Tumor Stiffness Measurement at Multifrequency MR Elastography to Predict Lymphovascular Space Invasion in Endometrial Cancer.

Background Pathologic lymphovascular space invasion (LVSI) is associated with poor outcome in endometrial cancer. Its relationship with tumor stiffness, which can be measured with use of MR elastography, has not been extensively explored. Purpose To assess whether MR elastography-based mechanical characteristics can aid in the noninvasive prediction of LVSI in patients with endometrial cancer. Materials and Methods This prospective study included consecutive adult patients with a suspected uterine tumor who underwent MRI and MR elastography between October 2022 and July 2023. A region of interest delineated on T2-weighted magnitude images was duplicated on MR elastography images and used to calculate c (stiffness in meters per second) and φ (viscosity in radians) values. Pathologic assessment of hysterectomy specimens for LVSI served as the reference standard. Data were compared between LVSI-positive and -negative groups with use of the Mann-Whitney U test. Multivariable logistic regression was used to determine variables associated with LVSI positivity and develop diagnostic models for predicting LVSI. Model performance was assessed with use of area under the receiver operating characteristic curve (AUC) and compared using the DeLong test. Results A total of 101 participants were included, 72 who were LVSI-negative (median age, 53 years [IQR, 48-62 years]) and 29 who were LVSI-positive (median age, 54 years [IQR, 49-60 years]). The tumor stiffness in the LVSI-positive group was higher than in the LVSI-negative group (median, 4.1 m/sec [IQR, 3.2-4.6 m/sec] vs 2.2 m/sec [IQR, 2.0-2.8 m/sec]; P < .001). Tumor volume, cancer antigen 125 level, and tumor stiffness were associated with LVSI positivity (adjusted odds ratio range, 1.01-9.06; P range, <.001-.04). The combined model (AUC, 0.93) showed better performance for predicting LVSI compared with clinical-radiologic model (AUC, 0.77; P = .003) and similar performance to the MR elastography-based model (AUC, 0.89; P = .06). Conclusion The addition of tumor stiffness as measured at MR elastography into a clinical-radiologic model improved prediction of LVSI in patients with endometrial cancer. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Ehman in this issue.

Altered gray matter volume and functional connectivity in lung cancer patients with bone metastasis pain.

Bone metastasis pain (BMP) is a severe chronic pain condition. Our previous studies on BMP revealed functional brain abnormalities. However, the potential effect of BMP on brain structure and function, especially gray matter volume (GMV) and related functional networks, have not yet been clearly illustrated. Voxel-based morphometry and functional connectivity (FC) analysis methods were used to investigate GMV and intrinsic FC differences in 45 right-handed lung cancer patients with BMP(+), 37 lung cancer patients without BMP(-), and 45 healthy controls (HCs). Correlation analysis was performed thereafter with all clinical variables by Pearson correlation. Compared to HCs, BMP(+) group exhibited decreased GMV in medial frontal gyrus (MFG) and right middle temporal gyrus (MTG). Compared with BMP(-) group, BMP(+) group exhibited reduced GMV in cerebelum_6_L and left lingual gyrus. However, no regions with significant GMV differences were found between BMP(-) and HCs groups. Receiver operating characteristic analysis indicated the potential classification power of these aberrant regions. Correlation analysis revealed that GMV in the right MTG was positively associated with anxiety in BMP(+) group. Further FC analysis demonstrated enhanced interactions between MFG/right MTG and cerebellum in BMP(+) patients compared with HCs. These results showed that BMP was closely associated with cerebral alterations, which may induce the impairment of pain moderation circuit, deficits in cognitive function, dysfunction of emotional control, and sensorimotor processing. These findings may provide a fresh perspective and further neuroimaging evidence for the possible mechanisms of BMP. Furthermore, the role of the cerebellum in pain processing needs to be further investigated.

Upfront allogeneic hematopoietic stem cell transplantation for adult T-cell acute lymphoblastic leukemia/lymphoma in first complete remission: a single-center study.

