Prognostic Nomogram for Patients with Nasopharyngeal Carcinoma after Intensity-Modulated Radiotherapy

This study was aimed to define possible predictors of overall survival in nasopharyngeal carcinoma (NPC). Patients were treated with intensity-modulated radiation therapy (IMRT), to establish an effective prognostic nomogram that could provide individualized predictions of treatment outcome in this setting. We reviewed the records of 533 patients with non-metastatic NPC who underwent IMRT with or without concurrent chemotherapy at the Department of Radiation Oncology of Sun Yat-Sen University from 2002 to 2009; none of these patients received induction or adjuvant chemotherapy. These data sets were used to construct a nomogram based on Cox regression. Nomogram performance was determined via a concordance index (C-index) and a calibration curve which was compared with the TNM staging system for NPC. The results were validated in an external cohort of 442 patients from the Department of Radiation Oncology of Wenzhou Medical College who were treated during the same period. Results showed that the greatest influence on survival were primary gross tumor volume, age, tumor stage and nodal stage (2002 Union for International Cancer Control [UICC] staging system), which were selected into the nomogram. The C-index of the nomogram for predicting survival was 0.748 (95%CI, 0.704–0.785), which was statistically higher than that of TNM staging system (0.684, P<0.001). The calibration curve exhibited agreement between nomogram-predicted and the actual observed probabilities for overall survival. In the validation cohort, the nomogram discrimination was superior to the TNM staging system (C-index: 0.768 vs 0.721; P = 0.026). In conclusion, the nomogram proposed in this study resulted in more-accurate prognostic prediction for patients with NPC after IMRT and compared favorably to the TNM staging system; this individualized information will aid in patient counseling and may be used for de-escalation trials in the future.     

Concurrent Chemotherapy for T4 Classification Nasopharyngeal Carcinoma in the Era of Intensity-Modulated Radiotherapy

Objective

To evaluate concurrent chemotherapy for T4 classification nasopharyngeal carcinoma (NPC) treated by intensity-modulated radiotherapy (IMRT).

Methods

From July 2004 to June 2011, 180 non-metastatic T4 classification NPC patients were retrospectively analyzed. Of these patients, 117 patients were treated by concurrent chemoradiotherapy (CCRT) using IMRT and 63 cases were treated by IMRT alone.

Results

The median follow-up time was 58.97 months (range, 2.79–114.92) months. For all the patients, the 1, 3 and 5-year local failure-free survival (LFFS) rates were 97.7%, 89.2% and 85.9%, regional failure free survival (RFFS) rates were 98.9%, 94.4% and 94.4%, distant failure-free survival (DFFS) rates were 89.7%, 79.9% and 76.2%, and overall survival (OS) rates were 92.7%, 78.9% and 65.3%, respectively. No statistically significant difference was observed in LFFS, RFFS, DFFS and OS between the CCRT group and the IMRT alone group. No statistically significant difference was observed in acute toxicity except leukopenia (p = 0.000) during IMRT between the CCRT group and the IMRT alone group.

Conclusion

IMRT alone for T4 classification NPC achieved similar treatment outcomes in terms of disease local control and overall survival as compared to concurrent chemotherapy plus IMRT. However, this is a retrospective study with a limited number of patients, such results need further investigation in a prospective randomized clinical trial.     

Effect of Prolonged Radiotherapy Treatment Time on Survival Outcomes after Intensity-Modulated Radiation Therapy in Nasopharyngeal Carcinoma

Purpose

To estimate the influence of prolonged radiation treatment time (RTT) on survival outcomes in nasopharyngeal carcinoma after continuous intensity-modulated radiation therapy.

Methods and Materials

Retrospectively review 321 patients with NPC treated between October 2009 and December 2010 and all of them underwent simultaneous accelerated intensity-modulated radiation therapy. The fractionated dose was 2–2.47 Gy/F (median 2.27 Gy), and the total dose for nasopharyngeal region was 64–74 Gy/ 28–33 fractions. The association of prolonged RTT and treatment interruption with PFS, LRFS and DFFS were assessed by univariate analysis and multivariate analysis. Survival analyses were carried out using Kaplan–Meier methodology and the log-rank test was used to assess the difference. The Cox regression proportional hazard model was used for multivariate analyses and evaluating the prognostic parameters for PFS, LRFS and DFFS.

