TraceIT TM Hydrogel Tissue Marker for Patients Receiving Definitive Chemoradiation for Bladder Cancer
Phase: NA
Conditions: Bladder Carcinoma
Sponsor: University of Washington

C 9 231(3 
Protocol 9798 / TraceITT" Hydrogel for Bladder Cancer 
UNIVERSITY OF WASHINTON SCHOOL OF MEDICINE 
FRED HUTCHINSON CANCER RESEARCH CENTER 
SEATTLE CANCER CARE ALLIANCE 
Traceltrm Hydrogel Tissue Marker for Patients Receiving Definitive 
Chemoradiation for Bladder Cancer 
Principal Investigator: 
Co-Investigators: 
Research Coordinator: 
Jing Zeng, MD 
Assistant Professor 
Department of Radiation Oncology 
University of Washington Medical Center 
1959 NE Pacific Street, Box 356043 
Seattle, Washington 98195-6043 
Phone: 206-598-4100 
Fax: 206-598-6218 
Email: jzeng13@uw.edu  
Jay Liao, MD 
Kenneth Russell, MD 
Jonathan Wright, MD 
Stephen Bowen, PhD 
Daniel Hippe, MS (statistician) 
Stephanie Schaub, MD 
Phone: 206-598-4100 
Fax: 206-598-3786 
Email: radoncrc@uw.edu  
Current version date: 02/24/17 
Previous version date: N/A 
FHCRC IRB Approval 
FEB 19 220 
Document Released Date 
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Protocol 9798 I TracelTrm Hydrogel for Bladder Cancer 
Study Summary 
Title 
Trace/P" Hydro gel Tissue Marker for Patients Receiving Definitive 
Chemoradiation for Bladder Cancer 
Short Title 
TraceIr m Hydro gel for Bladder Cancer 
Protocol Number 
CCIRB 9798 
Phase 
Pilot Study 
Methodology 
Single Arm Open-Label 
Study Duration 
1 year 
Study Center 
University of Washington Medical Center 
Objectives 
To utilize the Trace!Tim hydrogel tissue marker in localizing bladder 
tumors during TURBT (transurethral resection of bladder tumors), to 
improve identification of gross tumor location in patients receiving 
chemoradiation treatment for bladder cancers. The long-term goal 
being to reduce radiation field sizes to decrease radiation toxicity and 
improve tumor control. 
Number of Subjects 
12 evaluable subjects 
Diagnosis and Main 
Inclusion Criteria 
Patients diagnosed with non-metastatic bladder cancers receiving 
definitive Chemoradiation. 
Stud Product 
 
Dose Route 
y  , 
 
,  , 
Regime n 
Tracelr m Hydro gel Tissue Marker, FDA approved, will be injected into 
the bladder wall (at least 3 sites of injection around the peripheral of the 
tumor location) to mark the location of the bladder tumor during 
TURBT. 
Duration of 
Administration 
Tracelfm  Hydro gel Tissue Marker is absorbable and will start to 
breakdown after 3 months, fully absorbed by 6 months. 
Statistical 
Methodology 
Radiation treatment will be delivered daily for 4-8 weeks, with daily 
cone beam CT imaging prior to treatment. Location of the hydra gel will 
be visible on imaging, and tracked daily to monitor for interfraction 
variation in tumor bed size, shape, and location. Tumor location will 
also be compared against bony pelvic anatomy (pelvic brim), which is 
often used in aligning bladder cancer patients for their daily radiation 
treatment. lnterfraction variation in tumor bed size, shape, and location 
will be compared for each patient, as well as across patients. 
