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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 -
The Lancet. Oncology Feb 2023
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Disease Progression; Brain Neoplasms
PubMed: 36725143
DOI: 10.1016/S1470-2045(22)00552-6 -
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 -
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 -
Current Opinion in Neurology Dec 2009Treatment response of brain tumours is typically evaluated with gadolinium-enhanced MRI using the Macdonald criteria. These criteria depend on changes in the area of... (Review)
Review
PURPOSE OF REVIEW
Treatment response of brain tumours is typically evaluated with gadolinium-enhanced MRI using the Macdonald criteria. These criteria depend on changes in the area of enhancement. However, gadolinium enhancement of brain tumours primarily reflects impairment of the blood-brain barrier.
RECENT FINDINGS
Combined chemo-irradiation with temozolomide may induce in 20-30% of cases pseudoprogression, defined as an increase of contrast-enhancement and/or oedema on MRI without true tumour progression. Also, full-blown radiation necrosis may be more frequent after combined chemo-irradiation. After treatment with vascular endothelial growth factor receptor signalling pathway inhibitors pseudoresponse is frequent: a decrease in contrast-enhancement of brain tumours on MRI without a decrease of tumour activity. This to some extent explains the high response rate without a major increase in survival after treatment with these agents for recurrent glioblastoma.
SUMMARY
Both pseudo-phenomenona confuse the assessment of outcome of brain tumours in clinical practice and in clinical trials. To overcome these issues, alternative endpoints and response criteria are being developed by an international working party [response assessment in neuro-oncology (RANO)]. It is as yet unclear to what extent alternative imaging tools (positron emission tomography and MRI techniques) provide more reliable indicators of outcome.
Topics: Antineoplastic Agents; Brain Neoplasms; Dacarbazine; Diagnostic Imaging; Disease Progression; Glioma; Humans; Radionuclide Imaging; Temozolomide; Treatment Outcome
PubMed: 19770760
DOI: 10.1097/WCO.0b013e328332363e -
Journal of Neuro-oncology Sep 2017The wide variety of treatment options that exist for glioblastoma, including surgery, ionizing radiation, anti-neoplastic chemotherapies, anti-angiogenic therapies, and... (Review)
Review
Pseudoprogression, radionecrosis, inflammation or true tumor progression? challenges associated with glioblastoma response assessment in an evolving therapeutic landscape.
The wide variety of treatment options that exist for glioblastoma, including surgery, ionizing radiation, anti-neoplastic chemotherapies, anti-angiogenic therapies, and active or passive immunotherapies, all may alter aspects of vascular permeability within the tumor and/or normal parenchyma. These alterations manifest as changes in the degree of contrast enhancement or T2-weighted signal hyperintensity on standard anatomic MRI scans, posing a potential challenge for accurate radiographic response assessment for identifying anti-tumor effects. The current review highlights the challenges that remain in differentiating true disease progression from changes due to radiation therapy, including pseudoprogression and radionecrosis, as well as immune or inflammatory changes that may occur as either an undesired result of cytotoxic therapy or as a desired consequence of immunotherapies.
Topics: Brain; Brain Neoplasms; Disease Progression; Glioblastoma; Humans; Inflammation; Necrosis; Radiation Injuries
PubMed: 28382534
DOI: 10.1007/s11060-017-2375-2 -
American Journal of Cancer Research 2019Immunotherapy has achieved unprecedented clinical efficacy in patients with various types of advanced tumors; however, some patients experience delayed tumor shrinkage... (Review)
Review
Immunotherapy has achieved unprecedented clinical efficacy in patients with various types of advanced tumors; however, some patients experience delayed tumor shrinkage following an increase in tumor burden after such a therapeutic method. This phenomenon is called pseudoprogression and can lead to premature cessation of efficacious immunotherapeutic agents. Consequently, we summarized the available data on methods to differentiate pseudoprogression from true progression in patients who have been treated with immunotherapy including biomarkers, medical imaging techniques and biopsy. We also introduce hyperprogression and special pseudoprogression for improved evaluation of immunotherapy.
PubMed: 31497342
DOI: No ID Found -
Current Treatment Options in Oncology Sep 2011The post-treatment imaging assessment of high-grade gliomas remains challenging notwithstanding the increased utilization of advanced MRI and PET imaging. Several... (Review)
Review
The post-treatment imaging assessment of high-grade gliomas remains challenging notwithstanding the increased utilization of advanced MRI and PET imaging. Several post-treatment imaging entities are recognized including: late-delayed radiation injury, including radionecrosis mimicking tumor progression; early-delayed (within 6 months of temozolomide-based chemoradiation) post-treatment radiographic changes, herein referred to as pseudoprogression (the subject of this review); early post-treatment changes following local glioma therapy (i.e. biodegradable BCNU wafer implantation or stereotactic radiotherapy); and pseudoresponse, seen following treatment with angiogenic inhibition based therapy such as bevacizumab. A literature review searched specifically for "pseudoprogression" within the last 5 years (2005-2010). Approximately 24 recent papers were identified and reviewed in detail. Eight small population-based studies demonstrate 26-58% (median 49%) of glioblastoma patients treated with chemoradiotherapy manifest early disease progression at first post-radiotherapy imaging. Patients with early radiographic disease progression continued on planned therapy, and a median of 38% (range 28-66%) showed radiographic improvement or stabilization and were defined retrospectively as manifesting pseudoprogression. In conclusion, pseudoprogression is a frequent early post-treatment imaging change that at present is not easily differentiated from tumor progression by anatomic or physiologic brain imaging. Consequently, an operational definition of pseudoprogression has been adopted by the Response Assessment in Neuro-Oncology Working Group wherein either the index (i.e. target) lesion stabilizes or diminishes in size on continued post-radiation (temozolomide) therapy as determined by follow-up radiologic imaging.
Topics: Diagnostic Imaging; Disease Progression; Glioma; Humans; Neoplasm Staging
PubMed: 21594589
DOI: 10.1007/s11864-011-0157-1 -
Current Opinion in Oncology Nov 2021This review aims to cover current MRI techniques for assessing treatment response in brain tumors, with a focus on radio-induced lesions. (Review)
Review
PURPOSE OF REVIEW
This review aims to cover current MRI techniques for assessing treatment response in brain tumors, with a focus on radio-induced lesions.
RECENT FINDINGS
Pseudoprogression and radionecrosis are common radiological entities after brain tumor irradiation and are difficult to distinguish from real progression, with major consequences on daily patient care. To date, shortcomings of conventional MRI have been largely recognized but morphological sequences are still used in official response assessment criteria. Several complementary advanced techniques have been proposed but none of them have been validated, hampering their clinical use. Among advanced MRI, brain perfusion measures increase diagnostic accuracy, especially when added with spectroscopy and susceptibility-weighted imaging. However, lack of reproducibility, because of several hard-to-control variables, is still a major limitation for their standardization in routine protocols. Amide Proton Transfer is an emerging molecular imaging technique that promises to offer new metrics by indirectly quantifying intracellular mobile proteins and peptide concentration. Preliminary studies suggest that this noncontrast sequence may add key biomarkers in tumor evaluation, especially in posttherapeutic settings.
SUMMARY
Benefits and pitfalls of conventional and advanced imaging on posttreatment assessment are discussed and the potential added value of APT in this clinicoradiological evolving scenario is introduced.
Topics: Brain Neoplasms; Disease Progression; Humans; Radiation Injuries
PubMed: 34534142
DOI: 10.1097/CCO.0000000000000793