[Show abstract][Hide abstract] ABSTRACT: Simultaneous second primary tumors (SSPT) are not uncommon in patients with oral cavity squamous cell carcinoma (OSCC) living in areas where the habit of betel quid chewing is widespread. We sought to identify the main prognostic factors in OSCC patients with SSPT and incorporate them into a risk stratification scheme.
A total of 1822 consecutive patients with primary OSCC treated between January 1996 and February 2014 were analyzed for the presence of SSPT. The 18-month and 5-year overall survival (OS) rates served as the main outcome measures.
Of the 1822 patients, 77 (4%) were found to have SSPT (i.e, two malignancies identified within one month of each other). The 18-month and 5-year OS rates in patients without SSPT and with SSPT were 82% and 69%, and 72% and 53%, respectively (p = 0.0063). Patients with SSPT were further divided into patients with either esophageal cancer or hepatocellular carcinoma (eso-HCC subgroup, n = 8) and other tumors (NO eso-HCC subgroup, n = 69). After multivariate analysis, neck nodal extracapsular spread (ECS, n = 18) and the presence of eso-HCC were identified as independent adverse prognostic factors. The 18-month OS rates of SSPT patients with both eso-HCC and ECS (n = 5) vs. the remaining patients (n = 72) were 0% and 78%, respectively (p < 0.0001).
OSCC patients with neck nodal ECS and esophageal cancer or hepatocellular carcinoma as SSPT have a dismal short-term prognosis.
PLoS ONE 09/2015; 10(9):e0136918. DOI:10.1371/journal.pone.0136918 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this retrospective study was to investigate the clinical impact of F-FDG PET in patients with advanced lung adenocarcinoma stratified according to the epidermal growth factor receptor (EGFR) mutation status.
A total of 56 patients with advanced lung adenocarcinoma were included in the study. Thirty-one patients (55%) were EGFR mutation-positive, whereas the remaining 25 (45%) participants tested negative for EGFR mutations. All of the patients underwent F-FDG PET/CT for pretreatment planning. The main outcome measure was overall survival (OS) at 24 months. The following F-FDG PET/CT-derived variables were tested for their associations with OS: main tumor SUVmax, main tumor total lesion glycolysis, and target lesions TLG determined per RECIST (Response Evaluation Criteria In Solid Tumors) 1.1 criteria (TLGRECIST). We also investigated the clinical characteristics in relation to OS and EGFR mutation status.
In EGFR mutation-positive patients, neither the clinical characteristics nor F-FDG PET/CT-derived parameters were significantly associated with OS. In contrast, univariate analysis identified male sex, a positive history of smoking, and TLGRECIST greater than or equal to 412 g as adverse prognostic factors for OS in EGFR mutation-negative patients. After adjustment for potential confounders in multivariate analysis, TLGRECIST was the sole independent predictor of OS in this subgroup.
TLG determined per RECIST 1.1 criteria is an independent predictor of OS in EGFR mutation-negative patients with advanced lung adenocarcinoma. Further studies are needed to investigate whether this parameter may be a promising tool for stratifying such patients for risk-adapted therapies.
Clinical nuclear medicine 03/2015; 40(6). DOI:10.1097/RLU.0000000000000774 · 3.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background/aim:
The role of chemoradiotherapy (CRT) in the management of locally advanced pancreatic cancer is controversial. We aimed to explore this issue by retrospectively comparing the efficacy of concurrent CRT with or without induction (CT) versus CT alone in patients with locally advanced pancreatic cancer (LAPC).
Patients and methods:
Between January 2006 and December 2012, 55 patients with biopsy-proven LAPC were treated either with CRT (n=31) or CT alone (n=24) at the authors' Institution. CT before or after CRT were allowed. Radiation therapy was delivered with a median dose of 50.4 Gy in a single fraction of 1.8 Gy and concurrent CT was typically given with gemcitabine at a dose of 400 mg/m2 weekly. The majority of CT was gemcitabine-based (96%). Progression-free survival and overall survival were calculated from the date of diagnosis to the date of progression and to the date of death or last follow-up, respectively.
