Early Oral Tongue Squamous Cell Carcinoma Research Articles

Web-based prognostic tools for oral tongue cancer: An analysis of online predictors.

Oral tongue squamous cell carcinoma (OTSCC) often presents with aggressive clinical behaviour that may require multimodality treatment based on reliable prognostication. We aimed to evaluate the prognostic ability of five online web-based tools to predict the clinical behaviour of OTSCC resection and biopsy samples. A total of 135 OTSCC resection cases and 33 OTSCC biopsies were included to predict recurrence and survival. Area under the receiver operating characteristic curves (AUC), χ2 tests, and calibration plots constructed to estimate the prognostic power of each tool. The tool entitled 'Prediction of risk of Locoregional Recurrences in Early OTSCC' presented an accuracy of 82%. The tool, 'Head & Neck Cancer Outcome Calculator' for 10-year cancer-related mortality had an accuracy 77% and AUC 0.858. The other tool entitled 'Cancer Survival Rates' for 5-year mortality showed an accuracy of 74% and AUC of 0.723. For biopsy samples, 'Cancer Survival Prediction Calculators' predicted the recurrence free survival with an accuracy of 70%. Web-based tools can aid in clinical decision making of OTSCC. Three of five online web-based tools could predict recurrence risk and cancer-related mortality in resected OTSCC and one tool could help in clinical decision making for biopsy samples.

The prognostic role of single cell invasion and nuclear diameter in early oral tongue squamous cell carcinoma

BackgroundThe clinical significance of single cell invasion and large nuclear diameter is not well documented in early-stage oral tongue squamous cell carcinoma (OTSCC).MethodsWe used hematoxylin and eosin-stained sections to evaluate the presence of single cell invasion and large nuclei in a multicenter cohort of 311 cases treated for early-stage OTSCC.ResultsSingle cell invasion was associated in multivariable analysis with poor disease-specific survival (DSS) with a hazard ratio (HR) of 2.089 (95% CI 1.224–3.566, P = 0.007), as well as with disease-free survival (DFS) with a HR of 1.666 (95% CI 1.080–2.571, P = 0.021). Furthermore, large nuclei were associated with worse DSS (HR 2.070, 95% CI 1.216–3.523, P = 0.007) and with DFS in multivariable analysis (HR 1.645, 95% CI 1.067–2.538, P = 0.024).ConclusionSingle cell invasion and large nuclei can be utilized for classifying early OTSCC into risk groups.

Clinical significance of L1CAM expression and its biological role in the progression of oral squamous cell carcinoma.

L1 cell adhesion molecule (L1CAM) has been implicated in the progression and metastasis of numerous cancers. However, the role of L1CAM in oral squamous cell carcinoma (OSCC) is not well characterized. In the present study, the expression of L1CAM was examined in oral tongue squamous cell carcinoma (OTSCC) tissue samples by immunohistochemistry, the clinicopathological significance of L1CAM expression was evaluated by chi‑squared test, and the overall survival (OS) rate was analyzed using Kaplan‑Meier method according to the expression of L1CAM. In addition, it was aimed to elucidate the biological role of L1CAM and the underlying molecular mechanisms by which L1CAM functions in OSCC cells in relation to epithelial‑mesenchymal transition (EMT) and PI3K/AKT/ERK signaling pathways. Thus, the functions of L1CAM on the OSCC cell proliferation, migration and invasion, and the activation of EMT and PI3K/AKT/ERK signaling pathways were investigated invitro. Positive L1CAM expression was found in 32.5% of OTSCC cases and was significantly correlated with high histologic grade, greater depth of invasion, lymph node metastasis, perineural invasion, advanced stage, and survival status. Patients with positive L1CAM expression had significantly lower OS rate. Particularly in patients with early OTSCC, L1CAM expression was strongly associated with worse prognosis. Overexpression of the recombinant human L1CAM protein significantly increased cell proliferation, migration and invasion. By contrast, L1CAM knockdown using small interfering RNA significantly inhibited cell proliferation, migration, invasion and EMT. Moreover, phosphorylated (p)‑PI3K, p‑AKT and p‑ERK expression levels were significantly reduced by L1CAM knockdown. Taken together, the findings of the present study suggested that L1CAM could be a potential prognostic marker and a promising therapeutic target in OSCC.

