RAD 1203: Pilot Trial Evaluating Stereotactic Body Radiotherapy With Integrated Boost for Clinically Localized Prostate Cancer
Phase: NA
Conditions: Prostate Cancer, Prostate Adenocarcinoma, Radiation Toxicity, Sexual Dysfunction
Sponsor: John Fiveash, MD

Department of Radiation Oncology                                                                              RAD 1203                  
University of Alabama Birmingham 
Protocol Version: June 16, 2021  
 
 
 
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RAD 1203 – Pilot Trial Evaluating Stereotactic Body Radiotherapy with 
Integrated Boost for Clinically Localized Prostate Cancer 
 
 
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 
 
APPENDICES 
 
A. 
TOXICITY CRITERIA 
B. 
PERFORMANCE STATUS CRITERIA 
C. 
QUALITY OF LIFE QUESTIONNAIRES AND 
SURVEYS 
D. 
NCCN GUIDELINES FOR PROSTATE CANCER 
E. 
PARTIN TABLES 
 
Approval Dates:  
 
8/29/2012 
 
 
    ____1/9/2013 
 
 
 
 
 
CTRC  
 
 
 
  IRB 
 
Principle Investigator 
 
John B. Fiveash, MD 
University of Alabama at Birmingham  
Hazelrig-Salter Radiation Oncology Center  
1700 6th Avenue South, 176F, Suite 2230 
Birmingham, AL  35233  
Phone:  205-975-0224   
 
 
 
 
 
 
 

Department of Radiation Oncology                                                                              RAD 1203                  
University of Alabama Birmingham 
Protocol Version: June 16, 2021  
 
 
 
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Co-Investigators 
 
Michael Dobelbower, MD, PhD;  Rojymon Jacob, MD;  Robert Kim, MD; Andrew 
McDonald, MD; Eddy Yang, MD, PhD;  O. Lee Burnett, MD;  Peter Kolettis, MD; 
Richard Popple, PhD;  Rex Cardan, PhD; Jeffrey Nix, MD; Sunil Sudarshan, MD; 
Soroush Rais-Bahrami, MD; Jared Maas, MD 
 
Biostatistician 
 
Alan Cantor, PhD 
 
Research Nurse & Data Coordinator 
 
 
Regulatory 
 
Kristin Webb, CCRP 
 
 
Document History Table 
 
Version/ Update Date 
Protocol Update 
February 11, 2013 
Amendment # 1 
November 19, 2013 
Protocol Update 
October 23, 2014 
Amendment # 2 
January 23, 2017 
Amendment 3 
June 16, 2021 
 
 
 
 

Department of Radiation Oncology                                                                              RAD 1203                  
University of Alabama Birmingham 
Protocol Version: June 16, 2021  
 
 
 
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1.0  OBJECTIVES 
 
1.1 
Primary:  Clinically assess the early toxicity of SBRT with integrated 
boost for clinically localized prostate cancer 
 
1.2 
Secondary:  Determine the technical feasibility (see section 9.2) of 
stereotactic body radiotherapy (SBRT) with integrated boost for clinically 
localized prostate cancer 
 
1.2.1 Determine the treatment planning and dosimetric feasibility 
 
1.2.2 Evaluate the treatment delivery quality assurance 
 
1.3 
Secondary:  Clinically assess early efficacy, late toxicity, and quality of 
life for patients receiving SBRT with integrated boost for clinically 
localized prostate cancer 
2.0 
BACKGROUND AND RATIONALE 
 
2.1 
Prostate Cancer Overview 
 
Prostate cancer is the most common non-cutaneous cancer in men in the 
United States, with 186,000 new cases in 2008.  It is the second most 
common cause of cancer mortality, with 28,600 deaths per year1.  The 
median age at diagnosis is 70 years, and the vast majority of prostate 
cancers are pathologically classified as adenocarcinomas.  About two 
thirds of all prostate cancers arise in the peripheral zone of the prostate.  
Patients are often grouped into low, intermediate, or high risk cohorts 
according to risk stratification schemes based upon well established risk 
factors including PSA level, Gleason score, and clinical stage (see 
Appendix 1).   
 
Definitive treatment options for patients with clinically localized prostate 
cancer include radical prostatectomy, external beam radiotherapy, and 
brachytherapy or a combination of external beam radiotherapy and 
brachytherapy, with or without androgen deprivation2.    To date, no 
randomized trials have directly compared treatment modalities.  The 
selection of the appropriate treatment option involves a complex decision 
making process, with patients and their treating physicians weighing the 
risks and benefits of each option to select the appropriate treatment 
modality.   
 
Of those eligible for definitive treatment, a large cohort of patients will 
elect to undergo external beam radiotherapy.  This is generally delivered 
as a daily Monday through Friday, outpatient-based procedure, with each 

Department of Radiation Oncology                                                                              RAD 1203                  
University of Alabama Birmingham 
Protocol Version: June 16, 2021  
 
 
 
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treatment time lasting about 5-15 minutes per treatment and total treatment 
duration lasting between 5-8 weeks. 
 
 
2.2 
Prostate cancer has a low alpha/beta ratio 
 
Cell survival after doses of radiation is modeled by an exponential 
function with both a linear (alpha) and quadratic (beta) component.  The 
ratio of alpha/beta for normal tissues and tumors predicts the differential 
repair of normal tissues and tumor tissues with fractionated radiation 
therapy.  Normal tissues generally have an alpha/beta ratio of 
approximately 3, while the value for tumors is usually around 10, though 
this value can vary significantly between different types of tumors3.  
Initially these fundamental models, as well as clinical experience, lead to a 
standard treatment for prostate cancer that consists of approximately 8 
weeks of daily radiation treatments.   However, more recent biological and 
clinical data would suggest that the alpha/beta ratio for prostate cancer 
cells is lower than previously believed, with analytical estimations and 
clinical models revealing values for prostate cancer in the range of 1-4 
(Table 2.2).  Clinical investigators have accepted an alpha beta ratio of 
~1.5 as a foundation for formulating dose fractionations schemes when 
devising recent prostate SBRT clinical trials5,6.  This lower alpha beta ratio 
for prostate cancer would suggest a benefit in tumor control with shorter 
courses of radiation and larger doses per fraction.  A shorter treatment 
schedule would also be more convenient to patients and more cost 
effective as well.   
 
