Citations

Background: Multiple radiomics models have been proposed for grading glioma using different algorithms, features, and sequences of magnetic resonance imaging. The research seeks to assess the present overall performance of radiomics for grading glioma. Methods: A systematic literature review of the databases Ovid MEDLINE PubMed, and Ovid EMBASE for publications published on radiomics for glioma grading between 2012 and 2023 was performed. The systematic review was carried out following the criteria of Preferred Reporting Items for Systematic Reviews and Meta-Analysis. Results: In the meta-analysis, a total of 7654 patients from 40 articles, were assessed. R-package mada was used for modeling the joint estimates of specificity (SPE) and sensitivity (SEN). Pooled event rates across studies were performed with a random-effects meta-analysis. The heterogeneity of SPE and SEN were based on the χ2 test. Overall values for SPE and SEN in the differentiation between high-grade gliomas (HGGs) and low-grade gliomas (LGGs) were 84% and 91%, respectively. With regards to the discrimination between World Health Organization (WHO) grade 4 and WHO grade 3, the overall SPE was 81% and the SEN was 89%. The modern non-linear classifiers showed a better trend, whereas textural features tend to be the best-performing (29%) and the most used. Conclusions: Our findings confirm that present radiomics’ diagnostic performance for glioma grading is superior in terms of SEN and SPE for the HGGs vs. LGGs discrimination task when compared to the WHO grade 4 vs. 3 task.

Arterial spin labeling (ASL) has emerged as a promising noninvasive tool for the evaluation of both pediatric and adult arteriovenous malformations (AVMs). This paper reviews the advantages and challenges associated with the use of ASL in AVM assessment. An assessment of the diagnostic workup of AVMs and their variants in both adult and pediatric populations is proposed. Evaluation after treatments, whether endovascular or microsurgical, was similarly examined. ASL, with its endogenous tracer and favorable safety profile, offers functional assessment and arterial feeder identification. ASL has demonstrated strong performance in identifying feeder arteries and detecting arteriovenous shunting, although some studies report inferior performance compared with digital subtraction angiography (DSA) in delineating venous drainage. Challenges include uncertainties in sensitivity for specific AVM features. Detecting AVMs in challenging locations, such as the apical cranial convexity, is further complicated, demanding careful consideration due to the risk of underestimating total blood flow. Navigating these challenges, ASL provides a noninvasive avenue with undeniable merits, but a balanced approach considering its limitations is crucial. Larger-scale prospective studies are needed to comprehensively evaluate the diagnostic performance of ASL in AVM assessment.

Purpose: To better define the overall performance of the current radiomics-based models for the discrimination of pediatric posterior fossa tumors. Methods: A comprehensive literature search of the databases PubMed, Ovid MEDLINE, Ovid EMBASE, Web of Science, and Scopus was designed and conducted by an experienced librarian. We estimated overall sensitivity (SEN) and specificity (SPE). Event rates were pooled across studies using a random-effects meta-analysis, and the χ2 test was performed to assess the heterogeneity. Results: Overall SEN and SPE for differentiation between MB, PA, and EP were found to be promising, with SEN values of 93% (95% CI = 0.88–0.96), 83% (95% CI = 0.66–0.93), and 85% (95% CI = 0.71–0.93), and corresponding SPE values of 87% (95% CI = 0.82–0.90), 95% (95% CI = 0.90–0.98) and 90% (95% CI = 0.84–0.94), respectively. For MB, there is a better trend for LR classifiers, while textural features are the most used and the best performing (ACC 96%). As for PA and EP, a synergistic employment of LR and NN classifiers, accompanied by geometrical or morphological features, demonstrated superior performance (ACC 94% and 96%, respectively). Conclusions: The diagnostic performance is high, making radiomics a helpful method to discriminate these tumor types. In the forthcoming years, we expect even more precise models.

