Intensity Modulated Radiation Therapy for Prostate Cancer

BACKGROUND:

-This study represents a progression from findings in four previous National Cancer Institute
(NCI) Radiation Oncology Branch (ROB) protocols (02-C-0167A, 02-C-0207E, 03-C-0190B,
04-C-0171). In these previous works we have begun to develop techniques to obtain Magnetic
Resonance (MR) biological images and co-register tissue in prostate cancer patients.

OBJECTIVES:

-The primary objective of the first portion of this study is to assess the feasibility of
using Intensity-modulated radiation therapy (IMRT) to treat the at-risk lymph nodes in
prostate cancer. Also, if feasible, we hope optimize this technique with experience.

ELIGIBILITY:

- This is a study of image guided, targeted radiation therapy in patients with high risk
of nodal metastases from prostate cancer.

- Patients with prostate cancer who have more than 15% risk of lymph node (as defined by
the Partin tables) metastasis will be eligible for this study.

DESIGN:

- On the first 10 patients, we will perform approximately 5 computed tomography (CT)
simulations throughout the course of their therapy. On each simulation, the initial
treatment plan will be re-run. The dose-volume data from target and normal tissues will
then be re-analyzed. From this analysis we will be better able to determine the size of
margins needed to account for organ motion and changes such as varying amounts of gas in
the bowel and fluid in the bladder. To the best of our knowledge, no such analyses have
been published.

- If the initial part of this trial is feasible, we will proceed to a phase I dose
escalation trial of radiation to the at-risk lymph nodes. The primary statistical
objective of the phase I portion of this study is to estimate the Maximum Tolerated Dose
(MTD) of external beam radiation based on evaluating acute toxicity. The study will be
conducted with a dose-escalation design with 3 patients in each dose cohort. If fewer
than 2 of 3 patients experience an acute dose limiting toxicity (DLT) than patients will
be accrued to the next dose cohort. If 2 or more of 3 patients experience a DLT then the
MTD will be exceeded and the prior, lower dose cohort will be considered the MTD.
Secondary objectives of this study are to relate patterns in gene and protein expression
to response and toxicity and to evaluate the frequency of late term toxicity.

- Specific procedures and risks will be described in a separate consent to be obtained at
the time of biopsy. Tissue samples will be processed for complementary deoxyribonucleic
acid (cDNA) microarray testing and stored for future analysis in the Radiation Oncology
Branch, NCI.

- Anatomic Magnetic Resonance Imaging (MRI) and magnetic resonance (MR) biological images
of the prostate and pelvis will be obtained and tissue will be acquired with biopsy
locations precisely translated (co-registered) to an MR image of reference. A fiducial
marker (gold seed) will be left at the biopsy site as a fiducial marker to direct future
radiation therapy to the prostate. If necessary, additional fiducial markers will be
placed for prostate localization during treatment.

- INCLUSION CRITERIA:

Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

Pathology report confirming adenocarcinoma of the prostate

Risk of lymph node metastasis greater than or equal to15% as defined by the Partin tables
or biopsy proven positive lymph nodes

Tumor visible on magnetic resonance imaging (MRI)

No prior surgery, radiation, or chemotherapy for prostate cancer, with the exception of
hormone therapy which may be given neoadjuvantly for up to four (4) months.

Age greater than 18 years old and less than 90 years old.

EXCLUSION CRITERIA:

Cognitively impaired patients who cannot give informed consent.

Patients with metastatic disease beyond the pelvis

Contraindication to biopsy

- Bleeding disorder

- Prothrombin time (PT)/partial thromboplastin time (PTT) greater than or equal to 1.5
times the upper limit of normal

- Platelets less than or equal to 50K

- Artificial heart valve

Contraindication to MRI

- Patients weighing greater than136 kgs (weight limit for the scanner tables)

- Allergy to magnetic resonance (MR) contrast agent

- Patients with pacemakers, cerebral aneurysm clips, shrapnel injury or implantable
electronic devices.

Pre-existing and active prostatitis or proctitis

Other medical conditions deemed by the principal investigator (PI) or associates to make
the patient ineligible for protocol investigations, procedures, and high-dose external beam
radiotherapy.