Comparing the clinical outcomes of initial surgery and primary definitive radiotherapy with a dosage of 6600 cGy or higher in cT1-2N0M0 oral cavity squamous cell carcinoma: A nationwide cohort study.

BACKGROUND: To compare the clinical outcomes of two treatment modalities, initial surgery and primary definitive radiotherapy (RT), in Taiwanese patients diagnosed with cT1-2N0M0 oral cavity squamous cell carcinoma (OCSCC). METHODS: Between 2011 and 2019, we analyzed data for 13,542 cT1-2N0M0 patients who underwent initial surgery (n = 13,542) or definitive RT with a dosage of at least 6600 cGy (n = 145) for the treatment of OCSCC. To account for baseline differences, we employed propensity score (PS) matching, resulting in two well-balanced study groups (initial surgery, n = 580; definitive RT, n = 145). RESULTS: Before PS matching, the 5-year disease-specific survival (DSS) rates were 88% for the surgery group and 58% for the RT group. After PS matching, the 5-year DSS rates of the two groups were 86% and 58%, respectively. Similarly, the 5-year overall survival (OS) rates before PS matching were 80% for the surgery group and 36% for the RT group, whereas after PS matching, they were 73% and 36%, respectively. All these differences were statistically significant (p < 0.0001). A multivariable analysis identified treatment with RT, older age, stage II tumors, and a higher burden of comorbidities as independent risk factors for both DSS and OS. We also examined the 5-year outcomes for various subgroups (margin ≥5 mm, margin <5 mm, positive margins, RT combined with chemotherapy, and RT alone) as follows: DSS, 89%/88%/79%/63%/51%, respectively, p < 0.0001; OS, 82%/79%/68%/39%/32%, respectively, p < 0.0001. CONCLUSIONS: In Taiwanese patients with cT1-2N0M0 OCSCC, a remarkably low proportion (1.1%) completed definitive RT. A significant survival disparity of 30% was observed between patients who underwent initial surgery and those who received definitive RT. Interestingly, even patients from the surgical group with positive surgical margins exhibited a significantly superior survival compared to those in the definitive RT group.

Should sub-millimeter margins be deemed positive in oral cavity squamous cell carcinoma?

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.

Is elective neck dissection justified in cT2N0M0 oral cavity cancer defined according to the AJCC eighth edition staging system?

BACKGROUND: The current NCCN guidelines recommend considering elective neck dissection (END) for early-stage oral cavity squamous cell carcinoma (OCSCC) with a depth of invasion (DOI) exceeding 3 mm. However, this DOI threshold, determined by evaluating the occult lymph node metastatic rate, lacks robust supporting evidence regarding its impact on patient outcomes. In this nationwide study, we sought to explore the specific indications for END in patients diagnosed with OCSCC at stage cT2N0M0, as defined by the AJCC Eighth Edition staging criteria. METHODS: We examined 4723 patients with cT2N0M0 OCSCC, of which 3744 underwent END and 979 were monitored through neck observation (NO). RESULTS: Patients who underwent END had better 5-year outcomes compared to those in the NO group. The END group had higher rates of neck control (95% vs. 84%, p < 0.0001), disease-specific survival (DSS; 87% vs. 84%, p = 0.0259), and overall survival (OS; 79% vs. 73%, p = 0.0002). Multivariable analysis identified NO, DOI ≥5.0 mm, and moderate-to-poor tumor differentiation as independent risk factors for 5-year neck control, DSS, and OS. Based on these prognostic variables, three distinct outcome subgroups were identified within the NO group. These included a low-risk subgroup (DOI <5 mm plus well-differentiated tumor), an intermediate-risk subgroup (DOI ≥5.0 mm or moderately differentiated tumor), and a high-risk subgroup (poorly differentiated tumor or DOI ≥5.0 mm plus moderately differentiated tumor). Notably, the 5-year survival outcomes (neck control/DSS/OS) for the low-risk subgroup within the NO group (97%/95%/85%, n = 251) were not inferior to those of the END group (95%/87%/79%). CONCLUSIONS: By implementing risk stratification within the NO group, we found that 26% (251/979) of low-risk patients achieved outcomes similar to those in the END group. Therefore, when making decisions regarding the implementation of END in patients with cT2N0M0 OCSCC, factors such as DOI and tumor differentiation should be taken into account.

