Single-cell sequencing reveals immune features of treatment response to neoadjuvant immunochemotherapy in esophageal squamous cell carcinoma.

Neoadjuvant immunochemotherapy (nICT) has dramatically changed the treatment landscape of operable esophageal squamous cell carcinoma (ESCC), but factors influencing tumor response to nICT are not well understood. Here, using single-cell RNA sequencing paired with T cell receptor sequencing, we profile tissues from ESCC patients accepting nICT treatment and characterize the tumor microenvironment context. CXCL13+CD8+ Tex cells, a subset of exhausted CD8+ T cells, are revealed to highly infiltrate in pre-treatment tumors and show prominent progenitor exhaustion phenotype in post-treatment samples from responders. We validate CXCL13+CD8+ Tex cells as a predictor of improved response to nICT and reveal CXCL13 to potentiate anti-PD-1 efficacy in vivo. Post-treatment tumors from non-responders are enriched for CXCL13+CD8+ Tex cells with notably remarkable exhaustion phenotype and TNFRSF4+CD4+ Tregs with activated immunosuppressive function and a significant clone expansion. Several critical markers for therapeutic resistance are also identified, including LRRC15+ fibroblasts and SPP1+ macrophages, which may recruit Tregs to form an immunosuppressive landscape. Overall, our findings unravel immune features of distinct therapeutic response to nICT treatment, providing a rationale for optimizing individualized neoadjuvant strategy in ESCC.

A HIGH-RESOLUTION MICROENDOSCOPE IMPROVES ESOPHAGEAL CANCER SCREENING AND SURVEILLANCE: IMPLICATIONS FOR UNDERSERVED GLOBAL SETTINGS BASED ON AN INTERNATIONAL, RANDOMIZED CONTROLLED TRIAL.

BACKGROUND AND AIMS: Lugol's chromoendoscopy (LCE)-based detection of esophageal squamous cell neoplasia (ESCN) is limited by low specificity. High-resolution microendoscopy (HRME) was shown to improve specificity and reduce unnecessary biopsies when used by academic endoscopists. In this international, randomized controlled trial, we determined the clinical impact, efficiency, and performance of HRME in true global health contexts with a range of providers. METHODS: Subjects undergoing screening or surveillance for ESCN by expert and novice endoscopists were enrolled in China and the U.S. from diverse clinical settings. Subjects were randomized to LCE (standard-of-care) or LCE+HRME (experimental). Primary outcomes were efficiency and clinical impact of LCE vs. LCE+HRME, using gold-standard, consensus pathology. RESULTS: Among 916 consented subjects, 859 (93.8%) were recruited in China and 36 (3.9%) in the U.S.; 21 (2.3%) were excluded due to incomplete procedure or data. In the screening arm, 217 subjects were randomized to LCE, 204 to LCE+HRME; in the surveillance arm, 236 were randomized to LCE, 238 to LCE+HRME. HRME increased efficiency in screening: diagnostic yield (neoplastic/total biopsies) improved from 20.0% (95% confidence interval [CI] 12.7-29.2%) to 51.7% (95% CI 32.5-70.6%) with 65.2% (95% CI 54.6-74.9%) of biopsies potentially saved and 59.7% (95% CI 47.5-71.1%) of subjects potentially spared any biopsy. Six subjects (0.7%) had neoplasia missed by the endoscopist on HRME (false negatives); of these, 3 were moderate or high-grade dysplasia missed by novices. CONCLUSION: A low-cost microendoscope improves the efficiency and clinical impact of ESCN screening and surveillance when combined with LCE. HRME may spare unnecessary biopsies leading to cost savings in underserved global settings where the disease is prevalent. CLINICALTRIALS: gov, Number NCT02029937.

Concordance between four PD-L1 immunohistochemical assays and 22C3 pharmDx assay in esophageal squamous cell carcinoma in a multicenter study.

