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Clinical Oncology (Royal College of... Jun 2024Assess rates of true pseudoprogression in unconfirmed progressive disease (iUPD) in a pool of immunotherapy clinical trials for different cancers, analyze tumor...
AIMS
Assess rates of true pseudoprogression in unconfirmed progressive disease (iUPD) in a pool of immunotherapy clinical trials for different cancers, analyze tumor characteristics that drive iUPD classification, and investigate potentials predictors of pseudoprogression.
MATERIALS AND METHODS
Retrospective interpretation of prospectively acquired data. Patients from 18 immunotherapy clinical trials with two arms (RECIST 1.1, iRECIST), of 10 cancer types were selected. Pooled rate of true pseudoprogression among iUPD was estimated using a common effect meta-analysis. Target, Non-target, and new lesions as the trigger of confirmed-vs pseudo-progression were compared using Chi-Square and Fisher exact tests. Conditional logistic regression was used to investigate the association between age, sex, tumor burden at baseline, and number of follow ups and pseudoprogression.
RESULTS
60/287 (21%) patients (17 women) were classified as iUPD with at least one subsequent confirmatory timepoint. The overall pooled estimate of pseudoprogression was 15% (95%CI: 8%--26%). Nontarget lesions were significantly more frequent the cause of iUPD than change in Target lesions size (p< 0.001). Most observations of true pseudoprogression occurred in the first follow-up (77%), whereas confirmed progression occurred in later time points during the trial. Pseudoprogression was not significantly associated with age, sex, tumor burden at baseline, or number of timepoints.
CONCLUSION
In a pool of immunotherapy trials, the rate of true pseudoprogression was 15%, most often in the first timepoint after baseline than later in treatment. iUPD categorization was mostly driven by changes in NT lesions rather than objective changes in measurements of target lesions.
PubMed: 38937187
DOI: 10.1016/j.clon.2024.06.002 -
Genes Jun 2024Glioblastoma multiforme (GBM)is the most common and aggressive primary brain tumor. Although temozolomide (TMZ)-based radiochemotherapy improves overall GBM patients'...
Glioblastoma multiforme (GBM)is the most common and aggressive primary brain tumor. Although temozolomide (TMZ)-based radiochemotherapy improves overall GBM patients' survival, it also increases the frequency of false positive post-treatment magnetic resonance imaging (MRI) assessments for tumor progression. Pseudo-progression (PsP) is a treatment-related reaction with an increased contrast-enhancing lesion size at the tumor site or resection margins miming tumor recurrence on MRI. The accurate and reliable prognostication of GBM progression is urgently needed in the clinical management of GBM patients. Clinical data analysis indicates that the patients with PsP had superior overall and progression-free survival rates. In this study, we aimed to develop a prognostic model to evaluate the tumor progression potential of GBM patients following standard therapies. We applied a dictionary learning scheme to obtain imaging features of GBM patients with PsP or true tumor progression (TTP) from the Wake dataset. Based on these radiographic features, we conducted a radiogenomics analysis to identify the significantly associated genes. These significantly associated genes were used as features to construct a 2YS (2-year survival rate) logistic regression model. GBM patients were classified into low- and high-survival risk groups based on the individual 2YS scores derived from this model. We tested our model using an independent The Cancer Genome Atlas Program (TCGA) dataset and found that 2YS scores were significantly associated with the patient's overall survival. We used two cohorts of the TCGA data to train and test our model. Our results show that the 2YS scores-based classification results from the training and testing TCGA datasets were significantly associated with the overall survival of patients. We also analyzed the survival prediction ability of other clinical factors (gender, age, KPS (Karnofsky performance status), normal cell ratio) and found that these factors were unrelated or weakly correlated with patients' survival. Overall, our studies have demonstrated the effectiveness and robustness of the 2YS model in predicting the clinical outcomes of GBM patients after standard therapies.