Fibula Jaw-during-Admission.

BACKGROUND: Fibula Jaw-in-a-Day (JIAD) is considered the most advanced approach for segmental mandibular defect reconstruction and dental rehabilitation. However, it has limitations and challenges for further pursuit. We propose Fibula Jaw-during-Admission (JDA) as a solution. MATERIALS AND METHODS: From 2019 to 2021, six patients received fibula "Jaw-during-Admission." Segmental mandibulectomy, fibula transfer, and immediate dental implantation were performed simultaneously during a single surgery. Intraoral scans were used to fabricate temporary light occlusion contact dental prostheses while on the ward prior to discharge during the first and second week post operation. The prostheses were installed before discharge and changed to permanent ones with normal occlusal contact in the clinic at about six months after X-ray confirmation of bone healing. RESULTS: All six surgeries succeeded. Four patients received palatal muco-periosteal graft after debridement of peri-implant overgrown granulation tissue. Follow-up ranged from 12 to 34 months (average 21.2 months) and revealed good function and appearance in all patients. CONCLUSION: Fibula JDA is superior to the Fibula JIAD approach for simultaneous mandibular reconstruction with fibula and dental rehabilitation. There is no need for postoperative intermaxillary fixation. The surgery can be performed more reliably with less stress. It provides an additional opportunity for dental rehabilitation if initial dental prosthesis installation during JIAD fails. Postreconstruction intraoral scans provide greater precision and more flexibility in milling dental prosthesis which are mapped to the reconstructed mandible during the postoperative period.

Indications for elective neck dissection in cT1N0M0 oral cavity cancer according to the AJCC eight edition: A nationwide study.

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.

Early relapse is an adverse prognostic factor for survival outcomes in patients with oral cavity squamous cell carcinoma: results from a nationwide registry study.

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.

Optimizing margin status for improving prognosis in patients with oral cavity squamous cell carcinoma: A retrospective study from the two highest-volume Taiwanese hospitals.

Background: In the treatment of oral cavity squamous cell carcinoma (OCSCC), surgical quality measures which are expected to affect outcomes, including the achievement of a clear margin, are surgeon-dependent but might not be invariably associated with hospital volume. Our objective was to explore surgical margin variations and survival differences of OCSCC between two highest-volume hospitals in Taiwan. Materials and methods: A total of 2009 and 1019 patients with OCSCC who were treated at the two highest-volume Taiwanese hospitals (termed Hospital 1 and Hospital 2, respectively) were included. We examined how a pathological margin <5 mm impacted patient outcomes before and after propensity score (PS) matching. Results: The prevalence of margins <5 mm was markedly lower in Hospital 1 than in Hospital 2 (34.5%/65.2%, p<0.0001). Compared with Hospital 2, tumor severity was higher in Hospital 1. On univariable analysis, being treated in Hospital 2 (versus Hospital 1; hazard ratio [HR] for 5-year disease-specific survival [DSS] = 1.34, p=0.0002; HR for 5-year overall survival [OS] = 1.17, p=0.0271) and margins <5 mm (versus ≥5 mm; HR for 5-year DSS = 1.63, p<0.0001; HR for 5-year OS = 1.48, p<0.0001) were identified as adverse factors. The associations of treatment in Hospital 2 and margins <5 mm with less favorable outcomes remained significant after adjustment for potential confounders in multivariable analyses, as well as in the PS-matched cohort. The 5-year survival differences between patients operated in Hospital 1 and Hospital 2 were even more pronounced in the PS-matched cohort (before PS matching: DSS, 79%/74%, p=0.0002; OS, 71%/68%, p=0.0269; after PS matching: DSS, 84%/72%, p<0.0001; OS, 75%/66%, p<0.0001). In the entire cohort, the rate of adjuvant therapy was found to be lower in patients with margins ≥5 mm than in those with margins <5 mm (42.7%/57.0%, p<0.0001). Conclusions: Within the two highest-volume hospitals in Taiwan, patients with OCSCC with a clear margin status (≥5 mm) achieved more favorable outcomes. These results have clinical implications and show how initiatives aimed at improving the margin quality can translate in better outcomes. A clear margin status can reduce the need for adjuvant therapy, ultimately improving quality of life.