 
Table 2.2: Summary of alpha/beta estimates 
Author 
Type of Estimate 
Estimated alpha/beta ratio 
King 4 
Analytical estimation 
1.8 
Brenner 5 
Clinical Model 
1.2 
Williams 6 
Clinical Model 
3.7 
 
 
 
 

Department of Radiation Oncology                                                                              RAD 1203                  
University of Alabama Birmingham 
Protocol Version: June 16, 2021  
 
 
 
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2.3 
Short course (hypofractionated) radiation dose schedules are feasible 
Numerous institutions have implemented hypofractionated (short course) 
regimens for prostate cancer.  These regimens initially reduced treatment 
times from 8 weeks, to 5 weeks, with more recent reports of 1-2 week 
courses of radiation7-11.  The feasibility of delivering these 
hypofractionated dose levels has been greatly facilitated by the better daily 
targeting providing by advanced radiation techniques such as intensity 
modulated radiation therapy and daily CT-based image guidance.  The 
limit to abbreviating the treatment time is acute and late normal tissue 
toxicity; specifically, rectal, urethral, and bladder toxicity.  Recent reports 
from one to two week SBRT regimens have shown grade 3 (G3) or higher 
acute and late GU and GI  toxicities of less than 5% 9-11.  The Stereotactic 
Hypofractionated Accurate Radiation to the Prostate (SHARP) trial used a 
fraction regimen of  6.7 Gy in 5 fractions for a total of 33.5 Gy total for 
the treatment of low risk patients9.  Most of the patients on this trial were 
treated on consecutive days.  The toxicity of the SHARP regimen has been 
reported as less than 3% for acute G3 GU side effects and no acute G3 GI 
or late G3 GU or GI side effects were reported.  Based upon the favorable 
acute and late toxicity profiles, the SHARP investigators suggested that 
further dose escalation should be possible, thus future trials have 
attempted to increase the dose while closely monitoring for adverse side 
effects. 
 
In the prostate SBRT phase II clinical trial at Stanford University, patients 
were treated with 7.25 Gy per fraction to a total dose of 36.25 Gy with 
treatment initially being delivered once daily, then subsequent protocol 
modifications dictated that patients be treated in an every other day 
fashion.  This trial included mostly low-risk patients, but some selected 
intermediate risk patients were allowed as well if a limited number of 
biopsy cores involved adenocarcinoma.  A total of 67 patients were 
accrued to this trial, with two patients (3.5%) having G3 late urinary 
toxicity and none having G3 rectal toxicity, and no patient having any 
Grade 4 acute or late toxicities.  There were no instances of urinary 
incontinence, persistent hematuria, or complete urinary obstruction.  The 
4-year actuarial biochemical freedom from recurrence was 94% and the 
investigators concluded that their data supports consideration of SBRT as 
a therapeutic option for localized prostate cancer.  
 
In an effort to match dosages achieved in prostate HDR brachytherapy, the 
University of Texas Southwestern has reported a Phase I dose-escalation 
SBRT study (45  47.5  50 Gy in 5 fractions) for low- and 
intermediate-risk prostate cancer, once again demonstrating favorable 
acute and late toxicities, even at doses as high as 50 Gy in 5 fractions.  
These results are summarized in the table below. 
 

Department of Radiation Oncology                                                                              RAD 1203                  
University of Alabama Birmingham 
Protocol Version: June 16, 2021  
 
 
 
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Table 2.3: Summary of GU and GI toxicity from prostate SBRT trials 
Author 
Institution 
# Patients 
G3 Acute 
GU  
G3 Acute 
GI 
G3 
Late 
GU 
G3 
Late 
GI 
Madsen 9 
“SHARP” 
Virginia 
Mason  
40 
1 (2.5%) 
0 
0 
0 
King 10 
 
Stanford 
University 
67 
0 
0 
2 (3.5%) 
0 
Boike 11 
Texas 
Southwestern 
45 
0 
0 
2 (4.4%) 
0 
 
2.4 
Radiation dose escalation 
Radiation dose escalation has demonstrated a benefit in the treatment of 
prostate cancer.  Dose escalation has been shown to be safe and beneficial 
when using conventional fractionation schedules (8 weeks, 1.8 – 2.0 
Gy/day) comparing 78 Gy to 70 Gy12.  The efficacy of dose escalation has 
been tested through additional studies and has consistently shown a 
biochemical relapse free survival advantage for higher doses with only 
slightly higher incidences of acute GI toxicity13-14.  
 
In the SHARP trial, eligible patients received prostate SBRT with 6.7 Gy 
for 5 fractions for a total dose of 33.5 Gy. The PSA control rate was 70% 
at 40 months median follow-up.  This biochemical control rate is lower 
than what investigators initially projected and was somewhat lower than 
those reported in previous standard fractionation (1.8-2.0 Gy/fraction to 78 
Gy) and hypofractionated (2.5 Gy/fraction to 70 Gy) regimens 7,12-14. 
Subsequent prostate SBRT researchers have suggested that dose-
escalation above that utilized in the SHARP trial is necessary to improve 
efficacy.  Results from the updated Stanford experience have shown 
improved PSA control rates at 4-years (94%) over that of SHARP trial, 
with Stanford utilizing a slightly higher dose regimen of 7.5 Gy in 5 
fractions versus the SHARP regimen of 6.7 Gy in 5 fractions.   
The level of radiation dose escalation that is possible is limited by the 
toxicities of the adjacent normal tissues, but as technological advances in 

Department of Radiation Oncology                                                                              RAD 1203                  
University of Alabama Birmingham 
Protocol Version: June 16, 2021  
 
 
 
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treatment planning and delivery (IMRT, volumetric modulated arc 
therapy, IGRT) continue to improve, higher doses with favorable side 
effect profiles have become possible.   
 
