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Background: This study aimed to investigate the prognostic value of semiquantitative parameters derived from [68 Ga]Ga-fibroblast activation protein inhibitor (FAPI) PET/CT for patients with esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy. Methods: We conducted a retrospective analysis on patients from a prospective parent study (NCT04416165). A total of 45 patients with locally advanced ESCC who underwent [68 Ga]Ga-FAPI from December 2019 to March 2021 were included. The maximum standard uptake value (SUVmax), gross tumor volume (GTV), and total lesion-FAPI (TL-FAPI) of the primary tumor were calculated from the corresponding PET/CT image. Unpaired parameters were compared using Student's t test or the Mann–Whitney U test. Paired parameters were compared using the paired t test or the Wilcoxon matched-pairs signed-rank test. Kaplan–Meier curves were generated to calculate progression-free survival (PFS) and overall survival (OS) rates, and Cox regression analysis was performed to determine which PET/CT parameters were prognostic factors for PFS and/or OS. Results: Thirty-four of the 45 patients met the criteria, and the median follow-up time was 24 months (16–29 months). SUVmax-FAPI, GTVFAPI, and TL-FAPI in patients with stage T4 tumors were significantly higher than those in patients with stage T2/T3 tumors (all P < 0.01). In the univariate Cox regression analysis, T stage, N stage, GTVFAPI, and TL-FAPI were associated with PFS, and T stage, GTVFAPI, and TL-FAPI were associated with OS. Upon multivariable analysis, GTVFAPI was an independent prognostic factor for both PFS (hazard ratio (HR), 5.76; 95% confidence interval (CI), 2.13–15.57, P = 0.001) and OS (HR, 4.96; 95% CI, 2.55–18.79, P = 0.001). Conclusion: This pilot study revealed that [68 Ga]Ga-FAPI PET/CT may have prognostic value for patients with ESCC treated with definitive chemoradiotherapy. It may aid in personalized patient management by steering treatment modifications before therapy. Prospective studies with larger samples and longer observation periods are needed. [ABSTRACT FROM AUTHOR]

Circadian disruption in tumorigenesis has been extensively studied, but how circadian rhythm (CR) affects the formation of tumor microenvironment (TME) and the crosstalk between TME and cancer cells is largely unknown, especially in gliomas. Herein, we retrospectively analyzed transcriptome data and clinical parameters of glioma patients from public databases to explore circadian rhythm-controlled tumor heterogeneity and characteristics of TME in gliomas. Firstly, we pioneered the construction of a CR gene set collated from five datasets and review literatures. Unsupervised clustering was used to identify two CR clusters with different CR patterns on the basis of the expression of CR genes. Remarkably, the CR cluster-B was characterized by enriched myeloid cells and activated immune-related pathways. Next, we applied principal component analysis to construct a CRscore to quantify CR patterns of individual tumors, and the function of the CRscore in prognostic prediction was further verified by univariate and multivariate regression analyses in combination with a nomogram. The CRscore could not only be an independent factor to predict prognosis of glioma patients but also guide patients to choose suitable treatment strategies: immunotherapy or chemotherapy. A glioma patient with a high CRscore might respond to immune checkpoint blockade, whereas one with a low CRscore could benefit from chemotherapy. In this study, we revealed that circadian rhythms modulated tumor heterogeneity, TME diversity, and complexity in gliomas. Evaluating the CRscore of an individual tumor would contribute to gaining a greater understanding of the tumor immune status of each patient, enhancing the accuracy of prognostic prediction, and suggesting more effective treatment options. [ABSTRACT FROM AUTHOR]

