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Der Radiologe Aug 2020Cancer immunotherapies play an increasing role in the treatment of advanced cancer. In a subset of patients, atypical response patterns and unconventional adverse... (Review)
Review
BACKGROUND
Cancer immunotherapies play an increasing role in the treatment of advanced cancer. In a subset of patients, atypical response patterns and unconventional adverse events make diagnostic evaluation challenging for radiologists.
OBJECTIVES
In this article, we provide a review of the possibilities and limitations of imaging methods in monitoring immunotherapies, discuss the phenomena of pseudoprogression and hyperprogression, and introduce iRECIST as an evaluation standard for clinical studies with immunotherapies. In addition, we describe the most notable adverse events and their imaging features.
MATERIALS AND METHODS
This article is based on reviews and studies published since 2009. We used PubMed for the literature search and included the following search terms: "immunotherapy", "checkpoint inhibitor", "pseudoprogression", "iRECIST" and "immune related adverse events".
RESULTS AND CONCLUSION
With an incidence of up to 10%, pseudoprogression is a rare phenomenon. Currently, differentiation between pseudoprogression and true progressive disease is only possible by follow-up examinations. iRECIST, published in 2017, introduced immune unconfirmed progressive disease (iUPD) and immune confirmed progressive disease (iCPD) as new categories of therapeutic response. There is still no consensus on the time interval between examinations. Crucial adverse events include hypophysitis and pneumonitis, whereby the latter may present as different patterns of interstitial pneumonia making it difficult to differentiate between drug toxicity, infection, and tumor progression.
Topics: Humans; Immunotherapy; Neoplasms; Response Evaluation Criteria in Solid Tumors; Treatment Outcome
PubMed: 32710153
DOI: 10.1007/s00117-020-00726-x -
Bioengineering (Basel, Switzerland) Nov 2018Imaging plays a critical role in the management of the highly complex and widely diverse central nervous system (CNS) malignancies in providing an accurate diagnosis,... (Review)
Review
Imaging plays a critical role in the management of the highly complex and widely diverse central nervous system (CNS) malignancies in providing an accurate diagnosis, treatment planning, response assessment, prognosis, and surveillance. Contrast-enhanced magnetic resonance imaging (MRI) is the primary modality for CNS disease management due to its high contrast resolution, reasonable spatial resolution, and relatively low cost and risk. However, defining tumor response to radiation treatment and chemotherapy by contrast-enhanced MRI is often difficult due to various factors that can influence contrast agent distribution and perfusion, such as edema, necrosis, vascular alterations, and inflammation, leading to pseudoprogression and pseudoresponse assessments. Amino acid positron emission tomography (PET) is emerging as the method of resolving such equivocal lesion interpretations. Amino acid radiotracers can more specifically differentiate true tumor boundaries from equivocal lesions based on their specific and active uptake by the highly metabolic cellular component of CNS tumors. These therapy-induced metabolic changes detected by amino acid PET facilitate early treatment response assessments. Integrating amino acid PET in the management of CNS malignancies to complement MRI will significantly improve early therapy response assessment, treatment planning, and clinical trial design.
PubMed: 30487391
DOI: 10.3390/bioengineering5040104 -
International Journal of Molecular... Jul 2014Radiation therapy is an important modality used in the treatment of patients with brain metastatic disease and malignant gliomas. Post-treatment surveillance often... (Review)
Review
Radiation therapy is an important modality used in the treatment of patients with brain metastatic disease and malignant gliomas. Post-treatment surveillance often involves serial magnetic resonance imaging. A challenge faced by clinicians is in the diagnosis and management of a suspicious gadolinium-enhancing lesion found on imaging. The suspicious lesion may represent post-treatment radiation effects (PTRE) such as pseudoprogression, radiation necrosis or tumor recurrence. Significant progress has been made in diagnostic imaging modalities to assist in differentiating these entities. Surgical and medical interventions have also been developed to treat PTRE. In this review, we discuss the pathophysiology, clinical presentation, diagnostic imaging modalities and provide an algorithm for the management of pseudoprogression, radiation necrosis and tumor recurrence.
