Chun-Ta Liao

Chang Gung Memorial Hospital, T’ai-pei, Taipei, Taiwan

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Publications (184)702.49 Total impact

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    ABSTRACT: Ultra-deep targeted sequencing (UDT-Seq) has advanced our knowledge on the incidence and functional significance of somatic mutations. However, the utility of UDT-Seq in detecting copy number alterations (CNAs) remains unclear. With the goal of improving molecular prognostication and identifying new therapeutic targets, we designed this study to assess whether UDT-Seq may be useful for detecting CNA in oral cavity squamous cell carcinoma (OSCC). We sequenced a panel of clinically actionable cancer mutations in 310 formalin-fixed paraffin-embedded OSCC specimens. A linear model was developed to overcome uneven coverage across target regions and multiple samples. The 5-year rates of secondary primary tumors, local recurrence, neck recurrence, distant metastases, and survival served as the outcome measures. We confirmed the prognostic significance of the CNA signatures in an independent sample of 105 primary OSCC specimens. The CNA burden across 10 targeted genes was found to predict prognosis in two independent cohorts. FGFR1 and PIK3CAamplifications were associated with prognosis independent of clinical risk factors. Genes exhibiting CNA were clustered in the proteoglycan metabolism, the FOXO signaling, and the PI3K-AKT signaling pathways, for which targeted drugs are already available or currently under development. UDT-Seq is clinically useful to identify CNA, which significantly improve the prognostic information provided by traditional clinicopathological risk factors in OSCC patients.
    Oncotarget 06/2015; · 6.63 Impact Factor
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    ABSTRACT: Complications arising from anastomotic failure may occur after pharyngoesophageal reconstruction. In this report we present results of pharyngoesophageal reconstruction with free thigh flaps using a refined design and inset strategy in a series of patients. From May 2011 to December 2012, pharyngoesophageal oncologic defects were reconstructed in 12 men using thigh flaps. Flaps were designed to exceed defect circumference to allow draping of the excess over injury-prone vessels (so-called delta-inset). Patients were 39- to 68-years-old (mean, 51.8-years-old) at the time of surgery. BMI ranged from 17 to 28 kg/m(2) (average, 21.5 kg/m(2) ). The sites of defects were the hypopharynx in 11 cases and the pharynx in 1 case. Ten anterolateral thigh (ALT) flaps and 2 anteromedial thigh (AMT) flaps were used. All patients underwent radiation therapy. The average flap size was 22 × 9 cm (range: 16-26 × 7-11 cm(2) ). There were no partial or total flap losses, and no donor site complications. Follow-up was 19.3 months (range: 2.4-21.6 months) including 8 patients (75%) who succumbed to disease in the follow-up period. Oral intake was achieved in all patients. Recipient site complications occurred in 50% of cases and included fistula (2 cases), fistula and stricture (2 cases), stricture (1 case), and lymphocele (1 case). Four patients required revision for fistula. A refined thigh flap design and inset method in pharyngoesophageal reconstruction may circumvent complications arising from toxic drainage and vascular injury. However, there are insufficient data to make meaningful comparisons to alternative methods. © 2015 Wiley Periodicals, Inc. Microsurgery, 2015. © 2015 Wiley Periodicals, Inc.
    Microsurgery 06/2015; DOI:10.1002/micr.22432 · 2.42 Impact Factor
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    ABSTRACT: : It is not uncommon that after using a fibular flap for lower gum cancer reconstruction, nonunion, chronic osteomyelitis, or fibular bone exposure occurs, which requires a composite bone and soft tissue reconstruction. Radial forearm osteocutaneous flap possesses the risk of stress fracture. Ulnar forearm osteocutaneous flap can be another option for small bone defect reconstruction. Six patients who had undergone fibular flap for mandible reconstructions and sustained either bone exposure (3 patients), chronic osteomyelitis (1 patient), malocclusion (1 patient), or osteoradionecrosis (1 patient) underwent ulnar forearm osteocutaneous flap with 3-cm ulnar bone for touch-up procedure. The distal radioulnar joints were fused with a screw. Six ulnar forearm osteocutaneous flap dissections were also performed on 4 fresh frozen cadavers to clarify the anatomic distribution of the distal ulnar artery. All 6 ulnar forearm osteocutaneous flaps survived with one re-exploration for venous occlusion. All presented bone union. Comparable to the clinical dissection, the cadaveric distal ulnar artery demonstrates a periosteal branch that runs between the proper ulnar nerve and dorsal sensory nerve. This periosteal branch comes out of an ulnar artery approximately 3 cm proximal to the wrist joint. Ulnar forearm osteocutaneous flap can provide a secondary flap of wide skin paddle and small segment bone for specific mandibular defect after a fibular flap transfer.
