SEARCH

SEARCH BY CITATION

Keywords:

  • depth of invasion;
  • oral tongue cancer;
  • outcome;
  • prognostic factors

Abstract

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. FUNDING SOURCES
  7. REFERENCES

BACKGROUND:

The objective of this study was to report the authors' experience in the management of patients with early stage squamous cell cancer (SCC) of the oral tongue and determine clinicopathologic factors predictive of outcome.

METHODS:

Two hundred sixteen patients with early stage (cT1T2N0) SCC of the oral tongue were identified from a pre-existing database of patients with oral cancer who were treated at Memorial Sloan-Kettering Cancer Center from 1985 to 2005. Patient, tumor, and treatment characteristics were recorded. Overall survival (OS), disease-specific survival (DSS), and recurrence free survival (RFS) were calculated using the Kaplan-Meier method. Predictors of outcome were identified using multivariate analysis.

RESULTS:

With a median follow-up of 80 months (range, 1-186 months), the 5-year DSS, OS, and RFS rates were 86%, 79%,and 70%, respectively. Local, neck, and distant recurrences occurred in 24 patients (11%), 40 patients (18%), and 5 patients (2%), respectively. Multivariate analysis identified occult neck metastases as the main independent predictor of OS, DSS, and RFS; patients who had occult metastases had a 5-fold increased risk of dying of disease compared with patients who did not have occult metastases (5-year DSS, 85.5% vs 48.5%; P = .001). A positive surgical margin was the main independent predictor for local RFS (91% vs 66% for a negative surgical margin; P = .0004), and depth of invasion was the main predictor for neck RFS (91% vs 73% for depth of invasion <2 mm and >2 mm, respectively; P = .02).

CONCLUSIONS:

In the authors' experience, patients with early stage oral tongue cancer have excellent outcomes. In the current study, the presence of occult metastases was the main predictor of survival outcome. Cancer 2012;. © 2011 American Cancer Society.

Worldwide, there are an estimated 405,000 new cases of oral cancer diagnosed each year, and >50% are cancers of the oral tongue. The incidence of oral tongue squamous cell carcinoma in the United States has increased over the past 3 decades and currently is estimated at 3.0 per 100,000 population. In 2007, the 5-year disease-specific survival rate for patients with oral tongue cancer in the SEER registry was 60.2%, reflecting only a marginal improvement in the past 20 years.1 In patients with early stage disease (T1T2N0), outcomes generally are good, and the reported 5-year survival rates range between 75% and 89%.2-5 In the literature, there are few reports from studies that carried out a comprehensive analysis of the clinical and pathologic factors predictive of outcome in patients with early stage oral tongue cancer, because large numbers of patients are required to produce meaningful data supported by robust statistical analysis. Therefore the objective of the current study was to report our experience in the management of a large series of patients with early stage oral tongue cancer who were treated in a single institution and to identify the clinical and pathologic factors predictive of outcome using multivariate analysis.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. FUNDING SOURCES
  7. REFERENCES

After we received approval from the institutional review board of Memorial Sloan-Kettering Cancer Center (MSKCC), 216 patients with early stage (clinical [c] T1N0-cT2N0) squamous cell cancer of the oral tongue were identified from a pre-existing database of patients with squamous cell carcinoma of the oral cavity who received treatment at MSKCC between the 1985 and 2005. Only patients who underwent surgery and received postoperative radiation therapy (PORT) at MSKCC were analyzed. Patients who either underwent surgery or received radiation at other hospitals were excluded. Details on patient characteristics, tumor characteristics, index treatment, and surgical outcomes were available for analysis.

