We have created this section of our web site to inform our members of the status of Grants the Foundation has completed as well as the Grants that ECEF has made for the current year to various Institutions and Grants it is considering during the coming year and beyond. The funds we receive from donations are earmaked to cover our commitment to these projects and support the Grants in Process.
We have displayed these Grants in the following categories:
2004 $75,000 PAID
ECEF was established in 2003 with the main purpose at the time to raise the $75,000 that Memorial Sloan-Kettering Cancer Center deemed the cost to be to use its resources to establish a computer disk that people could use as a reference source if they were diagnosed with esophageal cancer. This CD ROM was completed in 2004 and it has been given to each esophageal cancer patient that has been so diagnosed at MSKCC. In addition this CD ROM is available on our web site as something you can request and ECEF will send that out to patients and caregivers who join ECEF at no cost to the person requesting it. It is ECEF’S intent not update this CD ROM since it is an expensive way of getting the message out about this disease. Instead we are awaiting MSKCC decision to place the contents of this CD updated on their web site. When this is done then ECEF will link to that file and have it available to ECEF members.
Grants:MEMORIAL SLOAN KETTERING CANCER CENTER
2012 $1,800 PAID
ECEF decided to give Memorial Sloan Kettering Cancer Center a $1,800 grant to cover the purchase of 100 books called 100 Questions & Anmswers About Esopjhageal Cancer to be distributed to patients who have been newly diagnosed with this disease.
PROJECT 2. MOUNT SINAI MEDICAL CENTER
FLUORESCENT STAIN FOR ENDOSCOPIC EXAMINATIONS
2012 $30,000 PAID
2013 $30,000 PAID
Esophageal adenocarcinoma (EAC) is one of the most rapidly rising cancers in the United States today and carries a poor five-year survival rate (<15%) due to late diagnosis. EAC arises in a condition known as Barrett’s esophagus and progresses to cancer through an intermediate stage known as dysplasia. While this would seem to allow ample opportunity for early detection and intervention, the current standard of endoscopic surveillance of Barrett’s esophagus is inadequate and has been shown to miss up to 57% of early cancers.
Advanced endoscopic imaging technologies, such as confocal microendoscopy, have arisen as a way of improving endoscopic surveillance. Confocal microendoscopy relies on the use of fluorescent contrast agents to provide tissue contrast and 1100x magnified images of the esophageal lining. This technology gives endoscopist’s the remarkable ability to see and remove cancer at an early, treatable stage. The technology has revolutionized the way gastroenterologists screen the esophagus, allowing cancer (and precancer) to be detected when it is < 1-2 mm in size and easily removeable. Current confocal endoscopes rely on non-specific contrast agents such as IV fluorescein. Unfortunately, current agents do not target the molecular ‘footprint’ of esophageal cancer.
In our project, we proposed to develop and test novel, molecule-specific contrast agents to specific markers of cancer for use with confocal microendoscopes. We believe that such contrast agents can be used to highlight areas of pre-cancer or cancer (“molecular beacon”) during real-time endoscopic surveillance thus enhancing early detection efforts and facilitating minimally invasive therapy. In our current project, we have evaluated multiple patients with varying grades of disease. We have noted differences in both the intensity and pattern of fluorescent imaging with progression to cancer. We are now trying to develop a larger repository of images and better understand the patterns that develop as Barrett’s progresses to cancer.
GRANTS IN PROCESS
With the support of ECEF, to date- Clinical trials: we have completed one prospective trial (project 2), completing the second prospective clinical trial (project 1), and are planing to initiate two new clinical trials based on the data that will be generated in Project 3. NCI Funding: ECEF support to projects 1 and 2 resulted in NCI peer-reviewed funding. Publications: Projects 1 and 2 resulted in 2 publications, third in preparation. Collaboration: Project 1 is being continued with Dr David R Jones as Co-PI with all thoracic surgery (TS) faculty participating, Project 2 was completed with Dr Nabil Rizk as co-PI, with participation from all TS faculty, Project 3 is being initiated in collaborations with Drs. Geoff Ku and Yelena Janjigian
PROJECT 1. MEMORIAL SLOAN KETTERING CANCER CENTER
BLOOD TEST TO DETECT ESOPHAGEAL CANCER
2012 -2015 $300,000 PAID
2016 $ to be determined
A prospective clinical trial to evaluate mesothelin as a biomarker for the clinical management of Barrett’s associated esophageal adenocarcinoma
Project description: In our search for a tumor marker that imparts aggressiveness and can be used as a prognostic marker in patients with esophageal cancer (EC), we observed that a protein named mesothelin is overexpressed in EC cells in 3 out of 4 patients. Most intriguingly, the protein expression is observed only when there is cancerous transformation in the Barrett’s esophagus (high grade dysplasia), and not expressed in low grade dysplasia or in acid reflux patients. This protein can be measured by a simple blood test. In fact, investigations revealed that more than two-thirds of EC patients had elevated blood levels of the cancer-specific protein. Acknowledging ECEF support, this study results were published in the American Association for Cancer Research, AACR journal, Cancer Epidemiology, Biomarkers and Prevention (http://www.ncbi.nlm.nih.gov/pubmed/22237988) in March 2012. Since then, other investigators have published confirming these results. Based on this convincing data that resulted from ECEF support, we were awarded National Cancer Institute, NCI R-21 award (1R21CA164585-01A1) to prospectively investigate the utility of the blood test as a biomarker in the management of esophageal adenocarcinoma. This prospective clinical trial is listed on clinical trials.gov (http://www.clinicaltrials.gov/ct2/show/NCT01393483?term=esophageal+cancer+mesothelin&rank=1).
