Value of third-generation of VNCa dual-energy CT for differentiating diffuse marrow infiltration of multiple myeloma from red bone marrow.

This study aims to investigate the ability of bone marrow imaging using third-generation dual-energy computed tomography (CT) virtual noncalcium (VNCa) to differentiate between multiple myeloma (MM) with diffuse bone marrow infiltration and red bone marrow (RBM). Bone marrow aspiration or follow-up results were used as reference. We retrospectively reviewed 188 regions of interests (ROIs) from 21 patients with confirmed MM and diffuse bone marrow infiltrations who underwent VNCa bone marrow imaging between May 2019 and September 2022. At the same time, we obtained 98 ROIs from 11 subjects with RBM for comparative study, and 189 ROIs from 20 subjects with normal yellow bone marrow for the control group. The ROIs were delineated by 2 radiologists independently, the interobservers reproducibility was evaluated by interclass correlation coefficients. The correlation with MRI grade results was analyzed by Spearman correlation coefficient. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal threshold for differentiating between these groups and to assess diagnostic performance. There were statistically significant differences in VNCa CT values of bone marrow among the MM, RBM, and control groups (all P < .001), with values decreasing sequentially. A strong positive rank correlation was observed between normal bone marrow, subgroup MM with moderately and severe bone marrow infiltration divided by MRI and their corresponding CT values (ρ = 0.897, 95%CI: 0.822 to 0.942, P < .001). When the CT value of VNCa bone marrow was 7.15 HU, the area under the curve (AUC) value for differentiating RBM and MM was 0.723, with a sensitivity of 50.5% and a specificity of 89.8%. When distinguishing severe bone marrow infiltration of MM from RBM, the AUC value was 0.80 with a sensitivity 70.9% and a specificity 78.9%. The AUC values for MM, RBM, and the combined group compared to the control group were all >0.99, with all diagnostic sensitivity and specificity exceeding 95%. VNCa bone marrow imaging using third-generation dual-energy CT accurately differentiates MM lesions from normal bone marrow or RBM. It demonstrates superior diagnostic performance in distinguishing RBM from MM with diffuse bone marrow infiltration.

Simulation of cancer progression in bone by a virtual thermal flux with a case study on lumbar vertebrae with multiple myeloma.

BACKGROUND: Two main problems examining the mechanism of cancer progression in the tissues using the computational models are lack of enough knowledge on the effective factors for such events in vivo environments and lack of specific parameters in the available computational models to simulate such complicated reactions. METHODS: In this study, it was tried to simulate the progression of cancerous lesions in the bone tissues by an independent parameter from the anatomical and physiological characteristics of the tissues, so to degrade the orthotropic mechanical properties of the bone tissues, a virtual temperature was determined to be used by a well-known framework for simulation of damages in the composite materials. First, the reliability of the FE model to simulate hyperelastic response in the intervertebral discs (IVDs) and progressive failure in the bony components were verified by simulation of some In-Vitro tests, available in the literature. Then, the progression of the osteolytic damage was simulated in a clinical case with multiple myeloma in the lumbar vertebrae. RESULTS: The FE model could simulate stress-shielding and diffusion of lesion in the posterior elements of the damaged vertebra which led to spinal stenosis. The load carrying shares associated with the anterior half and the posterior half of the examined vertebral body and the posterior elements were estimated equal to 41 %, 47 % and 12 %, respectively for the intact condition, that changed to 14 %, 16 % and 70 %, when lesion occupied one third of the vertebral body. CONCLUSION: Correlation of the FE results with the deformation shapes, observed in the MRIs for the clinical case study, indicated appropriateness of the procedure, proposed for simulation of the progressive osteolytic damage in the vertebral segments. The future studies may follow simulation of tumor growth for various metastatic tissues using the method, established here.

Diagnostic value of LGE and T1 mapping in multiple myeloma patients'heart.

