Comparison of efficacy and safety of combined chemoimmunotherapy with or without radiotherapy for stage IVB esophageal squamous cell carcinoma: a multicenter propensity score matching analysis.

PURPOSE: This study aimed to compare the efficacy and safety of combining first-line chemoimmunotherapy with radiotherapy versus chemoimmunotherapy alone in patients with stage IVB esophageal squamous cell carcinoma (ESCC). METHODS: We retrospectively examined 409 patients with stage IVB ESCC who received first-line chemotherapy and anti-PD-1 antibody, with or without radiotherapy of ≥ 40 Gy radiation dose to primary lesion, from four academic cancer centers between October 2018 and December 2022. Propensity score matching (PSM) was conducted to minimize the potential confounding effects. RESULTS: In the overall cohort of 409 patients, the group that received additional radiotherapy had superior overall survival (OS) (hazard ratio [HR]: 0.51, 95% confidence interval [CI]: 0.39-0.66, P < 0.001) and progression-free survival (PFS) (HR: 0.52, 95% CI: 0.40-0.66, P < 0.001) compared to the group that received chemoimmunotherapy alone. After 1:1 PSM, matching age, tumor location, and metastatic sites, a total of 250 patients were selected for further analysis. The results remained consistent and showed that the addition of radiotherapy significantly improved OS and PFS (median OS: 24.9 vs. 14.6 months, P = 0.003; median PFS: 14.2 vs. 10.6 months, P = 0.002). Multivariate Cox analysis including tumor location, T stage, metastatic sites, and treatment modality, revealed that radiotherapy was an independent prognostic factor for both OS (HR: 0.57, 95% CI: 0.41-0.81) and PFS (HR: 0.63, 95% CI: 0.47-0.86). Subgroup analyses revealed significant OS prolongation in patients with non-regional lymph node metastases only who received radiotherapy (HR: 0.49, 95% CI: 0.34-0.70). No OS survival benefit was observed in those with distant organ metastases (HR: 0.72, 95% CI: 0.46-1.13). Regarding safety, the group receiving additional radiotherapy had higher incidences of grade 3-4 lymphopenia (74.4% vs. 17.7%, P < 0.001) and esophagitis (11.2% vs. 2.4%, P = 0.006). CONCLUSION: The addition of radiotherapy to chemoimmunotherapy improved the survival of stage IVB ESCC patients with non-regional lymph nodes metastasis.

Rational and design of prophylactic cranial irradiation (PCI) and brain MRI surveillance versus brain MRI surveillance alone in patients with limited-stage small cell lung cancer achieving complete remission (CR) of tumor after chemoradiotherapy: a multicenter prospective randomized study.

BACKGROUND: Prophylactic cranial irradiation (PCI) is part of standard care in limited-stage small cell lung cancer (SCLC) at present. As evidence from retrospective studies increases, the benefits of PCI for limited-stage SCLC are being challenged. METHODS: A multicenter, prospective, randomized controlled study was designed. The key inclusion criteria were: histologically or cytologically confirmed small cell carcinoma, age ≥ 18 years, KPS ≥ 80, limited-stage is defined as tumor confined to one side of the chest including ipsilateral hilar, bilateral mediastinum and supraclavicular lymph nodes, patients have received definitive thoracic radiotherapy (regardless of the dose-fractionation of radiotherapy used) and chemotherapy, evaluated as complete remission (CR) of tumor 4-6 weeks after the completion of chemo-radiotherapy. Eligible patients will be randomly assigned to two arms: (1) PCI and brain MRI surveillance arm, receiving PCI (2.5 Gy qd to a total dose of 25 Gy in two weeks) followed by brain MRI surveillance once every three months for two years; (2) brain MRI surveillance alone arm, undergoing brain MRI surveillance once every three months for two years. The primary objective is to compare the 2-year brain metastasis-free survival (BMFS) rates between the two arms. Secondary objectives include 2-year overall survival (OS) rates, intra-cranial failure patterns, 2-year progression-free survival rates and neurotoxicity. In case of brain metastasis (BM) detect during follow-up, stereotactic radiosurgery (SRS) will be recommended if patients meet the eligibility criteria. DISCUSSION: Based on our post-hoc analysis of a prospective study, we hypothesize that in limited-stage SCLC patients with CR after definitive chemoradiotherapy, and ruling out of BM by MRI, it would be feasible to use brain MRI surveillance and omit PCI in these patients. If BM is detected during follow-up, treatment with SRS or whole brain radiotherapy does not appear to have a detrimental effect on OS. Additionally, this approach may reduce potential neurotoxicity associated with PCI.

