Day 0 (D0) D90 of Approximately 70% Correlates with Day 30 (D30) D 90 of 90% For Patients Undergoing Permanent I-125 Radioactive Seed Implant of the Prostate

Proceedings of the 53rd Annual ASTRO Meeting

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each implant. All treatment was delivered on an outpatient basis. Fifty one percent of the patients received concurrent/adjuvant androgen deprivation therapy (ADT). Biochemical failure was defined according to the Phoenix definition (nadir+2ng/ml). Patients were divided into 3 groups in accordance with the NCCN risk stratification system. Biochemical progression free survival curves were generated using the Kaplan-Meier method. Results: The median follow-up time was 37 months (range 8-62). The patient characteristics were as follows: mean age 69 (4789); mean pre-treatment PSA 9.24 (0.19-30.1); Gleason score 6 = 34%, 7 = 45%, and 8-10 = 21%. The 5 year biochemical progression-free survival for low-, intermediate-, and high-risk patients were 100%, 98.5%, and 71% respectively. Three of the six failing patients developed distant metastatic disease. Ten patients underwent post-treatment cystoscopy - two for gross hematuria, one for TURP, and three for urethral stricture. Four patients reported intermittent rectal bleeding. Conclusions: Excellent short-term biochemical outcomes can be achieved in all prostate cancer risk strata using a combination of EBRT followed by HDR brachytherapy boost with minimal toxicity. Author Disclosure: M.J. McDonough: None. N.H. Bittner: None. D.G. Mastras: None. R.D. Sorum: None. K.S. Bergman: None. K.E. Sanders: None. A.C. Pittier: None. A.N. Zemanek: None. H.L. Wang: None.

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Daily Rectal Dosimetry in Patients with Late Grade 2 or Greater Rectal Toxicity After Hypofractionated Image Guided Radiation Therapy for Prostate Cancer

J. Fiveash1, J. M. Bishop2, R. Jacob1, R. Y. Kim1, M. C. Dobelbower1, E. S. Yang1, A. McDonald3, H. Smith1, X. Wu1 1 University of Alabama Medical Center, Birmingham, AL, 2Birmingham Southern College, Birmingham, AL, 3University of Alabama School of Medicine, Birmingham, AL

Purpose/Objective(s): To determine if prostate cancer patients with late rectal toxicity from hypofractionated RT have a higher actual than planned rectal radiation dose. We hypothesize that the actual daily rectal dosimetry will be more predictive of toxicity than the initial radiation plan and that most patients with rectal toxicity will have a worse average daily rectal dosimetry than the treatment plan. Materials/Methods: Since 1/2005 patients with prostate cancer treated at the University of Alabama at Birmingham have been treated with daily CT-based image guidance. Patients were instructed to have a full bladder for treatment and were asked to attempt to have a bowel movement if significant rectal distention was observed on the image guidance study. After treatment with the most common dose schedule from 2005-2009, 70 Gy in 28 fractions of 2.5 Gy, ten patients developed late grade 2 or greater rectal toxicity. Daily dose reconstructions could be performed on eight of these ten patients for all 28 fractions. Utilizing a Tomotherapy treatment planning workstation (Tomotherapy Inc, Madison, Wisconsin) the rectum was contoured on each daily image guidance megavoltage CT scan (224 scans) and reviewed for agreement by two investigators. The actual dose delivered to the rectum was calculated for each fraction. For each patient the total delivered DVH was calculated by adding the daily DVHs. The volume (%) of rectum receiving a given dose in Gy (Vx) was calculated for the treatment plan and delivered dose for each patient. Results: The average daily standard deviation of the rectal volume was 12.74 %. The mean dosimetric parameters for the rectum on the treatment plans and as delivered are listed in the table. All patients had more than half of the fractions with V70 worse than plan. Overall 197/224 (88%) fractions had a numerically worse V70 than the treatment plan. Conclusions: Daily dosimetry may be predictive of rectal toxicity and additional effort to minimize or correct for these deviations from the planned dose are warranted. One weakness of this study is the lack of deformable image registration to track voxel dosimetry from fraction to fraction. Improvements in clinical software will be required for the advantages of adaptive dosimetry to be fully realized. Rectal Dosimetry (planned vs delivered)

