Ronald L. Bittner Award on Brain Tumor Research: Genomic divergence rates between matched brain metastases and extracranial disease sites

Sunday, May 5, 2024

2:43 PM – 2:48 PM CT

Location: S403ab

Presenting Author(s)

Ramin Morshed, MD

Fellow
Mayo Clinic
San Francisco, California, United States

Co-Author(s)

Manish Aghi, MD, PhD

PI
UCSF
San Francisco, California, United States
Mitchel S. Berger, MD (he/him/his)

UCSF BTRC Director, Professor of Neurosurgery
UCSF
San Francisco, California, United States
Ezequiel D. Goldschmidt, MD PhD

Assistant Professor
UCSF
San Francisco, California, United States
Shawn Hervey-Jumper, MD

Associate Professor
Department of Neurological Surgery, University of California, San Francisco
San Francisco, California, United States
HK

Harmon Khela, BS

Medical Student
UPenn, United States
NM

Noor Malik, MD PhD

Fellow
Mayo Clinic, United States
Michael W. McDermott, MD

Chair
Baptist Health - Miami Neuroscience Institute
Miami, FL, US
MN

Minh Nguyen, BS

Medical Student
UCSF, United States
Ian Parney, MD PhD

Professor
Mayo Clinic
Rochester, MN, US
Philip Theodosopoulos, MD (he/him/his)

Vice Chair
UCSF
San Francisco, California, United States
HV

Harish Vasudevan, MD PhD

Assistant Professor
UCSF, United States
Jacob S. Young, MD

Resident
UCSF
Charlottesville, Virginia, United States

Disclosure(s):

Ramin Morshed, MD: No financial relationships to disclose

Mitchel S. Berger, MD: No financial relationships to disclose

Shawn Hervey-Jumper, MD: No financial relationships to disclose

Michael W. McDermott, MD: Deinde Medical: Advisor (Ongoing), Stock Shareholder (excluding mutual funds) (Ongoing); Light Helmets: Stock Shareholder (excluding mutual funds) (Ongoing); Zap Surgical: Advisor (Ongoing), Stock Shareholder (excluding mutual funds) (Ongoing)

Ian Parney, MD PhD: Merck: Grant/Research Support (Ongoing)

Introduction: Genomic alterations and molecular subgrouping between brain metastases and extracranial disease sites may differ. This study examined genomic divergence rates between matched brain metastases and extracranial primary and metastatic disease sites by targeted next-generation sequencing of critical oncogenes.

Methods: A retrospective, single-center study was conducted on patients who underwent resection of brain metastases between 2014 and 2022 and had clinical and matched genomic data and/or molecular markers available for defining oncologic subgroups. Targeted next-generation sequencing of over 500 oncogenes was performed on resected tumors as part of clinical care (n=41 patients with matched specimens). Molecular subgroups for breast, melanoma, and non-small cell lung cancer subgroups were also assessed to evaluate rates of molecular-based subgroup swapping between sites.

Results: The cohort comprised 256 patients with matched tumors from multiple cancer types, most commonly from breast adenocarcinoma (n=108, 42.2%), melanoma (n=83, 32.4%), and NSCLC (n=43, 16.8%). When evaluating receptor subgroups for breast, melanoma, and NSCLC, subgroup swapping was observed most frequently across breast cancer (22.2%, n=24/108) with loss of ER/PR and gain of HER2 most frequently observed within brain metastases. Molecular subgroup swapping was rare within melanoma (7.2%, n=6/83) and NSCLC (14.0%, n=6/43) patients. When evaluating oncogenomic alterations in 41 patients with matched specimens undergoing targeted next-generation sequencing, 80.5% (33/41) of brain metastases demonstrated a unique oncogene alteration profile compared to an extracranial disease site. Within this subgroup of patients with evidence of genomic divergence, rates of mutational gains and losses in different oncogenes in brain metastases compared to matched sites were 84.8% (28/33) and 72.7% (24/33), respectively.

Conclusion : Brain metastases demonstrate high rates of genomic divergence compared to primary and extracranial metastatic disease sites. This data supports obtaining brain metastasis tissue to ensure appropriate CNS penetrant systemic therapies are selected.