CT

E226

International Journal of Radiation Oncology  Biology  Physics

placed for 1 week. Acute toxicity is reported in Table 1. At 3 months, the median PSA was 2.4 ng/mL. None of the observed 3-dimensional prostate displacements were 3mm over the elapsed treatment time. A Gamma passing rate of 95.64%4.28% was observed between planned and delivered dose profiles on radiochromic film analysis in the low-dose region. Conclusion: Delivering brachytherapy-like doses using SABR is feasible with an EIS and tight margins. This protocol appears well tolerated with minimal acute toxicity. Further follow-up is needed to document late toxicity, efficacy, quality of life, and cost-effectiveness.

5x105 cells). Five genome equivalents of M.SssI methylated WBC DNA (30 pg) were quantitatively detected in 20 ng excess unmethylated DNA by COMPARE-MS. The TMPRSS2-ERG gene rearrangement was detected from as few as 100 genome equivalents of VCaP cell line DNA spiked into 5 mL of whole blood by qPCR. Analysis of NGS libraries prepared from plasma isolates demonstrated preservation of input fragmentation patterns and >3 fold increased CpG density in enriched libraries (inputZ1.34% [99% CI, 0.79%-1.89%]; enrichedZ4.02% [99% CI, 2.79%-5.24%]; P<.01), suggesting unbiased amplification and robust methylation enrichment. NGS analysis revealed GSTP1 promoter hypermethylation only in a PCa containing enriched ctDNA library. Further analytical validation in reference samples is ongoing and an institutional review board (IRB)eapproved study for prospective validation is accruing healthy volunteers and men with high-risk PCa to determine background and cancer-specific changes, respectively. Conclusion: We report a novel molecular assay for detecting low copy number PCa-specific epigenetic and genetic alterations in blood and urine. Preclinical validation demonstrates sensitive and specific detection of ctDNA in biospecimens, supporting further testing to establish efficacy in monitoring treatment response. An IRB-approved study for prospective clinical validation had accrued 28 of 60 subjects at the time of submission. Author Disclosure: O.Y. Mian: None. M.C. Haffner: None. J.B. Coulter: None. D. Esopi: None. J. Meyers: None. C. Gergis: None. R.K. Assadi: None. W. Nelson: None. S. Yegnasubramanian: None. T.L. DeWeese: None.

Poster Viewing Abstracts 2562; Table 1

Acute toxicity#

Grade 1 n (%) Fatigue Genitourinary Pain (Urinary tract) Cystitis Frequency Retention Hematuria Gastrointestinal Flatulence Hemorrhoids Diarrhea GI bleeding Pain Proctitis Tenesmus Sexual Erectile dysfunction Decreased Libido

Grade 2 n (%)

6 (20) 16(53) 1 (3) 12 (40) 5 (17) 1 (3)

8 (27) 10 (33)*

1 (3) 1 (3) 2 (7) 1 (3) 3 (10) 1(3) 1 (3) 3 (10) 2 (7)

Author Disclosure: J. Helou: None. A.M. Nicolae: None. H.B. Musunuru: None. M.T. Davidson: None. K. Commisso: None. A. Deabreu: None. A. Marquez: None. P. Cheung: None. H.T. Chung: None. W. Chu: None. A. Ravi: None. D. Loblaw: None.

