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European Journal of Nuclear Medicine... Jul 2023Immune checkpoint inhibitors (ICIs) are widely used in metastatic melanoma and dramatically alter the treatment of these patients. Given the high cost and potential...
PURPOSE
Immune checkpoint inhibitors (ICIs) are widely used in metastatic melanoma and dramatically alter the treatment of these patients. Given the high cost and potential toxicity, a reliable method for evaluating treatment response is needed. In this study, we assessed tumor response in patients with metastatic melanoma treated with ICIs using three modified response criteria: PET Response Evaluation Criteria for Immunotherapy (PERCIMT), PET Response Criteria in Solid Tumors for up to Five Lesions (PERCIST5), and immunotherapy-modified PET Response Criteria in Solid Tumors for up to Five Lesions (imPERCIST5).
METHODS
Ninety-one patients with non-resectable stage IV metastatic melanoma who received ICIs were retrospectively enrolled in this study. Each patient had two [F]FDG PET/CT scans performed before and after ICI therapy. Responses at the follow-up scan were evaluated according to PERCIMT, PERCIST5, and imPERCIST5 criteria. Patients were classified into four groups: complete metabolic response (CMR), partial metabolic response (PMR), progressive metabolic disease (PMD), and stable metabolic disease (SMD). To assess the "disease control rate," two groups have been defined based on each criterion: patients with CMR, PMR, and SMD as "disease-controlled group (i.e., responders)" and PMD as the "uncontrolled-disease group (i.e., non-responders)". The correspondence between metabolic tumor response defined by these criteria and clinical outcome was assessed and compared.
RESULTS
The response and the disease control rates were 40.7% and 71.4%, 41.8% and 50.5%, and 54.9% and 74.7% based on the PERCIMT, PERCIST5, and imPERCIST5 criteria, respectively. PERCIMT and imPERCIST5 showed significantly different disease control rates from that of PERCIST5 (P < 0.001), whereas it was not significant between PERCIMT and imPERCIST5. Overall survival was significantly longer in the metabolic responder groups than in the non-responder groups based on PERCIMT and PERCIST5 criteria (PERCIMT: 2.48 versus 1.47 years, P = 0.003; PERCIST5: 2.57 versus 1.81 years. P = 0.017). However, according to imPERCIST5 criterion, this difference was not observed (P = 0.12).
CONCLUSION
Although the appearance of new lesions can be secondary to an inflammatory response to ICIs and indicative of pseudoprogression, given the higher rate of true progression, the appearance of new lesions should be interpreted deliberately. Of the three assessed modified criteria, PERCIMT appear to provide more reliable metabolic response assessment that correlates strongly with overall patient survival.
Topics: Humans; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Ipilimumab; Retrospective Studies; Radiopharmaceuticals; Melanoma; Immunotherapy; Metabolic Diseases
PubMed: 37140669
DOI: 10.1007/s00259-023-06247-8 -
Journal For Immunotherapy of Cancer Jun 2024The purpose of this commentary is to highlight the high occurrence of clinical pseudoprogression and delayed responses that have been observed to date with the locally...
The purpose of this commentary is to highlight the high occurrence of clinical pseudoprogression and delayed responses that have been observed to date with the locally injected oncolytic adenovirus, AdAPT-001, currently in a Phase 1/2 clinical trial (NCT04673942) for the treatment of treatment-refractory tumors. Not surprisingly, these have led to confusion about response assessment and whether to continue patients on treatment. AdAPT-001 carries a transforming growth factor (TGF)-beta trap (TGF-β), which sequesters TGF-β, a cytokine that potently regulates inflammation, fibrosis, and immunosuppression in cancer. Pseudoprogression (PsP) or progression prior to response or stabilization, has been widely recognized with radiotherapy for primary brain tumors and immune checkpoint inhibitors (ICIs). PsP has also been described and documented in the context of oncolytic virotherapy but perhaps to a lesser extent. However, repeated intratumoral injections with these immunostimulatory agents may induce a more intense immune response and release more antigenic epitopes than with ICIs, for example, which are strictly T-cell directed rather than also tumor-directed like AdAPT-001.
