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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 -
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 -
Cancer Imaging : the Official... Mar 2024Cutaneous squamous cell carcinoma (CSCC) has a propensity for perineural spread (PNS) which is associated with poorer treatment outcomes. Immunotherapy is the new...
BACKGROUND
Cutaneous squamous cell carcinoma (CSCC) has a propensity for perineural spread (PNS) which is associated with poorer treatment outcomes. Immunotherapy is the new standard of care treatment for advanced CSCC resulting in durable responses. PNS is not captured by traditional response assessment criteria used in clinical trials, e.g. RECIST 1.1, and there is limited literature documenting radiological PNS responses to immunotherapy. In this study we assess PNS responses to immunotherapy using a modified grading system.
METHODS
This is an Australian single-center retrospective review of patients with advanced CSCC who were treated with immunotherapy between April 2018 and February 2022 who had evidence of PNS on pre-treatment magnetic-resonance imaging (MRI). The primary outcome was blinded overall radiological response in PNS using graded radiological criteria, post-commencement of immunotherapy. Three defined timepoints (< 5 months, 5-10 months, > 10 months) were reviewed. Secondary outcomes included a correlation between RECIST 1.1 and PNS assessments and the assessment of PNS on fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT).
RESULTS
Twenty CSCC patients treated with immunotherapy were identified. Median age was 75.7 years and 75% (n = 15) were male. All patients had locoregionally advanced disease and no distant metastases. Median follow-up was 18.5 months (range: 2-59). 70% (n = 14) demonstrated a PNS response by 5 months. Three patients experienced pseudoprogression. One patient had PNS progression by the end of study follow up. RECIST 1.1 and PNS responses were largely concordant at > 10 months (Cohen's Kappa 0.62). 5/14 cases had features suspicious for PNS on FDG-PET/CT.
CONCLUSIONS
PNS response to immunotherapy can be documented on MRI using graded radiological criteria. High response rates were seen in PNS with the use of immunotherapy in this cohort and these responses were largely concordant with RECIST 1.1 assessments. FDG-PET/CT demonstrated limited sensitivity in the detection of PNS.
Topics: Humans; Male; Aged; Female; Skin Neoplasms; Carcinoma, Squamous Cell; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Tomography, X-Ray Computed; Australia; Retrospective Studies; Immunotherapy
PubMed: 38500235
DOI: 10.1186/s40644-024-00678-8 -
Translational Lung Cancer Research Feb 2024Programmed cell death protein-1/programmed cell death protein-ligand 1 (PD-1/PD-L1) inhibitor and chemotherapy are the standard treatment for advanced non-small cell...
BACKGROUND
Programmed cell death protein-1/programmed cell death protein-ligand 1 (PD-1/PD-L1) inhibitor and chemotherapy are the standard treatment for advanced non-small cell lung cancer (NSCLC) without sensitizing mutations. However, patients with untreated, symptomatic or recently-irradiated brain metastases (BMs) are mostly excluded from immunochemotherapy trials. This study aims to evaluate the intracranial response pattern, tolerability and biomarkers of tislelizumab plus chemotherapy in NSCLC with untreated, symptomatic or recently-irradiated BM.
METHODS
This multicenter, single-arm, phase 2 trial enrolled patients with treatment-naïve, brain-metastasized NSCLC. BM could be untreated or irradiated. Symptomatic or recently-irradiated BMs that were deemed clinically stable were allowed. Patients received tislelizumab (200 mg) plus pemetrexed (500 mg/m) and carboplatin (AUC =5) on day 1 every 3 weeks for 4 cycles, followed by maintenance with tislelizumab plus pemetrexed. Primary endpoint was 1-year progression-free survival (PFS) rate. Secondary endpoints included intracranial efficacy and tolerability. PD-L1 expression, tumor mutational burden (TMB) and genomic alterations were evaluated as potential biomarkers.
RESULTS
A total of 36 patients were enrolled, 19.2% had prior brain radiotherapy, 8.3% had symptomatic BMs that required corticosteroids ≤10 mg/d or antiepileptics. Confirmed systemic and intracranial ORR (iORR) was 43.8% and 46.7%, respectively. One-year systematic PFS rate and One-year iPFS rate was 36.8% and 55.8%, respectively. About 41.7% patients had neurological adverse events, 90% patients had concordant intracranial-extracranial responses. No intracranial pseudoprogression or hyperprogression occurred. Patients with prior brain radiation trended towards higher systemic (83.3% . 34.6%) and iORR (75.0% . 42.3%). Similar intracranial efficacy was observed in tumors with different PD-L1 and TMB levels, while alterations in cytokine receptors pathway predicted higher iORR (P=0.081), prolonged systematic PFS [hazard ratio (HR) =0.16, P=0.021] and overall survival (OS) (HR =0.71, P=0.029).
