Comparison of PSA Kinetics Between Hypofractionated Stereotactic Body Radiation Therapy, Conventionally Fractionated External Beam Radiation, and High-dose-rate Brachytherapy

S412 median IPSS scores at 36 months, while patients with pretreatment scores of <15 had no change in median scores. The low toxicity and improvement in IPSS score in patients with moderate to severe pretreatment urinary obstructive symptoms may be useful in decisions regarding the choice of treatment for this group of patients. Author Disclosure: R. Henderson: None. Z. Li: None. B.S. Hoppe: None. R.B. Marcus: None. W.M. Mendenhall: None. R.C. Nichols: None. C.G. Morris: None. C.R. Williams: None. J. Costa: None. N.P. Mendenhall: None.

2515 Long-term Experience of HDR Brachytherapy Boost for Localized Prostate Cancer S. Magnan,1 P. Despre´s,1,2 A. Martin,1,3 W. Foster,1 S. Aubin,1,2 L. Beaulieu,1,2 and E´. Vigneault1,3; 1De´partement de Radio-Oncologie du Centre Hospitalier Universitaire de Que´bec (CHUQ), Quebec, QC, Canada, 2De´partement de Physique, Ge´nie Physique et Optique de l’Universite´ Laval, Quebec, QC, Canada, 3Centre de Recherche du CHUQ (CRCHUQ), Quebec, QC, Canada Purpose/Objective(s): To present the long-term biochemical recurrencefree survival (bRFS) of patients with localized prostate cancer treated with high-dose-rate (HDR) brachytherapy boost. Materials/Methods: Between March 1999 and March 2008, 271 patients with localized prostate cancer were treated with external beam radiation therapy (EBRT) followed by a 192Ir HDR brachytherapy boost. The boost was given to the prostate using inverse planning with simulated annealing (IPSA). Doses were ranging from 40 to 45 Gy (20 to 25 fractions) for EBRT and from 15 to 24 Gy (1 to 4 fractions) for the brachytherapy boost. All the high risk patients and some of the intermediate risk patients also received androgen suppressive therapy (AST). Patients were followed prospectively at our institution afterward with PSA, digital rectal exam and GU and GI toxicity evaluation. PSA failure was determined according to the Phoenix consensus definition. PSA curves were also analyzed to distinguish true failures from PSA bounces. Survival curves were calculated with the Kaplan-Meier method and Mantel-Cox log-rank test was used for comparison between groups. Results: According to D’Amico risk definition, 80.4% of patients were intermediate risk and 19.6% were high risk. The Gleason score was  6/10 in 17.3% of patients, 7/10 in 76.4% and  8/10 in 6.3%. The median follow-up was 57 months. Thirty-two of the 271 patients showed a PSA failure according to the Phoenix consensus definition witch lead to a 5-year bRFS of 87.3% for the entire cohort and of 86.6% and 90.0% for the intermediate and high risk groups respectively (p Z 0,6). Of those 32 events, 66% (21) revealed to be transitory PSA bounces. They occurred in the first 3 years after the boost and were followed by a PSA decrease without any salvage therapy. Considering only the true failures, the 5-year bRFS was 95.5% for the entire cohort and 95.0% and 97.7% for the intermediate and high risk groups respectively. Patients treated with AST have significantly higher 5-year bRFS as compared to those treated without AST: 95.9% vs 83.6% respectively (p Z 0.006). Conclusions: HDR brachytherapy boost for localized prostate cancer yielded an excellent 5-year bRFS. AST leads to significantly improved bRFS. These excellent results corroborate others experience with HDR boost and need to be compared in a randomized study to standard high dose EBRT (IMRT). Author Disclosure: S. Magnan: None. P. Despre´s: None. A. Martin: None. W. Foster: None. S. Aubin: None. L. Beaulieu: None. E´. Vigneault: None.

