DNA Analysis Identifies Subtype of Pancreatic Cancer With Good Prognosis

MedicalResearch.com Interview with:

Nancy You, MD, MHSc, FACS Department of Surgical Oncology The University of Texas MD Anderson Cancer Center Houston

Dr. You

Nancy You, MD, MHSc, FACS
Department of Surgical Oncology
The University of Texas MD Anderson Cancer Center
Houston 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: This study was motivated by the emerging promise of precision medicine and the emerging evidence that immunotherapy may have phenomenal efficacy in particular molecular subtypes of cancers.  This specific molecular subtype shows deficiency in DNA mismatch repair mechanisms and therefore is thought to be more immunogenic.  DNA mismatch repair deficiency can arise from germline defects such as in the case of patients with Lynch Syndrome, an inherited cancer syndrome, or from epigenetic inactivation DNA mismatch repair genes.

Overall, pancreas cancer has seen limited success with conventional chemotherapy.  In our study, we demonstrated that there is a particular molecular subtype of pancreas cancer that is characterized by defect in DNA mismatch repair genes and by microsatelie instability that has a different prognosis than other pancreas cancers.  This subtype of pancreas cancer is suspected to also respond to immunotherapy.

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Comprehensive Study of Metabolic Inhibitors Reveals the Anti-Tumor Efficacy of Phenformin in Pancreatic Cancer

MedicalResearch.com Interview with:

Dr-Rajesh-Kumar.jpg

Dr. Rajesh Kumar NV

Rajesh Kumar NV, Ph.D.
Instructor of Oncology and Pathology,
Johns Hopkins University School of Medicine, Baltimore, MD, USA
Current affiliation
Senior Manager, Human Therapeutics Division,
Intrexon Corporation
Germantown, MD

MedicalResearch.com: What is the background for this study?

Response: Pancreatic ductal adenocarcinoma (a.k.a. pancreatic cancer) is one of the most deadly of all types of cancer and currently the third leading cause of cancer-related death in United States. Current therapeutic options for pancreatic cancer involve combination cytotoxic chemotherapy, which yield only minimal survival benefit. A multitude of Phase III clinical trials have failed to demonstrate efficacy, largely due to the aggressive growth of pancreatic tumors. Metabolic reprogramming is a hallmark of cancer cells, including pancreatic cancer. Altered metabolism is central to the pathogenesis of pancreatic cancer and contributes to promotion of proliferation, survival, invasiveness and chemo-resistance of cancer cells. Pharmacologic strategies targeting cancer metabolism might therefore represent a promising approach towards the development of effective drugs against pancreatic cancer.

We utilized a clinically relevant and genetically characterized platform of patient-derived pancreatic cancer xenografts, which we originally created from the freshly resected pancreatic cancer tissues of patients, to explore the in vivo anti-tumor efficacy of a panel metabolic inhibitors and investigated whether mutational status, gene expression and metabolite profile of tumors correlate with the sensitivity to metabolic inhibitors. To our knowledge, this is the largest preclinical trial which enrolled a large number of animals (over 500 mice) with established human pancreatic tumors for the comprehensive evaluation of key metabolic inhibitors in pancreatic cancer.  Continue reading

Distinct Mutational Signatures Correlate With Increased Immune Activity in Pancreatic Cancer

MedicalResearch.com Interview with
Dr. Ashton A. Connor, MD
PanCuRx Translational Research Initiative,
Ontario Institute for Cancer Research
Dr. Steven Gallinger MD, MSC
Division of General Surgery
Toronto General Hospital
Toronto, ON

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The etiology of pancreatic ductal adenocarcinoma (i.e. “pancreatic cancer”) and the relationship between the tumour and its characteristic dense, encroaching stroma are still poorly understood.

Using whole genome sequencing in two large cohorts, we show that there are four fundamental mutational processes that give rise to pancreatic cancer.
With expression data, we also show that the interaction between the tumour and the surrounding stroma varies with the type of mutational process found in the tumour. Specifically, tumours with defective DNA repair, either homologous recombination or mismatch repair deficiency, elicited strong anti-tumour immune responses, likely due to the relatively high numbers of neoantigens in these tumours.

Individually, these concepts have been studied in other cancer types, but we are first to apply either of these to pancreatic cancer, and we also the first to integrate these two aspects of cancer biology for any tumour, to our knowledge.

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DRD2 Inhibitors As Potential Therapy Against Pancreatic Cancer

MedicalResearch.com Interview with:
Dr. Pouria Jandaghi
Functional Genome Analysis, Deutsches Krebsforschungszentrum
Heidelberg, Germany
Department of Human Genetics, McGill University
University and Genome Quebec Innovation Centre
Montreal, Canada

MedicalResearch.com: What is the background for this study?

Response: Although the overall five-year survival of all patients with cancer stands at 63%, for pancreatic cancer patients, it is a disheartening 8% – a number that remains largely unchanged for three decades. Of the patients diagnosed with pancreatic cancer, about 85% exhibit pancreatic ductal adenocarcinoma (PDAC). Most of these patients die within 4 to 6 months after diagnosis. The poor prognosis is caused by the its detection at only late stages, and lack of effective options for chemotherapy. The widely used chemotherapeutic agent gemcitabine, confers a median survival advantage of only 6 months, and resistance to therapy develops in the vast majority of patients. Given this poor prognosis of patients with PDAC, there is an urgent need to find more effective therapies.

In this study, we set out to investigate potential therapeutic targets by dissecting gene expression profiles of tumors and control samples. Candidate targets were validated with respect to their suitability and analyzed functionally.
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New Onset Diabetes, Especially In Lean Patients, Can Be Marker of Pancreatic Cancer

MedicalResearch.com Interview with:
Dr. Pavel Škrha
Charles University, Prague
Czech Republic

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Incidence of pancreatic cancer (PAC) is still increasing. The main problem is in the late diagnosis of the cancer. It was found, that diabetes mellitus was much more frequent in the pancreatic cancer patients than in the general population. DM can be already the first symptom of the disease (secondry T3cDM).

