Bidimensional Measurements Research Articles

NIMG-70. COMPARISON OF VOLUMETRIC AND CROSS-SECTIONAL MEASUREMENTS IN DIFFUSE MIDLINE GLIOMAS: RETHINKING RESPONSE ASSESSMENT

Abstract BACKGROUND The Response Assessment in Pediatric Neuro-Oncology (RAPNO) criteria, which are based on bidimensional or cross-sectional product (CP) measurements of tumor size, are the standard for assessing treatment response in diffuse midline glioma (DMG). This study aims to investigate the correlation between CP and volumetric measurements in progressive disease (PD) and compare their prognostic impact in pediatric patients with DMG. METHODS We retrospectively reviewed clinical and imaging data from 27 subjects with newly diagnosed DMG, encompassing 16 subjects from the PNOC003 and PNOC007 clinical trials and 11 subjects from the Children’s Hospital of Philadelphia. Tumors were segmented using a pretrained pediatric-specific autosegmentation model followed by manual revisions. Tumor volume and CP measurements were automatically derived from the outlined tumor. Cox regression analysis was used to compare the performance of CP and volumetric measurements in predicting overall survival (OS). The correlation between CP and volumetric thresholds for PD was assessed by linear regression. Comparison of survival of patients classified as PD versus non-PD by CP and volumetric measurements at 7 months post-baseline scan was performed using log-rank analysis. RESULTS Cox regression analysis demonstrated that volumetric measurements were significantly associated with OS (p=0.04), whereas CP measurements were not a significant predictor (p=0.07). An approximate 55% increase in segmented volume corresponded to a 25% increase in CP, which is the definition of PD according to RAPNO criteria (R2 = 0.71). At 7 months, volumetric classification of PD more accurately predicted survival than the CP method (p=0.06 for volumetric vs 0.14 for CP). CONCLUSION Our study showed that volumetric measurements are better predictors of survival compared to bidimensional measurements. We are extending this analysis to a larger sample size, examining survival at additional time points, and incorporating other factors influencing OS, such as treatment approaches.

NIMG-54. AUTOMATED IMAGING RESPONSE EVALUATION SYSTEM (AIRES) FOR NEURO-ONCOLOGY: PROTOTYPE SOFTWARE TOOL FOR DETERMINING STANDARDIZED RADIOGRAPHIC RESPONSE ASSESSMENT FOR GLIOBLASTOMA CLINICAL TRIALS

Abstract Standardized radiographic response assessment criteria like Modified Response Assessment in Neuro-Oncology (mRANO) and now the RANO 2.0 are utilized for evaluating progression-free survival and objective response rate during glioblastoma clinical trials. After measuring tumor size with either bidimensional diameters or volumetric segmentations, the crucial and final time-consuming step of categorizing progression, stable disease, and response based on multiple criteria and numerical thresholds (e.g. ≥40% volumetric growth = progressive disease) is currently done manually. We developed an application prototype, Automated Imaging Response Evaluation System (AIRES) for Neuro-Oncology, that uses the mRANO criteria to label each timepoint as treatment response, stable disease, or disease progression based on either bidimensional or volumetric measurements as well as optional inputs of clinical status and corticosteroid dosage. These inputs may be uploaded via CSV files, which can integrate with automated tumor segmentation volumetry workflows, or entered in the AIRES graphical user interface (GUI). The AIRES GUI displays a patient report consisting of a table and graph that contain the lesion size, percent change from baseline, percent change from nadir, and the mRANO response category for each timepoint. To test AIRES in a real-world application, tumor size measurements from 367 scans across 41 patients from NUTMEG, a phase II multicenter clinical trial, were used to perform mRANO reads and calculate progression-free survival and time to response. AIRES-assisted reads performed by reader 1 were significantly quicker than fully manual reads performed by reader 2 (37.1±8.6 vs 107.7±58.6 seconds, P<0.0001). These results show that the AIRES app can make the reads quicker and potentially feasible for non-trained personnel, while reducing the amount of error-prone manual steps. Additionally, the underlying logic of AIRES is easily adaptable to integrate other response criteria including but not limited to RANO 2.0 and other future response assessment updates.

NCOG-23. ASSESSMENT OF NON-MEASURABLE DISEASE IN HIGH-GRADE GLIOMA: RANO-BASED 2D VS. 3D VOLUMETRICS

Abstract Non-measurable disease (NMD) in High grade glioma (HGG), defined as "longest perpendicular dimension of less than 10 mm”, is a limitation of RANO criteria that limits trial enrollment and biases trial populations to exclude patients with smaller tumors that eventually become measurable. Volumetric (3D) measurements may improve sensitivity and precision for measuring HGG of all sizes, however there is limited data comparing volumetric to 2D RANO measurements. AIMS: To investigate the correlation between RANO-based bidimensional 2D and 3D volumetric measurements in the postoperative setting of patients with HGG, including patients with NMD. METHODS: Contrast-enhanced (CE) postoperative and radiotherapy planning MRIs were utilized for 2D RANO measurements by neuroradiologists and volumetric (3D) measurements extracted from segmentations of CE disease. Pearson’s correlation between the 2D and 3D measurements were evaluated at each time point. The percentage of NMD based on RANO criteria and the range of tumor volumes for the NMD cases were reported. RESULTS: For 59 patients, there was lower concordance in the 2D and 3D measures at the postoperative MRI time point (Pearson =0.46) compared to the treatment planning MRI time point (Pearson=0.81). Interestingly, the postoperative time point had a higher percentage of NMD of 38% with the mean tumor volume of 13 cm3 (range: 0-21 cm3) compared to the treatment planning MRI with percentage NMD of 8% and mean tumor volume of 9 cm3 (range: 6-13cm3). CONCLUSION: In this study, higher rate of agreement was observed between RANO-based 2D and 3D volumetric tumor measurements at the time point of MR simulation when there was lower rate of NMD, suggesting NMD may contribute to the discrepancy between 2D and 3D measurements. Volumetric measurement tools may be a superior approach to improve the assessment especially of NMD in the postoperative period, improving trial enrollment for these patients.

