Early Changes in Multiparametric MRI in Response to Neoadjuvant Androgen Deprivation and External Beam Radiation Therapy for Prostate Cancer
Phase: NA
Conditions: Prostate Cancer
Sponsor: Dana-Farber Cancer Institute

 
Title: Early changes in multiparametric MRI in response to neoadjuvant androgen 
deprivation and external beam radiation therapy for prostate cancer   
NCT Number: NCT01959542   
  
IRB Approval Date: 09/09/2013  
  
Principal Investigator: Fiona Fennessy  
 

 
  
Status Page  
  
  
PROTOCOL 13-343  
  
  
  
  
  
Closed to New Accrual  
   
  
  
  
  
Closure Date: 08/23/2016  
  
  
  
No new subjects may be enrolled in the study as described 
above.  Any questions regarding this closure should be directed 
to the study’s Principal Investigator  
  
  

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Early changes in multiparametric MRI in response to neoadjuvant androgen deprivation and 
external beam radiation therapy for prostate cancer  
  
  
  
OUTLINE  
I 
Background and Significance  
II Specific Aims  
III Study Endpoints  
IV Subject Selection  
V Subject Enrollment  
VI Study Procedures  
VII Biostatistics  
VIII Risks and Discomforts  
IX Potential Benefits  
X Monitoring and QA  
XI Registration with QACT  
XII References  
  
  
  
 
I  Background and Significance  
  
a.  Multiparametric MRI (mpMRI) and it’s role in prostate cancer  
Prostate MRI is known to play an important role in prostate cancer detection and localization, and 
indeed prostate cancer staging[1]. It also aids in tumor detection when there is a biochemical suspicion 
of residual or recurrent disease after treatment[2],[3]. Compared to conventional prostate MR 
techniques from 5-10 years ago, which relied on morphology for tumor characterization, standard of 
care prostate MR in 2013 provides a wealth of information regarding tumor functionality[1]. mpMRI 
includes functional quantitative sequences such as Diffusion Weighted Imaging (DWI) and high 
temporal resolution Dynamic Contrast Enhanced (DCE) imaging. DWI is reflective of the random 
motion of water molecules at a cellular level, and is thus sensitive to cell membrane integrity, 
hypercellularity, enlargement of the nuclei and hyperchromatism. DWI (and more specifically, 
Apparent Diffusion Coefficient (ADC) derived from DWI) has been demonstrated on multiple 
occasions to correlate with Gleason score and serve as a biomarker for prostate tumor aggressiveness 
[4–9]. On DCE, prostate cancer shows early strong enhancement compared to surrounding normal 
prostate tissue. This enhancement pattern is thought to represent tumor angiogenesis and is necessary 
for further tumor growth[10],[11]. As a result, the number of vessels increases and these newly formed 
tumor vessels have higher permeability than do normal vessels because of weak integrity of the vessel 
wall. Studies have suggested that as the number of abnormal vessels in prostate cancer increases, the 
prognosis worsens[12][13]. Microvessel density in prostate cancer, an established independent 
predictor of pathologic stage, has been shown to correlate with DCE-MRI results[14].  
   

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b. EBRT and ADT for intermediate-high prostate cancer  
In the era of PSA screening, many men are diagnosed with early-stage prostate cancer and have a good 
chance of cure. However, there are some patients, specifically those who present with unfavorable 
cancer based upon well-established features such as high prostate specific antigen (PSA), high 
Gleason score and/or those with advanced local disease (T-stage T2b or higher) who remain at high 
risk for prostate- cancer mortality. Androgen deprivation therapy (ADT) is very effective in 
controlling metastatic prostate cancer and improves survival when added to radiotherapy for localized 
disease. A significant gain in overall survival in those with locally advanced prostate cancer using a 
combination of external beam radiotherapy (EBRT) and ADT has been demonstrated by both the 
European Organization for Research and Treatment of Cancer (EORTC)[15] and the Radiation 
Therapy Oncology Group (RTOG)[16] and in others[17]. These randomized trials evaluated ADT 
given from six to thirty-six months. Long term (≥2 years) of ADT confers a modest survival benefit in 
men treated with radiotherapy for locally advanced prostate cancer compared with 6 months of ADT, 
but it is associated with increased toxic effects[18]. Therefore, identification of men in whom 6 
months of ADT is sufficient for cure is important as is early identification of those who are not 
responding well to standard ADT.   
  
