Gastroenterology and Oncology

NewYork-Presbyterian: Focused on Detecting and Preventing High-Risk GI Cancers

    The Gastrointestinal Cancer Prevention and Genetics Program at NewYork-Presbyterian/Columbia is making significant strides towards cancer’s holy grail: the early detection of hard-to-treat cancers. The multidisciplinary program is at the forefront of genetic risk assessment and cancer prevention in familial gastrointestinal syndromes that raise the risk for pancreas, gastric, and colon cancers.

    Dr. Fay Kastrinos

    Dr. Fay Kastrinos

    Led by Fay Kastrinos, MD, MPH, a gastroenterologist at NewYork-Presbyterian/Columbia, the program is aimed at people with specific inherited susceptibility genes and uses genetic testing to screen those not yet diagnosed with the cancer. This gives doctors and patients a heads-up, allowing them to take action to prevent a cancer or to catch it before it can spread. “Once we identify families and individuals who are at highest risk, often through predictive genetic testing, we can offer them screening for the prevention or early detection of these gastrointestinal malignancies,” she says.

    Targeting a growing threat

    image of Dr. Sheila Rustgi

    Dr. Sheila Rustgi

    Pancreatic cancer, which kills almost 50,000 people each year, is a major focus. Rates of the disease are on the rise and it is predicted to be the second most common cause of cancer death, behind lung cancer, by 2030.

    “Pancreatic cancer is really tough because it's very difficult to detect,” says Sheila D. Rustgi, MD, a gastroenterologist at NewYork-Presbyterian/Columbia. “Most often when it's diagnosed, it’s already advanced, which limits the treatment options for patients.” Symptoms of this stealthy cancer include jaundice, pancreatitis, and weight loss, which can mimic other disorders, delaying diagnosis, she says.

    A number of hereditary cancer syndromes can increase the risk of malignancy, including but not limited to, hereditary breast and ovarian cancer syndrome (BRCA 1 and BRCA 2 gene mutations), Lynch syndrome, and familial atypical multiple mole melanoma. “About 10% of pancreatic cancer patients have some kind of familial component,” says Dr. Rustgi. “That includes patients who have a strong family history of pancreatic cancer and patients who have an underlying genetic mutation.”

    Malignant tumor in the pancreas

    Malignant tumor in the pancreas

    According to new guidelines, anyone diagnosed with pancreatic cancer should receive germline genetic testing to identify any inherited gene alterations. The tests can be used to alert other family members to a possible increased cancer risk as well as to steer treatment. “These guidelines were driven by the more favorable response to certain treatments in pancreatic cancers that are due to these genetic predispositions,” says Dr. Kastrinos.

    About 10% of pancreatic cancer patients have some kind of familial component. That includes patients who have a family history of pancreatic cancer and patients who have an underlying genetic mutation.

    — Dr. Sheila Rustgi

    High-risk patients in the program each year receive either magnetic resonance cholangiopancreatography (MRCP), a special type of MRI that visualizes the biliary and pancreatic ducts, or an endoscopic ultrasound, which transmits ultrasound waves internally to view the pancreas, says Dr. Kastrinos.

    The benefits of surveillance

    As part of the Cancer of Pancreas Screening-5 (CAPS5) consortia, NewYork-Presbyterian/Columbia collaborates with other institutions on research assessing the effectiveness of pancreatic cancer screening. Data from the multicenter study, published in the October 22, 2022, issue of the Journal of Clinical Oncology, tracked 1461 people at high risk for pancreatic cancer.

    Over the course of the study, there were 10 diagnosed cases of pancreatic cancer. Among patients in the program, seven had stage I tumors. One was diagnosed at stage II and another at stage III. The remaining cancer patient left the surveillance program and was diagnosed with advanced cancer four years later. “Surveillance programs work,” says Dr. Rustgi.

    NewYork-Presbyterian/Columbia also participates in the Pancreatic Cancer Early Detection (PRECEDE) Consortium, another multicenter initiative focused on pancreatic cancer detection and prevention.

