Implications of neuroendocrine tumor and diabetes mellitus on patient outcomes and care: A matched case control study.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 612-612
Author(s):  
Nina J. Karlin ◽  
Heidi E. Kosiorek ◽  
Matthew Buras ◽  
Kelley Rone ◽  
Patricia M. Verona ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Glycemic Control ◽  
Neuroendocrine Tumor ◽  
Cancer Diagnosis ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards Model ◽  
Rank Test ◽  
Matched Pairs ◽  
Kaplan Meier ◽  
The Impact

612 Background: The aim of this study was to examine the impact of diabetes mellitus (DM) on survival in neuroendocrine tumor and the impact of neuroendocrine tumor on glycemic control in DM. Methods: Patients with newly diagnosed neuroendocrine tumor with and without DM were matched 1:1 according to age, gender, and year of cancer diagnosis (2005-2017). The file was linked to the electronic medical record to obtain information on DM and neuroendocrine tumor therapies and laboratory results. There were 59 matched pairs (total 118 patients) included in the analysis. We compared characteristics between cases and controls and assessed survival with the Kaplan-Meier method and Cox proportional hazards model. Mixed models compared hemoglobin A1c and glucose levels over time. Results: Median age of patients at diagnosis was 67 (40-86); 41% had stage IV disease. Women constituted 49% of the study population; 22% had pancreatic neuroendocrine tumor and 45% had another GI primary neuroendocrine tumor. No differences in race/ethnicity, marital status, alcohol or tobacco use were detected between cancer patients with and without DM. Mean BMI was significantly different between DM and non-DM patients (31.0 [7.90] versus 26.4 [5.27]); p = 0.011. Among those with DM, mean HbA1c during the year following cancer diagnosis was 7.3%. Mean glucose was significantly different between DM (159.1 [43.5] versus non-DM pts 117 [31.5]); p < 0.001. Median follow-up time was 32.8 (2.4-165.4) months in alive patients. Three year survival was estimated at 72% (95% CI: 60-86%) for DM patients versus 80% (95% CI: 70-92%) in non-DM patients by Kaplan Meier method (p = 0.82 log rank test). Hazard ratio (stratification for matched pairs) = 1.33 (95% CI: 0.56 – 3.16; p = 0.51). Conclusions: DM did not adversely impact survival in patients with neuroendocrine tumor. Neuroendocrine tumor and its treatment did not affect glycemic control. This should be reassuring to oncologists and endocrinologists who treat patients with neuroendocrine tumors and diabetes.

scholarly journals MON-131 Mortality and Glycemic Control Among Patients with Leukemia and Diabetes Mellitus: A Case-Control Study

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Erin Wiedmeier ◽  
Luke Mountjoy ◽  
Patricia Verona ◽  
Heidi Kosiorek ◽  
Matthew Buras ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Glycemic Control ◽  
Hazard Ratio ◽  
Cox Proportional Hazards Model ◽  
Solid Organ ◽  
Matched Pairs ◽  
Total N ◽  
Kaplan Meier ◽  
The Impact ◽  
Over Time

Abstract Background: Unlike with solid organ cancers, little data is available on how diabetes mellitus (DM) and hematologic malignancies interact to affect survival and glycemic control. We examined the impact of DM on survival in patients with leukemia and the effect of leukemia on glycemic control. Materials and Methods: Patients with leukemia with and without DM were matched 1:1 (2007–2017), 70 matched pairs (total N=140 pts) were included in the analysis. We compared characteristics between cases and controls and assessed survival with the Kaplan-Meier method and Cox proportional hazards model. Mixed models compared hemoglobin A1c (HbA1c) and glucose levels over time. Results: The median age of patients at diagnosis was 56 (18–94); 60% were male and 89% had acute leukemia. Among those with DM, HbA1c was only recorded in 25 of 70 patients during the year following cancer diagnosis and was 6.8%. There was no change in HbA1c values over time in these DM patients. Mean glucose was significantly different between DM and non-DM patients (p&lt;0.001). Time (days since leukemia diagnosis) was significant (p&lt;0.001) and there was a significant interaction effect (p=0.01). Glucose values increased in the DM patients during the year following diagnosis, while remaining stable in those without DM. Median follow-up time was 23.2 months. Three-year survival was estimated at 46% for DM patients versus 45% in non-DM pts by Kaplan Meier method (p=0.79). Hazard ratio (stratification for matched pairs) was 1.05 (95% CI: 0.57 - 1.94; p=0.88). Three-year relapse-free survival was estimated at 34% for DM patients versus 43% for non-DM patients (p=0.58). Hazard ratio (stratification for matched pairs) = 1.10 (95% CI: 0.61–1.98; p=0.76). Conclusions: DM did not adversely impact survival in patients with leukemia. Leukemia and its treatment did not affect glycemic control. This should be reassuring to hematologists and endocrinologists who treat patients with leukemia and diabetes.

