SARS-CoV-2 vaccines in China could reduce COVID-19-related respiratory syndromes and deaths: A retrospective cohort study.

Background: Information is limited regarding the effectiveness of the inactivated vaccine for COVID-19 approved in China in preventing infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) when administered in real-world conditions. Methods: We retrospectively surveyed 1352 patients with a positive SARS-CoV-2 nucleic acid test treated at a major tertiary medical center in Foshan city (Guangdong, China) between November 2022 and February 2023. The exposure group was patients who had previously received the COVID-19 vaccine, which included patients who had received different doses of the vaccine and different vaccine types. The primary outcome of this study was the effectiveness of the vaccine in preventing severe disease and death among SARS-CoV-2-infected patients. Results: We found a mortality rate of 12.1 % associated with COVID-19. The results showed that an increase in the number of vaccine doses was associated with a reduction in in-hospital mortality. When compared to unvaccinated patients, vaccinated patients had an 8.5 % lower mortality rate. There was also a statistically significant reduction in the risk of death among vaccinated patients compared to unvaccinated patients (OR = 0.521 [95 % CI, 0.366 to 0.741]). Patients who had received the vaccine had a 22.8 % reduction in the risk of severe disease. In addition, the use of antiviral drugs decreased progressively with increasing vaccine doses (P < 0.05). Of these, anticoagulation, Paxlovid, and mechanical ventilation were used least frequently in the one-dose group. Conclusions: The vaccines approved in China mitigated the incidence of severe COVID-19 and reduced mortality. These findings suggest that COVID-19 vaccination can help to control the pandemic.

The clinical value of combining shear wave elastography, VOCAL technique, and T2* MRI of early gestation placenta to predict pre-eclampsia.

OBJECTIVE: To investigate the clinical value of combining shear wave elastography (SWE) with the Volumetric Organ Computer-Aided AnaLysis (VOCAL) technique and T2* magnetic resonance imaging (MRI) to predict pre-eclampsia (PE). METHODS: From December 2022 to March 2023, we recruited 31 pregnant women diagnosed with PE at our hospital as the observation group and 85 normal pregnant women as the control group. Differences in placental elasticity, vascularization index (VI), flow index (FI), vascularization flow index (VFI), and T2* MRI perfusion fraction (f) were compared between the two groups. Received operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of placental elasticity, VI, FI, VFI, f, and their combination for predicting PE. RESULTS: Placental elasticity was higher in the observation group than in the control group, while VI, FI, VFI, and f were lower in the observation group (all p < 0.05). The area under the curve (AUC) for placental elasticity, VI, FI, VFI, f, and their combination for predicting PE were 0.85, 0.77, 0.78, 0.84, 0.65, and 0.94, respectively. The sensitivity was 71%, 55%, 94%, 65%, 55%, and 81%. The specificity was 92%, 91%, 60%, 92%, 79%, and 98%. The combined prediction model had a higher AUC than the individual predictors (p < 0.05). CONCLUSION: SWE combined with VOCAL technique and T2* MRI has high value for predicting PE and can provide reference information for clinical diagnosis.

Utility of peripheral blood macrophage factor Apo10 and TKTL1 as markers in distinguishing malignant from benign lung nodules: a protocol for a prospective cohort study in Southern China.

INTRODUCTION: Lung nodules are one of the most prevalent diseases. Medical imaging methods have a high false positive rate for distinguishing malignant nodules from benign nodules. Therefore, developing new technologies with high accuracy for screening malignant nodules is of great importance for lung nodule surveillance. Use of flow cytometry to detect biomarkers in blood macrophages (epitop detect in macrophages/macrophages) has opened a new era for early and noninvasive diagnosis of cancer. This planned study aims to examine whether the peripheral blood macrophage factors Apo10 and TKTL1 accurately distinguish malignant nodules from benign nodules. METHODS AND ANALYSES: We plan to enrol in this study 3825 participants with lung nodules who will attend their annual physical examination at Sun Yat-sen University Cancer Center. Apo10 and TKTL1 levels in all patients will be tested at 60 min after their last meal every 6 months during their 3-year follow-up. Biopsy or surgical pathology results will be collected as the gold standard to assess the accuracy of Apo10 and TKTL1 in distinguishing malignant nodules from benign nodules. The sensitivity, specificity, positive predictive value, negative predictive value and area under the receiving operating characteristic curve will also be evaluated. ETHICS AND DISSEMINATION: The study is approved by the medical ethics committee of Sun Yat-sen University (SL-G2022-005-02). The results of this study will be disseminated in peer-reviewed publications and presentations at international scientific meetings and will also be disseminated to the participants. TRIAL REGISTRATION NUMBER: ChiCTR2300073823; Pre-results.

Spatial Patterns of Gallbladder and Biliary Tract Carcinoma in China From 1990 to 2019: An Analysis at the Provincial Level.

Background Despite a high rate of fatal malignancy, little is known regarding the spatial and temporal patterns of the disease burden of gallbladder and biliary tract carcinoma in China, especially at the provincial level. Methodology Using data from the 2019 Global Burden of Diseases, Injuries, and Risk Factors Study, we estimated the temporal trend of the disease burden of gallbladder and biliary tract carcinoma from 1990 to 2019 as well as its incidence, mortality, prevalence, and disability-adjusted life-years (DALYs). We estimated the spatial pattern of the disease burden of gallbladder and biliary tract carcinoma at the provincial level. Results The disease burden of gallbladder and biliary tract carcinoma significantly increased from 1990 to 2019 in China. The age-standardized incidence, prevalence, mortality, and DALYs increased by 28.3%, 50.5%, 13.0%, and 7.0%, respectively. The disease burden of gallbladder carcinoma revealed substantial heterogeneity at the provincial level with a higher disease burden in developed provinces or cities than in developing provinces. The disease burden of gallbladder and biliary tract carcinoma was also heavier among males than among females (e.g., age-standardized DALYs: 42.60 per 100,000 people among males vs. 33.57 per 100,000 people among females in 2019). Conclusions The disease burden of gallbladder and biliary tract carcinoma has shown rapid changes during the past three decades, with a higher burden in economically advantaged regions than in disadvantaged regions in China. New public health policies and initiatives are needed to address this rising disease burden.

Apo10 and TKTL1 in blood macrophages as biomarkers for differentiating lung cancer from benign lung lesions: a comparative study with conventional biomarkers.

The detection of biomarkers in blood macrophages is a new non-invasive cancer screening method, but its performance in early stage lung cancer screening remains undetermined. We evaluated the Apo10 and TKTL1 levels in blood macrophages of 156 early-stage lung cancer patients and 153 controls. APT (combination of Apo10 and TKTL1) level was significantly higher in the lung cancer group than that in the control group (P < 0.001). AUROC analysis showed that APT has high diagnostic value in differentiating early-stage lung cancer (AUC = 0.9132) and can be considered a biomarker for screening lung cancer patients from individuals with lung nodules.

Metabolomic differentiation of benign vs malignant pulmonary nodules with high specificity via high-resolution mass spectrometry analysis of patient sera.

Differential diagnosis of pulmonary nodules detected by computed tomography (CT) remains a challenge in clinical practice. Here, we characterize the global metabolomes of 480 serum samples including healthy controls, benign pulmonary nodules, and stage I lung adenocarcinoma. The adenocarcinoma demonstrates a distinct metabolomic signature, whereas benign nodules and healthy controls share major similarities in metabolomic profiles. A panel of 27 metabolites is identified in the discovery cohort (n = 306) to distinguish between benign and malignant nodules. The discriminant model achieves an AUC of 0.915 and 0.945 in the internal validation (n = 104) and external validation cohort (n = 111), respectively. Pathway analysis reveals elevation in glycolytic metabolites associated with decreased tryptophan in serum of lung adenocarcinoma vs benign nodules and healthy controls, and demonstrates that uptake of tryptophan promotes glycolysis in lung cancer cells. Our study highlights the value of the serum metabolite biomarkers in risk assessment of pulmonary nodules detected by CT screening.

Novel nutritional indicator as predictors among subtypes of lung cancer in diagnosis.

