Biochemical Outcomes for Patients With Intermediate-Risk Prostate Cancer Treated With Proton Therapy

E242

International Journal of Radiation Oncology  Biology  Physics

2601

Purpose/Objective(s): Although registration of planning magnetic resonance imaging (MRI) to computed tomography (CT) may improve delineation of the prostate gland and enable tumor segmentation, a technique for accurate registration without the use of implanted fiducial markers (FM) remains elusive. Reproducing set-up and using surrounding anatomical structures such as bone introduces error due to variation in bowel and bladder filling. Prostate-to-prostate registration is difficult due to a lack of common anatomical landmarks of structures to guide the registration algorithm. We investigated whether high-dose volumetric CT (HDVCT) could better depict intraprostatic structures common to MRI to aid in the registration process. Materials/Methods: Planning scans were obtained with conventional CT (CCT) (120 kV, 300 mAs, 3-mm-thick slices), HDVCT (120 kV, 2300 mAs, 80 slices of volumetric scan for the entire prostate gland), and 3T MRI (T2W). Two patients underwent HDVCT and MRI of the prostate post-FM insertion, and a further 9 patients underwent HDCT, CCT, and MRI at the time of treatment planning on a prospective clinical trial. Common naturally occurring landmarks within the prostate were identified on HDVCT, CCT, and MRI, consisting of small intraprostatic cysts identified as hypodense on CT and hyperintense on T2-weighted MRI. Rigid registration using a commercial mutual information algorithm or a pointbased technique was performed for the 2 patients with implanted FMs. Target registration error (TRE) was determined using implanted FMs as the gold-standard reference. Results: HDVCT was able to resolve more common intraprostatic anatomical landmarks with MRI (mean 4.2, range 3-6 per patient) compared with CCT (mean 1.6, range 1-3 per patient). A minimum of 3 landmarks to enable point-based registration were identified in all HDVCTs, and only 22% of CCTs. Rigid registration based on bony anatomy (mutual information) achieved an average TRE 2.6 mm (range 1.7-4.3). TRE was reduced to 1.00 mm (0.4-1.3) using point-based registration of common naturally occurring landmarks between HDVCT and MRI. Conclusion: This study provides evidence that accurate registration of the prostate on HDV-CT and MRI may be possible without the use of implanted FMs. Author Disclosure: A.J. McPartlin: None. A. Hosni: None. H. Alasti: None. C.N. Catton: None. Y. Cho: None. C. Menard: None.

Image Guidance is Associated With Decreased Gastrointestinal Toxicity in Patients Receiving Definitive External Beam Radiation Therapy for Prostate Cancer U. Mahmood,1 J. Huo,1 M. Koshy,2 T.J. Pugh,1 S.E. McGuire,3 S. Choi,1 S.J. Frank,1 A. Lee,4 D.A. Kuban,1 S. Giordano,1 T.A. Buchholz,1 B.D. Smith,1 and K.E. Hoffman1; 1MD Anderson Cancer Center, Houston, TX, 2University of Chicago, Chicago, IL, 3The University of Texas MD Anderson Cancer Center, Houston, TX, 4US Oncology, Irving, TX Purpose/Objective(s): Image guided radiation therapy (IGRT) is commonly used in the radiation treatment of prostate cancer; however, there are limited data demonstrating its clinical effectiveness. We conducted this study to evaluate the utilization of IGRT and its impact on morbidity in patients receiving definitive external beam radiation therapy (EBRT) for prostate cancer. Materials/Methods: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database, information was obtained for all patients aged >66 years old diagnosed with localized adenocarcinoma of the prostate who received EBRT (with or without androgen deprivation therapy) from 2000 to 2009. Current Procedural Terminology/Healthcare Common Procedure Coding System codes were used to determine whether IGRT was used and whether patients experienced any of the following radiation-related morbidities: gastrointestinal (GI) bleeding, nonbleeding GI toxicity, urinary incontinence, non-incontinence urinary toxicity, sexual dysfunction, or hip fracture. Multivariable analyses were performed to determine predictors of radiation-related morbidities, including all available patient, tumor, and treatment characteristics. Results: A total of 35,266 patients were identified, of which 17,831 (50.6%) received IGRT and 17,435 (49.4%) did not receive IGRT. Over the time period analyzed, IGRT use increased dramatically from 4.8% in 2000 to 97.9% in 2009. Multivariable analyses found that IGRT use was associated with decreased GI bleeding (hazard ratio [HR] 0.89; 95% CI: 0.840.94; P<.001) and nonbleeding GI toxicity (HR 0.90; 95% CI: 0.86-0.94; P<.001). On the other hand, IGRT use was not found to be a significant predictor of urinary incontinence (HR 1.01; 95% CI: 0.97-1.06; PZ.592), non-incontinence urinary toxicity (HR 1.03; 95% CI: 0.98-1.08; PZ.202), sexual dysfunction (HR 1.01; 95% CI: 0.95-1.08; PZ.726), or hip fracture (HR 1.07; 95% CI: 0.92-1.25; PZ.356). Although there were differences among the individual radiation-related morbidities, earlier year of diagnosis, increasing age, increasing Charlson comorbidity score, increasing tumor grade, increasing T stage, 2-D/3-D (vs. IMRT) radiation treatment, and use of androgen deprivation therapy generally predicted for increased toxicity. Conclusion: Among patients with localized prostate cancer, the addition of IGRT to definitive EBRT is associated with decreased GI toxicity. These findings help validate the widespread utilization of this relatively new technology. Further studies are warranted to examine the comparative effectiveness of different types of IGRT modalities. Author Disclosure: U. Mahmood: None. J. Huo: None. M. Koshy: None. T.J. Pugh: None. S.E. McGuire: None. S. Choi: None. S.J. Frank: Director; C4 Imaging. A. Lee: None. D.A. Kuban: None. S. Giordano: None. T.A. Buchholz: None. B.D. Smith: Research Grant; Varian. K.E. Hoffman: Research Grant; ASTRO. Consultant; Vanderbilt University. Vice-Chair; ASTRO. Chair; ASTRO.

