Recent Trends in the Incidence and Survival of Stage 1A Pancreatic Cancer: A Surveillance, Epidemiology, and End Results Analysis

Abstract Background Rapid access to pancreatic imaging and regular pancreatic surveillance may help identify stage I pancreatic cancer. We investigated recent trends in the stage of newly diagnosed pancreatic ductal adenocarcinoma (PDACs), age at diagnosis, and survival. Methods Trends in age-adjusted incidence of stage IA PDAC between 2004 and 2016 were determined from the National Cancer Institute’s Surveillance, Epidemiology and End Results database. All tests were two-sided. Results The incidence of stage IA PDAC cases diagnosed increased statistically significantly from 2004 to 2016 (annual percent change = 14.5, 95% confidence interval [CI] = 11.4 to 17.7; P < .001). During the study period, average age at diagnosis for stage IA and IB casesAQ3 declined by 3.5 years (95% CI = 1.2 to 5.9; P = .004) and 5.5 years (95% CI = 3.4 to 7.6; P < .001), whereas average age increased for higher-stage cases (by 0.6 to 1.4 years). Among stage IA cases, the proportion of blacks was smaller (10.2% vs 12.5%), and the proportion of other non-Caucasians was higher compared with higher-stage cases (11.9% vs 8.4%; P < .001). Stage IA cases were more likely to carry insurance (vs Medicaid or none) than higher-stage cases (cases aged younger than 65 years; odds ratio = 2.45, 95% CI = 1.96 to 3.06; P < .001). The 5-year overall survival for stage IA PDAC improved from 44.7% (95% CI = 31.4 to 63.7) in 2004 to 83.7% (95% CI = 78.6% to 89.2%) in 2012; 10-year survival improved from 36.7% (95% CI = 24.1 to 55.8) in 2004 to 49.0% (95% CI = 37.2% to 64.6%) in 2007. Conclusions In recent years, the proportion of patients diagnosed with stage IA PDAC has increased, their average age at diagnosis has decreased, and their overall survival has improved. These trends may be the result of improved early diagnosis and early detection.

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Somatic Mutation Profiling in the Liquid Biopsy and Clinical Analysis of Hereditary and Familial Pancreatic Cancer Cases Reveals KRAS Negativity and a Longer Overall Survival

Cancers ◽

10.3390/cancers13071612 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1612

Author(s):

Julie Earl ◽

Emma Barreto ◽

María E. Castillo ◽

Raquel Fuentes ◽

Mercedes Rodríguez-Garrote ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Somatic Mutation ◽

Disease Status ◽

Clinical Analysis ◽

Cytotoxic Agents ◽

Disease Stage ◽

Ductal Adenocarcinoma ◽

Familial Pancreatic Cancer ◽

Circulating Free Dna

Pancreatic ductal adenocarcinoma (PDAC) presents many challenges in the clinic and there are many areas for improvement in diagnostics and patient management. The five-year survival rate is around 7.2% as the majority of patients present with advanced disease at diagnosis that is treatment resistant. Approximately 10–15% of PDAC cases have a hereditary basis or Familial Pancreatic Cancer (FPC). Here we demonstrate the use of circulating free DNA (cfDNA) in plasma as a prognostic biomarker in PDAC. The levels of cfDNA correlated with disease status, disease stage, and overall survival. Furthermore, we show for the first time via BEAMing that the majority of hereditary or familial PDAC cases (around 84%) are negative for a KRAS somatic mutation. In addition, KRAS mutation negative cases harbor somatic mutations in potentially druggable genes such as KIT, PDGFR, MET, BRAF, and PIK3CA that could be exploited in the clinic. Finally, familial or hereditary cases have a longer overall survival compared to sporadic cases (10.2 vs. 21.7 months, respectively). Currently, all patients are treated the same in the clinic with cytotoxic agents, although here we demonstrate that there are different subtypes of tumors at the genetic level that could pave the way to personalized treatment.

