Efficacy of fosaprepitant combined with tropisetron plus dexamethasone in preventing nausea and emesis during fractionated radiotherapy with weekly cisplatin chemotherapy: interim analysis of a randomized, prospective, clinical trial using competing risk analysis.

PURPOSE: There are no well-recognized guidelines for antiemesis during concurrent chemoradiotherapy (CCRT) for cervical cancer (CC) and nasopharyngeal cancer (NPC) until now. The study was designed to assess the efficacy and safety of fosaprepitant combined with tropisetron and dexamethasone in preventing nausea and vomiting during 5 weeks of fractionated radiotherapy and concomitant weekly low-dose cisplatin chemotherapy in patients with CC or NPC. METHODS: Patients with CC or NPC were scheduled to receive fractionated radiotherapy and weekly cisplatin (25-40 mg/m2) chemotherapy for at least 5 weeks. Patients stratified by tumor type and induction chemotherapy were 1:1 randomly assigned to receive fosaprepitant, tropisetron, and dexamethasone or tropisetron plus dexamethasone as an antiemetic regimen. Efficacy was assessed primarily by the cumulative incidence of emesis after 5 weeks of treatment, and safety by adverse events (AEs). RESULTS: Between July 2020 and July 2022, 116 patients consented to the study of whom 103 were included in this interim analysis (fosaprepitant group [N = 52] vs control group [N = 51]). The cumulative incidence of emesis at 5 weeks (competing risk analysis) was 25% (95% CI 14.2-37.4) for the fosaprepitant group compared with 59% (95% CI 43.9-71.0) for the control group. There was a significantly lower cumulative risk of emesis in the fosaprepitant group (HR 0.35 [95% CI 0.19-0.64]; p < 0.001). Fosaprepitant was well tolerated as the incidences of adverse events in the two groups were comparable. CONCLUSION: The addition of fosaprepitant to tropisetron plus dexamethasone significantly reduced the risk of nausea and vomiting during 5 weeks of CCRT in patients with CC or NPC, and fosaprepitant was well tolerated. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov on October 3, 2022, number NCT05564286.

Identification of Tumor Antigens and Immune Subtypes of High-grade Serous Ovarian Cancer for mRNA Vaccine Development.

High-grade serous ovarian cancer (HGSC) is the most common pathology of ovarian cancer and has aggressive characteristics and poor prognosis. mRNA vaccines are a novel tool for cancer immune treatment and may play an important role in HGSC therapy. Our study aimed to explore tumour antigens for vaccine development and identify potential populations amenable to vaccine treatment. Based on transcription data from The Cancer Genome Atlas (TCGA), we identified four tumour-specific antigens for vaccine production: ARPC1B, ELF3, VSTM2L, and IL27RA. In addition to being associated with HGSC patient prognosis, the expression of these antigens was positively correlated with the abundances of antigen-presenting cells (APCs). Furthermore, we stratified HGSC samples into three immune subtypes (IS1-IS3) with different immune characteristics. A corhort from ICGC (International Cancer Genome Consortium) was used to validate. Patients of IS3 had the best prognosis, while patients of IS1 were most likely to benefit from vaccination. There was substantial heterogeneity in immune signatures and immune-associated molecule expression in HGSC. Finally, weighted gene coexpression network analysis (WGCNA) was employed to cluster immune-related genes and explore potential biomarkers related to vaccination. In conclusion, we identified four potential tumour antigens for mRNA vaccine production for HGSC treatment, and the immune subtype could be an important indicator to select suitable HGSC patients to receive vaccination.

Clinical characteristics, treatment patterns, and survival outcomes of pulmonary mucosa-associated lymphoid tissue lymphoma in the United States.