    Annals of plastic surgery 05/2015; 74 Suppl 2:S152-7. DOI:10.1097/SAP.0000000000000467 · 1.46 Impact Factor
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    ABSTRACT: Patients with advanced oral squamous cell carcinoma (OSCC) have heterogeneous outcomes that limit the implementation of tailored treatment options. Genetic markers for improved prognostic stratification are eagerly awaited. Herein, next-generation sequencing (NGS) was performed in 345 formalin-fixed paraffin-embedded (FFPE) samples obtained from advanced OSCC patients. Genetic mutations on the hotspot regions of 45 cancer-related genes were detected using an ultra-deep (>1000×) sequencing approach. Kaplan-Meier plots and Cox regression analyses were used to investigate the associations between the mutation status and disease-free survival (DFS). We identified 1269 non-synonymous mutations in 276 OSCC samples. TP53, PIK3CA, CDKN2A, HRAS and BRAF were the most frequently mutated genes. Mutations in 14 genes were found to predict DFS. A mutation-based signature affecting ten genes (HRAS, BRAF, FGFR3, SMAD4, KIT, PTEN, NOTCH1, AKT1, CTNNB1, and PTPN11) was devised to predict DFS. Two different resampling methods were used to validate the prognostic value of the identified gene signature. Multivariate analysis demonstrated that presence of a mutated gene signature was an independent predictor of poorer DFS (P = 0.005). Genetic variants identified by NGS technology in FFPE samples are clinically useful to predict prognosis in advanced OSCC patients.
    Oncotarget 04/2015; · 6.63 Impact Factor
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    ABSTRACT: Head and neck cancer (HNC) is a prevalent cancer worldwide; however, clinically useful tumor markers for HNC have not been identified. Here, we aimed to identify secretory proteins from the tumor microenvironment as candidate circulating tumor markers. Samples derived from seven pairs of tumor interstitial fluid (TIF) and normal interstitial fluid (NIF) samples from patients with HNC were analyzed. The proteomes were determined by gel-based-mass-spectrometry proteomic methods. The most up-regulated protein, fascin was confirmed in the cancer tissues and cell culture supernatant by immunoblotting and immunohistochemistry assays. Serum fascin was determined in 40 HNC and 40 normal individuals by ELISA. After proteomics analysis, 189 peptides were identified, corresponding to 75 proteins. Of the 21 proteins which were identified more than twice, five up-regulated proteins identified most frequently including fascin. The most elevated fascin was over-expressed in cancer tissues and cell culture supernatant. Serum fascin was significantly up-regulated in the cancer patients (p<0.001) and correlated with pathological lymph node metastasis (p=0.022). To assess the diagnostic efficacy, serum levels of fascin and another potential biomarker SCCA were determined. Fascin showed a high predictable value with an area under the curve (AUC) of 0.808 (95% CI 0.723-0.901) in the receiver operator curve (ROC), compared to 0.501 (95% CI 0.378-0.634) for SCCA. We have identified 75 potential circulating tumor markers associated with HNC, including fascin. Serum fascin could discriminate cancer patients from healthy individuals; thus, it may serve as a circulating biomarker for HNC.
    Clinical Chemistry and Laboratory Medicine 03/2015; DOI:10.1515/cclm-2014-1016 · 2.96 Impact Factor
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    ABSTRACT: CYFRA 21-1 (cytokeratin 19 fragment) and C-reactive proteins (CRP) were separately reported to be associated with prognosis of head and neck squamous cell carcinoma. The combined roles of CYFRA 21-1 and CRP levels were rarely investigated in oral squamous cell carcinoma (OSCC). The purpose of the present study was to analyze the relationship between preoperative levels of both CYFRA 21-1 and CRP, with clinicopathological factors and prognosis in OSCC patients. A retrospective study was performed on 130 OSCC patients between December 2010 and June 2013. Their serum CYFRA 21-1 and CRP levels were measured preoperatively. CYFRA 21-1 level of ≥3.3 ng/mL and CRP level of ≥5.0 mg/L were significantly associated with pathological tumor status (P < 0.001), tumor depth (>10 vs. ≤10 mm, P = 0.001), bone invasion (P = 0.001), skin invasion (P = 0.006), pathologic nodal metastasis (P = 0.012), and disease-free survival (P = 0.009). Higher CYPFRA 21-1 and CRP levels were also associated with higher risks of distant metastasis (log-rank test, P = 0.013, (HR [95 % CI]) 1.692 [1.097-2.414]). Preoperative CYFRA 21-1 and CRP levels are probable candidates as biomarkers for risk stratification in OSCC.
