Trial Information

Feasibility Study of Image-guided, Dynamic Dosimetry for Permanent Interstitial Prostate Brachytherapy

This will be a prospective Phase I study.

Subject Identification: Patient confidentiality will be maintained in accordance with Health
Information Portability and Accountability Act (HIPAA) guidelines.

All participants must sign an informed consent that will describe the objectives of the
study and potential risks. All patient data reported on the case reports forms will be
identified by the patient's initials and study code number only.Patients shall not be
identified by name. This should serve to protect the confidentiality of subjects enrolled on
the trial. Clinical data and records for all subjects studied including history and physical
findings, laboratory data, and results of interventions are to be maintained by the
investigators in a secure, locked location. Computerized data will require password
authorization(s) for access.

Description of the Recruitment Process:

Potential subjects will be identified at the time of consultation in the Department of
Radiation Oncology by Dr. Song or Dr. DeWeese. If Dr. DeWeese identifies a potential patient
during a consult he will refer them to Dr. Song so that Dr. Song can offer the patient the
opportunity to participate. Dr. DeWeese will not offer patients the opportunity to
participate but will only assist in identifying potential patients for the research team as
he sees many brachytherapy cases during his consultations.

Description of the Informed Consent Process:

Only the principal investigator and those listed as co-investigators will perform the
informed consent interview. The informed consent interview will take place before the
patient is to be treated to ensure that the patient has adequate time to discuss the
research project with family, friends, and/or other Health Care providers. During the
informed consent interview the interviewer (investigator) will take as much time as needed
to ensure that the potential subject understands the research project and also clearly
understands that he does not have to participate in this project to receive his cancer
treatment at Johns Hopkins. If the patient decides to enroll into the research project he
will sign three copies of the informed consent form. One will be for his own records,one
will be kept in the Clinical Research Office at Johns Hopkins, and the third one will be
kept in his medical records.

Subject Assignment:

6 patients will be enrolled onto the trial. The patients will have their brachytherapy
planned using a registered ultrasound and fluoroscopy (RUF) in combination with the CMS
Interplant system®.

Screening Procedures for Standard Brachytherapy:

- History and physical and KPS at the time of consultation.

- Volume of the prostate based on ultrasound at the time of diagnostic biopsy. If this is
not available, then patient will have prostatic volume estimated by digital rectal
examination at time of consultation and confirmatory ultrasound performed in the
clinic.

- Tumors are to be graded and Gleason score provided on the pathology report.

- Prostate specific antigen (PSA).

- CT scan of the pelvis. Nodes evaluated negative by imaging methods will be classified
as NX.Only nodes evaluated negative by surgical sampling will be classified as N0.

- Bone scan is optional, given the low risk of positive findings in this population.

- IPSS Symptom Score at the time of consultation.

Clinical Assessments:

Once informed consent has been obtained the following assessments will be performed on the
subject:

- Pre-Treatment Evaluation (to be performed within 6 weeks prior to day 1 of
brachytherapy): i. History and Physical ii. IPSS, SHIM, and EPIC questionnaires (See
Appendix 1 for questionnaires). iii. Serum PSA iv. Chest X-Ray v. Bone Scan (if
clinically indicated) vi. CT of pelvis vii. Ultrasound volume (to be done 4 weeks to 4
days prior to day 1 of brachytherapy)

- Day 1 of Brachytherapy:

i. Chest X-Ray> ii. CT of the Pelvis>

> These studies can be done the day after Brachytherapy

- Day 30: 30 days (+/- 7 days) from Brachytherapy:

i. History and Physical ii. IPSS, SHIM, EPIC questionnaires iii. Serum PSA iv. CT of
the Pelvis v. Chest X-Ray

- Month 3: 3 months (+/- 2 weeks) from Brachytherapy:

i. History and Physical ii. IPSS, SHIM, EPIC questionnaires iii. Serum PSA iv. Chest
X-Ray

- Month 6: 6 months (+/- 4 weeks) from Brachytherapy:

i. History and Physical ii. IPSS, SHIM, EPIC questionnaires iii. Serum PSA

- Month 9: 9 months (+/- 4 weeks) from Brachytherapy:

i. History and Physical ii. IPSS, SHIM, EPIC questionnaires iii. Serum PSA

- Month 12: 12 months (+/- 4 weeks) from Brachytherapy:

i. History and Physical ii. IPSS, SHIM, EPIC questionnaires iii. Serum PSA

- Post 12 month follow-up patients will be followed for an additional two more years :
(Note: In years 2 and 3, patients will be followed on a semiannual basis and will have
the following assessments performed): i. History and Physical ii. IPSS, SHIM, EPIC
questionnaires iii. Serum PSA Version 4: 07/11/2006 9

Data to be Collected:

The data that will be collected for this trial will be the results and/or findings of the
procedures and assessments that are previously outlined. R

Results/findings will be abstracted from the source documents (e.g. physician notes, nursing
notes, radiology reports, lab reports, etc…) and recorded onto study specific case report
forms. Only medical records that have been validated by the provider will be used as source
documents for data collection. The data manager assigned to this trial will be responsible
for the data collection. He/She will have access to patient medical records and will record
medical information from the medical record onto the case report form. The principal
investigator will review the data on a monthly basis for accuracy.

Research Interventions:

RADIATION THERAPY AND RESEARCH INTERVENTIONS

The patient population who will be offered this protocol are those who are currently offered
brachytherapy as standard treatment at our institution. Patients will experience no change
in the procedure other than an approximately 10% increase in the duration of fluoroscopy
'on' time during the procedure. There will also be one additional CT scan post-implant to
assess dosimetry at Day ~30. This is necessary to account for the effects of post-implant
edema on the dosimetric parameters and source positions measurements.

Implant Volumes:

The target volume definitions are, for the most part, based upon the ICRU Report 58, Dose
and Volume Specification for Reporting Interstitial Therapy.

Clinical Target Volume, CTV: Pre-implant TRUS definition of the prostate

Planning Target Volume, PTV: An enlargement of the CTV as follows:

1. Expand the TRUS definition of the prostate by 3 mm in the lateral dimension for each
TRUS axial image. Thus, the lateral dimension of the prostate will increase by
approximately 6 mm.

2. Expand the TRUS definition of the prostate by 3 mm in the anterior dimension for each
TRUS axial image.

3. Maintain the same posterior border of the prostate as defined by TRUS.

4. Project the expanded most cephalad axial definition to a plane 3 mm cephalad to the
cephalad most TRUS plane.

5. Project the expanded most caudad axial definition to a plane 3 mm caudad to the caudad
most TRUS plane. The PTV is approximately 6 mm longer in the caudad-cephalad dimension
than the CTV.

Evaluation Target Volume, ETV.

The ETV is defined as the post-implant CT definition of the prostate.