Pilot Study of Intra-Urethral Radiotransponder Beacon Guided Focal Prostate Stereotactic Body Radiotherapy
Phase: NA
Conditions: Prostate Cancer
Sponsor: University of Alabama at Birmingham

Department of Radiation Oncology                                                                              RAD 1801 
University of Alabama Birmingham 
Protocol Version: May 12, 2020 
Amendment  # 1 
 
 
 
 
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RAD 1801/UAB 1803 –Pilot Study of Intra-Urethral Radiotransponder 
Beacon Guided Focal Prostate Stereotactic Body Radiotherapy 
 
 
TABLE OF CONTENTS 
 
1.0 
OBJECTIVES 
2.0 
BACKGROUND AND RATIONALE 
3.0 
SCHEMA 
4.0 
PATIENT SELCTION CRITERIA 
5.0 
DRUG INFORMATION 
6.0 
TREATMENT PLAN 
7.0 
THERAPY MODIFICATIONS 
8.0 
STUDY PARAMETERS 
9.0 
EVALUATION CRITERIA 
10.0 
PATIENT REGISTRATION 
11.0 
STATISTICAL CONSIDERATIONS 
12.0 
REFERENCES 
 
TABLE OF CONTENTS 
 
A 
PATIENT QUESTIONNAIRES 
 
 
 
Approval Dates:  
 
 
 
                        __________ 
 
 
 
 
CTRC  
 
 
 
     IRB 
 
 
Principle Investigator 
 
Andrew M. McDonald, MD, MS 
University of Alabama at Birmingham  
Hazelrig-Salter Radiation Oncology Center  
1700 6th Avenue South, 176F, Suite 2230 
Birmingham, AL  35233  
Phone:  205-996-5669 
 
Urology Co-Principle Investigator 
 
Soroush Rais-Bahrami, MD 
University of Alabama at Birmingham  
Department of Urology 
1530 3rd Avenue South, FOT 1105 
Birmingham, AL 35294 
Phone:  205-975-0088 
 
Co-Investigators 
 
John Fiveash, MD; Michael Dobelbower, MD, PhD; Rojymon Jacob, MD; Robert Kim, 
MD; Eddy Yang, MD, PhD; Richard Popple, PhD; Rex Cardan, PhD; Ivan Brezovich, 
PhD; Jeffrey Nix, MD 
 
Biostatistician 
 
Robert A. Oster, PhD 

Department of Radiation Oncology                                                                              RAD 1801 
University of Alabama Birmingham 
Protocol Version: May 12, 2020 
Amendment  # 1 
 
 
 
 
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Research Nurse & Data Coordinator 
 
TBD 
 
Regulatory 
 
Kristin Webb, CCRP 
 
Document History Table 
 
Version/Update Date 
Amendment # 1 
May 12, 2020 
Original & Activation 
January 24, 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Department of Radiation Oncology                                                                              RAD 1801 
University of Alabama Birmingham 
Protocol Version: May 12, 2020 
Amendment  # 1 
 
 
 
 
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Summary of Changes 
 
Protocol Amendment # 1 
Protocol Version Date: May 12, 2020 
# 
Section 
Comments 
1 
Footer 
The protocol version and amendment number has been updated. 
2 
8.1 
Due to COVID-19, Amendment # 1 is to allow study procedures that may 
need to be conducted remotely, if necessary. 
3 
9.1 
The following sentence has been added as the last sentence of the 
paragraph, “Due to COVID-19, these study procedures may be conducted 
remotely, if necessary.” 
 
4 
9.5.2 
The following sentence has been added as the last sentence of the 
paragraph, “Some of these study procedures may be conducted remotely, 
if necessary.” 
 
5 
 
 

Department of Radiation Oncology                                                                              RAD 1801 
University of Alabama Birmingham 
Protocol Version: May 12, 2020 
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1.0 
OBJECTIVES 
 
1.1 
Primary:  Confirm the technical feasibility of focal prostate stereotactic 
body radiotherapy (SBRT) with real time guidance by intra-urethral 
radiotransponder beacons. 
  
1.2 
Secondary: Clinically assess early efficacy, late toxicity, and quality of life 
for men receiving focal prostate SBRT for low and low-intermediate risk 
prostate cancer.   
2.0 
BACKGROUND AND RATIONALE 
 
2.1 
Prostate cancer overview 
 
Prostate cancer is the most common non-cutaneous malignancy among 
men, with over 180,000 annual incident cases leading to an estimated 
28,600 deaths in 20161. Men with prostate cancer are grouped into low, 
intermediate, or high risk cohorts according to risk stratification schemes 
based upon well-established risk factors including PSA level, Gleason 
score (histologic grade), and clinical stage2. Definitive treatment options 
for patients with clinically localized prostate cancer include radical 
prostatectomy, external beam radiotherapy (RT), and brachytherapy or a 
combination of external beam RT and brachytherapy, with or without 
androgen deprivation (ADT)2.   
 
For men without high risk features, active surveillance is an alternative 
strategy to definitive treatment2. The decision to initiate therapy is based 
on the patient’s life expectancy, individual risk factors, and goals. 
Currently, the National Comprehensive Cancer Network (NCCN) 
recommends active surveillance for men with newly diagnosed low risk 
prostate cancer; however, more than half of men will develop indications 
for definitive treatment within 10 years3. 
 
2.2 
Rationale for focal therapy for prostate cancer 
 
Traditional prostate cancer therapies such as surgical resection 
(prostatectomy) and traditional radiation therapy involve treatment of the 
entire prostate gland.  Currently, men who are diagnosed with low or low-
intermediate risk prostate cancer must therefore choose between active 
surveillance or whole prostate treatments, which can result in significant 
morbidity4. Since many these men would likely have indolent prostate 
cancer that would not become life threatening, the morbidity of traditional 
whole prostate treatment options may not justify their use.   
 