Facial-submental island flap for reconstruction of hemitongue defects in young, middle-aged and elderly patients with early and middle stage oral tongue squamous cell carcinoma

BackgroundThis study evaluated the outcomes of facial-submental artery island flap (FSAIF) for reconstruction of the hemitongue following cancer ablation in patients with early and middle-stage oral tongue squamous cell carcinoma (OTSCC).MethodsIn total, 122 patients with early and middle-stage OTSCC were divided into young, middle-aged, and elderly groups. The Adult Comorbidity Evaluation-27 (ACE-27) index was used to determine the presence of comorbidities. The patients underwent surgical treatment with hemiglossectomy, neck dissection, and hemitongue reconstruction using FSAIF. In addition, stage I (n = 15) and II (n = 69) patients underwent ipsilateral selective neck dissection, whereas those with stage III (n = 38) underwent radical neck dissection. Six patients with T3N1 disease also underwent cobalt-60 adjuvant radiotherapy.ResultsYoung and elderly patients exhibited significant differences in comorbidities, as assessed by the ACE-27 (p < .05). The skin paddles in the young, middle-aged, and elderly patients were 3 × 9 to 4 × 12 cm, 3 × 11 to 4 × 12, and 3 × 10 to 5 × 13 cm in size, respectively. FSAIF failure occurred in four patients (success rate: 96.7%). No significant differences were observed in the skin paddle of the flap or rate of flap failure among the age groups (p > .05). Clavien-Dindo grades I, II, IIIa, IIIb, Iva, and IVb were assigned to 7.1, 36.1, 38.5, 9.8, 4.1, and 4.1% of the patients, respectively, with significant differences seen between the young and elderly patients (p < .05). In total, 52.5% of patients could eat normally, whereas 32.8% required a soft diet. Furthermore, 53.3 and 33.6% of patients achieved normal and intelligible speech, respectively. The aesthetic results were rated as excellent and good in 32.8 and 58.2% of patients, respectively. In total, 68.0% of the patients were alive and exhibited no evidence of disease, while 19.7% were alive with active disease. In addition, 12.3% of patients with stage III OTSCC died due to local recurrence or distant metastases. No differences in swallowing, speech, aesthetic, or survival outcomes were observed among the groups.ConclusionsFSAIF is a simple, safe, and reliable method for reconstructing hemitongue defects following cancer ablation in young, middle-aged, and elderly patients with early and middle-stage OTSCC.

Tertiary lymphoid structures associate with improved survival in early oral tongue cancer

BackgroundThe clinical significance of tertiary lymphoid structures (TLSs) is not well-documented in early oral tongue squamous cell carcinoma (OTSCC).MethodsA total of 310 cases of early (cT1-2N0) OTSCC were included in this multicenter study. Assessment of TLSs was conducted on hematoxylin and eosin-stained sections. TLSs were assessed both in the central part of the tumor and at the invasive front area.ResultsThe presence of TLSs associated with improved survival of early OTSCC as presented by Kaplan–Meier survival analyses for disease-specific survival (P = 0.01) and overall survival (P = 0.006). In multivariable analyses, which included conventional prognostic factors, the absence of TLSs associated with worse disease-specific survival with a hazard ratio (HR) of 1.96 (95% CI 1.09–3.54; P = 0.025) and poor overall survival (HR 1.66, 95% CI 1.11–2.48; P = 0.014).ConclusionHistological evaluation of TLSs predicts survival in early OTSCC. TLSs showed superior prognostic power independent of routine WHO grading and TNM staging system.

A change in surgical margin: do wider surgical margins lead to decreased rates of local recurrence in T1 and T2 oral tongue cancer?

