Association of very small nuclear circulating tumor cell (vsnCTC) with clinical outcomes in metastatic castration-resistant prostate cancer.

168 Background: Circulating tumor cells (CTCs) have arisen as contemporary noninvasive prognostic biomarkers for prostate cancer (PC). Previously, a subgroup of PC CTCs, with particularly small nuclei (<8.5 μm), were found to be correlated with the presence of visceral metastases. This subgroup was named very-small-nuclear CTCs (vsnCTCs). We proposed vsnCTCs as a putative biomarker of a lethal subtype in metastatic castration resistant PC (mCRPC). Methods: In this study, 76 patients with mCRPC were recruited for overall survival (OS) analysis. Of the 76 patients, 47 had available pre-treatment blood specimens prior to the initiation of androgen receptor signaling inhibitor (ARSI, e.g. abiraterone and enzalutamide) or taxane therapy. Using the NanoVelcro CTC Assay, CTCs were captured and subjected to immunofluorescence staining. CTCs were identified as DAPI+/CK+/CD45- with a round or oval nucleus. Additionally, CTC nuclear size was measured and defined as the square root of the product of the long axis and the short axis. Kaplan-Meier analysis and Cox proportional hazards model were conducted. Results: Patients with vsnCTC (i.e., vsnCTC+) had a significantly shortened OS compared with patients without vsnCTC (i.e., vsnCTC-). The median OS was 34 (vsnCTC+, n=49) vs. 149 (vsnCTC-, n=27) weeks (log-rank HR=2.6 with 95% CI 1.5 to 4.5, p=0.0006). Progression free survival (PFS) analysis was performed for the 47 patients with pre-treatment blood samples. The median PFS was 14 (vsnCTC+, n=29) vs. 26 (vsnCTC-, n=18) weeks (log-rank HR=2.2 with 95% CI 1.2 to 3.9, p=0.0069). We also found that the hazard ratio of overall survival increased significantly as the CTC nuclear size decreased using the p spline plot. Conclusions: Our study showed that nuclear size reduction has importance in CTCs in a fashion similar to its utility in tissue. This study points toward the importance of the vsnCTC in patients with mCRPC, as vsnCTC+ patients represented a group at risk for faster clinical progression who are at the highest risk for morality. We posit that the vsnCTC represents a new hallmark of an aggressive subtype of mCRPC. This has potential importance in optimizing therapeutic choices.

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Association between radiographic response and overall survival in men with metastatic castration-resistant prostate cancer receiving chemotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.7_suppl.118 ◽

2011 ◽

Vol 29 (7_suppl) ◽

pp. 118-118

Author(s):

G. Sonpavde ◽

G. R. Pond ◽

W. R. Berry ◽

R. De Wit ◽

M. A. Eisenberger ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Proportional Hazards ◽

Objective Assessment ◽

Objective Response ◽

Cox Proportional Hazards ◽

Phase Iii ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Kaplan Meier

118 Background: In men with metastatic castration resistant prostate cancer (CRPC),the association of measurable tumor responses with overall survival (OS) is unknown. We retrospectively evaluated the TAX327 phase III trial to study this relationship. Methods: Eligible patients for this analysis included those with WHO-defined measurable metastatic disease randomized to receive either docetaxel or mitoxantrone. OS was estimated using the Kaplan-Meier method and the prognostic relationship of WHO-defined radiologic response with OS was performed using Cox proportional hazards regression. Landmark analyses evaluated survival from baseline and 2, 3, 4 and 6 months after baseline. Results: Four hundred and twelve patients enrolled on the TAX327 trial had measurable tumors. Thirty-seven patients exhibited a complete or partial objective response (CR/PR, 9.0%), 116 had stable disease (SD, 28.2%), 99 had progressive disease (PD,24%) and 160 (38.8%) did not have a post-baseline objective assessment. Partial responders demonstrated longer median OS (29.0 months) than patients with SD (22.1 months), or those with PD (10.8 months) or those who were not assessed (12.7 months). These results remained after landmark analysis. We found a significant association between ≥30% PSA declines and radiologic response, with ≥30% PSA declines occurring in all patients with CR/PR, 79.8% of patients with SD and 34.4% with PD. Radiologic response remained a significant but modest post-treatment prognostic factor for OS after adjusting for treatment, pain-response and ≥30% PSA-decline (p=0.009). Conclusions: In men with metastatic CRPC and measurable disease receiving chemotherapy, objective tumor response was prognostic for OS, and appears to complement PSA assessment. [Table: see text]

