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Journal of Nuclear Medicine : Official... Jun 2023Accurate differentiation between tumor progression (TP) and pseudoprogression remains a critical unmet need in neurooncology. F-fluciclovine is a widely available...
Accurate differentiation between tumor progression (TP) and pseudoprogression remains a critical unmet need in neurooncology. F-fluciclovine is a widely available synthetic amino acid PET radiotracer. In this study, we aimed to assess the value of F-fluciclovine PET for differentiating pseudoprogression from TP in a prospective cohort of patients with suspected radiographic recurrence of glioblastoma. We enrolled 30 glioblastoma patients with radiographic progression after first-line chemoradiotherapy for whom surgical resection was planned. The patients underwent preoperative F-fluciclovine PET and MRI. The relative percentages of viable tumor and therapy-related changes observed in histopathology were quantified and categorized as TP (≥50% viable tumor), mixed TP (<50% and >10% viable tumor), or pseudoprogression (≤10% viable tumor). Eighteen patients had TP, 4 had mixed TP, and 8 had pseudoprogression. Patients with TP/mixed TP had a significantly higher 40- to 50-min SUV (6.64 + 1.88 vs. 4.11 ± 1.52, = 0.009) than patients with pseudoprogression. A 40- to 50-min SUV cutoff of 4.66 provided 90% sensitivity and 83% specificity for differentiation of TP/mixed TP from pseudoprogression (area under the curve [AUC], 0.86). A maximum relative cerebral blood volume cutoff of 3.672 provided 90% sensitivity and 71% specificity for differentiation of TP/mixed TP from pseudoprogression (AUC, 0.779). Combining a 40- to 50-min SUV cutoff of 4.66 and a maximum relative cerebral blood volume of 3.67 on MRI provided 100% sensitivity and 80% specificity for differentiating TP/mixed TP from pseudoprogression (AUC, 0.95). F-fluciclovine PET uptake can accurately differentiate pseudoprogression from TP in glioblastoma, with even greater accuracy when combined with multiparametric MRI. Given the wide availability of F-fluciclovine, larger, multicenter studies are warranted to determine whether amino acid PET with F-fluciclovine should be used in the routine posttreatment assessment of glioblastoma.
Topics: Humans; Glioblastoma; Prospective Studies; Magnetic Resonance Imaging; Carboxylic Acids; Positron-Emission Tomography; Amino Acids
PubMed: 36549916
DOI: 10.2967/jnumed.122.264812 -
Acta Neuropathologica Communications Dec 2023Post-resection radiologic monitoring to identify areas of new or progressive enhancement concerning for cancer recurrence is critical during patients with glioblastoma...
Post-resection radiologic monitoring to identify areas of new or progressive enhancement concerning for cancer recurrence is critical during patients with glioblastoma follow-up. However, treatment-related pseudoprogression presents with similar imaging features but requires different clinical management. While pathologic diagnosis is the gold standard to differentiate true progression and pseudoprogression, the lack of objective clinical standards and admixed histologic presentation creates the needs to (1) validate the accuracy of current approaches and (2) characterize differences between these entities to objectively differentiate true disease. We demonstrated using an online RNAseq repository of recurrent glioblastoma samples that cancer-immune cell activity levels correlate with heterogenous clinical outcomes in patients. Furthermore, nCounter RNA expression analysis of 48 clinical samples taken from second neurosurgical resection supports that pseudoprogression gene expression pathways are dominated with immune activation, whereas progression is predominated with cell cycle activity. Automated image processing and spatial expression analysis however highlight a failure to apply these broad expressional differences in a subset of cases with clinically challenging admixed histology. Encouragingly, applying unsupervised clustering approaches over our segmented histologic images provides novel understanding of morphologically derived differences between progression and pseudoprogression. Spatially derived data further highlighted polarization of myeloid populations that may underscore the tumorgenicity of novel lesions. These findings not only help provide further clarity of potential targets for pathologists to better assist stratification of progression and pseudoprogression, but also highlight the evolution of tumor-immune microenvironment changes which promote tumor recurrence.
Topics: Humans; Glioblastoma; Disease Progression; Brain Neoplasms; Chemoradiotherapy; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Tumor Microenvironment
PubMed: 38049893
DOI: 10.1186/s40478-023-01587-w -
Cancer Imaging : the Official... Jan 2020iRECIST for the objective monitoring of immunotherapies was published by the official RECIST working group in 2017.
BACKGROUND
iRECIST for the objective monitoring of immunotherapies was published by the official RECIST working group in 2017.