BACKGROUND: Real-world data on outcomes of upfront allogeneic hematopoietic stem cell transplantation (allo-HCT) for adult T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) patients in first complete remission (CR1) is still lacking. METHODS: A single center retrospective study was conducted from 94 consecutive patients received their first allo-HCT between 2010 and 2021, which include 76 patients received upfront allo-HCT and 18 patients received allo-HCT in non-upfront settings. RESULTS: There were no significant differences in most variables. In the upfront allo-HCT group, 52 (68%) patients achieved CR1 with one cycle of induction regimen. 24 (32%) patients achieved CR1 with more than one cycle. In the non-upfront group, there were 14 patients with active disease and 4 patients in second CR before transplant. The majority of patients received antithymocyte globulin-based graft-versus-host disease prophylaxis. Median follow-up time was 51 months for both groups. 5-year overall survival (OS) was 54% in the upfront allo-HCT group. While, in the non-upfront group, 5-year OS were 19% (P = 0.013). 5-year progression free survival in the upfront group was higher than that in the non-upfront group (50% versus 20%, P = 0.02). 5-year cumulative incidence relapse rate was significantly higher in non-upfront group (64% vs. 32%, P = 0.006). While, there was no difference in the 5-year non-relapse mortality (NRM) rate (19% versus 16%, P = 0.56). The most common cause of death was disease progression. In multivariable analysis, non-upfront allo-HCT (hazard ratios (HR) 2.14, P = 0.03) and HCT-CI (≥ 2) (HR 6.07, P = 0.002) were identified to be associated with worse OS. Non-upfront allo-HCT and HCT-CI (≥ 2) were also found to be independent risk factors for higher relapse rate. While, haploidentical-HCT was found to be associated with increased NRM. CONCLUSIONS: Our study indicated that allo-HCT remains an important curative treatment for adult patients with T-ALL, especially when it was performed in the upfront setting.

Single-center phase 2 study of PD-1 inhibitor combined with DNA hypomethylation agent + CAG regimen in patients with relapsed/refractory acute myeloid leukemia.

Anti-PD-1 monotherapy had limited clinical efficacy in relapsed/refractory (r/r) AML patients with higher PD-1 and PD-L1 expression. Hence, we investigated the efficacy and safety of PD-1 inhibitor with DNA hypomethylating agent (HMA) + CAG regimen in patients who had failed prior AML therapy. In this phase 2, single-arm study, r/r AML patients received azacitidine or decitabine plus CAG regimen with tislelizumab. Primary endpoints were efficacy (objective response rate [ORR]) and safety. Secondary endpoints included overall survival (OS), event-free survival (EFS) and duration of response (DOR). Statistical analyses were performed using Stata 14.0 and SPSS 20.0 software where P < 0.05 denoted significance. Twenty-seven patients were enrolled patients and completed 1 cycle, and 14 (51.9%) and 4 (14.8%) patients completed 2 and 3 cycles, respectively. ORR was 63% (14: complete remission [CR]/CR with incomplete hematologic recovery [CRi], 3: partial remission (PR), 10: no response [NR]). Median OS (mOS) and EFS were 9.7 and 9.2 months, respectively. With a median follow-up of 8.2 months (1.1-26.9), the mOS was not reached in responders (CR/CRi/PR) while it was 2.4 months (0.0-5.4) in nonresponders (P = 0.002). Grade 2-3 immune-related adverse events (irAEs) were observed in 4 (14.8%) patients and 3 nonresponders died of lung infection after treatment. Tislelizumab + HMA + CAG regimen showed improved outcomes in r/r AML patients with lower pretherapy leukemia burden. irAEs were mild and low-grade and higher pretherapy bone marrow CD4+ CD127+ PD-1+ T cells might serve as a predictor of treatment response.ClinicalTrials.gov identifier NCT04541277.

Brain network deficits in breast cancer patients after early neoadjuvant chemotherapy: A longitudinal MRI study.

Breast cancer (BC) patients who undergo chemotherapy are likely to develop chemotherapy-related cognitive impairment (CRCI). Recent studies of BC patients after chemotherapy have used graph theory to investigate the topological properties of the brain functional connectome. However, little is known about structural morphological networks in BC patients after early neoadjuvant chemotherapy (NAC). Brain morphological network organization in 47 female participants with BC was investigated before and after NAC. Topological properties of brain networks were ascertained based on morphological similarities in regional gray matter using a graph theory approach based on 3D T1-weighted MRI data. Nonparametric permutation testing was used to assess longitudinal-group differences in topological metrics. Compared with BC patients before NAC, BC patients after early NAC showed significantly increased global efficiency (p = .048), decreased path length (p = .033), and abnormal nodal properties and connectivity, mainly located in the central executive network (CEN). The change in the network efficiency of the right caudate was negatively correlated with the change in the Self-Rating Anxiety Scale score (r = -.435, p = .008), and the change in the nodal degree of the left superior frontal gyrus (dorsolateral part) was positively correlated with the change in the Functional Assessment of Cancer Therapy score (r = .547, p = .002). BC participants showed randomization in global properties and dysconnectivity in the CEN after early NAC. NAC may disrupt the cognitive balance of the brain morphological network in individuals with BC.

Magnesium enhances the graft-versus-tumor effect of donor lymphocytic infusion on hematologic malignancies.