Results

Univariate analysis revealed no significant associations between prolonged RTT and PFS, LRFS, DFFS when dichotomized using various cut-off values (all P>0.05). In multivariate analysis, RTT (range, 36–63 days) as a continuous variable, had no influence on any survival outcome as well (P>0.05). T and N classification were independent prognostic factors for PFS, LRFS and DFFS (all P<0.05, except T classification for LRFS, P = 0.057). Age was an independent prognostic factor for PFS (hazard ratio [HR], 1.033; P = 0.008) and DFFS (HR, 1.032; P = 0.043).

Conclusion

We conclude that no such association between survival outcomes and radiation treatment duration (range: 36–63 days) can be found in the present retrospective study, however, we have to remind that prolongation in treatment should be limited in clinical application and interruptions caused by any reason should be minimized as much as possible.     

Prognostic Value of Cavernous Sinus Invasion in Patients with Nasopharyngeal Carcinoma Treated with Intensity-Modulated Radiotherapy

Purpose

To investigate the prognostic value of cavernoussinus invasion (CSI) in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT).

Patients and Methods

Retrospective review of data from 1,087 patients with biopsy-proven, non-metastatic NPC. All patients were diagnosed using magnetic resonance imaging (MRI) scans and received IMRT as the primary treatment.

Results

The incidence of cavernoussinus invasion in this cohort was 12.1%. In univariate analysis, 5-year overall survival (OS) (70.6% vs. 88.5%, P < 0.001) and distant metastasis-free survival (DMFS) (71.4% vs. 87.7%, P < 0.001), but not locoregional relapse-free survival (LRFS) (93.9% vs. 93.7%, P = 0.341), were significantly different between patients with and without cavernoussinus invasion. In the T4 subgroup, the 5-year OS, DMFS, and LRFS of patients with and without cavernoussinus extension were 70.6% vs. 81.9% (P = 0.011), 71.4% vs. 84.1% (P = 0.011), and 91.2% vs. 89.7% (P = 0.501), respectively. In multivariate analysis, cavernoussinus invasion was an independent prognostic factor for poorer OS (HR = 1.782; P = 0.013) and DMFS (HR = 1.771; P = 0.016), but not LRFS (HR = 0.632; P = 0.294). In patients with lymph node metastasis, the DMFS rates of patients with and without cavernoussinus invasion were significantly different (P < 0.001). Preliminaryanalysis indicated that neoadjuvant chemotherapy led to better DMFS and OS in patients with cavernoussinus invasion than concurrent chemotherapy or radiotherapy alone; however, the differences were not significant.

Conclusions

In the IMRT era, cavernoussinus invasion remains a prognostic factor for poor DMFS and OS in NPC, even in patients with T4 disease.     

Comparing Long-Term Survival and Late Toxicities of Different Sequential Chemotherapy Regimens with Intensity-Modulated Radiotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma

OBJECTIVES: To evaluate long-term survival outcomes and late toxicities of the sequential chemotherapy regimen of gemcitabine plus cisplatin (GP) compared with cisplatin plus fluorouracil (PF) in locoregionally advanced nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: From June 2005 to December 2014, 235 patients with pathologically confirmed NPC treated with intensity-modulated radiotherapy (IMRT) combined with GP (n = 144) or PF (n = 91) were retrospectively analyzed. RESULTS: After a median follow-up of 61 months, the 5-year overall survival (OS) rates were not significantly different between GP and PF groups (84.2% vs. 74.4%, P = .208). The 5-year local control rates were significantly improved in the GP group (96.3% vs 84.1%, P = .010). Subgroup analysis demonstrated that the increased benefits of GP were from T1-3 classification (99% vs. 87.8%, P = .013) and stage III patients (100% vs. 82.4%, P = .017). The most common late adverse events were xerostomia and hearing impairment. The incidences of grade 3 to 4 late toxicities were relatively low and were similar in the two groups. CONCLUSIONS: Sequential chemotherapy combined with IMRT achieved satisfactory survival outcomes in locoregionally advanced NPC with acceptable late toxicities. The GP regimen significantly improved local control compared with PF regimen. Further phase III randomized clinical studies were warranted.     