Patient, tumor, and treatment characteristics are listed in Table 1. The median patient age was 59 years (range, 14-88 years), 53% of patients were men, 50% were smokers, and 36% were drinkers of alcohol. On clinical examination, 50% of tumors were classified as T2. One hundred seventy-nine patients (83%) underwent surgery as their only treatment, including 105 patients who underwent partial glossectomy and 74 patients who underwent partial glossectomy plus neck dissection. Thirty-seven patients (17%) underwent surgery and also received PORT, including 36 patients who underwent both partial glossectomy and neck dissection and 1 patient who underwent partial glossectomy without neck dissection. One hundred ten patients underwent elective neck dissection (END), the majority of whom underwent supraomohyoid neck dissection (103 patients; 93%). At our institution, levels I through IV are dissected routinely for supraomohyoid neck dissection because of the small risk of skip metastases to level IV for oral tongue cancers. For primary tumors, pathology revealed that 50% were pathologic T2 (pT2) tumors, and 18% had close or positive margins (a close margin was defined as a margin ≤1 mm), 58% had a tumor depth ≥2 mm, and 49% had a tumor depth ≥4 mm. Of the 110 patients who had a clinically negative neck, histopathologic examination revealed occult metastases in 31 patients (28%). Of these, 13 patients (42%) had evidence of extracapsular spread in the lymph nodes (8 patients had gross evidence, and 5 patients had microscopic evidence).

Table 1. Patient, Tumor, and Treatment Characteristics
CharacteristicNo. of Patients%
  1. Abbreviations: MRNS, modified radical neck dissection; ND, neck dissection; PG, partial glossectomy; PORT, postoperative radiotherapy; RND, radical neck dissection; S, surgery; SOHND, supraomohyoid neck dissection.

Age, y  
 <6011553
 ≥6010147
Sex  
 Men11553
 Women10147
Tobacco  
 None5626
 Yes10950
 Not recorded5124
Alcohol  
 None6229
 Yes7736
 Not recorded7736
Clinical tumor classification  
 cT111051
 cT210649
Pathologic tumor classification  
 pT110950
 pT210750
Pathologic lymph node status, n=110  
 pN07972
 pN11816
 pN2b1312
Extracapsular spread, n=31  
 None1652
 Yes1342
 Not recorded26
Depth of invasion, mm  
 <23818
 ≥212658
 <45927
 ≥410549
 Not recorded5224
Margin status  
 Negative17782
 Positive/close2813
 Not recorded115
Histologic grade  
 Well differentiated6530
 Moderately differentiated10147
 Poorly differentiated84
 Not recorded4219
Management  
 S17983
 S+PORT3717
Management class  
 PG alone10549
 PG+PORT10
 PG+ND7434
 PG+ND+PORT3617
ND  
 No10649
 Yes11051
Type of ND, n=110  
 SOHND10292
 MRND44
 RND22
 Bilateral22

Overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), local RFS (LRFS), neck RFS (NRFS), and distant RFS (DRFS) were determined by using the Kaplan-Meier method. To identify factors that were predictive of survival, the following variables were subjected to univariate analysis using the log-rank test: age, sex, tobacco and alcohol status, cT classification, pT classification, pathologic lymph node (pN) status, differentiation of tumor, margin status, depth of invasion, type of treatment, and PORT. Clinical and pathologic factors that were significant on univariate analysis were assessed next by multivariate analysis using a Cox regression model and the log-rank test. Statistical analyses were carried out using the statistical software packages SPSS for Windows (version 11.01; (SPSS Inc., Chicago, Ill) and JMP (version 4.0; SAS Institute Inc, Cary, NC).

RESULTS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. FUNDING SOURCES
  7. REFERENCES

At a median follow-up of 80 months (range, 1-186 months), the 5-year DSS, OS, and RFS rates for all patients were 86%, 79%, and 70%, respectively (Fig. 1). Overall, 59 patients developed recurrent disease, including 24 local recurrences (11%), 40 regional recurrences (18%), and 5 distant recurrences (2%). The factors that were predictive of OS, DSS, and RFS in univariate analysis are listed in Table 2. The factors that were predictive of LRFS, NRFS, DRFS in univariate analysis are listed in Table 3.

thumbnail image

Figure 1. Disease-specific survival (DSS), overall survival (OS), and recurrence-free survival (RFS) are illustrated for patients with early stage tongue cancer.

Download figure to PowerPoint

Table 2. Prognostic Factors for Overall, Disease-Specific, and Recurrence-Free Survival: Univariate Analysis
VariableNo. of Patients5-Year OS, %P5-Year DSS, %P5-Year RFS, %P
  • Abbreviations: DSS; disease-free survival; ND, neck dissection; OS, overall survival; PG, partial glossectomy; PORT, postoperative radiotherapy; RFS, recurrence-free survival; S, surgery.

