Imaging-guided prognostic score-based approach to assess the benefits of combotherapy versus monotherapy with immune checkpoint inhibitors in metastatic MSI-H colorectal cancer patients.

BACKGROUND: This retrospective study determined survival responses to immune checkpoint inhibitors (ICIs), comparing mono- (mono) and combo-immunotherapy (combo) in patients with microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) by analyzing quantitative imaging data and clinical factors. METHODS: One hundred fifty patients were included from two centers and divided into training (n = 105) and validation (n = 45) cohorts. Radiologists manually annotated chest-abdomen-pelvis computed tomography and calculated tumor burden. Progression-free survival (PFS) was assessed, and variables were selected through Recursive Feature Elimination. Cutoff values were determined using maximally selected rank statistics to binarize features, forming a risk score with hazard ratio-derived weights. RESULTS: In total, 2258 lesions were annotated with excellent reproducibility. Key variables in the training cohort included: total tumor volume (cutoff: 73 cm3), lesion count (cutoff: 20), age (cutoff: 60) and the presence of peritoneal carcinomatosis. Their respective weights were 1.13, 0.96, 0.91, and 0.38, resulting in a risk score cutoff of 1.36. Low-score patients showed similar overall survival and PFS regardless of treatment, while those with a high-score had significantly worse survivals with mono vs combo (P = 0.004 and P = 0.0001). In the validation set, low-score patients exhibited no significant difference in overall survival and PFS with mono or combo. However, patients with a high-score had worse PFS with mono (P = 0.046). CONCLUSIONS: A score based on total tumor volume, lesion count, the presence of peritoneal carcinomatosis, and age can guide MSI-H mCRC treatment decisions, allowing oncologists to identify suitable candidates for mono and combo ICI therapies.

EFSUMB Technical Review - Update 2023: Dynamic Contrast-Enhanced Ultrasound (DCE-CEUS) for the Quantification of Tumor Perfusion.

Dynamic contrast-enhanced ultrasound (DCE-US) is a technique to quantify tissue perfusion based on phase-specific enhancement after the injection of microbubble contrast agents for diagnostic ultrasound. The guidelines of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) published in 2004 and updated in 2008, 2011, and 2020 focused on the use of contrast-enhanced ultrasound (CEUS), including essential technical requirements, training, investigational procedures and steps, guidance regarding image interpretation, established and recommended clinical indications, and safety considerations. However, the quantification of phase-specific enhancement patterns acquired with ultrasound contrast agents (UCAs) is not discussed here. The purpose of this EFSUMB Technical Review is to further establish a basis for the standardization of DCE-US focusing on treatment monitoring in oncology. It provides some recommendations and descriptions as to how to quantify dynamic ultrasound contrast enhancement, and technical explanations for the analysis of time-intensity curves (TICs). This update of the 2012 EFSUMB introduction to DCE-US includes clinical aspects for data collection, analysis, and interpretation that have emerged from recent studies. The current study not only aims to support future work in this research field but also to facilitate a transition to clinical routine use of DCE-US.

BR55 Ultrasound Molecular Imaging of Clear Cell Renal Cell Carcinoma Reflects Tumor Vascular Expression of VEGFR-2 in a Patient-Derived Xenograft Model.

Standard imaging cannot reliably predict the nature of renal tumors. Among malignant renal tumors, clear cell renal cell carcinoma (ccRCC) is the most common histological subtype, in which the vascular endothelial growth factor 2 (VEGFR-2) is highly expressed in the vascular endothelium. BR55, a contrast agent for ultrasound imaging, consists of gas-core lipid microbubbles that specifically target and bind to the extracellular portion of the VEGFR-2. The specific information provided by ultrasound molecular imaging (USMI) using BR55 was compared with the vascular tumor expression of the VEGFR-2 by immunohistochemical (IHC) staining in a preclinical model of ccRCC. Patients' ccRCCs were orthotopically grafted onto Nod-Scid-Gamma (NSG) mice to generate patient-derived xenografts (PdX). Mice were divided into four groups to receive either vehicle or axitinib an amount of 2, 7.5 or 15 mg/kg twice daily. Perfusion parameters and the BR55 ultrasound contrast signal on PdX renal tumors were analyzed at D0, D1, D3, D7 and D11, and compared with IHC staining for the VEGFR-2 and CD34. Significant Pearson correlation coefficients were observed between the area under the curve (AUC) and the CD34 (0.84, p < 10-4), and between the VEGFR-2-specific signal obtained by USMI and IHC (0.72, p < 10-4). USMI with BR55 could provide instant, quantitative information on tumor VEGFR-2 expression to characterize renal masses non-invasively.

Synergic prognostic value of 3D CT scan subcutaneous fat and muscle masses for immunotherapy-treated cancer.

