Abrahm Levi, Edik Blais, John Davelaar, Matthew I Ebia, Angela Minasyan, Nima Nikravesh, Gillian Gresham, Lei Zheng, Jennifer W Chuy, Rachna T Shroff, Raymond Couric Wadlow, Patricia DeArbeloa, Lynn McCormick Matrisian, Emmanuel Petricoin, Michael J Pishvaian, Jun Gong, Andrew Eugene Hendifar, Arsen Osipov
{"title":"肺转移性胰腺癌和肝转移性胰腺癌的临床结果和分子特征：来自真实世界证据数据库的结果。","authors":"Abrahm Levi, Edik Blais, John Davelaar, Matthew I Ebia, Angela Minasyan, Nima Nikravesh, Gillian Gresham, Lei Zheng, Jennifer W Chuy, Rachna T Shroff, Raymond Couric Wadlow, Patricia DeArbeloa, Lynn McCormick Matrisian, Emmanuel Petricoin, Michael J Pishvaian, Jun Gong, Andrew Eugene Hendifar, Arsen Osipov","doi":"10.1093/oncolo/oyaf007","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Patients and methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":"30 3","pages":""},"PeriodicalIF":4.2000,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11904785/pdf/","citationCount":"0","resultStr":"{\"title\":\"Clinical outcomes and molecular characteristics of lung-only and liver-only metastatic pancreatic cancer: results from a real-world evidence database.\",\"authors\":\"Abrahm Levi, Edik Blais, John Davelaar, Matthew I Ebia, Angela Minasyan, Nima Nikravesh, Gillian Gresham, Lei Zheng, Jennifer W Chuy, Rachna T Shroff, Raymond Couric Wadlow, Patricia DeArbeloa, Lynn McCormick Matrisian, Emmanuel Petricoin, Michael J Pishvaian, Jun Gong, Andrew Eugene Hendifar, Arsen Osipov\",\"doi\":\"10.1093/oncolo/oyaf007\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Patients and methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":54686,\"journal\":{\"name\":\"Oncologist\",\"volume\":\"30 3\",\"pages\":\"\"},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2025-03-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11904785/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Oncologist\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/oncolo/oyaf007\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Oncologist","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/oncolo/oyaf007","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
Clinical outcomes and molecular characteristics of lung-only and liver-only metastatic pancreatic cancer: results from a real-world evidence database.
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.
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The Oncologist® is dedicated to translating the latest research developments into the best multidimensional care for cancer patients. Thus, The Oncologist is committed to helping physicians excel in this ever-expanding environment through the publication of timely reviews, original studies, and commentaries on important developments. We believe that the practice of oncology requires both an understanding of a range of disciplines encompassing basic science related to cancer, translational research, and clinical practice, but also the socioeconomic and psychosocial factors that determine access to care and quality of life and function following cancer treatment.
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