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Original Article |

Factors Associated With Long-term Speech and Swallowing Outcomes After Chemoradiotherapy for Locoregionally Advanced Head and Neck Cancer FREE

Kent W. Mouw, MD, PhD; Daniel J. Haraf, MD; Kerstin M. Stenson, MD; Ezra E. Cohen, MD; Xi Xi, BS; Mary Ellyn Witt, RN; Marcy List, PhD; Elizabeth A. Blair, MD; Everett E. Vokes, MD; Joseph K. Salama, MD
Arch Otolaryngol Head Neck Surg. 2010;136(12):1226-1234. doi:10.1001/archoto.2010.218.
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Published online

Objective  To identify factors that influence patient-centered measures of speech and swallowing function after successful use of chemoradiotherapy to treat cancers of the head and neck.

Design  Patients previously enrolled in a phase 2 trial using induction chemotherapy consisting of carboplatin and paclitaxel followed by chemoradiotherapy with paclitaxel, fluorouracil, hydroxyurea, and 1 of 3 radiation dose levels were assigned speaking and swallowing scores at follow-up ranging from 1 to 4, with 1 representing normal speech or swallowing and 4 representing significant sustained deficits.

Patients  One hundred eighty-four patients with locoregionally advanced head and neck cancer.

Main Outcome Measures  Speech and swallowing function after chemoradiotherapy.

Results  Of the 222 patients originally enrolled in the trial, 184 were alive and free of locoregional recurrence at the outset of this study. Of these eligible patients, 163 (88.6%) were assigned a speaking score of 1 through 4 at an average of 34.8 (range, 1.5-76.4) months after completion of treatment, whereas 166 patients (90.2%) were assigned a swallowing score of 1 through 4 at an average of 34.5 (range, 1.0-76.4) months after completion of treatment. Most patients (84.7% with speaking scores and 63.3% with swallowing scores) had no residual deficit and were assigned scores of 1. Factors that were associated with worse speaking outcomes included female sex, smoking history, hypopharyngeal or laryngeal primary sites, and poor response to induction chemotherapy; factors associated with worse swallowing outcomes included advanced patient age, poor performance status, primary site, and neck dissection.

Conclusions  Among patients successfully treated for locoregionally advanced cancers of the head and neck, several factors correlate with speaking and swallowing outcomes. Because advances in therapy have led to improved survival in these patients, understanding and controlling adverse effects of treatment should continue to be an active area of investigation.

Figures in this Article

Speaking and swallowing deficits are experienced by many survivors of primary cancers of the head and neck. Although it is often difficult to separate the individual contributions of the tumor and the treatment to these deficits, several studies have shown that, when compared with organ-removal surgery, chemoradiotherapy (CRT) with or without organ preservation surgery can minimize posttreatment speech and swallowing deficits while maintaining excellent tumor control.13

Studies that have aimed to characterize the adverse effects of CRT use a variety of techniques to estimate functional changes.47 Physician- and patient-reported systems have been widely used to monitor changes that occur throughout the treatment course and in the months after completion of treatment. These studies have highlighted the importance of primary tumor site, tumor stage, and treatment modality in determining speaking and swallowing outcomes after treatment.

In this study, we aim to analyze long-term speech and swallowing function in patients successfully treated with CRT for locoregionally advanced head and neck cancers. This retrospective analysis stems from a prospective analysis designed to examine local and distant tumor control using induction chemotherapy followed by CRT in the setting of organ preservation.3 Patients without locoregional recurrence were observed after completion of treatment and assigned speaking and swallowing scores based on objective, patient-centered measures of function.

A total of 222 patients with locoregionally advanced head and neck cancer (stage IV nonmetastatic or stage III base of tongue or hypopharyngeal tumors) were treated between November 1998 and August 2002 in a multi-institutional phase 2 study of induction chemotherapy followed by CRT. Briefly, patients in cohorts 1 and 2 were treated with 6 cycles of weekly carboplatin (area under the curve [AUC], 2 for 30 minutes) and paclitaxel (135 mg/m2 for 3 hours). Patients in cohort 3 were treated with carboplatin (AUC, 6 on day 1) and paclitaxel (100 mg/m2 on days 1, 8, and 15) every 4 weeks for 2 cycles as data emerged that this schedule resulted in higher response rates in non–small cell lung cancer.8 After the completion of induction therapy, patients underwent radiographic and clinical examinations to assess response to therapy and were characterized as having a complete response, a partial response, stable disease, or progressive disease. After this evaluation, 4 or 5 (depending on the extent of preprotocol surgery) 14-day cycles of CRT with paclitaxel (100 mg/m2 delivered in 1 hour on day 1), fluorouracil (600 mg/m2 per day of continuous infusion for days 1-5), hydroxyurea (500 mg orally every 12 hours on days 1-6), and 1.5 Gy of radiation (delivered twice daily on days 1 to 5) were administered.