scholarly journals Absence of Survival Improvement for Patients with Esthesioneuroblastoma Over the Past Two Decades: A Population-based Study

2021 ◽  
Author(s):  
Huy Gia Vuong ◽  
Duy Duc Nguyen ◽  
Edward El-Rassi ◽  
Tam N. M. Ngo ◽  
Ian F. Dunn
Keyword(s):  
Adjuvant Radiotherapy ◽  
Proportional Hazards Model ◽  
Tumor Resection ◽  
Cox Proportional Hazards Model ◽  
Rank Test ◽  
Tumor Diameter ◽  
Continuous Variables ◽  
The Past ◽  
Kaplan Meier ◽  
The Impact

Abstract Introduction: Esthesioneuroblastoma (ENB) is a rare malignancy of the sinonasal tract and its infrequency has confounded efforts at clearly describing the survival trends associated with this neoplasm over the years. In this study, we studied survival trends in ENB and investigated the impact of treatment extent and modality on patient outcomes.Methods: We accessed the Surveillance, Epidemiology, and End Result (SEER) program to identify ENB cases from 1998 to 2016. A Chi-square test was used to compare the categorical covariates whereas a t-test or Mann-Whitney U test was utilized for continuous variables. The impact of prognostic factors on survival was computed using a Kaplan-Meier analysis and multivariate Cox proportional hazards model. We divided ENB patients into four periods including 1998-2002, 2003-2007, 2008-2012, and 2013-2016, and investigated survival trends using the Kaplan-Meier curve and log-rank test.Results: ENB patients who underwent biopsy alone were associated with older age, larger tumor diameter, increased rates of tumor extension, nodal/distant metastases, and advanced stages as compared to patients undergoing tumor resection. Our results also demonstrated that surgical resection and adjuvant radiotherapy could confer survival advantages whereas chemotherapy was associated with reduced survival in patients with ENB. Over the past two decades, surprisingly, there has been no change in survival rates for patient with ENB (p = 0.793).Conclusion: Despite advanced diagnostic studies and modernized treatment approaches, ENB survival has remained unchanged over the years, calling for improved efforts to develop appropriate individualized interventions for this rare tumor entity. Our results also confirmed that surgery and adjuvant radiotherapy is associated with improved patient survival whereas the use of chemotherapy should be considered carefully.

Mortality and glycemic control among patients with gastric and esophageal cancer and diabetes mellitus.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 73-73
Author(s):  
Nina J. Karlin ◽  
Matthew Buras ◽  
Heidi E. Kosiorek ◽  
Patricia M. Verona ◽  
Curtiss B. Cook
Keyword(s):  
Diabetes Mellitus ◽  
Esophageal Cancer ◽  
Glycemic Control ◽  
Cancer Patients ◽  
Cancer Diagnosis ◽  
Cox Regression ◽  
Hazard Ratio ◽  
Matched Pairs ◽  
Cox Regression Analysis ◽  
The Impact

