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Neuro-oncology Practice Oct 2021The ability to accurately differentiate treatment-related changes (ie, pseudoprogression and radiation necrosis) from recurrent glioma remains a critical diagnostic... (Review)
Review
The ability to accurately differentiate treatment-related changes (ie, pseudoprogression and radiation necrosis) from recurrent glioma remains a critical diagnostic problem in neuro-oncology. Because these entities are treated differently and have vastly different outcomes, accurate diagnosis is necessary to provide optimal patient care. In current practice, this diagnostic quandary commonly requires either serial imaging or histopathologic tissue confirmation. In this article, experts in the field debate the utility of 2-deoxy-2[F]fluoro-d-glucose positron emission tomography (FDG PET) as an imaging tool to distinguish tumor recurrence from treatment-related changes in a patient with glioblastoma and progressive contrast enhancement on magnetic resonance (MR) following chemoradiotherapy.
PubMed: 34594566
DOI: 10.1093/nop/npab027 -
Cancer Jan 2020Patients with metastatic melanoma have variable responses to combination ipilimumab and nivolumab. The objectives of this study were to examine the patterns of response... (Clinical Trial)
Clinical Trial
BACKGROUND
Patients with metastatic melanoma have variable responses to combination ipilimumab and nivolumab. The objectives of this study were to examine the patterns of response and survival in patients treated with combination ipilimumab and anti-PD-1 therapy (IPI + PD1) and to explore the nature of pseudoprogression and acquired resistance.
METHODS
Patients with metastatic melanoma who received treatment with first-line IPI + PD1 had all metastases ≥5 mm measured on computed tomography/magnetic resonance imaging studies. The lesional response rate (LRR) and the overall response rate (ORR) were determined according to Response Evaluation Criteria in Solid Tumors, version 1.1.
RESULTS
In total, 140 patients who had 833 metastases were studied. The ORR and the overall complete response (CR) rate decreased as tumor burden or the number of metastases increased. Metastases that had a CR (49%) were smaller than metastases without a CR (median, 13 vs 17 mm; P < .0001). Soft-tissue and lung metastases had the highest LRR (79% and 77%, respectively), whereas liver metastases had the lowest (46%). In multivariate analysis, patients with lung metastases had superior ORR (odds ratio [OR], 2.75; P = .02) and progression-free survival (hazard ratio [HR], 0.46; P = .02), whereas those with liver metastases had inferior ORR (OR, 0.33; P = .02), progression-free survival (HR, 4.03; P < .01), and overall survival (HR, 3.17; P = .01). Pseudoprogression occurred in one-third of patients who had progressive disease as their best response, with an overall survival that was comparable to that of patients without disease progression. Acquired resistance occurred in 12% of responders after a median of 9.6 months, with an overall survival rate of 83% at 1 year from progression.
CONCLUSIONS
Metastases in different anatomical locations display distinct response patterns and also are associated with overall response and survival with combination immunotherapy. Specific sites of disease may hold unique mechanisms of resistance and should allow for more personalized treatment.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Female; Humans; Ipilimumab; Male; Melanoma; Middle Aged; Neoplasm Metastasis; Nivolumab; Programmed Cell Death 1 Receptor; Progression-Free Survival
PubMed: 31584722
DOI: 10.1002/cncr.32522 -
Journal of Cancer Research and... 2023Systemic therapy in lung cancer is mainstay of treatment as most patients present in advanced stages, with rising importance of new immunotherapy agents.
BACKGROUND
Systemic therapy in lung cancer is mainstay of treatment as most patients present in advanced stages, with rising importance of new immunotherapy agents.
PURPOSE
To compare the RECIST 1.1 and the immunotherapy Response Evaluation Criteria in Solid Tumors (iRECISTs) criteria for response assessment in lung cancer patients on immunotherapy. To find the incidence of pseudoprogression and associated imaging patterns.
MATERIAL AND METHODS
Retrospective study in 28 patients treated with immunotherapy for advanced metastatic NSCLC. End points were progression-free survival (PFS) and overall survival (OS). Response assessments were separately tabulated according to RECIST 1.1 and iRECIST and classified into dichotomous groups of responders and nonresponders. Agreement in assessments between RECIST 1.0 and iRECIST examined using Cohen kappa (κ) coefficient with 95% confidence intervals. Kaplan-Meier survival analysis was done for PFS and OS. Differences between RECIST 1.1 and iRECIST for both responder and nonresponder were evaluated by the log rank test, Breslow (Generalized Wilcoxon) test, and Tarone-Ware test.
RESULTS
Incidence of pseudoprogression was 7% (2/28). The RECIST1.1 and iRECIST were in disagreement in two patients. The agreement between RECIST and iRECIST was almost perfect. The PFS and the OS are significantly longer in duration for responders in comparison to nonresponders for both RECIST and iRECIST and the difference between two assessment criteria is not significant.
CONCLUSION
Although iRECIST aims to monitor treatment more precisely than conventional response criteria, this must be weighed against how infrequent pseudoprogression is and the cost of this therapy, both financially and in the potential delay in changing to a more effective treatment.
Topics: Humans; Lung Neoplasms; Response Evaluation Criteria in Solid Tumors; Nivolumab; Retrospective Studies; Carcinoma, Non-Small-Cell Lung; Treatment Outcome
PubMed: 37787285
DOI: 10.4103/jcrt.jcrt_1456_21 -
Journal of Magnetic Resonance Imaging :... Jan 2019Treatment evaluation of patients with glioblastomas is important to aid in clinical decisions. Conventional MRI with contrast is currently the standard method, but... (Review)
Review
Treatment evaluation of patients with glioblastomas is important to aid in clinical decisions. Conventional MRI with contrast is currently the standard method, but unable to differentiate tumor progression from treatment-related effects. Pseudoprogression appears as new enhancement, and thus mimics tumor progression on conventional MRI. Contrarily, a decrease in enhancement or edema on conventional MRI during antiangiogenic treatment can be due to pseudoresponse and is not necessarily reflective of a favorable outcome. Neovascularization is a hallmark of tumor progression but not for posttherapeutic effects. Perfusion-weighted MRI provides a plethora of additional parameters that can help to identify this neovascularization. This review shows that perfusion MRI aids to identify tumor progression, pseudoprogression, and pseudoresponse. The review provides an overview of the most applicable perfusion MRI methods and their limitations. Finally, future developments and remaining challenges of perfusion MRI in treatment evaluation in neuro-oncology are discussed. Level of Evidence: 3 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2019;49:11-22.
Topics: Brain; Brain Neoplasms; Contrast Media; Disease Progression; Edema; Glioblastoma; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Angiography; Neuroimaging; Reproducibility of Results
PubMed: 30561164
DOI: 10.1002/jmri.26306 -
Korean Journal of Radiology Aug 2021Immunotherapy is an effective treatment option for gynecological malignancies. Radiologists dealing with gynecological patients undergoing treatment with immune... (Review)
Review
Immunotherapy is an effective treatment option for gynecological malignancies. Radiologists dealing with gynecological patients undergoing treatment with immune checkpoint inhibitors should be aware of unconventional immune-related imaging features for the evaluation of tumor response and immune-related adverse events. In this paper, immune checkpoint inhibitors used for gynecological malignancies and their mechanisms of action are briefly presented. In the second part, patterns of pseudoprogression are illustrated, and different forms of immune-related adverse events are discussed.
Topics: Diagnostic Imaging; Female; Genital Neoplasms, Female; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Neoplasms; Radiologists
PubMed: 34047505
DOI: 10.3348/kjr.2020.1299 -
The British Journal of Radiology Dec 2011Although brain tumours are rare compared with other malignancies, they are responsible, in many cases, for severe physical and cognitive disability and have a high case... (Review)
Review
Although brain tumours are rare compared with other malignancies, they are responsible, in many cases, for severe physical and cognitive disability and have a high case fatality rate (13% overall survival at 5 years). Gliomas account for over 60% of primary brain tumours and usually present with one or more symptoms of raised intracranial pressure, progressive neurological deficit, seizures, focal or global cognitive decline. The diagnosis is made by a combination of imaging and histological examination of tumour specimen. Contrast-enhanced MRI is the gold standard imaging modality and provides highly sensitive anatomical information about the tumour. Advanced imaging modalities provide complementary information about brain tumour metabolism, blood flow and ultrastructure and are being increasingly incorporated into routine clinical sequences. Imaging is essential for guiding surgery and radiotherapy treatments and for monitoring response to, and progression of, therapy. However, changes in imaging over time may be misinterpreted and lead to incorrect assumptions about the effectiveness of treatments. Thus, the disappearance of contrast enhancement and resolution of oedema after anti-angiogenesis treatments is seen early while conventional T(2) weighted/FLAIR sequences demonstrate continual tumour growth (pseudoregression). Conversely imaging may suggest lack of efficacy of treatment e.g. increasing tumour size and contrast enhancement following chemoradiation for malignant gliomas (pseudoprogression), which then stabilise or resolve after a few months of continued treatment and that paradoxically may be associated with a better outcome. These factors have led to a re-evaluation of the role of standard sequences in the assessment of treatment response spurning interest in the development of quantitative biomarkers.
Topics: Brain Neoplasms; Contrast Media; Glioma; Humans; Image Enhancement; Magnetic Resonance Imaging; Medical Oncology
PubMed: 22433832
DOI: 10.1259/bjr/18061999 -
World Neurosurgery Mar 2024One of the most frequent phenomena in the follow-up of glioblastoma is pseudoprogression, present in up to half of cases. The clinical usefulness of discriminating this...
Glioblastoma Pseudoprogression Discrimination Using Multiparametric Magnetic Resonance Imaging, Principal Component Analysis, and Supervised and Unsupervised Machine Learning.
BACKGROUND
One of the most frequent phenomena in the follow-up of glioblastoma is pseudoprogression, present in up to half of cases. The clinical usefulness of discriminating this phenomenon through magnetic resonance imaging and nuclear medicine has not yet been standardized; in this study, we used machine learning on multiparametric magnetic resonance imaging to explore discriminators of this phenomenon.
METHODS
For the study, 30 patients diagnosed with IDH wild-type glioblastoma operated on at both study centers in 2011-2020 were selected; 15 patients corresponded to early tumor progression and 15 patients to pseudoprogression. Using unsupervised learning, the number of clusters and tumor segmentation was recorded using gap-stat and k-means method, adjusting to voxel adjacency. In a second phase, a class prediction was carried out with a multinomial logistic regression supervised learning method; the outcome variables were the percentage of assignment, class overrepresentation, and degree of voxel adjacency.
RESULTS
Unsupervised learning of the tumor in its diagnosis shows up to 14 well-differentiated tumor areas. In the supervised learning phase, there is a higher percentage of assigned classes (P < 0.01), less overrepresentation of classes (P < 0.01), and greater adjacency (55% vs. 33%) in cases of true tumor progression compared with pseudoprogression.
CONCLUSIONS
True tumor progression preserves the multidimensional characteristics of the basal tumor at the voxel and region of interest level, resulting in a characteristic differential pattern when supervised learning is used.
Topics: Humans; Glioblastoma; Unsupervised Machine Learning; Multiparametric Magnetic Resonance Imaging; Principal Component Analysis; Brain Neoplasms; Magnetic Resonance Imaging; Disease Progression
PubMed: 38253179
DOI: 10.1016/j.wneu.2024.01.074 -
Cureus Oct 2022Immunotherapy plays a vital role in the treatment of several types of malignancies. While the molecular targets of immunotherapy differ, the desired goal is to increase...
Immunotherapy plays a vital role in the treatment of several types of malignancies. While the molecular targets of immunotherapy differ, the desired goal is to increase the host immune response against neoplastic tissue. This upregulated immune state results in infiltration of the tumor with activated immune cells and may be misinterpreted as disease progression in anatomical and metabolic imaging studies, known as pseudoprogression. We present a case of pseudoprogression demonstrated on a fluoride-18 (F-18) fluciclovine positron emission tomography-computed tomography (PET-CT) scan of an 85-year-old male with metastatic castrate-resistant prostate cancer who underwent treatment with sipuleucel-T. An understanding of the pseudoprogression phenomenon and its manifestations is critical for both treating physicians and imaging specialists to facilitate decision-making regarding treatment.
