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Proffered Paper session - CNS tumours

4025 - Mutational and inflammatory microenvironment characteristics in primary and matched local recurrent non-small cell lung cancer brain metastases


19 Oct 2018


Proffered Paper session - CNS tumours


Tumour Immunology;  Pathology/Molecular Biology

Tumour Site

Central Nervous System Malignancies


Anna Sophie Berghoff


Annals of Oncology (2018) 29 (suppl_8): viii122-viii132. 10.1093/annonc/mdy273


A.S. Berghoff1, B. Erguener2, M.R. Schuster2, U. Rajky3, G. Ricken4, J.M. Frischer5, B. Gatterbauer5, C. Marosi6, K. Dieckmann7, G. Widhalm5, C. Bock2, M. Preusser8

Author affiliations

  • 1 Department Of Medicine 1, Medical University of Vienna, 1090 - Vienna/AT
  • 2 Austrian Academy Of Sciences, CeMM Research Center for Molecular Medicine, Vienna/AT
  • 3 Department Of Medicine 1, Medical University of Vienna, Vienna/AT
  • 4 Institute Of Neurology, Medical University of Vienna, Vienna/AT
  • 5 Department Of Neurosurgery, Medizinische Universitaet Wien (Medical University of Vienna), 1090 - Vienna/AT
  • 6 Department Of Medicine I - Clinical Division Of Oncology, Medizinische Universitaet Wien (Medical University of Vienna), 1090 - Vienna/AT
  • 7 Department Of Radiotherapy, Medizinische Universitaet Wien (Medical University of Vienna), 1090 - Vienna/AT
  • 8 Department Of Medicine I, Vienna General Hospital (AKH) - Medizinische Universität Wien, 1090 - Vienna/AT


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Abstract 4025


Tumor heterogeneity in mutational as well as inflammatory characteristics is a proposed major driver of treatment resistance and tumor progression. Given that the majority of patients with brain metastases (BM) develop brain relapse during their clinical course, we aimed to investigate the mutational and immunological heterogeneity in BM.


Patients treated with neurosurgical resection of a newly diagnosed BM from non-small cell lung cancer and subsequent neurosurgical resection of the local BM recurrence were identified from the Vienna Brain Metastasis Registry. Whole exome sequencing and analysis of tumor infiltrating lymphocytes (TILs) using immunohistochemistry was performed.


24 matched BM specimens from 12 patients (9/12 (75%) male; median age 60 years) were available for analysis. A high concordance in CD3+ TIL (p = 0.004) and CD8+ TIL (p = 0.004) density as well as in the tumor mutational burden (TMB; p < 0.001) was evident between the two specimens of the same patient. A single case (1/12 (8.3%)) changed from low CD3+ and CD8+ TIL density to high density although no radiotherapy or immunotherapy was applied in-between. TMB in the first resection specimen (median 39.2 mutations / Mb) correlated with TMB in the second resection specimen (39.3 mutations / Mb; p < 0.001). A single case (1/12 (8.3%)) presented with marked TMB increase (154 mutation/Mb to 217 mutation/Mb) after application of stereotactic radiotherapy to the resection cavity. No correlation of TIL density and TMB was evident in the investigated specimens (p > 0.05). Overall the mutational characteristics were stable between the two specimens at the same location but at different time points of the same patients as 88% (range 80%-93%) of mutations were shared by both samples.


High concordance in mutational and immunological characteristics was observed in this homogenous cohort of local non-small cell lung cancer BM recurrences. TIL density as well as TMB were consistent between BM and the matching local recurrence, although radiotherapy might impact the mutational characteristics. Further analysis of the mutational differences might reveal new therapeutic approaches for secondary BM prevention.

Clinical trial identification

Legal entity responsible for the study

Medical University of Vienna.


Has not received any funding.

Editorial Acknowledgement


All authors have declared no conflicts of interest.

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