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Neutrophil Count is Associated With Survival in Localized Prostate Cancer
E252
International Journal of Radiation Oncology Biology Physics
Results: We identified 296 patients with T1/T2 N0 prostate adenocarcinoma who underwent RP. Median age was 60 years with a median followup of 2.3 years. A total of 59% (nZ177) of patients had Gleason 7 disease and 54% (nZ154) had T1 disease. In addition, 40.8% (nZ121) of patients had biochemical failure following RP. After adjusting for clinical covariates, 4 genes were associated with differences in biochemical failure (Table 1). Specifically, increased RNA expression of E2F3 (hazard ratio [HR] 1.11, P<.001), CTNNB1 (HR 1.49, PZ.002), and AR (HR 1.21, P<.001) were seen in patients who experienced biochemical failure. Expression of TP53 (HR 0.75, p<.001) and Gleason 7 disease (HR 0.62 vs Gleason 8-10, P<.001) were associated with decreased likelihood of biochemical failure. Clustering by pathologic T stage accounted for 10% of variance in biochemical failure indicating that the 4 genes add important information to the prediction of biochemical recurrence. Conclusion: Genomic data augments pretreatment clinical data as well as pathologic staging data in the stratification of patients at risk for biochemical failure following RP. RNA expression of E2F3, CTNNB1, AR, and TP53 is associated with differences in biochemical failure following RP. Clinically, these genes could aid in identifying patients who may benefit from more regionally directed pelvic and prostate radiation therapy. Further studies of the relationship between these genes and the development of prostate cancer could aid in future targeted therapies. Author Disclosure: S. Aneja: None. C.P. Gross: Research Grant; 21st Century Oncology, Johnson and Johnson, Medtronic. P.M. Glazer: None. J.B. Yu: Research Grant; 21st Century Oncology.
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2626 Neutrophil Count is Associated With Survival in Localized Prostate Cancer H. Bahig, G. Delouya, D. Soulieres, A. Nadiri, A. Gagnon Jacques, B.C. Paule, and D. Taussky; Centre Hospitalier de l’Universite de Montreal, Montreal, QC, Canada Purpose/Objective(s): The prognostic value of leukocyte counts was previously reported in metastatic prostate cancer. The purpose of this study was to investigate the influence of readily available markers of systemic inflammation such as leucocyte counts and metabolic comorbidities on overall survival (OS) after curative radiation therapy for localized prostate cancer. Materials/Methods: We conducted a retrospective study of patients with localized prostate cancer treated with definitive external beam radiation therapy or brachytherapy. Univariate and multivariate Cox proportional hazards models were used to investigate the influence of the following factors on OS: age, neutrophils and lymphocytes counts, neutrophil-tolymphocyte ratio (NLR), Cancer of the Prostate Risk Assessment (CAPRA) score, as well as comorbidities associated with inflammation such as cardiac history, diabetes, and use of a statin, A stepwise selection of variable based on the Akaike information criterion (AIC) was used for multivariate analysis. Results: In total, 1772 patients were included; blood count data was available for 950 patients. Median age was 68 years (range 44-87). Actuarial 5-year OS and BFRS for the 1772 patients were 93% and 95%, respectively, with a median follow-up of 44 months (1-156 months). On univariate analysis, neutrophil count (PZ.04), cardiac history (PZ.008), age (PZ.001), and CAPRA (pZ.0002) were associated with OS. Lymphocytes, NLR, and comorbidities other than cardiac history were not associated with mortality. On multivariate analysis, neutrophil count (hazard ratio [HR] 1.18, 95% CI: 1.017-1.37, PZ.028), age (HR 1.06, 95% CI: 1.01-1.1, PZ.008), and CAPRA (HR 1.16, 95% CI: 1.03-1.31, PZ.015) were independent predictors of OS. Conclusion: Neutrophils, as possible markers of systemic inflammation, appear to be an independent prognostic factor for overall mortality in localized prostate cancer. A validation cohort is needed to corroborate these results. Author Disclosure: H. Bahig: Invited speaker Accuray symposium 22-092013; Accuray. G. Delouya: None. D. Soulieres: None. A. Nadiri: None. A. Gagnon Jacques: None. B. Paule: None. D. Taussky: None.