One of the purposes of the clinical trial was to determine whether decreased radiotherapy doses could maintain locoregional control of the tumor while decreasing treatment-related toxic effects. Planning treatment volumes (PTVs) were designed as follows: PTV1 included gross disease plus a 1.5-cm expansion, PTV2 included PTV1 plus the first echelon of uninvolved lymph nodes, and PTV3 included PTV2 plus the second uninvolved lymph node echelon. Volumes were modified to avoid spinal cord overlap or extension beyond the skin. Radiation dose prescription levels for PTV1, PTV2, and PTV3 were 75, 60, and 54 Gy for cohort 1; 75, 54, and 39 Gy for cohort 2; and 72, 51, and 36 Gy for cohort 3. Cohort 2 was found to provide the best therapeutic ratio.

Patients were allowed to undergo preprotocol organ-preserving surgery such as simple excision of a small primary tumor or a diagnostic modified neck dissection. In addition, patients with N2 or worse neck disease were recommended to undergo posttreatment selective neck dissection regardless of their response to treatment. Details of the studies and treatment outcomes have been published previously.3 Patients did not have percutaneous gastrostomy tubes placed prophylactically; instead, gastrostomy tubes were placed only on the basis of clinical need during the course of therapy.

Patients underwent evaluation every 3 months after the completion of protocol therapy in radiation oncology, medical oncology, and head and neck surgery clinics. In addition, after the completion of therapy, many patients underwent prospective evaluation using validated cancer quality-of-life metrics, such as the Performance Status Scale for Head and Neck Cancer Patients,9 Head and Neck Radiotherapy Questionnaire,10 and Functional Assessment of Cancer Therapy–Head and Neck Scale.9,11 Patients without evidence of locoregional progression were assigned speech and swallowing scores at the latest follow-up visit. Scores were assigned to patients by one of us (J.K.S.) according to a simple scale ranging from 1 to 4, with increasing scores corresponding to decreasing function (see Table 1 for scoring criteria). This scoring system was designed to measure patient-centered outcomes of speech and swallowing function and is similar to elements of the speech and swallowing measures within the validated surveys mentioned.911 Patients who underwent survey scoring had these scores converted into the scale used herein. If no formal quality-of-life evaluation was performed, scores were derived from the most recent note in the clinic record. If conflicting scores were found in these notes, the worst recorded score was used.

We used 2-tailed t tests to compare the means of speech or swallowing scores of different groups, with a P value of .05 or less considered to represent a significant difference. We calculated correlation coefficients using the Pearson method. A binary logistic regression model was created for multivariate analysis, and variables that were statistically significant on univariate analysis were included in this model. We used commercially available software (Microsoft Excel; Microsoft Corp, Redmond, Washington) to manage data and generate tables and graphs.

Of the 222 patients enrolled in the original trial, 184 were alive and free of local progression at the time this study was initiated (Table 2). Of these 184 eligible patients, 163 (88.6%) were assigned a speaking score an average of 34.8 (range, 1.5-76.4) months after completion of treatment. Swallowing scores were assigned to 166 of the 184 eligible patients (90.2%) at an average follow-up of 34.5 (range, 1.0-76.4) months. Speaking and swallowing scores were recorded for 160 patients (87.0%).

Most of the patients maintained normal or near-normal speaking and swallowing function after treatment (Figure 1A and B). There did not appear to be a correlation between the speaking or swallowing score and the length of time elapsed between the end of CRT and speaking/swallowing score assignment (r = −0.16 for speaking and r = −0.13 for swallowing; Figure 1C and D).

Place holder to copy figure label and caption
Figure 1.

Distribution and follow-up times for speaking and swallowing scores. A, Distribution of speaking scores among 163 patients (average speaking score, 1.29). B, Distribution of swallowing scores among 166 patients (average swallowing score, 1.73). C, Relationship between speaking scores and follow-up time in 163 patients (time elapsed between completion of treatment and score assignment). The average follow-up time was 34.8 (range, 1.5-76.4) months. D, Relationship between swallowing scores and follow-up time in 166 patients. The average follow-up time was 34.5 (range, 1.0-76.4) months. Percentages have been rounded and may not total 100. Speaking and swallowing scores range from 1 to 4, with increasing scores corresponding to decreasing function.

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Among the 160 patients assigned speaking and swallowing scores, most (n = 96) had a score of 1 in each category (Figure 2). Smaller subsets of patients had preservation of speaking or swallowing, but experienced a decrease in function in the other category. A small group of patients (n = 7) had the poorest outcomes, with scores of 4 for both functions.