BACKGROUND: Pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma is a relatively rare disease. We aimed to perform a large-scale study of clinical characteristics and optimal treatment for pulmonary MALT lymphoma patients. METHOD: Our study extracted data from the Surveillance, Epidemiology, and End Results (SEER) Program. The chi-square test was utilized to compare clinical factors. Overall survival (OS) was compared using the Kaplan-Meier (KM) method and Cox regression analysis. Cancer-specific survival (CSS) was compared by the Fine-Gray test. Propensity score matching (PSM) was used to balance confounders. RESULTS: Females and elderly individuals are more likely to suffer from pulmonary MALT lymphoma. The incidence rate is increasing, and most patients are diagnosed in the early stage without specific symptoms. Patients usually suffer from a favorable survival period, especially patients in the early stage. Patients in stage I-II can obtain a survival advantage from surgery, especially for patients older than 60 years, with unilateral lesions, with single-lung-lobe lesions, in stage I, and without B symptoms. Chemotherapy decreases the risk of death for advanced-stage patients, and males, caucasians, patients with stage IV disease, or patients with only unilateral lung involvement were especially recommended for chemotherapy. CONCLUSION: Pulmonary MALT lymphoma is an indolent tumor. Patients in different stages had different prognoses, and different treatments were recommended. We will conduct prospective research in the future.

Trifluoromethanesulfonic Acid Promoted Controllable Electrophilic Aromatic Nitration.

In this work, we developed a facile and controllable electrophilic aromatic nitration method with commercially available 68% HNO3 as the nitrating reagent and trifluoromethanesulfonic acid (HOTf) as the catalyst in hexafluoroisopropanol or under solvent-free conditions. The electrophilic nitration products of different arenes can be obtained in almost quantitative yields by tuning the loading of HOTf. The strong acidity and water absorbing property of HOTf allowed this transformation to reach completion in a short time at room temperature.

Cardio-cerebrovascular Outcomes in MODY, Type 1 Diabetes, and Type 2 Diabetes: A Prospective Cohort Study.

CONTEXT: Cardio-cerebrovascular events are severe complications of diabetes. OBJECTIVE: We aim to compare the incident risk of cardio-cerebrovascular events in maturity onset diabetes of the young (MODY), type 1 diabetes, and type 2 diabetes. METHODS: Type 1 diabetes, type 2 diabetes, and MODY were diagnosed by whole exome sequencing. The primary endpoint was the occurrence of the first major adverse cardiovascular event (MACE), including acute myocardial infarction, heart failure, stroke, unstable angina pectoris, and cardio-cerebrovascular-related mortality. Cox proportional hazards models were applied and adjusted to calculate hazard ratios (HRs) and 95% CIs for the incident risk of MACE in type 1 diabetes, type 2 diabetes, MODY, and MODY subgroups compared with people without diabetes (control group). RESULTS: Type 1 diabetes, type 2 diabetes, and MODY accounted for 2.7%, 68.1%, and 11.4% of 26 198 participants with diabetes from UK Biobank. During a median follow-up of 13 years, 1028 MACEs occurred in the control group, contrasting with 70 events in patients with type 1 diabetes (HR 2.15, 95% CI 1.69-2.74, P < .05), 5020 events in patients with type 2 diabetes (HR 7.02, 95% CI 6.56-7.51, P < .05), and 717 events in MODY (HR 5.79, 95% CI 5.26-6.37, P < .05). The hazard of MACE in HNF1B-MODY was highest among MODY subgroups (HR 11.00, 95% CI 5.47-22.00, P = 1.5 × 10-11). CONCLUSION: MODY diagnosed by genetic analysis represents higher prevalence than the clinical diagnosis in UK Biobank. The risk of incident cardio-cerebrovascular events in MODY ranks between type 1 diabetes and type 2 diabetes.

B(9)-OH-o-Carboranes: Synthesis, Mechanism, and Property Exploration.

Herein, we present a chemically robust and efficient synthesis route for B(9)-OH-o-carboranes by the oxidation of o-carboranes with commercially available 68% HNO3 under the assistance of trifluoromethanesulfonic acid (HOTf) and hexafluoroisopropanol (HFIP). The reaction is highly efficient with a wide scope of carboranes, and the selectivity of B(9)/B(8) is up to 98:2. The success of this transformation relies on the strong electrophilicity and oxidizability of HNO3, promoted through hydrogen bonds of the Brønsted acid HOTf and the solvent HFIP. Mechanism studies reveal that the oxidation of o-carborane involves an initial electrophilic attack of HNO3 to the hydrogen atom at the most electronegative B(9) of o-carborane. In this transformation, the hydrogen atom of the B-H bond is the nucleophilic site, which is different from the electrophilic substitution reaction, where the boron atom is the nucleophilic site. Therefore, this is an oxidation-reduction reaction of o-carborane under mild conditions in which N(V) → N(III) and H(-I) → H(I). The derivatization of 9-OH-o-carborane was further examined, and the carboranyl group was successfully introduced to an amino acid, polyethylene glycol, biotin, deoxyuridine, and saccharide. Undoubtedly, this approach provides a selective way for the rapid incorporation of carborane moieties into small molecules for application in boron neutron capture therapy, which requires the targeted delivery of boron-rich groups.