Background: The main limitation of current immune checkpoint inhibitors (ICIs) in the treatment of cervical cancer comes from the fact that it benefits only a minority of patients. The study aims to develop a classification system to identify immune subtypes of cervical squamous cell carcinoma (SCC), thereby helping to screen candidates who may respond to ICIs.Methods: A real-world cervical SCC cohort of 36 samples were analyzed. We used a nonnegative matrix factorization (NMF) algorithm to separate different expression patterns of immune-related genes (IRGs). The immune characteristics, potential immune biomarkers, and somatic mutations were compared. Two independent data sets containing 555 samples were used for validation.Results: Two subtypes with different immunophenotypes were identified. Patients in sub1 showed favorable progression-free survival (PFS) and overall survival (OS) in the training and validation cohorts. The sub1 was remarkably related to increased immune cell abundance, more enriched immune activation pathways, and higher somatic mutation burden. Also, the sub1 group was more sensitive to ICIs, while patients in the sub2 group were more likely to fail to respond to ICIs but exhibited GPCR pathway activity. Finally, an 83-gene classifier was constructed for cervical SCC classification.Conclusion: This study establishes a new classification to further understand the immunological diversity of cervical SCC, to assist in the selection of candidates for immunotherapy. [ABSTRACT FROM AUTHOR]

Purpose: The standardized uptake value (SUV) is widely used for quantitative evaluation in oncological FDG-PET but has well-known shortcomings as a measure of the tumor's glucose consumption. The standard uptake ratio (SUR) of tumor SUV and arterial blood SUV (BSUV) possesses an increased prognostic value but requires image-based BSUV determination, typically in the aortic lumen. However, accurate manual ROI delineation requires care and imposes an additional workload, which makes the SUR approach less attractive for clinical routine. The goal of the present work was the development of a fully automated method for BSUV determination in whole-body PET/CT. Methods: Automatic delineation of the aortic lumen was performed with a convolutional neural network (CNN), using the U-Net architecture. A total of 946 FDG PET/CT scans from several sites were used for network training (N = 366) and testing (N = 580). For all scans, the aortic lumen was manually delineated, avoiding areas affected by motion-induced attenuation artifacts or potential spillover from adjacent FDG-avid regions. Performance of the network was assessed using the fractional deviations of automatically and manually derived BSUVs in the test data. Results: The trained U-Net yields BSUVs in close agreement with those obtained from manual delineation. Comparison of manually and automatically derived BSUVs shows excellent concordance: the mean relative BSUV difference was (mean ± SD) = (– 0.5 ± 2.2)% with a 95% confidence interval of [− 5.1,3.8]% and a total range of [− 10.0, 12.0]%. For four test cases, the derived ROIs were unusable (< 1 ml). Conclusion: CNNs are capable of performing robust automatic image-based BSUV determination. Integrating automatic BSUV derivation into PET data processing workflows will significantly facilitate SUR computation without increasing the workload in the clinical setting. [ABSTRACT FROM AUTHOR]

Objective: Antimelanoma differentiation-associated protein 5 (anti-MDA5) autoantibody has been reported in dermatomyositis (DM) to be associated with rapidly progressive interstitial lung disease (RP-ILD). Our study is aimed at determining the clinical characteristics and prognostic factors underpinning anti-MDA5-associated RP-ILD.Methods: Patients with anti-MDA5-associated DM (aMDA5-DM) were identified at the Peking University People's Hospital. The presence of anti-MDA5 antibody was determined by immunoblotting. Kaplan-Meier, chi-square test, univariate, and multivariate data analyses were used.Results: Out of 213 patients with DM and clinically amyopathic dermatomyositis (CADM), 20.7% (44/213) of patients were identified as aMDA5-DM. Amongst the aMDA5-DM patients, 63.6% (28/44) were identified as having anti-MDA5-associated RP-ILD. During the follow-up, 32.1% (9/28) of patients with anti-MDA5-associated RP-ILD died of respiratory failure. We identified older age and periungual erythema as two independent risk factors for RP-ILD mortality. Age ≥ 57 years at disease onset was significantly associated with poor survival (P = 0.02) in patients with anti-MDA5-associated RP-ILD, while patients with periungual erythema had a better survival rate than those without periungual erythema (P < 0.05).Conclusions: Anti-MDA5-associated RP-ILD is significantly associated with poor survival rates in DM/CADM patients. More effective intervention should be administered to anti-MDA5-associated RP-ILD patients, especially to senior patients and those without periungual erythema. [ABSTRACT FROM AUTHOR]

