ABSTRACT
Fusarium graminearum, a devastating fungal pathogen, causes great economic losses to crop yields worldwide. The present study investigated the potential of Streptomyces pratensis S10 to alleviate F. graminearum stress in wheat seedlings based on plant growth-promoting and resistance-inducing assays. The bioassays revealed that S10 exhibited multiple plant growth-promoting properties, including the production of siderophores, 1-aminocyclopropane-1-carboxylic acid deaminase (ACC), and indole-3-acetic acid (IAA), phosphate solubilization, and nitrogen fixation. Meanwhile, the pot experiment demonstrated that S10 improved wheat plant development, substantially enhancing wheat height, weight, root activity, and chlorophyll content. Consistently, genome mining identified abundant genes associated with plant growth promotion. S10 induced resistance against F. graminearum in wheat seedlings. The disease incidence and disease index reduced by nearly 52% and 65% in S10 pretreated wheat seedlings, respectively, compared with those infected with F. graminearum only in the non-contact inoculation assay. Moreover, S10 enhanced callose deposition and reactive oxygen species (ROS) accumulation and induced the activities of CAT, SOD, POD, PAL, and PPO. Furthermore, the quantitative real-time PCR (qRT-PCR) results indicated that S10 pretreatment increased the expression of SA- (PR1.1, PR2, PR5, and PAL1) and JA/ET-related genes (PR3, PR4a, PR9, and PDF1.2) in wheat seedlings upon F. graminearum infection. In summary, S. pratensis S10 could be an integrated biological agent and biofertilizer in wheat seedling blight management and plant productivity enhancement.
ABSTRACT
BACKGROUND: All known randomized trials of stereotactic radiotherapy (SRT) versus whole brain radiotherapy (WBRT) for brain metastases (BMs) comprise mixed histologies. The phase III HYBRID trial (NCT02882984) attempted to evaluate the non-inferiority of SRT vs. WBRT specifically for EGFR-mutated non-small cell lung cancer (EGFRm NSCLC) BMs. METHODS: Inclusion criteria were ≤ 5 BMs (any size) from treatment-naïve EGFRm NSCLC. All patients started a first-generation tyrosine kinase inhibitor on the first day of WBRT (37.5 Gy/15 fractions) or SRT (25-40 Gy/5 fractions per tumor volume). The primary endpoint was 18-month intracranial progression-free survival (iPFS; intention-to-treat). RESULTS: The trial commenced in June 2015 and was closed in April 2021 after screening 208 patients but enrolling 85 (n = 41 WBRT, n = 44 SRT; median follow-up 31 and 36 months, respectively). Respectively, 9.5 % vs. 10.2 % of patients experienced intracranial progression at 18 months, and the median iPFS was 21.4 vs. 22.3 months (p > 0.05 for all). The SRT arm experienced higher overall survival and cognitive preservation (p < 0.05 for all). The most notable reason for low enrollment was patients not wishing to risk neurocognitive decline from WBRT. CONCLUSIONS: Although this phase III trial was underpowered, there was no evidence that SRT yielded outcome detriments compared to WBRT for EGFRm NSCLC BMs. Lessons from prematurely closed trials are valuable, as they often provide important experiential perspectives for investigators designing/executing future trials. In the current era, randomized trials involving WBRT without cognitive sparing measures may be at high risk of underaccrual; trial investigators are encouraged to carefully consider our experience when attempting to design such trials. However, trials of molecular-/biologically-stratified patients are highly recommended as the notion of "individualized medicine/oncology" continues to expand.
