title: Adjuvant Radiation Therapy for Margin-Positive Vulvar Squamous Cell Carcinoma: Defining the Ideal Dose-Response Using the National Cancer Data Base.
abstract: Positive surgical margins after radical vulvectomy for vulvar cancer portend a high risk for local relapse, which may be challenging to salvage. We assessed the impact of adjuvant radiation therapy (aRT) on overall survival (OS) and the dose-response relationship using the National Cancer Data Base.
  
  
  
  Patients with vulvar squamous cell carcinoma who underwent initial extirpative surgery with positive margins from 1998 to 2012 were included. Factors associated with aRT and specific dose levels were analyzed using logistic regression. Log-rank and multivariable Cox proportional hazards modeling were used for OS analysis.
  
  
  
  We identified 3075 patients with a median age of 66 years (range, 22-90 years); the median follow-up time was 36.4 months (interquartile range [IQR] 15.4-71.0 months). Stage IA/B disease represented 41.2% of the cohort. Sixty-three percent underwent lymph node assessment, with a 45% positivity rate. In total, 1035 patients (35.3%) received aRT, with a median dose of 54.0 Gy (IQR 48.6-60.0 Gy). The 3-year OS improved from 58.5% to 67.4% with aRT (P<.001). On multivariable analysis, age, Charlson-Deyo score ≥1, stage ≥II, tumors ≥4 cm, no aRT, and adverse nodal characteristics led to inferior survival. Dose of aRT was positively associated with OS as a continuous variable on univariate analysis (P<.001). The unadjusted 3-year OS for dose subsets 30.0 to 45.0 Gy, 45.1 to 53.9 Gy, 54.0 to 59.9 Gy, and ≥60 Gy was 54.3%, 55.7%, 70.1%, and 65.3%, respectively (P<.001). Multivariable analysis using a 4-month conditional landmark revealed that the greatest mortality reduction occurred in cumulative doses ≥54 Gy: 45.1 to 53.9 Gy (hazard ratio [HR] 0.94, P=.373), 54.0 to 59.9 Gy (HR 0.75, P=.024), ≥60 Gy (HR 0.71, P=.015). No survival benefit was seen with ≥60 Gy compared with 54.0 to 59.9 Gy (HR 0.95, P=.779).
  
  
  
  Patients with vulvar squamous cell carcinoma and positive surgical margins derive an OS benefit from aRT with a seemingly optimal dose in the range of 54.0 to 59.9 Gy.
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors.forename: Bhavana V
authors.initials: BV
authors.lastname: Chapman
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors.forename: Beant S
authors.initials: BS
authors.lastname: Gill
authors.affiliation: Department of Radiation Oncology Molecular Radiation Sciences, Johns Hopkins University, Baltimore, MD.
authors.forename: Akila N
authors.initials: AN
authors.lastname: Viswanathan
authors.affiliation: Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Goundappa K
authors.initials: GK
authors.lastname: Balasubramani
authors.affiliation: Department of Gynecologic Oncology, Magee-Womens Hospital of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Paniti
authors.initials: P
authors.lastname: Sukumvanich
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; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000401:mortality* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D016208:Databases, Factual; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D000072662:Margins of Excision; D008875:Middle Aged; D015233:Models, Statistical; D018714:Radiotherapy, Adjuvant / Q000401:mortality; D016019:Survival Analysis; D013997:Time Factors; D014846:Vulvar Neoplasms / Q000401:mortality* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery