Single-item discrimination of quality-of-life-altering dysphagia among 714 long-term oropharyngeal cancer survivors: Comparison of patient-reported outcome measures of swallowing.

BACKGROUND: Two patient-reported outcomes (PROs) of swallowing and their correlation to quality of life (QOL) were compared in long-term survivors of oropharyngeal cancer (OPC). METHODS: Scores on the single dysphagia item from the 28-item, multisymptom MD Anderson Symptom Inventory-Head and Neck (MDASI-HN-S) were compared with scores on the dysphagia-specific composite MD Anderson Dysphagia Inventory (MDADI) and the EuroQol visual analog scale (EQ-VAS) in 714 patients who had received definitive radiotherapy ≥12 months before the survey. An MDASI-HN-S score ≥6 and an MDADI composite score <60 were considered representative of moderate/severe swallowing dysfunction. RESULTS: Moderate/severe dysphagia was reported by 17% and 16% of respondents on the MDASI-HN-S and the composite MDADI, respectively. Both swallow PROs were predictive of QOL, and the MDASI-HN-S model was slightly more parsimonious for the discrimination of EQ-VAS scores compared with MDADI scores (Bayesian information criteria, 6062 vs 6076, respectively). An MDASI-HN-S cutoff score of ≥6 correlated best with a declining EQ-VAS score (P < .0001) and was associated with increased radiotherapy dose to several normal swallowing structures. CONCLUSIONS: In this cohort, the single-item MDASI-HN-S performed favorably for the discrimination of QOL compared with the multi-item MDADI. A time-efficient model for PRO measurement of swallowing is proposed in which the MDADI may be reserved for patients who score ≥6 on the MDASI-HN-S.

Modeling symptom drivers of oral intake in long-term head and neck cancer survivors.

PURPOSE: This study examined the relationship between self-reported symptom severity and oral intake in long-term head and neck cancer (HNC) survivors. METHODS: An observational survey study with retrospective chart abstraction was conducted. HNC patients who had completed an MD Anderson Symptom Inventory-Head and Neck (MDASI-HN) questionnaire and also had clinician graded oral intake ratings (Functional Oral Intake Scale [FOIS]) were included. Correlation coefficients were computed. FOIS scores were regressed on MDASI-HN symptom items using stepwise backwards elimination for multivariate models. RESULTS: One hundred and fifty-two survey pairings were included in the analysis (median 44 months follow-up, range 7-198). Per FOIS, 28% of survivors maintained a total oral diet with no restrictions, 67% reported a restricted oral diet (without tube), 3% were partially tube-dependent with some oral intake, and 2% were NPO. Of the 22 symptom items, the most severe items in decreasing order were dry mouth, difficulty swallowing\chewing, problems with mucus, tasting food, and choking/coughing. Significant bivariate correlations, after Bonferroni correction for multiple comparisons, were present for 8 of 22 symptoms with FOIS. On multivariate analysis, symptom severity for difficulty swallowing and problems with teeth/gums remained significantly associated with FOIS. CONCLUSIONS: Oral intake in HNC survivorship is a multidimensional issue and functional outcome that is impacted not only by dysphagia but also by dental status. Symptom drivers of oral intake likely differ in acute survivorship. Nonetheless, these findings highlight the lack of specificity in this end point and also the need for multidisciplinary supportive care to optimize oral intake in survivors.

Grading Dysphagia as a Toxicity of Head and Neck Cancer: Differences in Severity Classification Based on MBS DIGEST and Clinical CTCAE Grades.

Clinician-reported toxicity grading through common terminology criteria for adverse events (CTCAE) stages dysphagia based on symptoms, diet, and tube dependence. The new dynamic imaging grade of swallowing toxicity (DIGEST) tool offers a similarly scaled five-point ordinal summary grade of pharyngeal swallowing as determined through results of a modified barium swallow (MBS) study. This study aims to inform clinicians on the similarities and differences between dysphagia severity according to clinical CTCAE and MBS-derived DIGEST grading. A cross-sectional sample of 95 MBS studies was randomly selected from a prospectively-acquired MBS database among patients treated with organ preservation strategies for head and neck cancer. MBS DIGEST and clinical CTCAE dysphagia grades were compared. DIGEST and CTCAE dysphagia grades had "fair" agreement per weighted κ of 0.358 (95% CI .231-.485). Using a threshold of DIGEST ≥ 3 as reference, CTCAE had an overall sensitivity of 0.50, specificity of 0.84, and area under the curve (AUC) of 0.67 to identify severe MBS-detected dysphagia. At less than 6 months, sensitivity was 0.72, specificity was 0.76, and AUC was 0.75 while at greater than 6 months, sensitivity was 0.22, specificity was 0.90, and AUC was 0.56 for CTCAE to detect dysphagia as determined by DIGEST. Classification of pharyngeal dysphagia on MBS using DIGEST augments our understanding of dysphagia severity according to the clinically-derived CTCAE while maintaining the simplicity of an ordinal scale. DIGEST likely complements CTCAE toxicity grading through improved specificity for physiologic dysphagia in the acute phase and improved sensitivity for dysphagia in the late-phase.