2516 Initial Report of Toxicities in Men With Prostate Cancer Treated With Uniform Scanning Protons S.R. Keole,1 O. Zeidan,2 L. Doh,1 G. Larson,1 R. Barriger,3 and C. Vargas4; 1Radiation Medicine Associates, Oklahoma City, OK, 2 ProCure Proton Therapy Center, Oklahoma City, OK, 3Indiana University, Indianapolis, IN, 4Florida Radiation Oncology Group, Jacksonville, FL

International Journal of Radiation Oncology  Biology  Physics Poster Viewing Abstract 2516; Table

Toxicities versus time (months)

Month

AUA

EPIC GU

EPIC GI

EPIC sex fx (no ADT)

EPIC sex fx (ADT)

Pre-Treatment 3 6 12 18

8.20 7.29 7.45 7.66 7.34

88.2 87.6 88.0 86.4 88.0

93.4 92.7 92.3 92.3 94.6

59.4 56.7 56.1 52.6 55.5

42.4 24.5 40.4 41.5 N/A

Purpose/Objective(s): Proton therapy (PT) is a method of external beam radiation therapy, which can be used, for the definitive treatment of prostate cancer (PC). The most common PT delivery method is double scattering (DS), but more recent delivery methods include scanning techniques, both pencil beam scanning (PBS) and uniform scanning (US). US, versus DS, offers sharper lateral penumbra and, in theory, improved rectal and bladder dosimetry. Our center was the 1st in the world to offer an exclusively US backbone for treatment delivery. This report represents the initial outcomes for patients with PC treated at our center who have a minimum of one year follow up. Materials/Methods: Seventy-six patients with PC consented to the outcomes tracking protocol REG001-09 sponsored by the Proton Collaborative Group (PCG) and met the requirement of a minimum of one year of follow up with completed Expanded Prostate cancer Index Composite (EPIC) surveys. The median age of the patient cohort was 65 (range, 43 to 84). Patients were treated to a target dose of 79.2 GY (RBE) in 44 daily fractions, unless dose constraints to critical structures (rectum, bladder, or femoral heads) were violated. Thirty-five patients had low risk disease (stage I), 28 patients had intermediate risk disease (stage IIA), and 13 patients had high risk disease (stage IIB), as defined by AJCC 7th edition staging. Eleven patients received androgen deprivation therapy (ADT). Patients were asked to complete the Expanded (EPIC) and AUA pretreatment, at 3 months, 6 months, 12 months, 18 months and 24 months post-treatment. EPIC forms were not collected at the conclusion of RT. Results: Genitourinary (GU) and gastrointestinal (GI) function appeared to be stable in patients post-treatment starting as early as 3 months posttreatment. There was no decline seen up to 2 years post-RT. There appeared to be a slight decline in sexual score in men who did not receive ADT. There were a small number of men who did receive ADT and after testosterone recovery they did not see a decline in sexual function at 1 year post-treatment and beyond. Conclusions: Early toxicity results from US PT for PC demonstrates that the use of this modality is well-tolerated. Further follow up continues to be collected and will be reported in future reports. Author Disclosure: S.R. Keole: L. Stock Options; ProCure. P. Ownership Other; ProCure Proton Therapy Center, OKC. O. Zeidan: None. L. Doh: P. Ownership Other; ProCure Proton Therapy Center, OKC. G. Larson: P. Ownership Other; ProCure Proton Therapy Center, OKC. R. Barriger: None. C. Vargas: L. Stock Options; ProCure.

2517 Comparison of PSA Kinetics Between Hypofractionated Stereotactic Body Radiation Therapy, Conventionally Fractionated External Beam Radiation, and High-dose-rate Brachytherapy M.M. Anwar, V. Weinberg, I. Hsu, M. Roach, and A. Gottschalk; University of California San Francisco, San Francisco, CA Purpose/Objective(s): Clinical outcomes in prostate cancer patients have been linked to a lower PSA nadir and a more rapid decline in PSA after treatment (e.g. PSA kinetics). Furthermore, dose escalation with external beam radiation therapy (EBRT) has been associated with improved clinical outcomes. The evidence for a low a/b ratio for prostate cancer, and the desire to shorten treatment, has led to the use of hypofractionated radiation therapy to deliver a higher bioequivalent dose. At UCSF low and lowintermediate risk prostate cancer patients are treated definitively with hypofractionated stereotactic body radiation therapy (SBRT) monotherapy, with a dose and fractionation based on HDR brachytherapy monotherapy.

