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.

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 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.

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.

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.

Final report of a prospective randomized study on thoracic radiotherapy target volume for limited-stage small cell lung cancer with radiation dosimetric analyses.

BACKGROUND: The thoracic radiotherapy (TRT) target volume for limited-stage small-cell lung cancer (SCLC) has been controversial for decades. In this report, the final results of a prospective randomized trial on the TRT target volume before and after induction chemotherapy are presented. METHODS: After 2 cycles of etoposide and cisplatin, patients arm were randomized to receive TRT to the postchemotherapy or prechemotherapy tumor volume in a study arm and a control arm. Involved-field radiotherapy was received in both arms. TRT consisted of 1.5 grays (Gy) twice daily in 30 fractions to up to a total dose of 45 Gy. Lymph node regions were contoured, and intentional and incidental radiation doses were recorded. RESULTS: The study was halted early because of slow accrual. Between 2002 and 2017, 159 and 150 patients were randomized to the study arm or the control arm, respectively; and 21.4% and 19.1% of patients, respectively, were staged using positron emission tomography/computed tomography (P = .31). With a median follow-up of 54.1 months (range, 19.9-165.0 months) in survivors, the 3-year local/regional progression-free probability was 58.2% and 65.5% in the study and control arms, respectively (P = .44), and the absolute difference was -7.3% (95% CI, -18.2%, 3.7%). In the study and control arms, the median overall survival was 21.9 months and 26.6 months, respectively, and the 5-year overall survival rate was 22.8% and 28.1%, respectively (P = .26). Grade 3 esophagitis was observed in 5.9% of patients in the study arm versus 15.5% of those in the control arm (P = .01). The isolated out-of-field failure rate was 2.6% in the study arm versus 4.1% in the control arm (P = .46), and all such failures were located in the supraclavicular fossa or contralateral hilum. The regions 7, 3P, 4L, 6, 4R, 5, and 2L received incidental radiation doses >30 Gy. CONCLUSIONS: TRT could be limited to the postchemotherapy tumor volume, and involved-field radiotherapy could be routinely applied for limited-stage SCLC.

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.

Choice of immobilization of stereotactic body radiotherapy in lung tumor patient by BMI.

BACKGROUND: An accurate, reproducible, and comfortable immobilization device is essential for stereotactic radiotherapy (SBRT) in patients with lung cancer. This study compared thermoplastic masks (TMP) and vacuum cushion (VCS) system to assess the differences in interfraction and intrafraction setup accuracy and the impact of body mass index (BMI) with respect to the immobilization choice. METHODS: This retrospective study was conducted on patients treated with lung SBRT between 2012 and 2015 at the Zhejiang cancer hospital. The treatment setup accuracy was analyzed in 121 patients. A total of 687 cone beam computed tomography (CBCT) scans before treatment and 126 scans after treatment were recorded to determine the uncertainties, and plan target volume margins. Data were further stratified and analyzed by immobilization methods and patients' BMI. The t-test (Welch) was used to assess the differences between the two immobilization systems when stratified by the patients' BMI. RESULTS: For patients with BMI ≥ 24, the mean displacements for the TMP and VCS systems were 1.4 ± 1.2 vs. 2.4 ± 2.0 mm at medial-lateral (ML) direction (p < 0.001); 2.0 ± 1.9 vs. 2.0 ± 1.9 mm at cranial-caudal (CC) direction (p = 0.917); and 2.4 ± 1.4 vs. 2.6 ± 2.1 mm at anterior-posterior (AP) direction, (p = 0.546). The rate of acceptable errors increased dramatically when immobilized by TMP. In the case of patients with BMI < 24, the mean displacements for the TMP and VCS systems were 1.8 ± 1.4 vs. 2.1 ± 1.8 mm at ML direction (p = 0.098); 2.9 ± 2.3 vs. 2.2 ± 2.2 mm at CC direction (p = 0.001); and 1.8 ± 1.8 vs. 2.3 ± 2.0 mm at CC direction, (p = 0.006). The proportion of acceptable errors increased after immobilization by VCS. No difference was detected in the intrafraction setup error by different immobilization methods. CONCLUSIONS: The immobilization choice of SBRT for lung tumors depends on the BMI of the patients. For patients with BMI ≥ 24, TMP offers a better reproducibility with significantly less interfractional setup displacement than VCS, resulting in fewer CBCT scans. However, VCS may be preferred over TMP for the patients with BMI < 24. Therefore, an optimal immobilization system needs to be considered in different BMI groups for lung SBRT.

