Clinical and biochemical outcomes of men undergoing radical prostatectomy or radiation therapy for localized prostate cancer

David Schreiber,Justin Rineer,Jeffrey P. Weiss,Joseph Safdieh,Joseph Weiner,Marvin Rotman,David Schwartz 대한방사선종양학회 2015 Radiation Oncology Journal Vol.33 No.1

Purpose: We analyzed outcomes of patients with prostate cancer undergoing either radical retropubic prostatectomy (RRP) +/– salvage radiation or definitive radiation therapy (RT) +/– androgen deprivation. Materials and Methods: From 2003–2010 there were 251 patients who underwent RRP and 469 patients who received RT (≥7,560 cGy) for prostate cancer. Kaplan-Meier analysis was performed with the log-rank test to compare biochemical control (bCR), distant metastatic-free survival (DMPFS), and prostate cancer-specific survival (PCSS) between the two groups. Results: The median follow-up was 70 months and 61.3% of the men were African American. For low risk disease the 6-year bCR were 90.3% for RT and 85.6% for RRP (p = 0.23) and the 6-year post-salvage bCR were 90.3% vs. 90.9%, respectively (p = 0.84). For intermediate risk disease the 6-year bCR were 82.6% for RT and 59.7% for RRP (p < 0.001) and 82.6% vs. 74.0%, respectively, after including those salvaged with RT (p = 0.06). For high risk disease, the 6-year bCR were 67.4% for RT and 41.3% for RRP (p < 0.001) and after including those salvaged with RT was 67.4% vs. 43.1%, respectively (p < 0.001). However, there were no significant differences between the two groups in regards to DMPFS or PCSS. Conclusion: Treatment approaches utilizing RRP +/– salvage radiation or RT +/– androgen deprivation yielded equivalent DMPFS and PCSS outcomes. Biochemical control rates, using their respective definitions, appeared equivalent or better in those who received treatment with RT.

Long-term tolerance and outcomes for dose escalation in early salvage post-prostatectomy radiation therapy

Joseph J. Safdieh,David Schwartz,Joseph Weiner,Jeffrey P. Weiss,Justin Rineer,Isaac Madeb,Marvin Rotman,David Schreiber 대한방사선종양학회 2014 Radiation Oncology Journal Vol.32 No.3

Purpose: To study the long-term outcomes and tolerance in our patients who received dose escalated radiotherapy in the early salvage post-prostatectomy setting. Materials and Methods: The medical records of 54 consecutive patients who underwent radical prostatectomy subsequently followed by salvage radiation therapy (SRT) to the prostate bed between 2003–2010 were analyzed. Patients included were required to have a pre-radiation prostate specific antigen level (PSA) of 2 ng/mL or less. The median SRT dose was 70.2 Gy. Biochemical failure after salvage radiation was defined as a PSA level >0.2 ng/mL. Biochemical control and survival endpoints were analyzed using the Kaplan-Meier method. Univariate and multivariate Cox regression analysis were used to identify the potential impact of confounding factors on outcomes. Results: The median pre-SRT PSA was 0.45 ng/mL and the median follow-up time was 71 months. The 4- and 7-year actuarial biochemical control rates were 75.7% and 63.2%, respectively. The actuarial 4- and 7-year distant metastasis-free survival was 93.7% and 87.0%, respectively, and the actuarial 7-year prostate cancer specific survival was 94.9%. Grade 3 late genitourinary toxicity developed in 14 patients (25.9%), while grade 4 late genitourinary toxicity developed in 2 patients (3.7%). Grade 3 late gastrointestinal toxicity developed in 1 patient (1.9%), and grade 4 late gastrointestinal toxicity developed in 1 patient (1.9%). Conclusion: In this series with long-term follow-up, early SRT provided outcomes and toxicity profiles similar to those reported from the three major randomized trials studying adjuvant radiation therapy.

