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PURPOSE: High dose-rate (HDR) brachytherapy is integral for the treatment of numerous cancers. Preclinical studies involving HDR brachytherapy are limited. We aimed to describe a novel platform allowing multi-modality studies with clinical HDR brachytherapy and external beam irradiators, establish baseline dosimetry standard of a preclinical orthovoltage irradiator, to determine accurate dosimetric methods. METHODS: A dosimetric assessment of a commercial preclinical irradiator was performed establishing the baseline dosimetry goals for clinical irradiators. A 3D printed platform was then constructed with 14 brachytherapy channels at 1cm spacing to accommodate a standard tissue culture plate at a source-to-cell distance (SCD) of 1 cm or 0.4 cm. 4-Gy CT-based treatment plans were created in clinical treatment planning software and delivered to 96-well tissue culture plates using an Ir192 source or a clinical linear accelerator. Standard calculation models for HDR brachytherapy and external beam were compared to corresponding deterministic model-based dose calculation algorithms (MBDCAs). Agreement between predicted and measured dose was assessed with 2D-gamma passing rates to determine the best planning methodology. RESULTS: Mean (±standard deviation) and median dose measured across the plate for the preclinical irradiator was 423.7 ± 8.5 cGy and 430.0 cGy. Mean percentage differences between standard and MBDCA dose calculations were 9.4% (HDR, 1 cm SCD), 0.43% (HDR, 0.4 cm SCD), and 2.4% (EBRT). Predicted and measured dose agreement was highest for MBDCAs for all modalities. CONCLUSION: A 3D-printed tissue culture platform can be used for multi-modality irradiation studies with great accuracy. This tool will facilitate preclinical studies to reveal biologic differences between clinically relevant radiation modalities.
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OBJECTIVE: Recurrence remains a significant clinical problem for patients with cervical cancer, and early detection may improve outcomes. Serum squamous cell carcinoma antigen (SCCA) is a biomarker of prognosis and response to chemoradiotherapy. We hypothesized that elevated serum SCCA during surveillance is sensitive and specific for recurrence. METHODS: Pre-treatment and follow-up serum SCCA from patients treated with definitive-intent radiotherapy were measured via enzyme-linked immunosorbent assay in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory and analyzed retrospectively. Follow-up SCCA was defined as the value closest to recurrence, or as last available for patients without recurrence. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of follow-up SCCA for recurrence was determined for the whole cohort (Cohort 1), for patients with elevated (Cohort 2), and normal pre-treatment SCCA (Cohort 3). Patterns of failure were also evaluated. RESULTS: Of 227 patients in Cohort 1, 23% experienced recurrence, and 17% died of cervical cancer. Mean follow-up SCCA was 0.9 (±2.5) for patients with no recurrence and 6.0 (±18.7) for patients with recurrence (p=0.02). Sensitivity, specificity, PPV, and NPV of follow-up SCCA for recurrence in Cohort 1 were 38.5%, 97.1%, 80%, and 84.2%, and for patients in Cohort 2 were 54.5%, 95%, 78.3%, and 86.5%, respectively. Four of 86 patients in Cohort 3 had an elevated follow-up SCCA, two of these at the time of recurrence. Elevated pre-treatment SCCA and follow-up SCCA were associated with isolated pelvic recurrence. CONCLUSIONS: Surveillance serum SCCA has high specificity and NPV for recurrence, and may be of limited utility in patients with normal pre-treatment SCCA.