Place holder to copy figure label and caption
Figure 2.

Distribution of speaking and swallowing scores for 160 patients assigned both scores. Speaking and swallowing scores range from 1 to 4, with increasing scores corresponding to decreasing function.

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CHARACTERISTICS ASSOCIATED WITH SPEECH AND SWALLOWING OUTCOMES

We attempted to identify patient characteristics that correlated with speaking and swallowing outcomes after treatment. The average age at diagnosis was 56.0 (range, 24-77) years for patients with speaking scores and 56.2 (range, 24-77) years for patients with swallowing scores. We found that patients with swallowing scores of 1 or 2 (better swallowing outcomes) were significantly younger than patients with swallowing scores of 3 or 4 (P = .01; Table 3), whereas there was not a significant difference in the ages of patients with speaking scores of 1 to 2 compared with those with speaking scores of 3 to 4.

Most of the patients in this study were men (77.9% of the patients with speaking scores and 77.1% with swallowing scores). Swallowing outcomes were not significantly different between men and women, but men experienced significantly better speaking outcomes than women (P = .007; Table 3).

Patients with better performance status before initiation of treatment were found to have better functional outcomes after the completion of treatment. Patients with a pretreatment Eastern Cooperative Oncology Group (ECOG) performance status of 0 had significantly better swallowing outcomes than did patients with a pretreatment ECOG performance status of 1 or 2 (P = .02; Table 3). There was a trend toward better speaking function in patients with an ECOG score of 0 compared to those with a score of 1 to 2, but the difference was not statistically significant (P = .08).

Smoking has been linked to an increased risk of developing tumors of the head and neck; therefore, we were interested to see whether there was a correlation between smoking history and speaking and/or swallowing outcomes. Most of the patients had a smoking history (84.7% of patients with speaking scores and 84.3% of patients with swallowing scores). Patients with any smoking history were found to have worse speaking outcomes than nonsmokers (P = .047; Table 3); this difference was even more pronounced when speaking outcomes of nonsmokers were compared with those of patients with a history of smoking of more than 40 pack-years (P = .006; Table 3). There was no significant difference in swallowing outcomes between nonsmokers and smokers.

Alcohol consumption has also been linked to the development of head and neck cancer; however, we did not find a significant difference in speaking or swallowing outcomes when comparing patients with varying levels of alcohol exposure (data not shown).

TUMOR CHARACTERISTICS

We also investigated the possibility that specific tumor characteristics may correlate with speaking and swallowing outcomes. Most tumors in this study were squamous cell carcinomas (159 of the 163 patients with speaking scores and 162 of the 166 patients with swallowing scores). The other histological findings represented were lymphoepithelioma (2 patients), adenocarcinoma (1 patient), and mucoepidermoid tumors (1 patient).

There was also a spectrum of tumor grades represented in the study, ranging from well to poorly differentiated (Table 4). No association between tumor grade and speaking or swallowing scores was noted on our analysis.

Tumor location was found to be strongly associated with speaking outcomes because patients with hypopharyngeal or laryngeal tumors (n = 46) had worse speaking outcomes (average speaking score, 1.72) than patients with primary sites in other locations (average speaking score, 1.12; P < .001). There was also a trend toward worse swallowing outcomes in patients with hypopharyngeal or laryngeal tumors (P = .17).

All of the patients in this study had stage III or IV disease at enrollment. A breakdown of the nodal status of the patients is provided in Table 4. There was no correlation noted between nodal involvement and speaking or swallowing scores.

TREATMENT CHARACTERISTICS

We observed a trend toward improved long-term speech and swallowing function with decreasing radiation dose (Table 5). Average speaking scores for cohorts 1, 2, and 3 were 1.36, 1.29, and 1.21, respectively, whereas average swallowing scores were 1.91, 1.78, and 1.53. Although the average speaking and swallowing scores decreased with decreasing total radiation dose, the differences between cohorts were not statistically significant.

To assess whether radiotherapy technique affected speech and swallowing scores, we classified patients as being treated with or without intensity-modulated radiotherapy (IMRT). Of the patients treated herein, 41.1% who were assigned speaking scores and 39.8% who were assigned swallowing scores were treated with IMRT. Because each cohort was filled before accrual for the next cohort began and because the use of IMRT became more common during the 1998 to 2002 trial enrollment period, the percentage of patients in each cohort treated with IMRT increased from cohort 1 to cohort 3. However, no significant difference in speech or swallowing outcomes was noted between patients treated with IMRT and those treated with conventional 3-dimensional conformal radiotherapy (Table 5).

