Clinical and molecular characteristics of patients with brain metastasis secondary to pancreatic ductal adenocarcinoma

Mahmoud Yousef; Mark W. Hurd; Abdelrahman Yousef; Ethan B. Ludmir; Ashwathy B. Pillai; Jennifer Peterson; Eugene J. Koay; Sali Albarouki; Ching Wei Tzeng; Rebecca Snyder; Matthew H.G. Katz; Huamin Wang; Michael J. Overman; Anirban Maitra; Shubham Pant; Brandon G. Smaglo; Robert A. Wolff; James Yao; John P. Shen; Dan Zhao

doi:10.1093/oncolo/oyae182

Clinical and molecular characteristics of patients with brain metastasis secondary to pancreatic ductal adenocarcinoma

Mahmoud Yousef, Mark W. Hurd, Abdelrahman Yousef, Ethan B. Ludmir, Ashwathy B. Pillai, Jennifer Peterson, Eugene J. Koay, Sali Albarouki, Ching Wei Tzeng, Rebecca Snyder, Matthew H.G. Katz, Huamin Wang, Michael J. Overman, Anirban Maitra, Shubham Pant, Brandon G. Smaglo, Robert A. Wolff, James Yao, John P. Shen, Dan Zhao

Research output: Contribution to journal › Article › peer-review

Abstract

Background: The prognosis for patients with pancreatic ductal adenocarcinoma (PDAC) is poor. Secondary brain metastasis (Br-M) occurs in less than 1% of patients. Clinical characteristics and molecular alterations have not been characterized in this rare patients’ subset. Materials and methods: The Foundry software platform was used to retrospectively query electronic health records for patients with Br-M secondary to PDAC from 2005 to 2023; clinical, molecular, and overall survival (OS) data were analyzed. Results: Br-M was diagnosed in 44 patients with PDAC. Median follow-up was 78 months; median OS from initial PDAC diagnosis was 47 months. Median duration from PDAC diagnosis to Br-M detection was 24 months; median OS from Br-M diagnosis was 3 months. At Br-M diagnosis, 82% (n = 36) of patients had elevated CA19-9. Lung was the most common preexisting metastatic location (71%) with Br-M, followed by liver (66%). Br-M were most frequently observed in the frontal lobe (34%, n = 15), cerebellar region (23%, n = 10), and leptomeninges (18%, n = 8). KRAS mutations were detected in 94.1% (n = 16) of patients who had molecular data available (n = 17) with KRAS^G12V being the most frequent subtype 47% (n = 8); KRAS^G12D in 29% (n = 5); KRAS^G12R in 18% (n = 3). Patients who underwent Br-M surgical resection (n = 5) had median OS of 8.6 months, while median OS following stereotactic radiosurgery only (n = 11) or whole-brain radiation only (n = 20) was 3.3 and 2.8 months, respectively. Conclusion: Br-M is a late PDAC complication, resulting in an extremely poor prognosis especially in leptomeningeal disease. KRAS was mutated in 94.1% of the patients and the KRAS^G12V subtype was prevalent.

Original language	English (US)
Article number	oyae182
Journal	Oncologist
Volume	30
Issue number	1
DOIs	https://doi.org/10.1093/oncolo/oyae182
State	Published - Jan 1 2025

Keywords

KRAS
PDAC
brain metastases
genetic testing
mutation
pancreatic cancer

ASJC Scopus subject areas

General Medicine

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10.1093/oncolo/oyae182

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Yousef, M., Hurd, M. W., Yousef, A., Ludmir, E. B., Pillai, A. B., Peterson, J., Koay, E. J., Albarouki, S., Tzeng, C. W., Snyder, R., Katz, M. H. G., Wang, H., Overman, M. J., Maitra, A., Pant, S., Smaglo, B. G., Wolff, R. A., Yao, J., Shen, J. P., & Zhao, D. (2025). Clinical and molecular characteristics of patients with brain metastasis secondary to pancreatic ductal adenocarcinoma. Oncologist, 30(1), Article oyae182. https://doi.org/10.1093/oncolo/oyae182

