Toripalimab plus capecitabine in the treatment of patients with residual nasopharyngeal carcinoma: a single-arm phase 2 trial.

Patients with residual nasopharyngeal carcinoma after receiving definitive treatment have poor prognoses. Although immune checkpoint therapies have achieved breakthroughs for treating recurrent and metastatic nasopharyngeal carcinoma, none of these strategies have been assessed for treating residual nasopharyngeal carcinoma. In this single-arm, phase 2 trial, we aimed to evaluate the antitumor efficacy and safety of toripalimab (anti-PD1 antibody) plus capecitabine in patients with residual nasopharyngeal carcinoma after definitive treatment (ChiCTR1900023710). Primary endpoint of this trial was the objective response rate assessed according to RECIST (version 1.1). Secondary endpoints included complete response rate, disease control rate, duration of response, progression-free survival, safety profile, and treatment compliance. Between June 1, 2020, and May 31, 2021, 23 patients were recruited and received six cycles of toripalimab plus capecitabine every 3 weeks. In efficacy analyses, 13 patients (56.5%) had complete response, and 9 patients (39.1%) had partial response, with an objective response rate of 95.7% (95% CI 78.1-99.9). The trial met its prespecified primary endpoint. In safety analyses, 21 of (91.3%) 23 patients had treatment-related adverse events. The most frequently reported adverse event was hand-foot syndrome (11 patients [47.8%]). The most common grade 3 adverse event was hand-foot syndrome (two patients [8.7%]). No grades 4-5 treatment-related adverse events were recorded. This phase 2 trial shows that combining toripalimab with capecitabine has promising antitumour activity and a manageable safety profile for patients with residual nasopharyngeal carcinoma.

Using Genomics Feature Selection Method in Radiomics Pipeline Improves Prognostication Performance in Locally Advanced Esophageal Squamous Cell Carcinoma-A Pilot Study.

PURPOSE: To evaluate the prognostic value of baseline and restaging CT-based radiomics with features associated with gene expression in esophageal squamous cell carcinoma (ESCC) patients receiving neoadjuvant chemoradiation (nCRT) plus surgery. METHODS: We enrolled 106 ESCC patients receiving nCRT from two institutions. Gene expression profiles of 28 patients in the training set were used to detect differentially expressed (DE) genes between patients with and without relapse. Radiomic features that were correlated to DE genes were selected, followed by additional machine learning selection. A radiomic nomogram for disease-free survival (DFS) prediction incorporating the radiomic signature and prognostic clinical characteristics was established for DFS estimation and validated. RESULTS: The radiomic signature with DE genes feature selection achieved better performance for DFS prediction than without. The nomogram incorporating the radiomic signature and lymph nodal status significantly stratified patients into high and low-risk groups for DFS (p < 0.001). The areas under the curve (AUCs) for predicting 5-year DFS were 0.912 in the training set, 0.852 in the internal test set, 0.769 in the external test set. CONCLUSIONS: Genomics association was useful for radiomic feature selection. The established radiomic signature was prognostic for DFS. The radiomic nomogram could provide a valuable prediction for individualized long-term survival.

Nomogram for the prediction of primary distant metastasis of nasopharyngeal carcinoma to guide individualized application of FDG PET/CT.

PURPOSE: This study aimed to establish an effective nomogram to predict primary distant metastasis (DM) in patients with nasopharyngeal carcinoma (NPC) to guide the application of PET/CT. METHODS: In total, 3591 patients with pathologically confirmed NPC were consecutively enrolled. The nomogram was constructed based on 1922 patients treated between 2007 and 2014. Multivariate logistical regression was applied to identify the independent risk factors of DM. The predictive value of the nomogram was evaluated using the concordance index (C-index), calibration curve, probability density functions (PDFs), and clinical utility curve (CUC). The results were validated in 1669 patients enrolled from 2015 to 2016. Net reclassification improvement (NRI) was applied to compare performances of the nomogram with other clinical factors. The best cut-off value of the nomogram chosen for clinical application was analyzed. RESULTS: A total of 355 patients showed primary DM among 3591 patients, yielding an incidence rate of 9.9%. Sex, N stage, EBV DNA level, lactate dehydrogenase level, and hemoglobin level were independent predictive factors for primary DM. C-indices in the training and validation cohort were 0.796 (95% CI, 0.76-0.83) and 0.779 (95% CI, 0.74-0.81), respectively. The NRI indices demonstrated that this model had better predictive performance than plasma EBV DNA level and N stage. We advocate for a threshold probability of 3.5% for guiding the application of PET/CT depending on the clinical utility analyses. CONCLUSION: This nomogram is a useful tool to predict primary DM of NPC and guide the clinical application of PET/CT individually at the initial staging.