Advanced electrolysis sulfur-based biofiltration for simultaneous total nitrogen removal and estrogen toxicity reduction from low carbon-to-nitrogen ratio wastewater.

A sulfur-based biofilter enhanced by phosphate modified activated carbon as particle electrodes was constructed to simultaneously remove total nitrogen (TN) and estrogen from low carbon-to-nitrogen ratio (C/N) wastewater containing 1 mg/L 17-alpha-ethinylestradiol (EE2). Results showed that the enhanced biofilter achieved outstanding performance in EE2 removal (93.2 %) and TN reduction (effluent < 5 mg/L), demonstrating robustness against C/N fluctuations. It was noteworthy that it successfully reduced both acute toxicity (59.5 %) and estrogenic activity (88.6 %). Comprehensive characterization investigations and microbial community structure analysis revealed that enhanced electron transfer and increased microbial abundance likely contributed to improved biofilter performance. Core microorganisms, such as Pseudomonas and Chryseobacterium were identified as key contributors to synergistic estrogen degradation and denitrification. This study presented a feasible and promising strategy of combined process with three-dimensional electrodes and sulfur-based biofilter, highlighting substantial potential for advanced purification and safe reuse of wastewater.

Electrocatalytic denitrification biofilter for advanced purification of chlorophenols via ceramsite-based Ti/SnO2-Sb particle electrode: Performance, microbial community structure and mechanism.

In response to the demand for advanced purification of industrial secondary effluent, a new method has been developed for treating chlorophenol wastewater using the novel ceramsite-based Ti/SnO2-Sb particle electrodes (Ti/SnO2-Sb/CB) enhanced electrocatalytic denitrification biofilter (EDNBF-P) to achieve removal of chlorophenols (CPs), denitrification, and reduction of effluent toxicity. The results showed that significantly improved CPs and TN removal efficiency at low COD/N compared to conventional denitrification biofilter, with CPs removal rates increasing by 0.33%-59.27% and TN removal rates increasing by 12.53%-38.92%. Under the conditions of HRT = 2h, 3V voltage, charging times = 12h, and 25 °C, the concentrations of the CPs in the effluent of EDNBF-P were all below 1 mg/L, the TN concentration was below 15 mg/L, while the effluent toxicity reached the low toxicity level. Additionally, the Ti/SnO2-Sb/CB particle electrodes effectively alleviated the accumulation of NO2--N caused by applied voltage. The Silanimonas, Pseudomonas and Rhodobacter was identified as the core microorganism for denitrification and toxicity reduction. This study validated that EDNBF-P could achieve synergistic treatment of CPs and TN through electrocatalysis and microbial degradation, providing a methodological support for achieving advanced purification of chlorophenol wastewater with low COD/N in industrial applications.

Widely Targeted Metabolomic Profiling Combined with Transcriptome Analysis Provides New Insights into Lipid Biosynthesis in Seed Kernels of Pinus koraiensis.

Lipid-rich Pinus koraiensis seed kernels are highly regarded for their nutritional and health benefits. To ascertain the molecular mechanism of lipid synthesis, we conducted widely targeted metabolomic profiling together with a transcriptome analysis of the kernels in P. koraiensis cones at various developmental stages. The findings reveal that 148 different types of lipid metabolites, or 29.6% of total metabolites, are present in kernels. Among those metabolites, the concentrations of linoleic acid, palmitic acid, and α-linolenic acid were higher, and they steadily rose as the kernels developed. An additional 10 hub genes implicated in kernel lipid synthesis were discovered using weighted gene co-expression network analysis (WGCNA), gene interaction network analysis, oil body biosynthesis, and transcriptome analysis. This study used lipid metabolome and transcriptome analyses to investigate the mechanisms of key regulatory genes and lipid synthesis molecules during kernel development, which served as a solid foundation for future research on lipid metabolism and the creation of P. koraiensis kernel food.

A research on the improved rotational robustness for thoracic organ delineation by using joint learning of segmenting spatially-correlated organs: A U-net based comparison.

