Speech and swallowing outcomes after laryngectomy for the dysfunctional irradiated larynx.

PURPOSE: To characterize outcomes of total laryngectomy for the dysfunctional larynx after radiation. METHODS: Retrospective case series of all subjects who underwent total laryngectomy for the irradiated dysfunctional larynx between 2000 and 2018 at an NCI-designated comprehensive cancer center at a single tertiary care academic medical center. Main outcomes included enteral tube feeding dependency, functional tracheoesophageal speech, and number and timing of postoperative pharyngeal dilations. RESULTS: Median time from radiation to laryngectomy was 2.8 years (range 0.5-27 years). Functional outcomes were analyzed for the 32 patients with 1-year follow-up. Preoperatively, 81% required at least partial enteral tube feeding, as compared to 34% 1-year postoperatively (p = 0.0003). At 1 year, 81% had achieved functional tracheoesophageal speech, which was associated with cricopharyngeal myotomy (p = 0.04, HR 0.04, 95% CI 0.002-0.949). There were 34% of subjects who required at least one pharyngeal dilation for stricture by 1 year postoperatively. Over half (60%) of the cohort were dilated over the study period. CONCLUSIONS: Laryngectomy for the dysfunctional larynx improves speech and swallowing outcomes in many patients. Cricopharyngeal myotomy is associated with improved postoperative voice. While the need for enteral feeding is decreased, persistent postoperative swallowing dysfunction is common. Careful patient selection and education regarding functional expectations are paramount.

Effect of Augmentative Technology on Communication and Quality of Life After Tracheostomy or Total Laryngectomy.

OBJECTIVE: Surgical procedures that render patients acutely aphonic can cause them to experience significant anxiety and distress. We queried patient perceptions after tracheostomy or laryngectomy and investigated whether introducing augmentative technology was associated with improvement in patient-reported outcomes. METHODS: Participants included hospitalized patients who acutely lost the ability to speak due to tracheostomy or total laryngectomy from April 2018 to December 2019. We distributed questions regarding the patient communication experience and relevant questions from the validated V-RQOL questionnaire (Voice-Related Quality of Life). Patients were offered a tablet with the electronic communication application Verbally. Pre- and postintervention groups were compared with chi-square analyses. RESULTS: Surveys were completed by 35 patients (n = 18, preintervention; n = 17, postintervention). Prior to using augmentative technology, 89% of patients who were aphonic reported difficulty communicating, specifically noting breathing or suctioning (56%), treatment and discharge plans (78%), or immediate needs, such as pain and using the bathroom (39%). Communication difficulties caused anxiety (55%), depression (44%), or frustration (62%), and 92% of patients were interested in using an electronic communication device. Patients reported less trouble communicating after the intervention versus before (53% vs 89%, P = .03), including less difficulty communicating about treatment or discharge plans (35% vs 78%, P < .01). V-RQOL scores were unchanged. DISCUSSION: Acute loss of phonation arising from surgery can be highly distressing for patients, and use of augmentative technology may alleviate some of these challenges by improving communication. Further studies are needed to identify what additional strategies may improve overall well-being. IMPLICATIONS FOR PRACTICE: Electronic communication devices may benefit patients with acute aphonia.

Predictors of Stricture and Swallowing Function Following Salvage Laryngectomy.

BACKGROUND: Long-term functional outcomes are poorly characterized for salvage laryngectomy. We identified predictors of esophageal stricture and swallowing function after salvage laryngectomy in a large cohort. METHODS: A retrospective study of 233 patients who underwent salvage total laryngectomy for recurrent/persistent squamous cell carcinoma of the larynx or hypopharynx after radiation (XRT) or chemoradiation (CRT) was performed. Primary outcomes were esophageal dilation within 1 year, time to dilation, and gastrostomy tube dependence. Multivariate logistic and Cox regressions were used for statistical analysis. RESULTS: Dilation was performed in 29.9% of patients. Dilation was twice as likely in patients with post-operative fistula compared to those without (Hazard Ratio (HR) 2.10, 95% Confidence Interval (CI) 1.06-4.13, P = .03). Every year between XRT/CRT and salvage was associated with 10% increase in dilation (HR 1.09, 95% CI 1.03-1.17, P = .01). No factors were associated with dilation by 1 year. About 10% of patients were at least partially gastrostomy tube-dependent 1 year post-operatively. At last follow-up (median 29 months), this rate was 13%. Patients with supraglottic recurrence had an increased risk of gastrostomy tube dependence at 1 year compared to glottic (OR 16.7, 95% CI 1.73-160, P = .02). For every 10 pack years pre-salvage, the OR of requiring tube feeds at last follow-up was 1.24 (95% CI 1.04-1.48, P = .02). CONCLUSIONS: Fistula and pre-salvage smoking were associated with stricture post-salvage laryngectomy. No factors were associated with dilation by 1 year. Supraglottic recurrence and smoking were associated with gastrostomy tube dependence. These findings are important for pre-operative counseling prior to salvage laryngectomy. LEVEL OF EVIDENCE: Level 4 Laryngoscope, 131:1229-1234, 2021.