Dynamic Imaging Grade of Swallowing Toxicity (DIGEST): Scale development and validation.

BACKGROUND: The National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) is the universal framework for toxicity reporting in oncology trials. The objective of this study was to develop a CTCAE-compatible modified barium swallow (MBS) grade for the purpose of grading pharyngeal dysphagia as a toxicity endpoint in cooperative-group organ-preservation trials for head and neck cancer (HNC). It was hypothesized that a 5-point, CTCAE-compatible MBS grade (Dynamic Imaging Grade of Swallowing Toxicity [DIGEST]) based on the interaction of pharyngeal residue and laryngeal penetration/aspiration ratings would be feasible and psychometrically sound. METHODS: A modified Delphi exercise was conducted for content validation, expert consensus, and operationalization of DIGEST criteria. Two blinded raters scored 100 MBSs conducted before or after surgical or nonsurgical organ preservation. Intrarater and interrater reliability was tested with weighted κ values. Criterion validity against oropharyngeal swallow efficiency (OPSE), the Modified Barium Swallow Impairment Profile (MBSImP™©), the MD Anderson Dysphagia Inventory (MDADI), and the Performance Status Scale for Head and Neck Cancer Patients (PSS-HN) was assessed with a 1-way analysis of variance and post hoc pairwise comparisons between DIGEST grades. RESULTS: Intrarater reliability was excellent (weighted κ = 0.82-0.84) with substantial to almost perfect agreement between raters (weighted κ = 0.67-0.81). DIGEST significantly discriminated levels of pharyngeal pathophysiology (MBSImP™©: r = 0.77; P < .0001), swallow efficiency (OPSE: r = -0.56; P < .0001), perceived dysphagia (MDADI: r = -0.41; P < .0001), and oral intake (PSS-HN diet: r = -0.49; P < .0001). CONCLUSIONS: With the development of DIGEST, the MBS rating has been adapted to the CTCAE nomenclature of ordinal toxicity grading used in oncology trials. DIGEST offers a psychometrically sound measure for HNC clinical trials and investigations of toxicity profiles, dose responses, and predictive modeling. Cancer 2017;62-70. © 2016 American Cancer Society.

Cough strength and expiratory force in aspirating and nonaspirating postradiation head and neck cancer survivors.

OBJECTIVE: Expiratory functions that clear aspiration from the airway are compromised in patients with neurogenic dysphagia for whom cough and expiratory force may be impaired by the primary disease process. The relationship between expiratory function, cough, and aspiration is less clear in head and neck cancer (HNC) survivors for whom the disease process does not directly impact the lower respiratory system. Our objective was to compare mechanisms of airway clearance (expiratory force and cough) with aspiration status in postradiated HNC survivors. STUDY DESIGN: Cross-sectional study. METHODS: One hundred and three disease-free HNC survivors ≥ 3-months postradiotherapy referred for modified barium swallow studies were prospectively enrolled regardless of dysphagia status. Maximum expiratory pressures (MEPs) and peak cough flow (PCF) measures were taken at enrollment and examined as a function of aspiration status using generalized linear regression methods. RESULTS: Thirty-four (33%) patients aspirated. Maximum expiratory pressure and PCF demonstrated a moderate positive correlation (Pearson's r = 0.35). Adjusting for sex and age, MEPs were on average 19.2% lower (21.1 cm H2 O, 95% confidence interval [CI] 5.3, 36.8) among aspirators. Peak cough flow was also 14.9% lower (59.6 L/minute, 95% CI 15.8, 103.3) among aspirators after adjusting for age and sex. CONCLUSION: Expiratory functions were depressed in postradiated HNC aspirators relative to nonaspirators, suggesting that airway protection impairments may extend beyond disrupted laryngopharyngeal mechanisms in the local treatment field. Exercises to strengthen subglottic expiratory force-generating capacity may offer an adjunctive therapeutic target to improve airway protection in chronic aspirators after head and neck radiotherapy. LEVEL OF EVIDENCE: 2b. Laryngoscope, 128:1615-1621, 2018.