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Impact of circulating tumor cell (CTC) nucleus size on outcomes with abiraterone acetate (AA) therapy in men with metastatic castration-resistant prostate cancer (mCRPC).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.6_suppl.253 ◽

2017 ◽

Vol 35 (6_suppl) ◽

pp. 253-253

Author(s):

David Michael Gill ◽

Neeraj Agarwal ◽

Andrew W. Hahn ◽

Eric Johnson ◽

Austin Poole ◽

...

Keyword(s):

Prostate Cancer ◽

Proportional Hazards Model ◽

Multivariable Analysis ◽

Cox Proportional Hazards ◽

Significant Trend ◽

Cox Proportional Hazards Model ◽

Nuclear Size ◽

Nucleus Size ◽

Castration Resistant Prostate Cancer ◽

The Impact

253 Background: CTC enumeration but not CTC morphology has been reported to predict outcomes to treatment in men with mCRPC. Recently Chen JF et. al (Cancer, 2015) showed an association with nuclear size and incidence of visceral disease in metastatic prostate cancer. In this study, we investigate the impact of CTC nucleus size on outcomes in men treated with AA for mCRPC. Methods: In a cohort of men with mCRPC treated with first-line AA, who had CTCs identified by CellSearch (CS) analysis prior to initiating treatment, we retrospectively quantified the nuclear size of CTCs by ImageJ/Fiji 1.46 software and correlated with progression free survival (PFS) on AA. We analyzed with univariate in addition to pre-specified multivariable analysis adjusted for Gleason score and baseline log PSA to assess independent predictive value of CTC nuclear size on PFS. Median PFS was calculated by Kaplan-Meier analysis and p-values were determined from Cox proportional hazards model. Results: 22 men treated with AA for mCRPC were included. Median nucleus size was 23.8 µm. Patients were divided in to 2 cohorts: small nuclear cohort (CTC nucleus size < 23.8 µm) vs large nuclear cohort (CTC nucleus size ≥23.8 µm). There was a non-significant trend towards worsened PFS (5.8 versus 6.8 months) in the larger nuclear size arm (Table). Conclusions: In this cohort of men with CRPC treated with AA, there is a non-significant trend towards decreased PFS associated with larger CTC nucleus size. Data are hypothesis generating and require further interrogation in a larger cohort. [Table: see text]

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Early change in prostate-specific antigen levels as a predictive marker for overall survival during vintage hormonal therapy for metastatic hormone-sensitive prostate cancer

10.21203/rs.3.rs-79980/v1 ◽

2020 ◽

Author(s):

Shotaro Nakanishi ◽

Masato Goya ◽

Mitsuyoshi Tamaki ◽

Takuma Oshiro ◽

Seiichi Saito

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Prostate Specific Antigen ◽

Proportional Hazards ◽

Specific Antigen ◽

Predictive Marker ◽

Cox Proportional Hazards ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Hormone Sensitive