Early MRI Blood Volume Changes in Constrictor Muscles Correlate With Postradiation Dysphagia.

PURPOSE: Predicting individual patient sensitivity to radiation therapy (RT) for tumor control or normal tissue toxicity is necessary to individualize treatment planning. In head and neck cancer, radiation doses are limited by many nearby critical structures, including structures involved in swallowing. Previous efforts showed that imaging parameters correlate with RT dose; here, we investigate the role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) blood volume (BV) changes in predicting dysphagia. METHODS AND MATERIALS: This study included 32 patients with locally advanced oropharyngeal squamous cell carcinoma treated with definitive chemoradiation on an institutional protocol incorporating baseline and early midtreatment DCE-MRI. BV maps of the pharyngeal constrictor muscles (PCM) were created, and BV increases midtreatment were correlated with the following parameters at 3 and 12 months post-RT: RT dose, Dynamic Imaging Grade of Swallowing Toxicity swallow score, aspiration frequency, European Organisation for Research and Treatment of Cancer HN35 patient-reported outcomes, physician-reported dysphagia, and feeding tube (FT) dependence. RESULTS: The mean BV to the PCMs increased from baseline to fraction 10, which was significant for the superior PCM (P = .006) and middle PCM (P < .001), with a trend in the inferior PCM where lower mean doses were seen (P = .077). The factors associated with FT dependence at 3 months included BV increases in the total PCM (correlation, 0.48; P = .006) and middle PCM (correlation, 0.50; P = .004). A post-RT increase in aspiration was associated with a BV increase in the superior PCM (correlation, 0.44; P = .013),and the increase in the total PCMs was marginally significant (correlation, 0.34; P = .06). The best-performing models of FT dependence (area under the receiver operating curve [AUC] = 0.84) and aspiration increases (AUC = 0.78) included BV increases as well as a mean RT dose to middle PCM. CONCLUSIONS: Our results suggest that midtreatment BV increases derived from DCE-MRI are an early predictor of dysphagia. Further investigation of these promising imaging markers to assess individual patient sensitivity to treatment and the patient's subsequent risk of toxicities is warranted to improve personalization of RT planning.

Characterization of very late dysphagia after chemoradiation for oropharyngeal squamous cell carcinoma.

OBJECTIVES: Improved prognosis for p16+ oropharyngeal squamous cell carcinoma (OPSCC) has led to efforts to mitigate long-term complications of treatment, which remains poorly defined in late survivors. Here we characterize very late dysphagia in OPSCC. MATERIALS AND METHODS: Long-term review of 93 p16+ OPSCC patients treated with chemoradiation was performed. We scored videofluoroscopic swallow studies (VFSS) according to the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) scale. Very late dysphagia was defined >2.5 years from end of treatment. Fine-Gray regression models were used to assess dysphagia with competing risk of death. RESULTS: Median follow up was 10.5 years. 402 total VFSS were assessed (median 4 per patient, range 0-8). 15.1% of patients had a DIGEST score ≥2 very late after treatment. Very late DIGEST score ≥2 correlated with T-stage (HR 1.7, p = 0.049), second cancer (HR 6.5, p = 0.004), superior pharyngeal constrictor dose (HR 1.11, p = 0.050), total tongue dose (HR 1.07, p = 0.045), but not hypoglossal nerve dose (p > 0.2). Seven patients (7.5%) had late progressive dysphagia, defined as DIGEST score that increased by ≥2 beyond one year after treatment, and this correlated with higher ipsilateral hypoglossal nerve D1cc dose (75 vs 72 Gy, p = 0.037). CONCLUSION: In p16+ OPSCC patients treated with definitive chemoradiation, at least 7.5% developed late progressive dysphagia, and 15.1% experienced moderate dysphagia >2.5 years from treatment. Our study suggests that dose to tongue musculature may be associated with very late dysphagia, and hypoglossal nerve dose may be associated with late progressive dysphagia. More intensive long-term dysphagia survivorship monitoring is suggested.

Primary versus secondary tracheoesophageal puncture in salvage total laryngectomy following chemoradiation.