Purpose: 18F-FDG uptake in irradiated non-tumour-affected oesophagus (NTO) on restaging PET is a potential surrogate for the measurement of radiation-induced inflammation. Radiation-induced inflammation itself has been shown to be of high prognostic relevance in patients undergoing preoperative radiochemotherapy (RCT) for locally advanced oesophageal cancer. We assessed the prognostic relevance of FDG uptake in the NTO in an independent cohort of patients treated with definitive RCT.Methods: This retrospective evaluation included 72 patients with oesophageal squamous cell carcinoma treated with definitive RCT with curative intent. All patients underwent pretreatment and restaging FDG PET after receiving a radiation dose of 40-50 Gy. Standardized uptake values (SUVmax/SUVmean), metabolic tumour volume (MTV) and relative changes from pretreatment to restaging PET (∆SUVmax/∆SUVmean) were determined within the tumour and NTO. Univariate Cox regression with respect to overall survival (OS), local control (LC), distant metastases (DM) and treatment failure (TF) was performed. Independence of parameters was tested by multivariate Cox regression.Results: ∆SUVmax NTO and MTV were prognostic factors for all investigated clinical endpoints (OS, LC, DM, TF). Inclusion of clinical and PET tumour parameters in multivariate analysis showed that ∆SUVmax NTO was an independent prognostic factor. Furthermore, multivariate analysis of ∆SUVmax NTO using previously published cut-off values from preoperatively treated patients revealed that ∆SUVmax NTO was independent prognostic factor for OS (HR = 1.88, p = 0.038), TF (HR = 2.11, p = 0.048) and DM (HR = 3.02, p = 0.047).Conclusion: NTO-related tracer uptake during the course of treatment in patients with oesophageal carcinoma was shown to be of high prognostic relevance. Thus, metabolically activity of NTO measured in terms of ∆SUVmax NTO is a potential candidate for future treatment individualization (i.e. organ preservation). [ABSTRACT FROM AUTHOR]

• The relation between metagenomic next-generation sequencing (mNGS) and the prognosis of intensive care unit patients is not clear. • mNGS assay is associated with a better prognosis in intensive care unit for infectious diseases. • Absence of mNGS assay was an independent risk factor for increased mortality. • mNGS can improve the range of pathogens detection. To evaluate the relation between metagenomic next-generation sequencing (mNGS) and the prognosis of patients with infectious diseases undergoing mechanical ventilation in the intensive care unit (ICU). This is a single-center observational study, comparing nonrandomly assigned diagnostic approaches. We analyzed the medical records of 228 patients with suspected infectious diseases undergoing mechanical ventilation in the ICU from March 2018 to May 2020. The concordance of pathogen results was also assessed for the results of mNGS, culture, and polymerase chain reaction assays. The 28-day mortality of the patients in the mNGS group was lower after the baseline difference correction (19.23% (20/104) vs 29.03% (36/124) , P = 0.039). Subgroup analysis showed that mNGS assay was associated with improved 28-day mortality of patients who are not immunosuppressed (14.06% vs 29.82%, P = 0.018). Not performing mNGS assay, higher acute physiology and chronic health evaluation II score, and hypertension are independent risk factors for 28-day mortality. The mNGS assay presented an advantage in pathogen positivity (69.8% double-positive and 25.0% mNGS-positive only), and the concordance between these two assays was 79.0%. mNGS survey may be associated with a better prognosis by reducing 28-day mortality of patients with infectious diseases on mechanical ventilation in the ICU. This technique presented an advantage in pathogen positivity over traditional methods. [ABSTRACT FROM AUTHOR]