Outcome In Pancreatic Adenocarcinoma Research Articles

Real-world outcomes in pancreatic adenocarcinoma (PDAC) and persona types with implications for standard of care (SOC) therapy (Tx).

735 Background: Molecular profiling (MP) for PDAC has gained increased acceptance and we previously demonstrated that targeting actionable mutations can improve patient (pt) outcomes. However, the correlations of diverse patterns of molecular alterations with outcomes following SOC Tx are largely unknown. Methods: We analyzed longitudinal outcomes of 1355 PDAC pts who underwent MP and received SOC Tx. “Persona” types were established based on the molecular characteristics of each pt using unsupervised clustering, as well as a supervised review defined by our molecular tumor board, following classifications reported in previous studies. Progression-free survival (PFS) for each type was assessed based on the choice of first-line Tx (i.e. FOLFIRINOX [FFX] vs. gemcitabine + nab-paclitaxel [GA]). Statistical comparisons were made against all other types within a specific Tx group. Results: The prognostic/predictive value of the persona types for 1st-line Tx revealed distinct differences in outcomes (Table). As expected, the DDR deficiency type was associated with a significantly improved PFS for pts treated with FFX but not for GA. In addition, pts in the cell cycle type had a worse PFS compared to other persona types for both FFX and GA. Using this platform, we will further subdivide the persona types into molecular subtypes and associate these with pt outcomes. Conclusions: Our analyses demonstrate that specific molecular persona types exist in PDAC pts and can be linked to Tx outcomes. Ultimately, knowing the persona type/subtype early in a pt’s Tx course may help personalize Tx to improve outcomes. [Table: see text]

Tumour infiltrating lymphocytes and immune-related genes as predictors of outcome in pancreatic adenocarcinoma.

BackgroundWe investigated the correlation between pancreatic ductal adenocarcinoma patient prognosis and the presence of tumour infiltrating lymphocytes and expression of 521 immune system genes.MethodsIntratumoural CD3+, CD8+, and CD20+ lymphocytes were examined by immunohistochemistry in 12 PDAC patients with different outcomes who underwent pancreaticoduodenectomy. The results were correlated with gene expression profile using the digital multiplexed NanoString nCounter analysis system (NanoString Technologies, Seattle, WA, USA).ResultsTwenty immune system genes were significantly differentially expressed in patients with a good prognosis relative to patients with a worse prognosis: TLR2 and TLR7 (Toll-like receptor superfamily); CD4, CD37, FOXP3, PTPRC (B cell and T cell signalling); IRF5, IRF8, STAT1, TFE3 (transcription factors); ANP32B, CCND3 (cell cycle); BTK (B cell development); TNF, TNFRF1A (TNF superfamily); HCK (leukocyte function); C1QA (complement system); BAX, PNMA1 (apoptosis); IKBKE (NFκB pathway). Differential expression was more than twice log 2 for TLR7, TNF, C1QA, FOXP3, and CD37.DiscussionTumour infiltrating lymphocytes were present at higher levels in samples from patients with better prognosis. Our findings indicate that tumour infiltrating lymphocyte levels and expression level of the immune system genes listed above influence pancreatic ductal adenocarcinoma prognosis. This information could be used to improve selection of best responders to immune inhibitors.

Impact of pretreatment serum creatinine on outcomes in pancreatic adenocarcinoma.

e15749 Background: Pancreatic Adenocarcinoma (PA) is an aggressive malignancy with an estimated 5-year survival of 8.5%. PA was responsible for 7.3% of all cancer deaths in 2018 in the US. We aimed to evaluate the impact of pretreatment serum creatinine (SCr) level on Overall Survival (OS) in patients with PA. Methods: A retrospective review of electronic health records of patients with PA seen at our institution between 01/2014 and 01/2018 was done. We collected patients’ SCr at the time of diagnosis, and excluded patients with a glomerular filtration rate (GFR) below 60 mL/min per 1.73 m2 or SCr > 1.3 mg/dL. Patients were dichotomized around a SCr of 0.5 mg/dL. Kaplan-Meier survival estimate was performed to evaluate statistical significance. Results: A total of 83 patients, including 37 females and 46 males, with a median age at diagnosis of 67 years, were included. SCr of < 0.5 mg/dL was associated with a lower median OS as compared to a SCr of ≥0.5 mg/dL, (253 days versus 364 days; P = 0.035). There were more female patients in the low SCr group (71% vs 39%, P = 0.027). Patients with SCr of < 0.5 mg/dL had a lower mean BMI compared to patients with a SCr of ≥0.5 mg/dL, however this was not statistically significant (BMI = 22.45 versus 25.72; P = 0.49). Conclusions: Low SCr is predictive of a lower median OS in patients with PA. SCr has been suggested as a surrogate marker for muscle mass, which is closely associated with the degree of cancer cachexia. Our finding emphasizes the need for future larger studies to evaluate the utility of SCr as a prognostic indicator, as well as a cost-effective surrogate for measuring cancer cachexia. [Table: see text]