2563 A Novel Technology for Noninvasive Detection of Prostate Cancer DNA in the Blood and Urine of Men With High-Risk PCA Receiving Radiation Therapy and Androgen Suppression O.Y. Mian,1 M.C. Haffner,2 J.B. Coulter,2 D. Esopi,2 J. Meyers,2 C. Gergis,1 R.K. Assadi,1 W. Nelson,2 S. Yegnasubramanian,2 and T.L. DeWeese3; 1Johns Hopkins University School of Medicine, Baltimore, MD, 2Johns Hopkins University, Baltimore, MD, 3Johns Hopkins University Medical Center, Baltimore, MD Purpose/Objective(s): The absence of a reliable biomarker for monitoring response to radiation therapy (RT) during androgen suppression is a barrier to early salvage and risk-adapted treatment modification. We are developing a platform for noninvasive detection of cell-free tumor DNA (ctDNA) in blood and urine and testing its applicability to real-time assessment of response to RT. Materials/Methods: We evaluated the analytical and clinical performance of a novel molecular assay for parallel detection of tumor-specific hypermethylation, hypomethylation, copy number, and structural alterations in ctDNA. Genetic and epigenetic biomarker credentialing in prostate cancer (PCa) specimens and normal tissues was performed previously. Our assay relies on assessment of total input and enriched methylated fragments coupled with next-generation sequencing (NGS) for detection of ctDNA in the blood and urine of men with high-risk primary PCa. Results: We explored the ability to detect rare DNA molecules harboring methylation alterations and structural rearrangements. Combined methylCpG affinity purification and methylation sensitive restriction enzyme digestion (COMPARE-MS) allowed 637.7 (SEMZ24.88) fold enrichment of methylated DNA over unmethylated DNA and allowed detection of rare hypermethylated target genes from as few as 20 genome equivalents. Methylated tumor suppressor DNA was quantitatively detected in a dilution series of as few as 5 LNCaP cells in 100 mL of urine (range: 5 to

2564 Treatment Volumes Definition in Prostate Radiation Therapy: The Role of 18F-Choline PET/CT F. Alongi, S. Fersino, A. Fiorentino, R. Mazzola, F. Ricchetti, N. Giaj Levra, R. Ruggieri, and M. Salgarello; Sacro Cuore Hospital, Negrar-Verona, Italy Purpose/Objective(s): The impact of 18F-choline positron emission tomography/computed tomography (Cho- PET) in diagnosis and staging before definitive radiation therapy (RT) in localized prostate cancer patients is still debated. The aim of this analysis is to evaluate the role of Cho- PET in decision-making strategy for localized prostate cancer patients eligible for definitive RT. Materials/Methods: From January 2011 to December 2014, 65 patients (median age 73 years, range 60-81 years) with biopsy-proven prostate adenocarcinoma, with no prior treatment on primary tumor and staged with Cho-PET before RT were prospectively enrolled. Gleason score was 6 in 34 patients (pts), 7 in 15 pts, and 8 in 16 pts; median prostate-specific antigen (PSA) value at the diagnosis was 6.8 ng/mL (range 2.2-143 ng/ mL). All patients were treated with volumetric modulated arc therapy (VMAT) with simultaneous integrated boost in 28 to 30 fractions (moderate hypofractionation) as follows: for low-risk patients, prostate only; for intermediate-risk patients, prostate and seminal vesicles; and for high-risk patients, prostate, seminal vesicles, and pelvic lymph nodes. Androgen deprivation was prescribed according to National Comprehensive Cancer Network (NCCN) risk classification. Cho-PET findings were used to define the stage according to the detection of primary tumor (T), pelvic lymph nodes (N), and distant metastases (M). Therapeutic strategy based on the Cho-PET evaluation was compared to the strategy that would have been proposed in case of PET not available and/or not strictly indicated, following international and national prostate cancer guidelines. Results: Cho-PET was positive in 61 cases (95%): T (prostate gland only) in 49 (81% of all positive cases); T in combination with N in 8 (12.5%), and M (bone) in combination with T or N, or both, in 4 (6.5%). After the Cho-PET, patients were stratified according to NCCN risk classification as follows: 28 (43%) low risk, 10 (16%) intermediate risk and 27 (41%) high risk. Cho-PET shifted treatment indication in 14 cases (21%). Regarding RT volumes, 7 intermediate-risk pts (10.8%) shifted to high risk and consequently were irradiated on prostate, seminal vesicles, and pelvic nodes; in 7 high-risk pts (10.8%), the Cho-PET showed bone and/or pelvic lymph node uptake and consequently a simultaneous integrated boost on

Volume 93  Number 3S  Supplement 2015 PET-positive sites was prescribed. No upstaging of low-risk patients to a higher risk was observed. Conclusion: These findings showed that Cho-PET shows promise as a diagnostic tool in prostate cancer patients who are candidates for radical RT and in supporting the decision making in treatment planning, in particular in intermediate-high risk. Although a simultaneous integrated boost on Cho-PETepositive sites is still under investigation, it could be a possible option to intensify local RT in this setting. Author Disclosure: F. Alongi: None. S. Fersino: None. A. Fiorentino: None. R. Mazzola: None. F. Ricchetti: None. N. Giaj Levra: None. R. Ruggieri: None. M. Salgarello: None.