A Method for Highly Selective Halogenation of o-Carboranes and m-Carboranes.

A facile halogenation method for highly selective synthesis of 9-X-o-carboranes, 9,12-X2-o-carboranes, 9-X-12-X'-o-carboranes, 9-X-m-carboranes, 9,10-X2-m-carboranes, and 9-X-10-X'-m-carboranes (X, X' = Cl, Br, I) has been developed on the basis of our previous work. The success of this transformation relies on the usage of trifluoromethanesulfonic acid (HOTf), the easily available strong Brønsted acid. The addition of HOTf greatly increases the electrophilicity of N-haloamides through hydrogen bonding interaction, resulting in the low loading of N-haloamides, short reaction time, and mild reaction conditions. Additionally, the solvent 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) is also essential to further increase the acidity of HOTf.

A nomogram based on clinicopathological and ultrasound characteristics to predict central neck lymph node metastases in papillary thyroid cancer.

Purpose: Papillary thyroid cancer (PTC) has grown rapidly in prevalence over the past few decades, and central neck lymph node metastasis (CNLNM) is associated with poor prognoses. However, whether to carry out preventive central neck lymph node dissection (CNLND) is still controversial. We aimed to construct a prediction model of CNLNM to facilitate making clinical surgical regimens. Methods: A total of 691 patients with PTC between November 2018 and December 2021 were included in our study. Univariate and multivariate analyses were performed on basic information and clinicopathological characteristics, as well as ultrasound characteristics (American College of Radiology (ACR) scores). The prediction model was constructed and performed using a nomogram, and then discriminability, calibrations, and clinical applicability were evaluated. Results: Five variables, namely, male, age >55 years, clinical lymph node positivity, tumor size ≥1 cm, and ACR scores ≥6, were independent predictors of CNLNM in the multivariate analysis, which were eventually included to construct a nomogram model. The area under the curve (AUC) of the model was 0.717, demonstrating great discriminability. A calibration curve was developed to validate the calibration of the present model by bootstrap resampling, which indicated that the predicted and actual values were in good agreement and had no differentiation from the ideal model. The decision curve analysis (DCA) indicated that the prediction model has good clinical applicability. Conclusions: Our non-invasive prediction model combines ACR scores with clinicopathological features presented through nomogram and has shown good performance and application prospects for the prediction of CNLNM in PTCs.

Radiomics models based on CT at different phases predicting lymph node metastasis of esophageal squamous cell carcinoma (GASTO-1089).

Purpose: To investigate the value of radiomics models based on CT at different phases (non-contrast-enhanced and contrast-enhanced images) in predicting lymph node (LN) metastasis in esophageal squamous cell carcinoma (ESCC). Methods and materials: Two hundred and seventy-four eligible patients with ESCC were divided into a training set (n =193) and a validation set (n =81). The least absolute shrinkage and selection operator algorithm (LASSO) was used to select radiomics features. The predictive models were constructed with radiomics features and clinical factors through multivariate logistic regression analysis. The predictive performance and clinical application value of the models were evaluated by area under receiver operating characteristic curve (AUC) and decision curve analysis (DCA). The Delong Test was used to evaluate the differences in AUC among models. Results: Sixteen and eighteen features were respectively selected from non-contrast-enhanced CT (NECT) and contrast-enhanced CT (CECT) images. The model established using only clinical factors (Model 1) has an AUC value of 0.655 (95%CI 0.552-0.759) with a sensitivity of 0.585, a specificity of 0.725 and an accuracy of 0.654. The models contained clinical factors with radiomics features of NECT or/and CECT (Model 2,3,4) have significantly improved prediction performance. The values of AUC of Model 2,3,4 were 0.766, 0.811 and 0.809, respectively. It also achieved a great AUC of 0.800 in the model built with only radiomics features derived from NECT and CECT (Model 5). DCA suggested the potential clinical benefit of model prediction of LN metastasis of ESCC. A comparison of the receiver operating characteristic (ROC) curves using the Delong test indicated that Models 2, 3, 4, and 5 were superior to Model 1(P< 0.05), and no difference was found among Model 2, 3, 4 and Model 5(P > 0.05). Conclusion: Radiomics models based on CT at different phases could accurately predict the lymph node metastasis in patients with ESCC, and their predictive efficiency was better than the clinical model based on tumor size criteria. NECT-based radiomics model could be a reasonable option for ESCC patients due to its lower price and availability for renal failure or allergic patients.

