Locoregional radiotherapy improves survival outcomes in de novo metastatic nasopharyngeal carcinoma treated with chemoimmunotherapy.

BACKGROUND: We aimed to investigate the efficacy of locoregional radiotherapy (LRRT) in patients with de novo metastatic nasopharyngeal carcinoma (dmNPC) receiving chemotherapy combined with anti-programmed cell death receptor-1 monoclonal antibodies (anti-PD-1 mAbs) as first-line treatment and identify optimal candidates for LRRT. MATERIALS AND METHODS: We enrolled patients with dmNPC receiving platinum-based palliative chemotherapy and anti-PD-1 mAbs followed or not followed by LRRT from four centers. The endpoints were progression-free survival (PFS), objective response rate (ORR), and overall survival (OS). We used the inverse probability of treatment weighting (IPTW) to balance the baseline characteristics of the LRRT and non-LRRT groups to minimize selection bias before comparative analyses. Multivariate analyses were carried out using the Cox proportional hazards model. RESULTS: We included 163 patients with dmNPC (median follow-up: 22 months). The median PFS was 20 months, and the ORR was 92.0%; the median OS was not achieved. After IPTW adjustments, patients who received LRRT had a significant survival benefit over those not receiving LRRT (median PFS: 28 versus 15 months, P < 0.001). The Epstein-Barr virus DNA (EBV DNA) level after four to six cycles of anti-PD-1 mAbs [weighted hazard ratio (HR): 2.19, 95% confidence interval (CI) 1.22-3.92, P = 0.008] and LRRT (weighted HR: 0.58, 95% CI 0.34-0.99, P = 0.04) were independent prognostic factors. Patients with undetectable EBV DNA levels after four to six cycles of anti-PD-1 mAbs (early EBV DNA clearance) benefitted from LRRT (HR: 0.41, 95% CI 0.22-0.79, P = 0.008), whereas those with detectable levels did not (HR: 1.30, 95% CI 0.59-2.87, P = 0.51). CONCLUSIONS: Palliative chemotherapy combined with anti-PD-1 mAbs followed by LRRT was associated with improved PFS in patients with dmNPC, especially for patients with early EBV DNA clearance.

[Clinical trials on intrathecal pemetrexed treated leptomeningeal metastases from solid tumors].

Objective: To investigate the feasibility, safety and efficacy of intrathecal pemetrexed (IP) treated for patients with leptomeningeal metastases (LM) from solid tumors. Methods: Forty-seven patients receiving pemetrexed intrathecal chemotherapy in the First Hospital of Jilin University from 2017 to 2018 were selected. The study of pemetrexed intrathecal chemotherapy adopted the classical dose-climbing model and included 13 patients with meningeal metastasis of non-small cell lung cancer who had relapsed and refractory after multiple previous treatments including intrathecal chemotherapy. Based on the dose climbing study, 34 patients with meningeal metastasis of solid tumor who did not receive intrathecal chemotherapy were enrolled in a clinical study using pemetrexed as the first-line intrathecal chemotherapy combined with radiotherapy. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for influencing factor analysis. Results: The dose climbing study showed that the maximum tolerated dose of pemetrexed intrathecal chemotherapy was 10 mg per single dose, and the recommended dosing regimen was 10 mg once or twice a week. The incidence of adverse reactions was 10 cases, including hematological adverse reactions (7 cases), transaminase elevation (2 cases), nerve root reactions (5 cases), fatigue and weight loss (1 case). The incidence of serious adverse reactions was 4, including grade 4-5 poor hematology (2 cases), grade 4 nerve root irritation (2 cases), and grade 4 elevated aminotransferase (1 case). In the dose climbing study, 4 patients were effectively treated and 7 were disease controlled. The survival time was ranged from 0.3 to 14.0 months and a median survival time was 3.8 months. The clinical study of pemetrexed intrathecal chemotherapy combined with radiotherapy showed that the treatment mode of 10 mg pemetrexed intrathecal chemotherapy once a week combined with synchronous involved area radiotherapy 40 Gy/4 weeks had a high safety and reactivity. The incidence of major adverse reactions was 52.9% (18/34), including hematologic adverse reactions (13 cases), transaminase elevation (10 cases), and nerve root reactions (4 cases). In study 2, the response rate was 67.6% (23/34), the disease control rate was 73.5% (25/34), the overall survival time was ranged from 0.3 to 16.6 months, the median survival time was 5.5 months, and the 1-year survival rate was 21.6%. Clinical response, improvement of neurological dysfunction, completion of concurrent therapy and subsequent systemic therapy were associated with the overall survival (all P<0.05). Conclusions: Pemetrexed is suitable for the intrathecal chemotherapy with a high safety and efficacy. The recommended administration regimen was IP at 10 mg on the schedule of once or twice per week. Hematological toxicity is the main factor affecting the implementation of IP. Vitamin supplement can effectively control the occurrence of hematological toxicity.

