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Urinary Biomarkers Associated with Radiation Cystitis Hyperbaric Oxygen Therapy Outcomes
Ambrose Orr, MD1, Richard Bellemare, MD1, Daniel Mielcarz, PhD2, Suwen Wu, MS3, Janet Peacock, PhD4, Pamela Hannigan, RN1, Lawrence Bornt, RN1, William Bihrle, III, MD1, Sladjana Skopelja-Gardner, PhD5, Duncan Morhardt, MD, PhD1, Jay Buckey, MD5, Rachel Moses, MD, MPH1.
1Dartmouth Hitchcock Medical Center, Section of Urology, Lebanon, NH, USA, 2DartLab, Dartmouth Cancer Center, Geisel School of Medicine, Hanover, NH, USA, 3Geisel School of Medicine, Dartmouth College, Dept of Epidemiology, Lebanon, NH, USA, 4Geisel School of Medicine, Dartmouth College, Dept of Epidemiology, Hanover, NH, USA, 5Dartmouth Health, Dept of Medicine, Geisel SOM at Dartmouth College, Lebanon, NH, USA.

BACKGROUND: To evaluate updated results from our prospective study evaluating chronic radiation cystitis (RC) urinary biomarkers and association with response to Hyperbaric Oxygen (HBO2) treatment. METHODS: Patient demographics and mid-stream urine samples (pre, mid, post HBO2) were prospectively compared between adult patients with Radiation Therapy Oncology Group (RTOG) ≥ grade 2 RC and controls. Hematuria scores and Urogenital Distress Inventory (UDI) scores were compared pre- and post-HBO2. A priori urinary biomarker analysis (Luminex multiplex assay) was conducted following creatinine concentration normalization. Hematuria, UDI, and urine biomarker results were compared between RC participants versus controls and HBO2 responders versus non-responders.
RESULTS: 32 patients, age 61(±15) met inclusion criteria: n=17 with RC, n=5 HBO2 controls, and n=10 healthy controls. RC Patients received an average 66.9Gy radiation therapy, mostly for prostate cancer, and underwent an average of 57 HBO2 sessions. Four RC patients were HBO2 non-responders. RTOG Hematuria (p<0.0001) and UDI (p<0.001) improved following RC HBO2. Baseline RC urinary Interleukin-6 (IL-6) levels were elevated compared to healthy controls (p<0.001). RC-HBO2 non-responders (n=4) demonstrated a greater increase in IL-6 (p<0.01), Interleukin-8 (IL-8), (p=0.01), Granulocyte-Colony Stimulating Factor (G-CSF) (p<0.01), and amphiregulin (<0.01) at the mid and post treatment time points (Figure 1). Tumor Necrosis Factor- alfa (TNF-a) was only elevated in RC HBO2 non-responders at the mid treatment and remained elevated at the mid post-treatment time point.
CONCLUSIONS: Baseline urine IL-6 was increased in the RC cohort compared to controls. Urine IL-6, IL-8, G-CSF, Amphiregulin, and TNF-a increased mid treatment in HBO2 non-responders and may be mid treatment predictors of poor HBO2 response. Continued study expansion is required to understand if inflammatory cytokines can serve as HBO2 treatment response biomarkers.
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