Detection of immune-related adverse events by medical imaging in patients treated with anti-programmed cell death 1

Mekki, Ahmed; Dercle, Laurent; Lichtenstein, Philip; Marabelle, Aurélien; Michot, Jean‐Marie; Lambotte, Olivier; Pavec, Jérôme Le; Martin, Eléonora De; Balleyguier, Corinne; Champiat, Stéphane; Ammari, Samy

doi:10.1016/j.ejca.2018.03.006

Cited by 102 publications

(83 citation statements)

References 51 publications

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“…Medical imaging detects 74% of irAE in solid tumors and PET is known to be a highly sensitive modality. (30) The most frequent sites reported in solid tumors are lung, mediastinal lymph nodes (sarcoidosis-like), enterocolitis, hypophysitis, thyroiditis, hepatitis, arthritis, and pancreatitis. While we identified such irAE in our cohort, we also identified imaging findings suggestive of gastritis and hemolytic anemia.…”

Section: Discussionmentioning

confidence: 99%

Early ¹⁸F-FDG PET/CT Response Predicts Survival in Relapsed or Refractory Hodgkin Lymphoma Treated with Nivolumab

et al. 2019

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Anti-PD-1 monoclonal antibodies (anti PD-1 mAbs) such as nivolumab and pembrolizumab are associated with high response rates in patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (HL). To date, no prognostic factor for overall survival (OS) has been established with these agents in HL. We examined whether the first early response assessment evaluated using 18F-Fluorodeoxyglucose PET/CT (ePET 1), may be associated with OS in this setting. Methods: This retrospective study included 45 patients from 34 institutions. In a blinded, centralized review, three independent radiologists classified ePET 1 obtained at a median of 2.0 months (interquartile range: 1.7-3.7 months) after nivolumab initiation using existing criteria (i.e., Lugano 2014, LYRIC 2016). Patients were classified at ePET 1 according to 4 possible response categories: complete metabolic response (CMR), partial metabolic response (PMR), no metabolic response (NMR), or progressive metabolic disease (PMD). As the OS of patients with NMR and PMR were similar, they were grouped together. OS was estimated using the Kaplan-Meier method and compared between groups using log-rank testing. Results: Eleven patients (24%) died after a median follow-up of 21.2 months. The classification at ePET 1 was identical between Lugano and LYRIC since all 16 progression events at ePET 1 classified as indeterminate response per LYRIC were confirmed on subsequent evaluations. Both Lugano and LYRIC 2016 classified patients as CMR in 13 pts (29%), PMD in 16 pts (36%), NMR in 4 pts (9%) and PMR in 12 pts (27%). The 2-year OS [95CI] probability was significantly different in patients with

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Section: Discussionmentioning

confidence: 99%

Early ¹⁸F-FDG PET/CT Response Predicts Survival in Relapsed or Refractory Hodgkin Lymphoma Treated with Nivolumab

et al. 2019

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“…In this systematic review, we have observed that immune checkpoint inhibitors have a major impact on nuclear medicine imaging with changes in its interpretation, including the consideration of induced inflammation by new therapeutic evaluation criteria. In a monocentric retrospective study with the objective of describing the IrAE characteristics on medical imaging and their detection rate, Mekki et al found 39 (74%) abnormal medical imaging findings on 53 patients who had a co-occurrence of irAEs and medical imaging (CT, PET/CT, MRI, US of radiography) within 15 days [85]. Among the 12 performed 18 F-FDG PET/CT, 10 (83%) were abnormal with thoracic sarcoid-like reaction, enterocolitis, thyroiditis, hypophysitis, and pancreatitis [85].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, immune-related inflammation has to be reported even if they are not necessarily associated with clinically significant IrAE [89]. Illustrations of 18 F-FDG PET-detectable immune-related adverse effects are presented in several articles [85,88,90].…”

Section: Discussionmentioning

confidence: 99%

Immunotherapy by Immune Checkpoint Inhibitors and Nuclear Medicine Imaging: Current and Future Applications