Exploring the Prognosis of Breast Cancer with Synchronous Distant Nonregional Lymph Node Metastasis and Establishing a Predictive Model: A Population-Based Study.

BACKGROUND: We aimed to explore the prognosis of breast cancer patients with synchronous isolated distant-lymph node metastasis (SDLNM). METHODS: We extracted information from the Surveillance, Epidemiology, and End Results Program. Kaplan-Meier and Cox regression analyses were used to compare overall survival (OS). Fine-Gray test was utilized to compare breast cancer-specific survival (BCSS). We applied propensity score matching (PSM) to balance confounders. In total, 692 SDLNM patients were allocated into training and validation cohorts. Univariate and multivariate analyses were implemented to determine independent prognostic variables. A nomogram predicting OS of SDLNM patients was constructed. Calibration curves and receiver operating characteristic curves were utilized to access the predictive model. RESULTS: Cox regression and PSM analysis showed that the prognosis of SDLNM patients was similar to breast cancer patients in stage TnN3cM0 and superior to patients with other oligometastasis (SDLNM vs. TnN3cM0, p = 0.778; SDLNM vs. other oligometastasis: HR 0.767, 95% CI, 0.672-0.875, p < 0.001). A nomogram was established to predict 1-, 3-, and 5-year OS for SDLNM patients. All C-indexes and AUCs were greater than 0.7. Calibration curves implied accurate prediction. For patients receiving mastectomy, postoperative chemotherapy and radiotherapy were significant. CONCLUSIONS: Breast cancer with SDLNM has a similar OS and BCSS with locally advanced disease. Comprehensive treatment was associated with better prognosis compared with palliative therapy. We constructed a predictive model for SDLNM breast cancer. It will be necessary to design large-scale prospective trials to confirm our results and validate the predictive model.

A combined predicting model for benign esophageal stenosis after simultaneous integrated boost in esophageal squamous cell carcinoma patients (GASTO1072).

Purpose: We aimed to develop a combined predicting model for benign esophageal stenosis (BES) after simultaneous integrated boost (SIB) with concurrent chemotherapy in patients with esophageal squamous cell carcinoma (ESCC). Methods: This study included 65 patients with EC who underwent SIB with chemotherapy. Esophageal stenosis was evaluated using esophagograms and the severity of eating disorders. Risk factors were investigated using univariate and multivariate analyses. Radiomics features were extracted based on contrast-enhanced CT (CE-CT) before treatment. The least absolute shrinkage and selection operator (LASSO) regression analysis was used for feature selection and radiomics signature construction. The model's performance was evaluated using Harrell's concordance index and receiver operating characteristic curves. Results: The patients were stratified into low- and high-risk groups according to BES after SIB. The area under the curves of the clinical model, Rad-score, and the combined model were 0.751, 0.820 and 0.864, respectively. In the validation cohort, the AUCs of these three models were 0.854, 0.883 and 0.917, respectively. The Hosmer-Lemeshow test showed that there was no deviation from model fitting for the training cohort (p=0.451) and validation cohort (p=0.481). The C-indexes of the nomogram were 0.864 and 0.958 for the training and validation cohort, respectively. The model combined with Rad-score and clinical factors achieved favorable prediction ability. Conclusion: Definitive chemoradiotherapy could alleviate tumor-inducing esophageal stenosis but result in benign stenosis. We constructed and tested a combined predicting model for benign esophageal stenosis after SIB. The nomogram incorporating both radiomics signature and clinical prognostic factors showed favorable predictive accuracy for BES in ESCC patients who received SIB with chemotherapy. Trial registration number and date of registration: Registered in www.Clinicaltrial.gov, ID: NCT01670409, August 12, 2012.

Late Toxicities, Failure Patterns, Local Tumor Control, and Survival of Esophageal Squamous Cell Carcinoma Patients After Chemoradiotherapy With a Simultaneous Integrated Boost: A 5-Year Phase II Study.

