Global Burden of Lung Cancer Attributable to Household Fine Particulate Matter Pollution in 204 Countries and Territories, 1990 to 2019.

INTRODUCTION: Household particulate matter (PM) air pollution is substantially associated with lung cancer. Nevertheless, the global burden of lung cancer attributable to household PM2.5 is still uncertain. METHODS: In this study, data from the Global Burden and Disease Study 2019 are used to thoroughly assess the burden of lung cancer associated with household PM2.5. RESULTS: The number of deaths and disability-adjusted life-years (DALYs) attributable to household PM2.5 was found to be 0.08 million and 1.94 million, respectively in 2019. Nevertheless, the burden of lung cancer attributable to household PM2.5 decreased from 1990 to 2019. At the sociodemographic index (SDI) district level, the middle SDI region had the most number of lung cancer deaths and DALYs attributable to household PM2.5. Moreover, the burden of lung cancer was mainly distributed in low-SDI regions, such as Sub-Saharan Africa. Conversely, in high-SDI regions, the age-standardized mortality rate and age-standardized DALY rate of lung cancer attributable to household PM2.5 exhibit the most rapid declines. The burden of lung cancer attributable to household PM2.5 is heavier for men than for women. The sex difference is more obvious in the elderly. CONCLUSIONS: The prevalence of lung cancer attributable to household PM2.5 has exhibited a declining trend from 1990 to 2019 owing to a concurrent decline in household PM2.5 exposure.

Camrelizumab combined with apatinib in patients with first-line platinum-resistant or PD-1 inhibitor resistant recurrent/metastatic nasopharyngeal carcinoma: a single-arm, phase 2 trial.

Immunotherapy combined with antiangiogenic targeted therapy has improved the treatment of certain solid tumors, but effective regimens remain elusive for refractory recurrent/metastatic nasopharyngeal carcinoma (RM-NPC). We conducted a phase 2 trial to evaluate the safety and activity of camrelizumab plus apatinib in platinum-resistant (cohort 1, NCT04547088) and PD-1 inhibitor resistant NPC (cohort 2, NCT04548271). Here we report on the primary outcome of objective response rate (ORR) and secondary endpoints of safety, duration of response, disease control rate, progression-free survival, and overall survival. The primary endpoint of ORR was met for cohort 1 (65%, 95% CI, 49.6-80.4, n = 40) and cohort 2 (34.3%; 95% CI, 17.0-51.8, n = 32). Grade ≥ 3 treatment-related adverse events (TRAE) were reported in 47 (65.3%) of 72 patients. Results of our predefined exploratory investigation of predictive biomarkers show: B cell markers are the most differentially expressed genes in the tumors of responders versus non-responders in cohort 1 and that tertiary lymphoid structure is associated with higher ORR; Angiogenesis gene expression signatures are strongly associated with ORR in cohort 2. Camrelizumab plus apatinib combination effectiveness is associated with high expression of PD-L1, VEGF Receptor 2 and B-cell-related genes signatures. Camrelizumab plus apatinib shows promising efficacy with a measurable safety profile in RM-NPC patients.

The efficacy and safety of apatinib plus capecitabine in platinum-refractory metastatic and/or recurrent nasopharyngeal carcinoma: a prospective, phase II trial.

BACKGROUND: Previous studies have shown that monotherapy with apatinib, an oral tyrosine kinase inhibitor, has promising efficacy for treating recurrent or metastatic (RM) nasopharyngeal carcinoma (NPC) patients. In this study, we aimed to assess the efficacy and safety of apatinib combined with capecitabine as a second-line therapy or beyond for treating RM-NPC patients who failed the first-line platinum-based chemotherapy. METHODS: In this single-arm, phase II study, we enrolled RM-NPC patients who had at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1). The sample size was determined using Simon's two-stage design. All patients were administered with apatinib 500 mg once daily and capecitabine 1000 mg/m2 twice per day on days 1-14 of each 21-day cycle. The primary endpoint was the objective response rate (ORR), and the secondary endpoints comprised disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: We enrolled 64 patients from September 2018 to August 2020. The ORR and DCR were 39.1% (95% CI, 27.1-52.1) and 85.9% (95% CI, 75.0-93.4), respectively. The median DoR was 14.4 months (95% CI, 7.8-21.0). As of April 20, 2021, the median follow-up duration was 12.0 months. The median PFS was 7.5 months (95% CI, 5.0-10.0) and the median OS was 15.7 months (95% CI, 11.3-20.1). The most common toxicities of any grade were anemia (75.0%), hand-foot syndrome (65.6%), and proteinuria (64.0%). Grade 3-4 toxicities were observed in 36 (56.3%) patients, with hypertension (14.1%), mucositis (12.4%), and fatigue (10.9%) most commonly observed. CONCLUSIONS: Apatinib plus capecitabine shows promising efficacy as a second-line treatment option in pretreated platinum-refractory RM-NPC patients. Dose selection of this combination needs further investigation considering the toxicity. TRIAL REGISTRATION: Chi-CTR1800017229.

