Tze Ta Huang

Clinical application of tumor volume in advanced nasopharyngeal carcinoma to predict outcome

BackgroundCurrent staging systems have limited ability to adjust optimal therapy in advanced nasopharyngeal carcinoma (NPC). This study aimed to delineate the correlation between tumor volume, treatment outcome and chemotherapy cycles in advanced NPC.MethodsA retrospective review of 110 patients with stage III-IV NPC was performed. All patients were treated first with neoadjuvant chemotherapy, then concurrent chemoradiation, and followed by adjuvant chemotherapy as being the definitive therapy. Gross tumor volume of primary tumor plus retropharyngeal nodes (GTVprn) was calculated to be an index of treatment outcome.ResultsGTVprn had a close relationship with survival and recurrence in advanced NPC. Large GTVprn (≧13 ml) was associated with a significantly poorer local control, lower distant metastasis-free rate, and poorer survival. In patients with GTVprn ≧ 13 ml, overall survival was better after ≧4 cycles of chemotherapy than after less than 4 cycles.ConclusionsThe incorporation of GTVprn can provide more information to adjust treatment strategy.

Novel quantitative analysis of autofluorescence images for oral cancer screening

OBJECTIVESnVELscope® was developed to inspect oral mucosa autofluorescence. However, its accuracy is heavily dependent on the examining physicians experience. This study was aimed toward the development of a novel quantitative analysis of autofluorescence images for oral cancer screening.nnnMATERIALS AND METHODSnPatients with either oral cancer or precancerous lesions and a control group with normal oral mucosa were enrolled in this study. White light images and VELscope® autofluorescence images of the lesions were taken with a digital camera. The lesion in the image was chosen as the region of interest (ROI). The average intensity and heterogeneity of the ROI were calculated. A quadratic discriminant analysis (QDA) was utilized to compute boundaries based on sensitivity and specificity.nnnRESULTSn47 oral cancer lesions, 54 precancerous lesions, and 39 normal oral mucosae controls were analyzed. A boundary of specificity of 0.923 and a sensitivity of 0.979 between the oral cancer lesions and normal oral mucosae were validated. The oral cancer and precancerous lesions could also be differentiated from normal oral mucosae with a specificity of 0.923 and a sensitivity of 0.970.nnnCONCLUSIONnThe novel quantitative analysis of the intensity and heterogeneity of VELscope® autofluorescence images used in this study in combination with a QDA classifier can be used to differentiate oral cancer and precancerous lesions from normal oral mucosae.

Oral Mucosa Malignant Melanoma: Clinical Features, Diagnosis, Treatment, and a Case Report

Primary oral mucosa malignant melanoma is a rare and biologically aggressive neoplasm. It is estimated about 1~2% of all oral malignancies with the incidence increasing with age. The prognosis of oral mucosa malignant melanoma is poor with the five-year survival rate is approximately 15%. The diagnosis of oral melanoma is usually delayed because it is always asymptomatic at the beginning and it resembles the epulis, amalgam tattoo or other oral lesions. In addition, nearly a third of all oral melanoma are amelanotic and may lack a radial growth phase, which makes early and accurate diagnosis even difficult. Thus, regional and distant metastases happen more frequently. Surgery is the first choice of treatment, and clinically negative necklymph nodes with neck dissection or radiotherapy are also recommended because of the high risk of subclinical regional metastasis. In this article, we reviewed the clinical features, diagnosis, treatment, and presented a 70 y/o male who suffered from an easily bleeding lesion over right posterior palatal mucosa and gingiva who presented at hospital for help. We performed biopsy which revealed a malignant melanoma. He received supraomohyoid neck lymph node dissection, partial maxillectomy, and was reconstructed with anterior lateral thigh free fascia cutaneous flap. After surgical treatment, the patient kept regular follow-ups. The treatment outcome was good and the patient recovered with full swallowing and phonation function.