PURPOSE: To study the improved rotational robustness by using joint learning of spatially-correlated organ segmentation (SCOS) for thoracic organ delineation. The network structure is not our point. METHODS: The SCOS was implemented in a U-net-like model (abbr. SCOS-net) and evaluated on unseen rotated test sets. Two hundred sixty-seven patients with thoracic tumors (232 without rotation and 35 with rotation) were enrolled. The training and validation images came from 61 randomly chosen unrotated patients. The test data included two sets. One consisted of 3000 slices from the rest 171 unrotated patients. They were rotated by us by -30°âˆ¼30°. One was the images from the 35 rotated patients. The lung, heart, and spinal cord were delineated by experienced radiation oncologists and regarded as ground truth. The SCOS-net was compared with its single-task learning counterparts, two published multiple learning task settings, and rotation augmentation. Dice, 3 distance metrics (maximum and 95th percentile of Hausdorff distances and average surface distance (ASD)) and the number of cases where ASD = infinity were adopted. We analyzed the results using visualization techniques. RESULTS: In terms of no augmentation, the SCOS-net achieves the best lung and spinal cord segmentations and comparable heart delineation. With augmentation, SCOS performs better in some cases. CONCLUSION: The proposed SCOS can improve rotational robustness, and is promising in clinical applications for its low network capacity and computational cost.

A study of the prognosis of patients with limited-stage small cell lung cancer who did or did not receive prophylactic cranial irradiation after effective chemoradiotherapy.

Objective: To investigate the prognosis of patients with LS-SCLC who responded to chest chemoradiotherapy but did not receive PCI. Methods: A retrospective analysis was conducted on LS-SCLC patients who had achieved complete remission (CR) or partial remission (PR) after definitive chemoradiotherapy but did not receive PCI. The survival rates were calculated using Kaplan-Meier method. The prognosis was analyzed using Cox proportional hazard regression model. The main endpoint was OS. Results: Of the 500 patients with LS-SCLC admitted between June 2002 and January 2018, 327 achieved CR or PR after definitive chest chemoradiotherapy, 103 did not receive PCI, and 63 of them developed brain metastases (BM). The 1-year and 3-year OS rates in PCI group were 87.5% and 42.3% respectively, versus 70.4% and 20.9% for non-PCI group(P=0.002). The median survival time after BM was 8.7 months (range: 0.3-48.7), and 3-year OS rate was 15.0%, the median survival time of patients without BM was 20.1 months (range: 2.9-79.4), and 3-year OS was 33.4% (P=0.014). Patients with BM were subsequently treated with palliative therapy. Multivariate analysis showed that compared with no treatment, brain radiotherapy alone (HR: 0.131, 95%CI: 0.035-0.491, P=0.003) and radiotherapy combined with chemotherapy (HR: 0.039, 95%CI: 0.008-0.194, P<0.001) significantly reduced the risk of death. Multiple BM (HR: 2.391, 95%CI: 1.082-5.285, P=0.031) was an independent adverse prognostic factor for OS. Conclusion: LS-SCLC patients who achieved good response after chest chemoradiotherapy without receiving PCI were prone to develop BM and have a poor prognosis. Multiple BM was an independent adverse prognostic factor. PCI remains the standard of care for LS-SCLC patients.

Comparison of stereotactic body radiation therapy versus surgery for multiple primary lung cancers after prior radical resection: A multicenter retrospective study.

Background: Patients who previously underwent surgical resection of initial primary lung cancer are at a high risk of developing multiple primary lung cancers (MPLCs). The purpose of this study was to compare the efficacy and safety between stereotactic body radiation therapy (SBRT) and surgery for MPLCs patients after prior radical resection for the first lung cancers. Methods: In this multicenter retrospective study, eligible MPLC patients with tumor diameter of 5.0 cm or less at N0M0 who underwent SBRT or reoperation between January 2013 and August 2020 were enrolled. The primary endpoint was the 3-year locoregional recurrence and treatment-related toxicity. Kaplan-Meier method was used to calculate survival rates. The χ2 test was adapted to assess the difference of categorical variables between the two subgroup patients. Results: A total of 203 (73 in the SBRT group and 130 in the surgery group) patients from three academic cancer centers were evaluated with a median follow-up of 38.3 months. The cumulative 1-, 2-, and 3-year incidences of locoregional recurrence were 5.6 %, 7.0 % and 13.1 % in the SBRT group versus 3.2 %, 4.8 % and 7.4 % in the surgery group, respectively [hazard ratio (HR), 1.97; 95 % confidence interval (CI), 0.74-5.24; P = 0.14]. The cancer-specific survival rates were 95.9 %, 94.5 % and 88.1 % versus 96.9 %, 94.6 % and 93.8 % in the SBRT and surgery groups respectively (HR, 1.72; 95 % CI, 0.67-4.44; P = 0.23). In the SBRT group, two patients (2.7 %) suffered from grade 3 radiation pneumonitis, while in the surgery group, grade 3 complications occurred in four (3.1 %) patients, and four cases were expired due to pneumonia or pulmonary heart disease within 90 days after surgery. Conclusions: SBRT is an effective therapeutic option with limited toxicity compared to surgery for patients with MPLCs after prior radical surgical resection, and it could be considered as an alternative treatment for those patients.