Background: The prediction of response to immunotherapy mostly depends on the programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) status, and the 22C3 pharmDx assay has been approved in esophageal squamous cell carcinoma (ESCC). However, the widespread use of the 22C3 pharmDx assay is limited due to its availability. Thus, alternative PD-L1 assays are needed. We aimed to investigate the analytical and clinical diagnostic performances of four PD-L1 assays and to compare their concordances with the 22C3 pharmDx assay. Methods: The PD-L1 22C3 pharmDx assay was performed on the Dako Autostainer Link 48 platform, three testing assays (PD-L1 E1L3N XP antibody [Ab], PD-L1 BP6099 Ab and PD-L1 CST E1L3N Ab) on the Leica BOND-MAX/III platform, and one testing assay (PD-L1 MXR006 Ab) on the Roche VENTANA Benchmark Ultra platform. A total of 218 ESCC cases from four centers were included in this retrospective study. Professionals from each center stained and read the IHC slides independently and determined the combined positive score (CPS) and the tumor proportion score (TPS). Results: Regarding analytical performance, the four testing assays demonstrated good correlations with the 22C3 pharmDx assay when evaluated by the TPS or CPS (ρ > 0.8 for all four assays). Regarding diagnostic performance (CPS ≥ 10 was used as the cutoff), the four testing assays showed moderate concordances with the 22C3 pharmDx assay (kappa > 0.7 for all four assays). The overall percent agreements between each testing assay and the 22C3 pharmDx assay was at least 87.2 %. Conclusion: This study provides insight into the potential interchangeability of the four PD-L1 assays with the 22C3 pharmDx assay.

Radiological Features of Primary Pulmonary Invasive Mucinous Adenocarcinoma Based on 312 Consecutive Patients.

BACKGROUND: The aim of this study is to investigate the radiological features of primary pulmonary invasive mucinous adenocarcinoma (IMA) in a relatively large population to help improve its further understanding and its accuracy of initial diagnosis. METHODS: This retrospective study included consecutive patients with pathologically confirmed primary pulmonary IMA from January 2019 to December 2021. According to tumor morphology, IMAs were divided into regular nodule/mass, irregular, and large consolidative types. According to tumor density, IMAs were divided into solid, halo, part-solid, pure ground-glass, and cystic types. ANOVA, chi-square, or Fisher exact tests were used to analyze the differences in radiological and clinicopathological characteristics of IMA according to morphological and density subtypes. RESULTS: We analyzed 312 patients. Pulmonary IMA tended to occur in the elderly, with a slightly higher number of women than men. IMA showed a predominance in the lower lobe and adjacent to pleura. IMA of regular nodule/mass, irregular, and large consolidative types accounted for 80.8% (252/312), 13.8% (43/312), and 5.4% (17/312), respectively. Solid, halo, part-solid, pure ground-glass, and cystic IMAs accounted for 55.8% (174/312), 28.2% (88/312), 11.2% (35/312), 1.3% (4/312), and 3.5% (11/312), respectively. The lobulated (76.9%), spiculated (63.5%), and air bronchogram (56.7%) signs were common in IMA. Dead branch sign (88.2%), angiogram sign (88.2%), and satellite nodules/skipping lesions (47.1%) were common in large-consolidative-type IMA. Kirsten rat sarcoma viral oncogene mutations were common (56.1%), whereas epidermal growth factor receptor mutations were relatively rare (2.3%). CONCLUSIONS: Pulmonary IMA of regular nodule/mass type and solid type were the most common at the initial diagnosis. Detailed radiological features can aid in the differential diagnosis of IMA.

Neoadjuvant chemotherapy with or without camrelizumab in resectable esophageal squamous cell carcinoma: the randomized phase 3 ESCORT-NEO/NCCES01 trial.

Recent single-arm studies involving neoadjuvant camrelizumab, a PD-1 inhibitor, plus chemotherapy for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) have shown promising results. This multicenter, randomized, open-label phase 3 trial aimed to further assess the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy followed by adjuvant camrelizumab, compared to neoadjuvant chemotherapy alone. A total of 391 patients with resectable thoracic LA-ESCC (T1b-3N1-3M0 or T3N0M0) were stratified by clinical stage (I/II, III or IVA) and randomized in a 1:1:1 ratio to undergo two cycles of neoadjuvant therapy. Treatments included camrelizumab, albumin-bound paclitaxel and cisplatin (Cam+nab-TP group; n = 132); camrelizumab, paclitaxel and cisplatin (Cam+TP group; n = 130); and paclitaxel with cisplatin (TP group; n = 129), followed by surgical resection. Both the Cam+nab-TP and Cam+TP groups also received adjuvant camrelizumab. The dual primary endpoints were the rate of pathological complete response (pCR), as evaluated by a blind independent review committee, and event-free survival (EFS), as assessed by investigators. This study reports the final analysis of pCR rates. In the intention-to-treat population, the Cam+nab-TP and Cam+TP groups exhibited significantly higher pCR rates of 28.0% and 15.4%, respectively, compared to 4.7% in the TP group (Cam+nab-TP versus TP: difference 23.5%, 95% confidence interval (CI) 15.1-32.0, P < 0.0001; Cam+TP versus TP: difference 10.9%, 95% CI 3.7-18.1, P = 0.0034). The study met its primary endpoint of pCR; however, EFS is not yet mature. The incidence of grade ≥3 treatment-related adverse events during neoadjuvant treatment was 34.1% for the Cam+nab-TP group, 29.2% for the Cam+TP group and 28.8% for the TP group; the postoperative complication rates were 34.2%, 38.8% and 32.0%, respectively. Neoadjuvant camrelizumab plus chemotherapy demonstrated superior pCR rates compared to chemotherapy alone for LA-ESCC, with a tolerable safety profile. Chinese Clinical Trial Registry identifier: ChiCTR2000040034 .

Integrating MR radiomics and dynamic hematological factors predicts pathological response to neoadjuvant chemoradiotherapy in esophageal cancer.

Purpose: We aimed to integrate MR radiomics and dynamic hematological factors to build a model to predict pathological complete response (pCR) to neoadjuvant chemoradiotherapy (NCRT) in esophageal squamous cell carcinoma (ESCC). Methods: Patients with ESCC receiving NCRT and esophagectomy between September 2014 and September 2022 were retrospectively included. All patients underwent pre-treatment T2-weighted imaging as well as pre-treatment and post-treatment blood tests. Patients were randomly divided to training set and testing set at a ratio of 7:3. Machine learning models were constructed based on MR radiomics and hematological factors to predict pCR, respectively. A nomogram model was developed to integrate MR radiomics and hematological factors. Model performances were evaluated by areas under curves (AUCs), sensitivity, specificity, positive predictive value and negative. Results: A total of 82 patients were included, of whom 39 (47.6 %) achieved pCR. The hematological model built with four hematological factors had an AUC of 0.628 (95%CI 0.391-0.852) in the testing set. Two out of 1106 extracted features were selected to build the radiomics model with an AUC of 0.821 (95%CI 0.641-0.981). The nomogram model integrating hematological factors and MR radiomics had best predictive performance, with an AUC of 0.904 (95%CI 0.770-1.000) in the testing set. Conclusion: An integrated model using dynamic hematological factors and MR radiomics is constructed to accurately predicted pCR to NCRT in ESCC, which may be potentially useful to assist individualized preservation treatment of the esophagus.

The Battle for Accuracy: Identifying the Most Effective Grading System for Lung Invasive Mucinous Adenocarcinoma.