  • a

    Significant P value.

Age, y       
 <6011585 87.5 69.3 
 ≥6010171.6<.0001a83.2.2569.4.82
Sex       
 Men11580.8 85.5 69.1 
 Women10176.3.9885.8.8669.9.96
Tobacco       
 None5685 86 66.2 
 Yes10971.6<.0001a84.2.7372.7.32
Alcohol       
 None6288 89.5 72.5 
 Yes7775.3.01a84.9.4969.3.74
Clinical tumor classification       
 cT111084.2 91.8 72.2 
 cT210673.1.02a79.03a66.6.62
Pathologic tumor classification       
 pT110984 91.7 71.9 
 pT210773.3.03a79.3.04a66.9.69
Pathologic lymph node status       
 pN07980.3 85.5 69.4 
 pN11858.8 61.4 61.9 
 pN2b1345.8.007a48.5.001a31.2.04a
Extracapsular spread       
 None1656.2 56.2 50 
 Yes1350.854.7.5546.9.8
Depth of invasion, mm       
 <23889.2 97.1 79.1 
 ≥212673.7.004a79.9.02a62.06a
 <45985.7 94.1 74.6 
 ≥410572.7.003a78.4.01a61.09
Margin status       
 Negative17780 86.7 71.9 
 Positive/close2865.6.0672.5.003a49.1.04a
Histologic grade       
 Well differentiated6581.7 90.5 70.6 
 Moderately differentiated10173.4 79.5 66.7 
 Poorly differentiated871.4.2971.4.1457.1.86
Management       
 S17982.7 89.6 72.6 
 S+PORT3758.9.0002a66.2<.0001a54.2.05a
Management class       
 PG alone10583.2 92.4 74.7 
 PG+PORT1100 100 100 
 PG+ND7481.9 85.8 69.7 
 PG+ND+PORT3657.6.003a65.1<.0001a52.8.16
ND       
 No10683.3 92.5 75 
 Yes11073.8.0778.9.002a64.3.16
Table 3. Prognostic Factors for Local, Neck, and Distant Recurrence-Free Survival: Univariate Analysis
VariableNo. of Patients5-Year LRFS, %P5-Year NRFS, %P5-Year DRFS, %P
  • DRFS, disease recurrence-free survival; LRFS, local recurrence-free survival; ND, neck dissection; NRFS, neck recurrence-free survival; PG, partial glossectomy; PORT, postoperative radiotherapy; S, surgery.

  • a

    Significant P value.

Age, y       
 <6011586.7 80.2 96 
 ≥6010189.4.4976.8.7698.4.29
Sex       
 Men11591.8 74.5 96.6 
 Women10183.8.1683.2297.5.72
Tobacco       
 None5677.5 82 100 
 Yes10993.6.004a77.8.6696.4.21
Alcohol       
 None6285.6 82.8 100 
 Yes7792.10.2576.2.4398.4.35
Clinical tumor classification       
 cT111089.4 78.4 100 
 cT210686.50.8379.7993.7.02a
Pathologic tumor classification       
 pT110989.3 78.2 100 
 pT210786.70.8879.2.7393.8.02a
Pathologic lymph node status       
 pN07987.1 76.3 96.8 
 pN11877.9 93.8 86.5 
 pN2b1367.30.269.3.2980.11
Extracapsular spread       
 None1680.4 87.5 74.7 
 Yes1364.30.9175.52100.23
Depth of tumor invasion, mm       
 <23888 91 100 
 ≥212685.70.8172.8.02a96.5.28
 <45991.7 82.4 100 
 ≥410582.80.1574.1995.9.16
Surgical margin status       
 Negative17790.6 78.2 98.5 
 Positive/close2866.4.0004a80.7.8986.7.002a
Histologic grade       
 Well differentiated6585 81.7 100 
 Moderately differentiated10186.1 76.4 94.4 
 Poorly differentiated8100.5466.7.7685.7.08
Management       
 S17990.8 77.8 98.6 
 S+PORT3774.01a84.8.4788.1.003a
Management class       
 PG alone10592.2 79.1 100 
 PG+PORT1100 100 100 
 PG+ND7488.8 75.8 96.5 
 PG+ND+PORT3673.1.0784.3.8287.6.01a
ND       
 No10692.3 79.4 100 
 Yes11083.9.1978.2.8394.02a

Because of the small number of events for each outcome measure and the large number of variables that were significant on univariate analysis, we could not perform multivariate analysis on all clinical and pathologic variables in the same model. Therefore, we created a multivariate model for clinical predictors of outcome and a model for pathologic predictors of outcome (Tables 4 and 5).