    World Journal of Surgical Oncology 01/2015; 13(1):253. DOI:10.1186/s12957-015-0656-9 · 1.20 Impact Factor
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    ABSTRACT: The clinical usefulness of pretreatment imaging techniques for predicting neck control in patients with oropharyngeal or hypopharyngeal squamous cell carcinoma (OHSCC) treated with chemoradiation remains unclear. In this prospective study, we investigated the role of pretreatment dynamic contrast-enhanced perfusion MR imaging (DCE-PWI), diffusion-weighted MR imaging (DWI), and [18F]fluorodeoxyglucose-positron emission tomography (18F-FDG PET)/CT derived imaging markers for the prediction of neck control in OHSCC patients treated with chemoradiation. Patients with untreated OHSCC scheduled for chemoradiation between August, 2010 and July, 2012 were eligible for the study. Clinical variables and the following imaging parameters of metastatic neck lymph nodes were examined in relation to neck control: transfer constant, volume of blood plasma, and volume of extracellular extravascular space (Ve) on DCE-PWI; apparent diffusion coefficient (ADC) on DWI; maximum standardized uptake value, metabolic tumor volume, and total lesion glycolysis on 18F-FDG PET/CT. There were 69 patients (37 with oropharynx SCC and 32 with hypopharynx SCC) with successful pretreatment DCE-PWI and DWI available for analysis. After a median follow-up of 31 months, 25 (36.2%) participants had neck failure. Multivariate analysis identified hemoglobin level <14.3 g/dL (P = 0.019), Ve <0.23 (P = 0.040), and ADC >1.14×10-3 mm2/s (P = 0.003) as independent prognostic factors for 3-year neck control. A prognostic scoring system was formulated by summing up the three significant predictors of neck control. Patients with scores of 2-3 had significantly poorer neck control and overall survival rates than patients with scores of 0-1. We conclude that hemoglobin levels, Ve, and ADC are independent pretreatment prognostic factors for neck control in OHSCC treated with chemoradiation. Their combination may identify a subgroup of patients at high risk of developing neck failure.
    PLoS ONE 12/2014; 9(12):e115933. DOI:10.1371/journal.pone.0115933 · 3.23 Impact Factor
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    ABSTRACT: The aim of this single-center study was to investigate whether performing an additional PET/CT scan before adjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) can meaningfully improve disease-free (DFS) and disease-specific (DSS) 2-year survival rates. A total of 674 patients with oral cavity squamous cell carcinoma (OSCC) who received adjuvant therapy after radical surgery were included. Of them, 152 subjects were initially scheduled to receive an additional pre-RT/CCRT PET/CT scan within one week of starting adjuvant therapy. However, 16 patients were excluded due to either medical problems or refusal. Therefore, 136 subjects underwent a pre-RT/CCRT PET/CT scan (PET group), whereas 522 did not (NO PET group). All of the participants were followed-up for at least two years or censored at the last follow-up. The impact of pre-RT/CCRT PET/CT imaging was examined using Kaplan-Meier curves and Cox proportional hazard models. Two-year DFS (80% vs. 70%, P = 0.033) and DSS (84% vs. 75%, P = 0.010) rates were significantly higher in the PET than in the NO PET group. In the PET group, both DFS and DSS were higher in subjects with negative findings than in those without (88% vs. 22%, 91% vs. 36%, both P < 0.001). A prognostic scoring system based on the presence of the two independent risk factors in PET group (extracapsular spread and lymphatic invasion) predicted both DFS (P = 0.001, P < 0.001) and DSS (P = 0.001, P < 0.001). Nineteen patients (14%) had their treatment modified by pre-RT/CCRT PET/CT findings. Of them, 15 were treated with curative intent due to the presence of locoregional disease, whereas four received palliative care due to distant metastases. Seven of these patients are currently alive without disease. An additional pre-RT/CCRT PET/CT scan improves both DFS and DSS in patients with advanced OSCC. Copyright © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