The most mature clinical data for dose escalation involve homogenous 
dose escalation to the entire prostate12-14.  With improved imaging 
modalities there has also been recent interest in selectively boosting 
dominant prostate nodules or areas at high risk for local recurrence to even 
higher doses while treating the surrounding prostate to a more 
conventional dose level, rather than homogenously continuing to boost the 
entire prostate (see Section 2.5.1).   
 
2.5 
Magnetic resonance imaging (MRI) for prostate cancer 
 
MRI and MR spectroscopy (MRS) can provide valuable information 
regarding prostate tumor extent, localization, and aggressiveness15.  
Traditionally, prostate MRI was utilized for localizing prostate cancer 
when suspicion for malignancy was high (elevated PSA) and a previous 
trans-rectal ultrasound guided biopsy had failed to detect prostate cancer.  
Optimal MR imaging included use of 1.5 Tesla (T) strength magnetic field 
and an endorectal coil.  1.5T endorectal coil T2-weighted MRI and MRS 
images when combined yield a localization accuracy of ~80%16. 
 
With improvements in the precision of definitive treatment modalities, an 
accurate assessment of tumor extension has become increasingly 
important.  New high-field-strength MR scanners (ie, 3T) are becoming 
more widely available in the clinical setting. The increased signal-to-noise 
ratio inherent at 3T as compared with 1.5T offers advantages for clinical 
MRI/MRS such as shortening of acquisition time and increased spatial 
resolution, or a combination of these two. This may improve local staging 
and localization accuracy in prostate cancer patients17.  Studies have 
shown that 3T MR localization of prostate cancer without an endorectal 
coil is comparable to that of 1.5T with an endorectal coil18.    
 
 
2.5.1 The value of MRI/MRS in radiotherapy treatment planning  
 
Although the classic approach to external beam radiation therapy 
applies homogeneous dose distributions within the targeted tumor 
to avoid under-dosing tumor deposits, recent advances in imaging 
provide an approach to define anatomic subregions of the tumor 
according to their level of radiosensitivity or radioresistance. 
IMRT provides an approach for differential dose painting to 
selectively increase the dose to specific tumor-bearing regions. 
With IMRT techniques, radiation dose distributions can be 
produced that permit simultaneous delivery of different dose 

Department of Radiation Oncology                                                                              RAD 1203                  
University of Alabama Birmingham 
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prescriptions to multiple target sites. To be able to “dose paint” 
with IMRT, one needs to know the tumor location, volume, and 
extent.  MRI /MRS provide the best imaging modality for 
determining prostate cancer localization, volume, and extent15.   
 
Traditionally, the planning target volume for prostate external 
beam radiotherapy has included the whole prostate, with a goal of 
a homogenous dose distribution throughout the entirety of the 
prostate.  However, more recent tumor control probability models 
have suggested that a “selective boosting” technique that delivers 
higher radiotherapy dosages to high risk tumor subvolumes (versus 
homogenous dose escalation) may be optimal for prostate cancer 
local tumor control while minimizing side effects from 
radiotherapy damage to adjacent normal tissues19.  Similarly, dose 
distributions for prostate brachytherapy also utilize an approach 
that delivers higher doses to areas more likely harboring disease 
(peripheral zone), while relatively under-dosing areas less likely to 
have malignant cells yet are close to dose-limiting structures such 
as the transitional zone or peri-urtheral areas. 
 
2.5.2 Clinical usage of MRI/MRS for determination of high-risk 
prostate cancer volumes 
 
Treatment planning studies have shown that IMRT can be used to 
increase the dose to selected tumor-bearing regions within the 
prostate as identified with MRI/MRS20.  A Phase I study at the 
NCI proved feasibility for utilization of MRI for localization of 
dominant intra-prostatic lesions to deliver a simultaneous 
integrated boost (SIB) of 94.5 Gy at 2.25 Gy per fraction to the 
dominant lesion while the surrounding prostate received a dose of 
75.6 Gy at 1.8 Gy per fraction21.   
 
 
2.6 
Rationale for dose selection in the current trial 
 
Reports from the three aforementioned prospective prostate SBRT trials 
have demonstrated excellent toxicity profiles and good early efficacy for 
the treatment of low and intermediate risk prostate cancer.  The excellent 
side effect profile but less favorable biochemical control reported in the 
SHARP trial has led investigators to favor higher SBRT dosages.   
The optimal dose that achieves appropriate tumor control with a favorable 
side effect profile is yet to be determined.  In addition to the prospective 
trials outlined above, a retrospective report of a large cohort of patients (n 
= 234) having been treated by a 7.25 Gy per fraction for five fractions 
SBRT regimen has also reported excellent safety, quality of life, and early 
efficacy22.   

Department of Radiation Oncology                                                                              RAD 1203                  
University of Alabama Birmingham 
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At dosages as high as those administered for prostate SBRT, even slight 
increases in dose per fraction can have a significant impact on overall cell 
kill and calculated biological equivalent dose (BED).  
 
 
Where BED = biologically equivalent dose, D= total dose, d= dose per 
fraction, and α/β= the dose at which cell killing by nonrepairable damage 
is equal to that of repairable damage.  Table 3 demonstrates equivalent 
standard fractionation (2.0 Gy/fraction) BED’s for selected relevant 
prostate SBRT fractionation schemes when considering an alpha beta ratio 
of 1.5. 
 
