Prognostic factors of the loss of autonomy (LoA) in older patients with cancer receiving first-line chemotherapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9012-9012
Author(s):  
Pierre-Louis Soubeyran ◽  
Marianne Fonck ◽  
Laurent Hoppenreys ◽  
Stephanie Hoppe ◽  
Carine Bellera ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Performance Status ◽  
Clinical Information ◽  
Close Link ◽  
Risk Of Death ◽  
Increased Risk ◽  
Geriatric Evaluation ◽  
Pre Treatment ◽  
Ecog Ps ◽  
Line Chemotherapy

9012 Background: Actual data on prognostic geriatric factors of health outcomes are lacking. We aimed to examine whether a decrease in autonomy for activities of daily living (ADL) after a first cycle of chemotherapy influences elderly cancer pts prognosis, and to determine prognostic factors of this LoA from a range of biological and geriatric evaluation factors. Methods: Pts> 70 years receiving 1st-line chemotherapy for a range of cancers were included in this multicentre prospective study. A LoA was defined as a decrease of 0.5 or more points on the ADL scale between the beginning of treatment and the 2nd cycle (ADL scored 6 to 0). The association between a LoA and OS was examined and prognostic factors were sought from the pre-treatment Geriatric Assessment data (CIRS-G, IADL, MNA, MMSE, GDS et Get up and Go) and from baseline biological and clinical information (age, sex, tumor extension and localization, performance status, BMI, weight loss, albumin, CRP, haemoglobin levels, leucocyte and platelet count, creatinine clearance). Pts completely dependent at baseline (ADL score 0) were excluded as a LoA was not possible. Results: Among 364 pts included, 299 pts were evaluable and 50 experienced a LoA. A LoA was significantly associated with an increased risk of death (RR 1.518, 95%CI[1.079-2.135]). Biological and clinical factors were not associated with LoA but pre-treatment low GDS15, dependencies on the IADL, low MMS, slow Get Up and Go, low ECOG-PS and poor MNA were found to be prognostic of a LoA in univariate analyses. In the multivariate model, low GDS (OR 2.4, p=0.01, 95%CI [1.23-4.66]) and dependencies on the IADL (OR 3.0, p= 0.027, 95%CI = [1.13-9.09]) were independently associated with an increased risk of LoA. Conclusions: Our study underlines the close link between LoA during treatment and poorer prognosis of elderly pts with cancer. Pts with a pre-treatment low GDS15 and IADL-dependent were the most likely to experience LoA after the 1st chemotherapy cycle. This research suggests that the GDS15 and IADL should be included as part of any screening for elderly pts before treatment.

Prognostic factors in metastatic gastric cancer patients (pts) treated with second-line chemotherapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15169-15169
Author(s):  
V. Catalano ◽  
F. Graziano ◽  
D. Santini ◽  
A. M. Baldelli ◽  
P. Giordani ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Weight Loss ◽  
Prognostic Factors ◽  
Performance Status ◽  
Second Line ◽  
First Line ◽  
Second Line Chemotherapy ◽  
Metastatic Sites ◽  
Ecog Ps ◽  
Line Chemotherapy

15169 Background: Currently, there is no established second-line chemotherapy for pts with advanced gastric cancer who failed to respond or progressed after a first-line chemotherapy. Many of these pts still have a good performance status or have symptoms to be palliated at the time of first-line failure and are candidates for second-line chemotherapy. However, phase II trials demonstrate divergent results about pts more likely to benefit from second-line chemotherapy. We retrospectively analyzed the influence of various clinicopathologic factors on the survival of pts treated with second-line chemotherapy. Methods: Analysis is based on the data of 169 pts consecutively treated at 3 oncology department with a second-line chemotherapy. Univariate and multivariate analyses were performed to determine prognostic factors of survival. The variable used for analysis were: sex, age, ECOG performance status, a weight loss > 5 Kg in the last month; site of primary tumor, histopathology; hemoglobin, serum albumin, and CEA levels, number and site of metastatic disease, response to and time-to-progression (TTP) with the first- line chemotherapy. Results: The variables predictive of better survival were: ECOG PS 0–1 (p<0.001), no weight loss (p=0.001), hemoglobin level > 10 g/dl (p=0.01), CEA level <50 U/ml (p<0.02), number of metastatic sites = 2 (p=0.002), TTP of the first-line chemotherapy > 4 months (p=0.008). Peritoneal carcinomatosis was predictive of poor survival only when associated with one or more signs or symptoms as vomiting, anorexia, abdominal pain, ascites(p=0.03). Four factors were independently associated with better overall survival: ECOG PS 0–1 (p=0.002; HR 0.46; CI 95%, 0.29–0.75), CEA level <50 U/ml (p=0.008; HR 0.54; CI 95%, 0.35–0.85), one or two metastatic sites of disease (p=0.01; HR 0.58; CI 95%, 0.39–0.88), and TTP of the first-line chemotherapy > 4 months (p=0.02; HR 0.66; CI 95%, 0.45–0.95). Conclusions: In the absence of data deriving from randomized, controlled, clinical trials, this analysis suggests that some clinical factors may help clinicians to better select groups of pts with gastric cancer more likely to benefit from a second-line chemotherapy. No significant financial relationships to disclose.

