This cohort study aims to establish whether anterior vs posterior tumor extension may represent a prognostic factor in oral tongue and floor squamous cell carcinoma.
Key Points
Question
Can anterior vs posterior tumor extension be an additional prognostic factor in oral tongue and floor squamous cell carcinoma (OTFSCC)?
Findings
In this cohort study of 133 patients with OTFSCC, overall survival and time to recurrence were worse for patients with posterior OTFSCC. The poor prognosis conveyed by the posterior extension was independent of pT category, depth of invasion, age, margin status, and adjuvant treatments, and may be associated with propensity for nodal metastases.
Meaning
Patients with OTFSCC with a posterior tumor extension may have a higher risk for recurrence and death.
Abstract
Importance
The tongue and oral floor represent the most involved subsite by oral cancer, and there are no reported systems to classify anteroposterior tumor extension with prognostic effect. In other cancers, the anterior vs posterior tumor extension is a relevant prognostic factor.
Objective
To establish whether anterior vs posterior tumor extension may represent a prognostic factor in oral tongue and floor squamous cell carcinoma (OTFSCC).
Design, Setting, and Participants
This was a retrospective cohort study of patients who underwent surgery for OTFSCC from January 1, 2010, to December 31, 2021, at 2 tertiary-level academic institutions in Italy (University of Padua and University of Brescia). Patients eligible for the study had histologically proven primary OTFSCC; underwent surgery-based, curative treatment; and had available preoperative contrast-enhanced imaging.
Exposures
Four anatomical lines were designed to assess tumor extension: (1) chin-palate line (CPL), (2) chin-basion line, (3) Stensen duct line, and (4) lingual septum line. Preoperative imaging was re-evaluated, and tumor extension was classified as either anterior or posterior according to the lines.
Main Outcomes and Measures
Overall survival and time to recurrence (TTR) were evaluated according to tumor extension. These outcomes were reported as 5-year survival rates with 95% CIs.
Results
Of the 133 patients included, 79 (59.4%) were male, and the mean (SD) age was 62.7 (15.4) years. The 5-year TTR difference was higher for posterior vs anterior OTFSCC classified according to CPL (21.0%; 95% CI, 8.3%-33.7%), Stensen duct line (15.5%; 95% CI, 1.0%-30.0%), and lingual septum line (17.2%; 95% CI, 2.2%-32.3%). Overall survival analysis showed similar results. At the multivariable analysis on TTR, N status (adjusted hazard ratio [HR], 3.0; 95% CI, 1.2-7.1) and anteroposterior classification according to CPL (adjusted HR, 7.1; 95% CI, 0.9-54.6) were the variables associated with the highest adjusted HRs.
Conclusions and Relevance
In this cohort study, OTFSCC with a posterior extension to the CPL was associated with a higher risk of recurrence and death. This analysis suggests that the poor prognosis conveyed by the posterior tumor extension is independent of other relevant prognosticators except for the burden of nodal disease. This estimate is not precise and does not allow for definitive clinically important conclusions; therefore, further prospective studies are necessary to confirm these data.
Introduction
In 2020, carcinoma of the oral cavity and lip accounted for 377 713 incident cases and 177 757 deaths worldwide.1 More than 90% of these neoplasms are squamous cell carcinoma (SCC), and the tongue represents the most involved subsite (35.3%).2 The intricate lymphovascular drainage of the tongue offers connections across the midline, determining a substantial risk for bilateral node metastases, particularly for tumors abutting or crossing the midline. To date, the involvement of the midline is a predictor for decreased survival in oral tongue SCC.3 Other well-known prognostic factors are tumor size, depth of invasion (DOI), tongue base involvement, and neck lymph node metastasis.4,5,6,7,8,9 SCC arising from the mucosa of the oral floor poses similar challenges and displays similar behavior with respect to oral tongue SCC.