Enteral Nutrition Support Does Not Improve PNI in Radiotherapy Patients with Locally Advanced Esophageal Cancer.

OBJECTIVE: The assessment of prognostic nutritional index (PNI) before and during radiotherapy is an important parameter for the prognosis in patients with cancer. In this study, enteral tube feeding (ETF) was used during radiotherapy in patients with EC. Dynamic changes of various nutritional indicators (including PNI) were monitored. METHODS: Patients with EC who underwent radiotherapy between June 2016 and July 2017 were enrolled. ETF was performing with the energy of 25 kcal × kg/d. Nutritional status were evaluated. Least significant difference (LSD) was used for multiple comparisons between groups. RESULTS: A total of 148 patients were admitted, including 51 patients fed via ETF. For patients who were not scheduled to nutritional support, significant difference were observed in albumin (ALB) (P < 0.001), prealbimnin (PA) (P = 0.05) and PNI (P < 0.001) compared to levels before radiotherapy. In the patients fed via enteral tube, no significant difference were found in weight, BMI, ALB, retinol binding protein (RBP) and PA before and after radiotherapy, while PNI significantly decreased (P < 0.001). CONCLUSION: After preforming ETF with the energy of 25 kcal × kg/d in patients with EC during radiotherapy, PNI, the key nutritional index reflecting prognosis, significantly decreased.

Automatic segmentation of cardiac substructures from noncontrast CT images: accurate enough for dosimetric analysis?

PURPOSE: We evaluated the feasibility of using an automatic segmentation tool to delineate cardiac substructures from noncontrast computed tomography (CT) images for cardiac dosimetry and toxicity analyses for patients with nonsmall cell lung cancer (NSCLC) after radiotherapy. MATERIAL AND METHODS: We used an in-house developed multi-atlas segmentation tool to delineate 11cardiac substructures, including the whole heart, four heart chambers, and six greater vessels, automatically from the averaged 4D-CT planning images of 49 patients with NSCLC. Two experienced radiation oncologists edited the auto-segmented contours. Times for automatic segmentation and modification were recorded. The modified contours were compared with the auto-segmented contours in terms of Dice similarity coefficient (DSC) and mean surface distance (MSD) to evaluate the extent of modification. Differences in dose-volume histogram (DVH) characteristics were also evaluated for the modified versus auto-segmented contours. RESULTS: The mean automatic segmentation time for all 11 structures was 7-9 min. For the 49 patients, the mean DSC values (±SD) ranged from .73 ± .08 to .95 ± .04, and the mean MSD values ranged from 1.3 ± .6 mm to 2.9 ± 5.1 mm. Overall, the modifications were small; the largest modifications were in the pulmonary vein and the inferior vena cava. The heart V30 (volume receiving dose ≥30 Gy) and the mean dose to the whole heart and the four heart chambers were not different for the modified versus the auto-segmented contours based on the statistically significant condition of p < .05. Also, the maximum dose to the great vessels was no different except for the pulmonary vein. CONCLUSIONS: Automatic segmentation of cardiac substructures did not require substantial modifications. Dosimetric evaluation showed no significant difference between the auto-segmented and modified contours for most structures, which suggests that the auto-segmented contours can be used to study cardiac dose-responses in clinical practice.

Predictive Value of Nutritional Risk Screening 2002 and Prognostic Nutritional Index for Esophageal Cancer Patients Undergoing Definitive Radiochemotherapy.