Macrophages-based immune-related risk score model for relapse prediction in stage I-III non-small cell lung cancer assessed by multiplex immunofluorescence.

Background: Macrophages are critical players in regulating innate and adaptive immunity in the tumor microenvironment (TME). The prognostic value of macrophages and their heterogeneous phenotypes in non-small cell lung cancer (NSCLC) is still uncertain. Methods: Surgically-resected samples of 681 NSCLC cases were stained by multiplex immunofluorescence to examine macrophage phenotypes as well as the expression levels of program death-ligand 1 (PD-L1) on them in both tumor nest and tumor stroma, including pan-macrophage (CD68+), M1 (CD68+CD163-), and M2 macrophages (CD68+CD163+). Various other immune cell markers, including CD4, CD8, CD20, CD38, CD66B, FOXP3, and CD133, were also evaluated. Machine learning algorithm by Random Forest (RF) model was utilized to screen the robust prognostic markers and construct the CD68-based immune-related risk score (IRRS) for predicting disease-free survival (DFS). Results: The expression levels of CD68 were moderately correlated with the levels of PD-L1 (P<0.001), CD133 (P<0.001), and CD8 (P<0.001). Higher levels of CD68 (OR 1.03, 95% CI: 1.01-1.05, P<0.001) as well as M1 macrophage (OR 1.04, 95% CI: 1.01-1.06, P<0.001) indicated shorter DFS. Despite without statiscial significance, intratumoral M2 macrophage (OR 1.05, 95% CI: 0.99-1.10, P=0.081) was also associated with worse DFS. IRRS incorporating three intratumoral CD68-related markers and four intrastromal markers was constructed and validated to predict recurrence (high-risk group vs. low-risk group: OR 2.52, 95% CI: 1.89-3.38, P<0.001). The IRRS model showed good accuracy [area under the curve (AUC) =0.670, 0.709, 0.695, 0.718 for 1-, 3-, 5-year, and overall DFS survival, respectively] and the predictive performance was better than the single-marker model (area under the curve 0.718 vs. 0.500-0.654). A nomogram based on clinical characteristics and IRRS for relapse prediction was then established and exhibited better performance than the tumor-node-metastasis (TNM) classification and IRRS system (C-index 0.76 vs. 0.69 vs. 0.60, 0.74 vs. 0.67 vs. 0.60, 0.81 vs. 0.74 vs. 0.60 of the entire, training, testing cohort, respectively). Conclusions: Our study suggested close interactions between CD68 and other immune markers in TME, demonstrating the prognostic value of CD68 in relapse prediction in resectable NSCLC.

A multiethnic bidirectional Mendelian randomization study negates causal effects of C-reactive protein concentrations on lung cancer.