BACKGROUND: Our aim was to explore the prognostic value of anthropometric parameters in a large population of patients treated with immunotherapy. METHODS: We retrospectively included 623 patients with advanced non-small cell lung cancer (NSCLC) (n=318) or melanoma (n=305) treated by an immune-checkpoint-inhibitor having a pretreatment (thorax-)abdomen-pelvis CT scan. An external validation cohort of 55 patients with NSCLC was used. Anthropometric parameters were measured three-dimensionally (3D) by a deep learning software (Anthropometer3DNet) allowing an automatic multislice measurement of lean body mass, fat body mass (FBM), muscle body mass (MBM), visceral fat mass (VFM) and sub-cutaneous fat mass (SFM). Body mass index (BMI) and weight loss (WL) were also retrieved. Receiver operator characteristic (ROC) curve analysis was performed and overall survival was calculated using Kaplan-Meier (KM) curve and Cox regression analysis. RESULTS: In the overall cohort, 1-year mortality rate was 0.496 (95% CI: 0.457 to 0.537) for 309 events and 5-year mortality rate was 0.196 (95% CI: 0.165 to 0.233) for 477 events. In the univariate Kaplan-Meier analysis, prognosis was worse (p<0.001) for patients with low SFM (<3.95 kg/m2), low FBM (<3.26 kg/m2), low VFM (<0.91 kg/m2), low MBM (<5.85 kg/m2) and low BMI (<24.97 kg/m2). The same parameters were significant in the Cox univariate analysis (p<0.001) and, in the multivariate stepwise Cox analysis, the significant parameters were MBM (p<0.0001), SFM (0.013) and WL (0.0003). In subanalyses according to the type of cancer, all body composition parameters were statistically significant for NSCLC in ROC, KM and Cox univariate analysis while, for melanoma, none of them, except MBM, was statistically significant. In multivariate Cox analysis, the significant parameters for NSCLC were MBM (HR=0.81, p=0.0002), SFM (HR=0.94, p=0.02) and WL (HR=1.06, p=0.004). For NSCLC, a KM analysis combining SFM and MBM was able to separate the population in three categories with the worse prognostic for the patients with both low SFM (<5.22 kg/m2) and MBM (<6.86 kg/m2) (p<0001). On the external validation cohort, combination of low SFM and low MBM was pejorative with 63% of mortality at 1 year versus 25% (p=0.0029). CONCLUSIONS: 3D measured low SFM and MBM are significant prognosis factors of NSCLC treated by immune checkpoint inhibitors and can be combined to improve the prognostic value.

New calibration setup for quantitative DCE-US imaging protocol: Toward standardization.

BACKGROUND: The DCE-US (Dynamic Contrast-Enhanced Ultrasonography) imaging protocol predicts the vascular modifications compared with Response Evaluation Criteria in Solid Tumors (RECIST) based mainly on morphological changes. A quantitative biomarker has been validated through the DCE-US multi-centric study for early monitoring of the efficiency of anti-angiogenic cancer treatments. In this context, the question of transposing the use of this biomarker to other types of ultrasound scanners, probes and settings has arisen to maintain the follow-up of patients under anti-angiogenic treatments. As a consequence, radiologists encounter standardization issues between the different generations of ultrasound scanners to perform quantitative imaging protocols. PURPOSE: The aim of this study was to develop a new calibration setup to transpose the DCE-US imaging protocol to the new generation of ultrasound scanners using both abdominal and linear probes. METHODS: This calibration method has been designed to be easily reproducible and optimized, reducing the time required and cost incurred. It is based on an original set-up that includes using a concentration splitter to measure the variation of the harmonic signal intensity, obtained from the Area Under the time-intensity Curve (AUC) as a function of various contrast-agent concentrations. The splitter provided four different concentrations simultaneously ranging from 12.5% to 100% of the initial concentration of the SonoVue contrast agent (Bracco Imaging S.p.A., Milan, Italy), therefore, measuring four AUCs in a single injection. The plot of the AUC as a function of the four contrast agent concentrations represents the intensity variation of the harmonic signal: the slope being the calibration parameter. The standardization through this method implied that both generations of ultrasound scanners had to have the same slopes to be considered as calibrated. This method was tested on two ultrasound scanners from the same manufacturer (Aplio500, Aplioi900, Canon Medical Systems, Tokyo, Japan). The Aplio500 used the settings defined by the initial multicenter DCE-US study. The Mechanical Index (MI) and the Color Gain (CG) of the Aplioi900 have been adjusted to match those of the Aplio500. The reliability of the new setup was evaluated in terms of measurement repeatability, and reproducibility with the agreement between the measurements obtained once the two ultrasound scanners were calibrated. RESULTS: The new setup provided excellent repeatability measurements with a value of 96.8%. Once the two ultrasound scanners have been calibrated for both types of probes, the reproducibility was excellent with the agreement between their respective quantitative measurement was at the lowest 95.4% and at the best 98.8%. The settings of the Aplioi900 (Canon Medical Systems) were adjusted to match those of the Aplio500 (Canon Medical Systems) and these validated settings were for the abdominal probe: MI = 0.13 and CG = 34 dB; and for the linear probe: MI = 0.10 and CG = 38 dB. CONCLUSION: This new calibration setup provided reliable measurements and enabled the rapid transfer and the use of the DCE-US imaging protocol on new ultrasound scanners, thus permitting a continuation of the therapeutic evaluation of patients through quantitative imaging.