Towards an Improved Pathological Node Classification for Prognostic Stratification of Patients With Oral Cavity Squamous Cell Carcinoma: Results From a Nationwide Registry Study.

Background: To assess the prognostic significance of different nodal parameters [i.e., number of pathologically positive nodes, log odds of positive lymph nodes, lymph node ratio (LNR), and extra-nodal extension (ENE)] in Taiwanese patients with oral cavity squamous cell carcinoma (OCSCC), and to devise an optimized pN classification system for predicting survival in OCSCC. Methods: A total of 4287 Taiwanese patients with first primary OCSCC and nodal metastases were enrolled. Cox proportional hazards regression analysis with the spline method was applied to identify the optimal cut-off values for LNR, log odds of positive lymph nodes, and number of pathologically positive nodes. Results: On multivariable analysis, we identified a LNR ≥0.078/0.079, the presence of at least three pathologically positive nodes, and ENE as independent prognosticators for 5-year disease-specific survival (DSS) and overall survival (OS) rates. We therefore devised a four-point prognostic scoring system according to the presence or absence of each variable. The 5-year DSS and OS rates of patients with scores of 0-3 were 70%/62%/50%/36% (p <0.0001) and 61%/52%/40%25%, respectively (p <0.0001). On analyzing the AJCC 2017 pN classification, patients with pN3a displayed better survival rates than those with pN2 disease. The 5-year DSS and OS rates of patients with pN1/pN2/pN3a/pN3b disease were 72%/60%/67%/43% (p <0.0001) and 63%/51%/67%/33%, respectively (p <0.0001). Conclusions: Three nodal parameters (i.e., a LNR ≥0.078/0.079, the presence of at least three pathologically positive nodes, and ENE) assessed in combination provided a better prognostic stratification than the traditional AJCC pN classification.

Clinical outcomes of patients with pT4a and pT4b oral cavity squamous cell carcinoma who had undergone surgery: Results from a Taiwanese registry-based, nationwide cohort study.

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.

Improved prognostic stratification of patients with pN3b oral cavity cancer based on maximum standardized uptake value of metastatic nodes, lymph node ratio, and level of cervical nodal metastases.

OBJECTIVES: The prognosis of pN3b oral cavity squamous cell carcinoma (OCSCC) remains heterogeneous. We sought to improve the prognostic stratification of patients with pN3b OCSCC through a combined analysis of FDG-PET parameters and clinicopathological risk factors (RFs). METHODS: From 2001 to 2019, complete data on maximum standardized uptake values derived from FDG-PET of neck metastatic nodes (SUV-nodal-max) and clinicopathological RFs were available for 257 patients with pN3b disease. RESULTS: Using the 5-year disease-free survival (DFS) as the outcome of interest, the optimal cutoff points for SUV-nodal-max and lymph node ratio (LNR) were 15.9 and 0.17, respectively. The 5-year DFS rates/(number of cases) for patients with pN3b disease were as follows: SUV-nodal-max < 15.9 versus ≥ 15.9, 49%(226)/21%(31), p = 0.000003; LNR < 0.17 versus ≥ 0.17, 49%(230)/17%(27), p = 0.000117; absence versus presence of neck level IV/V metastases, 49%(230)/15%(27), p = 0.000004. Multivariable analyses revealed that SUV-nodal-max ≥ 15.9, LNR ≥ 0.17, and level IV/V metastases were independent prognosticators for 5-year distant metastases (DM), DFS, disease-specific survival (DSS), and overall survival (OS) rates. Based on these variables, we devised a scoring system that identified three distinct prognostic subgroups at low (score 0, n = 190), intermediate (score 1, n = 51), and high (scores 2-3, n = 16) risk. The 5-year rates of patients with pN3b disease deemed to be at low/intermediate/high risk were as follows: DM, 31%/52%/89%; DFS, 54%/26%/0%; DSS, 59%/36%/8%; OS, 42%/31%/6%, respectively; all p < 0.001. CONCLUSIONS: A scoring system based on SUV-nodal-max, LNR, and level IV/V metastases improves the prognostic stratification of OCSCC patients with pN3b disease.