BACKGROUND: The prognostic analysis of lung invasive mucinous adenocarcinoma (IMA) is deficient due to the lack of a universally recommended histological grading system, leading to unregulated treatment approaches. OBJECTIVE: We aimed to examine the clinical trajectory of IMA and assess the viability of utilizing the existing grading system for lung invasive non-mucinous adenocarcinoma in the context of IMA. METHODS: We retrospectively collected clinicopathological data from 265 IMA patients. Each case re-evaluated the tumor grade using the following three classification systems: the 4th Edition of the World Health Organization classification system, the International Association for the Study of Lung Cancer (IASLC) grading system, and a two-tier grading system. We performed a comparative analysis of these grading systems and identified the most effective grading system for IMA. RESULTS: The study comprised a total of 214 patients with pure IMA and 51 patients with mixed IMA. The 5-year overall survival (OS) rates for pure IMA and mixed IMA were 86.7% and 57.8%, respectively. All three grading systems proved to be effective prognostic classifiers for IMA. The value of area under the curve at 1-, 3-, and 5-year OS was highest for the IASLC grading system compared with the other grade systems and the clinical stage. The IASLC classification system was an independent prognostic predictor (p = 0.009, hazard ratio 2.243, 95% confidence interval 1.219-4.127). CONCLUSION: Mixed IMA is more aggressive than pure IMA, with an OS rate on par with that of high-grade pure IMA. The IASLC grading system can better indicate prognosis and is recommended for lung IMA.

KLF12 interacts with TRIM27 to affect cisplatin resistance and cancer metastasis in esophageal squamous cell carcinoma by regulating L1CAM expression.

Krüppel-like factor 12 (KLF12) has been characterized as a transcriptional repressor, and previous studies have unveiled its roles in angiogenesis, neural tube defect, and natural killer (NK) cell proliferation. However, the contribution of KLF12 to cancer treatment remains undefined. Here, we show that KLF12 is downregulated in various cancer types, and KLF12 downregulation promotes cisplatin resistance and cancer metastasis in esophageal squamous cell carcinoma (ESCC). Mechanistically, KLF12 binds to the promoters of L1 Cell Adhesion Molecule (L1CAM) and represses its expression. Depletion of L1CAM abrogates cisplatin resistance and cancer metastasis caused by KLF12 loss. Moreover, the E3 ubiquitin ligase tripartite motif-containing 27 (TRIM27) binds to the N-terminal region of KLF12 and ubiquitinates KLF12 at K326 via K33-linked polyubiquitination. Notably, TRIM27 depletion enhances the transcriptional activity of KLF12 and consequently inhibits L1CAM expression. Overall, our study elucidated a novel regulatory mechanism involving TRIM27, KLF12 and L1CAM, which plays a substantial role in cisplatin resistance and cancer metastasis in ESCC. Targeting these genes could be a promising approach for ESCC treatment.

(Ca0.25La0.5Dy0.25)CrO3 Ceramic Fiber@Biomass-Derived Carbon Aerogel with Enhanced Solute Transport Channels for Highly Efficient Solar Interface Evaporation.

The use of solar interface evaporation for seawater desalination or sewage treatment is an environmentally friendly and sustainable approach; however, achieving efficient solar energy utilization and ensuring the long-term stability of the evaporation devices are two major challenges for practical application. To address these issues, we developed a novel ceramic fiber@bioderived carbon composite aerogel with a continuous through-hole structure via electrospinning and freeze-casting methods. Specifically, an aerogel was prepared by incorporating perovskite oxide (Ca0.25La0.5Dy0.25)CrO3 ceramic fibers (CCFs) and amylopectin-derived carbon (ADC). The CCFs exhibited remarkable photothermal conversion efficiencies, and the ADC served as a connecting agent and imparted hydrophilicity to the aerogel due to its abundant oxygen-containing functional groups. After optimizing the composition and microstructure, the (Ca0.25La0.5Dy0.25)CrO3 ceramic fiber@biomass-derived carbon aerogel demonstrated remarkable properties, including efficient light absorption and rapid transport of water and solutes. Under 1 kW m-2 light intensity irradiation, this novel material exhibited a high temperature (48.3 °C), high evaporation rate (1.68 kg m-2 h-1), and impressive solar vapor conversion efficiency (91.6%). Moreover, it exhibited long-term stability in water evaporation even with highly concentrated salt solutions (25 wt%). Therefore, the (Ca0.25La0.5Dy0.25)CrO3 ceramic fiber@biomass-derived carbon aerogel holds great promise for various applications of solar interface evaporation.

