Adjuvant radiotherapy for margin-positive vulvar squamous cell carcinoma : Defining the ideal dose-response using the National Cancer Data Base
Menée à partir de données du registre national américain des cancers portant sur 3 075 patientes atteintes d'un carcinome épidermoïde de la vulve traité par chirurgie entre 1998 et 2012 et dont les marges de résection sont positives (âge médian : 66 ans ; durée médiane de suivi : 36,4 mois), cette étude évalue le bénéfice, en termes de survie globale à 3 ans, et la dose optimale de rayonnements d'une radiothérapie adjuvante
Purpose : Positive surgical margin following radical vulvectomy for vulvar cancer portends high risk for local relapse, which may be challenging to salvage. We assessed the impact of adjuvant radiotherapy (aRT) on overall survival (OS) and the dose-response relationship using the National Cancer Data Base. Methods and Materials : Patients with vulvar squamous cell carcinoma who underwent initial extirpative surgery with positive margins from 1998-2012 were included. Factors associated with aRT and specific dose levels were analyzed using logistic regression. Log-rank and multivariable Cox proportional hazards modeling were utilized for OS analysis. Results : We identified 3075 patients with a median age of 66 years (range 22-90); median follow-up was 36.4 months (interquartile range [IQR] 15.4-71.0). 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). Three-year OS improved from 58.5% to 67.4% with aRT (p<0.001). 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<0.001). The unadjusted 3-year OS for dose subsets, 30.0-45.0 Gy, 45.1-53.9 Gy, 54.0-59.9 Gy, and ≥60 Gy, was 54.3, 55.7, 70.1, and 65.3%, respectively (p<0.001). Multivariable analysis using a 4-month conditional landmark revealed the greatest mortality reduction occurred in cumulative doses ≥54 Gy: 45.1-53.9 Gy (HR 0.94, p=0.373), 54.0-59.9 Gy (HR 0.75, p=0.024), ≥60 Gy (HR 0.71, p=0.015). No survival benefit was seen with ≥60 Gy compared to 54.0-59.9 Gy (HR 0.95, p=0.779). Conclusions : 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 54.0-59.9 Gy.