Imaging challenges of immunotherapy and targeted therapy in patients with brain metastases: response, progression, and pseudoprogression

Norbert Galldiks; Martin Kocher; Garry Ceccon; Jan-Michael Werner; Anna Brunn; Martina Deckert; Whitney B Pope; Riccardo Soffietti; Emilie Le Rhun; Michael Weller; Jörg C Tonn; Gereon R Fink; Karl-Josef Langen

doi:10.1093/neuonc/noz147

Imaging challenges of immunotherapy and targeted therapy in patients with brain metastases: response, progression, and pseudoprogression

Neuro Oncol. 2020 Jan 11;22(1):17-30. doi: 10.1093/neuonc/noz147.

Authors

Norbert Galldiks^{1

2

3}, Martin Kocher^{2

4}, Garry Ceccon¹, Jan-Michael Werner¹, Anna Brunn⁵, Martina Deckert⁵, Whitney B Pope⁶, Riccardo Soffietti⁷, Emilie Le Rhun^{8

9

10}, Michael Weller¹⁰, Jörg C Tonn^{11

12}, Gereon R Fink^{1

2}, Karl-Josef Langen^{2

13}

Affiliations

¹ Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
² Institute of Neuroscience and Medicine, Research Center Juelich, Juelich, Germany.
³ Center of Integrated Oncology, Universities of Aachen, Bonn, Cologne, and Düsseldorf, Germany.
⁴ Department of Stereotaxy and Functional Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
⁵ Institute of Neuropathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
⁶ Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
⁷ Department of Neuro-Oncology, University and City of Health and Science Hospital, Turin, Italy.
⁸ Neuro-Oncology, General and Stereotaxic Neurosurgery Service, University Hospital Lille, Lille, France.
⁹ Breast Cancer Department, Oscar Lambret Center, Lille, France.
¹⁰ Department of Neurology & Brain Tumor Center, University Hospital and University of Zurich, Zurich, Switzerland.
¹¹ Department of Neurosurgery, Ludwig Maximilians University of Munich, Munich, Germany.
¹² German Cancer Consortium, partner site Munich, Germany.
¹³ Department of Nuclear Medicine, University Hospital Aachen, Aachen, Germany.

Abstract

The advent of immunotherapy using immune checkpoint inhibitors (ICIs) and targeted therapy (TT) has dramatically improved the prognosis of various cancer types. However, following ICI therapy or TT-either alone (especially ICI) or in combination with radiotherapy-imaging findings on anatomical contrast-enhanced MRI can be unpredictable and highly variable, and are often difficult to interpret regarding treatment response and outcome. This review aims at summarizing the imaging challenges related to TT and ICI monotherapy as well as combined with radiotherapy in patients with brain metastases, and to give an overview on advanced imaging techniques which potentially overcome some of these imaging challenges. Currently, major evidence suggests that imaging parameters especially derived from amino acid PET, perfusion-/diffusion-weighted MRI, or MR spectroscopy may provide valuable additional information for the differentiation of treatment-induced changes from brain metastases recurrence and the evaluation of treatment response.

Keywords: FET PET; brain metastasis; immune checkpoint inhibitors; lung cancer; melanoma; radiomics.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Brain Neoplasms / diagnostic imaging*
Brain Neoplasms / drug therapy*
Brain Neoplasms / secondary*
Disease Progression
Humans
Immune Checkpoint Inhibitors / therapeutic use*
Immunotherapy / methods
Molecular Targeted Therapy / methods
Neuroimaging / methods*
Treatment Outcome

Substances

Immune Checkpoint Inhibitors

Grants and funding

P50 CA211015/CA/NCI NIH HHS/United States