Abstract Purpose: Numerous radiomics-based models have been proposed to discriminate between central nervous system (CNS) gliomas and primary central nervous system lymphomas (PCNSLs). Given the heterogeneity of the existing models, we aimed to define their overall performance and identify the most critical variables to pilot future algorithms. Methods: A systematic review of the literature and a meta-analysis were conducted, focusing on studies reporting on radiomics to differentiate gliomas from PCNSLs. A comprehensive literature search was performed through PubMed, Ovid MEDLINE, Ovid EMBASE, Web of Science, and Scopus databases. Overall sensitivity (SEN) and specificity (SPE) were estimated. Event rates were pooled using a random-effects meta-analysis, and the heterogeneity was assessed using the χ2 test. Results: The overall SEN and SPE for differentiation between CNS gliomas and PCNSLs were 88% (95% CI = 0.83 – 0.91) and 87% (95% CI = 0.83 – 0.91), respectively. The best-performing features were the Gray Level Run Length Matrix (GLRLM; ACC 97%), followed by the Neighboring Gray Tone Difference Matrix (NGTDM; ACC 93%), and shape-based features (ACC 91%). The 18F-FDG-PET/CT was the best-performing imaging modality (ACC 97%), followed by the MRI CE-T1W (AUC 87% - 95%). Most studies applied a cross-validation analysis (92%). Conclusion: The current SEN and SPE of radiomics to discriminate CNS gliomas from PCNSLs are high, making radiomics a helpful method to differentiate these tumor types. The best-performing features are the GLRLM, NGTDM, and shape-based features. The 18F-FDG-PET/CTimaging modality is the best-performing, while the MRI CE-T1W is the most used.

Abstract Background: Bortezomib (VELCADE®) is a first-in-class, reversible proteasome inhibitor with activity in multiple myeloma (MM) and other malignancies. Bortezomib showed significant activity in previous phase 2 and 3 studies in patients (pts) with previously treated MM. This international multicenter open-label phase 3b study allowed expanded access to bortezomib therapy in pts with relapsed/refractory MM treated with ≥ 2 previous lines of therapy. Methods: Pts with MM were eligible if they had received ≥ 2 prior lines of therapy and required treatment due to relapsed or progressive disease. Pts with grade ≥ 2 peripheral neuropathy (PN) were excluded. Pts received 1.3 mg/m2 IV bolus bortezomib on days 1, 4, 8, and 11 of each 3-week cycle for up to 8 cycles; dexamethasone (20 mg/d PO on the day of and day after bortezomib dose) could be added after cycle 2 for progressive disease or after cycle 4 for stable disease. Adverse events (AEs) were assessed beginning at the start of treatment and continuing until 30–42 days after treatment and were graded based on NCI-CTC version 2.0. Efficacy assessment was performed based on changes in disease burden as measured by monoclonal (M)-protein concentration in serum and urine every 2 cycles (6 weeks). Response was assessed using modified SWOG criteria: complete response (CR) was a 100% reduction in M-protein; very good partial response (VGPR), 75–99% reduction; partial response (PR), 50–74% reduction; minimal response (MR), 25–49% reduction; and stable disease, < 25% reduction. Increasing M-protein levels indicated progressive disease. Results: 624 pts in 93 centers from 21 countries received at least 1 dose of treatment and were evaluable for safety (55.3% male; median age 62.7 years). 68% of pts received 3–11 lines of previous therapy. Karnofsky performance status was ≤70 in 25.6% of pts; 141 pts (22.6%) were ≥ 70 years of age. Pts completed a median of 5 cycles of therapy (range 0–13); 39.3% of pts completed all 8 planned cycles. Grade 3/4 treatment-emergent (related and unrelated) AEs were reported in 430 pts (68.9%), with thrombocytopenia (29.2%), neutropenia (13.3%), and anemia (11.7%) the most common hematologic AEs. Grade 3/4 PN was reported in 8.2% of pts. Overall, 165 pts (26.4%) discontinued therapy due to treatment-related AEs. Best responses among evaluable pts (n = 593) included 12.0% CR, 23.1% VGPR, 19.1% PR, and 16.5% MR, for an overall response rate of 70.7%. Median time to first response was 42 days (range 7–125), and median time to best response was 63 days (range 7–235). Conclusions: Bortezomib 1.3 mg/m2 administered biweekly q3 weeks was well tolerated with manageable toxicities in pts with relapsed and/or refractory MM. Response rates with bortezomib were high, even in heavily pretreated pts, inducing > 25% CR/VGPR. This study confirms results from initial clinical trials in a broader population.