Radiation-Induced Temporal Lobe Injury for Nasopharyngeal Carcinoma: A Comparison of Intensity-Modulated Radiotherapy and Conventional Two-Dimensional Radiotherapy

Background

To compare the radiation-induced temporal lobe injury (TLI) in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) or two-dimensional conventional radiotherapy (2D-CRT).

Patients and Methods

1276 cases of NPC treated with IMRT or 2D-CRT were retrospectively reviewed. A diagnosis of TLI was made on follow-up magnetic resonance imaging (MRI).

Results

The crude incidence of TLI was 7.5% and 10.8% (P = 0.048), and the actuarial 5-year incidence was 16% and 34.9% (P<0.001) for the IMRT and 2D-CRT groups, respectively. Multivariate analysis revealed both T stage (P<0.001) and radiation technique (P<0.001) as independent predictors. Patients with T1, T2 and T3 disease had a significantly higher risk when treated with 2D-CRT (P = 0.005, 0.016, <0.001, respectively). This trend was not evident for T4 patients (P = 0.680). The 2D-CRT group had a longer latency for the development of TLI (P<0.001). Those with T4 disease had a shorter median time to TLI (P = 0.006, 0.042, <0.001 when compared with T1, T2 and T3, respectively).

Conclusions

IMRT is superior to 2DRT for the management of T1-T3 NPC in terms of sparing the temporal lobe. The high incidence of TLI in T4 disease needs to be addressed.     

Prognostic Factors and Survival in Patients with Radiation-Related Second Malignant Neoplasms Following Radiotherapy for Nasopharyngeal Carcinoma

Purpose

To analyze the clinicopathological characteristics, treatment modalities, and potential prognostic factors of radiation-related second malignant neoplasms (SMNs) in a large group of nasopharyngeal carcinoma (NPC) cases.

Methods and Materials

Institutional electronic medical records of 39,118 patients with NPC treated by definitive radiotherapy between February 1964 and December 2003 were reviewed. A total of 247 patients with confirmed SMN attributable to radiotherapy were included.

Results

Median latency between radiotherapy for NPC and the diagnosis of SMN was 9.5 years (range, 3.1–36.8 years). Squamous cell carcinoma was the most common histologic type, followed by fibrosarcoma and adenocarcinoma. Median progression-free survival and overall survival (OS) of the 235 patients who underwent treatment were 17.3 months and 28.5 months, respectively. The 5-year OS rates were 42.9%, 23.7%, and 0% for the surgery, radiotherapy, and chemotherapy groups, respectively. The independent prognostic factors associated with survival were sex, histologic type, and treatment modality in both the early stage subgroup and the advanced stage subgroup of SMN.

Conclusions

Sex, histologic type, and treatment modality were the significant prognostic factors for SMN. Complete resection offers the best chance for long-term survival. In select patients with locally advanced and unresectable SMN, reirradiation should be strongly considered as a curative option.     

The Impact of Baseline Serum C-Reactive Protein and C-Reactive Protein Kinetics on the Prognosis of Metastatic Nasopharyngeal Carcinoma Patients Treated with Palliative Chemotherapy

Background

The aim of this study was to determine whether baseline C-reactive protein (CRP) levels and CRP kinetics predict the overall survival in metastatic nasopharyngeal carcinoma (mNPC) patients.

Methods

A total of 116 mNPC patients from January 2006 to July 2011 were retrospectively reviewed. Serum CRP level was measured at baseline and thereafter at the start of each palliative chemotherapy cycle for all patients.