CONCLUSIONS
Untreated or irradiated BMs in NSCLC follows a conventional response and progression pattern under immunochemotherapy with altered cytokine receptors pathway being a potential biomarker for systemic and intracranial outcomes.
PubMed: 38496686
DOI: 10.21037/tlcr-23-687 -
Cancers Feb 2024The activity of immune checkpoint inhibitors (ICIs) in patients with metastatic melanoma is often monitored using fluorine-18-fluorodeoxyglucose-positron emission...
Prospective Assessment of Fluorine-18-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography (FDG-PET/CT) for Early Identification of Checkpoint-Inhibitor-Induced Pseudoprogression.
The activity of immune checkpoint inhibitors (ICIs) in patients with metastatic melanoma is often monitored using fluorine-18-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) scans. However, distinguishing disease progression (PD) from pseudoprogression (PsPD), where increased FDG uptake might reflect immune cell activity rather than tumor growth, remains a challenge. This prospective study compared the efficacy of dual-time point (DTP) FDG-PET/CT with modified response criteria (PERCIMT) in differentiating PsPD from PD. From July 2017-January 2021, 41 patients suspected to have PsPD on an evaluation scan were prospectively included (29 evaluable). A subsequent DTP FDG-PET/CT scan was conducted within 14 days, followed by a confirmatory FDG-PET/CT scan. Additionally, PERCIMT were applied. DTP FDG-PET/CT identified 24% with PsPD and 76% with PD. Applying PERCIMT criteria, 69% showed PsPD, while 31% had PD. On follow-up, 10 patients (34%) demonstrated confirmed PsPD, while 19 (66%) exhibited PD. The sensitivity and specificity of DTP FDG-PET/CT were 20% and 74%, respectively, and for PERCIMT this was 80% and 37%, respectively. Our findings suggest limited efficacy of DTP FDG-PET/CT in distinguishing PsPD from PD in ICI-treated patients with metastatic melanoma. The use of PERCIMT could complement clinical assessment and be incorporated in multidisciplinary team conferences for enhanced decision-making.
PubMed: 38473325
DOI: 10.3390/cancers16050964 -
Cancer Treatment and Research... 2024Colorectal cancer (CRC) continues to be one of the most prevalent and lethal cancers worldwide. Over the past decades, immune checkpoint inhibitors (ICIs) have shown to... (Review)
Review
Colorectal cancer (CRC) continues to be one of the most prevalent and lethal cancers worldwide. Over the past decades, immune checkpoint inhibitors (ICIs) have shown to significantly improve patient outcomes in mismatch repair-deficient metastasized CRC. However, widening the scope of this novel treatment modality has been the object of growing interest. This article will review several landmark trials, while exploring various aspects of this rapidly evolving field, including potential neoadjuvant (or even entirely nonsurgical) and adjuvant indications in localized disease. We will also discuss differences between management of rectal and colon cancer, current and expected challenges (eg. resistance, toxicities, pseudoprogression, biomarkers) and other future opportunities including combinations with other therapeutic agents and the role of ICIs in the treatment of both deficient as well as proficient mismatch repair (dMMR and pMMR respectively) CRC.
Topics: Humans; Colorectal Neoplasms; DNA Mismatch Repair; Immune Checkpoint Inhibitors; Immunotherapy; Neoadjuvant Therapy
PubMed: 38461691
DOI: 10.1016/j.ctarc.2024.100807 -
Journal of Neuro-oncology Apr 2024We aimed to evaluate the prognostic factors and the role of stereotactic radiotherapy (SRT) as a re-irradiation technique in the management of progressive glioblastoma.
PURPOSE
We aimed to evaluate the prognostic factors and the role of stereotactic radiotherapy (SRT) as a re-irradiation technique in the management of progressive glioblastoma.
METHODS
The records of 77 previously irradiated glioblastoma patients who progressed and received second course hypofractionated SRT (1-5 fractions) between 2009 and 2022 in our department were evaluated retrospectively. Statistical Package for the Social Sciences (SPSS) version 23.0 (IBM, Armonk, NY, USA) was utilized for all statistical analyses.