BACKGROUND: Significantly rising plasma circulating C-reaction protein (CRP) concentrations are pervasive in lung cancer (LC) development, demonstrating a bidirectional relation. However, it remains uncertain whether the causation between them exists, and the degree to which the effect varies across different ethnic ancestries remains unknown. Therefore, we attempted to investigate the causal relationship between these two phenotypes. METHODS: With summary statistics of CRP-related single nucleotide polymorphisms (SNPs) identified by several large-scale genome-wide association studies (GWAS) datasets based on five ethnic ancestries coverage worldwide, we implemented bidirectional two-sample Mendelian randomization (MR) analyses. Genetic summary data of 11,348 LC cases and 15,861 controls from the International Lung Cancer Consortium (ILCCO) were applied. The inverse-variance weighted (IVW) approach was utilized as the principal analysis, supplemented by various complementary methods. RESULTS: MR study did not reveal the causal relationship shared across genetically predisposed CRP blood concentrations and LC risk (OR =1.022, 95% CI: 0.965-1.083, P=0.455) including pathological subtypes (OR =1.026, 95% CI: 0.947-1.112, P=0.534 for lung adenocarcinoma; OR =1.060, 95% CI: 0.970-1.158, P=0.201 for squamous cell lung cancer). Further analyses among East Asian, Hispanic/Latin American, European, African American/Afro-Caribbean, and South Asian populations revealed consistent null causation. Additionally, the causal effects of LC on CRP concentrations were not statically significant (OR =0.999, 95% CI: 0.977-1.021, P=0.923). CONCLUSIONS: We did not observe a bidirectional causal association between CRP blood concentrations on LC among East Asian, Hispanic/Latin American, European, African American/Afro-Caribbean, and South Asian ancestry individuals.

Breast-conserving therapy is safe both within BRCA1/2 mutation carriers and noncarriers with breast cancer in the Chinese population.

BACKGROUND: BRCA1/2 mutation is associated with a high risk of breast cancer, which may preclude breast cancer patients with BRCA1/2 mutation from breast-conserving therapy (BCT) [breast-conserving surgery (BCS), followed by radiotherapy, BCT]. It is debatable whether BCT could be a rational choice for Chinese breast cancer patients with a BRCA1/2 mutation. METHODS: The study comprised a cohort of women with invasive breast cancer either receiving BCT or mastectomy following the criteria for the germline BRCA1/2 mutation test. Germline DNA for BRCA1/2 testing was derived from blood samples. Survival analyses were performed. The correlations were analyzed between survival and distinct types of surgery. To compare the survival between different surgical management, Kaplan-Meier univariate analysis and multivariate Cox regression was used. RESULTS: In BRCA1/2 mutation carriers (N=176) and noncarriers (N=293), 25% and 27.3% of the patients received BCT, respectively (P=0.675). Patients receiving mastectomy (without radiotherapy or followed by radiotherapy) have larger tumor size (P<0.05 both in BRCA1/2 mutation carriers and noncarriers), prognostically worse tumor characteristics including significantly more advanced TNM stage (P=0.017 and P<0.0001 respectively) and more positive lymph nodes (P=0.008 and P<0.0001, respectively) both in BRCA1/2 mutation carriers and noncarriers. Still, more often received systemic therapy has also been observed. After adjustment for clinical-pathological characteristics and systemic treatment, patients who received BCT had a similar breast cancer disease-free survival compared with patients who received mastectomy, both in BRCA1/2 mutation carriers and noncarriers [HR BRCA1/2 =1.17, confidence interval (CI): 0.57-2.39, P=0.68; HRnoncarriers =0.91, CI: 0.47-1.77, P=0.79, respectively). The recurrence free survival after BCT did not differ from mastectomy in BRCA1/2 mutation carriers [BCT, 5-year cumulative recurrence-free survival (RFS) =0.95, CI: 0.89-1.00; mastectomy, 5-year cumulative RFS =0.93, CI: 0.85-1.00], even better for BCT in noncarriers (BCT, 5-year cumulative RFS =0.67, CI: 0.42-0.89; mastectomy, 5-year cumulative RFS =0.83, CI: 0.71-0.95). CONCLUSIONS: Thus, BCT may be a safe and rational choice for Chinese female breast cancer patients with a BRCA1/2 mutation. However, tumor size, the TNM stage, the number of positive lymph nodes, might be taken into consideration when choosing surgical management.

Correction to: Concurrent chemoradiotherapy with weekly docetaxel versus cisplatin in the treatment of locoregionally advanced nasopharyngeal carcinoma: a propensity score matched analysis.

In the original publication of this article [1], the first affiliation name in the Author details section should be updated to 'Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, China' because the affiliation has been renamed from Jun. 15th, 2019.

Concurrent chemoradiotherapy with weekly docetaxel versus cisplatin in the treatment of locoregionally advanced nasopharyngeal carcinoma: a propensity score-matched analysis.