In other cancers of the head and neck region, the anterior vs posterior tumor extension has proven to be a relevant prognostic factor. In laryngeal SCC, anteroposterior compartmentalization is a valid prognosticator, even more powerful than pT category. Anterior laryngeal SCC (as defined in respect to the plane passing through the arytenoid vocal process and perpendicular to the ipsilateral thyroid lamina) has better survival outcomes then posterior ones.10,11 In the sinonasal tract, the Ohngren line divides the maxillary sinus, with an oblique imaginary plane passing through the medial canthus of the eye and the angle of the mandible. Tumors located anteroinferior to this plane (known as infrastructure) have a better prognosis than malignant tumors originating posterosuperior (known as suprastructure).12 Since, in most cases, all of these tumors require upfront surgery, it is unclear whether the negative effect of specific compartment involvement is related to a reduced chance of performing radical surgery or to a more aggressive biological behavior. In the oral cavity, an anatomical landmark has been proposed to subdivide T4b tumors extending to the masticator space. According to the axial plane crossing the mandibular notch, a higher 5-year locoregional control and survival were found in patients with infranotch rather than supranotch T4b cancers.13,14 However, oral tongue and floor SCC (OTFSCC) rarely extends to the masticator space, and there are no reported systems to classify anteroposterior tumor extension with prognostic effect. Thus, the main aims of this retrospective cohort study were to establish whether anterior vs posterior tumor extension may represent a relevant prognostic factor in OTFSCC and to identify the anatomical threshold (if any) that best segregates prognosis of patients affected by OTFSCC.
Methods
Study Design and Participants
A retrospective study on patients who underwent surgery for OTFSCC from January 1, 2010, to December 31, 2021, at the Section of Otorhinolaryngology–Head and Neck Surgery at the University of Padua and the Department of Otorhinolaryngology–Head and Neck Surgery at the University of Brescia, both in Italy, was performed. The following inclusion criteria were applied: (1) histologically proven primary OTFSCC; (2) surgery-based, curative treatment; and (3) availability of preoperative contrast-enhanced imaging of the primary tumor with no puffed cheek. The following factors were considered exclusion criteria: (1) distant metastasis at presentation, (2) previous and/or synchronous head and neck cancer, (3) unavailable follow-up, (4) history of cancer within the past 5 years, and (5) previous radiotherapy (RT) in the head and neck. The Adult Comorbidity Evaluation–27 scoring system was used to assess comorbidities at the end of locoregional treatment. All pathological specimens were examined by dedicated head and neck pathologists. Patients were (re-)staged using the TNM Classification of Malignant Tumours, 8th edition; both pathologic DOI and extranodal extension (ENE) were consistently reported according to internationally accepted criteria.15 We defined surgical resections with margins 5 mm or greater as R0 and resections with positive margins or margins less than 5 mm as R1.
The study was conducted in accordance with the guidelines of the Declaration of Helsinki and the principles of Good Clinical Practice. All patients signed a detailed informed consent form regarding the processing and publication of their data. All data were anonymized and examined in accordance with the Italian privacy and sensitive data laws.
Treatment and Follow-Up
Each case was discussed in the multidisciplinary head and neck tumor board, and treatment followed the National Comprehensive Cancer Network guidelines. Adjuvant RT was performed with a standardized fractionation regimen (60-66 Gy on high-risk volume and 50-54 Gy on low-/intermediate-risk volume, in daily fractions of 1.8-2.0 Gy). Concomitant chemotherapy (ChT) consisted of cisplatin, either 100 mg/m2 every 3 weeks or 40 mg/m2 weekly. In the first 2 years after treatment, the follow-up schedule included clinical evaluation every 2 months and imaging assessment with contrast-enhanced computed tomography (CT) or contrast-enhanced magnetic resonance (MR) together with ultrasonography of the neck every 4 months. Clinical and imaging examinations were subsequently performed every 6 months up to the fifth year and yearly thereafter until the 10th year.16,17 CT of the thorax and abdomen, positron emission tomography (PET), PET/CT, or PET/MR were performed yearly during the first 5 years after treatment in patients deemed at high risk of systemic recurrence.
Lines Design and Tumor Classification
After searching for reliable landmarks to draw consistent and easily identifiable lines on imaging, the following 4 lines were designed:
Chin-palate line (CPL; Figure 1A): the line connecting the most caudal portion of the mental symphysis to the posterior nasal spine on the median sagittal plane.