cN+pN0 disease does not portend a less favorable prognosis compared with cN0pN0 in patients with resected oral cavity squamous cell carcinoma.

BACKGROUND: We compared the clinical outcomes of patients with oral cavity squamous cell carcinoma (OCSCC) with cN+pN0 versus cN0pN0 disease. METHODS: A total of 1309 OCSCC patients with pN0 disease were included. Of them, 1019 and 290 cases had cN0pN0 and cN+pN0 disease, respectively. For comparison purposes, we also examined 799 patients with pN+disease (cN0pN+/cN+pN+, n = 239/560). Subgroup analysis was performed in a propensity score-matched cohort with cN0pN0 and cN+pN0 disease (n = 284 each). RESULTS: Compared with cN0pN0, patients with cN+pN0 had a higher prevalence of the following variables: betel chewing, pT3-4, depth ≥10 mm, perineural invasion, and treatment with surgery and adjuvant therapy. The prognosis of patients with cN+pN0 (mean: 52 nodes) and cN0pN0 (mean: 39 nodes) disease was similar both in the original cohort and after propensity score matching. However, the 5-year outcomes were more favorable for cN+pN0/cN0pN0 compared with cN0pN+/cN+pN+ (local control, 88%/88%/83%/81%; neck control, 94%/93%/82%/76%; distant metastases, 4%/3%/13%/31%; disease-free survival, 84%/83%/68%/52%; disease-specific survival, 92%/92%/77%/57%; overall survival, 81%/82%/59%/42%; all p values <0.001; cN+pN0 versus cN0pN0, all p values >0.05). cN+pN0 disease (vs. cN0pN0) was not significantly associated with local control, neck control, distant metastases, and survivals either in univariable or multivariable analyses. CONCLUSIONS: Despite a higher risk factor burden, the prognosis of patients with cN+pN0 disease did not differ from that of cases with cN0pN0. The higher nodal yield and the more frequent use of adjuvant therapy in cN+pN0 disease may explain the lack of significant differences in terms of neck control compared with cN0pN0 disease.

Poor tumor differentiation is an independent adverse prognostic variable in patients with locally advanced oral cavity cancer--Comparison with pathological risk factors according to the NCCN guidelines.