Expiratory muscle strength training for radiation-associated aspiration after head and neck cancer: A case series.

OBJECTIVE/HYPOTHESIS: Expiratory muscle strength training (EMST) is a simple, inexpensive, device-driven exercise therapy. Therapeutic potential of EMST was examined among head and neck cancer survivors with chronic radiation-associated aspiration. STUDY DESIGN: Retrospective case series. METHODS: Maximum expiratory pressures (MEPs) were examined among n = 64 radiation-associated aspirators (per penetration-aspiration scale score ≥ 6 on modified barium swallow). Pre-post EMST outcomes were examined in a nested subgroup of patients (n = 26) who enrolled in 8 weeks of EMST (25 repetitions, 5 days/week, 75% load). Nonparametric analyses examined effects of EMST on the primary endpoint MEPs. Secondary measures included swallowing safety (Dynamic Imaging Grade of Swallowing Toxicity [DIGEST]), perceived dysphagia (M.D. Anderson Dysphagia Inventory [MDADI]), and diet (performance status scale for head and neck cancer patients [PSSHN]). RESULTS: Compared to sex-matched published normative data, MEPs were reduced in 91% (58 of 64) of aspirators (mean ± standard deviation: 89 ± 37). Twenty-six patients enrolled in EMST and three patients withdrew. MEPs improved on average 57% (87 ± 29 to 137 ± 44 cm H2 O, P < 0.001) among 23 who completed EMST. Swallowing safety (per DIGEST) improved significantly (P = 0.03). Composite MDADI scores improved post-EMST (pre-EMST: 59.9 ± 17.1, post-EMST: 62.7 ± 13.9, P = 0.13). PSSHN diet scores did not significantly change. CONCLUSION: MEPs were reduced in chronic radiation-associated aspirators relative to normative data, suggesting that expiratory strengthening could be a novel therapeutic target to improve airway protection in this population. Similar to findings in neurogenic populations, these data also suggest improved expiratory pressure-generating capabilities after EMST and translation to functional improvements in swallowing safety in chronic radiation-associated aspirators. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1044-1051, 2018.

Device Life of the Tracheoesophageal Voice Prosthesis Revisited.

Importance: Voice prosthesis (VP) device life is a limiting factor of tracheoesophageal (TE) voice restoration that drives patient satisfaction, health care costs, and overall burden. Historic data suggest that TE VPs have an average device life of generally 3 to 6 months, but these data are typically derived from small samples using only 1 or 2 devices. Objective: To reexamine current device life in a large, contemporary cancer hospital in the United States that uses a wide assortment of VPs. Design, Setting, and Participants: This retrospective observational study included 390 laryngectomized patients with a tracheoesophageal puncture (TEP) who had VP management at MD Anderson Cancer Center between July 1, 2003, and December 31, 2013. Main Outcomes and Measures: Tracheoesophageal voice-related outcomes were: (1) device life duration to VP removal, and (2) treatment-related and prosthetic-related factors influencing device failure. Primary independent variables included treatment history (extent of surgery and radiation history), VP type (indwelling vs nonindwelling, size, specialty features), and reason for removal (leakage, complication, other). Duration was examined using Kaplan-Meier analysis. Disease, treatment, and patient-specific factors were analyzed as predictors of duration. Results: Overall, 3648 VPs were placed in the 390 patients (median [range] age, 62 [34-92] years). Indwelling prostheses accounted for more than half (56%) of the devices placed (55%, 20-Fr diameter; 33%, 8-mm length). More than two-thirds (69%) of prostheses were removed because of leakage, while the rest were removed for other reasons. Median device life was 61 days for all prostheses. Indwelling and nonindwelling VPs had median device lives of 70 and 38 days, respectively. There was no significant difference between specialty prostheses compared with standard devices (median duration, 61 vs 70 days, respectively). The Provox ActiValve (Atos Medical) had the longest life. Neither radiation therapy nor extent of surgery had a meaningful impact on device life. Conclusions and Relevance: Our data suggest that VP duration demonstrates a lower durability than historically reported. This may reflect the intensification of treatment regimens that complicate TEP management in an era of organ preservation; however, further investigation is needed.

Symptom burden as a driver of decisional regret in long-term oropharyngeal carcinoma survivors.