Chin-basion line (CBL; Figure 1B): the line connecting the most caudal portion of the mental symphysis to the basion on the median sagittal plane.
Stensen duct line (SDL; Figure 1C): the line joining the oral ends of the Stensen duct on the axial plane.
Lingual septum line (LSL; Figure 1D): the line perpendicular to the point where the median lingual septum ends posteriorly, drawn on the axial plane passing through the genial tubercle.
Figure 1. Graphical Illustration of the 4 Anatomical Lines.
The anatomical lines studied herein are easily drawable on cross-sectional imaging, with 2 shown on the median sagittal plane (A and B) and 2 on the axial plane (C and D). A, The pink arrowhead points to the most caudal portion of the mental symphysis and the blue arrowhead to the posterior nasal spine. B, The pink arrowhead points to the most caudal portion of the mental symphysis and the yellow arrowhead to the basion. C, Arrowheads point to the oral ends of the Stensen duct. D, The top arrowhead points to the genial tubercle and the bottom arrowhead to the posterior end of the median lingual septum.
Lines were projected orthogonally on all slices (ie, forming a plane) to check the connection with the neoplasm. Preoperative imaging was studied by 3 researchers (G.C., A.S., M.C.), and tumor extension was retrospectively classified as either anterior or posterior according to the 4 anatomical lines. Tumors were classified as anterior if completely anterior to the anatomical line. Tumors that were either located completely posterior to the anatomical line or that crossed it were classified as posterior. Examples of tumor classification are shown in Figure 2. A 3-dimensional representation of a patient with a posterior tumor stratified according to CPL is reported in eFigure 1 in Supplement 1. Three months after primary classification, a researcher (G.C.) reclassified 30 randomly selected cases to assess intrarater reliability. Interrater reliability was assessed between a clinician (G.C.) and a radiologist (R.M.).
Figure 2. Examples of Tumor Extension Classification.
After contouring the tumor (green represents anterior tumors, and red represents posterior tumors) on contrast-enhanced imaging, anterior vs posterior extension with respect to each anatomical line can be easily determined. A, Tumor anterior to the chin-palate line (CPL) and the chin-basion line (CBL). B, Tumor anterior to the CBL and posterior to the CPL. C, Tumor anterior to the Stensen duct line (SDL) and the lingual septum line (LSL). D. Tumor posterior to both the SDL and the LSL.
Statistical Analysis
Interrater and intrarater reliability were measured through Cohen κ. The primary outcome of the prognostic study was time to recurrence (TTR), defined as time from diagnosis to recurrence of disease. Recurrence of disease was defined as event, whereas disease-free status and death with no evidence of disease were considered censors. The secondary outcome was overall survival (OS), defined as time from diagnosis to death of any cause. Death of any cause was defined as event; patients alive at latest evaluation were censored. The prognostic effect of anterior vs posterior tumor extension was tested through the following methods: (1) the Kaplan-Meier method, evaluating the association of tumor extension with outcomes through the hazard ratio (HR) with 95% CI and (2) via the adjusted HR with 95% CI calculated from a multivariable model. The discriminative power of anterior vs posterior tumor extension was estimated through the difference in terms of integral of the area under the curve within 60 months of follow-up determined by inclusion of this covariate into a multivariable Cox proportional hazards model of TTR. The multivariable model was built with a priori selection of covariates and was run to check for independence of anterior vs posterior classifications. Results are reported as adjusted HRs with 95% CIs. Assumptions of the model and multicollinearity were checked as appropriate. The best-performing line was identified by studying the aforesaid multivariable analyses. An analysis of association between anterior vs posterior classification and the following potential confounders was performed: (1) pT category, (2) DOI, (3) pN category, (4) number of involved lymph nodes, and (5) margin status. Moreover, the combined effect on survival of anterior vs posterior classification and T/N category and margin status was studied through the Kaplan-Meier method. The software RStudio, version 2022.07.2 (Posit PBC), was used for statistical analyses.