Topics: Brain Neoplasms; Diagnosis, Differential; Glioma; Humans; Radiation Injuries; Radiotherapy; Recurrence
PubMed: 24995696
DOI: 10.3390/ijms150711832 -
Journal of Clinical Medicine May 2023Immune checkpoint inhibitors are currently the standard of care for many advanced solid tumors, and they have been recently approved for the treatment of... (Review)
Review
Immune checkpoint inhibitors are currently the standard of care for many advanced solid tumors, and they have been recently approved for the treatment of relapsed/refractory Hodgkin lymphoma and primary mediastinal B cell lymphoma. Assessments of the response to immunotherapy may be complicated by the occurrence of the flare/pseudoprogression phenomenon, consisting of initial tumor enlargement and even the appearance of new lesions, followed by a response, which may initially be indistinguishable from true progression. There have been efforts to characterize and capture the new patterns of response observed during immunotherapy, namely, pseudoprogression and delayed response, and several immune-related response criteria have been proposed. Confirming progression on a subsequent scan and measuring the total tumor burden are both common in immune-related criteria. Due to the peculiarity of hematologic malignancies, lymphoma-specific immune-related criteria have been developed (LYRIC), and they have been evaluated in research studies in comparison to the Lugano Classification. In this review work, we illustrate the evolution of the response criteria in lymphomas from the first CT-based criteria to the development of the PET-based Lugano Classification, further refined to take into account the flare phenomenon encountered during immunotherapy. We also describe the additional contribution of PET-derived volumetric parameters to the interpretation of responses during immunotherapy.
PubMed: 37240602
DOI: 10.3390/jcm12103498 -
Frontiers in Oncology 2023This study aimed to elucidate the relationship between dynamic genomic mutation alteration and pseudoprogression (PsPD)/hyperprogressive disease (HPD) in...
INTRODUCTION
This study aimed to elucidate the relationship between dynamic genomic mutation alteration and pseudoprogression (PsPD)/hyperprogressive disease (HPD) in immunotherapy-treated advanced non-small-cell lung cancer (NSCLC), to provide clinical evidence for identifying and distinguishing between PsPD and HPD.
METHOD
Patients with advanced NSCLC who were treated with anti-PD1 were enrolled. Whole blood was collected at baseline and post image progression. Serum was separated and sequenced using 425-panel next-generation sequencing analysis (NGS).
RESULTS
NGS revealed that not only single gene mutations were associated with PsPD/HPD before treatment, dynamic monitoring of the whole-blood genome mutation spectrum also varied greatly. Mutational burden, allele frequency%, and relative circulating tumor DNA abundance indicated that the fold change after image progression was much higher in the HPD group.
DISCUSSION
The gene mutation profiles of PsPD and HPD not only differed before treatment, but higher genome mutation spectrum post image progression indicated true disease progression in patients with HPD. This suggests that dynamic whole-genome mutation profile monitoring as NGS can distinguish PsPD from HPD more effectively than single gene detection, providing a novel method for guiding clinical immune treatment.
PubMed: 38023206
DOI: 10.3389/fonc.2023.1231094 -
Radiologic Clinics of North America Nov 2019Radiographic monitoring of posttreatment glioblastoma is important for clinical trials and determining next steps in management. Evaluation for tumor progression is... (Review)
Review
Radiographic monitoring of posttreatment glioblastoma is important for clinical trials and determining next steps in management. Evaluation for tumor progression is confounded by the presence of treatment-related radiographic changes, making a definitive determination less straight-forward. The purpose of this article was to describe imaging tools available for assessing treatment response in glioblastoma, as well as to highlight the definitions, pathophysiology, and imaging features typical of true progression, pseudoprogression, pseudoresponse, and radiation necrosis.
Topics: Brain; Brain Neoplasms; Diagnostic Imaging; Disease Progression; Glioblastoma; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Multimodal Imaging; Necrosis; Positron-Emission Tomography; Radiation Injuries
PubMed: 31582045
DOI: 10.1016/j.rcl.2019.07.003 -
Neuroimaging Clinics of North America Feb 2021Radiographic monitoring of posttreatment glioblastoma is important for clinical trials and determining next steps in management. Evaluation for tumor progression is... (Review)
Review
Radiographic monitoring of posttreatment glioblastoma is important for clinical trials and determining next steps in management. Evaluation for tumor progression is confounded by the presence of treatment-related radiographic changes, making a definitive determination less straight-forward. The purpose of this article was to describe imaging tools available for assessing treatment response in glioblastoma, as well as to highlight the definitions, pathophysiology, and imaging features typical of true progression, pseudoprogression, pseudoresponse, and radiation necrosis.
Topics: Brain; Brain Neoplasms; Contrast Media; Diagnostic Imaging; Disease Progression; Fluorodeoxyglucose F18; Glioblastoma; Humans; Image Enhancement; Magnetic Resonance Imaging; Necrosis; Positron-Emission Tomography; Radiation Injuries; Radiopharmaceuticals; Treatment Outcome
PubMed: 33220823
DOI: 10.1016/j.nic.2020.09.010 -
Frontiers in Immunology 2021The inclusion of immune checkpoint inhibitors (ICIs) in therapeutic algorithms has led to significant survival benefits in patients with various metastatic cancers....
