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Anatomic Patterns of Recurrence Following Biochemical Relapse After Postprostatectomy Radiation Therapy: A Multi-institutional Study
E234
International Journal of Radiation Oncology Biology Physics
2569
S.A. Tomlins,1 R. Mera,1 T. Morgan,1 F.Y. Feng,1 and D.E. Spratt1; 1 University of Michigan, Ann Arbor, MI, 2University of Texas Southwestern Medical Center, Dallas, TX, 3University of Texas Southwestern Medical Center, Dallas, TX, United States, 4Department of Oncology, Sohag University, Sohag, Egypt, 5Texas Oncology, Irving, TX, 6Cedars-Sinai Medical Center, Los Angeles, CA
A Prospective Study Evaluating Registered Ultrasound and Fluoroscopy (RUF) for Intraoperative Dose Calculation: Improved Accuracy Compared to Current Ultrasound-based Intraoperative Dosimetry O.Y. Mian,1 C. Gergis,1 A. Ferro,1 Y. Le,1 S.P. Robertson,1 R.F. Hobbs,1 J. Prince,2 T.R. McNutt,1 T.L. DeWeese,1 J. Lee,1 and D. Song1; 1 Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 2 Department of Electrical and Computer Engineering, Johns Hopkins University School of Medicine, Baltimore, MD Purpose/Objective(s): Intraoperative transrectal ultrasound (TRUS) dosimetry during LDR prostate brachytherapy is imprecise due to sonographic distortion caused by seed echoes, needle tracks, and traumatic edema, which obscure seed positions or create false signals. We have previously described a system of combined ultrasound and fluoroscopy based real-time seed localization (RUF) for intraoperative dose calculation. Here we report the final results of a prospective study of 80 patients comparing RUF to standard TRUS based dosimetry. Materials/Methods: 80 patients undergoing permanent Pd-103 seed implantation for prostate cancer were prospectively enrolled between July 2011 and Aug 2014. Seed implantation was performed using standard ultrasound-based localization (USD). Intraoperatively, 6 fluoroscopic images were acquired using a non-isocentric C-arm; offline, a 3D seed cloud configuration was reconstructed from fluoroscopies and registered to axial ultrasound images of the implanted prostate. Images were not used for implant modification. CT/MRI scans were acquired on post-op day 1 for contouring and dose calculation. Standard dosimetric parameters were calculated for RUF, USD, and day 1 CT/MRI image sets. Differences between dosimetric measures were calculated and root mean square deviations were evaluated. Correlation coefficients and paired two-tailed Ttests were used to evaluate patient specific and aggregate pairwise similarity between USD, RUF, and CT/MRI data sets. Results: Of the 80 patients enrolled, 12 were excluded due to lack of postoperative MRIs. RUF based intraoperative dosimetry showed higher correlation with day 1 CT/MRI for all prostate dosimetric parameters (D90, V100, V150, V200; P<0.05) compared to USD with Pearson correlation for prostate D90 of 0.81 for RUF vs CT/MRI and 0.61 for USD vs CT/MRI (P<0.05). When compared to CT/MRI, RUF dosimetry showed a significant variation for 0 out of 8 dosimetric parameters analyzed, whereas US dosimetry varied significantly for 6 of 8 parameters (paired two-tailed T test, alpha < 0.01). Root mean squared differences from CT/ MRI were smaller for RUF for 6 of 8 parameters examined compared with USD. USD demonstrated a tendency to over-estimate dose to the prostate when compared to RUF. RUF demonstrated better predictive characteristics for prostatic dosimetry and identified cold implants more reliably than USD (P<0.05), however with a tendency to overestimate rectal dose, possibly attributable to deformation associated with the rectal probe. Conclusion: Intraoperative registered ultrasound and fluoroscopy (RUF) approximated post-operative CT/MRI prostate and urethral dosimetry to a greater degree than the current ultrasound-based intraoperative method. RUF is deployable in combination with a standard non-isocentric C-arm, and demonstrates potential to minimize prostate underdosage not otherwise detected. A confirmatory phase II trial utilizing RUF for intraoperative iterative plan modification is underway. Author Disclosure: O.Y. Mian: None. C. Gergis: None. A. Ferro: None. Y. Le: None. S.P. Robertson: None. R.F. Hobbs: None. J. Prince: None. T.R. McNutt: None. T.L. DeWeese: None. J. Lee: None. D. Song: None.
