Baseline health perceptions, dysphagia, and survival in patients with head and neck cancer

Authors

  • Miriam N. Lango MD,

    Corresponding author
    1. Department of Surgical Oncology, Head and Neck Surgery Section, Fox Chase Cancer Center, Temple University Health System, Philadelphia, Pennsylvania
    • Corresponding author: Miriam N. Lango, MD, Department of Surgical Oncology, Head and Neck Surgery Section, Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA 19111; Fax: (215) 214-4222; Miriam.Lango@fccc.edu

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  • Brian Egleston PhD,

    1. Department of Biostatistics, Fox Chase Cancer Center, Temple University Health System, Philadelphia, Pennsylvania
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  • Carolyn Fang PhD,

    1. Cancer Prevention and Control Program, Fox Chase Cancer Center, Temple University Health System, Philadelphia, Pennsylvania
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  • Barbara Burtness MD,

    1. Department of Medical Oncology, Fox Chase Cancer Center, Temple University Health System, Philadelphia, Pennsylvania
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  • Thomas Galloway MD,

    1. Department of Radiation Oncology, Fox Chase Cancer Center, Temple University Health System, Philadelphia, Pennsylvania
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  • Jeffrey Liu MD,

    1. Department of Surgical Oncology, Head and Neck Surgery Section, Fox Chase Cancer Center, Temple University Health System, Philadelphia, Pennsylvania
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  • Ranee Mehra MD,

    1. Department of Medical Oncology, Fox Chase Cancer Center, Temple University Health System, Philadelphia, Pennsylvania
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  • Barbara Ebersole CCCP,

    1. Department of Rehabilitation, Fox Chase Cancer Center, Temple University Health System, Philadelphia, Pennsylvania.
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  • Kathleen Moran CCCP,

    1. Department of Rehabilitation, Fox Chase Cancer Center, Temple University Health System, Philadelphia, Pennsylvania.
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  • John A. Ridge MD, PhD

    1. Department of Surgical Oncology, Head and Neck Surgery Section, Fox Chase Cancer Center, Temple University Health System, Philadelphia, Pennsylvania
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  • We would like to thank Sandy Schwartz, MS, SLP, for assistance in the initial implementation of this study, and Olga Tchuvatkina, MS, and Suresh Yalamanchi for database support.

Abstract

BACKGROUND

In head and neck cancer patients prior to treatment, dysphagia noted by patients is more common than aspiration on formal swallow studies. The authors hypothesized that patient-reported dysphagia impacts multiple domains of quality of life (QOL) and predicts disease recurrence and disease-related death.

METHODS

The Swal-QOL, a dysphagia-specific, swallowing-related, QOL measure, and the EuroQOL-5D-3L were administered to 159 patients before treatment with curative intent in this prospective cohort study. Logistic regression analysis evaluated associations among clinical and subjective measures. Multivariable competing risk regression tested the impact of clinical, tumor, and patient-reported measures on survival.

RESULTS

Baseline dysphagia, pain, and diminished patient-reported health state were found to be closely associated with weight loss before treatment and advanced T classification. However, only 58% of patients (23 of 40 patients) reporting dysphagia experienced > 5% weight loss. Dysphagia was found to be associated with pain and/or diminished patient-reported health state, independent of weight loss. Female patients were more likely to report pain and dysphagia, whereas male patients reported dysphagia alone. Dysphagia was found to be predictive of disease recurrence and disease-related death, adjusting for T and N classifications, ECOG performance status, smoking status, and weight loss, and accounting for competing risks of death (recurrence-free survival: hazards ratio, 3.8 [95% confidence interval, 1.7-8.4; P = .001] and disease-related death: hazards ratio, 4.2 [95% confidence interval, 1.04-5; P = .004]).

CONCLUSIONS

Baseline dysphagia affects multiple domains of QOL and general health perceptions in patients with head and neck cancer prior to treatment. A dysphagia measure captures the effort of maintaining nutrition, and identifies patients predisposed to disease recurrence and disease-related death. Cancer 2014;120:840–847. © 2013 American Cancer Society.