OBJECTIVES: The present study identified the prognostic nutritional factors and their relationships with survival outcome in patients with esophageal cancer treated with chemoradiotherapy (CRT). METHODS: A total of 97 esophageal cancer patients previously treated with CRT were enrolled in the study. The nutritional status was assessed by Nutrition Risk Screening 2002 (NRS-2002). Weight, total serum protein, albumin, prealbumin level, red blood cell, total lymphocyte count, and hemoglobin were also recorded. The prognostic nutritional index (PNI) was calculated. RESULTS: The proportion of patients at nutritional risk from baseline until the sixth week of radiotherapy was increased. In univariate analysis, the NRS-2002 cutoff score ≤3 at baseline was associated with improved 2-year overall survival (OS) than that ≥4. The maximum NRS-2002 cutoff score ≤2 during treatment was associated with an improved 2-year OS that ≥3. The baseline PNI or PNI at the end of CRT ≥45 was associated with improved 2-year OS than that <45. Cox regression analyses revealed that the TNM stage, NRS-2002 score at baseline, and PNI at the third week of CRT were independent risk factors for prognosis. CONCLUSIONS: The NRS2002 scores and PNI are simple and useful markers for predicting the long-term outcome in patients with esophageal cancer after CRT.

FOXP3 suppresses breast cancer metastasis through downregulation of CD44.

Forkhead box protein 3 (FOXP3) plays an important role in breast cancer as an X-linked tumor suppressor gene. However, the biological functions and significance of FOXP3 in breast cancer metastasis remain unclear. Here, we find that, clinically, nuclear FOXP3 expression is inversely correlated with breast cancer metastasis. Moreover, we demonstrate that FOXP3 significantly inhibits adhesion, invasion and metastasis of breast cancer cells in vivo and in vitro. In addition, the adhesion molecule CD44 is found to be suppressed by FOXP3 through transcriptome sequence analysis (RNA-seq). A luciferase reporter assay, chromatin immunoprecipitation and electrophoretic mobility shift assay identify CD44 as a direct target of FOXP3. The expression of CD44 is downregulated by FOXP3 in breast cancer cells. Importantly, anti-CD44 antibody reverses the FOXP3 siRNA-induced effects on the breast cancer cells in vitro and FOXP3 expression level in the nucleus of breast cancer cells is inversely correlated with CD44 expression level in clinic breast cancer tissues. Taken together, the results from the present study suggest that FOXP3 is a suppressor of breast cancer metastasis. FOXP3 directly binds to the promoter of CD44 and inhibits its protein expression, thereby suppressing adhesion and invasion of human breast cancer cells. This finding highlights the therapeutic potential of FOXP3-CD44 signaling to inhibit breast cancer metastasis.

UXT is a novel regulatory factor of regulatory T cells associated with Foxp3.

Regulatory T (Treg) cells are a constitutively immunosuppressive subtype of T cells that contribute to the maintenance of immunological self-tolerance and immune homeostasis. However, the molecular mechanisms involved in the regulation of Treg cells remain unclear. In the present study, we identified ubiquitously expressed transcript (UXT) to be a novel regulator of human Treg-cell function. In cultured human Treg cells, UXT associates with Foxp3 in the nucleus by interacting with the proline-rich domain in the N-terminus of Foxp3. Knockdown of UXT expression in Treg cells results in a less-suppressive phenotype, demonstrating that UXT is an important regulator of the suppressive actions of Treg cells. Depletion of UXT affects the localization stability of Foxp3 protein in the nucleus and downregulates the expression of Foxp3-related genes. Overall, our results show that UXT is a cofactor of Foxp3 and an important player in Treg-cell function.

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.

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.

TNFα induced FOXP3-NFκB interaction dampens the tumor suppressor role of FOXP3 in gastric cancer cells.

Controversial roles of FOXP3 in different cancers have been reported previously, while its role in gastric cancer is largely unknown. Here we found that FOXP3 is unexpectedly upregulated in some gastric cancer cells. To test whether increased FOXP3 remains the tumor suppressor role in gastric cancer as seen in other cancers, we test its function in cell proliferation both at basal and TNFα mimicked inflammatory condition. Compared with the proliferation inhibitory role observed in basal condition, FOXP3 is insufficient to inhibit the cell proliferation under TNFα treatment. Molecularly, we found that TNFα induced an interaction between FOXP3 and p65, which in turn drive the FOXP3 away from the promoter of the well known target p21. Our data here suggest that although FOXP3 is upregulated in gastric cancer, its tumor suppressor role has been dampened due to the inflammation environment.

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.

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.