Planned rectal dose (all patients) Delivered rectal dose Average difference in delivered dose

V70

V60

V50

V40

7.59% 10.28% +2.69%

13.03% 15.70% +2.67%

26.69% 31.27% +4.58%

51.92% 55.95% +4.03%

Author Disclosure: J. Fiveash: None. J.M. Bishop: None. R. Jacob: None. R.Y. Kim: None. M.C. Dobelbower: None. E.S. Yang: None. A. McDonald: None. H. Smith: None. X. Wu: None.

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Day 0 (D0) D90 of Approximately 70% Correlates with Day 30 (D30) D 90 of 90% For Patients Undergoing Permanent I-125 Radioactive Seed Implant of the Prostate

S. J. Rauth1, D. Shasha1, R. Ambrose1, E. Katsoulakis1, R. Patal2, W. Mourad1, L. B. Harrison1 1

Beth Israel Medical Center, New York, NY, 2Northwestern University Feinberg School of Medicine, Chicago, IL

Purpose/Objective(s): CT post-implant day 30 (D30) D90 of . 90% is the established benchmark defining an optimal prostate implant. Because transient post-implant volumetric changes in the gland will affect dosimetry over time, we have used same day post-implant CT to evaluate dosimetry. However, definition of optimal dosimetry before post-implant day 30 has not been established. This single institution, single physician experience examines the trajectory of sub-optimal dosimetry on the day of implant (D0) and attempts to extrapolate a corresponding D0 dosimetric constraint that is equivalent to D90 at D30. Materials/Methods: Between December 2005 and December 2010, 930 patients underwent TRUS guided interstitial LDR prostate I-125 brachytherapy either as monotherapy (MPD 144 Gy) or in combination with external irradiation (MPD 108 Gy).

I. J. Radiation Oncology d Biology d Physics

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Volume 81, Number 2, Supplement, 2011

Dosimetric evaluations were obtained from prospective CT scans done post-operatively on D0 and D30, (range D25-D35). Dosimetric parameters evaluated were prostate volume, D90, V100, V150, rectal and urethral doses. Multivariate and univariate analysis were calculated based on age, pre-implant prostate volume, change in prostate volume (pre-implant vs D0 and D30, and D0 vs D30), source strength, number of needles and number of seeds used in an attempt to find a predictive correlate between a D0 D90 90% of prescribed dose. Results: Of all patients implanted, 31 had sub-optimal dosimetry with a D0 D90 \ 90% of prescribed dose. The median CT -based prostate volume on D0 of 45.1 cc decreased to 35.3 cc on D30 (p-value \ 0.001). The mean D90 on D0 was 81.3% increasing on D30 to102.6% of prescribed dose, showing an average correction of 21.3% with a range 1.07-44.5% (p-value \ 0.001) Twenty-six of the 31 patients with suboptimal D0 dosimetry corrected by D30. Five patients (16%) did not achieve a D90 of 90% by D30. All could be explained retrospectively by extraneous causes such as loss of seeds in the bladder lowering total activity and reducing dosimetric coverage. Neither univariate nor multivariate analysis revealed any factors that correlated to correction of D90 on D30. Conclusions: The present study evaluating patients with a D0-D90 \ 90% reflects a 20% increase in D90 between D0 and D90, suggesting an optimal D0-D90 correlate would be approximately D70. Future studies will integrate PSA outcomes with these results to evaluate whether these findings are validated as curative outcomes. Author Disclosure: S.J. Rauth: None. D. Shasha: None. R. Ambrose: None. E. Katsoulakis: None. R. Patal: None. W. Mourad: None. L.B. Harrison: None.