Donor lymphocyte infusion (DLI) cures relapsed hematologic malignancies after allogeneic hematopoietic stem cell transplantation through the graft-versus-tumor (GVT) effect. Although the important role of magnesium in enhancing immunity has been mentioned in studies, limited clinical data have explored how magnesium affects the efficacy of DLI. Besides, although laboratory data demonstrate that magnesium can enhance CD8+ T cells effector function, whether magnesium regulates the tumor killing effect of peripheral blood mononuclear cells (PBMCs) remains to be explored. Here, for the retrospective study, we collected clinical data of relapsed patients receiving DLI and explored the relationship between different serum magnesium levels and patient outcomes. For in vitro studies, we investigated the effect of magnesium on the cytotoxicity of DLI cells which were PBMCs and preliminarily explored the mechanism. Eighty-one patients were enrolled in this study. It was found that the high post-DLI magnesium level was significantly associated with a higher incidence of complete remission (CR) or partial remission (CR/PR) and a higher possibility of survival. The magnesium level after DLI was an independent risk factor of overall survival. In vitro studies proved that increased magnesium enhanced the cytotoxic function of PBMCs on hematologic malignancies. Besides, magnesium modulated LFA-1 headpiece opening. When blocking the integrin-ligand interaction between LFA-1 and ICAM-1, the regulation effect of magnesium on PBMCs was weakened. Therefore, it was possible that magnesium regulated PBMCs effector function by stimulating LFA-1. These results show that serum magnesium levels affect immunological responses mediated by donor lymphocytes in hematologic malignancies.

Inversion-Recovery-Prepared Oscillating Gradient Sequence Improves Diffusion-Time Dependency Measurements in the Human Brain.

BACKGROUND: Oscillating gradient diffusion MRI (dMRI) enables measurements at a short diffusion-time (td ), but it is challenging for clinical systems. Particularly, the low b-value and low resolution may give rise to cerebrospinal fluid (CSF) contamination. PURPOSE: To assess the effect of CSF partial volume on td -dMRI measurements and efficacy of inversion-recovery (IR) prepared oscillating and pulsed gradient dMRI sequence to improve td -dMRI measurements in the human brain. STUDY TYPE: Prospective. SUBJECTS: Ten normal volunteers and six glioma patients. FIELD STRENGTH/SEQUENCE: A 3 T; three-dimensional (3D) IR-prepared oscillating gradient-prepared gradient spin-echo (GRASE) and two-dimensional (2D) IR-prepared oscillating gradient echo-planar imaging (EPI) sequences. ASSESSMENT: We assessed the td -dependent patterns of apparent diffusion coefficient (ADC) in several gray and white matter structures, including the hippocampal subfields (head, body, and tail), cortical gray matter, thalamus, and posterior white matter in normal volunteers. Pulsed gradient (0 Hz) and oscillating gradients at frequencies of 20 Hz, 40 Hz, and 60 Hz dMRI were acquired with GRASE and EPI sequences with or without the IR module. We also tested the td -dependency patterns in glioma patients using the EPI sequence with or without the IR module. STATISTICAL TESTS: The differences in ADC across the different td s were compared by one-way ANOVA followed by post hoc pairwise t-tests with Bonferroni correction. RESULTS: In the healthy subjects, brain regions that were possibly contaminated by CSF signals, such as the hippocampus (head, body, and tail) and cortical gray matter, td -dependent ADC changes were only significant with the IR-prepared 2D and 3D sequences but not with the non-IR sequences. In brain glioblastomas patients, significantly higher td -dependence was observed in the tumor region with the IR module than that without IR (slope = 0.0196 µm2 /msec2 vs. 0.0034 µm2 /msec2 ). CONCLUSION: The IR-prepared sequence effectively suppressed the CSF partial volume effect and significantly improved the td -dependent measurements in the human brain. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

XGBoost-based multiparameters from dual-energy computed tomography for the differentiation of multiple myeloma of the spine from vertebral osteolytic metastases.