BACKGROUND: The purpose of this study was to characterize decisional regret and its association with symptom burden in a large cohort of oropharyngeal carcinoma (OPC) survivors. METHODS: A cross-sectional survey was administered to 1729 OPC survivors. Survey items included a multisymptom inventory and a validated decisional regret inventory. Associations between regret and symptom scores were analyzed to determine and rank symptom drivers of decisional regret. RESULTS: Nine hundred seventy-two patients responded reporting a low level of decisional regret overall, although 15.5% communicated "moderate to strong" regret. Overall symptom score and treatment group were statistically significant predictors of decisional regret. Relative to other symptoms, difficulty swallowing and feeling sad were the strongest drivers of decisional regret. CONCLUSION: OPC survivors provide a robust description of their long-term outcomes with 15.5% expressing "moderate to high" regret that was significantly associated with late symptom burden and multimodality treatment. Difficulty swallowing was the strongest driver of decisional regret.

Symptom burden and dysphagia associated with osteoradionecrosis in long-term oropharynx cancer survivors: A cohort analysis.

OBJECTIVE: The purpose is to examine the relationship between mandibular osteoradionecrosis (ORN) and chronic dysphagia in long-term oropharynx cancer (OPC) survivors, and to determine the perceived symptom burden associated with ORN. MATERIALS AND METHODS: Medical records of 349 OPC patients treated with bilateral IMRT and systemic therapy were reviewed. ORN was graded using a published 4-point classification schema. Patients were considered to have chronic dysphagia if they had aspiration pneumonia, stricture or aspiration detected by fluoroscopy or endoscopy, and/or feeding tube dependence in long-term follow-up ⩾1year following radiotherapy. MD Anderson Symptom Inventory - Head and Neck Module (MDASI-HN) scores were analyzed in a nested cross-sectional survey sample of 118 patients. RESULTS: 34 (9.7%, 95% CI: 6.8-13.3%) patients developed ORN and 45 (12.9%, 95% CI: 9.6-16.9%) patients developed chronic dysphagia. Prevalence of chronic dysphagia was significantly higher in ORN cases (12/34, 35%) compared to those who did not develop ORN (33/315, 11%, p<0.001). ORN grade was also significantly associated with prevalence of dysphagia (p<0.001); the majority of patients with grade 4 ORN requiring major surgery (6 patients, 75%) were found to have chronic dysphagia. Summary MDASI-HN symptom scores did not significantly differ by ORN grade. Significantly higher symptom burden was reported, however, among ORN cases compared to those without ORN for MDASI-HN swallowing (p=0.033), problems with teeth and/or gums (p=0.016) and change in activity (p=0.015) item scores. CONCLUSIONS: ORN is associated with excess burden of chronic dysphagia and higher symptom severity related to swallowing, dentition and activity limitations.

Predicting two-year longitudinal MD Anderson Dysphagia Inventory outcomes after intensity modulated radiotherapy for locoregionally advanced oropharyngeal carcinoma.

OBJECTIVES/HYPOTHESIS: To determine the factors associated with longitudinal patient-reported dysphagia as measured by the MD Anderson Dysphagia Inventory (MDADI) in locoregionally advanced oropharyngeal carcinoma (OPC) survivors treated with split-field intensity modulated radiotherapy (IMRT). STUDY DESIGN: Retrospective patient analysis. METHODS: A retrospective analysis combined data from three single-institution clinical trials for stage III/IV head and neck carcinoma. According to trial protocols, patients had prospectively collected MDADI at baseline, 6, 12, and 24 months after treatment. OPC patients with baseline and at least one post-treatment MDADI were included. Longitudinal analysis was completed with multivariate linear mixed effects modeling. RESULTS: There were 116 patients who met inclusion criteria. Mean baseline MDADI composite was 88.3, dropping to 73.8 at 6 months, and rising to 78.6 and 83.3 by 12 and 24 months, respectively (compared to baseline, all P < .0001). Tumor stage and smoking status were significant predictors of longitudinal MDADI composite scores. Patients with T1, T2, and T3 tumors had 15.9 (P = .0001), 10.9 (P = .0049), and 7.5 (P = .0615), respectively, higher mean MDADI composite than those with T4 tumors, and current smokers had a 9.4 (P = .0007) lower mean MDADI composite than never smokers. CONCLUSIONS: Patients report clinically meaningful dysphagia early after split-field IMRT for locoregionally advanced OPC that remains apparent 6 months after treatment. MDADI scores recover slowly thereafter, but remain depressed at 24 months compared to baseline. Higher tumor stage and smoking status are important markers of patient-reported function through the course of treatment, suggesting these are important groups for heightened surveillance and more intensive interventions to optimize swallowing outcomes. LEVEL OF EVIDENCE: 4 Laryngoscope, 127:842-848, 2017.