 
i.  
Predicting those who will fail ADT therapy  
Time to PSA failure and the rate at which PSA rises are surrogates for prostate cancer specific 
mortality (PCSM). Very recently[19], PSA nadir of ≤ 0.3 ng/ml after 2-3 months of neoadjuvant ADT 
(prior to initiation of EBRT) has been shown to be associated with improved long-term biochemical 
prostate tumor control, reduction in distant metastases, and prostate cancer-related death. This initial 
PSA response during ADT may reflect the sensitivity of the prostate tumor to androgen deprivation 
and in turn to the radio-sensitivity bestowed by ADT on the subsequently irradiated prostate tumor. 
Pre-EBRT PSA nadir may therefore represent a valuable early predictor for improved outcomes after 
radiation therapy for prostate cancer.   
 ii.  
Predicting those who will fail 
ADT/EBRT therapy  
Looking further along the course of treatment with neoadjuvant ADT and 4 months of EBRT,  
D’Amico et al[20] used the Prentice criteria to assess whether measured lowest PSA concentrations 
(PSA nadir) or PSA immediately after treatment (PSA end) were early surrogates for prostate cancer- 
specific mortality, as both PSA end and nadir PSA are available before PSA failure. In this study they 
retrospectively reviewed 2 randomized controlled trials (cohort of 734 men), that showed improved 
overall and prostate cancer specific survival with radiotherapy and 6 months of androgen suppression 
compared with radio therapy alone. They found that men with PSA end values exceeding 0.5 ng/ml 
after EBRT and androgen suppression should be considered for long-term androgen suppression. 
Furthermore, an early endpoint such as PSA nadir after radiotherapy and at least 6 months of androgen 
suppression could identify men who are good candidates for future trials of additions of proven 
systemic therapies (i.e, one that extends survival in men with castration-resistant metastatic prostate 
cancer).   
  
c. mpMRI as a biomarker for response to therapy in prostate cancer  
A role for mpMRI as a non-invasive biomarker in assessing response to treatment options is currently 
an evolving area of great interest. In patients with low-risk prostate cancer on active surveillance, DWI 

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has been proposed to be a useful marker of prostate cancer progression and may help in identifying 
patients who may benefit from radical treatment [21],[22]. Recent studies have also investigated the 
use of mpMR to assess response to ADT[23] and radiotherapy[24],[25], with promising results.   
  
After ADT, prostate gland shrinkage and fibrosis makes tumor difficult to detect on routine T2WIs. A 
feasibility study[23] evaluated the use of mpMR in monitoring response to ADT, and suggested that 
DCE as a marker of angiogenesis may help demonstrate ADT resistance, and DWI may help 
determine tumor cell death vs. residual tumor. In contrast to cytotoxic therapy, where ADC values 
increase (due to a lessening of the restriction of water molecules), ADT may not result in significant 
necrosis of prostate cancer cells, and in fact ADC values of prostate cancer post 3 months of ADT 
have been shown to remain the same[23]. In contrast, ADC values of areas where focal tumor was not 
suspected were significantly reduced with ADT, possibly due to acinar hypertrophy, fibrosis and basal 
cell hyperplasia.   
  
Foltz et al. have looked at the very early post-radiotherapy changes in the prostate every 2 weeks up 
until 8 weeks of EBRT, and found that ADC was a possible candidate for early response to therapy, 
the optimal scan time being week 6 of EBRT[24]. Park et al have shown that ADC values in regions of 
tumor increased 1 and 3 weeks after initiating EBRT, and one month after completion of EBRT[25].  
  
Specific to DCE, there is known to be an anti-angiogenic role for ADT in the prostate (androgen 
ablation has been shown to suppress glandular epithelial production of VEGF and induce apoptosis of 
endothelial cells). As PSA gene expression is down-regulated by ADT, PSA reduction post ADT may 
be secondary to androgen suppression rather than tumor cell death. It is therefore possible that DCE 
may act as a stronger surrogate for angiogenesis, rather than PSA.   
  
There has been a pre-clinical study (on prostate zenograph models) evaluating a combination of 
parameters (ADC, DCE, tumor volume and PSA) which successfully predicted treatment response to a 
combination of ADT and radiotherapy, with a correlation coefficient of 0.85[26]. However, to our 
knowledge, no study has yet looked at a role for mpMRI in evaluating the effect of combined ADT 
and EBRT on prostate mpMR in humans. Nor has there been any work published on correlating PSA 
end with prostate mpMR, to determine if mpMR may act as an early biomarker in determining those 
who would benefit from long-term androgen suppression. We therefore propose to evaluate mpMR in 
response to combined therapy (ADT and EBRT), and to correlate quantitative mpMR parameters at 
early timepoints, with PSA end and PSA nadir.  
  
