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Functional Outcomes After Treatment of Squamous Cell Carcinoma of the Base of the Tongue
Mark A. Perlmutter, BS;
Jonas T. Johnson, MD;
Carl H. Snyderman, MD;
Elmer R. Cano, MD;
Eugene N. Myers, MD
Arch Otolaryngol Head Neck Surg. 2002;128:887-891.
ABSTRACT
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Objective To compare functional outcome and quality of life after various treatments
for squamous cell carcinoma of the base of the tongue.
Design Retrospective survey using statistical comparison.
Setting Academic medical center, institutional practice.
Participants Patients treated for squamous cell carcinoma of the base of the tongue
between 1976 and 2000. Living patients 3 or more months after treatment were
eligible. Questionnaire packets including validated site-specific quality-of-life
instruments were mailed to 105 qualifying patients. Sixty-one patients participated,
forming a volunteer sample. Patient responses were grouped according to treatment
modality, operative vs nonoperative.
Main Outcome Measures The planned outcome was that nonoperative therapy would result in better
function than operative treatment.
Results Most comparisons indicated no statistical difference in outcome between
operative and nonoperative groups. Significant differences (95% confidence
interval) were calculated for age, interval since treatment, and T stage.
Group comparisons of patient responses revealed significant differences only
in xerostomia and days hospitalized.
Conclusions The tongue remains dysfunctional after both surgical and nonoperative
treatment. Nonoperative treatment might more adversely affect saliva. Surgery
is associated with a longer hospital stay.
INTRODUCTION
SQUAMOUS CELL carcinoma (SCC) of the base of the tongue (BOT) is an
aggressive tumor associated with a poor prognosis. Generally, the stage of
the tumor is advanced at presentation. Over the years, various treatments
have been developed to improve survival rates and today, various therapeutic
approaches for SCC of the BOT are available.1
The optimal treatment may now be defined as that treatment that provides the
best disease control with the least functional morbidity and greatest quality
of life. Surgical resection for advanced tumors of the BOT provides significant
functional disability and in some patients, may require total laryngectomy.1 As a result, nonoperative therapies such as external
beam radiation therapy (XRT), chemoradiation, and brachytherapy have replaced
surgery in some centers.1 For smaller lesions,
there are various options. Some advocate that XRT alone or a combined treatment
of surgery followed by radiation is the best course of action.2
Others believe that for T1 or T2 tumors, surgery alone is the best treatment
because XRT causes xerostomia, tissue fibrosis, and osteoradionecrosis, and
may accelerate dental caries.3-4
In recent years, however, combined treatment has been shown to be superior
to any single therapy.2, 5-7
For example, primary XRT followed by brachytherapy resulted in an 85% 5-year
survival in one study, while at the same time enabling patients to achieve
excellent functional status and quality of life.8
Some centers have already compared primary surgery with primary XRT and concluded
that nonsurgical treatment led to better performance.9
Recently, one study recommended that XRT and brachytherapy be considered only
for T1 and T2 tumors.10 We evaluated patients
treated at the University of Pittsburgh Medical Center, Pittsburgh, Pa, for
SCC of the BOT to determine their functional outcome and quality of life.
This study does not assess survival, but does give insight into functional
capabilities of this patient group by therapeutic cohort.
PATIENTS AND METHODS
This research project was approved by the biomedical institutional review
board of the University of Pittsburgh Medical Center. The records of patients
presenting to the University of Pittsburgh Medical Center with SCC of the
BOT between 1976 and 2000 were reviewed. Patients with less than a 3-month
interval since treatment, with insufficient data in their record, or who were
deceased were excluded from the study. Three months was selected as the minimum
interval since treatment because by this time the acute effects from treatment
had likely stabilized.
A total of 105 patients who underwent treatment for SCC of the BOT were
eligible for study. The patients who qualified received questionnaire packets
by mail to evaluate their performance status. Each packet contained an explanatory
letter from a physician followed by 3 independent questionnaire instruments.
