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Practical Radiation Oncology Apr 2024A dedicated MRI Simulation(MRsim) for radiation treatment(RT) planning in high-grade glioma(HGG) patients can detect early radiological changes, including tumor...
BACKGROUND
A dedicated MRI Simulation(MRsim) for radiation treatment(RT) planning in high-grade glioma(HGG) patients can detect early radiological changes, including tumor progression after surgery and before standard of care chemoradiation. This study aimed to determine the impact of using post-op MRI vs. MRsim as the baseline for response assessment and reporting pseudo-progression on follow-up imaging at one month(FU1) after chemoradiation.
METHODS
Histologically confirmed HGG patients were planned for six weeks of RT in a prospective study for adaptive RT planning. All patients underwent post-op MRI, MRsim, and follow-up MRI scans every 2-3 months. Tumor response was assessed by three independent blinded reviewers using Response Assessment in Neuro-Oncology(RANO) criteria when baseline was either post-op MRI or MRsim. Interobserver agreement was calculated using light's kappa.
RESULTS
30 patients (median age 60.5 years; IQR 54.5-66.3) were included. Median interval between surgery and RT was 34 days (IQR 27-41). Response assessment at FU1 differed in 17 patients (57%) when the baseline was post-op MRI vs. MRsim, including true progression vs. partial response(PR) or stable disease(SD) in 11 (37%) and SD vs. PR in 6 (20%) patients. True progression was reported in 19 patients (63.3%) on FU1 when the baseline was post-op MRI vs 8 patients (26.7%) when the baseline was MRsim (p=.004). Pseudo-progression was observed at FU1 in 12 (40%) vs. 4 (13%) patients, when the baseline was post-op MRI vs. MRsim (p=.019). Interobserver agreement between observers was moderate (κ = 0.579; p<0.001).
CONCLUSIONS
Our study demonstrates the value of acquiring an updated MR closer to RT in patients with HGG to improve response assessment, and accuracy in evaluation of pseudo-progression even at the early time point of first follow-up after RT. Earlier identification of patients with true progression would enable more timely salvage treatments including potential clinical trial enrolment to improve patient outcomes.
PubMed: 38685448
DOI: 10.1016/j.prro.2024.04.009 -
Critical Reviews in Oncogenesis 2024Deep learning (DL) is poised to redefine the way medical images are processed and analyzed. Convolutional neural networks (CNNs), a specific type of DL architecture, are...
Deep learning (DL) is poised to redefine the way medical images are processed and analyzed. Convolutional neural networks (CNNs), a specific type of DL architecture, are exceptional for high-throughput processing, allowing for the effective extraction of relevant diagnostic patterns from large volumes of complex visual data. This technology has garnered substantial interest in the field of neuro-oncology as a promising tool to enhance medical imaging throughput and analysis. A multitude of methods harnessing MRI-based CNNs have been proposed for brain tumor segmentation, classification, and prognosis prediction. They are often applied to gliomas, the most common primary brain cancer, to classify subtypes with the goal of guiding therapy decisions. Additionally, the difficulty of repeating brain biopsies to evaluate treatment response in the setting of often confusing imaging findings provides a unique niche for CNNs to help distinguish the treatment response to gliomas. For example, glioblastoma, the most aggressive type of brain cancer, can grow due to poor treatment response, can appear to grow acutely due to treatment-related inflammation as the tumor dies (pseudo-progression), or falsely appear to be regrowing after treatment as a result of brain damage from radiation (radiation necrosis). CNNs are being applied to separate this diagnostic dilemma. This review provides a detailed synthesis of recent DL methods and applications for intratumor segmentation, glioma classification, and prognosis prediction. Furthermore, this review discusses the future direction of MRI-based CNN in the field of neuro-oncology and challenges in model interpretability, data availability, and computation efficiency.
Topics: Humans; Glioma; Prognosis; Brain Neoplasms; Neural Networks, Computer; Deep Learning; Magnetic Resonance Imaging; Image Processing, Computer-Assisted
PubMed: 38683153
DOI: 10.1615/CritRevOncog.2023050852 -
NMR in Biomedicine Apr 2024Arterial spin labeling (ASL) and dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) have shown potential for differentiating tumor progression from...
Influence of arterial transit time delays on the differentiation between tumor progression and pseudoprogression in glioblastoma by arterial spin labeling magnetic resonance imaging.