  
II Specific Aims  
1. The primary aim of this study is to explore the feasibility of mpMR as an early imaging 
biomarker to assess response of intermediate- and high-risk prostate cancer during 
treatment with neoadjuvant ADT.   
2. A secondary aim is to explore the feasibility of mpMR as an imaging biomarker to 
assess response of bulky localized prostate cancer to combined ADT/EBRT.  

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3. To ascertain if the information provided using the non-ecoil 3 Tesla MRI images prior 
to starting EBRT can supplement CT information for Radiation Treatment (RT) 
planning purposes in men who are planning to undergo RT for prostate cancer.  
  
  
III Study endpoints  
1. The primary endpoint of this study is whether mpMR parameters measured after 2 
months of neoadjuvant ADT therapy (TP1) correlate with nadir PSA post 8-weeks of 
ADT. In addition, we will determine whether mpMR parameters in areas of tumor (T) 
in those who fail neoadjuvant ADT (defined as PSA end ADT values >.3 ng/ml) are 
different to those who respond to ADT (defined as PSA end ADT ≤.3ng/ml).  
2. A secondary endpoint of this study is whether mpMR parameters measured after 6 
weeks of EBRT (TP2) and 8 weeks after completion of EBRT (TP3) correlate with end 
PSA (defined as PSA level immediately after EBRT treatment). In addition, we will 
determine whether mpMR parameters in areas of T in those likely to fail combined 
ADT/EBRT (defined as PSA end values >.5ng/ml) are different to those of responders 
(PSA end values ≤.5ng/ml).  
  
IV Subject selection  
1. Inclusion criteria:  
a. Adult males with unfavorable intermediate- to high-risk localized disease 
identified as one of the following three categories for unfavorable 
intermediatehigh risk factors, but must have visible disease on baseline MRI.  
i. 
Clinical or radiographic T2b-T4 primary tumor  
ii. Gleason score 7-10 in any core  
iii. PSA ≥ 10 prior to initiation of therapy  
b. Patients are deemed suitable for therapy with ADT and EBRT.  
c. Subjects must to able to provide informed written consent prior to study entry.  
  
2. Exclusion criteria:  
a. The standard exclusion criteria for MRI exams will apply which include 
patients with pacemakers, non-compatible intra-cranial vascular clips, inner ear 
implants, and severe claustrophobia.  
b. Patients who because of age, general medical or psychiatric condition, or 
physiologic status unrelated to the presence of prostate cancer are unlikely to be 
candidates for repeat MRIs, or cannot give valid informed consent.  
c. Patients unwilling or unable to undergo the ecoil placement or multiparametric 
MRI exam.  
d. Patients with a history of allergic reaction to latex or Gadolinium containing 
intravenous contrast agents.  

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e. Individuals with renal disease or other contraindications to gadolinium will be 
excluded.  The BWH standard MRI contrast screening criteria will be used to 
establish renal status.  
f. Patients who have had prior prostatectomy or prior androgen therapy.    
g. Patients with hip implant or any other metallic implant or device that results in 
significant distortion of the local magnetic field and compromise of the quality 
of the multiparametric MRI data.  
  
  
V Subject recruitment/enrollment  
Men with unfavorable intermediate‐to high‐risk prostate cancer are routinely seen at the 
multidisciplinary Lank Center for Genitourinary Oncology by a urologist,medical oncologist and 
radiation oncologist. The standard of care for this patient population is combination therapy 
consisting of complete androgen blockade and EBRT. Patients meeting eligibility criteria and 
choosing to have their ADT/EBRT care at Brigham and Women’s Hospital will be recruited by the 
treating radiation oncologist, and asked if they wish to participate in the study. The study staff (PI 
and study coordinator) will obtain a list of new patients to be seen in GU radiation oncology  
clinic for prostate cancer. They will review the clinic note in EPIC to determine which treatment 
option for prostate cancer was decided upon, if the patient meets inclusion criteria for the study, 
and if the patient had a baseline MRI prior to starting treatment. If eligible for the study, the 
treating radiation oncologist/oncologist will be emailed by the study PI (see attached email 
template) to ask their permission to approach the patient to determine if the patient is interested   
in being part of the study, or the treating radiation oncologist can ask the patient directly if 
interested in being part of the study, and obtain consent.  
 