Outcomes in pancreatic adenocarcinoma (PDA) patients (pts) with genetic alterations in DNA damage repair (DDR) pathways: Results from the Know Your Tumor (KYT) program.

191 Background: Up to 17% of PDAs harbor mutations in the DDR pathway. However, the purely prognostic relevance of these mutations is unclear. Furthermore, outcomes in response to platinum-based therapies in PDA pts harboring mutations in a broad range of DDR genes, particularly beyond BRCA1/2 and PALB2, remain unexplored. Methods: We evaluated PDA pts enrolled in the KYT registry for whom we collected cancer related exome sequencing and clinical outcomes. Pts were categorized as resected and advanced (LAPC and metastatic pts), and tumor genomic profiles were categorized as DDR mutated (DDRmut) based on the presence of pathogenic alterations in BRCA1/2, PALB2 (Group 1), ATM, ATR, ATRX (Group 2), or BAP1, BARD1, BRIP1, CHEK1/2, RAD50/51/51B, or FANCA/C/D2/E/F/G/L (Group 3). Tumors harboring no DDR mutations were labelled DDR proficient (pDDR). Median overall survival (OS) was measured from the date of diagnosis until death. Results: The OS was similar in all resected pts, irrespective of exposure to platinum therapy (see Table). However, for the pts with advanced disease, OS was significantly longer for DDRmut vs. pDDR pts, particularly in the platinum-treated group; but no such difference was identified in the platinum-naïve pts. Detailed outcomes for the 3 Groups will be presented, but in general the OS in pts with mutations in all 3 DDRmut Groups was greater than for the pDDR pts; but again this difference was lost in the platinum-naïve pts. Conclusions: Advanced DDRmut pts have an improved OS when treated with platinums, compared to pDDR pts. But, in the absence of platinum-based therapy, there is no OS difference observed in DDRmut vs. pDDR pts, suggesting that DDR status has no pure prognostic value. These findings support the need to test all pts with advanced PDA, to ensure that DDRmut pts are treated with platinum-based therapy. [Table: see text]

Provider-volume associated with variable receipt of therapy and outcomes for noncurative pancreas adenocarcinoma: A population-based analysis.

352 Background: While high-volume providers for pancreatic adenocarcinoma (PA) surgery yield better outcomes, variation in practice and the role of provider-volume has not been investigated for systemic therapy. We examined variation in practice and outcomes in the management of non-curative PA, based on medical oncology provider-volume. Methods: We conducted a population based retrospective cohort study of non-resected PA over 2005-2016 by linking administrative healthcare datasets. High-volume (HV) medical-oncology providers were defined as the 5th quintile of number of PA seen per provider per year. Outcomes were receipt of chemotherapy and overall survival (OS). Brown Forsythe Levene (BFL) test for equality of variances assessed outcomes variability between provider-volume quintiles (Q1 to 5). Multivariate regressions examined the association between management by HV provider and receipt of systemic therapy and OS. Results: Of 10,881 non-curative PA patients, 7,062 consulted with medical oncology. Among 341 medical oncology providers, 3% were HV, defined as > 16 patients/year. There was variability in receipt of chemotherapy based on provider-volume, with 44% (IQR: 25-54) for Q1 and 47% (IQR: 43-54) for Q5, and in median survival, with 4.1 months (IQR: 2.7-6.2) for Q1 and 7.5 months (IQR: 6.6-8.0) for Q5. Variability between provider-volume quintiles was significant for receipt of chemotherapy and median survival (both BFL p < 0.001). After adjusting for age, sex, comorbidity burden, rurality, income quintile, and diagnosis year, HV provider was independently associated with higher odds of receiving chemotherapy (OR 1.19 [1.05-1.34]), and superior OS (HR 0.79 [0.74-0.84]). Conclusions: There was significant variation in non-curative management and outcomes of PA based on provider-volume. Management by a HV provider was independently associated with higher odds of receiving chemotherapy and superior OS, after adjusting for case-mix. This information is important to inform disease care pathways and care organization. Cancer care systems could consider initiatives to increase the number of HV providers to reduce variation and improve outcomes.