Introduction: Lung cancer is a serious global health concern, and its subtypes are closely linked to lifestyle and dietary habits. Recent research has suggested that malnutrition, over-nutrition, electrolytes, and granulocytes have an effect on the development of cancer. This study investigated the impact of combining patient nutritional indicators, electrolytes, and granulocytes as comprehensive predictors for lung cancer treatment outcomes, and applied a machine learning algorithm to predict lung cancer. Methods: 6,336 blood samples were collected from lung cancer patients classified as lung squamous cell carcinoma (LUSC), lung adenocarcinoma (LUAD), and small cell lung cancer (SCLC). 2,191 healthy individuals were used as controls to compare the differences in nutritional indicators, electrolytes and granulocytes among different subtypes of lung cancer, respectively. Results: Our results demonstrated significant differences between men and women in healthy people and NSCLC, but no significant difference between men and women in SCLC patients. The relationship between indicators is basically that the range of indicators for cancer patients is wider, including healthy population indicators. In the process of predicting lung cancer through nutritional indicators by machine learning, the AUC of the random forest model was as high as 93.5%, with a sensitivity of 75.9% and specificity of 96.5%. Discussion: This study supports the feasibility and accuracy of nutritional indicators in predicting lung cancer through the random forest model. The successful implementation of this novel prediction method could guide clinicians in providing both effective diagnostics and treatment of lung cancers.

Histological types of lung cancer attributable to fine particulate, smoking, and genetic susceptibility.

BACKGROUND: Fine particulate matter (PM2.5), smoking, and genetic factors are associated with lung cancer. However, the relationship between PM2.5, smoking and subtypes of lung cancer remains unclear. Moreover, it is unclear whether genetic risk modifies the impact of PM2.5 and smoking on incident lung cancer. METHODS: A total of 298,069 participants from the UK Biobank study without lung cancer at baseline were included in this study. Hazard ratios (HRs) with 95 % confidence intervals (CIs) were estimated using multivariable Cox proportional models for the association of lung cancer and its subtypes with PM2.5, smoking, and genetic risk. Potential gene-smoking or gene-PM2.5 interactions were also estimated. We further estimated population attributable fractions for incident lung cancer. RESULTS: During 10.4 years of follow-up, 1683 incident lung cancer cases were identified. Our analysis found that genetic variants, smoking, and PM2.5 were significantly associated with incident lung cancer. For different histological types of lung cancer, the HRs for squamous cell lung carcinoma associated with PM2.5 (per 5 µg/m3 increment) and current smoking were 2.76 (95 % CI: 1.72, 4.42, p < 0.001) and 48.64 (95 % CI: 27.96, 84.61, p < 0.001), while the HRs for lung adenocarcinoma were 1.59 (95 % CI: 1.13, 2.23, p < 0.001) and 9.89 (95 % CI: 7.91, 12.36, p < 0.001), respectively. We further found that participants with high levels of PM2.5 pollution and high genetic risk had the highest risk of incident lung cancer (HR = 1.81, 95 % CI: 1.39, 2.35, p < 0.001), while the interaction between PM2.5 and genetic risk was not statistically significant. We observed that the population attributable fractions of lung cancer attributable to current smoking and high PM2.5 exposure were estimated to be 67.45 % and 17.59 %. CONCLUSION: Genetic susceptibility, smoking, and PM2.5 are important risk factors for lung cancer. Both smoking and PM2.5 are more closely associated with an elevated risk of squamous cell lung cancer.

Quantification of ferroptosis pathway status revealed heterogeneity in breast cancer patients with distinct immune microenvironment.