Prognostic significance of patient-physician disagreement about performance status in patients with advanced cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 9021-9021 ◽  
Author(s):  
I. D. Schnadig ◽  
E. K. Fromme ◽  
C. L. Loprinzi ◽  
J. A. Sloan ◽  
M. Mori ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Nutritional Status ◽  
Cox Regression ◽  
Performance Status ◽  
Prognostic Significance ◽  
Risk Of Death ◽  
Increased Risk ◽  
Advanced Malignancies ◽  
The Difference ◽  
Ecog Ps

9021 Background: Physician-reported performance status (PS) is an important prognostic factor in advanced malignancies and is a commonly used stratification variable in cancer clinical trials. However, the extent, predictors, and prognostic importance of disagreement in PS assessment between physicians and patients have not been examined. Methods: Using NCCTG clinical trials from 1987–1990 (J Clin Oncol 19(15):3539–3546, 2001), we analyzed the difference and agreement of PS (ECOG and Karnofsky [KPS]) and nutritional status assessments reported by physicians and patients individually. The degree of disagreement was analyzed using paired t-test. Overall mortality was estimated by Kaplan-Meier method. The effect of disagreement on overall survival was analyzed by Cox regression. Independent predictors of disagreement were identified by logistic regression. Results: 1,636 patients with advanced lung and colorectal cancer had a median survival of 9.8 months (95% CI, 9.4 to 10.4). Percent agreement between patients and physicians about KPS, ECOG PS, and appetite/nutritional status was 32.9%, 43.4% and 42.0% respectively. Physicians were more likely to rate patients better than individual patients were to rate themselves: ECOG (Mean 0.91 vs 1.30, p<.0001), KPS (Mean 83.3 vs. 81.7, p<0.0001), appetite/nutritional status (Mean 1.6 vs. 2.1, p<0.0001). Inability to work, depression and less than a high school education were independently associated with disagreement. An increased risk of death was observed for patient and physician disagreement on KPS (HR=1.15, 95% CI, 1.03 to 1.27 p=0.01) and appetite/nutritional status (HR=1.39, 95% CI, 1.26 to 1.54 p<0.0001). Conclusions: Patients and physicians frequently disagree about patient PS, with physicians tending to rate patients higher than patients do themselves. Baseline patient demographic factors that independently predict disagreement have been identified. Disagreement confers an increased risk of death in the setting of advanced malignancies. These findings illustrate limitations of physician-only assessed PS. No significant financial relationships to disclose.

scholarly journals Outcomes and Prognostic Factors in a Large Cohort of Hospitalized Cancer Patients With COVID-19

2021 ◽  
pp. 1084-1092
Author(s):  
Guilherme Nader Marta ◽  
Renata Colombo Bonadio ◽  
Odeli Nicole Encinas Sejas ◽  
Gabriel Watarai ◽  
Maria Cecilia Mathias Machado ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Mortality Rate ◽  
Group Performance ◽  
Lung Metastases ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Primary Lung Cancer ◽  
Patients With Cancer ◽  
Risk Of Death ◽  
Increased Risk

