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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.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.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.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.

We sought to compare the clinical outcomes of Taiwanese patients with resected oral cavity squamous cell carcinoma (OCSCC) who underwent reconstruction with free versus local flaps.From 2011 to 2017, we examined 8646 patients with first primary OCSCC who received surgery either with or without adjuvant therapy. Of these patients, 7297 and 1349 received free and local flap reconstruction, respectively. Two propensity score-matched groups of patients who underwent free versus local flap (n = 1268 each) reconstructions were examined. Margin status was not included as a propensity score-matched variable.Compared with local flaps, patients who received free flaps had a higher prevalence of the following variables: male sex, age 65 years, pT3-4, pN1-3, p-Stage III-IV, depth ≥ 10 mm, margin 4 mm, extranodal extension (ENE), and adjuvant therapy (all p 0.0001). Multivariable analysis identified the reconstruction method (local vs. free flaps, only overall survival [OS]), age ≥ 65 years, pT3-4, pN1-3, p-Stage III-IV, depth ≥ 10 mm (only OS), margins ≤ 4 mm, and ENE as independent adverse prognosticators for disease-specific survival (DSS) and OS. The results of propensity score-matched analyses revealed that, compared with free flaps, patients who underwent local flap reconstruction showed less favorable 5-year DSS (hazard ratio [HR] 1.26, 82%/77%; p = 0.0100) and OS (HR 1.21, 73%/68%; p = 0.0079).After adjusting for covariates using multivariate models, and also by propensity score modeling, OCSCC patients who underwent free flap reconstruction showed a higher frequency of clear margins and a significant survival advantage compared with those who received local flaps.

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. 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. 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

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.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.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.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.

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). 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. 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

Squamous cell carcinoma antigen (SCC-Ag) level and C-reactive protein (CRP) have been shown to be associated with tumor invasion, lymph node metastasis, staging and survival in patients with oral squamous cell carcinoma (OSCC). The purpose of the present study was to analyze the relationship between preoperative levels of both SCC-Ag and CRP, with clinicopathologic factors and prognosis in OSCC patients. A retrospective study was performed on 142 OSCC patients between March 2008 and March 2011. Their serum SCC-Ag and CRP levels were measured preoperatively. SCC-Ag level of ≥2.0 ng/ml and CRP level ≥5.0 mg/L were significantly associated with pathologic tumor status (P

We sought to determine the differences in clinical outcome of tongue and buccal carcinomas. Five-year locoregional control, distant metastasis, and survival rates were examined in 456 patients with tongue cancer and 407 patients with buccal cancer. 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. 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.

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.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.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.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.

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