Results

Patients with higher values of baseline CRP (≥ 3.4 mg/L) had significantly worse survival than those with lower baseline CRP values (< 3.4 mg/L). Patients were divided into four groups according to baseline CRP and CRP kinetics: (1) patients whose CRP < 3.4 mg/L and never elevated during treatment; (2) patients whose CRP < 3.4 mg/L and elevated at least one time during treatment; (3) patients whose CRP ≥ 3.4 mg/L and normalized at least one time during treatment; and (4) patients whose CRP ≥ 3.4 mg/L and never normalized during treatment. The patients were further assigned to non-elevated, elevated, normalized, and non-normalized CRP groups. Overall survival rates were significantly different among the four groups, with three-year survival rates of 68%, 41%, 33%, and 0.03% for non-elevated, elevated, normalized, and non-normalized CRP groups respectively. When compared with the non-elevated group, hazard ratios of death were 1.69, 2.57, and 10.34 in the normalized, elevated, and non-normalized groups (P < 0.001).

Conclusions

Baseline CRP and CRP kinetics may be useful to predict the prognosis of metastatic NPC patients treated with palliative chemotherapy and facilitate individualized treatment. A prospective study to validate this prognostic model is still needed however.     

Comparison of Long-Term Survival and Toxicity of Cisplatin Delivered Weekly versus Every Three Weeks Concurrently with Intensity-Modulated Radiotherapy in Nasopharyngeal Carcinoma

Background

We aimed to compare the long-term survival outcomes and acute toxicity of cisplatin administered weekly versus every three weeks concurrently with intensity-modulated radiotherapy (IMRT) in patients with nasopharyngeal carcinoma (NPC).

Methods

This was a retrospective review of 154 patients with histologically proven, non-disseminated NPC who were treated using IMRT between January 2003 and December 2007. Seventy-three patients (47.4%) received 5–7 weeks of 30–40 mg/m² cisplatin weekly; 81 patients (52.6%) received two or three cycles of 80 mg/m² cisplatin every three weeks. IMRT was delivered at 68 Gy/30 fractions to the nasopharyngeal gross target volume and 60–66 Gy to the involved neck area.

Results

The clinical characteristics and treatment factors of the two groups were well-balanced. The median follow-up was 74 months (range, 6–123 months), and the 5-year overall survival, disease-free survival, locoregional relapse-free survival, and distant metastasis–free survival rates were 85.2% vs. 78.9% (P = 0.318), 71.6% vs. 71.0% (P = 0.847), 93.5% vs. 92.6% (P = 0.904), and 80.9% vs. 80.1% (P = 0.925) for the group treated every three weeks and weekly, respectively. Subgroup analyses indicated no significant differences in the survival rates of the two groups among patients with early- or advanced-stage disease. The incidence of acute toxicities was similar between groups.

Conclusion

IMRT with concurrent cisplatin administered weekly or every three weeks leads to similar long-term survival outcomes and acute toxicity in NPC regardless of whether patients have early- or advanced-stage disease.     

Prognostic Significance of Tumor Volume in Locally Recurrent Nasopharyngeal Carcinoma Treated with Salvage Intensity-Modulated Radiotherapy

Introduction

To evaluate the prognostic value of gross tumor volume (TV) in patients with locally recurrent, nonmetastatic nasopharyngeal carcinoma.

Methods

Between 2001 and 2012, 291 consecutive patients with locally recurrent, nonmetastatic nasopharyngeal carcinoma underwent salvage IMRT were retrospectively reviewed. The correlations between TV and recurrent T classification were analyzed. Survival analyses were performed. Receiver operating characteristic (ROC) curves were calculated to identify cut-off point of TV. The Akaike information criterion and Harrell’s concordance index (c-index) were utilized to test the prognostic value.

Results

The median TV significantly increased with advancing recurrent T classification (P<0.001). The 5-year overall survival rate was 33.2% for the entire cohort. On multivariate analysis, TV was an independent negative prognostic factor for distant metastasis-free survival (hazard ratio =1.013, P =0.003), overall survival (hazard ratio = 1.015, P<0.001) and toxicity-related death (hazard ratio = 1.014, P<0.001). The 5-year overall survival rates were 63.1% and 20.8% for patients with a TV < 22 cm³ and TV ≥22 cm³, respectively (P < 0.001). In patient with TV <22 cm³, locoregional failure is the leading cause of death. In patients with TV≥22 cm³, distant metastasis rate is higher and occurred within short term after local recurrence; meanwhile, radiation-induced injuries became more common and led to half of deaths in this group. The Akaike information criterion and c-index analyses indicated that the predictive ability of recurrent T classification improved when combined with TV.