LTBK-06. IMPACT OF VORASIDENIB TREATMENT ON MUTANT IDH1 OR IDH2 DIFFUSE GLIOMA TUMOR GROWTH RATE: RESULTS FROM THE RANDOMIZED, DOUBLE-BLIND, PHASE 3 INDIGO STUDY

Abstract INTRODUCTION The INDIGO study (NCT04164901) showed that vorasidenib, an oral, brain-penetrant, dual inhibitor of mutant isocitrate dehydrogenase (mIDH) 1/2, significantly improved imaging-based progression-free survival and time-to-next-intervention compared with placebo in patients with grade 2 mIDH1/2 glioma previously treated with surgery only. Given the limitations of traditional bi-dimensional measurements, evaluating volumetry and tumor growth rate (TGR) is an additional method of measuring treatment effect in these diffuse growing tumors. METHODS Magnetic resonance imaging (MRI) scans were performed at baseline and every 12 weeks on-treatment; up to three pre-treatment MRI scans were requested when available. Tumor volumes were derived per blinded independent review committee using a semi-automated approach. TGR was defined as percentage change in tumor volume every 6 months. Patients with evaluable baseline and ≥ 1 MRI during the corresponding period were included in the analysis. The difference in TGR in each arm was assessed by slope of tumor growth over time using a linear mixed model. RESULTS 331 patients were randomized to vorasidenib (n=168) or placebo (n=163). Median follow-up was 14.2 months. On-treatment TGR was −2.5% (95% CI, −4.7, −0.2) with vorasidenib (n=167) and 13.9% (95% CI, 11.1, 16.8) with placebo (n=161). In patients with available imaging data, TGR pre- and post-treatment with vorasidenib (n=56) was 13.2% (95% CI, 10.3, 16.3) and −3.3% (95% CI, −5.2, −1.2), respectively, while placebo (n=67) was 18.3% (95% CI, 15.0, 21.7) and 12.2% (95% CI, 9.5, 14.9), respectively. In patients who crossed over from placebo with available imaging data (n=38), TGR pre- and post-crossover was 22.4% (95% CI, 15.7, 29.4) and 5.2% (95% CI, −3.8, 15.0), respectively. CONCLUSIONS Tumor growth was observed in patients with mIDH1/2 gliomas before receiving vorasidenib or placebo. Treatment with vorasidenib reduced the TGR and shrunk tumor volume, whereas continued growth in tumor volume was observed in patients receiving placebo.

NIMG-87. PEDIATRIC BRAIN TUMOR SEGMENTATION INITIATIVE AT CHILDREN’S BRAIN TUMOR NETWORK (CBTN); PROJECT UPDATE ON IMPROVED PERFORMANCE AND FUTURE PROSPECTS

Abstract Pediatric brain tumors (PBT) exhibit significant heterogeneity, and accurate assessment of tumor response is crucial for patient management. While bidimensional measurements of tumor size are commonly used, they may underestimate tumor dimensions. Our group previously developed a multi-institutional, and multi-histology model on the Children’s Brain Tumor Network (CBTN) imaging dataset to segment tumor subregions, recommended by the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group. In the most recent update, we utilized a self-configuring deep learning architecture called nnU-Net on a large dataset of well-annotated PBTs (233 training, and 60 withheld internal and 46 external test sets). The model was trained and validated on multiparametric MRI sequences and differentiated various tumor subregions, including enhancing tumor (ET), nonenhancing tumor (NET), edema (ED), and cystic component (CC) and the whole tumor (WT) regions. Clinical validity was assessed by comparing the volumes of tumor subregions predicted by the model with expert manual segmentations, demonstrating strong agreement, with statistically significant Pearson’s correlation coefficients of 0.93/0.69 for ET, 0.94/0.93 for NET, 0.78/0.93 for CC, and 0.94/0.50 for ED subregions (p< 0.001) for the internal/external test cohorts. The trained model showed excellent performance for the withheld internal test set and decent accuracy for the external test set. Median Dice scores for internal/external test sets were 0.94±0.10/0.90±0.07 for WT, 0.85±0.33/0.84±0.30 for ET, 0.80±0.32/0.64±0.31 for NET, 0.79±0.37/0.67±0.33 for CC, 0.70 ±0.42/0.37±0.43 for ED, and 0.86±0.19/0.80±0.21 for all nonenhancing components (combination of NET, CC, and ED), respectively. The proposed automated segmentation method provides accurate and reproducible volumetric measurements of RAPNO-defined subregions in PBTs. It exhibits robust performance and potential generalization to external datasets and the accuracy is higher compared to the previous DeepMedic model. We will continue to improve the model by constantly adding new training data to further improve the performance and sustain model robustness.

