.
abstract: OBJECTIVE
  For locally-advanced uterine cancer clinically extending to the cervix, two treatment paradigms exist: surgical staging radical hysterectomy with tailored adjuvant therapy or neoadjuvant therapy followed by a less extensive simple hysterectomy. Currently, insufficient data exists to guide consensus guidelines and practical application of preoperative radiotherapy.
  
  
  METHODS
  Retrospective IRB approved cohort study from 1999 to 2014 of 36 endometrial cancer patients with clinical involvement of cervix±parametria treated with neoadjuvant external beam radiotherapy (45-50.4Gy in 25-28 fractions) and image-based HDR brachytherapy (5-5.5Gy times 3-4 fractions)±chemotherapy followed by extrafascial hysterectomy performed at a median of 6weeks after radiotherapy.
  
  
  RESULTS
  All patients had clinical cervical extension, 50% also had parametria extension, and 31% had nodal involvement. At the time of surgery 91% had no clinical cervical involvement, 58% had no pathologic cervical involvement, and all had margin negative resection. The pathologic complete response rate was 24%. Median follow-up from the time of surgery was 20months (range: 0-153). The 3-year local control, regional control, distant control, disease free survival and overall survival rates were 96%, 89%, 84%, 73%, and 100%. The 3-year rate of grade 3 complications was 11%, with no grade 4+ toxicity.
  
  
  CONCLUSIONS
  Neoadjuvant radiation therapy±chemotherapy followed by extrafascial hysterectomy appears to be a viable option for patients with endometrial cancer clinically extending to the cervix and parametria. The HDR brachytherapy schema of 5-5.5Gy times 3-4 fractions, for a cumulative EQD2 of 60-70Gy, is well tolerated with high rates of clinical and pathological response.
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Vargo
authors.affiliation: Department of Gynecology Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Boisen
authors.affiliation: Department of Gynecology Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Comerci
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors.forename: Hayeon
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Houser
authors.affiliation: Department of Gynecology Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors.forename: Paniti
authors.initials: P
authors.lastname: Sukumvanich
authors.affiliation: Department of Gynecology Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors.forename: Alexander B
authors.initials: AB
authors.lastname: Olawaiye
authors.affiliation: Department of Gynecology Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Kelley
authors.affiliation: Department of Gynecology Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Edwards
authors.affiliation: Department of Gynecology Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors.forename: Marilyn
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Gynecology Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Courtney-Brooks
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA. Electronic address: beriwals@upmc.edu.
authors.forename: Sushil
authors.initials: S
authors.lastname: Beriwal
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D018262:Adenocarcinoma, Clear Cell / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D000231:Adenocarcinoma, Papillary / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D000328:Adult; D000368:Aged; D001918:Brachytherapy / Q000379:methods; D018269:Carcinoma, Endometrioid / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D002584:Cervix Uteri / Q000473:pathology; D059186:Chemoradiotherapy, Adjuvant; D015331:Cohort Studies; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D007044:Hysterectomy; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D017773:Pelvic Floor / Q000473:pathology; D018714:Radiotherapy, Adjuvant / Q000379:methods; D061089:Radiotherapy, Image-Guided / Q000379:methods; D012189:Retrospective Studies; D016896:Treatment Outcome
keywords: Cervix; Endometrial cancer; Extrafascial hysterectomy; Preoperative HDR brachytherapy; Stage II; Stage III