Undertreatment of noncurative pancreatic adenocarcinoma?: A population-based analysis of patterns of care.

439 Background: Noncurative pancreatic adenocarcinoma (PA) portends a guarded prognosis. Advancements in systemic therapy have improved this outlook. It is unknown whether patients get access to these therapies. We sought to define patterns of access to care and therapy for noncurative PA. Methods: We conducted a population-based analysis of nonresected PA over 2005-2016 by linking administrative healthcare datasets. Primary outcome was nonreceipt of cancer-directed therapy (radiation/chemotherapy; NRCDT). The first contact and overall consultations with specialized care (surgery, medical, or radiation oncology) were examined. Multivariate models examined factors associated with NRCDT. Results: Of 10,881 patients surviving a mean of 3.3 months (IQR: 1.2-8.5), 62% had NRCDT. More of patients of older age (65% of 71-80 years old, 89% of ≥81 years old), high comorbidity burden (68%), and lower socioeconomic status (69%), had NRCDT. Distance from residence to nearest cancer centre did not differ based on NRCDT. 35% of all patients did not see medical oncology, including 56% of NRCDT patients; 17% had no consultation with specialists. First contact with specialized care was surgery for 55% of all patients, and 50% with NRCDT. Most patients saw palliative care (81%) at median 27 days (IQR: 9-75) after diagnosis. Older age (OR 0.42 [0.37-0.48], and OR 0.14 [0.12-0.16] for 71-80 and ≥81 years old respectively), lowest income quintile (OR 0.62 [0.54-0.71]) and rurality (OR 0.63 [0.56-0.71]) were independently associated with lower odds of seeing medical oncology. First contact with oncology was independently associated with higher odds of receiving therapy (OR 1.48 [1.34-1.62]), compared to surgery. Conclusions: The majority of patients with noncurative PA did not receive cancer-directed therapy. Of those, more than half did not see medical oncology. While some patients may not be eligible to therapy, we identified disparities in receipt of cancer-directed therapy that indicate potential gaps in assessment for therapy and undertreatment, especially for vulnerable populations. This information is important to optimize access to and delivery of evidence-based care, and improve PA outcomes.

Pancreatic Adenocarcinoma in New Mexico Native Americans: Disparities in Treatment and Survival.

A retrospective review of patients treated for pancreatic adenocarcinoma at a university cancer center from 2002-2016 comparing demographic characteristics, disease presentation, treatment, and outcomes among three main ethnic groups in New Mexico. We identified 457 patients: 240 (52.5%) non-Hispanic Whites, 186 (40.7%) Hispanics, and 31 (6.8%) NA. Non-Hispanic Whites (OR 2.41; p=.026) and Hispanics (OR 2.37; p=.032) were more likely to receive or be offered chemotherapy than NA. More NA than non-Hispanic Whites died within one month of diagnosis (25.8% and 7.5%, respectively; p=.004). The NAs demonstrated a 26.2% one-year survival (CI 11.7-43.3), compared with 48.3% in non-Hispanic Whites (CI 40.9-55.2; p=.015). Significant disparities exist in the treatment and outcomes of pancreatic adenocarcinoma in New Mexico NA populations.

Can post-hoc video review of robotic pancreaticoduodenectomy predict portal/superior mesenteric vein margin status in pancreatic adenocarcinoma?

