Use of DPC-4 immunostaining of diagnostic cytology specimens to predict the pattern of tumor progression in locally advanced pancreatic cancer patients (LAPC).

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 209-209 ◽  
Author(s):  
C. H. Crane ◽  
J. S. Yordy ◽  
G. R. Varadhachary ◽  
W. Haque ◽  
R. A. Wolff ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Clinical Symptoms ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Locally Advanced Pancreatic Cancer ◽  
Disease Spread ◽  
Autopsy Study ◽  
Potential Biomarker ◽  
Significant Difference

209 Background: An autopsy study has identified DPC-4 as a potential biomarker of the pattern of disease spread in pancreatic cancer patients (Iacobuzio-Donahue et al, JCO, 2009). We sought to determine whether DPC-4 expression determined by immunohistochemistry (IHC) staining of primary tumor cytology specimens correlates with the clinical pattern of progression in patients with locally advanced pancreatic cancer (LAPC). Methods: LAPC patients with ECOG 0-1 PS were treated with gemcitabine (1000 mg/m2), oxaliplatin (100 mg/m2), and cetuximab for (500mg/m2) q2wks for 4 doses followed by XRT (50.4 Gy to the gross tumor only) with capecitabine (825 mg/m2 twice daily, days of radiation) and cetuximab on a multiinstitutional trial. Forty-one of 58 patients treated at our institution had cytology specimens suitable for IHC staining. The patterns of progression were determined based on radiographic studies and clinical symptoms. Findings were blinded from the IHC results. Patients were categorized as 1) local disease dominant, 2) distant disease dominant, 3) indeterminate pattern, and 4) no progression. The IHC scoring of DPC-4 was determined by an experienced cytopathologist who was blinded from the clinical data. Results: Median, 1yr and 3yr actuarial OS are 18.2 months, 67.2% and 18.5%. Dominant progression pattern was local (n=15), distant (n=14), indeterminate (n=8), and no progression (n=4). Intact DPC expression correlated with local dominant progression (11/15) and DPC-4 loss correlated with distant dominant progression (10/14), p=0.016. The median DM free survival rate was 18.0 for intact DPC-4 versus 12.5 mo for DPC-4 loss patients (p=NS). There was no significant difference in overall survival based on DPC-4 status. Conclusions: Determination of DPC-4 expression from cytology specimens is feasible. DPC-4 expression correlated with the pattern of progression and is consistent with previous autopsy data. DPC-4 expression does not appear to be predictive or prognostic. Prospective validation of DPC-4 as a biomarker of disease progression is warranted and may lead to personalized treatment strategies for patients with LAPC. [Table: see text]

Randomized Controlled Trial Of Dalteparin For Primary Thromboprophylaxis For Venous Thromboembolism (VTE) In Patients With Advanced Pancreatic Cancer (APC): Risk Factors Predictive Of VTE

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 580-580 ◽  
Author(s):  
Saroj Vadhan-Raj ◽  
Xiao Zhou ◽  
Gauri R. Varadhachary ◽  
Javle Milind ◽  
David Fogelman ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Baseline Risk ◽  
Activation Markers ◽  
Compression Ultrasound ◽  
Significant Difference ◽  
D Dimer