INTRODUCTION

Patient-reported measures have been shown to predict survival more effectively than clinical measures in both patients without[1-4] and with cancer.[5, 6] Patient-reported global quality of life (QOL) and physical functioning have been linked to performance status[6] and, in patients with advanced and metastatic cancer, cachexia.[7]

Dysphagia, pain, and weight loss in patients with previously untreated head and neck squamous cell carcinoma (HNSCC) have each been associated with diminished survival independent of traditional staging including T classification.[8-11] Weight loss in newly diagnosed patients with HNSCC is often associated with locally advanced disease. Reports of dysphagia are more common among patients with untreated head and neck cancer than aspiration on formal swallowing testing.[12] Patient-reported measures of dysphagia have outperformed formal swallowing tests in predicting survival.[13]

Pugliano et al developed a symptom-severity staging system based on the presence of several dysphagia-related symptoms and weight loss. However, symptoms were gleaned retrospectively from the medical record.[8-10] Patient-reported dysphagia, measured in swallowing-related QOL with validated questionnaires such as the Swal-QOL, a dysphagia-specific, swallowing-related, QOL measure, assesses the degree to which current swallowing-related function deviates from expected function. In response to a perception of disordered swallowing, patients may eat more slowly, change their diet, or persevere in eating despite a lack of appetite, fatigue or pain. We hypothesized that patient-reported dysphagia impacts multiple domains of QOL and predicts disease recurrence and disease-related death.

MATERIALS AND METHODS

This report was part of an Institutional Review Board-approved prospective study of swallowing in patients with HNSCC who were enrolled at the Fox Chase Cancer Center. Patients completed a self-administered questionnaire regarding dysphagia and general QOL. Study data were collected and managed using REDCap (Research Electronic Data Capture) tools hosted at our institution.[14]

Sample

Patients were identified as eligible for inclusion if they were newly diagnosed with HNSCC, had no history of prior treatment for head and neck cancer, had no evidence of distant metastases, and were able to provide informed consent. All patients were treated with curative intent. One patient who had not recovered from a diagnostic tonsillectomy and 2 patients whose questionnaires were lost were excluded. Only 1 patient who was approached refused participation. Compliance in completing questionnaires was good, with no subject found to have > 4% of their data missing. At the time of enrollment, no patient had a tracheotomy or feeding tube. Prophylactic feeding tube placement was recommended at the discretion of the multidisciplinary team but was not routinely used for patients undergoing chemoradiation.

Measures

The Swal-QOL is a 44-item instrument, the validity and reliability of which have been established in patients with dysphagia, including those with HNSCC.[15-17] The questionnaire generates 11 domain scores: Burden, Duration, Desire, Symptoms, Food Selection, Speech, Fear, Mental Health, Social Role, and Fatigue. Each item has a 5-item response range. Domain measures were converted into scores of 0 (worst score) to 100 (best score). The composite score for the Swal-QOL was calculated by averaging the domain scores, giving equal weight to each of the domains. The Cronbach α of the Swal-QOL was .964, suggesting adequate internal consistency. All subscales of the Swal-QOL had Cronbach α values > .70, ranging from .757 for the Fear subscale to .951 for the Social Role subscale.

The EuroQOL-5D-3L is a well-validated,[18, 19] preference-based, QOL instrument that measures health-related QOL in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) using 3 levels (no problems, some problems, and severe problems). A vertically oriented visual analog scale generates a self-reported current “health state.” This study was registered with the EuroQOL group (euroqol.org/home.html). In this article, the terms “general health perceptions” and “patient-reported health state” (PRHS) will be used interchangeably. Patients were asked their level of agreement with the statement, “I don't eat as much as I used to,” a principal investigator-generated item with 5 levels ranging from agree strongly to disagree strongly. The first 20 patients within the cohort filled out the Swal-QOL without the EuroQOL.

