TraceIT: A prospective pilot study of a temporary intravesical fiducial marker for bladder cancer radiation therapy.
Authors: Greer Matthew , Schaub Stephanie K. , Bowen Stephen R. , Liao Jay Justin , Russell Kenneth J. , Schade George R. , Gore John L. , Grivas Petros , Wright Jonathan L. , Zeng Jing 
Published: March 2021

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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.