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A Phase 2 Trial of Salvage Radiation and Concurrent Weekly Docetaxel After Rising PSA Post–Radical Prostatectomy
Poster Viewing Abstracts S431
Volume 90 Number 1S Supplement 2014
2551 Transperineal Ultrasound for Image Guidance in the Treatment of Prostate Cancer: A Comparison to Fiducial-Based CT Imaging H. Wallace,1 D. Hard,1 J. Archambault,1 D.T. Cooper,2 and M. Lachaine2; 1 Fletcher Allen Health Care, Burlington, VT, 2Elekta, Montreal, QC, Canada Purpose/Objective(s): Four-dimensional intrafractional imaging of the prostate can be performed using transperineal ultrasound (TPUS) with an autoscan probe. The purpose of this study was to compare 3D interfractional localization of the prostate with TPUS to that measured with fiducials and CT imaging. Materials/Methods: Seventeen patients with localized prostate cancer were enrolled under an IRB approved protocol. Patients had fiducials placed in the prostate to provide a minimum of three points of reference for CT localization. Each patient had CT and TPUS images acquired during the initial simulation providing a fused CT/TPUS reference. Simulation procedures were repeated on three occasions throughout the patient’s radiation therapy course. The goal of these additional simulations was to reproduce the treatment setup, with the benefit of having CT imaging for comparison. CT prostate shifts for each session were calculated by matching each individual fiducial in the CT images to their corresponding position in the reference CT. The mean fiducial position shifts were used as the CT prostate shift, and the standard deviation between fiducials as an estimate of the uncertainty in prostate localization. TPUS prostate shifts were calculated by matching grayscale images of the prostate in each session and comparing their position to the reference TPUS image for the given patient. Results: The first 4 patients were used to refine the comparison protocol and are not included in the analysis. A further 9 fractions were not used due to significant motion between the CT and TPUS image acquisition. A total of 30 sets of paired measurements are included in the analysis. The prostate shifts (mean standard deviation) as determined by CT/fiducials were 0.6 8.5 mm, -1.7 5.1 mm and -0.2 3.6 mm in the A/P, S/I and L/R directions, respectively. The prostate shifts as determined by TPUS were 0.7 9.0 mm, -2.1 5.2 mm and 0.2 3.9 mm respectively. The difference between the two modalities in each direction was found to be 0.1 2.3 mm, -0.4 2.9 mm and 0.4 3.0 mm. The standard deviation of fiducial localization measured by CT, due to prostate rotations and fiducial migrations between sessions, was 1.4 mm, 1.0 mm and 1.3 mm in each direction. Conclusions: The standard deviation in the shift difference between autoscan TPUS imaging and diagnostic CT with fiducials was found to be 2-3 mm in each direction. This is in part explained by the standard deviation between individual fiducials which is between 1 and 2 mm, as well as some expected motion between CT and TPUS acquisitions. The remainder of the differences is due to the uncertainties of TPUS localization and CT/ fiducial localization. Future analysis will include rotations, comparison to soft-tissue prostate localization on the CT images, as well as measurement of intrafractional motion with autoscan TPUS. Author Disclosure: H. Wallace: None. D. Hard: None. J. Archambault: None. D.T. Cooper: A. Employee; Elekta. M. Lachaine: A. Employee; Elekta.
