Comparison of Conventional Versus Hyperfractionated Chemoradiation for Bladder Preservation Treatment of Muscle Invasive Bladder Cancer in the National Cancer Database

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International Journal of Radiation Oncology  Biology  Physics

CIZ1.30-6.24). Among low, intermediate, and high risk groups, 3.7%, 20.6%, and 30.8% of patients experienced PSA failure, respectively. Allcause mortality occurred in 20.0%, 33.3%, and 51.7% of low, intermediate, and high risk groups, respectively. Stratified by risk group, minority patients did not have a significantly different hazard of 10-year PSA failure compared to Caucasian subjects (low risk group: HRZ0.70, 95% CIZ0.15-3.32; intermediate risk group: HRZ1.90, 95% CIZ0.59-6.08; high risk group: HRZ0.53, 95% CIZ0.19-1.47). Minority patients did not have a significantly different hazard of mortality compared to Caucasian subjects (low risk group: HRZ2.23, 95% CIZ0.14-36.74; intermediate risk group: HRZ0.45, 95% CIZ0.09-2.32; high risk group: HRZ1.13, 95% CIZ0.27-4.75). Conclusion: Our minority patients had similar BFS and OS outcomes compared to their Caucasian counterparts, and better than expected outcomes compared to historical controls. The military’s unique health care system with universal access to care and increased level of fitness may explain why our minority patients had improved outcomes. The influence of universal access to care upon treatment outcomes may be explained through increased prostate cancer risk assessment, improved rates of PSA screening, more reliable follow-up, and diagnosis at an earlier stage of disease, which all portend better outcomes. Further investigation is warranted regarding whether improved access to care may ameliorate racial disparities in prostate cancer outcomes. Author Disclosure: A.R. Horn: None. J.R. Bear: None. D. Brown: None. A.R. Chaurasia: None. A. Gutweiler: None. J.D. Kehrer: None. R.K. Takesuye: None. H.B. Wilds: None.

(100 %RLS) at 6 months post-RT. Initial prostate volume <35mL predicted for improved %RLS and initial DCE- correlated with improved % RLS (rZ-.24, pZ0.04). Lesions were most likely to exhibit a complete radiographic response if: initial lesion size was <1.1 cm, baseline prostate volume was <70cc, and baseline PSA was <12. Poor radiographic response was demonstrated in patients with: initial lesion size >1.1 cm, initial prostate volume >35cc, and an initial PSAD >0.35. Changes in ADC (rZ-0.41, pZ0.0004) and DCE (rZ-.35, pZ0.0028) status were highly correlative with %RLS. Conclusion: A rapid radiographic response on mpMRI was demonstrated at 6 months post-RT +/- ADT. A substantial percentage of patients have radiographically visible lesions at 6 months post-RT. Pre-treatment clinical and mpMRI characteristics can predict which lesions respond less rapidly and may benefit from intensification, such as focal dose escalation. Additional follow-up will be required to determine which pre-treatment or post-treatment factors are associated with local recurrence. Author Disclosure: A.R. Horn: None. U.T. Shankavaram: None. R.A. Madan: None. P.A. Pinto: None. A. Kaushal: None. A.V. Krauze: None. L. Rowe: None. E.E. Schott: None. T. Cooley-Zgela: None. P. Choyke: None. B. Turkbey: None. D.E. Citrin: Employee; US Army. Research Grant; National Institutes of Health.