OBJECTIVE: To compare the rate of postoperative wound-healing complications and voice fluency in primary vs secondary tracheoesophageal puncture (TEP) following chemoradiation. METHODS: Between 1998 and 2005, 30 patients underwent laryngectomy after chemoradiation therapy. Twenty patients underwent primary TEP and 10 patients underwent secondary TEP. Comorbidities, postoperative complications, speech fluency, and time to speech fluency were evaluated in each patient. RESULTS: Pharyngocutaneous fistula (PCF) occurred in 10 of 20 (50%) patients who underwent primary TEP and in 0 of 10 (0%) patients in the secondary TEP group (P < 0.05). Overall, 25 of 25 (100%) patients who had placement of a tracheoesophageal prosthesis achieved fluent speech. Median time to fluency was 63 days in the primary TEP group and 125 days in the secondary TEP group. CONCLUSION: There is an increased risk of PCF in patients undergoing primary TEP compared with secondary TEP following chemoradiation. No difference in acquisition of speech fluency was identified between the two groups. Patients undergoing primary TEP achieved fluent speech 62 days sooner than their secondary TEP counterparts.

Intensity-modulated radiotherapy of head and neck cancer aiming to reduce dysphagia: early dose-effect relationships for the swallowing structures.

PURPOSE: To present initial results of a clinical trial of intensity-modulated radiotherapy (IMRT) aiming to spare the swallowing structures whose dysfunction after chemoradiation is a likely cause of dysphagia and aspiration, without compromising target doses. METHODS AND MATERIALS: This was a prospective, longitudinal study of 36 patients with Stage III-IV oropharyngeal (31) or nasopharyngeal (5) cancer. Definitive chemo-IMRT spared salivary glands and swallowing structures: pharyngeal constrictors (PC), glottic and supraglottic larynx (GSL), and esophagus. Lateral but not medial retropharyngeal nodes were considered at risk. Dysphagia endpoints included objective swallowing dysfunction (videofluoroscopy), and both patient-reported and observer-rated scores. Correlations between doses and changes in these endpoints from pre-therapy to 3 months after therapy were assessed. RESULTS: Significant correlations were observed between videofluoroscopy-based aspirations and the mean doses to the PC and GSL, as well as the partial volumes of these structures receiving 50-65 Gy; the highest correlations were associated with doses to the superior PC (p = 0.005). All patients with aspirations received mean PC doses >60 Gy or PC V(65) >50%, and GSL V(50) >50%. Reduced laryngeal elevation and epiglottic inversion were correlated with mean PC and GSL doses (p < 0.01). All 3 patients with strictures had PC V(70) >50%. Worsening patient-reported liquid swallowing was correlated with mean PC (p = 0.05) and esophageal (p = 0.02) doses. Only mean PC doses were correlated with worsening patient-reported solid swallowing (p = 0.04) and observer-rated swallowing scores (p = 0.04). CONCLUSIONS: These dose-volume-effect relationships provide initial IMRT optimization goals and motivate further efforts to reduce swallowing structures doses to reduce dysphagia and aspiration.

Can IMRT or brachytherapy reduce dysphagia associated with chemoradiotherapy of head and neck cancer? The Michigan and Rotterdam experiences.

PURPOSE: Dysphagia is a major late complication of intensive chemoradiotherapy of head and neck cancer. The initial clinical results of intensity-modulated radiotherapy (IMRT), or brachytherapy, planned specifically to reduce dysphagia are presented. PATIENTS AND METHODS: Previous research at Michigan University has suggested that the pharyngeal constrictors and glottic and supraglottic larynx are likely structures whose damage by chemo-RT causes dysphagia and aspiration. In a prospective Michigan trial, 36 patients with oropharyngeal (n = 31) or nasopharyngeal (n = 5) cancer underwent chemo-IMRT. IMRT cost functions included sparing noninvolved pharyngeal constrictors and the glottic and supraglottic larynx. After a review of published studies, the retropharyngeal nodes at risk were defined as the lateral, but not the medial, retropharyngeal nodes, which facilitated sparing of the swallowing structures. In Rotterdam, 77 patients with oropharyngeal cancer were treated with IMRT, three dimensional RT, or conventional RT; also one-half received brachytherapy. The dysphagia endpoints included videofluoroscopy and observer-assessed scores at Michigan and patient-reported quality-of-life instruments in both studies. RESULTS: In both studies, the doses to the upper and middle constrictors correlated highly with the dysphagia endpoints. In addition, doses to the glottic and supraglottic larynx were significant in the Michigan series. In the Rotterdam series, brachytherapy (which reduced the doses to the swallowing structures) was the only significant factor on multivariate analysis. CONCLUSION: The dose-response relationships for the swallowing structures found in these studies suggest that reducing their doses, using either IMRT aimed at their sparing, or brachytherapy, might achieve clinical gains in dysphagia.

