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CT in Staging of Prostate Cancer Patient Prior to Radiation Therapy
Poster Viewing Abstracts S449
Volume 90 Number 1S Supplement 2014
2598 Long-Term Outcomes of Patients With High-Risk Prostate Cancer Treated With HDR Brachytherapy Boost A.J. Chang,1 M. Roach,1 A. Gottschalk,2 A.J. Cunha,2 Z.A. Seymour,1 J.A. Johnson,1 D. Raleigh,2 K. Shinohara,2 and I.J. Hsu2; 1University of California San Francisco, San Francisco, CA, 2University of California, San Francisco, San Francisco, CA Purpose/Objective(s): To report the long-term clinical outcomes of patients with high-risk adenocarcinoma of the prostate treated with pelvic radiation therapy followed by high-dose-rate (HDR) brachytherapy boost. Materials/Methods: 115 consecutive patients with high-risk prostate cancer (cT3, Gleason (GS) 8-10, or PSA20) treated between July 1997 and November 2005 were included in this study. All patients underwent whole pelvic radiation therapy to 45 Gy followed by HDR brachytherapy boost. HDR brachytherapy boost consisted of 6 Gy x 3 (38 patients) or 9.5 Gy x 2 (77 patients) to the prostate and seminal vesicles. 47%, 48%, and 5 % patients received long-term (>18 mos), short-term (4-6 mos), or no androgen deprivation therapy, respectively. Results: The median age at diagnosis was 64.8 yrs. 50 (43%), 90 (78.2%), and 24 (20.8%) patients were diagnosed with GS 8-10, cT3 disease, and PSA 20, respectively. Mean PSA was 14.94 (range 0.21-99.3). 21 patients (18.2%) had seminal vesicle invasion and 42 patients (37%) had at least 2 high-risk features. With a median follow-up time of 94 months, biochemical free survival as defined by the Phoenix definition was 78.2%. 4 patients (3.5%) failed locally as determined by biopsy without metastatic disease. Overall survival and disease specific survival were 84.3% and 95.7%, respectively. Six secondary malignancies (bladder 1 year posttreatment, colon, lung, melanoma, hepatocellular carcinoma) developed. One patient developed grade 3 ureteral stricture causing hydronephrosis and required stent placement. There were no other grade 3 or greater genitourinary or gastrointestinal toxicity. Conclusions: Pelvic radiation therapy followed by HDR brachytherapy boost is an effective treatment for high-risk prostate cancer with excellent long-term disease control and minimal toxicity. Author Disclosure: A.J. Chang: None. M. Roach: None. A. Gottschalk: None. A.J. Cunha: None. Z.A. Seymour: None. J.A. Johnson: None. D. Raleigh: None. K. Shinohara: None. I.J. Hsu: None.
2599 Impact of 68Ga-PSMA PET/CT in Staging of Prostate Cancer Patient Prior to Radiation Therapy F. Sterzing, H. Fiedler, M. Stefanova, A. Afshar-Oromieh, C. Kratochwil, J. Debus, U. Haberkorn, and F. Giesel; University Hospital, Heidelberg, Germany Purpose/Objective(s): The prostate cancer risk stratification is based on PSA, T-stage and Gleason score and this improves therapeutic treatment decision-making, clinical trial design and outcome reporting. The purpose of this retrospective investigation is to evaluate the impact of 68Ga-PSMA PET as a novel pre-treatment diagnostic factor in radiation therapy. Materials/Methods: 31 patients with prostate cancer were retrospectively analyzed in conventional CT and 68Ga-PSMA PET imaging. 11 patients presented with initial diagnosis, 20 patients with recurrence after total prostatectomy. 71% had high risk and 29% intermediate risk cancer according to the d’Amico criteria. In conventional CT lymph nodes were regarded as pathologically involved with a short axis diameter above 10mm. Lymph node involvement in 68Ga-PSMA PET was diagnosed with a maximum standardized uptake value (SUVmax) above 2. TNM-classification of two experienced readers was performed in a consensus read. Results: Seventeen out of 31 (54.8%) patients underwent a change in TNM-staging after 68Ga PSMA PET imaging. Among the different groups this was 6 patients (54.5%) with first diagnosis and 11 patients (55%) with recurrence. Within the group of recurrence 7 patients (35%) had a switch from N0 to N1, 6 patients (30%) M0 to M1a and 1 patient (5%) Tx to T2a. In 5 patients (45.5%) of the group with first diagnosis no metastases were
detected in 68Ga-PSMA PET /CT. After 68Ga-PSMA PET the 17 upstaged patients underwent a different therapeutic strategy. Nodal upstaging resulted in individualized simultaneous integrated boost IMRT. With detection of distant metastases no local radiation therapy was performed and systemic treatment was given. Conclusions: These results suggest that 68Ga-PSMA PET/CT enables molecular staging with an immense increase of precision, which can result in high percentage of changes in therapeutic strategies. This could be a key imaging modality for individualized dose escalated radiation therapy approaches. Author Disclosure: F. Sterzing: None. H. Fiedler: None. M. Stefanova: None. A. Afshar-Oromieh: None. C. Kratochwil: None. J. Debus: None. U. Haberkorn: None. F. Giesel: None.