Molecular subtypes of neuroendocrine carcinomas: A cross-tissue classification framework based on five transcriptional regulators.

Neuroendocrine carcinomas (NECs) are extremely lethal malignancies that can arise at almost any anatomic site. Characterization of NECs is hindered by their rarity and significant inter- and intra-tissue heterogeneity. Herein, through an integrative analysis of over 1,000 NECs originating from 31 various tissues, we reveal their tissue-independent convergence and further unveil molecular divergence driven by distinct transcriptional regulators. Pan-tissue NECs are therefore categorized into five intrinsic subtypes defined by ASCL1, NEUROD1, HNF4A, POU2F3, and YAP1. A comprehensive portrait of these subtypes is depicted, highlighting subtype-specific transcriptional programs, genomic alterations, evolution trajectories, therapeutic vulnerabilities, and clinicopathological presentations. Notably, the newly discovered HNF4A-dominated subtype-H exhibits a gastrointestinal-like signature, wild-type RB1, unique neuroendocrine differentiation, poor chemotherapeutic response, and prevalent large-cell morphology. The proposal of uniform classification paradigm illuminates transcriptional basis of NEC heterogeneity and bridges the gap across different lineages and cytomorphological variants, in which context-dependent prevalence of subtypes underlies their phenotypic disparities.

Medium- and High-Entropy Rare Earth Hexaborides with Enhanced Solar Energy Absorption and Infrared Emissivity.

The development of a new generation of solid particle solar receivers (SPSRs) with high solar absorptivity (0.28-2.5 µm) and high infrared emissivity (1-22 µm) is crucial and has attracted much attention for the attainment of the goals of "peak carbon" and "carbon neutrality". To achieve the modulation of infrared emission and solar absorptivity, two types of medium- and high-entropy rare-earth hexaboride (ME/HEREB6) ceramics, (La0.25Sm0.25Ce0.25Eu0.25)B6 (MEREB6) and (La0.2Sm0.2Ce0.2Eu0.2Ba0.2)B6 (HEREB6), with severe lattice distortions were synthesized using a high-temperature solid-phase method. Compared to single-phase lanthanum hexaboride (LaB6), HEREB6 ceramics show an increase in solar absorptivity from 54.06% to 87.75% in the range of 0.28-2.5 µm and an increase in infrared emissivity from 76.19% to 89.96% in the 1-22 µm wavelength range. On the one hand, decreasing the free electron concentration and the plasma frequency reduces the reflection and ultimately increases the solar absorptivity. On the other hand, the lattice distortion induces changes in the B-B bond length, leading to significant changes in the Raman scattering spectrum, which affects the damping constant and ultimately increases the infrared emissivity. In conclusion, the multicomponent design can effectively improve the solar energy absorption and heat transfer capacity of ME/HEREB6, thus providing a new avenue for the development of solid particles.

Case report: A 17-year-old male with primary pulmonary osteosarcoma.

Primary pulmonary osteosarcoma is one of the extraskeletal osteosarcomas originating from the lung with an extremely low incidence and highly invasive potential. Here we report a case of primary pulmonary osteosarcoma treated in our hospital with a literature review. The patient, a 17-year-old male, had a cough and hemoptysis for 20 days. Computed tomography (CT) and positron emission tomography (PET)/CT were performed in our hospital. According to pathological examination after surgery, the tumor was diagnosed as a high-grade sarcoma with remarkable osteogenesis and necrosis. Based on radiological and histological examinations, a diagnosis of primary pulmonary osteosarcoma originating was considered. The patient underwent surgery and adjuvant chemotherapy. This patient has been under consecutive follow-up for nearly 8 years, showing no signs of recurrence or distant metastasis. Primary pulmonary osteosarcoma is a rare lung malignancy that shows rapid progression, nonspecific symptoms and inapparent signs at an early stage. The diagnosis of primary pulmonary osteosarcoma highly relies on imaging and histological examinations, among which chest CT is the predominant method to check this disease.