 
To facilitate awareness of the study and to help with recruitment, we will post a flyer about the 
study in the physician and nursing radiation oncology clinical office for staff to see.  
 If the patient expresses interest in the study, they will be given a recruitment letter and a study 
consent form, which the radiation oncologist will review with them. Consent can be obtained at 
this time by the radiation oncologist. If so, the patient will be given a copy for their own record. 
However, there will be a second opportunity to consent the patient at the time of treatment 
planning for radiotherapy which occurs six weeks after the first LHRH injection.  Patients who are 
consented at six weeks will already have undergone their baseline MRI and PSA, which is the 
standard of care for all intermediate- and high-risk prostate cancer patients. At this time, the 
radiation oncologist may review the study with the patient and obtain consent or the study 
radiologist may review the study with the patient and obtain consent. Either way, the physician 
who obtains consent will inform the study staff (Fiona Fennessy, MD PhD and the study 
coordinator) of the patient’s interest in the study. Those patients who elect to participate in the 
study with be contacted by the study coordinator to schedule the study MRIs and the serum PSAs, 
and to answer any remaining questions.   
   
Any study patient may elect not to proceed with the study at any time.  
  

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VI Study Procedure  
  
The timeline of the study is outlined below.  
  
  
Baseline Standard of care prostate MRI and serum PSA will be obtained prior to starting ADT, as 
standard of care.   
After an 8-week course of neoadjuvant ADT, serum PSA nadir and a prostate MRI will be obtained 
(TP1). EBRT will commence after an 8-week course of ADT for an 8-week period. However, 6 weeks 
into EBRT, subjects will undergo serum PSA level and a prostate MRI (TP 2). An end PSA at the end 
of EBRT will also be obtained. Six months after starting ADT, they will have a final prostate MRI and 
serum PSA level (TP 3). (Please see section a, b, c, and d below for protocol on ADT, PSA, prostate 
MRI and EBRT respectively).  
  
  
1. ADT  
Androgen suppression therapy consists of combined androgen blockade. Patients receive an 
antiandrogen, typically biaclutamide (Casodex) and an LHRH-agonist, typically Lupron. AST is given 
for two months prior to radiotherapy and then continued for a total of six to 36 months, depending 
upon the treating physician and overall health of the patient.  
  

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2. PSA  
Serum PSA will be checked at baseline by treating physician, prior to commencing therapy. Serum 
PSA will also be subsequently checked on the same day as each follow-up MR is performed, i.e. TP 
1,2 and 3, and right after finishing EBRT.   
  
Parking at BWH for time spent for all 4 follow-up serum PSAs will be paid for.   
  
  
3. Prostate MRI  
The baseline prostate MRI is standard of care management, ordered by the radiation oncologist for 
staging and for EBRT planning. The 3 follow-up MRIs (at TP 1,2 and 3) are not standard of care 
management, and will be paid for by an NIH grant. However, all of the follow up prostate MRIs will 
use a standard BWH Radiology Department prostate non-endorectal coil MRI protocol. Subjects will 
need, to complete health screening and renal assessment forms completed prior to the MRI to 
determine if the patient is able to receive gadolinium.  Blood results measuring renal function within a 
3-week window prior to MR must be available, and if necessary, blood will be drawn to measure 
kidney function prior to administration of gadolinium. Subjects will be positioned lying on their back 
within the MRI magnet, which is a large cylindrical tube that allows strong magnetic fields to pass 
through the body. Earplugs and a padded table will be provided for the subject’s comfort. A radio 
frequency receiver coil encased in a plastic mold called a phased-array coil will be positioned around 
the subject’s pelvis. An endorectal coil will NOT be used for this study, as the endorectal probe will 
distort the prostate (making correlation with CT for planning difficult) and because of the risk of 
proctitis during EBRT.  
  
The standard imaging protocol will include fast spin echo (FSE) for T2WI, fast spoiled gradient 
(FSPGR) for T1WI and (Dynamic Contrast Enhanced) DCE-maps, and diffusion imaging for 
ADCmaps. If renal function is normal, the MR contrast agent gadopentetate dimeglumine (Magnavist) 
will be used for DCE. A dose of 0.1 mmol/kg is administered intravenously using an MR compatible 
power injector immediately before beginning the dynamic contrast enhancement (DCE) portion of the 
MRI exam. Magnevist is not given to patients with a history of prior allergic reaction, which is 
extremely rare. Possible use of light sedation for anxiety associated with the MRI exam should be 
discussed between the patient and referring physician prior to the MRI exam. If any anti-anxiety 
medication is prescribed, subjects should bring it to the examination and use as directed. Subjects will 
also be told to take all of their prescribed medications as regularly scheduled.  
  