    Journal of Nuclear Medicine 12/2014; 56(1). DOI:10.2967/jnumed.114.145300 · 5.56 Impact Factor
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    ABSTRACT: Purpose The question as to whether the regional textural features extracted from PET images predict prognosis in oropharyngeal squamous cell carcinoma (OPSCC) remains open. In this study, we investigated the prognostic impact of regional heterogeneity in patients with T3/T4 OPSCC. Methods We retrospectively reviewed the records of 88 patients with T3 or T4 OPSCC who had completed primary therapy. Progression-free survival (PFS) and disease-specific survival (DSS) were the main outcome measures. In an exploratory analysis, a standardized uptake value of 2.5 (SUV 2.5) was taken as the cut-off value for the detection of tumour boundaries. A fixed threshold at 42 % of the maximum SUV (SUVmax 42 %) and an adaptive threshold method were then used for validation. Regional textural features were extracted from pretreatment 18F-FDG PET/CT images using the grey-level run length encoding method and grey-level size zone matrix. The prognostic significance of PET textural features was examined using receiver operating characteristic (ROC) curves and Cox regression analysis. Results Zone-size nonuniformity (ZSNU) was identified as an independent predictor of PFS and DSS. Its prognostic impact was confirmed using both the SUVmax 42 % and the adaptive threshold segmentation methods. Based on (1) total lesion glycolysis, (2) uniformity (a local scale texture parameter), and (3) ZSNU, we devised a prognostic stratification system that allowed the identification of four distinct risk groups. The model combining the three prognostic parameters showed a higher predictive value than each variable alone. Conclusion ZSNU is an independent predictor of outcome in patients with advanced T-stage OPSCC, and may improve their prognostic stratification.
    European journal of nuclear medicine and molecular imaging 10/2014; 42(3). DOI:10.1007/s00259-014-2933-1 · 5.22 Impact Factor
  • Cancer Research 10/2014; 74(19 Supplement):4146-4146. DOI:10.1158/1538-7445.AM2014-4146 · 9.28 Impact Factor
  • Cancer Research 10/2014; 74(19 Supplement):3412-3412. DOI:10.1158/1538-7445.AM2014-3412 · 9.28 Impact Factor
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    ABSTRACT: Background Human papillomaviruses (HPV) seem to be related to distant metastasis (DM) in advanced oral cavity squamous cell carcinoma (OSCC) patients. Objectives This study aimed to investigate whether high-risk HPV viral load may predict DM among OSCC patients and stratify patients for risk-adapted treatment. Study design: Viral loads of E7 oncogenes for HPV 16/18 were measured by quantitative PCR tests in paraffin-embedded lesional specimens from 312 OSCC of which the HPV genotypes had been determined previously. Multivariable Cox regression analysis was used to identify the independent prognostic factors for 5-year DM and C statistics were further computed. Results By multivariable analysis, high HPV 16 E7 viral load (≥15.0 copies/genome); high HPV 18 E7 viral load (≥15.0 copies/genome); pathological N2 status (pN2); tumor depth ≥11 mm; extracapsular spread (ECS); and level IV/V metastases were independent risk factors for DM. We further identified three prognostic groups. In the high-risk group (level IV/V metastases or high HPV 16/18 E7 viral load plus pN2, tumor depth ≥11 mm, or ECS), the 5-year distant metastasis rate was 74%. In the intermediate-risk group (high HPV 16/18 E7 viral load, pN2, tumor depth ≥11 mm, or ECS), the 5-year DM rate was 17%. Finally, the 5-year DM rate was 1% in the low-risk group (no risk factors). The value of the C statistics was 0.78. Conclusions Among OSCC patients, high HPV 16/18 E7 viral load identifies a small subgroup of patients at high-risk of 5-year DM and suggest the need for more intensive treatments and follow-up strategies.