Normal Variation of the Lisfranc Joint: Tridimensional Analysis using Weight-Bearing Computed Tomography Imaging

Category: Midfoot/Forefoot; Trauma Introduction/Purpose: Untreated Lisfranc injuries can lead to chronic pain, midfoot arthritis, and functional disability 1,2,5. Approximately 20% of Lisfranc injuries are misdiagnosed or completely missed on initial evaluation, which can be attributed to a lack of parameters of what is within normal limits for subjects without injury in the Lisfranc complex3,4. The purpose of this study is to identify anatomic variations of unidimensional, bidimensional, and tridimensional (1D, 2D, 3D) measurements of the Lisfranc complex of normal individuals using weight-bearing computed tomography (WBCT) imaging. Our hypothesis is that there is some variation among individuals with a difference between right and left of the same individual of less than 10%. Methods: A total of 191 subjects with bilateral WBCT scans of the foot were collected from three tertiary medical centers from 2019-2022. Exclusion criteria included: history of Lisfranc injury, first to fourth metatarsal base fractures, Charcot arthropathy, midfoot arthritis, cuneiform fractures, and forefoot surgery proximal to the metatarsal neck region. The following Lisfranc joint measurements were collected6 bilaterally: joint volume (3D), area of the joint on a consistent axial slice (2D), and distance between the second metatarsal and medial cuneiform (1D). Foot alignment was assessed using lateral talar-first metatarsal angle (Meary’s Angle). Patient demographics (age, sex, weight, height, BMI) were also collected. Descriptive statistics were calculated for quantitative variables. Percent difference was used to assess volume, area, and distance variation between sides.7 Correlation between demographic data and Lisfranc measurements was assessed using Pearson Correlation tests. A T-test was used for categorical variables. A p-value < 0.05 was considered statistically significant. Results: The cohort included 61% female and 39% male with an average age of 45.2±17.3 years. The mean volume, area, and distance measurements of the Lisfranc joint for both left and right sides are shown in Figure 1. Overall, the mean percent difference between left and right sides were 11.9%, 14.9% and 13.9% for volume, area and diastasis, respectively (Figure 1). No association was found between age, BMI, or weight and the volume, area or distance measurements. A correlation (r=0.48, p= < 0.001) was found between height and left Lisfranc joint volume, but no other measurements. Significant difference between sex in volume (p < 0.001) and area (p < 0.001) measurements were found. Foot alignment did not have a correlation with a variation of the Lisfranc complex measurements. Conclusion: This study provides an objective characterizing of the anatomic variations of the Lisfranc joint amongst healthy individuals. Differences in the measurements and the large standard deviation in absolute measurements of volume, area, and distance suggests that percent difference with the contralateral side may be a better metric to use to diagnose Lisfranc instability. Our results showed that the difference between bilateral sides in a patient is less than 15% for volume, area, and diastasis. The results of this study can set the foundation for future studies to determine the cut-off value for the diagnosis of Lisfranc instability using WBCT imaging.

Evaluating automated longitudinal tumor measurements for glioblastoma response assessment.

Automated tumor segmentation tools for glioblastoma show promising performance. To apply these tools for automated response assessment, longitudinal segmentation, and tumor measurement, consistency is critical. This study aimed to determine whether BraTumIA and HD-GLIO are suited for this task. We evaluated two segmentation tools with respect to automated response assessment on the single-center retrospective LUMIERE dataset with 80 patients and a total of 502 post-operative time points. Volumetry and automated bi-dimensional measurements were compared with expert measurements following the Response Assessment in Neuro-Oncology (RANO) guidelines. The longitudinal trend agreement between the expert and methods was evaluated, and the RANO progression thresholds were tested against the expert-derived time-to-progression (TTP). The TTP and overall survival (OS) correlation was used to check the progression thresholds. We evaluated the automated detection and influence of non-measurable lesions. The tumor volume trend agreement calculated between segmentation volumes and the expert bi-dimensional measurements was high (HD-GLIO: 81.1%, BraTumIA: 79.7%). BraTumIA achieved the closest match to the expert TTP using the recommended RANO progression threshold. HD-GLIO-derived tumor volumes reached the highest correlation between TTP and OS (0.55). Both tools failed at an accurate lesion count across time. Manual false-positive removal and restricting to a maximum number of measurable lesions had no beneficial effect. Expert supervision and manual corrections are still necessary when applying the tested automated segmentation tools for automated response assessment. The longitudinal consistency of current segmentation tools needs further improvement. Validation of volumetric and bi-dimensional progression thresholds with multi-center studies is required to move toward volumetry-based response assessment.

