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Cancer Research Communications Sep 2023Immune checkpoint inhibitors (ICI) can induce atypical tumor responses including pseudoprogression in a subset of patients who may benefit from treatment beyond...
UNLABELLED
Immune checkpoint inhibitors (ICI) can induce atypical tumor responses including pseudoprogression in a subset of patients who may benefit from treatment beyond progression. While ICIs have emerged as frontline treatments for hepatocellular carcinoma (HCC) and are associated with clinical benefit in a minority of patients, it is unclear whether treatment beyond progression has utility in this disease type. In a multicenter cohort analysis, treatment beyond progression was associated with no new safety signals, objective responses in 5.8% of patients, and disease control in 44% of patients. Progression-free survival and overall survival were comparable between patients treated beyond progression and patients treated with subsequent therapies, demonstrating that treatment beyond progression was not detrimental to survival outcomes. Rather, treatment beyond progression may benefit select patients with HCC and could represent a viable strategy for maximizing treatment benefit in these patients.
SIGNIFICANCE
Treatment beyond progression with ICIs in patients with HCC is safe and may benefit a subset of patients due to later-onset tumor responses or disease stability. These findings may guide the design of trials testing ICIs in HCC and the use of treatment beyond progression in routine practice.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms
PubMed: 37772995
DOI: 10.1158/2767-9764.CRC-23-0025 -
BMC Medical Imaging Sep 2023To investigate the diagnostic performance of parameters derived from monoexponential, biexponential, and stretched-exponential diffusion-weighted imaging models in...
BACKGROUND
To investigate the diagnostic performance of parameters derived from monoexponential, biexponential, and stretched-exponential diffusion-weighted imaging models in differentiating tumour progression from pseudoprogression in glioblastoma patients.
METHODS
Forty patients with pathologically confirmed glioblastoma exhibiting enhancing lesions after completion of chemoradiation therapy were enrolled in the study, which were then classified as tumour progression and pseudoprogression. All patients underwent conventional and multi-b diffusion-weighted MRI. The apparent diffusion coefficient (ADC) from a monoexponential model, the true diffusion coefficient (D), pseudodiffusion coefficient (D*) and perfusion fraction (f) from a biexponential model, and the distributed diffusion coefficient (DDC) and intravoxel heterogeneity index (α) from a stretched-exponential model were compared between tumour progression and pseudoprogression groups. Receiver operating characteristic curves (ROC) analysis was used to investigate the diagnostic performance of different DWI parameters. Interclass correlation coefficient (ICC) was used to evaluate the consistency of measurements.
RESULTS
The values of ADC, D, DDC, and α values were lower in tumour progression patients than that in pseudoprogression patients (p < 0.05). The values of D* and f were higher in tumour progression patients than that in pseudoprogression patients (p < 0.05). Diagnostic accuracy for differentiating tumour progression from pseudoprogression was highest for α(AUC = 0.94) than that for ADC (AUC = 0.91), D (AUC = 0.92), D* (AUC = 0.81), f (AUC = 0.75), and DDC (AUC = 0.88).
CONCLUSIONS
Multi-b DWI is a promising method for differentiating tumour progression from pseudoprogression with high diagnostic accuracy. In addition, the α derived from stretched-exponential model is the most promising DWI parameter for the prediction of tumour progression in glioblastoma patients.
Topics: Humans; Glioblastoma; Diffusion Magnetic Resonance Imaging; Chemoradiotherapy; ROC Curve
PubMed: 37697237
DOI: 10.1186/s12880-023-01082-7 -
BMC Cancer Jul 2023In this phase Ib/II open-label study, tumor immune suppression was targeted in patients with advanced refractory solid tumors and patients with recurrent/refractory...
BACKGROUND
In this phase Ib/II open-label study, tumor immune suppression was targeted in patients with advanced refractory solid tumors and patients with recurrent/refractory non-small cell lung cancer (NSCLC) using galunisertib with nivolumab.