Conclusions

Our data suggests TV is a significant prognostic factor for predicting the distant metastasis, overall survival and toxicity-related death of patients with locally recurrent, nonmetastatic nasopharyngeal carcinoma after salvage IMRT. TV should be considered when designing personalized salvage treatments for these patients. For patients with bulky local recurrent tumor, radiation may need to be de-emphasized in favor of systemic treatment or best supportive care.     

Elevated Levels of Oxidized Low-Density Lipoprotein Correlate Positively with C-Reactive Protein in Patients with Acute Coronary Syndrome

The relationship between oxidized low-density lipoprotein (Ox-LDL) and C-reactive protein (CRP) in patients with acute coronary syndrome (ACS) is unknown. We, therefore, measured serum levels of Ox-LDL and high-sensitivity (hs)-CRP in 90 ACS patients, 45 stable angina pectoris (SAP) patients, and 66 healthy controls using sandwich ELISA. ACS patients were subdivided into: (1) acute myocardial infarction (AMI; n = 45); (2) unstable angina pectoris (UAP; n = 45) groups. In AMI patients, Ox-LDL (177.5 mmol/l) and hs-CRP (25.40 mg/l) levels were significantly higher (P < 0.01) than in UAP (Ox-LDL:107.5 mmol/l, hs-CRP:10.7 mg/l) and SAP (Ox-LDL:82.3 mmol/l, hs-CRP:2.10 mg/l) patients as well as controls (Ox-LDL:41.4 mmol/l, hs-CRP:1.76 mg/l). Ox-LDL/hs-CRP levels in UAP patients were significantly higher (P < 0.01) than in SAP patients and controls. Importantly, a positive correlation was found between Ox-LDL and CRP (r = 0.622; P < 0.01) levels. Serum levels of total, HDL, and LDL cholesterol did not differ among these patient groups. In conclusion, our data show that Ox-LDL and hs-CRP levels correlate positively in ACS patients, supporting the hypothesis that Ox-LDL and CRP may play a direct role in promoting the inflammatory component of atherosclerosis in these individuals. We suggest that Ox-LDL/CRP elevated levels may serve as markers of the severity of the disease in evaluation and management of ACS patients.     

ERCC1 Cys8092Ala and XRCC1 Arg399Gln Polymorphisms Predict Progression-Free Survival after Curative Radiotherapy for Nasopharyngeal Carcinoma

Background

Single nucleotide polymorphisms (SNPs) in DNA repair genes can alter gene expression and activity and affect response to cancer treatment and, correspondingly, survival. The present study was designed to evaluate the utility of the XRCC1 Arg399Gln and ERCC1 Cys8092Ala SNPs, measured in pretreatment biopsy samples, as predictors of response to radiotherapy in patients with non-metastatic nasopharyngeal carcinoma (NPC).

Materials and methods

The study included 75 consecutive patients with stage II-IVA-B NPC. XRCC1 Arg399Glu and ERCC1 Cys8092Ala SNPs were identified from paraffin-embedded biopsy specimens via Sanger sequencing. Expression of p53 and pAkt protein was analyzed by immunohistochemical staining. Potential relationships between genetic polymorphisms and progression-free survival (PFS) were analyzed by using a Cox proportional hazards model, the Kaplan-Meier method, and the log-rank test.