Organ preservation was a primary goal of this trial; however, patients were allowed to undergo organ-sparing surgery or diagnostic modified neck dissection before induction chemotherapy. In addition, many patients with N2 or worse disease underwent a posttreatment selective neck dissection to evaluate for residual disease. Of all the patients assigned speaking or swallowing scores, more than half underwent a neck dissection (90 of 163 patients with speaking scores and 91 of 166 patients with swallowing scores). Approximately one-third (32 of 90 patients with speaking scores and 33 of 91 patients with swallowing scores) of the neck dissections were performed before induction chemotherapy, whereas the remainder were performed after completion of CRT. Compared with patients who did not undergo any neck surgery, patients who underwent neck dissection had similar speaking outcomes, but significantly worse swallowing outcomes (P = .04; Table 6). There was no significant difference in speaking or swallowing outcomes between patients who underwent unilateral vs bilateral neck dissection (data not shown). In addition, there was a trend toward better speaking and swallowing outcomes in patients who underwent pretreatment neck dissection compared with those who underwent posttreatment neck dissection (P = .10 for speaking and P = .16 for swallowing; Table 6).

A small subset of patients underwent wide local excision of their primary tumor alone or in combination with a neck dissection before induction chemotherapy. These patients had excellent speaking outcomes: all 18 patients who were assigned speaking scores had normal speech (speaking score, 1) after completion of treatment; however, the small number of patients in this group precluded this difference from being statistical significant (P = .09).

RESPONSE CHARACTERISTICS

For speaking and swallowing end points, when using both clinical and radiological criteria, there was a trend toward worse scores with decreasing responsiveness of the tumor to induction chemotherapy (Table 7). There was a significant difference in speaking scores when those with clinically assessed stable disease (average speaking score, 1.69) were compared with patients with a complete or partial response (average speaking score, 1.22; P = .03).

Table Graphic Jump LocationTable 7. Treatment Response Characteristics

Response to treatment was also assessed after completion of CRT. As expected, far more patients were found to have a complete response after CRT than after induction chemotherapy. There was no significant difference in speaking or swallowing outcomes between patients who experienced a complete response and those who experienced a partial response (Table 7).

Data regarding the type and severity of adverse effects experienced by patients at several points throughout the treatment course were also recorded. One local adverse effect that might be predicted to influence future speaking and swallowing outcomes is mucositis. The presence and severity of mucositis (grades 0-4) were recorded after induction chemotherapy and CRT. In each case, there was no correlation between mucositis and speaking or swallowing outcomes (data not shown).

CHARACTERISTICS OF PATIENTS WITH POOREST SPEAKING AND SWALLOWING OUTCOMES

A subset of 7 of the 160 patients who underwent evaluation for speaking and swallowing had the poorest possible outcomes using our scale. In these 7 patients, speaking and swallowing scores of 4 were assigned, implying that the patients were unable to communicate by voice and depended on a gastrostomy tube for nutrition. Although the number of these patients with the poorest outcomes is not large enough for statistical analysis, we asked whether there were characteristics that were shared by these patients. Of interest, 6 of the 7 had a laryngeal or a hypopharyngeal tumor, 5 of the 7 patients had T4 disease, 3 of the 7 patients had N0 or N1 disease, none of the patients had preprotocol surgery, and all of the patients had a complete response after CRT. More data will be necessary to determine whether these results represent meaningful differences that could be used to predict speaking and swallowing outcomes.

CORRELATION OF SPEAKING AND SWALLOWING SCORES WITH OROPHARYNGEAL MOTILITY SCORES

A previous study by our group investigated swallowing outcomes in 95 of the patients before and 1 to 2 months after completion of CRT with the use of videofluorographic oropharyngeal motility (OPM) methods. Pretreatment and posttreatment scores of 1 to 7, with 1 reflecting normal swallowing and 7 reflecting severe impairment, were assigned to patients according to the results of the OPM study.

We asked how the results of these OPM studies correlated with the long-term measures of speaking and swallowing function assessed in this current study. Results are displayed in Figure 3. As previously published, a decrease in swallowing function (reflected by an increase in the OPM scores) is noted in the immediate posttreatment period (Figure 3C and D).4 We noted that the average pretreatment and posttreatment OPM scores for patients with speaking or swallowing scores of 1 were lower (ie, swallowing function was better) than the average pretreatment and posttreatment OPM scores for patients with speaking or swallowing scores of 2 to 4; in all but 1 comparison, the differences were statistically significant (Figure 3).

Place holder to copy figure label and caption
Figure 3.