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Precursors of pancreatic cancer in background of chronic opisthorchiasis

Medical Science And Education Of Ural ◽

10.36361/1814-8999-2021-22-1-118-121 ◽

2021 ◽

Vol 22 (1) ◽

pp. 118-121

Author(s):

V. U. Rayn ◽

◽

M. A. Persidskiy ◽

E. V. Malakhova ◽

I. V. Anuchina ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Pancreatic Ductal Adenocarcinoma ◽

Disease Free Survival ◽

Morphological Data ◽

Small Samples ◽

Ductal Adenocarcinoma ◽

Preneoplastic Lesions ◽

Opisthorchis Felineus ◽

Disease Free

Aim. To establish the association between pancreatic cancer precursor lesions and chronic opisthorchiasis. Materials and methods. A single center case-control study was conducted at a low-volume pancreatic surgery center in Khanty-Mansiysk. We retrospectively collected morphological data from 47 pancreatoduodenectomies performed for pancreatic ductal adenocarcinoma. The study group included 23 cases of pancreatic ductal adenocarcinoma with concomitant chronic Opisthorchis felineus invasion which were compared to 24 controls consisting of “pure” cancer. Qualitative analysis was performed using χ2 Pearson criterion. Exact Fisher test was used for small samples. Time to progression and overall survival rates were calculated using Kaplan-Meier survival analysis. Data were collected and analyzed in Statistica 7.0. Results. PanINs were seen in 41,7% pancreata resected for ductal adenocarcinoma of the head and in 95,7% cases of pancreatic cancer in background of chronic opisthorchiasis (р = 0,000; 95% CI 3,5-268). PanIN high grade were observed only in opisthorchiasis group. In mixed pathology invasive cancer component tended to be more dedifferentiated and advanced when compared to pure cancer group (p = 0,029). Median disease free survival was 9 mo. in both groups and overall survival was 13 mo. in non-opisthorchiasis group and 15,3 mo. in opisthorchiasis group (р = 0,437). Conclusion. Chronic opisthorchiasis is associated with pancreatic intraepithelial neoplasia. Pancreatic ductal adenocarcinoma in background of opisthorchiasis with preneoplastic lesions tend to be more advanced in stage and poorly differentiated. Disease free and overall survival have no statistically significant differences in patients with and without Opisthorchis felineus invasion.

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The Role of Nanoliposomal Irinotecan Plus Fluorouracil and Folinic Acid as Second-Line Treatment Option in Patients With Metastatic Pancreatic Ductal Adenocarcinoma

10.21203/rs.3.rs-489414/v1 ◽

2021 ◽

Author(s):

Se Jun Park ◽

Hyunho Kim ◽

Kabsoo Shin ◽

Tae Ho Hong ◽

Ja Hee Suh ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Adverse Events ◽

Pancreatic Ductal Adenocarcinoma ◽

Real World ◽

Median Overall Survival ◽

Ductal Adenocarcinoma ◽

Nanoliposomal Irinotecan ◽

Previously Treated ◽

Grade 3

Abstract BackgroundAccording to the NAPOLI-1 trial, nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) showed improved overall survival compared to fluorouracil alone for patients with metastatic pancreatic cancer who previously treated gemcitabine-based therapy. In that trial, Asian patients had frequent dose modification due to hematological toxicity. There has been limited information on the clinical benefit and toxicity of this regimen in a real-world setting. Herein, we assessed real-world experience of nal-IRI plus 5-FU/LV in patients with advanced pancreatic cancer after gemcitabine failure.MethodsWe conducted a single institution retrospective analysis of response, survival and safety in patients who had been treated with nal-IRI with 5-FU/LV. Patients with metastatic pancreatic ductal adenocarcinoma previously treated with gemcitabine-based therapy received nal-IRI (80mg/m2) with 5-FU/LV every 2 weeks. ResultsFifty-one patients received nal-IRI plus 5-FU/LV between January 2015 and December 2020. The median age was 67 years, and males were 58.8%. A total of 40 (78.4%) and 11 (21.6%) patients had received one and two lines of prior chemotherapy before enrollment, respectively. Median progression-free survival was 2.8 months (95% confidence interval [CI] 1.8-3.7) and median overall survival was 7.0 months (95% CI 6.0-7.9). Chemotherapy doses were reduced or delayed in 33 (64.7%) patients during the first 6 weeks and median relative dose intensity was 0.87. Thirty-six (70.6%) patients experienced any grade 3 or 4 adverse events. Most common grade 3 or 4 adverse event was neutropenia (58.8%) and most non-hematologic adverse events were under grade 2. Since the start of first-line chemotherapy, median overall survival was 16.3 months (95% CI 14.1-18.4).ConclusionsNal-IRI plus 5-FU/LV seems to be effective, with manageable toxicities, after gemcitabine-based treatment in patients with metastatic pancreatic ductal adenocarcinoma. Trial registration Retrospectively registered