In our study nearly 80 % of all the pancreatic cancer patients had DM/prediabetes and it was of new-onset (less than 2 years before the cancer diagnosis) in 73 % out of them. We have measured the current marker of PAC (CA 19-9) together with serum microRNA-196 and -200 (that we have chosen in the previous pilot study). All the markers were significantly elevated in the pancreatic cancer patients, without any difference between the subgroups according to DM presence/absence. While the sensitivity of CA 19-9 alone (to detect the cancer) was 85 % (specificity 73 %), combining all the three markers improved it to 95 % (specificity 77 %). In the pancreatic cancer group, there were only six patients with T1 or T2 stage (others had an advanced stage of the disease – T3, T4). While CA 19-9 alone identified only 2 patients of them, the combined test identified all the six patients (data not shown in the poster). Continue reading

Vitamin A May Inhibit Pancreatic Cancer by Preventing Desmoplasia That Surrounds Tumor

MedicalResearch.com Interview with:

Armando E. del Río Hernández, PhD European Research Council Fellow Head, Cellular and Molecular Biomechanics Laboratory http://biomechanicalregulation-lab.org/ Senior Lecturer, Department of Bioengineering Imperial College London

Dr. del Río Hernández

Armando E. del Río Hernández, PhD
European Research Council Fellow
Head, Cellular and Molecular Biomechanics Laboratory
http://biomechanicalregulation-lab.org/
Senior Lecturer, Department of Bioengineering
Imperial College London

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Pancreatic cancer is an extremely aggressive disease with an unacceptably low survival rate that has not changed during the last 40 years despite significant efforts aimed at developing therapies against cancer cells.

Pancreatic cancer is characterised by an extensive desmoplasia, which forms the majority of the tissue around the tumour. This desmoplastic tissue is known to help the tumour to grow and metastasize, and hinders drug delivery.

We have focused our efforts on understanding how pancreatic stellate cells (PSCs), which are the key effectors that orchestrate the desmoplastic reaction in pancreatic cancer, can promote tumour progression. PSCs in healthy pancreas have abundant vitamin A storage in their cytoplasm and exist in a quiescent state that guarantees a balanced tissue homeostasis. In pancreatic cancer, loss of this balance activates PSCs, which lose the vitamin A content and remodel the surrounding tissue to make it favourable for cancer cell invasion.
We found that treating PSCs which ATRA (All trans-retinoic acid), the active metabolite of vitamin A mechanically reprograms PSCs to promote quiescence in vitro. Quiescent PSCs are unable to remodel the microenvironment to allow pancreatic cancer cell invasion.

To get more information about our findings please find the article in the open access journal Nature Communications:http://www.nature.com/articles/ncomms12630

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Pancreatic Cancer Study Finds Abraxane Superior to Paclitaxel

MedicalResearch.com Interview with:

Rajesh Kumar NV, Ph.D. Instructor of Oncology and Pathology Johns Hopkins University School of Medicine Baltimore, MD, USA Current Affiliation: Senior Manager, Human Therapeutics Division, Intrexon Corporation, 20358 Seneca Meadows Parkway, Germantown, MD, USA

Dr. Rajesh Kumar NV

Rajesh Kumar NV, Ph.D.
Instructor of Oncology and Pathology
Johns Hopkins University School of Medicine
Baltimore, MD, USA
Current Affiliation: Senior Manager, Human Therapeutics Division, Intrexon Corporation, 20358 Seneca Meadows Parkway, Germantown, MD, USA

MedicalResearch.com: What is the background for this study?

Response: Pancreatic cancer remains as one of the most deadly malignancies in the world. Recently, a cremophor-free and albumin-bound formulation of paclitaxel (nab-PTX, Abraxane) in combination with gemcitabine (GEM, Gemzar) is recently approved as a standard of care treatment option for patients with metastatic pancreatic cancer. Majority of the newly diagnosed pancreatic cancer patients use the nab-PTX plus GEM regimen. Currently there are over 100 clinical trials at various stages with this regimen as a backbone to approved medicines or investigational agents. Since widely available cremophor-based paclitaxel (PTX, Taxol) is a key chemotherapy component for the treatment of several human malignancies and the treatment cost of nab-PTX is relatively higher than PTX, patients, clinicians, third party payers and regulatory agencies have a substantial interest in understanding whether these two drugs provide a similar level of therapeutic efficacy in pancreatic cancer.

We utilized orthotopic models of human pancreatic cancer, which were shown to better recapitulate the histologic and metastatic characteristics of disease, and compared the anticancer efficacy, effect on tumor stroma modulation, metastatic spreading to distant organs and survival following GEM, PTX, nab-PTX and combinations of GEM plus PTX or nab-PTX. The preclinical trial used a total of 300 mice with established orthotopic pancreatic tumors. The tumors used for implantation were originally resected from the primary tumors of patients with moderately differentiated and poorly differentiated pancreatic cancer.

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New Survival Prediction Model for Locally Advanced Pancreatic Cancer

MedicalResearch.com Interview with:

Dr-Dewi-VernereyDewi Vernerey PhD
Epidemiologist / Statistician
Methodology and quality of Life in oncology unit
University Hospital of Besançon

MedicalResearch.com: What is the background for this study?

Response: The management of locally advanced pancreatic cancer (LAPC) patients is still controversial. Better discrimination for the prediction of overall survival (OS) at diagnosis is needed. Currently, there is a lack of a staging system and an absence of a consensus regarding patient-specific risk profile for OS that can lead to confusion about the development of research strategy and to potentially inappropriate management of patients with locally advanced pancreatic cancer.

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Study Identifies Pathway Linking Obesity With Pancreatic Cancer Progression

Rakesh K. Jain, Ph.D. A.W.Cook Professor of Radiation Oncology (Tumor Biology) Director, E.L. Steele Laboratory Department of Radiation Oncology Harvard Medical School and Massachusetts General Hospital Boston, MA 02114

Dr. Rakesh Jain

MedicalResearch.com Interview with;
Dr. Rakesh K. Jain, PhD
A.W.Cook Professor of Radiation Oncology (Tumor Biology)
Director, E.L. Steele Laboratory
Department of Radiation Oncology
Harvard Medical School and
Massachusetts General Hospital
Boston, MA 02114

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death worldwide, and more than half of patients diagnosed with PDAC are overweight or obese. Among patients with PDAC, obesity more than doubles the already high risk of death, and our work aims to reveal the underlying mechanisms. Specifically, we identified that obesity increases desmoplasia – an accumulation of connective tissue and inflammation – hallmark of Pancreatic ductal adenocarcinoma and discovered underlying mechanisms.

In our report published online in Cancer Discovery, we describe how interactions among fat cells, immune cells and connective tissue cells in obese individuals create a microenvironment that promotes tumor progression while diminishing the response to chemotherapy. We demonstrated the negative impact of obesity on numerous aspects of tumor growth, progression and treatment response in several animal models of pancreatic ductal adenocarcinoma and confirmed some of our findings in samples from cancer patients. Along with finding that tumors from obese mice or patients exhibited elevated levels of adipocytes or fat cells and of desmoplasia, both of which fuel tumor progression and interfere with treatment response, we identified the underlying causes.

