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457 Background: Precision image-guided radiotherapy (RT) for patients (pts) with muscle-invasive bladder cancer (MIBC) is limited by daily anatomic variation and difficulty visualizing the tumor bed. We hypothesized that TraceIT, a radiopaque resorbable hydrogel, can be injected around the tumor bed to improve image guidance. We present the results of our pilot trial (NCT03125226) evaluating safety/feasibility of TraceIT in pts undergoing definitive RT. Methods: Eligibility included MIBC with plan to receive definitive RT +/- chemo. Fifteen patients were available for analysis (11 enrolled on trial from 2017-2018, plus an additional 4 received TraceIT off study). TraceIT was injected around the circumference of the tumor bed during pre-radiation maximal re-transurethral resection of bladder tumor (TURBT) for all pts, and again during the mid-radiation TURBT to improve visibility in n = 8 pts. The primary endpoint was assessment of interfraction motion on daily cone-beam CT (CBCTs) based on alignment to fiducial vs standard-of-care pelvic bone anatomy. Van Herk (VH) margin equation was used to determine the planning target volume margin optimized for the clinical target volume receiving at least 95%-prescription dose in 90% of pts. Recurrence rates and survival were estimated by Kaplan Meier. Toxicity was measured by CTCAE v4.03. Results: Patients underwent RT to a median total dose of 63.5 Gy (range 35.75-66.6), typically to an initial small pelvis field follow by a tumor boost. 14/15 received chemo with RT. Median TraceIT volume was 0.5cc (range 0.3-0.75) per injection site for 4 (range 4-6) sites per patient for total volume of 2cc (range 2-3). All pts demonstrated 100% visibility of TraceIT on initial simulation CT and day 1 CBCT. TraceIT visibility declined slightly over time, with 91.5% of patients having visible TraceIT by the end of the initial RT phase (usually week 5) and 82.5% by end of the boost phase. For the initial phase, alignment to fiducials over bone anatomy allowed for reduced VH margins (0.67cm vs 1.56cm). For the boost phase, the VH margin was similar between fiducial and bone alignment (1.01cm vs 0.96cm). There have been no acute or late complications from TraceIT placement. There were no grade grade (G) 4/5 toxicities; three pts had acute G 3 events, and three pts experienced late G 3 toxicity: two related to hematuria and one from ureteral stenosis. There were no late G≥2 GI toxicities. No patients have undergone cystectomy. At a median follow-up of 22 months, 2-yr OS was 79.1% and 2-yr PFS was 75.4%. Conclusions: TraceIT is safe and feasible for use in image-guided RT. TraceIT can increase the precision of RT by facilitating accurate target delineation of the bladder tumor bed and daily motion management which may allow for smaller radiation treatment margins to be used to reduce toxicity and to potentially facilitate safe dose escalation to tumor, which can improve tumor control. Clinical trial information: NCT03125226.

558 Background: High rates of local control are achievable with hypofractionated proton therapy with passive techniques for hepatocellular carcinoma (HCC), but may have limitations when tumors are adjacent to organs-at-risk (OARs), which may result in tumor underdosage and lead to inferior local control. We present the first reported series of HCC patients treated with pencil beam scanning (PBS) intensity-modulated proton therapy (IMPT) using a simultaneous-integrated boost and protection (SIB/SIP) technique to escalate tumor dose while protecting adjacent OARs. Methods: Twenty-five HCC patients were treated between 2015-2019 with a 15-fraction regimen using IMPT SIB/SIP. SIB/SIP dose levels generally ranged from 36.0-67.5 GyRBE to minimize dose to OARs at their respective dose-limiting thresholds (e.g. luminal gastrointestinal organs, chest wall). Radiation-induced liver disease (RILD) was defined by a Child-Pugh (CP) score increase of 2 or greater and/or any RTOG grade 3 enzyme elevation. Other toxicities were graded by CTCAEv5.0. Overall survival (OS), progression-free survival (PFS), and local control were calculated using the Kaplan-Meier method. Results: Patients most commonly had BCLC stage B or C disease (84%) and CP-A (80%) and ALBI grade 2 (60%) liver function. Median gross tumor volume (GTV) size and volume were 12.3 cm (range 2.17-20.57) and 461 cc (range 4.68-2439), and 32% had gross vascular invasion. Median mean and minimum dose delivered to the gross tumor volume (GTV) was 64.0 GyRBE (EQD2 76.1, BED 91.3, range 54.3-69.6) and 45.1 GyRBE (EQD2 48.9, BED 58.7, range 33.4-67.7), respectively. Median mean dose to liver minus GTV was 15.0 GyRBE (range, 8.2-19.6). 1-year OS, PFS, and local control were 66%, 32%, and 84%, respectively. No isolated local failures occurred. Two patients experienced RILD with no RILD-related deaths. Two grade 3 non-GI toxicities occurred: 1 rib fracture and 1 pneumonitis. No acute or late GI grade ≥2 occurred. Conclusions: In our series of HCC patients with large tumors near OARs, IMPT SIB/SIP allows for tumor dose escalation while sparing of OARs and results in favorable local control and acceptable toxicities.

444 Background: The albumin-bilirubin (ALBI) grade system was optimized to predict survival in hepatocellular carcinoma (HCC) patients; however, its applicability to patients treated with radiation therapy (RT) is unclear. We propose a novel analysis of the ALBI equation, designated ALBI-RT, to assess hepatotoxicity risk after RT. Methods: We retrospectively reviewed 48 consecutive HCC patients treated with RT (2013-2016). Raw ALBI values and Child-Pugh (CP) scores were calculated. Any patient deaths were examined for radiation induced liver disease (RILD). Raw ALBI was assessed as a continuous variable to perform ROC analyses to identify cutoffs for overall survival (OS) and RILD-specific survival (RILD-SS). Univariate predictors of OS and RILD-SS were evaluated using Cox regression to determine hazard ratios (HR). Results: Patient cohort was comprised of 60% CP-A and 39% CP-B/C. Median follow-up and OS was 13 and 10 months, respectively. There were 18 deaths with 6 ascribed to RILD. We identified a raw ALBI cutoff at -1.70 (AUC = 0.94, p = 0.008) that was predictive of RILD-SS with a sensitivity of 100% and specificity of 71%. Dichotimization of RILD-SS cutoff generated two ALBI-RT risk categories: low-risk A < -1.70 (n = 29) and high-risk B ≥ -1.70 (n = 18). ALBI-RT subdivided CP-A patients, identifying 14% at increased risk of RILD; conversely, ALBI-RT grade A identified 21% of CP-B/C patients at a decreased risk of RILD. For OS, raw ALBI as a continuous variable (HR 3.0, p = 0.02), and to a lesser degree ALBI-RT Grade B (HR 2.4, p = 0.06), performed similarly to traditional ALBI grade (HR 3.0, p = 0.01), and CP score (HR 1.4, p = 0.03). In contrast for RILD-SS, raw ALBI as a continuous variable (HR 25.1, p = 0.01) and ALBI-RT Grade B (HR 9.9, p = 0.04) were associated with an elevated relative risk of RILD than traditional ALBI grade (HR 5.8, p = 0.02) and CP score (HR 2.3, p = 0.003). Conclusions: ALBI-RT is a promising metric for pre-treatment assessment of HCC patients for predicting RILD-related death after RT with an elevated relative-risk compared to both CP and conventional ALBI grades. Future prospective evaluation and validation in independent data sets will strengthen the generalizability and utility of ALBI-RT.