Parking at BWH for time spent for 3 follow-up prostate MRIs will be paid for.   
  
Following the multiparametric MRI exam, the imaging data will be collected and archived. A standard 
clinical prostate MRI staging report will be issued in a timely fashion. The quantitative MR-based 
information (ADC-maps and DCE pharmokinetics) will be analyzed separately using Oncoquant 
software (GE Healthcare) and will not be included in the standard MRI report. Should the results of 
this additional analysis impact the interpretation rendered in the standard prostate report, the referring 
physician will be contacted and advised. Individual results will not be discussed with or returned to the 
participating patients.   

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4. EBRT  
Intensity-modulated EBRT will be given using daily pre-treatment imaging on implanted fiducials 
according to Brigham and Women’s standards. This is referred to as image-guided, intensity 
modulated radiotherapy, or IGRT. The IGRT targets the prostate and seminal vesicles and in some 
cases, the pelvic nodes as well according to well standardized department protocols. Each daily 
treatment, or fraction, delivers 1.8 Gy to a total of 75.6 Gy over 42 treatment days. Treatments are 
given five days per week.   
  
5. Fusion of the CT and 3T MRI images 
 
 
 
  3Tesla MRI is known to have a superior ability to visualize the prostatic apex and the prostatic 
rectal interface compared to CT. Therefore we seek to ascertain if the information provided using 
3Tesla MRI images can supplement CT information for Radiation Treatment (RT)planning 
purposes in men who are planning to undergo RT for prostate cancer. This protocol is acquiring 
3T MRI images without an endorectal coil in men planning to undergo RT for prostate cancer after 
fiducial marker placement and CT simulation but prior to the start of RT. We will perform a fusion 
of the CT and non‐endorectal coil 3T MRI images using the intraprostatic fiducial markers. The 
fusion will allow us to assess if improved delineation of the prostatic apex and prostatic rectal 
border translates into not losing any target (i.e. prostate gland) coverage but reduces the volume of 
rectum receiving radiation in excess of 70 Gray. We will use the validated rectal metrics of a rectal 
V70 < 20% and also <10cc as the measurement to make this assessment. If the rectal V70 can be 
reduced with MRI information then 
the risk of late RT induced rectal bleeding would be 
expected to decrease. The MR data will not be used in the RT treatment planning of these men but 
only for the assessment of whether the rectal V70 could be reduced.  
  
   
  
VII Biostatistics  
  
1. Correlation of ADC Change With PSA Nadir    
Zelefsky et al. report that 10-year relapse-free survival among patients with PSA nadir < 0.3 was 
74.3%, compared with 57.7% for patients with higher PSA nadir values (P = 0.001, N = 1045). In 
order to assess power for a test of whether mpMR parameters measured after 2 months neoadjuvant 
ADT therapy alone correlate with nadir PSA post 8-weeks of ADT therapy, we will make use of 
published data on the correlation between ADC change and nadir PSA. Foltz et al.[24] observed a 
correlation of 0.25 for nadir PSA with ADC percent change, between 6 weeks and the pre-RT baseline 
(N = 10).  With 30 subjects, we anticipate 80% power to detect an absolute correlation of 0.49 or 
greater. Although this is greater than the correlation Foltz observed, we note that with a sample of size 
10, using Fisher's transformation, an approximate 95% confidence interval for Foltz's estimate is  (-
0.45, 0.76), a wide interval which includes 0.49.     
  

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2. Within-Patient ADC Changes  
Foltz et al.[24] reported a change in ADC between six weeks RT and baseline of -0.29 in tumor (2.8%,  
N = 36) and -0.56 in healthy tissue (N=10), with  SDs of 0.23 and 0.18, respectively (in units of 10^  (-
3) mm^2/s). Using the average variance above, we estimate a SD for ADC of 0.20.  With N = 30 
subjects, using this SD, we expect to have 80% power to detect a significant within-subject absolute 
difference in ADC between two time points of 0.14 or greater, based on a paired t-test at the 0.05 
twotailed significance level, corrected for the 6 pairs of time points to be considered.  This is much 
smaller than the difference of 0.81 observed in healthy tissue described by Barrett et al.[23], but larger 
than the very small difference of 0.03 that they observed in tumor.  Foltz et al. observed changes in 
ADC between 4 weeks and baseline of 0.107 (B = 600) and 0.117 (B = 1200), both of which are less 
than 0.14.      
        