OBJECTIVES: To evaluate the performance of extreme gradient boosting (XGBoost) combined with multiparameters from dual-energy computed tomography (mpDECT) to differentiate between multiple myeloma (MM) of the spine and vertebral osteolytic metastases (VOM). METHODS: For this retrospective study, 28 patients (83 lesions) with MM of the spine and 23 patients (54 lesions) with VOM who underwent DECT were included. The mpDECT for each lesion, including normalized effective atomic number, slope of the spectral Hounsfield unit curve, CT attenuation, and virtual noncalcium (VNCa), was obtained. Boruta was used to select the key parameters, and then subsequently merged with XGBoost to yield a prediction model. The lesions were divided into the training and testing group in a 3:1 ratio. The highest performance of the univariate analysis was compared with XGBoost using the Delong test. RESULTS: The mpDECT of MM was significantly lower than that of VOM (all p < 0.05). In univariate analysis, VNCa had the highest area under the receiver operating characteristic curve (AUC) in the training group (0.81) and testing group (0.87). Based on Boruta, 6 parameters of DECT were selected for XGBoost model construction. The XGBoost model achieved an excellent and stable diagnostic performance, as shown in the training group (AUC of 1.0) and testing group (AUC of 0.97), with a sensitivity of 80%, a specificity of 95%, and an accuracy of 88%, which was superior to VNCa (p < 0.05). CONCLUSIONS: XGBoost combined with mpDECT yielded promising performance in differentiating between MM of the spine and VOM. KEY POINTS: • The multiparameters obtained from dual-energy CT of multiple myeloma differed significantly from those of vertebral osteolytic metastases. • The virtual noncalcium offered the highest AUC in the univariate analysis to distinguish multiple myeloma from vertebral osteolytic metastases. • Extreme gradient boosting combined with multiparameters from dual-energy CT had a promising performance to distinguish multiple myeloma from vertebral osteolytic metastases.

Extracellular volume fraction determined by equilibrium contrast-enhanced CT for the prediction of the pathological complete response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer.

OBJECTIVES: To determine the extracellular volume (ECV) fraction derived from equilibrium contrast-enhanced CT for predicting pathological complete response (pCR) after neoadjuvant chemoradiotherapy (NCRT) in locally advanced rectal cancer (LARC). METHODS: The ECV fraction before NCRT (ECVpre) and/or ECV after NCRT (ECVpost) of rectal tumors was assessed, and ECVΔ was calculated as ECVpost - ECVpre. The histopathologic tumor regression grading (TRG) was assessed. pCR (TRG 0 grade) was defined as the absence of viable tumor cells in the primary tumor and lymph nodes. Demographic and clinicopathological characteristics and ECV fraction were compared between the pCR and non-pCR groups. A mixed model was constructed by logistic regression. The performance for predicting pCR was assessed with the area under the receiver-operator curve (AUC). The AUCs of the different methods were compared by the method proposed by DeLong et al. RESULTS: Seventy-five patients were included; 17 achieved pCR, and 58 achieved non-pCR. The ECVpost (17.05 ± 2.36% vs. 29.94 ± 1.20%; p < 0.001) and ECVΔ (- 17.01 ± 3.01% vs. 0.44 ± 1.45%; p < 0.001) values in the pCR group were significantly lower than those in the non-pCR group. The mixed model that combined ECVpost with ECVΔ achieved an AUC of 0.92 (95% confidence interval (CI) = 0.81-0.98), which was higher than that of ECVpost (AUC, 0.91 (95% CI = 0.80-0.97); p = 0.60) or ECVΔ (AUC, 0.90 (95% CI = 0.79-0.97); p = 0.61). CONCLUSIONS: ECVpost and ECVΔ determined by using equilibrium contrast-enhanced CT were useful in distinguishing between pCR and non-pCR patients with LARC who received NCRT. KEY POINTS: • ECVpost and ECVΔ (ECVpost - ECVpre) differed significantly between the non-pCR and pCR groups. • ECVpre cannot be used to predict the efficacy of neoadjuvant chemoradiotherapy. • ECVpost combined with ECVΔ had the best performance with an AUC of 0.92 for predicting pCR after NCRT in LARC.

Quantitative parameters derived from dual-energy computed tomography for the preoperative prediction of early recurrence in patients with esophageal squamous cell carcinoma.