2552 A Phase 2 Trial of Salvage Radiation and Concurrent Weekly Docetaxel After Rising PSA PosteRadical Prostatectomy W. Jackson,1 F.Y. Feng,1 S. Daignault,1 M. Hussain,1 D. Smith,1 K. Cooney,1 K. Pienta,2 S. Jolly,1 B. Hollenbeck,1 K.B. Olson,1 H.M. Sandler,3 M.E. Ray,4 and D.A. Hamstra1; 1University of Michigan, Ann Arbor, MI, 2Johns Hopkins University School of Medicine, Baltimore, MD, 3Cedars-Sinai Medical Center, Los Angeles, CA, 4Martha Siekman Cancer Center, Appleton, WI Purpose/Objective(s): Many men treated with salvage radiation therapy (SRT) for a rising prostate specific antigen (PSA) after radical prostatectomy (RP) will again experience biochemical failure (BF). Docetaxel, a
known radiosensitizer, improves survival for patients with metastatic prostate cancer. We sought to assess the utility of docetaxel concurrently with SRT. Materials/Methods: A total of 19 men with BF post-RP were prospectively accrued on a single institutional IRB approved trial (3/07-5/09) when the trial closed early. Docetaxel was administered weekly (20 mg/ m2) with SRT for 8 weeks. Salvage RT used 3D-conformal RT to doses of 64.8-70.2 Gy (dose based upon pre-treatment PSA) in 1.8 Gy fractions. Acute (<90 days from end) and late toxicities were collected by CTCAE version 4. The primary endpoint was BF at 4 years compared to the Stephenson nomogram. Planned study characteristics: n Z 44, 20% improvement in BF, >80% power, one-sided, p Z 0.05. Kaplan-Meier methods were used to assess late toxicity, freedom from BF, and metastases (DM). An unplanned matched pair analysis was performed with 19 patients treated with SRT alone. Post-treatment quality of life (QOL) by EPIC was compared to a cohort treated with SRT alone. Results: Median follow-up was 4.7 years. Median pre-RT PSA was 0.7 ng/ mL. Forty-two percent of patients had a Gleason score > 7, 28% positive surgical margins, 17% seminal vesicle invasion, and 22% extra prostatic extension. All 8 cycles of docetaxel were completed in 17 (89%). Acute toxicities were seen in 79% for grade 1, 50% for grade 2, 58% for grade 3, and 11% for grade 4. For acute grade 1 toxicities 68% were related to fatigue, urinary, or bowel symptoms. For grade 2 toxicities 76% were neutropenia, fatigue, or urinary symptoms. The most common acute grade 3-4 toxicity was neutropenia (84% and 100%, respectively). All late toxicities were grade 1-2 with 89% related to bowel or urinary function. By the Stephenson nomogram predicted 4 year FFBF was 39% and observed was 42% (95% CI Z 24-60). There were no local clinical failures. On matched pairs analysis there was no significant improvement in BF (p Z 0.2, hazard ratio [HR] Z 0.6, 95% CI Z 0.3-1.3) or DM (p Z 0.1, HR Z 0.3, 95% CI Z 0.1-1.0) for patients receiving docetaxel compared to matched patients. There was also no difference between those treated with and without docetaxel for late bowel (p Z 0.3) or urinary toxicity (p Z 0.5). Post-treatment bowel and urinary QOL did not differ between those treated with and without docetaxel (all p > 0.5). Conclusions: It appears that docetaxel can safely be administered concurrently with SRT without impacting post-treatment toxicities or QOL. Neutropenia was the most significant acute toxicity. Larger studies are needed to determine the efficacy of concurrent docetaxel in this setting. Author Disclosure: W. Jackson: None. F.Y. Feng: None. S. Daignault: None. M. Hussain: None. D. Smith: None. K. Cooney: None. K. Pienta: None. S. Jolly: None. B. Hollenbeck: None. K.B. Olson: None. H.M. Sandler: G. Consultant; Sanofi-Aventis, Medivation, Bayer. K. Advisory Board; Eviti Medical. M.E. Ray: None. D.A. Hamstra: None.