Derived Neutrophil-Lymphocyte Ratio and C-Reactive Protein as Prognostic Factors for Early-Stage Non-Small Cell Lung Cancer Treated with Stereotactic Body Radiation Therapy.

Objectives: To explore the relationship between peripheral blood inflammation parameters and overall survival (OS) and progression-free survival (PFS) of early-stage non-small cell lung cancer patients who underwent stereotactic body radiotherapy (SBRT). Patients and methods: In this study, eligible patients treated with SBRT from 2013 to 2018, and both serum complete blood count and blood biochemical results were available prior to (within 60 days) radiotherapy were included. Results: A review of hospital registries identified 148 patients, and the 5-year OS and PFS of the entire cohort were 69.8% and 65.6%, respectively, with the median follow-up time was 52.8 months. Multivariable analysis showed that derived neutrophil-lymphocyte ratio (dNLR) ≥1.4 and C-reactive protein (CRP) ≥2.9 were statistically and independently associated with worse OS (HR = 4.62, 95% CI 1.89-11.27, p = 0.001; HR = 2.92, 95% CI 1.49-5.70, p = 0.002, respectively). The 5-year OS for patients with dNLR below and equal to or above the 1.4 were 85.3% and 62.9% (p = 0.002), respectively, and 76.7% for the low CRP group versus 58.5% for the high CRP group (p = 0.030). Higher serum level of post-treatment CRP also independent parameters for inferior PFS (HR = 4.83, 95% CI 1.28-18.25, p = 0.020). Conclusions: Our results demonstrate that dNLR and CRP are associated with the outcomes of early-stage NSCLC patients treated with SBRT, which may assist in selecting optimal nursing care and therapeutic scheme for every individual.

Effects of electrical stimulation on purification of secondary effluent containing chlorophenols by denitrification biofilter.

The coexistence of chlorophenols (CPs) and total nitrogen (TN) is common in advanced purification of industrial secondary effluent, which brings challenges to conventional denitrification biofilters (DNBFs). Electrical stimulation is an effective method for the degradation of CPs, However, the application of electrical stimulation in DNBFs to enhance the treatment of secondary effluent containing CPs remains largely unknown. Herein, this study conducted a systematic investigation towards the effects of electrical stimulation on DNBF through eight lab-scale reactors at room and low temperatures and different hydraulic retention times (HRTs). Results showed that the electrical stimulation effect was not greatly affected by temperature and the optimal applied voltage was 3 V. Overall, the removal rates of TN and CPs were increased by 114%-334% and 2.68%-34.79% respectively after electrical stimulation. When the influent concentration of NO3--N, COD and each CP of 25 mg/L, 50 mg/L and 5 mg/L, about 15 mg/L of effluent TN could be achieved and the removals of p-chlorophenol, 2,4-dichlorophenol and 2,4,6-trichlorophenol were increased by 10.58%, 5.78% and 34.79% respectively, under the voltage of 3 V and HRT of 4 h. However, the reduction rate of biotoxicity was decreased and could not achieve low toxicity grade in general. Electrical stimulation promoted the elevation of Hydrogenophaga and thus enhanced the removal of TN, and the increase of Microbacterium and Ahniella was significantly associated with the improvement of CPs removal rate. In addition, the obvious accumulation of nitrite was found to be significantly negatively correlated with the abundance of Nitrospira. This study highlighted a further need for the optimization of electrical stimulation in DNBFs treating industrial secondary effluent containing CPs to achieve the goal of pollutant removal and toxicity reduction simultaneously.

A combined predictive model based on radiomics features and clinical factors for disease progression in early-stage non-small cell lung cancer treated with stereotactic ablative radiotherapy.