Arterial spin labeling (ASL) and dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) have shown potential for differentiating tumor progression from pseudoprogression. For pseudocontinuous ASL with a single postlabeling delay, the presence of delayed arterial transit times (ATTs) could affect the evaluation of ASL-MRI perfusion data. In this study, the influence of ATT artifacts on the perfusion assessment and differentiation between tumor progression and pseudoprogression were studied. This study comprised 66 adult patients (mean age 60 ± 13 years; 40 males) with a histologically confirmed glioblastoma who received postoperative radio (chemo)therapy. ASL-MRI and DSC-MRI scans were acquired at 3 months postradiotherapy as part of the standard clinical routine. These scans were visually scored regarding (i) the severity of ATT artifacts (%) on the ASL-MRI scans only, scored by two neuroradiologists; (ii) perfusion of the enhancing tumor lesion; and (iii) radiological evaluation of tumor progression versus pseudoprogression by one neuroradiologist. The final outcome was based on combined clinical and radiological follow-up until 9 months postradiotherapy. ATT artifacts were identified in all patients based on the mean scores of two raters. A significant difference between the radiological evaluation of ASL-MRI and DSC-MRI was observed only for ASL images with moderate ATT severity (30%-65%). The perfusion assessment showed ASL-MRI tending more towards hyperperfusion than DSC-MRI in the case of moderate ATT artifacts. In addition, there was a significant difference between the prediction of tumor progression with ASL-MRI and the final outcome in the case of severe ATT artifacts (McNemar test, p = 0.041). Despite using ASL imaging parameters close to the recommended settings, ATT artifacts frequently occur in patients with treated brain tumors. Those artifacts could hinder the radiological evaluation of ASL-MRI data and the detection of true disease progression, potentially affecting treatment decisions for patients with glioblastoma.
PubMed: 38654579
DOI: 10.1002/nbm.5166 -
Frontiers in Neurology 2024Assessing the treatment response of glioblastoma multiforme during immunotherapy (IT) is an open issue. Treatment response assessment maps (TRAMs) might help distinguish...
INTRODUCTION
Assessing the treatment response of glioblastoma multiforme during immunotherapy (IT) is an open issue. Treatment response assessment maps (TRAMs) might help distinguish true tumor progression (TTP) and pseudoprogression (PsP) in this setting.
METHODS
We recruited 16 naïve glioblastoma patients enrolled in a phase II trial consisting of the Stupp protocol (a standardized treatment for glioblastoma involving combined radiotherapy and chemotherapy with temozolomide, followed by adjuvant temozolomide) plus IT with dendritic cells. Patients were followed up till progression or death; seven underwent a second surgery for suspected progression. Clinical, immunological, and MRI data were collected from all patients and histology in case of second surgery. Patients were classified as responders (progression-free survival, PFS > 12 months), and non-responders (PFS ≤ 12), HIGH-NK (natural killer cells, i.e., immunological responders), and LOW-NK (immunological non-responders) based on immune cell counts in peripheral blood. TRAMs differentiate contrast-enhancing lesions with different washout dynamics into hypothesized tumoral (conventionally blue-colored) vs. treatment-related (red-colored).
RESULTS
Using receiver operating characteristic (ROC) curves, a threshold of -0.066 in VV (volume of the blue portion of tumoral area/volume of contrast enhancement) variation between values obtained in the MRI performed before PsP/TTP and at TTP/PSP allowed to discriminate TTP from PsP with a sensitivity of 71.4% and a specificity of 100%. Among HIGH-NK patients, at month 6 there was a significant reduction compared to baseline and month 2 in median "blue" volumes.
DISCUSSION
In conclusion, in our pilot study TRAMs support the discrimination between tumoral and treatment-related enhancing features in immunological responders vs. non-responders, the distinction between PsP and TTP, and might provide surrogate markers of immunological response.
PubMed: 38651109
DOI: 10.3389/fneur.2024.1374737 -
Melanoma Research Aug 2024Pseudoprogression encapsulates a process of temporary radiographic growth followed by subsequent regression of metastatic melanoma lesions in response to immune...
Pseudoprogression encapsulates a process of temporary radiographic growth followed by subsequent regression of metastatic melanoma lesions in response to immune checkpoint blockade (ICB), such as the combination of anti-programmed cell death protein 1 (PD-1) and anticytotoxic T-lymphocyte-associated antigen 4 therapy. This occurs in approximately 5-10% of ICB-treated patients, but has not yet been described in the context of novel combination therapies. Here, we report a case of an 89-year-old patient with metastatic melanoma to the liver, lung and lymph nodes, who underwent treatment with Opdualag (combining anti-PD-1 nivolumab and anti-lymphocyte-activation gene 3 relatlimab ICBs), and developed pseudoprogression after two cycles of therapy. The patient experienced a radiographic increase in liver metastatic lesion size, but was found to have a subsequent reduction in these lesions. The patient has been on therapy for 18 months without evidence of disease progression and continues to be clinically well-appearing.
Topics: Humans; Melanoma; Skin Neoplasms; Aged, 80 and over; Programmed Cell Death 1 Receptor; Lymphocyte Activation Gene 3 Protein; Disease Progression; Male; Immune Checkpoint Inhibitors; Nivolumab; Antigens, CD
PubMed: 38640504
DOI: 10.1097/CMR.0000000000000974 -
Academic Radiology Apr 2024Gliomas are aggressive brain tumors with a poor prognosis. Assessing treatment response is challenging because magnetic resonance imaging (MRI) may not distinguish true... (Review)
Review
RATIONALE AND OBJECTIVES
Gliomas are aggressive brain tumors with a poor prognosis. Assessing treatment response is challenging because magnetic resonance imaging (MRI) may not distinguish true progression (TP) from pseudoprogression (PsP). This review aims to discuss imaging techniques and liquid biopsies used to distinguish TP from PsP.