Significant effect of posterior line treatment of HER2 positive advanced gastric cancer: A case report.

At present, there are few options for third line and above treatment of advanced gastric cancer and the single drug effect is poor. HER2 positive gastric cancer is an important subtype of gastric cancer and has certain immune characteristics. The combination of HER2 inhibitor and PD-1 inhibitor has a synergistic effect, and anti-tumor drugs targeting HER2 can play an anti-angiogenesis role by downregulating VEGF. We report a patient with HER2-positive gastric cancer who developed post-operative tumor recurrence and metastasis after adjuvant chemotherapy and radiotherapy. Trastuzumab combined with albumin paclitaxel was used as second-line treatment with progression-free survival for 9 months. In third line treatment, we retained trastuzumab and combined it with camrelizumab and apatinib. During the treatment period, although the patient stopped taking the drugs due to the side effects of camrelizumab and apatinib, he achieved a PFS of 10.4 months. Considering the good effect of the third line treatment, we added another PD-1 inhibitor and continued to combine trastuzumab treatment. We found that the patient still benefited from the treatment and continued to survive for another 4 months. At present, the patient is treated with DisitamabVedotin (HER2-ADC) combined with PD-1 inhibitor, and no overall survival outcome has been observed.

Radiological and clinical features of large consolidative-type pulmonary invasive mucinous adenocarcinoma.

BACKGROUND: This study aimed to investigate the radiological, pathological, and prognostic characteristics of large consolidative-type pulmonary invasive mucinous adenocarcinomas (IMA). METHODS: We retrospectively reviewed 738 patients who confirmed IMA between January 2010 and August 2022, and two radiologists reviewed imaging data to determine subtypes. We included 41 patients with pathologically large consolidative-type IMA. We analyzed their radiological, pathological, and prognostic characteristics. The recurrence-free survival (RFS) and overall survival (OS) were determined using the Kaplan-Meier method. RESULTS: Most lesions were located in the lower lobe, with 46.3% patients showing multiple lesions. Halo, angiogram, vacuole, air bronchogram, and dead branch sign were observed in 97.6%, 73.2%, 63.4%, 61.0%, and 61.0% of the cases, respectively. Unevenly low enhancement was observed in 88.89% of patients. T3 and T4 pathological stages were observed in 50.0% and 30.6% of patients, respectively. Lymph node metastasis was observed in 16.7% patients, with no distant metastasis. Spread-through air spaces and intrapulmonary dissemination were observed in 27.8% and 19.4% patients, respectively. Moreover, Kirsten rat sarcoma viral oncogene mutations were found in 68.6% of cases, and no epidermal growth factor receptor mutations were seen. Among all mutation sites, G12V mutation is the most common, accounting for 40%. The average RFS and OS were 19.4 and 66.4 months, respectively, with 3-year RFS and OS rates of 30.0% and 75.0%, respectively. Pleural invasion and lymph node metastasis were independent risk factors for diagnosis. CONCLUSION: Halo, vacuole, angiogram, and dead branch signs were frequently observed in consolidative-type IMA. Kirsten rat sarcoma viral oncogene mutations are common in consolidative-type IMA, especially site G12V, whereas epidermal growth factor receptor mutations were rare; therefore, gene immunotherapy was more difficult. Most patients were in stage T3-T4; however, lymph node metastasis was rare.