3. Comparison of Normal Tissue ADC With Tumor   
For comparisons between tumor and normal tissue, with 30 subjects we expect 80% power to detect an 
absolute difference in mean ADC of 0.19 or greater, based on a two-tailed two-sample t-test, adjusted 
for multiple comparison of time-points.  Barrett’s group observed a mean difference in ADC between 
tumor and healthy tissue of 0.20.    
     
4. Comparison of ADC Changes between Patients who Fail Treatment and Those who do 
not.         
We estimate that 25% of men with grade T2c or greater cancer will have end PSA greater than 0.5, and 
will fail therapy.  Barrett et al. reported a change in ADC between three months of ADT and a preADT 
baseline in tumor of -0.028 with a SD of 0.227 (N = 35), in 20 patients with tumor of stage T2c or 
greater. We therefore estimate that ultimately 25% of these patients failed.  We assume that the ADC 
changes in patients who fail and patients who do not fail are both normally distributed, with the same 
SD but different means.  We estimate this SD from the Barrett et al. data as 0.227/sqrt  
(0.25^2+0.75^2) = 0.287. In our study, with 30 patients, we expect approximately 8 treatment failures. 
Assuming 8 failures and a SD of 0.287, we will have 80% power to detect an absolute difference  
between the mean ADC change among those who fail treatment and those  who do not of 0.51 SDs, or 
0.51*0.287 = 0.15 x 10^ (-3) mm^2/s change  in ADC. Barrett observed a baseline ADC mean in 
tumor of 1.006, hence we expect to be able to detect a change from baseline and 3-months ADT in 
ADC of approximately +/- 15% or greater.    
  
5. Descriptive statistics will be used to enumerate the rectal V70's achieved using MRI 
versus CT data.    
  
  
  
VIII Risks and Discomforts  
Participants in this study will undergo a total of 3 follow up prostate MRIs. (Baseline standard of care 
prostate MRI prior to initiating therapy will be ordered by the treating physician). All MRIs will use a 
standard routine prostate MRI protocol without the use of an endorectal coil. Patients will receive 
Magnavist 0.1mmol/kg intravenously for each study, so renal function will need to be checked prior to 

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each study to confirm normal function. If renal function is abnormal, the contrast agent will not be 
administered. Unlike CT (which uses radiation to produce images), MRI uses powerful magnetic fields 
and radio waves to produce images. There are no known health risks associated with this exposure. 
The radio waves used can cause a warming sensation to the body, similar to exposure to hot weather, 
or localized heating adjacent to the torso coil or ecoil. Body temperature can be expected to rise 
temporarily, but less than 1o Centigrade or about 2o Fahrenheit. In the event of a localized heating 
sensation, the subject will be instructed to notify the MR technologist immediately. However, the MRI 
scanner and the coils used have been designed to prevent localized heating from happening and there 
have been no reports of localized heating in patients scanned to date.   
  
The MRI scanner also uses rapidly switched magnetic field gradients that make loud banging noises as 
it collects the information used to create images. Earplugs will be used to reduce this noise and will be 
offered to each subject. The switched gradients can, under certain circumstances, cause peripheral 
nerve stimulation that may be experienced as a mild twitching in the limbs and/or lower back muscles. 
Such effects are rare and scan settings are kept well below the levels where such effects are known to 
occur.   
  
Subjects will be carefully screened at the time of enrollment to make certain that they do not have any 
unsafe metal implants. People who feel uncomfortable in confined spaces (claustrophobia) may feel 
uncomfortable lying in the narrow cylinder of the MRI magnet. Subjects will be able to communicate 
with the MRI technologist for the entire time they are in the magnet. The MRI will be stopped at the 
subject’s request at any time he so wishes. In addition, all patients will be offered Ativan (.5-1 mg) by 
their treating radiation oncologist. They also have the option to take a second dose upon arrival if they 
feel tense. All are driven home by a friend or relative. 
 