The purpose of this study was to assess the impact of a change in macroscopic/surgical margin width upon histological margins and loco-regional failure in early oral tongue squamous cell carcinoma (OTSCC). In 2009, the surgical margin protocol was increased from 10 mm to 15 mm. A retrospective review was performed of all patients who underwent treatment for early OTSCC between 2009 and 2016 with a 15-mm surgical margin (n = 142), and these patients were compared to those treated between 1999 and 2008 with a 10-mm surgical margin (n = 78). There was a significant increase in the rate of clear histological margins (P < 0.001). The rates of close (P = 0.002) and involved (P < 0.001) histological margins decreased significantly. There were significant reductions in local (P < 0.001) and regional (P < 0.001) recurrence rates. This study demonstrated that a surgical margin of 15 mm delivered significantly lower rates of close/involved histological margins and improved local and regional disease recurrence in early OTSCC when compared with a surgical margin of 10 mm.

Emerging histopathologic markers in early-stage oral tongue cancer: A systematic review and meta-analysis.

Although there are many histopathologic prognosticators, grading of early oral tongue squamous cell carcinoma (OTSCC) is still based on morphological cell differentiation which has low prognostic value. Here we summarize the emerging histopathological markers showing powerful prognostic value, but are not included in pathology reports. Using PubMed, Scopus, Ovid Medline, and Web of Science databases, a systematic literature search was preformed to identify early OTSCC studies that investigated the prognostic significance of hematoxylin–eosin‐based histopathologic markers. Our meta‐analysis showed that tumor budding was associated with overall survival (hazard ratio [HR] 2.32; 95% CI 1.40–3.84; p < 0.01) and disease‐specific survival (DSS) (1.89; 95% CI 1.13–3.15; p = 0.02). Worst pattern of invasion was associated with disease‐free survival (DFS) (1.95; 95% CI 1.04–3.64; p = 0.04). Tumor–stroma ratio was also associated with DFS (1.75, 95% CI 1.24–2.48; p < 0.01) and DSS (1.69; 95% CI 1.19–2.42; p < 0.01). Tumor budding, worst pattern of invasion, and tumor–stroma ratio have a promising prognostic value in early OTSCC. The evaluation and reporting of these markers is cost‐effective and can be incorporated in daily practice.

Trans-lymphatic contrast-enhanced ultrasound with sentinel lymph node biopsy for detecting cervical skip metastasis to lymph nodes in early-stage oral tongue squamous cell carcinoma.

The purpose of this study was to assess whether trans-lymphatic contrast-enhanced ultrasound (CEUS) combined with sentinel lymph node biopsy can be used to assess the status of cervical lymph nodes and skip metastasis in patients with early squamous cell carcinoma (SCC) of the oral tongue. This study included 21 subjects with early oral tongue SCC who received multiple intramucosal peritumoral injections of Sonazoid. CEUS examinations were performed immediately after Sonazoid injection to identify sentinel lymph nodes (SLNs). The SLNs were excised for histological examination to determine if the lymph nodes has metastases. Thirty-five SLNs were detected by CEUS after Sonazoid injection in the subjects. SLNs were identified in 20 of the total 21 subjects. Four participants had metastasis to lymph nodes, and one had skip metastasis in level Ⅲ. In one subject, SLNs were successfully detected in level Ⅳ without skip metastasis. Trans-lymphatic CEUS combined with sentinel lymph node biopsy showed high accuracy for evaluating cervical lymph node status. This could be a reliable approach for detecting cervical skip metastases of lymph nodes in early-stage oral cancer patients.

Improving Risk Stratification of Early Oral Tongue Cancer with TNM-Immune (TNM-I) Staging System.