Subject(s)
Brain Neoplasms , Carcinoma, Non-Small-Cell Lung , ErbB Receptors , Lung Neoplasms , Radiosurgery , Humans , Carcinoma, Non-Small-Cell Lung/radiotherapy , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/genetics , Brain Neoplasms/radiotherapy , Brain Neoplasms/secondary , Brain Neoplasms/genetics , Lung Neoplasms/pathology , Lung Neoplasms/genetics , Lung Neoplasms/radiotherapy , Radiosurgery/methods , ErbB Receptors/genetics , Male , Female , Aged , Middle Aged , Cranial Irradiation/methods , Mutation , Early Termination of Clinical Trials , Adult , Progression-Free Survival , Aged, 80 and overABSTRACT
Patients with metastatic lung adenocarcinoma (MLA) and malignant pleural effusion (MPE) without driver gene mutations have a poor prognosis. None of the standard treatment strategies is recommended for such patients. We retrospectively analyzed the efficacy of the first-line treatment for this specific population: standard platinum-based doublet chemotherapy (CT), CT plus an immune checkpoint inhibitor (CT plus ICI), and CT plus bevacizumab (CT plus Bev). A total of 323 eligible patients were enrolled: CT alone (n = 166), CT plus Bev (n = 72), and CT plus ICI (n = 85). Treatment efficacy assessments were performed every two cycles according to the RECIST guidelines. The endpoints were overall survival (OS) and progression-free survival (PFS). Kaplan-Meier (KâM) curves and the log-rank test were used to compare OS and PFS. p < 0.05 was the threshold of significance (statistical software: SPSS). The median follow-up was 11.4 months (range, 2.1-49.6 months). PFS and OS in the CT plus ICI/CT plus Bev cohort were significantly longer than those in the CT group (PFS: 7.8/6.4/3.9 months, p < 0.0001; OS: 16.4/15.6/9.6 months, p < 0.0001, respectively). CT plus Bev had better PFS and OS than CT plus ICI/CT in PD-L1 < 1% patients (PFS: 8.4/5.0/3.8 months, p < 0.0001; OS: 15.6/12.9/9.3 months, p < 0.0001). Among patients with PD-L1 1-49%, CT plus ICI led to a longer PFS and OS (PFS: 8.9/5.8/4.2 months, p = 0.009; OS: 24.2/18.8/11.5 months, p = 0.03). In the cohort with PD-L1 ≥ 50%, CT plus ICI was still the best first-line treatment (PFS: 19.7/13.8/9.6 months, p = 0.033; OS: 27.2/19.6/14.9 months, p = 0.047). In driver gene-negative MLA with MPE, CT plus Bev or ICI better controlled MPE and significantly prolonged survival compared to CT alone. PD-L1 expression (negative/positive) may be a key factor influencing the choice of CT plus Bev or ICI.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Pleural Effusion, Malignant , Humans , Bevacizumab , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Immune Checkpoint Inhibitors/therapeutic use , B7-H1 Antigen , Pleural Effusion, Malignant/pathology , Retrospective Studies , Adenocarcinoma of Lung/drug therapy , Adenocarcinoma of Lung/geneticsABSTRACT
BACKGROUND: The immune system may influence prognosis, and lymphopenia is a frequent side effect of concurrent chemoradiotherapy (CCRT). Radical irradiation for locally advanced esophageal cancer (LA-EC) exposes significant vascular and heart volumes. In this study, we hypothesized that lymphopenia is linked to cardiac and pericardial doses and affects patient prognosis. METHODS AND MATERIALS: We identified 190 LA-EC patients who received radical CCRT. Multivariate analysis (MVA) was performed to correlate clinical factors and dosimetric parameters with overall survival (OS). We collected lymphocyte-related variables and ratios before and during CCRT. MVA was performed to correlate hematologic toxicity with OS. The relationship between dosimetric parameters and G4 lymphopenia was determined using logistic stepwise regression. Finally, a nomogram of G4 lymphopenia was developed and validated externally. RESULTS: Median follow-up time for all patients was 27.5 months. On MVA for OS, higher pericardial V30 (PV30 ) was linked to worse survival (HR: 1.013, 95% CI: 1.001-1.026, p = 0.039). The median OS stratified by PV30 > 55.3% and PV30 ≤ 55.3% was 24.0 months and 54.0 months, respectively (p = 0.004). G4 lymphopenia was shown to be linked with worse OS in the MVA of hematological toxicity with OS (HR: 2.042, 95% CI: 1.335-3.126, p = 0.001). Thirty of the 100 patients in the training set had G4 lymphopenia. Logistic stepwise regression was used to identify variables associated with G4 lymphopenia, and the final model consisted of stage-IVA (p = 0.017), platelet-to-lymphocyte ratio during CCRT (p = 0.008), Heart V50 (p = 0.046), and PV30 (p = 0.048). Finally, a nomogram predicting G4 lymphocytopenia were constructed and externally validated. The ROC curve showed an AUC for internal validation of 0.775 and external validation of 0.843. CONCLUSION: Higher doses of pericardial radiation might affect LA-EC patients' prognosis by inducing G4 lymphopenia during CCRT. Further prospective studies are warranted to confirm these findings, especially in the era of immune-checkpoint inhibitor treatment.