Volume 84  Number 3S  Supplement 2012 We undertook this retrospective study to compare the biological response (kinetics of PSA decline and PSA nadir) after definitive monotherapy with SBRT compared with EBRT and HDR. We hypothesize that the hypofractionated treatment regimen should result in a more rapid PSA decline than conventionally fractionated EBRT and be equivalent to HDR. Materials/Methods: One hundred eighty-two patients were retrospectively identified with low and intermediate risk defined as Gleason G3+3 PSA < 20 or G3+4 PSA < 15 treated with definitive external beam monotherapy to the prostate only, with at least 3 serial PSAs and 1 year of follow up. Patients were also excluded if they failed therapy by the ASTRO Phoenix definition. Twenty-seven patients treated with SBRT to the prostate with 38 Gy in 4 daily fractions met the same criteria, as did 13 patients treated with HDR, treated with either 950 cGy x 4 fractions or 1050 cGy x 3 fractions. PSA slope is the change in PSA versus time. Results: Median follow-up for the SBRT, EBRT, and HDR cohorts were 37, 62 and 19 months, respectively. The median PSA nadirs for SBRT, EBRT and HDR were 0.26, 0.66 and 0.20 ng/mL respectively, and the median PSA slopes were -.057, -0.003, and -0.054 ng/mL/month, respectively. The rate of PSA decline was significantly slower with EBRT compared with either SBRT or HDR (p < 0.001). The distributions of PSA nadir values statistically differed between all pairs of treatments, although the time to observed nadir was significantly longer with HDR. Conclusion: The hypofractionated regimen delivered by SBRT resulted in a rapid decline in PSA similar to HDR, but faster than EBRT, reflecting the similarity in dose and fractionation of SBRT and HDR. The short follow up for the HDR cohort, and the long median time to PSA nadir (74 months), does not allow comparison of the HDR nadir. The exclusion of failures and long follow up are reflected in the low PSA nadir for EBRT. SBRT does result in similar kinetics to HDR treatment, and is approaching PSA nadirs of HDR treatments in historical series, illustrating its biological equivalence to HDR. Author Disclosure: M.M. Anwar: None. V. Weinberg: None. I. Hsu: None. M. Roach: None. A. Gottschalk: None.

2518 Dosimetric and Clinical Comparison of 2 Seed Types (AS and NAS) Using Real-time US Dosimetry and Day 30 CT Dosimetry for Lowdose-rate Prostate Brachytherapy D.C. Schroyer, X. Wang, and J. Koopmeiners; University of Minnesota Affiliated Hospitals, Minneapolis, MN Purpose/Objective(s): To compare clinical and dosimetric outcomes between AS and NAS in our LDR prostate program. We hypothesized that AS would have less movement during and after implant and this in turn would lead to less variation in dosimetry and possibly less toxicity. Materials/Methods: We retrospectively reviewed 87 consecutive cases of LDR prostate brachytherapy beginning in 2006 (6 excluded). Implants were done with real-time intraoperative US planning using an applicator with a prescription dose of 144 Gy. I-125 seeds initially were NAS (n Z 43) then after 2009 were switched to AS (N Z 38). Prostate, rectum, urethra were contoured intra-operatively. Extra contours were later added that included segmenting the urethra: Total, Base (proximal 1 cm of urethra), Apex (distal 1 cm of urethra), and Mid (between base and apex) with uniform 0.5cm diameter. Identical dosimetry was done on day 30 with CT scan. The US plan was then fused with CT scan to determine urethra location. Urethral dosimetry included total and all segments with D99, Mean, and V200 for each. Prostate dosimetry included D90, V100%, Mean, Dmax (1cc). Rectal dosimetry included Mean, V100, Dmax (1cc). Patients were followed with AUA scores at each follow up and regular PSA values. Results: Pre-treatment characteristics were similar in both groups: (mean values) Age 62, Seeds 109, PSA 5.4, Volume 36 cc’s, AUA score 5, and Gleason 6 74% (rest 3+4), cT1c 88% (rest T2a). Comparing all US vs CT plans (mean values): ProsD90 (179 vs 192 Gy), ProsV100%(97 vs 98%), UMean(288 vs 348 Gy), ProsMean(207 vs 245 Gy), ProsDmax (593 vs 812 Gy) respectively (p < 0.05). US plans for AS vs NAS were overall