BackgroundAchieving margin negative resection is a significant determinant of outcome in pancreatic adenocarcinoma (PDA). However, because of the fibrotic nature of PDA, it can be difficult to discriminate fibrosis from active disease intra-operatively. We sought to determine if post-hoc video review of robotic pancreatico-duodenectomy (RPD) could predict the portal/superior mesenteric vein (PV/SMV) margin status on final pathology. MethodsExperienced pancreatic surgeons, blinded to patient and operative variables, reviewed the PV/SMV margin for available RPD videos of consecutive PDA patients from 9/2012 through 6/2017. Results107 RPD videos were reviewed. Of 76 patients (71%) predicted to have a negative vein margin on video review, 20 patients (26%) had a pathologic positive margin. 25 of 31 patients (81%) predicted to have positive margin on video review were positive on pathology. The specificity of video prediction was 90.3% with a sensitivity of 55.6% and an accuracy of 75.7%. ConclusionPost-hoc video review prediction is unable to reliably predict a positive (R1) margin at the portal vein/SMV, suggesting that intra-operative clinical assessment may be suboptimal in determining the need for more extensive resections.

Differences in Treatment and Outcome of Pancreatic Adenocarcinoma Stage I and II in the EURECCA Pancreas Consortium

BackgroundThe EUropean REgistration of Cancer CAre (EURECCA) consortium aims to investigate differences in treatment and to improve cancer care through Europe. The purpose of this study was to compare neo- and adjuvant chemotherapy (ACT) and outcome after tumor resection for pancreatic adenocarcinoma stage I and II in the EURECCA Pancreas consortium.MethodsThe eight, collaborating national, regional, and single-center partners shared their anonymized dataset. Patients diagnosed in 2012–2013 who underwent tumor resection for pancreatic adenocarcinoma stage I and II were investigated with respect to treatment and survival and compared using uni- and multivariable logistic and Cox regression analyses. All comparisons were performed separately per registry type: national, regional, and single-center registries.ResultsIn total, 2052 patients were included. Stage II was present in the majority of patients. The use of neo-ACT was limited in most registries (range 2.8–15.5%) and was only different between Belgium and The Netherlands after adjustment for potential confounders. The use of ACT was different between the registries (range 40.5–70.0%), even after adjustment for potential confounders. Ninety-day mortality was also different between the registries (range 0.9–13.6%). In multivariable analyses for overall survival, differences were observed between the national and regional registries. Furthermore, patients in ascending age groups and patients with stage II showed a significant worse overall survival.ConclusionsThis study provides a clear insight in clinical practice in the EURECCA Pancreas consortium. The differences observed in (neo-)ACT and outcome give us the chance to further investigate the best practices and improve outcome of pancreatic adenocarcinoma.

Outcomes of pancreatic adenocarcinoma that was not resected because of isolated para-aortic lymph node involvement

Survival appears to be poor in cases of pancreatic ductal adenocarcinoma (PDAC) with para-aortic lymph node involvement (PALN+). However, resection is still performed in these cases because the prognostic impact of PALN+remains controversial. PALN+was intraoperatively found in 14 patients (4.8%) with resectable PDAC who consequently did not undergo pancreatectomy. The median overall survival time after laparotomy was 21 months. The 1- and 3-year overall survival rates were 58.3% and 25%, respectively. We support the advisability of reconsidering pancreatectomy in patients with intraoperatively detected PALN+because the reported survival of such patients who undergo pancreatectomy is poorer than the survival observed for patients in our series.

Postoperative serum CA19-9, CEA and CA125 predicts the response to adjuvant chemoradiotherapy following radical resection in pancreatic adenocarcinoma

