Proceed ings o f the 40 th A n n u a l A S T R O Meet ing

1025 D E T E R M I N A T I O N O F POST- IMPLANT EDEMA F R O M SEED DISTRIBUTION O F P R O S T A T E IMPLANTS

Pouliot Jean, Ph.D., Roy Jean MD, M.Sc. Taschereau Richard, lng. Stag. and Vachon Martin.

Centre Hospitalier Universitaire de Quebec, Department of Radiation Oncology, Qu6bec, Canada

Purpose/Object lve: The aim of this work is the assessment of post-implant edema. A method based on the spatial seed distributions was developed to evaluate the volume variation of lhe prostate after a permanent transperincal implant.

Materials & Methods: For 32 patients, the spatial seed distributions were obtained from orthogonal radiographic films within few days following 1-125 or Pd-103 seeds implantation for prostatic carcinoma. For a few patients, films were taken at regular intervals for up to 200 days. After the complete reconstruction of the 3D coordinates of each seed, the average distance between all pair of seeds were computed. The average distance raised to the cubic power was then used to measure the volume variation of the prostate at different time intervals. For post-implant dosimetry, an average volume is computed from the volume variation weighted with the dose rate.

Results: Three days after implantation, the average increase of prostate volume for 30 patients is 35% with a 26% standard deviation (range 5 to 74%) relative to the planning volume. For a patient with known history of benign prostate hypertrophia treated with Iodine-125 for prostatic carcinoma and followed for a long period of time, the graph on the right shows an unusual large increase due to edema with its maximum reached around 12 days post-implant and was followed by slower decrease. This patient has suffered from urinary retention during the period of maximum edema. From the decreasing slope, it was possible to anticipate the moment when the patient would resume its normal urinary function, Seventy-six days after the implant, a new ultrasound study was performed and the prostate contoured to measure the exact volume. Films were also taken on the same day. The result of the echo study (open square) confirms (within 3 - 4 %) the volume status obtained from the film analysis. The prostate volume has reached its average dimension of the effective dose delivery period on the fifth day post-implant. Post-implant dosimetry based on the volume information five days post-implant would then best correspond to the dose effectively delivered to the patient.

°~ °°

Prostate Volume Variat ion

80 ~ 7 o ~ e 6 0 i ~so ~:40 e 3 0 ~.2o

o 0 10 20 30 40 50 60 70 80

i ' Elapsed Time Post-implant {days) Conclus ion: In conclusion, the post-implant edema can be investigated from the spatial seed distribution variation. In a cohort of 32 patients, large volume increase were observed. This emphasizes the need to chose a consistent and appropriate delay on the volume determination used for post-implant dosimetry. The sharp raise of volume in the days following the implant suggests that realistic post implant can be obtained if volume informations are obtained about one week after implantation. The best delay will have to be confirmed on a larger cohort of patients.

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1026 BIOCHEMICAL CONTROL AND ACUTE TOXICITY ASSOCIATED WITH HIGH DOSE RATE CONFORMAL BOOST BRACHYTHERAPY FOR PROSTATE CANCER: COMPARISON OF THREE-IMPLANT Vs TWO-IMPLANT REGIMENS

A. Martinez*, M. Wallace*, G. Gustafson*, P. Chen*, J. Gonzalcz+, W. Spencer+, G. Edmundson*, M. Hardy*, D. Brabbins*, F. Vicini*, J. Stromberg*.

Departments of Radiation Oncology* and Urology+, William Beaumont Hospital, Royal Oak, MI.

Purpose/Objective: To compare the biochemical freedom from disease and acute toxicity (AT) rates in patients with high risk localized prostate cancer treated with 3 conformal high dose rate (HDR) boost implants and external radiation to those treated with 2 implants and external beam. Materials & Methods: From 11/91-4/97, 105 patients with stages Tlc-T3c disease received 45.6 Gy pelvic irradiation and HDR Ir-192 conformal boost implants as part o f a prospective dose-escalating clinical trial. 58 patients stages T2b-T3c received 3HDR fractions o f 5.5-6.5 Gy each. 47 patients with either stages T2b-T3c or TI c-T2a disease with prostate specific antigen (PSA) >10 and/or Gleason (GS) >7 were subsequently treated with 2HDR fractions of 8.25-8.75 Gy each. No patient received hormones. PSA levels were recorded before & after treatment. Acute toxicity was graded according to the most severe reaction observed using a modified RTOG grading system. Biological equivalence was calculated using the Linear Quadratic (LQ) model. Biochemical freedom from disease (bNED) was analyzed. Biochemical failure was defined according to the ASTRO Consensus Panel on PSA guidelines as 3 consecutive increases in post-treatment PSA after nadir was achieved. The date of failure was recorded as the time midway between the nadir and first increase in PSA. The logrank test was used to determine statistical significance among groups. Results. Mean follow-up for the entire group was 2.1 yr (range: 0.1-5.7 yr). Mean f/u for 3HDR patients was 3yr (1-5.7 yr) ; 1 yr (0.1-2.3 yr) for the 2-implant group. Overall three-year actuarial bNED was 79%. Mean time to biochemical failure was 1.4 yr (0.1-4.9 yr). The three-yr actuarial bNED for 3HDR patients was 74% and for 2HDR at 2 yr was 100% (p-value = 0.021). The 3-yr actuarial bNED survival rates for 49 patients with GS < 6 was 88% ; 56 patients with GS >7 was 72% (p=0.095). Three-yr actuarial rates of bNED survival for the overall group were 100% for pre- treatment PSA <4ng/ml, 92% for PSA >4 and <10, 73% for PSA >10 to _<20, and 72% for PSA >20(p=0.22). For patients with GS <6 and PSA _<10 the 3-yr actuarial bNED survival rate was 100% while for those with GS _>7 and PSA > 10, it was 66% (p=0.04).

Table 1 Modified RTOG Acute Toxicity (AT)

Diarrhea Tencsmus N/V U-Freq. Dysuria Incontin. Retention ' Hematur. Hemsperm Perineal pain 3HDR Grade 2 29.3% 20.7% 0 32.7% 46.5% 3,4% 13.8% 41.4% 10.3% 3.4% 58 Pts. ' Grade 3 1.7% 0 0 0 3.4% 0 0 0 0 0

2HDR Grade 2 14.9% 12.8% 0 19.1% 21.3% 2.1% 6.4% 17.2% 4.2% 0 47 Pts. Grade 3 ' 0 0 0 0 0 0 0 0 0 0

Conclusions: Conformal brachytherapy boost xegimens using either 3HDR or 2HDR fractions for localized high risk prostate cancer have resulted in excellent bNED survival rates, including those with GS _> 7 and PSA > 10. The LQ model accurately predicted equivalence of AT. No increase in AT was noted with the 2-implant regimen compared with 3-implants. However deleting the tratLma of one implant was beneficial. We have completed accrual for 950cGy x 2 and have began 1050cGy x 2. Further patient accrual and dose escalation is planned using 2-implants..