The elevated desmoplasia in obese mouse models of PDAC was caused by the activation of pancreatic stellate cells through the angiotensin II type-1 receptor (AT1) signaling pathway. This activation was induced by interleukin-1 beta (IL-1ß) produced by fat cells as well as the immune cells called neutrophils within tumors. Inhibiting AT1 signaling with losartan, which is used clinically to treat hypertension, or the blockade of IL-1ß reduced obesity-associated desmoplasia and tumor growth and increased the response to chemotherapy in the obese mouse model but not in normal weight animals. Analysis of tumors from human PDAC patients revealed increased desmoplasia and fat deposits in samples from obese patients, and data from more than 300 patients showed that excess weight was associated with a reduction in patients.

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Paradoxical Cell Death Mechanism Accelerates Pancreatic Cancer Growth

MedicalResearch.com Interview with:

Dr. George Miller, MD Vice Chair for research, Department of Surgery Associate Professor, Department of Surgery Associate Professor, Department of Cell Biology NYU Langone’s Perlmutter Cancer Center

Dr. George Miller

Dr. George Miller, MD
Vice Chair for research, Department of Surgery
Associate Professor, Department of Surgery
Associate Professor, Department of Cell Biology
NYU Langone’s Perlmutter Cancer Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Miller: Cancer cell death is the goal of most therapeutic programs. Indeed, chemotherapy induces cancer cell death. We show that a novel form of cancer cell death entailing organized necrosis is a prominent way by which cancer cells die. However, paradoxically this form of cell death termed “necroptosis” actually accelerates pancreatic cancer growth in animals by inducing immune suppressive inflammation.

MedicalResearch.com: What should clinicians and patients take away from your report?

Dr. Miller: Novel agents are needed to block necroptosis in pancreatic cancer. This can potentially enhance the immune system’s ability to fight the cancer.

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Study Evaluates Obesity-Related Factors Leading to Pancreatic Cancer Progression

MedicalResearch.com Interview with:

Joao Incio MD Research Fellow in Radiation Oncology Harvard Medical School/MGH Boston, MA

Dr. Joao Incio

Joao Incio MD
Research Fellow in Radiation Oncology
Harvard Medical School/MGH
Boston, MA

MedicalResearch.com: What is the background for this study?

Dr. Incio: With  the  current  epidemic  of  obesity,  the  majority  of  pancreatic  cancer  patients  are  overweight  or  obese  at  diagnosis.  Importantly, obesity  worsens treatment  outcomes  in  pancreatic  cancer  patients.  Therefore,  understanding  the  mechanisms  that  underlie  the  poorer  prognosis  of  obese  cancer  patients  is  of  paramount importance.  Obesity  causes  inflammation  and  fibrosis  in  the  normal  pancreas  due  to  the  accumulation  of  dysfunctional  hypertrophic  adipocytes.  Importantly,  desmoplasia  -­  a fibroinflammatory  microenvironment  -­  is  a  hallmark  of  pancreatic  ductal  adenocarcinoma  (PDAC),  and  we  have  shown  that  activation  of  pancreatic  stellate  cells  (PSCs)  via angiotensin-­II  type  1  receptor  (AT1)  pathway  is  a  major  contribution  to  tumor  desmoplasia.  Whether  obesity  affects  desmoplasia  in  PDACs,  and  interferes  with  delivery  and response  of  chemotherapeutics,  was   the focus of our study.

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Breast and Pancreatic Cancer: Pathway Identified That Accelerates Tumors in Obese Patients

MedicalResearch.com Interview with:

Joao Incio, MD Edwin L. Steele Laboratory for Tumor Biology Massachusetts General Hospital | Harvard Medical School | Boston, MA, U.S.A Department of Internal Medicine | Hospital S. Joao | Porto, Portugal

Dr. Joao Incio

Joao Incio, MD
Edwin L. Steele Laboratory for Tumor Biology
Massachusetts General Hospital | Harvard Medical School | Boston, MA, U.S.A
Department of Internal Medicine | Hospital S. Joao | Porto, Portugal

 Medical Research: What is the background for this study? What are the main findings?

Dr. Incio:  The study focused on the effects of obesity on pancreatic and breast cancer, since more than half of those diagnosed with such tumors are overweight or obese. In addition, a number of large-scale studies have found that obesity leads to an increased risk of death in pancreatic, breast and other types of cancer. But prior to the current study the mechanism of obesity-induced pancreatic and breast cancer progression was unclear. We have uncovered a novel mechanism behind the ability of obesity to promote cancer progression.  We found an association between obesity and an overabundance of a factor called PlGF (placental growth factor) and that PlGF’s binding to its receptor VEGFR-1, which is expressed on immune cells within tumors, promotes tumor progression.

We found that obesity increased infiltration of tumor-promoting immune cells and the growth and metastasis of pancreatic cancers. Blocking VEGFR-1 signaling shifted the immune environment towards prevention of tumor progression in obese but not in lean mice in both pancreatic and breast cancer models. We also found that PlGF was present in excess in obesity and that reduction of PlGF produced similar results to VEGFR-1 inhibition in the tumors of obese mice. We also discovered that targeting the PlGF/VEGFR-1 interaction prevents weight gain in a genetically obese mouse model but worsens a diabetes-like condition, a worsening that was alleviated by use of the common diabetes drug metformin, which also had beneficial anti-tumor effects.

Our findings in cellular and animal models, as well as in patient tumor samples, indicate that targeting the PlGF/ VEGFR-1 pathway may be particularly effective in obese patients.

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Metformin May Inhibit Progression of Pancreatic Cancer In Obese Patients

More on Pancreatic Cancer on MedicalResearch.com

Dai Fukumura, M.D., Ph.D. Edwin L. Steele Laboratory Department of Radiation Oncology Massachusetts General Hospital Harvard Medical School

Dr. Dai Fukumura

MedicalResearch.com Interview with:
Dai Fukumura, M.D., Ph.D.
Joao Incio, M.D.
and Rakesh K. Jain, Ph.D
Edwin L. Steele Laboratory
Department of Radiation Oncology
Massachusetts General Hospital
Harvard Medical School

Medical Research: What is the background for this study? What are the main findings?

Dr. Fukumura: This study focused on pancreatic ductal adenocarcinoma, the most common form of pancreatic cancer, which accounts for almost 40,000 cancer death in the U.S. ever year. Half of those diagnosed with this form of pancreatic cancer are overweight or obese, and up to 80 percent have type 2 diabetes or are insulin resistant. Diabetic patients taking metformin – a commonly used generic medication for type 2 diabetes – are known to have a reduced risk of developing pancreatic cancer; and among patients who develop the tumor, those taking the drug may have a reduced risk of death. But prior to the current study the mechanism of metformin’s action against pancreatic cancer was unclear, and no potential biomarkers of response to metformin had been reported.