METHODS
Eligible patients were ≥ 18 years old, had an Eastern Cooperative Oncology Group performance status ≤ 1, and were treatment-naive for anti-programmed cell death-1, its ligand, or transforming growth factor β receptor 1 kinase inhibitors. Phase Ib was an open-label, dose-escalation assessment of the safety and tolerability of galunisertib with nivolumab in patients with advanced refractory solid tumors. Phase II evaluated the safety of galunisertib with nivolumab in NSCLC patients who had received prior platinum-based treatment but were immuno-oncology agent-naive.
RESULTS
This trial was conducted between October 2015 and August 2020. No dose-limiting toxicities were observed in phase I. In the phase II NSCLC cohort (n = 25), patients received 150 mg twice daily galunisertib (14 days on/14 days off dosing schedule for all phases) plus nivolumab at 3 mg/kg (intravenously every 2 weeks). In this phase, the most frequent treatment-related adverse events (AEs) were pruritus (n = 9, 36%), fatigue (n = 8, 32%), and decreased appetite (n = 7, 28%). No grade 4 or 5 treatment-related AEs were observed. Six (24%) patients had confirmed partial response (PR) and 4 (16%) had stable disease; 1 additional patient had confirmed PR after initial pseudo-progression. The median duration of response was 7.43 months (95% confidence interval [CI]: 3.75, NR). Among the 7 responders, including the delayed responder, 1 had high PD-L1 expression (≥ 50%). The median progression-free survival was 5.26 months (95% CI: 1.77, 9.20) and the median overall survival was 11.99 months (95% CI: 8.15, NR). Interferon gamma response genes were induced post-treatment and cell adhesion genes were repressed, although the association of these observations with tumor response and clinical outcomes was not statistically powered due to limited samples available.
CONCLUSIONS
The study met its primary endpoint as galunisertib combined with nivolumab was well tolerated. Preliminary efficacy was observed in a subset of patients in the Phase 2 NSCLC cohort.
TRIAL REGISTRATION
Trial registered with ClinicalTrials.gov (NCT02423343; 22.04.2015).
Topics: Adolescent; Humans; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Neoplasm Recurrence, Local; Nivolumab
PubMed: 37507657
DOI: 10.1186/s12885-023-11153-1 -
Neuro-oncology Practice Feb 2024
PubMed: 38222056
DOI: 10.1093/nop/npad078 -
Frontiers in Oncology 2023Pseudoprogression is rarely mentioned after radiotherapy except for central nervous system tumors. With the widespread of immunotherapy, the incidence of...
Pseudoprogression is rarely mentioned after radiotherapy except for central nervous system tumors. With the widespread of immunotherapy, the incidence of pseudoprogression of thoracic tumor after radiotherapy is increasing. This study summarized the clinical features of pseudoprogression in 4 patients who had underwent thoracic radiotherapy after and/or followed by immunotherapy. All of them had received chemotherapy and immunotherapy before thoracic radiotherapy. After radiotherapy, pseudoprogression occurred within 3 months after initiation of immune consolidation/rechallenge therapy. At least a 20% increase in the sum of the longest diameter of target lesions were measured on their chest image. During this period, patients' ECOG PS scores remained stable, specific serum tumor markers did not increase significantly. Treatment strategies did not change after pseudoprogression. The causes of radiographic pseudoprogression in this case series may be attributed to disturbances such as pneumonitis, atelectasis, mucus blockages and infection. In the era of immunotherapy, pseudoprogression of thoracic tumors after chest radiotherapy might become a common phenomenon. It is important for us to identify pseudoprogression based on patient's general status, radiological changes, and laboratory tests.
PubMed: 37576884
DOI: 10.3389/fonc.2023.1021253 -
European Journal of Nuclear Medicine... Nov 2023The O-(2-[F]-fluoroethyl)-L-tyrosine (FET) PET in Glioblastoma (FIG) trial is an Australian prospective, multi-centre study evaluating FET PET for glioblastoma patient...