Long-Term, Prospective Performance of the MD Anderson Dysphagia Inventory in "Low-Intermediate Risk" Oropharyngeal Carcinoma After Intensity Modulated Radiation Therapy.

PURPOSE: To characterize long-term MD Anderson Dysphagia Inventory (MDADI) results after primary intensity modulated radiation therapy (IMRT) for oropharyngeal carcinoma (OPC) among patients with "low-intermediate risk" OPC who would be eligible for current trials (eg, ECOG 3311, NRG HN002, CRUK PATHOS). METHODS AND MATERIALS: A retrospective pooled analysis combined data from 3 single-institution clinical trials for advanced-stage head and neck carcinoma. Inclusion criteria were clinical stage III/IV OPC (T1-2/N1-2b, T3/N0-2b) treated with definitive split-field IMRT and prospectively collected MDADI at baseline and at least 1 posttreatment interval available in trial databases. Patients were sampled to represent likely human papillomavirus (HPV)-associated disease (HPV+/p16+ or <10 pack-years if HPV/p16 unknown). The MDADI composite scores were collected at baseline and 6, 12, and 24 months after treatment. Pairwise tests were Bonferroni corrected for multiple comparisons. RESULTS: Forty-six patients were included. All received bilateral neck irradiation with a median dose of 70 Gy and systemic therapy (57% concurrent, 43% induction only). Overall the mean baseline MDADI composite score was 90.1, dropping to 74.6 at 6 months (P<.0001) and rising to 78.5 (P<.0001) and 83.1 (P=.002) by 12 and 24 months relative to baseline, respectively, representing a clinically meaningful drop in MDADI scores at 6 months that partially recovers by 24 months (6 vs 24 months, P=.05). Poor MDADI scores (composite <60) were reported in 4%, 11%, 15%, and 9% of patients at baseline and 6, 12, and 24 months, respectively. Fifteen percent of patients had a persistently depressed composite score by at least 20 points at the 24-month interval. CONCLUSION: "Low-intermediate risk" patients with OPC treated with laryngeal/esophageal inlet dose-optimized split-field IMRT are highly likely to report recovery of acceptable swallowing function in long-term follow-up. Only 15% report poor swallowing function and/or persistently depressed MDADI at 12 months or more after IMRT. These data serve as a benchmark future trial design and endpoint interpretation.

What is a clinically relevant difference in MDADI scores between groups of head and neck cancer patients?

OBJECTIVE/HYPOTHESIS: To describe clinically relevant between-group differences in MD Anderson Dysphagia Inventory (MDADI) scores among head and neck cancer (HNC) patients. STUDY DESIGN: Retrospective cross-sectional study was conducted in 1,136 HNC patients seen for modified barium swallow (MBS) studies. METHODS: The MDADI was administered by written questionnaire at the MBS appointment. MD Anderson Dysphagia Inventory global, composite, and subscale scores were calculated. Anchor-based methods were employed to determine clinically meaningful between-group differences by feeding tube status, aspiration status (per MBS study), and diet level. RESULTS: Mean MDADI scores for the 1,136 patients were: emotional 65.8 ± 17.3, functional 68.1 ± 19.6, physical 60.1 ± 18.6, global 59.3 ± 28.3, and composite 64.0 ± 17.1. Three hundred seventy-eight patients (33%) were feeding tube-dependent; 395 (34.8%) were aspirators; 122 (11%) were nothing per oral (Performance Status Scale-Head and Neck [PSS-HN] diet = 0); and 249 (22%) ate unrestricted, regular diets (PSS-HN diet = 100). Statistically significant (P < 0.0001) between-group differences (feeding tube vs. no feeding tube, aspirator vs. nonaspirator, oral vs. nonoral diet, PSS-HN diet levels) were observed for all mean MDADI scores (global, composite, and subscales). A mean difference of 10 points in composite MDADI scores differentiated feeding tube-dependent from nontube-dependent patients, aspirators from nonaspirators, and distinct PSS-HN diet levels. CONCLUSIONS: We identify that a 10-point between-group difference in composite MDADI scores was associated with clinically meaningful between-group differences in swallowing function. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:1108-1113, 2016.