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Two Stereotactic Ablative Radiation Therapy Treatments (2STAR) for Localized Prostate Cancer: Feasibility and Early Results
Volume 93 Number 3S Supplement 2015 Purpose/Objective(s): Published practice guidelines, including those from Alberta since January 2005, recommend referral of all high-risk prostate cancer patients to a radiation oncologist (RO) to discuss nonsurgical options including androgen deprivation therapy (ADT) and radiation therapy (RT). We hypothesized that RO referrals would increase over time in keeping with guideline recommendations. Our objective was to determine RO referral, ADT+RT and prostatectomy rates in 2005 and 2012 and to examine associated patient, disease, and treatment factors. Materials/Methods: The provincial cancer registry was used to identify the records of patients >18 years of age diagnosed with prostate cancer in Alberta in 2005 (nZ1792) and 2012 (nZ2148). High-risk disease was defined as Gleason score (GS) 8 or prostate-specific antigen (PSA) >20. Patient age, clinical risk group (CRG) score, a proxy for comorbidities, GS, pretreatment PSAs, and occurrences of a radiation oncology consultation and treatment were abstracted from the electronic medical record. Logistical regression modeling was used to determine the association between the observed RO referral rates and the available data elements. Results: High-risk disease was identified in 295 patients in 2005 and 504 in 2012. Median age was 71 years in both periods with no differences in CRG and Gleason scores. PSA scores varied (PZ.002) from 2005 and 2012. PSAs >20 were noted in 62% (2005) versus 50% (2012). Referral rates to RO decreased from 63% in 2005 to 56% in 2012 (PZ.06). Median time to referral was significantly shorter in 2012 (1.1 months vs 2.0 months, P<.001). In 2005, 61% of patients were treated with RT+ADT compared to 35% in 2012 (P<.001). The radical prostatectomy rate was 10% in 2005 and increased to 18% in 2012 (PZ.002). On regression analysis, older age (odds ratio [OR] 0.60, 95% CI: 0.49-0.73) and 2012 year of diagnosis (OR 0.54, 95% CI: 0.37-0.79) were associated with lower RO referral rates. Conclusion: Despite shorter wait times for RO referral in 2012 and guideline implementation in 2005, RO referral rates and ADT+RT use declined between 2005 and 2012. Radical prostatectomy rates increased. These observations suggest that compliance with provincial and international guidelines could be improved. Greater efforts need to be undertaken to improve the multidisciplinary management of high-risk prostate cancer in Alberta. Author Disclosure: M. Alghamdi: None. A. Taggar: None. M. Kerba: None. D. Tilley: None. X. Kostaras: None. M. Sia: Honoraria; Bayer Inc.
2561 Pilot Study of the Dose-Sparing Capability and Interfraction Repeatability of a Shape-Optimized Endorectal Balloon for Proton Beam Prostate Cancer Treatment X. Ding,1 C. Carpenter,2 H.T. Wu,3 and L.R. Rosen1; 1Willis-Knighton Cancer Center, Shreveport, LA, 2Siris Medical, Inc., Mountain View, CA, 3 Willis-Knighton Cancer Center, Shreveport, LA Purpose/Objective(s): The treatment of prostate cancer with proton beam radiation requires precise positioning of the patient to deliver the prescription dose to the target structure while sufficiently sparing critical structures. We evaluate the dose-sparing capability and interfaction repeatability throughout a patient’s treatment course using a new endorectal balloon (ERB). Materials/Methods: In this study, a new hourglass-shaped ERB is demonstrated on a proton prostate patient over a 9-week treatment course. This ERB incorporates a saddle shape to improve interfraction positioning repeatability and reduce inferior and superior prostate movement. During the 9 weeks’ treatment course, the patient received 4 additional re-CT simulations every 2 weeks to check the balloon position and dosimetric repeatability. The re-CTs were fused to the initial planning CT based on the position of 3 fiducial markers to simulate the day of treatment. For the geometry evaluation, we measured the prostate’s length in the A/P and M/ L direction, the distance from 3 fiducial markers to the middle of the balloon, and the posterior rectum wall, anterior prostate, and anterior balloon to the pubic symphysis. For dosimetric evaluation, we measured D99% of the prostate, D2cc, D10cc of the rectum, D2cc, D10cc of the bladder, and D2cc, D10cc of the ERB.