Opposite Roles of B7.1 and CD28 Costimulatory Molecules for Protective Immunity against HSV-2 Challenge in a gD DNA Vaccine Model

David B. Weiner,신정임 대한면역학회 2005 Immune Network Vol.5 No.2

Background: Costimulation is a critical process in Ag-specific immune responses. Both B7.1 and CD28 molecules have been reported to stimulate T cell responses during antigen presentation. Therefore, we tested whether Ag-specific immune responses as well as protective immunity are influenced by coinjecting with B7.1 and CD28 cDNAs in a mouse HSV-2 challenge model system. Methods: ELISA was used to detect levels of antibodies, cytokines and chemokines while thymidine incorporation assay was used to evaluate T cell proliferation levels. Results: Ag-specific antibody responses were enhanced by CD28 coinjection but not by B7.1 coinjection. Furthermore, CD28 coinjection increased IgG1 production to a significant level, as compared to pgD pcDNA3, suggesting that CD28 drives Th2 type responses. In contrast, B7.1 coinjection showed the opposite, suggesting a Th1 bias. B7.1 coinjection also enhanced Ag-specific Th cell proliferative responses as well as production of Th1 type cytokines and chemokines significantly higher than pgD pcDNA3. However, CD28 coinjection decreased Ag-specific Th cell proliferative responses as well as production of Th1 types of cytokines and chemokine significantly lower than pgD pcDNA3. Only MCP-1 production was enhanced by CD28. B7.1 coimmunized animals exhibited an enhanced survival rate as well as decreased herpetic lesion formation, as compared to pgD pcDNA3. In contrast, CD28 vaccinated animals exhibited decreased survival from lethal challenge. Conclusion: This study shows that B7.1 enhances protective Th1 type cellular immunity against HSV-2 challenge while CD28 drives a more detrimental Th2 type immunity against HSV-2 challenge, supporting an opposite role of B7.1 and CD28 in Ag-specific immune responses to a Th1 vs Th2 type.

Stereotactic radiotherapy of the prostate: fractionation and utilization in the United States

Weiner, Joseph P.,Schwartz, David,Shao, Meng,Osborn, Virginia,Choi, Kwang,Schreiber, David The Korean Society for Radiation Oncology 2017 Radiation Oncology Journal Vol.35 No.2

Purpose: To analyze the utilization and fractionation of extreme hypofractionation via stereotactic body radiotherapy (SBRT) in the treatment of prostate cancer. Materials and Methods: Data was analyzed on men diagnosed with localized prostate cancer between 2004-2012 and treated with definitive-intent radiation therapy, as captured in the National Cancer Database. This database is a hospital-based registry that collects an estimated 70% of all diagnosed malignancies in the United States. Results: There were 299,186 patients identified, of which 4,962 (1.7%) were identified as receiving SBRT as primary treatment. Of those men, 2,082 had low risk disease (42.0%), 2,201 had intermediate risk disease (44.4%), and 679 had high risk disease (13.7%). The relative utilization of SBRT increased from 0.1% in 2004 to 4.0% in 2012. Initially SBRT was more commonly used in academic programs, though as time progressed there was a shift to favor an increased absolute number of men treated in the community setting. Delivery of five separate treatments was the most commonly utilized fractionation pattern, with 4,635 patients (91.3%) receiving this number of treatments. The most common dosing pattern was $725cGy{\times}5fractions$ (49.6%) followed by $700cGy{\times}5fractions$ (21.3%). Conclusions: Extreme hypofractionation via SBRT is slowly increasing acceptance. Currently $700-725cGy{\times}5fractions$ appears to be the most commonly employed scheme. As further long-term data regarding the safety and efficacy emerges, the relative utilization of this modality is expected to continue to increase.

Opposite Roles of B7.1 and CD28 Costimulatory Molecules for Protective Immunity against HSV-2 Challenge in a gD DNA Vaccine Model

Weiner, David B.,Sin, Jeong-Im The Korean Association of Immunobiologists 2005 Immune Network Vol.5 No.2

Background: Costimulation is a critical process in Ag-specific immune responses. Both B7.1 and CD28 molecules have been reported to stimulate T cell responses during antigen presentation. Therefore, we tested whether Ag-specific immune responses as well as protective immunity are influenced by coinjecting with B7.1 and CD28 cDNAs in a mouse HSV-2 challenge model system. Methods: ELISA was used to detect levels of antibodies, cytokines and chemokines while thymidine incorporation assay was used to evaluate T cell proliferation levels. Results: Ag-specific antibody responses were enhanced by CD28 coinjection but not by B7.1 coinjection. Furthermore, CD28 coinjection increased IgG1 production to a significant level, as compared to pgD+pcDNA3, suggesting that CD28 drives Th2 type responses. In contrast, B7.1 coinjection showed the opposite, suggesting a Th1 bias. B7.1 coinjection also enhanced Ag-specific Th cell proliferative responses as well as production of Th1 type cytokines and chemokines significantly higher than pgD+pcDNA3. However, CD28 coinjection decreased Ag-specific Th cell proliferative responses as well as production of Th1 types of cytokines and chemokine significantly lower than pgD+pcDNA3. Only MCP-1 production was enhanced by CD28. B7.1 coimmunized animals exhibited an enhanced survival rate as well as decreased herpetic lesion formation, as compared to pgD+pcDNA3. In contrast, CD28 vaccinated animals exhibited decreased survival from lethal challenge. Conclusion: This study shows that B7.1 enhances protective Th1 type cellular immunity against HSV-2 challenge while CD28 drives a more detrimental Th2 type immunity against HSV-2 challenge, supporting an opposite role of B7.1 and CD28 in Ag-specific immune responses to a Th1 vs Th2 type.