Table 4. Clinical Factors Predictive of Outcome on Multivariate Analysis
 OSDSS
VariableHR (95% CI)PHR (95% CI)P
  1. Abbreviations: CI, confidence interval; DSS, disease-specific survival; HR, hazard ratio; OS, overall survival.

Age, y    
 <60Referent Referent 
 ≥603.1 (1.5-6.4).002 NS
Tobacco    
 NoneReferent   
 Yes NS 
Alcohol    
 NoneReferent   
 Yes NS 
Clinical tumor classification    
 cT1Referent Referent 
 cT2 NS2.2 (1-4.5).04
Table 5. Pathologic Factors Predictive of Outcome on Multivariate Analysis
 OSDSSRFSLRFSNRFS
VariableHR (95% CI)PHR (95% CI)PHR (95% CI)PHR (95% CI)PHR (95% CI)P
  1. Abbreviations: CI, confidence interval; DSS, disease-specific survival; LRFS, local recurrence-free survival; OS, overall survival; NRFS, neck recurrence-free survival; NS, nonsignificant; OR, odds ratio; RFS, recurrence-free survival.

Pathologic tumor classification          
 pT1Referent Referent Referent Referent   
 pT2 NS NS NS NS 
Pathologic lymph node status          
 pN0Referent Referent Referent Referent   
 pN11.4 (0.6-3.6)NS1.9 (0.6-5.6)NS0.9 (0.3-2.3)NS1.7 (0.4-6.8)NS  
 pN2b2.7 (1-6.9).044.8 (1.6-14.1).0042.6 (0.9-6.9).055.4 (1.3-21.4).02 
Depth of invasion, mm          
 <2Referent Referent Referent Referent Referent 
 ≥2 NS NS NS NS3.7 (1.1-12.2).03
Margin status          
 NegativeReferent Referent Referent Referent   
 Positive/close NS NS NS3.2 (1.1-9.3).04 

For OS, univariate analysis indicated that age >60 years, tobacco and alcohol use, T2 tumor classification, positive pN status, depth of the primary tumor (≥2 mm and ≥4 mm), and PORT were predictive of a poor outcome. Multivariate analysis of clinical predictors indicated that only age >60 years remained an independent predictor of OS (Table 4); patients aged >60 years had a 3-fold increased risk of dying compared with patients aged <60 years. Multivariate analysis of pathologic predictors revealed that only pathologic neck status remained an independent predictor of OS (Table 5); patients who had N2b neck status had a 2.7-fold increased risk of dying compared with patients who had N0 neck status.

For DSS, univariate analysis indicated that T2 tumor, positive pN status, depth of the primary tumor (≥2 mm and ≥4 mm), positive surgical margins, PORT, and neck dissection were predictive of a poor outcome. In a multivariate analysis of clinical predictors, only cT classification remained an independent predictor of DSS (Table 4, Fig. 2); patients with T2 tumors had a 2.2-fold increased risk of dying from disease compared with patients who had T1 tumors. Multivariate analysis of pathologic predictors indicated that only pathologic neck status remained an independent predictor of DSS (Table 5); patients who had pN2b neck status had a 4.8-fold increased risk of dying compared with patients who had N0 neck status (Fig. 3).

thumbnail image

Figure 2. Disease-specific survival (DSS) is illustrated for patients with early stage tongue cancer stratified according to clinical tumor (cT) classification.

Download figure to PowerPoint

thumbnail image

Figure 3. Disease-specific survival (DSS) is illustrated for patients with early stage tongue cancer stratified according to pathologic lymph node (pN) status.