OBJECTIVES: This study aimed to assess the efficacy of quantitative parameters derived from dual-energy computed tomography (DECT) for the preoperative prediction of early recurrence (ER) in patients with esophageal squamous cell carcinoma (ESCC). METHODS: In total, 78 patients with ESCC who underwent radical esophagectomy and DECT from June 2019 to August 2020 were enrolled in this study. Normalized iodine concentration (NIC) and electron density (Rho) in tumors were measured using arterial and venous phase images, whereas unenhanced images were used to determine the effective atomic number (Zeff). Univariate and multivariate Cox proportional hazards models were used to identify independent risk predictors of ER. Receiver operating characteristic curve analysis was performed using the independent risk predictors. ER-free survival curves were constructed using the Kaplan-Meier method. RESULTS: NIC in the arterial phase (A-NIC; hazards ratio [HR], 3.91; 95% confidence interval [CI], 1.79-8.56; p = 0.001) and pathological grade (PG; HR, 2.69; 95% CI, 1.32-5.49; p = 0.007) were identified as significant risk predictors of ER. The area under the curve of A-NIC for predicting ER in patients with ESCC was not significantly higher than that of PG (0.72 vs. 0.66, p = 0.441). In a stratified survival analysis, patients with high A-NIC or poorly differentiated ESCC had a higher rate of ER than those with low A-NIC or highly/moderately differentiated ESCC. CONCLUSIONS: A-NIC derived from DECT can be used to noninvasively predict preoperative ER in patients with ESCC, with an efficacy comparable to that of pathological grade. CLINICAL RELEVANCE STATEMENT: Preoperative quantitative measurement of dual-energy CT parameters can predict the early recurrence of esophageal squamous cell carcinoma and serve as an independent prognostic factor to guide clinical designation of personalized treatment. KEY POINTS: • Normalized iodine concentration in the arterial phase and pathological grade were independent risk predictors of early recurrence in patients with esophageal squamous cell carcinoma. • Normalized iodine concentration in the arterial phase may be a noninvasive imaging marker for preoperatively predicting early recurrence in patients with esophageal squamous cell carcinoma. • The efficacy of normalized iodine concentration in the arterial phase derived from dual-energy computed tomography for predicting early recurrence is comparable to that of pathological grade.

Targeted dosing of anti-thymocyte globulin in adult unmanipulated haploidentical peripheral blood stem cell transplantation: A single-arm, phase 2 trial.

Anti-thymocyte globulin (ATG) is widely used in allogeneic hematopoietic stem cell transplantation to prevent severe graft-versus-host disease (GVHD) and graft failure. However, overexposure to ATG may increase cytomegalovirus (CMV), Epstein-Barr virus (EBV) reactivation, non-relapse mortality, and disease recurrence. To investigate the optimal dosing of ATG, we established a targeted dosing strategy based on ATG concentration monitoring for haploidentical peripheral blood stem cell transplantation (haplo-PBSCT). The aim of this phase 2 trial is to evaluate the safety and efficacy of the ATG-targeted dosing strategy in adult unmanipulated haplo-PBSCT. ATG was administered for 4 days (-5 days to -2 days) during conditioning. The ATG doses on -3 days and -2 days were adjusted by our dosing strategy to achieve the optimal ATG exposure. The primary endpoint was CMV reactivation on +180 days. Between December 2020 and January 2022, 66 haplo-PBSCT patients were enrolled and 63 of them were evaluable with a median follow-up of 632 days. The cumulative incidence of CMV reactivation was 36.7% and that of EBV was 58.7%. The 1-year disease-free survival was 82.5%, overall survival was 92.1%, and CD4+ T-cell reconstruction on +100 days was 76.8%. The most common severe regimen-associated toxicities (> grade 3) were infections (51.5%) and gastrointestinal toxicity (25.5%). A total of 102 haplo-PBSCT patients who received the conventional fixed ATG dose (cumulative 10 mg/kg) comprised historical control. The outcomes in historical control were inferior to those of phase 2 trial cohort (CMV reactivation: 70.8%, p < .001; EBV reactivation: 76.0%, p = .024; CD4 + T-cell reconstruction: 54.1%, p = .040). In conclusion, ATG-targeted dosing strategy reduced CMV/EBV reactivation and improved survival without increasing GVHD after haplo-PBSCT. These advantages may be associated with accelerated immune reconstitution.

The impact of intestinal microbiota in antithymocyte globulin-based myeloablative allogeneic hematopoietic cell transplantation.