Abstract Background Risk of VTE is high in cancer patients, especially, in patients with APC. Treatment with chemotherapy further increases the risk. Purpose of the study was to evaluate the safety and efficacy of primary thromboprophylaxis with dalteparin in reducing the incidence of VTE in APC patients planned to start chemotherapy; and to determine the baseline risk factors/biomarkers predictive of VTE. Methods Patients with metastatic or locally advanced pancreatic cancer planned to start chemotherapy were randomized 1:1 to dalteparin vs control arms, stratified for the presence of metastasis and central venous catheter (CVC). The treatment arm received dalteparin 5000 U SQ daily for 16 weeks during chemotherapy and the control arm received chemotherapy alone. Bilateral compression ultrasound of the lower extremities was performed at baseline, and during study (weeks-8 and-16). In addition, blood was collected to identify biomarkers such as, plasma D-dimer levels, platelet activation markers (P-selectin), thrombin-antithrombin complex (TAT), prothrombin fragments 1 and 2 (F1+2), and cytokine levels. Univariate and multivariate logistic regression analysis of clinical and laboratory parameters were done to identify risk factors associated with the development of VTE. Results Of 87 patients enrolled, 75 were randomized to dalteparin (38 patients) or control (37 patients) arms; 8 did not meet the eligibility criteria (including 6 found positive for incidental VTE on screening ultrasound), and 4 withdrew consents before randomization. There were 41 males and 34 females; with median age 52 (range, 36-77 years). Over half of the patients (55% dalteparin arm and 54% control arm) completed 16 weeks on study. All 75 patients were evaluable for response in an intent-to-treat analysis. During the study, the incidence of VTE was 22% [8/37 patients; 2 pulmonary emboli (PE) and 6 deep vein thrombosis (DVT)] on the control arm as compared to 5% (2/38 patients; both DVT) on the dalteparin arm (p = 0.02). In the multivariate analysis, baseline plasma levels of D-dimer, ECOG performance status, presence of CVC, and prophylaxis with dalteparin were independent factors predictive of risk for VTE, as shown below. There was no statistically significant difference in overall survival between the two arms; however, there were higher proportion of patients with elevated baseline D-dimer levels in the dalteparin arm than the control arm (≥ 5000 ng/mL 16% vs 3%). Elevated baseline D-dimer level (≥ 5000 ng/mL) was also predictive of the presence of silent or asymptomatic VTE at screening for study entry (p=0.001), suggesting its potential value in identifying patients with silent VTE. Treatment with dalteparin was well tolerated; the main adverse events included minimal bruising (5/34, 15%), or pain (2/34, 6%) at the injection sites. There were no clinically significant bleeding episodes in the dalteparin arm. Conclusions The results of this study showed that the incidence of VTE is very high in patients with APC. Primary thromboprophylaxis with dalteparin was well tolerated and was associated with 75% reduction in the incidence of VTE in ambulatory patients with locally advanced or metastatic cancer while receiving chemotherapy. Baseline risk factors such as elevated D-dimer levels may help identify high risk patients for primary thromboprophylaxis as well as patients with the presence of asymptomatic VTE. Disclosures: Vadhan-Raj: Eisai: Research Funding. Off Label Use: Fragmin (Dalteparin): Prophylaxis of VTE in ambulatory cancer patients while receiving chemotherapy.

Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as prognostic factors for locally advanced pancreatic cancer patients.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 326-326
Author(s):  
Byung Min Lee ◽  
Seung Yeun Chung ◽  
Jee Suk Chang ◽  
Kyong Joo Lee ◽  
Si Young Song ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Cancer Patients ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Locally Advanced Pancreatic Cancer ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Pre Treatment

326 Background: It is well known that locally advanced pancreatic cancer patients have a poor prognosis. Recently, hematologic markers showing systemic inflammatory status such as neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have aroused much attention due to its potential to predict patient survival. In this study, we investigated whether pre-treatment NLR and PLR independently and in combination would be significant prognostic factors for survival in locally advanced pancreatic cancer patients. Methods: A total of 497 locally advanced (borderline resectable and unresectable) pancreatic cancer patients who received neoadjuvant or definitive chemoradiotherapy (CCRT) between January 2005 and December 2015 were included in this study. NLR and PLR prior to the start of treatment within 2 weeks were defined as pre-treatment NLR and PLR. We divided the patients with the median values of pre-treatment NLR and PLR; NLR < 2.44 group (n = 248), NLR ≥ 2.44 group (n = 249), PLR < 149 group (n = 248) and PLR ≥ 149 (n = 249) group. Overall survival (OS) and progression-free survival (PFS) were compared between each group for NLR and PLR. Results: Median overall survival was 15.7 months (range, 2.3-128.5 months). For NLR, the OS, PFS rates were significantly lower in the NLR ≥ 2.44 group, with 1-year OS rates of 67.9% and 61.5% (p = 0.003) and 1-year PFS rates of 38.1% and 32.4% (p = 0.003), for NLR < 2.44 and ≥ 2.44 group, respectively. The PLR ≥ 149 group also showed significantly poorer OS and PFS than PLR < 149 group. The 1-year OS rates were 68.1% and 61.3% (p = 0.029) and 1-year PFS rates were 37.9% and 32.5% (p = 0.027), for PLR < 149 and ≥ 149 group, respectively. When multivariate analysis was performed, NLR ≥ 2.44 remained as a significant adverse factor for OS (p = 0.011) and PFS (p = 0.026). PLR > 149 also proved to be a significant factor for poorer OS (p = 0.003) and PFS (p = 0.021). Conclusions: Elevated pre-treatment NLR and PLR independently and in combination significantly predicted poor OS and PFS. Pre-treatment NLR and PLR are useful prognostic factors for OS and PFS in locally advanced pancreatic cancer patients.

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