2833 Treatment Planning for a Phase 1 Trial of PSA-Activated PSA-PAH1 for Prostate Cancer

A. Boyer, L. Culp, V. Mistry, T. Kuehl, V. Runge, J. Milleman, K. Coffeld

Scott & White, Temple, TX

Purpose/Objective(s): PSA-PAH1 is a recombinant protoxin created by reengineering a bacterial protoxin molecule (proaero-lysin) such that it is activated by prostate specific antigen (PSA). The purpose of this work is to provide treatment planning anddose delivery procedures in support of a Phase I exploratory sequential dose-finding trial of PSA-PAH1 as a therapeutic agentfor PSA-elaborating tumor cells.

Materials/Methods: A brachytherapy treatment planning program (Variseed 7.1, Varian Medical Systems, Palo Alto,California) was enlisted to select needle insertion locations on a conventional perineal prostate brachytherapy template. Theprostate and urethera were visualized ultrasonically usng a 7.5 MHz transrectal ultrasonic probe (Model 2102 Hawk, B&KMedical. Herley, Denmark). Postmortem ex vivo prostate specimen fixed in a gel were injected with the PSA-PAH1 drug mixedwith gadolinium MRI contrast agent and methylene blue in preclinical experiments. High resolution images of the specimenwere acquired with a wrist coil and studied to observe the distribution of agent around the injection sites. The specimen weresectioned and processed for further histopathologic examination to evalulate the presence of necrosis and inflammation. Thegoal of the clinical procedure was to deposit PSA-PAH1 through 18 guage needles starting with a dose of 0.1mL of agent ineach cubic centimeter of the prostate volume, excluding the urethra guided by transrectal ultrasonic imaging.

Results: Based on the preclinical studies, too low a density of deposition sites failed to place agent in individual lobules thatappeared as dark regions in the MRI contrast studies. The deposited agent appeared to drain toward the urethra through thenative ductal system. A very high deposition site density would require an excessively long operative procedure. An optimaldeposition pattern was selected that placed an injection in the center of 1cm2 areas spaced uniformly over axial planes 0.5 cmthick that transacted the prostate. The deposition pattern was offset 0.5 cm laterally and 0.5 cm anteriorly in alternating planesand 0.05mL of agent was deposited at each location.

Conclusions: The deposition strategy produced a deposition pattern that filled the prostate volume uniformly with a densitysufficient to insure that the majority of the lobules received an injection within their volume. The brachytherapy software provedto be a valuable tool, providing an optimal deposition pattern that could be quickly and automatically computed. Print-outsprovided by the software were invaluable in keeping track of the needle insertion coordinates in the template and the incrementsby which the needles were withdrawn for each deposition of agent.

Author Disclosure: A. Boyer, Protox Therapeutics Inc. Vancouver, British Columbia, Canada, B. Research Grant; L. Culp,Protox Therapeutics Inc. Vancouver, British Columbia, Canada., B. Research Grant; V. Mistry, None; T. Kuehl, None; V.Runge, None; J. Milleman, None; K. Coffeld, Protox Therapeutics Inc. Vancouver, British Columbia, Canada, B. ResearchGrant.

2834 Breast Dose Reduction in Women Undergoing Mediastinal Radiotherapy Using a Custom ProneImmobilization Device

R. J. Kudchadker1, C. S. Ha1, C. Stokes1, S. M. Kirsner1, R. B. Wilder2

1UT M. D. Anderson Cancer Center, Houston, TX, 2Walter Reed Army Medical Center, Washington, DC

Purpose/Objective(s): Radiation induced breast cancer is one of the most significant long-term complications associated withradiation therapy to the mediastinum of female patients. The purpose of this study is to investigate the possibility of reducingradiation dose to the breasts, by treating these patients in the prone position using a custom immobilization device, rather thanin the more conventional supine position.

Materials/Methods: Twenty female patients with lymphoma who were to undergo mediastinal radiation therapy were accrued.A custom prone breast immobilization device was constructed for this study. Each patient underwent virtual simulation in bothsupine and prone positions, using the conventional AP-PA isocentric technique. The median prescription dose to themediastinum was 3600 cGy (range: 3060 cGy to 3960 cGy). To compare the dosimetric effect of these two setups, treatmentplans were generated and dose-volume histograms (DVHs) were collected from each treatment plan for left breast, right breast,left lung, right lung and heart. In addition, the distance between the medial edge of each axilla and midline of the patient wasalso compared between the two different positions. The Wilcox Matched-Pairs Signed Rank Test was used to calculate thestatistical significance (p �0.05 deemed significant) of the results.

Results: DVH analysis show that in 15 out of 20 patients, the volume of right breast receiving a dose greater than 5 Gy wasslightly greater in the prone setup than supine setup (p��0.008). In 17 out of 20 patients, the volume of left breast receivinga dose greater than 5 Gy was slightly greater in the prone setup than supine setup (p��0.0003). The difference betweenvolumes of right or left breast receiving a dose greater than 20 Gy became negligible between the prone and supine setup. In12 out of 20 patients, the lung DVH was slightly superior though not statistically significant (p��0.4) in the prone setup versusthe supine setup. In all 20 patients, the heart DVH was nearly equivalent between the prone setup and the supine setup. In 16out of 20 patients, the distance between the medial edge of each axilla and the midline of the patient was greater in the supinethan in the prone setup (p��0.005 for the right axilla and p��0.006 for the left axilla).

Conclusions: The supine position treatment plans had slightly superior breast DVH and approximately equivalent lung andheart DVH compared to the prone position treatment plans. It should be kept in mind during simulation that the breasts andaxillary lymph nodes tend to move more medially in the prone position than in the supine position. Also, by treating patientsin the prone position, gravity causes more of the breast volume to fall under the lung blocks. Future use of the custom proneimmobilization device with minor modifications, will allow for better breast repositioning under the lung blocks, thus reducingbreast volume exposed to radiation and minimize future secondary breast cancer.

Author Disclosure: R.J. Kudchadker, None; C.S. Ha, None; C. Stokes, None; S.M. Kirsner, None; R.B. Wilder, None.

S679Proceedings of the 48th Annual ASTRO Meeting