Patients' characteristics were not significantly different between the CRT group and CT-alone group. Nineteen (61%) patients received scheduled radiation dose of 50.4 Gy. The median cumulative dose of maintenance CT with gemcitabine after CRT was 6,500 mg/m2. The median survival was 14.6 versus 8.1 months (p=0.001) and progression-free survival was 8.7 versus 4.9 months (p<0.001) for the CRT group and CT-alone group, respectively.
Patients with LAPC treated with CRT conferred more favorable survival than those who did not receive CRT. CRT should be considered integrating into the management of LAPC.
Anticancer research 11/2014; 34(11):6755-61. · 1.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Overexpression of heterogeneous nuclear ribonucleoprotein K (hnRNP K), a DNA/RNA binding protein, is associated with metastasis in nasopharyngeal carcinoma (NPC). However, the mechanisms underlying hnRNP K-mediated metastasis is unclear. The aim of the present study was to determine the role of matrix metalloproteinase (MMP) in hnRNP K-mediated metastasis in NPC.
We studied hnRNP K-regulated MMPs by analyzing the expression profiles of MMP family genes in NPC tissues and hnRNP K-knockdown NPC cells using Affymetrix microarray analysis and quantitative RT-PCR. The association of hnRNP K and MMP12 expression in 82 clinically proven NPC cases was determined by immunohistochemical analysis. The hnRNP K-mediated MMP12 regulation was determined by zymography and Western blot, as well as by promoter, DNA pull-down and chromatin immunoprecipitation (ChIP) assays. The functional role of MMP12 in cell migration and invasion was demonstrated by MMP12-knockdown and the treatment of MMP12-specific inhibitor, PF-356231.
MMP12 was overexpressed in NPC tissues, and this high level of expression was significantly correlated with high-level expression of hnRNP K (P = 0.026). The levels of mRNA, protein and enzyme activity of MMP12 were reduced in hnRNP K-knockdown NPC cells. HnRNP K interacting with the region spanning −42 to −33 bp of the transcription start site triggered transcriptional activation of the MMP12 promoter. Furthermore, inhibiting MMP12 by MMP12 knockdown and MMP12-specific inhibitor, PF-356231, significantly reduced the migration and invasion of NPC cells.
Overexpression of MMP12 was significantly correlated with hnRNP K in NPC tissues. HnRNP K can induce MMP12 expression and enzyme activity through activating MMP12 promoter, which promotes cell migration and invasion in NPC cells. In vitro experiments suggest that NPC metastasis with high MMP12 expression may be treated with PF-356231. HnRNP K and MMP12 may be potential therapeutic markers for NPC, but additional validation studies are warranted.
BMC Cancer 05/2014; 14(1):348. DOI:10.1186/1471-2407-14-348 · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective/Hypothesis: The role of tumor volume in T4a laryngeal cancer remains unclear among different treatment modalities. Using tumor volumetry, we investigated the impact of primary tumor volume on this subset of patients. Study Design: Retrospective cohort study of 62 T4a laryngeal cancer patients Methods: From October 2002 to September 2010, 48 patients were treated with definitive chemoradiation therapy (CRT) and 14 patients had undergone total laryngectomy. Tumor volume was calculated and was correlated with the overall survival (OS), progression-free survival (PFS) and local control rate (LCR) data of each treatment group. Results: The 5-year OS, PFS and LCR were significantly lower in the CRT group with tumor volume ≥ 15 cm(3) (22.5% vs. 48.7%, P = 0.009; 32.2% vs. 64.3%, P = 0.003; 45.2% vs. 67.3%, P = 0.039). Multivariate analysis showed that tumor volume was an independent poor prognosticator for OS, PFS and LCR in the CRT group. For tumor volume ≥ 15 cm(3) , total laryngectomy provided a significantly higher 5-year OS and PFS (54.5% vs. 22.5%, P = 0.039; 80.0% vs. 32.2%, P = 0.017) than those treated with definitive CRT. Conclusion: Patients of T4a laryngeal cancer with primary tumor volume ≥ 15 cm(3) had poorer survival outcomes after definitive CRT compared with total laryngectomy. It was also an independent poor prognosticator on LCR, PFS and OS for those receiving definitive CRT. For patients with tumor volume ≥ 15 cm(3) , total laryngectomy provided a better survival outcome than definitive CRT.
