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Background: While several studies have indicated that a margin status of < 1 mm should be classified as a positive margin in oral cavity squamous cell carcinoma (OCSCC), there is a lack of extensive cohort studies comparing the clinical outcomes between patients with positive margins and margins < 1 mm., Methods: Between 2011 and 2020, we identified 18,416 Taiwanese OCSCC patients who underwent tumor resection and neck dissection. Of these, 311 had margins < 1 mm and 1013 had positive margins. To compare patients with margins < 1 mm and those with positive margins, a propensity score (PS)-matched analysis (n = 253 in each group) was conducted., Results: The group with margins < 1 mm displayed a notably higher prevalence of several variables: 1) tongue subsite, 2) younger age, 3) smaller depth of invasion), 4) early tumor stage, and 5) treatment with surgery alone. Patients with margins < 1 mm demonstrated significantly better disease-specific survival (DSS) and overall survival (OS) rates compared to those with positive margins (74 % versus 53 %, 65 % versus 43 %, both p < 0.0001). Multivariable analysis further confirmed that positive margins were an independent predictor of worse 5-year DSS (hazard ratio [HR] = 1.38, p = 0.0103) and OS (HR = 1.28, p = 0.0222). In the PS-matched cohort, the 5-year outcomes for patients with margins < 1 mm compared to positive margins were as follows: DSS, 71 % versus 59 %, respectively (p = 0.0127) and OS, 60 % versus 48 %, respectively (p = 0.0398)., Conclusions: OCSCC patients with a margin status < 1 mm exhibited distinct clinicopathological characteristics and a more favorable prognosis compared to those with positive resection margins., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Objectives: According to the NCCN guidelines, there is weak evidence to support the use of elective neck dissection (END) in early-stage oral cavity squamous cell carcinoma (OCSCC). We sought to examine the indications for END in patients with cT1N0M0 OCSCC defined according to the AJCC Staging Manual, Eight Edition., Methods: Of the 3886 patients diagnosed with cT1N0M0 included in the study, 2065 underwent END and 1821 neck observation., Results: The 5-year outcomes for patients who received END versus neck observation before and after propensity score matching (n = 1406 each) were as follows: neck control, 96 %/90 % (before matching), p < 0.0001; 96 %/90 % (after matching), p < 0.0001; disease-specific survival (DSS), 93 %/92 % (before matching), p = 0.0227; 93 %/92 % (after matching), p = 0.1436. Multivariable analyses revealed that neck observation, depth of invasion (DOI) > 2.5 mm, and poor differentiation were independent risk factors for 5-year outcomes. Upon the application of a scoring system ranging from 0 (no risk factor) to 3 (presence of the three risk factors), the following 5-year rates were observed: neck control, 98 %/95 %/84 %/85 %; DSS, 96 %/93 %/88 %/85 %; and overall survival, 90 %/86 %/79 %/59 %, respectively (all p < 0.0001). The survival outcomes of patients with scores of 0 and 1 were similar. The occult metastasis rates in the entire study cohort, DOI > 2.5 mm, and poor differentiation were 6.8 %/9.2 %/17.1 %, respectively., Conclusion: Because all patients who received neck observation had a score of 1 or higher, END should be performed when a DOI > 2.5 mm or poorly differentiated tumors are present. Under these circumstances, 48.6 % (1888/3886) of cT1N0M0 patients may avoid END without compromising oncological outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: The prognostic significance of the relapse interval in patients with resected oral cavity squamous cell carcinoma (OCSCC) is a matter of ongoing debate. In this large-scale, registry-based, nationwide study, we examined whether the time interval between surgery and the first disease relapse may affect survival outcomes in Taiwanese patients with OCSCC., Methods: Data made available by the Taiwan Health Promotion Administration as of 2004 were obtained. The study cohort consisted of patients who were included in the registry between 2011 and 2017. Disease staging was performed according to the American Joint Committee on Cancer (AJCC) Staging Manual, Eight Edition. We retrospectively reviewed the clinical records of 13,789 patients with OCSCC who received surgical treatment. A total of 2327 (16.9%) patients experienced a first disease relapse. The optimal cutoff value for the relapse interval was 330 days when both 5-year disease-specific survival (DSS) and overall survival (OS) (≤ 330/>330 days, n = 1630/697) were taken into account. In addition, we undertook a propensity score (PS)-matched analysis of patients (n = 654 each) with early (≤ 330 days) versus late (> 330 days) relapse., Results: The median follow-up time in the entire study cohort was 702 days (433 and 2001 days in the early and late relapse groups, respectively). Compared with patients who experienced late relapse, those with early relapse showed a higher prevalence of the following adverse prognostic factors: pT4, pN3, pStage IV, poor differentiation, depth of invasion ≥ 10 mm, and extra-nodal extension. Multivariable analysis revealed that early relapse was an independent adverse prognostic factor for both 5-year DSS and OS (average hazard ratios [AHRs]: 3.24 and 3.91, respectively). In the PS-matched cohort, patients who experienced early relapse showed less favorable 5-year DSS: 58% versus 30%, p < 0.0001 (AHR: 3.10 [2.69 - 3.57]) and OS: 49% versus 22%, p < 0.0001 (AHR: 3.32 [2.89 - 3.81])., Conclusion: After adjustment for potential confounders and PS matching, early relapse was an adverse prognostic factor for survival outcomes in patients with OCSCC. Our findings may have significant implications for risk stratification., (© 2023. The Author(s).)

Objectives: Perineural invasion (PNI) was quantitatively analyzed in oral squamous cell carcinoma (OSCC) specimens obtained by radical surgery to correlate with survival outcomes. Methods: This is a retrospective study that reviewed the Cancer registry data between 2009 and 2015. Inclusion criteria were oral cavity cancer, treatment by radical surgery, presence of PNI, and available pathologic samples for S100 staining. Patients with M1 disease and those with synchronous or metachronous cancer during staging work-up were excluded. All pathologic samples were reviewed to confirm PNI status and processed by immunohistochemical staining for S100 to quantify PNI. Pathologic information and staging results were also reviewed, and clinical outcomes were analyzed. Results: The retrospective study included 92 patients; 63 had intratumoral PNI (IPNI) and 29 had extratumoral PNI (EPNI). The average number of PNI foci (APNI) was higher in the EPNI group than in the IPNI group (6.7 vs 3.8, t -test 2-tail significance  =  0.021). The 3-year overall survival (OS) and time-to-recurrence (TTR) rates of all patients were 82.5% and 81.2%, respectively. Univariate analysis showed that pathological T4 or N2-3 stage correlated with poor OS, whereas APNI ≥4 correlated with poor TTR. In multivariate analysis, only the pathological N2-3 stage was significantly correlated with poor OS, whereas only APNI ≥ 4 was an independent factor of poor TTR. The 3-year TTR rates were 92.4% and 65.6% for diseases with APNI < 4 and ≥ 4, respectively ( P   =  .008). Conclusions: In patients with OSCC with PNI, a greater amount of PNI identified by S100 staining indicated a poorer TTR regardless of stage and other prognostic factors. Quantification of PNI by S100 immunohistochemistry is a potential method for prognosis prediction.

Objectives: While the NCCN guidelines maintain that T4b oral cavity squamous cell carcinoma (OCSCC) should undergo either non-surgical treatments or clinical trials, promising outcomes of T4b OCSCC having surgical excision have been reported. We analyzed and compared the clinical outcomes of Taiwanese patients with pT4a and pT4b OCSCC who had undergone surgical treatment., Methods: From 2011 to 2017, a total of 4031 and 355 patients with first primary pT4a and pT4b OCSCC were identified. A propensity score (PS)-matched analysis of patients (n = 351 each) for pT4a and pT4b tumors was also performed., Results: The 5-year disease-specific and overall survival (DSS/OS) rates were more favorable in patients with pT4a than in those with pT4b OCSCC (64%/55%, p < 0.0001; 55%/43%, p < 0.0001, respectively). Compared with pT4a, those with pT4b tumors had a higher burden of the following risk factors: buccal/retromolar/hard palate subsite, male sex, depth ≥ 10 mm, and positive margins. Before PS matching, multivariable analyses revealed that pT4b tumors (versus pT4a) were an adverse prognosticator for both 5-year DSS and OS (hazard ratios: 1.32 and 1.39, respectively). However, in the PS-matched cohort, no significant differences in 5-year DSS and OS rates were observed between pT4a and pT4b OCSCC (57%/56%, p = 0.4024; 48%/44%, p = 0.1807, respectively) CONCLUSIONS: No significant outcome differences were evident between pT4b and pT4a OCSCC after PS matching. The most plausible hypothesis for the observed survival difference between T4a and T4b tumors is that it was driven by positive margins. We suggest that T4b OCSCC should undergo initial surgical excision if adequate resection is possible., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: pStage IVB oral cavity squamous cell carcinoma (OCSCC) is defined as either pT4b or pN3 disease. We sought to devise an improved prognostic stratification of this patient group., Methods: Between December 2003 and January 2018, we retrospectively reviewed the clinical records of 1331 consecutive patients with OCSCC who received tumor excision and neck dissection. The number of patients with pT4a/pT4b, pT1N3b/pT2N3b/pT3N3b/pT4N3b, and pStage IVA/IVB was 370/83, 3/49/42/142, and 332/295, respectively., Results: The 5-year rates of disease-free survival (DFS) and disease-specific survival (DSS) for patients with pT4a/pT4b disease were 64%/63% (p = 0.973) and 72%/69% (p = 0.672), respectively. The 5-year DFS and DSS rates for patients with pT1N3b/pT2N3b/pT3N3b/pT4N3b disease were 67%/65%/40%/42% (p < 0.001; pT1-2N3b versus pT3-4N3b, p = 0.002) and 100%/68%/45%/49% (p < 0.001; pT1-2N3b versus pT3-4N3b, p = 0.002), respectively. We devised a new definition for pStage IV by considering patients with pT4bN0-2 and pT1-2N3b diseases as pStage-IVA. The number of patients with pStage IVA/IVB (pT3-4N3b) was 443/184. The 5-year rates of AJCC pStage IVA/IVB and the newly proposed pStage IVA/IVB (pT3-4N3b) were as follows: DFS, 74%/52% and 72%/42%; DSS, 83%/58% and 81%/47%; respectively, all p value < 0.001., Conclusions: The clinical outcomes of pT4b and pT4a OCSCC are similar. However, patients with pT3-4N3b disease have a less favorable 5-year prognosis compared with cases with pT1-2N3b. In light of the unfavorable outcomes, pT3-4N3b disease should continue to be classified as pStage IVB. Conversely, pT4bN0-2 and pT1-2N3b diseases portend a less adverse prognosis and should therefore be downstaged to pStage IVA., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: This large-scale cohort study was designed to compare the clinical outcomes of Taiwanese patients with squamous cell carcinoma (SCC) of the upper versus lower gum., Methods: Between 2004 and 2017, we identified 4244 patients with first primary SCC of the gum (694 upper gum; 3550 lower gum) who were treated with surgery either with or without adjuvant therapy. Of them, 1990 patients (329 upper gum; 1661 lower gum) enrolled from 2011 to 2017 had a higher number of histopathological variables and entered subgroup analyses. Five-year disease-specific survival (DSS) and overall survival (OS) rates served as outcome measures., Results: The 5-year DSS and OS rates of patients with upper gum SCC were lower than those of cases with lower gum SCC (65%/74%, p < 0.0001; and 55%/65%, respectively, p < 0.0001). Compared with lower gum SCC, upper gum SCC had a higher prevalence of the following variables: female sex, age ≥ 65 years, pNx (without neck dissection), no-betel chewing (2011-2017), no-smoking (2011-2017), and margin status ≤ 4 mm (positive and close margins, 2011-2017). On multivariable analysis, gum subsite (upper versus lower), age (≥65 versus < 65 years), pT (T3 - 4 versus T1 - 2), pN (N1 - 3 versus N0/Nx), depth (≥10 mm versus < 10 mm, 2011-2017), ENE (present versus absent, 2011-2017), and margins (≤4 mm versus > 4 mm 2011-2017, only DSS) were identified as independent adverse prognostic factors for 5-year DSS and OS., Conclusions: Compared to lower gum SCC, upper gum SCC had less favorable 5-year outcomes. Wide resection margins are recommended to improve prognosis of upper gum SCC., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Studies addressing both lymphovascular invasion (LVI) and perineural invasion (PNI) in patients with esophageal squamous cell carcinoma (ESCC) treated with or without neoadjuvant therapy are limited. We aimed to analyze the incidence and prognostic significance of LVI and PNI in patients with thoracic ESCC., Methods: This retrospective study included 520 patients with ESCC: 174 patients after neoadjuvant treatment followed by surgery and 346 after primary esophagectomy, from two medical centers. The relationships between LVI, PNI, and other histological factors were evaluated. The Cox regression model was used for survival analysis., Results: Positive LVI and PNI were noted in 35.6% and 22.4% of patients with residual primary tumor after neoadjuvant treatment and in 39.6% and 24.0% of patients who underwent primary esophagectomy, respectively. In patients with neoadjuvant treatments, the 5-year overall survival rates were 12.7% and 28.3% in patients with positive LVI and negative LVI, respectively (p = 0.001). The 5-year overall survival rates were 6.4% and 29.9% in patients with positive PNI and negative PNI, respectively (p < 0.001). In patients who did not receive neoadjuvant treatment, the 5-year overall survival rates were 28.2% and 61.1% in patients with positive LVI and negative LVI, respectively (p < 0.001). The 5-year overall survival rates were 30.2% and 52.5% in patients with positive PNI and negative PNI (p < 0.001). In subgroup analysis, the presence of PNI was an independent prognostic factor in patients with neoadjuvant treatments, whereas the presence of LVI had more significant prognostic impact in patients with node-negative ESCC after primary esophagectomy., Conclusions: Both LVI and PNI statuses are significant prognostic factors for patients with ESCC. However, the prognostic impact of LVI was majorly in the subgroup of node-negative patients who received primary esophagectomy.

Background: According to the AJCC third to seventh edition staging manuals (1988-2010), the presence of through cortex and/or skin invasion in oral cavity squamous cell carcinoma (OCSCC) identifies T4a tumors. The AJCC eighth edition (2018) introduced a depth of invasion (DOI) > 20 mm as a criterion for pT4a. Subsequently, a revision maintained that tumors > 4 cm with a DOI > 10 mm should be classified as pT4a. We sought to analyze the prognostic impact of the three distinct criteria identifying pT4a disease., Methods: We examined 667 consecutive patients with pT3-4 buccal/gum/hard palate/retromolar SCC who underwent surgery between 1996 and 2016. pT1/pT2 (n = 108/359) disease were included for comparison purposes., Results: The 5-year outcomes of patients with pT1/pT2/without (n = 406)/with tumor > 4 cm/DOI > 10 mm (n = 261), pT1/pT2/DOI ≤ 20 mm (n = 510)/> 20 mm (n = 157), and pT1/pT2/without (n = 305)/with through cortex/skin invasion (n = 362) were as follows: disease-specific survival (DSS), 98%/89%/79%/65%, p < 0.001, 98%/89%/78%/59%, p < 0.001, and 98%/89%79%/69%, p < 0.001; overall survival (OS), 90%/79%/63%/51%, p < 0.001, 90%/79%/63%/42%, p < 0.001, and 90%/79%/65%/52%, p < 0.001. In pT3-4 disease, a tumor > 4 cm/DOI > 10 mm was an independent adverse prognosticator for 5-year DSS rate, DOI > 20 mm was an independent adverse prognosticator for 5-year DSS and OS rates, whereas through cortex/skin invasion independently predicted 5-year OS rates., Conclusions: All of the three criteria (tumor > 4 cm/DOI > 10 mm, DOI > 20 mm, and through cortex/skin invasion) identify high-risk patients, which should be reflected in further revisions of pT4a classification in OCSCC.

Background: The impact of pathological complete response after neoadjuvant chemoradiotherapy on survival of patients with squamous cell carcinoma of esophagus is still controversial. We retrospectively investigated the survival outcome in this group of patients., Methods: Ninety-eight patients with locally advanced squamous cell carcinoma of esophagus, who received neoadjuvant chemoradiotherapy were included in this retrospective analysis. Treatment protocols were radiotherapy with standard dose 50.4 Gy/28 fr, and chemotherapy with cisplatin 20 mg/m 2 and 5-FU 800 mg/m 2 for 4 days given on week 1 and 5. After neoadjuvant chemoradiotherapy is completed, patients who were eligible for surgery received surgery within 4-6 weeks. Patients who were not suitable for surgery were shifted to definite chemoradiotherapy. The primary end points were overall survival and progression-free survival., Results: Sixty-eight patients out of the ninety-eight patients received surgery after neoadjuvant chemoradiotherapy. There were 32 patients who achieved pathological complete response with a pCR rate of 47%. Thirty patients were shifted to definite concurrent chemoradiotherapy. The 2-year overall survival rate was 81.3% in the patients whose tumors showed a pCR and 58.3% in the patients with tumors that had a pathological partial response (p = 0.025). The 2-year overall survival in patients who received neoadjuvant chemoradiotherapy followed by surgery and definite chemoradiotherapy were 69.1% and 40.0%, respectively. There are 13 patients experienced grade 3-4 adverse event., Conclusion: Pathological complete response after neoadjuvant chemoradiotherapy is associated with a significant survival benefit in patients with locally advanced squamous cell carcinoma of esophagus. The toxicities related to neoadjuvant chemoradiotherapy were tolerable., (Copyright © 2017. Published by Elsevier Taiwan LLC.)

Background: The identification of extrinsic tongue muscle invasion in oral cavity cancer remains challenging. Notably, the most recent American Joint Committee on Cancer (AJCC 2017, 8th edition) staging manual indicates that extrinsic muscle invasion does not lead to the diagnosis of a T4 tumor. Because this approach carries the risk of tumor downstaging, we compared the clinical outcomes of patients with oral tongue squamous cell carcinoma (SCC) staged as pT3 vs. pT4 according to the AJCC 2010, 7th edition criteria., Methods: We retrospectively examined the records of consecutive patients with pT3 (n = 135) and pT4 (n = 68) tongue SCC who underwent radical surgery. Of the 68 pT4 tongue SCC, 63 (93%) had extrinsic muscle involvement alone. The 5-year locoregional control (LRC), distant metastasis (DM), and disease-free survival (DFS) rates served as outcome measures., Results: Compared with pT3 tongue SCC, pT4 patients presented significantly more frequently with pN2 disease, extranodal extension, poor tumor differentiation, tumor depth >15 and >20 mm, margin status ≤4 mm, perineural invasion, vascular invasion, and were more frequently treated with surgery plus concurrent chemoradiotherapy. Less favorable 5-year outcomes were observed in patients with pT4 than pT3 tumors (LRC 50 vs. 75%, p < 0.001; DM 27 vs. 14%, p = 0.013; DFS 43 vs. 69%, respectively, p < 0.001). We identified pT4 disease (vs. pT3) as an independent adverse prognostic factor for LRC and DFS., Conclusions: We suggest classifying patients with tongue SCC and extrinsic muscle invasion as having pT4 disease.

Background: The National Comprehensive Cancer Network guidelines recommend that patients with oral cavity squamous cell carcinoma (OSCC) and cT4b disease should be either included in clinical trials or treated with a nonsurgical approach. However, surgery may be feasible in selected patients with adequate safety margins. Using the nationwide Taiwanese Cancer Registry Database, we examined the prognosis of cT4b OSCC patients in relation to their treatment approach., Methods: Of the 18,910 patients with previously untreated first primary OSCC identified between 2004 and 2010, 492 (2.6 %) had cT4b tumors. Of them, 327 (66 %) received initial treatment with surgery, whereas 165 (34 %) were initially treated with a nonsurgical approach. Of the latter group, 78 patients subsequently underwent surgery. A 5-year disease-specific survival (DSS) ≥45 % was considered as a favorable outcome., Results: Better 5-year DSS and overall survival (OS) rates were observed in cT4b patients initially treated with surgery (vs. nonsurgery; DSS, 51 vs. 38 %; OS, 43 vs. 27 %, respectively, p < 0.001). Of the participants initially treated with surgery, patients with cN0-2 disease had better 5-year survival rates (DSS: cN0, 59 %; cN1, 53 %; cN2, 46 %; OS: cN0, 49 %; cN1, 50 %; cN2, 37 %) than those with cN3 disease (DSS: 0 %; OS: 0 %). Among cT4b patients who initially received a nonsurgical treatment, subjects who subsequently underwent surgery showed better outcomes., Conclusions: Primary surgery is performed in approximately two-thirds of cT4b OSCC patients, with cN0-2 cases showing a good prognosis. Patients who initially received a nonsurgical approach can subsequently be treated with surgery and achieve favorable outcomes.

Background: To investigate the association between the diagnosis-to-treatment interval (DTI) and overall survival (OS) in patients with oral cavity squamous cell carcinoma (OSCC)., Methods: A total of 18,677 patients with first primary OSCC identified in the Taiwanese Cancer Registry Database between 2004 and 2010 were examined. The effect of DTI on 5-year OS rates was investigated with multivariate Cox regression analysis. After the identification of the optimal cutoff for DTI based on the 5-year OS rates, DTI was classified in the following 20-day groups: ≤20 days (57% of the study patients), 21-45 days (34%), 46-90 days (6%) and ≥91 days (3%). In additional exploratory analyses, DTI was reclassified in the following 30-day interval groups: ≤30 days (81% of the study patients), 31-60 days (14%), 61-90 days (2%) and ≥91 days (3%)., Results: Multivariate analyses identified DTI (≤20 days versus other subgroups), sex (female versus male), age (<65 versus ≥65 years), clinical stage (p-stage I versus p-stage II, III, IV) and treatment modality (initial surgery versus initial non-surgery) as independent prognostic factors for 5-year OS. Compared with a DTI ≤20 days, the DTI categories ≥91 days (hazard ratio [HR]: 1.28, P < 0.001), 46-90 days (HR: 1.25, P < 0.001) and 21-45 days (HR: 1.07, P = 0.007) were independently associated with a higher risk of 5-year mortality. Similar results were obtained for DTI ≤30 days groups., Conclusions: DTI is independently associated with 5-year OS in OSCC patients. A DTI longer than 30 days or even 20 days may potentially decrease survival., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: The purpose of this study was to investigate whether multidisciplinary team care (MDTC) is associated with outcomes in oral cavity squamous cell carcinoma (SCC)., Methods: We retrospectively examined 1616 patients with oral cavity SCC who underwent radical surgery between 1996 and 2011. The study participants were classified into 2 subgroups according to the use of MDTC., Results: Five-year outcomes were significantly better in the MDTC group than in the no-MDTC group (neck control, 88% vs 84%, p = .0397; disease-specific survival [DSS], 83% vs 78%, p = .0114; and overall survival [OS], 70% vs 64%, p = .0002, respectively). Among patients who were scheduled to undergo adjuvant therapy, the number who completed their adjuvant treatment was significantly higher in the MDTC group than in the no-MDTC group (90% vs 60% to 70%, p < .001)., Conclusion: The association of MDTC with improved outcomes may be potentially explained by a better therapeutic alliance between the patient and the tumor board, and/or a greater thoroughness in clinical management. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1544-E1553, 2016., (© 2016 Wiley Periodicals, Inc.)

The aim of this study was to explore the incidence and outcomes of patients with oral cavity squamous cell carcinoma (OSCC) and fourth primary tumors (PTs) in a betel-chewing endemic area.We retrospectively examined the records of 1836 OSCC patients who underwent radical tumor resection between 1996 and 2014. The outcome measures included the incidence and number of multiple PTs, the main risk factors, and their associations with overall survival (OS).Of the 1836 patients, 1400 (76.3%) had a single PT, 344 (18.7%) a second PT, 67 (3.6%) a third PT, and 25 (1.4%) a fourth PT. Univariate analyses (log-rank test) identified the following factors as significantly associated with a fourth PT: simultaneous first and second PTs, betel quid chewing, buccal subsite, and pT3-4 status. After allowance for the potential confounding effect of other risk factors, all of these factors retained their independent prognostic significance in stepwise multivariate analyses, the only exception being betel chewing. The incidences of second, third, and fourth PTs at 5 and 10 years were 20.2%/34.6%, 4.0%/8.6%, and 1.0%/2.3%, respectively. The 5 and 10-year OS rates (calculated from the diagnosis of each PTs) for patients with a single, second, third, and fourth PTs were 68%/61%, 43%/37%, 45%/39%%, and 30%/30%, respectively (P < 0.0001). Among patients with a fourth PT, those who underwent radical surgery showed a significantly higher 3-year OS than those who did not (57% vs 13%; P = 0.0442).Fourth PTs are rarely observed in OSCC patients in a betel quid-chewing endemic area. Long-term survival rates of patients treated with radical surgery seems acceptable, being 4-fold higher than their counterparts., Competing Interests: This study did not receive any specific funding. The authors report no conflicts of interest.

An improved prognostic stratification of patients with oral cavity squamous cell carcinoma (OSCC) and pathologically positive (pN+) nodes is urgently needed. Here, we sought to examine whether an ultra-deep targeted sequencing (UDT-Seq) gene panel may improve the prognostic stratification in this patient group.A mutation-based signature affecting 10 genes (including genetic mutations in 6 oncogenes and 4 tumor suppressor genes) was devised to predict disease-free survival (DFS) in 345 primary tumor specimens obtained from pN+ OSCC patients. Of the 345 patients, 144 were extracapsular spread (ECS)-negative and 201 were ECS-positive. The 5-year locoregional control, distant metastases, disease-free, disease-specific, and overall survival (OS) rates served as outcome measures.The UDT-Seq panel was an independent risk factor (RF) for 5-year locoregional control (P = 0.0067), distant metastases (P = 0.0001), DFS (P < 0.0001), disease-specific survival (DSS, P < 0.0001), and OS (P = 0.0003) in pN+ OSCC patients. The presence of ECS and pT3-4 disease were also independent RFs for DFS, DSS, and OS. A prognostic scoring system was formulated by summing up the significant covariates (UDT-Seq, ECS, pT3-4) separately for each survival endpoint. The presence of a positive UDT-Seq panel (n = 77) significantly improved risk stratification for all the survival endpoints as compared with traditional AJCC staging (P < 0.0001). Among ECS-negative patients, those with a UDT-Seq-positive panel (n = 31) had significantly worse DFS (P = 0.0005) and DSS (P = 0.0002). Among ECS-positive patients, those with a UDT-Seq-positive panel (n = 46) also had significantly worse DFS (P = 0.0032) and DSS (P = 0.0098).Our UDT-Seq gene panel consisting of clinically actionable genes was significantly associated with patient outcomes and provided better prognostic stratification than traditional AJCC staging. It was also able to predict prognosis in OSCC patients regardless of ECS presence.

Objectives: 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., Methods: 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., Results: 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)., Conclusion: OSCC patients with neck nodal ECS and esophageal cancer or hepatocellular carcinoma as SSPT have a dismal short-term prognosis.

Background: The fibula osteoseptocutaneous free flap is generally used for segmental mandibular reconstructions following resection of oral cavity squamous cell carcinoma (OSCC). However, less complex reconstructions may be feasible for patients with predicted poor survival. Herein, we sought to identify the main risk factors (RFs) associated with poor prognosis in OSCC patients undergoing segmental mandibulectomy to help decide between fibular and non-fibular reconstructions., Methods: Between 1996 and 2011, we examined the 5-year control, distant metastases, and survival rates in 310 consecutive, previously untreated patients with primary OSCC who underwent segmental mandibulectomy., Results: Margin status was the only independent RF for 5-year local control. Level IV/V metastases, extracapsular spread, and tumor depth ≥15 mm were independent RFs for poor 5-year survival. In the entire study cohort, 23% of the patients had 2 or 3 adverse RFs; such a high-risk group was characterized by a poor prognosis and may be suitable for non-fibular reconstructions. Overall, 70% of the study patients were cT1-4N0, cT1N2, cT2N1, or had tumor depth <15 mm; less than 5% of patients in this subgroup had 2 or 3 adverse RFs and were thus candidates for fibular reconstructions. Among the remaining 30% of patients who showed both advanced clinical stage (cT2N2, cT3-4N1-2) and tumor depth ≥15 mm, 70% exhibited 2 or 3 adverse RFs., Conclusions: Level IV/V metastases, extracapsular spread, and tumor depth ≥15 mm were independent predictors of poor prognosis in OSCC patients undergoing segmental mandibulectomy. The preoperative or intraoperative identification of adverse RFs may help decide between fibular and non-fibular mandibular reconstruction. High-risk patients bearing 2 or 3 adverse RFs have poor prognosis and should not be considered as candidates for fibular reconstructions.

Objectives: We have previously shown that the resection outcomes of cT4a and cT4b oral cavity squamous cell carcinoma (OSCC) are comparable, but whether similar conclusions can be applied for the pathological stage of this disease needs investigation. In this study, we sought to compare the outcomes and to identify the risk factors for both pT4a and pT4b tumors., Methods: We retrospectively examined 181 pT4 OSCC patients who had radical resections between 2003 and 2010. The 5-year control and survival rates were the main outcome measures., Results: Of the 181 resected pT4 OSCC patients, 133 (73%) had pT4a disease, and 48 (27%) had pT4b disease. All of the resected T4b tumors were below the mandibular notch (infra-notch pT4b). The 5-year outcomes of the patients with infra-notch pT4b and pT4a were comparable: local control, 80% vs. 78%, p=0.7275; neck control, 87% vs. 82%, p=0.4798; distant metastases, 22% vs. 23%, p=0.8871; disease-free survival, 63% vs. 55%, p=0.2813; disease-specific survival, 68% vs. 60%, p=0.3526; and overall survival, 62% vs. 44%, p=0.2643, respectively. Extracapsular spread was the only independent prognostic factor for 5-year survival rates in pT4a patients. Poor tumor differentiation and pN2 status were the independent 5-year survival prognostic factors for the infra-notch pT4b tumor patients., Conclusions: Infra-notch pT4b had outcomes comparable with those of pT4a tumors, although they displayed different risk factors. We therefore recommend that resectable infra-notch pT4b tumors should be classified as pT4a disease in the AJCC tumor staging., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

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.

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.

Our aim was to retrospectively assess the diagnostic performance from combined positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) for the detection of bone marrow invasion of the mandible or maxilla in patients with oral cavity squamous cell carcinoma (OCSCC). A total of 114 patients with OCSCC, arising from or abutting the upper or lower alveolar ridge, underwent staging PET/CT and MRI studies before surgery. The possibility of bone marrow invasion on PET/CT and MRI was graded retrospectively on a 5-point score. Histopathology was taken as the reference standard. Sensitivity, specificity, predictive values and likelihood ratios were calculated. Clinical factors affecting the performance, like tumor origin and dentate status were also explored. PET/CT was found to be more specific than MRI (83% vs. 61%, respectively, p=0.0015) but less sensitive (78% vs. 97%, respectively, p=0.0391). Dentate status and tumor origin affected the diagnostic performance of PET/CT. In patients with positive MRI, sensitivity and specificity of PET/CT were 78% and 100% in dentate patients with alveolar ridge tumors, 75% and 80% in dentate patient with buccal tumors, 90% and 33% in edentulous patients with alveolar ridge tumors and 0% and 63% for edentulous patients with buccal tumors, respectively. PET/CT is more specific than MRI and can be used to complement the role of MRI. A negative MRI result can confidently exclude the presence of bone marrow invasion, while in patients with positive MRI findings, a negative PET/CT may be useful to rule out bone marrow invasion in dentate patients., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Unlabelled: We prospectively evaluated the sensitivity and specificity of (18)F-FDG PET in the detection of neck lymph node metastases in patients with oral cavity squamous cell carcinoma (OSCC). We also sought to evaluate whether pretreatment PET visual scores in the neck lymph nodes may improve risk stratification., Methods: We enrolled 473 OSCC patients (445 men and 28 women; mean age ± SD, 50.9 ± 11.7 y) without distant metastases. All participants underwent (18)F-FDG PET within 2 wk before surgery and neck dissection. Histopathology was taken as the reference standard for neck lymph node status. The duration of follow-up was at least 24 mo in all surviving patients., Results: (18)F-FDG PET correctly diagnosed 164 of 211 patients with neck metastases and 152 of 262 subjects without pathologic neck metastases, resulting in a patient-based sensitivity and specificity of 77.7% and 58.0%, respectively. In Cox models adjusting for age, sex, traditional risk factors, and treatment modality, PET results at the neck lymph nodes were significantly and independently associated with rates of neck control, distant metastasis, disease-free survival, disease-specific survival, and overall survival. Notably, the results of the c-statistics demonstrated that PET score improved the accuracy of risk prediction in terms of overall and disease-free survival rates., Conclusion: PET findings at the neck lymph nodes have limited sensitivity and specificity for primary staging of OSCC but improve risk stratification beyond that of traditional risk factors.

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.

Purpose: A better understanding of the prognostic factors in oral cavity squamous cell carcinoma (OSCC) may optimize the therapeutic approach. In this study, we sought to investigate whether the combination of clinical information, pathologic results, and preoperative maximal standardized uptake value (SUVmax) at the primary tumor and regional lymph nodes might improve the prognostic stratification in this patient group., Methods and Materials: A total of 347 consecutive OSCC patients were investigated. All participants underwent fluorodeoxyglucose-positron emission tomography within 2 weeks before surgery and neck dissection. The duration of follow-up was at least 24 months in all surviving patients. The optimal cutoff values for SUVmax at the primary tumor (SUVtumor-max) and regional lymph nodes (SUVnodal-max) were selected according to the 5-year disease-free survival (DFS) rate. Independent prognosticators were identified by Cox regression analysis., Results: In multivariate analysis, a cutoff SUVtumor-max of 8.6, a cutoff SUVnodal-max of 5.7, and the presence of pathologic lymph node metastases were found to be significant prognosticators for the 5-year DFS. A scoring system using these three prognostic factors was formulated to define distinct prognostic groups. The 5-year rates for patients with a score between 0 and 3 were as follows: neck control, 94%, 86%, 77%, 59% (p < 0.0001); distant metastases, 1%, 7%, 22%, 47% (p < 0.0001); disease-specific survival, 93%, 85%, 61%, 36%, respectively (p < 0.0001)., Conclusion: Based on the study findings, the combined evaluation of pathologic node status and SUVmax at the primary tumor and regional lymph nodes may improve prognostic stratification in OSCC patients., (Copyright 2010 Elsevier Inc. All rights reserved.)

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.

Purpose: Survival in oral cavity squamous cell carcinoma (OSCC) depends heavily on locoregional control. In this prospective study, we sought to investigate whether preoperative maximum standardized uptake value of the neck lymph nodes (SUVnodal-max) may predict prognosis in OSCC patients., Methods and Materials: A total of 120 OSCC patients with pathologically positive lymph nodes were investigated. All subjects underwent a [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) scan within 2 weeks before radical surgery and neck dissection. All patients were followed up for at least 24 months after surgery or until death. Postoperative adjuvant therapy was performed in the presence of pathologic risk factors. Optimal cutoff values of SUVnodal-max were chosen based on 5-year disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS). Independent prognosticators were identified by Cox regression analysis., Results: The median follow-up for surviving patients was 41 months. The optimal cutoff value for SUVnodal-max was 5.7. Multivariate analyses identified the following independent predictors of poor outcome: SUVnodal-max >or=5.7 for the 5-year neck cancer control rate, distant metastatic rate, DFS, DSS, and extracapsular spread (ECS) for the 5-year DSS and OS. Among ECS patients, the presence of a SUVnodal-max >or=5.7 identified patients with the worst prognosis., Conclusion: A SUVnodal-max of 5.7, either alone or in combination with ECS, is an independent prognosticator for 5-year neck cancer control and survival rates in OSCC patients with pathologically positive lymph nodes.

Purpose: The pathologic tumor depth is an independent prognosticator for local control (LC) and survival in patients with oral cavity squamous cell carcinoma (OSCC). We sought to investigate the prognostic value of the preoperative maximal standardized uptake value (SUVmax) at the primary tumor in OSCC patients with pathologically positive lymph nodes., Methods and Materials: A total of 109 OSCC patients with pathologically positive lymph nodes were investigated. All patients underwent 2-deoxy-2[(18)F]fluoro-d-glucose-positron emission tomography within 2 weeks before surgery and neck dissection. All patients were followed for >or=24 months after surgery or until death. The optimal cutoff value for the primary tumor SUVmax was selected according to the 5-year LC rate. Independent prognosticators were identified by Cox regression analysis., Results: The median follow-up for all patients was 26 months (39 months for surviving patients). A cutoff SUVmax of 19.3 provided the greatest prognostic information for the 5-year LC rate (55% vs. 88%, p = 0.0135). A tumor depth >or=12 mm appeared to be the most appropriate cutoff for predicting the 5-year LC rate (76% vs. 95%, p = 0.0075). A scoring system using the primary tumor SUVmax and tumor depth was formulated to define distinct prognostic groups. Patients with both a SUVmax of >or=19.3 and tumor depth of >or=12 mm (n = 8) had significantly poorer 5-year LC, 5-year disease-free, 5-year disease-specific, and 5-year overall survival rates compared with the other patient groups., Conclusion: The combination of the primary tumor SUVmax (>or=19.3) and pathologic tumor depth (>or=12 mm) identified a subgroup of OSCC patients at greatest risk of poor LC and death.

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.

Background: The role of cheek skin excision in patients with squamous cell carcinoma of the buccal mucosa (BSCC) remains controversial. We sought to investigate when skin excision is needed to achieve an adequate local control., Methods: A total of 331 patients with BSCC were reviewed. Skin preservation was pursued when the distance between the tumor and the skin as determined by imaging was >or=13 mm (1 cm surgical margin plus 0.3 cm skin preservation). Two hundred and thirty patients (69.5%) underwent skin excision. Postoperative adjuvant radiotherapy (n = 182) was performed in patients with pathological T4 disease, metastases in cervical lymph nodes or close pathological margins (

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.

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.

Background: Relapse of tumors in patients with oral cavity squamous cell carcinoma (OSCC) is associated with a poor prognosis. In addition, salvage therapy may be a significant source of morbidity in patients with relapsing OSCC. The objective of the current study was to determine prognostic factors that predict which patients may benefit from such treatment., Methods: From 953 patients who underwent primary radical surgery between 1996 and 2005, 272 patients with early-relapsed OSCC (n = 161) or late-relapsed OSCC (n = 111) were identified. The optimum cutoff point for relapse was chosen on the basis of 5-year disease-specific survival (DSS) and overall survival (OS)., Results: The optimal cutoff value for relapse was 10 months. Late relapses were associated with a better prognosis than relapses that occurred within the first 10 months (P < .0001 for both 5-year DSS and 5-year OS). Among patients with early-relapsed OSCC, a primary tumor depth <10 mm was associated significantly and independently with a better 5-year DSS (P = .014) and OS (P = .011). Among patients with late-relapsed OSCC, neck recurrence was a significant risk factor for adverse outcomes (P < .001 for both 5-year DSS and 5-year OS)., Conclusions: A late relapse was associated with better survival than a relapse that occurred within the first 10 months. Patients with late-relapsed OSCC may benefit from salvage therapy, especially those who have a local recurrence. Among patients with early-relapsed OSCC, salvage therapy should be considered for those who have a primary tumor depth <10 mm., (2007 American Cancer Society)

Background: The number of patients with oral cavity squamous cell carcinoma (OSCC) is increasing. Because the characteristics of patients with OSCC who develop distant metastases (DM) remain uncertain, the authors analyzed potential risk factors., Methods: For this report, the authors retrospectively reviewed data from 889 consecutive patients with OSCC who underwent radical surgery from January 1996 to November 2004. Patients were divided into 2 groups according to whether they had either achieved locoregional control (Group A; n = 678 patients) or developed a locoregional recurrence (Group B; n = 211 patients). Cox proportional-hazards models were used to identify independent predictors of the 5-year DM rate., Results: In the entire study cohort, the 5-year DM rate was 9.6% (6.6% for Group A and 21.4% for Group B). In Group A, the number of positive lymph nodes (> or =5; P = .009) and the presence of extracapsular spread (ECS) (P < .001) were independent risk factors for DM. In Group B, the presence of ECS (P = .008), poor differentiation (P = .040), pathological stage > or =III (P = .036), and the presence of neck recurrence (P = .001) were independent prognosticators., Conclusions: The current results indicated that different risk factor categories according to locoregional control may be used to facilitate the selection of appropriate management for patients with OSCC after they undergo radical surgery.

We report the incidence, risk factor(s), and overall survival (OS) of second/multiple primary tumors (SPTs/MPTs) in oral cavity squamous cell carcinoma (OSCC) patients in betel quid chewing areas. Of 816 untreated OSCC patients who had radical surgery, 15.7% had either synchronous or metachronous SPTs. The SPTs (70.3%) were at the oral cavity. SPTs (18.8%) developed third primary tumors, with a significantly higher incidence in synchromous than metachronous SPTs (p=0.001). An optimal, but significantly lower, 5-year OS was observed in patients with SPTs/MPTs than without (54.0% vs. 67.2%, p=0.0195). By multivariate analyses, OSCC sub-sites (p=0.006) and lymphatic permeation (p=0.040) were independent risk factors for SPT rate. A significantly higher 5-year OS was observed in SPT patients receiving a second radical surgery at the oral cavity/soft palate than patients that did not (p=0.0001). A good survival rate can be obtained for OSCC patients with resectable SPTs/MPTs.

Background: According to the American Joint Commission on Cancer (AJCC, 5(th) edition) classification system, pT4 N0 oral cavity squamous cell carcinoma (OSCC) qualifies for stage IVA status, with its implied poor prognosis. However, preliminary observations suggested that patients with pT4 N0 OSCC might have better survival than other stage IVA categories. The authors sought to identify accurate prognosticators in patients with stage III/IVA OSCC., Methods: The authors retrospectively reviewed 513 consecutive patients with stage III/IVA OSCC who were undergoing radical surgery. Survival was plotted by Kaplan-Meier analysis., Results: One hundred seventy-eight patients were in stage III, and 335 were in stage IVA. The 335 stage IVA patients were divided into pT4 N0 (n = 105) and pT4 N1/TAny N2 (NO pT4 N0 M0, n = 230). By univariate analysis, 5-year neck control rates (P < .0001), distant metastases (P < .0001), disease-free survival rates (P < .0001), and overall survival rates (P < .0001) were significantly different in pT4 N0 compared with NO pT4 N0 patients. No significant difference in survival between pT4 N0 stage IVA and pstage III could be shown. Multivariate analysis for overall survival demonstrated that the following factors were independently associated with pT4 N0: tumor depth >or=35 mm, vessel invasion, lymph invasion, and perineural invasion. In contrast, tumor depth >or=25 mm, treatment with surgery alone, poor differentiation, extracapsular spread, and pathological nodal metastases (>or=8 lymph nodes) were independent predictors of overall survival in NO pT4 N0., Conclusions: In patients with stage IVA OSCC (AJCC, 1997), the survival rates for pT4 N0 are better than those for NO pT4 N0 and similar to those of patients with pstage III., ((c) 2007 American Cancer Society.)

The objective of this study was to understand if the age of the patient at onset of tongue cancer was an adverse factor for patient survival and distant metastasis (DM). Data were collected from a retrospective database (January 1996-June 2003, n=296). Local control rates, neck control rates, DM rates, and survival curves were assessed by the Kaplan-Meier method. Prognostic variables were assessed by the log-rank test and Cox proportional hazards regression method. For the young group (40 years, n=220). No significant differences were seen in 5-year local and neck controls, disease-free, disease-specific and overall survivals between these two groups. We concluded that being