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.

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.

Prognostic value of grading masticator space involvement in nasopharyngeal carcinoma according to MR imaging findings.

PURPOSE: To derive a suitable method for grading masticator space invasion in nasopharyngeal carcinoma on the basis of magnetic resonance (MR) images and to determine its prognostic value in patients undergoing intensity-modulated radiation therapy. MATERIALS AND METHODS: After institutional review board approval and informed consent were acquired, 808 patients with nasopharyngeal carcinoma who were treated with definitive intensity-modulated radiation therapy were analyzed retrospectively. The anatomic sites of masticator space involvement were identified with MR imaging. Overall survival, local relapse-free survival, and distant metastasis-free survival were calculated by using the Kaplan-Meier method and were compared by using the log-rank test. Potential prognostic factors were identified by means of multivariate analysis. RESULTS: Masticator space involvement was diagnosed in 163 of 808 patients (20.2%). Patients with lateral invasion (involvement of the lateral pterygoid muscle of the masticator space and beyond) had significantly poorer overall survival and distant metastasis-free survival than those with medial invasion (involvement of the medial pterygoid muscle of the masticator space) (P = .035 and P = .026, respectively). Furthermore, their overall survival, local relapse-free survival, and distant metastasis-free survival were significantly poorer compared with patients with stage T2 or T3 disease (all P ≤ .023) but similar to patients with stage T4 disease. The grade of masticator space involvement was an independent prognostic factor for overall survival, local relapse-free survival, and distant metastasis-free survival (all P ≤ .023). CONCLUSION: Masticator space involvement in nasopharyngeal carcinoma should be graded as medial (stage T2 disease) or lateral (stage T4 disease). This can facilitate staging of nasopharyngeal carcinoma and may be a suitable prognostic indicator of survival.

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.

Expression TGM2 and BNIP3 have prognostic significance in laryngeal cancer patients receiving surgery and postoperative radiotherapy: a retrospective study.

BACKGROUND: This study was designed to determine the pattern and correlation between expression of the HIF-1α transcriptional targets TGM2 and BNIP3 in laryngeal cancer, and investigate the association of BNIP3 and TGM2 with clinical outcome in laryngeal squamous cell carcinoma (SCC) patients receiving postoperative radiotherapy. METHODS: Immunostaining with antibodies specific to BNIP3 and TGM2 was performed in formalin-fixed, paraffin-embedded specimens from 148 laryngeal SCC patients. BNIP3 and TGM2 expression was scored as high or low, based on the number of tumor cells stained and the staining intensity. All patients received postoperative radiotherapy. Patient follow up and clinicopathological data were compared using the Chi-squared test, univariate and multivariate analyses, and survival curves were generated using the Kaplan-Meier method and log-rank test. RESULTS: The 3, 5 and 10-year overall survival rates (OS) for all patients were 77.7%, 71.6%, 56.4%, respectively. Primary tumor site, T stage, overall stage, lymph-node metastasis, BNIP3 expression and TGM2 expression were significant prognostic factors for OS in univariate analysis. Negative cervical lymph nodes, high BNIP3 expression and low TGM2 expression were independent prognostic factors of improved OS in multivariate analysis. BNIP3 expression correlates with TGM2 expression in laryngeal SCC (P = 0.012). CONCLUSIONS: This study indicates that lymph-node metastasis, BNIP3 expression and TGM2 expression are independent prognostic factors in laryngeal SCC patients receiving postoperative radiotherapy. Further studies are required to investigate how BNIP3 and/or TGM2 influence the prognosis of laryngeal SCC patients treated with postoperative radiotherapy, and to determine how TGM2 and BNIP3 expression are regulated.

Serum C-reactive protein as an important prognostic variable in patients with diffuse large B cell lymphoma.