BACKGROUND: Unidentified heart failure occurs in patients with multiple myeloma when their heart was involved. CMR with late gadolinium enhancement (LGE) and T1 mapping can identify myocardial amyloid infiltrations. PURPOSE: To explore the role of CMR with late gadolinium enhancement (LGE) and T1 mapping for detection of multiple myeloma patients'heart. MATERIAL AND METHODS: A total of 16 MM patients with above underwent CMR (3.0-T) with T1 mapping (pre-contrast and post-contrast) and LGE imaging. In addition, 26 patients with non-obstructive hypertrophic cardiomyopathy and 26 healthy volunteers were compared to age- and sex-matched healthy controls without a history of cardiac disease, diabetes mellitus, or normal in CMR. All statistical analyses were performed using the statistical software GraphPad Prism. The measurement data were represented by median (X) and single sample T test was adopted. Enumeration data were represented by examples and Chi-tested was adopted. All tests were two-sided, and P values < 0.05 were considered statistically significant. RESULTS: In MM group, LVEF was lower than healthy controls and higher than that of non-obstructive hypertrophic cardiomyopathy group, but without statistically significant difference (%: 49.1 ± 17.5 vs. 55.6 ± 10.3, 40.4 ± 15.6, all P > 0.05). Pre-contrast T1 values of MM group were obviously higher than those of healthy controls and non-obstructive hypertrophic cardiomyopathy group (ms:1462.0 ± 71.3vs. 1269.3 ± 42.3, 1324.0 ± 45.1, all P < 0.05). 16 cases (100%) in MM group all had LGE. CONCLUSION: LGE joint T1 mapping wider clinical use techniques and follow-up the patients'disease severity.

Expanding Myeloma Training and Care in Western Kenya Through the ECHO Model: The Pilot Phase.

PURPOSE: Multiple myeloma (MM) in rural western Kenya is characterized by under and late diagnosis with poor long-term outcomes. Inadequate skilled rural health care teams are partly to blame. The Extension for Community Healthcare Outcomes (ECHO) model attempts to bridge this skills gap by linking rural primary/secondary health care teams (spokes) to myeloma experts in a tertiary care center (hub) in a longitudinal training program. METHODS: A hub team comprising myeloma experts and administrators from Moi Teaching and Referral Hospital/Academic Model Providing Access to Healthcare was assembled and spoke sites were recruited from rural health care facilities across western Kenya. A curriculum was developed by incorporating input from spokes on their perceived skills gaps in myeloma. Participants joined sessions remotely through virtual meeting technology. ECHO sessions consisted of a spoke-led case presentation with guided discussion followed by an expert-led lecture. An end-of-program survey was used to evaluate participant satisfaction, knowledge, and practice patterns. RESULTS: A total of eight sessions were conducted between April and November 2021 with a median of 40 attendees per session drawn from diverse health care disciplines. Twenty-four spoke sites were identified from 15 counties across western Kenya. The majority of attendees reported satisfaction with the ECHO program (25 of 29) and improvement in their myeloma knowledge (24 of 29). There were 74 new myeloma diagnoses made at the hub site in 2021, representing a 35% increase from the previous 3-year average despite the COVID-19 pandemic that suppressed health care access globally. RECOMMENDATIONS: The pilot ECHO model was successfully implemented in myeloma training for rural-based health care teams. Key attributes included collaborative curriculum development, interactive case-based bidirectional learning, and multidisciplinary engagement.

Chemokine Receptor 4-Targeted PET/CT With 68 Ga-Pentixather Detects More Lesions Than 68 Ga-Pentixafor PET/CT in Multiple Myeloma.

ABSTRACT: An 83-year-old woman with newly diagnosed multiple myeloma (MM) was enrolled in our 68 Ga-pentixather and 68 Ga-pentixafor PET/CT trial for evaluation of tumor burden. 68 Ga-pentixather PET/CT detected more focal bone lesions, and the uptake levels of focal bone lesions on 68 Ga-pentixather PET/CT were higher than those on 68 Ga-pentixafor PET/CT. This suggests that 68 Ga-pentixather PET/CT may be an alternative imaging modality and more sensitive in detecting MM lesions than 68 Ga-pentixafor PET/CT.

The quantitative parameters based on marrow metabolism derived from synthetic MRI: A pilot study of prognostic value in participants with newly diagnosed multiple myeloma.