2575 Pretreatment Predictors of Rapid Prostate Lesion Response to Radiation Therapy Measured by Multiparametric MRI A.R. Horn,1 U.T. Shankavaram,2 R.A. Madan,3 P.A. Pinto,4 A. Kaushal,2 A.V. Krauze,2 L. Rowe,2 E.E. Schott,2 T. Cooley-Zgela,2 P. Choyke,5 B. Turkbey,5 and D.E. Citrin2; 1Walter Reed National Military Medical Center, Bethesda, MD, 2Radiation Oncology Branch, National Cancer Institute, Bethesda, MD, 3Genitourinary Malignancies Branch, National Cancer Institute, Bethesda, MD, 4Urologic Oncology Branch, National Cancer Institute, Bethesda, MD, 5Molecular Imaging Program, National Cancer Institute, Bethesda, MD Purpose/Objective(s): Multiparametric (mp) MRI has improved the detection of prostate cancer. We sought to prospectively study and model potential predictors of prostate lesion response to external beam radiotherapy (RT) using clinical factors including mpMRI. Materials/Methods: Patients were enrolled on an IRB approved protocol to prospectively evaluate pre-treatment and 6 month post-EBRT mpMRI for assessment of prostate cancer response. mpMRI consisted of endorectal coil T2W imaging, dynamic contrast enhanced (DCE) imaging, and diffusion weighted imaging (DWI) with apparent diffusion coefficient (ADC) maps. Prostate lesions were identified and measured prospectively by a prostate-dedicated radiologist based on detection in each sequence of mpMRI. Pearson’s product moment correlation coefficient was used to correlate potential predictors of lesion response with percent reduction in lesion size (%RLS), and cumulative incidence curves of %RLS with respect to subgroups were estimated and plotted. Decision tree analysis using classification and regression modeling was used to identify factors that may predict for %RLS. Results: 39 patients (73 prostate lesions) were included with a median of 2 lesions per patient (range 1-4). 53 lesions were confirmed as prostatic adenocarcinoma with MRI-US fusion biopsy. 7 lesions were Gleason score <7, 16 were Gleason score Z7, and 30 were Gleason score >7. 34/39 patients received androgen deprivation therapy (ADT) in addition to EBRT. Pre-treatment PSA ranged from 2.73 to 49.92 ng/mL (median 11.21), and PSA density (PSAD) ranged from 0.06 to 1.45. The median % RLS at the time of post-RT mpMRI was 68% (SD 34.03). After treatment, 48/73 lesions converted from ADC+ to ADC- and 37/70 lesions converted from DCE+ to DCE-. 32/73 lesions had a complete radiographic response

2576 Comparison of Conventional Versus Hyperfractionated Chemoradiation for Bladder Preservation Treatment of Muscle Invasive Bladder Cancer in the National Cancer Database C. Hui,1 Y.J. Rao,2 B.W. Fischer-Valuck,2 H.A. Gay,2 and J.M. Michalski3; 1 Saint Louis University School of Medicine, St. Louis, MO, 2Washington University School of Medicine, Department of Radiation Oncology, St. Louis, MO, 3Washington University School of Medicine, St. Louis, MO Purpose/Objective(s): It is unclear whether hyperfractionated (HF) chemoradiation therapy (CRT) results in a different overall survival (OS) outcomes compared to conventional daily fractionated CRT for bladder preservation treatment of muscle invasive bladder cancer. We compared these two treatment strategies using data from the National Cancer Database (NCDB). Materials/Methods: Using data from the NCDB between 2004 and 2013, we identified 3010 patients with bladder cancer treated with CRT for bladder preservation. Patients with stage T2-T4a transitional cell or squamous cell carcinoma of the bladder who received trans-urethral resection of bladder tumor (TURBT) and CRT were included. Average number of fractions delivered per week was calculated based on the total number of fractions of radiation, and the time interval between the first and last fraction in the NCBD. Conventional CRT was defined as five or fewer fractions per week, on average, over the course of CRT, and HF CRT was defined as more than five fractions a week on average. We compared the OS outcomes between the conventional CRT and HF CRT using the Kaplan-Meier method with log-rank statistics, and Cox univariate and multivariate analysis. Results: Of the 3010 patients analyzed, 2822 (93.8%) received conventional CRT and 188 (6.2%) received HF CRT. The median age was 78 (range, 37-90), and 2208 (73.4%) were males and 802 (26.6%) were females. The median follow up time was 42.2 months (range, 2.5-143 months) for surviving patients. The pathology was transitional cell carcinoma in 2,919 (97%) and squamous cell carcinoma in 91 (3%). Distribution of stages was 2,360 (78.4%) for T2, 371 (12.3%) for T3, and 279 (9.3%) for T4a. 5-year OS in patients treated with standard fractionation was 28.9% vs. HF treatment with 22.7% (pZ0.86). HF RT was associated with a similar hazard for death when compared to the standard radiation, which was 1.02 (95% CI 0.853-1.208, pZ0.863). Several variables were associated with improved OS on univariate analysis including: age, Charlson/Deyo comorbidity score, histology, T stage, N stage and total dose. After adjusting for these factors in a step-wise model, standard fractionation vs. HF was not significant (pZ0.396). Additionally, HF RT was not associated with improved OS compared to standard fractionated