Low value of whole-body dual-modality [18f]fluorodeoxyglucose positron emission tomography/computed tomography in primary staging of stage I-II nasopharyngeal carcinoma: a nest case-control study.

OBJECTIVES: The value of using PET/CT for staging of stage I-II NPC remains unclear. Hence, we aimed to investigate the survival benefit of PET/CT for staging of early-stage NPC before radical therapy. METHODS: A total of 1003 patients with pathologically confirmed NPC of stages I-II were consecutively enrolled. Among them, 218 patients underwent both PET/CT and conventional workup ([CWU], head-and-neck MRI, chest radiograph, liver ultrasound, bone scintigraphy) before treatment. The remaining 785 patients only underwent CWU. The standard of truth (SOT) for lymph node metastasis was defined by the change of size according to follow-up MRI. The diagnostic efficacies were compared in 218 patients who underwent both PET/CT and CWU. After covariate adjustment using propensity scoring, a cohort of 872 patients (218 with and 654 without pre-treatment PET/CT) was included. The primary outcome was overall survival based on intention to treat. RESULTS: Retropharyngeal lymph nodes were metastatic based on follow-up MRI in 79 cases. PET/CT was significantly less sensitive than MRI in detecting retropharyngeal lymph node lesions (72.2% [62.3-82.1] vs. 91.1% [84.8-97.4], p = 0.004). Neck lymph nodes were metastatic in 89 cases and PET/CT was more sensitive than MRI (96.6% [92.8-100.0] vs. 76.4% [67.6-85.2], p < 0.001). In the survival analyses, there was no association between pre-treatment PET/CT use and improved overall survival, progression-free survival, local relapse-free survival, regional relapse-free survival, and distant metastasis-free survival. CONCLUSIONS: This study showed PET/CT is of little value for staging of stage I-II NPC patients at initial imaging. KEY POINTS: • PET/CT was more sensitive than MRI in detecting neck lymph node lesions whereas it was significantly less sensitive than MRI in detecting retropharyngeal lymph node lesions. • No association existed between pre-treatment PET/CT use and improved survival in stage I-II NPC patients.

Aberrant Resting-State Functional Connectivity Density in Patients with Hepatitis B Virus-Related Cirrhosis.

There is increasing evidence that cirrhosis may affect functional connectivity among various brain regions in patients prior to onset of overt hepatic encephalopathy (HE). However, most investigators have focused mainly on alterations in functional connectivity strengths, and the changes in functional connectivity density (FCD) are largely unknown. Here, we investigated alterations in resting-state FCD in patients with hepatitis B virus-related cirrhosis (HBV-RC) without overt HE. Totally, 31 patients with HBV-RC without overt HE and 30 age- and sex-matched healthy controls underwent resting-state functional MRI examinations. FCD mapping was employed to compute local and global FCD maps. Then, short-range and long-range FCD values were calculated and voxel-based comparisons were performed between the two groups. The HBV-RC group showed significant decreases in FCD, including decreased short-range FCDs in the bilateral middle cingulum gyrus/precuneus, the bilateral cuneus, and the left lingual gyrus/inferior occipital gyrus and decreased long-range FCD in the bilateral cuneus/precuneus. In addition, the decreased long-range FCD in the bilateral cuneus/precuneus in the HBV-RC group was related to performance on the psychometric hepatic encephalopathy score (PHES) test. These findings suggest aberrant functional connectivity density in cirrhotic patients prior to overt HE onset, which may provide better insight into understanding the pathophysiological mechanisms underlying the cirrhotic-related cognitive impairment.