Download figure to PowerPoint

For RFS, univariate analysis indicated that positive pN status, depth of the primary tumor ≥2 mm, positive surgical margins, and PORT were predictive of a poor outcome. Multivariate analysis of pathologic predictors indicated that only pathologic neck status remained an independent predictor of RFS (Table 5); patients who had pN2b neck status had a 2.6-fold increased risk of developing recurrent disease compared with patients who had N0 neck status.

For LRSF, univariate analysis indicated that tobacco use, positive surgical margins, and PORT were predictive of outcome. Multivariate analysis of pathologic predictors indicated that pathologic neck status and margin status were independent predictors of LRFS (Table 5); patients who had pN2b neck status had a 5.4-fold increased risk of developing recurrent disease compared with patients who had N0 neck status, and patients who had positive or close margins had a 3.2-fold increased risk of local recurrence compared with patients who had negative margins (Fig. 4).

thumbnail image

Figure 4. Local recurrence-free survival (LRFS) is illustrated for patients with early stage tongue cancer stratified according to margin status (negative or positive).

Download figure to PowerPoint

For NRFS, univariate analysis indicated that depth of invasion ≥2 mm was predictive of outcome. Multivariate analysis of pathologic predictors indicated that only depth of invasion of the primary tumor remained an independent predictor of NRFS (Table 5); patients who had a depth of invasion >2 mm had a 3.7-fold increased risk of developing a regional recurrence compared with patients who had a depth of invasion <2 mm (Fig. 5). For DRFS, several factors were predictive on univariate analysis (T2 tumor, positive pN status, positive surgical margins, PORT, and neck dissection), but the number of distant recurrences were so small that multivariate analysis could not be carried out.

thumbnail image

Figure 5. Neck recurrence-free survival (NRFS) is illustrated for patients with early stage tongue cancer stratified according to the depth of invasion (DOI) of the primary tumor.

Download figure to PowerPoint

DISCUSSION

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. FUNDING SOURCES
  7. REFERENCES

In the current study of patients with early stage SCC of the oral tongue, we observed 5-year DSS and OS rates of 86% and 79%, respectively. These outcomes compare very favorably with those reported in the literature, which range from 75% to 89%.2-5 The main reason for failure in early stage oral tongue cancer is locoregional recurrence, and distant metastases are rare. In our study, the local recurrence rate of 11% and the regional recurrence rate of 18% were similar to those reported in the literature.6-8 Because of our large patient series, it was possible to perform statistical analysis to identify predictors of outcome. Multivariate analysis indicated that local recurrence was determined mainly by margin status. Our positive margin rate of 13% compares favorably with reports in the literature of positive margins in the range between 7% and 22%.8, 9 With regard to neck recurrence, we observed that depth of invasion of the primary tumor was the main predictor, and patients who had tumors >2 mm in depth had an almost 4-fold risk of neck recurrence.