BACKGROUND: Promising efficacy and manageable toxicity of docetaxel-based concurrent chemoradiotherapy (CCRT) were reported in head and neck cancer. In addition, the effect of CCRT in combination with cisplatin and/or 5-fluorouracil on both locoregionally advanced and metastatic/recurrent nasopharyngeal carcinoma (NPC) was verified. However, CCRT with docetaxel for locoregionally advanced NPC are not well studied. This study aimed to compare effectiveness and toxicities of CCRT with weekly docetaxel versus tri-weekly cisplatin for locoregionally advanced NPC. METHODS: Clinical data of patients with locoregionally advanced NPC newly diagnosed between January 2010 and December 2014 receiving CCRT with either weekly docetaxel (15 mg/m2) or tri-weekly cisplatin (80-100 mg/m2) were reviewed. Propensity score matching at a 1:1 ratio was performed to balance baseline characteristics. Adverse events and survival were compared between the two groups. RESULTS: A total of 962 patients were included as the whole cohort, and 448 patients were matched and were regarded as the matched cohort. The median follow-up duration was 48 months for the whole cohort. The 3-year nodal recurrence-free survival rate was significantly increased for patients treated with docetaxel in both the whole (hazard ratio [HR] = 0.37, 95% confidence interval [CI] 0.19-0.72, P = 0.030) and matched cohorts (HR = 0.33, 95% CI 0.14-0.79, P = 0.023). However, no significant differences were observed in overall survival, local recurrence-free survival, and distant metastasis-free survival between the two groups in both cohorts. Significantly higher rates of grade 3 radiodermatitis (6.7% vs. 1.8%, P = 0.001), mucositis (74.5% vs. 37.9%, P < 0.001), and leucopenia (2.2% vs. 11.6%, P < 0.001) were observed in the docetaxel group, but any grade of renal injury (1.8% vs. 15.1%, P < 0.001), vomiting (18.8% vs. 88.3%, P < 0.001), and ALT elevation (19.2% vs. 31.3%, P = 0.027) were more common in the cisplatin group. CONCLUSIONS: CCRT with weekly low-dose docetaxel is an effective and tolerable therapeutic regimen for locally advanced NPC. It provides a survival benefit mainly by improving the control of regional lymph node metastases, especially for patients with low pretreatment EBV DNA levels.

The Characteristics and Survival Outcomes in Patients Aged 70 Years and Older with Nasopharyngeal Carcinoma in the Intensity-Modulated Radiotherapy Era.

PURPOSE: We aim to examine nasopharyngeal carcinoma (NPC) characteristics and survival outcomes in patients aged 70 years and older in the intensity-modulated radiotherapy (IMRT) era. METHODS AND MATERIALS: From 2006 to 2013, 126 non-metastatic NPC patients aged ≥ 70 years who were treated with IMRT +/‒ chemotherapy were included. Adult Comorbidity Evaluation 27 (ACE-27) was used to measure patient comorbidities. The overall survival (OS) and cancer-specific survival (CSS)were calculatedwith the Kaplan-Meier method, and differenceswere compared using the log-rank test. The Cox proportional hazards model was used to carry out multivariate analyses. RESULTS: For the entire group, only two patients (1.6%) presented stage I disease, and up to 84.1% patients had stage III-IVB disease. All patients had a comorbidity score of 0 in 24 (19.0%), 1 in 45 (35.7%), 2 in 42 (33.3%), and 3 in 15 (11.9%) patients. The main acute grade during radiotherapy was 3-4 adverse events consisting of mucositis (25.4%), bone marrow suppression (16.7%), and dermatitis (8.7%). After treatment, four patients (3.2%) developed temporal lobe injury. Five-year CSS and OS rates were 67.3% (95% confidence interval [CI], 58.6% to 77.4%) and 54.0% (95% CI, 45.6% to 63.9%), respectively. Five-year OS was significantly higher for ACE-27 score 0-1 than ACE-27 score 2-3 (72.9% and 39.9%, respectively; p < 0.001). Multivariate analyses showed ACE-27 score 0-1 was significantly associated with superior OS (hazard ratio [HR], 3.02; 95% CI, 1.64 to 5.55; p < 0.001). In addition, the rate of OS was higher for stage I-III than that of stage IV, with borderline significance (HR, 1.67; 95% CI, 0.99 to 2.82; p=0.053). But no significant advantage was observed in OS when chemotherapy was used (p > 0.05). CONCLUSION: Our findings suggest IMRT +/- chemotherapy has a manageable toxicity and provides an acceptable survival in patients aged ≥ 70 years with NPC. ACE-27 score was significantly associated with survival outcomes in this group population.