Topics: Humans; Disease Progression; Oncolytic Virotherapy; Oncolytic Viruses; Neoplasms; Adenoviridae
PubMed: 38886116
DOI: 10.1136/jitc-2024-008809 -
Current Oncology (Toronto, Ont.) Aug 2023Gliomas are the most frequent intrinsic central nervous system tumors. The new 2021 WHO Classification of Central Nervous System Tumors brought significant changes into... (Review)
Review
Gliomas are the most frequent intrinsic central nervous system tumors. The new 2021 WHO Classification of Central Nervous System Tumors brought significant changes into the classification of gliomas, that underline the role of molecular diagnostics, with the adult-type diffuse glial tumors now identified primarily by their biomarkers rather than histology. The status of the isocitrate dehydrogenase (IDH) 1 or 2 describes tumors at their molecular level and together with the presence or absence of 1p/19q codeletion are the most important biomarkers used for the classification of adult-type diffuse glial tumors. In recent years terminology has also changed. IDH-mutant, as previously known, is diagnostically used as astrocytoma and IDH-wildtype is used as glioblastoma. A comprehensive understanding of these tumors not only gives patients a more proper treatment and better prognosis but also highlights new difficulties. MR imaging is of the utmost importance for diagnosing and supervising the response to treatment. By monitoring the tumor on followup exams better results can be achieved. Correlations are seen between tumor diagnostic and clinical manifestation and surgical administration, followup care, oncologic treatment, and outcomes. Minimal resection site use of functional imaging (fMRI) and diffusion tensor imaging (DTI) have become indispensable tools in invasive treatment. Perfusion imaging provides insightful information about the vascularity of the tumor, spectroscopy shows metabolic activity, and nuclear medicine imaging displays tumor metabolism. To accommodate better treatment the differentiation of pseudoprogression, pseudoresponse, or radiation necrosis is needed. In this report, we present a literature review of diagnostics of gliomas, the differences in their imaging features, and our radiology's departments accumulated experience concerning gliomas.
Topics: Humans; Adult; Brain Neoplasms; Diffusion Tensor Imaging; Mutation; Glioma; Biomarkers
PubMed: 37754483
DOI: 10.3390/curroncol30090568 -
Quantitative Imaging in Medicine and... Aug 2023Positron emission tomography (PET) imaging is a promising molecular neuroimaging technique and has been proposed as one of the criteria for glioma management. However,...
BACKGROUND
Positron emission tomography (PET) imaging is a promising molecular neuroimaging technique and has been proposed as one of the criteria for glioma management. However, there is some controversy concerning the diagnostic accuracy of PET using different radiotracers to differentiate between glioma pseudoprogression (PsP) and true progression (TPR). The purpose of this meta-analysis was to systematically evaluate the methodological quality and clinical value of original studies for distinguishing PsP from TPR in glioma.
METHODS
The Medline, Web of Science, Embase, Cochrane Library, and ClinicalTrials.gov were searched from inception until September 1, 2022. Retrieved clinical studies only investigated the PsP cases but did not include the cases of radiation necrosis or other treatment-related changes. Eligible studies were screened for data extraction and evaluated by 2 independent reviewers using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. A random effects model was used to describe summary receiver operating characteristics. Meta-regression and subgroup analyses were applied to identify any sources of heterogeneity.
RESULTS
The meta-analysis included 20 studies, comprising 317 (30.9%) patients with PsP and 708 (69.1%) with TPR. The summary sensitivity and specificity of general PET for identifying PsP were 0.86 [95% confidence interval (CI): 0.77-0.91] and 0.84 (95% CI: 0.79-0.88), respectively. The statistical heterogeneity was explained by sample size, study design, World Health Organization (WHO) grade, gold standard, and radiotracer type. The summary sensitivity and specificity of O-(2-F-fluoroethyl)-L-tyrosine (F-FET PET) were 0.80 (95% CI: 0.68-0.88) and 0.81 (95% CI: 0.75-0.85), respectively. The maximum tumor-to-brain ratio (TBRmax) and the mean tumor-to-brain ratio (TBRmean) both showed excellent diagnostic performance in F-FET studies, the summary sensitivity was 0.83 (95% CI: 0.72-0.91) and 0.79 (95% CI: 0.65-0.98), respectively, and the specificity was 0.76 (95% CI: 0.68-0.84) and 0.78 (95% CI: 0.64-0.88), respectively.