We have uncovered a novel mechanism behind the ability of the diabetes drug metformin to inhibit the progression of pancreatic cancer. Metformin decreases the inflammation and fibrosis characteristic of the most common form of pancreatic cancer. We found that metformin alleviates desmoplasia – an accumulation of dense connective tissue and tumor-associated immune cells that is a hallmark of pancreatic cancer – by inhibiting the activation of the pancreatic stellate cells that produce the extracellular matrix and by reprogramming immune cells to reduce inflammation. Our findings in cellular and animal models and in patient tumor samples also indicate that this beneficial effect may be most prevalent in overweight and obese patients, who appear to have tumors with increased fibrosis.

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Pancreatic Cancer May Be Inhibited By Signaling Peptide

Prof. Dr. Véronique Orian-Rousseau Group Leader Karlsruher Institut für Technologie (KIT) Institut für Toxikologie und Genetik (ITG) Campus Nord Karlsruhe Germany

Dr. Orian-Rousseau

MedicalResearch.com Interview with:
Prof. Dr. Véronique Orian-Rousseau

Group Leader
Karlsruher Institut für Technologie (KIT)
Institut für Toxikologie und Genetik (ITG)
Campus Nord
Karlsruhe Germany

Medical Research: What is the background for this study? What are the main findings?

Response: Our group is working on the role of cell adhesion molecules in development and in tumor progression and metastasis. One protein in focus is CD44, a molecule that controls proliferation, differentiation and survival of cells. We have shown that one member of this family, namely CD44v6 acts as a co-receptor for receptor tyrosine kinases (RTKs) such as MET and VEGFR-2. CD44v6 has a dual function. It controls both the activation and signaling from the RTKs. We have identified a sequence in CD44v6 that is crucial for its function as a co-receptor. From this sequence we made a peptide that inhibits MET and VEGFR2 activation and signaling.

The CD44v6 peptide was used in several independent mouse models of pancreatic cancer including the transgenic PDAC mouse model. It could inhibit the growth of the primary tumor, metastasis and in addition could eliminate already established metastases.

In addition, we could show that MET and CD44v6 expression correlates with poor prognosis and metastasis in a cohort of pancreatic cancer patients.

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Regional, Racial Differences in Surgical Resections for Pancreatic Cancer

Jason S. Gold MD FACS Chief of Surgical Oncology, VA Boston Healthcare System Assistant Professor of Surgery, Harvard Medical School Brigham and Women’s Hospital

Dr.  Jason Gold

MedicalResearch.com Interview with:
Jason S. Gold MD FACS

Chief of Surgical Oncology, VA Boston Healthcare System
Assistant Professor of Surgery, Harvard Medical School
Brigham and Women’s Hospital

Medical Research: What is the background for this study?

Dr. Gold: Pancreas cancer is a lethal disease. While advances in the best available care for pancreas cancer are desperately needed, improvements can be made in addressing disparities in care. This study aimed to evaluate associations of social and demographic variables with the utilization of surgical resection as well as with survival after surgical resection for early-stage pancreas cancer.

Medical Research: What are the main findings?

Dr. Gold: The main findings are the following:

1:     We found that less than half of patients with early-stage pancreas cancer undergo resection in the United States. Interestingly, the rate of resection has not changed with time during the eight-year study period.

2.  We also found significant disparities associated with the utilization of surgical resection for early-stage pancreas cancer in the United States. African American patients, Hispanic patients, single patients, and uninsured patients were significantly less likely to have their tumors removed. There were regional variations in the utilization of surgical resection as well. Patients in the Southeast were significantly less likely to have a pancreas resection for cancer compared to patients in the Northeast.

3. Among the patients who underwent surgical resection for early-stage pancreas cancer, we did not see significant independent associations with survival for most of the social and demographic variables analyzed. Surprisingly, however, patients from the Southeast had worse long-term survival after pancreas cancer resection compared to those in other regions of the United States even after adjusting for other variables.

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Repositioning Bazedoxifene For Use Against Pancreatic Cancer

Jiayuh Lin, Ph.D. Associate Professor, College of Medicine, The Ohio State University

Dr. Lin

MedicalResearch.com Interview with:
Jiayuh Lin, Ph.D.

Associate Professor,
College of Medicine,
The Ohio State University

Medical Research: What is the background for this study? What are the main findings?

Dr. Jiayuh Lin: Pancreatic cancer is one of the most serious forms of cancer.  Because of the poor response to chemotherapy as conventionally used, patients with any stage of pancreatic cancer may appropriately be considered candidates for clinical trials using novel agents.

IL-6 signaling plays an important role in oncogenesis and high serum IL-6 levels is a poor prognostic factor for overall survival in pancreatic cancer. Therefore, IL-6 is considered as a viable target for pancreatic cancer therapy.  We utilized a drug discovery method with Multiple Ligand Simultaneous Docking and drug repositioning to identify an existing FDA-approved drug Bazedoxifene with previously unknown biological function as an IL-6/GP130 inhibitor.  Bazedoxifene can inhibit cell viability of pancreatic cancer cells expressing IL-6 and suppressed pancreatic tumor growth in vivo.

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Insurance Expansion Increased Access To Pancreatic Cancer Surgery

MedicalResearch.com Interview with:

Andrew P. Loehrer, MD David Torchiana Fellow in Health Policy and Management Massachusetts General Physicians Organization Research Fellow Codman Center for Clinical Effectiveness in Surgery Department of Surgery Massachusetts General Hospital Andrew P. Loehrer, MD
David Torchiana Fellow in Health Policy and Management
Massachusetts General Physicians Organization
Research Fellow
Codman Center for Clinical Effectiveness in Surgery
Department of Surgery
Massachusetts General Hospital

Medical Research: What is the background for this study? What are the main findings?

Dr. Loehrer: The incidence of pancreatic cancer is increasing and is on pace to become the second leading cause of cancer mortality by the year 2020. While surgery remains the only chance for long-term survival, significant and persistent disparities in evaluation for and receipt of surgery remain for underinsured patients across the United States. The Affordable Care Act aims to increase access to care through expansion of health insurance coverage and was modeled on previous reform in the Commonwealth of Massachusetts.

We evaluated the impact of the 2006 Massachusetts health reform on rates of surgery for pancreatic cancer. We found the insurance expansion to be independently associated with a 67% increased rate of resection for pancreatic cancer. While disparities in resection rates by insurance status decreased after the health reform, significant gaps remain between privately-insured patients and government-subsidized/self-pay patients.