2602 Potential Role of High-Dose Volumetric CT in Enabling MRI-CT Registration Based on Common Anatomical Landmarks A.J. McPartlin,1,2 A. Hosni,3 H. Alasti,4 C.N. Catton,5 Y.B. Cho,4 and C. Menard5; 1Princess Margaret Cancer Centre, Toronto, ON, Canada, 2The Christie NHS Foundation Trust, Manchester, England, 3 Mansoura University, Mansoura, Egypt, 4Princess Margaret Cancer Center / University of Toronto, Toronto, ON, Canada, 5Princess Margaret Cancer Centre / University of Toronto, Toronto, ON, Canada

2603 Biochemical Outcomes for Patients With Intermediate-Risk Prostate Cancer Treated With Proton Therapy C.M. Bryant,1 W.M. Mendenhall,2 B.S. Hoppe,2 R.H. Henderson,1 R.C. Nichols, Jr,1 Z. Su,1 C.R. Williams,3 C.G. Morris,1 Z. Li,3 and N.P. Mendenhall1; 1University of Florida Health Proton Therapy Institute, Jacksonville, FL, 2University of Florida, Gainesville, FL, 3 University of Florida, Jacksonville, FL Purpose/Objective(s): To report outcomes for patients treated with image guided proton therapy (PT) for patients with intermediate-risk prostate cancer and to determine the clinical predictors of biochemical failure. Materials/Methods: The medical records of 536 men treated for intermediate-risk prostate cancer with PT at our institution between 2006 and 2010 were retrospectively reviewed. Patients were treated with definitive PT to the prostate and proximal seminal vesicles or to the prostate alone. PT was prescribed at 1.8 to 2 Gy (RBE) per fraction to a total dose of 75.6 to 82 Gy (RBE). Proton therapy was delivered using passive-beam scattering, typically with 2 beams to deliver the prescribed dose in a left and right anterior oblique arrangement. Ninety-eight percent of patients received 78 Gy (RBE) or higher and the median dose to the proximal seminal vesicles was 46 Gy (RBE). Androgen deprivation therapy (ADT) was received by 9.7% of patients for a median of 4 months. Biochemical progression-free survival (bPFS) with biochemical failure defined by the Phoenix definition, cause-specific survival, distant metastasis-free survival, and overall survival rates are reported. Clinical predictors of biochemical failure found on multivariate analysis are also reported. Results: The median follow-up was 4.9 years. Median prostate-specific antigen (PSA) nadir for patients who did not receive ADT was 0.3 ng/mL

