Determining Combined Modality Dosimetric Constraints by Integration of IMRT and LDR Prostate Brachytherapy Dosimetry <h3>Purpose/Objective(s)</h3> Combined external beam radiation therapy (EBRT) and prostate brachytherapy is one standard of care for men with prostate cancer. Dosimetric correlation of organ at risk (OAR) has been limited by the lack of spatial registration and differences in biological effectiveness between EBRT and brachytherapy dose. This study utilized a validated technique to spatially combine three-dimensional biological effective dose (BED) distributions from different modalities to more accurately depict a composite dose. We use this technique to correlate dosimetry with genitourinary (GU) and gastrointestinal (GI) toxicity in an effort to propose conservative dosimetric tolerances for OARs during combination therapy for prostate cancer. <h3>Materials/Methods</h3> The study cohort consisted of 144 intermediate and high-risk prostate cancer patients treated with combination therapy. Patients received 45 Gy using IMRT, either by static field or modulated arc, and 100 Gy using <sup>103</sup>Pd. Dosimetry was converted voxel-by-voxel to BED and combined using deformable image or inherent DICOM registration. Acute and late GU and GI toxicity was scored using CTCAE and correlated with combined BED. Biological effective doses for each toxicity group were compared using analysis of variance (α=0.05). <h3>Results</h3> Using dose methodology, the mean prostate BED was 223.5 ± 24.2 Gy. Mean urethral dose and D10 were 182.5 ± 22.8 and 232.0 ± 37.0 respectively. Mean rectal dose and D2cc were 33.2 ± 7.9 and 86.4 ± 24.4 respectively. CTCAE toxicity is reported in Table 1. Overall, there was minimal grade 3+ toxicity. No statistical differences were noted among any of the toxicity grades and there was no correlation between urethral or rectal dose and toxicity. <h3>Conclusion</h3> This study demonstrates the feasibility of using the spatial combination of biologic effective doses for OARs in combination EBRT and brachytherapy for prostate cancer. In this study cohort, the level of toxicity was generally less than reported elsewhere. This dataset serves as an opportunity to propose using combined constraints as a conservative estimate for future studies to estimate OAR tolerances. Initially, we propose conservative combination constraints equal to one standard deviation below our mean patient dosimetry: Urethra D10 < 160 Gy and Rectum D2cc < 60 Gy. The process of establishing a useful BED between two different treatments can help redefine OAR tolerances and has applicability for other treatment sites with combined therapy such as cervix cancer and re-irradiation.