MATERIALS AND METHODS
This review synthesizes existing literature to examine advances in imaging techniques, such as magnetic resonance diffusion imaging (MRDI), perfusion-weighted imaging (PWI) MRI, and liquid biopsies, for identifying TP or PsP through tumor markers and tissue characteristics.
RESULTS
Advanced imaging techniques, including MRDI and PWI MRI, have proven effective in delineating tumor tissue properties, offering valuable insights into glioma behavior. Similarly, liquid biopsy has emerged as a potent tool for identifying tumor-derived markers in biofluids, offering a non-invasive glimpse into tumor evolution. Despite their promise, these methodologies grapple with significant challenges. Their sensitivity remains inconsistent, complicating the accurate differentiation between TP and PSP. Furthermore, the absence of standardized protocols across platforms impedes the reliability of comparisons, while inherent biological variability adds complexity to data interpretation.
CONCLUSION
Their potential applications have been highlighted, but gaps remain before routine clinical use. Further research is needed to develop and validate these promising methods for distinguishing TP from PsP in gliomas.
PubMed: 38614827
DOI: 10.1016/j.acra.2024.03.019 -
Radiologia 2024MRI is the cornerstone in the evaluation of brain metastases. The clinical challenges lie in discriminating metastases from mimickers such as infections or primary...
MRI is the cornerstone in the evaluation of brain metastases. The clinical challenges lie in discriminating metastases from mimickers such as infections or primary tumors and in evaluating the response to treatment. The latter sometimes leads to growth, which must be framed as pseudo-progression or radionecrosis, both inflammatory phenomena attributable to treatment, or be considered as recurrence. To meet these needs, imaging techniques are the subject of constant research. However, an exponential growth after radiotherapy must be interpreted with caution, even in the presence of results suspicious of tumor progression by advanced techniques, because it may be due to inflammatory changes. The aim of this paper is to familiarize the reader with inflammatory phenomena of brain metastases treated with radiotherapy and to describe two related radiological signs: "the inflammatory cloud" and "incomplete ring enhancement", in order to adopt a conservative management with close follow-up.
Topics: Humans; Radiography; Radiology; Brain Neoplasms; Conservative Treatment; Radiation Injuries
PubMed: 38614532
DOI: 10.1016/j.rxeng.2024.03.003 -
Clinical Nuclear Medicine Apr 2024A 43-year-old woman diagnosed with refractory diffuse large B-cell lymphoma was referred to chimeric antigen receptor T-cell therapy at our institution. After 3 cycles...
A 43-year-old woman diagnosed with refractory diffuse large B-cell lymphoma was referred to chimeric antigen receptor T-cell therapy at our institution. After 3 cycles of bridging therapy, preinfusion 18F-FDG PET/CT suggested a complete metabolic response. 18F-FDG PET/CT 1 month after chimeric antigen receptor T-cell infusion showed 2 foci of elevated activity in the spleen, which was finally confirmed as pseudoprogression.
PubMed: 38598485
DOI: 10.1097/RLU.0000000000005221 -
Ocular Immunology and Inflammation Apr 2024We report two patients who displayed evidence of localized ocular inflammation after CAR T-cell infusion. To manage the resulting severe visual impairment, systemic...
We report two patients who displayed evidence of localized ocular inflammation after CAR T-cell infusion. To manage the resulting severe visual impairment, systemic corticosteroids were administered to both patients. This treatment led to a reduction in local inflammation and restored vision in one of the patients.
PubMed: 38579172
DOI: 10.1080/09273948.2024.2333393 -
Cureus Feb 2024Tumor-treating fields (TTFields) is an established treatment modality for glioblastoma. False progression to chemoradiation is a known problem in patients with...
Tumor-treating fields (TTFields) is an established treatment modality for glioblastoma. False progression to chemoradiation is a known problem in patients with glioblastoma multiforme (GBM), with most cases occurring within three months of radiation therapy. In this report, we present two cases of delayed pseudoprogression caused by TTFields. Two patients with GBM who received TTFields showed signs of radiographic progression six months after the completion of radiation therapy. Patient 1 was a 37-year-old female with a glioblastoma in the right temporal lobe. Patient 2 was a 70-year-old male with glioblastoma in the left temporal lobe. Both patients received radiation therapy, followed by temozolomide (TMZ) maintenance therapy and TTFields. Patient 1 underwent a second resection; however, the pathology revealed only a treatment effect, and the final diagnosis was a pseudoprogression. In Case 2, the disease resolved with steroid therapy alone. In both patients, the lesions appeared later than during the typical pseudoprogression period. A recent study reported that TTFields increase the permeability of the plasma cell membrane, which may result in further leakage of gadolinium into the extracellular lumen. Further studies are needed to better characterize delayed pseudoprogression and improve treatment outcomes.
PubMed: 38558596
DOI: 10.7759/cureus.55147