73 Background: This study evaluated the impact of diabetes mellitus (DM) on survival in gastric and esophageal cancer patients, and examined the impact of these cancers on glycemic control in DM. Methods: Patients with newly diagnosed gastric and esophageal cancers with DM (n = 92) were identified from the Institutional Cancer Registry and matched to 92 gastric and esophageal cancer patients without DM according to age, gender and year of cancer diagnosis (2006 to 2016). The electronic medical record provided information on DM and cancer therapies and laboratory results. Overall survival (OS) was estimated with the Kaplan-Meier method and compared by Cox regression analysis using stratification for matched pairs. Mixed models were used to compare hemoglobin A1c (HbA1c) and glucose during the year following cancer diagnosis. Results: Mean age of the entire cohort was 68 years, 91% were white, 78% were men, and 53% had stage III/IV disease. Adenocarcinoma (79%) was the most common histologic type. BMI was significantly different between DM and non-DM patients (p = 0.006). Alcohol use at time of cancer diagnosis was more prevalent in non-DM patients vs. DM (p = 0.018). Among those with DM, mean HbA1c during the year following cancer diagnosis was 6.8%. Mean glucose was significantly different between DM and non-DM patients (149 mg/dL vs. 116 mg/dL, p < 0.001). For glucose, there was a significant interaction effect (p = 0.005) as DM patients demonstrated a decrease in glucose values over time compared to non-DM patients. Median follow-up time was 35 months. Three year OS was estimated at 46% (95% CI: 36-58%) for DM patients versus 52.0% (95% CI: 41-64%) in non-DM (p = 0.25). Hazard ratio (stratification for matched pairs) was 1.95 (95% CI: 1.14 – 3.43; p = 0.02). Three year PFS was estimated at 40% (95% CI: 31-53%) for DM patients versus 50% (95% CI: 40-63%) for non-DM patients (p = 0.12). Hazard ratio (stratification for matched pairs) was 1.74 (95% CI: 1.04-2.90; p = 0.03). Conclusions: Gastric and esophageal cancer and its treatment did not affect glycemic control. Risks of death and progression are greater in DM patients as compared to non-DM.

scholarly journals Serum Endocan as a Survival Predictor for Patients with Liver Cirrhosis

2015 ◽  
Vol 29 (8) ◽  
pp. 427-430 ◽  
Author(s):  
Nobuyuki Toshikuni ◽  
Kazuaki Ozaki ◽  
Joseph George ◽  
Mikihiro Tsutsumi
Keyword(s):  
Liver Cirrhosis ◽  
Proportional Hazards Model ◽  
Survival Rates ◽  
Elevated Serum ◽  
Cox Proportional Hazards Model ◽  
Rank Test ◽  
Hepatic Decompensation ◽  
Cumulative Survival ◽  
Kaplan Meier ◽  
Survival Predictor

BACKGROUND: The relationship between endocan expression and outcome in patients with chronic liver disease is not fully understood.OBJECTIVE: To examine whether serum endocan level is predictive of outcome in patients with liver cirrhosis.METHODS: A total of 68 patients with liver cirrhosis were enrolled. Outcome predictors were analyzed using the Cox proportional hazards model. The overall survival rates were calculated using the Kaplan-Meier method, and differences were evaluated using the log-rank test.RESULTS: During the median follow-up period (7.1 years), nine patients had hepatocellular carcinoma (HCC) and 10 patients died. Of the deceased patients, nine died due to hepatic decompensation or associated conditions. No significant factors were found to be predictive of the occurrence of HCC. In contrast, an elevated serum endocan level (≥2.0 ng/mL; HR 2.34 [95% CI 1.05 to 7.03]; P=0.037) and high Child-Pugh grade B/C (HR 2.65 [95% CI 1.30 to 6.89; P=0.006) were predictive of poor survival. Kaplan-Meier analysis revealed that the respective cumulative survival rates at five and 10 years were 97.1% and 87.4% in patients with serum endocan levels <2.0 ng/mL and 85.8% and 64.4% in patients with levels ≥2.0 ng/mL (P=0.009), respectively. Moreover, the cumulative survival rates were significantly different among the patient groups divided according to serum endocan level and Child-Pugh grade (P=0.002).CONCLUSION: These findings suggest that serum endocan level may be a survival predictor for patients with liver cirrhosis.