PURPOSE Patients with cancer are at increased risk for unfavorable outcomes from COVID-19. Knowledge about the outcome determinants of severe acute respiratory syndrome coronavirus 2 infection in this population is essential for risk stratification and definition of appropriate management. Our objective was to evaluate prognostic factors for all-cause mortality in patients diagnosed with both cancer and COVID-19. METHODS All consecutive patients with cancer hospitalized at our institution with COVID-19 were included. Electronic medical records were reviewed for clinical and laboratory characteristics potentially associated with outcomes. RESULTS Five hundred seventy-six consecutive patients with cancer and COVID-19 were included in the present study. An overall in-hospital mortality rate of 49.3% was demonstrated. Clinical factors associated with increased risk of death because of COVID-19 were age over 65 years, Eastern Cooperative Oncology Group performance status > 0 zero, best supportive care, primary lung cancer, and the presence of lung metastases. Laboratory findings associated with a higher risk of unfavorable outcomes were neutrophilia, lymphopenia, and elevated levels of D-dimer, creatinine, C-reactive protein, or AST. CONCLUSION A high mortality rate in patients with cancer who were diagnosed with COVID-19 was demonstrated in the present study, emphasizing the need for close surveillance in this group of patients, especially in those with unfavorable prognostic characteristics.

scholarly journals A Retrospective Cross Sectional Study of Clinical Characteristics and Prognostic Factors of Covid 19 Patients Admitted to a Gambian Teaching Hospital

2021 ◽  
Author(s):  
Sheikh Omar Bittaye ◽  
Abubacarr Jagne ◽  
Abdoulie Badjan ◽  
Babakunta Fofana ◽  
Ebrima Barrow ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Prognostic Factors ◽  
Oxygen Saturation ◽  
Respiratory Rate ◽  
Health Facility ◽  
Teaching Hospital ◽  
Clinical Characteristics ◽  
Risk Of Death ◽  
Increased Risk ◽  
Lower Level Health Facility

Abstract Background: The first case of Novel coronavirus disease (COVID 19) was diagnosed in The Gambia on the 17th March 2020. We therefore investigate the clinical characteristics and prognostic factors of COVID 19 patients admitted at a Gambian teaching Hospital. Method: Out of 407 suspected COVID 19 patients, 137 (33.7%) tested positive for COVID 19 and were recruited. Clinical features, treatment and outcomes were recorded. Univariate and multivariate logistic regression analyses were used to assess prognostic factors of survival in our patients. Results: The median age of our patients was 60 years (19-100) and 86 (62.8%) were men. Eighty nine (64.9%) patients had co-morbidities, mostly Hypertension 51 (37.2%) and Diabetes Mellitus 47 (34.3%). The most common symptoms were cough 71 (51.8%) and dyspnea 53 (38.7%) and majority of patients presented with SPO ≤ 93% 75 (54.7%). Patients with SPO2 ≤ 93% were older 63.2 vs. 53.1 years (p=0.001), more likely to present with dyspnea (p=0.002), Cough (0.035), higher respiratory rate (p<0.001) and co-morbidities (p=0.009) compared to patients with SPO2>93%. Non survivors were older 63.2 vs 53.1 years (p=0.001), more likely to present with higher respiratory rate (p=0.014), lower oxygen saturation (p=<0.001), to be referred from lower level health facility (p=0.012) and to have Diabetes mellitus (p=0.007) as compared to survivors. Our cumulative mortality is 49 (35.8%) and mortality rate of patients referred from lower level heath facilities was 46 % as compared to 25 % for self referred patients. Multivariate analysis showed increasing odds of mortality independently associated with Age≥ 60 years (odd ratio, 2.87: 95% CI, 1.21 to 6.83, p=0.012), Diabetes mellitus (odd ratio, 3.47: 95% CI, 1.44 to 8.36, p=0.006), oxygen saturation ≤ 93% (odd ratio, 3.18: 95% CI, 1.27 to 7.99, p=0.014) and referral from lower level health facility (odd ratio, 2.87: 95% CI, 1.11 to 6.82, p=0.017).Conclusion: Older patients, patients with Diabetes Mellitus, hypoxemia or patients referred from lower level health facilities are at increased risk of death. In resource limited countries where critical care/emergency medicine resources are limited, our results may help guide the clinical management of patients with severe COVID-19.

Prognostic impact of chemoradiation-related lymphopenia in patients with gastric and gastroesophageal cancer.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 249-249
Author(s):  
Daniel W Kim ◽  
Grace Lee ◽  
Theodore S. Hong ◽  
Guichao Li ◽  
Eric Roeland ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Cox Model ◽  
Gastroesophageal Junction ◽  
Concurrent Chemotherapy ◽  
Rank Test ◽  
Prognostic Impact ◽  
Poor Prognostic Factor ◽  
Risk Of Death ◽  
Increased Risk ◽  
Ecog Ps