Table 3:  Biological equivalent doses for prostate SBRT dose 
schedules 
 
 
 
 
 
Based on earlier prostate SBRT trials and clinical models suggesting a 
benefit for a selective boosting technique, this protocol is designed for 
administration of 7.25 Gy X 5 fractions to whole prostate with an 
additional 0.75 Gy integrated boost (for a total of 8.0 Gy per fraction) to a 
high-risk area administered in an every-other-day fashion.  Thus, the 
whole prostate would receive 36.25 Gy while a smaller sub-volume of the 
prostate would receive 40 Gy over a total of five treatments.  The high-risk 
boost volume will be determined from prostate MRI/MRS, biopsy results, 
and clinical exam findings (see section 6.2.1).   
 
 
 
 
 
 
 
 
Prostate SBRT 
Dose schema 
2.0 Gy per fraction 
equivalent 
6.70 Gy x 5 
78.5   Gy 
7.25 Gy x 5 
90.6   Gy 
8.00 Gy x 5 
108.5 Gy 
10.0 Gy x 5 
130.0 Gy 

Department of Radiation Oncology                                                                              RAD 1203                  
University of Alabama Birmingham 
Protocol Version: June 16, 2021  
 
 
 
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The current trial will attempt to determine the early clinical toxicity of SBRT with 
integrated boost for clinically localized prostate cancer.  Technical feasibility, early 
efficacy, late toxicity, and quality-of-life will also be investigated. 
 
 
 
3.0 
SCHEMA 
 
 
 
3.1 
Patients will be accrued after a pathological diagnosis of prostate 
adenocarcinoma is made and patient meets enrollment criteria.  We 
anticipate a total of 30 patients to be accrued. 
 
3.2 
Enrolled patients will undergo a 3-T MRI/MRS evaluation of the prostate 
without the use of an endorectal coil.  If a pre-biopsy MRI/MRS has been 
obtained within s ix months of patient enrollment and is deemed clinically 
acceptable for treatment planning purposes by the treating physician, then 
reacquisition of post-biopsy MRI/MRS is not necessary.   
 
3.3 
Patients may have gold-fiducial markers placed in the prostate under trans-
rectal ultrasound guidance, but decision and timing of fiducial placement 
is optional and at the discretion of the treating physician. 
 
3.4 
Utilizing available clinical data (biopsy, physical exam, MRI/MRS, and 
CT-simulation) physicians, medical dosimetrists, and physicists will create 
Biopsy-proven prostate adenocarcinoma: low and 
intermediate risk patients N=30 
Boost Volume Determination:  3-T Prostate 
MRI/MRS and/or Saturation Biopsy 
Treatment planning – IMRT approach 
simultaneous integrated boost to high risk areas 
Treatment delivery - SBRT with integrated boost,
7.25/8.00 Gy for five fractions  
Safety, technical feasibility, efficacy, and quality of life 
evaluations with follow-up clinical exams 

Department of Radiation Oncology                                                                              RAD 1203                  
University of Alabama Birmingham 
Protocol Version: June 16, 2021  
 
 
 
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and approve a treatment plan if all dosimetric and quality assurance 
measurements are met (see section 6.1.2).  Prescribed dose will be 8.0 Gy 
per fraction to the high risk area and 7.25 Gy to the surrounding prostate 
for a total of five fractions, delivered via a simultaneous integrated boost 
technique. 
 
3.5 
SBRT will be delivered in 7 to 17 calendar days, with every other day 
fashion in an outpatient clinic setting with an every-other day fashion 
treatment schedule recommended though not required (see section 6.7.1)  
 
3.6 
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).   
 
4.0 
PATIENT SELCTION CRITERIA 
 
4.1 
Inclusion criteria 
 
4.1.1 All patients must have histologically confirmed prostate 
adenocarcinoma, with biopsies obtained within twelve months of 
patient registration 
 
4.1.2 NCCN risk category very low, low,  or intermediate risk 
(Appendix D) 
 
 Combined Gleason score ≤ 7 
 
 PSA within three months of enrollment <20 ng/ml 
 
 Clinical stage T1a-cN0M0 or clinical stage T2aN0M0 
 
Patients that have prostate MRI “upstaging” 
showing cT2bN0M0 or cT2cN0M0 disease will 
still be considered intermediate risk and eligible 
for study 
 
Patients that have prostate MRI “upstaging” to 
cT3N0M0 disease are not eligible 
 
4.1.3 Life expectancy >5 years 
 
4.1.4 Risk of malignant lymph node involvement < 15% as calculated on 
Partin tables (Appendix E).   
 
4.1.5 Karnofsky performance status (KPS) ≥ 60 (Appendix B) 
 

Department of Radiation Oncology                                                                              RAD 1203                  
University of Alabama Birmingham 
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4.1.6 Age > 19 years 
 
4.1.7 Subjects given written informed consent 
 
 
4.2 
Exclusion criteria 
 
4.2.1 History of inflammatory bowel disease 
 
4.2.2 Prior radical prostate surgery, transurethral resection of the 
prostate (TURP), or prostate cryotherapy 
 
4.2.3 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 are not considered an exclusion criteria.   
 
4.2.4 Platelet count < 70 
 
4.2.5 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. 
 
4.2.6 Pre-SBRT prostate volume >120 cc as estimated by trans-rectal 
ultrasound at time of prostate biopsy (TRUS biopsy). 
 
4.2.7 Risk of malignant lymph node involvement > 15% as calculated on 
Partin tables 
 
5.0 
DRUG INFORMATION 
 
5.1 
No experimental drugs are utilized in this study. 
 
 
6.0 
TREATMENT PLAN 
 
6.1 
Treatment planning CT-simulation and contour/volume delineation 
 
6.1.1 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. 
 