PubMed: 36407177
DOI: 10.7759/cureus.30380 -
Scientific Reports Aug 2022Peritumoral cerebral edema is reported to be a side effect that can occur after stereotactic radiosurgery. We aimed to determine whether intratumoral necrosis (ITN) is a...
Peritumoral cerebral edema is reported to be a side effect that can occur after stereotactic radiosurgery. We aimed to determine whether intratumoral necrosis (ITN) is a risk factor for peritumoral edema (PTE) when gamma knife radiosurgery (GKRS) is performed in patients with meningioma. In addition, we propose the concept of pseudoprogression: a temporary volume expansion that can occur after GKRS in the natural course of meningioma with ITN. This retrospective study included 127 patients who underwent GKRS for convexity meningioma between January 2019 and December 2020. Risk factors for PTE and ITN were investigated using logistic regression analysis. Analysis of variance was used to determine whether changes in tumor volume were statistically significant. After GKRS, ITN was observed in 34 (26.8%) patients, and PTE was observed in 10 (7.9%) patients. When postoperative ITN occurred after GKRS, the incidence of postoperative PTE was 18.970-fold (p = 0.009) greater. When a 70% dose volume ≥ 1 cc was used, the possibility of ITN was 5.892-fold (p < 0.001) higher. On average, meningiomas with ITN increased in volume by 128.5% at 6 months after GKRS and then decreased to 94.6% at 12 months. When performing GKRS in meningioma, a 70% dose volume ≥ 1 cc is a risk factor for ITN. At 6 months after GKRS, meningiomas with ITN may experience a transient volume expansion and PTE, which are characteristics of pseudoprogression. These characteristics typically improve at 12 months following GKRS.
Topics: Edema; Follow-Up Studies; Humans; Meningeal Neoplasms; Meningioma; Necrosis; Radiosurgery; Retrospective Studies; Treatment Outcome
PubMed: 35953695
DOI: 10.1038/s41598-022-17813-9 -
Cancer Immunology, Immunotherapy : CII Mar 2022Immune checkpoint inhibitors (ICIs) have become the standard of care for a variety of cancers, including non-small cell lung cancer (NSCLC). In this study, we...
BACKGROUND
Immune checkpoint inhibitors (ICIs) have become the standard of care for a variety of cancers, including non-small cell lung cancer (NSCLC). In this study, we investigated the frequency of pseudoprogression and hyperprogression in lung cancer patients treated with ICIs in the real world and aimed to discover a novel candidate marker to distinguish pseudoprogression from hyperprogression soon after ICI treatment.
METHODS
This study included 74 patients with advanced NSCLC who were treated with PD-1/PD-L1 inhibitors at Chungnam National University Hospital (CNUH) between January 2018 and August 2020. Chest X-rays were examined on day 7 after the first ICI dose to identify changes in the primary mass, and the response was assessed by computed tomography (CT). We evaluated circulating regulatory T (Treg) cells using flow cytometry and correlated the findings with clinical outcomes.
RESULTS
The incidence of pseudoprogression was 13.5%, and that of hyperprogression was 8.1%. On day 7 after initiation of treatment, the frequency of CD4CD25CD127FoxP3 Treg cells was significantly decreased compared with baseline (P = 0.038) in patients who experienced pseudoprogression and significantly increased compared with baseline (P = 0.024) in patients who experienced hyperprogression. In the responder group, the frequencies of CD4CD25CD127FoxP3 Treg cells and PD-1CD4CD25CD127FoxP3 Treg cells were significantly decreased 7 days after commencement of treatment compared with baseline (P = 0.034 and P < 0.001, respectively).
CONCLUSION
Circulating Treg cells represent a promising potential dynamic biomarker to predict efficacy and differentiate atypical responses, including pseudoprogression and hyperprogression, after immunotherapy in patients with NSCLC.
Topics: Aged; Aged, 80 and over; B7-H1 Antigen; Biomarkers; Female; Humans; Immune Checkpoint Inhibitors; Immunophenotyping; Lung Neoplasms; Lymphocyte Count; Male; Middle Aged; Molecular Targeted Therapy; Prognosis; Programmed Cell Death 1 Receptor; T-Lymphocytes, Regulatory; Treatment Outcome
PubMed: 34278517
DOI: 10.1007/s00262-021-03018-y