Role of curcumin in the management of pathological pain.

BACKGROUND: Pathological pain conditions can be triggered after peripheral nerve injury and/or inflammation. It is a major clinical problem that is poorly treated with available therapeutics. Curcumin is a phenolic compound derived from Curcuma longa, being widely used for its antioxidant, anti-inflammatory and immunomodulatory effects. PURPOSE: This review systematically summarized updated information on the traditional uses of curcumin in order to explore antinociceptive effects in pathological pain and evaluate future therapeutic opportunities clinically. Moreover, some structure-activity relationships would greatly enrich the opportunity of finding new and promising lead compounds and promote the reasonable development of curcumin. METHODS: PubMed were searched and the literature from the year 1976 to January 2018 was retrieved using keywords pain and curcumin. RESULTS: This review systematically summarized updated information on the traditional uses, chemical constituents and bioactivities of curcumin, and highlights the recent development of the mechanisms of curcumin in the pathological pain by sciatic nerve injury, spinal cord injury, diabetic neuropathy, alcoholic neuropathy, chemotherapy induced peripheral neuroinflammtion, complete Freund's adjuvant (CFA) injection or carrageenan injection. Importantly, the clinical studies provide a compelling justification for its use as a dietary adjunct for pain relief. And we also present multiple approaches to improve bioavailability of curcumin for the treatment of pathological pain. CONCLUSION: This review focuses on pre-clinical and clinical studies in the treatment of pathological pain. Although the mechanisms of pain mitigating effects are not very clear, there is compelling evidence proved that curcumin plays an essential role. However, further high-quality clinical studies should be undertaken to establish the clinical effectiveness of curcumin in patients suffering from pathological pain. Potential methods of increase the water solubility and bioavailability of curcumin still need to be studied. These approaches will help in establishing it as remedy for pathological pain.

High MMP-26 expression in glioma is correlated with poor clinical outcome of patients.

To date the management of glioma remains a great challenge in cancer therapy worldwide. The identification of novel diagnostic and therapeutic methods is required. Although there is data indicating that matrix metalloproteinase (MMP)-26 serves an important role in many human cancer types, its clinical significance in glioma remains uncertain. The present study aimed to evaluate MMP-26 expression in human astrocytic glioma specimens, and investigate its role and significance in the progression of astrocytic glioma. Immunohistochemistry was performed to assess MMP-26 expression in astrocytic glioma tissues. The levels of MMP-26 expression and its relevance to the clinicopathological features and prognostic factors in patients with astrocytic glioma patients were then investigated. The results demonstrated that MMP-26 expression was significantly assocaited with the World Health Organization grade (P<0.05). Additionally, it was identified that MMP-26 expression was an effective predictor of the overall survival of patients with astrocytic glioma (P<0.05). Analyses of univariate and multivariate Cox regression confirmed that MMP-26 expression was an independent factor for evaluating the prognosis of astrocytic glioma patients (P<0.05). The current results support that MMP-26 may be a novel indicator of diagnosis and an independent factor for evaluating prognosis in patients with glioma.

The Novel Prognostic Score Combining Red Blood Cell Distribution Width and Body Mass Index (COR-BMI) Has Prognostic Impact for Survival Outcomes in Nasopharyngeal Carcinoma.