Abstract Background The effect of early changes in prostate-specific antigen (PSA) levels after androgen deprivation therapy (ADT) in metastatic hormone-sensitive prostate cancer (mHSPC) patients has not been well investigated. Here, we evaluated the effect of factors that lead to castration-resistant prostate cancer (CRPC) progression and overall survival (OS) in mHSPC. Methods Medical records of 71 consecutive primary mHSPC patients treated with ADT were analyzed. Factors predicting the time to CRPC and OS in these patients were evaluated at 3 months after ADT induction. Results The median times to CRPC and OS were 15 months and 92 months, respectively. In multivariate analysis using Cox proportional hazards regression, a Gleason score of 8 or more (p = 0.004), extent of disease value (EOD) of 2 or more (p = 0.004), and a PSA level of 1% or more of the pretreatment levels after 3 months of ADT (p = 0.017) were independent predictors of shorter time to CRPC. For OS, a PSA level of 1% or more after 3 months of ADT was the independent predictor (p = 0.004). Conclusion % PSA was an important factor that correlated with poor prognosis at 3 months after ADT induction.

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Oncological outcomes of metastatic castration resistant prostate cancer (mCRPC) treated with different therapies sequences after completion of docetaxel: a retrospective study in Songklanagarind Hospital

Insight Urology ◽

10.52786/isu.a.35 ◽

2021 ◽

Vol 42 (2) ◽

pp. 131-137

Author(s):

Isaris Chaokhamin ◽

◽

Worapat Attawettayanon ◽

Virote Chalieopanyarwong ◽

Monthira Tanthanuch ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Proportional Hazards ◽

Multivariable Analysis ◽

Abiraterone Acetate ◽

Cox Proportional Hazards ◽

Castration Resistant Prostate Cancer ◽

Oncological Outcomes ◽

Castration Resistant ◽

Docetaxel Chemotherapy

Objective: Many treatment options of metastatic castration-resistant prostate cancer (mCRPC) after docetaxel chemotherapy have proved efficacious in clinical trials but, to date, knowledge regarding oncological outcomes is limited. Materials and Methods: We assessed the oncological outcome of 4 drugs (abi- raterone acetate, cabazetaxel, enzalutamide and ketoconazole) in a normal clinical setting in a university-based hospital. Our cohort consisted of 69 patients with post-docetaxel mCRPC. The primary endpoint was overall survival (OS). The secondary endpoint was predicted factor associated overall survival with all sec- ond-line mCRPC treatment outcomes according to the Cox proportional hazards regression model. Results: This cohort consisted of 69 patients with progressive mCRPC after docetaxel chemotherapy. Median overall survival following treatment with abiraterone acetate and ketoconazole was 25.92 and 9.59 months respectively (p < 0.05). Overall survival rates at 1-year following abiraterone acetate, cabazetaxel, enzalutamide and ketoconazole therapy were 76.3%, 83.3%, 100% and 41.9%, respectively. Multivariable analysis found that abiraterone acetate, cabazitaxel and enzalutamide significantly improved survival in comparison to ketoconazole (p < 0.001). Conclusion: Analysis of overall survival following second-line treatment of mCRPC post docetaxel in our study statistically significantly confirmed that abiraterone acetate, cabazitaxel and enzalutamide improve overall survival in comparison to ketoconazole. The study also found that enzalutamide treatment resulted in better outcomes in comparison to the other drugs.

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A novel nomogram to predict the overall survival in esthesinoeroblastoma

10.21203/rs.3.rs-22163/v2 ◽

2020 ◽

Author(s):

Lijie Jiang ◽

Tengjiao Lin ◽

Yu Zhang ◽

Wenxiang Gao ◽

Jie Deng ◽

...

Keyword(s):

Overall Survival ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Validation Cohort ◽