PURPOSE: We aimed to evaluate the long-term outcomes of concurrent chemoradiotherapy (CCRT) with a simultaneous integrated boost (SIB) of radiotherapy for esophageal squamous cell carcinoma (ESCC). METHODS AND MATERIALS: Eighty-seven patients with primary ESCC enrolled in this phase II trial. The majority (92.0%) had locoregionally advanced disease. They underwent definitive chemoradiotherapy. The radiotherapy doses were 66 Gy for the gross tumor and 54 Gy for the subclinical disease. Doses were simultaneously administered in 30 fractions over 6 weeks. The patients also underwent concurrent and adjuvant chemotherapy, which comprised cisplatin and fluorouracil. The study end points were acute and late toxicities, first site of failure, locoregional tumor control, and overall survival rates. RESULTS: The median follow-up time was 65.7 (range, 2.2-97.5) months for all patients and 81.5 (range, 19.4-97.5) months for those alive. There were 17 cases (19.5%) of severe late toxicities, including four cases (4.6%) of grade 5 and seven (8.0%) of grade 3 esophageal ulceration, four (4.6%) of grade 3 esophageal stricture, and two (2.3%) of grade 3 radiation-induced pneumonia. Twenty-three (26.4%) patients had locoregional disease progression. Most (86.7%) locally progressive lesions were within the dose-escalation region in the initial radiation plan, while majority of the recurrent lymph nodes were found out-of-field (83.3%) and in the supraclavicular region (75.0%). The 1-, 2-, 3-, and 5-year locoregional tumor control and overall survival rates were 79.2%, 72.4%, 72.4%, 70.8%, and 82.8%, 66.6%, 61.9%, 58.4%, respectively. Incomplete tumor response, which was assessed immediately after CCRT was an independent risk predictor of disease progression and death in ESCC patients. CONCLUSIONS: CCRT with SIB was well tolerated in ESCC patients during treatment and long-term follow-up. Moreover, patients who underwent CCRT with SIB exhibited improved local tumor control and had better survival outcomes compared to historical data of those who had standard-dose radiotherapy.

Protective Effects of ACEI/ARB on Left Ventricular Function in Anthracycline-Induced Chronic Cardiotoxicity: A Meta-Analysis of Randomized Controlled Trials.

PURPOSE: Cardiotoxicity is an important side effect of anthracycline. Cardioprotective drugs for anthracycline remain inconclusive. We attempted to determine the role of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-receptor blockers (ARB) in the prevention of anthracycline-induced cardiotoxicity. HYPOTHESIS: Prophylactic use of ACEI/ARB reduces the clinical or subclinical cardiotoxicity of anthracycline. METHODS: Randomized controlled trials (RCTs) of ACEI/ARB in the prevention of anthracycline-induced cardiotoxicity were obtained by searching Pubmed, Embase, Web of Science, and Cochrane databases. 7 studies were finally included. A meta-analysis was performed on the 7 studies. The end points were changes in left ventricle ejection fraction (LVEF), early and late diastolic peak velocity ratio (E/A), and occurrence of hypotensive events. RESULTS: Prophylactic use of ACEI/ARB has potential benefits for anthracycline-induced cardiotoxicity. LVEF was better preserved in the experimental group than in the control group (weighted mean difference [WMD] -3.16%, 95% confidence interval [CI] [-5.78, -0.54], p = 0.02). Follow-up time, tumor type, drug type, and geographical region did not affect the results. There was no significant benefit of E/A in the experimental group (WMD 0.02, 95% CI [-0.06, 0.11], p = 0.58), and no increase in the incidence of hypotension (risk ratio 3.79, 95% CI [0.44, 32.89], p = 0.23). CONCLUSIONS: We found that prophylactic use of ACEI/ARB reduced the clinical or subclinical cardiotoxicity of anthracycline, and the increase in hypotensive events was not significant. Due to the relatively small number of clinical studies and participants, more related studies are necessary to further verify our results.

Heterogeneity of IFN-Mediated Responses and Tumor Immunogenicity in Patients with Cervical Cancer Receiving Concurrent Chemoradiotherapy.