Implications of pancreatic cancer with diabetes mellitus on patient outcomes and care: A matched case-control study.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 239-239
Author(s):  
Nina J. Karlin ◽  
Shailja Amin ◽  
Matthew Buras ◽  
Heidi E. Kosiorek ◽  
Patricia M. Verona ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Glycemic Control ◽  
Cancer Diagnosis ◽  
Case Control Study ◽  
Case Control ◽  
Kaplan Meier ◽  
The Impact ◽  
Control Study ◽  
Over Time

239 Background: The aim of this case-control study was to determine the impact of DM on survival in pancreatic cancer patients, and to examine the impact of pancreatic cancer on glycemic control in DM. Methods: Ninety-two patients with newly diagnosed pancreatic cancer from 2007 to 2015 with DM were identified from the institutional Cancer Registry and matched to ninety-two pancreatic cancer patients without DM according to age, gender, and year of pancreatic cancer diagnosis. The file was linked to the electronic medical record to obtain information on DM and pancreatic cancer therapies, and laboratory results. Overall survival (OS) was estimated with the Kaplan-Meier method and compared by Cox regression analysis. Mixed models were used to compare hemoglobin A1c (HbA1c) and glucose over time. Results: Mean age of the entire pancreatic cancer cohort was 70 years, most (92%) were white, most common (88%) histology was adenocarcinoma, and majority (41%) were stage IV. No differences in age, race/ethnicity, histology, or tumor stage were detected between patients with and without DM, although DM patients had higher body mass index (P = 0.014). Mean ca 19-9 (U/ml) was 804 for diabetics, and 395 for non-diabetics. Among those with DM the mean HbA1c during the year following cancer diagnosis was 7.3%. Time (days since diagnosis) was significant in DM patients (p = 0.014) as HbA1c decreased over time. Mean glucose during the year following diagnosis among DM patients was significantly higher compared to non-DM patients [160.6 (SD = 38.0) versus 117.2 (SD = 19.0); p < 0.001]. Both groups had a decline in glucose over time (p = 0.008). In Kaplan-Meier survival analysis (median follow-up time of 11.9 months), 2 year overall survival was estimated at 15% [95% CI: 8-24%] for DM patients versus 26% [95% CI: 17-36%] in non-DM patients. Hazard ratio (for matched pairs) was 1.15 (95% CI: 0.75-1.77; p = 0.51). Conclusions: DM did not adversely impact survival in patients with pancreatic cancer. Pancreatic cancer did not affect glycemic control. Elevated ca 19-9 in diabetic patients may be an unreliable marker for gauging disease progression.

scholarly journals Impact of Prior Cancer History on Outcomes in Thymoma

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.

scholarly journals Implications of neuroendocrine tumor and diabetes mellitus on patient outcomes and care: a matched case–control study

2021 ◽  
pp. FSO684
Author(s):  
Yael N Kusne ◽  
Heidi E Kosiorek ◽  
Matthew R Buras ◽  
Patricia M Verona ◽  
Kyle E Coppola ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Glycemic Control ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Kaplan Meier ◽  
Matched Case ◽  
After Cancer ◽  
The Impact ◽  
Matched Case Control Study ◽  
Control Study

Aim: We aimed to determine the impact of diabetes mellitus (DM) on survival of patients with neuroendocrine tumors (NETs) and of NETs on glycemic control. Patients & methods: Patients with newly diagnosed NETs with/without DM were matched 1:1 by age, sex and diagnosis year (2005–2017), and survival compared (Kaplan–Meier and Cox proportional hazards). Mixed models compared hemoglobin A1c (HbA1c) and glucose during the year after cancer diagnosis. Results: Three-year overall survival was 72% (95% CI: 60–86%) for DM patients versus 80% (95% CI: 70–92%) for non-DM patients (p = 0.82). Hazard ratio was 1.33 (95% CI: 0.56–3.16; p = 0.51); mean DM HbA1c, 7.3%. Conclusion: DM did not adversely affect survival of patients with NET. NET and its treatment did not affect glycemic control.