Survival was defined as the interval in months since enrollment in the study. Patients lost to follow-up were censored at the time of their last contact. Staging was assigned based on American Joint Committee on Cancer criteria.[20] The percentage weight loss was determined by assessing weight loss within the last 6 months and dividing the current weight by the prior weight. No distinction was made between intentional and unintentional weight loss. Performance status was graded according to criteria established by the Eastern Cooperative Oncology Group (ECOG). Comorbidity was graded according to the Adult Comorbidity Evaluation-27.[21]

Data Analysis

The data were analyzed using STATA statistical software (version 12; StataCorp, College Station, Tex). Dichotomized scores using the lowest quartile as the cutpoint defined those with perceptions of poor general health or severe dysphagia. Associations were tested using the chi-square test, nonparametric testing (Mann-Whitney U test), or logistic regression, as appropriate. The odds ratio represents the odds of experiencing the outcome by subjects from the high-risk group divided by the odds of experiencing the outcome by the lower-risk group, with 1 indicating no relationship. Indices of model fit in logistic regression were used as described by Cohen et al.[22] Overall survival was analyzed using Cox proportional hazards regression analysis. Disease-specific and recurrence-specific survival were analyzed using the Gray and Fine proportional hazards regression model.[23] Statistically significant clinical predictors of disease recurrence, disease-specific survival, and overall survival were included in the multivariable models. Each QOL variable was considered separately. A statistical significance level of P < .05 was used for statistical testing.

RESULTS

Patient Characteristics

From December 2006 through December 2012, 159 patients with newly diagnosed HNSCC were recruited. The demographic and clinical characteristics of this sample are listed in Table 1. Greater than 25% of patients reported weight loss of at least 5%. Six patients (4%) had a body mass index of < 20. None had a baseline albumin < 3.2, or hemoglobin < 12 g/dL. All patients underwent treatment with curative intent. During a median follow-up of 32 months for surviving patients (range, 1 month-71 months), 39 patients died at a median of 10 months after enrollment (range, 2 months-51 months). The most common cause of death was tumor progression (24 patients; 62% of deaths). Of the remaining 14 deaths, 5 were related to treatment (14%), 5 were due to second cancers (13%), 3 were from unknown causes (8%), and 2 deaths were from other medical reasons (4%).

Table 1. Clinicopathologic Characteristics (N=159)
  No.Percentage
  1. Abbreviations: ACE-27, Adult Comorbidity Evaluation-27; AJCC, American Joint Committee on Cancer.

SexMale12680%
Overall AJCC stage of disease
I/II4730%
III3019%
IV8251%
Tumor site
Unknown primary43%
Nasopharynx21%
Oral cavity5837%
Oropharynx7245%
Larynx/hypopharynx2314%
T classification
T14226%
T25736%
T33623%
T42415%
N classification
N06943%
N12013%
N26239%
N385%
M classification
M100%
ECOG Performance status
09459%
16541%
ACE-27 grade
0-112176%
>23824%
Weight loss
0%-5%11774%
>5%-10%2818%
>10%138%
% Weight lossMedian: 0.7% (range, 0%-16%)
Median patient age (range), y60 (32-85)
Median pack-y smoking (range)25 (0-120)

Clinical Correlates of Patient-Reported Measures

Patients with newly diagnosed HNSCC infrequently reported problems with mobility, self-care, or performing usual activities. Pain/discomfort and anxiety/depression were reported more often (Table 2).

Table 2. General and Swallowing Related Quality-of-Life Prior to Treatment
EuroQOL Domains  Median ScoreIQR
  1. Abbreviations: Euro-QOL, EuroQOL-5D-3L quality-of-life instrument; IQR, interquartile range; PRHS, patient-reported health state; Swal-QOL, dysphagia-specific swallowing-related quality-of-life questionnaire.

  2. a

    Lower scores on the PRHS and dysphagia measure indicated worse perceived health and swallowing-related quality of life, respectively.