Synthetic MR image generation of macrotrabecular-massive hepatocellular carcinoma using generative adversarial networks.

PURPOSE: The purpose of this study was to develop a method for generating synthetic MR images of macrotrabecular-massive hepatocellular carcinoma (MTM-HCC). MATERIALS AND METHODS: A set of abdominal MR images including fat-saturated T1-weighted images obtained during the arterial and portal venous phases of enhancement and T2-weighted images of 91 patients with MTM-HCC, and another set of MR abdominal images from 67 other patients were used. Synthetic images were obtained using a 3-step pipeline that consisted in: (i), generating a synthetic MTM-HCC tumor on a neutral background; (ii), randomly selecting a background among the 67 patients and a position inside the liver; and (iii), merging the generated tumor in the background at the specified location. Synthetic images were qualitatively evaluated by three radiologists and quantitatively assessed using a mix of 1-nearest neighbor classifier metric and Fréchet inception distance. RESULTS: A set of 1000 triplets of synthetic MTM-HCC images with consistent contrasts were successfully generated. Evaluation of selected synthetic images by three radiologists showed that the method gave realistic, consistent and diversified images. Qualitative and quantitative evaluation led to an overall score of 0.64. CONCLUSION: This study shows the feasibility of generating realistic synthetic MR images with very few training data, by leveraging the wide availability of liver backgrounds. Further studies are needed to assess the added value of those synthetic images for automatic diagnosis of MTM-HCC.

Body Composition to Define Prognosis of Cancers Treated by Anti-Angiogenic Drugs.

Background: Body composition could help to better define the prognosis of cancers treated with anti-angiogenics. The aim of this study is to evaluate the prognostic value of 3D and 2D anthropometric parameters in patients given anti-angiogenic treatments. Methods: 526 patients with different types of cancers were retrospectively included. The software Anthropometer3DNet was used to measure automatically fat body mass (FBM3D), muscle body mass (MBM3D), visceral fat mass (VFM3D) and subcutaneous fat mass (SFM3D) in 3D computed tomography. For comparison, equivalent two-dimensional measurements at the L3 level were also measured. The area under the curve (AUC) of the receiver operator characteristics (ROC) was used to determine the parameters' predictive power and optimal cut-offs. A univariate analysis was performed using Kaplan−Meier on the overall survival (OS). Results: In ROC analysis, all 3D parameters appeared statistically significant: VFM3D (AUC = 0.554, p = 0.02, cutoff = 0.72 kg/m2), SFM3D (AUC = 0.544, p = 0.047, cutoff = 3.05 kg/m2), FBM3D (AUC = 0.550, p = 0.03, cutoff = 4.32 kg/m2) and MBM3D (AUC = 0.565, p = 0.007, cutoff = 5.47 kg/m2), but only one 2D parameter (visceral fat area VFA2D AUC = 0.548, p = 0.034). In log-rank tests, low VFM3D (p = 0.014), low SFM3D (p < 0.0001), low FBM3D (p = 0.00019) and low VFA2D (p = 0.0063) were found as a significant risk factor. Conclusion: automatic and 3D body composition on pre-therapeutic CT is feasible and can improve prognostication in patients treated with anti-angiogenic drugs. Moreover, the 3D measurements appear to be more effective than their 2D counterparts.

Better than RECIST and Faster than iRECIST: Defining the Immunotherapy Progression Decision Score to Better Manage Progressive Tumors on Immunotherapy.

PURPOSE: The objective of the study is to propose the immunotherapy progression decision (iPD) score, a practical tool based on patient features that are available at the first evaluation of immunotherapy treatment, to help oncologists decide whether to continue the treatment or switch rapidly to another therapeutic line when facing a progressive disease patient at the first evaluation. EXPERIMENTAL DESIGN: This retrospective study included 107 patients with progressive disease at first evaluation according to RECIST 1.1. Clinical, radiological, and biological data at baseline and first evaluation were analyzed. An external validation set consisting of 31 patients with similar baseline characteristics was used for the validation of the score. RESULTS: Variables were analyzed in a univariate study. The iPD score was constructed using only independent variables, each considered as a worsening factor for the survival of patients. The patients were stratified in three groups: good prognosis (GP), poor prognosis (PP), and critical prognosis (CP). Each group showed significantly different survivals (GP: 11.4, PP: 4.4, CP: 2.3 months median overall survival, P < 0.001, log-rank test). Moreover, the iPD score was able to detect the pseudoprogressors better than other scores. On the validation set, CP patients had significantly worse survival than PP and GP patients (P < 0.05, log-rank test). CONCLUSIONS: The iPD score provides oncologists with a new evaluation, computable at first progression, to decide whether treatment should be continued (for the GP group), or immediately changed for the PP and CP groups. Further validation on larger cohorts is needed to prove its efficacy in clinical practice.