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Incidence patterns for primary malignant spinal cord gliomas: a Surveillance, Epidemiology, and End Results study

Journal of Neurosurgery Spine ◽

10.3171/2011.1.spine10351 ◽

2011 ◽

Vol 14 (6) ◽

pp. 742-747 ◽

Cited By ~ 24

Author(s):

Steven Hsu ◽

Marisa Quattrone ◽

Quinn Ostrom ◽

Timothy C. Ryken ◽

Andrew E. Sloan ◽

...

Keyword(s):

Spinal Cord ◽

Surgical Techniques ◽

Incidence Rates ◽

Primary Site ◽

Age At Diagnosis ◽

P Value ◽

Histological Subtype ◽

Adjusted Incidence ◽

Over Time ◽

End Results

Object Primary malignant spinal glioma represents a significant clinical challenge due to the devastating effect on clinical outcomes in the majority of cases. As they are infrequently encountered in any one center, there has been limited population-based data analysis on the incidence patterns of these aggressive tumors. The objective of this study was to use publically available Surveillance, Epidemiology and End Results (SEER) program data to examine the overall incidence and incidence patterns over time with regard to age at diagnosis, sex, race, primary site of tumor, and histological subtype in patients in whom primary malignant spinal cord gliomas were diagnosed between 1973 and 2006. Methods The study population of interest was limited to primary, malignant, pathologically confirmed spinal cord gliomas based on data drawn from the SEER 9 standard registries for patients diagnosed between 1973 and 2006. Variables of interest included age at diagnosis, sex, race, primary site of tumor, and histological subtype of tumor. The SEER*Stat 6.5.2 program was used to calculate frequencies, age-adjusted incidence rates with 95% CIs, and annual percentage change (APC) statistics with a 2-sided p value. In addition, linear correlation coefficients (R2) were calculated for the time association stratified by variables of interest. Results The overall age-adjusted incidence rate for primary malignant spinal gliomas was 0.12 per 100,000, which increased significantly over the study period (APC = 1.74; p = 0.0004; R2 = 0.36). The incidence was highest in patients diagnosed at ages 35–49 (0.17 per 100,000), males (0.14 per 100,000), whites (0.13 per 100,000), and those with ependymomas (0.07 per 100,000). Over the study period, the incidence of ependymomas increased significantly (APC = 3.17; p < 0.0001; R2 = 0.58) as did the incidence of these tumors in whites (APC = 2.13; p = 0.0001) and for both males (APC = 1.90, p value < 0.0001) and females (APC = 1.60, p < 0.0001). The authors found no significant changes in the incidence over time by age of diagnosis. Conclusions This study demonstrates an increasing overall incidence of primary, malignant spinal cord glioma over the past 3 decades. Notably, for ependymoma the incidence has increased, whereas the incidence of most other glioma subtypes remained stable. This may be due to improved diagnostic and surgical techniques, changes in histological classification criteria, and changes in neuropathology diagnostic criteria. Although primary, malignant spinal cord gliomas are rare, an improved understanding of the incidence will assist investigators and clinicians in planning potential studies and preparing for allocation of resources to care for these challenging patients.

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Clinical Characteristics and Overall Survival in Patients with Anaplastic Pancreatic Cancer

The American Surgeon ◽

10.1177/000313481408000218 ◽

2014 ◽

Vol 80 (2) ◽

pp. 117-123 ◽

Cited By ~ 3

Author(s):

Clancy J. Clark ◽

Janani S. Arun ◽

Rondell P. Graham ◽

Lizhi Zhang ◽

Michael Farnell ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Pancreatic Ductal Adenocarcinoma ◽