Tumor stroma ratio, tumor stroma maturity, tumor-infiltrating immune cells in relation to prognosis, and neoadjuvant therapy response in esophagogastric junction adenocarcinoma.

Accurate predictions on prognosis and neoadjuvant therapy response are crucial for esophagogastric junction adenocarcinoma (EGJA) patients. Therefore, we aimed to investigate the predictive abilities of several indicators, including tumor stroma ratio (TSR), tumor stroma maturity (TSM), and the density and spatial distribution of tumor-infiltrating immune cells (TIICs), such as T cells, B cells, and tumor-associated macrophages (TAMs). Resection and biopsy specimens of a total of 695 patients were included, obtained from the National Cancer Center (NCC) and The Cancer Genome Atlas (TCGA) cohorts. TSR and TSM were evaluated based on histological assessment. TIICs were quantified by QuPath following immunohistochemical (IHC) staining in resection specimens, while the Klintrup-Mäkinen (KM) grade was employed for evaluating TIIC in biopsy specimens. Patients with high stromal levels or immature stroma had relatively worse prognoses. Furthermore, high CD8+T cell count in the tumor periphery, as well as low CD68+ TAM count either in the tumor center or in the tumor periphery, was an independent favorable prognostic factor. Significantly, the combination model incorporating TSM and CD163+TAMs emerged as an independent prognostic factor in both two independent cohorts (HR 3.644, 95% CI 1.341-9.900, p = 0.011 and HR 1.891, 95% CI 1.195-2.99, p = 0.006, respectively). Additionally, high stromal levels in preoperative biopsies correlated with poor neoadjuvant therapy response (p < 0.05). In conclusion, our findings suggest that TSR, TSM, CD8+T cell, CD68+TAMs, and CD163+TAMs predict the prognosis to some extent in patients with EGJA. Notably, the combined model incorporating TSM and CD163+TAM can contribute significantly to prognostic stratification. Additionally, high stromal levels evaluated in preoperative biopsy specimens correlated with poor neoadjuvant therapy response.

MR radiomics predicts pathological complete response of esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy: a multicenter study.

BACKGROUND: More than 40% of patients with resectable esophageal squamous cell cancer (ESCC) achieve pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT), who have favorable prognosis and may benefit from an organ-preservation strategy. Our study aims to develop and validate a machine learning model based on MR radiomics to accurately predict the pCR of ESCC patients after nCRT. METHODS: In this retrospective multicenter study, eligible patients with ESCC who underwent baseline MR (T2-weighted imaging) and nCRT plus surgery were enrolled between September 2014 and September 2022 at institution 1 (training set) and between December 2017 and August 2021 at institution 2 (testing set). Models were constructed using machine learning algorithms based on clinical factors and MR radiomics to predict pCR after nCRT. The area under the curve (AUC) and cutoff analysis were used to evaluate model performance. RESULTS: A total of 155 patients were enrolled in this study, 82 in the training set and 73 in the testing set. The radiomics model was constructed based on two radiomics features, achieving AUCs of 0.968 (95%CI 0.933-0.992) in the training set and 0.885 (95%CI 0.800-0.958) in the testing set. The cutoff analysis resulted in an accuracy of 82.2% (95%CI 72.6-90.4%), a sensitivity of 75.0% (95%CI 58.3-91.7%), and a specificity of 85.7% (95%CI 75.5-96.0%) in the testing set. CONCLUSION: A machine learning model based on MR radiomics was developed and validated to accurately predict pCR after nCRT in patients with ESCC.

Gastric tubular adenocarcinoma with diffuse neutrophils infiltrating: characteristics and probable treatment strategy.

