Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Proffered Paper session - CNS tumours

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

Date

19 Oct 2018

Session

Proffered Paper session - CNS tumours

Presenters

Anna Sophie Berghoff

Citation

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

Authors

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
More

Resources

Abstract 4025

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Funding

Has not received any funding.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings