Fascin is a circulating tumor marker for head and neck cancer as determined by a proteomic analysis of interstitial fluid from the tumor microenvironment.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Office-based narrow band imaging-guided flexible laryngoscopy tissue sampling: A cost-effectiveness analysis evaluating its impact on Taiwanese health insurance program.

BACKGROUND/PURPOSE: Narrow band imaging (NBI)-guided flexible laryngoscopy tissue sampling for laryngopharyngeal lesions is a novel technique. Patients underwent the procedure in an office-based setting without being sedated, which is different from the conventional technique performed using direct laryngoscopy. Although the feasibility and effects of this procedure were established, its financial impact on the institution and Taiwanese National Health Insurance program was not determined. METHODS: This is a retrospective case-control study. From May 2010 to April 2011, 20 consecutive patients who underwent NBI flexible laryngoscopy tissue sampling were recruited. During the same period, another 20 age-, sex-, and lesion-matched cases were enrolled in the control group. The courses for procedures and financial status were analyzed and compared between groups. RESULTS: Office-based NBI flexible laryngoscopy tissue sampling procedure took 27 minutes to be completed, while 191 minutes were required for the conventional technique. Average reimbursement for each case was New Taiwan Dollar (NT$)1264 for patients undergoing office-based NBI flexible laryngoscopy tissue sampling, while NT$10,913 for those undergoing conventional direct laryngoscopy in the operation room (p < 0.001). The institution suffered a loss of at least NT$690 when performing NBI flexible laryngoscopy tissue sampling. CONCLUSION: Office-based NBI flexible laryngoscopy tissue sampling is a cost-saving procedure for patients and the Taiwanese National Health Insurance program. It also saves the procedure time. However, the net financial loss for the institution and physician would limit its popularization unless reimbursement patterns are changed.

OncomiR-196 promotes an invasive phenotype in oral cancer through the NME4-JNK-TIMP1-MMP signaling pathway.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Outcome analyses of unusual site neck recurrence in oral cavity cancer.

AIM: To understand the frequency, clinical significance, and benefits of salvage therapy in oral cavity squamous cell carcinoma (OSCC) patients with regional nodal recurrence at unusual sites (prelaryngeal area, parotid area, and retropharyngeal area). METHODS: We examined 178 patients with neck recurrence at levels I-V (usual group) and 26 patients outside levels I-V (unusual group). The 5-year survival rates served as the main outcome measure. RESULTS: Of the 26 unusual group patients, the neck recurrence sites were as follows: 5 at the prelaryngeal area, 13 at the parotid area, and 8 at the retropharyngeal area. Multivariate analyses demonstrated that poor differentiation, pN2, extracapsular spread (ECS), tumor depth≥10 mm, relapse time≤10 months, local recurrence, neck recurrence at unusual sites, and distant metastases were independent prognostic factors for 5-year disease-specific survival (DSS), whereas pN2, ECS, tumor depth≥10 mm, relapse time≤10 months, neck recurrence at unusual sites, and distant metastases were independent prognostic factors for 5-year overall survival (OS). The 6-month and 18-month survival rates after the N-relapse date for the salvaged-usual group, the salvaged-unusual group, and the nonsalvaged patients were 73%/46%, 40%/0%, and 10%/0% (P<0.0001), respectively [DSS: salvaged-unusual group (hazard ratio/95 % confidence interval), 2.060/1.058-4.008, P=0.033; salvaged-usual group, 6.420/4.340-9.496, P<0.001; OS: salvaged-unusual group, 2.100/1.080-4.081, P=0.029; salvaged-usual group, 6.514/4.418-9.606, P<0.001]. CONCLUSIONS: Our findings demonstrate that OSCC patients with regional nodal recurrence at unusual sites had poor outcomes.

NBI flexible laryngoscopy targeted tissue sampling in head and neck cancer patients with difficult airways.