Simple SummarySome patients with early-stage oral tongue cancer suffer from poor survival. The currently used classification requires further improvement to better predict the prognosis. Immune-related parameters (such as assessment of infiltrating lymphocytes) can be used as a modifier for the classification and that can aid in improving the prognostication. We included 290 cases of early-stage oral tongue cancer in this study. Lymphocytes were scored and divided as low or high and incorporated in the traditional tumor-node-metastasis (TNM) classification to form our proposed TNM-Immune staging system. The TNM-Immune staging system allowed for a significant distinction between T1 and T2. The TNM-Immune staging system showed a powerful ability to identify cases with poor survival. TNM-Immune staging forms a step towards a more personalized classification of early-stage oral tongue cancer.Although patients with early-stage oral tongue squamous cell carcinoma (OTSCC) show better survival than those with advanced disease, there is still a number of early-stage cases who will suffer from recurrence, cancer-related mortality and worse overall survival. Incorporation of an immune descriptive factor in the staging system can aid in improving risk assessment of early OTSCC. A total of 290 cases of early-stage OTSCC re-classified according to the American Joint Committee on Cancer (AJCC 8) staging were included in this study. Scores of tumor-infiltrating lymphocytes (TILs) were divided as low or high and incorporated in TNM AJCC 8 to form our proposed TNM-Immune system. Using AJCC 8, there were no significant differences in survival between T1 and T2 tumors (p > 0.05). Our proposed TNM-Immune staging system allowed for significant discrimination in risk between tumors of T1N0M0-Immune vs. T2N0M0-Immune. The latter associated with a worse overall survival with hazard ratio (HR) of 2.87 (95% CI 1.92–4.28; p < 0.001); HR of 2.41 (95% CI 1.26–4.60; p = 0.008) for disease-specific survival; and HR of 1.97 (95% CI 1.13–3.43; p = 0.017) for disease-free survival. The TNM-Immune staging system showed a powerful ability to identify cases with worse survival. The immune response is an important player which can be assessed by evaluating TILs, and it can be implemented in the staging criteria of early OTSCC. TNM-Immune staging forms a step towards a more personalized classification of early OTSCC.

The Potential of MET Immunoreactivity for Prediction of Lymph Node Metastasis in Early Oral Tongue Squamous Cell Carcinoma.

ObjectiveMET positivity is independently associated with survival in oral squamous cell carcinoma (OSCC). Since MET is a known orchestrator of invasive tumor growth, we investigated its association with LNM in early oral tongue squamous cell carcinoma (OTSCC). As it is recommended by the NCCN to use tumor depth of invasion (DOI) in making decisions on elective neck dissection (END), the results obtained for MET positivity were aligned with those for DOI > 4 mm. The cutoff value used in our institution.MethodsTumor samples from patients who underwent primary tumor resection and neck dissection between 1995 and 2013, were collected from the archives of the Leiden and Erasmus University Medical Center. Immunohistochemistry with D1C2 was performed to identify MET negative (< 10% uniform positivity) and MET positive (≥ 10% uniform positivity) cancers. ROC curve analysis and the Chi-squared test were used to investigate the association of MET positivity with LNM (pN+ and occult). Binary logistic regression was used to investigate the association of MET positivity with LNM.ResultsForty-five (44.1%) of the 102 cancers were MET positive. Ninety were cN0 of which 20 were pN+ (occult metastasis). The remaining 12 cancers were cN+, of which 10 were proven pN+ and 2 were pN0. MET positivity was associated with LNM with a positive predictive value (PPV) of 44.4% and a negative predictive value (NPV) of 82.5% for pN+. For the occult group, the PPV was 36.8% and the NPV was 88.5%. Regression analysis showed that MET positivity is associated with pN+ and occult LNM (p-value < 0.05).ConclusionMET positivity is significantly associated with LNM in early OTSCC, outperforming DOI. The added value of MET positivity could be in the preoperative setting when END is being considered during the initial surgery. For cases with DOI ≤ 4 mm, MET positivity could aid in the clinical decision whether regular follow-up, watchful waiting, or END is more appropriate. Realizing that these preliminary results need to be independently validated in a larger patient cohort, we believe that MET positivity could be of added value in the decision making on END in early OTSCC.