Poster Viewing Abstracts S413 similar. Comparing CT plans showed AS had numerically less doses for all urethral dosimetry except MidV200 (p < 0.05 for Apex and Base V200, GUDMax(0.5cc), GUDMean) but higher RectDmax. Comparing changes in dosimetry with US vs CT plans for each patient, AS patients had numerically less change in all urethral and prostate variables (p < 0.05 for BaseV200, MidD99, MidMean, ProsMean, ProsDmax) and for RectMean. The mean maximum change in AUA score after implant was 12 and on multivariate analysis only age was significant. There was no significant rectal toxicity. Mean last PSA value was 0.6 with no difference in seed type with a mean follow up of 19 months. Conclusions: For all patients day 30 CT dosimetry showed significantly higher doses than intra-op US. AS patients had improved day 30 CT dosimetry, while also having less change between intra-op US and day 30 CT dosimetry, giving more confidence that the treatment plan developed intra-operatively will be the treatment plan the patient actually receives over time. However, these dosimetric differences were small and did not translate into any measurable clinical differences. Author Disclosure: D.C. Schroyer: None. X. Wang: None. J. Koopmeiners: None.

2519 Iodine and Palladium Implants of High-Risk Prostate Cancers Both Achieve Excellent Biochemical Failure-free Survival D.M. Berlach,1 D. Shasha,1 W. Mourad,1,2 W. Atallah,1 K. Rattanakorn,1 R. Salant,3 and L. Harrison1; 1Beth Israel Medical Center Department of Radiation Oncology, New York, NY, 2Albert Einstein College of Medicine, New York, NY, 3Beth Israel Medical Center Department of Urology, New York, NY Purpose/Objectives: Recent studies have reported excellent long term biochemical failure free survival (BFFS) for patients with high risk prostate cancer (HRPCa) when treated with combined external beam radiation therapy (EBRT) and low dose rate brachytherapy (BRT) with either I125 or Pd103. Due to hypothetical biologic advantage, Pd103 has been more commonly used for HRPCa. Several factors, including I125’s longer isotope half-life relative to post implant edema, lower cost and greater ease to achieve desired dose distribution, compelled us to evaluate both isotopes. We now present comparative BFFS of I125 vs Pd103 in a large series of HRPCa patients. Materials/Methods: This is a single institution retrospective study with IRB approval. Between April 1998 and January 2010, 181 patients with NCCN HRPCa (Gleason score > 7 or PSA > 20 or T3a or higher) underwent combined EBRT and either I125 (N Z 128; MPD Z 108 Gy) or Pd103 (N Z 53; MPD Z 90 Gy). Patient and disease characteristics were not significantly different between the 2 treatment groups. Median age was 66 years (range, 48 - 80). Median pretreatment PSA was 21 (range, 2.76-142) stratified as 46 patients with PSA 20 ng/mL. Twenty-seven patients had a Gleason score 7 (2 unknown). Sixty-one patients had T1c tumors, 49 had T2a-c tumors and 49 patients had T3a or T3b tumors (22 Tx). Of patients treated with I125 the mean day 0 D90 was 99.6% compared to 102.5% in the Pd103 group. Of patients treated with I125 8% had day 0 D90 < 90% compared to 11% in the Pd103 group. Dosimetric characteristics were not significantly different between the 2 groups. EBRT consisted of initial 45 Gy/25# to standard 4 field pelvis, followed by 5.4 Gy/3# to prostate and seminal vesicles. Androgen deprivation (LHRH agonist  anti-androgen) was administered to 53 (100%) PD103 patients, and to 114 (89%) in the I125. Both groups had a median androgen deprivation duration of 25 months. Biochemical failure was defined as PSA nadir + 2 ng/mL. Statistical analysis was performed using chi-squared analyses predicting for biochemical failure. Results: Minimum follow-up was 24 months and median follow-up was 62 months (range, 24-152). BFFS was 83% for all patients. BFFS was significantly better for patients treated with I125 83.6% vs Pd 81.1% (p Z 0.01). Similarly OS was significantly better in the I125 group at 95.3% compared to 90.6% in the Pd103 (p Z 0.01). Conclusion: This study demonstrates achieved excellent BFFS when treating HRPCa with combined EBRT and LDR with either I125 or Pd103.