Pan­immune­inflammation value as a novel prognostic biomarker in nasopharyngeal carcinoma.

The pan-immune-inflammation-value (PIV) is a comprehensive biomarker that integrates different peripheral blood cell subsets. The present study aimed to evaluate the prognostic ability of PIV in patients with nasopharyngeal carcinoma (NPC) undergoing chemoradiotherapy. PIV was assessed using the following equation: (Neutrophil count × platelet count × monocyte count)/lymphocyte count. The Kaplan-Meier method and Cox hazards regression models were used for survival analyses. The optimal cut-off values for PIV and systemic immune-inflammation index (SII) were determined using receiver operating characteristic analysis to be 428.0 and 1032.7, respectively. A total of 319 patients were recruited. Patients with a low baseline PIV (≤428.0) accounted for 69.9% (n=223) and patients with a high baseline PIV (>428.0) accounted for 30.1% (n=96). Compared with patients with low PIV, patients with a high PIV had significantly worse 5-year progression-free survival [PFS; 66.8 vs. 77.1%; hazard ratio (HR), 1.97; 95% confidence interval (CI), 1.22-3.23); P=0.005] and 5-year overall survival (OS; 68.7 vs. 86.9%, HR, 2.71; 95% CI, 1.45-5.03; P=0.001). PIV was also a significant independent prognostic indicator for OS (HR, 2.19; 95% CI, 1.16-4.12; P=0.016) and PFS (HR, 1.86; 95% CI, 1.14-3.04; P=0.013) and outperformed the SII in multivariate analysis. In conclusion, the PIV was a powerful predictor of survival outcomes and outperformed the SII in patients with NPC treated with chemoradiotherapy. Prospective validation of the PIV should be performed to better stratify radical treatment of patients with NPC.

Treating radiation­related nasopharyngeal necrosis with endostar in patient with nasopharyngeal carcinoma: A report of two cases and a literature review.

Radiation-related nasopharyngeal necrosis (RRNN) is a rare and often fatal complication in patients with nasopharyngeal carcinoma (NPC). Currently, no standard treatments are recommended for RRNN. The effects of traditional conservative treatments are suboptimal, and surgery for RRNN cannot be performed by inexperienced doctors. In the present study, the use of Endostar in two patients with RRNN was evaluated. Two patients with RRNN were treated at the Department of Oncology, Panyu Central Hospital (Guangzhou, China). Endostar was administrated (15 mg/day from day 1 to day 7, every three weeks) intravenously for four and seven cycles in a male and a female patient, respectively. The effects of Endostar were assessed using magnetic resonance imaging (MRI) and a nasopharyngoscope. The symptoms of RRNN in both patients were relieved after treatment with Endostar. MRI and nasopharyngoscope analysis revealed that necrosis of the nasopharynx was substantially decreased and nasopharyngeal ulcers were healed. Endostar has the potential to be a novel, effective therapy for the treatment of patients with RRNN. However, clinical trials are required to confirm the results of the present study.

Efficiency and toxicity of nab-paclitaxel and camrelizumab in the second or above line treatment of advanced non-small cell lung cancer: a retrospective cohort study.