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Table of Contents 
1. Introduction 
1.1. Background 
1.2. Rationale for Traceltrm Hydrogel Tissue Marker 
2. Study Objectives 
3. Study Design 
3.1. General Design 
3.2. Eligibility Criteria 
3.3. Ineligibility Criteria 
3.4. Primary Study Endpoints 
3.5. Secondary Study Endpoints 
4. Study Registration 
5. Radiation Therapy 
5. Radiation Therapy 
5.1. Dose Specifications 
5.2. Localization, simulation and immobilization 
5.3. Target Volumes 
5.4. Critical Structures 
5.5. Treatment Planning 
5.6. Radiation Quality Assurance Reviews 
5.7. Radiation Toxicity 
5.8. Criteria for Removal/Withdrawal from Treatment 
6. Statistical Plan 
7. Data and Safety Monitoring Plan 
7.1. Early Stopping Rules 
7.2. Interim Data Review 
8. Data Management/Confidentiality 
9. References 
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1. Introduction 
This document is a protocol for a human research study. This study is to be conducted 
according to US and international standards of Good Clinical Practice (FDA Title 21 part 312 
and International Conference on Harmonization guidelines), applicable government regulations 
and Institutional research policies and procedures. 
1.1 Background 
For patients with muscle invasive bladder cancer, one treatment alternative to a radical 
cystectomy is bladder preservation with chemoradiation [1-4]. Ideal patients for bladder 
preservation therapy with chemoradiation should have a single tumor, completely 
resected by TURBT (transurethral resection of bladder tumor), no CIS (carcinoma-in-
situ), T2 tumors, urothelial histology, and no evidence of hydronephrosis [4]. For this 
ideal patient population, 5-year overall survival is around 60% when treated with bladder 
preservation therapy, comparable to radical cystectomy results. There are also patients 
with bladder cancers that are not ideal candidates for bladder preservation therapy with 
chemoradiation, but elect to undergo chemoradiation due to a variety of reasons, such 
as patient preference or medically inoperable due to comorbidities. 
Bladder preservation with chemoradiation carries the potential for significant toxicity due 
to the bladder's proximity to adjacent normal tissues. Patient first undergo maximum 
possible tumor resection with TURBT, and then 4-8 weeks of concurrent 
chemoradiation. Common chemotherapy regimens used during chemoradiation for 
bladder cancer treatment include cisplatin based regimen, mitomycin and 5-FU, and 
gemcitabine. These chemoradiation regimens typically result in grade 3-4 toxicities of 
10-36% acutely, with main acute toxicities being hematologic, gastrointestinal (e.g. 
diarrhea), and genitourinary (e.g. bladder urgency, frequency, discomfort with urination). 
There is also a <10% risk of late Grade 3+ toxicity. Overall complete tumor response to 
chemoradiation is around 70%, with 40% locoregional recurrence risk at 5 years (mix of 
invasive and non-invasive bladder cancer recurrence). Strategies are needed to both 
improve tumor control and decrease toxicity of treatment. 
Radiation is typically given in daily 1.8 Gy fractions to >60 Gy total over 4-8 weeks [5, 6]. 
Standard radiation field cover a "mini-pelvis" field (Figure 1), typically covering an area 
Figure 1. Typical radiation field for bladder cancer treatment. LEFT: anterior radiation field outlined; 
RIGHT: left lateral radiation field outlined. Black outline is the bladder. Gray outline is the rectum. 
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from S3 vertebral body superiorly to below the obturator foramen inferiorly, laterally to 
provide a 1-2 cm margin around the bony pelvis, anteriorly and posteriorly with 1-2 cm 
margin around the bladder. After treating this larger field to about 45-50 Gy, there is 
typically a boost to the bladder tumor bed to >60 Gy, depending on normal tissue 
tolerance in the region. This boost is typically determined based on a radiation 
oncologist's estimation of bladder tumor location prior to TURBT, based on scan reports 
and urology operative reports describing the tumor location. 
Prior to the each daily radiation treatment, images are taken to ensure the patient is set 
up in the proper location, and then radiation treatment is delivered. Since the bladder 
tumor bed is not visible on x-rays and CT scans, bony anatomy is often used for patient 
setup alignment. Daily cone beam CT scans performed on the linear accelerator are 
typically obtained to ensure that the bladder is inside the radiation treatment volume, and 
make further adjustments in patient position as needed to target the bladder tumor. 