Results
eTable 1 in Supplement 1 summarizes the main characteristics of patients and tumors. Of the 133 patients included, 79 (59.4%) were male, and the mean (SD) age was 62.7 (15.4) years. Seventy-one patients (53.4%) were smokers. Patients’ general conditions were classified according to the Adult Comorbidity Evaluation–27: 45 patients (33.8%) had a grade of 0, 43 (32.3%) had a grade of 1, 24 (18.0%) had a grade of 2, 7 (5.3%) had a grade of 3, and 14 (10.5%) had a grade of 9. Available preoperative imaging included contrast-enhanced MR for 92 patients (69.2%), contrast-enhanced CT for 16 (12.0%), and PET/MR for 25 (18.8%). Classification of OTFSCC was based on T2-weighted images (2- to 3-mm slice thickness) and fat-saturated, contrast-enhanced T1-weighted images (1-mm slice thickness) on contrast-enhanced MR and PET/MR, and contrast-enhanced, soft-tissue window images (≤1 mm) on contrast-enhanced CT.
The number (and relative percentage) of anterior and posterior tumors stratified according to the 4 anatomical lines was 33 (24.8%) and 100 (75.2%), 71 (53.4%) and 62 (46.6%), 40 (30.1%) and 93 (69.9%), and 64 (48.1%) and 69 (51.9%) for CPL, CBL, SDL, and LSL, respectively. Intrarater and interrater agreement was moderate to strong for all lines considered measured through the Cohen κ. Intrarater agreement was 0.86 (95% CI, 0.67-1.00), 0.93 (95% CI, 0.79-1.00), 0.78 (95% CI, 0.55-1.00), and 0.93 (95% CI, 0.79-1.00) for CPL, CBL, SDL, and LSL, respectively. Interrater agreement was 0.93 (95% CI, 0.79-1.00), 1.00 (95% CI, 1.00-1.00), 0.93 (95% CI, 0.79-1.00), and 0.93 (95% CI, 0.79-1.00) for CPL, CBL, SDL, and LSL, respectively.
At histopathology, the majority of patients with OTFSCC had advanced disease (pT3-pT4 category, 81 [60.9%]) that was moderately/poorly differentiated (grade 2-3, 118 [88.7%]). Fifty-six patients (42.1%) had nodal metastases (15 with pN1, 1 with pN2a, 15 with pN2b, 7 with pN2c, and 18 with pN3b). Perineural and lymphovascular invasion were found in 76 (35.3%) and 42 (25.9%) tumors, respectively. R0 resection was achieved in 76 patients (57.1%), while 57 (42.9%) had R1 resection (positive margins, 7 [5.3%]; close margins, 50 [37.6%]). Surgery was followed by adjuvant RT in 76 patients (57.1%), and 28 (21.1%) received concomitant ChT.
The mean (SD) follow-up time was 38.6 (33.2) months. The median (range) follow-up time was 29 (3-130) months. During the follow-up, 18 patients (13.5%) died of the disease, 12 (9.0%) died of other causes, and 28 (21.1%) had tumor relapse: 8 (6.0%) local, 10 (7.5%) regional, 7 (5.3%) locoregional, and 7 (5.3%) developed distant metastasis. One hundred patients (75.2%) were alive without disease at last contact.
TTR estimates at 1, 3, and 5 years were 83.6% (95% CI, 77.2%-90.4%), 80.0% (95% CI, 72.9%-87.8%), and 76.5% (95% CI, 78.4%-85.6%), respectively. OS estimates at 1, 3, and 5 years were 87.6% (95% CI, 81.9%-93.7%), 79.0% (95% CI, 71.5%-87.2%), and 71.4% (95% CI, 62.0%-82.2%), respectively. TTR and OS were worse for posterior OTFSCC classified according to CPL, SDL, and LSL (Figure 3). The 5-year TTR difference when comparing anterior with posterior OTFSCC was 21.0% (95% CI, 8.3%-33.7%), 15.5% (95% CI, 1.0%-30.0%), and 17.2% (95% CI, 2.2%-32.3%) for CPL, SDL, and LSL, respectively, and unadjusted HRs were 9.9 (95% CI, 4.3-22.9), 4.1 (95% CI, 1.8-8.9), and 3.1 (95% CI, 1.5-6.4), respectively. No relevant differences in terms of TTR and OS were observed for cancers stratified according to CBL (5-year TTR difference, 6.2% [95% CI, 0.0%-24.6%]; HR, 1.5 [95% CI, 0.7-3.2]).