Influence of Different Measurement Methods of Arterial Input Function on Quantitative Dynamic Contrast-Enhanced MRI Parameters in Head and Neck Cancer.

BACKGROUND: Head and neck cancer (HNC) is the sixth most prevalent cancer worldwide. Dynamic contrast-enhanced MRI (DCE-MRI) helps in diagnosis and prognosis. Quantitative DCE-MRI requires an arterial input function (AIF), which affects the values of pharmacokinetic parameters (PKP). PURPOSE: To evaluate influence of four individual AIF measurement methods on quantitative DCE-MRI parameters values (Ktrans , ve , kep , and vp ), for HNC and muscle. STUDY TYPE: Prospective. POPULATION: A total of 34 HNC patients (23 males, 11 females, age range 24-91) FIELD STRENGTH/SEQUENCE: A 3 T; 3D SPGR gradient echo sequence with partial saturation of inflowing spins. ASSESSMENT: Four AIF methods were applied: automatic AIF (AIFa) with up to 50 voxels selected from the whole FOV, manual AIF (AIFm) with four voxels selected from the internal carotid artery, both conditions without (Mc-) or with (Mc+) motion correction. Comparison endpoints were peak AIF values, PKP values in tumor and muscle, and tumor/muscle PKP ratios. STATISTICAL TESTS: Nonparametric Friedman test for multiple comparisons. Nonparametric Wilcoxon test, without and with Benjamini Hochberg correction, for pairwise comparison of AIF peak values and PKP values for tumor, muscle and tumor/muscle ratio, P value ≤ 0.05 was considered statistically significant. RESULTS: Peak AIF values differed significantly for all AIF methods, with mean AIFmMc+ peaks being up to 66.4% higher than those for AIFaMc+. Almost all PKP values were significantly higher for AIFa in both, tumor and muscle, up to 76% for mean Ktrans values. Motion correction effect was smaller. Considering tumor/muscle parameter ratios, most differences were not significant (0.068 ≤ Wilcoxon P value ≤ 0.8). DATA CONCLUSION: We observed important differences in PKP values when using either AIFa or AIFm, consequently choice of a standardized AIF method is mandatory for DCE-MRI on HNC. From the study findings, AIFm and inflow compensation are recommended. The use of the tumor/muscle PKP ratio should be of interest for multicenter studies. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Outcomes of mandibular reconstruction using three-dimensional custom-made porous titanium prostheses.

BACKGROUND: Our aim was to report the long-term outcomes of mandibular reconstruction using CAD-CAM-designed 3D-printed porous titanium implants in patients not amenable to a free vascularized fibula flap reconstruction. METHODS: The implants were designed with ProPlan CMF® 2.2 software and manufactured with a Selective Laser Melting (SLM) "layer-by-layer" 3D-printing of pure porous titanium powder beds. Primary endpoints were implant exposure and implant removal calculated using Gray's tests. Secondary endpoints were predictive factors of implant exposure and implant removal, and rates of dental rehabilitation. RESULTS: Thirty-six patients were operated between 2015 and 2017 and were included in this study. Reconstruction using a porous titanium 3D-printed implant was proposed due to medical contraindication for a fibula free flap (n = 13), due to the failure of a previous fibula free flap reconstruction (n = 7), or due to refusal of a fibula free flap reconstruction by the patient (n = 16). The medical indications for mandibular reconstruction were a primary tumor requiring mandibulectomy in nine patients, mandibular osteoradionecrosis requiring mandibulectomy in nineteen patients, and secondary reconstruction in eight patients. The 2-year rates of implant exposure and implant removal were 69.4% and 52.8%. Reconstruction of the symphysis was a high-risk exposure variable (OR 30; p = 0.0003). Only one patient underwent a successful dental rehabilitation. CONCLUSION: The use of a porous titanium 3D- implant for mandibular reconstruction in head and neck cancer patients resulted in high rates of implant exposure and of implant removal, notably when symphysis involvement.

Generative adversarial networks (GAN)-based data augmentation of rare liver cancers: The SFR 2021 Artificial Intelligence Data Challenge.