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Attacking Pancreatic Cancer Stem Cells May Lead To Better Treatment

Patricia Sancho, PhD, Lecturer Barts Cancer Institute - a Cancer Research UK Centre of Excellence Queen Mary University of London Centre for Stem Cells in Cancer & Ageing / John Vane Science Centre, Charterhouse Square, London EC1M 6BQMedicalResearch.com Interview with:
Patricia Sancho, PhD, Lecturer

Barts Cancer Institute – a Cancer Research UK Centre of Excellence
Queen Mary University of London
Centre for Stem Cells in Cancer & Ageing / John Vane Science Centre, Charterhouse Square, London

Medical Research: What is the background for this study? What are the main findings?

Dr. Sancho: Cancer cells commonly rely on glycolysis, the type of metabolism that does not use oxygen to generate their energy however, we have now found that not all cancer cells are alike when it comes to metabolism. Pancreatic Cancer Stem cells (PancCSCs) can make use of a more efficient form of metabolism, called oxidative phosphorylation or OXPHOS, which does use oxygen. OXPHOS uses a part of the cell called mitochondria and it is this which can be targeted with anti-diabetic drug, metformin. Some PancSCs are however able to escape this treatment by being much more flexible in their metabolism, leading to a recurrence of the cancer, but we also found a way to prevent such resistance and force all Pancreatic Cancer Stem cells to keep using OXPHOS.

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miRNA-based Blood Test May Detect Early Pancreatic Cancer

Jenny Permuth Wey, PhD, MS Assistant Member Departments of Cancer Epidemiology and Gastrointestinal Oncology Moffitt Cancer Cente
MedicalResearch.com Interview with:
Jenny Permuth Wey, PhD, MS
Assistant Member
Departments of Cancer Epidemiology and Gastrointestinal Oncology
Moffitt Cancer Center

 

Medical Research: What is the background for this study? What are the main findings?

Dr. Wey: Pancreatic cancer is one of the deadliest cancers world-wide. It is currently the fourth leading cause of cancer-related deaths in the United States, and is predicted to become the second leading cause by 2030. Currently there are no accurate methods to diagnose pancreatic cancer early when a patient may be eligible for surgery to remove the tumor and hopefully survive longer. To beat this disease, early detection is key, and our team has dedicated efforts to studying pancreatic cancer in its ‘precancerous’ state because we and other researchers believe that the identification and treatment of precancerous pancreatic lesions offers a promising strategy to reduce the number of people losing their lives to this disease.

Similar to how colon polyps can progress into colon cancer, we now know that certain types of pancreatic cystic lesions can progress into pancreatic cancer. Pancreatic cancer precursors/pre-cancers known as intraductal papillary mucinous neoplasms (IPMNs) account for nearly one-half of the estimated 150,000 asymptomatic pancreatic cysts detected as ‘incidental findings’ on computed tomography (CT) scans or magnetic resonance imaging (MRI) scans each year during the clinical work-up for an unrelated condition.  Imaging alone cannot reliably distinguish between benign, pre-cancerous, and cancerous cysts, and cannot differentiate ‘low-risk’intraductal papillary mucinous neoplasms‘ (defined as low- or moderate-grade disease) that can be monitored from ‘high-risk’ IPMNs (defined as high-grade or invasive disease) that should be surgically removed.  The decision to undergo pancreatic surgery is not trivial for the patient and medical team since pancreatic surgery can be associated with an estimated 40% chance of complications and a 4% chance of death. Noninvasive tests are needed to accurately detect precancerous lesions of the pancreas so that personalized risk assessment and care can be provided.

microRNAs (miRNAs) are small molecules that act as ‘master-regulators’ of cancer-related processes in the body. One of the main purposes of our ‘proof of principle’ study was to measure miRNAs in the blood and determine whether a set of miRNAs could distinguish patients with IPMNs from healthy individuals. We then sought to determine whether a set of miRNAs could distinguish patients known to have ‘low-risk’ IPMNs from those with ‘high-risk’ IPMNs.  We show that new, relatively inexpensive digital technology could reliably measure miRNAs in blood plasma (the pale yellow liquid component of blood) from individuals newly-diagnosed with pancreatic cancer precursors (IPMNs) and healthy individuals.  Thirty miRNAs out of 800 tested showed higher levels in IPMN patients compared to healthy individuals, providing a preliminary ‘miRNA signature’ that may be found only in people with early pancreatic disease, suggesting it could serve as an early diagnostic tool.  Furthermore, we also provide preliminary data to suggest that a 5-miRNA signature can partially distinguish high-risk IPMNs that warrant resection from low-risk IPMNs that can be watched.  This is important clinically because it would be opportune to personalize care such that high-risk IPMNs that warrant resection are properly identified while individuals with low-risk IPMNs are spared the substantial  risks of mortality and morbidity associated with overtreatment from unnecessary surgery.

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Urine Biomarker Panel Detects Early Pancreatic Cancer

Tatjana Crnogorac-Jurcevic MD PhD Reader Centre for Molecular Oncology Barts Cancer Institute, Queen Mary, University of London London UKMedicalResearch.com Interview with:
Tatjana Crnogorac-Jurcevic MD PhD
Reader Centre for Molecular Oncology
Barts Cancer Institute, Queen Mary
University of London
London UK 

Medical Research: What is the background for this study? What are the main findings?
Dr. Crnogorac-Jurcevic: Pancreatic adenocarcinoma (PDAC) is one of the most difficult cancers to detect. More than 80% of patients usually present at a late stage, with either locally advanced or with already metastatic disease. This is one of the major reasons for a bleak prognosis of this malignancy, which is typically 3-6 months and with <5% five-year survival. However, if patients are diagnosed with stage II disease, the survival rate is 20%, and at stage I, in patients with very small tumours, the five-year survival can increase up to 60%.

In order to find biomarkers for early detection of this disease, we have performed in depth GeLC/MS/MS (SDS-PAGE-liquid chromatography-tandem mass spectrometry) analysis of 18 proteomes of urine samples collected from healthy controls, chronic pancreatitis, and patients with Pancreatic adenocarcinoma and obtained around 1500 non-redundant proteins. From these, three proteins, LYVE-1, REG1A, and TFF1, were selected for further analysis based on their known biological functions and statistical difference in comparisons of the experimental groups. These biomarkers were subsequently validated using ELISA assays in a multicenter cohort of urine samples: 87 from healthy people, 92 from patients with chronic pancreatitis, and 192 from PDAC patients.