Topics: Humans; Glioblastoma; Brain Neoplasms; Male; Female; Magnetic Resonance Imaging; Middle Aged; Prognosis; Adult; Aged; Disease Progression; Temozolomide; Genomics; Survival Rate; Clinical Relevance
PubMed: 38927654
DOI: 10.3390/genes15060718 -
AJNR. American Journal of Neuroradiology Jun 2024Radiographic assessment plays a crucial role in the management of patients with central nervous system (CNS) tumors, aiding in treatment planning and evaluation of... (Review)
Review
Radiographic assessment plays a crucial role in the management of patients with central nervous system (CNS) tumors, aiding in treatment planning and evaluation of therapeutic efficacy by quantifying response. Recently, an updated version of the Response Assessment in Neuro-Oncology (RANO) criteria (RANO 2.0) was developed to improve upon prior criteria and provide an updated, standardized framework for assessing treatment response in clinical trials for gliomas in adults. This article provides an overview of significant updates to the criteria including (1) the use of a unified set of criteria for high and low grade gliomas in adults; (2) the use of the post-radiotherapy MRI scan as the baseline for evaluation in newly diagnosed high-grade gliomas; (3) the option for the trial to mandate a confirmation scan to more reliably distinguish pseudoprogression from tumor progression; (4) the option of using volumetric tumor measurements; and (5) the removal of subjective non-enhancing tumor evaluations in predominantly enhancing gliomas (except for specific therapeutic modalities). Step-by-step pragmatic guidance is hereby provided for the neuroradiologist and imaging core lab involved in operationalization and technical execution of RANO 2.0 in clinical trials, including the display of representative cases and in-depth discussion of challenging scenarios.ABBREVIATIONS: BTIP = Brain Tumor Imaging Protocol; CE = Contrast-Enhancing; CNS = Central Nervous System; CR = Complete Response; ECOG = Eastern Cooperative Oncology Group; HGG = High-Grade Glioma; IDH = Isocitrate Dehydrogenase; IRF = Independent Radiologic Facility; LGG = Low-Grade Glioma; KPS = Karnofsky Performance Status; MR = Minor Response; mRANO = Modified RANO; NANO = Neurological Assessment in Neuro-Oncology; ORR = Objective Response Rate; OS = Overall Survival; PD = Progressive Disease; PFS = Progression-Free Survival; PR = Partial Response; PsP = Pseudoprogression; RANO = Response Assessment in Neuro-Oncology; RECIST = Response Evaluation Criteria In Solid Tumors; RT = Radiation Therapy; SD = Stable Disease; Tx = Treatment.
PubMed: 38926092
DOI: 10.3174/ajnr.A8396 -
Magnetic Resonance Imaging Jun 2024This review examines the advancements in magnetic resonance imaging (MRI) techniques and their pivotal role in diagnosing and managing gliomas, the most prevalent... (Review)
Review
This review examines the advancements in magnetic resonance imaging (MRI) techniques and their pivotal role in diagnosing and managing gliomas, the most prevalent primary brain tumors. The paper underscores the importance of integrating modern MRI modalities, such as diffusion-weighted imaging and perfusion MRI, which are essential for assessing glioma malignancy and predicting tumor behavior. Special attention is given to the 2021 WHO Classification of Tumors of the Central Nervous System, emphasizing the integration of molecular diagnostics in glioma classification, significantly impacting treatment decisions. The review also explores radiogenomics, which correlates imaging features with molecular markers to tailor personalized treatment strategies. Despite technological progress, MRI protocol standardization and result interpretation challenges persist, affecting diagnostic consistency across different settings. Furthermore, the review addresses MRI's capacity to distinguish between tumor recurrence and pseudoprogression, which is vital for patient management. The necessity for greater standardization and collaborative research to harness MRI's full potential in glioma diagnosis and personalized therapy is highlighted, advocating for an enhanced understanding of glioma biology and more effective treatment approaches.