Subject(s)
Esophageal Neoplasms , Lymphopenia , Humans , Prognosis , Lymphopenia/chemically induced , Chemoradiotherapy/adverse effects , Chemoradiotherapy/methods , PericardiumABSTRACT
BACKGROUND AND PURPOSE: Currently, there is no standard treatment for patients with lung cancer with deteriorated pulmonary function. In this study, we aimed to assess the efficacy of thoracic radiotherapy for unresectable non-small cell lung cancer (NSCLC) with baseline severe pulmonary dysfunction and severe acute radiation pneumonitis (SARP). METHODS: Patients were categorized into a radiotherapy group and a nonradiotherapy group, followed by analysis of clinical variables. A Cox regression was used to evaluate the impact of various factors on overall survival (OS). Each SARP factor's predictive value was assessed using logistic regression, receiver operating characteristic curve, and Kaplan-Meier analyses. RESULTS: The median OS in the radiotherapy group was 21.6 months vs 8.9 months in the nonradiotherapy group. Cox analysis revealed that chemotherapy (HR, 0.221; 95% CI, 0.149-0.329; P < .001) and radiotherapy (HR, 0.589; 95% CI, 0.399-0.869; P = .008) are independent prognostic factors for the current cohort. The data suggested that the ipsilateral lung V10 (ilV10, the percentage of the lung volume that received more than 10 Gy) was an independent predictor of SARP. CONCLUSIONS: Our findings suggested that thoracic radiotherapy might be associated with clinical benefits to inoperable NSCLC in patients with severe pulmonary dysfunction and that ilV10 may be involved in the prediction of risk for SARP in these patients.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Radiation Pneumonitis , Humans , Carcinoma, Non-Small-Cell Lung/complications , Carcinoma, Non-Small-Cell Lung/radiotherapy , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/complications , Lung Neoplasms/radiotherapy , Lung Neoplasms/drug therapy , Radiation Pneumonitis/etiology , Lung , Radiotherapy DosageABSTRACT
PURPOSE: This study evaluated whether antibiotic treatment before chemoradiotherapy influenced outcomes in patients with locally advanced non-small cell lung cancer (LA-NSCLC). METHODS: The records of LA-NSCLC patients treated with chemoradiotherapy between 2010 and 2017â¯at West China Hospital of Sichuan University were retrospectively examined together with their antibiotic use (antibiotic type, duration of treatment, and time between discontinuation and chemoradiotherapy). The influence of antibiotics on progression-free survival (PFS) and overall survival (OS) was evaluated with Kaplan-Meier curves and univariate and multivariate Cox regression. RESULTS: Of 522 patients, 176 had received intravenous broad-spectrum antibiotics in the month before chemoradiotherapy. Antibiotic use was linked to both reduced PFS (7.9 vs. 13.4 months, pâ¯< 0.001) and OS (20.4 vs. 25.3 months, pâ¯= 0.049). Multivariate regression demonstrated that antibiotic treatment was an unfavorable independent prognostic factor for LA-NSCLC patients who received chemoradiotherapy (HR 1.234; 95% CI 1.019-1.494; pâ¯= 0.031). Prognosis was also influenced by antibiotic type, length of treatment, and interval between discontinuation and chemoradiotherapy initiation. ßlactamase inhibitors were found to be the most harmful (median OS for ßlactamase inhibitors/fluoroquinolones/cephalosporins: 16.5/19.9/25.9 months, pâ¯= 0.045). Cutoff values for interval and duration calculated by the Xtile procedure showed that intervals of 7-16 days or durations ≤â¯6 days did not significantly affect OS relative to untreated patients (intervals: pâ¯= 0.9; duration: pâ¯= 0.93). CONCLUSION: Antibiotic treatment for longer than 6 days, especially with ßlactamase inhibitors, was associated with poor prognosis. Furthermore, delaying chemoradiotherapy for 7-16 days after antibiotic discontinuation may reduce these negative effects.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/radiotherapy , Retrospective Studies , Anti-Bacterial Agents/therapeutic use , beta-Lactamase Inhibitors/therapeutic use , Prognosis , Chemoradiotherapy/methodsABSTRACT