Tumor Stage ◽

Ductal Adenocarcinoma ◽

Rank Test ◽

Poor Overall Survival ◽

Perioperative Morbidity ◽

Log Rank Test ◽

Kaplan Meier

Anaplastic pancreatic cancer (APC) is a rare undifferentiated variant of pancreatic ductal adenocarcinoma with poor overall survival (OS). The aim of this study was to evaluate the clinical outcomes of APC compared with differentiated pancreatic ductal adenocarcinoma. We conducted a retrospective review of all patients treated at the Mayo Clinic with pathologically confirmed APC from 1987 to 2011. After matching with control subjects with pancreatic ductal adenocarcinoma, OS was evaluated using Kaplan-Meier estimates and log-rank test. Sixteen patients were identified with APC (56.3% male, median age 57 years). Ten patients underwent exploration of whom eight underwent pancreatectomy. Perioperative morbidity was 60 per cent with no mortality. The median OS was 12.8 months. However, patients with APC who underwent resection had longer OS compared with those who were not resected, 34.1 versus 3.3 months ( P = 0.001). After matching age, sex, tumor stage, and year of operation, the median OS was similar between patients with APC and those with ductal adenocarcinoma treated with pancreatic resection, 44.1 versus 39.9 months, ( P = 0.763). Overall survival for APC is poor; however, when resected, survival is similar to differentiated pancreatic ductal adenocarcinoma.

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Modified IPCW model: A method for adjusting for bias in the estimation of overall survival due to the use of second and third line therapies in locally advanced or metastatic pancreatic cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e15787 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e15787-e15787

Author(s):

N. E. Iznaga Escobar ◽

Patricia Lorenzo Luaces ◽

Lizet Sanchez Valdes ◽

Carmen Valenzuela Silva ◽

Tania Crombet Ramos ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Cancer Patients ◽

Cox Regression ◽

Locally Advanced ◽

Secondary Analysis ◽

Metastatic Pancreatic Cancer ◽

Fixed Dose ◽

Line Treatment ◽

Newly Diagnosed

e15787 Background: Nimotuzumab, a unique and affinity differentiated anti-EGFR antibody had been used in combination with gemcitabine on the treatment of pancreatic cancer patients. The aim of the study was to evaluate overall survival. Methods: Patients with newly diagnosed, locally advanced or metastatic pancreatic cancer, KPS ≥ 70 %, 18-72 years old, with adequate renal and liver function were included. Pts received gemcitabine 1000 mg/m2and nimotuzumab or placebo fixed dose of 400 mg once a wk, for 3 wks, followed by a 1-wk rest (d1, 8, 15, q28) until disease progression or unacceptable toxicity. The primary endpoint was OS and secondary PFS, ORR, CBR, safety and QoL. For OS determination, a KM log-rank test was used and a modified IPCW with a cox regression as a secondary analysis. On this evaluation using a modified IPCW model, 41.7% of pts from treatment arm and 42.7% from control arm who received 2nd and 3rd line treatment were censored after progression, while pts that did not receive 2nd and 3rd line treatment were weighted to compensate for the bias created by censoring switchers to 2nd and 3rd line treatment. Results: 192 pancreatic cancer pts were recruited. Ninety-six pts (62 male and 34 female) with a median age of 67 years, range (31, 83) were randomized to treatment arm and 96 pts (57 male and 39 female) with a median age of 64 years, range (41, 82) were randomized to control arm. In the primary analysis, median OS [95% CI] in the treatment arm was 8.57 mo [5.93, 10.90] vs 6.03 mo [4.97, 7.60] in the control arm. The HR [95% CI], 0.83 [0.62, 1.12] and p = 0.23 and when a modified IPCW model as a secondary analysis was used to remove the effect of 2nd and 3rd line therapies, the median OS was statistically significant with a HR [95% CI], 0.81 [0.67, 0.98] and a p = 0.030. The median PFS [95% CI] was 4.43 mo [3.67, 6.00] in the treatment arm vs 3.47 mo [2.60, 4.03] in the control arm with a HR [95% CI] 0.68 [0.51, 0.92] and p = 0.012. Conclusions: A modified IPCW model had proven that addition of nimotuzumab to gemcitabine increases median overall survival of newly diagnosed chemotherapy-naïve locally advanced or metastatic pancreatic cancer patients. Clinical trial information: NCT00561990.