Background: A novel inflammation-and nutrition-based scoring system based on red blood cell distribution width and body mass index (COR-BMI) has prognostic value in nasopharyngeal carcinoma (NPC). Here, we assessed the prognostic value of COR-BMI in NPC. Methods: Retrospective study of 2,318 patients with non-metastatic NPC treated at Sun Yat-sen University Cancer Center was conducted. Patients were stratified into three groups using the COR-BMI score, which is based on two objective and easily measurable parameters: red blood cell distribution width (RDW) and body mass index (BMI). Kaplan-Meier survival analyses were used to compare groups; multivariate Cox proportional models were used to calculate overall survival (OS) and disease-free survival (DFS). Results: Four-year overall survival (OS) rates were 88.7%, 84.5%, and 71.4% for patients with COR-BMI scores of 0, 1, and 2 respectively (P = 0.006). Multivariate Cox proportional hazard analysis revealed COR-BMI was an independent predictor of OS (HR for COR-BMI 1: 1.239, 95% CI: 1.012-1.590; HR for COR-BMI 2: 2.367, 95% CI: 1.311-4.274, P = 0.013), but not DFS (P = 0.482). In subgroup analysis of metastatic NPC, OS rates decreased as COR-BMI increased. In patients with a COR-BMI score of 1, radiotherapy plus chemotherapy led to better OS than radiotherapy alone. Conclusions: COR-BMI may serve as an indicator of poor prognosis in both NPC and metastatic NPC. Radiotherapy plus chemotherapy may benefit patients with a COR-BMI score of 1.

Cervical lymph node carcinoma metastasis from unknown primary site: a retrospective analysis of 154 patients.

Despite advances in diagnosis and treatment, the existence of cervical lymph node carcinoma of unknown primary site (CCUP) has always been an urgent problem worldwide. There is still no consensus on the optimal management for CCUP. In this retrospective review, we analyze the clinical characteristics of CCUP patients treated at our institution and examine how these characteristics and treatments were associated with survival. Clinicopathologic features, treatments, and survival outcomes of 154 CCUP patients were collected from the hospital records and analyzed. Survival was estimated by Kaplan-Meier methods and compared by the log-rank test. Cox proportional hazards regression analysis was used to assess the factors independently associated with overall survival (OS) and progression-free survival (PFS). Median follow-up period was 26.44 months (range, 0.53-146.53 months). Multivariate analysis showed N stage, pathologic type, and lymph node extranodal extension (ENE) to be independent prognostic factors for OS in CCUP patients, but not PFS. Subgroup analysis of patients who received radiotherapy showed that radiotherapy to the pharyngeal mucosa was associated with better OS (P = 0.045), but not with better PFS. Advanced N stage, nonsquamous cell carcinoma, and lymph node ENE predict poor prognosis in patients with CCUP. In addition, radiotherapy to suspicious mucosa is accompanied by better OS. These study findings should be useful to clinicians when selecting the treatment approach.

Dynamic changes in plasma Epstein-Barr virus DNA load during treatment have prognostic value in nasopharyngeal carcinoma: a retrospective study.

Circulating plasma Epstein-Barr virus DNA (EBV DNA) is related to tumor recurrence and metastasis and has potential as a dynamic, sensitive, and specific marker in nasopharyngeal carcinoma (NPC). We investigated the clinical significance of assessing plasma EBV DNA load at various time points during treatment. Patients with NPC (n = 949) for whom plasma EBV DNA load was measured by real-time quantitative polymerase chain reaction (RT-qPCR) before treatment (pre-EBV) and at midtreatment (mid-EBV), end of treatment (end-EBV), and 3 months after completing treatment (3 m-EBV) were retrospectively assessed. Receiver operating characteristic (ROC) curve analysis was used to identify the optimal EBV DNA cutoff point for each time point. Overall survival (OS), distant metastasis-free survival (DMFS), and progression-free survival (PFS) were compared using Kaplan-Meier estimates. High pre-EBV, high mid-EBV, high end-EBV, and high 3 m-EBV were all associated with significantly poorer OS, DMFS, and PFS in the entire cohort. Detectable end-EBV and 3 m-EBV was associated with significantly poorer OS, DMFS, and PFS. Among patients with detectable end-EBV, adjuvant therapy significantly improved OS (HR 2.419; 95% CI 1.297-4.51, P = 0.03) and DMFS (HR 2.45; 95% CI 1.243-4.828, P = 0.04), but not PFS (P = 0.17). EBV DNA represents a dynamic biomarker for monitoring treatment and predicting survival in NPC. Assessing plasma EBV DNA before, during, and after chemoradiotherapy could be clinically valuable and enable selection of patients most likely to benefit from additional therapy and improve assessment of treatment response and disease surveillance. Further multicenter prospective investigations are warranted.

