Advanced Stage Pancreatic Cancer Research Articles

Geographic distribution and accessibility of clinic trials for advanced-stage pancreatic cancer in the United States: A focus on rural and minority health disparities.

11048 Background: Our research delves into the geographical distribution and accessibility of clinical trials for metastatic pancreatic cancer patients in the U.S., spotlighting the challenges faced by rural communities and minority groups. Prior research indicated nearly half of these patients would have to commute over an hour to reach a trial site. [1] Our study provides a refreshed perspective on this issue, offering a more comprehensive analysis. Methods: Utilizing the ClinicalTrials.gov portal, we identified active interventional clinical trials for metastatic pancreatic cancer patients as of November 25, 2022. We obtained distinct zip codes linked to these trials and, using 2020 census data, gauged the proportion of the U.S. populace residing within specific distances from these sites. Our analysis encompassed factors like urbanity, ethnicity, and other socio-economic parameters. We also developed illustrative maps to visually represent the U.S. clinical trial accessibility landscape. Results: The majority of Americans diagnosed with metastatic pancreatic cancer have clinical trials within their reach. A significant 65.7% of the U.S. populace resides within a 30-mile radius of a relevant clinical trial site. However, a closer look reveals pronounced disparities based on urban-rural demarcations and racial lines, with American Indians facing the most pronounced accessibility challenges. Conclusions: Our data underscores the uneven geographical spread of these trials. This skewed distribution poses accessibility hurdles for specific demographics, especially those in rural areas and certain racial groups. Our findings underscore the pressing need for strategic initiatives to rectify these disparities, ensuring clinical trials are within reach for every individual, irrespective of their location or background.

Abstract 7134: Treatment of pancreatic cancer cells with tumor treating fields (TTFields) and PARP inhibitors

Abstract Background: Therapeutic options for advanced stage pancreatic cancer are limited. Patients harboring germline BRCA mutations benefit from PARP inhibitors (PARPi); unfortunately, such mutations are rare in pancreatic cancer. Tumor Treating Fields (TTFields), electric fields that disrupt cellular processes crucial for cancer cell viability, have shown effectiveness against pancreatic cancer cells, and are currently under clinical investigation for the treatment of patients with pancreatic cancer. The mechanism of action of TTFields in various cancer types has suggested involvement of BRCA downregulation. The current study examined the potential sensitization of BRCA wild-type pancreatic cancer cell lines to PARPi with TTFields application. Methods: BxPC3 and AsPC1 human pancreatic BRCA wild-type cancer cells were treated for 72 h with TTFields (frequency of 150 kHz; intensity of 1 and 0.5 V/cm RMS, respectively), using the inovitro device. The PARPi niraparib and olaparib were each administered to the cells at various concentrations, with or without co-application of TTFields. At treatment cessation, cell count, colony formation, and apoptosis were measured. Results: Applying PARPi to pancreatic cell lines yielded a dose-dependent cytotoxic and anti-clonogenic effects, and induced apoptosis. TTFields application also induced such effects when applied alone, while delivery of TTFields together with PARPi amplified the effects demonstrated by PARPi alone. Conclusions: Concomitant application of TTFields and PARPi in BRCA wild type pancreatic cancer cells exhibits a potential improvement relative to the mono-therapies. This could be rationalized based on the previously demonstrated ability of TTFields to induce a state of BRCAness in cancer cells, and suggests benefit for TTFields and PARPi co-treatment in the absence of background BRCA mutations. Citation Format: Hila Ene, Kerem Ben Meir, Antonia Martinez-Conde, Roni Frechtel-Gerzi, Hila Gabay, Daria Gerasimova, Rotem Engelman, Eyal Dor-On, Adi Haber, Moshe Giladi, Yoram Palti. Treatment of pancreatic cancer cells with tumor treating fields (TTFields) and PARP inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7134.

Advanced pancreatic cancer outcomes and the impact of COVID-19 pandemic: The experience of an academic cancer center.