Volume 93  Number 3S  Supplement 2015 and the median time to nadir was 39 months (2 to 89 months). The 5-year bPFS rate was 95.4%. The 5-year distant metastasis-free, cause-specific, and overall survival rates were 98.9%, 99.6%, and 95.3%, respectively. On multivariate analysis, the number of intermediate-risk factors (1 vs multiple) significantly predicted biochemical recurrence (hazard ratio [HR] 0.4, PZ.028) as patients with multiple risk factors had worse biochemical control. The use of ADT did not significantly improve biochemical control at 5 years (HR 1.8, PZ.325). A separate multivariate analysis was performed including only patients with 10 or more zones biopsied at the time of diagnosis. The number of intermediate-risk factors remained a predictor of biochemical relapse-free survival (HR 0.3, PZ.037). A primary Gleason score of 4 (4+3Z7) versus a primary Gleason score of 3 (3+3Z6 or 3+4Z7) also predicted worse biochemical control (HR 0.2, PZ0.028). Conclusion: PT provided excellent biochemical control for patients with intermediate-risk prostate cancer. Multiple intermediate-risk factors significantly increased the risk for biochemical failure. In patients with at least a 10-zone biopsy, a primary Gleason score of 4 also predicted worse biochemical relapse-free survival. Short-term ADT did not improve biochemical control, but selection bias likely mitigated its effects. Author Disclosure: C.M. Bryant: None. W.M. Mendenhall: None. B.S. Hoppe: None. R.H. Henderson: None. R. Nichols: None. Z. Su: None. C.R. Williams: None. C.G. Morris: None. Z. Li: None. N.P. Mendenhall: None.

2604 Focal Nodal SBRT or Elective Nodal Protracted Salvage Radiation Therapy for Prostate Cancer Patients With a Choline PET-CT Positive Nodal Relapse G. Crehange,1 P. Maingon,2 A. Cueff,2 G. Truc,3 K. Peignaux,4 F. Mazoyer,3 N. Vulquin,1 M. Quivrin,1 S. Naudy,1 and E. Martin1; 1Centre Georges-Francois Leclerc, Dijon Cedex, France, 2Centre Georges Franc¸ois Leclerc, Dijon, France, 3Centre Georges Franc¸ois Leclerc, Dijon, France, 4Centre GF Leclerc, Dijon, France Purpose/Objective(s): 18F or 11C choline positron emission tomographyecomputed tomography (PET-CT) has significantly improved the detection of occult nodal relapse in prostate cancer patients with a rising prostate-specific antigen (PSA) level after radical prostatectomy and/or external radiation therapy (RT). In parallel, focal hypofractionated stereotactic body RT (fSBRT) is an emerging salvage RT (sRT) for oligometastatic diseases. It allows delivery of a very high biologically effective dose (BED) in few fractions but to a small volume (e.g., involved node only). In this preliminary report, we aimed to assess short-term biochemical response of focal SBRT versus protracted ENI in node-positive recurrent prostate cancer on choline PET-CT. Materials/Methods: Between 2009 and 2014, 102 patients underwent choline PET-TDM in our center. Of these, 37 had sRT without hormones for nodal relapse only. Patients underwent either fSBRT (nZ28) or protracted elective nodal irradiation (nZ 9) combined with a protracted boost to positive nodes (pENI). Patients treated with fSBRT received 30 to 45 Gy in 3 to 6 fractions while patients treated with pENI had 60 to 66Gy in 25 to 33 fractions. Failure was defined as PSA rising higher than pre-sRT on 2 consecutive samples or the initiation of any second salvage therapy. PSA nadir (nPSA), time to nPSA, and time to failure (TTF) were assessed. Results: The characteristics of patients and tumor at time of relapse were similar. The median PSA values at the time of sRT were 5.9 ng/mL (1.3; 17.3) with fSBRT and 6.9 ng/mL (0.5; 13.8) with pENI (PZNS); The median follow-up was 1.95 years (95% CI: 0.54-1.52). Fifteen failures occurred with fSBRT (51.7%) and 4 failures with pENI (44.4%). The median PSA nadir at 2 years was 0.57 (0.01-4.52) with fSBRT and 0.02 (0.01-0.07) with pENI (PZ.0004). The time to nPSA at 2 years was 17.61 months (0.20-23.62) with fSBRT and 8.46 months (5.19-18.37) with pENI (PZ.05). The median TTF was 2.89 years (95% CI: 1.24-4.65) with fSBRT and 4.73 years (95% CI: 0.40-ND) with pENI (PZ NS). Conclusion: Patients with a nodal relapse on fluorocholine PET-CT who were treated with pENI experienced a lower nPSA and shorter time to nPSA 2 years following completion of sRT than with fSBRT, consistent

Poster Viewing Session E243 with the eradication of micrometastatic disease in PET-negative nodes. Whether this translates into improved biochemical control and/or a clinical relapse needs longer follow-up. Author Disclosure: G. Crehange: None. P. Maingon: None. A. Cueff: None. G. Truc: None. K. Peignaux: None. F. Mazoyer: None. N. Vulquin: None. M. Quivrin: None. S. Naudy: None. E. Martin: None.