Loss of LKB1 Expression Decreases the Survival and Promotes Laryngeal Cancer Metastasis.

Background: Given recent results indicating that diminished LKB1 expression in laryngeal cancer correlates with shorter survival. We aim to perform an analysis estimate the role of decreased liver kinase B1(LKB1) and in the prognostication of human laryngeal squamous cell carcinoma (LSCC). Methods: We conducted a retrospective study and evaluate the expression of LKB1 and p16INK4a (p16) in 208 clinical advanced-stage LSCC tissue samples by using immunohistochemistry. The specimens were received at Sun Yat-sen University Cancer Center (Guangzhou, China). To evaluate the independent prognostic relevance of LKB1, univariate and multivariate Cox regression models were used, overall survival (OS) and distant metastasis-free survival (DMFS) were compared using the Kaplan-Meier method. Results: Immunohistochemical analyses revealed that 80/208 (38.5%) of the LSCC tissue samples expressed high LKB1. Low LKB1 expression was associated with a significantly shorter OS and DMFS than high LKB1 expression (P = 0.041 and 0.028, respectively; log-rank test), and there was a poorer OS in the p16-positive than p16-negative group. In the subgroup stratified by p16 status, the shorter OS were also seen with low LKB1 expression. Multivariate survival analysis indicated that high LKB1 expression was an independent prognostic factor for OS (hazard ratio [HR]: 1.628, 95% confidence interval [CI]: 1.060-2.500, P = 0.026) and DMFS (HR: 2.182, 95% CI: 1.069-4.456, P = 0.032). Conclusions: Our data indicated that low expression of LKB1 was significantly associated with poor prognosis and it may represent a marker of tumor metastasis in patients with LSCC. When combined with p16, LKB1 was also of prognostic value.

Meta-analysis of the clinical characteristics and prognostic relevance of NOTCH1 and FBXW7 mutation in T-cell acute lymphoblastic leukemia.

The NOTCH1 signaling pathway is crucial for T-cell development, and NOTCH1 and/or FBXW7 mutations are frequently detected in T-cell acute lymphoblastic leukemia (T-ALL). We performed a systematic review and meta-analysis of 18 randomized controlled trials (RCTs) to assess the prognostic impact of mutations in the NOTCH1 pathway. After retrieving relevant articles from PubMed, EMBASE, and the Cochrane Library, we investigated overall survival (OS) and event-free survival (EFS) with hazard ratios (HRs) using fixed-effects or random-effects models and conducted subgroup analyses based on population and mutation status. NOTCH1/FBXW7 mutations correlated significantly with better prognosis (5-year EFS: HR, 0.57; 95% confidence interval [CI], 0.46 to 0.68; P < 0.001 and 5-year OS: HR, 0.61; 95% CI, 0.51 to 0.74; P < 0.001). The HR for 5-year EFS and OS with NOTCH1 mutations were 0.63 (95% CI, 0.53 to 0.75) and 0.76 (95% CI, 0.60 to 0.95), respectively; with FBXW7 mutations, they were 0.82 (95% CI, 0.60 to 1.11) and 0.79 (95% CI, 0.55 to 1.12), respectively. However, differences between children and adults showed no significance. We conclude that the presence of NOTCH1/FBXW7 mutations is an independent prognostic factor for 5-year EFS and 5-year OS.

DNA-dependent protein kinase catalytic subunit functions in metastasis and influences survival in advanced-stage laryngeal squamous cell carcinoma.