Erlotinib after initial platinum-doublet chemotherapy in patients with epidermal growth factor receptor (EGFR) wild-type (WT) non-small cell lung cancer (NSCLC): Results of a combined patient-level analysis of the BR.21 and SATURN trials.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8080-8080 ◽  
Author(s):  
Raymond U Osarogiagbon ◽  
Federico Cappuzzo ◽  
Tudor-Eliade Ciuleanu ◽  
Larry Leon
Keyword(s):  
Egfr Mutation ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Sensitivity Analyses ◽  
Egfr Mutations ◽  
Rank Test ◽  
Double Blind ◽  
Mutation Status ◽  
The Impact

8080 Background: Two double-blind, prospective, randomized, placebo-controlled trials demonstrated survival benefit in unselected populations with advanced NSCLC in the 2nd/3rd line (BR.21) and maintenance setting (SATURN). The efficacy of erlotinib in patients with EGFR WT NSCLC has been questioned. We examined the impact of erlotinib vs placebo in confirmed EGFR WT patients in both studies. Methods: Combined re-analysis of progression-free survival (PFS) (from date of randomization to investigator-assessed progression or death from any cause), and overall survival (OS) (from date of randomization to death from any cause) in patients with known WT EGFR. PFS and OS were estimated by Kaplan-Meier curves and compared by 2-sided log-rank test. Cox proportional hazards model was used to estimate hazard ratios (HR) adjusted for potential confounders. Sensitivity analyses assessed comparability of patients with known and unknown EGFR mutation status to determine generalizability of the two study populations. Results: 74% of the BR.21 population (n=150) and 89% of the SATURN population (n=388) with known EGFR mutation status had WT EGFR. PFS and OS for individual and combined analyses are shown (Table). Adjusting for non-randomized therapy after study therapy discontinuation, HR for OS was 0.74 (0.61–0.91); p<0.01. Baseline characteristics were similar for patients with known and unknown EGFR status, suggesting generalizability of the EGFR WT data. Erlotinib benefit was sustained in all clinical subsets. Conclusions: Erlotinib provided a consistent and significant improvement in survival for patients with EGFR WT NSCLC in both studies, individually and in combination. The benefit of erlotinib does not appear to be limited to patients with activating EGFR mutations. [Table: see text]

Results of the randomized phase II portion of NRG Oncology/RTOG 0848 evaluating the addition of erlotinib to adjuvant gemcitabine for patients with resected pancreatic head adenocarcinoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4007-4007 ◽  
Author(s):  
Howard Safran ◽  
Kathryn A Winter ◽  
Ross A. Abrams ◽  
William Regine ◽  
Karyn A. Goodman ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Pancreatic Head ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Rank Test ◽  
Adjuvant Radiation ◽  
Pancreatic Head Cancer ◽  
Hazards Model ◽  
Kaplan Meier