MAIN BODY
Immune-checkpoint inhibitors represent one of the most important therapy advancements in modern oncology. They are currently used for treatment of multiple malignant diseases especially at advanced, metastatic stages which were poorly therapeutically accessible in the past. Promising results of recent studies suggest that their application will further grow in the near future, particularly when used in combination with chemotherapy. A challenging aspect of these immunotherapies is that they may show atypical therapy response patterns such as pseudoprogression and demonstrate a different imaging spectrum of adverse reactions, both of which are crucial for radiologists to understand. In 2017 the RECIST working group published a modified set of response criteria, iRECIST, for immunotherapy, based on RECIST 1.1 which was developed for cytotoxic therapies and adapted for targeted agents.
CONCLUSION
This article provides guidance for response assessment of oncologic patients under immunotherapy based on iRECIST criteria.
Topics: Humans; Immunotherapy; Neoplasms; Practice Guidelines as Topic; Response Evaluation Criteria in Solid Tumors
PubMed: 31900236
DOI: 10.1186/s40644-019-0281-x -
Therapeutic Advances in Medical Oncology 2023Immune checkpoint inhibitors (ICIs) have revealed significant clinical values in different solid tumors and hematological malignancy, changing the landscape for the... (Review)
Review
Immune checkpoint inhibitors (ICIs) have revealed significant clinical values in different solid tumors and hematological malignancy, changing the landscape for the treatment of multiple types of cancer. However, only a subpopulation of patients has obvious tumor response and long-term survival after ICIs treatment, and many patients may experience other undesirable clinical features. Therefore, biomarkers are critical for patients to choose exact optimum therapy. Here, we reviewed existing preclinical and clinical biomarkers of immunotherapeutic efficacy and immune-related adverse events (irAEs). Based on efficacy prediction, pseudoprogression, hyperprogressive disease, or irAEs, these biomarkers were divided into cancer cell-derived biomarkers, tumor microenvironment-derived biomarkers, host-derived biomarkers, peripheral blood biomarkers, and multi-modal model and artificial intelligence assessment-based biomarkers. Furthermore, we describe the relation between ICIs efficacy and irAEs. This review provides the overall perspective of biomarkers of immunotherapeutic outcome and irAEs prediction during ICIs treatment.
PubMed: 37113734
DOI: 10.1177/17588359231163807 -
Journal of Cancer Research and Clinical... Dec 2020Immune checkpoint inhibitors are associated with clinical benefit in lung cancer. However, response patterns to immunotherapy, including pseudoprogression and... (Review)
Review
PURPOSE
Immune checkpoint inhibitors are associated with clinical benefit in lung cancer. However, response patterns to immunotherapy, including pseudoprogression and hyperprogression, are difficult to diagnose, and their mechanisms remain unclear. This review aimed to describe two response patterns observed in lung cancer, namely pseudoprogression and hyperprogression, including their epidemiology, diagnostic characteristics, and plausible mechanisms.
METHODS
We performed a comprehensive literature search in the PubMed database, using keywords "pseudoprogression", "hyperprogression", and "lung cancer", among others. The literature was examined for pseudoprogression and hyperprogression characteristics and plausible mechanisms.
RESULTS
Pseudoprogression manifests in multiple forms; however, the immune system-related response criteria and biopsy data are helpful to make accurate diagnosis. Serological biomarkers, such as neutrophil-to-lymphocyte ratio (NLR) and circulating tumor DNA (ctDNA), might help distinguish pseudoprogression from true progression. The incidence of hyperprogression ranges within 5-19.2%, depending on definition. The unique response pattern of rapid progression is observed not only with immunotherapy, but also with other treatment regimens. Molecular mutations and amplifications may result in hyperprogression; however, the exact mechanism remains unclear.
CONCLUSION
Atypical response patterns, such as pseudoprogression and hyperprogression, are increasingly common in clinical practice. Immune-related response criteria can help diagnose pseudoprogression. Molecular mechanisms of hyperprogression remain unclear. Biomarkers for pseudoprogression and hyperprogression are required.
Topics: Circulating Tumor DNA; Disease Progression; Humans; Immunologic Factors; Lung Neoplasms; Lymphocytes; Neutrophils; Response Evaluation Criteria in Solid Tumors
PubMed: 32857178
DOI: 10.1007/s00432-020-03360-1 -
Cancers Sep 2023Glioma and glioblastoma multiform (GBM) remain among the most debilitating and life-threatening brain tumors. Despite advances in diagnosing approaches, patient... (Review)
Review
Glioma and glioblastoma multiform (GBM) remain among the most debilitating and life-threatening brain tumors. Despite advances in diagnosing approaches, patient follow-up after treatment (surgery and chemoradiation) is still challenging for differentiation between tumor progression/recurrence, pseudoprogression, and radionecrosis. Radiomics emerges as a promising tool in initial diagnosis, grading, and survival prediction in patients with glioma and can help differentiate these post-treatment scenarios. Preliminary published studies are promising about the role of radiomics in post-treatment glioma/GBM. However, this field faces significant challenges, including a lack of evidence-based solid data, scattering publication, heterogeneity of studies, and small sample sizes. The present review explores radiomics's capabilities in following patients with glioma/GBM status post-treatment and to differentiate tumor progression, recurrence, pseudoprogression, and radionecrosis.
