Abstract
Purpose
We sought to examine prognostic and therapeutic implications, including cost-effectiveness, of elective neck dissection in the management of patients with clinically-determined T1N0 oral tongue carcinoma.
Materials and methods
A retrospective review of patients with cT1N0 oral tongue squamous cell carcinoma who underwent surgical extirpation of primary tumor, with or without elective neck dissection, at UCLA Medical Center from 1990 to 2009 was performed. Cox proportional hazards regression was used to assess effects of variables on time to first loco-regional recurrence. A healthcare costs analysis of elective neck dissection was performed by querying the SEER-Medicare linked database.
Results
Of the 123 patients identified with cT1N0 squamous cell carcinoma of the oral tongue, 88 underwent elective neck dissection at the time of tumor resection while 35 did not. For all patients, disease-free survival at 3, 5, and 10 years was 93%, 82%, and 79%. Of the 88 patients undergoing elective neck dissection, 20 (23%) demonstrated occult metastatic disease. Male gender, tumor size, perineural invasion, and occult metastatic disease were individually associated with higher rates of loco-regional recurrence. There was no significant difference in loco-regional recurrence between those who underwent elective neck dissection and those who did not (HR = 0.76, p = 0.52). On cost analysis, neck dissection was not associated with any significant difference in Medicare payments.
Conclusions
The high rate of occult metastasis (23%) following elective neck dissection, which did not confer additional healthcare costs, leads to the recommendation of elective neck dissection in patients with cT1N0 oral tongue squamous cell carcinoma.
1
Introduction
Surgical resection of early primary squamous cell carcinomas (SCC) of the oral tongue has been accepted as the standard of care . However, the question of whether the patient with a clinically negative neck should undergo elective neck dissection versus observation remains unanswered. In particular, T1N0 and T1N1 oral tongue cancers generally portend favorable prognostic outcomes: the five year disease-free outcomes of T1N0 and T1N1 oral tongue SCC have been shown to be 76% and 71%, respectively . Recurrence occurs in approximately 23% of T1 oral tongue cancers, and is primarily regional rather than local . Prognosis following recurrence is debated: some report excellent control of nodal recurrence of a T1 primary tumor , while others report salvage as the exception rather than the rule .
The optimal management of a clinically-negative neck in stage I and stage II SCC of the oral tongue has remained controversial over the past three decades. The issue is of more than academic interest since cervical nodal metastasis has been shown to be the most significant prognosticator of survival for patients with SCC of the oral tongue, due to a decrease in survival in patients with cervical metastases as well as poor clinical outcomes with salvage therapy . Previous retrospective studies have reported the incidence of neck metastasis and recurrence rates with a wide range of values varying from 6% to 46% , and 27% to 42% , respectively.
The decision to treat the neck, therefore, is not made lightly in early-stage SCC of the oral tongue. While primary neck dissection fulfills diagnostic and therapeutic purposes, surgical intervention, which necessarily increases general anesthesia duration, is not without morbidity. It becomes imperative to clarify the role that elective neck dissection may play in patient outcome.
In an attempt to predict the risk of occult cervical metastases further, recent studies have demonstrated the importance of tumor depth, suggesting that the significantly increased risk of occult cervical metastases in tumors with a depth of invasion greater than 4 mm should undergo elective neck dissection . However, lack of a consensus toward measurement techniques, study populations, and cut-off values has slowed the adoption of tumor thickness and depth of invasion as a primary decision-making tool for neck dissection .
The aim of this study was to evaluate the patterns of recurrence and survival in patients with cT1N0 oral tongue SCC who underwent elective neck dissection with primary surgical resection compared to that of patients who did not undergo initial neck dissection. In order to delineate the clinical course of this disease as stratified by primary management, a retrospective analysis of 123 patients with cT1N0 oral tongue SCC treated at the University of Los Angeles, California (UCLA) Medical Center over an 18-year period was undertaken.
2
Materials and methods
Permission to perform the study was granted by the institutional review board. Patients diagnosed with SCC of the oral tongue during the period of 1992 and 2009 at UCLA Medical Center were considered. Inclusion criteria included patients who presented with clinically-determined T1N0 (cT1N0) disease, as specified by the American Joint Committee on Cancer (AJCC) , who underwent primary surgical resection of the tumor with or without neck dissection. Cases of cancer involving the base of tongue or recurrent oral tongue cancer were excluded from the study.
A retrospective chart review was performed to determine gender; stage of primary tumor; pathological features, including presence of metastases in neck dissection specimens, if performed; length of follow-up; and status of disease during follow-up.