2570 Anatomic Patterns of Recurrence Following Biochemical Relapse After Postprostatectomy Radiation Therapy: A Multi-institutional Study W.C. Jackson,1 N.B. Desai,2 V. Tumati,3 J.Y. Lee,1 R.T. Dess,1 P.D. Soni,1 A. Abugharib,4 D.A. Hamstra,5 J.W.D. Hearn,1 H.M. Sandler,6 Z.S. Zumsteg,6 J. Montgomery,1 B. Hollenbeck,1 G. Palapattu,1
Purpose/Objective(s): The patterns of failure for patients receiving postradical prostatectomy (RP) radiation therapy (RT) have not been well described. We sought to characterize the frequency of recurrence and development of distant metastases (DM) and describe the most common anatomic sites of DM in a cohort of men who received post-RP RT. Materials/Methods: A retrospective multi-institutional study was performed on 608 consecutive men who underwent a RP with limited pelvic lymph node dissection and received post-operative RT (adjuvant or salvage) between 1986 and 2013. Lymph node positive patients were excluded. The median RT dose was 66.6 Gy. Patients with a subsequent rising PSA after post-operative RT were restaged with CT imaging of the chest, abdomen, or pelvis. DM free-survival (DMFS) rates were calculated with Kaplan Meier methods. Patterns of anatomic failure were classified as local (prostate bed), lymphotropic (lymph nodes), and osteotropic (bones). Cox proportional-hazard modeling was used to assess predictors of DM. Results: Median follow-up post-RT was 82 months. Local recurrence was documented in only 17 men (3%), and 128 men (21%) developed DM. The 7-year rate of DM was 19.9%. The median time to DM was 71 months after post-operative RT. No patient developed DM without prior BF. The most common anatomic patterns of DM were osteotropic (44%), lymphotropic in the retroperitoneal lymph nodes (LNs) (19%), pelvic LNs (16%), or other nodal stations (20%). Isolated pelvic LNs as a first recurrence occurred in only 10 men (1.6%). 112 men (18%) received RT to the pelvic LNs, and none of these men experienced recurrence in the pelvic LNs. On univariate analysis, factors associated with DM included pre-RT PSA (P<0.001), post-RT PSA nadir (P<0.001), Gleason score (P<0.001), pathologic T stage (P<0.001), and an inverse association with positive surgical margins (SM) (P Z 0.003). There was no association with the time from RP to RT. On multivariate analysis pre-RT PSA (HR 1.2, 95% CI 1.1-1.3), post-RT PSA nadir (HR 1.1, 95% CI 1.1-1.2), Gleason score (HR 1.7, 95% CI 1.3-2.1), and +SM (HR 0.5, 95% CI 0.3-0.8) all retained a significant association with the development of DM. For patients with a pre-RT PSA 0.5 ng/mL, post-RT PSA nadir 0.2 ng/mL, or a Gleason score 9, the 7-year rate of DM was 29.5% vs. 7.6% for men with none of these features (P<0.001). Conclusion: Development of metastatic disease occurs in approximately 20% of men following post-RP RT. Isolated pelvic LN recurrences are uncommon, and the benefit of pelvic nodal RT in this context is unclear. Patients with a pre-RT PSA 0.5 ng/mL, detectable PSA nadir, or a Gleason score of 9 or higher are at a significantly increased for DM, and these men should be considered for clinical trials with intensification of therapy. Author Disclosure: W.C. Jackson: None. N.B. Desai: None. V. Tumati: None. J.Y. Lee: None. R.T. Dess: None. P.D. Soni: None. A. Abugharib: None. D.A. Hamstra: Consultant; Myriad. J.W. Hearn: None. H.M. Sandler: None. Z.S. Zumsteg: None. J. Montgomery: None. B. Hollenbeck: None. G. Palapattu: None. S.A. Tomlins: Research Grant; Alfred Taubman Medical Research Institute. Advisor; Medivation/Astellas, Jannsse. R. Mera: Research Grant; Prostate cancer foundation. T. Morgan: Research Grant; Prostate Cancer Foundation, Alfred Taubman Medical Research Institute, MDXHealth, Myriad Genetics. Advisor; MDxHeatlh, Myriad Genetics. F.Y. Feng: Research Grant; Varian, Medivation/Astellas, Celgene. Advisor; Medivation/Astellas, GenomeDx, Nanostring, Celgene. D.E. Spratt: Research Grant; Prostate Cancer Foundation.