Department of Radiation Oncology                                                                              RAD 1203                  
University of Alabama Birmingham 
Protocol Version: June 16, 2021  
 
 
 
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6.1.2 CT-simulation images will be electronically fused with MRI/MRS 
images where applicable within the treatment planning software 
and are to be used for contours and treatment planning. 
 
6.1.2.1 The treating physician will define the prostate volume, high 
risk boost volume, and adjacent organs at risk.  Boost 
volume is to be defined as the area most likely to harbor 
malignant cells, as determined by available clinical data 
including prostate MRI, clinical exam, and biopsy 
localization. In some cases MR spectroscopy and this 
information will be included if available to determine the 
target volume. 
 
6.1.2.2 Boost volume must not be >50% of the prostate volume.  
 
6.1.2.3 Clinical target volume 1 (CTV1) will encompass the entire 
prostate volume minus the high risk boost volume . 
 
6.1.2.4 CTV2 be the high risk boost volume.  The volume of the 
CTV2 must not be >50% of the volume of the prostate. 
 
6.1.2.5 Planning target volume 1 (PTV1) consists of a volumetric 
expansion of the CTV1 by 5mm in all directions except for 
posteriorly, as a 3mm expansion is utilized.  
 
6.1.2.6 PTV2 consists of a volumetric expansion of CTV2 by 5mm 
in all directions except for posteriorly, as a 3mm expansion 
is utilized. 
 
6.1.2.7 Adjacent organs at risk to be contoured include the bladder, 
rectum, bilateral femoral heads, bowel, urethra, and penile 
bulb. 
 
6.2 
SBRT dose specifications 
 
6.2.1 The prescribed dose will be 36.25 Gy to the PTV1 and 40.0 Gy to 
the PTV2, delivered as 7.25 Gy and 8.0 Gy per fraction, 
respectively, for a total of five fractions. 
 
6.2.2 For the PTV2, 95% of the PTV2 prescription must cover ≥ 95% of 
the PTV2.   
 
6.2.3 In addition, 95% of the PTV1 must be encompassed by at least that 
34.4 Gy isodose line (95% of PTV1 prescription dose).  Attempts 
should be made to normalize plans to deliver 100% of the PTV1 
prescription dose (36.25 Gy) to 95% of the PTV1 volume.  The 

Department of Radiation Oncology                                                                              RAD 1203                  
University of Alabama Birmingham 
Protocol Version: June 16, 2021  
 
 
 
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minimum PTV1 dose must be > 34.4 Gy (95% of PTV1 
prescription). 
 
6.2.4 Rapid dose falloff outside the PTV is to be prioritized over PTV 
dose uniformity and may result in considerable dose heterogeneity 
within the PTV. 
 
6.2.5 Prescribed dose to pelvic lymph nodes will not be allowed 
 
6.3 
Critical structures 
 
6.3.1 Rectal dose-volume histogram (DVH) goals are <50% of the 
volume of the rectum receiving 50% of PTV1 prescription dose, 
<20% receiving 80% of PTV1 dose, <10% receiving 90% of PTV1 
dose), < 5% receiving 100% of PTV1 dose, and maximum dose 
(defined as 1 cc volume) <105% of PTV1 prescription.  Only less 
than 3cc’s of rectum may receive more than 34.4 Gy. 
 
6.3.2 Bladder dose-volume histogram (DVH) goals are <50% of the 
volume of the bladder receiving 50% of PTV1 prescription dose, 
<10% receiving 90% of PTV1 prescription dose, and maximum 
dose (defined as 1cc volume) <105% of PTV1 prescription.   
 
6.3.3 Maximum urethra dose <107% of PTV1 prescription. 
 
6.3.4 Femoral head maximum point dose <30 Gy and the volume 
receiving >20 Gy must not exceed 10 cc (cumulative, both sides). 
 
6.3.5 The dose to a small volume of the PTV1 or PTV2 may be reduced 
below the prescription to meet the above constraints at the 
discretion of the treating radiation oncologist.  Thus, coverage of 
PTV1 or PTV2 may be relaxed if the treating physician cannot 
meet critical structure dose constraints. 
 
 
6.4 
Treatment plan physics quality assurance 
 
6.4.1 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. 
 
6.4.2 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 

Department of Radiation Oncology                                                                              RAD 1203                  
University of Alabama Birmingham 
Protocol Version: June 16, 2021  
 
 
 
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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. 
 
6.5 
Technical factors 
 
6.5.1 All treatment plans will be devised utilizing an intensity modulated 
radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), 
or helical tomotherapy platform utilizing a simultaneous integrated 
boost approach.   
 
6.5.2 Treatments will be delivered on appropriately selected linear 
accelerators at the discretion of the treating physician 
 
6.6 
Treatment delivery 
 
6.6.1 Patients will be instructed to have a full bladder and empty rectum 
for treatments.  Utilization of bowel preparation with oral or 
suppository medications is left up to the treating physician.  
Endorectal balloons may be utilized at the discretion of the treating 
physician. 
 
6.6.2 Image-guidance with kilovolatage orthogonal x-rays and cone-
beam CT scans (or equivalent tomotherapy imaging) 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 fiducial marker 
seeds (preferably) or the prostate-rectum interface if there are no 
fiducial markers.   
 
6.7 
Treatment delivery schedule 
 
6.7.1 Radiation treatments will be delivered per the standard outpatient 
setting radiation oncology clinic. Treatment must be completed in 
within the time frame of 7 to 17 calendar days, with day of first 
treatment being considered day 1.  Treatment must not be given on 
five consecutive days, and an every-other day fashion treatment 
schedule is recommended though not required.  Exact treatment 
schedule is left to the discretion of the treating physician. 
 