249 Background: Limited data exists on how chemoradiation (CRT)-induced lymphopenia affects survival outcomes in patients with gastric and gastroesophageal junction (GEJ) cancer. We evaluated the association between severe lymphopenia and its association with survival in gastric and GEJ cancer patients treated with CRT. We hypothesized that severe lymphopenia would be a poor prognostic factor. Methods: We performed a retrospective analysis of 154 patients with stage 1-3 gastric or GEJ cancer who underwent CRT at our institution. Patients underwent photon-based radiation therapy (RT) with a median dose of 50.4 Gy (IQR 45.0-50.4 Gy) over 28 fractions and concurrent chemotherapy (CTX) with carboplatin/paclitaxel, 5-fluorouracil based regimen, or capecitabine. 49% received CTX prior to RT. 84% underwent surgical resection, 57% pre-CRT and 26% post-CRT. Absolute lymphocyte count (ALC) at baseline and at 2 months since initiating RT were analyzed. Severe lymphopenia, defined as Grade 3 or worse lymphopenia (ALC < 0.5 k/μl), was analyzed for any association with overall survival (OS). Results: Median time of follow up was 48 months. Median age was 65. 77% were male and 86% were Caucasian. ECOG PS was 0 or 1 in 90% and 2 in 10%. Tumor location was stomach in 38% and GEJ in 62%. Timing of CRT was preoperative among 68% and postoperative among 32%. The median ALC at baseline for the entire cohort was 1.6 k/ul (range 0.3-7.0 k/ul). At 2 months post-CRT, 49 (32%) patients had severe lymphopenia. Patients with severe lymphopenia post-CRT had a slightly lower baseline TLC compared to patients without severe lymphopenia (median TLC 1.4 k/ul vs. 1.6 k/ul; p = 0.005). There were no differences in disease and treatment characteristics between the two groups. On the multivariable Cox model, severe lymphopenia post-CRT was significantly associated with increased risk of death (HR = 3.99 [95% CI 1.55-10.28], p = 0.004). ECOG PS 2 (HR = 34.97 [95% CI 2.08-587.73], p = 0.014) and postoperative CRT (HR = 5.55 [95% CI 1.29-23.86], p = 0.021) also predicted worse OS. The 4-year OS among patients with severe lymphopenia was 41% vs. 61% among patients with vs. without severe lymphopenia (log-rank test p = 0.041). Conclusions: Severe lymphopenia significantly correlated with poorer OS in patients with gastric or GEJ cancer treated with CRT. CRT-induced lymphopenia may be an important prognostic factor for survival in this patient population. Closer observation in high-risk patients and treatment modifications may be potential approaches to mitigating CRT-induced lymphopenia.

Complications following symptom-limited thoracentesis using suction

2020 ◽  
Vol 56 (5) ◽  
pp. 1902356 ◽  
Author(s):  
Ala Eddin S. Sagar ◽  
Maria F. Landaeta ◽  
Andres M. Adrianza ◽  
Grecia L. Aldana ◽  
Leonardo Pozo ◽  
...  
Keyword(s):  
Pleural Fluid ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Chest Discomfort ◽  
Mediastinal Shift ◽  
Increased Risk ◽  
Procedural Complications ◽  
Ecog Ps ◽  
Current Guidelines

BackgroundThoracentesis using suction is perceived to have increased risk of complications, including pneumothorax and re-expansion pulmonary oedema (REPO). Current guidelines recommend limiting drainage to 1.5 L to avoid REPO. Our purpose was to examine the incidence of complications with symptom-limited drainage of pleural fluid using suction and identify risk factors for REPO.MethodsA retrospective cohort study of all adult patients who underwent symptom-limited thoracentesis using suction at our institution between January 1, 2004 and August 31, 2018 was performed, and a total of 10 344 thoracenteses were included.ResultsPleural fluid ≥1.5 L was removed in 19% of the procedures. Thoracentesis was stopped due to chest discomfort (39%), complete drainage of fluid (37%) and persistent cough (13%). Pneumothorax based on chest radiography was detected in 3.98%, but only 0.28% required intervention. The incidence of REPO was 0.08%. The incidence of REPO increased with Eastern Cooperative Oncology Group performance status (ECOG PS) ≥3 compounded with ≥1.5 L (0.04–0.54%; 95% CI 0.13–2.06 L). Thoracentesis in those with ipsilateral mediastinal shift did not increase complications, but less fluid was removed (p<0.01).ConclusionsSymptom-limited thoracentesis using suction is safe even with large volumes. Pneumothorax requiring intervention and REPO are both rare. There were no increased procedural complications in those with ipsilateral mediastinal shift. REPO increased with poor ECOG PS and drainage ≥1.5 L. Symptom-limited drainage using suction without pleural manometry is safe.