Clinical significance and biological functions of the ferroptosis pathway were addressed in all aspect of cancer regarding multi-omics level; however, the overall status of ferroptosis pathway alteration was hard to evaluate. The aim of this study is to comprehensively analyze the putative biological, pathological, and clinical functions of the ferroptosis pathway in breast cancer on a pathway level. By adopting the bioinformatic algorithm "pathifier", we quantified five programmed cell death (PCD) pathways (KO04210 Apoptosis; KO04216 Ferroptosis; KO04217 Necroptosis; GO:0070269 Pyroptosis; GO:0048102 Autophagic cell death) in breast cancer patients, and we featured the clinical characteristics and prognostic value of each pathway in breast cancer and found significantly activated PCD in cancer patients, among which ferroptosis demonstrated a significant correlation with the prognosis of breast cancer. Correlation analysis between PCD pathways identified intra-tumor heterogeneity of breast cancer. Therefore, clustering of patients based on the status of PCD pathways was done. Comparisons between subgroups highlighted specifically activated ferroptosis in cluster 2 patients, which showed the distinct status of tumor immunity and microenvironment from other clusters, indicating putative correlations with ferroptosis. NDUFA13 was identified and selected as a putative biomarker for cluster 2 patients. Experimental validations were executed on cellular level and NDUFA13 showed an important role in regulating ferroptosis activation and can work as a biomarker for ferroptosis pathway status. In conclusion, the status of the ferroptosis pathway significantly correlated with the clinical outcomes and intra-tumor heterogeneity of breast cancer, and NDUFA13 expression was identified as a positive biomarker for ferroptosis pathway activation in breast cancer patients.

The Emergence of a Multidrug-Resistant and Pathogenic ST42 Lineage of Staphylococcus haemolyticus from a Hospital in China.

Staphylococcus haemolyticus is an opportunistic pathogen associated with hospital-acquired infections. However, the genetic diversity of S. haemolyticus among the patients and the hospital environment is largely unknown. Here, we isolated 311 S. haemolyticus strains from different sampling sites of patients and hospital environment. Genomic analysis showed that ST42 is an emerging clone widely disseminated in the hospital. S. haemolyticus ST42 strains exhibited decreased susceptibilities for multiple antibiotics compared with other STs and carried significantly more antibiotic resistance genes (ARGs). Furthermore, ST42 strains harbored more virulence genes per isolate than in other STs, and the capsular biosynthesis genes capDEFG were more prevalent in ST42 strains. Using the Galleria mellonella infection model, we demonstrated that ST42 strains are highly virulent compared with non-ST42 strains. Taken together, our data identified an emerging ST42 clone of S. haemolyticus with aggregated ARGs and virulence determinants in the hospital, representing a significant health threat in terms of both disease and treatment. IMPORTANCES. haemolyticus is an emerging opportunistic pathogen with a high burden of antimicrobial resistance. We performed molecular epidemiological analysis of S. haemolyticus that was isolated from a hospital, and found that the phylogenetic lineages are diverse accompanied by a dominant epidemic clonal lineage ST42. We demonstrated that S. haemolyticus ST42 strains have been disseminated among patients and the hospital environment. The data provide mechanistic insight and indicate that S. haemolyticus ST42 strains are multidrug-resistance and virulent clones via accumulating more ARGs and virulence genes.

Abnormal placental DNA methylation variation in spontaneous preterm birth.

OBJECTIVE: Preterm birth (PTB) has become a major public health concern as the leading cause of neonatal death, but little is understood about its etiology. Children born preterm are also at increased risk of long-term consequences such as neurodevelopmental disorders, adulthood hypertension and diabetes. Recent studies have indicated that DNA methylation may be involved in the occurrence of PTB as well as related adverse outcomes. The latest Infinium EPIC BeadChip extends the coverage of the genome and provides a better tool to help investigate the involvement of DNA methylation in these conditions. METHODS: We conducted this case-control study in three Women and Children's hospitals in South China, and enrolled 32 spontaneous preterm births and 16 term births. We assessed placental DNA methylation profiling of these participants with the Infinium EPIC BeadChip. We identified PTB and gestational age (GA)-associated CpG sites with limma regression model, and applied seqlm to identify PTB-associated regions. We performed gene ontology analysis to further interpret functional enrichment of the identified differentially methylated genes in PTB. RESULTS: We identified a total of 8 differentially methylated positions (DMPs) that were significantly associated with PTB (FDR < 0.1) and a total of 15 DMPs that were associated with GA (FDR < 0.1). In the regional analysis, one differentially methylated region in the SLC23A1 gene overlapped with PTB-associated CpG site. The differentially methylated CpG sites in PTB were mapped to the genes involving in biological processes mainly regarding neurodevelopment, regulation of inflammation and metabolism. CONCLUSION: Our findings suggested that preterm placenta have distinct DNA methylation alterations, and these alteration patterns established at birth provide insight into the long-term consequences of preterm birth.