The Performance Status Scale for Head and Neck Cancer Patients (List Questionnaire)
assesses 3 areas of function: eating in public, understandability of speech,
and normalcy of diet.11 Eating in public and
understandability of speech are measured using an ordinal scale of 25, 50,
75, and 100. Normalcy of diet is measured using an ordinal scale from 1 to
100 with increments of 10. This scale has been shown to be both reliable and
sensitive to functional differences.11 This
scale was modified to instruct patients to self-report. The University of
Washington Quality of Life Instrument12 (UW-QOL)
more thoroughly analyzes outcome and quality of life. Patients assessed their
own pain, appearance, activity, recreation, swallowing, chewing, speech, shoulder,
taste, saliva, and quality of life. Analysis of performance characteristics
of the UW-QOL has shown this instrument to be highly consistent and reliable
over time.13 Finally, we developed a third
set of questions, the History of Treatment, to evaluate the hardships patients
experienced directly due to their treatment (Figure 1). Self-addressed stamped envelopes were included in the
packets to encourage patient participation. These questionnaires were administered
once.
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History of Treatment questionnaire.
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Of the 105 eligible patients, 61 agreed to participate in the study.
Participating patients were characterized according to therapy. General cohort
characteristics analyzed included age, interval since treatment, T stage,
TNM stage, and presence of a comorbidity. Comorbidity was defined as a previous
or current condition that could affect a patient's response or cohort assignment.
Recurrences, second primary tumors, persistent disease, and other cancers
were included in the comorbidity category. One patient was previously diagnosed
as having pharyngeal stenosis and thus was considered to have a comorbidity.
Patients were separated into 2 groups: operative vs nonoperative. The
operative group included all patients who had resection as part of their therapeutic
plan. The nonoperative group consisted of patients treated with radiation
therapy with or without chemotherapy or brachytherapy. The primary surgery
cohort consisted of 43 patients. Each surgery performed was reflective of
the stage of the primary tumor. All patients had a neck dissection appropriate
to the preoperative staging. Transhyoid pharyngotomy was used to resect T1
and T2 tumors. These patients were reconstructed with primary closure. Patients
with advanced primary disease underwent more extensive resections through
a variety of approaches. Our data do not allow comparison of functional outcome
among these surgical subgroups. The average age during treatment was 58.8
years. Following surgery, 87% (53/61) of the cohort underwent postoperative
XRT. Eight patients did not receive adjuvant radiation due to refusal or prior
XRT for positive neck nodes, carcinoma in the neck, or carcinoma of the larynx.
Postsurgical brachytherapy of the BOT was used in 3 patients in addition to
adjuvant XRT. Chemotherapy was given concurrently with radiation therapy in
8 patients. The primary surgery group had a mean interval since treatment
of 66.8 months with a range of 4 months to 286 months.
The nonoperative cohort was composed of 18 patients. Their average age
during treatment was 67.3 years. This cohort includes 1 patient (6%) who underwent
chemoradiation; 1 (6%), brachytherapy; 2 (11%), XRT; 3 (17%), chemotherapy
with brachytherapy; 4 (22%), XRT with brachytherapy; and 7 (39%), chemoradiation
with brachytherapy. The chemotherapeutic approach varied according to protocol.
Comparison of groups treated by different drugs was not possible. The nonoperative
group had a mean interval since treatment of 29.5 months with a range of 3
months to 101 months.
The List Questionnaire already had a scale incorporated into it for
analysis. A similar scale was necessary for the UW-QOL. The response to each
question was translated into an ordinal scale—1 being the worst and
3, 4, 5, or 6 being the best, depending on the number of options for a particular
question. No such scale was necessary for the History of Treatment instrument.
Initially, descriptive statistics (means, medians, and SDs) were used
to examine the distributions of the variables. Exploratory data analytical
techniques (boxplots) were used to determine any outliers. For continuous
variables, the t test corrected for inequality of
variances was used to compare group means (operative vs nonoperative). For
ordinal variables and for skewed distributions, the Mann-Whitney test was
used to compare groups. The  2 test was used for nominal variables.
The Fisher exact test was used for tables with small cell sizes. The Spearman
rank correlation test was used to examine the collinearity within each of
the 3 instruments. To control for possible confounding variables, multivariate
analysis (multiple linear regression and multiple logistic regression) was
used to compare the groups after adjustment. Statistical significance was
set at .05, assuming a 95% confidence interval. Statistical analysis was performed
using SPSS software (SPSS Inc, Chicago, Ill).