Focal therapy for prostate cancer may offer an ability to improve the risk-
benefit ratio of therapy for early prostate cancer by reducing the morbidity 
of treatment while maintaining oncologic efficacy.  Since about half of 
men who initially elect for active surveillance will undergo definitive 
treatment within 10 years, earlier intervention with focal therapy may 

Department of Radiation Oncology                                                                              RAD 1801 
University of Alabama Birmingham 
Protocol Version: May 12, 2020 
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actually have the potential to lower the overall symptom burden from 
prostate cancer by reducing the need for more toxic treatments. 
 
2.3 
Current state of focal therapy for prostate cancer 
 
Focal therapy options have yet to be fully endorsed by national 
professional groups such as the NCCN or American Urological 
Association; however, national patterns of care studies indicate that focal 
therapy is becoming increasingly utilized5-7.  The three most common 
forms of focal therapy utilized currently are high-intensity focal ultrasound 
(HIFU), photodynamic therapy, and cryoablation, with each modality 
having 
relative 
strengths 
and 
weaknesses. 
 
While 
significant 
heterogeneity among previous studies, biochemical control among well-
selected patients who have also undergone multiparametric MRI appear 
to fall within the range of 60-85% at 5-years8.  By comparison, the 5-year 
biochemical control of men with low-risk prostate cancer who undergo 
definitive radiation therapy or radical prostatectomy exceeds 90% among 
nearly all modern series. 
 
2.4 
SBRT for prostate cancer 
 
The rationale for prostate SBRT stems from a combination of the 
theorized sensitivity of prostate cancer to larger fractions of radiation (i.e. 
low α/β) in combination with the ability of modern radiation planning, 
targeting, and delivery techniques to accurately administer higher doses 
of radiation with small uncertainty margins.  A growing body of literature 
supports that prostate SBRT, typically with a dose of 36.25 Gy to the 
entire prostate over 5 fractions, is associated with toxicity rates similar to 
fractionated regimens9.  Early efficacy results also support that whole 
prostate SBRT is associated with high rates of biochemical control for 
men with NCCN defined low or low-intermediate risk prostate cancer9.  
Recently, prostate SBRT was endorsed by the American Society for 
Therapeutic Radiation Oncology as an option for first-line therapy for men 
with low-risk prostate cancer. 
 
At the University of Alabama at Birmingham prostate SBRT, has generally 
been performed as part of a recently completed prospective clinical trial 
(NCT01856855).  In this study, the entire prostate gland was treated to a 
dose of 36.25 Gy in 5 fractions and MRI-defined focal nodules received a 
simultaneous integrated boost to 40 Gy in 5 fractions.  This study met its 
primary safety endpoint of fewer than 15% of patients experiencing acute 
urinary retention requiring temporary placement of a Foley catheter (7.7% 
observed rate).  Biochemical follow-up data are maturing.   
 
2.5 
Rationale of SBRT for focal treatment 
 
Despite the fact that whole gland prostate SBRT is associated low rates 
of severe grade 3 genitourinary (GU) and gastrointestinal (GI), with 
adverse effects rates on the order of 1%, lower grade late toxicities are 

Department of Radiation Oncology                                                                              RAD 1801 
University of Alabama Birmingham 
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significantly more common.  The most common grade 2 late 
complications 
include 
hematochezia 
(5-15%), 
diarrhea 
(5-10%), 
hematuria (10-15%), and urethral structuring causing urinary retention (5-
10%)9.  Erectile dysfunctional will also manifest in more than half of men 
who are sexually active prior to radiation therapy10.  By reducing the 
irradiated volume with focal SBRT, radiation dose to the tissues 
responsible for the toxicities associated with whole-prostate radiation may 
be reduced.   
 
One key advantage of SBRT over current focal therapy modalities is the 
ability to account for microscopic disease extension beyond the imaging 
abnormality.  Whole mount pathology correlate studies have consistently 
shown that microscopic prostate cancer may extend up to 1 cm beyond 
the lesion seen on MRI11.  This discrepancy between imaging and 
pathologic tumor extension poses a challenge for conventional focal 
therapies such as HIFU and cryotherapy due to the relatively small area 
of tumoricidal effect around the interstitial probe8.  In order to account for 
this limitation, the probe is generally placed in multiple positions in and 
around the lesion; however, this technique is operator dependent and 
time consuming8.  In contrast, SBRT planning techniques allow for the 
target volume to be enlarged to account for microscopic disease 
extension (i.e. a clinical target volume expansion) beyond the MRI-
defined nodule.  Since expansions will generally consist of a geometric 
margin around the nodule they are less susceptible to inter-operator 
differences.   
 
Another potential advantage of the SBRT technique proposed in this trial 
over previously described focal therapy techniques is the ability to 
administer treatment without violating the perineum.  Cryotherapy, HIFU, 
and photodynamic therapy all require placement of a transperineal 
interstitial probe.  Though the rate of severe complication from probe 
placement is extremely low8, this invasive procedure is uncomfortable and 
necessitates the use of sedation or anesthesia.   
 
2.6 
Role of radiotransponder beacons in prostate cancer 
 
The primary technical challenge anticipated for the use of SBRT as a 
focal therapy modality is managing inter- and intra-treatment target 
position verification and monitoring without interfering with our ability to 
accurately delineate the focal nodule.  Accurate target verification and 
monitoring is a vital component of SBRT since it allows for reduction in 
the size of the planning target volume (PTV) expansion.   
 