Background: Paclitaxel-based chemotherapy represented by nanoparticle albumin-bound paclitaxel (nab-ptx) combined with programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors has become the standard model for the 1st treatment of advanced non-small cell lung cancer (NSCLC) with negative driver genes (such as EGFR, ALK, etc.), indicating that nab-ptx and PD-1/PD-L1 inhibitors are synergistic. Considering PD-1/PD-L1 inhibitors alone or chemotherapy single has limited efficiency in the 2nd line or above of NSCLC, so it is of great significance to explore the combination of PD-1/PD-L1 inhibitors and nab-ptx to further improve the therapeutic efficiency in such field. Methods: We retrospectively collected the date of these advanced NSCLC patients who accept the combination treatment of PD-1/PD-L1 inhibitor and nab-ptx in the 2nd or above line. We further analysed baseline clinical characteristics, therapeutic efficacy, treatment-related adverse events (AEs) and followed up survival. The main parameters of the study were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and AEs. Results: A total of 53 patients were enrolled in this study. The preliminary results indicated that the ORR of the combination of camrelizumab and nab-ptx was about 36% in the 2nd or above line of NSCLC, with 19 cases of partial response (PR), 16 of stable disease (SD), and 18 cases of progressive disease (PD); the mean PFS and OS were 5 months and 10 months, respectively. Further subgroup analysis demonstrated that the expression of PD-L1 level and the decrease of regulatory T cell (Treg) correlated with the efficiency. the main adverse reactions were neuropathy, bone marrow suppression, fatigue, and hypothyroidism, most of which were mild and tolerable, indicating such regimen was higher efficiency and lower cytotoxicity for NSCLC. Conclusions: The combination of nab-ptx and camrelizumab shows promising efficiency and lower toxicities for advanced NSCLC in the 2nd or above line treatment. The mechanism of action may be related to depleting Treg ratio; such a regimen may have the potential to become an effective treatment approach for NSCLC. However, due to the limitation of sample size, the real value of this regimen needs to be further confirmed in the future.

EBV-positive large-cell and small-cell neuroendocrine carcinoma of the nasopharynx: A case report and review of the literature.

Neuroendocrine carcinoma (NEC) of the nasopharynx is rare and its clinical and pathologic characteristics have remained to be fully elucidated. The present study reported on a case of Epstein-Barr virus (EBV)-positive NEC of the nasopharynx that exhibited features of large-cell NEC and small-cell NEC, as confirmed by immunohistochemical staining. The patient received three cycles of induction chemotherapy (with docetaxel-cisplatin) that was followed by concurrent chemoradiotherapy (a total of 70 Gy delivered in 33 fractions). Remission of the tumor was achieved and no recurrence or metastasis was detected 6 months after treatment. This is the first report of a patient with EBV-positive large-cell and small-cell NEC of the nasopharynx. The patient achieved good complete remission. Based on the features of this case and a literature review, it was concluded that immunohistochemical staining is important for the differential diagnosis of NEC. Furthermore, there is currently no standard treatment and thus, further clinical information on similar cases is required to optimize treatment outcomes.

Weekly versus triweekly cisplatin-based concurrent chemoradiotherapy for nasopharyngeal carcinoma: a systematic review and pooled analysis.

Background: Weekly and triweekly cisplatin-based concurrent chemoradiotherapy (CCRT) have been used in the treatment of nasopharyngeal carcinoma (NPC). Objective: This study aimed to compare the benefits and risks between the two treatments. Methods: We systematically searched electronic databases for prospective and retrospective clinical studies of NPC patients who received weekly compared with triweekly cisplatin-based CCRT. The primary endpoints comprised overall, failure-free, distant metastasis-free, and locoregional recurrence-free survivals (OS, FFS, DMFS, and LRFS). Secondary endpoints were toxicities. Results: Six studies were included in the systematic review, of which four with 1515 NPC patients were eligible for further pooled analysis. There were no significant differences between weekly and triweekly groups in terms of 5-year OS (odds ratio [OR] 0.95, 95% confidence interval [CI] 0.51-1.79), FFS (OR 1.09, 95% CI 0.67-1.76), DMFS (OR 1.25, 95% CI 0.54-2.92), and LRFS (OR 0.83, 95% CI 0.55-1.25). For grade ≥ 3 toxicities, the weekly group had higher risks of anemia (risk ratio [RR] 2.96, 95% CI 1.12-7.81) and thrombocytopenia (RR 2.75, 95% CI 1.54-4.90), but a lower incidence of vomiting (RR 0.34, 95% CI 0.18-0.63) versus the triweekly group. Conclusion and Relevance: Both weekly and triweekly schedules could be recommended to NPC patients during CCRT. Additionally, hematologic adverse events in weekly strategy and non-hematologic adverse events in triweekly strategy are of higher concern.

Outcomes of Adding Induction Chemotherapy to Concurrent Chemotherapy for Nasopharyngeal Carcinoma Patients with Moderate-Risk in the Intensity-Modulated Radiotherapy Era.

