Impact of Tumor Size, Shape and Patterns of Response to Chemoradiation in Locally Advanced Cervical Cancer Patients

Abstract

To study the evolution of tumor size, shape and its prognostic value in a large cohort of cervical cancer patients receiving definitive chemoradiotherapy plus image—guided adaptive brachytherapy (IGABT). Clinical records of consecutive patients treated in our Institution between February 2004 and November 2015 by concurrent chemoradiotherapy (45Gy in 25 fractions +/- lymph node boosts) followed by a magnetic resonance imaging (MRI)-guided adaptive pulse-dose rate brachytherapy were included. The evolution of tumor volume, size, and shape and its prognostic value after chemoradiotherapy were examined. Measurements of tumor volume were performed on MRI scans at time of diagnosis and at brachytherapy (T2-weighted sequence). All measures and measurement cutoff were selected using time-dependent Area Under the Curve for 3-year progression-free survival (PFS). Tumor evolution between diagnosis and the time of brachytherapy was assessed in 247 patients with FIGO ≥ 2B tumors in 68% patients. After chemoradiotherapy, complete response was observed in 75 patients (28%). Patients with a wider than high tumor at diagnosis (p<0.001) or at the time of brachytherapy (p<0.001) had poorer overall survival (OS) and PFS (p<0.001). Estimated 5-year- local control (LC) was 24% (95%CI: 16 - 37) vs. 94% (95%CI: 89 - 98) in patients without or with tumor width ≥ 25mm at brachytherapy. D90 high-risk clinical target volume (HR-CTV) was significantly correlated with tumor width at brachytherapy (p<0.001, r=-0.28). Patients with a wider than high tumor shape (axial and sagittal measurement) at diagnosis also exhibited a lower volumetric response rate (p<0.001). Reduction in tumor width was significantly associated with an OS benefit, optimal cutoff was 50% reduction (p<0.001). Patients with neutrophilia at diagnosis had a lower tumor width response rate (p<0.001). Considering tumor evolution, a wider than high tumor shape that modified into a higher tumor after chemoradiotherapy was associated with an improved OS, PFS and LC as compared to a higher tumor that became a wider tumor after chemoradiotherapy (p<0.001). In multivariate analysis, incorporating the FIGO, N+ stage, neutrophilia, anemia, and HR-CTV coverage above 80Gy, both the tumor shape (higher than wide) at diagnosis and the tumor width optimal reduction after chemoradiotherapy were independently associated with improved OS and PFS. In patients undergoing chemoradiotherapy and IGABT for locally-advanced cervical cancer, tumor shape and its evolution over treatment is strongly associated with OS and PFS.