Evaluating Immunotherapy Responses in Neuro-Oncology for Glioblastoma and Brain Metastases: A Brief Review Featuring Three Cases

Overview

Journal Cancer Control

Specialty Oncology

Date 2025 Feb 15

PMID 39953938

Authors

Neyran Kertmen

Gozde Kavgaci

Serkan Akin

Gokcen Coban

Ahmet Ilkay Isikay

Gozde Yazici

Affiliations

Soon will be listed here.

Abstract

Introduction: Recent advancements in immunotherapy have offered new possibilities for treating aggressive glioblastoma (GBM) and brain metastases. However, evaluating treatment responses remains complex, prompting the development of the immunotherapy-specific Response Assessment in Neuro-Oncology (iRANO) criteria. Herein, we present case reports illustrating the intricacies of interpreting imaging changes post-immunotherapy, emphasizing the need for a comprehensive approach to assessing treatment effectiveness.

Case Reports: Case 1 discusses a 41-year-old male with GBM, highlighting the challenges of differentiating tumor progression from treatment-induced pseudoprogression. Case 2 discusses a 45-year-old female with brain metastatic malignant melanoma, presenting radiological evidence of progressive disease while undergoing nivolumab treatment. Case 3 discusses a 37-year-old male with GBM, where radiological evidence indicates progressive disease while receiving pembrolizumab treatment.

Management And Outcomes: In case 1, we discussed the challenges of distinguishing true tumor progression from treatment-induced pseudoprogression, leading to the continuation of the same treatment due to pseudoprogression. In case 2, post-surgery pathology revealed radionecrosis and treatment-related changes, guiding the continuation of nivolumab therapy. Case 3 involved a pathologically confirmed progression, and the patient received best supportive care due to his performance status.

Discussion: Despite aggressive treatment regimens, the prognosis for GBM patients remains poor, underscoring the necessity for innovative therapeutic strategies. Immunotherapy holds promise in reshaping the treatment landscape for GBM and brain metastases, but further research and refinement of assessment criteria are crucial. Throughout our cases, we discuss the iRANO criteria, developed to overcome the limitations of the RANO criteria in capturing immunotherapy responses, particularly pseudoprogression.

References

Huettner C, Paulus W, Roggendorf W . Messenger RNA expression of the immunosuppressive cytokine IL-10 in human gliomas. Am J Pathol. 1995; 146(2):317-22. PMC: 1869855. View

Rong L, Li N, Zhang Z . Emerging therapies for glioblastoma: current state and future directions. J Exp Clin Cancer Res. 2022; 41(1):142. PMC: 9013078. DOI: 10.1186/s13046-022-02349-7. View

LaPointe S, Perry A, Butowski N . Primary brain tumours in adults. Lancet. 2018; 392(10145):432-446. DOI: 10.1016/S0140-6736(18)30990-5. View

Stupp R, Hegi M, Mason W, van den Bent M, Taphoorn M, Janzer R . Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009; 10(5):459-66. DOI: 10.1016/S1470-2045(09)70025-7. View

Li Y, Ma Y, Wu Z, Xie R, Zeng F, Cai H . Advanced Imaging Techniques for Differentiating Pseudoprogression and Tumor Recurrence After Immunotherapy for Glioblastoma. Front Immunol. 2021; 12:790674. PMC: 8656432. DOI: 10.3389/fimmu.2021.790674. View

Vik-Mo E, Nyakas M, Mikkelsen B, Moe M, Due-Tonnesen P, Suso E . Therapeutic vaccination against autologous cancer stem cells with mRNA-transfected dendritic cells in patients with glioblastoma. Cancer Immunol Immunother. 2013; 62(9):1499-509. PMC: 3755221. DOI: 10.1007/s00262-013-1453-3. View

Floeth F, Wittsack H, Engelbrecht V, Weber F . Comparative follow-up of enhancement phenomena with MRI and Proton MR Spectroscopic Imaging after intralesional immunotherapy in glioblastoma--Report of two exceptional cases. Zentralbl Neurochir. 2002; 63(1):23-8. DOI: 10.1055/s-2002-31579. View