BACKGROUND: The value of SyMRI-derived parameters from lumbar marrow for predicting early treatment response and optimizing the risk stratification of the Revised International Staging System (R-ISS) in participants with multiple myeloma (MM) is unknown. METHODS: We prospectively enrolled participants with newly diagnosed MM before treatment. The SyMRI of lumbar marrow was used to calculate T1, T2, and PD values and the clinical features were collected. All participants were divided into good response (≥VGPR) and poor response (

Construction and validation of an 18F-FDG-PET/CT-based prognostic model to predict progression-free survival in newly diagnosed multiple myeloma patients.

OBJECTIVE: To investigate the relationship between 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) related parameters and the prognosis of multiple myeloma and to establish and validate a prediction model regarding the progression-free survival (PFS) of multiple myeloma. METHODS: A retrospective analysis of 126 newly diagnosed multiple myeloma patients who attended Nanjing Drum Tower Hospital from 2014-2021. All patients underwent PET/CT before treatment and were divided into a training cohort (n = 75) and a validation cohort (n = 51). Multivariate Cox proportional hazard regression analysis incorporated PET/CT-related parameters and clinical indicators. A nomogram was established to individually predict PFS in MM patients. The model was evaluated by calculating the C-index and calibration curve. RESULTS: Here, 4.2 was used as the cut-off value of SUVmax to divide patients into high and low groups. PFS significantly differed between patients in the high-SUVmax group and low-SUVmax group, and SUVmax was an independent predictor of PFS in newly diagnosed multiple myeloma (NDMM) patients. Univariate and multivariate cox regression analysis suggested that lactate dehydrogenase (LDH), bone marrow plasma cell (BMPC), and SUVmax affected PFS. These factors were incorporated to construct a nomogram model for predicting PFS at 1 and 2 years in NDMM patients. The C-index and calibration curves of the nomogram exhibited good accuracy and consistency, and the DCA curves suggested that the model had good clinical utility. CONCLUSION: The PET/CT parameter SUVmax is closely related to the prognosis of myeloma patients. The nomogram constructed in this study based on PET/CT-related parameters and clinical indicators individually predicts the PFS rate of NDMM patients and enables further risk stratification of NDMM patients.

3D CNN-based Deep Learning Model-based Explanatory Prognostication in Patients with Multiple Myeloma using Whole-body MRI.

Although magnetic resonance imaging (MRI) data of patients with multiple myeloma (MM) are used to predict prognosis, few reports have applied artificial intelligence (AI) techniques for this purpose. We aimed to analyze whole-body diffusion-weighted MRI data using three-dimensional (3D) convolutional neural networks (CNNs) and Gradient-weighted Class Activation Mapping (Grad-CAM), an explainable AI, to predict prognosis and explore the factors involved in prediction. We retrospectively analyzed the MRI data of a total of 142 patients with MM obtained from two medical centers. We defined the occurrence of progressive disease after MRI evaluation within 12 months as a poor prognosis and constructed a 3D CNN-based deep learning model to predict prognosis. Images from 111 cases were used as the training and internal validation data; images from 31 cases were used as the external validation data. Internal validation of the AI model with stratified 5-fold cross-validation resulted in a significant difference in progression-free survival (PFS) between good and poor prognostic cases (2-year PFS, 91.2% versus [vs.] 61.1%, P = 0.0002). The AI model clearly stratified good and poor prognostic cases in the external validation cohort (2-year PFS, 92.9% vs. 55.6%, P = 0.004), with an area under the receiver operating characteristic curve of 0.804. According to Grad-CAM, the MRI signals of the spleen and bones of the vertebrae and pelvis contributed to prognosis prediction. This study is the first to show that image analysis of whole-body MRI using a 3D CNN without any other clinical data is effective in predicting the prognosis of patients with MM.

Development of a whole spinal MRI-based tumor burden scoring method in participants with multiple myeloma: a pilot study of prognostic significance.