However, since there currently exists no standard method to reliably delineate the 
bladder tumor bed on CT scan, during the radiation treatment planning phase, radiation 
oncologists typically contour a generous target volume that likely encompasses the 
tumor bed, and then add an additional 1-2 cm treatment "margin" around the suspected 
tumor bed to account for expected daily bladder motion, as well as daily changes in 
bladder filling which can change the bladder size and shape. Better visualization of the 
bladder tumor location could result in decreasing these added treatment margins needed 
to ensure the radiation field does not miss the tumor, thereby decreasing the amount of 
normal tissues that are receiving radiation, and potentially increasing our ability to give 
more radiation dose to the tumor, without causing excess toxicity. 
1.2  Rationale for Tracelfm Hydro gel Tissue Marker 
The TraceITTm Tissue Marker (Augmenix, Waltham, MA) is an injectable polyethylene 
glycol based hydrogel marker designed to be visible under CT, cone beam computed 
tomography (CBCT, commonly used for daily pre-radiation treatment imaging for patient 
alignment), MR and ultrasound imaging for three months after implantation, and then to 
absorb within six months. Peer reviewed abstracts by other groups have shown that it is 
possible to inject the hydrogel safely into patients with bladder cancer, undergoing 
chemoradiation treatment (Figure 2)[7]. Each injection is about 0.3-0.4 ml in volume. 
Figure 2. TraceITTm hydrogel injected into bladder, and visualized on CT (Ref 
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This gel technology is in routine clinical use in patients with prostate cancer to create a 
space between the rectum and prostate so as to protect the rectum in patients receiving 
radiation to the prostate. The formulation being used in the bladder, TraceITTm, is 
modified so that it is visible on imaging and is used as a marker rather than a spacer. 
TraceITTm has FDA approval for use as a marker, and there have been abstracts with 
small patient numbers describing its use in bladder cancer, but its reliability for daily 
radiation treatment alignment has not been studied. 
Accurately visualizing the tumor bed can help reduce the volume of tissue that is treated 
with radiation, which can decrease toxicity, and make it possible to further escalate the 
radiation dose without causing excess toxicity. However, there is no data on the daily 
variation in tumor bed size and shape, which occurs naturally with daily changes in 
bladder filling. We presume that the standard radiation treatment contouring guidelines 
accurately encompasses the tumor bed, but without a reliable method of marking the 
tumor bed during cystoscopy, this is actually not known. It is possible that there is 
greater daily variation in the bladder tumor bed location than routinely accounted for in 
radiation planning, and this could lead to under dosing of the tumor bed in some 
patients, contributing to the rate of local failure. There is also no data on the relationship 
between tumor location marked by hydrogel, and pelvic bony anatomy. Again, a greater 
than expected discrepancy between the two can lead to tumor under dosing. We 
propose this study, with the objectives outline below, to explore these questions. 
This study also serves as proof of concept in the use of TraceITTm as a fiducial marker in 
a thin walled organ that has not be able to reliably undergo markings with traditional 
solid fiducial markers (as these other markers are not reliably retained in the bladder wall 
). Other similar organs that might benefit in the future from better delineating of tumor 
locations and where traditional fiducials are not well anchored include small and large 
bowel, esophagus, and the mucosal lining of the upper aero digestive tract. 
2. Study Objectives 
Primary Objective: 
To utilize the TraceITT" hydrogel tissue marker in localizing bladder tumors during TURBT 
(transurethral resection of bladder tumors), to improve identification of gross tumor or tumor bed 
location in patients receiving chemoradiation treatment for bladder cancers. There is currently 
no standard method of marking tumor location in bladder cancer patients undergoing 
chemoradiation, and the daily tumor bed motion is unknown. Radiation treatment will be 
delivered daily for 4-8 weeks with daily cone beam CT imaging per current standard of care. 
