Content Type: Poster
John Davelaar 1, Arsen Osipov 1 , Edik M Blais 2, Natalie Moshayedi 1 , Nima Nikravesh 1, Gillian Gresham 1 , Lei Zheng 3 , Autumn McRee 4, Jennifer Chuy 5 , Rachna Shroff 6 , Raymond Wadlow 7 , Gary L Gregory 2, Patricia DeArbeloa 2, Lynn M Matrisian 8, Emanuel F Petricoin III 2, Michael J Pishvaian 3 , Shant Thomassian 1, Jun Gong 1, Andrew E Hendifar 1
1Cedars-Sinai Medical Center, Los Angeles, CA; 2Perthera, Inc, Holliston, MA; 3Johns Hopkins University, Baltimore, MD; 4UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC; 5Montefiore Medical Center, Bronx, NY; 6University of Arizona Cancer Center, Tucson, AZ; 7Inova Schar Cancer Institute, Fairfax, VA; 8The Pancreatic Cancer Action Network, Manhattan Beach, CA
BACKGROUND:
Pancreatic cancer (PDAC) remains one of the most lethal malignancies following metastatic presentation, most commonly occurring in the lung and liver. Approximately 15-20% of patients have upfront resectable disease; however, 80% percent of these patients develop disease recurrence. Additionally, over 40% present with metastatic disease. Previous studies have observed variable survival outcomes in PDAC patients depending on site of metastases. Molecular phenotypes of varying sites of metastasis which may drive disease biology based on site of metastasis have not been fully elucidated. Here, we aim to understand survival outcomes and molecular features for PDAC based on involvement of lung versus liver metastases.
METHODS:
We retrospectively analyzed longitudinal clinical outcomes across 852 patients with PDAC with next generation sequencing (NGS) from Perthera’s Real-World Evidence database whose tumors first metastasized to either the lung or the liver. Median overall survival (mOS) was measured from either the date of initial diagnosis (resectable cases only, stage I-III) or advanced diagnosis (stage IV) until death. Differences in survival and frequencies of mutations were evaluated between patients with lungspecific and liver-specific metastases using Cox regression and Fisher’s exact test, respectively.
RESULTS:
Among resectable patients, mOS from initial diagnosis was significantly shorter in patients that developed liver only metastasis compared to those with lung only metastasis (2.3 vs 5.1 years, p=2.036e-08). In the advanced PDAC cohort, mOS from diagnosis of advanced disease was also significantly shorter in liver only versus lung only metastasis (1.3 vs 2.0 years, p=0.001246). PDAC tumors presenting to the liver first were modestly enriched (unadjusted p<0.05) for TP53 mutations (81.4% in liver vs 69.2% in lung), MYC amplifications (8.6% vs 3.0%), and inactivating CDK2NA alterations (51.5% vs 39.1%) whereas lung-specific mutation frequencies were higher for STK11 mutations (2.4% in liver vs 7.5% in lung), CCND1 amplifications (0.5% vs 3.0%) , GNAS alterations (2.0% vs 8.5%). Differences in treatment-specific outcomes were not significant supporting a potential prognostic role for lung only metastases. No differences in KRAS mutations nor specific isoforms were noted between lung vs liver only metastasis.
CONCLUSIONS:
Novel Insight: Are molecular markers predictive of better OS in lung- vs liver-only metastasizing PDAC?
- Moderately enriched mutational frequencies in liver-only cohort were SMAD4, TP53, MYC, CDK2NA with the lung-only cohort exhibiting moderate enrichment in STK11, CCND1, and GNAS.
- Lung only metastasis in both resectable and advanced PDAC confers a significant survival advantage compared to liver only metastasis. This is not likely attributed to differences in actionable markers.
- More research is needed to better understand the molecular drivers behind the enrichments identified above. These differences were more prominent than previous analyses of primary vs metastatic lesions.
Currently in peer review. Not Published.