Growth-regulated oncogene-α from oral submucous fibrosis fibroblasts promotes malignant transformation of oral precancerous cells

BACKGROUNDnOral squamous cell carcinoma (OSCC) is a common human malignancy and is usually preceded by the oral precancerous lesions. Oral submucous fibrosis (OSF) is one of the oral precancerous lesions with high incidence of malignant transformation. In addition to cancer cells, cancer-associated fibroblasts in the tumor microenvironment are correlated with cancer progression, but the role of fibroblasts from OSF in tumorigenesis and progression is still unknown. Growth-regulated oncogene-α (GRO-α), a member of CXC chemokine family, is related to tumorigenesis in several cancers. In this study, we would like to explore the role of GRO-α from OSF-associated fibroblasts in oral cancer progression.nnnMETHODSnWe isolated primary culture fibroblasts of normal, precancerous, and tumor tissues from patients with OSCC accompanied with OSF. A cytokine array was used to screen cytokine secretions in the conditioned media of the fibroblasts. A wound healing migration assay, WST-1 cell proliferation assay, rhodamine-phalloidin staining, and soft agar colony formation assay were used to investigate the effects of GRO-α on a dysplastic oral keratinocyte cell line (DOK) cell migration, growth, and anchorage-independent growth.nnnRESULTSnGRO-α was identified to be increased in conditioned media of OSF-associated fibroblasts. GRO-α promotes DOK cells proliferation, migration, and anchorage-independent growth through enhancing the EGFR/ERK signaling pathway, F-actin rearrangement, and stemness properties, respectively. Moreover, GRO-α neutralizing antibodies downregulated the conditioned medium-induced cell proliferation and migration of DOK.nnnCONCLUSIONnGRO-α from OSF-associated fibroblasts paracrinally promotes oral malignant transformation and significantly contributes to OSCC development.

Outcome Analysis and Unexpected-Scenario Prediction in 2-Stage Orthodontic Lower Third Molar Extraction

PURPOSEnWe propose a 2-stage orthodontic lower third molar extraction procedure to reduce iatrogenic inferior alveolar nerve injury. We tested our hypothesis that there are factors that can predict both dislodgement of the root portion and limited traction distances.nnnPATIENTS AND METHODSnFifteen patients (mean age, 25.7xa0years; age range, 17 to 65xa0years) with 20 lower third molars were enrolled. Panoramic films and cone beam computed tomography were analyzed. Dislodgement of the root portion, traction distance, duration of the orthodontic phase, and postoperative complications were documented. The predictive factors were analyzed and discussed.nnnRESULTSnThree teeth had dislodgements of the root portion. The mean traction duration was 59.2xa0days (range, 33 to 77xa0days), and the mean traction distance was 2.60xa0mm (range, 0.27 to 5.20xa0mm). Root apex cortical bone indentation and root curvature were significantly associated with traction distance. Pulpitis symptoms were documented in 1 tooth, and no postoperative nerve disturbances occurred.nnnCONCLUSIONSnOur proposed 2-stage orthodontic lower third molar extraction procedure reduced iatrogenic inferior alveolar nerve injury. Cortical bone indentation and root curvature predicted dislodgement of the root portion and limited traction distances.

Regular recreational physical activity and risk of head and neck cancer

BackgroundAlthough substantial evidence supports a 20–30% risk reduction of colon cancer, breast cancer, and endometrial cancer by physical activity (PA), the evidence for head and neck cancer (HNC) is limited. Three published studies on the association between PA and HNC have generated inconsistent results. The current study examined the association between recreational PA (RPA) and HNC risk with a more detailed assessment on the intensity, frequency, duration, and total years of RPA.MethodsData on RPA were collected from 623 HNC cases and 731 controls by in-person interview using a standardized questionnaire. The association between RPA and HNC risk was assessed using unconditional logistic regression, adjusted for sex, age, educational level, use of alcohol, betel quid, and cigarette, and consumption of vegetables and fruits.ResultsA significant inverse association between RPA and HNC risk was observed in a logistic regression model that adjusted for sex, age, and education (odds ratio (OR)xa0=xa00.65, 95% confidence interval (CI): 0.51-0.82). However, after further adjustment for the use of alcohol, betel quid, and cigarette, and consumption of vegetables and fruits, RPA was no longer associated with HNC risk (OR =0.97, 95% CI: 0.73-1.28). No significant inverse association between RPA and HNC risk was observed in the analysis stratified by HNC sites or by the use of alcohol, betel quid, or cigarette.ConclusionResults from our study did not support an inverse association between RPA and HNC risk. The major focus of HNC prevention should be on cessation of cigarette smoking and betel chewing, reduction of alcohol drinking, and promotion of healthy diet that contains plenty of fruits and vegetables.