Primary renal synovial sarcoma: computed tomography imaging findings.

BACKGROUND: A synovial sarcoma arising from the kidney is extremely rare. To date, few data are available on their radiological features. PURPOSE: To identify the computer tomography (CT) imaging findings of primary renal synovial sarcomas (PRSSs). MATERIAL AND METHODS: Five cases of PRSS confirmed by histopathological and cytogenetic studies were retrospectively analyzed. All patients had undergone unenhanced and multiphase enhanced CT examinations (one patient underwent CT twice). The CT characteristics, including shape, size, margin, attenuation, and enhancement pattern after intravenous contrast medium injection, were analyzed. RESULTS: The study involved two female and three male patients (mean age, 27.4 years; range, 15-43 years). Unenhanced CT showed completely or partly well-defined masses, with heterogeneous (n = 5) or homogeneous (n = 1) patchy low density. On multiphase contrast-enhanced CT, in five of the six CT examinations, the tumors appeared as solid-cystic masses with cyst walls or pseudo-capsules, and demonstrated moderately heterogeneous (n = 5) and/or septate enhancement (n = 2), with a "rapid wash-in and slow wash-out" pattern of enhancement in the solid component. Only one tumor showed a simple cyst appearance and developed an irregular, intratumoral, septate soft density 8 months later. A renal vein and inferior vena cava thrombus was noticed in one patient, while lymphadenopathy was not observed in any patient. CONCLUSION: PRSS should be included in the differential diagnosis when an adolescent or young adult presents with a renal neoplasm appearing as a solid-cystic mass with well-defined borders, a cystic wall or pseudo-capsule, heterogeneous or septate enhancement, a "rapid wash-in and slow wash-out" pattern of enhancement in the solid component, and no sign of lymphadenopathy.

Abnormal baseline brain activity in patients with HBV-related cirrhosis without overt hepatic encephalopathy revealed by resting-state functional MRI.

Neurocognitive dysfunction of varying degrees is common in patients with hepatitis B virus-related cirrhosis (HBV-RC) without overt hepatic encephalopathy (OHE). However, the neurobiological mechanisms underlying these dysfunctions are not well understood. We sought to identify changes in the neural activity of patients with HBV-RC without OHE in the resting state by using the amplitude of low-frequency fluctuation (ALFF) method and to determine whether these changes were related to impaired cognition. Resting-state functional MRI data from 30 patients with HBV-RC and 30 healthy controls matched for age, sex, and years of education were compared to determine any differences in the ALFF between the two groups. Cognition was measured with the psychometric hepatic encephalopathy score (PHES), and the relationship between these scores and ALFF variation was assessed. Compared with controls, patients showed widespread lower standardized ALFF (mALFF) values in visual association areas (bilateral lingual gyrus, middle occipital gyrus, and left inferior temporal gyrus), motor-related areas (bilateral precentral gyrus, paracentral lobule, and right postcentral gyrus), and the default mode network (bilateral cuneus/precuneus and inferior parietal lobule). Higher mALFF values were found in the bilateral orbital gyrus/rectal gyrus. In patients, mALFF values were significantly positive correlated with the PHES in the right middle occipital gyrus and bilateral precentral gyrus. Our findings of resting-state abnormalities in patients with HBV-RC without OHE suggest that neurocognitive dysfunction in patients with HBV-RC without OHE may be caused by abnormal neural activity in multiple brain regions.

Abnormal regional homogeneity of resting-state brain activity in patients with HBV-related cirrhosis without overt hepatic encephalopathy.