The most important finding in our study was the impact that occult regional metastases had on survival. In our multivariate analysis, the main independent predictor for DSS and OS was the status of the neck; patients who had occult metastases had a 5-fold increased risk of dying from disease compared with patients who had no occult metastases. In our study, the incidence of occult metastases was 28%, which is similar to that reported by Pimenta Amarel et al10 (23%) and Kligerman et al5 (21%). It is well recognized that the status of the clinically positive neck is a major determinant of survival outcome in other head and neck cancers. Our study indicates that this holds true even in the occult metastases scenario for oral tongue cancer. Because the status of the neck has a major impact on outcome, treatment of the neck is an important aspect in the management of these patients. There are many studies in the literature reporting on the therapeutic benefit of END.5, 11-13 END is advocated in general for the majority of tongue cancers except for very early stage (cT1), superficial tumors. In addition, END has the extra advantage of enabling the accurate staging of patients, which then allows for better patient counseling with regard to prognosis as well as allowing the clinician to identify patients who are at high risk of a poor outcome and selecting patients who need PORT. Recently, reports by Yuen et al3 and D'Cruz et al14 have advocated a policy of observation of the N0 neck in patients with early stage tongue cancer. Yuen et al3 carried out a prospective randomized trial of END versus observation and reported similar DSS in both groups. In that study, 11 of 35 patients in the observation group developed neck recurrence compared with 2 patients in the neck dissection group. This result corresponds to an occult metastases rate of 30%, which is similar to that reported in our current study. Despite the high incidence of recurrence in the observation group, all of the patients in the study by Yuen et al were salvaged because of a policy of strict surveillance. Thus, in that study, DSS in the observation group after salvage was similar to that in the END group. The authors concluded that a policy of observation was safe provided a policy of strict neck surveillance was implemented. However, this policy depends on regular follow-up and the use of regular imaging studies, such as ultrasound, to identify patients with neck recurrence. In general, such a management policy can be carried out only in large academic centers. In the report by D'Cruz et al14 on 359 patients, similar DSS was observed in patients who underwent neck dissection and those who were observed (DSS rate, 74% vs 68%, respectively). However, that was not a prospective randomized trial, and there were no data indicating whether patients were matched adequately with regard to depth of invasion, margin status, histologic grade, and tumor size. Therefore, those results are susceptible to selection bias. Recent evidence against neck observation from Tsang et al15 indicated that patients with early tongue cancer who underwent observation had poor survival. In our study, we did not include treatment (type of primary surgery, neck dissection, and the receipt of PORT) in our multivariate analyses because of the inherent selection bias from the physician, patient, and institutional preferences involved in treatment decision making. A flow diagram illustrating DSS in our patients stratified according to neck dissection, pN status, and PORT is provided in Figure 6. On univariate analysis, patients who underwent partial glossectomy alone had better survival than patients who underwent both partial glossectomy and neck dissection (DSS rate: 92% vs 79%; P = .002). However, an analysis of the pathology of the primary tumors in each cohort indicated that patients in the partial glossectomy group were highly selected and were more likely to have small T1 tumors that were not deeply infiltrating (Table 6). Thus, neck observation can be justified in some patients who have small, superficial tumors. Clearly, the identification of factors that predict for the presence of occult metastases is important. Previous studies have reported that the depth of invasion of the primary tumor is predictive of occult metastases.5, 16-27 A recent meta-analysis by Huang et al28 concluded that a primary tumor thickness ≥4 mm was the most predictive tumor thickness for occult metastases. Other studies also have reported that poor histologic grade23 was predictive of occult metastases. When we analyzed these factors in our cohort, we produced similar results (Table 7); 100% of patients with occult metastases had primary tumors with ≥2 mm depth of invasion, and 92% had tumors with ≥4 mm depth of invasion. In addition, 93% patients with occult metastases had either moderately or poorly differentiated tumors. Therefore, occult metastases were never identified in patients who had superficial, well differentiated tumors. The difficulty is how to assess depth of invasion at the time of surgery. Frozen section analysis may be helpful, but this may be restricted to centers where it is readily available with experienced head and neck pathologists. An alternative method currently being investigated by several groups is the use of preoperative ultrasonography and intraoperative ultrasonography.29, 30 This method reportedly demonstrated a high correlation between ultrasound measurement and pathologic measurement of tumor thickness with an accuracy of >90%. Therefore, this method may be used to select patients with thin tumors who can be offered partial glossectomy alone without END.

thumbnail image

Figure 6. This flow diagram illustrates the management of patients with early stage tongue cancer stratified according to neck dissection, pathologic lymph node (pN) status, and postoperative radiotherapy (PORT). cT indicates clinical tumor classification; DSS, disease-specific survival

Download figure to PowerPoint

Table 6. Pathologic Comparison of the Partial Glossectomy Cohort Versus the Partial Glossectomy and Neck Dissection Cohort
VariablePG AlonePG+NDPa
  • Abbreviations: ND, neck dissection; PG, partial glossectomy.

  • a

    P values were calculated using the chi-square test.

  • b

    Significant P value.

Pathologic tumor classification   
 pT17726 
 pT22848<.0001b
Depth of invasion, mm   
 <2308 
 ≥23954<.0001b
 <44216 
 ≥42746<.0001b
Margin status   
 Negative9164 
 Positive/close76.73
Grade   
 Well differentiated3823 
 Moderately differentiated3339 
 Poorly differentiated22.16
Table 7. Pathologic Factors Predictive of Occult Metastases in Patients With Early Stage Squamous Cell Cancer of the Oral Tongue
 Pathologic Lymph Node Status 
VariableNegativePositivePa
  • a

    P values were calculated using the chi square test.