Background: DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is known to function in several types of cancer. In this study, we investigated the expression and clinicopathologic significance of DNA-PKcs in laryngeal squamous cell carcinoma (LSCC). Methods: We conducted a retrospective study of 208 patients with advanced-stage LSCC treated at Sun Yat-sen University Cancer Center, Guangzhou, China. We assessed DNA-PKcs and p16INK4a (p16) status using immunohistochemistry. We examined the association between DNA-PKcs expression and clinicopathologic features and survival outcomes. To evaluate the independent prognostic relevance of DNA-PKcs, we used univariate and multivariate Cox regression models. We estimated overall survival (OS) and distant metastasis-free survival (DMFS) using the Kaplan-Meier method. Results: Immunohistochemical analyses revealed that 163/208 (78.4%) of the LSCC tissue samples exhibited high DNA-PKcs expression. High DNA-PKcs expression was significantly associated with survival outcomes (P = 0.016) and distant metastasis (P = 0.02; chi-squared test). High DNA-PKcs expression was associated with a significantly shorter OS and DMFS than low DNA-PKcs expression (P = 0.029 and 0.033, respectively; log-rank test), and was associated with poor OS in the p16-positive subgroup (P = 0.047). Multivariate analysis identified DNA-PKcs as an independent prognostic indicator of OS and DMFS in all patients (P = 0.039 and 0.037, respectively). Conclusions: Our results suggest that patients with LSCC in whom DNA-PKcs expression is elevated have a higher incidence of distant metastasis and a poorer prognosis. DNA-PKcs may represent a marker of tumor progression in patients with p16-positive LSCC.

Elevated peripheral blood lymphocyte-to-monocyte ratio predicts a favorable prognosis in the patients with metastatic nasopharyngeal carcinoma.

INTRODUCTION: Patients with metastatic nasopharyngeal carcinoma (NPC) have variable survival outcomes. We have previously shown that an elevated peripheral blood lymphocyte-to-monocyte ratio (LMR) is associated with an increased metastatic risk in patients with primary NPC. The present study aimed to investigate the prognostic value of pretreatment LMR in a large cohort of metastatic NPC patients. METHODS: Clinical data of 672 patients with metastatic NPC diagnosed between January 2003 and December 2009 were analyzed. The peripheral lymphocyte and monocyte counts were retrieved, and LMR was calculated. Receiver operating characteristic (ROC) curve analysis and univariate and multivariate COX proportional hazards analyses were performed to evaluate the association of LMR with overall survival (OS). RESULTS: Univariate analysis revealed that an elevated absolute lymphocyte count (≥1.390×10(9)/L) and LMR (≥2.475) as well as a decreased monocyte count (<0.665×10(9)/L) were significantly associated with prolonged OS. Multivariate Cox proportional hazard analysis showed that LMR (hazard ratio [HR]=0.50, 95% confidence interval [CI]=0.41-0.60, P<0.001), absolute lymphocyte count (HR=0.77, 95% CI=0.64-0.93, P=0.007), and monocyte count (HR=1.98, 95% CI=1.63-2.41, P<0.001) were independent prognostic factors. By stratification analyses, only LMR remained a significant predictor of prognosis. CONCLUSION: We identified pretreatment LMR as an independent prognostic factor for patients with metastatic NPC. Independent validation of our findings is needed.

Impact of body mass index on survival of esophageal squamous carcinoma patients in southern China.

BACKGROUND: Although high body mass index (BMI) increases risk for developing esophageal adenocarcinoma (EAC), the prognostic influence of BMI is unknown in esophageal squamous carcinoma. METHODS: BMI was calculated using measured height and weight at the first diagnosis and categorized as overweight (25 to 29.9 kg/m(2)), normal (18.5 to 24.9 kg/m(2)) or underweight (<18.5 kg/m(2)). Survival was compared by using the log-rank test on the Kaplan-Meier life table. Multivariate Cox regression analysis was used to evaluate whether BMI was an independent prognostic factor for disease-specific survival (DSS). RESULTS: Among 1,176 esophageal squamous carcinoma patients, 146 (12.4%) were categorized as overweight, and 277 (23.6%) underweight. More patients in the underweight group had anemia (P=0.001), weight loss (P=0.035) and R1 resection (P<0.001). Less patients in the underweight group received adjuvant chemotherapy (P=0.01). Patients in the overweight group had a higher incidence rate of high blood pressure (P<0.001), diabetes (P<0.001) and coronary artery diseases (P<0.001). Moreover, more patients in the overweight group had a lower TNM stage (P=0.003). In the univariated analysis, high BMI was significantly associated with better DSS (P=0.013). CONCLUSIONS: After adjusting for covariates enrolled for study, high BMI was an independent prognostic factor in weight loss esophageal squamous carcinoma patients.