Early Hb Response to ESA Treatment May Be An Indicator of Better Survival Prognosis

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4587-4587
Author(s):  
Jesse A Berlin ◽  
Peter Bowers ◽  
Sudhakar Rao ◽  
Suresh Aravind ◽  
Steven Sun ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Performance Status ◽  
Epoetin Alfa ◽  
Survival Prognosis ◽  
Risk Of Death ◽  
Hazards Model ◽  
Kaplan Meier ◽  
Increased Risk ◽  
Baseline Covariates

Abstract Chemotherapy induced anemia patients who respond to ESA treatment have hemoglobin increases within 4–8 weeks. Patients with inadequate Hb response after several weeks treatment often have their ESA dose escalated.. We conducted an exploratory analysis to test the hypothesis that safety outcomes in randomized studies of epoetin alfa might differ depending on the Hb response after 4–8 weeks of treatment. Methods: The analysis compared the survival across subsets of epoetin-alfa treated patients. Specifically, a landmark analysis was used, which defines a hemoglobin responder at a pre-specified point in time (in this case 4 & 8 weeks post treatment), and then examines survival subsequent to that point in time.Patients were categorized as “Hb responder” when their Hb increased by &gt;0.5 g/dL; “Hb stable” when Hb change within ≤ 0.5g/dL; “Hb non-responder” when the Hb decreased &gt;0.5 g/dL, compared to the value prior to epoetin-alfa treatment. Survival was estimated using the Kaplan-Meier method and comparisons were made between the responders and non-responders versus the stable group. Cox’s proportional hazards model was used to adjust for the following baseline covariates: hemoglobin prior to treatment, baseline performance status, and advanced disease at baseline. All analyses were stratified by study to account for any differences in the study populations and study conduct. Results: These exploratory findings suggest the possibility that patients identified as non-responders to ESAs after 4 or 8 weeks of ESA treatment may be at increased risk of death, and that this effect is most pronounced in the studies that treated patients beyond the correction of anemia. Although these analyses were adjusted for several key baseline covariates, it is unclear whether these effects result from treatment, or whether patients who fail to respond to epoetin alfa are inherently at increased risk of death (e.g., due underlying malignancy), regardless of their treatment status.

Expression of Phosphorylated Signal Transducer and Activator of Transcription 5 (pSTAT5) Is Associated with An Increased Risk of Death In Acute Myeloid Leukemia.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1675-1675
Author(s):  
Anna Brady ◽  
Sarah Gibson ◽  
Lisa Rybicki ◽  
Eric Hsi ◽  
Edward Copelan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Myeloid Leukemia ◽  
Signal Transducer ◽  
Newly Diagnosed ◽  
Risk Of Death ◽  
Increased Risk ◽  
History Of ◽  
Acute Myeloid