Motegi H, Kamoshima Y, Terasaka S, Kobayashi H, Yamaguchi S, Tanino M . IDH1 mutation as a potential novel biomarker for distinguishing pseudoprogression from true progression in patients with glioblastoma treated with temozolomide and radiotherapy. Brain Tumor Pathol. 2012; 30(2):67-72. DOI: 10.1007/s10014-012-0109-x. View

Maxwell R, Jackson C, Lim M . Clinical Trials Investigating Immune Checkpoint Blockade in Glioblastoma. Curr Treat Options Oncol. 2017; 18(8):51. DOI: 10.1007/s11864-017-0492-y. View

10.

Szulzewsky F, Pelz A, Feng X, Synowitz M, Markovic D, Langmann T . Glioma-associated microglia/macrophages display an expression profile different from M1 and M2 polarization and highly express Gpnmb and Spp1. PLoS One. 2015; 10(2):e0116644. PMC: 4320099. DOI: 10.1371/journal.pone.0116644. View

11.

Okada H, Weller M, Huang R, Finocchiaro G, Gilbert M, Wick W . Immunotherapy response assessment in neuro-oncology: a report of the RANO working group. Lancet Oncol. 2015; 16(15):e534-e542. PMC: 4638131. DOI: 10.1016/S1470-2045(15)00088-1. View

12.

Ma B, Blakeley J, Hong X, Zhang H, Jiang S, Blair L . Applying amide proton transfer-weighted MRI to distinguish pseudoprogression from true progression in malignant gliomas. J Magn Reson Imaging. 2016; 44(2):456-62. PMC: 4946988. DOI: 10.1002/jmri.25159. View

13.

Omuro A . Immune-checkpoint inhibitors for glioblastoma: what have we learned?. Arq Neuropsiquiatr. 2022; 80(5 Suppl 1):266-269. PMC: 9491432. DOI: 10.1590/0004-282X-ANP-2022-S129. View

14.

Lim M, Xia Y, Bettegowda C, Weller M . Current state of immunotherapy for glioblastoma. Nat Rev Clin Oncol. 2018; 15(7):422-442. DOI: 10.1038/s41571-018-0003-5. View

15.

Pouleau H, Sadeghi N, Baleriaux D, Melot C, De Witte O, Lefranc F . High levels of cellular proliferation predict pseudoprogression in glioblastoma patients. Int J Oncol. 2011; 40(4):923-8. PMC: 3584626. DOI: 10.3892/ijo.2011.1260. View

16.

Reardon D, Kim T, Frenel J, Simonelli M, Lopez J, Subramaniam D . Treatment with pembrolizumab in programmed death ligand 1-positive recurrent glioblastoma: Results from the multicohort phase 1 KEYNOTE-028 trial. Cancer. 2021; 127(10):1620-1629. DOI: 10.1002/cncr.33378. View

17.

Kang H, Kim C, Han J, Choe G, Kim J, Kim J . Pseudoprogression in patients with malignant gliomas treated with concurrent temozolomide and radiotherapy: potential role of p53. J Neurooncol. 2010; 102(1):157-62. DOI: 10.1007/s11060-010-0305-7. View

18.

Nduom E, Weller M, Heimberger A . Immunosuppressive mechanisms in glioblastoma. Neuro Oncol. 2015; 17 Suppl 7:vii9-vii14. PMC: 4625890. DOI: 10.1093/neuonc/nov151. View

19.

Bloch O, Crane C, Kaur R, Safaee M, Rutkowski M, Parsa A . Gliomas promote immunosuppression through induction of B7-H1 expression in tumor-associated macrophages. Clin Cancer Res. 2013; 19(12):3165-75. PMC: 3742575. DOI: 10.1158/1078-0432.CCR-12-3314. View

20.

White N, McDonald C, McDonald C, Farid N, Kuperman J, Karow D . Diffusion-weighted imaging in cancer: physical foundations and applications of restriction spectrum imaging. Cancer Res. 2014; 74(17):4638-52. PMC: 4155409. DOI: 10.1158/0008-5472.CAN-13-3534. View