2553 Recent Trends in the Management of Localized Prostate Cancer: Results From the National Cancer Data Base P.J. Gray,1 C. Lin,2 A. Jemal,2 and J.A. Efstathiou1; 1Massachusetts General Hospital, Boston, MA, 2American Cancer Society, Atlanta, GA Purpose/Objective(s): The management of localized prostate cancer (PC) is evolving. We sought to analyze recent management trends using a large national database. Materials/Methods: Data on all patients presenting with a new diagnosis of PC between 2004 and 2011 were extracted from the National Cancer Data Base. Patients with nodal or distant metastases were excluded. Patients were categorized as low risk (LR), intermediate risk (IR), or high risk (HR) according to the National Comprehensive Cancer Network’s (NCCN) guidelines. Multivariate logistic regression models were constructed to identify factors associated with the receipt of surgery or radiation therapy. Results: A total of 823,977 patients met the study criteria, with 38.5% of patients classified as LR, 42.7% as IR and 18.9% as HR. Between 2004 and 2011, for LR patients rates of observation after diagnosis increased from 12.4% to 18.5% and receipt of prostatectomy increased from 40.3% to 54.4% (trend analyses p both <.001). In contrast, during the same
Volume 90 Number 1S Supplement 2014
2551 Transperineal Ultrasound for Image Guidance in the Treatment of Prostate Cancer: A Comparison to Fiducial-Based CT Imaging H. Wallace,1 D. Hard,1 J. Archambault,1 D.T. Cooper,2 and M. Lachaine2; 1 Fletcher Allen Health Care, Burlington, VT, 2Elekta, Montreal, QC, Canada Purpose/Objective(s): Four-dimensional intrafractional imaging of the prostate can be performed using transperineal ultrasound (TPUS) with an autoscan probe. The purpose of this study was to compare 3D interfractional localization of the prostate with TPUS to that measured with fiducials and CT imaging. Materials/Methods: Seventeen patients with localized prostate cancer were enrolled under an IRB approved protocol. Patients had fiducials placed in the prostate to provide a minimum of three points of reference for CT localization. Each patient had CT and TPUS images acquired during the initial simulation providing a fused CT/TPUS reference. Simulation procedures were repeated on three occasions throughout the patient’s radiation therapy course. The goal of these additional simulations was to reproduce the treatment setup, with the benefit of having CT imaging for comparison. CT prostate shifts for each session were calculated by matching each individual fiducial in the CT images to their corresponding position in the reference CT. The mean fiducial position shifts were used as the CT prostate shift, and the standard deviation between fiducials as an estimate of the uncertainty in prostate localization. TPUS prostate shifts were calculated by matching grayscale images of the prostate in each session and comparing their position to the reference TPUS image for the given patient. Results: The first 4 patients were used to refine the comparison protocol and are not included in the analysis. A further 9 fractions were not used due to significant motion between the CT and TPUS image acquisition. A total of 30 sets of paired measurements are included in the analysis. The prostate shifts (mean standard deviation) as determined by CT/fiducials were 0.6 8.5 mm, -1.7 5.1 mm and -0.2 3.6 mm in the A/P, S/I and L/R directions, respectively. The prostate shifts as determined by TPUS were 0.7 9.0 mm, -2.1 5.2 mm and 0.2 3.9 mm respectively. The difference between the two modalities in each direction was found to be 0.1 2.3 mm, -0.4 2.9 mm and 0.4 3.0 mm. The standard deviation of fiducial localization measured by CT, due to prostate rotations and fiducial migrations between sessions, was 1.4 mm, 1.0 mm and 1.3 mm in each direction. Conclusions: The standard deviation in the shift difference between autoscan TPUS imaging and diagnostic CT with fiducials was found to be 2-3 mm in each direction. This is in part explained by the standard deviation between individual fiducials which is between 1 and 2 mm, as well as some expected motion between CT and TPUS acquisitions. The remainder of the differences is due to the uncertainties of TPUS localization and CT/ fiducial localization. Future analysis will include rotations, comparison to soft-tissue prostate localization on the CT images, as well as measurement of intrafractional motion with autoscan TPUS. Author Disclosure: H. Wallace: None. D. Hard: None. J. Archambault: None. D.T. Cooper: A. Employee; Elekta. M. Lachaine: A. Employee; Elekta.