BACKGROUND AND PURPOSE: The role of postoperative radiotherapy (PORT) in uncertain resection of pN2 non-small cell lung cancer (NSCLC) with highest mediastinal lymph node positive has not been determined. We aim to evaluate the effect of PORT and driver gene mutation status (DGMS) on survival in such patients. METHODS: 140 selected patients were grouped according to whether they received PORT and their DGMS. Locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) of each group were evaluated by Kaplan-Meier analyses. COX regression was used to evaluate the effects of various factors on DFS and OS. RESULTS: Of 140 patients, thirty-four patients (24.3%) received PORT, and forty (28.6%) had positive driver gene mutation status (DGp). PORT significantly prolonged LRFS (p = 0.002), DFS (p = 0.019) and OS (p = 0.02), but not DMFS (p = 0.062). By subgroup analysis, in patients with negative driver gene mutation status (DGn), those receiving PORT had notably longer LRFS (p = 0.022) and DFS (p = 0.033), but not DMFS (p = 0.060) or OS (p = 0.215), compared to those not receiving PORT. Cox analysis showed that the number of positive lymph nodes (PLNs) and administration of PORT were independent prognostic factors of DFS, and pathology, PLNs, and DGMS may be prognostic factors of OS (all p < 0.05). CONCLUSION: Postoperative radiotherapy may improve locoregional recurrence-free and disease-free survival in patients with pN2 NSCLC with positive highest mediastinal lymph nodes, while driver gene mutation status impacted OS significantly. Only patients with positive driver gene mutations experienced significant overall survival benefits from postoperative radiotherapy.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/radiotherapy , Carcinoma, Non-Small-Cell Lung/surgery , Lung Neoplasms/genetics , Lung Neoplasms/radiotherapy , Lung Neoplasms/surgery , Neoplasm Staging , Neoplasm Recurrence, Local , Survival Analysis , Lymph Nodes/pathology , Retrospective Studies , Prognosis , Radiotherapy, AdjuvantABSTRACT
BACKGROUND: To determine whether antibiotic use before chemotherapy is associated with chemotherapy responses and patient outcomes among NSCLC patients and define the optimal interval between chemotherapy initiation and antibiotic treatment. MATERIALS AND METHODS: One thousand four hundred and four advanced NSCLC patients receiving first-line platinum-based doublets therapy were retrospectively analyzed. Kaplan-Meier curve evaluated the impact of antibiotic use and type of antibiotics on the survival of patients. The factors affect the patient's prognosis were further confirmed by Cox regression. The optimal interval between antibiotic treatment and the initiation of chemotherapy was determined by the X-tile program. RESULTS: NSCLC patients of 33.5% advanced underwent broad-spectrum antibiotic treatment prior to chemotherapy. In the chemotherapy only (Chemo) and chemotherapy plus antiangiogenesis (Chemo-angio) treatment groups, prior antibiotic treatment was associated with worse OS (Chemo: 13.8 vs. 17.6 months, p < 0.001; Chemo-angio:11.9 vs. 18.1 months, p = 0.012) and PFS (Chemo: 3.7 vs. 5.8 months, p < 0.001; Chemo-angio: 3.1 vs. 5.9 months, p < 0.001). Cox regression analysis revealed prior antibiotic administration as an independent predictor of OS and PFS (HR for PFS/OS: 1.925/1.452, both p < 0.001). Antibiotic usage duration (HR for PFS/OS: 1.030/1.036, p = 0.009/0.001) and type (PFS/OS: p < 0.001/p = 0.01) also showed significant association with patient prognosis, with calculated interval time cutoff values of 2, 4, and 2 days for fluoroquinolones, ß-lactamase inhibitors, and cephalosporins, respectively. CONCLUSION: Antibiotic use before first-line chemotherapy was associated with poor results in advanced NSCLC patients; treatment length and type being strongly correlated with patient outcomes. Appropriate prolongation of the time between two treatments may enhance patient survival. Further prospective research is however necessary.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Anti-Bacterial Agents/therapeutic use , Retrospective Studies , Prognosis , Antineoplastic Combined Chemotherapy Protocols/adverse effectsABSTRACT
PURPOSE: This study aimed to assess pathogen distributions and antimicrobial sensitivity characteristics in patients with non-small cell lung cancer (NSCLC) with severe radiation pneumonitis (SRP) and secondary infections. METHODS AND MATERIALS: Data from 1746 patients with NSCLC and SRP after thoracic radiation therapy from January 2009 to December 2020 were retrospectively analyzed. Pneumonia incidence, causative pathogens, and antibiotic resistance characteristics in patients with secondary lung infections were analyzed. Risk factors associated with mortality were identified through univariate and multivariate analyses. Antifungal drug efficacy and duration-related effects were assessed with Forest plots and receiver operating characteristic curves. RESULTS: Overall, 44.5% of patients with NSCLC and SRP (777 of 1746 patients) were diagnosed with secondary lung infections. In total, 899 bacterial strains were isolated from these patients, with Acinetobacter baumannii (n = 206; 27%), Klebsiella