BACKGROUND: The aim of this study was to evaluate the efficacy of induction chemotherapy (IC) in nasopharyngeal carcinoma (NPC) patients with moderate-risk treated with intensity-modulated radiotherapy (IMRT). METHODS: We retrospectively assessed 506 patients with T1-2N1M0 or T3-4N0-1M0 NPC (according to the 2010 UICC/AJCC staging system) who received concurrent chemoradiotherapy (CCRT) with or without IC at a single center in China between 2005 and 2010. Survival outcomes were compared between the IC + CCRT and CCRT groups using the Kaplan-Meier method, Log-rank test and a Cox regression model. RESULTS: Among the 506 patients, CCRT alone resulted in equivalent overall survival (86.8% vs 88.5%, p=0.661), progression-free survival (79.6% vs 79.6%, p=0.756), locoregional relapse-free survival (90.2% vs 87.0%, p=0.364) and distant metastasis-free survival (88.0% vs 89.8%, p=0.407) to IC plus CCRT. In multivariate analysis, IC did not lower the risk of death (HR 0.76, 95% CI 0.46-1.25, p=0.278), progression (HR 0.78, 95% CI 0.51-1.19, p=0.244), locoregional relapse (HR 1.06, 95% CI 0.81-1.42, p=0.651) or distant metastasis (HR 0.66, 95% CI 0.38-1.15, p=0.140) in the entire cohort; similar results were obtained in stratified analysis based on N category (N0 vs N1) and EBV DNA (< vs ≥4000 copies/mL). CONCLUSION: Addition of IC to CCRT does not improve survival outcomes in moderate-risk NPC; the use of IC should be carefully considered in these patients, though additional prospective trials are warranted to confirm the conclusions of this study.

[Effect of electroacupuncture preconditioning of "Neiguan"(PC6) on myocardial LKB1/AMPK/PFK2 pathway in myocardial ischemia rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) preconditioning on the expression of liver protein kinase 1 (LKB1), adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and 6-phosphofructo-2-kinase (PFK2) in cardiomyocytes of rats with acute myocardial ischemia (AMI), so as to explore its mechanisms underlying cardioprotective effect. METHODS: Thirty male Wistar rats were randomly divided into sham-operation, model and EA pretreatment groups (n＝10 rats per group). The AMI model was established by ligation of the left anterior descending branch of coronary artery. Before modeling, EA preconditioning (2 Hz/15 Hz, 1 mA) was applied to bilateral "Neiguan"(PC6) for 30 min, once daily for 14 days. Histopathological changes of myocardium was observed by microscope after H．E. staining. The level of lactate dehydrogenase (LDH) in serum was detected by ELISA. The expression of autophagy-associated proteins and mRNAs as LKB1, AMPKa1, AMPKa2 and PFK2 were detected by Western blot and real-time PCR, respectively. RESULTS: Compared with the sham-operation group, serum LDH content, and expression levels of myocardial AMPKa2 and PFK2 proteins and mRNAs were significantly up-regulated (P<0.01), and those of LKB1 and AMPKa1 proteins and mRNAs were increased in the model group (P<0.05). Following the intervention, serum LDH were apparently down-regulated (P<0.01), and expression levels of myocardial LKB1, AMPKa1 and PFK2 proteins and mRNAs were apparently up-regulated (P<0.01), but that of AMPKa2 protein and mRNA was remarkably down-regulated in the EA group (P<0.01). H．E. staining showed cell swelling, disordered arrangement of myocardial fibers with obvious rupture, interstitial bleeding and inflammatory infiltration, which was relatively milder in the EA preconditioning group. CONCLUSION: EA pretreatment can trigger LKB1/AMPK/PFK2 signaling pathway in AMI rats, which may contribute to its cardioprotective effect against ischemic myocardial injury by activating autophagy of cardiomyocytes.　.

Prognostic impact of family history of cancer in Southern Chinese patients with esophageal squamous cell cancer.