    Journal of Clinical Virology 10/2014; 61(2). DOI:10.1016/j.jcv.2014.07.007 · 3.47 Impact Factor
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    ABSTRACT: MicroRNA-196 (miR-196), which is highly up-regulated in oral cancer cells, has been reported to be aberrantly expressed in several cancers; however, the significance of miR-196 in oral cancer has not yet been addressed. Cellular functions in response to miR-196 modulation were examined, including cell growth, migration, invasion and radio/chemosensitivity. Algorithm-based studies were used to identify the regulatory target of miR-196. The miR-196 target gene and downstream molecular mechanisms were confirmed by RT-qPCR, western blot, luciferase reporter and confocal microscopy analyses. miR-196 expression was determined in paired cancer and adjacent normal tissues from oral cancer patients. Both miR-196a and miR-196b were highly over-expressed in the cancer tissue and correlated with lymph node metastasis (P = 0.001 and P = 0.006, respectively). Functionally, miR-196 actively promoted cell migration and invasion without affecting cell growth. Mechanistically, miR-196 performed it's their function by inhibiting NME4 expression and further activating p-JNK, suppressing TIMP1, and augmenting MMP1/9. miR-196 contributes to oral cancer by promoting cell migration and invasion. Clinically, miR-196a/b was significantly over-expressed in the cancer tissues and correlated with lymph node metastasis. Thus, our findings provide new knowledge of the underlying mechanism of cancer metastasis. miR-196 may serve as a promising marker for better oral cancer management.
    Molecular Cancer 09/2014; 13(1):218. DOI:10.1186/1476-4598-13-218 · 5.40 Impact Factor
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    ABSTRACT: Importance The current American Joint Committee on Cancer (AJCC) staging system for oral cancer demonstrates wide prognostic variability within each primary tumor stage and provides suboptimal staging and prognostic information for some patients.Objective To determine if a modified staging system for oral cancer that integrates depth of invasion (DOI) into the T categories improves prognostic performance compared with the current AJCC T staging.Design, Setting, and Participants Retrospective analysis of 3149 patients with oral squamous cell carcinoma treated with curative intent at 11 comprehensive cancer centers worldwide between 1990 and 2011 with surgery ± adjuvant therapy, with a median follow-up of 40 months.Main Outcomes and Measures We assessed the impact of DOI on disease-specific and overall survival in multivariable Cox proportional hazard models and investigated for institutional heterogeneity using 2-stage random effects meta-analyses. Candidate staging systems were developed after identification of optimal DOI cutpoints within each AJCC T category using the Akaike information criterion (AIC) and likelihood ratio tests. Staging systems were evaluated using the Harrel concordance index (C-index), AIC, and visual inspection for stratification into distinct prognostic categories, with internal validation using bootstrapping techniques.Results The mean and median DOI were 12.9 mm and 10.0 mm, respectively. On multivariable analysis, DOI was a significantly associated with disease-specific survival (P < .001), demonstrated no institutional prognostic heterogeneity (I2 = 6.3%; P = .38), and resulted in improved model fit compared with T category alone (lower AIC, P < .001). Optimal cutpoints of 5 mm in T1 and 10 mm in T2-4 category disease were used to develop a modified T staging system that was preferred to the AJCC system on the basis of lower AIC, visual inspection of Kaplan-Meier curves, and significant improvement in bootstrapped C-index.Conclusions and Relevance We propose an improved oral cancer T staging system based on incorporation of DOI that should be considered in future versions of the AJCC staging system after external validation.
    07/2014; 140(12). DOI:10.1001/jamaoto.2014.1548
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    ABSTRACT: Squamous cell carcinoma antigen (SCC-Ag) and C-reactive protein (CRP) levels have been successfully used to stratify risk groups in primary oral squamous cell carcinoma (OSCC) patients; however, related biomarkers have rarely been investigated in recurrent OSCC. The purpose of the present study was to analyze the relationships of SCC-Ag and CRP levels at the time of recurrence with clinical factors and prognosis. We retrospectively recruited patients with recurrence in a cohort of 534 OSCC patients between March 2001 and July 2013. One hundred patients had recurrence. The serum SCC-Ag and CRP levels were measured at the time of cancer diagnosis, 3 to 6 months after treatment with clinical disease-free, and at the time of recurrence. The SCC-Ag levels were significantly lowered after treatment (paired t-test: p = 0.001) and re-elevated at the time of recurrence (paired t-test: p = 0.027). An SCC-Ag level ≥2.0 ng/ml and a CRP level ≥5.0 mg/L at the time of recurrence were significantly associated with recurrent tumor status (P<0.001), recurrent nodal metastasis (χ2 trend test: P = 0.020), distant metastasis (P<0.001), and overall survival (P<0.001). Moreover, the influence of both elevated SCC-Ag and CRP levels on overall survival (P<0.001, H.R. [95% CI]: 5.406 [2.210-13.222]) still existed after adjusting for the recurrent tumor stage and patient age. The present study demonstrates that concurrent high levels of both SCC-Ag and CRP at the diagnosis of recurrence acts as a predictor of recurrent tumor status, recurrent advanced tumor stage, distant metastasis, and survival after the diagnosis of recurrence. This study expands the applicability of these two markers in the risk stratification in recurrent OSCC.