Results

Multivariate analysis showed that carriers of the ERCC1 8092 Ala/Ala genotype [hazard ratio (HR) 1.882; 95% confidence interval (CI) 1.031–3.438; P = 0.039] and heavy smokers (≥20 pack-years) carrying the XRCC1 Arg/Arg genotype (HR 2.019; 95% CI 1.010–4.036; P = 0.047) had significantly lower PFS rates. Moreover, combined positive expression of p53 and pAkt led to significantly increased PFS in subgroups carrying the XRCC1 Gln allele (HR 7.057; 95% CI 2.073–24.021; P = 0.002) or the ERCC1 Cys allele (HR 2.568; 95% CI 1.056–6.248; P = 0.038).

Conclusions

The ERCC1 Cys8092Ala polymorphism is an independent predictor of response to radiotherapy for NPC, and the XRCC1 Arg399Glu mutation combined with smoking status seems to predict PFS as well. Our results further suggest a possible correlation between these genetic polymorphisms and p53 protein status on survival.     

Prognoses and Long-Term Outcomes of Nasopharyngeal Carcinoma in Han and Uyghur Patients Treated with Intensity-Modulated Radiotherapy in the Xinjiang Autonomous Region of China

Objectives

The objective of this study was to investigate the long-term outcomes and prognostic factors for nasopharyngeal carcinoma (NPC) in Han and Uyghur patients treated with intensity-modulated radiotherapy (IMRT) in the Xinjiang region of China.

Materials and Methods

One hundred twenty-one Han and 60 Uyghur patients with newly diagnosed NPC without distant metastasis received IMRT at the Affiliated Tumor Hospital of Xinjiang Medical University between 2005 and 2008. The Kaplan-Meier method was used to estimate survival rates, and the log-rank test was used to evaluate differences in survival.

Results

Comparing Han and Uyghur patients, the 5-year overall survival (OS), disease-free survival (DFS), local control (LC), regional control (RC), and distant metastasis-free survival (DMFS) rates were 81.9% vs 77.6% (P = 0.297), 72.1% vs 65.6% (P = 0.493), 88.3% vs 86.5% (P = 0.759), 95.0% vs 94.6% (P = 0.929), and 79.1% vs 75.2% (P = 0.613), respectively. Multivariate Cox proportional hazards regression identified the following independent prognostic factors in Han patients: N stage (P = 0.007) and age (P = 0.028) for OS, and age (P = 0.028) for DFS. OS differed significantly between Han and Uyghur patients >60 years old group (P = 0.036). Among Uyghur patients, the independent prognostic factors were age for OS (P = 0.033), as well as N stage (P = 0.037) and age (P = 0.021) for DFS. Additionally, Uyghur patients were less likely to experience mucositis and dermatitis than Han patients.

Conclusion

Han and Uyghur patients with NPC had statistically significant differences in age, smoking history, and N staging. There was no significant difference in overall treatment outcomes with IMRT between these 2 ethnic populations in Xinjiang, China.     

Factors Predict Prolonged Wait Time and Longer Duration of Radiotherapy in Patients with Nasopharyngeal Carcinoma: A Multilevel Analysis

Purpose

Radiotherapy with or without chemotherapy is the primary treatment for patients with nasopharyngeal carcinoma (NPC). It wastes time from diagnosis to treatment. Treatment time of radiotherapy generally takes at least seven weeks. The current study aimed to evaluate factors associated with prolonged wait time and longer duration of radiotherapy in NPC patients.

Methods and Materials

From Taiwan''s National Health Insurance research database, we identified 3,605 NPC patients treated with radiotherapy between 2008 and 2011. Wait time was calculated from the date of diagnosis to the start of radiotherapy. The impact of each variable on wait time and duration of radiotherapy was examined by multilevel analysis using a random-intercept model.

Results

The mean wait time and duration of radiotherapy were 1.78±3.33 and 9.72±7.27 weeks, respectively. Multilevel analysis revealed prolonged wait time in patients aged 45–65 years, those receiving radiotherapy alone, those with more comorbidities, those with low SES, and those living in eastern Taiwan. A prolonged duration of radiotherapy was associated with receipt of concurrent chemoradiotherapy, more comorbidities, and moderate SES.

Conclusions

Understanding the factors associated with longer wait times and duration of radiotherapy in patients with NPC may help healthcare providers better assist both these patients and potentially those with other head-and-neck cancers.     