  • b

    Significant P value.

Pathologic tumor classification   
 pT1266 
 pT25325.15
Depth of invasion, mm   
 <280 
 ≥25927.02b
Depth of invasion, mm   
 <4152 
 ≥45225.07
Margin status   
 Negative6224 
 Positive/close137.53
Tumor grade   
 Well differentiated252 
 Moderately differentiated4225 
 Poorly differentiated33.004b

An alternative option to having all patients undergo END may be sentinel lymph node biopsy (SLNB). Given our high incidence of occult metastases, SLNB may be particularly useful in these patients. The majority of oral tongue cancers are visualized easily and, in general, are accessible to direct injection. This technique for squamous cell carcinoma of the oral cavity was reported first in 2001 by Shoaib et al,31 who used SLNB before END in patients who had clinically negative neck status. Ross et al32 investigated 57 SLNBs in 48 patients with clinically N0 neck status and reported that 15 patients (35%) were upstaged by SLNB, and 28 patients (65%) were staged as sentinel lymph node-negative. At a mean follow-up of 18 months, only 1 patient developed regional neck disease after being staged negative on SLNB. The overall sensitivity of the technique was 94%. Since then, 2 multicenter prospective trials in Europe33 and the United States,34 with 5-year and 3-year follow-up data, respectively, have reported that the technique is a reliable and reproducible method for staging the neck. In the most recent study reported by Civantos et al34 on 140 patients with T1T2 oral cancer, SLNB correctly predicted a pathologically negative neck in 96% of patients. However, this technique does require experience and currently is recommended only for centers with the necessary expertise and the appropriate volume of patients, because, as demonstrated by Ross et al,35 centers that perform this technique with <10 patients per year have much lower sensitivity. Technical problems of “shine through,” in which the radioactivity level in the primary site potentially obscures the sentinel lymph node, is 1 potential problem. The role of SLNB in larger tumors also can be limited because of false-negative biopsies resulting from obstruction of lymphatic flow caused by tumor and redirecting of flow to neighboring lymph nodes.

The significant negative effect of occult metastases on outcome in patients who undergo neck dissection is illustrated in Figures 6 and 7, which indicated that, even when patients with occult metastases receive PORT, their DSS still is poorer compared with patients who have pathologically negative necks (DSS rate, 60% vs 87%). Although PORT improves neck recurrence rates in patients with head and neck cancer,36-39 it does not improve DSS to rates comparable to the rates for patients who have a pathologically negative neck. It is noteworthy that, among the patients who had pathologically positive cervical lymph nodes, 42% (13 of 31 patients) had extracapsular spread. These patients did not receive postoperative chemoradiation. However, it is now accepted that extracapsular spread, along with positive margin status, is the main criterion for chemoradiation after surgery.40, 41 Our current study was for the years 1985 through 2005, when PORT was our normal practice in these patients. However, since then, patients with positive neck disease and extracapsular spread have received chemoradiation. It is possible that this may improve DSS for these patients. Our results clearly suggest that strategies using chemotherapeutic agents or new molecular therapies are required to improve the survival of patients with occult metastases. Such therapies can arise only from a better understanding of the genetic events involved in invasion and metastases in tongue cancer.

thumbnail image

Figure 7. Disease-specific survival (DSS) is illustrated for patients with early stage tongue cancer stratified according to neck dissection (ND), pathologic lymph node (pN) status (negative [−ve] or positive [+ve]), and postoperative radiotherapy (PORT).

Download figure to PowerPoint

In conclusion, our experience in the management of patients with early stage tongue cancer indicates that these patients have a good prognosis. However, just as the presence of clinically positive neck disease is the main predictor of outcome in patients with head and neck cancer, the presence of occult neck metastases is the main predictor of outcome in patients with early stage tongue cancer.

FUNDING SOURCES

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. FUNDING SOURCES
  7. REFERENCES

No specific funding was disclosed.

CONFLICT OF INTEREST DISCLOSURES

The authors made no disclosures.

REFERENCES

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. FUNDING SOURCES
  7. REFERENCES