c-Met Overexpression in Cervical Cancer: A Prognostic Factor and a Potential Molecular Therapeutic Target T. Refaat,1,2 E.D. Donnelly,3 S. Sachdev,3 V. Parimi,2 S. El Achy,1 P. Dalal,2 M. Farouk,4 K.N. Berg,2 I. Helenowksi,5 J. Gross,2 J. Lurain,2 J.B. Strauss,3 G.E. Woloschak,2 J.J. Wei,2 and W. Small, Jr6; 1Alexandria University, Alexandria, Egypt, 2Northwestern University, Chicago, IL, 3 Northwestern University Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, 4Alexandria University, Alexandria, Egypt, Alexandria, Egypt, 5Feinberg School of Medicine, Northwestern University, Chicago, IL, 6Loyola University Medical Center, Maywood, IL Purpose/Objective(s): This study aimed to assess the association between pretreatment c-Met overexpression in local-regional advanced cervical cancer patients treated definitively with concurrent chemoradiation (CRT) and treatment outcomes including overall survival (OS), progression-free survival (PFS), distant metastases control (DM), and local-regional control (LC). Materials/Methods: This IRB-approved study included cervical cancer patients treated definitively and consecutively with CRT at our institution between 1983 and 2009. The chart review yielded 129 eligible patients; of them, 28 had tissue available from the pathology core facility for immunohistochemistry (IHC). c-Met (Clone C-28) IHC was performed on formalin-fixed paraffin tissue microarray sections using a polymer-based detection system with horseradish peroxidase. Evaluation of cytoplasmic immunoreactivity for c-Met was performed and scored semi quantitatively by 3 pathologists, who were blinded to the treatment outcomes, and incorporated the intensity and percentage of immunoreactivity in invasive carcinoma (H-score). Treatment-induced adverse events and outcomes including OS, PFS, LC, and DM were reviewed and reported. Outcomes were stratified by c-Met overexpression and other relevant tumor characteristics. OS, PFS, LC, and DC rates were obtained via the Kaplan-Meier method and differences between groups were evaluated by log-rank test. Hazard ratios (HR) associated with these rates were obtained via Cox regression for both univariate and multivariate analyses. Results: The mean patient age in this cohort was 5110 years. In terms of International Federation of Gynecology and Obstetrics stages, 10.71%, 53.57%, 17.86%, and 17.86% of the patients had stages IB, IIB, IIIB, and IV, respectively. Squamous cell carcinoma was present in 89.29% of the patients, and 10.71% had adenocarcinoma. Almost two-thirds of the patients had clinical node-negative disease. The 5-year OS, PFS, LC, and DC were 57.18%, 48.07%, 72.11%, and 62.85%, respectively. Ten patients (35.7%) had c-Met H-index >30 and 18 patients (64.3%) had c-Met Hindex 30. c-Met overexpression (H index > 30) was significantly associated with worse 3-year and 5-year OS (PZ.003), PFS (PZ.002), LC (PZ.01), and DC (PZ.0003). Patients with a c-Met H-score index >30 had a HR of 6.297 for the risk of death, 5.782 for risk of disease progression, 6.28 for risk of local recurrence, and 18.173 for risk of distant metastases compared to those with Met H-index 30. There was no significant association between c-Met expression and the incidence of treatment-induced adverse events. Conclusion: c-Met overexpression was a strong prognostic marker in this study. It might be a potential therapeutic target (cabozantinib; a tyrosine kinase inhibitor that targets MET, VEGFR2, and RET pathways) for localregional advanced cervical cancer patients treated definitively with CRT. Author Disclosure: T. Refaat: None. E.D. Donnelly: None. S. Sachdev: None. V. Parimi: None. S. El Achy: None. P. Dalal: None. M. Farouk: None. K.N. Berg: None. I. Helenowksi: None. J. Gross: None. J. Lurain: None. J.B. Strauss: None. G.E. Woloschak: None. J. Wei: None. W. Small: None.