The Laryngoscope 05/2014; 124(5). DOI:10.1002/lary.24461 · 2.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study is the first to use genome-wide association study (GWAS) data to evaluate the multidimensional genetic architecture underlying nasopharyngeal cancer. Since analysis of data from GWAS confirms a close and consistent association between elevated risk for nasopharyngeal carcinoma (NPC) and major histocompatibility complex class 1 genes, our goal here was to explore lesser effects of gene-gene interactions. We conducted an exhaustive genome-wide analysis of GWAS data of NPC, revealing two-locus interactions occurring between single nucleotide polymorphisms (SNPs), and identified a number of suggestive interaction loci which were missed by traditional GWAS analyses. Although none of the interaction pairs we identified passed the genome-wide Bonferroni-adjusted threshold for significance, using independent GWAS data from the same population (Stage 2), we selected 66 SNP pairs in 39 clusters with P<0.01. We identified that in several chromosome regions, multiple suggestive interactions group to form a block-like signal, effectively reducing the rate of false discovery. The strongest cluster of interactions involved the CREB5 gene and a SNP rs1607979 on chromosome 17q22 (P = 9.86×10(-11)) which also show trans-expression quantitative loci (eQTL) association in Chinese population. We then detected a complicated cis-interaction pattern around the NPC-associated HLA-B locus, which is immediately adjacent to copy-number variations implicated in male susceptibility for NPC. While it remains to be seen exactly how and to what degree SNP-SNP interactions such as these affect susceptibility for nasopharyngeal cancer, future research on these questions holds great promise for increasing our understanding of this disease's genetic etiology, and possibly also that of other gene-related cancers.
PLoS ONE 12/2013; 8(12):e83034. DOI:10.1371/journal.pone.0083034 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Radioresistance of EBV-associated nasopharyngeal carcinoma (NPC) is associated with poor prognosis for patients with this form of cancer. Here, we found that NPC patients had increased serum levels of leukemia inhibitory factor (LIF) and that higher LIF levels correlated with local tumor recurrence. Furthermore, in vitro studies with NPC cells and in vivo xenograft mouse studies demonstrated that LIF critically contributes to NPC tumor growth and radioresistance. Using these model systems, we found that LIF treatment activated the mTORC1/p70S6K signaling pathway, enhanced tumor growth, inhibited DNA damage responses, and enhanced radioresistance. Treatment with either soluble LIF receptor (sLIFR), a LIF antagonist, or the mTOR inhibitor rapamycin reversed LIF-mediated effects, resulting in growth arrest and increased sensitivity to γ irradiation. Immunohistochemical (IHC) analyses of human NPC biopsies revealed that LIF and LIFR were overexpressed in tumor cells and that LIF expression correlated with the presence of the activated p-p70S6K. Finally, we found that the EBV-encoded protein latent membrane protein 1 (LMP1) enhances LIF production. Together, our findings indicate that LIF promotes NPC tumorigenesis and suggest that serum LIF levels may predict local recurrence and radiosensitivity in NPC patients.
The Journal of clinical investigation 11/2013; 123(12). DOI:10.1172/JCI63428 · 13.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this cohort study was to examine the role of the chemokine (C-X-C motif) ligand 9 (CXCL9) on nasopharyngeal carcinoma (NPC).
Sera from 205 NPC patients and 231 healthy individuals, and 86 NPC tumor samples were enrolled. CXCL9 expression in tissue samples was analyzed by quantitative real-time PCR and immunohistochemistry. CXCL9 serum concentrations were measured by enzyme-linked immunosorbent assay.