2571 Characteristics and National Trends of Patients Receiving Prostate or Pelvic Radiation for Metastatic Prostate Cancer S. Sinha,1,2 V. Muralidhar,2 and P.L. Nguyen3; 1Brigham and Women’s Hospital, Boston, MA, 2Harvard Medical School, Boston, MA, 3Brigham
International Journal of Radiation Oncology Biology Physics
2569
S.A. Tomlins,1 R. Mera,1 T. Morgan,1 F.Y. Feng,1 and D.E. Spratt1; 1 University of Michigan, Ann Arbor, MI, 2University of Texas Southwestern Medical Center, Dallas, TX, 3University of Texas Southwestern Medical Center, Dallas, TX, United States, 4Department of Oncology, Sohag University, Sohag, Egypt, 5Texas Oncology, Irving, TX, 6Cedars-Sinai Medical Center, Los Angeles, CA
A Prospective Study Evaluating Registered Ultrasound and Fluoroscopy (RUF) for Intraoperative Dose Calculation: Improved Accuracy Compared to Current Ultrasound-based Intraoperative Dosimetry O.Y. Mian,1 C. Gergis,1 A. Ferro,1 Y. Le,1 S.P. Robertson,1 R.F. Hobbs,1 J. Prince,2 T.R. McNutt,1 T.L. DeWeese,1 J. Lee,1 and D. Song1; 1 Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 2 Department of Electrical and Computer Engineering, Johns Hopkins University School of Medicine, Baltimore, MD Purpose/Objective(s): Intraoperative transrectal ultrasound (TRUS) dosimetry during LDR prostate brachytherapy is imprecise due to sonographic distortion caused by seed echoes, needle tracks, and traumatic edema, which obscure seed positions or create false signals. We have previously described a system of combined ultrasound and fluoroscopy based real-time seed localization (RUF) for intraoperative dose calculation. Here we report the final results of a prospective study of 80 patients comparing RUF to standard TRUS based dosimetry. Materials/Methods: 80 patients undergoing permanent Pd-103 seed implantation for prostate cancer were prospectively enrolled between July 2011 and Aug 2014. Seed implantation was performed using standard ultrasound-based localization (USD). Intraoperatively, 6 fluoroscopic images were acquired using a non-isocentric C-arm; offline, a 3D seed cloud configuration was reconstructed from fluoroscopies and registered to axial ultrasound images of the implanted prostate. Images were not used for implant modification. CT/MRI scans were acquired on post-op day 1 for contouring and dose calculation. Standard dosimetric parameters were calculated for RUF, USD, and day 1 CT/MRI image sets. Differences between dosimetric measures were calculated and root mean square deviations were evaluated. Correlation coefficients and paired two-tailed Ttests were used to evaluate patient specific and aggregate pairwise similarity between USD, RUF, and CT/MRI data sets. Results: Of the 80 patients enrolled, 12 were excluded due to lack of postoperative MRIs. RUF based intraoperative dosimetry showed higher correlation with day 1 CT/MRI for all prostate dosimetric parameters (D90, V100, V150, V200; P<0.05) compared to USD with Pearson correlation for prostate D90 of 0.81 for RUF vs CT/MRI and 0.61 for USD vs CT/MRI (P<0.05). When compared to CT/MRI, RUF dosimetry showed a significant variation for 0 out of 8 dosimetric parameters analyzed, whereas US dosimetry varied significantly for 6 of 8 parameters (paired two-tailed T test, alpha < 0.01). Root mean squared differences from CT/ MRI were smaller for RUF for 6 of 8 parameters examined compared with USD. USD demonstrated a tendency to over-estimate dose to the prostate when compared to RUF. RUF demonstrated better predictive characteristics for prostatic dosimetry and identified cold implants more reliably than USD (P<0.05), however with a tendency to overestimate rectal dose, possibly attributable to deformation associated with the rectal probe. Conclusion: Intraoperative registered ultrasound and fluoroscopy (RUF) approximated post-operative CT/MRI prostate and urethral dosimetry to a greater degree than the current ultrasound-based intraoperative method. RUF is deployable in combination with a standard non-isocentric C-arm, and demonstrates potential to minimize prostate underdosage not otherwise detected. A confirmatory phase II trial utilizing RUF for intraoperative iterative plan modification is underway. Author Disclosure: O.Y. Mian: None. C. Gergis: None. A. Ferro: None. Y. Le: None. S.P. Robertson: None. R.F. Hobbs: None. J. Prince: None. T.R. McNutt: None. T.L. DeWeese: None. J. Lee: None. D. Song: None.