Problems with: EuroQOL: PRHSa8570-90
Mobility Dysphagia Compositea8979-95
Moderate vs none13 (9%) vs 126 (91%)Swal-QOL subscales:  
Self-care Burden8884-100
Moderate vs none3 (2%) vs 136 (98%)Duration10075-100
Performing usual activitiesDesire10083-100
Moderate vs none19 (14%) vs 120 (86%)Symptoms865-95
Pain/discomfort Food Selection10075-100
None vs69 (50%)Speech10075-100
Moderate/severe62 (45%)/8 (5%)Fear10075-100
Anxiety/depression Social Role10094-100
None vs83 (60%)Mental Health10075-100
Moderate/severe52 (37%)/4 (3%)Fatigue7860-90

Patients reporting dysphagia with values in the lowest quartile were more likely to also report problems with mobility, problems performing usual activities, pain/discomfort, anxiety/depression, and diminished general health perceptions or patient-reported health state (PRHS) (Table 3). Overall disease stage, N classification, age, comorbidity score, body mass index, marital status, and primary tumor site were not found to be significantly associated with any patient-reported measure. In contrast, advanced T classification and weight loss were found to be significantly associated with multiple measures, including dysphagia, pain, problems with usual activities, and diminished PRHS (Table 4).

Table 3. Baseline Dysphagiaa Associated With Problems in Other Quality-of-Life Domains
Moderate/Severe Problems With:P
  1. Abbreviation: PRHS patient-reported health state.

  2. a

    Dysphagia scores in the lowest quartile.

  3. b

    PRHS scores in the lowest quartile.

Mobility20% vs 6%.02
Self-care3% vs 2%.74
Usual activities27% vs 10%.02
Pain/discomfort80% vs 40%.0001
Anxiety/depression60% vs 30%.002
PRHSb51% vs 20%.0001
Table 4. Associations Among Clinical Factors and Patient-Reported Measuresa
 PRHSbUsual ActivitiescPain/DiscomfortcAnxiety/DepressioncDysphagiab
Clinical FactorsOR (P)dOR (P)dOR (P)dOR (P)dOR (P)d
  1. Abbreviations: OR, odds ratio; PRHS, patient-reported health state; PS performance status.

  2. a

    Patient-reported measures are the dependent variable in unadjusted logistic regression.

  3. b

    Values in the lowest quartile.

  4. c

    Moderate or severe.

  5. d

    Bold type indicates statistical significance.

Female sex1.4 (.39)1.9 (.22)3.3 (.01)1.8 (.16)1.3 (.12)
T4 vs T0-T32.7 (.04)2.4 (.001)1.9 (.01)1.5 (.09)5.9 (.0001)
PS >01.6 (.19)3.6 (.02)2.3 (.02)1.5 (.22)3.3 (.003)
>5% weight loss3.8 (.002)3.4 (.02)4.5 (.001)1.5 (.09)7.6 (.0001)
Smoking (pack-y)1.0 (.83)1.1 (.71)1.1 (.52)1.02 (.02)1.01 (.04)

Patients reporting dysphagia, pain/discomfort, or diminished PRHS were more likely to note weight loss, even when accounting for advanced T classification and other clinical variables (Table 5). The addition of dysphagia, pain/discomfort, or PRHS contributed substantially to the incremental prediction of pretreatment weight loss exhibited by a decrease in model deviance and an increase in pseudo-R2 measures of model fit (data not shown). Thus, most patient-reported measures tested were associated with pretreatment weight loss: not only dysphagia and pain, but also more global measures such as perceptions of diminished health. Patients reporting dysphagia or pain were more likely to note having already lost weight. Patients reporting diminished health were also more likely to have lost weight, or have locally advanced disease (T-4 classification) (Table 5). Overall, a history of recent weight loss, more than any other clinical feature, was associated with reported decrements in QOL across numerous domains of functioning.

Table 5. Predictors of Pre-Treatment Weight Loss, Including Patient-Reported Measures
 UnadjustedAdjustedWith DysphagiaWith Pain/DiscomfortWith PRHS
Clinical FactorsORPbORPbORPbORPbORPb
  1. Abbreviations: ACE-27, Adult Comorbidity Evaluation-27; OR, odds ratio; PRHS, patient-reported health state; PS, performance status.