626 Background: The COVID-19 pandemic increased all-cause mortality and disrupted healthcare delivery in the United States. Interruptions in cancer screening and surveillance because of the pandemic resulted in delayed diagnosis, diagnosis at later stages, and worse cancer-related outcomes. However, the effect of COVID-19 on pancreatic cancer outcomes has not been reported. This study aimed to investigate this question. Methods: We studied consecutive patients with unresectable and metastatic pancreatic cancer treated at the University of Cincinnati Cancer Center. Patients were divided into 2 cohorts: from January 2018 to December 2019 (pre-COVID) and from January of 2020 to December of 2021 (during-COVID). Descriptive data on patient characteristics, ECOG performance status (PS), laboratory values, therapies, and mortality were obtained by pre- and during-COVID. The categorical variables were compared using the Pearson Chi-square test for contingency tables (or Fisher’s exact test when the expected frequency within any cell was less than 5 in the contingency table), and the t-test or ANOVA was used for continuous variables. For overall survival time, the Kaplan-Meier curves were compared between pre- and during-COVID using log rank test. We fitted univariable Cox proportional-hazards model for each interest variable, and the multivariable Cox models, which includes only significant variables. Results: There were 81 and 64 patients in the pre- and during-COVID cohorts, respectively. Patients diagnosed during COVID were more likely to be female, have better PS, have higher proportion of alcohol use, and were more likely to receive 5-FU-based (compared with gemcitabine-based) chemotherapy upfront. There was no overall survival difference between the two cohorts. A Cox proportional hazards model showed that PS at diagnosis, history of chronic pancreatitis, any chemotherapy compared to no chemotherapy, serum albumin prior to initial chemotherapy, and body mass index at time of diagnosis were associated with survival. Conclusions: We observed no difference in overall survival in patients diagnosed with advanced stage pancreatic cancer during the first two years of the COVID-19 pandemic compared with the two prior years. While some differences were observed between patient groups and treatment selection before and during the pandemic, a concerted effort to maintain cancer care appears to have minimized the impact of the pandemic. Further analyses on patients undergoing treatment are being conducted.

Anticancer Effects of Fucoxanthin in a PDX Model of Advanced Stage Pancreatic Cancer with Alteration of Several Multifunctional Molecules

Pancreatic cancer (PC) is one of the most fatal cancers, and there is an urgent need to develop new anticancer agents with fewer side effects for the treatment of this condition. A patient-derived xenograft (PDX) mouse model transplanted with cancer tissue from patients is widely accepted as the best preclinical model for evaluating the anticancer potential of drug candidates. Fucoxanthin (Fx) is a highly polar carotenoid contained in edible marine brown algae and possesses anticancer activity. However, there is a lack of data on the effects of Fx in PDX models. We investigated the anticancer effects of Fx in PDX mice transplanted with cancer tissues derived from a patient with PC (PC-PDX) using comprehensive protein expression assay. Fx administration (0.3%Fx diet) ad libitum for 27 days significantly abrogated tumor development (0.4-fold) and induced tumor differentiation in PC-PDX mice, as compared to those in the control mice. Fx significantly upregulated the expression of non-glycanated DCN (2.4-fold), tended to increase the expressions of p-p38(Thr180/Tyr182) (1.6-fold) and pJNK(Thr183/Tyr185) (1.8-fold), significantly downregulated IGFBP2 (0.6-fold) and EpCAM (0.7-fold), and tended to decrease LCN2 (0.6-fold) levels in the tumors of the PC-PDX mice, as compared to those in the control mice. Some of the protein expression patterns were consistent with the in vitro experiments. That is, treatment of fucoxanthinol (FxOH), a prime metabolite derived from dietary Fx, enhanced non-glycanated DCN, p-p38(Thr180/Tyr182), and pJNK(Thr183/Tyr185) levels in human PC PANC-1 and BxPC-3 cells.These results suggested that Fx exerts anticancer and differentiation effects in a PC-PDX mice through alterations of some multifunctional molecules.

Associations of Overall Survival with Geriatric Nutritional Risk Index in Patients with Advanced Pancreatic Cancer.

Nutritional assessment is critical in cancer care to maintain quality of life and improve survival. The Geriatric Nutritional Risk Index (GNRI) may be a practical tool to assess nutritional status and predict survival. This study aimed to examine survival using GNRI in advanced-stage pancreatic cancer (PC). The retrospective analysis used data of patients with stage III or IV PC. Inclusion criteria: age > 18 and hospital admission for at least three days at or following diagnosis between 2014 and 2017. Data collected: demographics, albumin levels, BMI and weight. Days between the first and last admission, median survival and GNRI scores calculated. Patients categorized into groups: any nutritional risk (GNRI ≤ 98) and no nutritional risk (GNRI > 98). 102 patients had a median survival of 87.5 days and mean GNRI of 98.7. Patients surviving longer than 90 days showed higher mean weight (p = 0.0128), albumin (p = 0.0002) and BMI (p = 0.0717) at the first admission. Mean survival days for patients at any nutritional risk were 110 days compared to 310 days for no nutritional risk (p = 0.0002). GNRI score at first admission after diagnosis is associated with survival. It is vital to monitor nutritional status using weight and albumin to promote increased survival from diagnosis.