The most common technique to confirm the positioning of the prostate 
before and during treatment is transperineal implantation of radiopaque 
fiducial markers or Calypso radiotransponder beacons within the prostate 
gland.  The position of radiopaque beacons can be confirmed prior to 
treatment with orthogonal kV radiographs and cone beam CT.  
Orthogonal radiographs can also be performed during radiation delivery 

Department of Radiation Oncology                                                                              RAD 1801 
University of Alabama Birmingham 
Protocol Version: May 12, 2020 
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to provide intra-treatment of target positioning.  The position of 
radiotransponder 
beacons 
are 
continuously 
assessed 
via 
an 
electromagnetic tracing station which is placed slightly above the patient.  
The advantage of radiotransponder beacons over radiopaque fiducial 
markers is that the Calypso system allows for constant verification of the 
3-dimensional position of the beacons whereas each kV radiograph 
provides only a 2-dimensional projection. 
 
2.7 
Rationale for intra-urethral radiotransponder beacons 
 
Unfortunately, both radiopaque fiducial markers and radiotransponder 
beacons have the potential to significantly interfere with accurate 
targeting of MRI-defined focal nodules.  For instance, markers placed into 
the prostate prior to MRI acquisition will result in significant artifact that 
may obscure visualization of the nodule.  On the other hand, if the 
markers are placed into the prostate after the MRI is acquired, this could 
result in subtle changes in prostate anatomy that have the potential to 
result in a marginal miss.  Historically this issue was considered of little 
clinical significance since the target volume has consisted of the entire 
prostate gland which, unlike focal nodules, is visible on the CT scan 
obtained for SBRT planning.  However, we believe that the ability to 
accurately delineate the focal nodules is paramount for focal therapy thus 
another method is needed to maintain MRI image quality. 
 
Temporary placement of radiotransponder beacons within the urethra (via 
a Foley catheter, with technique to be described subsequently) will allow 
for removal of the beacons during imaging to prevent artifact.  Since the 
radiotransponder beacons will be removed following delivery of SBRT, 
future MRIs obtained for follow-up will not be subject to severe artifact.  
An 
additional 
advantage 
of 
intraurethral 
placement 
of 
the 
radiotransponder beacons is that this technique will obviate the need for 
needle placement through the perineum 

Department of Radiation Oncology                                                                              RAD 1801 
University of Alabama Birmingham 
Protocol Version: May 12, 2020 
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3.0 
SCHEMA 
 
 
3.1 
Patients who meet the enrollment criteria will be enrolled following the 
decision to proceed with RT for pathologically proven prostate 
adenocarcinoma.  N=10 patients will be enrolled in the study. 
 
3.2 
Baseline urinary symptoms, rectal symptoms, sexual function, and global 
quality of life will be assessed using validated patient-reported 
questionnaires.   
 
3.3 
A 3-Tesla pelvic MRI containing an axial T2 sequence will be performed 
without a rectal coil.  The use of IV contrast is at the discretion of the 
treating physician.  If an MRI obtained within 3 months prior to enrollment 

Department of Radiation Oncology                                                                              RAD 1801 
University of Alabama Birmingham 
Protocol Version: May 12, 2020 
Amendment  # 1 
 
 
 
 
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is deemed clinically acceptable for treatment purposes by the treating 
physician then reacquisition is not necessary. 
 
3.4 
CT simulation will be performed with a Foley catheter in place.  
Radiopaque dummy seeds will be used to mark the anticipated location of 
the radiotransponder beacons within the catheter.   
 
3.5 
Utilizing available clinical data (biopsy, physical exam, MRI/MRS, and CT-
simulation) physicians, medical dosimetrists, and physicists will create 
and approve a treatment plan if all dosimetric and quality assurance 
measurements are met (see sections 6.3 – 6.5).  Prescribed dose will be 
8.0 Gy per fraction for a total of  5 fractions. 
 
3.6 
SBRT will be delivered in 9 to 17 calendar days, with every other day 
fashion in an outpatient clinic setting with an every-other day fashion 
treatment schedule (see section 6.8).  Intraurethral radiotransponder 
guidance will be performed for all treatments (see section 6.6.4).   
 
3.7 
Following completion of treatment, patients will be evaluated with clinical 
exams, laboratory PSA testing, and quality-of-life questionnaires at 
regular intervals (1, 3, 6, 9, 12, 18, and 24 months post-radiation) 
 
3.8 
Post-treatment multiparametric MRI and biopsy 1 year from completion of 
SBRT.  
 
4.0 
PATIENT SELECTION CRITERIA 
 
4.1 
Inclusion criteria 
 
4.1.1 All patients must have histologically confirmed adenocarcinoma of 
the prostate, with biopsies obtained within 12 months of 
registration 
4.1.1.1 Gleason score 3+3 or 3+4 
 
4.1.1.2 PSA <10 ng/mL within 3 months of enrollment 
 
4.1.1.3 Clinical stage T1a-T2a by digital rectal exam 
 
4.1.1.4 Up to 2 intraprostatic nodules visible on MRI, with 
combined volume <50% of the total prostate volume 
 
4.1.2 Karnofsky Performance Status (KPS) >70%. 
 
4.1.3 Life expectancy >10 years 
 
4.1.4 Age ≥ 19 years 
 

Department of Radiation Oncology                                                                              RAD 1801 
University of Alabama Birmingham 
Protocol Version: May 12, 2020 
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4.1.5 Subjects given written informed consent 
 
 
4.2 
Exclusion criteria 
 
4.2.1 >2 MRI defined nodules representing prostate cancer 
4.2.2 Total volume of MRI nodules exceeding 50% of total prostate 
volume 
4.2.3 Positive biopsy core in sextant region without MRI defined nodule 
(i.e. biopsy proven MRI occult prostate cancer) 
4.2.4 American Urological Association (AUA) urinary score ≥ 18.  
4.2.5 History of inflammatory bowel disease. 
4.2.6 Prior pelvic surgery 
 
4.2.7 Prior treatment for prostate cancer 
 
4.2.8 Patients using immunosuppressive medications or other 
medications that may increase radiation toxicity such as 
methotrexate, sirolimus, tacrolimus, or colchicine that are unable 
to discontinue these medications during SBRT course.  Use of 
corticosteroids is not considered an exclusion criteria. 
 