  2. aDependent variable in logistic regression.

  3. bBold type indicates statistical significance.

  4. cValues in the lowest quartile.

Predictors of >5% Weight Lossa
T4 vs T0-T32.1.0012.2.0031.7.161.5.071.8.03
PS >03.0.0031.8.181.5.541.2.441.8.25
ACE-27 grade > 11.9.031.3.441.1.361.3.321.53
Smoking (pack-y)1.02.0031.01.041.01.081.01.141.01.15
 With patient-reported measures4.2.0014.2.0013.2.02

Of patients reporting dysphagia, 17 (42%) did not report weight loss. Even in the absence of weight loss, patients reporting dysphagia were more likely to report pain (OR 3.8, 95% CI 1.4–10, P = .007), anxiety/ depression (OR 3.6, 95% CI 1.4–9, P = .004) and/ or poor health (OR 2.7, 95% 1.1–7, P = .03), controlling for advanced T classification. Thus, weight loss was not a prerequisite for the associated perceptions of dysphagia, pain, and poor health. However, the frequency and magnitude of patient-reported problems was greater in patients with weight loss, and increased as the degree of weight loss increased. For example, the median values of associated measures of dysphagia and PRHS diminished significantly with increasing weight loss (<5% weight loss: 92 and 85, respectively; 5% to 10% weight loss: 83 and 80, respectively; and > 10% weight loss: 63 and 60, respectively [P = .0001]). Thus, the onset of weight loss was associated with a substantial decrement in several associated QOL measures.

Patients with dysphagia, pain, and/or poor PRHS reported a decrease in dietary intake. Overall, 40% of patients (61 of 151 patients) agreed or strongly agreed with the statement “I do not eat as much as I used to,” including 77% of patients (30 of 39 patients) reporting dysphagia (vs 27% of those without dysphagia) (P = .0001). Patients reporting dysphagia were more likely to undergo subsequent placement of a feeding tube (60% vs 31%; P = .001).

Pain/discomfort was more closely associated with dysphagia than any other patient-reported measure, but was not equally reported between sexes. Although dysphagia scores did not differ significantly between female and male patients (P = .68), women were significantly more likely to report pain that was moderate (55% of female vs 42% of male patients) or severe (17% of female vs 3% of male patients) (P = .002). Female sex was found to be an independent predictor for reporting of pain/discomfort when accounting for clinical factors (T classification, performance status, and weight loss) and other patient-reported measures (anxiety/depression, PRHS, problems performing usual activities, and dysphagia) (odds ratio, 4; 95% confidence interval, 1.3-12 [P = .01]).

Survival Analysis

An initial assessment of the impact of clinical and tumor-related variables on survival outcomes (Table 6) was followed by an assessment of patient-reported outcome measures (Table 7). Finally, significant variables were analyzed in a multivariable model (Table 8).

Table 6. Unadjusted Clinical and Tumor-Related Predictors of Death From Disease and Any Cause (OS)
 DODOS
 HRPHRP
  1. Abbreviations: ACE-27, Adult Comorbidity Evaluation-27; AJCC, American Joint Committee on Cancer; DOD, death from disease; HR, hazards ratio; N+, lymph node metastases; OS, overall survival or death from any cause.

Overall AJCC stage    
I/IIReferent.03Referent.015
III3.4.162.9.09
III6.6.014.5.005
T classification    
T0-T2Referent.01Referent.003
T31.8.231.8.15
T44.2.0023.7.001
N classification    
N+ vs N01.4.031.3.015
Site Non-oropharynx vs other sites 1.4.391.4.39
Sex Female vs male 2.2.071.3.47
ACE-27 grade    
2-3 vs 0-12.1.072.05
Performance status    
1 vs 02.3.042.4.007
Patient age1.01.721.01.24
Smoking history (pack-y)1.01.191.02.003
>5% weight loss3.4.0032.9.001
Table 7. Unadjusted Patient-Reported Measures as Predictors of Death From Disease and Death From Any Cause
 ContinuousLowest Quartile   
Swal-QOLPaHRPaHREuroQOLPaHR
  1. Abbreviations: EuroQOL, EuroQOL-5D-3L quality-of-life instrument; HR, hazards ratio; PRHS, patient-reported health state; Swal-QOL, dysphagia-specific swallowing-related quality-of-life questionnaire.