2015-2016 progress: To date, with the excellent help of MSKCC Research Study Assistants, more than 300 patients are accrued to the study with 50 active patients. Among all the patients, 243 patients completed the study (evaluable 185). We have identified 60 patients with baseline serum, tissue, and postresection surgical tissue along with post resection blood samples available. While we continue to accrue new patients, we will obtain serial peripheral blood specimens form patients who are already recruited. We plan to analyze the data (Interim analysis) at the beginning of 2016 as many patients need to complete 2 years on study for analysis.
Plans for 2016-2017: We have initiated and started treating patients in our phase I ‘mesothelin-targeted CAR (chimeric antigen receptor) T-cell clinical trial’, wherein lung, breast cancer and mesothelioma patients were treated with their own immune cells genetically engineered to target and kill mesothelin-expressing cancer. I have initiated collaboration with Dr Yelena Janjigian at MSK to test mesothelin-targeted CAR T cells efficacy in EC patient-derived xenograft (PDX) models. This data will be crucial to submit to FDA and obtain approval to extend the trial to EC patients. We hope to utilize the ECEF award to conduct these investigations with an ultimate goal to initiate the trial for EC patients.
PROJECT 2. MEMORIAL SLOAN KETTERING CANCER CENTER
WIRELESS PULSE OXIMETRY TO PREVENT SURGICAL LEAKS
2013 – 2014 $80,000 PAID
2015 No Additional Funding Required
Real-time intraoperative detection of tissue oxygenation by Wireless Pulse Oximetry (WiPOX)
Project description: The most effective approach todate to treat EC is to resect the esophagus and restore the continuity by anastomosing (joining) the stomach to the resected esophagus. Dehiscence or leakage from anastomotic sites following esophageal surgery occurs in one of six patients, and is associated with significant morbidity and mortality. Currently, following stomach mobilization, surgeons assess tissue viability and blood supply by simple visual inspection. Increasingly, esophageal operations are performed by minimally invasive techniques, which add complexity to the problem of assessing stomach oxygenation prior to the anastomosis.
We have motivated a group of senior bioengineering students at the City College of Bioengineering, New York to develop a handheld device that measures tissue oxygenation during surgery by use of a simple Wireless Pulse Oximeter (WiPOX). This device is validated in animal studies (http://www.ncbi.nlm.nih.gov/pubmed/20972585) and is tested in a pilot trial at the MSKCC. The thoracic surgeons at MSKCC utilized this device in a prospective clinical trial (http://clinicaltrials.gov/ct2/show/NCT01551433?term=wipox&rank=1) to measure tissue oxygenation in real-time ensuring the viability of surgical anastomoses, thereby reducing the morbidity and mortality of esophageal cancer operations. With the help of the preliminary data obtained by ECEF support, we were scored high in a NIH application and were awarded partial support for the study.
2014-2015 progress: This prospective clinical trial is successfully completed in accruing patients and testing the device. The study will remain open till the last follow-up information is obtained from all the patients. We have now completed data collection, follow-up and the primary and secondary events. The data is intriguing that – a) among patients who participated in the study (WiPOX used), the leak rate is three-fold lower than our historical leak rate, b) among patients that participated in the study (WiPOX used), the leak rate is two-fold lower than in patients who did not participate in the study during the same study period, and c) the leak rate is back to historical control after the study is completed (no device being used). We are submitting these results to American Association of Thoracic Surgery, AATS annual meeting as late breaking clinical trial abstract and are in the process of writing the manuscript.
Project 3. MEMORIAL SLOAN KETTERING CANCER CENTER
IMMUNE MICROENVIRONMENT IN ESOPHAGEAL CANCER
2015 $100,000 PAID
2016 to be determined
Our laboratory principle focus is investigating tumor immunology and immunotherapy. The tumor immune microenvironment in EC is not well studied. To advance immunotherapy, it is essential to understand the basic immune microenvironment of this cancer. With this in mind, we would like to develop a well-annotated clinicopathological database along with well characterized tissue from a cohort of EC patients. Our team has performed this task for lung cancer (>2000 patients) and published more than 20 publications to date including in the Journal of Clinical Oncology and Journal of The National Cancer Institute. To date, we are updating the clinical database and identifying the patients where proper tissue is available. We have made significant progress on a new technology – multispectral immune imaging to quantify and characterize immune cells phenotypes on a tumor slide (see representative picture to the right). Within next 2-3 months, we anticipate investigating EC patient tumors and analyzing.
This analysis and the knowledge acquired will be the key to subsequent correlative studies of EC checkpoint blockade immunotherapy with Dr Ku and EC CAR T-cell therapy in collaboration with Dr Janjigian. Furthermore, we will compare and contrast the tumoral and stromal microenvironment in patient tumors and PDX models.
Project 4. MEMORIAL SLOAN KETTERING CANCER CENTER
SENTINEL LYMPH NODE MAPPING
2016 to be determined
A prospective, image-guided, esophageal cancer surgery study to investigate sentinel lymph node mapping and its utilization to improve outcomes of esophagetomy. This study can change the way we perform surgery in patients with esophageal cancer, decreasing preoperatve morbidity, improving staging and selection for adjuvant therapy and possibly enhancing survival and quality of life.
ECEF has set $100,000 as a research goal at a minimum for 2016.