Risk Groups ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Cancer Center ◽

P Value ◽

Training Cohort

Abstract Background Increasing evidence indicates that the pathology and the modified Kadish system have some influence on the prognosis of esthesioneuroblastoma (ENB). However, an accurate system to combine pathology with a modified Kadish system has not been established. Methods This study aimed to set up and evaluate a model to predict overall survival (OS) accurately in ENB, including clinical characteristics, treatment and pathological variables. We screened the information of patients with ENB between January 1, 1976, and December 30, 2016 from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program as a training cohort. The validation cohort consisted of patients with ENB at Sun Yat-sen University Cancer Center and The First Affiliated Hospital of Sun Yat-sen University in the same period, and 87 patients were identified. The Pearson’s chi-squared test was used to assess significance of clinicopathological and demographic characteristics. We used the Cox proportional hazards model to examine univariate and multivariate analyses. The model coefficients were used to calculate the Hazard ratios (HR) with 95% confidence intervals (CI). Prognostic factors with a p- value < 0.05 in multivariate analysis were included in the nomogram. The concordance index (c-index) and calibration curve were used to evaluate the predictive power of the nomogram. Results The c-index of training cohort and validation cohort are 0.737 (95% CI, 0.709 to 0.765) and 0.791 (95% CI, 0.767 to 0.815) respectively. The calibration curves revealed a good agreement between the nomogram prediction and actual observation regarding the probability of 3-year and 5-year survival. We used a nomogram to calculate the 3-year and 5-year growth probability and stratified patients into three risk groups. Conclusions The nomogram provided the risk group information and identified mortality risk and can serve as a reference for designing a reasonable follow-up plan.

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Integration of bone scan (BS) and computerized tomography (CT) findings as an endpoint to assess bone metastasis in metastatic castration-resistant prostate cancer (mCRPC).

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.2_suppl.191 ◽

2016 ◽

Vol 34 (2_suppl) ◽

pp. 191-191

Author(s):

Scott J. Parker ◽

Gregory Russell Pond ◽

Guru Sonpavde ◽

Anitha Alex ◽

Marta Elise Heilbrun ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Bone Metastasis ◽

Proportional Hazards ◽

Statistical Significance ◽

Cox Proportional Hazards ◽

Bone Lesions ◽

Castration Resistant Prostate Cancer ◽

Ct Findings ◽

Significant Difference

191 Background: Progression of bone metastasis in mCRPC is assessed solely by BS findings and correlates modestly with overall survival (OS). Given the lack of reliability of BS findings and the ready availability of routinely performed CT scans, which commonly identify bone metastases, we aimed to better assess progression in bone by integrating BS and CT findings and to explore their association with OS. Methods: Data were obtained from patients treated at the University of Utah receiving docetaxel-based chemotherapy (D) or post-docetaxel therapy with orteronel (O). Patients with both baseline and on-therapy CT and BS within 90 days were eligible for analysis. CT and BS underwent central radiology review for bone lesions by a single radiologist. Progressive disease (PD) was defined as ≥ 1 new lesion. Survival was measured from start of therapy. Cox proportional hazards regression was used to explore potential prognosticators of overall survival (OS). Statistical significance was defined as 2-sided p < 0.05. Therapy was a stratification factor. Results: Twenty-eight patients were evaluable including 18 patients receiving D, and 10 receiving O post-docetaxel. The mean age of these patients was 71.4 years and median (95% CI) overall survival was 18.4 (9.7-35.4) months. Four patients had PD on both BS and CT, while 2 (7%) had PD on CT but not BS and 3 had PD on BS but not CT. Patients with PD on BS or CT had worse OS (HR = 2.68, 95% CI = 1.04-6.90, p = 0.041) than those with no PD on either CT or BS. Looking at individual lesions, 4 (14%) patients had new lesions identified on CT which was not observed using BS, and they were associated with worse OS (HR = 3.72, 1.01-13.66, p = 0.048). Conversely, no significant difference in OS was observed for 4 patients with lesions identified on BS which were not observed using CT (HR = 2.67, 0.58-12.32, p = 0.21). Conclusions: This hypothesis-generating study suggests that CT can complement and enhance the ability of BS to capture PD and predict OS. Integration of BS findings using Prostate Cancer Working Group (PCWG)-3 guidelines to define PD and CT bone findings should be investigated in a larger study as an intermediate endpoint.