Figure 3. Kaplan-Meier Plots Illustrating Time to Recurrence (TTR) and Overall Survival (OS) Rate Overall and in Anterior vs Posterior Tumors.
Posterior tumors defined according to chin-palate line, Stensen duct line, and lingual septum line had a worse prognosis in terms of TTR and OS. HR indicates hazard ratio.
At the multivariable analysis on TTR (including anteroposterior extension, T category, N status, margin status, and adjuvant RT), N status (adjusted HR, 3.0 [95% CI, 1.2-7.1]) and anteroposterior classification according to CPL (adjusted HR, 7.1 [95% CI, 0.9-54.6]) were the variables associated with the highest adjusted HR (Table). The gain in integral of the area under the curve of TTR multivariable models determined by the inclusion of anteroposterior classification according to CPL, CBL, SDL, and LSL was 0.03, 0.00, 0.02, and 0.02, respectively (eFigure 2 in Supplement 1), thus demonstrating poor discriminative power gain. No relevant differences were found in terms of pT category, DOI, number of nodal metastases, and rate of margin involvement comparing anterior with posterior OTFSCC classified according to CPL (eFigure 3 in Supplement 1). Nodal status (classified as N positive vs NX-N0) and ENE were more frequent in posterior vs anterior OTFSCC (rate of patients with nodal metastases, 53.0% [95% CI, 43.3%-62.5%] vs 15.2% [95% CI, 6.7%-30.9%]; rate of nodal metastases with ENE, 19.0% [95% CI, 12.5%-27.8%] vs 0.0% [95% CI, 0.0%-10.4%]; eFigure 4 in Supplement 1). Furthermore, TTR and OS were stratified according to (1) CPL position and pT category, (2) CPL position and N category, and (3) CPL position and margin status (Figure 4). Stratification was relevant in terms of both TTR and OS: the worst prognosis was observed for (1) posterior T3 to T4 OTFSCC, (2) posterior tumors with positive neck nodes, and (3) posterior tumors with close or involved margins. Moreover, (1) anterior T3 to T4 OTFSCC was associated with better prognosis than posterior T1 to T2 cancers, (2) anterior N-positive tumors had better prognosis than posterior NX or N0 cancers, and (3) anterior R1 tumors were associated with better prognosis than posterior R0 cancers.
Table. Results of the Multivariate Analysis on Time to Recurrence.
| Covariate | Adjusted hazard ratio (95% CI) | |||
|---|---|---|---|---|
| Chin-palate line | Chin-basion line | Stensen duct line | Lingual septum line | |
| Position | ||||
| Chin-palate line | ||||
| Anterior | 1 [Reference] | NA | NA | NA |
| Posterior | 7.08 (0.92-54.62) | NA | NA | NA |
| Chin-basion line | ||||
| Anterior | NA | 1 [Reference] | NA | NA |
| Posterior | NA | 1.02 (0.45-2.29) | NA | NA |
| Stensen duct line | ||||
| Anterior | NA | NA | 1 [Reference] | NA |
| Posterior | NA | NA | 2.68 (0.77-9.36) | NA |
| Lingual septum line | ||||
| Anterior | NA | NA | NA | 1 [Reference] |
| Posterior | NA | NA | NA | 2.13 (0.87-5.18) |
| Pathological T category | ||||
| T1-T2 | 1 [Reference] | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| T3-T4 | 1.70 (0.64-4.54) | 2.13 (0.74-6.12) | 1.76 (0.64-4.85) | 1.86 (0.68-5.08) |
| N category | ||||
| NX-N0 | 1 [Reference] | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| N positive | 3.03 (1.22-7.14) | 3.45 (1.37-8.33) | 3.03 (1.23-7.14) | 2.86 (1.18-7.14) |
| Margin status | ||||
| R0 | 1 [Reference] | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| R1 | 1.19 (0.56-2.54) | 1.09 (0.51-2.33) | 1.09 (0.51-2.31) | 1.06 (0.50-2.25) |
| Adjuvant treatment | ||||
| None | 1 [Reference] | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| Radio(chemo)therapy | 0.54 (0.22-1.31) | 0.67 (0.26-1.55) | 0.62 (0.25-1.52) | 0.68 (0.28-1.65) |
Abbreviation: NA, not applicable.