Background: First degree family history of cancer is associated with developing esophageal cancer and sparse data is about the impact on poor survival among established esophageal squamous cell cancer (ESCC) patients. In this study, we investigated the prognoses of patients with ESCC with a family history. Methods: A total of 479 ESCC patients were retrospectively enrolled from a Southern Chinese institution. A positive family history was defined as having malignant cancer among parents and siblings. Kaplan-Meier plots and Cox proportional hazards regressions were applied for overall survival (OS) and progression-free survival (PFS). Results: Among 479 patients, 119 (24.8%) and 68 (14.2%) reported a first-degree family history of cancer and digestive tract cancer, respectively. Compared with patients without a family history of cancer, the adjusted hazard ratios (HR) among those with it were 1.40 (95% CI, 1.08-1.82, p=0.011) for death, 1.36 (95% CI, 1.05-1.76, p=0.018) for progression. Similar results were observed in those with a family history of digestive tract cancer (HR=1.69, 95%CI, 1.24-1.98, p=0.001 for death and HR=1.77, 95%CI, 1.30-2.37, p<0.001 for progression, respectively). Furthermore, there was a trend for increasing risk of overall mortality (p=0.021, p=0.004, respectively), and progression (p=0.022, p=0.001, respectively) with an increasing number of affected family members. Conclusion: A first-degree family history of cancer, especially digestive tract cancer is associated with poor survival for established ESCC patients and plays an important role in prognosis. The patients with a family history of cancer might need a greater intensity of treatment and more frequent follow-up.

Prognostic impact of cigarette smoking on the survival of patients with established esophageal squamous cell carcinoma receiving radiotherapy: A retrospective study from southern China.

Cigarette smoking is associated with the development of esophageal squamous cell carcinoma (ESCC); however, the influence of smoking on survival of patients with ESCC receiving radiotherapy, with or without chemotherapy, has remained elusive. The present study retrospectively analyzed 479 patients with ESCC from southern China who were categorized based on their smoking history (never, previous or current). To consider the cumulative effect of smoking, the number of pack years (PYs) was used as a representative variable. Associations between cigarette smoking and survival were evaluated using the Kaplan-Meier analysis and Cox proportional hazards model. Among the 497 patients, 308 (64.3%) had reported a history of cigarette smoking. The 5-year overall survival for patients void of a smoking history, former smokers and current smokers was 50.9, 27.0 and 34.3%, respectively. The adjusted hazard ratios (HRs) for previous and current smoking vs. no smoking history were 1.57 [95% confidence interval (CI), 1.06-2.32] and 3.01 (95% CI, 1.15-7.86), respectively. Heavy smokers with a high number of PYs had a HR for death of 1.75 (95% CI, 1.28-2.41) compared with light smokers. In the cohort of 407 patients treated with intensity-modulated radiotherapy/three-dimensional conformal radiotherapy, similarly significant results were obtained. In conclusion, cigarette smoking is an independent and poor prognostic factor for patients with ESCC treated with radiotherapy and/or chemotherapy. It is associated with an increased risk of death, and the risk increases with the increase in PYs. This result may help to manage tobacco use among patients with ESCC. The smoking status should be taken into consideration in prospective studies on ESCC. More frequent follow-ups are recommended for those patients with ESCC with a history of smoking.

[Induction chemotherapy with docetaxel plus cisplatin (TP regimen) followed by concurrent chemoradiotherapy with TP regimen versus cisplatin in treating locally advanced nasopharyngeal carcinoma].