Correlation of speaking and swallowing scores with pretreatment and posttreatment oropharyngeal motility (OPM) scores. A subset of the patients assigned speaking and/or swallowing scores in this study had been assigned an OPM score (ranging from 1-7) before initiation of treatment and again at 1 to 2 months after completion of treatment. A, Correlation of speaking scores with pretreatment OPM scores. B, Correlation of speaking scores with posttreatment OPM scores. C, Correlation of swallowing scores with pretreatment OPM scores. D, Correlation of swallowing scores with posttreatment OPM scores. Speaking and swallowing scores range from 1 to 4, with increasing scores corresponding to decreasing function.

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MULTIVARIATE ANALYSIS

To further investigate the association of specific factors with speaking and swallowing outcomes, multivariate analysis using a binary logistic regression model was performed. For speaking outcomes, patient sex, smoking status (nonsmokers compared with patients with any smoking history), primary tumor site (hypopharyngeal and laryngeal compared with all other primary sites), performance status (ECOG score of 0 compared with scores of 1 and 2), and preprotocol surgery (biopsy alone compared with organ-sparing surgery) were included in the analysis. As had been identified in univariate analysis, sex, smoking status, and primary tumor site were all found to be strongly associated with speaking outcomes (Table 8).

Patient age (patients aged >56 years compared with ≤56 years), primary tumor site (hypopharyngeal and laryngeal compared with all other primary sites), performance status (ECOG score of 0 compared with 1 or 2), preprotocol surgery (biopsy alone compared with organ-sparing surgery), and postprotocol neck dissection were included in the regression model for swallowing outcomes (Table 8). Patient age remained strongly associated with outcomes. Performance status and neck dissection found to be less strongly associated with swallowing outcomes on multivariate analysis, whereas primary tumor site became more strongly associated with swallowing outcomes when compared with its association in the univariate analysis.

In this study, we have attempted to characterize features of the patient, tumor, treatment type, and treatment response that are correlated with long-term, patient-centered speaking and swallowing outcomes after successful use of combined CRT with or without organ-preserving surgery to treat primary cancers of the head and neck. As the success rate of treatment for these cancers continues to improve, it will become increasingly important to understand and attempt to minimize speech and swallowing deficits after completion of treatment.

The decision to use a simplified scale for rating speaking and swallowing outcomes was based on a desire to focus on tangible outcomes that are likely to affect the patient's day-to-day experiences. Similar outcome measures are often encompassed within validated quality-of-life scales or can be extrapolated from image-based studies or other physiological measures.911 Indeed, results from the simplified speaking and swallowing scale used in this study correlate well with previous OPM measurements obtained from the same patients (Figure 3). That these 2 sets of results strongly correlate suggests that the present scale is useful in representing differences in outcomes among patients.

Another aspect that makes these data unique is the length of follow-up. The average length of time between completion of treatment and assignment of a speaking and/or swallowing score was nearly 3 years. The length of follow-up did not seem to correlate with the speaking or swallowing score (Figure 1C and D). This finding suggests that the speech and swallowing deficits experienced by patients in the immediate posttreatment period may serve as a reasonable approximation of the type and severity of residual deficits that the patient can expect to experience in the future. Further evidence is provided by the strong correlation between OPM scores, which were recorded within 2 months after completion of therapy, and the speaking and swallowing scores analyzed herein, which were, on average, assigned much later.

This study includes a large cohort of patients, which provides the statistical power to identify multiple factors that correlate with speech and swallowing deficits. However, one of the remarkable features of the data is that most of the patients experienced minimal residual speech or swallowing deficits (Figures 1 and 2). Although differences detected by more advanced modalities may exist between these patients and healthy subjects, it is encouraging to note that, when day-to-day activities are used as a metric, most patients experience a return to normal or near-normal function. However, it is worth noting the percentage of the patients (17.2% with speaking scores and 16.2% with swallowing scores) who had tracheostomy tubes in place at the time of last follow-up, which may not directly affect the speaking and swallowing outcomes measured herein but may affect patients' lifestyle nonetheless.

Because this study assigns scores for speaking and swallowing to most of the patients, we can compare how well these outcomes correlate in single patients. As shown in Figure 2, most of the patients had excellent outcomes for both speaking and swallowing. This result not only reflects the success of the treatment in eliminating the tumor while preserving function but also highlights the overlapping anatomic and functional requirements for speaking and swallowing.

A small subset of patients had the worst possible outcome in our scoring system (speaking and swallowing scores of 4). Although the numbers were not large enough to be statistically significant, patients with laryngeal or hypopharyngeal primary sites and T4 tumors appeared to be overrepresented in this group. Poor outcomes have been described previously in patients with primary tumors involving the larynx and hypopharynx.12 Although OPM-measured swallowing function in patients with T4 tumors has actually been shown to improve from the pretreatment to the immediate (1-2 months) posttreatment period, there is likely to be significant residual dysfunction after treatment of these large tumors.4 All 7 of the patients with the worst adverse effect profile experienced a complete clinical response after treatment, highlighting that significant adverse effects are not restricted to patients in whom treatment is less efficacious.