CONCLUSIONS
PET imaging is generally accurate in identifying glioma PsP. Considering the credibility of meta-evidence and the practicability of using radiotracer, F-FET PET holds the highest clinical value, while TBRmax and TBRmean should be regarded as reliable parameters. PET used with the radiotracers and multiple-parameter combinations of PET with magnetic resonance imaging (MRI) and radiomics analysis have broad research and application prospects, whose diagnostic values for identifying glioma PsP warrant further investigation.
PubMed: 37581048
DOI: 10.21037/qims-22-1340 -
Medicine Jul 2023Radiotherapy (RT) is an essential treatment for patients with high-grade gliomas. however, a consensus on the target area of RT has not yet been achieved. In this study,... (Observational Study)
Observational Study
Radiotherapy (RT) is an essential treatment for patients with high-grade gliomas. however, a consensus on the target area of RT has not yet been achieved. In this study, we aimed to analyze progression-free survival (PFS), recurrence patterns, and toxicity in patients who received reduced volume intensity-modulated radiotherapy with simultaneous integrated boost (rvSIB-IMRT). In addition, we attempted to identify prognostic factors for recurrence. Twenty patients with high-grade gliomas who received rvSIB-IMRT between July 2011 and December 2021 were retrospectively analyzed. For rvSIB-IMRT, clinical target volume 1/2 was set at a 5 to 10 mm margin on each gross tumor volume (GTV) 1 (resection cavity and enhanced lesion) and GTV2 (high-signal lesion of T2/fluid-attenuated inversion recovery). RT doses were prescribed to 60 Gy/30 fractions (fxs) for planning target volume (PTV)1 and 51 to 54 Gy/30 fxs for PTV2. The median PFS and overall survival of the total cohorts were 10.6 and 13.6 months, respectively. Among the 12 relapsed patients, central, in-field, and marginal recurrences were identified in 8 (66.7%), 2 (16.7%), and 1 patient (8.3%), respectively. Distant recurrence was identified in 3 patients. Gross total resection (GTR) and high Ki-67 index (>27.4%), and subventricular involvement (SVI) were identified as significant factors for PFS in the multivariate analysis. During the follow up, 4 patients showed pseudoprogression and 1 patient showed radiation necrosis. The rvSIB-IMRT for high-grade gliomas resulted in comparable PFS and tolerable toxicity. Most recurrences were central/in-field (10 cases of 12, 83.4%). GTR, high Ki-67 index (>27.4%), and SVI were significant factors for recurrence.
Topics: Humans; Radiotherapy, Intensity-Modulated; Radiotherapy Dosage; Retrospective Studies; Ki-67 Antigen; Radiotherapy Planning, Computer-Assisted; Glioma; Recurrence
PubMed: 37443476
DOI: 10.1097/MD.0000000000033955 -
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 -
Surgical Neurology International 2023The management of vestibular schwannoma has evolved over the past hundred years. In the last decades, surgery has been gradually replaced by radiation therapy as a...
BACKGROUND
The management of vestibular schwannoma has evolved over the past hundred years. In the last decades, surgery has been gradually replaced by radiation therapy as a primary treatment modality, particularly for small tumors, due to the less invasive nature and the compared reported outcomes in tumor control and hearing preservation. However, irradiation sometimes fails to stop tumor growth. In a long-term follow-up after primary fractionated stereotactic radiotherapy, the rate of treatment failure was reported as 3% and needed surgical salvage. For single-fraction modality, Hasegawa . reported salvage treatment after primary Gamma Knife radiosurgery in 8%, where 90% of these underwent surgery and 50% of those who were treated with a second gamma knife surgery required surgical intervention later. An increase in tumor volume by more than 10-20%, tumor growth after three years, and no return to pretreatment volume after transient swelling have been considered as tumor recurrence rather than pseudoprogression, a transient increase in tumor volume after radiotherapy that occurs up to 30% of cases. It has been reported that microsurgery after radiotherapy is more difficult, with most authors reporting a loss of defined arachnoid planes and worse cranial nerve outcomes, especially for hearing and facial nerve function.