Placental weight mediates association between prenatal exposure to cooking oil fumes and preterm birth.

Background: There are some reports on association between maternal prenatal cooking oil fume (COF) exposure and preterm birth (PTB), but its mechanism remains poorly understood. Therefore, this study aims to assess whether placental weight mediates their associations.Method: We enrolled 619 pregnant women delivering PTB newborns as cases and 1701 delivering full-term appropriate for gestational age newborns as controls. They were inquired with a self-reported questionnaire about prenatal COF exposure, socio-demographics and obstetric characteristics at Women and Children's Hospitals of Shenzhen and Foshan. After controlling for the potential confounders, a series of logistic and linear regressions were conducted to assess associations among COF exposure, placental weight and PTB, and the mediation of placental weight in the association between COF exposure and PTB.Results: Maternal prenatal COF exposure was significantly associated with PTB and the frequency of prenatal COF exposure was negatively associated with placental weight. Compared with mother who never cooked, those cooking occasionally, sometimes or often increased the risk of PTB, and similarly, those cooking between half to an hour was also showed a higher risk of PTB. Typical Chinese cooking methods including stir-frying, pan-frying and deep-frying were also associated with PTB. Different oil types mainly used, including peanut oil, corn oil and animal oil were associated with PTB as well. Mediation analysis illustrated that placental weight partially mediated 13.60% (95% CI = 10.62-33.20%) of the effects on the association between the frequency of maternal prenatal COF exposure and PTB.Conclusion: Maternal cooking during pregnancy and the frequency of prenatal COF exposure might increase the risk of PTB, in which placenta might play mediation role.

Supplemental folic acid and/or multivitamins in pregnancy is associated with a decreased risk of childhood and adolescent nasopharyngeal carcinoma.

The aim of this study was to evaluate the association between prenatal and neonatal period exposures and the risk of childhood and adolescent nasopharyngeal carcinoma (NPC). From January 2009 to January 2016, a total of 46 patients with childhood and adolescent NPC (i.e., less than 18 years of age) who were treated at Sun Yat-sen University Cancer Center were screened as cases, and a total of 45 cancer-free patients who were treated at Sun Yat-sen University Zhongshan Ophthalmic Center were selected as controls. The association between maternal exposures during pregnancy and obstetric variables and the risk of childhood and adolescent NPC was evaluated using logistic regression analysis. Univariate analysis revealed that compared to children and adolescents without a family history of cancer, those with a family history of cancer had a significantly higher risk of childhood and adolescent NPC [odds ratios (OR) = 3.15, 95% confidence interval (CI) = 1.02-9.75, P = 0.046], and the maternal use of folic acid and/or multivitamins during pregnancy was associated with a reduced risk of childhood and adolescent NPC in the offspring (OR = 0.07, 95% CI = 0.02-0.25, P < 0.001). After multivariate analysis, only the maternal use of folic acid and/or multivitamins during pregnancy remained statistically significant. These findings suggest that maternal consumption of folic acid and/or multivitamins during pregnancy is associated with a decreased risk of childhood and adolescent NPC in the offspring.

The Influence of Articulatory Suppression on Reading Among Chinese Children With Developmental Dyslexia: An Eye-Movement Study.

Objective: The study aimed to examine how the phonological loop influences reading ability and processing in Chinese children with developmental dyslexia (DD). Methods: This study included 30 children with DD and 37 children without DD. Two types of articles (i.e., scenery prose and narrative story) and two conditions (under the conditions of articulatory-suppression and silent reading) were applied. An eye-link II High-Speed Eye Tracker was used to track a series of eye-movement parameters. The data were analyzed by the linear Mixed-Effects model. Results: Compared with children without DD, Children with DD had lower reading achievement (RA), frequency of saccades (FS) and frequency of fixations (FF), longer reading time (RT) and average fixation duration (AFD), slower reading speed (RS), shorter average saccade amplitude (ASA) and fixation distance (FD), more number of fixations (NF), and number of saccades (NS). There were significant interactions between participant group and articulatory suppression on RT and FD. We also observed interaction effects between article types and articulatory suppression on RA, AFD, ASA, and FS. Conclusion: Children DD exhibit abnormal phonological loop and eye movements while reading. The role of articulatory suppression on reading varies with the presentation of DD and the article type.