Poster Viewing Session E225 Results: Through the re-CT throughout the treatment course, the average dose of 99% prostate volume in the re-CT received 99.9%0.16% of the initial planning dose (7924 cGyE). The average dose of 2 cc and 10 cc rectum received 99.59%0.92%, 97.75%5.87%, of the initial planning dose (7981 cGyE, 7673cGyE), respectively. The average dose of 10 cc and 20 cc bladder received 99.54%0.42%, 96.87%2.22% of the initial planning dose (7981 cGyE, 7896 cGyE) respectively. The average dose of 10 cc and 20 cc ERB received 97.18%3.16%, 79.25%18.88% of the initial planning dose (7960 cGyE, 7306 cGyE), respectively. Interfraction organ position repeatability was generally between 1 and 2 mm. The distance from ERB center to the fiducial markers was as follows: superior marker, 2.70.2cm; middle marker, 3.50.1cm; inferior marker, 3.50.2cm. The prostate shape was 5.20.05cm in the M/L direction and 5.50.3cm in the A/P direction. The distance from the anterior prostate, anterior balloon, and posterior rectum to the pubic symphysis was 1.40.3 cm, 5.90.3 cm, and 9.90.3 cm, respectively. In the fourth re-CT, the balloon was found underinflated about 10 cc fluids. However, with the image guided radiation therapy align to the 3 fiducial markers, target, and organs at risk were still received consistent dose compared to the initial plan. Conclusion: This study shows that the ERB stabilizes the prostate gland and rectum during daily treatment and interfraction organs and balloon position is repeatable. Author Disclosure: X. Ding: None. C. Carpenter: Other; Siris Medical, Inc. Stock; Siris Medical, Inc. leader; Siris Medical, Inc. H. Wu: None. L.R. Rosen: Leader; Willis-Knighton Cancer Center.
2562 Two Stereotactic Ablative Radiation Therapy Treatments (2STAR) for Localized Prostate Cancer: Feasibility and Early Results J. Helou,1,2 A.M. Nicolae,1 H.B. Musunuru,1 M.T. Davidson,1 K. Commisso,1 A. Deabreu,1 A. Marquez,1 P. Cheung,2,3 H.T. Chung,1,4 W. Chu,2 A. Ravi,1,2 and D.A. Loblaw1,2; 1Sunnybrook Health Sciences Centre-Odette Cancer Centre, Toronto, ON, Canada, 2University of Toronto, Toronto, ON, Canada, 3Sunnybrook Health Science Centre, Odette Cancer Centre, Toronto, ON, Canada, 4Sunnybrook Health Sciences Centre-Odette Cancer Centre, Toronto, ON, Canada Purpose/Objective(s): Hypofractionated treatment protocols hold the promise of improved convenience, fewer side effects, and decreased cost without sacrificing cancer control. The aim of this study was to assess the acute toxicity and feasibility of a 2-fraction stereotactic ablative radiation therapy (SABR) treatment delivered with a novel endorectal immobilization system (EIS) in place. Materials/Methods: This first-in-man, prospective, phase 1/2 study was performed wherein a dose of 26 Gy in 2 fractions over 1 week was delivered using volumetric arc therapy for low- or intermediate-risk prostate cancer (cT1-2b, Gleason Score 7, prostate-specific antigen [PSA] 20). Treatment was delivered with an EIS in place and a comfortably full bladder. Daily image guidance and intrafraction prostate motion was captured using pre- and posttreatment cone beam computed tomography, gold seed fiducials were used for accurate setup along with a 6 degree-of-freedom treatment couch. The clinical target volume consisted of the prostate gland alone. The planning target volume was an additional 3-mm margin in all directions. Radiochromic film embedded within the EIS was used as a quality assurance measure of the delivered dose. Acute toxicity was assessed at weeks 1, 4, and 12 using Common Terminology Criteria for Adverse Events version 4.0. Quality of life changes will be presented at the time of conference; efficacy and cost-effectiveness will be presented at a later date. Results: As of January 2015, the target accrual of 30 patients had been reached; all had completed treatment with at least 3 months of follow-up. Median age was 67 years, median PSA was 8.0 ng/mL (range: 0.4-15.8 mL), and median prostate volume was 32 mL (23-89 mL). Five patients received a short course of androgen deprivation therapy (ADT). Treatment was very well tolerated with no grade 3 or 4 toxicity. One patient presented with urinary retention following his first fraction and had a Foley catheter
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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
2561 Pilot Study of the Dose-Sparing Capability and Interfraction Repeatability of a Shape-Optimized Endorectal Balloon for Proton Beam Prostate Cancer Treatment X. Ding,1 C. Carpenter,2 H.T. Wu,3 and L.R. Rosen1; 1Willis-Knighton Cancer Center, Shreveport, LA, 2Siris Medical, Inc., Mountain View, CA, 3 Willis-Knighton Cancer Center, Shreveport, LA Purpose/Objective(s): The treatment of prostate cancer with proton beam radiation requires precise positioning of the patient to deliver the prescription dose to the target structure while sufficiently sparing critical structures. We evaluate the dose-sparing capability and interfaction repeatability throughout a patient’s treatment course using a new endorectal balloon (ERB). Materials/Methods: In this study, a new hourglass-shaped ERB is demonstrated on a proton prostate patient over a 9-week treatment course. This ERB incorporates a saddle shape to improve interfraction positioning repeatability and reduce inferior and superior prostate movement. During the 9 weeks’ treatment course, the patient received 4 additional re-CT simulations every 2 weeks to check the balloon position and dosimetric repeatability. The re-CTs were fused to the initial planning CT based on the position of 3 fiducial markers to simulate the day of treatment. For the geometry evaluation, we measured the prostate’s length in the A/P and M/ L direction, the distance from 3 fiducial markers to the middle of the balloon, and the posterior rectum wall, anterior prostate, and anterior balloon to the pubic symphysis. For dosimetric evaluation, we measured D99% of the prostate, D2cc, D10cc of the rectum, D2cc, D10cc of the bladder, and D2cc, D10cc of the ERB.