Distinct Survival Outcomes in Subgroups of Stage III Pancreatic Cancer Patients: Taiwan Cancer Registry and Surveillance, Epidemiology and End Results registry

PurposePancreatic cancer is one of the most malignant cancers with poor survival. The latest edition of the American Joint Committee on Cancer (AJCC) staging system classifies the majority of operable pancreatic cancer patients as stage-III, while dramatic heterogeneity is observed among these patients. Therefore, subgrouping is required to accurately predict their prognosis and define a treatment plan. This study conducts a cohort study to provide a more precise classification system for stage-III pancreatic cancer patients by utilizing clinical variables.MethodsWe analyzed survival using log-rank tests, univariate Cox-regression models, and Kaplan-Meier survival curves for stage-III pancreatic ductal adenocarcinoma (PDAC) patients from the Taiwan Cancer Registry (TCR). Patients were further divided into subgroups using classification and regression tree (CART) algorithm. All results were validated using the SEER database.ResultsAmong stage-III PDAC patients, lymph node and tumor grade showed significant association with survival. Patients with N2 stage had higher mortality risks (hazard ratio [HR] = 2.30, 95% confidence interval [CI] 1.71–3.08, p < 0.0001) than N0 patients. Patients with grade 3 also had higher risk of mortality (HR = 3.80, 95% CI 2.25–6.39, p < 0.0001) than grade 1 patients. The CART algorithm stratified stage-III patients into four subgroups with significantly different survival rates. The median survival of the four subgroups was 23.5, 18.4, 14.5, and 9.0 months, respectively (p < 0.0001). Similar results were observed with SEER data.ConclusionsLymph node involvement and tumor grade are predictive factors for survival in stage-III PDAC patients. This new precise classification system can be used to guide treatment planning in advanced-stage pancreatic cancer.

Combined inhibition of CXCL12 and PD-1 in MSS colorectal and pancreatic cancer: modulation of the microenvironment and clinical effects

BackgroundImmunotherapy in microsatellite stable colorectal or pancreatic cancer has not shown promising results. It has been hypothesized that targeting immunosuppressive molecules like SDF1-alpha/CXCL12 could contribute to immunotherapy and animal models...

A single-institutional analysis of racial disparities in clinicopathologic characteristics, treatment selections, and outcomes in advanced-stage pancreatic cancer patients.

Background:To investigate racial disparities among unresectable/metastatic pancreatic ductal adenocarcinoma (PDA) patients treated with contemporary chemotherapy regimens at an urban center.Methods:Retrospective review of all PDA patients treated at a single institution between 2012–2017. Continuous and categorical variables were tested using t-test, Mann-Whitney U, chi-squared or Fisher’s exact test as appropriate. Kaplan-Meier curves were generated and Cox proportional hazards models were used to analyze survival outcomes.Results:One hundred and forty-five patients identified as: White [69], African American (AA, 34), Asian [15], and Other [27]. Fifty-five-point-seven percent of patients received gemcitabine-based therapy vs. 36.6% received fluorouracil (5-FU) based therapy, specifically 26.1% received FOLFIRINOX and 43.7% received gemcitabine/nab-paclitaxel. In a univariable model, Asians had significantly worse overall survival (OS) than Whites [hazard ratio (HR) 2.74, P=0.013], but there were no OS differences between AA vs. Whites (HR 1.51, P=0.297) nor Other vs. Whites (HR 2.05, P=0.062). On multivariable analysis, Asians had worse OS compared to Whites (HR 2.62, P=0.018), and gemcitabine-based therapy was inferior to 5-FU-based therapy (HR 2.65, P=0.005). There were no OS differences between AA vs. Whites nor Other vs. Whites (HR 1.12, P=0.769 and HR 0.8, P=0.763, respectively).Conclusions:In this series of advanced PDA patients treated with contemporary chemotherapy, AA and White patients had comparable outcomes, but Asians had worse OS than White patients.