Yousef, M, Hurd, MW, Yousef, A, Ludmir, EB, Pillai, AB, Peterson, J, Koay, EJ, Albarouki, S, Tzeng, CW, Snyder, R, Katz, MHG, Wang, H, Overman, MJ, Maitra, A, Pant, S, Smaglo, BG, Wolff, RA, Yao, J, Shen, JP & Zhao, D 2025, 'Clinical and molecular characteristics of patients with brain metastasis secondary to pancreatic ductal adenocarcinoma', Oncologist, vol. 30, no. 1, oyae182. https://doi.org/10.1093/oncolo/oyae182

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title = "Clinical and molecular characteristics of patients with brain metastasis secondary to pancreatic ductal adenocarcinoma",

abstract = "Background: The prognosis for patients with pancreatic ductal adenocarcinoma (PDAC) is poor. Secondary brain metastasis (Br-M) occurs in less than 1% of patients. Clinical characteristics and molecular alterations have not been characterized in this rare patients{\textquoteright} subset. Materials and methods: The Foundry software platform was used to retrospectively query electronic health records for patients with Br-M secondary to PDAC from 2005 to 2023; clinical, molecular, and overall survival (OS) data were analyzed. Results: Br-M was diagnosed in 44 patients with PDAC. Median follow-up was 78 months; median OS from initial PDAC diagnosis was 47 months. Median duration from PDAC diagnosis to Br-M detection was 24 months; median OS from Br-M diagnosis was 3 months. At Br-M diagnosis, 82% (n = 36) of patients had elevated CA19-9. Lung was the most common preexisting metastatic location (71%) with Br-M, followed by liver (66%). Br-M were most frequently observed in the frontal lobe (34%, n = 15), cerebellar region (23%, n = 10), and leptomeninges (18%, n = 8). KRAS mutations were detected in 94.1% (n = 16) of patients who had molecular data available (n = 17) with KRASG12V being the most frequent subtype 47% (n = 8); KRASG12D in 29% (n = 5); KRASG12R in 18% (n = 3). Patients who underwent Br-M surgical resection (n = 5) had median OS of 8.6 months, while median OS following stereotactic radiosurgery only (n = 11) or whole-brain radiation only (n = 20) was 3.3 and 2.8 months, respectively. Conclusion: Br-M is a late PDAC complication, resulting in an extremely poor prognosis especially in leptomeningeal disease. KRAS was mutated in 94.1% of the patients and the KRASG12V subtype was prevalent.",

keywords = "KRAS, PDAC, brain metastases, genetic testing, mutation, pancreatic cancer",

author = "Mahmoud Yousef and Hurd, {Mark W.} and Abdelrahman Yousef and Ludmir, {Ethan B.} and Pillai, {Ashwathy B.} and Jennifer Peterson and Koay, {Eugene J.} and Sali Albarouki and Tzeng, {Ching Wei} and Rebecca Snyder and Katz, {Matthew H.G.} and Huamin Wang and Overman, {Michael J.} and Anirban Maitra and Shubham Pant and Smaglo, {Brandon G.} and Wolff, {Robert A.} and James Yao and Shen, {John P.} and Dan Zhao",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024. Published by Oxford University Press.",

year = "2025",

month = jan,

day = "1",

doi = "10.1093/oncolo/oyae182",

language = "English (US)",

volume = "30",

journal = "Oncologist",

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TY - JOUR

T1 - Clinical and molecular characteristics of patients with brain metastasis secondary to pancreatic ductal adenocarcinoma

AU - Yousef, Mahmoud

AU - Hurd, Mark W.

AU - Yousef, Abdelrahman

AU - Ludmir, Ethan B.

AU - Pillai, Ashwathy B.

AU - Peterson, Jennifer

AU - Koay, Eugene J.

AU - Albarouki, Sali

AU - Tzeng, Ching Wei

AU - Snyder, Rebecca

AU - Katz, Matthew H.G.