 
 
 

Department of Radiation Oncology                                                                              RAD 1203                  
University of Alabama Birmingham 
Protocol Version: June 16, 2021  
 
 
 
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7.0 
THERAPY MODIFICATIONS 
 
7.1 
No dose escalation or de-escalation modifications are to be made outside 
of the selected prescription dose for this study 
 
7.2 
Non-Study Treatment 
 
7.2.1 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 
 
7.2.2 Hormonal blockade agents such as leuprolide or bicalutamide 
administered for purposes of treatment or prostate downsizing are 
permitted if administered within 9 months of study enrollment.  
Concurrent or adjuvant usage of hormonal blockade agents is 
permitted as well, and usage thereof at the discretion of the treating 
physician  
 
7.2.3 The use of standard prescription or non-prescription medication to 
manage symptoms of disease or treatment is left up to 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 
 
7.3 
Concomitant Medication 
 
7.3.1 All medications administered since protocol enrollment will be 
recorded in the medical record 
 
7.3.2 No cytotoxic chemotherapies are to be administered during the 
study evaluation period 
 
7.3.3 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.   
 
7.3.4 Prophylactic (or continued) usage of tamsulosin or alfuzosin (or 
other alpha-blocker medication) is mandated.  This medication 
must be started on the day of (or before) the first radiotherapy 
treatment and will continue to at least 30 days after the last 
radiotherapy treatment.   
 
7.3.5 Androgen deprivation therapy (ADT) will be utilized at the 
discretion of the treating physician.  Investigators suggest no 
androgen deprivation for NCCN low risk patients, and short term 
(3-6 months) neoadjuvant/concurrent ADT where appropriate for 

Department of Radiation Oncology                                                                              RAD 1203                  
University of Alabama Birmingham 
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intermediate risk patients.  Long term androgen deprivation 
therapy is not recommended. 
 
 
7.4 
Adverse Events (AE’s) and Serious Adverse Events (SAE’s) 
 
7.4.1 Definition of AE:  Any untoward medical occurrence, which does 
not necessarily have a causal relationship with the study 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.   
 
7.4.2 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 (section 
9.0) 
 Urinary retention/obstruction requiring catheterization, 
though officially scored as a grade 2 toxicity by CTCAE 
v4.0, will be considered a SAE on this protocol.   
 
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. 
 
7.5 
Guidelines for adverse event recording 
 
7.5.1 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 
 

Department of Radiation Oncology                                                                              RAD 1203                  
University of Alabama Birmingham 
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7.5.2 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 
2 
Unlikely 
The adverse event is doubtfully related to the 
investigational treatment 
1 
Unrelated 
The adverse event clearly not related to the 
investigational treatment 
 
 
 
7.6 
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). 
 
7.7 
Adverse event reporting 
 
7.7.1 Notification of all SAE’s must be reported to the Principal 
Investigator (Dr. John Fiveash) 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. 
 
7.7.2 Adverse events will be reported to the Clinical Trials Monitoring 
Committee. 
 
 
 
 

Department of Radiation Oncology                                                                              RAD 1203                  
University of Alabama Birmingham 
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7.8 
Data and safety monitoring plan 
 
7.8.1 This protocol will follow the UAB Data and Safety Monitoring 
Plan maintained by the UAB Comprehensive Cancer Center. 
 
7.8.2 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.  
 
 
7.9 
Early Termination 
 
Patients may be discontinued from study prior to completion of study 
requirements for any of the following reasons: 
 
7.9.1 The patient has a clinically significant adverse event as determined 
by the principal investigator 
 
7.9.2 The patient requests to be withdrawn from the study 
 
7.9.3 The patient fails to comply with the requirement for study 
evaluation/visits 
 
7.9.4 Other conditions for which, in the investigator’s opinion, it is in 
the patient’s best interest to be withdrawn from the study 
 
7.9.5 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.   
 

Department of Radiation Oncology                                                                              RAD 1203                  
University of Alabama Birmingham 
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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.   
 
8.5 
An optional median long-term quality of life evaluation will take place 
after the required evaluations and therapies. AUA Symptom Score, SHIM, 
and EPIC questionnaire (Appendix C) will be mailed to study participants 
who are > 3 years from completion of radiotherapy.  
Table 8.1 Required evaluations and therapies 
 
Baseline Week 1-2 
Week 
5/Mo 1 
Mo 3, 6, 9, 
12, 18, 24  
>3 year 
from 
completion 
of RT 
PSA 
x+ 
 
x 
x 
 
H and P 
x^ 
 
x^ 
x^ 
 
Karnofsky PS 
x 
 
x 
x 
 
Quality of Life 
Indices/Questionnaires* 
x 
x#, ^ 
x 
x 
 
Optional QOL* 
 
 
 
 
X 
CTCAE v4.0 Toxicity 
Grading 
x 
x 
x 
x 
 
SBRT 
 
xxxxx 
 
 
 
*   AUA Symptom Score, SHIM, and  EPIC questionnaire – Appendix C                                      
#   To be completed on the final day of treatment 
^   Medications will be recorded 
+   PSA value within 3 months of enrollment is acceptable as “baseline” 
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). 

Department of Radiation Oncology                                                                              RAD 1203                  
University of Alabama Birmingham 
Protocol Version: June 16, 2021  
 
 
 
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 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.   
9.2 
Technical feasibility 
For the purposes of this study, technical feasibility encompasses two 
major components:  treatment planning and treatment delivery.  Treatment 
planning includes integration of clinical data (exam, biopsy, and medical 
imaging) to create targets (PTV1 and PTV2) 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. 
9.2.1 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 6.2 and 6.3.  Feasibility will be defined as 
the ability of the treatment planner to create a plan that meets the 
following criteria: 
 100% of PTV1 prescription (36.25 Gy) covers ≥ 95% of 
the PTV1 
 At least 95% of the PTV2 prescription (38.0 Gy) covers 
95% of PTV2 volume 
 All normal tissue dose constraints are met (see section 6.2 
and 6.3) 
 

Department of Radiation Oncology                                                                              RAD 1203                  
University of Alabama Birmingham 
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9.2.2 Treatment delivery 
 
9.2.3 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.  Treatment delivery will be considered 
feasible if each pre-treatment set up images are approved by the 
treating physician(s) prior to administration of radiotherapy.    
9.3 
Treatment phase 
9.3.1 The patient will be evaluated at least once by the treating physician 
during the time that he is undergoing radiotherapy treatment.   
9.3.2 On the final day of treatment (fraction five), 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. 
9.4 
Follow-up 
9.4.1 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. 
9.4.2 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. 