PURPOSE: To ask whether the expression of immune markers and IFN signaling in tumor biopsies changes during concurrent chemoradiotherapy (CCRT). EXPERIMENTAL DESIGN: Tumor biopsies and peripheral mononuclear blood cells (PMBC) before and immediately after 20 Gy/10 fractions (F) of radiation treatment (RT) from 30 patients with cervical cancer receiving CCRT were evaluated by IHC and qRT-PCR for immune markers and correlated with the short-term response. RESULTS: Tumor immune response to radiation before and after 10F RT as reflected by CD8+ T-cell infiltration had substantial heterogeneity with increases, decreases, and no change all evident. Increases in CD8+ T cells during CCRT correlated with the presence of nuclear IRF1 in tumor cells (r = 0.68, P < 0.0001) and the patient short-term response (P < 0.01). Similarly, in a subset of patients (∼40%) PD-L1 positivity in tumor cells increased, which also correlated with nuclear IRF1 staining (r = 0.48, P < 0.01). Patients with augmented PMBC IFN signature expression after 10F had a significantly higher probability of PD-L1 induction (83% vs. 7%, P < 0.0001). Most patients exhibited abundant expression of SERPINB9 and CD47 in tumor cells, and tumor infiltration by CD68+ cells. SERPINB9 expression correlated with STAT1 signaling in tumor cells. CONCLUSIONS: CCRT leads to differential tumor immunogenicity and IFN signaling in patients with cervical cancer, suggesting radiation induction of immunity is limited to a subset of patients and may reflect the heterogeneity of intratumoral induction of IFNs.See related commentary by Mondini and Deutsch, p. 3815.

Imaging biomarkers of contrast-enhanced computed tomography predict survival in oesophageal cancer after definitive concurrent chemoradiotherapy.

BACKGROUND: This study aimed to evaluate the predictive potential of contrast-enhanced computed tomography (CT)-based imaging biomarkers (IBMs) for the treatment outcomes of patients with oesophageal squamous cell carcinoma (OSCC) after definitive concurrent chemoradiotherapy (CCRT). METHODS: Altogether, 154 patients with OSCC who underwent definitive CCRT were included in this retrospective study. All patients were randomised to the training cohort (n = 99) or the validation cohort (n = 55). Pre-treatment contrast-enhanced CT scans were obtained for all patients and used for the extraction of IBMs. An IBM score, was constructed by using the least absolute shrinkage and selection operator with Cox regression analysis, which was equal to the log-partial hazard of the Cox model in the training cohort and tested in the validation cohort. IBM nomograms were built based on IBM scores for individualised survival estimation. Finally, a decision curve analysis was performed to estimate the clinical usefulness of the nomograms. RESULTS: Altogether, 96 IBMs were extracted from each contrast-enhanced CT scan. IBM scores were constructed from 11 CT-based IBMs for overall survival (OS) and 8 IBMs for progression-free survival (PFS), using the LASSO-Cox regression method in the training cohort. Multivariate analysis revealed that IBM score was an independent prognostic factor correlated with OS and PFS. In the training cohort, the C-indices of IBM scores were 0.734 (95% CI 0.664-0.804) and 0.658 (95% CI 0.587-0.729) for OS and PFS, respectively. In the validation cohort, C-indices were 0.672 (95% CI 0.578-0.766) and 0.666 (95% CI 0.574-0.758) for OS and PFS, respectively. Kaplan-Meier survival analysis showed a significant difference between risk subgroups in the training and validation cohorts. Decision curve analysis confirmed the clinical usefulness of the IBM score. CONCLUSIONS: The IBM score based on pre-treatment contrast-enhanced CT could predict the OS and PFS for patients with OSCC after definitive CCRT. Further multicentre studies with larger sample sizes are warranted.

A Combined Model to Improve the Prediction of Local Control for Lung Cancer Patients Undergoing Stereotactic Body Radiotherapy Based on Radiomic Signature Plus Clinical and Dosimetric Parameters.