Location of the hydrogel will be visible on imaging, and daily interfraction variation in tumor bed 
size, shape, and location will be tracked. 
Hypothesis:  
The hydrogel will show the bladder tumor bed motion on a daily basis, with changes in size, 
shape, and location due to daily variation in bladder filling. We plan to characterize the changes 
in size, location, and deformability to inform the design of future radiation fields. Field design for 
this protocol will use the standard treatment margins in current clinical use. We expect that the 
tumor bed location will remain inside the planning target volume (PTV), predefined by the 
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radiation oncologist prior to starting radiation treatment. We have the means to replan the 
radiation fields if this is not the case and deemed medically necessary. 
Secondary Objective 
a) To report adverse events surrounding the placement of the TraceITTm Tissue Marker. 
Hypothesis:  
We predict placement of the TraceITTm Tissue Marker will be a well-tolerated procedure 
without any significant adverse events within the time after placement to the initiation of 
radiation therapy. 
b) To calculate the actual dose received by the bladder tumor bed, as delineated by the 
hydrogel. Since daily CBCTs will be obtained, actual daily dose to bladder tumor bed can be 
calculated daily. 
Hypothesis:  
There will be adequate coverage of the tumor bed in most patients, due to large margins 
used in current standard radiation treatment planning, although the margins can likely be 
reduced if markers are used to delineate the tumor bed. 
c) To compare the dosimetric impact to the tumor bed of daily patient alignment to the pelvic 
bones, versus alignment to the whole bladder, versus alignment to the hydrogel markers. 
Standard of care for radiation treatment is daily alignment to pelvic bony anatomy or whole 
bladder, since there is currently no standard way to delineate the tumor bed. 
Hypothesis:  
Using hydrogel to localize bladder tumor location will lead to more accurate targeting of 
the bladder tumor with radiation. 
d) To calculate the amount of normal tissue radiation dose decrease achievable without losing 
tumor coverage, with better tumor targeting with hydrogel placement. 
Hypothesis:  
Using hydrogel to better localize the bladder tumor can lead to smaller margins being 
used in radiation planning, which can make it possible to increase radiation dose to the 
tumor without excess radiation to surround normal tissues. We hypothesize that a 5 mm 
margin around the hydrogel markers will encompass >95% of daily motion, which is 
significantly smaller than the 2 cm margin commonly used in current radiation treatment 
planning. 
3. Study Design 
3.1  General Design 
This is a pilot study to utilize the TraceITTm hydrogel tissue marker in localizing bladder 
tumors during TURBT (transurethral resection of bladder tumors), to improve 
identification of gross tumor location in patients receiving chemoradiation treatment for 
bladder cancers. The long-term goal being to reduce radiation field sizes to decrease 
radiation toxicity and improve tumor control. All patients will undergo hydrogel injection 
during TURBT. All patients will receive standard of care chemoradiation for bladder 
cancer. As part of this standard chemoradiation, patients undergo daily imaging prior to 
radiation treatment for alignment. Patients are aligned per pelvic bony anatomy per 
standard of care, but the hydrogel will also be visible on imaging, and its location relative 
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to the pelvic bony anatomy will be analyzed. See Table 1 below for summary of study 
assessments. 
