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. 2025 Mar 10;30(3):oyaf007.
doi: 10.1093/oncolo/oyaf007.

Clinical outcomes and molecular characteristics of lung-only and liver-only metastatic pancreatic cancer: results from a real-world evidence database

Abrahm Levi  1 , Edik Blais  2 , John Davelaar  1 , Matthew I Ebia  1 , Angela Minasyan  1 , Nima Nikravesh  1 , Gillian Gresham  1 , Lei Zheng  3 , Jennifer W Chuy  4 , Rachna T Shroff  5 , Raymond Couric Wadlow  6 , Patricia DeArbeloa  2 , Lynn McCormick Matrisian  7 , Emmanuel Petricoin  2 , Michael J Pishvaian  3   8 , Jun Gong  1 , Andrew Eugene Hendifar  1 , Arsen Osipov  1
Affiliations

Clinical outcomes and molecular characteristics of lung-only and liver-only metastatic pancreatic cancer: results from a real-world evidence database

Abrahm Levi et al. Oncologist. .

Abstract

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.

Keywords: genetic profile; metastasis; pancreatic cancer; prognostic factors; treatment outcome.

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Conflict of interest statement

EB reports employment, inventor, and ownership interest at Perthera, Inc. RTS reports advisory board/consultation relationships with: AstraZeneca, Boehringer Ingelheim, Clovis, Genentech, Incyte, Merck, QED Therapeutics, Servier, Taiho, Zymeworks, Elevar Therapeutics, Ability Pharma, Duo Oncology, Hookipa Pharma, Natera, and Astellas. RTS also reports research funding from: Bayer, BMS, Bristol-Myers, Exelixis, IMV Inc., LOXO, Novocure, NUCANA, QED, Rafael Pharmaceuticals, Seagen, and Taiho. EP reports compensated consultation for: Perthera, Inc., Ignite Proteomics, Inc., and Ceres Nanosciences, Inc. MJP reports Ad Hoc Advisory roles for: AstraZeneca, Ideaya, Seattle Genetics, Merus, Merck, and Moderna. JG reports consultant or advisory roles for: Eisai, Exelixis, Janssen Biotech, Myovant/Pfizer, EMD Serono, Incyte, AVEO, Bayer, Seagan, Agenus, Taiho Pharmaceutical, and Caper Labs. All other authors have no known conflicts of interest to report currently.

Figures

Figure 1.
Figure 1.
Overall survival outcomes within the Analysis Cohort compared between patients with lung-only vs. liver-only distant lesions at onset of metastatic disease while using the advanced diagnosis date as the start of the OS interval (note: any stage was eligible at initial diagnosis for the Analysis Cohort).
Figure 2.
Figure 2.
(A) Overall survival outcomes for the Resectable Cohort, a subset of the Analysis Cohort with earlier stage disease that resulted in successful resection, analyzed between lung-only vs liver-only cases using Cox regression while using date of initial diagnosis as the start of the OS interval. (B) Overall survival analysis between lung-only vs liver-only cases in the Advanced Cohort based on the initial diagnosis date, which aligns with the advanced diagnosis date since these subjects were not considered eligible for curative surgery.
Figure 3.
Figure 3.
(A) Median OS relative to diagnosis of advanced disease for the subset receiving 1st-line 5FU-based SOC in lung-only vs. liver-only subsets of the mPDAC Analysis Cohort. (B) Median OS relative to diagnosis of advanced disease for the subset receiving 1st-line Gemcitabine/nab-Paclitaxel SOC in lung-only vs. liver-only subsets of the mPDAC Analysis Cohort.
Figure 4.
Figure 4.
(A) Median OS relative to diagnosis of advanced disease for the subset receiving 1st-line 5FU-based SOC vs. 1st-line Gemcitabine/nab-Paclitaxel SOC in the liver-only subset of the mPDAC Analysis Cohort. (B) Median OS relative to diagnosis of advanced disease for the subset receiving 1st-line 5FU-based SOC vs. 1st-line Gemcitabine/nab-Paclitaxel SOC in the lung-only subset of the mPDAC Analysis Cohort.
Figure 5.
Figure 5.
Genomic alteration frequencies in lung- vs. liver-metastasizing PDAC.
See this image and copyright information in PMC

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