2600 Radiation-Mediated Inhibition of IFN Signaling Sensitizes VSV Resistant Prostate Cancer Cells T. Udayakumar, M. Patel, D. Betancourt, T. Han, G. Barber, and A. Pollack; University of Miami, Miami, FL Purpose/Objective(s): Many cancer cell lines are susceptible to Vesicular stomatitis virus (VSV) infection and oncolysis which selectively targets tumor cells, but there still remain resistant cell lines. A major determinant of cellular susceptibility to oncolysis from VSV is the interferon (IFN) pathway; an intact pathway confers resistance. We hypothesized that radiation therapy (RT) influences resistance and would sensitize prostate cancer cells to VSVhIFN mediated oncolysis. The inclusion of IFNb in the vector has been shown to promote antitumor immunity in other tumor models, inducing significant humoral and cellular immune responses. Materials/Methods: PC3 and LNCaP cells were cultured and infected with VSVhIFN for 24h. RT (5Gy) treatment was added 24h after VSVhIFNb treatment. Real time cell analysis (RTCA) and MTT assay were carried out for cell proliferation and viability. Apoptosis was measured by caspase-3/7 assay. Western analyses and clonogenic assay were carried out. For in vivo studies, male athymic nude mice with orthotopic LNCaP tumors or subcutaneous PC3 tumors were infected intravenously with VSVhIFN followed by RT. Serum PSA levels (LNCaP), tumor weight and TV (LNCaP and PC3) was measured. Statistical significance was determined by ANOVA. Results: A dose dependent decrease in cell proliferation and viability was observed in vitro when RT was combined with VSVhIFNb [1.5-100MOI (PC3) and 0.00016-0.01MOI (LNCaP)] compared to either of the treatment given alone. A significant increase in caspase-3/7 activity (p<0.05) was observed when VSVhIFNb was combined with RT compared to VSVhIFNb. Clonogenic cell survival was also reduced to a greater degree when VSVhIFNb was combined with RT. Western blot analyses showed a decrease in interferon receptor-1 (IFNAR1) and phosphorylated JAK1 when VSVhIFNb was combined with RT, suggesting that interferon signaling was impaired in both these cells after VSVhIFNb+RT treatment. For orthotopic LNCaP tumors, VSVhIFNb dose of 1x101 PFU was selected after a dose response study. PSA levels and tumor weight in LNCaP tumors decreased significantly after VSVhIFNb+RT treatement. The average PSA values for VSVhIFNb+RT was 5.9ng/ml compared to VSVhIFNb/HI 44.1ng/ml. PC3 tumor studies showed no significant difference in TV after 23 days, between VSVhIFNb (1x105 PFU) given alone (258mm3) compared to untreated control (229mm3). However, combination treatment with VSVhIFNb+RT resulted in a significant decrease in average TV (63mm3). Conclusions: The combination of VSVhIFNb and RT was found to be more effective in killing prostate cancer cells than either treatment given alone in VSV sensitive and resistant cell lines. The data indicate that addition of radiation lessens resistance through disruption of interferon signaling, making the combination an attractive approach for high risk prostate cancer. Author Disclosure: T. Udayakumar: None. M. Patel: None. D. Betancourt: None. T. Han: None. G. Barber: None. A. Pollack: None.