CXCL9 expression was significantly higher in tumors than in normal epithelium. CXCL9 serum concentrations were also significantly higher in NPC patients compared to those in healthy individuals (516.8±617.6 vs. 170.7±375.0 pg/mL, P<0.0001). Serum CXCL9 levels were significantly higher in NPC patients with higher tumor stages, nodal stages, and overall stages (P<0.001, P = 0.001, and P<0.001, respectively). We found a statistically significant correlation between the concentrations of CXCL9 and EBV DNA load in the NPC patients (Spearman's correlation analysis; r = 0.473, P<0.001; 95% confidence interval, 0.346-0.582). Moreover, NPC patients with higher CXCL9 levels (>290 pg/mL, median) before treatment had worse prognoses for overall survival and disease-free survival (P = 0.045 and P = 0.008, respectively). Multivariate logistic regression analyses also indicated that higher CXCL9 serum levels were an independent prognostic factor for disease-free survival (P = 0.015).
Our study demonstrated that CXCL9 is associated with tumor burden and aggressiveness of NPC tumors and the serum level of this ligand may be useful as a prognostic indicator.
PLoS ONE 11/2013; 8(11):e80052. DOI:10.1371/journal.pone.0080052 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
This prospective phase II clinical trial evaluated the efficacy and toxicity of cisplatin, oral tegafur-uracil, leucovorin, and mitomycin C in patients with recurrent or metastatic nasopharyngeal carcinoma.
Patients with histologically proven non-keratinizing or undifferentiated nasopharyngeal carcinoma were prospectively enrolled from April 2002 to June 2005. Cisplatin 50 mg/m(2) on day 1, 22 and mitomycin C 6 mg/m(2) on day 1 were administered. Oral tegafur-uracil 300 mg/m(2)/day and oral leucovorin 60 mg/day were given on day 1-14 and day 22-35, respectively. Each cycle was repeated every 6 weeks. Primary and secondary endpoints are response rate and toxic profiles with survivals, respectively.
Twenty-two patients with the median age of 47 (35-69) years were enrolled in the study. Sixteen (72.7%) patients had undifferentiated nasopharyngeal carcinoma. The regimen was well-tolerated by all patients with the exception of one patient (4.6%) who experienced grade IV anorexia, and two patients (9.1%) who had grade IV vomiting. There was no treatment-related death. The overall response rate was 59.1%, including 3 (13.6%) complete remissions. The median duration of response was 15.9 months, the median time to tumor progression was 10.0 months, and the median overall survival was 16.0 months.
This outpatient chemotherapy regimen is acceptably effective and toxic among patients with recurrent or metastatic nasopharyngeal carcinoma.
[Show abstract][Hide abstract] ABSTRACT: Hypofractionated radiotherapy (RT) has been employed to treat hepatocellular carcinoma (HCC). The present study aimed to report the treatment effects, the dose-response associations and the factors that are associated with radiation-induced liver disease (RILD) in a high-dose hypofractionated RT procedure. A total of 40 patients with non-metastatic HCC who underwent RT for local control of irradiated tumors were studied. The treatment technique was that of three-dimensional conformal or intensity-modulated radiation therapy, with a fraction size of 3 Gy and a total dose of 40-66 Gy in 14-23 fractions. The biologically-effective dose (BED) was 52.0-85.8 Gy10 (median, 74.1 Gy10). Tumor regression was observed in 28 patients (70.0%) with a complete response, partial response, stable disease and progressive disease status in 11 (27.5%), 17 (42.5%), five (12.5%) and seven patients (17.5%), respectively. The one-, two- and five-year overall survival (OS) and in-field control (IFC) rates were 60, 40 and 21% and 73, 62 and 56%, respectively. A positive correlation also emerged between the radiation dose and the IFC (P=0.035). Eight of the 40 patients (20%) developed non-classic RILD. A higher Cancer of the Liver Italian Program score was associated with a higher probability of non-classic RILD (P=0.02). The tumor response and IFC rate of HCC following irradiation were significantly dose-dependent. High-dose hypofractionated X-ray RT is a feasible and effective treatment for HCC in patients with good liver function and for those who meet the criteria for a curative attempt.