BACKGROUND
The inclusion of immune checkpoint inhibitors (ICIs) in therapeutic algorithms has led to significant survival benefits in patients with various metastatic cancers. Concurrently, an increasing number of neurological immune related adverse events (IRAE) has been observed. In this retrospective analysis, we examine the ICI-induced incidence of cerebral pseudoprogression and propose a classification system.
METHODS
We screened our hospital information system to identify patients with any in-house ICI treatment for any tumor disease during the years 2007-2019. All patients with cerebral MR imaging (cMRI) of sufficient diagnostic quality were included. cMRIs were retrospectively analyzed according to immunotherapy response assessment for neuro-oncology (iRANO) criteria.
RESULTS
We identified 12 cases of cerebral pseudoprogression in 123 patients treated with ICIs and sufficient MRI. These patients were receiving ICI therapy for lung cancer (n=5), malignant melanoma (n=4), glioblastoma (n=1), hepatocellular carcinoma (n=1) or lymphoma (n=1) when cerebral pseudoprogression was detected. Median time from the start of ICI treatment to pseudoprogression was 5 months. All but one patient developed neurological symptoms. Three different patterns of cerebral pseudoprogression could be distinguished: new or increasing contrast-enhancing lesions, new or increasing T2 predominant lesions and cerebral vasculitis type pattern.
CONCLUSION
Cerebral pseudoprogression followed three distinct patterns and was detectable in 3.2% of all patients during ICI treatment and in 9.75% of the patients with sufficient brain imaging follow up. The fact that all but one of the affected patients developed neurological symptoms, which would be classified as progressive disease according to iRANO criteria, mandates vigilance in the diagnosis and treatment of ICI-induced cerebral lesions.
Topics: Adult; Aged; Brain; Brain Neoplasms; Female; Humans; Immune Checkpoint Inhibitors; Male; Middle Aged; Retrospective Studies
PubMed: 35046955
DOI: 10.3389/fimmu.2021.798811 -
Frontiers in Pharmacology 2021Immunotherapy, which takes advantage of the immune system to eliminate cancer cells, has been widely studied and applied in oncology. Immune checkpoint inhibitors (ICIs)... (Review)
Review
Immunotherapy, which takes advantage of the immune system to eliminate cancer cells, has been widely studied and applied in oncology. Immune checkpoint inhibitors (ICIs) prevent the immune system from being turned off before cancer cells are eliminated. They have proven to be among the most promising and effective immunotherapies, with significant survival benefits and durable responses in diverse tumor types. However, an increasing number of retrospective studies have found that some patients treated with ICIs experience unusual responses, including accelerated proliferation of tumor cells and rapid progression of the disease, with poor outcomes. Such unexpected adverse events are termed hyperprogressive disease (HPD), and their occurrence suggests that ICIs are detrimental to a subset of cancer patients. HPD is common, with an incidence ranging between 4 and 29% in several cancer types. However, the mechanisms of HPD remain poorly understood, and no clinical predictive factors of HPD have been identified. In this review, we summarize current findings, including retrospective studies and case reports, and focus on several key issues including the defining characteristics, predictive biomarkers, potential mechanisms of HPD, and strategies for avoiding HPD after ICI treatment.
PubMed: 34290608
DOI: 10.3389/fphar.2021.678409 -
Frontiers in Neuroscience 2022Management of gliomas following initial diagnosis requires thoughtful presurgical planning followed by regular imaging to monitor treatment response and survey for new... (Review)
Review
Management of gliomas following initial diagnosis requires thoughtful presurgical planning followed by regular imaging to monitor treatment response and survey for new tumor growth. Traditional MR imaging modalities such as T1 post-contrast and T2-weighted sequences have long been a staple of tumor diagnosis, surgical planning, and post-treatment surveillance. While these sequences remain integral in the management of gliomas, advances in imaging techniques have allowed for a more detailed characterization of tumor characteristics. Advanced MR sequences such as perfusion, diffusion, and susceptibility weighted imaging, as well as PET scans have emerged as valuable tools to inform clinical decision making and provide a non-invasive way to help distinguish between tumor recurrence and pseudoprogression. Furthermore, these advances in imaging have extended to the operating room and assist in making surgical resections safer. Nevertheless, surgery, chemotherapy, and radiation treatment continue to make the interpretation of MR changes difficult for glioma patients. As analytics and machine learning techniques improve, radiomics offers the potential to be more quantitative and personalized in the interpretation of imaging data for gliomas. In this review, we describe the role of these newer imaging modalities during the different stages of management for patients with gliomas, focusing on the pre-operative, post-operative, and surveillance periods. Finally, we discuss radiomics as a means of promoting personalized patient care in the future.
PubMed: 35281485
DOI: 10.3389/fnins.2022.787755