Association of Chemoradiotherapy Regimens and Survival Among Patients With Nasopharyngeal Carcinoma: A Systematic Review and Meta-analysis.

Importance: The role of induction chemotherapy (IC) or adjuvant chemotherapy (AC) in the treatment of locoregionally advanced nasopharyngeal carcinoma (NPC) remains controversial. Objectives: To update meta-analyses on the association of survival outcomes with IC and AC regimens in patients with locoregionally advanced NPC and assess whether the current evidence is conclusive by a trial sequential analysis (TSA) approach. Data Sources: PubMed, Embase, and Web of Science were searched for articles published from inception until June 1, 2019. Study Selection: Randomized clinical trials that assessed the efficacy of radiotherapy with or without chemotherapy among previously untreated patients and patients with nondistant metastatic NPC. Data Extraction and Synthesis: Data were extracted by 2 investigators from each trial independently and synthesized by the 2 investigators. All trial results were combined and analyzed by a fixed- or random-effects model. Main Outcomes and Measures: Overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS). Results: A total of 8036 patients (median age, 46.5 years; 5872 [73.1%] male) from 28 randomized clinical trials were included in the analysis. Pooled analyses revealed that concurrent chemoradiotherapy (CCRT) was significantly associated with improved OS, PFS, DMFS, and LRFS compared with radiotherapy across all subgroups. The TSA confirmed the treatment outcomes of CCRT compared with radiotherapy. The additional IC regimen was associated with an improvement in OS (hazard ratio [HR], 0.84; 95% CI, 0.74-0.95), PFS (HR, 0.73; 95% CI, 0.64-0.84), DMFS (HR, 0.67; 95% CI, 0.59-0.78), and LRFS (HR, 0.74; 95% CI, 0.64-0.85). These findings were consistent in subgroup analyses of multicenter trials with sample sizes greater than 250, years of survival rate of 5 or greater, median follow-up longer than 5 years, or low risk of bias. However, the additional AC regimen was not associated with a survival benefit in OS (HR, 0.98; 95% CI, 0.78-1.23), PFS (HR, 0.86; 95% CI, 0.70-1.07), DMFS (HR, 0.84; 95% CI, 0.64-1.10), or LRFS (HR, 0.80, 95% CI, 0.59-1.09). The TSA provided sound evidence on the additional benefit of IC but not AC. Conclusions and Relevance: These data suggest a significant association of survival outcomes with CCRT in patients with locoregionally advanced NPC. The addition of IC instead of AC could achieve survival benefits. The potential therapeutic gain of AC should be explored in the future.

The up-regulation of IL-6 in DRG and spinal dorsal horn contributes to neuropathic pain following L5 ventral root transection.

Our previous works have shown that pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) plays an important role in neuropathic pain produced by lumber 5 ventral root transection (L5-VRT). In the present work we evaluate the role of interleukin-6 (IL-6), another key inflammatory cytokine, in the L5-VRT model. We found that IL-6 was up-regulated in the ipsilateral L4 and L5 dorsal root ganglian (DRG) neurons and in bilateral lumbar spinal cord following L5-VRT. Double immunofluorescence stainings revealed that in DRGs the increased immunoreactivity (IR) of IL-6 was almost restricted in neuronal cells, while in the spinal dorsal horn IL-6-IR up-regulated in both glial cells (astrocyte and microglia) and neurons. Intrathecal administration of IL-6 neutralizing antibody significantly delayed the induction of mechanical allodynia in bilateral hindpaws after L5-VRT. Furthermore, inhibition of TNF-α synthesis by intraperitoneal thalidomide prevented both mechanical allodynia and the up-regulation of IL-6 in DRGs following L5-VRT. These data suggested that the increased IL-6 in afferent neurons and spinal cord contribute to the development of neuropathic pain following motor fiber injury, and that TNF-α is responsible for the up-regulation of IL-6.

Serotype and genotype diversity of infectious bronchitis viruses isolated during 1985-2008 in Guangxi, China.

The genetic diversity of the hypervariable region I of S1 gene (HVR I) of infectious bronchitis (IB) vaccine strains H120, Ma5 and 4/91 was compared to that of 26 infectious bronchitis virus (IBV) strains isolated from the field in Guangxi province of China during the years 1985-2008, and the field isolates were classified into five major genotypes. Monovalent antisera against three vaccine strains and seven field isolates of different genotypes were prepared by immunizing rabbits with mineral oil adjuvant preparations containing viruses propagated in chicken embryos. Virus neutralization (VN) tests were performed in tracheal organ cultures (TOCs) using these 10 strains with the antisera, and a one-way VN test was then used to compare the relationship of 10 monovalent antisera to the other 19 field isolates. As a result, seven different serotypes were classified based on the results of VN tests with the 26 isolates plus the three vaccine strains. We found that different serotypes were prevalent during different time periods, that more new serotypes have been prevalent in more recent years, and the prevalence of the original dominant serotype has been in constant decline since 2004. In addition, the concordance rate of the 26 field isolates between the S1 genotypes and serotypes was 57.7%.

[Evaluation of antigenic relationship of Guangxi isolates of infectious bronchitis virus].

Monovalent antisera of 3 vaccine strains and 7 representative field isolates were prepared based on the comparison of genetic diversity of the hypervariable region I of S1 gene (HVR I from 3 infectious bronchitis (IB) vaccine strains (H120, Ma5 and 4/91) ,one reference strain M41 and 26 IB field isolates. These 30 strains were classified in 7 different genotypes, respectively. Virus-neutralizing test on tracheal organ cultures (TOC) with chicken embryo were used to evaluate relatedness values of the antigenicity based on the antibody titer, to analyze the antigenic relationships between the isolates and vaccine strains, as well as to determine the serotypes of 26 IB viruses isolated from the field in Guangxi between 1985 and 2008. The results showed 30 strains were classified into 7 distinct serotypes and there were two predominant serotypes within the 26 isolates, serotypes 1 (totally 13 isolates) and serotype 2 (totally 5 isolates), respectively. In addition, there were some differences observed between the results of serotyping and the genotyping (including the S1, N, M and 3'UTR). The results of the study demonstrated that there were different predominant serotypes and multiple serotypes of IBV circulated in Guangxi in recent years, antigenic variation existed between Guangxi field isolates and vaccine strains.