Purpose: To accurately assess disease progression after Stereotactic Ablative Radiotherapy (SABR) of early-stage Non-Small Cell Lung Cancer (NSCLC), a combined predictive model based on pre-treatment CT radiomics features and clinical factors was established. Methods: This study retrospectively analyzed the data of 96 patients with early-stage NSCLC treated with SABR. Clinical factors included general information (e.g. gender, age, KPS, Charlson score, lung function, smoking status), pre-treatment lesion status (e.g. diameter, location, pathological type, T stage), radiation parameters (biological effective dose, BED), the type of peritumoral radiation-induced lung injury (RILI). Independent risk factors were screened by logistic regression analysis. Radiomics features were extracted from pre-treatment CT. The minimum Redundancy Maximum Relevance (mRMR) and the Least Absolute Shrinkage and Selection Operator (LASSO) were adopted for the dimensionality reduction and feature selection. According to the weight coefficient of the features, the Radscore was calculated, and the radiomics model was constructed. Multiple logistic regression analysis was applied to establish the combined model based on radiomics features and clinical factors. Receiver Operating Characteristic (ROC) curve, DeLong test, Hosmer-Lemeshow test, and Decision Curve Analysis (DCA) were used to evaluate the model's diagnostic efficiency and clinical practicability. Results: With the median follow-up of 59.1 months, 29 patients developed progression and 67 remained good controlled within two years. Among the clinical factors, the type of peritumoral RILI was the only independent risk factor for progression (P< 0.05). Eleven features were selected from 1781 features to construct a radiomics model. For predicting disease progression after SABR, the Area Under the Curve (AUC) of training and validation cohorts in the radiomics model was 0.88 (95%CI 0.80-0.96) and 0.80 (95%CI 0.62-0.98), and AUC of training and validation cohorts in the combined model were 0.88 (95%CI 0.81-0.96) and 0.81 (95%CI 0.62-0.99). Both the radiomics and the combined models have good prediction efficiency in the training and validation cohorts. Still, DeLong test shows that there is no difference between them. Conclusions: Compared with the clinical model, the radiomics model and the combined model can better predict the disease progression of early-stage NSCLC after SABR, which might contribute to individualized follow-up plans and treatment strategies.

A new LDH based sustained-release carbon source filter media to achieve advanced denitrogenation of low C/N wastewater at low temperature.

Advanced denitrogenation of wastewater is now facing major challenges brought by low C/N ratio and low temperature. The development of sustained-release materials with good and stable carbon release properties was an effective countermeasure. FeNi-Layered double-metal hydroxides (LDH)- sodium carboxymethyl cellulose (CMC) filter media and its potential use in heterotrophic and sulfur-based mixotrophic denitrification biological filter (DNBF), was firstly reported. It demonstrated stable structure and good carbon release performance with a mass transfer coefficient (K) of 4.40 mg·L-1·s-1. When the influent NO3--N of 50 mg/L with the C/N ratio of 3 at 10 °C, the maximum nitrogen loading rate of 0.22 kg·N/(m3·d) and effluent TN close to 5 mg/L (nitrogen removal of almost 90 %) could be achieved. The slowly released carbon source and the leached iron increased the abundance of denitrifying bacteria and functional genes, and the augmentation of Sulfuritalea and the secretion of biofilm protein stimulated by sulfur also played a synergistic role. This study provided a new potentially effective strategy to enhance advanced denitrification of wastewater of low C/N wastewater at low temperature.

A Phase III Multicenter Randomized Clinical Trial of 60 Gy versus 50 Gy Radiation Dose in Concurrent Chemoradiotherapy for Inoperable Esophageal Squamous Cell Carcinoma.