METHODS: We sought to compare the prognostic impact of tumor differentiation with respect to adverse risk factors (RFs) identified by the National Comprehensive Cancer Network (NCCN) guidelines--including extranodal extension (ENE), positive/close margins, perineural invasion, lymphatic invasion, and vascular invasion--in patients with locally advanced oral cavity squamous cell carcinoma (OCSCC). RESULTS: Between 1996 and 2018, 1179 consecutive patients with first primary pT3-4 OCSCC were included. A three-level grading system was adopted--in which the final classification was assigned according to the most prevalent tumor grade. We identified 382/669/128 patients with well/moderately/poorly differentiated tumors, respectively. Compared with well/moderately differentiated tumors, poorly differentiated OCSCC had a higher prevalence of the following variables: female sex (4%/6%/11%), ENE, (14%/36%/61%), positive margins (0.5%/2%/4%), close margins (10%/14%/22%), perineural invasion (22%/50%/63%), lymphatic invasion (2%/9%/17%), vascular invasion (1%/4%/10%), and adjuvant therapy (64%/80%/87%). The 5-year rates of patients with well/moderately/poorly differentiated OCSCC were as follows: local control (LC, 85%/82%/84%, p = 0.439), neck control (NC, 91%/83%/70%, p < 0.001), distant metastases (DM, 6%/18%/40%, p < 0.001), disease-free survival (DFS, 78%/63%/46%, p < 0.001), disease-specific survival (DSS, 85%/71%/49%, p < 0.001), and overall survival (OS, 68%/55%/39%, p < 0.001). Multivariable analysis identified the following variables as independent prognosticators for 5-year outcomes: ENE (LC/NC/DM/DFS/DSS/OS), poorly differentiated tumors (NC/DM/DFS/DSS/OS), positive margins (LC/DFS), lymphatic invasion (DFS/DSS/OS), perineural invasion (DM), and age ≥65 years (OS). CONCLUSIONS: In addition to ENE, poor tumor differentiation was identified as the second most relevant adverse RF for patients with pT3-4 OCSCC. We suggest that the NCCN guidelines should include poor tumor differentiation as an adverse RF to refine and tailor clinical management.

Prognostic stratification of patients with AJCC 2018 pStage IVB oral cavity cancer: Should pT4b and pN3 disease be reclassified?

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.

Reconstruction of mandibular defects involving the central segment with fibula osteoseptocutaneous free flap following ameloblastoma resection: Patient-reported outcomes.

OBJECTIVES: Mandibular defects involving the central segment are challenging. This study analyzes the impact of defect extent and reconstruction method on quality of life (QOL) and obstructive sleep apnea (OSA). MATERIALS AND METHODS: Twenty-nine ameloblastoma patients received segmental mandibulectomy involving the C-segment and immediate fibula free flap reconstruction were recruited. Defects: (C: 2, LC: 11, LCL: 19). Mean defect length: 8.79 cm (± 2.34). Inset: Low-single-barrel (n: 19), with secondary distraction osteogenesis (n: 8/19), high-single-barrel (n: 7), double barrel (n: 3). Patients were surveyed using University of Washington Quality of Life (UW-QOL) and Berlin risk of postoperative sleep apnea questionnaires. RESULTS: Flap failure: None. Mean follow-up: 109.6 ±â€¯92.8 months. UW-QOL: Physical function 91.83 (± 14.92); social function 90.17 (± 17.19). No statistical difference between C, LC, and LCL was found, but C group which received low-single-barrel had the lowest score in appearance and chewing domains. In health-related QOL (HR-QOL) compared with 1 month before cancer, 69% reported best results. "Appearance" was the most important issue for the past 7 days, followed by "Chewing," prevailing in LC and C groups that predominately reconstructed by low-single-barrel. Berlin score: 7 patients (4 LCL, 3 LC≥8 cm) were at high risk for postoperative OSA. CONCLUSION: "Like-with-like" reconstruction with immediate endosteal dental implants yields the best results. Inset of fibula bone could affect outcomes, favoring double-barrel or single-high-barrel inset. Appearance and chewing remain the main concerns, largely, in those with low-single-barrel inset and no dental restoration. After long/extensive LCL and LC mandibulectomies, postoperative OSA warrants further investigation, and modification of resection/reconstruction techniques.

Clinical outcomes of Taiwanese patients with resected squamous cell carcinoma of the upper and lower gum.

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.

Surgical Margins Status and Prognosis after Resection of Oral Cavity Squamous Cell Carcinoma: Results from a Taiwanese Nationwide Registry-Based Study.

(1) Background: The optimal cutoff value that maximizes the prognostic value of surgical margins in patients with resected oral cavity squamous cell carcinoma has not yet been identified. (2) Methods: Data for this study were retrieved from the Taiwan Cancer Registry Database. A total of 13,768 Taiwanese patients with oral cavity squamous cell carcinoma were identified and stratified according to different margin statuses (0, 0.1-4 and > 4 mm). The five-year local control, disease-specific survival and overall survival rates were the main outcome measures. (3) Results: The 5-year local control, disease-specific survival and overall survival rates of patients with close margins (0 and 0.1-4 mm) were significantly lower than those observed in patients with clear margins (> 4 mm; all p values < 0.001). In multivariate analysis, margin status, depth of invasion and extra-nodal extension were identified as independent adverse prognostic factors for 5-year local control. (4) Conclusions: A thorough assessment of surgical margins can provide a reliable prognostic prediction in patients with OCSCC. This has potential implications for treatment approaches tailored to the individual level. The achievement of clear margins (>4 mm) should be considered a key surgical goal to improve outcomes in this patient group.

Long-term outcome of patients with or without osseointegrated implants after resection of mandibular ameloblastoma and reconstruction with vascularized bone graft: Functional assessment and quality of life.

BACKGROUND: The optimal management after the resection of mandibular ameloblastoma has been very challenging to surgeons. The aim of this study is to evaluate the functional, aesthetic, and quality of life outcomes of patients who had a segmental mandibular resection and immediate reconstruction with or without osseointegrated implants. METHOD: Patients' demographics, tumor characteristics, treatment, and complications were retrieved. Patients were divided into two groups: dental rehabilitated vs. nondental rehabilitated depending on the placement of osseointegrated implants followed by an implanted-retained prosthesis. Functional outcomes and quality of life were assessed using the Performance Status Scale, the University of Washington Quality of Life (UW-QOL) scale, and the 14-item Oral Health Impact Profile (OHIP-14). Aesthetic outcome was evaluated by patients using a Visual Analog Scale. RESULTS: Thirty-four patients were reviewed. Twenty-two patients were included in the dental rehabilitated group and 12 in the nondental rehabilitated group. No recurrence of the tumor was found during the average follow-up period of 7.4 years. Although both groups reported a similar satisfaction in appearance, patients in the dental rehabilitated group scored significantly higher in masticatory function and "eating in public" (p < 0.01). There were significant differences (p < 0.05) regarding "chewing," "activity," and "anxiety" when assessed using the UW-QOL scale. Indeed, patients in the dental rehabilitated group showed a definitively better outcome in "physical disability" and "psychological discomfort" dimensions when assessed using the OHIP-14. CONCLUSION: Vascularized bone graft reconstruction followed by immediate or delayed placement of osseointegrated implants showed as an ideal and predictable treatment modality for patients with ameloblastoma. The results suggested that patients with osseointegrated implants had a significantly better masticatory function, improved quality of life, and less psychological consequences.

Subgingival microbiota in individuals with severe chronic periodontitis.

BACKGROUND/PURPOSE: Subgingival microorganisms are potentially associated with periodontal diseases. However, the correlation between the variance in the periodontal microbiome and the prevalence and severity of periodontitis remains unclear. The aim of this study was to determine the subgingival microbiota in Taiwanese individuals with severe chronic periodontitis (SP). METHODS: The composition of the subgingival microbiota in healthy and diseased individuals was compared using a 16S rRNA metagenomic approach and quantitative polymerase chain reaction (qPCR). A total of 20 samples, including 10 from healthy individuals and 10 from SP patients, were analyzed. RESULTS: We found high microbial diversity, with an average of 774 classified phylotypes per sample and a total of six bacterial phyla across all samples. Cluster analysis by principal component analysis and heat map showed that the bacterial communities were different in the two groups. Streptococcus dominated across all the healthy samples, whereas Prevotella, Porphyromonas, and Treponema were highly abundant across all diseased samples. At least 13 bacterial genera were conserved among all the samples. Only eight genera, including Lautropia, Parvimonas, Actinomyces, Capnocytophaga, Paludibacter, Streptococcus, Haemophilus, and Corynebacterium, were significantly enriched in the healthy group, and six genera, including Porphyromonas, Treponema, Tannerella, Aggregatibacter, Peptostreptococcus, and Filifactor, were significantly enriched in the diseased group. Furthermore, a trend of abundance of bacteria at the species level measured by qPCR in all samples was consistent with the 16S rRNA metagenomics results. CONCLUSION: This study is the first in Taiwan to provide a picture of the microbiome in SP via 16S rRNA metagenomics.