PURPOSE: The 2021 edition of the Artificial Intelligence Data Challenge was organized by the French Society of Radiology together with the Centre National d'Études Spatiales and CentraleSupélec with the aim to implement generative adversarial networks (GANs) techniques to provide 1000 magnetic resonance imaging (MRI) cases of macrotrabecular-massive (MTM) hepatocellular carcinoma (HCC), a rare and aggressive subtype of HCC, generated from a limited number of real cases from multiple French centers. MATERIALS AND METHODS: A dedicated platform was used by the seven inclusion centers to securely upload their anonymized MRI examinations including all three cross-sectional images (one late arterial and one portal-venous phase T1-weighted images and one fat-saturated T2-weighted image) in compliance with general data protection regulation. The quality of the database was checked by experts and manual delineation of the lesions was performed by the expert radiologists involved in each center. Multidisciplinary teams competed between October 11th, 2021 and February 13th, 2022. RESULTS: A total of 91 MTM-HCC datasets of three images each were collected from seven French academic centers. Six teams with a total of 28 individuals participated in this challenge. Each participating team was asked to generate one thousand 3-image cases. The qualitative evaluation was performed by three radiologists using the Likert scale on ten randomly selected cases generated by each participant. A quantitative evaluation was also performed using two metrics, the Frechet inception distance and a leave-one-out accuracy of a 1-Nearest Neighbor algorithm. CONCLUSION: This data challenge demonstrates the ability of GANs techniques to generate a large number of images from a small sample of imaging examinations of a rare malignant tumor.

Predicting immunotherapy outcomes in patients with MSI tumors using NLR and CT global tumor volume.

Background: Anti-PD-(L)1 treatment is indicated for patients with mismatch repair-deficient (MMRD) tumors, regardless of tumor origin. However, the response rate is highly heterogeneous across MMRD tumors. The objective of the study is to find a score that predicts anti-PD-(L)1 response in patients with MMRD tumors. Methods: Sixty-one patients with various origin of MMRD tumors and treated with anti-PD-(L)1 were retrospectively included in this study. An expert radiologist annotated all tumors present at the baseline and first evaluation CT-scans for all the patients by circumscribing them on their largest axial axis (single slice), allowing us to compute an approximation of their tumor volume. In total, 2120 lesions were annotated, which led to the computation of the total tumor volume for each patient. The RECIST sum of target lesions' diameters and neutrophile-to-lymphocyte (NLR) were also reported at both examinations. These parameters were determined at baseline and first evaluation and the variation between the first evaluation and baseline was calculated, to determine a comprehensive score for overall survival (OS) and progression-free survival (PFS). Results: Total tumor volume at baseline was found to be significantly correlated to the OS (p-value: 0.005) and to the PFS (p-value:<0.001). The variation of the RECIST sum of target lesions' diameters, total tumor volume and NLR were found to be significantly associated to the OS (p-values:<0.001, 0.006,<0.001 respectively) and to the PFS (<0.001,<0.001, 0.007 respectively). The concordance score combining total tumor volume and NLR variation was better at stratifying patients compared to the tumor volume or NLR taken individually according to the OS (pairwise log-rank test p-values: 0.033,<0.001, 0.002) and PFS (pairwise log-rank test p-values: 0.041,<0.001, 0.003). Conclusion: Total tumor volume appears to be a prognostic biomarker of anti-PD-(L)1 response to immunotherapy in metastatic patients with MMRD tumors. Combining tumor volume and NLR with a simple concordance score stratifies patients well according to their survival and offers a good predictive measure of response to immunotherapy.

An artificial intelligence model predicts the survival of solid tumour patients from imaging and clinical data.

BACKGROUND: The need for developing new biomarkers is increasing with the emergence of many targeted therapies. Artificial Intelligence (AI) algorithms have shown great promise in the medical imaging field to build predictive models. We developed a prognostic model for solid tumour patients using AI on multimodal data. PATIENTS AND METHODS: Our retrospective study included examinations of patients with seven different cancer types performed between 2003 and 2017 in 17 different hospitals. Radiologists annotated all metastases on baseline computed tomography (CT) and ultrasound (US) images. Imaging features were extracted using AI models and used along with the patients' and treatments' metadata. A Cox regression was fitted to predict prognosis. Performance was assessed on a left-out test set with 1000 bootstraps. RESULTS: The model was built on 436 patients and tested on 196 patients (mean age 59, IQR: 51-6, 411 men out of 616 patients). On the whole, 1147 US images were annotated with lesions delineation, and 632 thorax-abdomen-pelvis CTs (total of 301,975 slices) were fully annotated with a total of 9516 lesions. The developed model reaches an average concordance index of 0.71 (0.67-0.76, 95% CI). Using the median predicted risk as a threshold value, the model is able to significantly (log-rank test P value < 0.001) isolate high-risk patients from low-risk patients (respective median OS of 11 and 31 months) with a hazard ratio of 3.5 (2.4-5.2, 95% CI). CONCLUSION: AI was able to extract prognostic features from imaging data, and along with clinical data, allows an accurate stratification of patients' prognoses.