Craniocervical junction dural arteriovenous fistulas (dAVFs) are rare vascular lesions with a potentially dangerous natural history due to the onset of neurological deficit secondary to intracranial hemorrhage or myelopathy due to venous congestion. Despite advances in endovascular techniques, many dAVFs located in this area continue to require surgical treatment as embolization is often not feasible or safe. In this video, the authors illustrate a patient with a symptomatic craniocervical junction dAVF who had undergone attempted Onyx embolization at another institution. Because of persistent filling of the fistula and worsening myelopathy after the previous attempt, the patient was referred to the authors’ clinic for definitive surgical treatment. The video illustrates the typical location of the early draining vein in most craniocervical junction dAVFs immediately below the emergence of the vertebral artery from the dura. The patient underwent successful definitive clip ligation of the fistula, which was exposed through a lateral suboccipital craniotomy. The video can be found here: https://youtu.be/Bvg6VKLgwO0 .

Abstract Background: The efficacy of immunotherapy, including therapeutic strategies capable of modulating innate/adaptive immune resistance, varies greatly across tumor types. As the number of available immunotherapies accelerates, the study of predictive markers by IHC (e.g. PDL1 expression) is under intense investigation. However, staining protocol inconsistency, variation across scoring systems, and subjective interpretation of the immunostaining have produced conflicting results thus far. This work explored the role of Laser Capture Microdissection (LCM) coupled with Reverse Phase Protein Microarray (RPPA) as an alternative high throughput, quantitative, operator independent platform for measuring PDL1 expression across tumor types. Material and Methods: Pure epithelial cells were isolated via LCM from 178 samples including: 72 ovarian cancers (OC), 57 lung adenocarcinomas (LC), 30 metastatic breast cancers (MBC), and 19 pancreatic cancers (PC). PDL1 expression was measured on a continuous scale using quantitative RPPA based analysis. Each tumor type was processed and arrayed independently. Experimental samples and reference standards used for inter-assay normalization were printed in triplicates. Results: PDL1 expression varied greatly across tumor types. LC were characterized by the greatest intra-tumor fold dynamic range (&gt; 35-fold), followed by OC (&lt; 13-fold), MBC (&lt; 4-fold), and PC (&lt; 2-fold). PDL1 expression of 46/57 (80.7%) LC, 17/30 (56.7%) MBC, 6/19 (31.5%) PC, and 20/72 (27.8%) OC was greater than the population median of all tumors combined. Within the LC samples with PDL1 expression equal to the top quartile of the population, 10 (71.4%) were KRAS mutant lesions and 4 (28.6%) were WT tumors. Finally, amongst LC and PC harboring a KRAS mutation, PC showed an overall lower expression of PDL1 with only 2/19 (10.5%) cases been above the population median and none within the top quartile of the population. Conclusions: The LCM-RPPA workflow has the unique ability to capture immune checkpoint expression on a continuous quantitative scale as well as capture its broad dynamic range. Because RPPA is unconstrained by antigen retrieval issues as well as subjectivity of IHC interpretation, this approach may generate more accurate cut-point of therapeutic response prediction. Overall the dynamic range of PDL1 was broader in LC compared to other solid tumors, and LC had a much higher proportion of patients with tumors expressing high levels of PDL1. These quantitative differences may explain therapeutic efficacy of PDL1 inhibition across tumor types. Such speculative hypothesis should be further validated in prospective clinical trials. Finally, these preliminary data suggest that organ specific microenvironments more than specific driving mutations (e.g. KRAS) may strongly influence PDL1 expression in malignant lesions. Citation Format: Elisa Baldelli, Valerie Calvert, K. Alex Hodge, Maria Isabella Sereni, Guido Gambara, Eric B. Haura, Lucio Crino', Bryant Dunetz, Sergio Pecorelli, David J. Perry, Stephen P. Anthony, Nicholas Robert, Donald W. Northfelt, Mohammad Jahanzeb, Emanuel F. Petricoin, Mariaelena Pierobon. Quantitative measurement of PDL1 expression across tumor types using laser capture microdissection and reverse phase protein microarray [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5656. doi:10.1158/1538-7445.AM2017-5656