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Fish intake and the risk of fatal prostate cancer: findings from a cohort study in Japan

Public Health Nutrition ◽

10.1017/s1368980008003182 ◽

2009 ◽

Vol 12 (5) ◽

pp. 609-613 ◽

Cited By ~ 24

Author(s):

Truong-Minh Pham ◽

Yoshihisa Fujino ◽

Tatsuhiko Kubo ◽

Reiko Ide ◽

Noritaka Tokui ◽

...

Keyword(s):

Prostate Cancer ◽

Cohort Study ◽

Fish Consumption ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Inverse Association ◽

High Intake ◽

Risk Of Death

AbstractObjectiveWe investigated the relationship between the intake of fish and the risk of death from prostate cancer.DesignData were derived from a prospective cohort study in Japan. Fish consumption obtained from a baseline questionnaire was classified into the two categories of ‘low intake’ and ‘high intake’. The Cox proportional hazards model was used to estimate hazard ratios (HR) and 95 % confidence intervals.SubjectsData for 5589 men aged 30–79 years were analysed.ResultsA total of twenty-one prostate cancer deaths were observed during 75 072 person-years of follow-up. Mean age at baseline study of these twenty-one subjects was 67·7 years, ranging from 47 and 79 years old. Results showed a consistent inverse association of this cancer between the high v. low intake groups. The multivariate model adjusted for potential confounding factors and some other food items showed a HR of 0·12 (95 % CI 0·05, 0·32) for the high intake group of fish consumption.ConclusionsThese results support the hypothesis that a high intake of fish may decrease the risk of prostate cancer death. Given the paucity of studies examining the association between prostate cancer and fish consumption, particularly in Asian populations, these findings require confirmation in additional cohort studies.

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Impact of Prior Cancer History on Outcomes in Thymoma

10.21203/rs.3.rs-41041/v2 ◽

2020 ◽

Author(s):

Shilong Wu ◽

Mengyang Liu ◽

Weixue Cui ◽

Guilin Peng ◽

Jianxing He

Keyword(s):

Overall Survival ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Cancer History ◽

Treatment Methods ◽

Hazards Model ◽

Kaplan Meier ◽

The Impact

Abstract Background Thymoma is an uncommon intrathoracic malignant tumor and has a long natural history. It is uncertain whether the survival of thymoma patient is affected by prior cancer history. Finding out the impact of a prior cancer history on thymoma survival has important implications for both decision making and research. Method The Surveillance, Epidemiology, and End Results (SEER) database was queried for thymoma patients diagnosed between 1975 and 2015. Kaplan-Meier methods and Cox proportional hazards model were used to analyze overall survival across a variety of stages, age, and treatment methods with a prior cancer history or not. Results A total of 3604 patients with thymoma were identified including 507 (14.1%) with a prior cancer history. The 10-year survival rate of patients with a prior cancer history (53.8%) was worse than those without a prior cancer history (40.32%, 95%CI 35.24-45.33, P < 0.0001). However, adjusted analyses showed that the impact of a prior cancer history was heterogenous across age and treatment methods. In subset analyses, prior cancer history was associated with worse survival among patients who were treated with chemoradiotherapy (HR: 2.80, 95% CI: 1.51-5.20, P = 0.001) and age ≤ 65 years (HR: 1.33, 95%CI: 1.02-1.73, P = 0.036). Conclusions Prior cancer history provides an inferior overall survival for patients with thymoma. But it does not worsen the survival in some subgroups and these thymoma patients should not be excluded from clinical trials.

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A novel nomogram to predict the overall survival in esthesinoeroblastoma

10.21203/rs.3.rs-22163/v1 ◽

2020 ◽

Author(s):

Lijie Jiang ◽

Tengjiao Lin ◽

Yu Zhang ◽

Wenxiang Gao ◽

Jie Deng ◽

...