BACKGROUND: The correlation between intestinal microbiota and clinical outcomes after allogeneic hematopoietic stem cell transplantation (allo-HCT) has been reported in platforms with T-cell depletion or postcyclophosphamide-based graft-vs-host disease (GVHD) prophylaxis regimens. It is still unclear whether it is the same in platforms of antithymocyte globulin (ATG)-based myeloablative allo-HCT. METHODS: A total of 603 fecal specimens from 100 consecutive patients receiving allo-HCT were collected between December 2018 and July 2020. Fetal samples were profiled with next-generation sequencing of bacterial 16S ribosomal RNA (rRNA) genes. RESULTS: The diversity decreased to the lowest level at approximately day 12 after allo-HCT and then increased over time. According to the diversity of 314 samples that were collected from 86 patients during the engraftment period, patients were grouped into the low- and high-diversity groups. Two-year overall survival in the high-diversity group was significantly longer than that in the low-diversity group (83.7% vs 60.6%, P = .026). Further analysis revealed that worse outcomes for patients with low diversity were associated with increased risk of worse outcomes for patients with low diversity (adjusted hazard ratio, 4.95; P = .046). Its association with relapse and GVHD was not found. Compositional analysis of fecal microbiota revealed that the abundance of bacteroides decreased greatly during allo-HCT, whereas that of Enterococcus, Klebsiella, and Escherichia was found to be increased. CONCLUSIONS: This study indicates that gut dysbiosis in platforms of ATG-based myeloablative allo-HCT featured loss of bacterial diversity. The diversity of the intestinal flora at the engraftment period was an independent predictor of longer survival. LAY SUMMARY: The correlation between intestinal microbiota and clinical outcomes after allogeneic hematopoietic stem cell transplantation (allo-HCT) is reported in platforms with T-cell depletion or postcyclophosphamide-based graft-vs-host disease (GVHD) prophylaxis regimens. It is still unclear whether it is the same pattern in platforms of antithymocyte globulin (ATG)-based T-cell repletion myeloablative allo-HCT. Our study indicated that gut dysbiosis in platforms of ATG-based myeloablative allo-HCT also features loss of bacterial diversity. The diversity of the intestinal flora at the engraftment period is an independent predictor of longer survival.

Early alterations in cortical morphology after neoadjuvant chemotherapy in breast cancer patients: A longitudinal magnetic resonance imaging study.

There is growing evidence that chemotherapy may have a significant impact on the brains of breast cancer patients, causing changes in cortical morphology. However, early morphological alterations induced by chemotherapy in breast cancer patients are unclear. To investigate the patterns of those alterations, we compared female breast cancer patients (n = 45) longitudinally before (time point 0, TP0) and after (time point 1, TP1) the first cycle of neoadjuvant chemotherapy, using voxel-based morphometry (VBM) and surface-based morphometry (SBM). VBM and SBM alteration data underwent correlation analysis. We also compared cognition-related neuropsychological tests in the breast cancer patients between TP0 and TP1. Reductions in gray matter volume, cortical thickness, sulcal depth, and gyrification index were found in most brain areas, while increments were found to be mainly concentrated in and around the hippocampus. Reductions of fractal dimension mainly occurred in the limbic and occipital lobes, while increments mainly occurred in the anterior and posterior central gyrus. Significant correlations were found between altered VBM and altered SBM mainly in the bilateral superior frontal gyrus. We found no significant differences in the cognition-related neuropsychological tests before and after chemotherapy. The altered brain regions are in line with those associated with impaired cognitive domains in previous studies. We conclude that breast cancer patients showed widespread morphological alterations soon after neoadjuvant chemotherapy, despite an absence of cognitive impairments. The affected brain regions may indicate major targets of early brain damage after chemotherapy.

Increased risk of nonrelapse mortality post T-cell-replete haploidentical stem cell transplantation in patients with recurrence of acute graft-versus-host disease.

Acute graft-versus-host disease (aGVHD) causes significant morbidity and mortality. While most studies focus on classic or late aGVHD, some patients with previous aGVHD achieve complete remission and later develop another episode of aGVHD. Data on recurrence of aGVHD (RaGVHD) are lacking. This study aimed to identify the incidence, risk factors, and impacts of RaGVHD after T-cell-replete haploidentical hematopoietic cell transplantation (haplo-HCT) without posttransplantation cyclophosphamide. We evaluated patients with RaGVHD after haplo-HCT between 2017 and 2019 and compared their outcomes to those of patients with no aGVHD and those of patients with one episode of de novo aGVHD. Of 199 patients included in the analysis, 45 experienced 50 cases of RaGVHD with a 1-year cumulative incidence of 19.0% (95% CI: 14.5-24.6). Grade III-IV aGVHD was more common in RaGVHD than in previous aGVHD (22.2% vs. 4.4%, p = 0.01). Female donor to male recipient was strongly associated with RaGVHD (HR: 2.5, p = 0.009). The most common death in patients with RaGVHD was GVHD-related, which was different from controls who mostly died from relapse (p = 0.008). RaGVHD was an independent risk factor for chronic GVHD (HR: 2.6, p = 0.006) and nonrelapse mortality (HR: 2.4, p = 0.019) and a significant predictor of lower GVHD relapse-free survival (HR: 1.9, p = 0.020) and cGVHD relapse-free survival (HR: 2.1, p = 0.007). In conclusion, clinical manifestations and negative impacts of RaGVHD needs to be recognized independently.

Elevated REG3α predicts refractory aGVHD in patients who received steroids-ruxolitinib as first-line therapy.