Clinical and biochemical outcomes of men undergoing radical prostatectomy or radiation therapy for localized prostate cancer

Schreiber, David,Rineer, Justin,Weiss, Jeffrey P.,Safdieh, Joseph,Weiner, Joseph,Rotman, Marvin,Schwartz, David The Korean Society for Radiation Oncology 2015 Radiation Oncology Journal Vol.33 No.1

Purpose: We analyzed outcomes of patients with prostate cancer undergoing either radical retropubic prostatectomy (RRP) +/- salvage radiation or definitive radiation therapy (RT) +/- androgen deprivation. Materials and Methods: From 2003-2010 there were 251 patients who underwent RRP and 469 patients who received RT (${\geq}7,560cGy$) for prostate cancer. Kaplan-Meier analysis was performed with the log-rank test to compare biochemical control (bCR), distant metastatic-free survival (DMPFS), and prostate cancer-specific survival (PCSS) between the two groups. Results: The median follow-up was 70 months and 61.3% of the men were African American. For low risk disease the 6-year bCR were 90.3% for RT and 85.6% for RRP (p = 0.23) and the 6-year post-salvage bCR were 90.3% vs. 90.9%, respectively (p = 0.84). For intermediate risk disease the 6-year bCR were 82.6% for RT and 59.7% for RRP (p < 0.001) and 82.6% vs. 74.0%, respectively, after including those salvaged with RT (p = 0.06). For high risk disease, the 6-year bCR were 67.4% for RT and 41.3% for RRP (p < 0.001) and after including those salvaged with RT was 67.4% vs. 43.1%, respectively (p < 0.001). However, there were no significant differences between the two groups in regards to DMPFS or PCSS. Conclusion: Treatment approaches utilizing RRP +/- salvage radiation or RT +/- androgen deprivation yielded equivalent DMPFS and PCSS outcomes. Biochemical control rates, using their respective definitions, appeared equivalent or better in those who received treatment with RT.

Stereotactic radiotherapy of the prostate: fractionation and utilization in the United States

Joseph P. Weiner,David Schwartz,Meng Shao,Virginia Osborn,Kwang Choi,David Schreiber 대한방사선종양학회 2017 Radiation Oncology Journal Vol.35 No.2

Purpose: To analyze the utilization and fractionation of extreme hypofractionation via stereotactic body radiotherapy (SBRT) in the treatment of prostate cancer. Materials and Methods: Data was analyzed on men diagnosed with localized prostate cancer between 2004–2012 and treated with definitive-intent radiation therapy, as captured in the National Cancer Database. This database is a hospital-based registry that collects an estimated 70% of all diagnosed malignancies in the United States. Results: There were 299,186 patients identified, of which 4,962 (1.7%) were identified as receiving SBRT as primary treatment. Of those men, 2,082 had low risk disease (42.0%), 2,201 had intermediate risk disease (44.4%), and 679 had high risk disease (13.7%). The relative utilization of SBRT increased from 0.1% in 2004 to 4.0% in 2012. Initially SBRT was more commonly used in academic programs, though as time progressed there was a shift to favor an increased absolute number of men treated in the community setting. Delivery of five separate treatments was the most commonly utilized fractionation pattern, with 4,635 patients (91.3%) receiving this number of treatments. The most common dosing pattern was 725 cGy × 5 fractions (49.6%) followed by 700 cGy × 5 fractions (21.3%). Conclusions: Extreme hypofractionation via SBRT is slowly increasing acceptance. Currently 700-725 cGy × 5 fractions appears to be the most commonly employed scheme. As further long-term data regarding the safety and efficacy emerges, the relative utilization of this modality is expected to continue to increase.