  2. a

    Bold type indicates statistical significance.

Predictors of Death From Disease     
Dysphagia composite score.00011.04.00014Problems with mobility  
Burden.0091.02.0013.5Moderate or severe vs none.191.9
Duration.00011.02.0033.5Problems with self-care  
Desire.00011.03.0023.6Moderate or severe vs none.670.06
Symptoms.061.03.211.6Problems performing usual activities  
Food Selection.00011.03.0083Moderate or severe problems vs none.142.7
Speech.041.02.052.2Pain and discomfort.05 
Fear.371.02.272None.07Referent
Social Role.00011.03.022.9Moderate pain.102.8
Mental Health.0041.02.052.5Severe pain.038.3
Fatigue.031.02.022.6Depression and anxiety  
EuroQOL    None.005Referent
Health state no. (PRHS).0071.03.0063.5Moderate depression/anxiety.014
     Severe depression/anxiety.00410
Predictors of Death From Any Cause     
Dysphagia composite score.00011.03.0012.8Problems with mobility  
Burden.00011.02.00013.7Moderate or severe vs none.381.5
Duration.00011.02.0072.4Problems with self-care  
Desire.00011.03.0022.8Moderate or severe vs none.781.3
Symptoms.0081.03.022.2Problems performing usual activities  
Food Selection.0011.02.0042.6Moderate/severe vs none.0232.9
Speech.031.01.161.6Pain and discomfort  
Fear.321.01.181.6None.001Referent
Social Role.0011.02.00013.2Moderate.1431.8
Mental Health.021.01.071.8Severe.00017.3
Fatigue.021.02.022.1Anxiety/depression  
EuroQOL    None.035Referent
Health state no. (PRHS).021.02.0062.7Moderate.0642.4
     Severe.4834.1
Table 8. Adjusted Survival Analysis
 P-valueHR(95% CI)
  1. Abbreviations: PRHS, patient-reported health state; HR, hazard ratio; CI, confidence interval.

  2. a

    Adjusting for T and N-classification, performance status, smoking and weight-loss.

Disease recurrencea   
DysphagiaP = .0013.8(1.7-8.4)
Pain/ discomfortP = .122(.83-4.9)
PRHSP = .062.3(.94-5.8)
Death from diseasea   
DysphagiaP = .0044.2(1.04-5)
Pain/ discomfortP = .063(.95-9)
PRHSP = .082.7(.88-8)
Death from any causea   
DysphagiaP = .072(.93-4)
Pain/ discomfortP = .052.4(1.1-5.6)
PRHSP = .072.1(.94-5)

In the adjusted analysis that included T and N classification, performance status, smoking, and weight loss, many of the measures lost significance or became borderline significant. Dysphagia remained a potent independent predictor of disease recurrence and death from disease when accounting for competing causes of death (Table 8). Significance remained regardless of whether the continuous or dichotomized values for dysphagia were used. Of the dysphagia subscales, “Food Selection” and “Desire” were found to be the most powerful independent predictors of death from disease.