ObjectiveTo evaluate the prediction of benefits from adjuvant chemoradiotherapy by postoperative serum CA19-9, CA125 and CEA. MethodsThe relations between benefits from adjuvant chemoradiotherapy and levels of postoperative serum CA19-9, CA125 and CEA were investigated in 804 pancreatic adenocarcinoma patients who received radical resection. ResultsAdjuvant chemoradiotherapy was an independent factor for late recurrence [12.2 vs. 8.5 months, P = 0.001 for recurrence free survival (RFS)] and long survival [23.7 vs. 17.0 months, P < 0.001 for overall survival (OS)] in resected pancreatic adenocarcinoma. Postoperative serum CA19-9, CA125 and CEA were independent risk predictors for poor surgical outcome in pancreatic adenocarcinoma (P < 0.001 for all). Adjuvant chemradiotherapy (hazard ratio: 0.359, 95% confidence interval: 0.253–0.510, P < 0.001 for OS; hazard ratio: 0.522, 95% confidence interval: 0.387–0.705, P < 0.001 for RFS) were confirmed to improve the surgical outcome in patients with abnormal levels of any one of the three postoperative markers, but not in patients with normal levels of the three postoperative markers. In the subgroup of patients with negative lymph node, its improvement of surgical outcome was also significant in patients with abnormal levels of any one of postoperative serum CA19-9, CA125 and CEA (hazard ratio: 0.412, 95% confidence interval: 0.244–0.698, P = 0.001 for OS; hazard ratio: 0.546, 95% confidence interval: 0.352–0.847, P = 0.007 for RFS). ConclusionPostoperative serum CA19-9, CA125 and CEA could serve as predictors of response for adjuvant chemoradiotherapy even if the status of lymph nodes is negative.

Complement levels as predictors of survival in pancreatic adenocarcinoma.

315 Background: Novel biomarkers to predict outcomes in pancreatic adenocarcinoma (PDA) are urgently needed. Complement activation, an important mediator of inflammatory processes, has been reported in some solid tumors but its role in PDA is unknown. We evaluated the prognostic role of complement in a prospective cohort of PDA patients. Methods: Blood samples were collected from consenting PDA patients at study entry (prior toany new regimen) in a prospective biorepository protocol at Cleveland Clinic from 2013-2016. Samples were processed for C3a, C4a, and C5a levels using ELISA on serum samples (BD Biosciences). Data on clinical variables, treatment, and survival were collected from medical records. Resectability was defined using Intergroup criteria. Statistically significant univariable associations and a priori prognostic variables were tested in multivariable models; adjusted hazard ratios (HR) are presented. Results: The study population comprised 48 consecutive patients. Median age was 65 years (range, 41-84); 60% (n=29) were female; 33 (69%) had potentially curable (resectable or borderline resectable) disease. Overall, 43 (93%) received chemotherapy; 22 (46%) received radiation; 29 (60%) underwent surgery. Median follow-up was 17 months. Median OS was 10.9 (1.6-54.5) months. Baseline levels, and associations with stage and OS are shown in Table. Increasing levels of C3a, C4a and C5a were associated with worsened survival (HR 1.00-1.03 per each unit increase in baseline level) despite not being significantly associated with stage. Conclusions: Levels of C3a, C4a, and C5a are detected in nearly all patients with PDA. Increased levels correlate with OS. Complement activation has not been reported previously in PDA and may be a potential therapeutic target. Our findings suggest that complement levels may serve as novel biomarkers. [Table: see text]

Therapeutic management in patients with exocrine pancreatic insufficiency (EPI): First experience with the 13C-mixed triglyceride breath test (Pancreo-kit®)

To evaluate the prediction of benefits from adjuvant chemoradiotherapy by postoperative serum CA19-9, CA125 and CEA.The relations between benefits from adjuvant chemoradiotherapy and levels of postoperative serum CA19-9, CA125 and CEA were investigated in 804 pancreatic adenocarcinoma patients who received radical resection.Adjuvant chemoradiotherapy was an independent factor for late recurrence [12.2 vs. 8.5 months, P = 0.001 for recurrence free survival (RFS)] and long survival [23.7 vs. 17.0 months, P < 0.001 for overall survival (OS)] in resected pancreatic adenocarcinoma. Postoperative serum CA19-9, CA125 and CEA were independent risk predictors for poor surgical outcome in pancreatic adenocarcinoma (P < 0.001 for all). Adjuvant chemradiotherapy (hazard ratio: 0.359, 95% confidence interval: 0.253–0.510, P < 0.001 for OS; hazard ratio: 0.522, 95% confidence interval: 0.387–0.705, P < 0.001 for RFS) were confirmed to improve the surgical outcome in patients with abnormal levels of any one of the three postoperative markers, but not in patients with normal levels of the three postoperative markers. In the subgroup of patients with negative lymph node, its improvement of surgical outcome was also significant in patients with abnormal levels of any one of postoperative serum CA19-9, CA125 and CEA (hazard ratio: 0.412, 95% confidence interval: 0.244–0.698, P = 0.001 for OS; hazard ratio: 0.546, 95% confidence interval: 0.352–0.847, P = 0.007 for RFS).Postoperative serum CA19-9, CA125 and CEA could serve as predictors of response for adjuvant chemoradiotherapy even if the status of lymph nodes is negative.