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Prognostic Significance and Immune Infiltration of Microenvironment‐related Signatures in Pancreatic Cancer

10.21203/rs.3.rs-60885/v1 ◽

2020 ◽

Author(s):

Qian Lu ◽

Yu Zhang ◽

Weihong Gu ◽

Xinrong Ji ◽

Zhong Chen

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Immune Cell ◽

Differential Expression Analysis ◽

Prognostic Significance ◽

Ductal Adenocarcinoma ◽

Immune Infiltration ◽

Protein Protein Interaction ◽

Tumor Tissues ◽

Cox Analysis

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the highly fatal and most aggressive types of malignancies and accounts for the vast majority of Pancreatic Cancer (PC). Numerous studies have reported that the tumor microenvironment (TME) was significantly correlated with the oncogenesis, progress, and prognosis of various malignancies. Therefore, mining of TME-related genes is reasonably important to improve the overall survival (OS) of patients with PDAC. Methods: The Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm was applied to identify differential expressed genes (DEGs). Functional and pathway enrichment analyses, protein–protein interaction (PPI) network construction and module analysis, overall survival analysis and tumor immune estimation resource (TIMER) database analysis were then performed on DEGs. Results: Data analysis indicated that higher immune scores were correlated with better overall survival (P = 0.033). Differential expression analysis obtained 90 intersection genes influencing both stromal and immune scores. Among these intersection genes, CA9, EBI3, SPOCK2, WDFY4, CD1D and CCL22 were significantly correlated with OS in PDAC patients. Moreover, multivariate Cox analysis revealed that CA9, SPOCK2 and CD1D were the most significant prognostic genes, and were closely correlated with immune infiltration in TCGA cohort. Further analysis indicated that CD1D were significantly related with immune cell biomarkers for PDAC patients. Conclusions: In summary, our findings provide a more comprehensive insight into TME and show a list of prognostic immune associated genes in PDAC. However, further studies on these genes need to be performed to gain additional understanding of the association between TME and prognosis in PDAC.

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Meta-analysis of 1,200 transcriptomic profiles identifies a prognostic model for pancreatic ductal adenocarcinoma

10.1101/355602 ◽

2018 ◽

Cited By ~ 2

Author(s):

Vandana Sandhu ◽

Knut Jorgen Labori ◽

Ayelet Borgida ◽

Ilinca Lungu ◽

John Bartlett ◽

...

Keyword(s):

Gene Expression ◽

Pancreatic Cancer ◽

Overall Survival ◽

Pancreatic Ductal Adenocarcinoma ◽

Prognostic Model ◽

Meta Analysis ◽

Early Death ◽

Receiver Operating Curve ◽

Ductal Adenocarcinoma ◽

Survival Predictor

ABSTRACTBackgroundWith a dismal 8% median 5-year overall survival (OS), pancreatic ductal adenocarcinoma (PDAC) is highly lethal. Only 10-20% of patients are eligible for surgery, and over 50% of these will die within a year of surgery. Identify molecular predictors of early death would enable the selection of PDAC patients at high risk.MethodsWe developed the Pancreatic Cancer Overall Survival Predictor (PCOSP), a prognostic model built from a unique set of 89 PDAC tumors where gene expression was profiled using both microarray and sequencing platforms. We used a meta-analysis framework based on the binary gene pair method to create gene expression barcodes robust to biases arising from heterogeneous profiling platforms and batch effects. Leveraging the largest compendium of PDAC transcriptomic datasets to date, we show that PCOSP is a robust single-sample predictor of early death (≤1 yr) after surgery in a subset of 823 samples with available transcriptomics and survival data.ResultsThe PCOSP model was strongly and significantly prognostic with a meta-estimate of the area under the receiver operating curve (AUROC) of 0.70 (P=1.9e-18) and hazard ratio (HR) of 1.95(1.6-2.3) (P=2.6e-16) for binary and survival predictions, respectively. The prognostic value of PCOSP was independent of clinicopathological parameters and molecular subtypes. Over-representation analysis of the PCOSP 2619 gene-pairs (1070 unique genes) unveiled pathways associated with Hedgehog signalling, epithelial mesenchymal transition (EMT) and extracellular matrix (ECM) signalling.ConclusionPCOSP could improve treatment decision by identifying patients who will not benefit from standard surgery/chemotherapy and may benefit from alternate approaches.AbbreviationsAUROCArea under the receiver operating curveGOGene annotationOSOverall survivalPCOSPPancreatic cancer overall survival predictorPDACPancreatic ductal adenocarcinomaTSPTop scoring pairs.