Structural variants in the Chinese population and their impact on phenotypes, diseases and population adaptation.

A complete characterization of genetic variation is a fundamental goal of human genome research. Long-read sequencing has improved the sensitivity of structural variant discovery. Here, we conduct the long-read sequencing-based structural variant analysis for 405 unrelated Chinese individuals, with 68 phenotypic and clinical measurements. We discover a landscape of 132,312 nonredundant structural variants, of which 45.2% are novel. The identified structural variants are of high-quality, with an estimated false discovery rate of 3.2%. The concatenated length of all the structural variants is approximately 13.2% of the human reference genome. We annotate 1,929 loss-of-function structural variants affecting the coding sequence of 1,681 genes. We discover rare deletions in HBA1/HBA2/HBB associated with anemia. Furthermore, we identify structural variants related to immunity which differentiate the northern and southern Chinese populations. Our study describes the landscape of structural variants in the Chinese population and their contribution to phenotypes and disease.

Trajectories of EBV DNA and identifying the potential long-term survivors in metastatic nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is highly incident in southern China. Distant metastasis is the leading cause of death in NPC patients. However, the phenotypical feature of this patient population is largely undefined. The current study aimed to categorize metastatic NPC patients into novel subgroups based on their EBV DNA trajectories. In this retrospective study, 446 eligible patients with metastatic NPC treated at Sun Yat-Sen University Cancer Center between 2012 and 2016 were analyzed. Using a mixture model analysis, we identified distinct trajectories based on longitudinal EBV DNA measurements. We evaluated their associations with metastatic NPC mortality using Cox regression analysis. The two-class trajectory model provided the best fit, in which 272 patients were classified as non-sustained EBV DNA class and 174 patients as sustained EBV DNA class. After a median follow-up of 60.8 months, the median OS was 61.7 months in the sustained EBV DNA clearance class versus 20.0 months in the non-sustained EBV DNA clearance class (P<0.001). Compared with patients in the non-sustained EBV DNA clearance class, patients in the sustained EBV DNA clearance class demonstrated superior PFS (HR, 3.238; 95% CI, 2.601-4.032; P<0.001). Forty-three patients experienced disease-free for longer than 36 months, defined as long-term survivors (LTS). Notably, 41 patients were presented in the sustained EBV DNA clearance class (95.3%), along with only 2 patients in the non-sustained EBV DNA clearance class. Collectively, we identified two EBV DNA trajectory sub-phenotypes of patients with metastatic NPC, providing more reliable survival information for physicians and patients during their informed decision-making process.

Fermitin family member 2 promotes melanoma progression by enhancing the binding of p-α-Pix to Rac1 to activate the MAPK pathway.

We identified fermitin family member 2 (FERMT2, also known as kindlin-2) as a potential target in A375 cell line by siRNA library screening. Drugs that target mutant BRAF kinase lack durable efficacy in the treatment of melanoma because of acquired resistance, thus the identification of novel therapeutic targets is needed. Immunohistochemistry was used to identify kindlin-2 expression in melanoma samples. The interaction between kindlin-2 and Rac1 or p-Rac/Cdc42 guanine nucleotide exchange factor 6 (α-Pix) was investigated. Finally, the tumor suppressive role of kindlin-2 was validated in vitro and in vivo. Analysis of clinical samples and Oncomine data showed that higher levels of kindlin-2 predicted a more advanced T stage and M stage and facilitated metastasis and recurrence. Kindlin-2 knockdown significantly inhibited melanoma growth and migration, whereas kindlin-2 overexpression had the inverse effects. Further study showed that kindlin-2 could specifically bind to p-α-Pix(S13) and Rac1 to induce a switch from the inactive Rac1-GDP conformation to the active Rac1-GTP conformation and then stimulate the downstream MAPK pathway. Moreover, we revealed that a Rac1 inhibitor suppressed melanoma growth and metastasis and the combination of the Rac1 inhibitor and vemurafenib resulted in a better therapeutic outcome than monotherapy in melanoma with high kindlin-2 expression and BRAF mutation. Our results demonstrated that kindlin-2 promoted melanoma progression, which was attributed to specific binding to p-α-Pix(S13) and Rac1 to stimulate the downstream MAPK pathway. Thus, kindlin-2 could be a potential therapeutic target for treating melanoma.