    PLoS ONE 07/2014; 9(7):e103265. DOI:10.1371/journal.pone.0103265 · 3.23 Impact Factor
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    ABSTRACT: MicroRNAs (miRNAs) have a major impact on regulatory networks in human carcinogenesis. In this study, we sought to investigate the prognostic significance of miRNAs in patients with oral cavity squamous cell carcinoma (OSCC). In a discovery phase, RNA was extracted from 58 OSCC tumor samples and paired normal tissues. MiRNAs expression was evaluated with TaqMan Array Card and TaqMan MicroRNA assays. The prognostic significance of the miRNA signature identified in the discovery phase was validated by qRT-PCR in a replication set consisting of 141 formalin-fixed, paraffin-embedded (FFPE) samples. We identified a miRNA regulatory network centered on the three hub genes (SP1, MYC, and TP53) that predicted distinct clinical endpoints. Three miRNAs (miR-218, miR-125b, and let-7g) and their downstream response genes had a concordant prognostic significance on disease-free survival and disease-specific survival rates. In addition, patients with a reduced expression of miR-218, miR-125b, and let-7g have a higher risk of poor outcomes in presence of specific risk factors (p-stage III-IV, pT3-4, or pN+). Our findings indicate that specific miRNAs have prognostic significance in OSCC patients and may improve prognostic stratification over traditional risk factors.
    PLoS ONE 07/2014; 9(7):e102403. DOI:10.1371/journal.pone.0102403 · 3.23 Impact Factor
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    ABSTRACT: A study was conducted to assess for prognostic heterogeneity within the N2b and N2c classifications for oral cancer based on the number of metastatic lymph nodes and to determine whether laterality of neck disease provides additional prognostic information. An international multicenter study of 3704 patients with oral cancer undergoing surgery with curative intent was performed. The endpoints of interest were disease-specific survival and overall survival. Model fit was assessed by the Akaike Information Criterion and comparison of models with and without the covariate of interest using a likelihood ratio test. The median number of metastatic lymph nodes was significantly higher in patients with N2c disease compared to those with N2b disease (P < .001). In multivariable analyses stratified by study center, the addition of the number of metastatic lymph nodes improved model fit beyond existing N classification. Next, the authors confirmed significant heterogeneity in prognosis based on the number of metastatic lymph nodes (≤ 2, 3-4, and ≥ 5) in patients with both N2b and N2c disease (P < .001). A proposed reclassification combining N2b and N2c disease based on the number of metastatic lymph nodes demonstrated significant improvement in prognostic accuracy compared with the American Joint Committee on Cancer staging system, and no improvement was noted with the addition of a covariate for contralateral or bilateral neck disease (P = .472). The prognosis of patients with oral cancer with N2b and N2c disease appears to be similar after adequate adjustment for the burden of lymph node metastases, irrespective of laterality. Based on this finding, the authors propose a modified lymph node staging system that requires external validation before implementation in clinical practice. Cancer 2014. © 2014 American Cancer Society.