Posterior Reversible Encephalopathy Syndrome Following Chemotherapy and Immune Checkpoint Inhibitor Combination in a Patient with Small-Cell Lung Cancer.

Posterior reversible encephalopathy syndrome (PRES) is a rare neurological complication that occurs following a sudden blood pressure increase. We report the case of a 64-year-old patient presenting PRES several hours after the administration of a combination of chemotherapy and a checkpoint inhibitor (carboplatin-etoposide-atezolizumab) for small-cell lung cancer. He presented consciousness disorders associated with partial epileptic seizure secondarily generalized. His arterial blood pressure was elevated and brain imaging showed multiple bilateral subcortical parietal, temporal, occipital and cerebellar T2 high signals, predominantly in the posterior region. There were no abnormal T1 signals nor bleeding but a left apparent diffusion coefficient restriction was noted. On arterial spin labelling perfusion sequences, there was an increased perfusion within the left temporo-parieto-occipital, left thalamic and right cerebellar regions. Finally, the neurological symptoms completely regressed after several days of optimal antihypertensive and antiepileptic treatment. The clinical context and radiological features, as well as the progressive resolution of the neurological symptoms, were all in favor of PRES. PRES can occur after the administration of chemotherapy and/or immunotherapy. Prompt diagnosis is crucial through a spectrum of suspicious clinical and radiological characteristics that must be rapidly recognized to quickly anticipate the optimal therapeutic strategy and avoid unnecessary complications.

Events prediction after treatment in HPV-driven oropharyngeal carcinoma using machine learning.

OBJECTIVES: Our objective was to develop a predictive model using a machine learning signature to identify patients at high risk of relapse or death after treatment for HPV-positive oropharyngeal carcinoma. MATERIALS AND METHODS: Pre-treatment variables of 450 patients with HPV-positive oropharyngeal carcinoma treated with a curative intent comprised clinical items, imaging parameters and histological findings. The events considered were progression or residual disease after treatment, the recurrent disease after a disease-free interval and death. The endpoints were the prediction of events and progression-free survival. After feature Z-score normalisation and selection, random forest classifier models were trained. The best models were evaluated on recall, the F-score, and the ROC AUC metric. The clinical relevance of the best prediction model was evaluated using Kaplan-Meier analysis with a log-rank test. RESULTS: The best random forest model predicted the 5-year risk of relapse-free survival with a recall of 79.1%, an F1-score of 81.08%, and an AUC of the ROC curve of 0.89. The models performed poorly for the prediction of specific events of progression only, recurrence only or death only. The clinical relevance of the model was validated with a 5-year relapse-free survival of high-risk patients versus low-risk patients of 23.5% and 80%, respectively (p < 0.0001). CONCLUSION: Patients with HPV-driven oropharyngeal carcinoma at high risk of relapse-free survival could be identified with a predictive machine learning model using patient data before treatment.

Quantification and reduction of cross-vendor variation in multicenter DWI MR imaging: results of the Cancer Core Europe imaging task force.

OBJECTIVES: In the Cancer Core Europe Consortium (CCE), standardized biomarkers are required for therapy monitoring oncologic multicenter clinical trials. Multiparametric functional MRI and particularly diffusion-weighted MRI offer evident advantages for noninvasive characterization of tumor viability compared to CT and RECIST. A quantification of the inter- and intraindividual variation occurring in this setting using different hardware is missing. In this study, the MRI protocol including DWI was standardized and the residual variability of measurement parameters quantified. METHODS: Phantom and volunteer measurements (single-shot T2w and DW-EPI) were performed at the seven CCE sites using the MR hardware produced by three different vendors. Repeated measurements were performed at the sites and across the sites including a traveling volunteer, comparing qualitative and quantitative ROI-based results including an explorative radiomics analysis. RESULTS: For DWI/ADC phantom measurements using a central post-processing algorithm, the maximum deviation could be decreased to 2%. However, there is no significant difference compared to a decentralized ADC value calculation at the respective MRI devices. In volunteers, the measurement variation in 2 repeated scans did not exceed 11% for ADC and is below 20% for single-shot T2w in systematic liver ROIs. The measurement variation between sites amounted to 20% for ADC and < 25% for single-shot T2w. Explorative radiomics classification experiments yield better results for ADC than for single-shot T2w. CONCLUSION: Harmonization of MR acquisition and post-processing parameters results in acceptable standard deviations for MR/DW imaging. MRI could be the tool in oncologic multicenter trials to overcome the limitations of RECIST-based response evaluation. KEY POINTS: • Harmonizing acquisition parameters and post-processing homogenization, standardized protocols result in acceptable standard deviations for multicenter MR-DWI studies. • Total measurement variation does not to exceed 11% for ADC in repeated measurements in repeated MR acquisitions, and below 20% for an identical volunteer travelling between sites. • Radiomic classification experiments were able to identify stable features allowing for reliable discrimination of different physiological tissue samples, even when using heterogeneous imaging data.

