title: Extended field intensity modulated radiation therapy with concomitant boost for lymph node-positive cervical cancer: analysis of regional control and recurrence patterns in the positron emission tomography/computed tomography era.
abstract: OBJECTIVE
  Positron emission tomography/computed tomography (PET/CT) is commonly used for nodal staging in locally advanced cervical cancer; however the false negative rate for para-aortic disease are 20% to 25% in PET-positive pelvic nodal disease. Unless surgically staged, pelvis-only treatment may undertreat para-aortic disease. We have treated patients with PET-positive nodes with extended field intensity modulated radiation therapy (IMRT) to address the para-aortic region prophylactically with concomitant boost to involved nodes. The purpose of this study was to assess regional control rates and recurrence patterns.
  
  
  METHODS
  Sixty-one patients with cervical cancer (stage IBI-IVA) diagnosed from 2003 to 2012 with PET-avid pelvic nodes treated with extended field IMRT (45 Gy in 25 fractions with concomitant boost to involved nodes to a median of 55 Gy in 25 fractions) with concurrent cisplatin and brachytherapy were retrospectively analyzed. The nodal location was pelvis-only in 41 patients (67%) and pelvis + para-aortic in 20 patients (33%). There were a total of 179 nodes, with a median number of positive nodes of 2 (range, 1-16 nodes) per patient and a median nodal size of 1.8 cm (range, 0.7-4.5 cm). Response was assessed by PET/CT at 12 to 16 weeks.
  
  
  RESULTS
  Complete clinical and imaging response at the first follow-up visit was seen in 77% of patients. At a mean follow-up time of 29 months (range, 3-116 months), 8 patients experienced recurrence. The sites of persistent/recurrent disease were as follows: cervix 10 (16.3%), regional nodes 3 (4.9%), and distant 14 (23%). The rate of para-aortic failure in patients with pelvic-only nodes was 2.5%. There were no significant differences in recurrence patterns by the number/location of nodes, largest node size, or maximum node standardized uptake value. The rate of late grade 3+ adverse events was 4%.
  
  
  CONCLUSIONS
  Extended field IMRT was well tolerated and resulted in low regional recurrence in node-positive cervical cancer. The dose of 55 Gy in 25 fractions was effective in eradicating disease in involved nodes, with acceptable late adverse events. Distant metastasis is the predominant mode of failure, and the OUTBACK trial may challenge the presented paradigms.
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors.forename: John A
authors.initials: JA
authors.lastname: Vargo
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors.forename: Hayeon
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors.forename: Serah
authors.initials: S
authors.lastname: Choi
authors.affiliation: Department of Gynecologic Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors.forename: Paniti
authors.initials: P
authors.lastname: Sukumvanich
authors.affiliation: Department of Gynecologic Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors.forename: Alexander B
authors.initials: AB
authors.lastname: Olawaiye
authors.affiliation: Department of Gynecologic Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Kelley
authors.affiliation: Department of Gynecologic Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Edwards
authors.affiliation: Department of Gynecologic Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors.forename: John T
authors.initials: JT
authors.lastname: Comerci
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania. Electronic address: beriwals@upmc.edu.
authors.forename: Sushil
authors.initials: S
authors.lastname: Beriwal
mesh_terms: D000328:Adult; D000368:Aged; D001011:Aorta; D059248:Chemoradiotherapy / Q000379:methods*; D018450:Disease Progression; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000000981:diagnostic imaging / Q000473:pathology; D015182:Lymphatic Irradiation / Q000379:methods*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D064847:Multimodal Imaging / Q000379:methods*; D009364:Neoplasm Recurrence, Local; D058958:Organs at Risk / Q000528:radiation effects; D010388:Pelvis; D049268:Positron-Emission Tomography / Q000379:methods*; D011832:Radiation Injuries / Q000473:pathology; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed / Q000379:methods; D002583:Uterine Cervical Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D055815:Young Adult