Clinical assessment of radiotherapy-induced vaginal toxicity with multiparametric ultrasound imaging

PROJECT SUMMARY/ABSTRACT
Pelvic radiotherapy is the standard of care for numerous gynecological and anorectal cancers affecting
women. Post-operative intravaginal brachytherapy (IVRT) is used to prevent cancer recurrence at the vaginal
cuff for high-intermediate risk endometrial cancer patients. IVRT delivers conformal radiation dose to the
vagina cuff and canal. This results in high rates of acute and late vaginal toxicities, such as vaginal stenosis,
which is defined as the abnormal tightening and shortening of the vagina due to fibrosis. These effects can
lead to debilitating pain, sexual dysfunction, and poor quality of life. Current clinical assessments of vaginal
toxicity are subjective and based on clinician and patient reported grading scales that leads to variability. There
is a clinical need for objective measurements of vaginal tissue health, and we propose a multiparametric
ultrasound imaging approach for vaginal tissue characterization before and after IVRT. In this study, we will
develop a system and methodology for three-dimensional (3D) multiparametric imaging of the vaginal wall
using B-mode, ultrasensitive microvessel imaging (UMI), shear-wave elastography (SWE), and tissue
microstructure characterization with quantitative ultrasound (QUS). As a secondary objective, we will test the
system in a clinical study with fifteen endometrial cancer patients receiving IVRT to identify associations
between multiparametric ultrasound metrics and current clinical assessments of vaginal toxicity. This will be
the first study using a multimodal ultrasound approach for characterization of vaginal tissue. We hypothesize
that multiparametric ultrasound will be produce metrics that are sensitive to anatomical changes (B-mode),
microvascular damage (UMI), fibrosis stage (SWE), and tissue microstructure and cellular death (QUS). There
is increasing awareness of radiation-induced toxicities and considerable effort has gone into strategies to
reduce toxicities and improve overall quality of life and sexual functioning. Multiparametric ultrasound imaging
offers a non-subjective, quantitative approach for detecting and characterizing vaginal health, which is typically
overlooked with current medical imaging. Ultimately, this approach will lead to predictive imaging biomarkers
that clinicians can use as outcome metrics of novel treatment strategies and interventions aimed at preventing
and treating radiotherapy-induced vaginal toxicities. If successful, the research will introduce a safe, cost-
effective imaging platform to improve the health of women suffering from this chronic gynecological condition.

Grant Number: 5R21CA290252-02
NIH Institute/Center: NIH
Principal Investigator: Mark Burgess