鼻咽癌的放射治疗技术探究

目的:通过比较鼻咽癌放射治疗的不同技术方法,了解其优势及不同点,以期找到更有效并切合实际的技术方法,提高鼻咽癌的放疗技术水平。方法:常规外照射技术;等中心整体挡铅技术;三维适形放射治疗技术。结果:三种技术方法各具优缺点,结论:三维适形放射治疗技术最具优势,但设备和技术要求高;常规外照射技术经济实用,技术稳定性较差;等中心整体挡铅技术质量稳定。     

Combination of High-Sensitivity C-Reactive Protein and Homocysteine Predicts the Post-Stroke Depression in Patients with Ischemic Stroke

In this study, we examined the changes in high-sensitivity C-reactive protein (Hs-CRP) and homocysteine (HCY) levels, two of the risk factors, during the acute period of ischemic stroke (IS) and evaluated the relationship between these two factors and long-term post-stroke depression (PSD). In this study, 259 patients with IS had finished the follow-up and were included. Based on the symptoms, diagnoses of depression were made in accordance with DSM-IV criteria for depression at 1 year after stroke. The influence of Hs-CRP/CHY levels on PSD was performed by binary logistic regression analysis and receiver operating characteristic curves (ROC). Totally, 94 out of the 259 patients were diagnosed as PSD (36.3%; 95% CI 30.4–42.1%). In multivariate logistic regression analysis, the third and fourth quartiles of Hs-CRP or HCY were significantly associated with PSD during the observation period compared to the first quartile group (P < 0.05). In addition, patients with depression were older and more frequently were female, living with offspring, widowhood, higher initial stroke severity, and BMI. HCY improved the ability of Hs-CRP [0.72 (95% CI 0.66–0.79)] to diagnose PSD (AUC of the combined model 0.76; 95% CI 0.69–0.82; P = 0.021). The patient group with higher levels of both Hs-CRP and HCY (> median) had an OR of 6.05 (95 % CI 3.13–10.15; P < 0.001) for PSD compared with patients with lower levels of both factors (< median). The data suggests that elevated serum levels of Hs-CRP and HCY were associated with the risk of developing PSD 1 year after the stroke onset, and those two factors combined to add prognostic information in the early evaluation of PSD.     

Pre-Treatment Levels of C-Reactive Protein and Squamous Cell Carcinoma Antigen for Predicting the Aggressiveness of Pharyngolaryngeal Carcinoma

The levels of squamous cell carcinoma antigen (SCC-Ag) and C-reactive protein (CRP) can be used to predict tumor invasion, lymph node metastasis, staging and survival in patients with oral cavity cancer. The present study analyzed the relationship between pre-treatment levels of SCC-Ag and CRP in relation to clinicopathological factors in patients with pharyngolaryngeal cancer (PLC) and determined whether elevated levels of CRP and SCC-Ag were associated with tumor metabolic activity via [18F] fluorodeoxyglucose positron emission tomography (FDG-PET). We retrospectively recruited one hundred and six PLC patients between June 2008 and December 2011. All patients received computed tomography (CT)/magnetic resonance imaging (MRI) and FDG-PET staging analyses, and the serum levels of SCC-Ag and CRP in these patients were measured prior to treatment. A SCC-Ag level ≥2.0 ng/ml and a CRP level ≥5.0 mg/L were significantly associated with clinical stage (P<0.001), clinical tumor status (P<0.001), and clinical nodal status (P<0.001). The elevation of both SCC-Ag and CRP levels was correlated with the standardized uptake value (SUV) max of the tumor (≥8.6 mg/L) and lymph nodes (≥5.7 ng/ml) (P = 0.019). The present study demonstrated that the presence of high levels of both pre-treatment SCC-Ag and CRP acts as a predictor of clinical stage, clinical tumor status, and clinical nodal status in patients with PLC. Moreover, elevated levels of SCC-Ag and CRP were associated with a high metabolic rate as well as the proliferative activity measured according to the SUVmax of the tumor and lymph nodes. Therefore, elevated levels of these two factors have the potential to serve as biomarkers for the prediction of tumor aggressiveness in cases of PLC.     