BACKGROUND: Many studies have reported that cognitive deficits exist in cirrhotic patients without overt hepatic encephalopathy (OHE). However, the neurobiological mechanisms underlying these deficits are still not fully understood. AIM: To investigate regional activity abnormalities in patients with hepatitis B virus-related cirrhosis (HBV-RC) without OHE using resting-state functional MRI (Rs-fMRI), and to examine the relationship between regional activity abnormalities and impaired cognition. METHODS: A newly reported regional homogeneity (ReHo) approach was used to compare the local synchronization of Rs-fMRI signals in 32 patients with HBV-RC without OHE and 32 well-matched healthy controls. Cognition was measured in all patients using psychometric hepatic encephalopathy score (PHES) tests, and the relationship between ReHo variation and PHES was analysed. RESULTS: Relative to healthy controls, the cirrhosis group showed high ReHo in the prefrontal cortex, and widespread low ReHo in visual association areas (left lingual gyrus, middle temporal gyrus and right middle occipital gyrus), motor association areas (bilateral precentral gyrus and paracentral lobule) and the bilateral precuneus. Correlation analysis of the mean ReHo values in different brain areas and PHES in cirrhotic patients revealed a significantly positive correlation in the left lingual gyrus (r = 0.352; P = 0.048), right middle occipital gyrus (r = 0.453; P = 0.009) and bilateral precentral gyrus (left: r = 0.436, P = 0.013; right: r = 0.582, P < 0.001), paracentral lobule (r = 0.485; P = 0.005) and precuneus (r = 0.468; P = 0.007). CONCLUSIONS: Our results provide information on the pathophysiological mechanisms underlying cognitive alterations in cirrhotic patients and demonstrate the feasibility of using Rs-fMRI with ReHo analysis as a noninvasive modality with which to detect the progression of cognitive changes in cirrhotic patients.

Regional homogeneity changes in heroin-dependent individuals: resting-state functional MR imaging study.

PURPOSE: To identify heroin-related modulations of neural activity in the resting state in heroin-dependent individuals (HDIs) by using resting-state functional magnetic resonance (MR) imaging and a regional homogeneity method and to investigate whether these changes of neural activity can be related to duration of heroin use and to decision-making deficits in HDIs. MATERIALS AND METHODS: This prospective study was approved by the appropriate ethics committee, and written informed consent was obtained from each participant. Thirty-one HDIs receiving methadone-maintained treatment and 24 control subjects participated. Resting-state functional MR imaging was performed by using a gradient-echo echo-planar imaging sequence. Regional homogeneity was calculated by using software. Voxel-based analysis of the regional homogeneity maps between control and HDI groups was performed with two-sample t tests by using software. Statistical maps were set at P less than .05 and were corrected for multiple comparisons. The Iowa gambling task (IGT) was used to assess participant decision making during uncertainty. Abnormal clusters revealed by group comparison were extracted and correlated with behavioral performance at the IGT and with duration of heroin use. RESULTS: Regional homogeneity was diminished in the bilateral medial orbitofrontal cortex (OFC), bilateral dorsal medial thalamus, bilateral cuneus, and lingual gyrus in HDIs compared with control subjects. There were negative correlations between mean regional homogeneity in the medial OFC, bilateral cuneus, and lingual gyrus and duration of heroin use. There was a positive correlation between mean regional homogeneity in the medial OFC and performance level at the IGT. CONCLUSION: The present study reveals resting-state abnormalities in HDIs that may lead to further improvement of the understanding of the neural substrates of cognitive impairment in HDIs.

[Application of dynamic contrast-enhanced magnetic resonance imaging in evaluating liver fibrosis].

OBJECTIVE: To analyze the value of time-signal intensity curve (TIC) in dynamic contrast-enhanced magnetic resonance imaging (DEC-MRI) in the evaluation of liver fibrosis. METHODS: Thirty-six consecutive patients and healthy volunteers were divided into 4 groups according to the stages of fibrosis, namely the normal group (n=9), mild fibrosis group (n=5), moderate to severe fibrosis group (n=7), and liver cirrhosis group (n=15). All the subjects underwent conventional and DEC-MRI, and the TIC was generated automatically to evaluate the peak height, TTP, MSI and MSD. The correlations between the TIC parameters and the stage of fibrosis were assessed. Receiver operating characteristic (ROC) curve analyses were conducted to evaluate the value of the TIC parameters in the evaluation of fibrosis stage. RESULTS: Moderate but significant inverse correlations of the peak height, MSI, and to fibrosis stage were noted in these patients (P<0.05); the peak time was positively correlated to the fibrosis stage (P<0.05). In patients with a fibrosis stage ≥1, the AUC of the measured TIC parameters ranged from 0.747 to 0.783, with the MSD of the spleen had the highest AUC (0.783). For a fibrosis stage ≥3, the AUC of the indices ranged between 0.728 and 0.877, highest for liver MSI of the arterial phase, followed by the portal vein MSI, liver MSI of portal venous phase, liver MSD, splenic MSI of arterial phase and splenic MSD. In the diagnosis of liver cirrhosis, the AUC (range 0.742-0.821) decreased in the order of liver MSI of the portal venous phase, liver MSD, liver MSI of the arterial phase, the portal vein MSI, splenic MSI of the arterial phase and splenic MSD. CONCLUSION: TIC of DEC-MRI can be used to evaluate hemodynamic changes in the liver, and may serve as a practical non-invasive functional imaging modality for assessing the severity of liver fibrosis.