Several demographic variables of the patients treated in the original trial seem to correlate with speaking and swallowing outcomes. Older patients had significantly worse swallowing outcomes, as did patients with worse performance status before initiation of treatment (Tables 3 and 8). In each of these cases, it is possible that decreased functional reserve secondary to advanced age or comorbidities may result in more severe or nonreversible damage to the swallowing musculature and thus ultimately lead to worse swallowing outcomes. Worse dysphagia with increasing age has also been reported by others.13

Cancers of the head and neck have been linked to alcohol consumption and tobacco use.14 In this study, no correlation between alcohol consumption and outcomes was identified, perhaps because of insufficient sample size or inaccuracies in patient-reported alcohol use. However, we did note that patients with a smoking history had worse speaking outcomes than nonsmokers, and that the difference was even more pronounced when nonsmokers were compared with heavy smokers (Tables 3 and 8). Smoking before or during treatment may not only sensitize speaking-related structures to damage incurred during treatment but also decrease the body's ability to recapitulate speaking function after treatment. It is also interesting to speculate that the molecular etiology of the cancer may influence outcomes because tumors in smokers are more likely to result from an accumulation of genetic insults, whereas tumors in nonsmokers are more likely to be mediated by agents such as human papillomavirus that may require fewer genetic changes to produce malignant transformation.

As has been reported previously, we found that patients with a primary tumor of the larynx or hypopharynx experienced significantly worse speaking and swallowing outcomes than did patients with primary tumors at other sites.12 Tumor involvement of structures required for voice production necessitates exposure of these structures to the full dose of radiation, thus increasing the likelihood of severe or permanent damage. However, this risk must be weighed against the known morbidity of a laryngectomy or other surgery that sacrifices structures essential for voice production. Likewise, the proximity of pharyngeal and hypopharyngeal tumors to the pharyngeal constrictors, which have been shown to be sensitive to concurrent CRT,15 may be responsible for the increased swallowing impairment experienced by patients with tumors at these primary sites.

In addition to the primary site, nodal involvement was examined as a possible predictor of speech and swallowing outcomes. All patients enrolled in the initial phase 2 trial had stage III or IV disease, but nodal involvement varied from N0 to N3, with most of the patients having N2 disease. No significant correlation between pretreatment N stage and speech or swallowing outcomes was noted, although there was a trend toward increasing swallowing scores from N1 to N3 disease. Swallowing scores were noted to be significantly better in patients who did not undergo neck dissection compared with those who did (Table 6). The timing of neck dissection (pretreatment vs posttreatment) did not correlate with scores; however, there was a trend toward worse swallowing outcomes in patients who had neck dissections performed after completion of protocol therapy. The worse swallowing outcomes noted in patients who underwent neck dissection may be because these patients had more advanced disease (postprotocol neck dissection was recommended for patients with N2 or worse disease) or by the morbidity associated with the surgical procedure. This finding is similar to a large pooled analysis from the Radiation Therapy Oncology Group, which also demonstrated that functional outcomes were poorer in patients who underwent post-CRT neck dissection.13

The subset of patients who underwent bilateral neck dissections did not have significantly different speech or swallowing function than patients who underwent unilateral dissection, suggesting that the benefit or harm in addressing both sides of the neck was not apparent at the level of speaking or swallowing outcomes. In addition, the small subset of patients who underwent wide local excision of a primary tumor all had normal speaking function at follow-up; therefore, when possible, it appears that organ-preserving surgery does not negatively affect long-term speech and swallowing outcomes.

One important result of the phase 2 trial in which these patients were enrolled was the identification of a radiotherapy dose that minimized acute adverse effects without sacrificing local control. In this study, we asked whether there were differences in long-term speech and swallowing adverse effects among patients receiving different radiation doses and found that there was a nonstatistically significant trend toward improved speaking and swallowing with decreased total radiation dose (Table 5). When late toxic effects were investigated by the Radiation Therapy Oncology Group, there was no radiation dose response; however, speech and swallowing were not specifically reported.13

Use of IMRT to spare swallowing organs has been associated with decreased adverse effects after treatment for head and neck cancer.16 However, the radiation technique did not appear to be related to speaking or swallowing outcomes in this study, although patients treated with IMRT were more likely to have received less total radiation.

Many of the factors associated with long-term speech and swallowing outcomes that have been addressed in this study can be identified before the initiation of treatment (age, smoking history, tumor stage, etc). However, we were also interested in identifying features of the patients’ initial response to treatment that could be used to predict long-term outcomes. Characterizing the patients’ early response to treatment has the potential to be especially useful because it captures real-time information regarding the patients' current performance status, tumor response, and adverse effect profile. If features that are associated with severe long-term adverse effects are identified during treatment, it is possible that subsequent treatment could be altered (or prophylactic measures instituted) to minimize these long-term effects.