Predictors of the Extent of Carotid Atherosclerosis in Patients Treated with Radiotherapy for Nasopharyngeal Carcinoma

Objective

To determine the predictors of the extent of carotid atherosclerosis in patients treated with radiotherapy (RT) for nasopharyngeal carcinoma (NPC).

Methods

The present study investigated 129 post-RT NPC patients. Carotid atherosclerotic parameters, such as carotid intima-media thickness, carotid arterial stiffness and carotid plaque burden (plaque score, the presence of plaque and ≥50% stenosis) were assessed using ultrasonography. The association between carotid atherosclerotic parameters and nine potential predictors, including age, gender, post-RT duration, radiation dose, chemotherapy, diabetes mellitus, hypertension, hypercholesterolemia, and smoking, were determined using multiple regression. The cutoff values of age, post-RT duration and number of cardiovascular risk factors for the presence of carotid plaque or ≥50% carotid stenosis were analyzed using receiver operating characteristic (ROC) curve analysis. Multiple testing was corrected using Benjamini-Hochberg false discovery rate.

Results

Age, post-RT duration and number of cardiovascular risk factors were significantly associated with carotid plaque burden (corrected P value, P_cor<0.05). Age of 44.5 years (sensitivity = 99.2% and specificity = 50%, P_cor<0.01) and post-RT duration of 8.5 years (sensitivity = 75.7% and specificity = 64.3%, P_cor<0.001) were the cutoff values for detecting carotid plaque, while post-RT duration of 13.5 years (sensitivity = 66.7% and specificity = 71.6%, P_cor<0.001) and 1.5 cardiovascular risk factors (sensitivity = 40.7% and specificity = 84.3%, P_cor<0.05) were the cutoff values for screening ≥50% carotid stenosis.

Conclusions

Age, post-RT duration and number of cardiovascular risk factors are significant predictors of carotid atherosclerosis in post-RT NPC patients. Post-RT NPC patients, who are at least 45 years old, with post-RT duration of 9 years or above, and/or have ≥2 cardiovascular risk factors, are more susceptible to carotid atherosclerosis.     

Elevated C-Reactive Protein Levels and Enhanced High Frequency Vasomotion in Patients with Ischemic Heart Disease during Brachial Flow-Mediated Dilation

Purpose

The physiological role of vasomotion, rhythmic oscillations in vascular tone or diameter, and its underlying mechanisms are unknown. We investigated the characteristics of brachial artery vasomotion in patients with ischemic heart disease (IHD).

Methods

We performed a retrospective study of 37 patients with IHD. Endothelial function was assessed using flow-mediated dilation (FMD), and power spectral analysis of brachial artery diameter oscillations during FMD was performed. Frequency-domain components were calculated by integrating the power spectrums in three frequency bands (in ms²) using the MemCalc (GMS, Tokyo, Japan): very-low frequency (VLF), 0.003–0.04 Hz; low frequency (LF), 0.04–0.15 Hz; and high frequency (HF), 0.15–0.4 Hz. Total spectral power (TP) was calculated as the sum of all frequency bands, and each spectral component was normalized against TP.

Results

Data revealed that HF/TP closely correlated with FMD (r = −0.33, p = 0.04), whereas VLF/TP and LF/TP did not. We also explored the relationship between elevated C-reactive protein (CRP) levels and vasomotion. HF/TP was significantly increased in subjects with high CRP levels (CRP;>0.08 mg/dL) compared with subjects with low CRP levels (0.052±0.026 versus 0.035±0.022, p<0.05). The HF/TP value closely correlated with CRP (r = 0.24, p = 0.04), whereas the value of FMD did not (r = 0.023, p = 0.84). In addition, elevated CRP levels significantly increased the value of HF/TP after adjustment for FMD and blood pressure (β = 0.33, p<0.05).

Conclusion

The HF component of brachial artery diameter oscillation during FMD measurement correlated well with FMD and increased in the presence of elevated CRP levels in subjects with IHD.