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Serum gamma-glutamyltransferase and the overall survival of metastatic pancreatic cancer

10.21203/rs.2.10892/v3 ◽

2019 ◽

Author(s):

Yuanyuan Xiao ◽

Haijun Yang ◽

Jian Lu ◽

Dehui Li ◽

Chuanzhi Xu ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Ductal Adenocarcinoma ◽

Gamma Glutamyltransferase ◽

Cancer Occurrence ◽

Cox Proportional Hazards Models ◽

Adequate Evaluation ◽

Underlying Mechanisms

Abstract Background: Accumulating evidence suggests that Gamma-glutamyltransferase (GGT) may be involved in cancer occurrence and progression. However, the prognostic role of serum GGT in pancreatic cancer (PC) survival lacks adequate evaluation. In this study, we aimed to analyze the association between serum GGT measured at diagnosis and overall survival (OS) in patients with metastatic PC. Methods: We identified 320 patients with histopathologically confirmed metastatic pancreatic ductal adenocarcinoma (PDAC) diagnosed during 2015 and 2016 at a specialized cancer hospital in southwestern China. Univariate and multivariate Cox proportional-hazards models were used to determine associations between serum GGT and OS in metastatic PDAC. Results: Controlled for possible confounding factors, serum GGT was significantly associated with OS: serum GGT >48 U/L yielded a hazard ratio of 1.53 (95%CI: 1.19-1.97) for mortality risk. A significant dose-response association between serum GGT and OS was also observed. Subgroup analysis showed a possible interaction between GGT and blood glucose level. Conclusion: Serum GGT could be a potential indicator of survival in metastatic PDAC patients. Underlying mechanisms for this association should be investigated.

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Cathepsin D Expression and Gemcitabine Resistance in Pancreatic Cancer

JNCI Cancer Spectrum ◽

10.1093/jncics/pkz060 ◽

2019 ◽

Vol 4 (1) ◽

Cited By ~ 1

Author(s):

Ujjwal M Mahajan ◽

Elisabetta Goni ◽

Enno Langhoff ◽

Qi Li ◽

Eithne Costello ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Cathepsin D ◽

Median Overall Survival ◽

Validation Cohort ◽

Multivariable Analysis ◽

Predictive Marker ◽

Acid Sphingomyelinase ◽

Ductal Adenocarcinoma ◽

Gemcitabine Resistance

Abstract Background Cathepsin-D (CatD), owing to its dual role as a proteolytic enzyme and as a ligand, has been implicated in cancer progression. The role of CatD in pancreatic ductal adenocarcinoma is unknown. Methods CatD expression quantified by immunohistochemistry of tumor-tissue microarrays of 403 resected pancreatic cancer patients from the ESPAC-Tplus trial, a translational study within the ESPAC (European Study Group for Pancreatic Cancer) trials, was dichotomously distributed to low and high H scores (cut off 22.35) for survival and multivariable analysis. The validation cohort (n = 69) was recruited based on the hazard ratio of CatD from ESPAC-Tplus. 5-fluorouracil-, and gemcitabine-resistant pancreatic cancer cell lines were employed for mechanistic experiments. All statistical tests were two-sided. Results Median overall survival was 23.75 months and median overall survival for patients with high CatD expression was 21.09 (95% confidence interval [CI] = 17.31 to 24.80) months vs 27.20 (95% CI = 23.75 to 31.90) months for low CatD expression (χ2LR, 1DF = 4.00; P = .04). Multivariable analysis revealed CatD expression as a predictive marker in gemcitabine-treated (z stat = 2.33; P = .02) but not in 5-fluorouracil-treated (z stat = 0.21; P = .82) patients. An independent validation cohort confirmed CatD as a negative predictive marker for survival (χ2LR, 1DF = 6.80; P = .009) and as an independent predictive marker in gemcitabine-treated patients with a hazard ratio of 3.38 (95% CI = 1.36 to 8.38, P = .008). Overexpression of CatD was associated with a concomitant suppression of the acid sphingomyelinase, and silencing of CatD resulted in upregulation of acid sphingomyelinase with rescue of gemcitabine resistance. Conclusions Adjuvant gemcitabine is less effective in pancreatic ductal adenocarcinoma with high CatD expression, and thus CatD could serve as a marker for biomarker-driven therapy.

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