2565 Positive Correlation of Decreased Urinary Flow Rate With Urethral Dose After Seed Implant Brachytherapy for Prostate Cancer K. Kikuchi, R. Nakamura, R. Kato, H. Kakuhara, S. Yamaguchi, H. Oikawa, and H. Ariga; Iwate Medical University School of Medicine, Morioka, Japan Purpose/Objective(s): The aim of this study was to clarify the effect of urethral radiation exposure by seed implant brachytherapy (LDR) on urinary toxicity in prostate cancer patients. Correlations of the predictive factors were reassessed with urinary flow reduction rates after LDR in substitutes for the magnitude of symptoms having repetitively been used in previous studies with inconsistent results. Materials/Methods: From December 2004 to September 2011, 242 patients with organ-confined prostate cancer were treated with LDR by realtime transrectal ultrasound (US)-guided implantation (prescribed dose of 160 Gy) in our hospital. Computed tomographic (CT) images on Day 30 were used for dosimetry of the prostate and urethra contoured by 5 mmeach side triangles positioned at the same place as that of Day 1 CT with urinary catheter through image fusion module. Uroflowmetry was performed before and 1, 3, 6, 9, and 12 months after LDR in an outpatient clinic to evaluate maximum urinary flow rate (Qmax) as well as voiding volume (Vcomp) and average flow rate (Qave). Residual urine volume (RV) was measured by US. Patients were divided into groups based on Qmax decline rates; beyond 50% (declined-pts) or the others (spared-pts) compared to rates before LDR. Urethral dosimetric parameters, age (mean 66.7 years, range 51-78 years), pre-LDR international prostate symptom score (8.1, range 0-34), prostate volume (28.1 mL, range 10-50 mL), and the number of implanted seeds (74.8, range 40-101) and needles (23.4, range 12-35) were compared between the 2 groups. Results: Before LDR, the mean values of Vcomp, Qmax, Qave, and RV were 290162 mL, 17.610.3 mL, 9.75.0 mL, and 38.059.8 mL, respectively. Overall, uroflowmetric parameters decreased and RVs increased after LDR. Qmax reduction rates in all, declined-pts, and sparedpts were 36%39%, 65%10%, and 16%40%, respectively. Compared to the spared-pts, the mean prostate D90 (PZ.013), prostate V150 (PZ.040), urethral D90 (PZ.045), urethral V150 (PZ.042), and urethral V200 (PZ.019) values in the declined-pts were significantly increased. There were no significant differences in the other risk factors evaluated. Conclusion: Objective quantitation of urinary disturbances revealed an apparent correlation of urethral dose escalation with toxicity. Urethral dose constraints during LDR may thus prevent intractable urinary adverse effects after seed implant brachytherapy. Author Disclosure: K. Kikuchi: None. R. Nakamura: None. R. Kato: None. H. Kakuhara: None. S. Yamaguchi: None. H. Oikawa: None. H. Ariga: None.