    “We participate in both because we feel that that the more we know from our high-risk individuals about screening, the better we can inform guidelines, the better we can also test screening strategies and validate new biomarkers,” says Dr. Kastrinos. “Also, we have families that have striking histories without identified gene mutations. So it opens the door to new gene discovery. It all comes from the hard work of multiple institutions working together in these consortia.”

    We participate in [research consortia] because we feel that that the more we know from our high-risk individuals about screening, the better we can inform guidelines, the better we can also test strategies and validate new biomarkers.

    — Dr. Fay Kastrinos

    Dr. Kastrinos’ team uses simulation modeling to advance knowledge as well. “Prospective longitudinal studies take many years and many patients to complete,” she says. “We are focusing on simulation modeling to inform guidelines and clinical management, and determine cost effectiveness.”

    The power of prevention

    Intensive screening and surveillance is also critical for people with gastric and colon cancer. Hereditary diffuse gastric cancer, which also confers a greater risk for breast cancer, is caused by an alteration in the CDH-1 gene. The cancer usually affects the entire stomach rather than one part of it.

    “The risk for gastric cancer is high among carriers with pathogenic variants in the CDH-1 gene and it spans across multiple generations,” says Dr. Kastrinos. “We do intensive screening with endoscopy and also recommend risk-reducing surgeries like prophylactic gastrectomy as a method to keep select high-risk individuals cancer free.”

    Although rates of colon cancer are dropping overall, early-onset cancers—those that develop before age 50—are on the rise. As a result, “the United States Preventive Services Task Force recently recommended to start screening people at the age of 45 instead of 50,” says Dr. Rustgi.

    digital illustration of colorectal cancer

    Illustration of colorectal cancer

    Early-onset colon cancers can frequently have a genetic origin, says Dr. Kastrinos. “In people over 50 diagnosed with colon cancer, about 3-5% of individuals will have an inherited gene alteration, predominantly for Lynch syndrome,” she says. “In individuals younger than age 50 , about 10% will have Lynch syndrome, and in those less than 35 years old, that number goes up to nearly 25% for Lynch syndrome.”

    Colonoscopy has the benefit of not only detecting cancer but preventing it by removing precancerous lesions and polyps, Dr. Kastrinos says. However, removal of the colon may be necessary to manage some high-risk conditions, including familial adenomatous polyposis, which causes multiple adenomatous polyps and can lead to colon cancer and malignancies in other digestive organs.

    “Our surveillance programs are focused on balancing the benefits and risks of screening and other risk-reducing interventions such as surgery,” says Dr. Kastrinos. “The goal is to detect cancers at an early stage so patients have the most favorable outcomes.”

      For More Information

      The Multicenter Cancer of Pancreas Screening Study: Impact on Stage and Survival. Mohamad Dbouk, Bryson W. Katona, Randall E. Brand, Amitabh Chak, Sapna Syngal, James J. Farrell, Fay Kastrinos, Elena M. Stoffel, Amanda L. Blackford, Anil K. Rustgi, Beth Dudley, Linda S. Lee, Ankit Chhoda, Richard Kwon, Gregory G. Ginsberg, Alison P. Klein, Ihab Kamel, Ralph H. Hruban, Jin He, Eun Ji ShinAnne Marie Lennon, Marcia Irene Canto, Michael Goggins. Journal of Clinical Oncology. 2022 Oct 1; 40(28): 3257–3266.

      Familial Predisposition and Genetic Risk Factors Associated with Pancreatic Cancer. Sheila D Rustgi, Kimberly J Hilfrank , Fay Kastrinos. Gastrointestinal Endoscopy Clinics of North America. 2022 Jan;32(1):1-12.

      Inherited predisposition to pancreatic cancer. Seminars in Oncology. 2021 Feb;48(1):2-9. Kimberly J Hilfrank, Sheila D Rustgi, Fay Kastrinos

      For more information

      Dr. Fay Kastrinos
      Dr. Fay Kastrinos
      [email protected]
      Dr. Sheila D Rustgi
      Dr. Sheila D Rustgi
      [email protected]