Stromal categorization in early oral tongue cancer

Stromal categorization has been used to classify many epithelial cancer types. We assessed the desmoplastic reaction and compared its significance with other stromal characteristics in early (cT1-2N0) oral tongue squamous cell carcinoma (OTSCC). In this multi-institutional study, we included 308 cases treated for early OTSCC at five Finnish university hospitals or at the A.C. Camargo Cancer Center in São Paulo, Brazil. The desmoplastic reaction was classified as immature, intermediate, or mature based on the amount of hyalinized keloid-like collagen and myxoid stroma. We compared the prognostic value of the desmoplastic reaction with a stromal grading system based on tumor-stroma ratio and stromal tumor-infiltrating lymphocytes. We found that a high amount of stroma with a weak infiltration of lymphocytes was associated statistically significantly with a worse disease-free survival with a hazard ratio (HR) of 2.68 (95% CI 1.26–5.69), worse overall survival (HR 2.95, 95% CI 1.69–5.15), and poor disease-specific survival (HR 2.66, 95% CI 1.11–6.33). Tumors having a high amount of stroma with a weak infiltration of lymphocytes were also significantly associated with a high rate of local recurrence (HR 4.13, 95% CI 1.67–10.24), but no significant association was found with lymph node metastasis (HR 1.27, 95% CI 0.37–4.35). Categorization of the stroma based on desmoplastic reaction (immature, intermediate, mature) showed a low prognostic value for early OTSCC in all survival analyses (P > 0.05). In conclusion, categorization of the stroma based on the amount of stroma and its infiltrating lymphocytes shows clinical relevance in early OTSCC superior to categorization based on the maturity of stroma.

Elective Neck Dissection Versus Observation in cT1-T2 Oral Tongue Squamous Cell Carcinoma: A Meta-Analysis of 11,973 Patients.

The surgical management of the clinical negative neck node in early oral tongue squamous cell carcinoma (OTSCC) has been the topic of debate since few decades. As the occult cervical lymph node metastasis is considered to be the prime prognostic factor in early OTSCC, this meta-analysis has been carried out to find the risk of regional nodal recurrence, disease specific survival and overall survival rates in outcome of Elective neck dissection (END) versus patients under observation. The articles were electronically retrieved from Ovid Medline, PubMed, Cochrane and Scholar for comparison of END versus Observation in early OTSCC. The search strategy identified 37 relevant review articles from April 1979 to April 2020 from different search engines. A total of 11,973 patients from 32 retrospective analysis, 4 prospective and 1 randomised control trial were included in this meta-analysis. Statistical analysis revealed Overall test (OR: 5.31 95% CI: - 2.132-14.698) with t-test 1.919 and p value 0.113 which is not statistically significant but the readings says that there is always better Disease specific survival with END patients rather than patients kept on observation. Overall test revealed (OR: 13.02 95% CI: 1.360-17.154) with t test 2.382 and p value 0.023 which is statistically significant and showed that End significantly reduced the risk of regional nodal recurrence. Overall test revealed (OR: 7.93 95% CI: - 15.461-4.238) with t test - 1.347 and p value 0.220 which is statistically insignificant and but showed that to some extent Overall survival improves in patient with END than the patients kept on observation. This meta-analysis find that there is statistically significant relationship when Elective neck dissection was performed which reduced the risk of regional nodal recurrence. This analysis didn't statistically find any significance in Disease specific survival and Overall survival with Elective neck dissection patients rather than patients kept on observation but however showed good prognosis when elective neck dissection was performed.

Assessment of Tumor-infiltrating Lymphocytes Predicts the Behavior of Early-stage Oral Tongue Cancer.

Tumor-infiltrating lymphocytes (TILs) have shown a promising prognostic value in many epithelial cancers. We sought to assess the prognostic value of TILs in a multicenter cohort of early oral tongue squamous cell carcinoma (OTSCC). The percentage of TILs was assessed on the surgical resection slides stained with hematoxylin and eosin. The assessment of TILs was performed in the stromal compartment and in the intraepithelial compartment (at the invasive front and at the center of the tumor). We followed the method that was described recently by the International Immuno-Oncology Biomarker Working Group for the assessment of TILs. A total of 308 cases from the 5 Finnish university hospitals and from A.C. Camargo Cancer Center, São Paulo, Brazil, were included. We found a promising prognostic value for stromal TILs at the invasive front in the multivariable analysis with a hazard ratio of 2.61 (95% confidence interval [CI], 1.77-3.83; P<0.001) for overall survival, 1.99 (95% CI, 1.07-3.69; P=0.040) for disease-specific survival, and 1.94 (95% CI, 1.14-3.29; P=0.020) for disease-free survival. In conclusion, evaluation of TILs is simple and can aid in identifying the high-risk cases of early OTSCC. The method introduced by the International Immuno-Oncology Biomarker Working Group can be used for standardized determination of TILs in early OTSCC.