Multiple logistic regression was then applied: when comparing Pancreatic adenocarcinoma with healthy urine specimens, the resulting areas under the receiver-operating characteristic curves (AUC) of the three biomarkers combined into a panel were 0.89 (95% confidence interval: 0.84–0.94) in the training dataset (70% of the data) and 0.92 (95% confidence interval: 0.86–0.98) in the validation dataset (30% of the data). When the results from the analysis of PDAC stage I–II (n=71) urine samples were compared with the healthy urine specimens, the panel achieved AUCs of 0.90 (95% confidence interval: 0.84–0.96) and 0.93 (95% confidence interval: 0.84–1.00) in the training and validation datasets, respectively. In comparison to matching plasma CA19.9 values, the only Pancreatic adenocarcinoma biomarker in widespread clinical use (albeit mostly for monitoring of the disease), the panel achieved a higher AUC of 0.97 (95% confidence interval: 0.94–0.99) than CA19.9 (AUC 1/4 0.88; 95% confidence interval: 0.81–0.95, P=0.005). When combined with CA19.9, increased AUC of 0.99 (95% confidence interval: 0.97–1.00, P=0.04) was achieved, but this was not seen in a panel combined with plasma CA19.9 in stage I–IIA PDAC (n =17) vs. healthy sample comparison.

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New Therapeutic Target May Make Chemotherapy More Effective Against Pancreatic Cancer

Dr. Janaiah Kota Assistant Professor, Department of Medical and Molecular Genetics Indiana University School of Medicine Indianapolis, IN,MedicalResearch.com Interview with:
Dr. Janaiah Kota
Assistant Professor, Department of Medical and Molecular Genetics
Indiana University School of Medicine
Indianapolis, IN,


Medical Research: What is the background for this study?

Dr. Kota: Pancreatic cancer tumors are surrounded by a thick fibrotic shell known as “stroma” which protects the cancer cells from anticancer drugs such as chemotherapy. However, complete depletion of tumor stroma leads to more aggressive disease and decreases survival. The stromal abundance needs to be appropriately moderated (i.e. not too much nor too little) in pancreatic tumors. None of the current anti-stromal therapies have been effective enough to resolve this problem. Unless we understand the molecular signatures associated with tumor stroma, it will be challenging to develop an effective therapeutic strategy.

There is a desperate need to develop new therapies for pancreatic cancer as only 7 percent of people with the disease survive more than 5 years after diagnosis. According to the National Cancer Institute, there will be an estimated 48,960 new cases of pancreatic cancer and 40,560 deaths from the disease in 2015.

Medical Research: What are the main findings?

Dr. Kota: We found that the loss of microRNA-29 (miR-29) is a common phenomenon of pancreatic cancer stromal cells, and that by restoring it, the viability and growth of the cancerous cells and stromal accumulation was reduced. The use of miR-29 as a therapeutic agent may be more effective in targeting reactive stroma, as a single miRNA regulates the expression of several genes associated with disease mechanisms. We expect that this novel approach has the potential to overcome the problems associated with current anti-stromal drugs and could lead to improved therapeutic strategies, enhanced drug delivery to the tumor bed, and, in the future, improved patient survival.
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Genetic Diversity of Pancreatic Cancer May Lead To Therapeutic Targets

Dr. Agnieszka Witkiewicz MD Associate Professor of Pathology Harold C. Simmons Comprehensive Cancer Center UT SouthwesternMedicalResearch.com Interview with:
Dr. Agnieszka Witkiewicz MD
Associate Professor of Pathology
Harold C. Simmons Comprehensive Cancer Center
UT Southwestern

MedicalResearch: What is the background for this study?

Dr. Witkiewicz: Pancreatic ductal adenocarcinoma (PDA) has a dismal prognosis, with a five year survival rate of approximately 6%. This poor outcome is related to multiple factors, including the relatively late stage of diagnosis, many patients presenting with unresectable disease, and therapy recalcitrance resulting in disease recurrence in spite of operable disease and systemic therapy. Thus far, insights into how to target the treatment of Pancreatic ductal adenocarcinoma have remained unclear in spite of prior sequencing efforts.

MedicalResearch: What are the main findings?

Dr. Witkiewicz: The underlying critical finding of the study was that Pancreatic ductal adenocarcinoma is genetically diverse and that, in principle, this diversity could be exploited for the treatment of disease.   Specifically, many cases harbored deregulation in pathways that are the target for drug development.   For example, we identified cases that were driven by BRAF V600E and that were sensitive to the FDA approved drug Vemurafenib.   Similarly, multiple cases harbored defects in DNA repair processes that impart sensitivity to select chemotherapeutic agents and PARP inhibitors.  Common pathway deregulation was observed in reference to beta-catenin, notch, hedgehog, chromatin remodeling, and cell cycle regulatory pathways that are all targets for therapeutic intervention.

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Signaling Pathways That Lead Pancreatic Cancer Identified

Peter Storz, Ph.D. Associate Professor & Consultant Department of Cancer Biology Mayo Clinic Jacksonville, FL 32224MedicalResearch.com Interview with:
Peter Storz, Ph.D.
Associate Professor & Consultant Department of Cancer Biology
Mayo Clinic
Jacksonville, FL 32224

 

Medical Research: What is the background for this study? What are the main findings?

Dr. Storz:   Our study focuses on cellular signaling mechanisms that lead to the initiation of pancreatic cancer. After acquisition of an oncogenic mutation of Kras, pancreatic acinar cells can undergo a transdifferentiation process to a phenotype that gives rise to pancreatic intraepithelial lesions (PanINs). These lesions then can further progress to pancreatic cancer.

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Familial Pancreatic Cancer Linked To Increased Melanoma and Endometrial Cancer Risk

MedicalResearch.com Interview with:
Jeremy L. Humphris MBBS

The Kinghorn Cancer Center, Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia and

Andrew V. Biankin
Regius Professor of Surgery
Director, Wolfson Wohl Cancer Research Centre,
University of Glasgow
Garscube Estate, Switchback Road, Bearsden, Glasgow Scotland
United Kingdom

Medical Research: What are the main findings of the study?

Response: Familial pancreatic cancer (FPC) is a family with at least 2 first degree (parent-child or siblings) with pancreatic cancer. We found these patients represent nearly 9% of our cohort. In addition we found those with familial pancreatic cancer were more likely to have other first degree relatives with a history of extra-pancreatic cancer, in particular melanoma and endometrial cancer. Patients with familial pancreatic cancer had more high grade precursor lesions in the pancreas adjacent to the tumour but the outcome was similar. Smoking was more prevalent in sporadic pancreatic cancer and active smoking was associated with significantly younger age at diagnosis in both groups. Long-standing diabetes mellitus (> 2 years duration) was associated with poorer survival in both groups.
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Pancreatic Cancer: Chemotherapy Effect May Be Enhanced By Chokeberry Extract

MedicalResearch.com: Interview
Bashir A. Lwaleed PhD, FRCPath, CBiol FSB, FIBMS Senior Lecturer
Faculty of Health Sciences
University of Southampton
Southampton General Hospital
Southampton United Kingdom

Medical Research: What are the main findings of the study?