2628 A Model for High-Quality Community-Based Brachytherapy for Cervical Cancer: Quality Metrics and Early Outcomes S. Jabbari,1 L. Delic,1 M. Norton,1 R. Decastro,1 D. Loomis,1 S. Topalian,1 R. Michaels,1 P.G. Zentner,2 B. Duggan,1 and A. Bahador1; 1Sharp Healthcare, San Diego, CA, 2Sharp Chula Vista Medical Center, Chula Vista, CA
International Journal of Radiation Oncology Biology Physics
Results: We identified 296 patients with T1/T2 N0 prostate adenocarcinoma who underwent RP. Median age was 60 years with a median followup of 2.3 years. A total of 59% (nZ177) of patients had Gleason 7 disease and 54% (nZ154) had T1 disease. In addition, 40.8% (nZ121) of patients had biochemical failure following RP. After adjusting for clinical covariates, 4 genes were associated with differences in biochemical failure (Table 1). Specifically, increased RNA expression of E2F3 (hazard ratio [HR] 1.11, P<.001), CTNNB1 (HR 1.49, PZ.002), and AR (HR 1.21, P<.001) were seen in patients who experienced biochemical failure. Expression of TP53 (HR 0.75, p<.001) and Gleason 7 disease (HR 0.62 vs Gleason 8-10, P<.001) were associated with decreased likelihood of biochemical failure. Clustering by pathologic T stage accounted for 10% of variance in biochemical failure indicating that the 4 genes add important information to the prediction of biochemical recurrence. Conclusion: Genomic data augments pretreatment clinical data as well as pathologic staging data in the stratification of patients at risk for biochemical failure following RP. RNA expression of E2F3, CTNNB1, AR, and TP53 is associated with differences in biochemical failure following RP. Clinically, these genes could aid in identifying patients who may benefit from more regionally directed pelvic and prostate radiation therapy. Further studies of the relationship between these genes and the development of prostate cancer could aid in future targeted therapies. Author Disclosure: S. Aneja: None. C.P. Gross: Research Grant; 21st Century Oncology, Johnson and Johnson, Medtronic. P.M. Glazer: None. J.B. Yu: Research Grant; 21st Century Oncology.
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2626 Neutrophil Count is Associated With Survival in Localized Prostate Cancer H. Bahig, G. Delouya, D. Soulieres, A. Nadiri, A. Gagnon Jacques, B.C. Paule, and D. Taussky; Centre Hospitalier de l’Universite de Montreal, Montreal, QC, Canada Purpose/Objective(s): The prognostic value of leukocyte counts was previously reported in metastatic prostate cancer. The purpose of this study was to investigate the influence of readily available markers of systemic inflammation such as leucocyte counts and metabolic comorbidities on overall survival (OS) after curative radiation therapy for localized prostate cancer. Materials/Methods: We conducted a retrospective study of patients with localized prostate cancer treated with definitive external beam radiation therapy or brachytherapy. Univariate and multivariate Cox proportional hazards models were used to investigate the influence of the following factors on OS: age, neutrophils and lymphocytes counts, neutrophil-tolymphocyte ratio (NLR), Cancer of the Prostate Risk Assessment (CAPRA) score, as well as comorbidities associated with inflammation such as cardiac history, diabetes, and use of a statin, A stepwise selection of variable based on the Akaike information criterion (AIC) was used for multivariate analysis. Results: In total, 1772 patients were included; blood count data was available for 950 patients. Median age was 68 years (range 44-87). Actuarial 5-year OS and BFRS for the 1772 patients were 93% and 95%, respectively, with a median follow-up of 44 months (1-156 months). On univariate analysis, neutrophil count (PZ.04), cardiac history (PZ.008), age (PZ.001), and CAPRA (pZ.0002) were associated with OS. Lymphocytes, NLR, and comorbidities other than cardiac history were not associated with mortality. On multivariate analysis, neutrophil count (hazard ratio [HR] 1.18, 95% CI: 1.017-1.37, PZ.028), age (HR 1.06, 95% CI: 1.01-1.1, PZ.008), and CAPRA (HR 1.16, 95% CI: 1.03-1.31, PZ.015) were independent predictors of OS. Conclusion: Neutrophils, as possible markers of systemic inflammation, appear to be an independent prognostic factor for overall mortality in localized prostate cancer. A validation cohort is needed to corroborate these results. Author Disclosure: H. Bahig: Invited speaker Accuray symposium 22-092013; Accuray. G. Delouya: None. D. Soulieres: None. A. Nadiri: None. A. Gagnon Jacques: None. B. Paule: None. D. Taussky: None.