Deep learning automates bidimensional and volumetric tumor burden measurement from MRI in pre- and post-operative glioblastoma patients

Tumor burden assessment by magnetic resonance imaging (MRI) is central to the evaluation of treatment response for glioblastoma. This assessment is, however, complex to perform and associated with high variability due to the high heterogeneity and complexity of the disease. In this work, we tackle this issue and propose a deep learning pipeline for the fully automated end-to-end analysis of glioblastoma patients. Our approach simultaneously identifies tumor sub-regions, including the enhancing tumor, peritumoral edema and surgical cavity in the first step, and then calculates the volumetric and bidimensional measurements that follow the current Response Assessment in Neuro-Oncology (RANO) criteria. Also, we introduce a rigorous manual annotation process which was followed to delineate the tumor sub-regions by the human experts, and to capture their segmentation confidences that are later used while training deep learning models. The results of our extensive experimental study performed over 760 pre-operative and 504 post-operative adult patients with glioma obtained from the public database (acquired at 19 sites in years 2021–2020) and from a clinical treatment trial (47 and 69 sites for pre-/post-operative patients, 2009–2011) and backed up with thorough quantitative, qualitative and statistical analysis revealed that our pipeline performs accurate segmentation of pre- and post-operative MRIs in a fraction of the manual delineation time (up to 20 times faster than humans). Volumetric measurements were in strong agreement with experts with the Intraclass Correlation Coefficient (ICC): 0.959, 0.703, 0.960 for ET, ED, and cavity. Similarly, automated RANO compared favorably with experienced readers (ICC: 0.681 and 0.866) producing consistent and accurate results. Additionally, we showed that RANO measurements are not always sufficient to quantify tumor burden. The high performance of the automated tumor burden measurement highlights the potential of the tool for considerably improving and simplifying radiological evaluation of glioblastoma in clinical trials and clinical practice.

Effect of head rotation on two-dimensional cephalometric measurements using cone beam-computed tomography.

The purpose of this study was to identify the variation of bi-dimensional cephalometric measurements following real head rotation. Thirty cone beam-computed tomography (CBCT) head films were oriented according to three axes: horizontal Frankfort plane, transverse bi-orbital plane, and Opisthion-Nasion median plane. Axial rotation of 2°, 4°, 6°, and 8° from the Odontoïdale point were performed. Horizontal and vertical linear and angular measurements were studied on lateral cephalograms derived from each rotation T0, T2, T4, T6, and T8. A paired t-test was applied to compare the measurements between T0 and each rotational angle. Of the 18 measurements, 55% showed statistically significant differences (P < 0.05) and 22% showed clinically significant differences, mostly at T6 and T8. Horizontal linear measurements Ba-A and N-Ba decreased, and vertical linear measurement G-Sn increased gradually, as the angle of head rotation increased. Angular measurements studied did not vary. Head malpositions during X-ray acquisition should be avoided and rotated lateral CBCT cephalograms should be corrected and recentered to prevent any variation in linear measurements.

Evolution and implementation of radiographic response criteria in neuro-oncology.

Radiographic response assessment in neuro-oncology is critical in clinical practice and trials. Conventional criteria, such as the MacDonald and response assessment in neuro-oncology (RANO) criteria, rely on bidimensional (2D) measurements of a single tumor cross-section. Although RANO criteria are established for response assessment in clinical trials, there is a critical need to address the complexity of brain tumor treatment response with multiple new approaches being proposed. These include volumetric analysis of tumor compartments, structured MRI reporting systems like the Brain Tumor Reporting and Data System, and standardized approaches to advanced imaging techniques to distinguish tumor response from treatment effects. In this review, we discuss the strengths and limitations of different neuro-oncology response criteria and summarize current research findings on the role of novel response methods in neuro-oncology clinical trials and practice.

Evaluation of Volumetric Lymph Node Measurements in Cutaneous T-Cell Lymphoma Patients Enrolled in the Mavoric Trial: An Interim Analysis

Lymph node assessment is an important component of staging, classification, and treatment response assessment in cutaneous T-cell lymphoma (CTCL). Although a biopsy is the only definitive way to assess nodal involvement, radiologic evaluation is commonly used in practice given its practicality. Current radiologic criteria are adapted from guidelines for lymphomas with primarily nodal involvement and have not been validated in CTCL patients. These criteria are limited by linear measurements which fail to accurately capture small and/or asymmetric nodal involvement in CTCL and may lead to flawed estimations of the overall disease burden. Furthermore, unidimensional and bidimensional measurements are subject to significant inter- and intra-observer variability. More accurate methods of lymph node evaluation are needed to improve risk stratification and treatment response assessment in CTCL. Recent advances in digital imaging techniques have made it possible to obtain volumetric tumor measurements. This technique has shown promise as a more accurate imaging biomarker than unidimensional measurements in several solid cancer types, offering improved sensitivity for changes in tumor burden during treatment. Volumetric lymph node measurements have been shown to be superior to unidimensional measurements in distinguishing between benign and malignant lymph nodes in systemic lymphoma, however volumetric measurements have never been studied in CTCL. The aim of this study was to assess the utility of volumetric lymph node measurements in CTCL using this novel imaging technique. We analyzed imaging and clinical data from the mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC) trial which included 372 CTCL patients randomized to receive either mogalizumab or vorinostat. The majority of patients randomized to vorinostat crossed over to mogalizumab due to disease progression or intolerance. As part of the trial, patients underwent computed tomography (CT) scans at baseline and regular follow-up intervals to assess for lymph node response to treatment. In our study, target lymph nodes in serial CT scans were measured by a team of radiologists using a response assessment system built on open-source software known as the Weasis imaging platform. Semi-automated segmentation algorithms were used to quantify unidimensional and bidimensional measurements as well as lymph node volumes. Our preliminary data suggests that there is a correlation between unidimensional, bidimensional, and volumetric lymph node measurements. For the first time, we validate volumetric lymph node measurement as a viable method of lymph node assessment in CTCL. This implicates lymph node volume as an alternative metric for lymph node assessment in CTCL that has the potential to improve the accuracy of current nodal assessment criteria. Additional research is underway to determine whether volumetric lymph node measurements are superior to uni- and bidimensional measurements in assessing treatment response and predicting clinical outcomes in CTCL.