[Show abstract][Hide abstract] ABSTRACT: Blood coagulation is an extremely complicated and dynamic physiological process. Monitoring of blood coagulation is essential to predict the risk of hemorrhage and thrombosis during cardiac surgical procedures. In this study, a high throughput microfluidic chip has been developed for the investigation of the blood coagulation process under temperature and hematocrit variations. Electrical impedance of the whole blood was continuously recorded by on-chip electrodes in contact with the blood sample during coagulation. Analysis of the impedance change of the blood was conducted to investigate the characteristics of blood coagulation process and the starting time of blood coagulation was defined. The study of blood coagulation time under temperature and hematocrit variations was shown a good agreement with results in the previous clinical reports. The electrical impedance measurement for the definition of blood coagulation process provides a fast and easy measurement technique. The microfluidic chip was shown to be a sensitive and promising device for monitoring blood coagulation process even in a variety of conditions. It is found valuable for the development of point-of-care coagulation testing devices that utilizes whole blood sample in microliter quantity.
PLoS ONE 10/2013; 8(10):e76243. DOI:10.1371/journal.pone.0076243 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Current standard treatment of nasopharyngeal carcinoma (NPC) is either radiotherapy alone or combined chemoradiotherapy. Surgery in the form of nasopharyngectomy is usually only offered when there is evidence of local recurrence or persistent disease. Recurrent NPC (rNPC) can be detected earlier with the utilization of Epstein-Barr virus molecular diagnosis. This may result in early management with salvage surgery and hence improved survival. The facial translocation approach enhanced our ability to access the nasopharynx. Through a multidisciplinary approach with the collaboration of neurosurgeons, the surgical indication of salvage surgery is extended. This allowed improved respectability in locally advanced disease and involved the skull base and intracranial extension with reasonable morbidity and mortality. Endoscopic nasopharyngectomy is a choice for recurrent NPC with central roof or floor lesions with minimal lateral extension. Multivariate analysis indicated that gender, parapharyngeal space involvement, surgical margin, and the modality of adjuvant therapy impact significantly on local control. The impact on survival is indicated by the dura or brain involvement, local recurrence and modality of adjuvant therapy. It is apparent that recurrent NPC patients who underwent surgery had a significantly better survival rate than the re-radiation therapy group.
[Show abstract][Hide abstract] ABSTRACT: Objective:
In this study, we investigated the usefulness and limitations of EBV-DNA follow-up in patients who had treated localized nasopharyngeal carcinoma.
Study subjects comprised 389 patients who had received treatment for localized nasopharyngeal carcinoma in our department. Copy numbers of EBV-DNA in plasma were assessed by real-time quantitative PCR. Patients in whom disease recurrence was suspected underwent image evaluation, esp. PET scan, and tissue proof if it is feasible. Lesions of undermined nature were confirmed by sequential follow-up.
Plasma EBV-DNA was detectable in 60 of 63 (95%) patients with metastatic disease and all had positive PET findings. In addition, of the 45 patients with localized recurrent disease, plasma EBV-DNA was detectable in 23 (51%) patients and positive PET scan results were obtained in 40 (89%) of the patients. Of the 284 patients who were disease free, plasma EBV-DNA was detected in 90 (32%) patients. Of the 19 patients in disease free group who were suspected disease recurrence receiving PET scanning, 7 positive PET images were found including 3 second primary malignancy and 4 non-cancer lesions. Two lymphoma cases with positive EBV-DNA value sequentially attacked before or after their NPC were diagnosed. With the cutoff value of 400copies/ml of EBV-DNA, the positive predict value was 73.5% and the negative predict value was 82.1%. The sensitivity was 0.46 and the specificity was 0.94.
EBV-DNA was a good marker for detecting metastatic failure in treated localized NPC. However, careful interpretation with complements from image examination was needed for locoregional failure and other false positive or false negative situations.