Clinical decision making in the era of immunotherapy for high grade-glioma: report of four cases
Surabhi Ranjan, Martha Quezado, Nancy Garren, Lisa Boris, Christine Siegel, Osorio Lopes Abath Neto, Brett J Theeler, Deric M Park, Edjah Nduom, Kareem A Zaghloul, Mark R Gilbert, Jing Wu, Surabhi Ranjan, Martha Quezado, Nancy Garren, Lisa Boris, Christine Siegel, Osorio Lopes Abath Neto, Brett J Theeler, Deric M Park, Edjah Nduom, Kareem A Zaghloul, Mark R Gilbert, Jing Wu
Abstract
Background: Immune checkpoint inhibitors (ICPIs) are being investigated in clinical trials for patients with glioblastoma. While these therapies hold great promise, management of the patients receiving such treatment can be complicated due to the challenges in recognizing immune-related adverse events caused by checkpoint inhibitor treatment. Brain imaging changes that are the consequence of an inflammatory response may be misinterpreted as disease progression leading to inappropriate premature cessation of treatment. The aim of this study was to, by way of a series of cases, underscore the challenges in determining the nature of contrast-enhancing masses that develop during the treatment of patients with glioblastoma treated with ICPIs.
Case presentation: We reviewed the clinical course and management of 4 patients on ICPIs who developed signs of tumor progression on imaging. These findings were examined in the context of Immunotherapy Response Assessment in Neuro-Oncology (iRANO) guidelines. Although all 4 patients had very similar imaging findings, 2 of the 4 patients were later found to have intense inflammatory changes (pseudoprogression) by pathologic examination.
Conclusions: A high index of suspicion for pseudoprogression needs to be maintained when a patient with brain tumor on immunotherapy presents with worsening in an area of a pre-existing tumor or a new lesion in brain. Our findings strongly suggest that pathological diagnosis remains the gold standard for distinguishing tumor progression from pseudoprogression in patients receiving immunotherapy. There is a large unmet need to develop reliable non-invasive imaging diagnostic techniques.
Trial registration: ClinicalTrials.gov NCT02311920. Registered 8 December 2014.
Keywords: CTLA-4; Immune checkpoint inhibitors; Immunotherapy; Ipilimumab; Nivolumab; PD-1; Pseudoprogression; iRANO.
Conflict of interest statement
Ethics approval and consent to participateAll the patients reported above were enrolled in a clinical trial approved by the National Cancer Institute institutional review board and the National Cancer Institute ethics committee of the National Institutes of Health. A written informed consent was obtained directly from all patients who participated in this study.
Consent for publicationAll 4 patients provided written informed consents for publication of their medical data, images and histopathology slides in this article.
Competing interestsThe authors declare that that they have no competing interests.
Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Source: PubMed