Cost evaluation of an exercise oncology intervention: The exercise in all chemotherapy trial.

BackgroundThere is strong evidence supporting the efficacy of exercise oncology programs to improve physical and psychosocial outcomes during active treatment. However, there is a paucity of evidence on the effect of exercise on healthcare utilization and cost analyzes of exercise oncology programs.AimsOur objective was to assess the effects of a pragmatic exercise oncology program (ENACT) during active chemotherapy treatment on healthcare utilization and associated costs.MethodsWe conducted post‐hoc analyzes on 160 ENACT participants and 75 comparison participants matched on cancer site, stage, age range, and gender. We obtained complete healthcare utilization histories for each patient (specific to emergency department [ED] visits and hospital admissions) coinciding with their participation in ENACT. A sub‐analysis was conducted for advanced stage breast, gastrointestinal, and pancreatic cancer patients.ResultsHealthcare costs for patients who participated in the ENACT exercise oncology intervention were numerically lower than healthcare costs for the comparison group, even after accounting for the cost of the intervention. However, the differences were not statistically significant.ConclusionOur findings suggest that an exercise oncology program during active chemotherapy treatment are at least cost neutral for all cancer patients, including advanced stage cancers. Additional research is warranted to evaluate the potential for exercise oncology programs to reduce healthcare utilization, particularly in advanced cancer patients.

Endoscopic Ultrasound-guided Radio-frequency Ablation for Pancreatic Cancer

Prognosis of unresectable pancreatic cancer is poor with the rate of surviving more than 5 years is less than 10% despite multi-modalities treatment. The American Society of Clinical Oncology suggested that all patients with metastatic pancreatic cancer should be offered information about clinical trials. Endoscopic ultrasound guided radio frequency ablation has been recently used in patients with advanced stage pancreatic cancer in a few studies. This article has reviewed information from published articles using endoscopic ultrasound guided radio frequency ablation for advanced pancreatic cancer.

The Association between Body Composition and Overall Survival of Advanced Stage Pancreatic Cancer Patients Treated with FOLFIRINOX

Introduction: Pancreatic cancer (PC) is one of the most fatal malignancies, with a 5-year survival rate of less than 7%. Currently, the most effective chemotherapy regimen for PC is FOLFIRINOX. Body composition can influence chemotherapy toxicity and overall survival (OS). We investigated the prevalence and impact of cachexia and sarcopenia on outcome in patients with advanced stage PC treated with FOLFIRINOX. Methods: Of 66 patients studied, nine were excluded because they were eligible for resection after response following FOLFIRINOX. Skeletal muscle was analyzed using CT-scans at the third lumbar vertebra with Slice-O-Matic™ software and normalized for height (skeletal muscle index, SMI). Cachexia was defined according to the international consensus statement for cancer cachexia. Sarcopenia was defined using sex and BMI-specific cut-off points of SMI. The association between body composition parameters and complications as well as OS was evaluated. Results: Twenty-two locally advanced (LAPC) and 35 metastatic PC (MPC) patients were identified. Thirty (53%) patients were male and 27 (47%) were female. Thirteen (59%) LAPC patients, and 22 (63%) MPC patients were sarcopenic. For cachexia, this was 20 (91%) and 22 patients (63%), respectively. Sarcopenic LAPC patients experienced more CTCAE grade 3/4 complications (mean occurrence/cycle 0.57±0.36 vs. 0.29±0.34, p = 0.039). In metastatic disease, median OS was shorter for cachectic patients compared to non-cachectic patients (HR 7.23, 95%CI 4.82–9.64 vs. 8.03, 95%CI 0.00–17.38, p = 0.039). Multivariate analysis identified disease stage (HR 2.36, 95%CI 1.21–4.57, p = 0.06) and weight loss at diagnosis (HR 1.05, 95%CI 1.01–1.09, p = 0.02) as independent prognostic factors for survival in LAPC and MPC patients. Conclusion: Sarcopenia and cachexia were present in the majority of patients with advanced PC. Cachexia was associated with reduced overall survival in MPC patients and increased complications in LAPC patients. Body composition analysis may identify patients at risk for treatment complications and reduced overall survival.