3D-echocardiography for evaluation of the right ventricle in patients with repaired Tetralogy of Fallot: a comparison study with cardiac magnetic resonance

Abstract Background Patients with repaired Tetralogy of Fallot (ToF) need periodic instrumental assessments, due to complications they can meet during lifetime. Right ventricle (RV) dilation and dysfunction are some examples that explain why those patients regularly undergo Cardiac Magnetic Resonance (CMR), currently the gold standard method to detect these complications. Purpose 3D-echocardiography is an emerging tool to study RV, but there is little data supporting its use in congenital heart diseases. This study aimed at evaluating its accuracy in assessing RV dimensions and systolic function in ToF patients, in comparison to CMR. Methods 34 patients were prospectively enrolled after CMR performance. They all underwent standard 2D-echocardiography and Multi-Beat-ECG-triggered 3D Full-Volume acquisition. RV End Diastolic Volume (RV-EDV), End Systolic Volume and Ejection Fraction (RV-EF) were defined both in 3D-echocardiography and CMR. Results Post-hoc analysis of 3D images was performed through a vendor-independent software in 30 patients, resulting in a feasibility of 88%. A Bland-Altman analysis was performed, showing that 3D-echocardiography underestimates the RV-EDV/BSA of −27.39 mL/m2 on average (CI 95%: −29.46; −25.31, SD: 5.68 mL/m2), compared to CMR, as expected. However, when compared to normality reference, 3D-echocardiography identified RV dilatation with a significant correlation to CMR (V=0.66, p&amp;lt;0.001). Moreover, ROC curves showed that 3D-echo-RV-EDV/BSA is the echocardiographic measure that best correlates to CMR in detecting RV dilatation (AUC 1, CI 95%: 1.00; 1.00), followed by RVOT diameter in PLAX (AUC 0.89, CI 95%: 0.69; 0.99). Youden analysis suggested 77 mL/m2 (Se 95%, Sp 100%; J 0,95) as optimal limit to define RV dilatation in 3D-echocardiography. Regarding the RV-EF, the Bland-Altman analysis showed that 3D-echocardiography overestimates the RV-EF by 1,97% on average (CI 95%: 0.01; 3.95, SD: 5.43), compared to CMR. Secondly, accuracy of different echocardiographic parameters (both 2D and 3D) in detecting a RV systolic impairment was analyzed: ROC curves showed that RV-EF in 3D echocardiography is the measurement that best correlates to CMR in detecting RV dysfunction (AUC 0.92, CI 95%: 0.79–1.00), followed by Fractional Area Change (FAC) (AUC 0.78, CI 95%: 0.60; 0.96). Tricuspid Annular Plane Systolic Excursion (TAPSE) and tricuspid valve annular motion velocities in systole (S'-TDI), instead, showed very poor correlation. Conclusions 3D-echocardiography showed good agreement with CMR in defining RV dimensions and systolic function in ToF patients, even more than the bidimensional measurements cardiologists are used to. This could lead to a wider use of this tool in daily clinical practice, involving a reduction in the execution of the numerous CMR patients usually undergo. Moreover, it could be a valid instrument in patients with contraindication to CMR. Funding Acknowledgement Type of funding sources: None.

The Effect of Intrathoracic Lesion Location on Initial Tyrosine Kinase Inhibitor Response in Advanced Oncogene-Addicted Non-Small Cell Lung Cancer: A Comparison Between RECIST 1.1 and a Novel Method of Response Assessment (MAX)

IntroductionDifferent subtypes of non-small cell lung cancer (NSCLC) are associated with different patterns of metastatic spread. Anatomic location of lesions in the chest may influence patterns of cancer growth and the shrinkage to therapy. Consequently, lesion location could affect apparent response rates per RECIST. We sought to explore this and develop, as needed, treatment response assessments less affected by the location. MethodsCases of advanced oncogene-addicted NSCLC (EGFR, ALK, and ROS1) with pre- and on-therapy imaging during initial targeted therapy were identified. Lesions located in the lung parenchyma, pleural space or intra-thoracic lymph nodes were identified and analyzed separately from each other by RECIST 1.1 (unidimensional measurements) and by a novel MAX methodology (bidimensional measurements) which takes the axis with the greatest absolute percentage change on therapy in each location as the representative measurement. ResultsThree hundred three patients with 446 unidimensional measured lesions were included for RECIST analysis. Two hundred forty nine patients with 386 bidimensional measured lesions were included for MAX analysis, as well as the analysis comparing RECIST and MAX. Intrathoracic location significantly impacted percentage shrinkage and the response rate per RECIST. The response rates for pleural, intra-parenchymal and nodal lesions were 34.1%, 49.6%, and 68.3%, respectively (P = .0002). The MAX methodology both increased the apparent treatment effect and made it consistent between intrathoracic locations. For pleural, parenchymal and nodal lesions, the MAX calculated response rate were 83.7%, 72.2%, and 75.4%, respectively (P-value = .24). ConclusionIntrathoracic lesion location affects RECIST-based treatment effectiveness estimations. The MAX methodology neutralizes location effect when examining impact of treatment and should be explored further.