Delineation and agreement of FET PET biological volumes in glioblastoma: results of the nuclear medicine credentialing program from the prospective, multi-centre trial evaluating FET PET In Glioblastoma (FIG) study-TROG 18.06.
PURPOSE
The O-(2-[F]-fluoroethyl)-L-tyrosine (FET) PET in Glioblastoma (FIG) trial is an Australian prospective, multi-centre study evaluating FET PET for glioblastoma patient management. FET PET imaging timepoints are pre-chemoradiotherapy (FET1), 1-month post-chemoradiotherapy (FET2), and at suspected progression (FET3). Before participant recruitment, site nuclear medicine physicians (NMPs) underwent credentialing of FET PET delineation and image interpretation.
METHODS
Sites were required to complete contouring and dynamic analysis by ≥ 2 NMPs on benchmarking cases (n = 6) assessing biological tumour volume (BTV) delineation (3 × FET1) and image interpretation (3 × FET3). Data was reviewed by experts and violations noted. BTV definition includes tumour-to-background ratio (TBR) threshold of 1.6 with crescent-shaped background contour in the contralateral normal brain. Recurrence/pseudoprogression interpretation (FET3) required assessment of maximum TBR (TBR), dynamic analysis (time activity curve [TAC] type, time to peak), and qualitative assessment. Intraclass correlation coefficient (ICC) assessed volume agreement, coefficient of variation (CoV) compared maximum/mean TBR (TBR/TBR) across cases, and pairwise analysis assessed spatial (Dice similarity coefficient [DSC]) and boundary agreement (Hausdorff distance [HD], mean absolute surface distance [MASD]).
RESULTS
Data was accrued from 21 NMPs (10 centres, n ≥ 2 each) and 20 underwent review. The initial pass rate was 93/119 (78.2%) and 27/30 requested resubmissions were completed. Violations were found in 25/72 (34.7%; 13/12 minor/major) of FET1 and 22/74 (29.7%; 14/8 minor/major) of FET3 reports. The primary reasons for resubmission were as follows: BTV over-contour (15/30, 50.0%), background placement (8/30, 26.7%), TAC classification (9/30, 30.0%), and image interpretation (7/30, 23.3%). CoV median and range for BTV, TBR, and TBR were 21.53% (12.00-30.10%), 5.89% (5.01-6.68%), and 5.01% (3.37-6.34%), respectively. BTV agreement was moderate to excellent (ICC = 0.82; 95% CI, 0.63-0.97) with good spatial (DSC = 0.84 ± 0.09) and boundary (HD = 15.78 ± 8.30 mm; MASD = 1.47 ± 1.36 mm) agreement.
CONCLUSION
The FIG study credentialing program has increased expertise across study sites. TBR and TBR were robust, with considerable variability in BTV delineation and image interpretation observed.
Topics: Humans; Glioblastoma; Ficus; Brain Neoplasms; Nuclear Medicine; Prospective Studies; Australia; Positron-Emission Tomography; Tyrosine; Magnetic Resonance Imaging
PubMed: 37563351
DOI: 10.1007/s00259-023-06371-5 -
BMC Medical Imaging Nov 2023We focused on Differentiated pseudoprogression (PPN) of progression (PN) and the response to radiotherapy (RT) or chemoradiotherapy (CRT) using diffusion and metabolic...
BACKGROUND
We focused on Differentiated pseudoprogression (PPN) of progression (PN) and the response to radiotherapy (RT) or chemoradiotherapy (CRT) using diffusion and metabolic imaging.
METHODS
Seventy-five patients with glioma were included in this prospective study (approved by the Iranian Registry of Clinical Trials (IRCT) (IRCT20230904059352N1) in September 2023). Contrast-enhanced lesion volume (CELV), non-enhanced lesion volume (NELV), necrotic tumor volume (NTV), and quantitative values of apparent diffusion coefficient (ADC) and magnetic resonance spectroscopy (Cho/Cr, Cho/NAA and NAA/Cr) were calculated by a neuroradiologist using a semi-automatic method. All patients were followed at one and six months after CRT.
