TY - JOUR
T1 - Clinical outcomes and molecular characteristics of lung-only and liver-only metastatic pancreatic cancer
T2 - results from a real-world evidence database
AU - Levi, Abrahm
AU - Blais, Edik
AU - Davelaar, John
AU - Ebia, Matthew I.
AU - Minasyan, Angela
AU - Nikravesh, Nima
AU - Gresham, Gillian
AU - Zheng, Lei
AU - Chuy, Jennifer W.
AU - Shroff, Rachna T.
AU - Wadlow, Raymond Couric
AU - DeArbeloa, Patricia
AU - Matrisian, Lynn Mc Cormick
AU - Petricoin, Emmanuel
AU - Pishvaian, Michael J.
AU - Gong, Jun
AU - Hendifar, Andrew Eugene
AU - Osipov, Arsen
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/3/1
Y1 - 2025/3/1
N2 - Background: Previous research demonstrates longer survival for patients with lung-only metastatic pancreatic adenocarcinoma (mPDAC) compared to liver-only mPDAC. The objective of this study is to understand the survival differences, impact of chemotherapy, and associated genomic features of mPDAC that is isolated to either the liver or lung. Patients and methods: Longitudinal clinical outcomes and molecular sequencing data were retrospectively analyzed across 831 patients with PDAC across all stages whose tumors first metastasized to the liver or lung. Survival differences were evaluated using Cox regression. Mutational frequency differences were evaluated using Fisher’s exact test. Results: Median overall survival (mOS) was shorter in patients with liver-only metastasis (1.3y [1.2-1.4], n = 689) compared to lung-only metastasis (2.1y [1.9-2.5], n = 142) (P = .000000588, HR = 2.00 [1.53-2.63]. Survival differences were observed regardless of choice of 1st-line standard-of-care therapy. For 5-fluorouracil-based therapies, mOS for liver-only mPDAC was 1.4y [1.3-1.6] (n = 211) compared to 2.1y [1.8-3.3] for lung-only mPDAC (n = 175) (P = .008113, HR = 1.75 [1.16-2.65]). For gemcitabine/nab-paclitaxel therapy, mOS for liver-only mPDAC was 1.2y [1.1-1.5] (n = 175) compared to 2.1y [1.6-3.4] for lung-only disease (n = 32) (P = .01863, HR = 1.84 [1.11-3.06]). PDAC tumors with liver-only metastases were modestly enriched (unadjustable P < .05) for: TP53 mutations, MYC amplifications, inactivating CDK2NA alterations, inactivating SMAD alterations, and SWI/SWF pathway mutations. PDAC tumors with lung-only metastases were enriched for: STK11 mutations, CCND1 amplifications, and GNAS alterations. Conclusion: Patients with lung-only mPDAC demonstrate an improved prognosis relative to those with liver-only mPDAC. Responses to chemotherapy do not explain these differences. Organotropic metastatic tumor diversity is mirrored at the molecular level in PDAC.
AB - Background: Previous research demonstrates longer survival for patients with lung-only metastatic pancreatic adenocarcinoma (mPDAC) compared to liver-only mPDAC. The objective of this study is to understand the survival differences, impact of chemotherapy, and associated genomic features of mPDAC that is isolated to either the liver or lung. Patients and methods: Longitudinal clinical outcomes and molecular sequencing data were retrospectively analyzed across 831 patients with PDAC across all stages whose tumors first metastasized to the liver or lung. Survival differences were evaluated using Cox regression. Mutational frequency differences were evaluated using Fisher’s exact test. Results: Median overall survival (mOS) was shorter in patients with liver-only metastasis (1.3y [1.2-1.4], n = 689) compared to lung-only metastasis (2.1y [1.9-2.5], n = 142) (P = .000000588, HR = 2.00 [1.53-2.63]. Survival differences were observed regardless of choice of 1st-line standard-of-care therapy. For 5-fluorouracil-based therapies, mOS for liver-only mPDAC was 1.4y [1.3-1.6] (n = 211) compared to 2.1y [1.8-3.3] for lung-only mPDAC (n = 175) (P = .008113, HR = 1.75 [1.16-2.65]). For gemcitabine/nab-paclitaxel therapy, mOS for liver-only mPDAC was 1.2y [1.1-1.5] (n = 175) compared to 2.1y [1.6-3.4] for lung-only disease (n = 32) (P = .01863, HR = 1.84 [1.11-3.06]). PDAC tumors with liver-only metastases were modestly enriched (unadjustable P < .05) for: TP53 mutations, MYC amplifications, inactivating CDK2NA alterations, inactivating SMAD alterations, and SWI/SWF pathway mutations. PDAC tumors with lung-only metastases were enriched for: STK11 mutations, CCND1 amplifications, and GNAS alterations. Conclusion: Patients with lung-only mPDAC demonstrate an improved prognosis relative to those with liver-only mPDAC. Responses to chemotherapy do not explain these differences. Organotropic metastatic tumor diversity is mirrored at the molecular level in PDAC.
KW - genetic profile
KW - metastasis
KW - pancreatic cancer
KW - prognostic factors
KW - treatment outcome
UR - http://www.scopus.com/inward/record.url?scp=105000342902&partnerID=8YFLogxK
U2 - 10.1093/oncolo/oyaf007
DO - 10.1093/oncolo/oyaf007
M3 - Article
C2 - 40079530
AN - SCOPUS:105000342902
SN - 1083-7159
VL - 30
JO - Oncologist
JF - Oncologist
IS - 3
M1 - oyaf007
ER -