From Dose Reduction to Contrast Maximization: Can Deep Learning Amplify the Impact of Contrast Media on Brain Magnetic Resonance Image Quality? A Reader Study.

OBJECTIVES: The aim of this study was to evaluate a deep learning method designed to increase the contrast-to-noise ratio in contrast-enhanced gradient echo T1-weighted brain magnetic resonance imaging (MRI) acquisitions. The processed images are quantitatively evaluated in terms of lesion detection performance. MATERIALS AND METHODS: A total of 250 multiparametric brain MRIs, acquired between November 2019 and March 2021 at Gustave Roussy Cancer Campus (Villejuif, France), were considered for inclusion in this retrospective monocentric study. Independent training (107 cases; age, 55 ± 14 years; 58 women) and test (79 cases; age, 59 ± 14 years; 41 women) samples were defined. Patients had glioma, brain metastasis, meningioma, or no enhancing lesion. Gradient echo and turbo spin echo with variable flip angles postcontrast T1 sequences were acquired in all cases. For the cases that formed the training sample, "low-dose" postcontrast gradient echo T1 images using 0.025 mmol/kg injections of contrast agent were also acquired. A deep neural network was trained to synthetically enhance the low-dose T1 acquisitions, taking standard-dose T1 MRI as reference. Once trained, the contrast enhancement network was used to process the test gradient echo T1 images. A read was then performed by 2 experienced neuroradiologists to evaluate the original and processed T1 MRI sequences in terms of contrast enhancement and lesion detection performance, taking the turbo spin echo sequences as reference. RESULTS: The processed images were superior to the original gradient echo and reference turbo spin echo T1 sequences in terms of contrast-to-noise ratio (44.5 vs 9.1 and 16.8; P < 0.001), lesion-to-brain ratio (1.66 vs 1.31 and 1.44; P < 0.001), and contrast enhancement percentage (112.4% vs 85.6% and 92.2%; P < 0.001) for cases with enhancing lesions. The overall image quality of processed T1 was preferred by both readers (graded 3.4/4 on average vs 2.7/4; P < 0.001). Finally, the proposed processing improved the average sensitivity of gradient echo T1 MRI from 88% to 96% for lesions larger than 10 mm ( P = 0.008), whereas no difference was found in terms of the false detection rate (0.02 per case in both cases; P > 0.99). The same effect was observed when considering all lesions larger than 5 mm: sensitivity increased from 70% to 85% ( P < 0.001), whereas false detection rates remained similar (0.04 vs 0.06 per case; P = 0.48). With all lesions included regardless of their size, sensitivities were 59% and 75% for original and processed T1 images, respectively ( P < 0.001), and the corresponding false detection rates were 0.05 and 0.14 per case, respectively ( P = 0.06). CONCLUSION: The proposed deep learning method successfully amplified the beneficial effects of contrast agent injection on gradient echo T1 image quality, contrast level, and lesion detection performance. In particular, the sensitivity of the MRI sequence was improved by up to 16%, whereas the false detection rate remained similar.

Radiomics-Based Method for Predicting the Glioma Subtype as Defined by Tumor Grade, IDH Mutation, and 1p/19q Codeletion.

Gliomas are among the most common types of central nervous system (CNS) tumors. A prompt diagnosis of the glioma subtype is crucial to estimate the prognosis and personalize the treatment strategy. The objective of this study was to develop a radiomics pipeline based on the clinical Magnetic Resonance Imaging (MRI) scans to noninvasively predict the glioma subtype, as defined based on the tumor grade, isocitrate dehydrogenase (IDH) mutation status, and 1p/19q codeletion status. A total of 212 patients from the public retrospective The Cancer Genome Atlas Low Grade Glioma (TCGA-LGG) and The Cancer Genome Atlas Glioblastoma Multiforme (TCGA-GBM) datasets were used for the experiments and analyses. Different settings in the radiomics pipeline were investigated to improve the classification, including the Z-score normalization, the feature extraction strategy, the image filter applied to the MRI images, the introduction of clinical information, ComBat harmonization, the classifier chain strategy, etc. Based on numerous experiments, we finally reached an optimal pipeline for classifying the glioma tumors. We then tested this final radiomics pipeline on the hold-out test data with 51 randomly sampled random seeds for reliable and robust conclusions. The results showed that, after tuning the radiomics pipeline, the mean AUC improved from 0.8935 (±0.0351) to 0.9319 (±0.0386), from 0.8676 (±0.0421) to 0.9283 (±0.0333), and from 0.6473 (±0.1074) to 0.8196 (±0.0702) in the test data for predicting the tumor grade, IDH mutation, and 1p/19q codeletion status, respectively. The mean accuracy for predicting the five glioma subtypes also improved from 0.5772 (±0.0816) to 0.6716 (±0.0655). Finally, we analyzed the characteristics of the radiomic features that best distinguished the glioma grade, the IDH mutation, and the 1p/19q codeletion status, respectively. Apart from the promising prediction of the glioma subtype, this study also provides a better understanding of the radiomics model development and interpretability. The results in this paper are replicable with our python codes publicly available in github.