We started a single-arm, phase II, open-label, prospective clinical trial using steroids-ruxolitinib as the first-line therapy for intermediate- to high-risk aGVHD (NCT04397367). Here, we report the association of a biomarker panel (sST2, REG3α, sTNFR1, IL-6 and IL-8) with responses to GVHD therapy. The novel first-line therapy for 39 patients with newly diagnosed aGVHD consisted of 1 mg/kg methylprednisolone and 5 mg/day ruxolitinib. The serum concentrations of the biomarkers were prospectively detected at planned time points. Of the 39 patients, the complete response rate at day 28 was 82.05%. In patients who achieved CR, the concentrations of REG3α (P14 = 0.01; P28 = 0.10) and sTNFR1 (P14 = 0.42; P28 = 0.04) declined at day 14 and day 28 compared with the pre-enrolment levels. In refractory patients, the levels of REG3α at day 14 were higher than those pre-enrolment (P = 0.04). REG3α (P = 0.02) was elevated in the refractory patients compared with the patients achieving CR at day 14 after enrolment, while there was no significant difference in the levels of sST2, sTNFR1 or IL-6. Elevated REG3α levels may predict refractory aGVHD after novel first-line therapy with steroids-ruxolitinib.

Eltrombopag in the treatment of patients with persistent thrombocytopenia after haploidentical peripheral blood stem cell transplantation: a single-center experience.

Persistent thrombocytopenia (PT) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with an increased risk of bleeding and poor survival. The exact pathogenesis underlying PT remains unclear, and its management is difficult. Here we conducted a retrospective study to evaluate the efficacy and safety of eltrombopag (EPAG) in 34 patients with PT after allo-HSCT. Seven patients suffered from prolonged isolated thrombocytopenia (PIT), and 27 had secondary failure of platelet recovery (SFPR). For most patients, the initial dose was 25 mg or 50 mg daily, then adjusted to the maximum dose of 50-100 mg per day according to the response of platelet recovery and toleration of patients. The cumulative incidence (CI) of platelet recovery to at least 20 × 109/L and 50 × 109/L without transfusion support for at least 7 days was 72.1% and 60.7%, respectively. Nineteen (86.4%) of 22 responders were able to taper off the medication; furthermore, the platelet counts remained stable 1 month after withdrawal of EPAG. Although two patients discontinued EPAG during treatment due to headache and nausea, no patients developed grade 3 or 4 toxicities. Hypoplasia of bone marrow and decreased megakaryocytes (MKs) were found to be risk factors for overall response (OR) and complete response (CR) in multivariate analysis, respectively. Overall, our results indicated that EPAG can be used in the treatment of PT and that continuous exposure to EPAG may not be necessary.

Chemotherapy-associated steatohepatitis was concomitant with epicardial adipose tissue volume increasing in breast cancer patients who received neoadjuvant chemotherapy.

OBJECTIVES: To investigate the prevalence of chemotherapy-associated steatohepatitis, quantitate the epicardial adipose tissue (EAT) volume in breast cancer patients, and explore the mediating effect of liver fat content on EAT volume in breast cancer patients who received neoadjuvant chemotherapy (NAC). METHODS: From October 2018 to April 2020, patients were retrospectively reviewed and divided into breast cancer non-NAC and NAC groups. The prevalence of chemotherapy-associated steatohepatitis was evaluated through quantitative MRI mDIXON-Quant examinations by using defined proton density fat fraction cutoffs of liver fat. The EAT volume was quantified on chest CT by semi-automatic volume analysis software. Bootstrap analysis was used in the breast cancer NAC group to test the significance of the mediating effect of liver fat content on EAT volume. RESULTS: A total of 662 breast cancer patients (non-NAC group: 445 patients; NAC group: 217 patients) were included. The prevalence of chemotherapy-associated steatohepatitis in the NAC group was significantly higher than the prevalence of hepatic steatosis in the non-NAC group (42.8% vs. 33.3%, p < 0.001). EAT volume was measured in 561 of 662 breast cancer patients, and was significantly higher in the NAC group than in the non-NAC group (137.26 ± 53.48 mL vs. 125.14 ± 58.77 mL, p = 0.020). In the breast cancer NAC group, the indirect effect of liver fat content on EAT volume was 2.545 (p < 0.001), and the contribution rate to the effect was 69.1%. CONCLUSIONS: EAT volume was significantly higher in the BC-NAC group than in the BC-non-NAC group. KEY POINTS: • The prevalence of CASH was as high as 42.8% in BC patients. • NAC significantly increased the EAT volume in BC patients. • The liver fat content caused the change of EAT volume through mediating effect.

Basiliximab for steroid-refractory acute graft-versus-host disease: A real-world analysis.