pneumonia (n = 200; 26.2%), and Pseudomonas aeruginosa (n = 104; 13.6%) being the most common. Carbapenem and cefoperazone-sulbactam resistance rates of 52.7% and 32.2%, 28.8% and 26.4%, and 23.7% and 20.2% were observed for these isolates, respectively. Infection-related deaths occurred in 22.4% of patients with SRP. Independent risk factors for infection-related death included poor performance status scores, inappropriate empirical antimicrobial treatment, bacteria/fungal coinfection, and lack of empirical antifungal treatment. Receiver operating characteristic curves showed that the cutoff value of empirical antifungal treatment duration was 9 (area under the curve: 0.819). CONCLUSIONS: For patients with SRP and secondary lung infections, appropriate empirical antimicrobial treatment could decrease infection-related mortality, and cefoperazone-sulbactam may be an appropriate antibacterial drug. Empirical antifungal treatment for a minimum of 9 days might contribute to better outcomes. Although this represents a promising treatment approach for patients with SRP and secondary lung infections before antibacterial susceptibility testing, further prospective validation is essential.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Coinfection , Lung Neoplasms , Radiation Pneumonitis , Anti-Bacterial Agents/therapeutic use , Antifungal Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/radiotherapy , Coinfection/drug therapy , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/radiotherapy , Microbial Sensitivity Tests , Radiation Pneumonitis/drug therapy , Retrospective StudiesABSTRACT
PURPOSE: This study sought to design and validate a nomogram capable of predicting outcomes in extensive-stage small-cell lung cancer (ES-SCLC) patients with superior vena cava syndrome (SVCS) based upon the timing of their radiotherapy treatment. METHODS: We retrospectively analyzed data from 175 ES-SCLC patients with SCVS, comparing outcomes between those that underwent upfront thoracic radiotherapy (initial radiotherapy with simultaneous chemotherapy) and those that underwent consolidative thoracic radiotherapy (following 4-6 cycles of chemotherapy). Significant predictors of patient outcomes were identified using a Cox proportional hazard model and were used to construct our nomogram. This model was subsequently validated using receiver operating characteristic (ROC) curves, concordance index (C-index) values, and a risk classification system in order to evaluate its discriminative and predictive accuracy. RESULTS: The overall survival (OS) of ES-SCLC patients with SVCS that underwent chemotherapy (CT), consolidative thoracic radiotherapy (cc-TRT), and upfront thoracic radiotherapy (cu-TRT) was 8.2, 11.7, and 14.9 months, respectively (pâ¯< 0.001), with respective progression-free survival (PFS) durations of 3.3, 5.0, and 7.3 months (pâ¯< 0.001). A multivariate regression analysis revealed age, gender, ECOG performance status, sites of tumor metastasis, and treatment approach to all be independent predictors of survival outcomes. A nomogram was therefore developed incorporating these factors. Cindex values upon internal and external validation of this nomogram were 0.7625 and 0.7959, respectively, and ROC and calibration curves revealed this model to be accurate and consistent. CONCLUSIONS: We found that upfront thoracic radiotherapy in combination with chemotherapy may be associated with a positive impact on outcomes in ES-SCLC patients with SVCS.
Subject(s)
Lung Neoplasms , Small Cell Lung Carcinoma , Superior Vena Cava Syndrome , Humans , Neoplasm Staging , Nomograms , Prognosis , Retrospective Studies , Small Cell Lung Carcinoma/radiotherapy , Superior Vena Cava Syndrome/etiology , Superior Vena Cava Syndrome/radiotherapyABSTRACT
Tobacco viruses may cause a wide range of diseases that heavily reduce tobacco quality and yield worldwide. In order to detect viral diseases in tobacco fields, a one-step reverse transcription loop-mediated isothermal amplification (RT-LAMP) method was established. Nucleotide amplification could be observed clearly after adding SYBR Green I, within 60 min under isothermal conditions, at 63-65 °C with a set of primers targeting the viral coat protein (CP) genes of tobacco viruses including cucumber mosaic virus (CMV), potato virus Y (PVY), tobacco etch virus (TEV), tobacco mosaic virus (TMV) and tobacco vein banding mosaic virus (TVBMV). This method has high specificity and sensitivity. The sensitivity of the RT-LAMP was 10 to 100 times higher than that of the conventional RT-PCR method. The RT-LAMP assay was proven reliable for virus diagnosis of tobacco samples from the field.