Allergy symptoms, serum total immunoglobulin E, and risk of head and neck cancer

PurposeAllergy symptoms have been associated with a reduced head and neck cancer (HNC) risk, while elevated blood immunoglobulin E (IgE) levels have been associated with an increased HNC risk. According to the “prophylaxis hypothesis,” allergic reaction is the body’s way of expelling carcinogens. IgE level may be increased by exposure to environmental carcinogens, including alcohol and cigarette smoke. We hypothesized that individuals with elevated serum IgE without allergy symptoms (i.e., asymptomatic atopic) would have the highest HNC risk.MethodsA case–control study of HNC (576 cases and 740 controls) was conducted to evaluate the association between allergy symptoms or serum total IgE and HNC risk and the effect modification of allergy symptoms on the association between serum total IgE and HNC risk.ResultsElevated serum total IgE was associated with a significantly increased HNC risk [odds ratio (OR) 1.71, 95xa0% confidence interval (CI) 1.21–2.42]. Having allergy symptoms was associated with a significantly reduced HNC risk (OR 0.56, 95xa0% CI 0.43–0.73). Compared to subjects with normal serum total IgE and no allergy symptoms, asymptomatic atopic individuals had a significantly increased HNC risk (OR 2.12, 95xa0% CI 1.33–3.35).ConclusionsOur results provided further evidence to support the “prophylaxis hypothesis.” Further investigations regarding the immune profiles of asymptomatic atopic individuals may provide additional clues for the biological mechanisms underlying the association between allergy symptoms, IgE, and HNC risk.

OUTCOME ANALYSIS OF CONDYLAR PROSTHESIS IN LARGE HEAD AND NECK NEOPLASM RECONSTRUCTION

Reconstruction of the condyle after an ablative procedure for mouth neoplasms remains a surgical challenge because these patients with advanced cancer involving the condyle are subjected to massive ablative surgery, and subsequent major reconstruction with free flap and/or reconstruction prosthesis, the prognosis being poor. Therefore, reports of condylar prosthesis in head and neck cancer reconstruction are rare and with mixed results. This report is for the review of the literature and case series study of the condylar prosthesis. As with virtual technique improvement nowadays, an innovation CAD CAM technique is applied for the treatment plan for these patients. We analyze a serial case of advanced oral neoplasms who receives tumor ablation, i.e., mandibulectomy and disarticular resection, and gains symmetrical mandibular architecture after reconstruction with plate and condylar prosthesis. There is still high complication rate (41.7%) noted, namely condylar prosthesis displacement (two cases), impinge on external ear canal (two cases), and erosion of cranial base (one case). The reasons are attributed to massive flap burden, scar contraction, poor dental articulation, and possible technique error during the operation. According to the outcome analysis, virtual technique including with reconstruction plate and condylar prosthesis in conjunction with flap reconstruction are feasible treatment modality for this serial case of advanced oral neoplasms.