 
  
  
  
IX Potential Benefit  
No direct benefits from the study should be expected by individuals participating in this study. Results 
from this study, however, may indicate that mpMRI is an early non-invasive biomarker that may 
predict those that will respond to ADT/EBRT and in particular, determine those who may benefit from 
long-term androgen suppression or use of non-standard hormone therapies that are now being explored 
in patients with metastatic disease. As mpMRI of the prostate evaluates tumor physiology and 
functionality within the entire prostate gland, it offers information about underlying tumor 
heterogeneity and how these tumors respond to ADT alone and in combination with EBRT. The hope 
is that results from this study may offer preliminary information on how functional evaluation of the 
entire prostate could aid in strategizing patients for an optimal patient-specific therapy plan.  
  
X Monitoring and QA  
All subjects will complete the safety screening form, which will be reviewed by the MRI technician. 
During the multiparametric MRI exam, the subject will be monitored for safety in the MR 
environment by the MRI technologist. The quality of the MR data will be monitored by the MRI 
technologist as it is being acquired and by the study doctors on an ongoing basis.  

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All patient records will be kept on site and confidential. No individual identifiers will be used in any 
reports or publications resulting from this study. Data security will be controlled by limiting its 
electronic transmission and storage using secure networks and protected data archives at Brigham and 
Women’s Hospital.   
  
Standard monitoring software supplied by the manufacturer of the MR scanner will be used to insure 
compliance with specific FDA guidelines regarding power deposition, gradient slew-rates, and field 
strength. MRSI quality assurance will be monitored using phantom studies performed within one week 
prior to any patient study to assure the MR scanner is functioning properly for reproducible data 
acquisition.   
  
All serious adverse events will be reported directly to the DFCI Office for Human Research
 Studies (OHRS).These include any serious adverse events such as an untoward medical occurrence that 
results in death or is life threatening (at the time of the event) or requires inpatient hospitalization or 
results in persistent of significant disability or incapacity. Expected adverse events from MRI are not 
serious and include claustrophobia while in the MRI magnet, a warming sensation while in the MRI 
magnet, or infiltration of intravenous contrast in the subcutaneous tissues at the time of its 
administration. All reasonable measures will be taken to avoid these adverse events. 
 
  
XI: Registration with QACT  
 
 
The registration procedure will be as follows:  
1. Obtain written informed consent from the participant prior to the performance of any 
non0standard of care prostate MRI.   
2. Complete the protocol-specific eligibility checklist using the eligibility assessment documented 
in the participant’s medical/research record. To be eligible for registration to the study, the 
participant must meet each inclusion and exclusion criteria listed on the eligibility  
3. Fax the eligibility checklist(s) and all pages of the consent form(s) to the QACT at checklist. 
 
 
  
4. The QACT Registrar will (a) validate eligibility and (b) register the participant on the study  
5. The QACT Registrar will send an email confirmation of the registration and/or randomization 
to the person initiating the registration immediately following the registration and/or 
randomization.  
 
 
 
 
  
XII References.  
[1] 
J. V Hegde, R. V Mulkern, L. P. Panych, F. M. Fennessy, A. Fedorov, S. E. Maier, and C. M.  

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C. Tempany, “Multiparametric MRI of prostate cancer: An update on state-of-the-art techniques 
and their performance in detecting and localizing prostate cancer.,” Journal of magnetic 
resonance imaging : JMRI, vol. 37, no. 5, pp. 1035–54, May 2013.  
[2] 
L. M. Wu, J.-R. Xu, H. Y. Gu, J. Hua, J. Zhu, J. Chen, W. Zhang, and J. Hu, “Role of magnetic 
resonance imaging in the detection of local prostate cancer recurrence after external beam 
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Protocol 13-343:    
  
  
  
Early changes in multiparametric MRI in 
response to neoadjuvant ADT and EBRT 
for prostate cancer  
  
Aim of Study: To determine if there are measurable 
changes in prostate MRI that will help predict those who will 
or will not respond to ADT/EBRT   
  
Eligibility Criteria:   
1. Unfavorable intermediate- to high-risk localized disease:  
- Clinical or radiographic T2b-T4 primary tumor or  
- Gleason score 7-10 in any core or  
- PSA ≥ 10 prior to initiation of therapy  
2. Patients deemed suitable for therapy with ADT and EBRT 
and able to provide informed consent  
  
What This Study Involves:   
After confirming eligibility and obtaining consent:  
• Baseline non-coil prostate MRI prior to the start of  
ADT/EBRT   
• 3 additional non-coil prostate MRIs over the next six 
months   
• PSA testing   
o The patient will not be charged for the MRIs, PSA levels, or for 
parking.  

 
For more information, please contact: Study 
Coordinator:  
 or  
Study PI: Fiona 
Fennessy, M.D., Ph.D.  
  