PubMed: 37760399
DOI: 10.3390/cancers15184429 -
Memo 2018Immunotherapies comprise of a class of cancer therapies that are increasingly used for treatment of several cancer entities. Active immunotherapies encompassing immune... (Review)
Review
Immunotherapies comprise of a class of cancer therapies that are increasingly used for treatment of several cancer entities. Active immunotherapies encompassing immune checkpoint inhibitors are the most widespread class of immunotherapies, with indications for melanoma, non-small lung cancer, renal cell carcinoma, urothelial carcinoma, head and neck squamous cell carcinoma, and Hodgkin's lymphoma. Immune checkpoint inhibitors have demonstrated unique response patterns that are not adequately captured by traditional response criteria such das the Response Evaluation Criteria in Solid Tumors (RECIST) and World Health Organization criteria. Consequently, adaptions of these criteria have been released such as the immune-related RECIST and immune RECIST, which account for the specialities of immunotherapies. Immunotherapies can cause a distinct set of adverse events such as pneumonitis, colitis, and hypophysitis. In addition, atypical treatment response patterns termed pseudoprogression have been observed. Thereby, new or enlarging lesions appear after treatment start and mimic tumor progression, which is followed by an eventual decrease in total tumor burden. In this review article we will describe pitfalls in the radiological response assessment of immunotherapies, focusing on pseudoprogression and imaging appearances of common immune-related adverse events.
PubMed: 29983829
DOI: 10.1007/s12254-018-0389-x -
Revista Espanola de Medicina Nuclear E... 2021The treatment of cancer by immunotherapy has been a revolution, as it is the first strategy that manages to control the disease for prolonged periods of time. Its...
The treatment of cancer by immunotherapy has been a revolution, as it is the first strategy that manages to control the disease for prolonged periods of time. Its efficacy is associated with different imaging response patterns and the appearance of new toxicities. We would highlight two patterns of tumour response: pseudoprogression, or growth of tumour lesions after the start of immunotherapy treatment, followed by a significant reduction in lesions, and hyperprogression, acceleration of tumour progression and metastasis early after the start of treatment. The emergence of such patterns has generated new metabolic response criteria, such as PECRIT, PERCIMT, imPERCIST and IPERCIST. Of particular interest are the new immunoPET-specific biomarkers, as they allow the identification of patients presenting the tumour target and are useful for predicting response to immunotherapy.
PubMed: 33674234
DOI: 10.1016/j.remn.2021.02.001 -
Journal of Thoracic Oncology : Official... Jul 2018
Topics: Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Humans; Lung Neoplasms; Programmed Cell Death 1 Receptor
PubMed: 29935844
DOI: 10.1016/j.jtho.2018.05.011 -
Expert Review of Neurotherapeutics Nov 2017Initial diagnostics and follow-up of gliomas is usually based on contrast-enhanced MRI. However, the capacity of standard MRI to differentiate neoplastic tissue from... (Review)
Review
Initial diagnostics and follow-up of gliomas is usually based on contrast-enhanced MRI. However, the capacity of standard MRI to differentiate neoplastic tissue from posttherapeutic effects such as pseudoprogression is limited. Advanced neuroimaging methods may provide relevant additional information, which allow for a more accurate diagnosis especially in clinically equivocal situations. This review article focuses predominantly on PET using radiolabeled amino acids and advanced MRI techniques such as perfusion-weighted imaging (PWI) and summarizes the efforts of these methods regarding the identification of pseudoprogression after glioma therapy. Areas covered: The current literature on pseudoprogression in the field of brain tumors, with a focus on gliomas is summarized. A literature search was performed using the terms 'pseudoprogression', 'temozolomide', 'glioblastoma', 'PET', 'PWI', 'radiochemotherapy', and derivations thereof. Expert commentary: The present literature provides strong evidence that PWI MRI and amino acid PET can be of great value by providing valuable additional diagnostic information in order to overcome the diagnostic challenge of pseudoprogression. Despite various obstacles such as the still limited availability of amino acid PET and the lack of standardization of PWI, the diagnostic improvement probably results in relevant benefits for brain tumor patients and justifies a more widespread use of these diagnostic tools.
Topics: Brain Neoplasms; Disease Progression; Glioma; Humans; Neuroimaging
PubMed: 28862482
DOI: 10.1080/14737175.2017.1375405