Table 1. Study Calendar 
Screening 
Prior to Start of 
Radiation Treatment 
(<8 weeks ptior to R7) 
During Radiation 
Treatment (weekly) 
(4-8 weeks, >60 Gy) 
Informed Consent 
X*a  
Medical History 
X 
X 
Physical Exam 
Xb  
X 
Toxicity Evaluation 
X 
TURBT 
X 
Tracelrm Hydrogel 
injection during TURBT 
(at least 3 sites, around 
tumor periphery) 
X* 
CT Simulation for 
Radiation Planning 
X 
Daily Imaging for 
Radiation Treatment 
X 
* Denotes a research procedure, all others are standard of care 
Indicates the day of study entry 
b Within 60 days of study entry 
3.2  Eligibility Criteria 
Conditions for patient eligibility: 
• 
Histologically confirmed malignancy of the bladder 
• 
No prior cystectomy 
• 
Treatment plan for bladder must include at least 4 weeks of daily radiation 
treatment (most patients will receive chemotherapy concurrent with radiation, but 
this is not required for trial enrollment) 
• 
Patient must undergo TracelTn" hydrogel placement within 8 weeks prior to 
starting radiation therapy for bladder cancer 
• 
Age ?. 18 years 
• 
Participants must have a complete history and physical examination within 60 
days of study entry 
• 
Participants must be able to provide informed consent for treatment and trial 
participation 
• 
No restrictions on prior treatment to be eligible 
3.3  Ineligibility Criteria 
Conditions for patient ineligibility: 
• 
Prior cystectomy 
• 
Unable to have TraceITTm hydrogel placement <8 weeks prior to beginning 
radiation treatment 
• 
Treatment for metastatic bladder cancer 
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Protocol 9798 / TraceITTm Hydrogel for Bladder Cancer 
• 
Women of child-bearing age unwilling to use acceptable forms of contraception. 
3.4  Primary Study Endpoints 
In this study, patients with bladder cancers receiving chemoradiation as definitive 
treatment will undergo injection of the TraceITTm hydrogel during TURBT. During daily 
radiation treatment, a cone beam CT will be captured and x/y/z coordinates will be 
assigned to each hydrogel marker, which allows for calculation of interfraction motion 
(day to day) of the markers, as well as size and deformation of the tumor bed due to 
bladder filling changes. These changes will be tracked during the entire radiation course 
(typically 4-8 weeks), and compared across different patients. 
 
3.5  Secondary Study Endpoints 
For secondary objective (a), toxicity data will be collected from routine clinical follow up 
visits. 
For secondary objective (b), daily pre-radiation imaging will be used to run the radiation 
treatment plan, to calculate the daily dose to the PTV (planning tumor volume) based on 
hydrogel location. Total radiation dose to the PTV can then be calculated as the sum of 
the daily dose. 
For secondary objective (c), daily pre-radiation imaging will be used to run the radiation 
treatment plan, to calculate the daily dose to the PTV (planning tumor volume) based on 
alignment to the hydrogel location, versus alignment to whole bladder location, versus 
alignment to bony anatomy. 
For secondary objective (d), daily pre-radiation imaging will be used to identify the 
smallest setup margin required for consistent coverage of the gross tumor volume 
(GTV), which is likely smaller than the current standard of care setup margin of at least 2 
cm around the GTV. A smaller margin around the GTV will mean that dose to the 
normal tissues can be decreased, without decreasing the tumor coverage compared with 
standard of care radiation therapy. 
4. Study Registration 
Subjects will be registered by the FHCRC/UW Study Coordinator and entered into the 
Protocol Accrual Tracking System (PATS). Information regarding the PATS system is 
available  at  http://cancerconsorti um . orq/en/support/resou rces/system s/pats. html.  A 
complete, signed, study consent, and HIPAA consent are required for registration. 
Registration will occur after study participant signs consent. 
5. Radiation Therapy 
5.1. Dose Specifications 
This protocol does not specific radiation dose, which will be per standard of care at 
the discretion of the treating radiation oncologist. This protocol does require that the 
patient is receiving at least 4 weeks of daily radiation treatment, to allow for 
longitudinal tracking of marker location. Standard of care radiation treatment for 
curative treatment of bladder cancer is typically 4-8 weeks of daily radiation, with 
chemotherapy. 