[Characteristics and clinical significance of pulmonary function test and KL-6 in ASSD-ILD and IPF].

Objective: To study the characteristics and clinical significance of pulmonary function test and kerbs von den lungen 6 (KL-6) in anti-synthetase syndrome related interstitial lung disease (ASSD-ILD) and idiopathic pulmonary fibrosis (IPF). Methods: The clinical data of 43 patients with ASSD-ILD (ASSD-ILD group) from May 2015 to May 2017 were collected retrospectively, including 12 males and 31 females, and 34 patients with IPF (IPF group) treated in the First Affiliated Hospital of Zhengzhou University during the same period, including 28 males and 6 females, were also included. The basic information, and the value of pulmonary function test [pulmonary function parameters included the forced vital capacity expressed as percent predicted (FVC%pred), the forced expiratory volume in 1 second expressed as percent predicted (FEV(1)%pred), the ratio of FVC to FEV(1) (FVC/FEV(1)), the peak expiratory flow expressed as percent predicted (PEF%pred), the forced expiratory flow at 25%, 50%, 75% of FVC as percent predicted (FEF(25)%pred, FEF(50)%pred, and FEF(75)%pred), the maximum mid-expiratory flow as percent predicted (MMEF% pred), and the diffusing capacity for carbon monoxide as percent predicted (DLCO% pred)], and serum KL-6 level in ASSD-ILD and IPF were compared. Results: The FEV(1)%pred, FEF(50)%pred, FEF(75)%pred, and MMEF%pred values in ASSD-ILD group were significantly lower than those in IPF group (all P<0.05), while the FVC% pred, FVC/FEV(1), PEF% pred, FEF(25)%pred, and DLCO% pred values in ASSD-ILD group had no significant difference compared with IPF group (all P>0.05). There was no significant difference in serum KL-6 level between ASSD-ILD group and IPF group [(1 169±911) vs (1 210±908) U/ml, t=0.62, P=0.463]. Follow-up analysis showed that the serum KL-6 level of ASSD-ILD patients who died within two years was significantly higher than that of survivors [(2 060±1 168) vs (1 042±858) U/ml, t=2.93, P=0.041]. The serum KL-6 level of patients who died within two years of IPF patients was also significantly higher than that of patients who survived [(1 767±865) vs (1 089±894) U/ml, t=2.53, P=0.026]. The serum KL-6 level in ASSD-ILD group was negatively correlated with FVC%pred (r=-0.43, P=0.004), FEV(1)%pred (r=-0.39, P=0.010) and DLCO% pred (r=-0.41, P=0.006). There was no correlation between serum KL-6 level and pulmonary function test indexes in IPF group (all P>0.05). Conclusions: There is difference in pulmonary function test between ASSD-ILD patients and IPF patients. High serum KL-6 level will be predictive of poor prognosis.

[Diagnostic value of HBP, PCT combined with APACHE â ¡ score respectively in ventilator-associated pneumonia].