Machine learning application for prediction of locoregional recurrences in early oral tongue cancer: a Web-based prognostic tool

Estimation of risk of recurrence in early-stage oral tongue squamous cell carcinoma (OTSCC) remains a challenge in the field of head and neck oncology. We examined the use of artificial neural networks (ANNs) to predict recurrences in early-stage OTSCC. A Web-based tool available for public use was also developed. A feedforward neural network was trained for prediction of locoregional recurrences in early OTSCC. The trained network was used to evaluate several prognostic parameters (age, gender, T stage, WHO histologic grade, depth of invasion, tumor budding, worst pattern of invasion, perineural invasion, and lymphocytic host response). Our neural network model identified tumor budding and depth of invasion as the most important prognosticators to predict locoregional recurrence. The accuracy of the neural network was 92.7%, which was higher than that of the logistic regression model (86.5%). Our online tool provided 88.2% accuracy, 71.2% sensitivity, and 98.9% specificity. In conclusion, ANN seems to offer a unique decision-making support predicting recurrences and thus adding value for the management of early OTSCC. To the best of our knowledge, this is the first study that applied ANN for prediction of recurrence in early OTSCC and provided a Web-based tool.

Small oral tongue cancers (≤ 4cm in diameter) with clinically negative neck: from the 7th to the 8th edition of the American Joint Committee on Cancer.

One of the main changes in the 8th edition of the American Joint Committee on Cancer (AJCC) for staging of oral cancer is the inclusion of depth of invasion (DOI) in the T category. However, cancers in different oral subsites have variable behavior, with oral tongue squamous cell carcinoma (OTSCC) being the most aggressive one even at early stage. Thus, it is necessary to evaluate the performance of this new T category in homogenous cohort of early OTSCC. Therefore, we analyzed a large cohort of patients with a small (≤ 4cm) OTSCC to demonstrate the differences in T stage between the AJCC 7th and 8th editions. A total of 311 early-stage cases (AJCC 7th) of OTSCC were analyzed. We used 5mm and 10mm DOI for upstaging from T1 to T2 and from T2 to T3 respectively, as in the AJCC 8th. We further reclassified the cases according to our own proposal suggesting 2mm to upstage to T2 and 4mm to upstage to T3. According to AJCC 7th, there were no significant differences in the survival analysis. When we applied the 8th edition, many cases were upstaged to T3 and thus associated with worse disease-specific survival (HR 2.37, 95% CI 1.12-4.99) and disease-free survival (HR 2.12, 95% CI 1.09-4.08). Based on our proposal, T3 cases were associated with even worse disease-specific survival (HR 4.19, 95% CI 2.27-7.74). The 8th edition provides better survival prediction for OTSCC than the 7th and can be further optimized by lowering the DOI cutoffs.

Preoperative ultrasonography for tumor thickness evaluation in guiding management in patients with early oral tongue squamous cell carcinoma.

Objectives:(1) To assess the statistical correlation between the tumor thickness (TT) by ultrasonography (USG) and microscopic measurement in cases of early oral tongue squamous cell carcinoma (OTSCC). (2) To assess the predictive capacity of TT by ultrasound in detecting nodal metastasis.Materials and Methods:Prospective analysis was performed in 24 patients for a period of 2 years from 2012 to 2013. Nodal status and TT measurement was done preoperatively by neck and intraoral USG respectively in cases of early (pT1 & T2, clinically N0) OTSCC. As per the institution protocol after histopathological confirmation of malignancy, all patients underwent resection of primary lesion and ipsilateral elective neck dissection (Level - I to IV). Measurement of TT was obtained intraoperatively from fresh glossectomy specimen and postoperatively from histopathological paraffin section examination. The statistical correlation between TT measured by USG and histopathology was assessed by Pearson's correlation coefficient. Chi-square test was used to find the association of pathological T stage, TT with pathological nodal status.Results:Significant statistical correlation was seen between TT by USG and microscopic measures. Between the two, TT measurements were within 1 mm in 37.5% (9/24) of cases, within 2 mm in 29.16% (7/24), and was greater than 2 mm in 8 cases. The Pearson's correlation r is 0.678 (P < 0.001) and ICC (interclass correlation coefficient) is 0.808. The average difference between microscopic and US thickness (Bias) is -0.14637 and the limits of agreement is (4.717, -4.863) with 95% limits of agreement. The rate of occult nodal metastasis was 16.6% and TT of <4 mm had no incidence of nodal metastasis.Conclusion:Ultrasonographic evaluation is reliable and cost-effective tool to measure the TT preoperatively, which will be of help in deciding the management in early OTSCC. TT of 4 mm and above was predictor of occult cervical nodal metastasis.