2570 Anatomic Patterns of Recurrence Following Biochemical Relapse After Postprostatectomy Radiation Therapy: A Multi-institutional Study W.C. Jackson,1 N.B. Desai,2 V. Tumati,3 J.Y. Lee,1 R.T. Dess,1 P.D. Soni,1 A. Abugharib,4 D.A. Hamstra,5 J.W.D. Hearn,1 H.M. Sandler,6 Z.S. Zumsteg,6 J. Montgomery,1 B. Hollenbeck,1 G. Palapattu,1
Purpose/Objective(s): The patterns of failure for patients receiving postradical prostatectomy (RP) radiation therapy (RT) have not been well described. We sought to characterize the frequency of recurrence and development of distant metastases (DM) and describe the most common anatomic sites of DM in a cohort of men who received post-RP RT. Materials/Methods: A retrospective multi-institutional study was performed on 608 consecutive men who underwent a RP with limited pelvic lymph node dissection and received post-operative RT (adjuvant or salvage) between 1986 and 2013. Lymph node positive patients were excluded. The median RT dose was 66.6 Gy. Patients with a subsequent rising PSA after post-operative RT were restaged with CT imaging of the chest, abdomen, or pelvis. DM free-survival (DMFS) rates were calculated with Kaplan Meier methods. Patterns of anatomic failure were classified as local (prostate bed), lymphotropic (lymph nodes), and osteotropic (bones). Cox proportional-hazard modeling was used to assess predictors of DM. Results: Median follow-up post-RT was 82 months. Local recurrence was documented in only 17 men (3%), and 128 men (21%) developed DM. The 7-year rate of DM was 19.9%. The median time to DM was 71 months after post-operative RT. No patient developed DM without prior BF. The most common anatomic patterns of DM were osteotropic (44%), lymphotropic in the retroperitoneal lymph nodes (LNs) (19%), pelvic LNs (16%), or other nodal stations (20%). Isolated pelvic LNs as a first recurrence occurred in only 10 men (1.6%). 112 men (18%) received RT to the pelvic LNs, and none of these men experienced recurrence in the pelvic LNs. On univariate analysis, factors associated with DM included pre-RT PSA (P<0.001), post-RT PSA nadir (P<0.001), Gleason score (P<0.001), pathologic T stage (P<0.001), and an inverse association with positive surgical margins (SM) (P Z 0.003). There was no association with the time from RP to RT. On multivariate analysis pre-RT PSA (HR 1.2, 95% CI 1.1-1.3), post-RT PSA nadir (HR 1.1, 95% CI 1.1-1.2), Gleason score (HR 1.7, 95% CI 1.3-2.1), and +SM (HR 0.5, 95% CI 0.3-0.8) all retained a significant association with the development of DM. For patients with a pre-RT PSA 0.5 ng/mL, post-RT PSA nadir 0.2 ng/mL, or a Gleason score 9, the 7-year rate of DM was 29.5% vs. 7.6% for men with none of these features (P<0.001). Conclusion: Development of metastatic disease occurs in approximately 20% of men following post-RP RT. Isolated pelvic LN recurrences are uncommon, and the benefit of pelvic nodal RT in this context is unclear. Patients with a pre-RT PSA 0.5 ng/mL, detectable PSA nadir, or a Gleason score of 9 or higher are at a significantly increased for DM, and these men should be considered for clinical trials with intensification of therapy. Author Disclosure: W.C. Jackson: None. N.B. Desai: None. V. Tumati: None. J.Y. Lee: None. R.T. Dess: None. P.D. Soni: None. A. Abugharib: None. D.A. Hamstra: Consultant; Myriad. J.W. Hearn: None. H.M. Sandler: None. Z.S. Zumsteg: None. J. Montgomery: None. B. Hollenbeck: None. G. Palapattu: None. S.A. Tomlins: Research Grant; Alfred Taubman Medical Research Institute. Advisor; Medivation/Astellas, Jannsse. R. Mera: Research Grant; Prostate cancer foundation. T. Morgan: Research Grant; Prostate Cancer Foundation, Alfred Taubman Medical Research Institute, MDXHealth, Myriad Genetics. Advisor; MDxHeatlh, Myriad Genetics. F.Y. Feng: Research Grant; Varian, Medivation/Astellas, Celgene. Advisor; Medivation/Astellas, GenomeDx, Nanostring, Celgene. D.E. Spratt: Research Grant; Prostate Cancer Foundation.
2571 Characteristics and National Trends of Patients Receiving Prostate or Pelvic Radiation for Metastatic Prostate Cancer S. Sinha,1,2 V. Muralidhar,2 and P.L. Nguyen3; 1Brigham and Women’s Hospital, Boston, MA, 2Harvard Medical School, Boston, MA, 3Brigham