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Adjuvant Radiation Therapy In Older Patients With T2 N0 Bladder Cancer Undergoing Limited Surgical Resection: A SEER Database Analysis

R. J. Burri, A. K. Jain, D. P. Horowitz, I. Deutsch, K. S. C. Chao Columbia University Medical Center, New York, NY Purpose/Objective(s): The role of radiation therapy (RT) in the management of bladder cancer remains controversial. Organpreserving surgical management followed by radical radiation therapy is a strategy advocated by some but not widely practiced. The goal of this study was to assess the impact of adjuvant radiation therapy on overall survival (OS) and cause-specific survival (CSS) in patients greater than or equal to 70 years old with T2 N0 bladder cancer managed surgically with trans-urethral resection of the bladder tumor (TURBT). Materials/Methods: The SEER database was reviewed, and 3,074 patients were selected. All patients were diagnosed between 2004 and 2007 with T2 N0 bladder cancer and underwent primary surgical treatment with TURBT and not cystectomy. Minimum age was 70 years, and median age was 81 (range 70 - 105). Of all patients, 770 (25.0%) received adjuvant radiation therapy. Overall and cause-specific survival times were calculated using the Kaplan-Meier method with covariates assessed using the log-rank test, and multivariable Cox regression analysis was utilized to investigate the relationship of potential variables on overall and cause-specific survival. Results: Median overall survival for all patients was 14 months. Median OS for patients treated with TURBT alone was 13 months (1-year OS 52.7% and 2-year OS 35.4%) versus 19 months (1-year OS 67.0% and 2-year OS 41.8%) for those patients receiving radiation therapy after surgery (p\0.001). Adjuvant radiation therapy was also associated with prolonged CSS (p\0.001). Multivariable analysis revealed that lack of adjuvant radiation, increasingly older age at diagnosis, female sex, and higher grade were associated with poorer OS and CSS. Conclusions: Adjuvant radiation therapy is associated with improved survival in older patients with T2 N0 bladder cancer undergoing limited surgical resection. Author Disclosure: R.J. Burri: None. A.K. Jain: None. D.P. Horowitz: None. I. Deutsch: None. K.S.C. Chao: None.

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Radical Cystectomy (RC) versus Bladder Preservation Therapy (BPT): Influence of Stage Discrepancy on Comparative Effectiveness

J. E. Bekelman1, E. Handorf1, T. Guzzo1, M. Resnick1, S. Swisher-McClure1, C. Pollack2, T. Ten Have1, N. Mitra1 1

Hospital of the University of Pennsylvania, Philadelphia, PA, 2Johns Hopkins, Baltimore, MD

Purpose/Objective(s): To examine bladder-cancer specific survival (BCSS) and overall survival (OS) in a population-based cohort of patients with muscle-invasive urothelial carcinoma of the bladder (UCB) treated with RC vs BPT. Materials/Methods: The study was a retrospective, observational cohort study using SEER-Medicare data. We identified patients age . 65 years diagnosed with stage II/III UCB between 1995 and 2005 who received RC (n = 1,455) or cisplatin-based BPT (n = 428) and were followed through December 31, 2008. Kaplan-Meier methods compared unadjusted BCSS and OS. To adjust for measured confounders, we constructed Cox proportional hazard models, adjusting for propensity score. We calculated propensity scores using multivariable logistic regression with receipt of RC as the outcome. Independent variables included patient (age, comorbidity, race, sex, ethnicity), tumor (stage, grade), physician (practice years), hospital (beds, teaching status), and contextual (year, area population, area median income) variables that could influence treatment assignment and/or outcomes. Because prognostically important discrepancies have been reported between pathologic and clinical staging for UC, we conducted simulation studies to examine what effect pathologic upstaging of BPT patients would have on the observed differences in BCSS and OS. We simulated 1,000 datasets in which a proportion of BPT patients were randomly upstaged from stage II to stage III. We varied the proportion of BPT patients upstaged from 10% to 60% (a plausible range based on published literature). Results: Unadjusted 5-year BCSS was 63.2% in the RC group vs 50.4% in the BPT group and 5-year OS was 44.8% in the RC group vs 25.0% in the BPT group. After propensity score adjustment, BPT was associated with lower BCSS (HR for death 1.49; 95% CI, 1.11 - 2.00) and OS (HR 1.45; 95% CI, 1.20 - 1.75). Stage III was reported in 41.4% of RC and 16.6% of BPT patients,