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Protocol 9798 / TraceITTH Hydrogel for Bladder Cancer 
5.2. Localization, simulation, and immobilization 
Patients should undergo simulation and immobilization per standard of care at the 
discretion of the treating radiation oncologist. Daily cone beam CT (CBCT) will be 
required prior to daily radiation treatment, which is currently standard of care. 
5.3. Target Volumes 
Target volumes will be contoured per standard of care at the discretion of the 
treating radiation oncologist. Bladder must be contoured as one of the target 
volumes, which is part of routine standard radiation treatment planning. 
5.4. Critical Structures 
This protocol does not require any specific normal structure to be contoured as a 
critical structure. Radiation treatment planning will be per standard of care at the 
discretion of the treating radiation oncologist. Typically, rectum, bowel, and femoral 
heads are contoured as critical structures in treatment planning. 
5.5. Treatment Planning 
This protocol does not specific target or normal tissue dose constraints. Radiation 
treatment planning will be per standard of care at the discretion of the treating 
radiation oncologist. 
5.6. Radiation Quality Assurance Reviews 
All patients treated on this protocol will undergo standard review in the Department 
of Radiation Oncology. At least two physicians will review the patient history, 
imaging findings, tumor contours, and radiation plan. 
5.7. Radiation Toxicity 
Toxicity will be graded based on CTCAE 4.0. Grade 3 and higher adverse events 
(AEs) will be recorded as well as adverse events that require a treatment 
interruption. In accordance with institutional policy, all adverse events which in the 
opinion of the principal investigator are unexpected and related or possibly related to 
the research and serious or suggest that the research places research participants 
or others at greater risk of physical or psychological harm than was previously 
known or recognized will be reported to the IRB within 10 calendar days of learning 
of the problem. 
5.8. Criteria for Removal/Withdrawal from Treatment 
Patients will be withdrawn from treatment if their clinical conditions decline so they 
are no longer able to tolerate radiation, or are unlikely to clinically benefit from further 
therapy. Patients will still receive follow up care per standard of care even if they 
withdraw from the study. 
6. Statistical Plan 
A total of 12 evaluable patients will be enrolled onto this study at an accrual rate of 12 patients 
per year. We expect to consent approximately 15 patients to obtain 12 evaluable patients. We 
will calculate the daily changes in individual hydrogel marker positions, and daily changes in 
tumor bed size and shape as delineated by the hydrogel. We will compare daily changes 
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Protocol 9798 I TraceITTm Hydrogel for Bladder Cancer 
across the patient group as well as within each subjects' treatment course. During daily 
radiation treatment, a cone beam CT will be captured and x/y/z coordinates will be assigned to 
each hydrogel marker, which allows for calculation of interfraction motion (day to day) of the 
markers, as well as size and deformation of the tumor bed due to bladder filling changes. 
These changes will be tracked during the entire radiation course (typically 4-8 weeks), yielded a 
distribution of x/y/z positions for each patient. Independent non-parametric testing of systematic 
(mean) errors in hydrogel marker position and tumor bed size variation between patients, as 
well as testing of random (root-mean-square error, pooled deviation) residual errors in hydrogel 
marker position between patients, will be conducted using Kruskal-Wallis ANOVA (k patient 
samples). While non-parametric testing sacrifices statistical power, it relaxes the criteria for 
normality in the presence of small sample size. For completeness, we will also perform 
parametric ANOVA testing in the 12 patient sample size, in order to detect differences in 
hydrogel positioning error in the range of 5-10 mm at 80% power and 5% Type I error rate. 
7. Data and Safety Monitoring Plan 
Institutional support of trial monitoring will be in accordance with the FHCRC/University of 
Washington Cancer Consortium Institutional Data and Safety Monitoring Plan. Under the 
provisions of this plan, FHCRC Clinical Research Support coordinates data and compliance 
monitoring conducted by consultants, contract research organizations, or FHCRC 
employees unaffiliated with the conduct of the study. Independent monitoring 
visits occur at specified intervals determined by the assessed risk level of the study and the 
findings of previous visits per the institutional DSMP. 