CASE DESCRIPTION
A 43-year-old female patient was incidentally (asymptomatic) diagnosed on a magnetic resonance imaging (MRI) scan harboring a left vestibular schwannoma, grade T2 (Hannover classification), in 2015. Neurologic examination was unremarkable, and audiometry testing was normal. She was initially treated with observation. Three years later, in 2018, the lesion had enlarged, becoming a grade T3a and reaching the cistern of the cerebellopontine angle. The tumor was then treated with fractionated stereotactic radiosurgery (5 sessions of 5 Gy). MRI scans in 2019 and 2020 showed slight tumor growth. This enlargement was attributed to a pseudoprogression after radiosurgery, and only observation was advocated. In 2022, 4 years later, after radiosurgery, the tumor was still growing, and the patient began to suffer from hearing loss. A failure treatment was considered, and microsurgery was indicated. The patient was counseled about the risk of functional nerve impairment, and surgical consent was obtained. A retro sigmoid approach was planned. A gross total resection was attempted due to the clear subperineural plane during tumor dissection and because it was the only option that would provide a cure for the patient. The adjacent neurovascular structures were firmly adhered to the tumor capsule, which represented a major challenge for microdissection. The tumor was soft, without significant bleeding. A total resection was achieved, and the facial nerve was anatomically preserved. The patient developed facial paresis (House-Brackmann III) in the immediate postoperative period, which improved at the 6-month follow-up. Hearing loss did not improve. Postoperative MRI showed total resection.
CONCLUSION
Microsurgery after radiotherapy for vestibular schwannoma is challenging in terms of indication, when to indicate, resection target, difficulty in dissection due to local changes, and outcome. Gross total resection may be considered, as it is the only treatment that may provide a cure for the patient. However, the patient should be counseled about the risks.
PubMed: 38213456
DOI: 10.25259/SNI_875_2023 -
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 -
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 -
Neuro-oncology May 2024Radiological progression may originate from progressive disease (PD) or pseudoprogression/treatment-associated changes. We assessed radiological progression in... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Radiological progression may originate from progressive disease (PD) or pseudoprogression/treatment-associated changes. We assessed radiological progression in O6-methylguanine-DNA methyltransferase (MGMT) promoter-methylated glioblastoma treated with standard-of-care chemoradiotherapy with or without the integrin inhibitor cilengitide according to the modified response assessment in neuro-oncology (RANO) criteria of 2017.
METHODS
Patients with ≥ 3 follow-up MRIs were included. Preliminary PD was defined as a ≥ 25% increase of the sum of products of perpendicular diameters (SPD) of a new or increasing lesion compared to baseline. PD required a second ≥25% increase of the SPD. Treatment-associated changes require stable or regressing disease after preliminary PD.
RESULTS
Of the 424 evaluable patients, 221 patients (52%) were randomized into the cilengitide and 203 patients (48%) into the control arm. After chemoradiation with or without cilengitide, preliminary PD occurred in 274 patients (65%) during available follow-up, and 88 of these patients (32%) had treatment-associated changes, whereas 67 patients (25%) had PD. The remaining 119 patients (43%) had no further follow-up after preliminary PD. Treatment-associated changes were more common in the cilengitide arm than in the standard-of-care arm (24% vs. 17%; relative risk, 1.3; 95% CI, 1.004-1.795; P = .047). Treatment-associated changes occurred mainly during the first 6 months after RT (54% after 3 months vs. 13% after 6 months).
CONCLUSIONS
With the modified RANO criteria, the rate of treatment-associated changes was low compared to previous studies in MGMT promoter-methylated glioblastoma. This rate was higher after cilengitide compared to standard-of-care treatment. Confirmatory scans, as recommended in the modified RANO criteria, were not always available reflecting current clinical practice.
Topics: Humans; Glioblastoma; Snake Venoms; Brain Neoplasms; DNA Modification Methylases; Chemoradiotherapy; Female; Male; DNA Repair Enzymes; Middle Aged; Promoter Regions, Genetic; DNA Methylation; Aged; Tumor Suppressor Proteins; Adult; Magnetic Resonance Imaging; Follow-Up Studies; Disease Progression; Prognosis; Aged, 80 and over
PubMed: 38219019
DOI: 10.1093/neuonc/noad247