4.2.9 Platelet count < 70,000/µL 
 
4.2.10 Patients unable to discontinue anti-platelet or anti-coagulant 
medicine such as clopidogrel, dabigatran, warfarin, or low 
molecular weight heparin.  Use of aspirin is not an exclusion 
criteria. 
 
4.2.11 Contraindication to MRI such as implanted devices. 
 
4.2.12 Metallic pelvic implants resulting in imaging artifact within the 
prostate on MRI or CT. 
 
 
5.0 
DRUG INFORMATION 
 
No experimental drugs are utilized in this study. 
 
6.0 
TREATMENT PLAN 
 
6.1 
MRI acquisition 
 

Department of Radiation Oncology                                                                              RAD 1801 
University of Alabama Birmingham 
Protocol Version: May 12, 2020 
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Patients enrolled on this study will undergo acquisition of a 3-T MRI 
containing an axially acquired T2 sequence without a rectal coil. If a pre-
biopsy 3T MRI has been obtained within three months of patient 
enrollment and is deemed clinically acceptable for treatment planning 
purposes by the treating physician, then reacquisition of post-biopsy MRI 
is not necessary.   
 
6.2 
Treatment planning CT-simulation and contour/volume delineation 
 
6.2.1   Patients will undergo a pre-treatment CT-simulation scan in the 
supine position.  Patients will be instructed to have a full bladder 
and an empty rectum during CT-simulation. A 16-french Foley 
catheter will be placed with dummy seeds instead of 
radiotransponder beacons (see Section 6.7).   
 
6.2.2   CT-simulation images will be electronically fused with MRI images 
within the treatment planning software and are to be used for 
contours and treatment planning 
 
6.2.3   The treating physician will define the prostate, gross tumor volume 
(GTV), and adjacent organs at risk.  The GTV will be defined as 
the T2 hypodense nodule along with any other area suspicious for 
tumor based on other available clinical data such as other 
sequences from the multiparametric MRI. 
 
6.2.4   The clinical target volume (CTV) will consist of a 0.5 cm expansion 
around the GTV but shall not extend beyond the capsule of the 
prostate or into the urethra.   
 
6.2.4.1  A CTV expansion of 0.5 cm was chosen after considering 
reports of studies correlating MRI imaging findings with 
whole-mount pathology specimens11. 
 
6.2.5   The planning target volume (PTV) consists of a volumetric 
expansion of the CTV by 3mm in all directions. 
 
6.2.6   Adjacent organs at risk to be contoured include the bladder, 
rectum, bilateral femoral heads, bowel, urethra, and penile bulb. 
 
6.2.7   Naming conventions for target volumes and organs at risk will 
follow the AAPM TG-263 recommendations. 
 
6.2.8   The dummy seeds placed in the urethral catheter will be contoured 
and reviewed by a physicist. 
 
6.2.8.1  The dummy seed contours will be projected onto the 
reference DRRs of an orthogonal pair of setup fields. 
 

Department of Radiation Oncology                                                                              RAD 1801 
University of Alabama Birmingham 
Protocol Version: May 12, 2020 
Amendment  # 1 
 
 
 
 
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6.2.8.2  The DICOM coordinates of the centroid of each dummy 
seed and the isocenter will be transferred to the Calypso 
workstation. 
 
6.2.8.3  The Calypso system will be configured for Gating, Usage 
Mode: Set zero and track. 
 
 
 
6.3 
SBRT dose specifications 
 
6.3.1   The prescribed dose will be 40 Gy to the PTV, delivered at 8.0 Gy 
per fraction for a total of 5 fractions.   
 
6.3.2   At least 95% of the PTV should receive 100% of the prescribed 
dose.   
 
6.3.2.1    Coverage of 90-95% of the PTV by 100% of the 
prescribed dose will be considered a minor but 
acceptable deviation whereas coverage of <90% by 
100% of the prescription dose will be considered a major 
unacceptable deviation. 
 
6.3.3    Rapid dose falloff outside the PTV is to be prioritized over PTV 
dose uniformity and may result in considerable dose heterogeneity 
within the PTV, but the maximum dose within the PTV should be 
limited to 130% of the prescription.   
 
6.4 
Critical Structures 
 
The organ at risk planning guidelines for the study are given below.  All 
reasonable attempts should be maintained to minimize radiation to 
organs at risk if PTV coverage is not compromised.   
 
 
Pilot cohort (40 Gy in 5 fractions)* 
 
Organ 
Volume 
Dose (Gy) 
Rectum 
Maximum point dose (1cc) 
≤ 38.06 Gy 
 
Less than 3cc 
< 34.4 Gy 
 
90% of the rectum 
≤ 32.625 Gy 
 
80% of the rectum 
≤ 29 Gy 
 
50% of the rectum 
≤ 18.125 Gy 
Bladder 
Maximum point dose (1cc) 
≤ 38.06 Gy 
 
90% of the bladder 
≤ 32.625 Gy 
 
50% of the bladder 
≤ 18.125 Gy 
Urethra 
Maximum point dose 
≤ 38.78 Gy 
Femoral heads Less than 10cc cumulative (both sides) 20 Gy 

Department of Radiation Oncology                                                                              RAD 1801 
University of Alabama Birmingham 
Protocol Version: May 12, 2020 
Amendment  # 1 
 
 
 
 
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Maximum point dose 
30 Gy 
 
*Constraints used in prior UAB protocol of prostate SBRT that included 40 Gy in 5 
fraction focal boost (NCT01856855). 
 
6.5 
Treatment plan physics quality assurance 
 
6.5.1   All treatment plan dose distributions will be verified by UAB staff 
physicists and must meet the quality assurance standards set 
forth by the Department of Radiation Oncology prior to patient 
SBRT administration. 
 