Oncolytic viral therapy for pancreatic cancer.

Outcomes of pancreatic adenocarcinoma (PDA) remain dismal despite extensive clinical investigation. Combination chemotherapy provides modest improvements in survival above best supportive care, and immunotherapy has thus far not proven effective. Nevertheless, growing insight into antitumor immunity and the tumor microenvironment has inspired the discovery of novel agents targeting PDA. Oncolytic viruses represent an emerging class of immunotherapeutic agents that have undergone extensive preclinical investigation and warrant further investigation in well-designed clinical trials.

Total laparoscopic pancreaticoduodenectomy at a specialized high volume center with a focus on outcomes for pancreatic adenocarcinoma

Total laparoscopic pancreaticoduodenectomy at a specialized high volume center with a focus on outcomes for pancreatic adenocarcinoma

Randomized phase II study of the safety, efficacy, and immune response of GVAX pancreas (with cyclophosphamide) and CRS-207 with or without nivolumab in patients with previously treated metastatic pancreatic adenocarcinoma (STELLAR).

TPS486 Background: A heterologous prime-boost vaccination strategy using GVAX pancreas and CRS-207 is showing promise in patients with pancreatic adenocarcinoma (PDA) (Le, JCO 2015). Furthermore, blockade of the immune checkpoint programmed death-1 (PD-1) is active in some cancers. Combinatorial strategies aimed at priming tumor antigen-specific T cells while simultaneously blocking negative checkpoints may be necessary to improve outcomes in PDA. GVAX is composed of allogeneic pancreatic cancer cells modified to express GM-CSF and induces a broad response against multiple tumor antigens. GVAX is given with low-dose cyclophosphamide (CY) to inhibit regulatory T cells. CRS-207 is live-attenuated Listeria monocytogenes engineered to express the tumor-associated antigen mesothelin. CRS-207 boosts responses against mesothelin and is unique in its capacity to stimulate both innate and adaptive immunity by activating T cells and NK cells. Nivolumab is an antibody against PD-1. Methods: This is a phase 2 study comparing CY/GVAX and CRS-207 with or without nivolumab in subjects with PDA who failed only one chemotherapy regimen for metastatic disease. Subjects are randomized in a 1:1 ratio to receive either 2 doses of CY/nivolumab/GVAX and 4 doses of nivolumab/CRS-207 (Arm A) or 2 doses of CY/GVAX and 4 doses of CRS-207 (Arm B). The primary objective is to compare OS between Arms A and B. Secondary/exploratory objectives include: assessment of safety and clinical responses (tumor assessments and CA19-9 levels) and correlation of Lm- and mesothelin-specific T cell and other immunological responses with OS, progression-free survival and best overall response. Clinical trial information: NCT02243371.

Treatment of Pancreatic Adenocarcinoma in Elderly Patients over 75 Years of Age: A Retrospective Series of 129 Patients.

To better know the presentation and outcome of pancreatic adenocarcinoma in patients above 75 years of age. Retrospective analysis of consecutive patients with a pancreatic adenocarcinoma seen in the Comprehensive Cancer Center of Marseille between January 2002 and January 2012 was used. During these 10 years, 129 patients older than 75 years of age were seen, 61 females and 68 males, median age 78. At diagnosis, the tumor was metastatic in 45%. First line treatments were: surgical resection in 22 cases, radio-chemotherapy in 20 cases (1 operated on later), systemic chemotherapy in 59 cases, and best supportive care alone in 28 cases. Resection was possible in 19 cases and was R0 in 17; post-operative mortality was 0%, and half received adjuvant chemotherapy. Median overall survival was 43 months with a 2-year overall survival of 64%. For locally advanced tumor, 16 received best supportive care and 33 a specific treatment (20 cases of radio-chemotherapy). Median overall survival was 9.1 months and 2-year overall, survival was 6.1%. Among the 58 metastatic patients, 79% received systemic chemotherapy (most by gemcitabine); tolerance was correct in half. Median overall survival was 4.7 months, with a 2-year overall survival of 5.3%. Surgery of pancreatic adenocarcinoma is feasible and safe in elderly patients with good outcomes. In advanced and metastatic patients, the outcome is poor despite a correct tolerance of systemic chemotherapy. Randomized trials specially designed for this population are urgently needed.