Evaluation of the response assessment criteria in newly diagnosed and recurrent glioblastoma.

2020 Background: The Response Assessment in Neuro-Oncology (RANO) and modified RANO (mRANO) criteria are the two most widely used criteria to evaluate treatment response in glioblastoma (GBM) clinical trials. Unlike RANO, mRANO omits the evaluation of FLAIR sequence and requires a repeat scan to confirm responses. It also uses the post-radiation (RT) MRI as a baseline MRI in the newly diagnosed setting instead of the pre-RT MRI used in RANO. We sought to compare the 2 response assessment criteria and evaluate the differences between them in a large patient population. We also sought to compare them to immunotherapy RANO (iRANO) in patients who received immunotherapy. Methods: We conducted a retrospective review of consecutive patients with newly diagnosed (nGBM) and recurrent (rGBM) IDH wild-type GBM treated at Dana-Farber Cancer Institute from 2014 to 2020. Bidimensional measurements of enhancing disease and evaluation of FLAIR sequences were performed by two independent readers on patients’ brain MRIs obtained before change of treatment, and discrepancies were evaluated by a third reader. Dates of disease progression (PD) were identified using RANO, mRANO, iRANO, and other response assessment criteria variations. Spearman’s correlations between PFS and OS were calculated using an iterative multiple imputation method to account for any right-censoring. Results: 526 and 580 patients were included in the newly diagnosed and recurrent cohorts, respectively. Spearman’s correlations were not significantly different between RANO and mRANO in the nGBM (0.69 [95% CI 0.62 to 0.75] vs. 0.67 [0.60, 0.73]) and rGBM (0.45 [0.37, 0.52] vs. 0.50 [0.42, 0.57]) cohorts. Evaluation of FLAIR sequences did not improve the correlation between PFS and OS in patients who received antiangiogenic therapy. Addition of confirmation scans was associated with stronger Spearman’s correlations only when PD was identified within 12 weeks of completion of RT in the nGBM cohort, but did not affect the Spearman’s correlations in the rGBM cohort. The use of the post-RT MRI as a baseline was associated with a higher Spearman’s correlation in nGBM than the use of pre-RT MRI (0.67 [0.60, 0.73] vs. 0.53 [0.42, 0.62]). Among 98 patients with nGBM and 175 patients with rGBM who received immunotherapy, the Spearman’s correlations (nGBM and rGBM) with iRANO (0.63 [0.44, 0.76] and 0.34 [0.17, 0.49]) were similar to RANO (0.73 [0.60, 0.82] and 0.42 [0.28, 0.54]) and mRANO (0.65 [0.48, 0.77] and 0.43 [0.28, 0.56]). Conclusions: RANO and mRANO demonstrated similar correlation between PFS and OS. The evaluation of FLAIR can be omitted, while confirmation scans appear to be only beneficial in the nGBM settings during the first 12 weeks of completion of RT. There was a nonsignificant trend in favor of the use of post-RT MRI as the baseline scan in the nGBM setting. The application of iRANO criteria did not add significant benefit in patients who received immunotherapy.

Comparison of volumetric and bidimensional measurement of the thymic gland to determine interobserver variability

Aim: Thymic measurements should be interpreted relative to normal measurement values according to age groups and gender. Thymic gland measurement may vary between radiologists. In our study we wanted to determine the interobserver variability of thymic size measurements on CT by comparing volumetric calculations to commonly used bidimensional measurements.&#x0D; Material and Method: The chest CT scans of 156 patients who had any oncological problems or disorders influencing the thymic size were retrospectively evaluated. The shape (quadrilateral or triangular), anteroposterior (AP) and transverse (TR) diameters, as well as the thickness of each lobe and thymus volume were measured independently by two radiologists. Interobserver variability was determined according to these parameters by Pearson correlation test.&#x0D; Results: The shape of the thymic gland was triangular in 72% (n:113) and quadrilateral in 28% (n: 43) of all subjects. According to the results of the correlation test, a moderate relationship in terms of AP length, a weak relationship in terms of TR length, a negligible relationship in terms of right lobe thickness and a weak relationship in terms of left lobe thickness were obtained, but a very strong relationship was found between the two radiologists for volumetric measurements.&#x0D; Conclusions: Volumetric measurements can be used as a basis for thymic imaging, reducing the differences among radiologists, and unnecessary and advanced examinations can be avoided.

Control of measurements along the Z axis in optical measuring instruments

Quality control in industrial environments is associated with the verification of compliance with design specifications, among which we find dimensional verification. Coordinate Measuring Machines (CMMs) have been traditionally used, which allow traceable 3D measurements of the parts. However, at the micro- and nano-scale, these types of tools cannot always be applied. Parts of these dimensions made with processes such as Direct Metal Laser Sintering (DMLS) may suffer damage and not meet specifications. Among the most widely used quality control tools in industry and research centers to perform measurements in these scales are optical measuring instruments. Some of these instruments add the Z-coordinate to the bidimensional measurements of a traditional microscope, allowing 3D measurements of the samples to be obtained and used as a small-scale CMM. In this article we present a calibration procedure to provide traceability to the measurements made on the Z axis of a confocal microscope.