6.5.2   Dose will be validated by either an ion chamber/film combination in 
a solid water phantom or a dose calibrated diode array. In either 
case, the phantom will be irradiated with the same plan as the 
patient including all couch angles and beam projections. A dose 
plane will be calculated and exported from the treatment planning 
system and will be compared with the measured dose plane from 
the one of the above techniques. Dose comparisons will be 
analyzed using the gamma criteria of 3%/3mm and will be 
considered valid if 95% of points have gamma values of less than 
1. 
 
6.6 
Technical factors 
 
6.6.1   All treatment plans will be devised utilizing a volumetric modulated 
arc therapy (VMAT) approach.  No restrictions are placed on the 
number and position of treatment arcs. 
 
6.6.2   Treatments will be delivered on appropriately selected linear 
accelerators at the discretion of the treating physician 
 
6.7 
Treatment delivery 
 
6.6.1   Patients will be instructed to arrive in the clinic at least 1 hour prior 
to planned treatment delivery and a 16-french Foley catheter will 
be placed and urine allowed to drain.  A Henschke style catheter 
containing 3 Calypso radiotransponder beacons will be placed into 
the urinary lumen of the Foley catheter as shown below: 
 

Department of Radiation Oncology                                                                              RAD 1801 
University of Alabama Birmingham 
Protocol Version: May 12, 2020 
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6.6.2   Patients will be instructed to have an empty rectum for treatments.  
Utilization of bowel preparation with oral or suppository 
medications is left up to the treating physician.  Endorectal 
balloons are not allowed on this study. 
 
6.6.3   Image-guidance with kilovoltage orthogonal x-rays and cone beam 
CT scans are to be utilized prior to administration of each 
radiotherapy fraction.  A physician is to approve appropriate 
patient positioning based upon set-up imaging, with the patient 
being aligned to the urinary catheter and prostate-rectum 
interface. 
 
6.6.4   The positions of the transponders of the kV orthogonal x-rays and 
the CBCT will be compared with the dummy seed reference 
contours. The catheter position will be adjusted as needed. After 

Department of Radiation Oncology                                                                              RAD 1801 
University of Alabama Birmingham 
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the patient is correctly positioned, the Calypso reference position 
(zero) will be set. 
 
6.8 
Treatment delivery schedule 
 
Radiation treatments will be delivered per the standard outpatient setting 
radiation oncology clinic. Treatment must be completed in within 17 
calendar days, with day of first treatment being considered day 1.  Exact 
treatment schedule is left to the discretion of the treating physician.  
 
 
7.0 
THERAPY MODIFICATIONS 
 
7.1 
Non-Study Treatment 
 
7.1.1 All medications and other treatment taken by the subject during 
the study, including those treatments initiated prior to study 
enrollment, must be recorded within the medical record 
 
7.1.2 Hormonal blockade agents such as leuprolide or bicalutamide will 
not be allowed in this study. 
 
7.1.3 The use of standard prescription or non-prescription medication to 
manage symptoms of disease or treatment is left to the discretion 
of the treating physician.  Examples of common medications 
prescribed for treatment of disease or radiation-related side 
effects will likely include tamsulosin, phenazopyridine, and/or 
loperamide 
 
7.2 
Concomitant Medication 
 
7.2.1 All medications administered since protocol enrollment will be 
recorded in the medical record 
 
7.2.2 No cytotoxic chemotherapies or hormonal therapies are to be 
administered during the study evaluation period 
 
7.2.3 Immediate pre or post-treatment usage of steroids (for example, 
dexamethasone 4 mg po one hour prior to radiation) is at the 
discretion of the treating physician.   
 
7.2.4 Prophylactic (or continued) usage of tamsulosin or alfuzosin (or 
other alpha-blocker medication) allowed at the discretion of the 
treating physician.  
 
7.3 
Adverse Events (AE’s) and Serious Adverse Events (SAE’s) 
 
7.3.1 Definition of AE:  Any untoward medical occurrence, which does 
not necessarily have a causal relationship with the study 

Department of Radiation Oncology                                                                              RAD 1801 
University of Alabama Birmingham 
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treatment.  This includes any physical or clinical change 
experienced by the subject, whether or not considered related to 
the study treatment.  An AE can therefore be any unfavorable or 
unintended sign (including an abnormal lab finding, for example), 
symptom, or disease (including the onset of new illness and the 
exacerbation of pre-existing conditions) temporally associated with 
the study treatment.  Progressive prostate cancer disease is not 
considered to be an AE.  Typical symptoms of radiotherapy 
treatment including grade ≤ 3 urinary or gastrointestinal toxicity will 
not be considered an AE, though they will be documented in the 
medical record (section 9.0). AE’s will be recorded in the medical 
record.   
 
7.3.2 Definition of SAE:  Any event occurring during the study 
evaluation period that results in any of the following outcomes 
• 
Death 
• 
Inpatient hospitalization 
• 
Bleeding requiring administration of blood products 
• 
Any grade ≥ 3 urinary or gastrointestinal toxicity  
  
Note that urinary retention requiring temporary urinary catheter 
placement is considered a grade 2 toxicity by the CTCAE 4.03 
 
All SAE’s must be recorded in the medical record.  The onset and 
end dates, severity, duration, effect on study administration 
(discontinuation/cancellation, for example), relationship to study 
treatment, and administration of any drugs or therapies to treat the 
SAE’s will be recorded in the medical record. 
 