The aim of the study was to develop a new whole spinal MRI-based tumor burden scoring method in participants with newly diagnosed multiple myeloma (MM) and to explore its prognostic significance. We prospectively recruited participants with newly diagnosed MM; performed whole spinal MRI (sagittal FSE T1WI, sagittal IDEAL T2WI, and axial FLAIR T2WI) on them; and collected their clinical data, early treatment response, progression-free survival (PFS), and overall survival (OS). We developed a new tumor burden scoring method according to the extent of bone marrow infiltration in five MRI patterns. All participants were divided into good response and poor response groups after four treatment cycles. Univariate, multivariate analyses, and ROC were used to determine the performance of independent predictors. Thresholds for PFS and OS were calculated using X-tile, and their prognostic significance were assessed by Kaplan-Meier. The Kruskal-Wallis H test was used to compare the differences of tumor burden score between the revised International Staging System (R-ISS) stages. The new tumor burden scoring method was used in 62 participants (median score, 12; range, 0-18). The tumor burden score (OR 1.266, p = 0.002) was an independent predictor of poor response and the AUC was 0.838. Higher tumor burden scores were associated with shorter PFS (p = 0.002) and OS (p = 0.011). The tumor burden score was higher in R-ISS-III than in R-ISS-I and R-ISS-II (p = 0.016 and p = 0.006, respectively). The tumor burden score was an excellent predictor of prognosis and may serve as a supplemental marker for R-ISS.

CD38-Specific Gallium-68 Labeled Peptide Radiotracer Enables Pharmacodynamic Monitoring in Multiple Myeloma with PET.

The limited availability of molecularly targeted low-molecular-weight imaging agents for monitoring multiple myeloma (MM)-targeted therapies has been a significant challenge in the field. In response, a first-in-class peptide-based radiotracer, [68Ga]Ga-AJ206, is developed that can be seamlessly integrated into the standard clinical workflow and is specifically designed to noninvasively quantify CD38 levels and pharmacodynamics by positron emission tomography (PET). A bicyclic peptide, AJ206, is synthesized and exhibits high affinity to CD38 (KD: 19.1 ± 0.99 × 10-9 m) by surface plasmon resonance. Further, [68Ga]Ga-AJ206-PET shows high contrast within 60 min and suitable absorbed dose estimates for clinical use. Additionally, [68Ga]Ga-AJ206 detects CD38 expression in cell line-derived xenografts, patient-derived xenografts (PDXs), and disseminated disease models in a manner consistent with flow cytometry and immunohistochemistry findings. Moreover, [68Ga]Ga-AJ206-PET successfully quantifies CD38 pharmacodynamics in PDXs, revealing increased CD38 expression in the tumor following all-trans retinoic acid (ATRA) therapy. In conclusion, [68Ga]Ga-AJ206 exhibits the salient features required for clinical translation, providing CD38-specific high-contrast images in multiple models of MM. [68Ga]Ga-AJ206-PET could be useful for quantifying total CD38 levels and pharmacodynamics during therapy to evaluate approved and new therapies in MM and other diseases with CD38 involvement.

MRI-based bone marrow radiomics for predicting cytogenetic abnormalities in multiple myeloma.

AIM: To develop a radiomics signature applied to magnetic resonance imaging (MRI)-images to predict cytogenetic abnormalities in multiple myeloma (MM). MATERIALS AND METHODS: Patients with newly diagnosed MM were enrolled retrospectively from March 2019 to September 2022. They were categorised into the high-risk cytogenetics (HRC) group and standard-risk cytogenetics (SRC) group. The patients were allocated randomly at a ratio of 7:3 into training and validation cohorts. Volumes of interest (VOI) was drawn manually on fat suppression T2-weighted imaging (FS-T2WI) and copied to the same location of the T1-weighted imaging (T1WI) sequence. Radiomics features were extracted from two sequences and selected by reproducibility and redundant analysis. The least absolute shrinkage selection operation (LASSO) algorithm was applied to build the radiomics signatures. The performance of the radiomics signatures to distinguish HRC with SRC was evaluated by ROC curves. The area under the curve (AUC), specificity, and sensitivity were also calculated. RESULTS: A total of 105 MM patients were enrolled in this study. The four and 11 most significant and relevant features were selected separately from T1WI and FS-T2WI sequences to build the radiomics signatures based on the training cohort. Compared to the T1WI sequence, the radiomics signature based on the FS-T2WI sequence achieved better performance with AUCs of 0.896 and 0.729 in the training and validation cohorts respectively. A sensitivity of 0.833, specificity of 0.667, and Youden index of 0.500 were achieved for the FS-T2WI radiomics signature in the validation cohort. CONCLUSIONS: The radiomics signature based on MRI provides a non-invasive and convenient tool to predict cytogenetic abnormalities in MM patients.