Keyword(s):

Overall Survival ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Validation Cohort ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Cancer Center ◽

Training Cohort ◽

Chi Squared ◽

Set Up

Abstract BackgroundIncreasing evidence indicates that the pathology and the modified Kadish system have some influence on the prognosis of esthesioneuroblastoma (ENB). However, an accurate system to combine pathology with a modified Kadish system has not been established.MethodsThis study aimed to set up and evaluate a model to predict overall survival (OS) accurately in ENB, including clinical characteristics, treatment and pathological variables. We screened the information of patients with ENB between January 1, 1976, and December 30, 2012 from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program as a training cohort. The validation cohort consisted of patients with ENB at Sun Yat-sen University Cancer Center and The First Affiliated Hospital of Sun Yat-sen University in the same period, and 87 patients were identified. The Pearson’s chi-squared test was used to assess significance of clinicopathological and demographic characteristics. We used the Cox proportional hazards model to examine univariate and multivariate analyses. The model coefficients were used to calculate the Hazard ratios (HR) with 95% confidence intervals (CI). Prognostic factors with a p-value < 0.05 in multivariate analysis were included in the nomogram. The concordance index (c-index) and calibration curve were used to evaluate the predictive power of the nomogram.ResultsThe c-index of training cohort and validation cohort are 0.737 (95% CI, 0.709 to 0.765) and 0.791 (95% CI, 0.767 to 0.815) respectively. The calibration curves revealed a good agreement between the nomogram prediction and actual observation regarding the probability of 3-year and 5-year survival. We used a nomogram to calculate the 3-year and 5-year growth probability and stratified patients into three risk groups.ConclusionsThe nomogram provided the risk group information and identified mortality risk and can serve as a reference for designing a reasonable follow-up plan.# Co-first authors: Lijie Jiang and Tengjiao Lin contributed equally to this article.

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The Real-World status and risk factors for a poor prognosis in elderly patients with primary central nervous system malignant lymphomas: a multicenter retrospective cohort study of the Tohoku Brain Tumor Study Group

10.21203/rs.3.rs-291646/v1 ◽

2021 ◽

Author(s):

Kenichiro Asano ◽

Yoji Yamashita ◽

Takahiro Ono ◽

Manabu Natsumeda ◽

Takaaki Beppu ◽

...

Keyword(s):

Risk Factors ◽

Central Nervous System ◽

Nervous System ◽

Poor Prognosis ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Hazards Model ◽

Pre Treatment

Abstract Introduction The number of elderly patients with primary central nervous system malignant lymphoma(EL-PCNSL) has been increasing. However, due to their poor pre-treatment Karnofsky Performance Status(KPS) and many comorbidities, it is possible that sufficient treatment has not been performed. We therefore conducted a retrospective cohort study to evaluate risk factors associated with a poor prognosis of the Real-World status of EL-PCNSL in the Tohoku Brain Tumor Study Group. Methods Patients aged ≥ 71 years with PCNSL were enrolled from 8 centers. Univariate analysis was performed by the log-rank test. A Cox proportional hazards model was used for multivariate analysis. Results Three of total 142 cases received best supportive care(BSC) from the beginning. Treatment was given to 30 cases without a pathological diagnosis, 3 cases with a cerebrospinal fluid diagnosis, and 100 cases with CD20-positive DLBCL diagnosis. Total 133 cases(median age 76 years) were included. The median pre-treatment KPS was 50%. There were 117(88.0%) patients with 213 pre-treatment comorbidities(1.8 comorbidities per patient). PFS and OS were 16 months and 24 months, respectively. Risk factors associated with poor prognosis on Cox proportional hazards model were pre-treatment cardiovascular disease and central nervous system disease comorbidities, post-treatment pneumonia and other infections, and the absence of radiation or chemotherapy. Conclusions EL-PCNSL was actively treated and BSC was only a few. Pre-treatment comorbidities and post-treatment complications would influence the prognosis. Radiation and chemotherapy were found to be effective, but no conclusions could be drawn regarding the content of chemotherapy and whether additional radiation therapy should be used.

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