Prediction of Early Response to Immunotherapy: DCE-US as a New Biomarker.

PURPOSE: The objective of our study is to propose fast, cost-effective, convenient, and effective biomarkers using the perfusion parameters from dynamic contrast-enhanced ultrasound (DCE-US) for the evaluation of immune checkpoint inhibitors (ICI) early response. METHODS: The retrospective cohort used in this study included 63 patients with metastatic cancer eligible for immunotherapy. DCE-US was performed at baseline, day 8 (D8), and day 21 (D21) after treatment onset. A tumor perfusion curve was modeled on these three dates, and change in the seven perfusion parameters was measured between baseline, D8, and D21. These perfusion parameters were studied to show the impact of their variation on the overall survival (OS). RESULTS: After the removal of missing or suboptimal DCE-US, the Baseline-D8, the Baseline-D21, and the D8-D21 groups included 37, 53, and 33 patients, respectively. A decrease of more than 45% in the area under the perfusion curve (AUC) between baseline and D21 was significantly associated with better OS (p = 0.0114). A decrease of any amount in the AUC between D8 and D21 was also significantly associated with better OS (p = 0.0370). CONCLUSION: AUC from DCE-US looks to be a promising new biomarker for fast, effective, and convenient immunotherapy response evaluation.

Can Deep Learning Replace Gadolinium in Neuro-Oncology?: A Reader Study.

MATERIALS AND METHODS: This monocentric retrospective study leveraged 200 multiparametric brain MRIs acquired between November 2019 and February 2020 at Gustave Roussy Cancer Campus (Villejuif, France). A total of 145 patients were included: 107 formed the training sample (55 ± 14 years, 58 women) and 38 the separate test sample (62 ± 12 years, 22 women). Patients had glioma, brain metastases, meningioma, or no enhancing lesion. T1, T2-FLAIR, diffusion-weighted imaging, low-dose, and standard-dose postcontrast T1 sequences were acquired. A deep network was trained to process the precontrast and low-dose sequences to predict "virtual" surrogate images for contrast-enhanced T1. Once trained, the deep learning method was evaluated on the test sample. The discrepancies between the predicted virtual images and the standard-dose MRIs were qualitatively and quantitatively evaluated using both automated voxel-wise metrics and a reader study, where 2 radiologists graded image qualities and marked all visible enhancing lesions. RESULTS: The automated analysis of the test brain MRIs computed a structural similarity index of 87.1% ± 4.8% between the predicted virtual sequences and the reference contrast-enhanced T1 MRIs, a peak signal-to-noise ratio of 31.6 ± 2.0 dB, and an area under the curve of 96.4% ± 3.1%. At Youden's operating point, the voxel-wise sensitivity (SE) and specificity were 96.4% and 94.8%, respectively. The reader study found that virtual images were preferred to standard-dose MRI in terms of image quality (P = 0.008). A total of 91 reference lesions were identified in the 38 test T1 sequences enhanced with full dose of contrast agent. On average across readers, the brain lesion SE of the virtual images was 83% for lesions larger than 10 mm (n = 42), and the associated false detection rate was 0.08 lesion/patient. The corresponding positive predictive value of detected lesions was 92%, and the F1 score was 88%. Lesion detection performance, however, dropped when smaller lesions were included: average SE was 67% for lesions larger than 5 mm (n = 74), and 56% with all lesions included regardless of their size. The false detection rate remained below 0.50 lesion/patient in all cases, and the positive predictive value remained above 73%. The composite F1 score was 63% at worst. CONCLUSIONS: The proposed deep learning method for virtual contrast-enhanced T1 brain MRI prediction showed very high quantitative performance when evaluated with standard voxel-wise metrics. The reader study demonstrated that, for lesions larger than 10 mm, good detection performance could be maintained despite a 4-fold division in contrast agent usage, unveiling a promising avenue for reducing the gadolinium exposure of returning patients. Small lesions proved, however, difficult to handle for the deep network, showing that full-dose injections remain essential for accurate first-line diagnosis in neuro-oncology.