Poster Viewing Session E225 Results: Through the re-CT throughout the treatment course, the average dose of 99% prostate volume in the re-CT received 99.9%0.16% of the initial planning dose (7924 cGyE). The average dose of 2 cc and 10 cc rectum received 99.59%0.92%, 97.75%5.87%, of the initial planning dose (7981 cGyE, 7673cGyE), respectively. The average dose of 10 cc and 20 cc bladder received 99.54%0.42%, 96.87%2.22% of the initial planning dose (7981 cGyE, 7896 cGyE) respectively. The average dose of 10 cc and 20 cc ERB received 97.18%3.16%, 79.25%18.88% of the initial planning dose (7960 cGyE, 7306 cGyE), respectively. Interfraction organ position repeatability was generally between 1 and 2 mm. The distance from ERB center to the fiducial markers was as follows: superior marker, 2.70.2cm; middle marker, 3.50.1cm; inferior marker, 3.50.2cm. The prostate shape was 5.20.05cm in the M/L direction and 5.50.3cm in the A/P direction. The distance from the anterior prostate, anterior balloon, and posterior rectum to the pubic symphysis was 1.40.3 cm, 5.90.3 cm, and 9.90.3 cm, respectively. In the fourth re-CT, the balloon was found underinflated about 10 cc fluids. However, with the image guided radiation therapy align to the 3 fiducial markers, target, and organs at risk were still received consistent dose compared to the initial plan. Conclusion: This study shows that the ERB stabilizes the prostate gland and rectum during daily treatment and interfraction organs and balloon position is repeatable. Author Disclosure: X. Ding: None. C. Carpenter: Other; Siris Medical, Inc. Stock; Siris Medical, Inc. leader; Siris Medical, Inc. H. Wu: None. L.R. Rosen: Leader; Willis-Knighton Cancer Center.
2562 Two Stereotactic Ablative Radiation Therapy Treatments (2STAR) for Localized Prostate Cancer: Feasibility and Early Results J. Helou,1,2 A.M. Nicolae,1 H.B. Musunuru,1 M.T. Davidson,1 K. Commisso,1 A. Deabreu,1 A. Marquez,1 P. Cheung,2,3 H.T. Chung,1,4 W. Chu,2 A. Ravi,1,2 and D.A. Loblaw1,2; 1Sunnybrook Health Sciences Centre-Odette Cancer Centre, Toronto, ON, Canada, 2University of Toronto, Toronto, ON, Canada, 3Sunnybrook Health Science Centre, Odette Cancer Centre, Toronto, ON, Canada, 4Sunnybrook Health Sciences Centre-Odette Cancer Centre, Toronto, ON, Canada Purpose/Objective(s): Hypofractionated treatment protocols hold the promise of improved convenience, fewer side effects, and decreased cost without sacrificing cancer control. The aim of this study was to assess the acute toxicity and feasibility of a 2-fraction stereotactic ablative radiation therapy (SABR) treatment delivered with a novel endorectal immobilization system (EIS) in place. Materials/Methods: This first-in-man, prospective, phase 1/2 study was performed wherein a dose of 26 Gy in 2 fractions over 1 week was delivered using volumetric arc therapy for low- or intermediate-risk prostate cancer (cT1-2b, Gleason Score 7, prostate-specific antigen [PSA] 20). Treatment was delivered with an EIS in place and a comfortably full bladder. Daily image guidance and intrafraction prostate motion was captured using pre- and posttreatment cone beam computed tomography, gold seed fiducials were used for accurate setup along with a 6 degree-of-freedom treatment couch. The clinical target volume consisted of the prostate gland alone. The planning target volume was an additional 3-mm margin in all directions. Radiochromic film embedded within the EIS was used as a quality assurance measure of the delivered dose. Acute toxicity was assessed at weeks 1, 4, and 12 using Common Terminology Criteria for Adverse Events version 4.0. Quality of life changes will be presented at the time of conference; efficacy and cost-effectiveness will be presented at a later date. Results: As of January 2015, the target accrual of 30 patients had been reached; all had completed treatment with at least 3 months of follow-up. Median age was 67 years, median PSA was 8.0 ng/mL (range: 0.4-15.8 mL), and median prostate volume was 32 mL (23-89 mL). Five patients received a short course of androgen deprivation therapy (ADT). Treatment was very well tolerated with no grade 3 or 4 toxicity. One patient presented with urinary retention following his first fraction and had a Foley catheter
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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