Ophir Gilad, MD - CGA-IGC Communications Committee
Hereditary Cancer Week is a great opportunity to give an update on ongoing research in hereditary diffuse gastric cancer syndrome.
Individuals with germline pathogenic/likely pathogenic variants in CDH1 are at risk of developing early-onset, multigenerational cases of diffuse gastric cancer.
Lifetime gastric cancer risk in hereditary diffuse gastric cancer syndrome varies between studies and is estimated to be 10-70% depending on family history.
Current guidelines recommend prophylactic total gastrectomy or endoscopic surveillance in those who opt not to undergo surgery. Gastric cancer surveillance in CDH1 carriers poses challenges as signet ring cell carcinoma (SRCC) can remain indolent throughout a patient’s lifetime or have an aggressive phenotype. Predictors of aggressive disease are needed to enable risk stratification to guide management recommendations and improve outcomes.
A multicenter consortium called GASTRIC (Group of investigAtors STriving toward Research In CDH1) was established in late 2023 and currently includes 10 centers across the United States. The goals of the GASTRIC consortium are to report on the outcomes of CDH1 carriers who choose to undergo endoscopic surveillance or prophylactic surgery, to evaluate the penetrance of the syndrome in a large cohort, and to identify predictors of the aggressive phenotype.
Here are some initial data from the study:
To date, 233CDH1 carriers have been included. Mean age 48.6, 64% are female, and 14.6% are from racial/ethnic minorities.
Eleven (4.7%) patients were diagnosed when they already had metastatic disease.
Overall, 195 carriers underwent 369 upper endoscopies (range 1-9 per patient).
Of these, 51 carriers (26.1%) were found to have SRCC foci, the majority of which (72.5%) were found in the first-ever upper endoscopy and in the proximal parts of the stomach.
A quarter of the patients found to have SRCC foci on upper endoscopies chose to continue endoscopic surveillance.
In total, 123 carriers (52.7%) underwent gastrectomy. Of these, 24 (19.5%) were found to have no SRCC foci on surgical specimen, 80 (65.1%) had non-aggressive disease with SRCCs confined to the mucosa, and only 7 (5.9%) were found to have a more aggressive phenotype.
We aspire to become the largest consortium studying hereditary diffuse gastric cancer syndrome. To that end, the GASTRIC consortium is still growing as new centers continue to join this collaborative effort.
If you are following CDH1 carriers and want to help us investigate this syndrome further, please contact @OphirGilad. We would be glad to extend an invitation to join our study.
Additionally, if you’d like to hear more about our results, be sure to come to the 2024 CGA-IGC annual meeting where we will be presenting more of our data.
____________________________________________________________________________
Interested in more Gastric cancer-related content? Consider listening to the following podcasts;
Interested in other educational content? Our webinars are a valuable member benefit, and we encourage you to sign up as a member so you can join the live webinars and access our earlier webinar series on demand!
Also, are you looking for other educational resources? If you enjoy webinars, you may like our Journal Club podcast series (Seasons 3, 4, 5, 6 & 7) presented by the CGA-IGC Education Committee. Or explore our Expert Approach to Hereditary Gastrointestinal Cancers podcast series (Seasons 1 and 2). We're also on Spotify!