Long-term tolerance and outcomes for dose escalation in early salvage post-prostatectomy radiation therapy

Safdieh, Joseph J.,Schwartz, David,Weiner, Joseph,Weiss, Jeffrey P.,Rineer, Justin,Madeb, Isaac,Rotman, Marvin,Schreiber, David The Korean Society for Radiation Oncology 2014 Radiation Oncology Journal Vol.32 No.3

Purpose: To study the long-term outcomes and tolerance in our patients who received dose escalated radiotherapy in the early salvage post-prostatectomy setting. Materials and Methods: The medical records of 54 consecutive patients who underwent radical prostatectomy subsequently followed by salvage radiation therapy (SRT) to the prostate bed between 2003-2010 were analyzed. Patients included were required to have a pre-radiation prostate specific antigen level (PSA) of 2 ng/mL or less. The median SRT dose was 70.2 Gy. Biochemical failure after salvage radiation was defined as a PSA level >0.2 ng/mL. Biochemical control and survival endpoints were analyzed using the Kaplan-Meier method. Univariate and multivariate Cox regression analysis were used to identify the potential impact of confounding factors on outcomes. Results: The median pre-SRT PSA was 0.45 ng/mL and the median follow-up time was 71 months. The 4- and 7-year actuarial biochemical control rates were 75.7% and 63.2%, respectively. The actuarial 4- and 7-year distant metastasis-free survival was 93.7% and 87.0%, respectively, and the actuarial 7-year prostate cancer specific survival was 94.9%. Grade 3 late genitourinary toxicity developed in 14 patients (25.9%), while grade 4 late genitourinary toxicity developed in 2 patients (3.7%). Grade 3 late gastrointestinal toxicity developed in 1 patient (1.9%), and grade 4 late gastrointestinal toxicity developed in 1 patient (1.9%). Conclusion: In this series with long-term follow-up, early SRT provided outcomes and toxicity profiles similar to those reported from the three major randomized trials studying adjuvant radiation therapy.

Invited Review : DNA Vaccines against Infectious Diseases and Cancer

Duk Jae Han,David B. Weiner,Jeong Im Sin 한국응용약물학회 2010 Biomolecules & Therapeutics(구 응용약물학회지) Vol.18 No.1

THE EVOLUTION OF STAR FORMATION HISTORIES OF QUIESCENT GALAXIES

Pacifici, Camilla,Kassin, Susan A.,Weiner, Benjamin J.,Holden, Bradford,Gardner, Jonathan P.,Faber, Sandra M.,Ferguson, Henry C.,Koo, David C.,Primack, Joel R.,Bell, Eric F.,Dekel, Avishai,Gawiser, Er American Astronomical Society 2016 The Astrophysical Journal Vol.832 No.1

<P>Although there has been much progress in understanding how galaxies evolve, we still do not understand how and when they stop forming stars and become quiescent. We address this by applying our galaxy spectral energy distribution models, which incorporate physically motivated star formation histories (SFHs) from cosmological simulations, to a sample of quiescent galaxies at 0.2 < z < 2.1. A total of 845 quiescent galaxies with multi-band photometry spanning rest-frame ultraviolet through near-infrared wavelengths are selected from the Cosmic Assembly Near-IR Deep Extragalactic Legacy Survey (CANDELS) data set. We compute median SFHs of these galaxies in bins of stellar mass and redshift. At all redshifts and stellar masses, the median SFHs rise, reach a peak, and then decline to reach quiescence. At high redshift, we find that the rise and decline are fast, as expected, because the universe is young. At low redshift, the duration of these phases depends strongly on stellar mass. Low-mass galaxies (log(M*/M-circle dot) similar to 9.5) grow on average slowly, take a long time to reach their peak of star formation (greater than or similar to 4 Gyr), and then the declining phase is fast (less than or similar to 2 Gyr). Conversely, high-mass galaxies (log(M*/M-circle dot) similar to 11) grow on average fast (less than or similar to 2 Gyr), and, after reaching their peak, decrease the star formation slowly (greater than or similar to 3). These findings are consistent with galaxy stellar mass being a driving factor in determining how evolved galaxies are, with high-mass galaxies being the most evolved at any time (i.e., downsizing). The different durations we observe in the declining phases also suggest that low- and high-mass galaxies experience different quenching mechanisms, which operate on different timescales.</P>