Prevalence and comparative analysis of the type IV secretion system in Aggregatibacter actinomycetemcomitan.

BACKGROUD/PURPOSE: Aggregatibacter actinomycetemcomitans has emerged as one of the aetiological agents in periodontal disease. Although Type IV secretion systems (T4SSs) are widely distributed in many bacteria, the genetic features and distribution of T4SSs in A. actinomycetemcomitans remain unclear. In this study, we investigated the prevalence of A. actinomycetemcomitans serotypes and their T4SSs in a Taiwanese population. METHODS: A comparative analysis of 20 A. actinomycetemcomitans genomes and their T4SSs deposited in GenBank was performed. One hundred subjects, including 20 periodontitis and 80 normal subjects, were enrolled and PCR identification of A. actinomycetemcomitans serotypes and T4SS genes were performed. RESULTS: Of 100 subjects, serotypes C (22%) and E (11%) were most common. In addition, T4SSs were distributed in all of the serotypes. The prevalence of T4SSs and their location in plasmids in periodontitis subjects were 1.28-2 fold higher but not significantly different compared to normal subjects. Of 20 A. actinomycetemcomitans genomes, only ten with complete T4SS modules could be detected, which was highly correlated with localized aggressive periodontitis (p < 0.1). Nine of ten T4SS modules were from periodontitis subjects. Phylogenetic analysis of 10 T4SSs in A. actinomycetemcomitans showed that they were clustered into two groups, T4SSAaI and T4SSAaII, with only T4SSAaI appearing in the Taiwanese subjects. CONCLUSION: A. actinomycetemcomitans strains with different serotypes carrying T4SSAaI are widely distributed in a Taiwanese population. This is the first report to show the distribution and detailed comparative genomics of T4SSs in A. actinomycetemcomitans.

MART-10, a newly synthesized vitamin D analog, represses metastatic potential of head and neck squamous carcinoma cells.

Even with multidisciplinary treatment, the prognosis and quality of life of patients diagnosed with head and neck squamous cell carcinoma (HNSCC) are still not satisfactory. Previously, 19-Nor-2α-(3-hydroxypropyl)-1α,25(OH)2D3 (MART-10), the new brand 1α,25(OH)2D3 analog, has been demonstrated to be an effective drug to inhibit HNSCC growth in vitro. Since most cancer patients die of metastasis, in this study, the antimetastatic effect of MART-10 on HNSCC was investigated. Our results reveal that both 1α,25(OH)2D3 and MART-10 effectively repressed the migration and invasion of HNSCC cells, with MART-10 being much more potent than 1α,25(OH)2D3. The antimetastatic effect of 1α,25(OH)2D3 and MART-10 was mediated by attenuation of epithelial-mesenchymal transition (EMT), which was supported by the finding that the expression of EMT-inducing transcriptional factors, Sail and Twist, was inhibited by 1α,25(OH)2D3 and MART-10. The upregulation of E-cadherin and downregulation of N-cadherin in FaDu cells induced by both drugs further confirmed the repression of EMT. In addition, 1α,25(OH)2D3 and MART-10 treatment inhibited intracellular MMP-9 expression and extracellular MMP activity in FaDu cells. Collectively, our results suggest that the less-calcemia 1α,25(OH)2D3 analog, MART-10, is a promising drug for HNSCC treatment. Further clinical studies are warranted.