C-reactive protein (CRP) is an acute-phase reactant that is a promising biomarker in patients with cancer of many kinds. The aim of this retrospective study was to evaluate significant changes in CRP levels as a parameter for the response effect and long-term survival of patients with diffuse large B cell lymphoma (DLBCL). Serum CRP data were collected in 94 patients with DLBCL from October 2006 to August 2009 in Cancer Center, Sun Yat-Sen University. Results were correlated with clinical data. The median CRP serum level in patients with DLBCL was 30.91 ± 53.35 in male and 22.39 ± 29.89 mg/L in female. Base line CRP levels were correlated with International Prognostic Index (IPI) scores (p = 0.03). Among the patients with an IPI score of 1-2, base line CRP levels were correlated with long-term survival (p = 0.001). Base line CRP levels were also correlated with OS (p = 0.001) and varied with different clinical stages (p = 0.03). The corresponding CRP levels in the patients with 2 cycles of chemotherapy were correlated with short-term treatment response (p = 0.003) and OS (p = 0.04) or TTP (p = 0.03). CRP serum levels can be used as additional prognostic parameter in patients with diffuse large B cell type lymphoma.

Radiofrequency ablation combined with systemic chemotherapy in nasopharyngeal carcinoma liver metastases improves response to treatment and survival outcomes.

BACKGROUND: Systemic chemotherapy is the major treatment modality for nasopharyngeal carcinoma (NPC) liver metastases. We investigated the effectiveness of radiofrequency ablation (RFA) treatment, which has not been well explored in this disease. METHODS: One-hundred and thirty-four cases of NPC with liver metastases treated with chemotherapy, chemotherapy with RFA, or RFA alone were retrospectively analyzed. Patient survival was evaluated by the log-rank test. Survival was analyses using the Kaplan-Meier method. Cox multivariate analyses of clinicopathological features and different treatment approaches were conducted. RESULTS: Local response rates were 58% in the RFA group, 78% in the chemotherapy group and 93% in the chemotherapy with RFA group (P < 0.001). Increased progression-free survival (PFS) and overall survival (OS) were observed in the chemotherapy with RFA group (P < 0.001). Cox multivariate analysis indicated that the number of liver metastases (1 vs. >1), the dimension of the largest liver metastases (≤3 cm vs. >3 cm), evaluation of treatment (response vs. no response) and disease-free survival (≤12 months vs. >12 months) were independent prognostic factors. CONCLUSIONS: RFA combined with chemotherapy is a promising treatment for NPC metastatic liver disease with improved local response, PFS, and OS compared to current chemotherapy protocols.

[Chromaticity and optical spectrum colorimetry of the tongue color in different syndromes of primary hepatic carcinoma].

OBJECTIVE: In this study, the optical data of tongue color of different syndromes in primary hepatic carcinoma (PHC) were detected by optical spectrum colorimetry, and the chromaticity of tongue color was compared and analyzed. The tongue color characteristics of different syndromes in PHC and the relationship between different syndromes and tongue color were also investigated. METHODS: Tongue color data from 133 eligible PHC patients were collected by optical spectrum colorimetry and the patients were divided into 4 syndrome groups according to their clinical features. The syndrome groups were liver depression and spleen deficiency (LDSD), accumulation of damp-heat (ADH), deficiency of liver and kidney yin (DLKY), and qi stagnation and blood stasis (QSBS). The variation characteristics of chromaticity coordinates, dominant wavelength, excitation purity and the distribution in the International Commission on Illumination (CIE) LAB uniform color space were measured. At the same time, the differences of overall chromatism, clarity, chroma, saturation and hue were also calculated and analyzed. RESULTS: PHC patients in different syndrome groups exhibited differences in chromaticity coordinates. The dominant wavelength of QSBS was distinctly different from that of the other 3 syndromes. Excitation purity in the syndromes of LDSD, ADH and DLKY showed gradual increases (P<0.01). Different syndromes in the CIE LAB color three-dimensional space showed differences in tongue color distribution areas. The CIE hue-angle value of QSBS was negative, and different from that of the other 3 syndromes (P<0.01). CIE chroma in the syndromes of LDSD, ADH and DLKY showed gradual increases (P<0.01), the same as excitation purity. In the comparison of chromatism, tongue color variations in different syndromes were quantified by human observation. CONCLUSION: This study shows that tongue color diagnosis according to the syndrome classifications of traditional Chinese medicine can be quantified with optical spectrum colorimetry technology. Different syndromes in PHC exhibit distinct chromatisms of tongue color through the calculation and analysis of chromaticity parameters of CIE, combined with colorimetric system and CIE LAB color space, and these are consistent with the characteristics of clinical tongue color. Applying optical spectrum colorimetry technology to tongue color differentiation has the potential to serve as a reference point in standardizing traditional Chinese medicine syndrome classification in PHC.