Figure 4. Kaplan-Meier Plots Illustrating Time to Recurrence (TTR) and Overall Survival (OS) Rate Stratified by Chin-Palate Line (CPL) Position and Category or Margin Status.
Hazard ratios and 95% CIs of TTR and OS are reported in eTable 2 in Supplement 1. The CPL posterior position with T1 to T2/R0/NX to N0 disease has a worse to comparable prognosis than anterior T3 to T4/R1/N-positive oral tongue and floor squamous cell carcinoma.
Discussion
The present study was designed to specifically investigate the prognostic significance of anteroposterior tumor extension in OTFSCC. Four anatomical lines were identified to classify OTFSCC into anterior or posterior. The Japanese Society of Oral Oncology guidelines defined cancers of the oral cavity floor as anterior or posterior according to the boundary connecting the spaces between the canine and first premolar bilaterally.18 However, patients with oral cavity cancers often drink alcohol and smoke and have poor oral hygienic conditions and subsequent partial or total edentulism. The boundaries analyzed in the present study, on the other hand, are based on consistent, easy-to-identify, and reliable anatomical landmarks and were proven to be easily reproducible, as intrarater and interrater agreements resulted optimal.
In this study, patients with posterior OTFSCC had a worse prognosis in terms of OS and TTR. The prognostic difference was more evident when tumors were stratified according to CPL. Thus, CPL was recognized as the most clinically relevant line in terms of prognosis. Of note, CPL was arbitrarily defined in an attempt to provide reliable anatomical landmarks but does not correspond to an anatomical structure separating the tongue and floor of mouth in an anterior and posterior compartment. The worse prognosis of posterior tumors was irrespective of other potential confounders, and all classic prognostic factors but N status and ENE rate were evenly distributed between anterior and posterior tumors (eFigures 3 and 4 in Supplement 1). Presence of regional metastasis and/or ENE were more frequent in posterior tumors, which have likely affected the prognosis to a substantial extent. However, both N status and anteroposterior classification according to CPL showed a high effect size at multivariable analysis (Table). In a recent study of 62 patients with cancer of the oral cavity floor,19 Oikawa et al classified tumors according to the Japanese guidelines and found that anterior tumor extension was an independent risk factor for multiple primary cancer development and was more commonly associated with pN2 to pN3 cervical lymph node metastasis. Of note, the worse prognosis of anterior oral floor cancers was attributed to the higher propensity toward synchronous primaries development, which was an exclusion criterion in the present study.
OTFSCC has a high potential for regional spread to neck lymph nodes.2 Burden of nodal disease is deemed to be the most relevant prognostic factor, since the presence of a single metastatic node at presentation is associated with a 50% drop in 5-year survival.20 It is possible that posterior tumor extension increases the risk of lymph node metastasis and thus worsens prognosis. Posterior tumors might have access to a denser lymphatic network, which is referred to as the T-N tract.21 In fact, patients with T-N tract involvement were found to develop lymph node metastases more frequently than those without.21 Another hypothesis that could explain the worse prognosis for posterior tumors is the easier access to a wide spectrum of local pathways of spread (ie, styloglossus, genioglossus and hyoglossus, main branches of lingual and hypoglossal nerves).22 It has been postulated that a more complex geometry of growth pattern could increase the difficulty of achieving adequate resection margins in posterior tumors.23 Indeed, the results shown herein do not support this conclusion, as we found no relevant differences in terms of margin status between anterior and posterior tumors (eFigure 3 in Supplement 1). However, it is worth noting that positive and close margins were merged in a single category (ie, R1) to avoid generation of too-small subcohorts at survival analysis. This represented a necessary approximation but might lead to underestimating the rate of positive margins in posterior OTFSCC.