4007 Background: NRG/RTOG 0848 is a 2-step study designed to determine whether erlotinib (E) added to gemcitabine (G) (randomized Ph II) &/or adjuvant radiation with concurrent 5-FU or capecitabine following 6 months of systemic chemotherapy (Ph III), improve survival in patients (pts) with resected pancreatic head adenocarcinoma. The erlotinib results are reported here. Methods: Eligible pts include those with resected pancreatic head adenocarcinoma, pathologic stage T1-T3, N0-1, M0; PS 0-1, & CA19-9 ≤ 180 IU/L. Pts in Arms 1 & 2 received G 1 gm/m2 weekly for 3 weeks in a 28-day cycle for 6 cycles. Pts in Arm 2 also received E 100 mg/day. The primary hypothesis for the E portion was that G+E would increase overall survival (OS) compared to G alone. With a 1-sided alpha of 0.15, 200 OS events provide 80%/90% power to detect a signal for an increase in median OS from 22 to 28.8/30.6 months (mos). OS was estimated by the Kaplan-Meier method & arms compared using the log rank test. The Cox proportional hazards model was used to analyze treatment effect. Results: 336 pts were randomized from 11/17/2009 to 2/28/2014, with 163 pts evaluable for G and 159 for G+E. Median age was 63 years (39-86). Most pts had pathologic T3 disease (78%) & CA19-9 ≤ 90 (93%). There are 32 pts (20%) with grade 4 adverse events (AEs) & 2 pts (1%) with grade 5 AEs on G and 27 (17%) & 3 (2%) on G+E arm, respectively. There are fewer grade ≥ 3 GI AEs on the G arm (22%) as compared to the G+E arm (28%), and 110 (69.2%) & 93 (59.6%) pts received at least 85% of planned G dose for the G & G+E arms, respectively. 58% of E pts received at least 85% of planned E dose. The median follow-up for alive pts is 42.5 mos (min-max: < 1-75). With 203 deaths, median & 3-yr OS (95% CI) are 29.9 mos (21.7-33.4) & 39% (30, 45) for G and 28.1 mos (20.7-30.9) & 39% (31, 47) for G+E; log-rank p = 0.62. The hazard ratio (95% CI) comparing OS of G+E to G is 1.04 (0.79- 1.38). Conclusions: The addition of adjuvant E to G did not provide a signal for increased OS in pts with resected pancreatic head cancer compared to G alone. Accrual to the trial is continuing to answer the Ph III radiation question. Clinical trial information: NCT01013649.

Glucocorticoid receptor (GR) expression in circulating tumor cells (CTCs) to prognosticate overall survival (OS) for metastatic castration-resistant prostate cancer (mCRPC) patients (pts) treated with androgen receptor signaling inhibitors (ARSi).

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 194-194 ◽  
Author(s):  
David Wise ◽  
James Kelvin ◽  
Ryon Graf ◽  
Nicole A. Schreiber ◽  
Brigit McLaughlin ◽  
...  
Keyword(s):  
Protein Expression ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Predictive Biomarker ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Castration Resistant Prostate Cancer ◽  
Hazards Model ◽  
Kaplan Meier ◽  
The Impact

194 Background: Upregulation of GR protein expression in metastatic biopsies from pts with CRPC has previously been shown to correlate with resistance to enzalutamide and has been validated as a therapeutic target in pre-clinical studies. We sought to determine whether upregulated GR protein expression in CTCs from pts with progressing mCRPC predicted clinical outcomes following treatment with enzalutamide (E) or abiraterone (A). Methods: Pre-therapy blood samples from 54 pts with progressing mCRPC were subjected to CTC analysis using the Epic Sciences platform. Samples were examined to identify CK+ (CK+, CD45- cells, with intact nuclei, morph distinct) CTCs for GR protein expression. GR+ CTCs were defined as having expression greater than the 95th percentile of GR expression in the GR negative LNCAP cell line. Kaplan-Meier analysis was used to test the impact of GR+ CTCs on OS following treatment with A or E. A Cox proportional hazards model with CTC number and GR positivity was used in a multivariate analysis. Results: 37 out of 54 pts (69%) had detectable and viable CK+ CTCs. 28 out of 37 pts (76%) had CTCs with upregulated GR staining with a median of 6 GR+/CK+ cells/ml per patient (range 0.7 – 244 cells/ml). The OS of patients with GR+ CTCs treated with ARSi was significantly worse than that of patients without detectable GR+ CTCs (11.4 mo. vs NA, p < 0.01), an effect independent and additive to the presence of viable CTCs, a previously described prognostic biomarker (see Table). Conclusions: GR protein upregulation in CTCs can be detected in a significant percentage of pts with progressing mCRPC and the presence of GR+ CTCs predicts worse OS in response to ARSi. The data supports previously reported pre-clinical data proposing a pathogenic role for GR in mediating resistance to ARSi therapy. Detection of GR in patient CTCs may be a useful predictive biomarker to guide GR-directed therapies. [Table: see text]

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