RESULTS
The median time to progression from the end of initial radiotherapy was 14 months (range, 6-68 months). The most common SRT schedule was 30 Gy (range, 18-50 Gy) in 5 fractions (range, 1-5 fractions). The median follow-up after SRT was 9 months (range, 3-80 months). One-year overall (OS) and progression-free survival (PFS) rates after SRT were 46% and 35%, respectively. Re-irradiation dose and the presence of pseudoprogression were both significant independent positive prognostic factors for both OS (p = 0.009 and p = 0.04, respectively) and PFS (p = 0.008 and p = 0.04, respectively). For PFS, progression-free interval > 14 months was also a prognostic factor (p = 0.04). The treatment was well tolerated without significant acute toxicity. During follow-up, radiation necrosis was observed in 17 patients (22%), and 14 (82%) of them were asymptomatic.
CONCLUSION
Hypofractionated SRT is an effective treatment approach for patients with progressive glioblastoma. Younger patients who progressed later than 14 months, received higher SRT doses, and experienced pseudoprogression following SRT had improved survival rates.
Topics: Humans; Glioblastoma; Brain Neoplasms; Retrospective Studies; Re-Irradiation; Neoplasm Recurrence, Local; Dose Fractionation, Radiation; Radiosurgery
PubMed: 38383875
DOI: 10.1007/s11060-024-04607-4 -
Oncoimmunology 2024This study aimed to develop a computed tomography (CT)-based radiomics model capable of precisely predicting hyperprogression and pseudoprogression (PP) in patients with...
Noninvasive radiomic biomarkers for predicting pseudoprogression and hyperprogression in patients with non-small cell lung cancer treated with immune checkpoint inhibition.
This study aimed to develop a computed tomography (CT)-based radiomics model capable of precisely predicting hyperprogression and pseudoprogression (PP) in patients with non-small cell lung cancer (NSCLC) treated with immunotherapy. We retrospectively analyzed 105 patients with NSCLC, from three institutions, treated with immune checkpoint inhibitors (ICIs) and categorized them into training and independent testing set. Subsequently, we processed CT scans with a series of image-preprocessing techniques, and 6008 radiomic features capturing intra- and peritumoral texture patterns were extracted. We used the least absolute shrinkage and selection operator logistic regression model to select radiomic features and construct machine learning models. To further differentiate between progressive disease (PD) and hyperprogressive disease (HPD), we developed a new radiomics model. The logistic regression (LR) model showed optimal performance in distinguishing PP from HPD, with areas under the receiver operating characteristic curve (AUC) of 0.95 (95% confidence interval [CI]: 0.91-0.99) and 0.88 (95% CI: 0.66-1) in the training and testing sets, respectively. Additionally, the support vector machine model showed optimal performance in distinguishing PD from HPD, with AUC of 0.97 (95% CI: 0.93-1) and 0.87 (95% CI: 0.72-1) in the training and testing sets, respectively. Kaplan‒Meier survival curves showed clear stratification between PP predicted by the radiomics model and true progression (HPD and PD) (hazard ratio = 0.337, 95% CI: 0.200-0.568, < 0.01) in overall survival. Our study demonstrates that radiomic features extracted from baseline CT scans are effective in predicting PP and HPD in patients with NSCLC treated with ICIs.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Immune Checkpoint Inhibitors; Lung Neoplasms; Radiomics; Retrospective Studies; Disease Progression; Biomarkers
PubMed: 38343749
DOI: 10.1080/2162402X.2024.2312628 -
Seminars in Nuclear Medicine Mar 2024Following the previous part of the narrative review on artificial intelligence (AI) applications in positron emission tomography (PET) using tracers rather than... (Review)
Review
Application of Artificial Intelligence in Oncologic Molecular PET-Imaging: A Narrative Review on Beyond [F]F-FDG Tracers Part II. [F]F-FLT, [F]F-FET, [C]C-MET and Other Less-Commonly Used Radiotracers.