Dr. Lwaleed: That constituent(s) of Chokeberries has a supra-additive cytotoxic effect in combination with the drug gemcitabine, which is used clinically for this condition, when applied to a pancreatic carcinoma cell line in vitro.

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Pancreatic Cancer: Combination Chemotherapy Increases Survival

Andrea Wang-GillamMD, PhD Assistant Professor, Department of Medicine Oncology Division, Medical Oncology Section Washington University School of Medicine in St. LouisMedicalResearch.com Interview with:
Andrea Wang-GillamMD, PhD
Assistant Professor, Department of Medicine
Oncology Division, Medical Oncology Section
Washington University School of Medicine in St. Louis


Medical Research: What are the main findings of the study?

Dr. Wang-Gillam: This is a global randomized phase III trial of MM398 plus 5FU/LV vs. MM398 vs. 5FU/LV in patients with metastatic pancreatic cancer who had received prior gemcitabine-based therapy. The primary endpoint was overall survival (OS). The secondary endpoints included progression-free survival (PFS), response rate (RR), biochemical response and safety. The trial achieved its primary endpoint. The median overall survival was statistically longer with the combination of MM398 plus 5FU/LV compared with 5FU/LV alone (6.1 months vs 4.2 months; HR of 0.67; p=0.0122). A superior progression-free survival was also seen in the MM398 plus 5FU/LV group compared with the 5FU/LV alone group (3.1 months vs 1.5 months; HR of 0.56; p=0.0001). A higher response rate was observed in the combination regimen compared with the 5FU/LV group (16% vs 1%). There were no differences in overall survival or PFS between the MM 398 monotherapy and 5FU/LV groups.
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Pancreatic Cancer: Vaccine-Based Therapy May Make Tumors More Susceptible To Treatment

Lei Zheng, M.D., Ph.D. Assistant Professor of Oncology and Surgery Gastrointestinal Cancer Program Division of Immunology The Sidney Kimmel Comprehensive Cancer Center and Department of Oncology Johns Hopkins University School of Medicine The Bunting-Blaustein Cancer Research Building (CRB1) Baltimore, MD 21231MedicalResearch.com Interview with:
Lei Zheng, M.D., Ph.D.
Assistant Professor of Oncology and Surgery
Gastrointestinal Cancer Program
Division of Immunology
The Sidney Kimmel Comprehensive Cancer Center and
Department of Oncology
Johns Hopkins University School of Medicine
The Bunting-Blaustein Cancer Research Building (CRB1)
Baltimore, MD 21231

MedicalResearch: What are the main findings of the study?

Dr. Zheng: This study shows for the first time that treatment with a vaccine-based immunotherapy directly re-programs the pancreatic cancer microenvironment, allowing the formation of lymphoid aggregates, which are organized, lymph node-like, functional immune structures and which convert an immunologically quiescent tumor into an immunologically active tumor.  Continue reading

Green Tea Ingredient Changes Metabolism of Pancreatic Cancer Cells

Wai-Nang Paul Lee, M.D. Division Chief, Division of Pediatric Endocrinology and Metabolism Professor of Pediatrics Director of Biomedical Mass Spectrometry LaboratoryMedicalResearch.com Interview with:
Wai-Nang Paul Lee, M.D.
Division Chief, Division of Pediatric Endocrinology and Metabolism
Professor of Pediatrics
Director of Biomedical Mass Spectrometry Laboratory
Harbor-UCLA

MedicalResearch: What are the main findings of the study?

Dr. Wai-Nang Lee: The study reports that EGCG, the active biologic constituent in green tea, changed the metabolism of pancreatic cancer cells by suppressing the
expression of an enzyme associated with cancer, LDHA.

The researchers also compared the effects of EGCG with those of an enzyme
inhibitor, oxamate, which is known to reduce LDHA activity, and found that
they both operated in a similar manner by disrupting the pancreatic cancer
cells metabolic system.

Scientists had believed they needed a molecular mechanism to treat cancer,
but this study shows that they can change the metabolic system and have an
impact on cancer.
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Pancreatic Cancer: MMP3 Drives Progression Through Oncogenic Protein Activation

Dr. Derek Radisky PhD Associate Professor and Consultant Mayo Clinic Cancer CenterMedicalResearch.com Interview with
Dr. Derek Radisky PhD
Associate Professor and Consultant
Mayo Clinic Cancer Center

MedicalResearch: What are the main findings of the study? 

Dr. Radisky: The study used human tissue biopsies to find that production of matrix metalloproteinse-3 (MMP3)  in pancreatic cancer biopsies was associated with poorer patient prognosis, and showed through transgenic animal and cell culture experiments that this was due to activation of the oncogenic protein Rac1b.  The study thus identifies an MMP3-Rac1b signaling axis that drives pancreatic cancer progression.
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Mucin Profiling of Pancreatic Cysts to Improve Pancreatic Cancer Detection

Dr. Karolina Sjöberg Jabbar, MD, Medicine Policlinic II, Bla Straket 5, Sahlgrenska University Hospital Gothenburg, SwedenMedicalResearch.com Interview with
Dr. Karolina Sjöberg Jabbar, MD,

Medicine Policlinic II, Bla Straket 5, Sahlgrenska University Hospital
Gothenburg, Sweden

 

MedicalResearch.com: What are the main findings of the study?

Answer: The main finding of this study is that the presence of mucin proteins in pancreatic cyst fluid, as evaluated by mass spectrometry, can predict with high accuracy (97%) which pancreatic cysts contain premalignant and malignant tumours. This is important, given that pancreatic cystic lesions are an increasingly common incidental finding on imaging. While most of them pose no threat to the patient, a minor proportion has malignant potential, and may be considered precursors to pancreatic cancer.

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Pancreatic Cancer: Frequent Nut Consumption May Reduce Risk

MedicalResearch.com Interview with:
dr_ying_baoYing Bao, MD, ScD
Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School
Boston, MA.

MedicalResearch.com: What are the main findings of the study?

Dr. Bao: Frequent nut consumption is inversely associated with risk of pancreatic cancer in women, independent of other potential risk factors for pancreatic cancer.