579 Pre-operative computed tomography evaluation of suprarenal aortic burden predicts post-procedural acute kidney injury after transcatheter aortic valve replacement: the spread-AKI study

Abstract Aims Acute kidney injury (AKI) is a potential complication of transcatheter aortic valve replacement (TAVR). Athero-embolization linked to catheter manipulation in the supra-renal aorta is a possible pathogenetic mechanism of AKI after TAVR. We sought to determine the impact of supra-renal aortic atheroma burden (AB) on AKI, and the potential role of pre-operative multislice computed tomography (PO-MSCT) in evaluating the supra-renal aortic atherosclerosis and the pre-operative risk of AKI. Methods and results We collected PO-MSCT, as well as baseline, procedural, and post-procedural characteristics of 222 consecutive patients who underwent TAVR from January 2018 to December 2020 at a single, high-volume, Italian centre. PO-MSCT was performed using a dedicated TAVR protocol with an ECG-triggered high-pitch spiral acquisition. The non-contrast aortic valve calcium score (AV-CS) was calculated by a dedicated software. Angiographic data were analysed on a dedicated 3D workstation. Bidimensional measurements, total renal volume (TRV), and presence of significant (≥50%) renal artery stenosis (RAS) were recorded. The supra-renal AB was quantified using a ‘plaque analysis’ module that automatically segments the entire aortic root, from the sino-tubular junction to the renal arteries, by drawing a centreline across the aortic lumen and delineating the inner and outer vessel walls (including the plaque). Manual correction was applied. A set of Hounsfield unit (HU) intensity ranges were defined and mapped to a color overlay to visualize the various elements of atherosclerotic lesion by using the plaque density classification of the Society of Cardiovascular Computed Tomography (necrotic core, fibro-fatty, fibrous, and calcified plaque); calcified plaque were subcategorized on a voxel-level basis into three strata: low- (351–700 HU), mid- (701–1000 HU), and high-calcium (&amp;gt;1000 HU, termed 1K plaque). Post-procedural complications were defined according to Valve Academic Research Consortium (VARC-3) criteria. Mean age was 83.3 ± 5.7 years, and 95 (42.8%) patients were males. AKI occurred in 67/222 (30.2%). Patients who developed AKI had higher supra-renal AB (17.6 ± 5.1% vs. 13.9 ± 4.3%, P &amp;lt; 0.001), TRV indexed for body surface area (TRVBSA; 153.7 ± 43.1 vs. 134.9 ± 38.7, P = 0.002), mid-calcium plaque (2.2 ± 1.5% vs. 1.3 ± 1.1%, P &amp;lt; 0.001), 1K plaque (5.4 ± 3.7% vs. 2.4 ± 2.4%, P &amp;lt; 0.001) and suffered more post-procedural major/life-threatening (severe) bleedings [9/67 (13.4%) vs. 5/155 (3.2%), P = 0.004], whereas there was no difference in AV-CS (P = 0.691) and RAS (P = 0.077). Multivariate logistic regression analysis adjusted for other univariate predictors (male sex, baseline eGFR, baseline ejection fraction, baseline mean aortic gradient, and RAS) showed percent supra-renal AB (HR: 1.15, 95% CI: 1.06–1.26, P = 0.002), mid-to-high calcium plaque (HR: 5.67, 95% CI: 2.49–13.77, P &amp;lt; 0.001), severe bleedings (HR: 4.93, 95% CI: 1.09–24.69, P = 0.043), and TRVBSA (HR: 1.015, 95% CI: 1.01–1.02, P = 0.021) as independent predictors of AKI. Finally, a 3-knots spline curve analysis identified percent of supra-renal AB &amp;gt; 15.0% as the optimal threshold to predict an increased risk of AKI. Conclusions Suprarenal AB is associated with the occurrence of AKI, and this association is strengthened as the percentage of calcified plaque increases. Quantitative and qualitative pre-operative MSCT assessment of aortic atherosclerosis may help in early identification of patients at high-risk for AKI who could benefit from higher peri-operative surveillance.

568 Echocardiography and impedance cardiography as determinants of successful slow Levosimendan infusion in patients with acute advanced heart failure