PubMed: 38914147
DOI: 10.1016/j.mri.2024.06.004 -
Frontiers in Oncology 2024Pediatric low-grade gliomas (pLGG) are the most common brain tumor in children and encompass a wide range of histologies. Treatment may pose challenges, especially in...
INTRODUCTION
Pediatric low-grade gliomas (pLGG) are the most common brain tumor in children and encompass a wide range of histologies. Treatment may pose challenges, especially in those incompletely resected or those with multiple recurrence or progression.
CASE DESCRIPTION
We report the clinical course of a girl diagnosed with pilocytic astrocytoma and profound hydrocephalus at age 12 years treated with subtotal resection, vinblastine chemotherapy, and focal proton radiotherapy. After radiotherapy the tumor increased in enhancement temporarily with subsequent resolution consistent with pseudoprogression. Despite improvement in imaging and radiographic local control, the patient continues to have challenges with headaches, visual and auditory concerns, stroke-like symptoms, and poor quality of life.
CONCLUSION
pLGG have excellent long-term survival; thus, treatments should focus on maintaining disease control and limiting long-term toxicities. Various treatment options exist including surgery, chemotherapy, targeted agents, and radiation therapy. Given the morbidity associated with pLGG, individualized treatment approaches are necessary, with a multi-disciplinary approach to care focused on minimizing treatment side effects, and promoting optimal quality of life for patients.
PubMed: 38912055
DOI: 10.3389/fonc.2024.1366251 -
European Journal of Nuclear Medicine... Jun 2024To determine the long-term prognosis of immune-related response profiles (pseudoprogression and dissociated response), not covered by conventional PERCIST criteria, in...
AIM
To determine the long-term prognosis of immune-related response profiles (pseudoprogression and dissociated response), not covered by conventional PERCIST criteria, in patients with non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICPIs).
METHODS
109 patients were prospectively included and underwent [F]FDG-PET/CT at baseline, after 7 weeks (PET1), and 3 months (PET2) of treatment. On PET1, tumor response was assessed using standard PERCIST criteria. In the event of PERCIST progression at this time-point, the study design provided for continued immunotherapy for 6 more weeks. Additional response patterns were then considered on PET2: pseudo-progression (PsPD, subsequent metabolic response); dissociated response (DR, coexistence of responding and non-responding lesions), and confirmed progressive metabolic disease (cPMD, subsequent homogeneous progression of lesions). Patients were followed up for at least 12 months.
RESULTS
Median follow-up was 21 months. At PET1, PERCIST progression was observed in 60% (66/109) of patients and ICPI was continued in 59/66. At the subsequent PET2, 14% of patients showed PsPD, 11% DR, 35% cPMD, and 28% had a sustained metabolic response. Median overall survival (OS) and progression-free-survival (PFS) did not differ between PsPD and DR (27 vs 29 months, p = 1.0; 17 vs 12 months, p = 0.2, respectively). The OS and PFS of PsPD/DR patients were significantly better than those with cPMD (29 vs 9 months, p < 0.02; 16 vs 2 months, p < 0.001), but worse than those with sustained metabolic response (p < 0.001). This 3-group prognostic stratification enabled better identification of true progressors, outperforming the prognostic value of standard PERCIST criteria (p = 0.03).
CONCLUSION
[F]FDG-PET/CT enables early assessment of response to immunotherapy. The new wsPERCIST ("wait and see") PET criteria proposed, comprising immune-related atypical response patterns, can refine conventional prognostic stratification based on PERCIST criteria.
TRIAL REGISTRATION
HDH F20230309081206. Registered 20 April 2023. Retrospectively registered.