Following the previous part of the narrative review on artificial intelligence (AI) applications in positron emission tomography (PET) using tracers rather than F-fluorodeoxyglucose ([F]F-FDG), in this part we review the impact of PET-derived radiomics data on the diagnostic performance of other PET radiotracers, F-O-(2-fluoroethyl)-L-tyrosine ([F]F-FET), F-Fluorothymidine ([F]F-FLT) and C-Methionine ([C]C-MET). [F]F-FET-PET, using an artificial amino acid taken up into upregulated tumoral cells, showed potential in lesion detection and tumor characterization, especially with its ability to reflect glioma heterogeneity. [F]F-FET-PET-derived textural features appeared to have the potential to reveal considerable information for accurate delineation for guiding biopsy and treatment, differentiate between low-grade and high-grade glioma and related wild-type genotypes, and distinguish pseudoprogression from true progression. In addition, models built using clinical parameters and [F]F-FET-PET-derived radiomics features showed acceptable results for survival stratification of glioblastoma patients. [F]F-FLT-PET-based characteristics also showed potential in evaluating glioma patients, correlating with Ki-67 and patient prognosis. AI-based PET-volumetry using this radiotracer as a proliferation marker also revealed promising preliminary results in terms of guide-targeting bone marrow-preserving adaptive radiation therapy. Similar to [F]F-FET, the other amino acid tracer which reflects cellular proliferation, [C]C-MET, has also shown acceptable performance in predicting tumor grade, distinguishing brain tumor recurrence from radiation necrosis, and treatment monitoring by PET-derived radiomics models. In addition, PET-derived radiomics features of various radiotracers such as [F]F-DOPA, [F]F-FACBC, [F]F-NaF, [Ga]Ga-CXCR-4 and [F]F-FMISO may also provide useful information for tumor characterization and predict of disease outcome. In conclusion, AI using tracers beyond [F]F-FDG could improve the diagnostic performance of PET-imaging for specific indications and help clinicians in their daily routine by providing features that are often not detectable by the naked eye.
Topics: Humans; Fluorodeoxyglucose F18; Artificial Intelligence; Neoplasm Recurrence, Local; Positron-Emission Tomography; Brain Neoplasms; Glioma; Amino Acids
PubMed: 38331629
DOI: 10.1053/j.semnuclmed.2024.01.002 -
European Review For Medical and... Jan 2024This study aimed to explore the value of 3.0T magnetic resonance three-dimensional arterial spin labeling imaging (3D-ASL) technology in the differential diagnosis of...
OBJECTIVE
This study aimed to explore the value of 3.0T magnetic resonance three-dimensional arterial spin labeling imaging (3D-ASL) technology in the differential diagnosis of recurrence and pseudo-progression of high-grade gliomas.
PATIENTS AND METHODS
Fifty patients with high-grade glioma were selected as research objects. All 50 patients were examined by magnetic resonance imaging (MRI), and the lesions were found to be enlarged or abnormally enhanced. All the patients were examined using the 3.0T MR 3D-ASL technique. With targeted biopsy pathology as the gold standard, the diagnostic results of the 3.0T MR 3D-ASL technique were analyzed, and the cerebral blood flow (rCBFmax) ratio was compared between patients with recurrent glioma and patients with pseudo-progression [maximum blood flow value/contralateral mirror area (CBFmax/contralateral mirror area), CBFmax/contralateral white matter, CBFmax/contralateral gray matter].
RESULTS
Among 50 glioma patients, 31 (62.00%) were diagnosed with recurrence through pathological examination, and 19 (38.00%) were diagnosed with pseudo-progression. 30 patients with recurrence (60.00%) and 20 patients with pseudo-progression (40.00%) were diagnosed using 3.0T magnetic resonance 3D-ASL technology. The diagnostic accuracy of 3.0T magnetic resonance 3D-ASL technology was 96.77% (30/31) (p > 0.05). Using pathological results as the "gold standard", the relevant parameters of 3.0T magnetic resonance 3D-ASL technology under different pathological results were analyzed. The results showed that the CBFmax/contralateral mirror area, CBFmax/contralateral white matter, and CBFmax/contralateral gray matter ratios of advanced glioma recurrence patients were significantly higher than those of pseudo-progression (p < 0.05).
CONCLUSIONS
The application of 3.0T MR 3D-ASL in high-grade glioma can effectively distinguish recurrence and pseudo-progression, with significant diagnostic value.
Topics: Humans; Brain Neoplasms; Neoplasm Recurrence, Local; Glioma; Magnetic Resonance Imaging; Neoplasm Grading; Cerebrovascular Circulation
PubMed: 38305610
DOI: 10.26355/eurrev_202401_35065