Based on the evidence that posterior tumors have a greater tendency for lymph node metastasis and regional recurrence, some clinical implications can be hypothesized. Assessment of neck status in posterior tumors should be performed more carefully. For instance, upfront elective neck dissection may be considered in posterior tumors with a DOI less than 4 mm, which is below the most-accepted threshold that mandates elective neck treatment in oral SCC.4 Another potential change of practice is in regard to adjuvant treatment. The posterior extension could be regarded as an indication for treatment intensification, for instance irradiating the tumor bed of pT1 to pT2 disease and/or the neck in pNX to pN0 disease, even without other risk factors (eg, positive margins, perineural invasion, lymphovascular invasion). This is consistent with the proposal of considering T-N tract involvement an indication for adjuvant RT,24 as even small OTFSCC with DOI of 10 mm or less, if posteriorly located, might easily involve structures of the T-N tract and thus become more prone to metastasize regionally. Moreover, concomitant ChT could be taken into consideration for posterior pT3 to pT4 cancer, irrespective of the presence of ENE and/or margins involvement, which are the classic factors dictating the need for concomitant treatment. Doubtlessly, all of these are potential indications deriving from the present retrospective analysis and should be rigorously assessed in clinical trials prior to considering their application in routine practice. We do not advocate for any deviation from the standard of care in view of the preliminary evidence presented herein.
Limitations
The main limitations of the present study are its retrospective nature and limited sample size, which result in potential multivariable model overfitting.
Conclusions
In this cohort study, OTFSCC with a posterior extension to the CPL was associated with a higher risk of recurrence and death. Despite the limitations of the restricted sample size and potential model overfitting, this analysis suggests that the poor prognosis conveyed by the posterior tumor extension is independent of other relevant prognosticators except for the burden of nodal disease. The estimate of this study is not precise and does not allow for definitive clinically important conclusions; therefore, further prospective studies are necessary to confirm these data.
eFigure 1. A 3D representation of a posterior tumor: the tongue, the mandible, and their relationship with the blue plane (CPL) are shown
eFigure 2. Discriminative power of multivariable time-to-recurrence (TTR) models including anterior-vs-posterior tumor extension, measured as integral of the area under the curve (iAUC) within 60 months of follow-up
eFigure 3. Association analysis assessing the combination of anterior-vs-posterior classification according to chin-palate line (CPL) and potential prognostic confounders: pathological depth of invasion (pDOI), T category, N category, and margin status
eFigure 4. Distribution between anterior and posterior tumors stratified according to CPL in terms of nodal status (N status and extranodal extension)
eTable 1. Main clinical features of the 133 patients included in the study
eTable 2. Summary of hazard ratios (HR) and 95%-confidence intervals (95%-CI) of the combined effect on time-to-recurrence (TTR) and overall survival (OS) of anterior-vs-posterior classification and T-/N-category and margin status displayed in Figure 4
Data Sharing Statement
References
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
eFigure 1. A 3D representation of a posterior tumor: the tongue, the mandible, and their relationship with the blue plane (CPL) are shown
eFigure 2. Discriminative power of multivariable time-to-recurrence (TTR) models including anterior-vs-posterior tumor extension, measured as integral of the area under the curve (iAUC) within 60 months of follow-up
eFigure 3. Association analysis assessing the combination of anterior-vs-posterior classification according to chin-palate line (CPL) and potential prognostic confounders: pathological depth of invasion (pDOI), T category, N category, and margin status
eFigure 4. Distribution between anterior and posterior tumors stratified according to CPL in terms of nodal status (N status and extranodal extension)
eTable 1. Main clinical features of the 133 patients included in the study
eTable 2. Summary of hazard ratios (HR) and 95%-confidence intervals (95%-CI) of the combined effect on time-to-recurrence (TTR) and overall survival (OS) of anterior-vs-posterior classification and T-/N-category and margin status displayed in Figure 4
Data Sharing Statement