BACKGROUND AND OBJECTIVE: Clinical trials on docetaxel plus cisplatin (DDP) (TP regimen) in treating nasopharyngeal carcinoma (NPC) are still uncertain due to limited samples. This study was to compare the short-term efficacy and toxicity of induction chemotherapy with TP regimen followed by concurrent chemoradiotherapy with TP regimen versus DDP in treating locally advanced NPC. METHODS: Fifty-seven patients with stage T3-4N2-3M0 NPC diagnosed pathologically from December 2005 to December 2006 were randomized into TP group (30 patients) and DDP group (27 patients). Both groups received TP regimen as induction chemotherapy with docetaxel (70 mg/m(2)) on Day 1 and DDP (80 mg/m(2)) on Day 2, repeating every 21 days for 2 cycles. For concurrent chemotherapy, TP group were administered docetaxel (60 mg/m(2)) on Day 1 and DDP (80 mg/m(2)) on Day 2; DDP group were administered DDP (80 mg/m(2)) on Day 1. Both schedules were repeated every 21 days for 2 cycles. Linear accelerator was used as radioactive source. Irradiation field was designed with CT-simulation and conventional fractions. RESULTS: The 57 patients received 111 cycles of induction chemotherapy, and 53 of them received 103 cycles of concurrent chemotherapy; four patients ceased induction chemotherapy and three ceased concurrent chemotherapy. All patients completed radiotherapy. The major toxicity of induction chemotherapy was hematologic toxicity; the main toxicities of concurrent chemoradiotherapy were hematologic toxicity and mucositis. The occurrence rates of Grade 3-4 leucopenia and Grade 3-4 neutropenia were significantly higher in TP group than in DDP groups (p <0.05). In concurrent chemoradiotherapy, the application rate of granulocyte colony stimulating factor (G-CSF) was significantly higher in TP group than in DDP group (100% vs. 72.0%, p<0.05). After concurrent chemoradiotherapy, the complete remission (CR) rates of the nasopharynx and regional lymph nodes were 93.3% and 92.9% in TP group, and were 96.3% and 91.3% in DDP group (p>0.05). CONCLUSIONS: The short-term efficacy of induction chemotherapy with TP regimen followed by concurrent chemoradiotherapy with TP regimen on locally advanced NPC is similar to that of TP regimen followed by concurrent chemoradiotherapy with DDP. The toxicity of the former schedule is severer than that of the latter, but it is tolerable with the use of G-CSF. The long-term efficacy of induction chemotherapy with TP regimen followed by concurrent chemoradiotherapy with TP regimen need to be further studied.

[Comparison of efficacy of docetaxel combined cisplatin (TP regimen) and cisplatin combined 5-fluorouracil (PF regimen) on locally advanced nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: Docetaxel and cisplatin (DDP) are effective drugs for head and neck tumors. Stage II-III clinical trial of TP regimen (docetaxel combined DDP) for head and neck tumors has completed. This study was to compare the efficacy and toxicity of TP regimen and PF regimen [DDP combined 5-fluorouracil (5-FU)] in treating nasopharyngeal carcinoma (NPC), to provide a new chemotherapeutic regimen for NPC. METHODS: Twenty NPC patients treated in Cancer Center of Sun Yat-sen University between Oct. 1, 2005 and Mar. 1, 2006 were subjected to study group (TP group). Twenty patients were chosen randomly from the 45 NPC patients treated with PF regimen between May 1, 2004 and Sep. 30, 2005 as control group (PF group). Both groups received concurrent radiotherapy. The efficacy and adverse events of the 2 groups were compared. RESULTS: The mean number of chemotherapy cycles was significantly higher in TP group than in PF group (3.85 cycles vs. 2.75 cycles, P<0.001). After induction chemotherapy, in TP group, 18 achieved partial remission (PR) and 2 had stable disease (SD) for nasopharyngeal lesions, 7 achieved complete remission (CR), 11 achieved PR and 2 had SD for regional lymph nodes; in PF group, 17 achieved PR and 3 had SD for nasopharyngeal lesions, 2 achieved CR, 15 achieved PR and 1 had SD for regional lymph nodes. After concurrent chemoradiotherapy, all in TP group and 18 in PF group achieved CR for nasopharyngeal lesions, and 19 in TP group and 15 in PF group achieved CR for regional lymph nodes. There was no significant difference in efficacy between the 2 groups (P>0.05). The occurrence rates of grade 3-4 neutropenia were significantly higher in TP group than in PF group (40.5% vs. 0% after induction chemotherapy, 40.5% vs. 10.2% after concurrent radiochemotherapy, P<0.05). The occurrence rates of anemia and thrombocytopenia were significantly lower in TP group than in PF group (P<0.05). The uses of antibiotics and parenteral nutritional support in the 2 groups were similar. CONCLUSION: The efficacy of TP regimen on NPC is similar to that of PF regimen, and the adverse events are tolerable, but the long-term outcomes and toxicities need to be further investigated.

[Prognosis and treatment strategies of primary B-cell and NK/T-cell nasopharyngeal non-Hodgkin's lymphoma at early stage].