Abstract 3314: DNA methylome analysis identifies epigenetic silencing of FHIT as a determining factor for radiosensitivity in oral cancer and its implication in treatment and outcome prediction

Radioresistance is still an emerging problem for radiotherapy of oral cancer. Aberrant epigenetic alterations play an important role in cancer development, yet the role of such alterations in radioresistance of oral cancer is not fully explored. Using Illumina 27K methylation BeadChip microarray, we identified promoter hypermethylation of FHIT (fragile histidine triad) in radioresistant OML1-R cells, established from hypo-fractionated irradiation (5-Gy by 10 fractions) of parental OML1 radiosensitive oral cancer cells. Further analysis confirmed that transcriptional repression of FHIT was due to promoter hypermethylation and H3K27me3 as demonstrated by MBDcap-PCR, bisulfite pyrosequencing and ChIP-PCR. These phenomenon were partially attributed to overexpression of EZH2 and DNMT3a, 3b in OML1-R cells. In consistent with these observations, treatment of 5-azaDC, EZH2 inhibitor (GSK343) or depletion of EZH2 by lentiviral knockdown restored FHIT expression in OML1-R cells. Interestingly, knockdown of EZH2 also reversed histone modifications (increased of H3K4me3 and decreased of H3K27me3) and reduced promoter methylation of FHIT thus suggesting that H3K27me3 linked to DNA methylation in this loci. We also analyzed the expression of FHIT in primary human oral keratinocyte (HOK) and four other oral cancer cell lines (OCSL, SCC25, SAS, and SCC4). FHIT expression demonstrated a tight inverse relationship with its promoter methylation. Ectopic expression of FHIT restored radiosensitivity (single fraction, 10-Gy) in OML1-R cells and oral cancer cells (SAS, SCC25) showing epigenetic silencing of FHIT. These phenomenon may be due to restoration of Chk2 phosphorylation, induction of apoptosis and G2/M check point. Reciprocal experiments also showed that depletion of FHIT in OSCL cells, which highly express FHIT, slightly enhanced radioresistance. Clinically, bisulfite pyrosequencing and iummnohistochemistry revealed that promoter hypermethylation of FHIT inversely correlated with its expression. Patients with higher FHIT methylation (methylation>10%, n = 22) are associated with lower locoregional control (P Citation Format: Hon-Yi Lin, Shih-Kai Hung, Moon-Sing Lee, Wen-Yen Chiou, Tze-Ta Huang, Chih-En Tseng, Liang-Yu Shih, Ru-Inn Lin, Jora Lin, Yi-Hui Lai, Chia-Bin Chang, Feng-Chun Hsu, Liang-Cheng Chen, Shiang-Jiun Tsai, Yu-Chieh Su, Szu-Chi Li, Hung-Chih Lai, Wen-Lin Hsu, Dai-Wei Liu, Chien-Kuo Tai, Shu-Fen Wu, Michael W. Chan. DNA methylome analysis identifies epigenetic silencing of FHIT as a determining factor for radiosensitivity in oral cancer and its implication in treatment and outcome prediction. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3314. doi:10.1158/1538-7445.AM2015-3314

Treatment Results and Prognostic Factors for Locally Advanced Buccal Cancer

Abstract Objective The aim of this study was to retrospectively analyze locally advanced buccal cancer in order to determine tumor characteristics and any other prognostic factors that may influence the survival of patients with the disease. Patients and Methods The records of 54 patients with stage III to IV locally advanced buccal cancer (TNM system) who were seen from August 2000 to June 2008 at one institution were reviewed. The patients received radical surgery and then adjuvant treatment. The adjuvant treatment in cluded concurrent chemoradiotherapy or radiotherapy alone. The chemotherapy protocol consisted of two 4-weekly courses of concurrent cisplatin and 5-fluorouracil followed by another two 4-weekly courses after radiotherapy, with regimens of cisplatin (60–100 mg/m 2 /day) on day 1 and 5-fluorouracil (1000 mg/m 2 /day) on days 1–5. Results The 3-year cumulative overall survival, disease-specific survival, disease-free survival, locoregional control, and distant metastasis-free survival rates were 66%, 69%, 58%, 65%, and 92%, respectively. Univariate analysis indicated that the pN classification, the surgical margin, and the presence of extracapsular spread were significantly associated with overall survival. On multivariate analysis, pN classification and surgical margin significantly affected disease-free survival. The pN classification (pN0 vs. pN1–3) and the surgical margin ( vs. ≥ 1 mm) were the two most significant factors affecting clinical outcome. Conclusion The presence of lymph node involvement, the presence of extracapsular spread and a surgical margin