Perendoscopic Placement of Palliative Stent for Obstructive Jaundice Caused by Head of Pancreas Malignancy in Dr Moewardi General Hospital-Surakarta

Pancreatic cancer is difficult to diagnose in early stage. Malignant bile duct obstruction is a severe complication of pancreatic cancer, which can lead to poor outcomes including cholangitis, delayed treatment, reduced quality of life, and increased mortality. Perendoscopic placement of stents is a method widely used in the management of various malignant and benign pancreatico-biliary abnormalities. A 70-year-old woman came to Dr Moewardi General Hospital in Surakarta with the chief complaint of yellowish skin and eyes since one month before hospital admission. Patient was diagnosed with obstructive jaundice due to suspected of advanced stage pancreatic cancer. Subsequently, patient underwent endoscopic retrograde cholangiopancreatography (ERCP) which revealed an intrahepatic and extrahepatic bile ducts dilatation due to pancreatic tumor which infiltrated common bile duct, thus self expandable metallic stent (SEMS) placement was performed. Furthermore, patients received palliative therapy due to inadequate chemotherapy requirement.

A real-world comparison of efficacy and toxicity of FOLFIRINOX and gemcitabine to nab-paclitaxel in treatment of advanced stage pancreatic cancer.

e16728 Background: Pancreatic adenocarcinoma is a dreaded malignancy accounting for 7% of all cancer related deaths in the United States. The two most used chemotherapeutic regimens are a combination of 5- fluorouracil, leucovorin, oxaliplatin and irinotecan (FFX) and a combination of gemcitabine nab paclitaxel (GN). Both improve survival when compared to gemcitabine alone but have not been compared directly. Methods: Retrospective chart review of 83 chemotherapy naïve patients with metastatic cancer of exocrine pancreas who underwent chemotherapy between February 2011 and June 2017. Patients who completed at least one cycle of chemotherapy regimen were included. Characteristics, efficacy and adverse events between the two regimens were compared using appropriate statistical analyses. Results: 83 patients met selection criteria. 39 patients received FFX and 44 received GN. Mean age of FFX and GN patients was 69.7 (SD 8.7) (Median 66) and 72.3 (SD 8.8) (Median 69) yrs respectively (p = 0.100). The proportion of patients with ECOG performance scale ≤1 receiving FFX vs. GN was 50.8% vs. 49.2% and &gt; 2 receiving FFX vs. GN was 33.3% vs 66.7% (p = .286). Of the 23 patients &gt; 75 yrs., 7 received FFX and 16 received GN (p = .086). Median overall survival was 10.1 months (95% CI: 5.4-18.7) in FFX and 7.2 months in GN (95% CI: 5.4-11.3) [p = 0.037]. Median survival based on site of tumor was 10.2 months (95% CI: 6.7-13.8) in head and 10.1 months (95% CI: 4.3-14.7) in body and tail tumors [p = 0.776]. Incidence of vomiting in FFX / GN was 94.1% / 73.7% (p =.027), vomiting requiring hospital admission was 55.9% / 21.1% (p = 0.003). Other events requiring admission included: diarrhea 31.4% / 17.9%; anemia 5.7% / 10.3%; thrombocytopenia 11.4% / 7.7%; febrile neutropenia 28.6% / 12.8% and acute kidney injury 25.7% / 15.4%; no statistically significant differences between groups. Conclusions: Patients treated with FFX had a longer survival in this retrospective review. FFX is associated with an increased incidence of vomiting requiring hospitalization. FFX remains a preferred regimen in treating patients with good performance status regardless of age.

Elevated expression of exosomal microRNA-21 as a potential biomarker for the early diagnosis of pancreatic cancer using a tethered cationic lipoplex nanoparticle biochip.