Department of Radiation Oncology                                                                              RAD 1203                  
University of Alabama Birmingham 
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9.4.3 After the required follow-up visits and evaluations, an optional 
quality of life evaluation using AUA Symptom score, SHIM, and 
EPIC questionnaire (Appendix C) will be mailed to study 
participants who are > 3 years from completion of radiotherapy. 
Study participants will be contacted by phone call no more than 
three times in order to notify them that they received quality of life 
questionnaires and to remind them to complete and return these 
forms. Study participants will return the completed quality of life 
questionnaires by mail or in person to: 
University of Alabama at Birmingham (UAB) 
Department of Radiation Oncology 
Research and Clinical Trials Office 
Care of: Jared Maas, MD 
1700 6th Avenue South (HSROC), 
Suite 1242 
Birmingham, Alabama 35233 
9.4.4 Research participants will be contacted by phone call using the 
following script: “Hello, I am calling to reach [Study participant]. 
[Study participant will confirm identity with name and date of 
birth]. This is [Researcher’s name] at UAB Radiation Oncology 
calling from [Attending physician’s name]’s office. I am calling 
you because you are a participant in the RAD 1203 Prostate 
Radiosurgery trial. We are hoping to collect some final long-term 
quality of life data from you, so I wanted to notify you that we 
have mailed you quality of life questionnaires to your address. 
[Confirm address and receipt of forms]. These forms are the same 
forms you have previously completed during your follow up clinic 
visits to assess short term quality of life.  Please complete these 
forms at your earliest convenience and return the completed forms 
to our office either by mail or in person. [Provide mailing address]. 
If you have any additional questions, please call our office at 
[Provide phone number]. Thank you! Goodbye. 
 
10.0 PATIENT REGISTRATION 
Patients can be registered by calling 205-975-2879. 
 
 
 

Department of Radiation Oncology                                                                              RAD 1203                  
University of Alabama Birmingham 
Protocol Version: June 16, 2021  
 
 
 
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11.0 STATISTICAL CONSIDERATIONS 
11.1 
The primary endpoint of this study is to clinically assess early toxicity – 
specifically, to determine whether the rate of urinary retention or 
obstruction requiring catheterization is >15%. 
 
11.2 
Secondary endpoints include technical feasibility and clinical toxicity and 
efficacy assessments. 
   
11.2.1 Determine the technical feasibility of stereotactic body 
radiotherapy (SBRT) with integrated boost for clinically localized 
prostate cancer 
 
11.2.2 Clinically assess early toxicity, early efficacy, late toxicity, and 
quality of life for patients receiving SBRT with integrated boost 
for clinically localized prostate cancer 
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, 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 
Toxicity rates 
Urinary retention or obstruction requiring catheterization occurring in 
>15% of patients is considered significantly higher than the catheterization 
rate occurring for the standard UAB prostate hypofractionation scheme 
(70 Gy at 2.5 Gy/fraction) and prostate low-dose rate brachytherapy.   
11.5 
Sample Size 
Sample size (N=25-30) is determined based upon the statistical power 
needed to confidently identify urinary retention toxicity (requiring 
catheterization) rates in enrolled patients significantly exceeding the rates 
noted for UAB hypofractionated prostate radiotherapy and LDR 

Department of Radiation Oncology                                                                              RAD 1203                  
University of Alabama Birmingham 
Protocol Version: June 16, 2021  
 
 
 
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brachytherapy experiences. Urinary retention or obstruction requiring 
catheterization occurring in >15% of patients will be considered 
significantly higher than the catheterization rate occurring for the standard 
UAB prostate hypofractionation scheme (70 Gy at 2.5 Gy/fraction) and 
that of prostate brachytherapy (two radiotherapy treatment options given 
most often for this subset of patients). A one sided exact binomial test of 
the null hypothesis that the catheterization rate is 15% vs the alternative 
that it exceeds 15% will be performed at the 0.20 significance level.  If the 
actual rate is 30% that test will have 80% power. 
12.0 REFERENCES 
 
 
1. Jemal A, Segal R, Ward E, et al.  Cancer statistics, 2008.  Cancer:  A Cancer 
Journal for Clinicians. 2008; 58:71-96.   
 
2. National Comprehensive Cancer Network.  Clinical Guidelines:  Prostate 
Cancer.  Version 4.2011.  www.NCCN.org.   
    
3. Hall EJ. Radiobiology for the Radiobiologist, sixth edition, J. B. Lippincott 
Company, Philadelphia. 2006. 
 
4. King CR, Fowler JF. A simple analytic derivation suggests that prostate cancer 
alpha/beta ratio is low.  International Journal of Radiation Oncology, Biology and 
Physics.  2001; 51: 213-214. 
 
5. Brenner DJ, Martinez AA, Edmundson GK, et al.  Direct evidence that prostate 
tumors show high sensitivity to fractionation (low alpha/beta ratio), similar to 
late-responding normal tissue. International Journal of Radiation Oncology, 
Biology and Physics. 2002; 52(1):6-13. 
 