In addition, protocols are reviewed at least annually and as needed by the Consortium Data 
and Safety Monitoring Committee (DSMC), FHCRC Scientific Review Committee (SRC) 
and the FHCRC/University of Washington Cancer Consortium Institutional Review Board 
(IRB). The review committees evaluate accrual, adverse events, stopping rules, and 
adherence to the applicable data and safety monitoring plan for studies actively enrolling or 
treating patients. The IRB reviews the study progress and safety information to assess 
continued acceptability of the risk-benefit ratio for human under the provisions of the DSMB, 
the Cancer Consortium Clinical Trial Support Office subjects. Approval of committees as 
applicable is necessary to continue the study. 
The trial will comply with the standard guidelines set forth by these regulatory committees 
and other institutional, state and federal guidelines. 
7.1 Early Stopping Rules 
Early stopping of this trial will be any grade 4 or 5 adverse events (AEs) occurring 
within 5 30 days after the end of treatment defined as possibly, probably, or definitely 
related to treatment (per CTCAE, v.4.0). All AEs will be immediately monitored and 
reviewed by Pl. 
7.2 Interim Data Review 
Interim reports with statistical analyses will be prepared twice per year until the initial 
treatment results have been presented or published. In general, the interim reports 
will contain the following information: 
• Patient accrual rate with a projected completion date (while the study is still 
accruing) 
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• Total patients accrued 
• Frequencies and severity of adverse events 
8. Data Management/Confidentiality 
The investigator will ensure that data collected conform to all established guidelines. Each 
subject is assigned a unique patient number to assure subject confidentiality. Subjects will 
not be referred to by this number, by name, or by any other individual identifier in any 
publication or external presentation. The licensed medical records department, affiliated 
with the institution where the subject receives medical care, maintains all original inpatient 
and outpatient chart documents. 
Subject research files are stored in a secure place (or database). Access is restricted to 
authorized personnel. 
9. References 
1. 
Arcangeli, G., S. Arcangeli, and L. Strigari, A systematic review and meta-analysis of clinical trials 
of bladder-sparing trimodality treatment for muscle-invasive bladder cancer (MIBC). Crit Rev 
Oncol Hematol, 2015. 94(1): p. 105-15. 
2. 
Mak, R. H., et at. Long-term outcomes in patients with muscle-invasive bladder cancer after 
selective bladder-preserving combined-modality therapy: a pooled analysis of Radiation Therapy 
Oncology Group protocols 8802, 8903, 9506, 9706, 9906, and 0233. J Clin Oncol, 2014. 32(34): 
p. 3801-9. 
3. 
James, N.D., et al., Radiotherapy with or without chemotherapy in muscle-invasive bladder 
cancer. N Engl J Med, 2012. 366(16): p. 1477-88. 
4. 
Ploussard, G., et al., Critical analysis of bladder sparing with trimodal therapy in muscle-invasive 
bladder cancer: a systematic review. Eur Urol, 2014. 66(1): p. 120-37. 
5. 
Mitin, T., et at., Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or 
fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients 
with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase 2 trial. 
Lancet Oncol, 2013. 14(9): p. 863-72. 
6. 
Kaufman, D.S., et al., Phase I-II RTOG study (99-06) of patients with muscle-invasive bladder 
cancer undergoing transurethral surgery, paclitaxel, cisplatin, and twice-daily radiotherapy 
followed by selective bladder preservation or radical cystectomy and adjuvant chemotherapy. 
Urology, 2009. 73(4): p. 833-7. 
7. 
Chamie, K., et al., INITIAL MULTICENTER EXPERIENCE UTILIZING AN ABSORBABLE 
RADIOPAQUE HYDROGEL FOR PATIENTS WITH INVASIVE BLADDER TUMORS. Journal of 
Urology, 2014. 191(4S): p. e689-690. 
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