DISCUSSION

Baseline patient-reported assessments in untreated patients with cancer provide distinct prognostic information beyond standard clinical measures in cancer clinical trials.[5, 24-27] Prognostically significant patient-reported measures such as general health perceptions have been speculated to reflect global functional or performance status[5, 24] or, alternatively, an aspect of cancer severity or the cancer “state.”[27] In the current study, general health perceptions and most of the other patient-reported measures were found to be strongly associated with weight loss, whereas performance status was related to patient age and comorbidity. Of the patient-reported measures, dysphagia was the most effective predictor of disease-specific survival. Dysphagia predicted disease recurrence and death from disease (when adjusting for weight loss and tumor and clinical factors, and accounting for competing causes of death). Pain and general health perceptions, both of which were highly associated with dysphagia, were also found to be borderline significant in the multivariable survival analysis. Dysphagia was a better predictor of survival than weight loss. Patient-reported measures might possibly provide some specificity in identifying the drivers of cancer-related weight loss, even at an early stage of the disease trajectory. Among the dysphagia subscales, those that were found to be most prognostic were Food Selection (“It is difficult for me to find foods that I like and can eat,” “Figuring out what I can and can't eat is a problem for me,”) and Desire (“Most days I don't care if I eat or not,” “I'm rarely hungry any more,” “I don't enjoy eating anymore”). Most of the patients in our cohort attributed their diminished dietary intake primarily to dysphagia rather than to pain, and attributed as much to loss of appetite as to problems swallowing. The reported decline in oral intake may be a consequence of all these factors.

Most patient-reported measures tested were found to be highly associated with pretreatment weight loss, but the associations among dysphagia, pain, and diminished health perceptions were observed even in the absence of preexisting weight loss. This suggests that patients may become aware of the effort to maintain oral nutrition even before losing weight, thereby influencing perceptions of their global health. The onset of weight loss is associated with greater dysphagia and worse perceived general health, both of which are aggravated by the degree of weight loss. Patient-reported measures such as dysphagia provide independent prognostic information that is readily obtained from the patient and that is likely less related to the individual's functional status than to their cancer's intrinsic behavior.

The presence of dysphagia, pain, and weight loss at the time of diagnosis has long been associated with impaired survival in patients with HNSCC.[8-11] However, the causes of weight loss in patients with HNSCC may be heterogeneous and are not well understood, having been attributed to mechanical, social-behavioral,[28] or humoral factors.[29] Conventionally, weight loss attributed to mechanical obstruction causing starvation is distinguished from weight loss from cachexia, a multifactorial metabolic syndrome characterized by the disproportionate loss of lean muscle mass (which cannot be fully reversed by conventional nutritional support) and leading to progressive functional impairment.[30] In patients with head and neck cancer, cachexia often presents in conjunction with locally advanced disease.[31] Hence, an understanding of the mechanisms for weight loss in this population remains limited.

The best supportive interventions for patients presenting with dysphagia with or without weight loss before treatment is far from clear. At the study institution, all patients about to embark on treatment for head and neck cancer undergo an evaluation by speech and language pathologists experienced in caring for individuals with head and neck cancer. Patients with weight loss may receive a nutritional assessment and undergo placement of a feeding tube, although prophylactic feeding tube placement is not common for those without preexisting weight loss. Although the majority of patients with dysphagia subsequently underwent placement of feeding tubes, most underwent delayed rather than prophylactic feeding tube placement. The effect of the timing of feeding tube placement on long-term swallowing function is unclear,[32] and is a question that the current study was not designed to answer. The relationship between pretreatment dysphagia and posttreatment dysphagia in survivors of head and neck cancer merits further investigation but is difficult because many patients with pretreatment dysphagia do not survive their cancer.

The use of patient-reported measures in clinical cancer care remains limited. In highlighting the distinct prognostic information afforded by dysphagia-related symptoms, the findings of the current study validate these measures. Instruments that are not only validated but also clinically significant are more likely to be incorporated into clinical care. Patient-reported dysphagia could prove to be an important stratification variable in clinical trials for head and neck cancer. However, the use of patient-reported measures as endpoints in supportive care or therapeutic trials warrants additional investigation.

FUNDING SUPPORT

This study was supported by an institutional grant from the American Cancer Society (IRG-92-027-12).

CONFLICT OF INTEREST DISCLOSURES

Dr. Egleston received support from a National Institutes of Health/National Cancer Institute grant (P30CA006927) for work related to the current study and personal fees from Teva Pharmaceuticals for work unrelated to the current study.

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