PURPOSE: Stereotactic body radiotherapy (SBRT) is an important treatment modality for lung cancer patients, however, tumor local recurrence rate remains some challenge and there is no reliable prediction tool. This study aims to develop a prediction model of local control for lung cancer patients undergoing SBRT based on radiomics signature combining with clinical and dosimetric parameters. METHODS: The radiomics model, clinical model and combined model were developed by radiomics features, incorporating clinical and dosimetric parameters and radiomics signatures plus clinical and dosimetric parameters, respectively. Three models were established by logistic regression (LR), decision tree (DT) or support vector machine (SVM). The performance of models was assessed by receiver operating characteristic curve (ROC) and DeLong test. Furthermore, a nomogram was built and was assessed by calibration curve, Hosmer-Lemeshow and decision curve. RESULTS: The LR method was selected for model establishment. The radiomics model, clinical model and combined model showed favorite performance and calibration (Area under the ROC curve (AUC) 0.811, 0.845 and 0.911 in the training group, 0.702, 0.786 and 0.818 in the validation group, respectively). The performance of combined model was significantly superior than the other two models. In addition, Calibration curve and Hosmer-Lemeshow (training group: P = 0.898, validation group: P = 0.891) showed good calibration of combined nomogram and decision curve proved its clinical utility. CONCLUSIONS: The combined model based on radiomics features plus clinical and dosimetric parameters can improve the prediction of 1-year local control for lung cancer patients undergoing SBRT.

Prognostic and Diagnostic Significance of circRNA Expression in Esophageal Cancer: A Meta-analysis.

BACKGROUND AND AIMS: Circular RNA (circRNA) demonstrates potential biological application in various solid tumors. We intended to evaluate the diagnostic, prognostic, and clinicopathological value of circRNA for esophageal cancer (EC). METHODS: We screened relative studies from Pubmed, Embase, Web of Science, and Cochrane Library. The diagnostic role of circRNAs was testified by pooled sensitivity and specificity. Pooled odds ratio (OR) and pooled hazard ratio (HR) were computed to appraise the clinicopathological and prognostic value, respectively. RESULTS: There were total 15 articles suitable with our included criteria, in which 7 for diagnosis, 8 for prognosis, and 9 for clinicopathological features. The pooled sensitivity and specificity were 0.77 and 0.80, respectively, while the AUC was 0.85. Patients with aberrant expression of circRNAs had a 2.92-fold increased risk of developing EC. The proportion of EC patients with normal circRNA expression only accounted for 29%. Upregulated expression of oncogenic circRNA was correlated with poor clinicopathological features, including lymph node metastasis, tumor size, and T classification, while downregulation of tumor-suppressor circRNA was contributed to worse TNM stage. As for prognosis, upregulated expression of circRNA carried out a diverse survival outcome, with a pooled HR of 2.76 for tumor promoter and that of 0.21 for tumor suppressor. High expression of oncogenic circRNA in both plasma and tumor tissue would lead to a shorter survival duration. CONCLUSION: circRNAs might be a promising biomarker for diagnosis, prognosis, and clinicopathological features of EC.

Establishing a predicted model to evaluate prognosis for initially diagnosed metastatic Her2-positive breast cancer patients and exploring the benefit from local surgery.

BACKGROUND: For patients initially diagnosed with metastatic Her2-positive breast cancer (MHBC), we intended to construct a nomogram with risk stratification to predict prognosis and to explore the role of local surgery. METHODS: We retrieved data from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier (KM) method and log-rank test were used for the selection of significant variables. Cox regression analysis and Fine-Gray test were utilized to confirm independent prognostic factors of overall survival (OS) and breast cancer-specific survival (BCSS). A nomogram predicting 1-year, 3-year, and 5-year OS was developed and validated. Patients were stratified based on the optimal cut-off values of total personal score. KM method and log-rank test were used to estimate OS prognosis and benefit from local surgery and chemotherapy. RESULTS: There were 1680 and 717 patients in the training and validation cohort. Age, race, marriage, T stage, estrogen receptor (ER) status, visceral metastasis (bone, brain, liver and lung) were identified as independent prognostic factors for OS and BCSS, while histology was also corelated with OS. C-indexes in the training and validation cohort were 0.70 and 0.68, respectively. Calibration plots indicated precise predictive ability. The total population was divided into low- (<141 points), intermediate- (142-208 points), and high-risk (>208 points) prognostic groups. Local surgery and chemotherapy brought various degrees of survival benefit for patients with diverse-risk prognosis. CONCLUSIONS: We constructed a model with accurate prediction and discrimination. It would provide a reference for clinicians' decision-making. Surgery on the primary lesion was recommended for patients with good physical performance status, while further study on optimal surgical opportunity was needed.