Objective: To evaluate the diagnostic value of the heparin-binding protein (HBP), procalcitonin (PCT) and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score in ventilator-associated pneµmonia (VAP). Methods: A total of 160 patients who required tracheotomy or intubation and assisted breathing with invasive mechanical ventilator from the First Affiliated Hospital of Zhengzhou University from January 2015 to January 2017 was included in this prospective study,and divided into VAP group and no-VAP group based on if VAP happened or not; the VAP group was further divided into deterioration group and improvement group based on the curative effect after anti-infective treatment for 1 week. A total of 40 community acquired pneumonia (CAP) patients and 30 healthy volunteers were also included as control groups. The levels of HBP and PCT in blood of the subjects were tested with enzyme-linked immuno sorbent assay (ELISA) and chemiluminescence immunoassay (ECLIA) respectively, APACHE Ⅱ score was utilized to assess the severity of illness. The difference of HBP, PCT levels and APACHE Ⅱ score among the groups were analyzed. Receiver operating characteristic(ROC) curve was utilized to analyze the diagnostic value of HBP, PCT, APACHE Ⅱ score in VAP. Results: A total of 230 subjects participated in this study, including 68 VAP patients, 92 non-VAP patients, 40 CAP patients and 30 healthy volunteers. Before administration of mechanical ventilation, there were no statistically significant differences in HBP, PCT and APACHE Ⅱ score between VAP group and non-VAP group (all P>0.05). The levels of HBP,PCT and APACHE Ⅱ score were (41.4±21.3) µg/L,(0.355±0.254) µg/L,(13.4±2.5) respectively when the VAP was diagnosed,which were higher than those within the first 12 h of mechanical ventilation (7.3±2.7) µg/L, (0.080±0.038) µg/L, (8.4±2.0), all P<0.001). The HBP, PCT and APACHE Ⅱ score had no significant difference between within the first 12 h of mechanical ventilation and after mechanical ventilation in non-VAP group (all P>0.05). The levels of HBP was positively correlated with PCT and APACHE Ⅱ score (r=0.82, 0.68, all P<0.001). In deterioration group,the HBP,PCT and APACHE Ⅱ score after 1 week of anti-infective treatment were higher than those when the VAP was diagnosed (all P<0.001). No matter it is when the VAP was diagnosed or after anti-infective treatment for 1 week,the levels of HBP, PCT and APACHE Ⅱ score in deterioration group were higher than those in the improvement group (all P<0.001). The area under curve (AUC) of HBP+APACHE Ⅱ score, PCT+APACHE Ⅱ score for VAP diagnosis was 0.98, 0.95 respectively. The sensitivity of HBP+APACHE Ⅱ score in the diagnosis of VAP was lower than PCT+APACHE Ⅱ score (94.1% vs 95.6%),and the specificity was higher (92.4% vs 82.6%). Conclusion: The diagnostic value of HBP+APACHE Ⅱ score for early VAP is superior to PCT+APACHE Ⅱ score.

[Predictive value of Wells Score, Revised Geneva Score combined with D-dimer for Pulmonary Embolism in patients with acute exacerbation of chronic obstructive pulmonary disease].

Objective: To evaluate the predictive value of Wells score, revised Geneva score combined with D-dimer for the risk of pulmonary embolism in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: In this study, 234 AECOPD patients underwent CT pulmonary angiography from March 1, 2013 to December 31, 2015 in the First Affiliated Hospital of Zhengzhou University. The basic data of the patients were collected and the patients were classified into AECOPD combined with pulmonary embolism group(pulmonary embolism group) and AECOPD group according to CT pulmonary angiography results. All patients were scored by Wells score and revised Geneva score. The receiver operating characteristic (ROC) curves were generated and the Z test was applied to evaluate the predictive value by comparing the area under the ROC curves (AUC). Results: Totally 32(13.7%) patients had pulmonary embolism out of the 234 AECOPD patients. The AUC by Wells score, revised Geneva score, D-dimer, Wells score + D-dimer, revised Geneva score + D-dimer were 0.869 (95% CI: 0.789-0.949), 0.710 (95% CI: 0.588-0.832), 0.866 (95% CI: 0.790-0.941), 0.926 (95% CI: 0.874-0.977), 0.855 (95% CI: 0.751-0.959). The AUC of Wells score and D-dimer were significantly greater than that of revised Geneva score (Z=2.14, 2.12, both P<0.05); the AUC of Wells score + D-dimer was significantly greater than revised Geneva score + D-dimer (Z=2.73, P<0.05). Conclusion: The predictive value of Wells score + D-dimer for pulmonary embolism in AECOPD patients is higher than revised Geneva score + D-dimer.

Increased expression of CXCR5 and CXCL13 in mice with experimental autoimmune myocarditis.

OBJECTIVE: Myocarditis is an inflammatory heart muscle disease associated with cardiac dysfunction, and autoimmunity is considered to play an important role in the pathogenesis of myocarditis. CXCL13 and its receptor CXCR5 have been reported to be associated with many diseases including some cancers and inflammatory diseases, but so far there has been no report on CXCR5/CXCL13 expression in myocarditis. MATERIALS AND METHODS: With a mouse experimental autoimmune myocarditis (EAM) model, it was found that the mRNA and protein expression of both CXCR5 and CXCL13 were increased in myocardial tissue in the EAM mice. This revealed certain connection between CXCR5/CXCL13 with autoimmune myocarditis, so CXCR5 and CXCL13 may be used as a biomarker for autoimmune myocarditis diagnosis. RESULTS: The results also demonstrated increased expression of pro-inflammatory cytokines IL-1ß, IL-6, IL-17 and TNF-α in the serum of myocardial tissue in the EAM mice. These pro-inflammatory cytokines may be important targets for developing new drugs in treating myocarditis. CONCLUSIONS: The current study established an association between CXCR5/CXCL13, autoimmune myocarditis and pro-inflammatory cytokines, and provided sound basis for further studies on mechanism and treatment of autoimmune myocarditis.