BACKGROUND: Gastric adenocarcinoma is a highly heterogeneous malignancy with varying prognoses. In clinicopathological practice, we noticed a special tubular adenocarcinoma with diffuse neutrophils infiltrating (TADNI). However, the proportion and characteristics of TADNI remain unclear. This study aimed to evaluate the features of TADNI and explore probable treatments. METHODS: We divided 289 tubular adenocarcinoma cases into the TADNI and non-TADNI (nTADNI) groups by histological neutrophil quantity and performed immunohistochemistry of treatment-associated markers (CXCR1, CXCR2, PD-L1, CD8, HER2 and VEGFR2). Then we evaluated the clinical and morphological features in these cases. We also compared the value of histological features and peripheral blood neutrophil test. In addition, multiomics bioinformatic analyses were performed using the public datasets. RESULTS: In our cohort, TADNI accounted for 10.4% of all tubular adenocarcinoma cases. These cases had worse prognoses (especially the neutrophils mainly outside the tubes) than nTADNI cases. The histological identification of TADNI had more prognostic value than peripheral blood neutrophils. CXCR1/CXCR2 expression was significantly high in TADNI group which indicated that CXCR1/CXCR2 inhibitors might be beneficial for TADNI patients. There were no significant differences in the expression of PD-L1, CD8, HER2 and VEGFR2. The analyses of TCGA data confirmed that TADNI cases had poorer prognoses and higher CXCR1/CXCR2 expression. Bioinformatic results also revealed molecular features (more hsa-mir-223 expression, fewer CD8-positive T cells and regulatory T cells, tighter communication between tumor cells' CXCR1/CXCR2 and neutrophils' CXCL5/CXCL8) of this type. CONCLUSIONS: TADNI is a special morphological subtype with poorer prognoses and unique molecular characteristics, which might benefit from CXCR1/CXCR2 inhibitors.

Dual-layer spectral-detector CT for predicting microsatellite instability status and prognosis in locally advanced gastric cancer.

OBJECTIVE: To construct and validate a prediction model based on dual-layer detector spectral CT (DLCT) and clinico-radiologic features to predict the microsatellite instability (MSI) status of gastric cancer (GC) and to explore the relationship between the prediction results and patient prognosis. METHODS: A total of 264 GC patients who underwent preoperative DLCT examination were randomly allocated into the training set (n = 187) and validation set (n = 80). Clinico-radiologic features and DLCT parameters were used to build the clinical and DLCT model through multivariate logistic regression analysis. A combined DLCT parameter (CDLCT) was constructed to predict MSI. A combined prediction model was constructed using multivariate logistic regression analysis by integrating the significant clinico-radiologic features and CDLCT. The Kaplan-Meier survival analysis was used to explore the prognostic significant of the prediction results of the combined model. RESULTS: In this study, there were 70 (26.52%) MSI-high (MSI-H) GC patients. Tumor location and CT_N staging were independent risk factors for MSI-H. In the validation set, the area under the curve (AUC) of the clinical model and DLCT model for predicting MSI status was 0.721 and 0.837, respectively. The combined model achieved a high prediction efficacy in the validation set, with AUC, sensitivity, and specificity of 0.879, 78.95%, and 75.4%, respectively. Survival analysis demonstrated that the combined model could stratify GC patients according to recurrence-free survival (p = 0.010). CONCLUSION: The combined model provides an efficient tool for predicting the MSI status of GC noninvasively and tumor recurrence risk stratification after surgery. CRITICAL RELEVANCE STATEMENT: MSI is an important molecular subtype in gastric cancer (GC). But MSI can only be evaluated using biopsy or postoperative tumor tissues. Our study developed a combined model based on DLCT which could effectively predict MSI preoperatively. Our result also showed that the combined model could stratify patients according to recurrence-free survival. It may be valuable for clinicians in choosing appropriate treatment strategies to avoid tumor recurrence and predicting clinical prognosis in GC. KEY POINTS: • Tumor location and CT_N staging were independent predictors for MSI-H in GC. • Quantitative DLCT parameters showed potential in predicting MSI status in GC. • The combined model integrating clinico-radiologic features and CDLCT could improve the predictive performance. • The prediction results could stratify the risk of tumor recurrence after surgery.