Volume 90 Number 1S Supplement 2014
2598 Long-Term Outcomes of Patients With High-Risk Prostate Cancer Treated With HDR Brachytherapy Boost A.J. Chang,1 M. Roach,1 A. Gottschalk,2 A.J. Cunha,2 Z.A. Seymour,1 J.A. Johnson,1 D. Raleigh,2 K. Shinohara,2 and I.J. Hsu2; 1University of California San Francisco, San Francisco, CA, 2University of California, San Francisco, San Francisco, CA Purpose/Objective(s): To report the long-term clinical outcomes of patients with high-risk adenocarcinoma of the prostate treated with pelvic radiation therapy followed by high-dose-rate (HDR) brachytherapy boost. Materials/Methods: 115 consecutive patients with high-risk prostate cancer (cT3, Gleason (GS) 8-10, or PSA20) treated between July 1997 and November 2005 were included in this study. All patients underwent whole pelvic radiation therapy to 45 Gy followed by HDR brachytherapy boost. HDR brachytherapy boost consisted of 6 Gy x 3 (38 patients) or 9.5 Gy x 2 (77 patients) to the prostate and seminal vesicles. 47%, 48%, and 5 % patients received long-term (>18 mos), short-term (4-6 mos), or no androgen deprivation therapy, respectively. Results: The median age at diagnosis was 64.8 yrs. 50 (43%), 90 (78.2%), and 24 (20.8%) patients were diagnosed with GS 8-10, cT3 disease, and PSA 20, respectively. Mean PSA was 14.94 (range 0.21-99.3). 21 patients (18.2%) had seminal vesicle invasion and 42 patients (37%) had at least 2 high-risk features. With a median follow-up time of 94 months, biochemical free survival as defined by the Phoenix definition was 78.2%. 4 patients (3.5%) failed locally as determined by biopsy without metastatic disease. Overall survival and disease specific survival were 84.3% and 95.7%, respectively. Six secondary malignancies (bladder 1 year posttreatment, colon, lung, melanoma, hepatocellular carcinoma) developed. One patient developed grade 3 ureteral stricture causing hydronephrosis and required stent placement. There were no other grade 3 or greater genitourinary or gastrointestinal toxicity. Conclusions: Pelvic radiation therapy followed by HDR brachytherapy boost is an effective treatment for high-risk prostate cancer with excellent long-term disease control and minimal toxicity. Author Disclosure: A.J. Chang: None. M. Roach: None. A. Gottschalk: None. A.J. Cunha: None. Z.A. Seymour: None. J.A. Johnson: None. D. Raleigh: None. K. Shinohara: None. I.J. Hsu: None.
2599 Impact of 68Ga-PSMA PET/CT in Staging of Prostate Cancer Patient Prior to Radiation Therapy F. Sterzing, H. Fiedler, M. Stefanova, A. Afshar-Oromieh, C. Kratochwil, J. Debus, U. Haberkorn, and F. Giesel; University Hospital, Heidelberg, Germany Purpose/Objective(s): The prostate cancer risk stratification is based on PSA, T-stage and Gleason score and this improves therapeutic treatment decision-making, clinical trial design and outcome reporting. The purpose of this retrospective investigation is to evaluate the impact of 68Ga-PSMA PET as a novel pre-treatment diagnostic factor in radiation therapy. Materials/Methods: 31 patients with prostate cancer were retrospectively analyzed in conventional CT and 68Ga-PSMA PET imaging. 11 patients presented with initial diagnosis, 20 patients with recurrence after total prostatectomy. 71% had high risk and 29% intermediate risk cancer according to the d’Amico criteria. In conventional CT lymph nodes were regarded as pathologically involved with a short axis diameter above 10mm. Lymph node involvement in 68Ga-PSMA PET was diagnosed with a maximum standardized uptake value (SUVmax) above 2. TNM-classification of two experienced readers was performed in a consensus read. Results: Seventeen out of 31 (54.8%) patients underwent a change in TNM-staging after 68Ga PSMA PET imaging. Among the different groups this was 6 patients (54.5%) with first diagnosis and 11 patients (55%) with recurrence. Within the group of recurrence 7 patients (35%) had a switch from N0 to N1, 6 patients (30%) M0 to M1a and 1 patient (5%) Tx to T2a. In 5 patients (45.5%) of the group with first diagnosis no metastases were
detected in 68Ga-PSMA PET /CT. After 68Ga-PSMA PET the 17 upstaged patients underwent a different therapeutic strategy. Nodal upstaging resulted in individualized simultaneous integrated boost IMRT. With detection of distant metastases no local radiation therapy was performed and systemic treatment was given. Conclusions: These results suggest that 68Ga-PSMA PET/CT enables molecular staging with an immense increase of precision, which can result in high percentage of changes in therapeutic strategies. This could be a key imaging modality for individualized dose escalated radiation therapy approaches. Author Disclosure: F. Sterzing: None. H. Fiedler: None. M. Stefanova: None. A. Afshar-Oromieh: None. C. Kratochwil: None. J. Debus: None. U. Haberkorn: None. F. Giesel: None.