PURPOSE: In this multicenter phase 3 trial, the efficacy and safety of 60 Gy and 50 Gy doses delivered with modern radiotherapy technology for definitive concurrent chemoradiotherapy (CCRT) in patients with inoperable esophageal squamous cell carcinoma (ESCC) were evaluated. PATIENTS AND METHODS: Patients with pathologically confirmed stage IIA‒IVA ESCC were randomized 1:1 to receive conventional fractionated 60 Gy or 50 Gy to the tumor and regional lymph nodes. Concurrent weekly chemotherapy (docetaxel 25 mg/m2; cisplatin 25 mg/m2) and two cycles of consolidation chemotherapy (docetaxel 70 mg/m2; cisplatin 25 mg/m2 days 1‒3) were administered. RESULTS: A total of 319 patients were analyzed for survival, and the median follow-up was 34.0 months. The 1- and 3-year locoregional progression-free survival (PFS) rates for the 60 Gy group were 75.6% and 49.5% versus 72.1% and 48.4%, respectively, for the 50 Gy group [HR, 1.00; 95% confidence interval (CI), 0.75‒1.35; P = 0.98]. The overall survival rates were 83.7% and 53.1% versus 84.8% and 52.7%, respectively (HR, 0.99; 95% CI, 0.73‒1.35; P = 0.96), whereas the PFS rates were 71.2% and 46.4% versus 65.2% and 46.1%, respectively (HR, 0.97; 95% CI, 0.73‒1.30; P = 0.86). The incidence of grade 3+ radiotherapy pneumonitis was higher in the 60 Gy group (nominal P = 0.03) than in the 50 Gy group. CONCLUSIONS: The 60 Gy arm had similar survival endpoints but a higher severe pneumonitis rate compared with the 50 Gy arm. Fifty Gy should be considered as the recommended dose in CCRT for ESCC.

Activation of PI3K/AKT Pathway Is a Potential Mechanism of Treatment Resistance in Small Cell Lung Cancer.

PURPOSE: Here, we have investigated treatment resistance mechanisms in small cell lung cancer (SCLC) by focusing on comparing the genotype and phenotype in tumor samples of treatment-resistant and treatment-sensitive SCLC. EXPERIMENTAL DESIGN: We conducted whole-exome sequencing on paired tumor samples at diagnosis and relapse from 11 patients with limited-stage (LS)-SCLC and targeted sequencing of 1,021 cancer-related genes on cell-free DNA at baseline and paired relapsed samples from 9 additional patients with LS-SCLC. Furthermore, we performed label-free mass spectrometry-based proteomics on tumor samples from 28 chemo-resistant and 23 chemo-sensitive patients with extensive-stage (ES)-SCLC. The main findings were validated in vitro in chemo-sensitive versus chemo-resistant SCLC cell lines and analyses of transcriptomic data of SCLC cell lines from a public database. RESULTS: Genomic analyses demonstrated that at relapse of LS-SCLC, genes in the PI3K/AKT signaling pathway were enriched for acquired somatic mutations or high-frequency acquired copy-number variants. Pathway analysis on differentially upregulated proteins from ES-SCLC cohort revealed enrichment in the HIF-1 signaling pathway. Importantly, 7 of 62 PI3K/AKT pathway genes containing acquired somatic copy-number amplifications were enriched in HIF-1 pathway. Analyses of transcriptomic data of SCLC cell lines from public databases confirmed upregulation of PI3K/AKT and HIF-1 pathways in chemo-resistant SCLC cell lines. Furthermore, chemotherapy-resistant cell lines could be sensitive to PI3K inhibitors in vitro. CONCLUSIONS: PI3K/AKT pathway activation may be one potential mechanism underlying therapeutic resistance of SCLC. This finding warrants further investigation and provides a possible approach to reverse resistance to chemo/radiotherapy.

Five-year survival rate analysis: the combination of fortnightly-administration of endostar and concurrent chemoradiotherapy versus concurrent chemoradiotherapy in the treatment of inoperable locally advanced non-small cell lung cancer.

BACKGROUND: A prospective phase II study showed that Endostar combined with concurrent chemoradiotherapy (CCRT) can improve overall survival (OS) in patients with inoperable locally advanced non-small cell lung cancer (NSCLC). This study aimed to retrospectively compare the 5-year survival rates of patients with inoperable locally advanced NSCLC who received a combination of Endostar and CCRT to that of patients receiving CCRT. METHODS: Treatment-naive patients with inoperable locally advanced NSCLC who had long-term follow-up data were included in this study. Patients in CCRT + Endostar group were treated with Endostar plus radical CCRT, and patients in CCRT group received radical CCRT. For patients with a radiation dose ≥60 Gy, Kaplan-Meier method was used for survival analysis, and Cox proportional-hazards regression model was used for univariate analysis. RESULTS: A total of 104 participants were included in the CCRT + Endostar group with 89 participants included in the CCRT group. There were 88 (84.6%) and 74 (83.1%) male patients, respectively. The median follow-up times of two groups were 73.6 (95% CI: 65.6 to 81.7 months) and 66.3 months (95% CI: 52.7 to 79.9 months), respectively. The median overall survival (OS) was 29.7 (95% CI: 22.8 to 36.6 months) and 21.3 months (95% CI: 15.9 to 26.7 months), respectively. CONCLUSIONS: This study showed that the 5-year survival of those patients who received the combination treatment of Endostar and radical CCRT was significantly superior to those who received radical CCRT.