PubMed: 38896129
DOI: 10.1007/s00259-024-06794-8 -
Cancers May 2024Immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized contemporary oncology, presenting efficacy in various solid tumors and lymphomas. However, ICIs... (Review)
Review
Immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized contemporary oncology, presenting efficacy in various solid tumors and lymphomas. However, ICIs may potentially overstimulate the immune system, leading to immune-related adverse events (irAEs). IrAEs may affect multiple organs, such as the colon, stomach, small intestine, kidneys, skin, lungs, joints, liver, lymph nodes, bone marrow, brain, heart, and endocrine glands (e.g., pancreas, thyroid, or adrenal glands), exhibiting autoimmune inflammation. F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) is commonly used in oncology for staging and assessment of therapy responses, but it may also serve as a tool for detecting irAEs. This review aims to present various patterns of metabolic activation associated with irAEs due to ICI treatment, identifiable through F-FDG PET/CT. It describes the advantages of early detection of irAEs, but also presents the challenges in differentiating them from tumor progression. It also delves into aspects of molecular response assessment within the context of pseudoprogression and hyperprogression, along with typical imaging findings related to these phenomena. Lastly, it summarizes the role of functional PET imaging in oncological immunotherapy, speculating on its future significance and limitations.
PubMed: 38893111
DOI: 10.3390/cancers16111990 -
Journal For Immunotherapy of Cancer Jun 2024The purpose of this commentary is to highlight the high occurrence of clinical pseudoprogression and delayed responses that have been observed to date with the locally...
The purpose of this commentary is to highlight the high occurrence of clinical pseudoprogression and delayed responses that have been observed to date with the locally injected oncolytic adenovirus, AdAPT-001, currently in a Phase 1/2 clinical trial (NCT04673942) for the treatment of treatment-refractory tumors. Not surprisingly, these have led to confusion about response assessment and whether to continue patients on treatment. AdAPT-001 carries a transforming growth factor (TGF)-beta trap (TGF-β), which sequesters TGF-β, a cytokine that potently regulates inflammation, fibrosis, and immunosuppression in cancer. Pseudoprogression (PsP) or progression prior to response or stabilization, has been widely recognized with radiotherapy for primary brain tumors and immune checkpoint inhibitors (ICIs). PsP has also been described and documented in the context of oncolytic virotherapy but perhaps to a lesser extent. However, repeated intratumoral injections with these immunostimulatory agents may induce a more intense immune response and release more antigenic epitopes than with ICIs, for example, which are strictly T-cell directed rather than also tumor-directed like AdAPT-001.
Topics: Humans; Disease Progression; Oncolytic Virotherapy; Oncolytic Viruses; Neoplasms; Adenoviridae
PubMed: 38886116
DOI: 10.1136/jitc-2024-008809 -
BMJ Case Reports Jun 2024A man in his 70s with metastatic colorectal cancer presented with worsening clinical symptoms and imaging studies concerning for disease progression. He had received two...
A man in his 70s with metastatic colorectal cancer presented with worsening clinical symptoms and imaging studies concerning for disease progression. He had received two cycles of pembrolizumab, but due to his symptomatic presentation and significant decline in performance status, there was concern for worsening disease. Transitioning to hospice was briefly considered, given his clinical decline and the notable increase in tumour size. Despite the presence of clinical symptoms and radiographic findings, pseudoprogression-defined as an increase in the size(s) of and/or visual appearance of new lesion(s), followed by a response-was also considered as part of the diagnostic possibilities. Consequently, the decision was made to proceed with a third cycle of pembrolizumab. During his subsequent outpatient follow-up, the patient showed significant symptomatic improvement and reported a decrease in his palpable right flank mass. With further immunotherapy, the patient continued to demonstrate symptomatic and radiological improvement.
Topics: Humans; Male; Colorectal Neoplasms; Disease Progression; Antibodies, Monoclonal, Humanized; Aged; Antineoplastic Agents, Immunological; Neoplasm Metastasis
PubMed: 38871645
DOI: 10.1136/bcr-2023-258816 -
Journal of Neuro-oncology Jun 2024
Correction to: Umbrella review and network meta-analysis of diagnostic imaging test accuracy studies in differentiating between brain tumor progression versus pseudoprogression and radionecrosis.
PubMed: 38858340
DOI: 10.1007/s11060-024-04718-y