Abstract Abstract 1675 Background: Acute myeloid leukemia (AML) is characterized by rapid growth, resistance to therapy, and poor overall survival. Clinical and biologic prognostic markers can help define pathogenesis, guide treatment, and identify novel therapies. Phosphorylated signal transducer and activator of transcription 5 (pSTAT5) is one such potential marker. The transcription factor STAT5 regulates many aspects of cell growth, survival, and differentiation. Constitutive activation of STAT5 (by phosphorylation) has been identified in a number of malignancies, including AML. We investigated whether the level of pSTAT5 expression correlates with complete remission (CR) rates, progression-free survival (PFS), and overall survival (OS) in patients (pts) with newly diagnosed AML. Methods: From 1999 to 2005, all adult pts with newly diagnosed AML (WHO criteria) receiving induction chemotherapy and with an available diagnostic bone marrow biopsy performed at our institution were evaluated. B5-fixed bone marrow core biopsies were reviewed for areas with the highest concentration of blasts. A tissue microarray was constructed using 1 mm cores. The cores were arrayed in duplicate in the majority of samples. Immunohistochemistry was performed for pSTAT5 with anti-pSTAT5 a/b Y695/99 mouse monoclonal antibody (AX1; Advantex Bioreagents) using automated stainers and heat-induced epitope retrieval. In each case, five hundred blasts were counted. The percentage of cells staining positive for pSTAT5 expression was determined by a pathologist blinded to clinical results. Standard metaphase karyotypes were classified into cytogenetic (CG) risk groups by CALGB criteria. Cox proportional hazards analysis was used to identify univariate and multivariate prognostic factors for CR, PFS, and OS, including age at diagnosis, history of an antecedent hematologic disorder (AHD), WBC at diagnosis, pSTAT5 expression, and CG risk group. Results: Adequate tissue and clinical data were available in 112 pts. The median age was 57 years, and median WBC at diagnosis 12.0 K/ μL. Twenty six percent of pts had favorable CG, 41% intermediate risk, 27% high risk, and 6% other (unknown or could not be classified). Nineteen percent of pts had an AHD. pSTAT5 expression was absent in 58% of pts. The remainder of the pts had: 1–5% pSTAT5 (25% of pts), 10% pSTAT5 (11% of pts), 20% pSTAT5 (4% of pts), 30% pSTAT5 (1% of pts), and 50% pSTAT5 (2% of pts). Seventy percent of all pts achieved a CR following induction chemotherapy. Sixty-four percent of pts received post-remission chemotherapy, 3.6% an autologous transplant, and 13.6% an allogeneic transplant in first CR. Median PFS and OS were 9.6 months and 16.0 months, respectively. On univariate analysis, age, history of AHD, WBC at diagnosis, CG risk, and any pSTAT5 expression were prognostic factors for PFS and OS. In multivariable analyses controlling for the above prognostic factors, pSTAT5 expression > 0 was also significantly associated with an increased risk of death (HR 1.96, 95% CI 1.19–3.23, p=0.008), progression or death (HR 1.64, 95% CI 1.01–2.66, p=0.046), and relapse after achieving CR (HR 2.31, 95% CI 1.16–4.63, p=0.018). pSTAT5 expression was not a predictor of achievement of CR. Conclusions: pSTAT5 expression in newly diagnosed adults with AML is associated with a decreased PFS, decreased OS, and increased risk of relapse. Validation of its prognostic value requires additional study. Agents targeting this signaling pathway might improve the outcome of pts with AML. Disclosures: No relevant conflicts of interest to declare.

Study of genotypic variations and protein expression of the xCT subunit of cystine/glutamate transporter in pancreatic cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 210-210
Author(s):  
T. J. Huang ◽  
D. Li ◽  
Y. Li ◽  
S. P. Kar ◽  
S. Krishnan ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Protein Expression ◽  
Cox Regression ◽  
Performance Status ◽  
Glutamate Transporter ◽  
Supporting Evidence ◽  
Cox Regression Analysis ◽  
Risk Of Death ◽  
Increased Risk

210 Background: The plasma membrane xCT cystine-specific subunit of the cystine/glutamate transporter contributes to chemotherapy resistance in pancreatic cancer by regulating intracellular glutathione levels and protecting cancer cells against oxidative stress. We previously noted that the rs7674870 single nucleotide polymorphism (SNP) of xCT correlated with overall survival in pancreatic cancer and may be predictive of platinum resistance. There are no data regarding xCT protein expression in pancreatic cancer or the functional significance of this SNP. Methods: Paraffin-embedded core and surgical biopsy tumor specimens from 49 patients with metastatic pancreatic adenocarcinoma were analyzed by immunohistochemistry (IHC) using an xCT specific antibody (Novus Biologicals). xCT protein IHC expression scores (product of intensity and percentage of staining cells) were analyzed in relation to overall survival and genotype of the patients using the one factor ANOVA test, Kaplan-Meier plot, log-rank test, and Cox regression analysis. Overall survival was measured from the date of diagnosis to the date of death or last follow-up. Results: Positive xCT expression was detected in 38 (78%) of the 49 samples, and 9 (18%) patients had high levels of expression. High xCT expression was associated with lower overall survival as compared with low expression (5.1 months versus 8.8 months; p = 0.119). In a multivariate Cox regression model with adjustment for prognostic parameters of age, sex, performance status and CA19-9 level, high xCT expression was associated with a 2.1-fold increased risk of death (p = 0.096). Performance status also correlated with overall survival (p = 0.027). Preliminary analysis on the genotype-phenotype association (n = 12) indicated that xCT expression was higher with the TT genotype than the TC/CC genotype (p = 0.115), which is consistent with the previous observation that the TT genotype was associated with reduced survival. Conclusions: These data provide supporting evidence for a possible role of cystine/glutamate transporter xCT subunit in pancreatic cancer progression and survival. Further pharmacogenomic and clinicopathologic studies are ongoing. No significant financial relationships to disclose.

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