Pancreatic cancer (PC) has a poor prognosis due to the lack of effective molecular biomarkers for early diagnosis. Recent studies have investigated the use of exosomal microRNAs (exmiRs) as diagnostic biomarkers in cancer. The present study examined exmiR-21, exmiR-10b and exmiR-212-3p expression in patients with PC and healthy individuals. The expression levels of exmiR-21, exmiR-10b and exmiR-212-3p were examined in the peripheral blood plasma of 36 patients with PC and 65 healthy controls, using tethered cationic lipoplex nanoparticle biochip. The levels of exmiR-21 in the plasma of 34 mice were also evaluated. The expression levels of exmiR-21 and exmiR-10b were significantly greater in patients with PC compared with the control group. The receiver operating characteristic (ROC) analysis indicated that exmiR-21 had better diagnostic performance (P=0.0003; AUC, 0.7171) compared with the other two exmiRs. The diagnostic value of exmiR-21 improved when combined with exmiR-10b (P<0.0001; AUC, 0.791). Furthermore, exmiR-21 was capable of distinguishing patients with early-stage PC from controls and advanced-stage PC (P<0.05, early stage vs. healthy; P<0.001, early stage vs. advanced stage). The results of the present study revealed that the plasma levels of exmiR-21 and exmiR-10b were upregulated in patients with PC. The ROC analyses indicated that exmiR-21 had the best diagnostic performance among the three exmiRs. Furthermore, exmiR-21 was capable of discriminating patients with early-stage PC from healthy controls. These findings indicate the potential of determining the expression of exmiR-21 from serum using a tethered cationic lipoplex nanoparticle biochip as a novel non-invasive strategy for the early diagnosis of PC.

From state-of-the-art treatments to novel therapies for advanced-stage pancreatic cancer.

Improvements in the outcomes of patients with pancreatic ductal adenocarcinoma (PDAC) have lagged behind advances made in the treatment of many other malignancies over the past few decades. For most patients with PDAC, cytotoxic chemotherapy remains the mainstay of treatment. For patients with resectable disease, modified 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (mFOLFIRINOX) is the standard-of-care adjuvant therapy, although data from several randomized trials have shown improved outcomes with neoadjuvant treatment strategies. For patients with advanced-stage or metastatic disease, comprehensive genomic profiling has revealed several potentially actionable alterations in small subsets of patients and the feasibility of implementing such strategies is beginning to be confirmed. Novel therapies targeting certain aberrations, most notably BRCA1/2 mutations, mismatch repair (MMR) deficiencies or NTRK1-3 fusions, have shown considerable activity in clinical trials, and larotrectinib, entrectinib and pembrolizumab have received FDA approval for the treatment of patients with tumours harbouring NTRK fusions and MMR deficiencies, respectively, regardless of primary tumour histology. In this Review, we describe the available data on the activity of these and other agents in patients with PDAC. Our discussion is structured according to the acronym 'PRIME' to organize the various treatment strategies currently undergoing evaluation in clinical trials: Pathway inhibition, alteration of DNA Repair pathways, Immunotherapy, cancer Metabolism and targeting the Extracellular tumour microenvironment.

The Impact of Serum Glucose in the Treatment of Locoregionally Advanced Pancreatic Cancer.

Studies have consistently identified an increased risk of pancreatic cancer in diabetics, yet the role hyperglycemia may play in predicting prognosis is less clear. This work aims to evaluate the impact of glycemic state and antidiabetics on outcomes after systemic and local treatment for locoregionally advanced pancreatic cancer. This retrospective study consisted of 303 patients with newly diagnosed advanced-stage pancreatic cancer treated from 2004 to 2014. Kaplan-Meier survival analysis method was used to estimate time to event for overall survival, distant metastasis, and locoregional control. Blood glucose values (n=8599) were assessed both as continuous and categorical variables in univariate and multivariable Cox proportional hazard regression models to estimate hazard ratios (HRs) and identify independent prognostic factors. A 6-month conditional landmark analysis excluding patients with <6 months follow-up or survival was conducted. Median follow-up and survival was 18.1 and 18.4 months, respectively. On univariate analysis, maximum pretreatment glucose value was associated with reduced overall survival (HR 1.005, P=0.023) and locoregional control (HR 1.001, P=0.001). A pretreatment glucose value ≥200 mg/dL was associated with increased mortality in multivariable analysis (adjusted HR 1.01, P=0.015). After conditional analysis, glucose ≥200 mg/dL before local treatment was associated with reduced overall survival (adjusted HR 1.562; 95% confidence interval [CI], 1.16-2.11; P=0.003). Elevated blood glucose before treatment of locoregionally advanced pancreatic cancer was associated with poorer outcomes. These findings should be incorporated in future clinical trial design.

Telotristat Ethyl to Promote Weight Stability in Patients With Advanced Stage Pancreatic Cancer

Telotristat Ethyl to Promote Weight Stability in Patients With Advanced Stage Pancreatic Cancer

Targeting Tumor Metabolism With Statins During Treatment for Advanced-stage Pancreatic Cancer.