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Bohn

2020

Cancers

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Immunotherapy by using immune checkpoint inhibitors is a revolutionary development in oncology. Medical imaging is also impacted by this new therapy, particularly nuclear medicine imaging (also called radionuclide imaging), which uses radioactive tracers to visualize metabolic functions. Our aim was to review the current applications of nuclear medicine imaging in immunotherapy, along with their limitations, and the perspectives offered by this imaging modality. Method: Articles describing the use of radionuclide imaging in immunotherapy were researched using PubMed by April 2019 and analyzed. Results: More than 5000 articles were analyzed, and nearly 100 of them were retained. Radionuclide imaging, notably 18F-FDG PET/CT, already has a major role in many cancers for pre-therapeutic and therapeutic evaluation, diagnoses of adverse effects, called immune-related adverse events (IrAE), and end-of-treatment evaluations. However, these current applications can be hindered by immunotherapy, notably due to atypical response patterns such as pseudoprogression, which is defined as an increase in the size of lesions, or the visualization of new lesions, followed by a response, and hyperprogression, which is an accelerated tumor growth rate after starting treatment. To overcome these difficulties, new opportunities are offered, particularly therapeutic evaluation criteria adapted to immunotherapy and immuno-PET allowing us to predict responses to immunotherapy. Moreover, some new technological solutions are also promising, such as radiomic analyses and body composition on associated anatomical images. However, more research has to be done, notably for the diagnosis of hyperprogression and pseudoprogression. Conclusion: Immunotherapy, by its major impact on cancer and by the new patterns generated on images, is revolutionary in the field of medical images. Nuclear medicine imaging is already established and will be able to help meet new challenges through its plasticity.

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“…IrAEs often result in abnormalities that may be identified on CT, Magnetic Resonance Imaging (MRI), Ultrasound (US), or Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) performed for restaging and/or surveillance. Mekki et al found that medical imaging (CT, MRI, US, plain radiographs, and FDG-PET/CT) were able to detect 74% of irAEs grade ≥ 2 in patients treated with anti-PD-1 [40]. Patients with ICIs-related toxicity may have a dynamic clinical course, and imaging is only a snapshot taken in a specific time point of an evolving clinical scenario.…”

Section: Most Relevant Imaging Findings In Iraesmentioning

confidence: 99%

“…Mekki et al found that 83% of patients with irAEs that underwent 18F-FDG PET-CT showed a high glucose uptake in relation with sarcoidosis-like syndrome, thyroiditis, hypophysitis, enterocolitis, and pancreatitis [40]. PET-detectable hepatitis, pneumonitis, arthritis, enthesitis, and myositis have also been reported [74].…”

Section: Pet-ct: Confounder or Problem-solving?mentioning

confidence: 99%

Imaging of Adverse Events Related to Checkpoint Inhibitor Therapy

et al. 2020

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Immunotherapy with checkpoint inhibitors (ICIs) is becoming standard of practice for an increasing number of cancer types. ICIs enhance T-cell action against the cancer cells. By unbalancing the immune system ICIs may cause dysimmune toxicities, a series of disorders broadly defined immune-related adverse events (irAEs). IrAEs may affect any organ or apparatus and most frequently involve skin, colon, endocrine organs, liver, and lungs. Early identification and appropriate treatment of irAEs can improve patient outcome. The paper aims at reviewing mechanisms of the occurrence of irAEs, the importance of a proper diagnosis and the main pillars of therapy. To provide effective guidance to the comprehension of major irAEs imaging findings will be reviewed.

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Detection of immune-related adverse events by medical imaging in patients treated with anti-programmed cell death 1

Cited by 102 publications

References 51 publications

Early ¹⁸F-FDG PET/CT Response Predicts Survival in Relapsed or Refractory Hodgkin Lymphoma Treated with Nivolumab

Early ¹⁸F-FDG PET/CT Response Predicts Survival in Relapsed or Refractory Hodgkin Lymphoma Treated with Nivolumab

Immunotherapy by Immune Checkpoint Inhibitors and Nuclear Medicine Imaging: Current and Future Applications

Imaging of Adverse Events Related to Checkpoint Inhibitor Therapy

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Detection of immune-related adverse events by medical imaging in patients treated with anti-programmed cell death 1

Cited by 102 publications

References 51 publications

Early 18F-FDG PET/CT Response Predicts Survival in Relapsed or Refractory Hodgkin Lymphoma Treated with Nivolumab

Early 18F-FDG PET/CT Response Predicts Survival in Relapsed or Refractory Hodgkin Lymphoma Treated with Nivolumab

Immunotherapy by Immune Checkpoint Inhibitors and Nuclear Medicine Imaging: Current and Future Applications

Imaging of Adverse Events Related to Checkpoint Inhibitor Therapy

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Product

Resources

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Early ¹⁸F-FDG PET/CT Response Predicts Survival in Relapsed or Refractory Hodgkin Lymphoma Treated with Nivolumab

Early ¹⁸F-FDG PET/CT Response Predicts Survival in Relapsed or Refractory Hodgkin Lymphoma Treated with Nivolumab