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Pancreatic Cancer: Short Course Radiation May Benefit Elderly Patients

MedicalResearch.com Interview with: Dr. Raphael Yechieli
Department of Radiation Oncology at Henry Ford Hospital in Detroit:

MedicalResearch.com: What are the main findings of the study?

Dr. Yechieli:  The main findings of the study are that elderly patients with pancreatic cancer who also have significant co-morbidities can still be safely and effectively treated with a short course of radiation treatment. Furthermore, the local control and survival data from our study are similar to previously published data, where patients were treated with more intense and longer courses of treatment.

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Study examines screening for pancreatic cancer in high-risk populations

OAK BROOK, Ill. – July 25, 2011 – Researchers from New England report in a new study that using a tumor marker, serum CA 19-9, combined with an endoscopic ultrasound if the tumor marker is elevated, is more likely to detect stage 1 pancreatic cancer in a high-risk population than by using the standard means of detection. The study appears in the July issue of GIE: Gastrointestinal Endoscopy, the monthly peer-reviewed scientific journal of the American Society for Gastrointestinal Endoscopy (ASGE).

Pancreatic cancer is the fourth leading cause of cancer death in the United States. Advanced disease at diagnosis correlates directly with worse overall survival. Symptoms of abdominal pain, jaundice, and/or weight loss often do not appear until the tumor is locally advanced or metastatic, at which point effective treatment options are very limited. By contrast, detection and resection of pancreatic cancer, when it is confined to the pancreas (stage 1 disease), improves overall survival. An effective screening protocol is urgently needed to detect earlier stage tumors. Imaging methods that have been used for pancreatic cancer screening include endoscopic ultrasound (EUS), CT, endoscopic retrograde cholangiopancreatography (ERCP) and magnetic resonance imaging/MRCP.

There has been limited success in screening younger populations using the tumor marker CA19-9, so more recent pancreatic cancer screening protocols have focused on high-risk populations. It is estimated that 10 percent of patients in whom pancreatic cancer develops have at least one first-degree relative with the disease. Multiple cohort and case-control studies have demonstrated that a family history of a first-degree relative with pancreatic cancer significantly increases a patient’s risk of the development of pancreatic cancer, approximately two to five-fold. The risk of the development of pancreatic cancer increases significantly as the number of affected family members increases. Advanced age is also a significant risk factor, and 93 percent of patients with pancreatic cancer present after the age of 50.

“Our hypothesis was that a high-risk population identified by age and at least one first-degree relative with pancreatic cancer can be successfully screened. Our objective was to determine whether early pancreatic neoplasia can be detected in a high-risk population by using tumor marker CA 19-9 followed by targeted endoscopic ultrasound. We also sought to determine whether this protocol was more likely to detect early stage pancreatic cancer than standard means of detection,” said study lead author Richard Zubarik, MD, Fletcher Allen Health Care, University of Vermont. “Our results showed that potentially curative pancreatic adenocarcinoma can be identified with this screening protocol. Stage 1 pancreatic cancer is more likely to be detected by using this screening protocol than by using standard means of detection.”

Methods

This prospective cohort study was conducted at the University of Vermont (UVM) and the Dartmouth-Hitchcock Medical Center (DHMC). Patients were enrolled from September 2006 to July 2009. Patients included were between the ages of 50 and 80 and had at least one first-degree relative (parent, sibling, or child) with pancreatic cancer. Enrollment was initiated at age 45 if a patient had two first-degree relatives with pancreatic cancer and at age 40 if the person had a BRCA2 mutation or Peutz-Jeghers syndrome.

Serum CA 19-9 testing was performed on all patients. It was chosen as the initial screening method because it is acceptable to patients, easily obtainable, widely available, inexpensive, and relatively sensitive for the disease. Endoscopic ultrasound was performed only in patients with an elevated CA 19-9 level (a CA 19-9 value greater than 37 U/mL was considered elevated) regardless of whether only one or more than one family member was affected with pancreatic cancer.

Patients who were diagnosed with pancreatic cancer at UVM (but were not enrolled in the CA 19-9/EUS study) during the same period were prospectively identified and used as the comparison group. These patients were identified by the Cancer Data Registry at the University of Vermont. Charts were then reviewed to verify tumor type, staging data and survival.

Results

A total of 546 patients were enrolled in the study. CA 19-9 was elevated in 27 patients (4.9 percent). Neoplastic or malignant findings were detected in five patients (0.9 percent), and pancreatic cancer in one patient (0.2 percent). The patient with pancreatic cancer detected as part of this study was one of two patients presenting to the University of Vermont with stage 1 cancer. One-year follow-up contact was performed by telephone in 519 patients (95 percent), by chart review in 24 patients (four percent), and by review of the social security death index in three patients (less than one percent). Pancreatic cancer was not detected at the one-year follow-up in any additional patients.

In the comparison group, a total of 124 patients received a diagnosis of pancreatic cancer between September 2006 and July 2009. Staging of the comparison group at the time of presentation was as follows: stage 1, one patient (0.9 percent); stage 2, 52 patients (45.6 percent); stage 3, 20 patients (17.5 percent); stage 4, 41 patients (36 percent). The patient detected in the CA 19-9/EUS study had stage 1 disease, whereas only 0.9 percent of patients in the comparison group presented with stage 1 disease. This difference was statistically significant despite only having one patient with pancreatic cancer detected in the study group because the detection of stage 1 cancer in the comparison group was so rare. Median survival for the 122 subjects in the comparison group was seven months, with a 2-year survival rate of 10 percent.

The results conclude that potentially curative pancreatic cancer can be identified with CA 19-9 and targeted EUS. Stage 1 pancreatic cancer is more likely to be detected by using this screening protocol than by using standard means of detection. Potential advantages include acceptable rates of disease diagnosis and exclusion as well as acceptable costs (cost to detect 1 pancreatic neoplasia was $8,431, while the cost to detect 1 pancreatic cancer was $41,133). In particular, the patient with pancreatic cancer detected with this screening protocol is alive without evidence of recurrence three years after surgical resection and is the longest survivor of pancreatic cancer detected in a published screening protocol. Also, evidence of pancreatic cancer did not develop in subjects with negative screening studies, at least in short-term follow-up.

The researchers note that the sample size is adequate only to demonstrate the feasibility of this approach, but summarized that this trial successfully screened a high-risk patient population for pancreatic cancer based on age and genetic predisposition. Early pancreatic cancer, associated with prolonged disease-free survival, can be detected as part of this pancreatic screening protocol. Stage 1 pancreatic cancer was more likely to be detected with CA 19-9 and targeted EUS, and it appears to be superior to the standard means of pancreatic cancer detection.