Quantitative assessment of bone marrow infiltration and characterization of tumor burden using dual-layer spectral CT in patients with multiple myeloma.

BACKGROUND: The aim of the study was to evaluate whether virtual calcium subtraction (VNCa) image extracted from dual-layer spectral CT could estimate bone marrow (BM) infiltration with MRI as the reference standard and characterize tumor burden in patients with multiple myeloma (MM). PATIENTS AND METHODS: Forty-seven patients with newly diagnosed MM were retrospectively enrolled. They had undergone whole-body low-dose dual-layer spectral CT (DLCT) and whole-body MRI within one week. VNCa images with calcium-suppressed (CaSupp) indices ranging from 25 to 95 at an interval of 10 and apparent diffusion coefficient (ADC) maps were quantitatively analyzed on vertebral bodies L1-L5 at the central slice of images. The optimal combination was selected by correlation analysis between CT numbers and ADC values. Then, it was used to characterize tumor burden by correlation analysis and receiver operating characteristic (ROC) curves analysis, including plasma cell infiltration rate (PCIR), high serum-free light chains (SFLC) ratio and the high-risk cytogenetic (HRC) status. RESULTS: The most significant quantitative correlation between CT numbers of VNCa images and ADC values could be found at CaSupp index 85 for averaged L1-L5 (r = 0.612, p < 0.001). It allowed quantitative evaluation of PCIR (r = 0.835, p < 0.001). It could also anticipate high SFLC ratio and the HRC status with area under the curve (AUC) of 0.876 and 0.760, respectively. CONCLUSIONS: The VNCa measurements of averaged L1-L5 showed the highest correlation with ADC at CaSupp index 85. It could therefore be used as additional imaging biomarker for non-invasive assessment of tumor burden if ADC is not feasible.

Positron Emission Tomography/Computed Tomography Transformation of Oncology: Multiple Myeloma.

This article provides a comprehensive review of the role of 2-deoxy-2-[18F]fluoro-d-glucose (18F FDG) positron emission tomography/computed tomography (PET/CT) in multiple myeloma (MM) and related plasma cell disorders. MM is a hematologic malignancy characterized by the neoplastic proliferation of plasma cells. 18F FDG PET/CT integrates metabolic and anatomic information, allowing for accurate localization of metabolically active disease. The article discusses the use of 18F FDG PET/CT in initial diagnosis, staging, prognostication, and assessing treatment response. Additionally, it provides valuable insights into the novel imaging targets including chemokine receptor C-X-C motif 4 and CD38.

Microarray-Based CD38 Peptide Probe Screening for Multiple Myeloma Imaging.

Assessing CD38 expression in vivo has become a significant element in multiple myeloma (MM) therapy, as it can be used to detect lesions and forecast the effectiveness of treatment. Accurate diagnosis requires a multifunctional, high-throughput probe screening platform to develop molecular probes for tumor-targeted multimodal imaging and treatment. Here, we investigated a microarray chip-based strategy for high-throughput screening of peptide probes for CD38. We obtained two new target peptides, CA-1 and CA-2, from a 105 peptide library with a dissociation constant (KD) of 10-7 M. The specificity and affinity of the target peptides were confirmed at the molecular and cellular levels. Peptide probes were labeled with indocyanine green (ICG) dye and 68Ga-DOTA, which were injected into a CD38-positive Ramos tumor-bearing mouse via its tail vein, and small animal fluorescence and positron emission tomography (PET) imaging showed that the peptide probes could show specific enrichment in the tumor tissue. Our study shows that a microchip-based screening of peptide probes can be used as a promising imaging tool for MM diagnosis.

The role of conventional and novel PET radiotracers in assessment of myeloma bone disease.

