Quantifying Radiation Induced Vaginal Stenosis for the Development of a Novel Dilator Device: A Prospective Cohort Study of Patients with Cervical Cancer Treated with Definitive Chemoradiation Therapy

Abstract

Chemoradiation therapy (CRT) is the standard of care for the treatment of locally advanced cervical cancer (LACC). Vaginal stenosis (VS) is a common side effect of CRT and leads to sexual dysfunction, pain, and difficulty with vaginal intercourse, resulting in decreasing quality-of-life (QOL). However, there is scant data on the timeline of VS development, and patient use and satisfaction with a standard vaginal dilator (VD). In this study, we plan to develop a standardized technique to assess VS using physical exam measurements at specified timepoints after CRT. Secondarily, we will assess patient preferences and use of available VDs with the goal of developing a novel VD device with our multidisciplinary engineering team. We report the rationale, methods, and objectives of this clinical study. Patients with LACC treated with CRT and brachytherapy are eligible. CT-based imaging pre-CRT and 3-months post-CRT to assess radiographic changes in the vaginal length and width will be collected. Vaginal measurements and physical exam will be recorded at baseline and 3-, 6-, and 12-months following CRT. Patients will also be given a set of VDs that range in diameter and length. Patient vaginal capacity, defined as the largest VD that can be comfortably accommodated in the vagina during pelvic exam, and compliance with VD use will be recorded at each visit. Patients will be given the EORTC Sexual Health Questionnaire (EORTC SHQ-22). Toxicity grading will use the CTCAE v5. We plan to assess patient preference using a VD-specific questionnaire to help guide the development of a personalized VD. For the primary analysis, we will examine the VS CTCAE v5 toxicity at baseline vs 1 year for 20 patients. The sample size we propose is sufficient to achieve at least 80% power at 5% significance level for detecting a significant non-zero proportion with a margin of 20%. For the secondary analysis, we will test the Spearman's coefficient and Kendall's tau between VS CTCAE and EORTC questions: "has the treatment affected your sexual activity?"; "have you felt pain during/after sexual activity?"; "have you been sexually active?" We will use permutation tests in which the ID will be permuted for vaginal stricture but kept as original for the EORTC questions. We will test the null hypothesis of no correlation by comparing the observed Spearman's coefficient and Kendall's tau to the permutation distributions. We plan to incorporate the specific VD questionnaire responses into the development of a novel device using qualitative measures. This clinical trial is an observational cohort study that aims to quantify CRT-induced VS, obtain patient reported sexual health, and understand specific preferences and compliance with VD use for the development of a novel engineered device.