Prognostic influence of prevertebral space involvement in nasopharyngeal carcinoma: A retrospective study.

PURPOSE: To evaluate how prevertebral space involvement (PSI) and degree of tumor extension within the space affects prognosis in nasopharyngeal carcinoma (NPC). PARTICIPANTS AND METHODS: Data of patients with newly-diagnosed nonmetastatic NPC (n = 757) were retrospectively analyzed. Patients were separated into groups according to presence or absence of PSI and degree of tumor spread. Overall survival (OS), failure-free survival (FFS), local relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were compared between the groups. RESULTS: Prevalence of PSI, simple prevertebral muscle involvement (PMI), and behind prevertebral muscle involvement (BPMI) were 44.9% (340/757), 22.5% (170/757), and 22.5% (170/757), respectively. OS, FFS, LRFS, and DMFS for patients with and without PSI were 64% vs. 84.8%, 68% vs. 85.6%, 85.8% vs. 94.4%, and 78.5% vs. 92.8%, respectively (all P < 0.001). PSI was an independent predictor of OS, FFS, LRFS, and DMFS. OS, FFS, and DMFS for patients with simple PMI and with BPMI were 72.7% vs. 54.8% (P = 0.002), 75.8% vs. 59.8% (P = 0.003), and 85.5% vs. 71.2% (P = 0.002), respectively. Degree of PSI extension was related to OS, FFS, and DMFS. OS, FFS, LRFS, and DMFS were significantly poorer in patients with PSI in T2-3 stage than in patients without PSI in T3 stage (P < 0.05), but comparable to those in patients with T4 stage (P > 0.05). CONCLUSIONS: PSI predicts poor prognosis in NPC. Survival is poorer in patients with BPMI than in those with simple PMI. NPC with PSI should be classified as T4 stage.

Influence of tumor necrosis on treatment sensitivity and long-term survival in nasopharyngeal carcinoma.

PURPOSE: To assess the impact of tumor necrosis on treatment sensitivity and long-term survival in patients with nasopharyngeal carcinoma (NPC) treated using intensity-modulated radiation therapy (IMRT). PARTICIPANTS AND METHODS: In total, 757 patients with non-metastatic, histologically confirmed NPC were retrospectively examined. All patients were treated using IMRT; 93.7% patients with stage T3-T4/N1-N3 disease also received cisplatin-based chemotherapy. RESULTS: The incidence rates of tumor necrosis in primary tumor, retropharyngeal lymph nodes, neck lymph nodes, and total tumor were 2%, 17.7%, 21.5%, and 31.4%. Overall, 40.8% patients with necrosis of the total tumor achieved complete response (CR) and 54.7% patients without tumor necrosis achieved CR at the end of treatment (χ2 = 12.728, P < 0.001). The estimated 7-year overall survival (OS), failure-free survival (FFS), distant metastasis-free survival (DMFS), and loco-regional relapse-free survival (LRRFS) for patients with tumor necrosis and without tumor necrosis of the total tumor were 68.5% vs. 88.4%, 70.5% vs. 88.1%, 77.6% vs. 90.6%, and 85.9% vs. 91.3%, respectively (all P < 0.001). Multivariate analyses indicated that necrosis of the total tumor was an independent predictor of OS, FFS, DMFS, and LRRFS. The impact of lymph node necrosis on long-term survival was similar to that of necrosis of the total tumor. ROC curves verified that inclusion of lymph node necrosis improved the predictive value of the current N classification criteria (P = 0.006). CONCLUSIONS: Tumor necrosis served as a predictor of treatment sensitivity and poor prognosis for patients with NPC. Lymph node necrosis significantly improved the prognostic value of the current N classification criteria for NPC.