Over 80 % of patients with multiple myeloma (MM) experience osteolytic bone lesions, primarily due to an imbalanced interaction between osteoclasts and osteoblasts. This imbalance can lead to several adverse outcomes such as pain, fractures, limited mobility, and neurological impairments. Myeloma bone disease (MBD) raises the expense of management in addition to being a major source of disability and morbidity in myeloma patients. Whole-body x-ray radiography was the gold standard imaging modality for detecting lytic lesions. Osteolytic lesions are difficult to identify at an earlier stage on X-ray since the lesions do not manifest themselves on conventional radiographs until at least 30 % to 50 % of the bone mass has been destroyed. Hence, early diagnosis of osteolytic lesions necessitates the utilization of more complex and advanced imaging modalities, such as PET. One of the PET radiotracers that has been frequently investigated in MM is 18F-FDG, which has demonstrated a high level of sensitivity and specificity in detecting myeloma lesions. However, 18F-FDG PET/CT has several restrictions, and therefore the novel PET tracers that can overcome the limitations of 18F-FDG PET/CT should be further examined in assessment of MBD. The objective of this review article is to thoroughly examine the significance of both conventional and novel PET radiotracers in the assessment of MBD. The intention is to present the information in a manner that would be easily understood by healthcare professionals from diverse backgrounds, while minimizing the use of complex nuclear medicine terminology.

CD46-Targeted Theranostics for PET and 225Ac-Radiopharmaceutical Therapy of Multiple Myeloma.

PURPOSE: Multiple myeloma is a plasma cell malignancy with an unmet clinical need for improved imaging methods and therapeutics. Recently, we identified CD46 as an overexpressed therapeutic target in multiple myeloma and developed the antibody YS5, which targets a cancer-specific epitope on this protein. We further developed the CD46-targeting PET probe [89Zr]Zr-DFO-YS5 for imaging and [225Ac]Ac-DOTA-YS5 for radiopharmaceutical therapy of prostate cancer. These prior studies suggested the feasibility of the CD46 antigen as a theranostic target in multiple myeloma. Herein, we validate [89Zr]Zr-DFO-YS5 for immunoPET imaging and [225Ac]Ac-DOTA-YS5 for radiopharmaceutical therapy of multiple myeloma in murine models. EXPERIMENTAL DESIGN: In vitro saturation binding was performed using the CD46 expressing MM.1S multiple myeloma cell line. ImmunoPET imaging using [89Zr]Zr-DFO-YS5 was performed in immunodeficient (NSG) mice bearing subcutaneous and systemic multiple myeloma xenografts. For radioligand therapy, [225Ac]Ac-DOTA-YS5 was prepared, and both dose escalation and fractionated dose treatment studies were performed in mice bearing MM1.S-Luc systemic xenografts. Tumor burden was analyzed using BLI, and body weight and overall survival were recorded to assess antitumor effect and toxicity. RESULTS: [89Zr]Zr-DFO-YS5 demonstrated high affinity for CD46 expressing MM.1S multiple myeloma cells (Kd = 16.3 nmol/L). In vitro assays in multiple myeloma cell lines demonstrated high binding, and bioinformatics analysis of human multiple myeloma samples revealed high CD46 expression. [89Zr]Zr-DFO-YS5 PET/CT specifically detected multiple myeloma lesions in a variety of models, with low uptake in controls, including CD46 knockout (KO) mice or multiple myeloma mice using a nontargeted antibody. In the MM.1S systemic model, localization of uptake on PET imaging correlated well with the luciferase expression from tumor cells. A treatment study using [225Ac]Ac-DOTA-YS5 in the MM.1S systemic model demonstrated a clear tumor volume and survival benefit in the treated groups. CONCLUSIONS: Our study showed that the CD46-targeted probe [89Zr]Zr-DFO-YS5 can successfully image CD46-expressing multiple myeloma xenografts in murine models, and [225Ac]Ac-DOTA-YS5 can effectively inhibit the growth of multiple myeloma. These results demonstrate that CD46 is a promising theranostic target for multiple myeloma, with the potential for clinical translation.

Analysis of baseline circulating tumor cells integrated with PET/CT findings in transplant-ineligible multiple myeloma.