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.

Treatment results and prognostic factors of patients undergoing postoperative radiotherapy for laryngeal squamous cell carcinoma.

Postoperative radiotherapy (PRT) is widely advocated for patients with squamous cell carcinomas of the head and neck that are considered to be at high risk of recurrence after surgical resection. The aims of this study were to evaluate the treatment outcomes of PRT for patients with laryngeal carcinoma and to identify the value of several prognostic factors. We reviewed the records of 256 patients treated for laryngeal squamous cell carcinoma between January 1993 and December 2005. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Log-rank test was employed to identify significant prognostic factors for DFS and OS. The Cox proportional hazards model was applied to identify covariates significantly associated with the aforementioned endpoints. Our results showed the 3-, 5-, and 10-year DFS for all patients were 69.9%, 59.5%, and 34.9%, respectively. The 3-, 5-, and 10-year OS rates were 80.8%, 68.6%, and 38.8%, respectively. Significant prognostic factors for both DFS and OS on univariate analysis were grade, primary site, T stage, N stage, overall stage, lymph node metastasis, overall treatment times of radiation, the interval between surgery and radiotherapy, and radiotherapy equipment. Favorable prognostic factors for both DFS and OS on multivariate analysis were lower overall stage, no cervical lymph node metastasis, and using 60Co as radiotherapy equipment. In conclusion, our data suggest that lower overall stage, no cervical lymph node metastasis, and using 60Co as radiotherapy equipment are favorable prognostic factors for DFS and OS and that reducing the overall treatment times of radiation to 6 weeks or less and the interval between surgery and radiotherapy to less than 3 weeks are simple measures to remarkably improve treatment outcome.

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.

Prognostic significance of Oct4 and Sox2 expression in hypopharyngeal squamous cell carcinoma.

BACKGROUND: Oct4 and Sox2 are two major transcription factors related to the stem cell self-renewal and differentiation. The aim of this study was to examine the association between Oct4 and Sox2 expression levels with both the clinicopathological characteristics and prognoses of patients with hypopharyngeal squamous cell carcinoma. METHOD: Tumor tissue samples from 85 patients with hypopharyngeal squamous cell carcinoma were collected, and the clinical follow-up data of these patients were recorded, and expression status of Oct4 and Sox2 were examined in these tissue samples by immunohistochemistry (IHC). RESULTS: Oct4 expression was found to be an independent predictive factor for overall survival (p = 0.004) in patients with hypopharyngeal squamous cell carcinoma and was independently related to loco-regional control (p = 0.001). Although Sox2 expression status showed no significant association with overall survival (p = 0.166), disease-free survival (p = 0.680) or loco-regional control (p = 0.383), when using a subgroup analysis, the subgroup with both high Oct4 and Sox2 expression had the best prognosis (p = 0.000). Sox2 expression could be a potential prognostic predictor for patients with hypopharyngeal squamous cell carcinoma. Simultaneous analyses of Oct4 and Sox2 expression could be more effective in evaluating the prognoses of patients with hypopharyngeal squamous cell carcinoma. CONCLUSION: Oct4 expression is an independent predictive factor for patients with hypopharyngeal squamous cell carcinoma, suggesting that Oct4 expression may be a useful indicator for predicting the prognosis of hypopharyngeal squamous cell carcinoma.

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.

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.

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.