  
MRI protocol schedule 
For patient: XXX  
  
  
  
Baseline  
(Time point 1)  
Time Point 2  
Time Point 3  
  
Time Point 4  
MRI   
Date   
(time)  
  
  
Nov 1, 2013  
(11 AM)  
  
Dec 27, 2013  
(10AM)  
  
Feb 7, 2014  
(11 AM)  
  
  
April 18, 2014  
(10AM)  
PSA  
Date  
  
  
Nov 1, 2013  
  
Dec 27, 2013  
  
Feb 7, 2014  
  
Feb 21, 2014  
  
April 18, 2014  
(Notes)  
Baseline, prior 
to any therapy  
8 weeks into  
ADT;   
Friday before  
XRT begins  
Friday of week 
6 of XRT  
Last OTV day 
of XRT  
Day of 3rd 
hormone 
injection OR 
day when 3rd  
hormone 
injection  
WOULD  
HAVE BEEN   
  
 
  
  

 
  
  
  
Recruitment letter for study entitled “Early changes in multiparametric MRI in response to 
neoadjuvant androgen deprivation and external beam radiation therapy for prostate cancer”  
  
  
  
  
  
Dear Patient,  
  
I would like to invite you to be part of a research study for which I am the principal 
investigator. This study is for patients with intermediate- to high-risk prostate cancer who are 
going to be treated with hormone therapy and radiotherapy. The purpose of this study is to 
evaluate whether MRI scans of the prostate can predict who will or will not respond to these 
treatments. It is expected that about 30 patients will take part in this study.  
  
As outlined in detail in the consent form, this study involves a total of 3 follow up prostate 
MRI scans during the course of hormone therapy and radiotherapy. The study also requires 
providing a small blood sample (about ½ teaspoon) for PSA measurement on the same day 
as the prostate MRI, and an additional PSA blood test on the last day of radiotherapy. 
Should you decide to enroll in this research study, your participation will last 6 months.  
  
Your participation in this study is voluntary. You may withdraw from this study at any time. 
Whether you participate or not will not affect your care. You will have access to the MRI 
reports as a result of your participation in this research study, but the MRIs will not affect 
your clinical care and participating in the study will not contribute to your health.  
  
Please contact the study coordinator 
 or by email at  
, if you have any questions or would like to learn more about the  
study.  
  
Thank you in advance for considering this protocol.  
  
  
Sincerely,  
  
  
  
Fiona Fennessy, M.D., Ph.D.  
  
  
   
Email script from PI Radiologist to treating Radiation Oncologist:  
  

 
  
“Dear Dr ______  
Upon review of the medical records of your patient XX, DOB X/X/X, it would appear 
that he meets the eligibility criteria for our MRI research study protocol entitled "Early 
changes in multiparametric MRI in response to neoadjuvant androgen deprivation and 
external beam radiation therapy for prostate cancer”.   
  
  
SCENARIO 1: He is due to be seen by you in clinic on X/X/X. If you deem him to 
be an acceptable candidate, can you please discuss this study with him, and provide 
him with the attached recruitment letter. If he is interested and willing to be part of  
the study, can you obtain consent? I am available by phone to answer any questions  
you or he may have 
  
  
SCENARIO 2: He was seen by you in clinic on x/X/X. Do you think he is an 
acceptable research candidate for this study, and do I have your permission to contact 
him to discuss the study with him and determine his interest in participating, and if 
possible to obtain his consent?  
  
For your convenience, the aim of the study, eligibility criteria, and what the study 
involves for your patient are as follows:  
  
Aim of Study: To determine if there are measurable changes in prostate MRI that will 
help predict those who will or will not respond to ADT/EBRT  
   
Eligibility Criteria:  
1. Unfavorable intermediate‐ to high‐risk localized disease:  
‐ Clinical or radiographic T2b‐T4 primary tumor or  
‐ Gleason score 7‐10 in any core or  
‐ PSA ≥ 10 prior to initiation of therapy  
2. Patients deemed suitable for therapy with ADT and EBRT and able to provide 
informed consent  
   
What This Study Involves:  
After confirming eligibility and obtaining consent:  
Baseline non‐coil prostate MRI prior to the start of ADT/EBRT   
3 additional non‐coil prostate MRIs over the next six months  
PSA testing  
   
The patient will not be charged for the additional MRIs, PSA levels, or for parking.  
  

 
Sincerely,   
Fiona Fennessy