6. Williams SG, Taylor JM, Liu N, et al.  Estimation of the α/β ratio of prostate 
cancer using a multivariate analysis of the individual fraction size data of 3756 
patients.  International Journal of Radiation Oncology, Biology and Physics. 
2006; 676 (35): S10. 
 
7. Kupelian PA, Thakkar VV, Khunita D, et al. Hypofractionated intensity-
modulated radiotherapy (70 Gy at 2.5 Gy per fraction) for localized prostate 
cancer: long term results. International Journal of Radiation Oncology, Biology 
and Physics.  2005; 63(5): 1463-1468. 
 
8. Pollack A, Hanlon AL, Horwitz EM, et al.  Dosimetry and preliminary acute 
toxicity in the first 100 men treated for prostate cancer on a randomized 
hypofractionation dose escalation trial.  International Journal of Radiation 
Oncology, Biology and Physics.  2006; 64(2):518-26.  
 

Department of Radiation Oncology                                                                              RAD 1203                  
University of Alabama Birmingham 
Protocol Version: June 16, 2021  
 
 
 
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9. Madsen BL, His RA, Pham HT, et al.  Stereotactic hypofractionated accurate 
radiotherapy of the prostate (SHARP), 33.5 Gy in five fractions for localized 
disease:  first clinical triall results.  International Journal of Radiation Oncology, 
Biology and Physics.  2007; 67(4):1099-1105. 
 
10. King CR, Brooks JD, Gill H, et al.  Long term outcomes of a prospective trial of 
stereotactic body radiotherapy for low risk prostate cancer.  International Journal 
of radiation Oncology, Biology and Physics.  2012; 2:877-882. 
 
 
11. Boike TP, Lotan Y, Cho C, et al.  Phase I dose-escalation study of stereotactic 
body radiation therapy for low- and intermediate-risk prostate cancer.  Journal of 
Clinical Oncology.  2011; 29(15): 2020-2025. 
 
12. Kuban DA, Tucker SL, Dong L, et al.  Long term results of the M.D. Anderson 
dose escalation trial for prostate cancer.  International Journal of Radiation 
Oncology, Biology and Physics.  2008; 70(1): 67-74. 
 
13. Zietman AL, DeSilvio ML, Slater JD, et al. Comparison of conventional-dose vs. 
high-dose conformal radiation therapy in clinically localized adenocarcinoma of 
the prostate. Journal of the American Medical Association.  2005; 294(10): 1233-
1239. 
 
14. Zelfeskey MJ, Leibel SA, Gaudin PB, et al. Dose escalation with three-
dimensional conformal radiation therapy affects the outcome in prostate cancer.  
International Journal of Radiation Oncology, Biology and Physics. 1998; 41(3):  
491-500. 
 
15. Hricack H, Choyke PL, Eberhardt SC, et al.  Imaging prostate cancer:  a 
multidisciplinary perspective.  Radiology.  2007; 243 (1): 28-53. 
 
16. Fütterer JJ, Heijmink SW, Scheenen TW, et al. Prostate cancer localization with 
dynamic contrast-enhanced MR imaging and proton MR spectroscopic 
imaging. Radiology.  2006; 241:449-458.  
 
17. Fütterer JJ, Berentz JO.  3T MRI of prostate cancer.  Applied Radiology.   2009; 
38 (1).   
 
18. Sosna J, Pedrosa I, Dewolf WC, et al.  MR imaging of the prostate at 3 Tesla: 
Comparison of an external phased-array coil to imaging with an endorectal coil at 
1.5 Tesla. Academic Radiology. 2004; 11:857-862. 
 
19. Kim Y,  Tome WA.  Is it beneficial to selectively boost high-risk tumor 
subvolumes?  A comparison of selectively boosting high-risk tumor subvolumes 
versus homogeneous dose escalation of the entire tumor based on equivalent EUD 
plans.  Acta Oncoligica. 2008; 47(5): 906–916. 

Department of Radiation Oncology                                                                              RAD 1203                  
University of Alabama Birmingham 
Protocol Version: June 16, 2021  
 
 
 
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20. van Lin EN, Futterer JJ, Heimink SW, et al.  IMRT boost dose planning on 
dominant intraprostatic lesions:  gold marker-based three-dimensional fusion of 
CT with dynamic contrast enhanced and 1H-spectroscopic MRI.  International 
Journal of Radiation Oncology, Biology and Physics. 65: 291-303, 2006. 
 
21. Singh AK, Guion P, Sears-Crouse N, et al.  Simultaneous integrated boost of 
biopsy proven, MRI-defined dominant intra-prostatic lesion to 95 Gy with IMRT:  
early results of a phase I NCI study.  Radiation Oncology.  2:36, 2007.   
 
22. Katz AJ, Santoro M, Ashley R, et al.  Stereotactic body radiotherapy for organ-
confined prostate cancer.  BMC Urology.  2010.  10:1.  
www.biomedcentral.com/1471-2490/10/1. 
 
23. Fleiss J, Levin B, and Paik MC.  Statistical Methods for Rates and Proportions 
(3rd edition).  2003.  New York:  John Wiley & Sons.  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 

Department of Radiation Oncology                                                                              RAD 1203                  
University of Alabama Birmingham 
Protocol Version: June 16, 2021  
 
 
 
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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 . All 
investigators should have access to a copy of the CTCAE version 4.0.  
 
 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 
 
 
 
 

Department of Radiation Oncology                                                                              RAD 1203                  
University of Alabama Birmingham 
Protocol Version: June 16, 2021  
 
 
 
Page 29 of 29 
 
 
Appendix D: NCCN Clinical Practice Guidelines in Oncology 
 
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.  
 
 
Appendix E: Partin Tables 
 
This study will utilize the Partin Tables to generate a table value that reflects the 
pathologic stage of prostate cancer. The Partin Tables can be accessed at: 
http://urology.jhu.edu/prostate/partintables.php