A growing body of preclinical data suggests that statins may exert potent antitumor effects, yet the interactions of these medications with standard therapies and clinical outcomes in this population is less clear. We assessed the impact of statin use on outcomes in patients with advanced-stage pancreatic adenocarcinoma undergoing various treatments. After institutional review board approval, we conducted a retrospective-cohort study consisting of 303 newly diagnosed advanced-stage pancreatic adenocarcinoma patients to determine the impact of statin use on outcomes. Univariate and multivariable Cox proportional hazard regression models were utilized to estimate hazard ratios (HRs). Time-to-event was estimated using Kaplan-Meier survival analysis for overall survival, distant metastasis, and locoregional failure. Baseline and active statin usage were assessed and to mitigate risk of immortal time bias, subanalysis excluding patients with under 6 months of follow-up was conducted. Both prior (P=0.021) and active (P=0.030) statin usage correlated with improved survival in this cohort. Surgery, chemoradiation, and statin use improved 2-year survival rates (84.1% vs. 55.0%; P<0.001). On multivariable analysis, statin exposure was associated with overall survival (HR, 0.662; P=0.027) and trended to significance for freedom from distant metastasis (HR, 0.577; P=0.060). Comorbid conditions were not significantly associated with outcomes. Statin use was associated with improved overall survival in advanced-stage pancreatic adenocarcinoma patients. This data supports previous findings in early-stage pancreatic adenocarcinoma and other cancer sites. To our knowledge this is the first report to examine the efficacy of statin use as a supplementary treatment option in advanced-stage pancreatic adenocarcinoma patients.

Clinical Effectiveness and Potential Survival Benefit of US-Guided High-Intensity Focused Ultrasound Therapy in Patients with Advanced-Stage Pancreatic Cancer.

Pancreatic cancer (PaC) is a life-limiting tumor with a wide range of incapacitating symptoms such as cancer pain in more than 80 % of patients. This prospective interventional study addresses the clinical effectiveness of ultrasound-guided high-intensity focused ultrasound (HIFU) treatment for patients with advanced-stage PaC, including pain perception, tumor size and survival benefit. 50 patients with late-stage PaC underwent HIFU. Clinical assessment included evaluation of tumor volume by imaging and pain burden (pain severity, pain sensation, interference with daily activities) using the Brief Pain Inventory at baseline and follow-up. Median overall survival, progression-free survival and time to local progression were estimated using Kaplan-Meier analysis. In 84 % of patients, significant early relief of cancer-induced abdominal pain was achieved by HIFU independent of metastatic status; it persisted during follow-up. Tumor volume reduction was 37.8 ± 18.1 % after 6 weeks and 57.9 ± 25.9 % after 6 months. 21 % of HIFU-treated patients had local tumor progression with a median time of 14.4 months from intervention. The median overall survival and progression-free survival were 16.2 and 16.9 months from diagnosis and 8.3 and 6.8 months from intervention. In patients with advanced pancreatic cancer and otherwise limited treatment options, HIFU resulted in significant early and long-lasting pain relief and tumor size reduction over time independent of metastatic status. Clinical data suggest an additional potential survival benefit.

Engineered T lymphocytes eliminate lung metastases in models of pancreatic cancer.

Pancreatic cancer is known as one of the most lethal cancers in the world. A majority of advanced stage pancreatic cancer patients are diagnosed with distant metastasis and given poor prognoses, calling for a better therapeutic option. Mesothelin, which is overexpressed in pancreatic cancer and other solid tumors, is a potential target for pancreatic cancer immunotherapy. Adoptive transfer of T cells engineered with chimeric antigen receptors (CART cells) was effective for treating CD19-positive leukemia, but it is more difficult for CART cells to eliminate solid tumors. Because distal metastasis is an important malignant behavior of solid tumors, we investigated whether meso-CART cells exert anti-tumor effects against distant metastases. After expressing meso-CAR in human primary T lymphocytes, the resultant meso-CART cells released cytokines in response to and exhibited cytolytic effects on mesothelin-positive tumor cells in vitro. Injection of meso-CART cells into tumor-bearing mice moderately delayed subcutaneous tumor growth and eliminated lung metastases. This is the first study to show that meso-CART cells are effective against lung metastases induced by intravenous injection of pancreatic tumor cells. Our results suggest that meso-CART cells may be an effective clinical treatment for mesothelin-positive primary and metastatic tumors in pancreatic cancer patients.