Steroid-refractory (SR) acute graft-versus-host disease (aGVHD) is one of the leading causes of early mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We investigated the efficacy, safety, prognostic factors, and optimal therapeutic protocol for SR-aGVHD patients treated with basiliximab in a real-world setting. Nine hundred and forty SR-aGVHD patients were recruited from 36 hospitals in China, and 3683 doses of basiliximab were administered. Basiliximab was used as monotherapy (n = 642) or in combination with other second-line treatments (n = 298). The cumulative incidence of overall response rate (ORR) at day 28 after basiliximab treatment was 79.4% (95% confidence interval [CI] 76.5%-82.3%). The probabilities of nonrelapse mortality and overall survival at 3 years after basiliximab treatment were 26.8% (95% CI 24.0%-29.6%) and 64.3% (95% CI 61.2%-67.4%), respectively. A 1:1 propensity score matching was performed to compare the efficacy and safety between the monotherapy and combined therapy groups. Combined therapy did not increase the ORR; conversely, it increased the infection rates compared with monotherapy. The multivariate analysis showed that combined therapy, grade III-IV aGVHD, and high-risk refined Minnesota aGVHD risk score before basiliximab treatment were independently associated with the therapeutic response. Hence, we created a prognostic scoring system that could predict the risk of having a decreased likelihood of response after basiliximab treatment. Machine learning was used to develop a protocol that maximized the efficacy of basiliximab while maintaining acceptable levels of infection risk. Thus, real-world data suggest that basiliximab is safe and effective for treating SR-aGVHD.

Initial Investigation of Clinical Value of Noise-Optimized Virtual Monoenergetic Images Derived From Dual-Energy Computed Tomography Angiography in Preoperative Perforator Planning of Anterolateral Thigh Flap Transplantation.

OBJECTIVE: To objectively and subjectively assess the image characteristics of noise-optimized virtual monoenergetic images [MEI (+)] and polyenergetic images (PEIs) from dual-energy computed tomography angiography and then to explore the clinical value of the optimal MEI (+) in preoperative perforator planning of anterolateral thigh (ALT) flap transplantation. METHODS: Sixteen patients (32 thighs) who underwent lower extremity run-off dual-energy computed tomography angiography for planning ALT flap transplantation were enrolled. One standard PEI and 5 MEI (+) in 10-keV intervals (range, 40-80 keV) were reconstructed. First, we compared the image quality subjectively (branch order, image quality, and vascular network continuity) and objectively (vascular attenuation, image noise, signal-to-noise ratio, and the contrast-to-noise ratio). Then, we compared the clinical value (number, type, source artery, pedicle length, caliber, and location of all sizable perforators) between the optimal MEI (+) and PEI groups. RESULTS: The 40-keV MEI (+) was rated superior subjective and objective image quality metrics to PEI (all P < 0.001). Compared with PEI, 40 keV MEI (+) increased the number of visible perforators, the percentage of perforators with identifiable types, and the measurable length of perforator pedicle (all P < 0.001). CONCLUSIONS: We recommend 40 keV MEI (+) for the visualization of perforators and their contribution to the selection and location of suitable perforators in preoperative planning for ALT flaps.

Prediction of the number of metastatic axillary lymph nodes in breast cancer by radiomic signature based on dynamic contrast-enhanced MRI.

BACKGROUND: The number of metastatic axillary lymph nodes (ALNs) play a crucial role in the staging, prognosis and therapy of patients with breast cancer. PURPOSE: To predict the number of metastatic ALNs in breast cancer via radiomics. MATERIAL AND METHODS: We enrolled 197 patients with breast cancer who underwent dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). A total of 3386 radiomic features were extracted from the early- and delayed-phase subtraction images. To classify the number of metastatic ALNs, logistic regression was used to develop a radiomic signature and nomogram. RESULTS: The radiomic signature were constructed to distinguish the N0 group from the N+ (metastatic ALNs ≥ 1) group, which yielded area under the curve (AUC) values of 0.82 and 0.81 in the training and test group, respectively. Based on the radiomic signature and BI-RADS category, a nomogram was further developed and showed excellent predictive performance with AUC values of 0.85 and 0.89 in the training and test groups, respectively. Another radiomic signature was constructed to distinguish the N1 (1-3 ALNs) group from the N2-3 (≥4 metastatic ALNs) group and showed encouraging performance with AUC values of 0.94 and 0.84 in training and test group, respectively. CONCLUSIONS: We developed a nomogram and a radiomic signature that can be used to predict ALN metastasis and distinguish the N1 from the N2-3 group. Both nomogram and radiomic signature may be potential tools to assist clinicians in assessing ALN metastasis in patients with breast cancer.