    Cancer 07/2014; 120(13). DOI:10.1002/cncr.28686 · 4.90 Impact Factor
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    ABSTRACT: Objectives: We sought to investigate whether there is evidence of field cancerization in patients with oral cavity squamous cell carcinoma (OSCC) enrolled in a betel quid chewing area. We also assessed whether betel quid chewing is an independent risk factor for field cancerization in OSCC patients. Methods: We retrospectively examined the records of 1570 OSCC patients who underwent radical tumor resection between 1996 and 2011. A total of 1243 study participants (79%) had a positive history of betel quid chewing before surgery. Of the 767 patients treated with surgery alone, 599 (78%) were preoperative chewers, whereas a history of preoperative betel quid chewing was identified in 644 (80%) of the 803 patients who received adjuvant therapy. The 5-year control, survival, and second primary tumors (SPTs) rates served as the main outcome measures. Results: Regardless of the treatment modality, more than 70% of the SPTs were located in the oral cavity or soft palate. Despite a similar risk profile in terms of tumor depth, lymph node metastasis, and pathological margin status, preoperative chewers showed a significantly higher incidence of 5-year SPTs and local recurrences compared with non-chewers. Moreover, multivariate analysis demonstrated that preoperative betel quid chewing was an independent prognostic factor for 5-year local control and SPTs occurrence rates. Conclusions: Our results demonstrate that preoperative betel quid chewers had a higher incidence of local recurrence and SPTs than non-chewers, suggesting that field cancerization may occur in OSCC patients with a history of betel quid chewing.
    Oral Oncology 05/2014; 50(8). DOI:10.1016/j.oraloncology.2014.04.010 · 3.03 Impact Factor
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    ABSTRACT: Background: To evaluate the efficacy and adverse events of cisplatin, tegafur, and leucovorin concomitantly with radiotherapy for patients with advanced, non-metastatic squamous cell carcinoma (SCC) of the oropharynx and hypopharynx. Methods: The PTL regimen consisted of cisplatin (P) 50 mg/m 2 on day 1, oral tegafur (T) 800 mg/day plus leucovorin (LV) 60 mg/day on days 1 through 14. It was repeated every 2 weeks through the radiotherapy course. Conventional radiotherapy with 1.8-2.0 Gy/day, 5 days per week, was delivered in a total dose of between 70 and 72 Gy. Results: Sixty-five patients with stage III or IV of SCC of the head and neck were consecutively treated between May 2002 and November 2005. Forty-six (70.7%) patients had complete response after concomitant chemoradiotherapy (CCRT). With a median follow-up of 54.0 months (range 1-103 months), the 5-year locoregional control, progression-free survival, and overall survival rates were 50.6%, 40.7%, and 59.7%, respectively. Three (4.6%) patients had toxic death during treatment. Fifty-one (80.0%) patients experienced grade 3-4 mucositis which occurred in about 35% of the CCRT duration. The functional preservation rate among post-CCRT complete responders was 93.5% (43/46). The median cisplatin accumulated dosage was 150 mg, and the rate of hearing impairment among the survivors was 7.8%. Conclusion: CCRT with outpatient-based PTL for advanced SCC of oropharynx and hypopharynx is feasible and has comparative efficacy and acceptable adverse events.
    05/2014; 37(3):133-40. DOI:10.4103/2319-4170.117893
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    ABSTRACT: The aim of this study was to identify factors associated with unmet supportive care needs in family caregivers of patients with oral cancer after surgery. In a cross-sectional study, we recruited patient-family caregiver dyads from the otolaryngology head and neck surgery wards of a medical center in northern Taiwan. Patients were assessed using a set of structured questionnaires to measure symptom distress, sleep quality, and depression. Social support and supportive care needs of family caregivers were measured. Of the 102 dyads surveyed, needs for supportive care in information domain and healthcare professional/healthcare services domain were highest. Patients with more severe symptoms and family caregivers who received less social support from family were associated with greater overall unmet supportive care needs. Family caregivers report the need for more information and healthcare services after a family member has had oral surgery. Caregiving training programs should be developed for caregivers on the basis of meeting reported needs. Copyright © 2014 John Wiley & Sons, Ltd.
    Psycho-Oncology 05/2014; 23(5):569-577. DOI:10.1002/pon.3458 · 4.04 Impact Factor

Publication Stats

3k Citations
702.49 Total Impact Points


  • 2001–2015
    • Chang Gung Memorial Hospital
      • • Department of Otorhinolaryngology
      • • Division of Radiation Oncology
      T’ai-pei, Taipei, Taiwan
  • 2014
    • The Australian Society of Otolaryngology Head & Neck Surgery
      Evans Head, New South Wales, Australia
  • 2007–2014
    • Chang Gung University
      • • Department of Otolaryngology
      • • College of Medicine
      Hsin-chu-hsien, Taiwan, Taiwan
  • 2006
    • Xiamen Chang Gung Hospital
      Amoy, Fujian, China
  • 2004
    • National Yang Ming University
      T’ai-pei, Taipei, Taiwan