ABSTRACT: We aimed to improve prognostic predictors in patients with transplant-ineligible multiple myeloma (TIE-MM) by combining baseline circulating clonal tumor cells (CTCs) and positron emission tomography/computed tomography (PET/CT) findings. The factors associated with prognosis were retrospectively investigated in 126 patients with TIE-MM who underwent CTC quantification by multiparameter flow cytometry and PET/CT at the initial presentation. The total lesion glycolysis (TLG) level was calculated using the Metavol software. The median percentage of CTC was 0.06% (range, 0%-4.82%), and 54 patients (42.9%) demonstrated high CTC levels. High CTC levels were associated with significantly poorer progression-free survival (PFS, 2-year 43.4% vs 68.1%; P < .001) and overall survival (OS, 5-year 39.0% vs 68.3%; P < .001). Similarly, high TLG levels significantly worsened the PFS (2-year, 41.2% vs 67.6%; P = .038) and OS (5-year, 37.7% vs 63.1%; P = .019). The multivariate analyses showed that Revised International Staging System (R-ISS) III, high CTC and TLG levels, and complete response were significant prognostic factors for PFS and OS. A novel predictive model was constructed using CTCs, TLG, and R-ISS III. The patients were stratified into 3 groups according to the number of risk factors, revealing an extremely high-risk group with a 2-year PFS of 0% and a 5-year OS of 20%. Patients without any high-risk features had better prognosis, with a 2-year PFS of 78.6% and a 5-year OS of 79.5%. The combination of CTCs and volumetric assessment of PET/CT at diagnosis augments the existing stratification systems and may pave the way for a risk-adapted treatment approach.

Muscle and fat composition in patients with newly diagnosed multiple myeloma.

Measures of muscle and adipose tissue mass have been associated with outcomes in several malignancies, but studies in multiple myeloma (MM) are inconsistent. The aim of this study was to evaluate the association between muscle and fat areas and radiodensity, and overall survival (OS) in patients with newly diagnosed MM. We included 341 patients diagnosed with MM from 2010-2019 who had an 18F-fluorodeoxyglucose positron emission tomography/computed tomography at diagnosis. A cross-sectional image at the third lumbar vertebrae was segmented into muscle and fat components. Median follow up was 5.7 years. There was no association between sarcopenia and baseline disease characteristics or OS. Low muscle radiodensity was associated with higher disease stage, anemia, and renal failure. OS was 5.6 vs. 9.0 years in patients with muscle radiodensity in the lower vs. middle/upper tertiles, respectively (P = 0.02). High subcutaneous adipose tissue (SAT) radiodensity was associated with higher stage, anemia, thrombocytopenia, hypercalcemia, renal failure, and high LDH. OS was 5.4 years vs. not reached in patients with SAT radiodensity in the upper vs. middle/lower tertiles, respectively (P = 0.001). In conclusion, sarcopenia was not associated with OS in MM patients. High SAT radiodensity and low muscle radiodensity were associated with advanced disease stage and adverse laboratory characteristics.

Apparent diffusion coefficient measurements of bone marrow infiltration patterns in multiple myeloma for the assessment of tumor burden - a feasibility study.

BACKGROUND: The purpose of our study was to explore and compare the tumor burden of different bone marrow infiltration patterns and evaluate the feasibility of apparent diffusion coefficient (ADC) value to identify patterns in multiple myeloma (MM). PATIENTS AND METHODS: Ninety-three patients with newly diagnosed multiple myeloma and 23 controls had undergone routine magnetic resonance imaging (MRI) and diffusion-weighted MRI (DWI) from January 2019 to November 2020. Five bone marrow (BM) infiltration patterns were allocated according to routine MRI. The laboratory data and ADC values of patterns were analyzed and compared. ROC analysis was used to establish the best diagnostic ADC threshold value for identifying these patterns and distinguishing normal pattern from controls. Besides, the correlation between the ADC values of diffuse pattern and the plasma cells ratio was assessed. RESULTS: The values of hemoglobin, beta-2 microglobulin (ß2-MG), plasma cell, M protein, the percentages of stage, high-risk fluorescence in situ hybridization, and ADC values showed significant difference among patterns. ADCmean at a specific value (368.5×10-6 mm2/s) yielded a maximum specificity (95.5%) and sensitivity (92.0%) in diagnosing MM. A specific value (335.5×10-6mm2/s) yielded a maximum specificity (84.7%) and sensitivity (88.0%) in discriminating visually normal pattern in MM from controls. There was a moderate positive correlation between the plasma cells ratio and ADCs of diffuse infiltration patterns (r = 0.648, P < 0.001). CONCLUSIONS: The bone marrow infiltration patterns in MM patients can indicate the tumor burden and ADC value has the ability to discriminate these patterns objectively.