For early-stage oral tongue cancer, depth of invasion and worst pattern of invasion are the strongest pathological predictors for locoregional recurrence and mortality.

Despite early diagnosis and treatment, almost 20% of patients with early-stage (cT1-cT2N0) oral tongue squamous cell carcinoma (OTSCC) still die of their disease. The prognosis of OTSCC patients is influenced by several demographic, clinical, and histopathologic factors. The aim of this multicenter international study was to find which of the factors age, gender, stage, grade, lymphocytic host response, perineural invasion, worst pattern of invasion, or depth of invasion has the strongest prognostic power in early-stage OTSCC. Patient data of 479 patients with early-stage (cT1-2N0) OTSCC in Finland, Brazil, and the USA were retrieved and analyzed using Cox proportional hazards regression models. Our results indicate that depth of invasion (DOI) and worst pattern of invasion (WPOI) are the strongest pathological predictors for locoregional recurrence, with a hazard ratio (HR) for 4 mm DOI of 1.67 (95% confidence interval (CI) 1.07-2.60) and HR for WPOI of 1.46 (95% CI 0.95-2.25). In addition, mortality from early OTSCC was also predicted by DOI (HR 2.44, 95% CI 1.34-4.47) and by WPOI (HR 2.34, 95% CI 1.26-4.32). We suggest that clinically early-stage oral tongue carcinomas 4 mm or deeper, or with a growth pattern of small cell islands or satellites, should be considered as high-risk tumors which require multimodality treatment.

A simple novel prognostic model for early stage oral tongue cancer

The prognostication of patient outcome is one of the greatest challenges in the management of early stage oral tongue squamous cell carcinoma (OTSCC). This study introduces a simple histopathological model for the prognostication of survival in patients with early OTSCC. A total of 311 cases (from Finland and Brazil) with clinically evaluated early stage OTSCC (cT1–T2cN0cM0) were included in this multicentre retrospective study. Tumour budding (B) and depth of invasion (D) were scored on haematoxylin–eosin-stained cancer slides. The cut-off point for tumour budding was set at 5 buds (low <5; high ≥5) and for depth of invasion at 4mm (low <4mm; high ≥4mm). The scores of B and D were combined into one model: the BD predictive model. On multivariate analysis, a high risk score (BD score 2) correlated significantly with loco-regional recurrence (P=0.033) and death due to OTSCC (P<0.001) in early stage OTSCC. The new BD model is a promising prognostic tool to identify those patients with aggressive cases of early stage OTSCC who might benefit from multimodality treatment.

Predictors of Locoregional Recurrence in T1-2N0 Tongue Cancer Patients

Locoregional recurrence of oral tongue squamous cell carcinoma (OTSCC) has been considered a poor prognostic entity in terms of survival rate. The purpose of this study was to evaluate the incidence of locoregional recurrence and to identify significant risk factors for locoregional recurrence in early-stage OTSCC. We retrospectively reviewed the records of 58 patients who underwent radical surgery for T1-2N0 OTSCC. The local recurrence and regional recurrence rates were 10.3 % (6/58 patients) and 15.5 % (9/58 patients) in this study, respectively. The survival rate of patients with local recurrence was 66.7 %, which was significantly lower than that (96.2 %) of patients without local recurrence, whereas the survival rates of patients with or without regional recurrence were not significantly difference. Pattern of invasion (POI), neoadjuvant chemotherapy (NAC) and the status of the surgical margin were identified as factors influencing local recurrence. In particular, the status of the deep surgical margin was a high potential independent risk factor. The deep surgical margin was resected closely in many NAC-treated cases, suggesting that NAC may lead to local recurrence and a poor outcome. No efficacy of NAC was observed, suggesting that the standard treatment for early OTSCC is surgery alone.