Tumor Shrinkage During Chemoradiation in Locally Advanced Cervical Cancer Patients: Prognostic Significance, and Impact for Image-Guided Adaptive Brachytherapy

Purpose: To study the prognostic value of gross tumor volume (GTV) shrinkage and its dosimetric implication in a large cohort of patients with cervical cancer receiving definitive chemoradiotherapy plus image guided adaptive brachytherapy. Methods and Materials: Clinical records of consecutive patients treated in our institution between February 2004 and November 2015 by concurrent chemoradiotherapy (45 Gy in 25 fractions +/- lymph node boosts) followed by a magnetic resonance imaging-guided adaptive pulse-dose rate brachytherapy were included. The prognostic value of GTV and its evolution after chemoradiotherapy were examined first on initial staging magnetic resonance imaging and then at time of brachytherapy. All measures and measurement cutoffs were selected using time-dependent area under the curve for 3-year progression-free survival (PFS). Results: GTV evolution between diagnosis and the time of brachytherapy was assessed in 247 patients. After chemoradiotherapy, complete response was observed in 75 patients (28%). Optimal cutoffs were GTV=55 cm(3) at diagnosis, GTV=7.5 cm(3) at brachytherapy, and GTV reduction >= 90%. All patients with volume above or reduction below these cutoffs had significant reduced overall survival, PFS, local control, and distant metastasis control (P <.001). Patients with anemia at diagnosis had a lower tumor volume response rate (P <.001). In multivariate analysis, incorporating the International Federation of Gynecology and Obstetrics stage, N+ stage, anemia, and dosimetric parameters for image guided adaptive brachytherapy, GTVoptimal volume reduction after chemoradiotherapy was independently associated with improved overall survival, PFS, local control, and distant metastasis control (P <.001). Conclusions: These results could provide a rationale for dose de-escalation studies in brachytherapy for patients displaying optimal GTV volumetric reduction after chemoradiotherapy and may reinforce the need for dose escalation in poorly responding patients. (C) 2018 Elsevier Inc. All rights reserved.