Volume 99  Number 2S  Supplement 2017 RT in subsets including patients with: stage T2 (pZ0.507), T3 (pZ0.331), and T4a (pZ0.208). Conclusion: HF CRT resulted in similar overall survival when compared to standard fractionated CRT in patients with T2-T4a bladder cancer receiving bladder preservation therapy. Author Disclosure: C. Hui: None. Y.J. Rao: None. B.W. Fischer-Valuck: None. H.A. Gay: None. J.M. Michalski: Independent Contractor; Sheila Michalski and Associates. Research Grant; NCI. Co-Principal Investigator; Veterans Affairs; NRG Oncology. oversight of clinical trial proposals related to GU cancers.; NCI. Board member; National Children’s Cancer Society.

2577 Dosimetry Comparison Between Intraoperatively Built Custom Linked Seeds and Loose Seeds in Permanent Prostate Brachytherapy: Do Intraoperative Built Custom Linked Seeds Improve Dosimetry of Prostate Margin? M. Inada, IV, K. Nakamatsu, K. Ishikawa, and Y. Nishimura; Department of Radiation Oncology, Kindai University Faculty of Medicine, Osaka, Japan Purpose/Objective(s): For permanent prostate brachytherapy (PPB), periprostatic brachytherapy doses are important. However, periprostatic seed placements may lead seed migrations and make dose distribution of periprostatic area worse. Intraoperatively built custom linked seeds (IBCL) are thought to be stable and less migration due to linking. Therefore, IBCL can be easily placed into periprostatic area. The aim of this study is to compare post-implant dose-volume histogram (DVH) parameters including those of prostate with margin for PPB by IBCL or loose seeds (LS), retrospectively. Materials/Methods: From July 2014 to June 2016, a total 74 patients with localized prostate cancer were included. Thirty-nine patients were treated with PPB alone (monotherapy) and 35 patients were treated with PPB with supplemental external beam radiotherapy (combined therapy). Among the 39 patients treated with monotherapy, 18 were treated with IBCL and 21 were treated with LS. Among the 35 patients treated by combined therapy, 19 were treated with IBCL and 16 were treated with LS. Prescribed brachytherapy radiation doses were 144 Gy for monotherapy and 100 or 110 Gy for combined therapy. All the patients underwent computed tomography based post-implant dosimetry analyses 1 month after implant. For post-implant dosimetry, DVH parameters for prostate (CTV-P) and prostate plus 3-mm margin (CTV-PM) were evaluated. V100, V150, and D90 of both CTV-P and CTV-PM, urethral D10, and rectal V100 were calculated. The two-sample Welch’s t-test was used to compare the DVH parameters. Probability (p) values of <0.05 were considered significant. Results: For the monotherapy group, there was no significant difference between IBCL group and LS group in the patient’s characteristics. On the other hands, for combined therapy group, prostate volume and implanted seed number were larger in LS group compared with IBCL group. Regarding to DVH parameters, for the monotherapy group, V100s and D90s of both CTV-P (pZ0.047 and pZ0.025, respectively) and CTV-PM (p<0.001 and p<0.001, respectively) were significantly better in IBCL group than in LS group. For the combined therapy group, V100 and D90 of both CTV-P and CTV-PM were not significantly different between two group. On the other hands, V150s of both CTV-P and CTV-PM and urethral D10 were lower in IBCL group compared with LS group were higher in IBCL group compared with LS group. Conclusion: Current study revealed that IBCL improved prescribed dose coverage for both CTV-P and CTV-PM for the monotherapy group. These improvements were especially noted in CTV-PM. For the combined therapy group, advantages of IBCL were observed in dose homogeneity and urethral dose. These advantages by IBCL may improve patient’s oncologic outcome and quality of life. Author Disclosure: M. Inada: None. K. Nakamatsu: None. K. Ishikawa: None. Y. Nishimura: None.