2.1
Pathological analysis
For initial pathological analysis, all tissues were fixed in buffered formalin and submitted for histology after standard overnight machine processing. After processing, tissues were embedded in paraffin wax. These cassettes were then cut into 5-micron sections, placed on glass slides, and stained with hematoxylin and eosin. Cases were reviewed by a designated head and neck pathologist at the David Geffen School of Medicine at UCLA, and the presence of lymph node metastases was reported. Depth of tumor invasion was variably reported in specimens prior to 2000, and therefore, this was not further stratified herein. Variables were independently tested for their relation to recurrence using Cox proportional hazards regression, and Kaplan–Meier curves were generated to assess effects of variables on survival.
2.2
Healthcare costs analysis
To perform a cost analysis, the SEER-Medicare linked database was queried. Records of patients meeting the following inclusion criteria were analyzed in two separate groups: in the first group, patients with T1N0 SCC of the oral tongue who underwent partial glossectomy with neck dissection, and in the second group, patients with T1N0 SCC of the oral tongue who underwent partial glossectomy without neck dissection. Median and mean total Medicare payment amounts were calculated in a manner analogous to previously published work . A literature review yielded additional estimates of healthcare costs associated with radiation therapy.
2
Materials and methods
Permission to perform the study was granted by the institutional review board. Patients diagnosed with SCC of the oral tongue during the period of 1992 and 2009 at UCLA Medical Center were considered. Inclusion criteria included patients who presented with clinically-determined T1N0 (cT1N0) disease, as specified by the American Joint Committee on Cancer (AJCC) , who underwent primary surgical resection of the tumor with or without neck dissection. Cases of cancer involving the base of tongue or recurrent oral tongue cancer were excluded from the study.
A retrospective chart review was performed to determine gender; stage of primary tumor; pathological features, including presence of metastases in neck dissection specimens, if performed; length of follow-up; and status of disease during follow-up.
2.1
Pathological analysis
For initial pathological analysis, all tissues were fixed in buffered formalin and submitted for histology after standard overnight machine processing. After processing, tissues were embedded in paraffin wax. These cassettes were then cut into 5-micron sections, placed on glass slides, and stained with hematoxylin and eosin. Cases were reviewed by a designated head and neck pathologist at the David Geffen School of Medicine at UCLA, and the presence of lymph node metastases was reported. Depth of tumor invasion was variably reported in specimens prior to 2000, and therefore, this was not further stratified herein. Variables were independently tested for their relation to recurrence using Cox proportional hazards regression, and Kaplan–Meier curves were generated to assess effects of variables on survival.
2.2
Healthcare costs analysis
To perform a cost analysis, the SEER-Medicare linked database was queried. Records of patients meeting the following inclusion criteria were analyzed in two separate groups: in the first group, patients with T1N0 SCC of the oral tongue who underwent partial glossectomy with neck dissection, and in the second group, patients with T1N0 SCC of the oral tongue who underwent partial glossectomy without neck dissection. Median and mean total Medicare payment amounts were calculated in a manner analogous to previously published work . A literature review yielded additional estimates of healthcare costs associated with radiation therapy.
3
Results
We identified 123 patients with cT1N0 oral tongue SCC who fulfilled all inclusion criteria ( Table 1 ). Sixty-four were male and 59 were female. Age at the time of tumor resection ranged from 27 to 92 years, with a mean of 56 years. Length of follow-up ranged from 1 to 196 months, with a median of 29 months. For the entire study population, disease-free survival at 3, 5, 10 years was 93%, 82%, and 79% respectively ( Fig. 1 ).
| Age (years) | |
| Mean | 56 |
| Range | 27–92 |
| Gender | |
| Male | 64 (52%) |
| Female | 59 (48%) |
| Length of follow-up (months) | |
| Mean | 29 |
| Range | 1–196 |
| Degree of differentiation of primary tumor | |
| Well differentiated | 23 (19%) |
| Moderately differentiated | 82 (67%) |
| Poorly differentiated | 11 (9%) |
| Not reported | 7 (6%) |
| Perineural invasion in primary tumor | |
| Present | 35 (28%) |
| Absent | 37 (30%) |
| Not reported | 51 (41%) |
| Ipsilateral neck dissection at time of primary resection | |
| Performed | 88 (72%) |
| Not performed | 35 (28%) |
| Occult metastases in neck dissection specimen | |
| Present | 20 (23%) |
| Absent | 68 (77%) |
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