Abstract Aims Despite new therapeutic options, patients with heart failure (HF) still progress to advanced stage. Among new therapeutic options, Levosimendan was recently approved in order to treat patients hospitalized for acute decompensated heart failure (ADHF) with severe systolic dysfunction. The pharmacological effects of Levosimendan consist of inotropy, vasodilatation, and cardioprotection through the increase of calcium sensitivity. These effects should be monitored with echocardiography and in particular with speckle tracking and tri-dimensional echocardiography which appear to be useful in LV systolic function detection and monitoring. In this study we aim to evaluate the effect of slow infusion of Levosimendan on the non-invasive measurement of cardiac output, the speckle tracking parameters and the tri-dimensional echocardiography measurements in advanced ADHF patients. Methods and results This is a prospective observational study evaluating Levosimendan efficacy through advanced echocardiography. We enrolled 11 patients with diagnosis of ADHF who respect the recent ESC criteria of ‘advanced heart failure’. Patients underwent to blood sample examination to measure electrolytes, creatinine, and NTproBNP. Patients underwent to advanced echocardiography examination (performed for each patient pre- and post-Levosimendan infusion) with tri-dimensional echocardiography and global longitudinal strain assessment. Furthermore patients underwent to non-invasive cardiac output and cardiac index collection through impedance cardiography pre- and post-Levosimendan infusion. All patients were followed for 30 days after discharge for all cause of mortality and HF re-hospitalization. A total of 11 patients affected by advanced ADHF were included in this study. Mean age was 73.8 ± 4.7 years. 72.7% (n 8) patients were men. 81.9% (n 9) of patients recognize ischaemic heart disease as HF etiology. At admission mean systolic arterial pressure was 100 ± 17 mmHg, mean NTproBNP was 24 445 ± 12 194 pg/ml and mean serum creatinine was 1.55 ± 0.84 mg/dl. At tri-dimensional echocardiography mean LV ejection fraction (LVEF) was 19.7 ± 5.7% and at bi-dimensional echocardiography mean tricuspid anular plane systolic excursion (TAPSE) and pulmonary arterial systolic pressure (PASP) were, respectively, 12.5 ± 2.7 mm and 48 ± 16 mmHg. Mean LV global longitudinal strain (GLS) was −3.0 ± 1.8. Mean furosemide in-hospital infusion was 306 ± 102 mg/die and mean urine output 1436 ± 496 ml. None developed significant ventricular or supraventricular arrhythmias. All patients were treated with betablockers during infusion. At 30 days of follow-up two patients died and 1 patient was re-hospitalized. Evaluating the differences among our variables pre- and post-Levosimendan infusion, we found that NTproBNP was significantly reduced post-Levosimendan infusion (P = 0.01). Among ICG non-invasive measurement, we found significant differences in stroke volume (SV) and cardiac output (CO) in terms of significant improvement (P = 0.001 for both). Analysing tri-dimensional echocardiography variables, we observed a significant improvement of LVEF (P = 0.003), SV (P = 0.03) and 3-D LV GLS (P = 0.002). Furthermore, we observed a significant reduction in end-systolic volume (ESV) post-Levosimendan infusion (P = 0.02). Among bi-dimensional echocardiography measurements, there was a significant reduction in end-diastolic diameter of right ventricle (EDDRV) and in B-lines count (respectively, P = 0.02 and P = 0.002). Moreover, we observed a significant improvement in TAPSE (P = 0.003) and in LV GLS (P = 0.004). Conclusions Our study showed that slow Levosimendan infusion (12.5 mg at velocity of 0.05–1 mcg/kg/min) without bolus could be considered in advanced ADHF patients to improve cardiac performance without severe adverse events. ICG and echocardiography in-hospital evaluation seemed to be necessary to understand treatment success and patients status improvement as well as cardiac function benefit.

Intratumoral G100 Induces Systemic Immunity and Abscopal Tumor Regression in Patients with Follicular Lymphoma: Results of a Phase 1/ 2 Study Examining G100 Alone and in Combination with Pembrolizumab

Intratumoral G100 Induces Systemic Immunity and Abscopal Tumor Regression in Patients with Follicular Lymphoma: Results of a Phase 1/ 2 Study Examining G100 Alone and in Combination with Pembrolizumab

Comparison of Measurement Techniques and Response Criteria for MR Imaging Follow-up in Adult Primary Central Nervous System Lymphoma.

Current guidelines proposed for the measurement of primary central nervous system lymphoma in 2005 have indicated that unidimensional and bidimensional measurements may be used, using the same threshold for response categorization, because no clinical study has evaluated the agreement among the measurement techniques. Hence, our study assessed the agreement among different measurements. In this retrospective study, primary central nervous system lymphoma lesions were measured with different techniques (longest 1D, axial 1D, 2D, 3D, and the Response Evaluation Criteria in Solid Tumor) on consecutive MR images. Intra- and interobserver correlations were calculated with intraclass correlation coefficients. Correlations between raw measurements and variations in size compared with baseline were evaluated with the Spearman rank correlation, and agreement among response categories was evaluated. A total of 304 examinations obtained in 40 patients was assessed. The intraobserver intraclass correlation coefficient for 3D, 2D, and longest 1D were ≥0.993. The interobserver intraclass correlation coefficient was ≥0.967. The correlations in raw measurements and size variation in comparison with 3D were respectively; 0.99 and 0.98 for 2D; 0.94 and 0.92 for longest 1D; 0.94 and 0.83 for axial 1D; and 0.90 and 0.79 for Response Evaluation Criteria in Solid Tumor. With 20%-30% and 25%-50% thresholds for unidimensional techniques, response categorizations were 95% and 95% for 2D, 92.5% and 90% for the longest 1D, 87.5% and 82.5% for axial 1D, and 90% and 85% for the Response Evaluation Criteria in Solid Tumor. Both longest 1D and 2D demonstrated excellent correlations with 3D measurements. The longest 1D could be used for the follow-up of primary central nervous system lymphoma. If unidimensional measurements were used, 20% and 30% cutoffs should be used for defining response categorization instead of the current guidelines.