Efficacy of Concurrent Chemoradiotherapy With S-1 vs Radiotherapy Alone for Older Patients With Esophageal Cancer: A Multicenter Randomized Phase 3 Clinical Trial.

IMPORTANCE: Most older patients with esophageal cancer cannot complete the standard concurrent chemoradiotherapy (CCRT). An effective and tolerable chemoradiotherapy regimen for older patients is needed. OBJECTIVE: To evaluate the efficacy and toxic effects of CCRT with S-1 vs radiotherapy (RT) alone in older patients with esophageal cancer. DESIGN, SETTING, AND PARTICIPANTS: A randomized, open-label, phase 3 clinical trial was conducted at 23 Chinese centers between June 1, 2016, and August 31, 2018. The study enrolled 298 patients aged 70 to 85 years. Eligible participants had histologically confirmed esophageal cancer, stage IB to IVB disease based on the 6th edition of the American Joint Committee on Cancer (stage IVB: only metastasis to the supraclavicular/celiac lymph nodes) and an Eastern Cooperative Oncology Group performance status of 0 to 1. Data analysis was performed from August 1, 2020, to March 10, 2021. INTERVENTIONS: Patients were stratified according to age (<80 vs ≥80 years) and tumor length (<5 vs ≥5 cm) and randomly assigned (1:1) to receive either CCRT with S-1 or RT alone. MAIN OUTCOMES AND MEASURES: The primary end point was the 2-year overall survival rate using intention-to-treat analysis. RESULTS: Of the 298 patients enrolled, 180 (60.4%) were men. The median age was 77 (interquartile range, 74-79) years in the CCRT group and 77 (interquartile range, 74-80) years in the RT alone group. A total of 151 patients (50.7%) had stage III or IV disease. The CCRT group had a significantly higher complete response rate than the RT group (41.6% vs 26.8%; P = .007). Surviving patients had a median follow-up of 33.9 months (interquartile range: 28.5-38.2 months), and the CCRT group had a significantly higher 2-year overall survival rate (53.2% vs 35.8%; hazard ratio, 0.63; 95% CI, 0.47-0.85; P = .002). There were no significant differences in the incidence of grade 3 or higher toxic effects between the CCRT and RT groups except that grade 3 or higher leukopenia occurred in more patients in the CCRT group (9.5% vs 2.7%; P = .01). Treatment-related deaths were observed in 3 patients (2.0%) in the CCRT group and 4 patients (2.7%) in the RT group. CONCLUSIONS AND RELEVANCE: In this phase 3 randomized clinical trial, CCRT with S-1 was tolerable and provided significant benefits over RT alone in older patients with esophageal cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02813967.

Comparative transcriptomic analysis reveals the coordinated mechanisms of Populus × canadensis 'Neva' leaves in response to cadmium stress.

Cadmium (Cd), a heavy metal element has strong toxicity to living organisms. Excessive Cd accumulation directly affects the absorption of mineral elements, inhibits plant tissue development, and even induces mortality. Populus × canadensis 'Neva', the main afforestation variety planted widely in northern China, was a candidate variety for phytoremediation. However, the genes relieving Cd toxicity and increasing Cd tolerance of this species were still unclear. In this study, we employed transcriptome sequencing on two Cd-treated cuttings to identify the key genes involved in Cd stress responses of P. × canadensis 'Neva' induced by 0 (CK), 10 (C10), and 20 (C20) mg/L Cd(NO3)2 4H2O. We discovered a total of 2,656 (1,488 up-regulated and 1,168 down-regulated) and 2,816 DEGs (1,470 up-regulated and 1,346 down-regulated) differentially expressed genes (DEGs) between the CK vs C10 and CK vs C20, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses in response to the Cd stress indicated that many DEGs identified were involved in the catalytic activity, the oxidoreductase activity, the transferase activity, and the biosynthesis of secondary metabolites. Based on the enrichment results, potential candidate genes were identified related to the calcium ion signal transduction, transcription factors, the antioxidant defense system, and transporters and showed divergent expression patterns under the Cd stress. We also validated the reliability of transcriptome data with the real-time PCR. Our findings deeper the understanding of the molecular responsive mechanisms of P. × canadensis 'Neva' on Cd tolerance and further provide critical resources for phytoremediation applications.

