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Intracranial disease control for EGFR-mutant and ALK-rearranged lung cancer with large volume or symptomatic brain metastases

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Abstract

Purpose/objective(s)

Tyrosine kinase inhibitors (TKIs) are commonly employed for patients with brain metastases from lung cancer and specific driver mutations. We sought to identify the correlation between intracranial tumor burden and outcomes in patients with brain metastases treated with TKIs.

Materials/methods

We identified and retrospectively reviewed cases of EGFR-mutant or ALK-rearranged lung cancer with brain metastases at any time during their cancer course. Clinical characteristics and treatment information were abstracted from the medical records. Brain metastases were contoured to calculate total volume of disease at diagnosis and after initial therapy. High intracranial burden was defined as either > 10 brain metastases, volume of brain metastases > 15 cc, or largest lesion > 3 cm. Intracranial response was determined according to Response Assessment in Neuro-Oncology (RANO) criteria on the patient level. We determined the correlation between clinical and imaging characteristics and intracranial progression free survival (IC-PFS) and overall survival (OS).

Results

Fifty-seven patients with EGFR (n = 49) and ALK (n = 8) alterations were identified. Median follow-up from initial brain metastasis diagnosis was 17 months. Neurological symptoms were present in 54% at brain metastasis diagnosis. For those receiving TKIs alone or TKIs with radiation, at least a partial intracranial response (≥ 65% volume reduction) at 3 months from starting therapy was achieved in 94% and 58%. Progressive intracranial disease at 3 months occurred in 6.3% and 8.3%. Patients with high intracranial burden (n = 21) had a median 17 brain metastases, 6.5 cc volume, and 1.9 cm maximal tumor diameter. Median IC-PFS and OS for patients with high intracranial burden was 13.9 and 35.4 months. Patients with high intracranial burden and neurological symptoms at diagnosis had similar IC-PFS and OS compared to those with low burden and absence of neurological symptoms (p > 0.05 for each).

Conclusion

Most patients receiving TKIs as part of their initial therapy achieve an early and durable volumetric intracranial response, irrespective of presenting disease burden or neurologic symptoms.

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Authors and Affiliations

  1. Department of Radiation Oncology, University of Virginia, PO Box 800383, Charlottesville, VA, 22908, USA

    Sunil W. Dutta, Marie L. Mack, Eric Aliotta, Kristin A. Ward, Donald A. Muller & James M. Larner

  2. Department of Neurology, University of Virginia, Charlottesville, VA, USA

    Camilo E. Fadul

  3. Department of Medicine, University of Virginia, Charlottesville, VA, USA

    Richard D. Hall & Ryan D. Gentzler

  4. Department of Neurological Surgery, University of Virginia, Charlottesville, VA, USA

    Jason P. Sheehan

Authors
  1. Sunil W. Dutta
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  2. Marie L. Mack
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  3. Eric Aliotta
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  4. Kristin A. Ward
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  5. Donald A. Muller
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  6. James M. Larner
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  7. Camilo E. Fadul
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  8. Richard D. Hall
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Correspondence to Sunil W. Dutta.

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All authors declare that they have no conflict of interest.

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Research data: Patient level data not allowed to be shared per IRB. Author responsible for statistical analysis: SWD.

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Dutta, S.W., Mack, M.L., Aliotta, E. et al. Intracranial disease control for EGFR-mutant and ALK-rearranged lung cancer with large volume or symptomatic brain metastases. J Neurooncol 149, 357–366 (2020). https://doi.org/10.1007/s11060-020-03615-4

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  • DOI: https://doi.org/10.1007/s11060-020-03615-4

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