RESULTS
The results of the study showed statistically significant changes before and six months after RT-CRT for M-CELV in all glioma types (𝑝 < 0.05). In glioma cell types, the changes in M-ADC, M-Cho/Cr, and Cho/NAA indices for PN were incremental and greater for PPN patients. M-NAA/Cr ratio decreased after six months which was significant only on PN for GBM, and Epn (𝑝 < 0.05). A significant difference was observed between diffusion indices, metabolic ratios, and CELV changes after six months in all types (𝑝 < 0.05). None of the patients were suspected PPN one month after treatment. The DWI/ADC indices had higher sensitivity and specificity (98.25% and 96.57%, respectively).
CONCLUSION
The results of the present study showed that ADC values and Cho/Cr and Cho/NAA ratios can be used to differentiate between patients with PPN and PN, although ADC is more sensitive and specific.
Topics: Humans; Prospective Studies; Brain Neoplasms; Iran; Glioma; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Diffusion Magnetic Resonance Imaging; Chemoradiotherapy
PubMed: 37932656
DOI: 10.1186/s12880-023-01135-x -
Cancers Aug 2023Glioblastoma (GB) is a malignant brain tumour that is challenging to treat, often relapsing even after aggressive therapy. Evaluating therapy response relies on magnetic...
BACKGROUND
Glioblastoma (GB) is a malignant brain tumour that is challenging to treat, often relapsing even after aggressive therapy. Evaluating therapy response relies on magnetic resonance imaging (MRI) following the Response Assessment in Neuro-Oncology (RANO) criteria. However, early assessment is hindered by phenomena such as pseudoprogression and pseudoresponse. Magnetic resonance spectroscopy (MRS/MRSI) provides metabolomics information but is underutilised due to a lack of familiarity and standardisation.
METHODS
This study explores the potential of spectroscopic imaging (MRSI) in combination with several machine learning approaches, including one-dimensional convolutional neural networks (1D-CNNs), to improve therapy response assessment. Preclinical GB (GL261-bearing mice) were studied for method optimisation and validation.
RESULTS
The proposed 1D-CNN models successfully identify different regions of tumours sampled by MRSI, i.e., normal brain (N), control/unresponsive tumour (T), and tumour responding to treatment (R). Class activation maps using Grad-CAM enabled the study of the key areas relevant to the models, providing model explainability. The generated colour-coded maps showing the N, T and R regions were highly accurate (according to Dice scores) when compared against ground truth and outperformed our previous method.
CONCLUSIONS
The proposed methodology may provide new and better opportunities for therapy response assessment, potentially providing earlier hints of tumour relapsing stages.
PubMed: 37568818
DOI: 10.3390/cancers15154002 -
Cancers Dec 2023The follow-up of glioma patients after therapeutic intervention remains a challenging topic, as therapy-related changes can emulate true progression in contrast-enhanced... (Review)
Review
F-Fluoroethyl-L Tyrosine Positron Emission Tomography Radiomics in the Differentiation of Treatment-Related Changes from Disease Progression in Patients with Glioblastoma.
The follow-up of glioma patients after therapeutic intervention remains a challenging topic, as therapy-related changes can emulate true progression in contrast-enhanced magnetic resonance imaging. F-fluoroethyl-tyrosine (F-FET) is a radiopharmaceutical that accumulates in glioma cells due to an increased expression of L-amino acid transporters and, contrary to gadolinium, does not depend on blood-brain barrier disruption to reach tumoral cells. It has demonstrated a high diagnostic value in the differentiation of tumoral viability and pseudoprogression or any other therapy-related changes, especially when combining traditional visual analysis with modern radiomics. In this review, we aim to cover the potential role of 18F-FET positron emission tomography in everyday clinical practice when applied to the follow-up of patients after the first therapeutical intervention, early response evaluation, and the differential diagnosis between therapy-related changes and progression.
PubMed: 38201621
DOI: 10.3390/cancers16010195 -
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