AU - Wang, Huamin

AU - Overman, Michael J.

AU - Maitra, Anirban

AU - Pant, Shubham

AU - Smaglo, Brandon G.

AU - Wolff, Robert A.

AU - Yao, James

AU - Shen, John P.

AU - Zhao, Dan

PY - 2025/1/1

Y1 - 2025/1/1

N2 - Background: The prognosis for patients with pancreatic ductal adenocarcinoma (PDAC) is poor. Secondary brain metastasis (Br-M) occurs in less than 1% of patients. Clinical characteristics and molecular alterations have not been characterized in this rare patients’ subset. Materials and methods: The Foundry software platform was used to retrospectively query electronic health records for patients with Br-M secondary to PDAC from 2005 to 2023; clinical, molecular, and overall survival (OS) data were analyzed. Results: Br-M was diagnosed in 44 patients with PDAC. Median follow-up was 78 months; median OS from initial PDAC diagnosis was 47 months. Median duration from PDAC diagnosis to Br-M detection was 24 months; median OS from Br-M diagnosis was 3 months. At Br-M diagnosis, 82% (n = 36) of patients had elevated CA19-9. Lung was the most common preexisting metastatic location (71%) with Br-M, followed by liver (66%). Br-M were most frequently observed in the frontal lobe (34%, n = 15), cerebellar region (23%, n = 10), and leptomeninges (18%, n = 8). KRAS mutations were detected in 94.1% (n = 16) of patients who had molecular data available (n = 17) with KRASG12V being the most frequent subtype 47% (n = 8); KRASG12D in 29% (n = 5); KRASG12R in 18% (n = 3). Patients who underwent Br-M surgical resection (n = 5) had median OS of 8.6 months, while median OS following stereotactic radiosurgery only (n = 11) or whole-brain radiation only (n = 20) was 3.3 and 2.8 months, respectively. Conclusion: Br-M is a late PDAC complication, resulting in an extremely poor prognosis especially in leptomeningeal disease. KRAS was mutated in 94.1% of the patients and the KRASG12V subtype was prevalent.

AB - Background: The prognosis for patients with pancreatic ductal adenocarcinoma (PDAC) is poor. Secondary brain metastasis (Br-M) occurs in less than 1% of patients. Clinical characteristics and molecular alterations have not been characterized in this rare patients’ subset. Materials and methods: The Foundry software platform was used to retrospectively query electronic health records for patients with Br-M secondary to PDAC from 2005 to 2023; clinical, molecular, and overall survival (OS) data were analyzed. Results: Br-M was diagnosed in 44 patients with PDAC. Median follow-up was 78 months; median OS from initial PDAC diagnosis was 47 months. Median duration from PDAC diagnosis to Br-M detection was 24 months; median OS from Br-M diagnosis was 3 months. At Br-M diagnosis, 82% (n = 36) of patients had elevated CA19-9. Lung was the most common preexisting metastatic location (71%) with Br-M, followed by liver (66%). Br-M were most frequently observed in the frontal lobe (34%, n = 15), cerebellar region (23%, n = 10), and leptomeninges (18%, n = 8). KRAS mutations were detected in 94.1% (n = 16) of patients who had molecular data available (n = 17) with KRASG12V being the most frequent subtype 47% (n = 8); KRASG12D in 29% (n = 5); KRASG12R in 18% (n = 3). Patients who underwent Br-M surgical resection (n = 5) had median OS of 8.6 months, while median OS following stereotactic radiosurgery only (n = 11) or whole-brain radiation only (n = 20) was 3.3 and 2.8 months, respectively. Conclusion: Br-M is a late PDAC complication, resulting in an extremely poor prognosis especially in leptomeningeal disease. KRAS was mutated in 94.1% of the patients and the KRASG12V subtype was prevalent.

KW - KRAS

KW - PDAC

KW - brain metastases

KW - genetic testing

KW - mutation

KW - pancreatic cancer

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Clinical and molecular characteristics of patients with brain metastasis secondary to pancreatic ductal adenocarcinoma

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