2605 Are Results From Intermediate-Risk Prostate Cancer Patients Treated Within Clinical Trials Applicable to Real Life? D. Taussky,1 J.P. Bahary,2 C. Lambert,1 M.C. Beauchemin,2 G. Delouya,1 M. Barkati,3 and X. Liem4; 1Centre Hospitalier de l’Universite de Montreal, Montreal, QC, Canada, 2Hopital Notre-Dame du CHUM, Montreal, QC, Canada, 3Centre Hospitalier de l’Universite´ de Montre´al (CHUM), Montreal, QC, Canada, 4Univesrite Montreal, Montreal, QC, Canada Purpose/Objective(s): There is some doubt on whether clinical studies (CSs) have selective inclusion criteria that might not represent real-life patients (RLPs) and may limit their applicability to daily clinical practice. Patients in CSs and RLPs might have different comorbidities which can have an impact on overall survival. We assessed whether patients from CSs differ from patients not included in terms of comorbidity, prostate cancer aggressiveness, and biochemical recurrence. Materials/Methods: We identified 468 patients with D’Amico intermediaterisk prostate cancer from our institutional database all treated with external beam radiation therapy only. Three hundred seven patients were treated in a CS, including 2, multinational randomized trials (PROFIT and RTOG 0126), each including >80 patients from our center; one in-house phase 2 with >40 patients and some smaller randomized studies with <13 patients each. These CS patients were compared to 161 patients (RLPs) who were not included in any CS. Patients treated in CSs were compared to the RLPs using nonparametric tests. Logistic regression was performed to explore predictive factors of CS inclusion. Biochemical recurrence rate was estimated using the Kaplan-Meier method and compared using the log-rank test. Results: Median follow-up was 56 months (interquartile range 36-78 months). There was no difference in age (mean 70 years for both, PZ.95) or in cancer aggressiveness between both groups: PSA >10 ng/mL in 28% of CS patients and in 32% of RLPs (PZ.37). Gleason score 4+3 was found in 29% of CS patients and in 30% of RLPs (PZ.58). CS patients had more frequently hypertension (60% CS vs 46% RLPs, PZ.01), and more often hypercholesterolemia (51% for CS vs 43% in RLPs, PZ.01). In univariate analysis, myocardial infarction (PZ.05) and hypertension (PZ.003) were predictive of CS inclusion. On multivariate analysis, only hypertension was a significant predictor (hazard ratio [HR] 0.6, 95% confidence interval [CI] 0.4-0.9, PZ.012). The Cancer of the Prostate Risk Assessment score showed a trend toward a higher score in patients not treated in a CS (HR 1.15, 95 %CI 0.98-1.32, PZ.09). Biochemical recurrence-free survival was similar between both groups with a 5-year rate of 94% in both groups (PZ.65). Conclusion: In our exploratory analysis, we found that patients treated in CSs did not differ from RLPs in terms of age, prostate cancer aggressiveness, or biochemical outcome. Patients with comorbidity were more often included in CSs. The impact on overall survival remains unclear. In our institution, conclusions from CS can be transferred to daily practice. Author Disclosure: D. Taussky: None. J. Bahary: None. C. Lambert: None. M. Beauchemin: None. G. Delouya: None. M. Barkati: None. X. Liem: None.

2606 Results of Scanning Beam Proton Therapy (SCBT) for the Treatment of Patients With High-Risk Prostate Cancer S. Choi,1 Q. Nguyen,1 T.J. Pugh,1 U. Mahmood,1 S.E. McGuire,2 K.E. Hoffman,1 S.J. Frank,1 D.A. Kuban,1 and A.K. Lee3; 1MD Anderson Cancer Center, Houston, TX, 2The University of Texas MD Anderson Cancer Center, Houston, TX, 3Texas Center for Proton Therapy, Irving, TX