7.4 
Guidelines for adverse event recording 
 
7.4.1 The Common Terminology Criteria for Adverse Events version 4.0 
(CTCAE v4.0, 
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-       
14_QuickReference_5x7.pdf) will be used for grading adverse 
events 
 
7.4.2 The investigator must assess the relationship of any AE or SAE to 
the use of study treatment using the following guidelines outlined 
in the table below: 
 
Table 7.5.3                  ATTRIBUTION OF ADVERSE EVENTS 
Code 
Descriptor 
Definition 
5 
Definite 
The adverse event is clearly related to the 
investigational treatment 
4 
Probable 
The adverse event is likely related to the 
investigational treatment 
3 
Possible 
The adverse event may be related to the 
investigational treatment 

Department of Radiation Oncology                                                                              RAD 1801 
University of Alabama Birmingham 
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2 
Unlikely 
The adverse event is doubtfully related to the 
investigational treatment 
1 
Unrelated 
The adverse event clearly not related to the 
investigational treatment 
 
 
7.5 
Monitoring of adverse events 
 
Subjects having AE’s or SAE’s will be monitored with relevant clinical 
assessments and laboratory tests as determined by the subject’s treating 
physician.  All adverse events must be followed to satisfactory resolution 
or stabilization of the event(s).  Any actions taken and follow-up results 
must be recorded in the subject’s medical record.  For all AE’s or SAE’s 
which require the subject to be discontinued from the study, relevant 
clinical assessments and laboratory tests will be repeated as clinically 
indicated, until final resolution or stabilization of the event(s). 
 
7.6 
Adverse event reporting 
 
7.6.1 Notification of all SAE’s must be reported to the Principal 
Investigator (Dr. Andrew McDonald) or his designee by calling 
(205) 975-2880.  A written report should be submitted to the 
appropriate Institutional Review Board (IRB) and UAB Clinical 
Trials Monitoring Committee per institutional policy. 
 
7.6.2 Adverse events will be reported to the Clinical Trials Monitoring 
Committee. 
 
7.7 
Data and safety monitoring plan 
 
7.7.1 This protocol will follow the UAB Data and Safety Monitoring Plan 
maintained by the UAB Comprehensive Cancer Center. 
 
7.7.2 Serious adverse events will be reviewed in the UAB radiation 
oncology treatment planning or new patient conference and the 
Department of Radiation Oncology Quality Assurance committees.  
 
7.8 
Early Termination 
 
Patients may be discontinued from study prior to completion of study 
requirements for any of the following reasons: 
 
7.8.1 The patient has a clinically significant adverse event as 
determined by the principal investigator 
 
7.8.2 The patient requests to be withdrawn from the study 
 

Department of Radiation Oncology                                                                              RAD 1801 
University of Alabama Birmingham 
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7.8.3 The patient fails to comply with the requirement for study 
evaluation/visits 
 
7.8.4 Other conditions for which, in the investigator’s opinion, it is in the 
patient’s best interest to be withdrawn from the study 
 
7.8.5 Patient did not meet eligibility requirements 
 
8.0 
STUDY PARAMETERS 
 
8.1 
For the purposes of this study, acute toxicity will be defined as event(s) 
that occur within 90 days of the completion of radiotherapy.  Acute toxicity 
will be determined by both intra-treatment examinations and by scheduled 
follow-up evaluations after the treatment has completed.  Late toxicity will 
be defined as any toxicity occurring > 90 days after the completion of 
treatment. 
 
8.2 
Baseline evaluations of enrolled patients must occur within six weeks of 
study enrollment 
 
8.3 
“Day 1” will be defined as the date of the first radiotherapy treatment.  
“Day 42/Week 5/Month 1” will represent the one month follow-up visit 
after the completion of the last radiotherapy treatment.  Day 1 and Day 
43/Week 5/Month 1 evaluations may be done within +/- 7 days of the 
specified day.   
 
8.4 
 “Month 1, 3, 6, 9, 12, 18, and 24” will be defined as the respective follow 
up visits after the completion of radiotherapy.  Month 3-24 evaluations 
may be done within +/- 30 days of the specified day.   
Table 8.1 Required evaluations and therapies 
 
Baseline Week 1-2 
Week 5/Mo 
1 
Mo 3, 6, 9, 12, 
18, 24  
PSA 
x+ 
 
x 
x 
H and P** 
x^ 
 
x^ 
x^ 
Karnofsky PS 
x 
 
x 
x 
Platelet count or CBC 
x 
 
 
 
Quality of Life 
Indices/Questionnaires*/ ** 
x 
x#, ^ 
x 
x 
CTCAE v4.0 Toxicity 
Grading 
x 
x 
x 
x 
SBRT 
 
xxxxx 
 
 
Prostate Biopsy 
x 
 
 
Month 12 
 
*   AUA Symptom Score, SHIM, and EPIC questionnaire - Appendix                                      
#   To be completed on the final day of treatment 
^   Medications will be recorded 

Department of Radiation Oncology                                                                              RAD 1801 
University of Alabama Birmingham 
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+   PSA value within 3 months of enrollment is acceptable as “baseline” 
** Due to COVID-19, these study procedures may be conducted remotely, if necessary. 
 
9.0 
EVALUATION CRITERIA 
9.1 
Pretreatment evaluations (baseline) 
• 
Complete medical history 
• 
Physical examination including digital rectal/prostate examination  
• 
Vital signs including weight 
• 
Karnofsky performance status (Appendix B) 
• 
Prostate MRI (a subset of patients may also have MR spectroscopy). 
• 
Completion of quality of life patient questionnaires and surveys, 
including an American Urological Association (AUA) symptom score 
survey, Sexual Health Inventory for Men survey,  and an Expanded 
Prostate Cancer Index Composite (EPIC) questionnaire for bowel, 
sexual, and urinary quality of life.  (Appendix C) 
• 
PSA blood work 
To be eligible for enrollment, the patient must meet all inclusion criteria.   
Results of all baseline or screening evaluations, which assure that all 
inclusion and exclusion criteria have been satisfied, must be reviewed by 
the investigator prior to enrollment of each patient.  In addition, the patient 
must be thoroughly informed about all aspects of the study, including the 
study visit schedule, required evaluations, and all regulatory requirements 
for informed consent.  The written informed consent must be obtained 
from the patient prior to enrollment.  Due to COVID-19, these study 
procedures may be conducted remotely, if necessary. 
9.2 
Technical feasibility 
For the purposes of this study, technical feasibility encompasses two 
major components: implementation of the intraurethral radiotransponder 
motion management technique and treatment planning and treatment 
delivery of single fraction focal SBRT.  Treatment planning includes 
integration of clinical data (exam, biopsy, and medical imaging) to create 
targets for radiotherapy treatment.  Treatment delivery includes the ability 
to administer planned radiotherapy dose accurately, including pre-
treatment physics quality assurance and accurate patient positioning and 
image guidance. 