Amplitude low-frequency oscillation abnormalities in the heroin users: a resting state fMRI study.

Functional neuroimaging studies have revealed abnormal functional organization of the heroin users' brain, including reward circuit, cognitive control circuit, memory circuit, motivation and salience evaluation circuits and so on. In the current study, we aimed to explore the functional changes in the regional brain of heroin users using the amplitude of low-frequency oscillations in the Blood Oxygenation Level Dependent (BOLD) signals. With fMRI data acquired during resting state from 24 chronic heroin users (all subjects were being treated with methadone) and 24 non-addicted controls, we investigated addiction related altered in the amplitude low-frequency fluctuate (ALFF) between the two groups. Compared with controls, we found that heroin addicts had decreased ALFF in the bilateral dorsal anterior cingulate cortex (dACC), bilateral medial orbit frontal cortex (mOFC), left dorsal lateral prefrontal cortex (dlPFC), left middle temporal gyrus, left inferior temporal gyrus, posterior cingulate cortex and left cuneus as well as increased ALFF in the bilateral angular gyrus, bilateral precuneus, bilateral supramarginal gyrus, left post cingulate cortex and left middle frontal gyrus. Moreover, we also found that the increased ALFF in the bilateral parietal lobe had a significantly positive correlation with the methadone does, thus we inferred that the reduced ALFF may due to heroin consumption, nevertheless, the increased ALFF in the bilateral parietal lobe may have resulted from the methadone treatment. This resting-state fMRI study suggests that the changed spontaneous neuronal activity of these regions may be implicated in the underlying pathophysiology of heroin addicts.

[Value of multi-slice spiral CT in the diagnosis and therapeutic effect evaluation of gastrointestinal stromal tumors].

OBJECTIVE: To analyze the CT manifestations of gastrointestinal stromal tumors, and explore the value of CT in the diagnosis and therapeutic effect evaluation of these tumors. METHODS: A retrospectively analysis of the medical imaging data was conducted in 39 cases of gastrointestinal stromal tumors confirmed by surgery and pathology in comparison with the pathological findings. RESULTS: Of the 39 patients with gastrointestinal stromal tumors, 2 had esophageal stromal tumors, 23 had gastric stromal tumor, 7 had duodenal stromal tumor, 4 had jejunal stromal tumors, 2 had ileal stromal tumors, and 1 had colon stromal tumor. Twenty-five patients were found to have highly malignant tumors, and 11 had low-grade tumors, with the other 3 having tumors of unidentifiable nature. CT displayed exogenous or endogenous mass in these cases, and the tumors had a maximum diameter ranging from 3 to 45 cm (<5 cm in 12 cases and >or=5 cm in 27 cases). Of the 27 cases with a tumor diameter over 5 cm, 23 had malignant stromal tumors, and the tumor mass showed heterogeneous density with central necrosis and cystic and the solid portion of the tumor exhibited mild to moderate enhancement. Six patients were found to have intratumoral punctate calcification, and 17 with malignant tumors showed high peripheral enhancement, with the solid portion of the tumors showing delayed enhancement. The 6 patients with unresectable tumors received chemotherapy resulting in significantly reduced tumor diameter and cystic and necrotic foci in the tumor. CONCLUSION: Multi-slice spiral CT allows precise localization and qualitative assessment of gastrointestinal stromal tumors, and also helps in the evaluation of the therapeutic effect.