Thus, we attempted to find a correlation between response to induction chemotherapy and long-term speech and swallowing deficits. As the response to induction chemotherapy increased, there was a trend toward improved speaking and swallowing outcomes; however, the differences were not statistically significant (Table 7). Because all the patients in this study achieved long-term remission of their cancer, this trend is not fully explained by better overall outcomes of the patients with the strongest response to induction chemotherapy. It is possible that, with more patient data or more precise means for measuring patient response, significant differences among treatment responses could be identified and used to guide further therapy.

Correspondence: Joseph K. Salama, MD, Department of Radiation Oncology, Duke University Medical Center, PO Box 3085, Durham, NC 27710 (joseph.salama@duke.edu).

Submitted for Publication: March 31, 2010; final revision received June 16, 2010; accepted September 19, 2010.

Author Contributions: Drs Haraf, Vokes, and Salama had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Mouw, Haraf, List, Vokes, and Salama. Acquisition of data: Haraf, Stenson, Cohen, Witt, Blair, and Vokes. Analysis and interpretation of data: Mouw, Haraf, Xi, Vokes, and Salama. Drafting of the manuscript: Mouw, Witt, Vokes, and Salama. Critical revision of the manuscript for important intellectual content: Mouw, Haraf, Stenson, Cohen, Xi, List, Blair, and Salama. Statistical analysis: Mouw and Xi. Obtained funding: Haraf and Vokes. Administrative, technical, and material support: Mouw, Haraf, Witt, Blair, and Vokes. Study supervision: Haraf, Blair, and Salama. Speech and swallowing outcomes: List.

Financial Disclosure: None reported.

Funding/Support: This study was supported by the Robert and Valda Svendsen Foundation.

Previous Presentation: This study was presented at the annual meeting of the American Head and Neck Society; April 28, 2010; Las Vegas, Nevada.

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Browman  GPLevine  MNHodson  DI  et al.  The Head and Neck Radiotherapy Questionnaire: a morbidity/quality-of-life instrument for clinical trials of radiation therapy in locally advanced head and neck cancer. J Clin Oncol 1993;11 (5) 863- 872
PubMed
Cella  DFTulsky  DSGray  G  et al.  The Functional Assessment of Cancer Therapy Scale: development and validation of the general measure. J Clin Oncol 1993;11 (3) 570- 579
PubMed
Logemann  JARademaker  AWPauloski  BR  et al.  Site of disease and treatment protocol as correlates of swallowing function in patients with head and neck cancer treated with chemoradiation. Head Neck 2006;28 (1) 64- 73
PubMed Link to Article
Caudell  JJSchaner  PEMeredith  RF  et al.  Factors associated with long-term dysphagia after definitive radiotherapy for locally advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys 2009;73 (2) 410- 415
PubMed Link to Article
Piccirillo  JF Importance of comorbidity in head and neck cancer. Laryngoscope 2000;110 (4) 593- 602
PubMed Link to Article
Feng  FYKim  HMLyden  TH  et al.  Intensity-modulated radiotherapy of head and neck cancer aiming to reduce dysphagia: early dose-effect relationships for the swallowing structures. Int J Radiat Oncol Biol Phys 2007;68 (5) 1289- 1298
PubMed Link to Article
Eisbruch  ALevendag  PCFeng  FY  et al.  Can IMRT or brachytherapy reduce dysphagia associated with chemoradiotherapy of head and neck cancer? the Michigan and Rotterdam experiences. Int J Radiat Oncol Biol Phys 2007;69 (2) ((suppl)) S40- S42
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.

Distribution and follow-up times for speaking and swallowing scores. A, Distribution of speaking scores among 163 patients (average speaking score, 1.29). B, Distribution of swallowing scores among 166 patients (average swallowing score, 1.73). C, Relationship between speaking scores and follow-up time in 163 patients (time elapsed between completion of treatment and score assignment). The average follow-up time was 34.8 (range, 1.5-76.4) months. D, Relationship between swallowing scores and follow-up time in 166 patients. The average follow-up time was 34.5 (range, 1.0-76.4) months. Percentages have been rounded and may not total 100. Speaking and swallowing scores range from 1 to 4, with increasing scores corresponding to decreasing function.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Distribution of speaking and swallowing scores for 160 patients assigned both scores. Speaking and swallowing scores range from 1 to 4, with increasing scores corresponding to decreasing function.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

Correlation of speaking and swallowing scores with pretreatment and posttreatment oropharyngeal motility (OPM) scores. A subset of the patients assigned speaking and/or swallowing scores in this study had been assigned an OPM score (ranging from 1-7) before initiation of treatment and again at 1 to 2 months after completion of treatment. A, Correlation of speaking scores with pretreatment OPM scores. B, Correlation of speaking scores with posttreatment OPM scores. C, Correlation of swallowing scores with pretreatment OPM scores. D, Correlation of swallowing scores with posttreatment OPM scores. Speaking and swallowing scores range from 1 to 4, with increasing scores corresponding to decreasing function.