Department of Radiation Oncology                                                                              RAD 1801 
University of Alabama Birmingham 
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9.2.1 Intraurethral radiotransponder feasibility 
Feasibility of implementing the intraurethral transponder technique 
will be determined by  
• 
Successful use of the treatment planning system to 
anticipate the location of the radiotransponder beacons 
based on the CT simulation scan anatomy 
• 
Successful placement of the beacon-loaded Foley catheter 
by the treatment planning team 
• 
Appropriate detection of the beacons by the Calypso 
detection unit 
• 
Transponder beacons continually monitored without 
interruption during treatment delivery 
9.2.2 Treatment planning feasibility 
The treatment planning feasibility will be determined by the ability 
of the treating physician and involved dosimetrists and physicists 
to produce a radiotherapy treatment plan that meets the 
specifications in section 6.3 and 6.4.   
9.3 
Treatment delivery 
 
9.3.1 All treatment plan dose distributions will be verified by UAB staff 
physicists and must meet the quality assurance standards set 
forth by the Department of Radiation Oncology prior to patient 
SBRT administration.  Pre-treatment tissue phantom quality 
assurance checks will be completed.  The phantom will be 
irradiated with the same plan as the patient including all couch 
angles and beam projections. A dose plane will be calculated and 
exported from the treatment planning system and will be 
compared with the measured dose plane from the one of the 
above techniques. Dose comparisons will be analyzed using the 
gamma criteria of 3%/3mm and will be considered valid if 95% of 
points have gamma values of less than 1. 
 
Once plans have met physics quality assurance parameters, 
treatment delivery will commence.  Clinical treatment delivery 
feasibility will be determined by the ability of the patient to be set 
up accurately with confirmation of appropriate geometry on 
kilovoltage imaging.   
9.4 
Treatment phase 

Department of Radiation Oncology                                                                              RAD 1801 
University of Alabama Birmingham 
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9.4.1 The patient will be evaluated at least once by the treating 
physician during the time that he is undergoing radiotherapy 
treatment.   
9.4.2 On the final day of treatment the patient will complete an AUA 
symptom score, SHIM, and EPIC questionnaires and the treating 
physician will give toxicity grades for any toxicity present at the 
time. 
9.5 
Follow-up 
9.5.1 As outlined in section 8.0, follow-up examinations will occur at 
regularly scheduled intervals, occurring every three months for 
one year and then every six months at the year one to two interval 
in order to appropriately monitor acute and late toxicity, quality of 
life, and PSA response. 
9.5.2 For each follow up visit, the treating physician will complete an 
updated medical history and perform a physical examination, 
evaluate KPS, and grade any toxicity noted.  Symptom score 
surveys and questionnaires will be completed by the patient and 
PSA lab draws will be performed. Some of these study procedures 
may be conducted remotely, if necessary. 
10.0 
PATIENT REGISTRATION 
Patients can be registered by calling 205-975-2879. 
11.0 
STATISTICAL CONSIDERATIONS 
 
11.1 
Endpoints and measure of success 
11.1.1 The primary endpoint of the pilot portion of this study is feasibility 
of focal treatment using the intra-urethral radiotransponder beacon 
technique as defined in section 9.2. 
11.1.2 This pilot study will be considered successful if at least 9 of 10 
patients who begin treatment are able to complete treatment using 
the described technique. 
11.2 
Secondary endpoints include clinical toxicity and efficacy       
assessments. 
   
11.2.1 Clinically assess early toxicity, early efficacy, late toxicity, and 
quality of life for patients receiving focal prostate SBRT. 
 
11.3 
Toxicity evaluation 
 
11.3.1 Acute and late toxicity will be graded per the Common 
Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0, 

Department of Radiation Oncology                                                                              RAD 1801 
University of Alabama Birmingham 
Protocol Version: May 12, 2020 
Amendment  # 1 
 
 
 
 
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http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-
14_QuickReference_5x7.pdf). 
 
11.3.2 Definition of acute toxicity: any possible, probable, or definite 
treatment-related AE or SAE occurring within three months of the 
completion of radiotherapy. 
 
11.3.3 Definition of late toxicity: any possible, probable, or definite 
treatment-related AE or SAE occurring after three months of the 
completion of radiotherapy. 
 
11.4 
Efficacy assessments of secondary endpoints 
 
11.4.1 Efficacy will be assessed using PSA measurements and biopsy 
results. Efficacy assessments will be made at the time points 
indicated in Table 8.1 (“Required evaluations and therapies”). 
 
11.4.2 Quality of life will be assessed using the American Urological 
Association Benign Prostatic Hyperplasia Symptom Score (AUA 
Symptom Score), the Sexual Health Inventory for Men (SHIM) and 
The Expanded Prostate Cancer Index Composite (EPIC). EPIC 
includes bowel, urinary, and sexual assessments. Quality of life 
assessments will be made at the time points indicated in Table 8.1 
(“Required evaluations and therapies”).  
 
11.5 
Statistical Analyses 
 
11.5.1 All statistical analyses will be descriptive. No formal statistical 
comparisons are planned. Descriptive statistics will be calculated 
at baseline and at various follow-up time points as indicated in 
Table 8.1 (“Required evaluations and therapies”). These include 
means, standard deviations, medians, and ranges for continuous 
variables and frequencies and percentages for categorical 
variables. In addition, 95% confidence intervals will be calculated 
for means and exact binomial 95% confidence intervals will be 
calculated for proportions (such as toxicity rates). 
 