Direct suspension laryngoscopic biopsy of neoplasms in larynx, oropharynx, and hypopharynx was an arduous procedure in patients with a history of head and neck cancer and difficult airways. This preliminary study was aimed to report the efficacy and safety of a narrow band imaging-guided biopsy of this category by flexible laryngoscopy. This is a retrospective chart review study conducted in setting of tertiary referral centre. Nineteen consecutive head and neck cancer patients with difficulty in general anesthesia and rigid endoscopic approach due to trismus, craniofacial deformities, and/or limited neck extension after cancer therapy were referred for endoscopic biopsy of their suspicious lesions in larynx, hypopharynx, or parts of oropharynx. Following topical anesthesia, a flexible laryngoscope was introduced through the nose into the pharynx. Under narrow band imaging magnified view, the specified tumor foci were biopsied in an office-based setting. All of the lesions were reached and biopsied to obtain sufficient tissue samples. The procedure took <20 min in every case. Twelve of the 19 pathologic examinations disclosed the malignancies at the first biopsy, and another underwent a second biopsy to prove cancer recurrence. The other six patients with benign lesions received further follow-up for at least 6 months and showed no recurrence. There were no complications associated with the technique. This study introduced that flexible laryngoscopy with narrow band imaging has the advantages of nimbleness, precision, and minimal morbidity. This combined technique may be a safe and promising method for tissue sampling of suspicious recurrence in head and neck cancer patients with difficult airways.

Risk stratification in oral cavity squamous cell carcinoma by preoperative CRP and SCC antigen levels.

BACKGROUND: Squamous cell carcinoma antigen (SCC-Ag) level and C-reactive protein (CRP) have been shown to be associated with tumor invasion, lymph node metastasis, staging and survival in patients with oral squamous cell carcinoma (OSCC). The purpose of the present study was to analyze the relationship between preoperative levels of both SCC-Ag and CRP, with clinicopathologic factors and prognosis in OSCC patients. METHODS: A retrospective study was performed on 142 OSCC patients between March 2008 and March 2011. Their serum SCC-Ag and CRP levels were measured preoperatively. RESULTS: SCC-Ag level of ≥2.0 ng/ml and CRP level ≥5.0 mg/L were significantly associated with pathologic tumor status (P < 0.001), pathologic nodal metastasis (P = 0.001), tumor depth (≥10 mm vs. <10 mm, P < 0.001), disease-free survival (P ≤ 0.001) and overall survival (P ≤ 0.001). The influence of SCC-Ag and CRP level on disease-free survival (hazard ratio 4.046, 95 % confidence interval 1.698-9.692) and overall survival (hazard ratio 3.655, 95 % confidence interval 1.464-9.130) still existed after adjusting for tumor status, lymph node metastasis and tumor cell differentiation. CONCLUSIONS: Concurrent high levels of both preoperative SCC-Ag and CRP levels act as a predictor for lymph node metastasis, advanced tumor stage and tumor recurrence. It therefore has significant potential as a biomarker for risk stratification in OSCC.

Impact of a second FDG PET scan before adjuvant therapy for the early detection of residual/relapsing tumours in high-risk patients with oral cavity cancer and pathological extracapsular spread.

PURPOSE: Extracapsular spread (ECS) to the cervical lymph nodes is a major adverse prognostic factor in oral cavity squamous cell carcinoma (OSCC). We prospectively examined the value of FDG PET immediately before postoperative radiotherapy/concurrent chemoradiotherapy (pre-RT/CCRT PET) to detect residual/relapsing disease in the early postsurgical follow-up period in high-risk OSCC patients with ECS. METHODS: We examined 183 high-risk OSCC patients with ECS who underwent preoperative FDG PET/CT for staging purposes. Of these patients, 29 underwent a second pre-RT/CCRT FDG PET/CT scan. The clinical utility of the second FDG PET/CT was examined using Kaplan-Meier curve analysis. RESULTS: Patients who underwent the second FDG PET/CT scan had baseline clinicopathological characteristics similar to those who did not undergo a second scan. Of the patients who underwent the second scan, seven (24 %) had unexpected, newly discovered lesions. Five eventually died of the disease, and two had no evidence of recurrence after a change in RT field and dose. In an event-based analysis at 2 months, rates of neck control (6/29 vs. 6/154, p = 0.001), distant metastases (3/29 vs. 4/154, p = 0.046), and disease-free survival (7/29 vs. 10/154, p = 0.003) were significantly higher in patients who received a second PET scan than in those who did not. The second pre-RT/CCRT PET scan was of particular benefit for detecting new lesions in OSCC patients with both ECS and lymph node standardized uptake value (SUV) of ≥ 5.2 in the first PET scan. CONCLUSION: The present findings support the clinical value of pre-RT/CCRT FDG PET for defining treatment strategy in OSCC patients with both ECS and high nodal SUV, even when FDG PET had already been performed during the initial staging work-up.

Cyclin D1 overexpression and poor clinical outcomes in Taiwanese oral cavity squamous cell carcinoma.

BACKGROUND: Cyclin D1 gene regulates cell cycle and plays an important role in the tumorigenesis of human cancers. The association between cyclin D1, clinicopathologic parameters and prognosis in oral cavity squamous cell carcinoma (OSCC) is inconclusive. METHODS: A total of 264 male OSCCs were examined for cyclin D1 protein expression using immunohistochemistry (IHC). The expression levels of cyclin D1 were defined as overexpression when more than 10% of tumor cells displayed nuclear staining with moderate to strong intensity. RESULTS: Overexpression of cyclin D1 was found in 97 (36.7%) OSCCs. Cyclin D1 protein overexpression was significantly associated with lymph node metastasis (P = 0.002), tumor cell differentiation (P = 0.031) and tumor stage (P = 0.051), but not associated with age onset, cigarette smoking, alcohol drinking, or areca quid chewing. Overexpression of cyclin D1 was also significantly associated with poor clinical outcomes in terms of disease-free survival (DFS, P = 0.002) and overall survival (OS, P < 0.001). The effects of cyclin D1 protein overexpression on DFS (hazard ratio (HR) = 1.540; 95% confidence interval (CI), 1.068 - 2.222) and OS (HR = 1.702; 95% CI, 1.168 - 2.480) were still existed after adjusting for clinicopathological parameters (such as age, primary tumor status, tumor cell differentiation, and lymph node metastasis) using logistic multivariate analysis. CONCLUSION: Cyclin D1 protein worked as an independent prognostic factor and can be as a biomarker for the aggressiveness of OSCC.

Clinical significance of genome-wide minimally deleted regions in oral squamous cell carcinomas.

Oral squamous cell carcinoma (OSCC) has the highest rate of increase among male cancers in Taiwan. An understanding of the molecular pathogenesis of this disease as well as the development of prognostic markers for the clinical management of this disease is very important. Thus, a systematic loss of heterozygosity (LOH) analysis was performed to define minimally deleted regions (MDRs) in 63 male OSCCs using 400 polymorphic microsatellite markers. For increasing reliability, genomic DNA was extracted from >90% tumor cells that had been purified by LCM, and only when a microsatellite marker provided LOH information in >30% of the OSCCs was there considered to be successful allelotyping. A correlation of the various MDRs with clinicopathological parameters and prognosis was carried out. In total, 32 MDRs were identified and ten were noted as novel. In addition, six MDRs were found to be associated with cigarette smoking. Among these markers, a loss of MDR c7r2 (7q32.2-q35) was significantly associated with poor disease-free survival (DFS) and ten MDRs were associated with allelic imbalance (AI) in tumors. Among the latter, a loss of MDR c14r1 (14q24.2-q32.12) and c11r1 (11q13.4-q25) had a synergistic effect on poor DFS and were able to reduce further the DFS rate in patients with MDR c7r2 loss. Taken together, the results generated in this study provide new insights that help with exploring the molecular mechanisms associated with OSCC tumorigenesis and cigarette smoking. They also should aid the development of potential prognostic markers for the clinical management of OSCC.

Identification of a high-risk subgroup of patients with resected pT3 oral cavity cancer in need of postoperative adjuvant therapy.

BACKGROUND: The NCCN 2010 guidelines recommend the use of postoperative adjuvant radiotherapy (RT) for patients with pT3 oral cavity squamous cell carcinoma (OSCC). We sought to determine whether postoperative adjuvant RT improves outcomes in pT3N0 OSCC patients. METHODS: A total of 119 consecutive patients with pT3N0 disease were involved. A total of 42 patients received postoperative adjuvant RT, while the remaining 77 did not. The 5-year rates of control, distant metastasis, and survival were the main outcome measures. RESULTS: We found no differences in the risk profile of patients with and without postoperative adjuvant RT, the only exceptions being a higher frequency of tumor depth ≥10 mm (78.6% vs. 48.0%, P = .001) and close margins ≤4 mm (11.9 % vs. 2.7%, P = .043) in those treated by adjuvant RT. Tumor depth ≥10 mm was the only independent prognostic factor for 5-year local control, disease-free survival, and disease-specific survival in multivariable analysis. Tumor depth ≥13 mm was the only independent prognostic factor for the 5-year rate of distant metastases (16% [7 of 50] vs. 2% [1 of 67]). After stratification for tumor depth and adjuvant RT, patients with pT3N0 disease who received adjuvant RT did not show a survival advantage. CONCLUSIONS: Tumor depth ≥10 mm was the only prognostic factor identified in patients with pT3N0 disease. Adjuvant RT did not improve outcomes in pT3N0 patients, regardless of tumor depth. Patients with pT3N0 and tumor depth ≥13 mm (43% of pT3N0) were at the highest risk for distant metastases.

MicroRNA 29c is down-regulated in nasopharyngeal carcinomas, up-regulating mRNAs encoding extracellular matrix proteins.

Using highly sensitive microarray-based procedures, we identified eight microRNAs (miRNAs) showing robust differential expression between 31 laser-capture-microdissected nasopharyngeal carcinomas (NPCs) and 10 normal healthy nasopharyngeal epithelial samples. In particular, miRNA mir-29c was expressed at one-fifth the levels in tumors as in normal epithelium. In NPC tumors, the lower mir-29c levels correlated with higher levels of multiple mRNAs whose 3' UTRs can bind mir-29c at target sequences conserved across many vertebrates. In cultured cells, introduction of mir-29c down-regulated these genes at the level of mRNA and inhibited expression of luciferase encoded by vectors having the 3' UTRs of these genes. Moreover, for each of several genes tested, mutating the mir-29c target sites in the 3' UTR abrogated mir-29c-induced inhibition of luciferase expression. Most of the mir-29c-targeted genes identified encode extracellular matrix proteins, including multiple collagens and laminin gamma1, that are associated with tumor cell invasiveness and metastatic potential, prominent characteristics of NPC. Thus, we identify eight miRNAs differentially expressed in NPC and demonstrate the involvement of one in regulating genes involved in metastasis.

Tongue and buccal mucosa carcinoma: is there a difference in outcome?

BACKGROUND: We sought to determine the differences in clinical outcome of tongue and buccal carcinomas. METHODS: Five-year locoregional control, distant metastasis, and survival rates were examined in 456 patients with tongue cancer and 407 patients with buccal cancer. RESULTS: Five-year rates for patients with tongue and buccal carcinomas were as follows: local control, 85% and 87% (P = 0.9366); neck control, 81% and 87% (P = 0.0304); distant metastasis, 8% and 14% (P = 0.0052); disease-free survival, 70% and 72% (P = 0.9978); disease-specific survival, 79% and 78% (P = 0.2435), respectively. After stratification according to pathological lymph node status, patients with buccal cancer and pN0/pNx disease (without neck dissection) had a higher 5-year neck control rate than those with tongue cancer (93% versus 86%, P = 0.0115). In contrast, buccal cancer with pN+ disease had a higher 5-year distant metastasis rate compared with tongue cancer (30% versus 18%, P = 0.0231). In pN0/pNx subjects, neck control was predicted by perineural invasion and the absence of neck dissection in tongue cancer, and by poor differentiation in buccal cancer. In pN+ patients, distant metastases were predicted by pT3-4 disease, age at onset ≤40 years, poor differentiation, and pN+ ≥ 5 nodes in tongue cancer, and by poor differentiation and pN+ ≥ 5 nodes in buccal cancer. CONCLUSIONS: There are significant differences in the failure pattern of tongue and buccal carcinomas. Prognostic models for these malignancies should allow stratification of patients for a risk-adapted approach to treatment.

Outcome analysis of patients with pN2 oral cavity cancer.

BACKGROUND: The American Joint Committee on Cancer staging system suggests that squamous-cell carcinoma of the oral cavity (OSCC) with pN2 should be classified as stage IVA. The objective of the current study was to determine the outcome of patients with pN2 OSCC cancer according to different T status. METHODS: Between January 1996 and September 2007, a total of 270 patients with pN2 OSCC cancer were analyzed. All participants had a follow-up of at least 2 years or were censored on the date of last follow-up. The outcome measures for this study were the 5-year rates of locoregional control, distant metastases, and survival. RESULTS: Five-year disease-specific survival and overall survival rates in pT1 (n = 9), pT2 (n = 98), pT3 (n = 70), and pT4 (n = 93) patients were 78%, 66%, 49%, 35% (P = 0.0031), and 78%, 52%, 35%, 23% (P = 0.0001), respectively. Multivariable analysis revealed that pT3-4, level IV/V metastases, extracapsular spread, and poor differentiation were independent risk factors for 5-year disease-specific survival in the entire study cohort. Specific independent prognostic factors for 5-year disease-specific survival according to T stage were found. CONCLUSIONS: The results of this study suggest that patients with pN2 OSCC cancer have different outcomes and prognostic factors according to their T status. In the light of these findings, treatment strategies may be quite different.

Carcinoma ex pleomorphic adenoma of soft palate with cavernous sinus invasion.

BACKGROUND: Carcinoma ex pleomorphic adenoma (CXPA) is an aggressive salivary gland malignancy and rare in minor salivary gland. A soft palate CXPA initially presenting as direct cavernous sinus (CS) invasion is very rare. CASE PRESENTATION: A 60-year-old male had a 3-month history of a small soft palatal mass with progressing left cheek numbness, proptosis, and disturbed vision. Biopsy of soft palatal tumor showed pleomorphic adenoma. Magnetic resonance imaging showed a tumor involving left maxilla, and extended from pterygopalatine fossa, inferior orbital fissure to CS. Excision of tumor revealed CXPA. Adjuvant concomitant chemo-radiation therapy (CCRT) was given. The tumor recurred 5 months later in left CS which was re-treated with CCRT. The disease status was stable at 2 years after the diagnosis of CXPA. CONCLUSION: We present this case to emphasize that patients with symptoms such as facial numbness, proptosis and disturbed vision should be carefully investigated for lesions invading CS by perineural spread.

Sulfotransferase 1A1 haplotypes associated with oral squamous cell carcinoma susceptibility in male Taiwanese.

We have previously demonstrated that betel quid containing safrole induced DNA adducts are highly associated with the development of oral squamous cell carcinoma (OSCC) in Taiwan. Sulfotransferase (SULT) is essential for the formation of these adducts. To elucidate the effects of SULT1A1 haplotypes on OSCC susceptibility, 160 male OSCC cases and 218 age- and sex-matched controls were screened for single-nucleotide polymorphisms within the coding region of SULT1A1 by sequencing. We found that 445C>T (His149Tyr) and 507C>T polymorphisms were significantly associated with increased risk of OSCC. Based on the genotype analysis, haplotypes were constructed for 445C>T (His149Tyr), 507C>T, 600G>C and 638G>A (Arg213His) using GENECOUNTING software. After adjustment for age, cigarette smoking and betel quid chewing, we found that haplotype c containing 445C>T (His149Tyr), 507C>T or 600G>C but not 638G>A (Arg213His) variant was significantly associated with increased risk of OSCC (odds ratio, 3.24; 95% confidence interval, 1.57-6.68) when compared with the haplotype a (wild-type). We analyzed the activity in sulfonation of 2-naphthol and 1'-hydroxysafrole of recombinant His149Tyr (445C>T) variant, which led to 51 and 33% reduced activity, respectively; Arg213His (638G>A) variant led to 72 and 54% reduced activity, respectively, when compared with the wild-type. Taken together, haplotype analysis provides a novel evaluation of the SULT1A1 gene as a risk modifier on environmental carcinogen in OSCC and the association of SULT1A1 haplotypes with the risk of OSCC might be modified by betel quid chewing.

Risk stratification of patients with oral cavity squamous cell carcinoma and contralateral neck recurrence following radical surgery.

Clinical outcome of patients with oral cavity squamous cell carcinoma (OSCC) and contralateral neck recurrence (CLNR) remains poor. We sought to identify factors associated with CLNR and incorporate them into a risk stratification scheme. Between January 1996 and June 2006, a total of 913 consecutive OSCC patients treated by radical surgery were investigated. Postoperative adjuvant therapy was performed in the presence of pathological risk factors. The duration of follow-up was at least 24 months in all surviving patients. Outcome measures were the 5-year CLNR and overall survival rates. In the entire study cohort, the 5-year CLNR rate was 7% (55/913). Specifically, it was 18% (17/132) in patients with local recurrence (LR), and 5% (38/781) in those without (P = 0.0002). In multivariate analysis, extracapsular spread (ECS) was the only independent risk factor for CLNR in patients with LR. Tumor subsite, poor differentiation, and presence of pN + disease were significant predictors of CLNR in patients without LR. We identified two groups of patients with high CLNR rates. The first group consisted of patients with ECS at the initial diagnosis and LR. The second group consisted of subjects with tongue cancer without LR harboring at least two risk factors. We conclude that, in patients who achieved local control, postoperative contralateral neck treatment is recommended for subjects with tongue cancer and at least two risk factors. Once LR occurs, contralateral neck treatment is recommended in patients with ECS.

Preoperative [18F]-fluorodeoxyglucose positron emission tomography standardized uptake value of neck lymph nodes may aid in selecting patients with oral cavity squamous cell carcinoma for salvage therapy after relapse.

PURPOSE: Relapse of tumours in patients with oral cavity squamous cell carcinoma (OSCC) is associated with a dismal outcome. In this prospective study, we sought to investigate the clinical significance of the preoperative maximal standardized uptake value (SUVmax) at the neck lymph nodes in selecting patients with OSCC for salvage therapy after relapse. METHODS: Between 2002 and 2007, 108 patients with early relapse of OSCC (n=75) or late relapse of OSCC (n=33) were identified. Salvage therapy was performed in 47 patients. All patients underwent 2-deoxy-2[(18)F]-fluoro-D: -glucose positron emission tomography during the 2 weeks before surgery and neck dissection. All patients were followed for 12 months or more after surgery or until death. The optimal cut-off value for the neck lymph node SUVmax (SUVnodal-max) was selected according to the 5-year disease-specific survival (DSS) rate. Independent risk factors were identified by Cox regression analysis. RESULTS: The mean follow-up for all patients was 20.3 months (41.1 months for surviving patients). In the early relapse group, several prognostic factors were identified in univariate and multivariate analyses, including a SUVnodal-max value of >or=4.2. A scoring system based on univariate analysis was formulated. Patients with a score of 0 had a better 5-year DSS than those with scores of 1 or higher (58% vs. 5%, p=0.0003). In patients with late relapse, a SUVnodal-max value of >or=4.2 had the highest prognostic value for predicting the 5-year DSS (45% vs. 0%, p=0.0005). CONCLUSION: Among patients with relapsed OSCC, the SUVnodal-max value may aid in selecting patients for salvage therapy.

Treatment outcome of combined modalities for buccal cancers: unilateral or bilateral neck radiation?

PURPOSE: To evaluate the outcome of treatment for buccal cancers and assess the impact of unilateral vs. bilateral adjuvant neck radiation. METHODS AND MATERIALS: We retrospectively reviewed the course of 145 patients newly diagnosed with buccal squamous cell carcinoma without distant metastases who completed definitive treatment between January 1994 and December 2000. Of 145 patients, 112 (77%) had Stage III or IV disease. All underwent radical surgery with postoperative radiotherapy (median dose, 64 Gy), including unilateral neck treatment in most (n = 120, 82.8%). After 1997, cisplatin-based concomitant chemoradiotherapy was given for high-risk patients with more than two involved lymph nodes, extracapsular spread, and/or positive margins. RESULTS: The 5-year disease-specific survival rate for Stages I-IV was 87%, 83%, 61%, and 60%, respectively (p = 0.01). The most significant prognostic factor was N stage, with the 5-year disease-specific survival rate for N0, N1, and N2 being 79%, 65%, and 54%, respectively (p = 0.001). For patients with more than two lymph nodes or positive extracapsular spread, cisplatin-based concomitant chemoradiotherapy improved locoregional control (p = 0.02). Locoregional control did not differ between patients undergoing unilateral or bilateral neck treatments (p = 0.95). Contralateral neck failure occurred in only 2.1%. CONCLUSIONS: In patients with buccal carcinoma after radical resection, ipsilateral neck radiation is adequate. Bilateral prophylactic neck treatment does not confer an added benefit.

Does adjuvant radiation therapy improve outcomes in pT1-3N0 oral cavity cancer with tumor-free margins and perineural invasion?

PURPOSE: The criteria for administration of adjuvant radiation therapy (RT) in oral cavity squamous cell carcinoma (OSCC) remain controversial, and it is unclear whether patients with pT1-3N0 disease benefit from adjuvant radiation in the presence of free margins and perineural invasion. The goal of this report was to determine whether this group would benefit from adjuvant radiation therapy in terms of 5-year local control rate and overall survival rate. METHODS AND MATERIALS: We retrospectively reviewed our case records from January 1996 to May 2005. In all, 460 pT1-3N0 OSCC patients had tumor-free margins, of whom 68 had perineural invasion. Postoperative adjuvant RT was performed in patients with pT4 tumors, positive lymph nodes, or close margins (< or =4 mm). In addition, selected OSCC patients with large pT3 tumors or perineural invasion received postoperative adjuvant RT. Local control and overall survival rates were plotted by Kaplan-Meier analysis. RESULTS: There were no significant differences in 5-year local control (p = 0.1936) and overall survival (p = 0.5580) rates between patients with perineural invasion compared with those without. Among patients with perineural invasion, the addition of adjuvant radiotherapy did not significantly alter the 5-year local control rate (p = 0.3170) or the overall survival rate (p = 0.0935). CONCLUSION: Altogether, these data seem to indicate that radical surgical resection alone should be considered a sufficient treatment for OSCC patients with pT1-3N0 disease, even in the presence of perineural invasion.

Analysis of risk factors of predictive local tumor control in oral cavity cancer.

BACKGROUND: Survival in oral cavity squamous cell carcinoma (OSCC) depends heavily on locoregional control. In this study, we sought to determine the independent prognosticators for local tumor control, disease-specific survival (DSS), and overall survival (OS) rates in a series of OSCC patients undergoing radical surgery. METHODS: We retrospectively reviewed 827 consecutive OSCC patients undergoing radical surgery from January 1998 to March 2005. Postoperative radiotherapy was performed in patients with pT4 tumors, positive lymph node(s), or close margins (< or = 4 mm). Local control rates and survivals were plotted using the Kaplan-Meier method. RESULTS: On multivariate analysis (MVA), unfavorable prognostic factors for local control were pathological margins < or = 7 mm (P < 0.001), pathological tumor depth > or = 10 mm (P < 0.001), pathological positive lymph node(s) (P = 0.001), and the presence of betel quid chewing (P = 0.012). The same predictors, with the exception of betel quid chewing and pathological positive lymph node(s), were independently associated with DSS and OS in MVA. A prognostic scoring system was formulated by summing up the four significant local control covariates from MVA. Patients with scores of 3-4 had a significantly poorer local control rate compared to patients with scores of 0-2 (score 3 versus score 0-2: P < 0.001; score 4 versus score 0-2: P < 0.001) CONCLUSIONS: Taken together, our data suggest that pathological margins and pathological tumor depth are major independent prognosticators not only for local tumor control, but also for DSS and OS.