Pregnane X Receptor Expression in Human Pancreatic Adenocarcinoma: Associations With Clinicopathologic Parameters, Tumor Proliferative Capacity, Patients' Survival, and Retinoid X Receptor Expression.

Pregnane X receptor (PXR) has been involved in human malignancy, either by directly affecting carcinogenesis or by inducing drug-drug interactions and chemotherapy resistance. The present study aimed to assess the clinical significance of PXR in pancreatic adenocarcinoma. Pregnane X receptor and its heterodimers' PXR/retinoid X receptor α (RXR-α), RXR-β, and RXR-γ expression were assessed immunohistochemically on tumoral samples from 55 pancreatic adenocarcinoma patients and were associated with clinicopathologic parameters, tumor proliferative capacity, and patients' survival. Enhanced PXR expression was noted in 24 (43.6%) of 55 pancreatic adenocarcinoma cases. Pancreatic adenocarcinoma patients presenting increased histological grade of tumor differentiation showed a significant increased incidence of elevated PXR expression (P = 0.023). Enhanced PXR/RXR-β expression was significantly associated with smaller tumor size and earlier clinical stage (P = 0.005 and P = 0.003, respectively). Elevated PXR/RXR-γ expression was significantly associated with smaller tumor size and earlier clinical stage (P = 0.012 and P = 0.014, respectively) and borderline with the absence of lymph node metastases (P = 0.056). In addition, pancreatic adenocarcinoma patients presenting enhanced PXR/RXR-γ expression showed marginally longer survival times compared with those with decreased expression (log-rank test, P = 0.053). This study supported evidence that PXR and its copartners' overexpression may be associated with favorable clinicopathologic parameters and better outcome in pancreatic adenocarcinoma.

Pancreatic adenocarcinoma in adolescent and young adults (18-44): Characteristics and clinical outcomes from Canada and France.

e15215 Background: Epidemiology and clinical outcomes for pancreatic adenocarcinoma (PDAC) are not well described in adolescent and young adult (AYA) population. Furthermore, treatments’ efficacy f...

Accumulation of FOXP3+T-cells in the tumor microenvironment is associated with an epithelial-mesenchymal-transition-type tumor budding phenotype and is an independent prognostic factor in surgically resected pancreatic ductal adenocarcinoma.

Here we explore the role of the interplay between host immune response and epithelial-mesenchymal-transition (EMT)-Type tumor-budding on the outcome of pancreatic adenocarcinoma (PDAC). CD4+, CD8+, and FOXP3+T-cells as well as iNOS+ (M1) and CD163+-macrophages (M2) were assessed on multipunch tissue-microarrays containing 120 well-characterized PDACs, precursor lesions (PanINs) and corresponding normal tissue. Counts were normalized for the percentage of tumor/spot and associated with the clinico-pathological features, including peritumoral (PTB) and intratumoral (ITB) EMT-Type tumor-budding and outcome. Increased FOXP3+T-cell-counts and CD163-macrophages and decreased CD8+T-cell-counts were observed in PDACs compared with normal tissues and PanINs (p < 0.0001). Increased peritumoral FOXP3+T-cell-counts correlated significantly with venous invasion, distant metastasis, R1-status, high-grade ITB, PTB and independently with reduced survival. Increased intratumoral FOXP3+T-cells correlated with lymphatic invasion, N1-stage, PTB and marginally with adverse outcome. High peritumoral CD163-counts correlated with venous invasion, PTB and ITB. High intratumoral CD163-counts correlated with higher T-stage and PTB. PDAC-microenvironment displays a tumor-favoring immune-cell composition especially in the immediate environment of the tumor-buds that promotes further growth and indicates a close interaction of the immune response with the EMT-process. Increased peritumoral FOXP3+T-cell density is identified as an independent adverse prognostic factor in PDAC. Patients with phenotypically aggressive PDACs may profit from targeted immunotherapy against FOXP3.