11.5.2 Continuous variables include PSA measurements and the 
composite scores from all three quality of life questionnaires, i.e. 
the composite AUA Symptom Score, the composite SHIM score, 
and the composite EPIC score. Categorical variables include 
toxicity results and biopsy results. 
 
11.5.3 Statistical analyses will be performed using SAS, version 9.4 or 
later (SAS Institute, Inc.; Cary, NC). 
 
11.6 
Sample Size 
 

Department of Radiation Oncology                                                                              RAD 1801 
University of Alabama Birmingham 
Protocol Version: May 12, 2020 
Amendment  # 1 
 
 
 
 
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11.6.1 A total of 10 patients will be enrolled into this feasibility study. The 
study will be considered successful if at least 9 of 10 patients who 
begin treatment are able to complete treatment using the 
described technique. A success rate of 90% in 10 patients will 
lead to an exact binomial 95% confidence interval of (0.5550, 
0.9975). This wide confidence interval (width=0.4425) is expected 
given our small sample size. If all 10 patients are able to complete 
treatment, the lower confidence limit of the corresponding exact 
binomial 95% confidence interval will be 0.6915. 
 
 

Department of Radiation Oncology                                                                              RAD 1801 
University of Alabama Birmingham 
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12.0 
REFERENCES 
 
 
1. 
Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA: a cancer journal for 
clinicians 2017;67:7-30. 
2. 
Mohler JL, Armstrong AJ, Bahnson RR, et al. Prostate Cancer, Version 1.2016. 
Journal of the National Comprehensive Cancer Network : JNCCN 2016;14:19-30. 
3. 
Hamdy FC, Donovan JL, Lane JA, et al. 10-Year Outcomes after Monitoring, 
Surgery, or Radiotherapy for Localized Prostate Cancer. The New England journal of 
medicine 2016;375:1415-24. 
4. 
Lardas M, Liew M, van den Bergh RC, et al. Quality of Life Outcomes after 
Primary Treatment for Clinically Localised Prostate Cancer: A Systematic Review. 
European urology 2017. 
5. 
Crouzet S, Murat FJ, Pasticier G, Cassier P, Chapelon JY, Gelet A. High intensity 
focused ultrasound (HIFU) for prostate cancer: current clinical status, outcomes and 
future perspectives. International journal of hyperthermia : the official journal of 
European Society for Hyperthermic Oncology, North American Hyperthermia Group 
2010;26:796-803. 
6. 
Shafirstein G, Bellnier D, Oakley E, et al. Interstitial Photodynamic Therapy-A 
Focused Review. Cancers 2017;9. 
7. 
Loppenberg B, Sood A, Dalela D, et al. Variation in Locoregional Prostate Cancer 
Care and Treatment Trends at Commission on Cancer Designated Facilities: A National 
Cancer Data Base Analysis 2004 to 2013. Clinical genitourinary cancer 2017. 
8. 
Ouzzane A, Betrouni N, Valerio M, Rastinehad A, Colin P, Ploussard G. Focal 
therapy as primary treatment for localized prostate cancer: definition, needs and future. 
Future oncology (London, England) 2017;13:727-41. 
9. 
Kishan AU, King CR. Stereotactic Body Radiotherapy for Low- and 
Intermediate-Risk Prostate Cancer. Seminars in radiation oncology 2017;27:268-78. 
10. 
Potosky AL, Davis WW, Hoffman RM, et al. Five-year outcomes after 
prostatectomy or radiotherapy for prostate cancer: the prostate cancer outcomes study. 
Journal of the National Cancer Institute 2004;96:1358-67. 
11. 
Priester A, Natarajan S, Khoshnoodi P, et al. Magnetic Resonance Imaging 
Underestimation of Prostate Cancer Geometry: Use of Patient Specific Molds to 
Correlate Images with Whole Mount Pathology. The Journal of urology 2017;197:320-6. 
 
 

Department of Radiation Oncology                                                                              RAD 1801 
University of Alabama Birmingham 
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APPENDICES 
Appendix A: Toxicity Criteria 
This study will utilize NCI Common Terminology Criteria for Adverse Events (CTCAE) 
version 4.0 for toxicity and Adverse Event Reporting. A copy of the CTCAE version 4.0 
can be downloaded from the CTEP web site at: 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm 
 
 Appendix B: Karnofsky Performance Status (KPS) 
 
100  
Normal.  No complaints; No evidence of disease 
90 
 Able to carry on normal activity; minor signs or symptoms of 
disease 
80  
Normal activity with effort; some signs or symptoms of 
disease 
70  
Cares for self; unable to carry on normal activity or do active 
work 
60 
Requires occasional assistance, but is able to care for most 
personal needs 
50  
Requires considerable assistance and frequent medical care 
40  
Disabled; requires special care and assistance 
30  
Severely disabled; hospital admission is indicated although 
death is not imminent 
20  
Very sick; hospital admission necessary, active supportive 
treatment necessary 
10  
Moribund; fatal processes progressing rapidly 
0  
Dead 
 
 
 
Appendix C: Quality of Life Questionnaires and Surveys (Please see attached) 
 
 
-American Urological Association Symptom Index (AUA SI) 
 
-Sexual Health Inventory for Men (SHIM) 
 
-The Expanded Prostate Index Composite (EPIC) 
 
 
*Bowel Assessment 
 
 
*Urinary Assessment 
 
 
*Sexual Assessment 
 
 
Appendix D: NCCN Clinical Practice Guidelines in Oncology 
 

Department of Radiation Oncology                                                                              RAD 1801 
University of Alabama Birmingham 
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This study will utilize the NCCN Guidelines for Prostate Cancer. The NCCN Guidelines 
outlined at http://www.nccn.org/professionals/physicians_gls/f_guidelines.asp#site will 
be used to divide patients into the following risk categories: very low, low, or 
intermediate.