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2578 High Dose Rate Brachytherapy With Hypofractionated External Beam Radiation Therapy for High-Risk Prostate Cancer Y. Ishii,1 Y. Hashimoto,1 S. Kono,1 S. Izumi,1 J. Iizuka,2 and K. Karasawa3; 1Department of Radiation Oncology, Tokyo Women’s Medical University, Tokyo, Japan, 2Department of Urology, Tokyo Women’s Medical University, Tokyo, Japan, 3Department of Radiation Oncology, Tokyo Women’s Medical University, Tokyo, Japan Purpose/Objective(s): Based from the reports of a lower alpha-beta ratio of prostate cancer, high dose rate brachytherapy (HDR-BT) with hypofractionated external beam radiation therapy (EBRT) could be an ideal treatment for localized prostate cancer. Many randomized trials showed the efficacy of HDR-BT with EBRT for prostate cancer, especially to high-risk disease. However, the treatment protocols were not standardized. The aim of this study is to evaluate a long-term outcome of our protocol in high-risk patients. Materials/Methods: A total of 99 patients with localized D’Amico’s highrisk prostate cancer treated with this protocol was retrospectively analyzed. Patient’s median age was 67 years old with a range from 50 to 79 years old. All patients had received moderately hypofractionated EBRT (45 Gy in 15 fractions, three times a week during five weeks) followed by HDR-BT (18 Gy in 2 fractions in one day) between June 1, 2007 and September 30, 2011 at one institution. Androgen deprivation therapies (ADT) were performed 3 to 6 months before and during radiotherapy and 6 month after radiotherapy. No biochemical evidence of disease (bNED) survival rates was calculated from the start of radiotherapy to an event of biochemical failure (serum PSA nadir + 2.0 ng/mL) or local/distant recurrence (including starting ADT), or death from any causes. The patient-reported outcomes were assessed using the expanded prostate cancer index composite, and the clinician-reported outcomes were assessed based on the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer Toxicity criteria. Results: The median follow-up period was 62 months, with a range between 51 to 76 months. Twenty-one of 99 patients (21.2%) had experienced biochemical failure. The median time from start of radiotherapy to biochemical failure was 42.8 months, with a range between 28.4 to 64.3 months. The 5-year overall survival rate was 98.9% and of 5-year bNED survival rate was 82.6%. At the time of analysis, only one patient had died from disease other than prostate cancer. The 21 patients with biochemical failure included 3 bone metastases, 2 pelvic lymph node recurrence, and 16 diagnosed with PSA failure alone. In terms of toxicities, the score for the general urinary domain of the EPIC dropped significantly at 1 month after radiotherapy, and then returned to the baseline level by 3 months. Acute genitourinary toxicities were graded 0 to 1 in 91 patients, grade 2 in 6 patients, and grade 3 in one patient. Late genitourinary toxicities were graded 0 to 1 in 96 patients and grade 2 in 3 patients. Late gastrointestinal toxicities included rectal bleeding were grades 0 to 1 in 98 patients and grade 2 in one patient. Conclusion: This study demonstrated that HDR-BT with moderately hypofractionated EBRT of our protocol was feasible and good toleration for high-risk prostate cancer. Author Disclosure: Y. Ishii: None. Y. Hashimoto: None. S. Kono: None. S. Izumi: None. J. Iizuka: None. K. Karasawa: None.

2579 Long-Term Outcomes of Proton Therapy for Prostate Cancer in Japan: Retrospective Analysis of a Multi-institutional Survey H. Iwata,1,2 H. Ishikawa,3 M. Takagi,4,5 T. Okimoto,5 S. Murayama,6 T. Akimoto,7 H. Wada,8 T. Arimura,9 Y. Sato,10 M. Araya,11 J.E. Mizoe,1 H. Shirato,12 and H. Sakurai3; 1Department of Radiation Oncology, Nagoya Proton Therapy Center, Nagoya City West Medical Center, Nagoya, Japan, 2Department of Radiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan, 3Department of Radiation Oncology, University of Tsukuba Faculty of Medicine, Tsukuba,