BACKGROUND & OBJECTIVE: Nasopharynx is a commonly involved site of non-Hodgkin's lymphoma (NHL), but the differences of clinical characteristics, prognosis, and treatment strategy between B-cell and NK/T-cell nasopharyngeal NHL have seldom been reported. This study was to investigate the clinical manifestations and treatment outcomes of primary B-cell and NK/T-cell nasopharyngeal NHL at early stage, and evaluate the prognostic differences, so as to provide evidences for treatment optimization. METHODS: Clinical data of 80 patients with previously untreated nasopharyngeal NHL at early stage, admitted from May 1987 to Nov. 2003, were reviewed. Of the 80 cases, 48 were B-cell original (B group), 32 were NK/T-cell original (T group). Of the 80 patients, 42 received chemoradiotherapy, 31 received chemotherapy alone, and 7 received radiotherapy alone. Most chemotherapy-treated patients received CHOP regimen (cyclophosphamide, vincristine, adriamycin, and prednisone) for 1-10 cycles (median 5 cycles). Radiotherapy was given with high energy photon beams combined with high energy electron beams in conventional fractionation, with the total dose of 30-70 Gy (median 52 Gy). Treatment patterns of the 2 groups were similar, but B group received more chemotherapy cycles than T group did. RESULTS: The 5-year overall survival rate and 5-year progression-free survival rate were significantly higher in B group than in T group (69.5% vs. 35.5%, P=0.003; 53.3% vs. 28.9%, P=0.032). Cox multivariate regression analysis suggested that B-cell phenotype, no B symptoms, and local control were independent favorable predictors of overall survival, while B-cell phenotype and good treatment response were independent favorable predictors of progression-free survival. Univariate stratified analysis with Kaplan-Meier method showed that, for B group, the cumulative 5-year overall survival rate was 68.1% in the 19 patients received chemotherapy alone, 61.7% in the 25 patients received chemoradiotherapy, and 100% in the 4 patients received radiotherapy alone (P=0.311); for T group, the cumulative 5-year overall survival rate was 0% in the 12 patients received chemotherapy alone, 44.1% in the 17 patients received chemoradiotherapy, and 33.3% in the 3 patients received radiotherapy alone (only 1 patient survived for 60 months)(P=0.020). CONCLUSIONS: Among the patients with primary nasopharyngeal NHL at early stage, those with B-cell phenotype may have better prognosis as compared with those with NK/T-cell phenotype. The patients with NK/T-cell phenotype often suffered from B symptoms, with poor response to chemotherapy. Radiotherapy or chemoradiotherapy should be more emphasized in this group of patients.

[Clinical characters of aged nasopharyngeal carcinoma patients].

BACKGROUND & OBJECTIVE: The influence of age on treatment outcome and survival of nasopharyngeal carcinoma (NPC) patients has seldom been reported. This study was to explore the clinical characters of aged NPC patients. METHODS: A total of 754 patients with histopathologically proven NPC from Jan. 1, 2000 to May 1, 2002 were divided to adult group (<60 years old, 647 patients) and aged group (> or =60 years old, 107 patients). The difference of disease characters, treatment patterns, and other complications between these two groups were analyzed. The influence of age on survival was analyzed with COX regression model. RESULTS: There was no difference between the two groups in disease characters, radiation dose, and interval time. However, the proportion of the patients received chemotherapy was significantly larger in adult group than in aged group (254/647 vs. 29/107, P=0.016), while the occurrence of complications was more frequent in aged group than in adult group (40/107 vs. 19/647, P<0.001). The 3-year tumor-specific survival rate was significantly lower in aged group than in adult group (72.90% vs. 82.95%, P=0.010). COX multivariable analysis showed that age and '92 Fuzhou N stage were independent prognostic factors, and the odds ratio (OR) of age was 1.604 (95% CI: 0.929-2.768) (P=0.026). CONCLUSIONS: Aged NPC patients have worse 3-year survival than adult patients, which may be related to the high risk of chemotherapy and less possibility to tolerate enough doses and cycles. But age itself is still a poor prognostic factor when excluding the influence of chemotherapy.