c-Met Overexpression in Cervical Cancer: A Prognostic Factor and a Potential Molecular Therapeutic Target T. Refaat,1,2 E.D. Donnelly,3 S. Sachdev,3 V. Parimi,2 S. El Achy,1 P. Dalal,2 M. Farouk,4 K.N. Berg,2 I. Helenowksi,5 J. Gross,2 J. Lurain,2 J.B. Strauss,3 G.E. Woloschak,2 J.J. Wei,2 and W. Small, Jr6; 1Alexandria University, Alexandria, Egypt, 2Northwestern University, Chicago, IL, 3 Northwestern University Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, 4Alexandria University, Alexandria, Egypt, Alexandria, Egypt, 5Feinberg School of Medicine, Northwestern University, Chicago, IL, 6Loyola University Medical Center, Maywood, IL Purpose/Objective(s): This study aimed to assess the association between pretreatment c-Met overexpression in local-regional advanced cervical cancer patients treated definitively with concurrent chemoradiation (CRT) and treatment outcomes including overall survival (OS), progression-free survival (PFS), distant metastases control (DM), and local-regional control (LC). Materials/Methods: This IRB-approved study included cervical cancer patients treated definitively and consecutively with CRT at our institution between 1983 and 2009. The chart review yielded 129 eligible patients; of them, 28 had tissue available from the pathology core facility for immunohistochemistry (IHC). c-Met (Clone C-28) IHC was performed on formalin-fixed paraffin tissue microarray sections using a polymer-based detection system with horseradish peroxidase. Evaluation of cytoplasmic immunoreactivity for c-Met was performed and scored semi quantitatively by 3 pathologists, who were blinded to the treatment outcomes, and incorporated the intensity and percentage of immunoreactivity in invasive carcinoma (H-score). Treatment-induced adverse events and outcomes including OS, PFS, LC, and DM were reviewed and reported. Outcomes were stratified by c-Met overexpression and other relevant tumor characteristics. OS, PFS, LC, and DC rates were obtained via the Kaplan-Meier method and differences between groups were evaluated by log-rank test. Hazard ratios (HR) associated with these rates were obtained via Cox regression for both univariate and multivariate analyses. Results: The mean patient age in this cohort was 5110 years. In terms of International Federation of Gynecology and Obstetrics stages, 10.71%, 53.57%, 17.86%, and 17.86% of the patients had stages IB, IIB, IIIB, and IV, respectively. Squamous cell carcinoma was present in 89.29% of the patients, and 10.71% had adenocarcinoma. Almost two-thirds of the patients had clinical node-negative disease. The 5-year OS, PFS, LC, and DC were 57.18%, 48.07%, 72.11%, and 62.85%, respectively. Ten patients (35.7%) had c-Met H-index >30 and 18 patients (64.3%) had c-Met Hindex 30. c-Met overexpression (H index > 30) was significantly associated with worse 3-year and 5-year OS (PZ.003), PFS (PZ.002), LC (PZ.01), and DC (PZ.0003). Patients with a c-Met H-score index >30 had a HR of 6.297 for the risk of death, 5.782 for risk of disease progression, 6.28 for risk of local recurrence, and 18.173 for risk of distant metastases compared to those with Met H-index 30. There was no significant association between c-Met expression and the incidence of treatment-induced adverse events. Conclusion: c-Met overexpression was a strong prognostic marker in this study. It might be a potential therapeutic target (cabozantinib; a tyrosine kinase inhibitor that targets MET, VEGFR2, and RET pathways) for localregional advanced cervical cancer patients treated definitively with CRT. Author Disclosure: T. Refaat: None. E.D. Donnelly: None. S. Sachdev: None. V. Parimi: None. S. El Achy: None. P. Dalal: None. M. Farouk: None. K.N. Berg: None. I. Helenowksi: None. J. Gross: None. J. Lurain: None. J.B. Strauss: None. G.E. Woloschak: None. J. Wei: None. W. Small: None.
2628 A Model for High-Quality Community-Based Brachytherapy for Cervical Cancer: Quality Metrics and Early Outcomes S. Jabbari,1 L. Delic,1 M. Norton,1 R. Decastro,1 D. Loomis,1 S. Topalian,1 R. Michaels,1 P.G. Zentner,2 B. Duggan,1 and A. Bahador1; 1Sharp Healthcare, San Diego, CA, 2Sharp Chula Vista Medical Center, Chula Vista, CA