RESULTS
Table 1 provides general
characteristics of our sample population. The mean age and interval since
treatment were 61.2 years and 56.2 months, respectively. The T stage was T3
or T4 in 26 patients (43%). The TNM stage was III or IV in 49 patients (80%).
Twenty-eight percent (17/61) of the sample population had a significant comorbidity.
In addition to these general characteristics, Table 1 also provides insight into how this sample population as
a whole responded on the 3 quality-of-life instruments.
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Table 1. Descriptive Characteristics of the Study Group*
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All cohort comparisons are listed in Table 2. The primary surgery cohort compared with the primary nonoperative
cohort was younger, had a longer interval since treatment, and a lower T stage
(P = .003, .003, and .04, respectively). The mean
age was 58.8 years for the surgical cohort and 67.3 years for the nonoperative
cohort. The mean interval since treatment was 66.8 months for the surgical
cohort and 29.5 months for the nonoperative cohort. The primary tumor stage
was T3/T4 in 37% (16/43) of the surgical cohort and 72% (13/18) for the nonoperative
cohort.
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Table 2. Univariate Comparisons of Descriptive Characteristics by Cohort*
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There were no statistically significant differences between the surgical
and nonoperative cohorts according the List Questionnaire. The UW-QOL results
revealed that patients treated with surgery were left with significantly better
saliva production (P = .02) when compared with patients
treated nonoperatively. Nine patients (21%) in the surgical cohort had a saliva
score of 4. Of the nonoperative cohort, 1 patient (6%) had a score of 4 or
greater on the saliva scale. The History of Treatment questionnaire revealed
a significant difference in days hospitalized between the surgical and nonoperative
cohorts. The surgical cohort's mean days hospitalized was 12.3 days vs the
nonoperative cohort's mean of 6.3 days. The corresponding P value was .002.
After these initial cohort comparisons, the variables in Table 2 were reanalyzed multivariately, adjusting for age, interval
since treatment, and T stage. However, due to the small sample sizes in the
surgical (n = 43) and nonoperative (n = 18) groups, it was impossible to incorporate
all 3 variables in the same equation. Adjusting only for age was possible
due to the fairly symmetric distribution. The adjustment did not change the
direction or significance of any of the dependent variables. Adjusting only
T stage resulted in cells with zero frequency. Adjusting only for interval
since treatment was too skewed and would require further transformations.
COMMENT
The treatment of SCC of the BOT continues to evolve. While patient survival
remains our primary concern, the development of new therapeutic modalities
and the growing recognition of the importance of quality of life and functional
outcome have stimulated new introspection. If survival outcomes for certain
treatment modalities are similar, then cost to the individual (quality of
life) and to society (expenses) assume increasing importance.
There are now numerous acceptable treatments for SCC of the BOT. While
these therapies can be used in almost any combination to create a complete
multimodality treatment, they can also be reduced to 2 basic categories—operative
and nonoperative. We used this basic distinction between the various therapeutic
options to assess differences in quality of life or function. We were surprised
at the overall similarity in perceived morbidity and quality of life between
the surgical and nonoperative cohorts. Even so, some differences did appear.
To determine if the significant differences calculated could be attributed
to general cohort characteristics, patient responses underwent multivariate
analysis according to age, interval since treatment, and T stage. TNM stage
was not significantly different between the 2 cohorts. When reanalyzed according
to age, there were no significant changes in the data. Therefore, patients'
responses could not have been affected by age. This result confirms that the
8-year difference in age between the 2 primary cohorts does not affect function
or quality of life.
Due to the small sample sizes, the data could not be reanalyzed after
accounting for interval since treatment. While this study cannot determine
if any patient responses were affected by interval since treatment, our experience
is that pain usually diminishes as the interval since treatment increases.
Pain is subjective and can be affected by patient outlook. It seems that long-term
survivors place less emphasis on the details of their daily functioning and
are simply happy to have been cured. Furthermore, we expected that the number
of days hospitalized would have been affected by interval since treatment;
health care economics has caused a shift toward briefer hospital stays in
the last few years.
The data also could not be reanalyzed accounting for T stage. While
this study could not determine if any patient responses were affected by T
stage, we expected that patients treated surgically for large tumors to have
more extensive dysfunction than for small tumors. While TNM stage predicts
survival, T stage may predict the extent of tissue damage and consequently
function.
The UW-QOL revealed a significant difference in saliva production. The
general cohort characteristics have been shown not to affect these categories.
The surgical cohort fared better in saliva production than the nonoperative
cohort. These results were surprising since surgical patients usually receive
postoperative XRT. However, almost 20% of the surgical patients in this study
did not receive XRT. These patients might have skewed the results since postoperative
XRT is the mainstay of surgical treatment. The results may also be due to
differences in tumor stage and location, which affect the radiation field
and dosage. Nonetheless, these results emphasize that nonoperative treatment
affects saliva, potentially more severely than surgical therapy. A final important
result from the UW-QOL is the absence of any differences between the 3 quality-of-life
assessment questions or in the summation of these 3 questions into 1 total
score. These questions try to unmask differences in the populations other
than for what is being tested. These results indicate that the populations
are likely similar in other ways.
The History of Treatment questions that we developed also provided important
insights. There was a significant difference between the cohorts calculated
for days hospitalized. The nonoperative cohort had a more favorable outcome
than the surgical cohort. This implies that surgery could impede more on the
patient's life. This extra impedance could be costly to the patient; however,
the measurement ability of this instrument has not been examined. More accurate
assessment of cost requires direct investigation of these factors.
Our results reveal that patients treated with cytoreductive therapy
have similar dysfunction as patients treated surgically. The similarity between
the surgical and nonoperative cohorts is the most striking finding of this
study. We expected the nonoperative cohort would report significantly better
function as measured by chewing, swallowing, and speech. These results indicate
that after radiation therapy, significant morbidity results from fibrosis,
xerostomia, and other side effects.
Additionally, this study uses 2 different instruments that attempt to
measure the outcome of treatment for head and neck cancer patients. The List
Questionnaire did not reveal any significant differences between cohorts while
the UW-QOL revealed 1 difference. This result could indicate that the UW-QOL
might be more sensitive to the outcomes of this particular patient population;
however, a more thorough comparison is needed to determine if one instrument
has greater utility over the other.
There are a number of limitations to our study. While we were pleased
with the percentage of eligible patients that responded, there were still
44 patients who did not respond. This is a potential source of sampling bias.
Nevertheless, our study was not institutional review board approved for additional
attempts at patient participation. Unfortunately, the 2 cohorts consisted
of relatively small populations. Even if every category initially showed differences
between the surgical and nonoperative cohorts, the small populations may have
prevented these differences from being statistically significant due to a
reduced statistical power. A multicenter study could afford larger populations,
allowing for statistical tools to be more sensitive to differences in patient
responses.
In addition, for 2 of the 3 instruments used, patients were forced to
choose from limited scales. The patients might have been forced into replies
that were either too constricting or too broad. The first 2 questionnaires
asked about current functioning and thus the large range in interval since
treatment did not affect the accuracy of responses. The third instrument,
however, asked patients about the details of their treatment. Accurate recall
about the treatment decreases as interval since treatment increases. Finally,
as with many quality-of-life assessments, the study is subjective in nature.
It relies on patients selecting what they considered their level of functioning
to be in the various categories. There is potential for skewed results in
any subjective analysis. A long-term survivor who is relieved to be cured
might believe his or her functional outcome to be better than that witnessed
by an objective grader. However, this raises the question of which is more
important: the actual outcome or the patient's perception of the outcome.
Nevertheless, one recent self-assessment study that measures the impact of
dysphagia on quality of life of patients with head and neck cancer has been
shown to be valid and reliable.14 This study
could prove valuable for future assessments.
While the results of this study are both surprising and interesting,
it calls for further investigation. Larger populations could better account
for age, interval since treatment, T stage, and subjectivity in patient responses,
further elucidating how patients function after the various treatments currently
offered for SCC for the BOT.
AUTHOR INFORMATION
Accepted for publication February 13, 2002.
Corresponding author: Jonas T. Johnson, MD, Department of Otolaryngology,
The University of Pittsburgh School of Medicine, The Eye and Ear Institute,
Suite 500, 200 Lothrop St, Pittsburgh, PA 15213.
From the Departments of Otolaryngology (Mr Perlmutter and Drs Johnson,
Snyderman, and Myers) and Radiation Oncology (Dr Cano), The University of
Pittsburgh School of Medicine, Pittsburgh, Pa.
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