Microscopic analysis towards rhamnolipid-mediated adhesion of Thiobacillus denitrificans: A QCM-D study.

Rhamnolipid was proved to increase the abundance of Thiobacillus denitrificans in the mixotrophic denitrification biofilm while its microscopic mechanism remains to be explored. Effect of rhamnolipids on deposition of macromolecular substances and adhesion of Thiobacillus denitrificans at room (20 °C) and low temperature (10 °C) were systematically investigated by the quartz crystal microbalance with dissipation monitoring (QCM-D) for the first time. Results showed that low concentration of rhamnolipids (20-80 mg/L) could promote the deposition of macromolecular substances by reducing hydraulic repulsion force, with the maximum deposition amount increased by 4.28 times than that of the control at room temperature. Deposition amount of microorganisms could be improved by increasing its concentration at room temperature while it didn't work at low temperature. Meanwhile, low temperature could significantly inhibit adhesion of Thiobacillus denitrificans (p < 0.05) and deposited layers under low concentration of rhamnolipids were generally rigid, resulting in the negative feedback effect on the microorganisms' adhesion. While high concentration of rhamnolipids (120-200 mg/L) could regulate the biofilm from rigid to viscoelastic and significantly promote the initial adhesion of Thiobacillus denitrificans on SiO2 surface (p < 0.05). This study demonstrated the microscopic mechanism of rhamnolipids on the initial biofilm formation, that is, the reduction of hydration repulsion force was responsible for the enhanced deposition of macromolecules while the regulation of biofilm properties was account for the promoted adhesion of Thiobacillus denitrificans.

Correction to: Timing of thoracic radiotherapy is more important than dose intensification in patients with limited-stage small cell lung cancer: a parallel comparison of two prospective studies.

Correction to: Strahlenther Onkol 2019 https://doi.org/10.1007/s00066-019-01539-1 The original version of this article unfortunately contained a mistake. The correct version of the funding information are given ….

Timing of thoracic radiotherapy is more important than dose intensification in patients with limited-stage small cell lung cancer: a parallel comparison of two prospective studies.

PURPOSE: The optimal radiotherapy dose/fraction for limited-stage small cell lung cancer (SCLC) is undefined. Our objectives were to compare efficacy between hyperfractionated thoracic radiotherapy (TRT; 1.5 Gy 2 times per day [bid] in 30 fractions) and hypofractionated TRT (2.5 Gy once per day [qd] in 22 fractions), and to explore prognostic factors influencing the prognosis, such as the timing of TRT. METHODS: Patients enrolled in two independent prospective studies were combined and analyzed. The primary endpoint was local/regional control (LRC). The prognosis was analyzed using the Cox proportional hazards regression model. RESULTS: Ninety-two and 96 patients were treated with hyperfractionated TRT and hypofractionated TRT, respectively. The 1­ and 2­year LRC rates of the two arms were 82.1 and 60.7%, and 84.9 and 68.8% (P = 0.27), respectively. The median overall survival (OS) times (months) were 28.3 (95% confidence interval, CI 16.4-40.1) and 22.0 (95% CI 16.4-27.5), while the 1­year, 3­year, and 5­year OS rates were 85.2, 40.8, and 27.1%, and 76.9, 34.3, and 26.8% (P = 0.37), respectively. Using a multivariate Cox regression study, time (days) from the initiation of chemotherapy to TRT (TCT) ≤43 was associated with improved LRC (hazard radio, HR 0.39, 95% CI 0.20-0.76; P = 0.005). Time (days) from the start of chemotherapy to the end of TRT (SER) ≤63 (HR 0.50, 95% CI 0.32-0.80; P = 0.003) and prophylactic cranial irradiation (HR 0.43; 95% CI 0.29-0.63; P = 0.000) were favorably related to OS. Grade 2/3 acute radiation esophagitis was observed in 37.0 and 17.7% of patients in the hyperfractionated and hypofractionated arms, respectively (P = 0.003). CONCLUSION: Both hyperfractionated and hypofractionated TRT schedules achieved good LRC and OS for patients with limited-stage SCLC in this study. Keeping TCT ≤43 and SER ≤63 resulted in a better prognosis. The incidence of acute esophagitis was significantly higher in the hyperfractionated arm.