2600 Radiation-Mediated Inhibition of IFN Signaling Sensitizes VSV Resistant Prostate Cancer Cells T. Udayakumar, M. Patel, D. Betancourt, T. Han, G. Barber, and A. Pollack; University of Miami, Miami, FL Purpose/Objective(s): Many cancer cell lines are susceptible to Vesicular stomatitis virus (VSV) infection and oncolysis which selectively targets tumor cells, but there still remain resistant cell lines. A major determinant of cellular susceptibility to oncolysis from VSV is the interferon (IFN) pathway; an intact pathway confers resistance. We hypothesized that radiation therapy (RT) influences resistance and would sensitize prostate cancer cells to VSVhIFN mediated oncolysis. The inclusion of IFNb in the vector has been shown to promote antitumor immunity in other tumor models, inducing significant humoral and cellular immune responses. Materials/Methods: PC3 and LNCaP cells were cultured and infected with VSVhIFN for 24h. RT (5Gy) treatment was added 24h after VSVhIFNb treatment. Real time cell analysis (RTCA) and MTT assay were carried out for cell proliferation and viability. Apoptosis was measured by caspase-3/7 assay. Western analyses and clonogenic assay were carried out. For in vivo studies, male athymic nude mice with orthotopic LNCaP tumors or subcutaneous PC3 tumors were infected intravenously with VSVhIFN followed by RT. Serum PSA levels (LNCaP), tumor weight and TV (LNCaP and PC3) was measured. Statistical significance was determined by ANOVA. Results: A dose dependent decrease in cell proliferation and viability was observed in vitro when RT was combined with VSVhIFNb [1.5-100MOI (PC3) and 0.00016-0.01MOI (LNCaP)] compared to either of the treatment given alone. A significant increase in caspase-3/7 activity (p<0.05) was observed when VSVhIFNb was combined with RT compared to VSVhIFNb. Clonogenic cell survival was also reduced to a greater degree when VSVhIFNb was combined with RT. Western blot analyses showed a decrease in interferon receptor-1 (IFNAR1) and phosphorylated JAK1 when VSVhIFNb was combined with RT, suggesting that interferon signaling was impaired in both these cells after VSVhIFNb+RT treatment. For orthotopic LNCaP tumors, VSVhIFNb dose of 1x101 PFU was selected after a dose response study. PSA levels and tumor weight in LNCaP tumors decreased significantly after VSVhIFNb+RT treatement. The average PSA values for VSVhIFNb+RT was 5.9ng/ml compared to VSVhIFNb/HI 44.1ng/ml. PC3 tumor studies showed no significant difference in TV after 23 days, between VSVhIFNb (1x105 PFU) given alone (258mm3) compared to untreated control (229mm3). However, combination treatment with VSVhIFNb+RT resulted in a significant decrease in average TV (63mm3). Conclusions: The combination of VSVhIFNb and RT was found to be more effective in killing prostate cancer cells than either treatment given alone in VSV sensitive and resistant cell lines. The data indicate that addition of radiation lessens resistance through disruption of interferon signaling, making the combination an attractive approach for high risk prostate cancer. Author Disclosure: T. Udayakumar: None. M. Patel: None. D. Betancourt: None. T. Han: None. G. Barber: None. A. Pollack: None.