Graphic Jump Location

References

Department of Veterans Affairs Laryngeal Cancer Study Group, Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. N Engl J Med 1991;324 (24) 1685- 1690
PubMed Link to Article
Boscolo-Rizzo  PStellin  MFuson  RMarchiori  CGava  ADa Mosto  MC Long-term quality of life after treatment for locally advanced oropharyngeal carcinoma: surgery and postoperative radiotherapy versus concurrent chemoradiation. Oral Oncol 2009;45 (11) 953- 957
PubMed Link to Article
Salama  JKStenson  KMKistner  EO  et al.  Induction chemotherapy and concurrent chemoradiotherapy for locoregionally advanced head and neck cancer: a multi-institutional phase II trial investigating three radiotherapy dose levels. Ann Oncol 2008;19 (10) 1787- 1794
PubMed Link to Article
Salama  JKStenson  KMList  MA  et al.  Characteristics associated with swallowing changes after concurrent chemotherapy and radiotherapy in patients with head and neck cancer. Arch Otolaryngol Head Neck Surg 2008;134 (10) 1060- 1065
PubMed Link to Article
List  MASiston  AHaraf  D  et al.  Quality of life and performance in advanced head and neck cancer patients on concomitant chemoradiotherapy: a prospective examination. J Clin Oncol 1999;17 (3) 1020- 1028
PubMed
Nguyen  NPFrank  CMoltz  CC  et al.  Analysis of factors influencing dysphagia severity following treatment of head and neck cancer. Anticancer Res 2009;29 (8) 3299- 3304
PubMed
Pauloski  BRRademaker  AWLazarus  CBoeckxstaens  GKahrilas  PJLogemann  JA Relationship between manometric and videofluoroscopic measures of swallow function in healthy adults and patients treated for head and neck cancer with various modalities. Dysphagia 2009;24 (2) 196- 203
PubMed Link to Article
Belani  CPBarstis  JPerry  MC  et al.  Multicenter, randomized trial for stage IIIB or IV non–small-cell lung cancer using weekly paclitaxel and carboplatin followed by maintenance weekly paclitaxel or observation. J Clin Oncol 2003;21 (15) 2933- 2939
PubMed Link to Article
List  MAD’Antonio  LLCella  DF  et al.  The Performance Status Scale for Head and Neck Cancer Patients and the Functional Assessment of Cancer Therapy–Head and Neck Scale: a study of utility and validity. Cancer 1996;77 (11) 2294- 2301
PubMed Link to Article
Browman  GPLevine  MNHodson  DI  et al.  The Head and Neck Radiotherapy Questionnaire: a morbidity/quality-of-life instrument for clinical trials of radiation therapy in locally advanced head and neck cancer. J Clin Oncol 1993;11 (5) 863- 872
PubMed
Cella  DFTulsky  DSGray  G  et al.  The Functional Assessment of Cancer Therapy Scale: development and validation of the general measure. J Clin Oncol 1993;11 (3) 570- 579
PubMed
Logemann  JARademaker  AWPauloski  BR  et al.  Site of disease and treatment protocol as correlates of swallowing function in patients with head and neck cancer treated with chemoradiation. Head Neck 2006;28 (1) 64- 73
PubMed Link to Article
Caudell  JJSchaner  PEMeredith  RF  et al.  Factors associated with long-term dysphagia after definitive radiotherapy for locally advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys 2009;73 (2) 410- 415
PubMed Link to Article
Piccirillo  JF Importance of comorbidity in head and neck cancer. Laryngoscope 2000;110 (4) 593- 602
PubMed Link to Article
Feng  FYKim  HMLyden  TH  et al.  Intensity-modulated radiotherapy of head and neck cancer aiming to reduce dysphagia: early dose-effect relationships for the swallowing structures. Int J Radiat Oncol Biol Phys 2007;68 (5) 1289- 1298
PubMed Link to Article
Eisbruch  ALevendag  PCFeng  FY  et al.  Can IMRT or brachytherapy reduce dysphagia associated with chemoradiotherapy of head and neck cancer? the Michigan and Rotterdam experiences. Int J Radiat Oncol Biol Phys 2007;69 (2) ((suppl)) S40- S42
PubMed Link to Article

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