2566 Endoscopic Evaluation of Radiation Proctitis After Radiation Therapy for Prostate Cancer: Spatial Distribution of the Mucosal Lesion Correlated With Radiation Dose K. Okajima,1 Y. Oguma,1 T. Matsuura,1 K. Ishikawa,2 H. Tatebe,2 K. Fukuda,3 and Y. Nishimura2; 1Nara Hospital, Kinki University, Ikoma, Japan, 2Kinki University Faculty of Medicine, Osaka-Sayama, Japan, 3 Kinki University Faculty of Medicine, Osaka, Japan

Poster Viewing Session E227 Purpose/Objective(s): To determine the extent of correlation between radiation dose distribution and area of mucosal damage, the features of rectal mucositis evaluated by endoscopic studies were analyzed. Materials/Methods: From February 2000 to January 2014, 225 patients with prostate cancer were treated with curative radiation therapy (median age 70, range 54-89 years; Stage I/II/III/IV Z 20/124/73/8, respectively). Before December 2009, 108 were treated by conformal radiation therapy (CRT) with an orthogonal 4-field isocentric technique; the remaining 117 patients underwent intensity modulated radiation therapy (IMRT) after October 2010. The planned target volume (PTV) was 10 mm and 8 mm beyond the clinical target volume (8 mm and 5mm posterior) for CRT and IMRT, respectively. Total radiation therapy dose was 66 to 70 Gy for CRT and 78 Gy for IMRT. All patients were followed for more than 12 months (median: 54 months), and rectal hemorrhage was evaluated and graded according to the Common Terminology Criteria for Adverse Events version 4.0. Endoscopic examinations were performed for all patients with grade 2-3 rectal hemorrhage or symptomatic grade 1 hemorrhage. Distribution of the mucositis was divided into 3 groups; limited to the anterior rectal wall, involvement of more than half the circumference, and involvement of the entire circumference. Presence of mucositis was defined as lesions with a Vienna Rectoscopy Score 2. Extent of proctitis was compared between the CRT and IMRT groups and statistically compared using the Mann-Whitney U-test. Results: Incidence of grade 0, 1, 2, or 3 rectal hemorrhage was 74, 19, 10, and 5 in the CRT group and 98, 12, 5, and 2 in the IMRT group (p<.05). Colon endoscopy was performed in 25 of 33 and 14 of 19 patients with grade 1 hemorrhage in the CRT and IMRT groups, respectively. Distribution of mucositis was limited to the anterior rectal wall, involved more than half the circumference, and involved the entire circumference in 6, 11, and 8 patients in the CRT group and 10, 4, and 0 patients in the IMRT group, respectively (P<.01). Mean dose for the posterior rectal wall was >33 Gy in the CRT group because the 4-fields technique was used. In the IMRT group, maximum dose for the posterior rectal wall was <39 Gy. Mucosal damage caused by radiation therapy often involved the entire circumference of the rectal wall if minimum dose for the rectal wall exceeded 33 Gy. Conclusion: The distribution of rectal mucosal lesions resulting from radiation therapy does not depend on the maximum dose but on the extent of a moderately irradiated area (33-35 Gy). The minimum dose to which the posterior rectal mucosa was exposed were more important prognostic factors for radiation proctitis and rectal hemorrhage. To determine the extent of correlation between radiation dose distribution and area of mucosal damage, the features of rectal mucositis evaluated by endoscopic studies were analyzed. Author Disclosure: K. Okajima: None. Y. Oguma: None. T. Matsuura: None. K. Ishikawa: None. H. Tatebe: None. K. Fukuda: None. Y. Nishimura: None.

2567 Does Prostate Brachytherapy Really Induce Long-term Urinary Dysfunction? A. Hassouni, C. Udrescu, A. Ruffion, and O. Chapet; Centre Hospitalier Lyon Sud, Lyon, France Purpose/Objective(s): The present study aims to report a prospective analysis of urinary function evolution using the International Prostate Symptom Score (IPSS) for patients treated with brachytherapy for localized prostate cancer. Materials/Methods: A total of 97 patients were used for this study. An iodine-125 linked-seeds technique of brachytherapy was used. The delivered dose was between 145 Gy (74%) and 160 Gy (25.8%). For dosimetric constraints calculation during the procedure, the delineation of the urethra was based on a Foley catheter balloon, and a uniform security margin of 2 mm was added to the urethra. A second margin of 7 mm was added to the rectum and no seed should be implanted on it. The dosimetry criteria were as follows: the volume receiving 100% of the dose 95% of the prostate, the dose to 90% of the prostate between 160 Gy and 180 Gy, the volume of