2552 A Phase 2 Trial of Salvage Radiation and Concurrent Weekly Docetaxel After Rising PSA PosteRadical Prostatectomy W. Jackson,1 F.Y. Feng,1 S. Daignault,1 M. Hussain,1 D. Smith,1 K. Cooney,1 K. Pienta,2 S. Jolly,1 B. Hollenbeck,1 K.B. Olson,1 H.M. Sandler,3 M.E. Ray,4 and D.A. Hamstra1; 1University of Michigan, Ann Arbor, MI, 2Johns Hopkins University School of Medicine, Baltimore, MD, 3Cedars-Sinai Medical Center, Los Angeles, CA, 4Martha Siekman Cancer Center, Appleton, WI Purpose/Objective(s): Many men treated with salvage radiation therapy (SRT) for a rising prostate specific antigen (PSA) after radical prostatectomy (RP) will again experience biochemical failure (BF). Docetaxel, a
known radiosensitizer, improves survival for patients with metastatic prostate cancer. We sought to assess the utility of docetaxel concurrently with SRT. Materials/Methods: A total of 19 men with BF post-RP were prospectively accrued on a single institutional IRB approved trial (3/07-5/09) when the trial closed early. Docetaxel was administered weekly (20 mg/ m2) with SRT for 8 weeks. Salvage RT used 3D-conformal RT to doses of 64.8-70.2 Gy (dose based upon pre-treatment PSA) in 1.8 Gy fractions. Acute (<90 days from end) and late toxicities were collected by CTCAE version 4. The primary endpoint was BF at 4 years compared to the Stephenson nomogram. Planned study characteristics: n Z 44, 20% improvement in BF, >80% power, one-sided, p Z 0.05. Kaplan-Meier methods were used to assess late toxicity, freedom from BF, and metastases (DM). An unplanned matched pair analysis was performed with 19 patients treated with SRT alone. Post-treatment quality of life (QOL) by EPIC was compared to a cohort treated with SRT alone. Results: Median follow-up was 4.7 years. Median pre-RT PSA was 0.7 ng/ mL. Forty-two percent of patients had a Gleason score > 7, 28% positive surgical margins, 17% seminal vesicle invasion, and 22% extra prostatic extension. All 8 cycles of docetaxel were completed in 17 (89%). Acute toxicities were seen in 79% for grade 1, 50% for grade 2, 58% for grade 3, and 11% for grade 4. For acute grade 1 toxicities 68% were related to fatigue, urinary, or bowel symptoms. For grade 2 toxicities 76% were neutropenia, fatigue, or urinary symptoms. The most common acute grade 3-4 toxicity was neutropenia (84% and 100%, respectively). All late toxicities were grade 1-2 with 89% related to bowel or urinary function. By the Stephenson nomogram predicted 4 year FFBF was 39% and observed was 42% (95% CI Z 24-60). There were no local clinical failures. On matched pairs analysis there was no significant improvement in BF (p Z 0.2, hazard ratio [HR] Z 0.6, 95% CI Z 0.3-1.3) or DM (p Z 0.1, HR Z 0.3, 95% CI Z 0.1-1.0) for patients receiving docetaxel compared to matched patients. There was also no difference between those treated with and without docetaxel for late bowel (p Z 0.3) or urinary toxicity (p Z 0.5). Post-treatment bowel and urinary QOL did not differ between those treated with and without docetaxel (all p > 0.5). Conclusions: It appears that docetaxel can safely be administered concurrently with SRT without impacting post-treatment toxicities or QOL. Neutropenia was the most significant acute toxicity. Larger studies are needed to determine the efficacy of concurrent docetaxel in this setting. Author Disclosure: W. Jackson: None. F.Y. Feng: None. S. Daignault: None. M. Hussain: None. D. Smith: None. K. Cooney: None. K. Pienta: None. S. Jolly: None. B. Hollenbeck: None. K.B. Olson: None. H.M. Sandler: G. Consultant; Sanofi-Aventis, Medivation, Bayer. K. Advisory Board; Eviti Medical. M.E. Ray: None. D.A. Hamstra: None.
2553 Recent Trends in the Management of Localized Prostate Cancer: Results From the National Cancer Data Base P.J. Gray,1 C. Lin,2 A. Jemal,2 and J.A. Efstathiou1; 1Massachusetts General Hospital, Boston, MA, 2American Cancer Society, Atlanta, GA Purpose/Objective(s): The management of localized prostate cancer (PC) is evolving. We sought to analyze recent management trends using a large national database. Materials/Methods: Data on all patients presenting with a new diagnosis of PC between 2004 and 2011 were extracted from the National Cancer Data Base. Patients with nodal or distant metastases were excluded. Patients were categorized as low risk (LR), intermediate risk (IR), or high risk (HR) according to the National Comprehensive Cancer Network’s (NCCN) guidelines. Multivariate logistic regression models were constructed to identify factors associated with the receipt of surgery or radiation therapy. Results: A total of 823,977 patients met the study criteria, with 38.5% of patients classified as LR, 42.7% as IR and 18.9% as HR. Between 2004 and 2011, for LR patients rates of observation after diagnosis increased from 12.4% to 18.5% and receipt of prostatectomy increased from 40.3% to 54.4% (trend analyses p both <.001). In contrast, during the same