Impact of xerostomia on dysphagia after chemotherapy-intensity-modulated radiotherapy for oropharyngeal cancer: Prospective longitudinal study.

BACKGROUND: The purpose of this study was to assess how xerostomia affects dysphagia. METHODS: Prospective longitudinal studies of 93 patients with oropharyngeal cancer treated with definitive chemotherapy-intensity-modulated radiotherapy (IMRT). Observer-rated dysphagia (ORD), patient-reported dysphagia (PRD), and patient-reported xerostomia (PRX) assessment of the swallowing mechanics by videofluoroscopy (videofluoroscopy score), and salivary flow rates, were prospectively assessed from pretherapy through 2 years. RESULTS: ORD grades ≥2 were rare and therefore not modeled. Of patients with no/mild videofluoroscopy abnormalities, a substantial proportion had PRD that peaked 3 months posttherapy and subsequently improved. Through 2 years, highly significant correlations were observed between PRX and PRD scores for all patients, including those with no/mild videofluoroscopy abnormalities. Both PRX and videofluoroscopy scores were highly significantly associated with PRD. On multivariate analysis, PRX score was a stronger predictor of PRD than the videofluoroscopy score. CONCLUSION: Xerostomia contributes significantly to PRD. Efforts to further decrease xerostomia, in addition to sparing parotid glands, may translate into improvements in PRD. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1605-E1612, 2016.

Hemiglossectomy tongue reconstruction: Modeling of elevation, protrusion, and functional outcome using receiver operator characteristic curve.

BACKGROUND: The purpose of this study was to model >12 month speech and the oral phase of swallowing outcomes with the reconstructive metrics of tongue elevation and protrusion in patients reconstructed with the rectangle tongue template for a hemiglossectomy defect. METHODS: We conducted a study using 40 surviving patients (23 men, 17 women) treated between 2000 and 2012. Statistically significant correlations of elevation and protrusion with functional outcomes were modeled with receiver operator characteristic (ROC) curves to understand the performance and reliability of the rectangle tongue reconstruction. RESULTS: Tongue elevation (1.8-1.9 cm) reliably produces best outcomes in nutritional mode, range of liquids, and ≥4/6 for range of solids. Greater tongue elevation (2.1-2.2 cm) reliably produces best outcomes for eating and speaking in public and understandability of speech. Tongue protrusion (0.8-1.0 cm) reliably produces best scores across all assessed outcomes except ≥4/6 for range of solids and ≥4/5 understandability of speech. CONCLUSION: ROC curves are useful for assessing reliability and relating reconstructive objectives to functional outcomes. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1066-1073, 2016.

Comparisons of dysphagia and quality of life (QOL) in comparable patients with HPV-positive oropharyngeal cancer receiving chemo-irradiation or cetuximab-irradiation.

PURPOSE: Compare functional outcomes of radiotherapy (RT) concurrent with cetuximab (cet-RT) or with chemotherapy (chemo-RT) for comparable, good prognosis patients with human papillomavirus related (HPV+) oropharyngeal cancer (OPC). METHODS: Outcomes of patients with stage III/IV HPV+ OPC patients with minimal smoking history and non-T4/N3/N2C, treated on prospective protocol of RT concurrent with cetuximab (cet-RT), were compared to similar patients on prospective chemo-RT protocols. In both groups, videofluoroscopy (VF), observer rated dysphagia (ORD), and validated QOL questionnaires: xerostomia questionnaire (XQ), head and neck QOL, and University of Washington QOL, were performed periodically and compared to pretreatment. Mixed effects models with adjustment for baseline assessed differences between groups. RESULTS: 26 cet-RT patients were compared to 27 chemo-RT patients with similar baseline characteristics. In the chemo-RT group, no recurrences occurred. In the cet-RT group, 1 patient had persistent microscopic disease on salvage neck dissection and 1 distant failure. Both groups had mild VF-based swallowing dysfunction pre-treatment, worsened at 3 months (P<0.02) and persisted at 12 months, not differing between groups (P>0.11). For both groups ORD was very low pretreatment, worsened at 3 months and improved at 12 months, without differences between treatment groups (P=0.26). QOL Summary and domain scores for eating were good pretreatment, worse at 3 mo, and then improved to near baseline at 12 months, without differences between the groups in any QOL domains (P>0.10). CONCLUSION: Both groups had excellent clinical outcomes without significant differences in objective or subjective functions. These data question using cetuximab instead of chemotherapy for treatment de-intensification for HPV+ OPC.

Voice and swallowing outcomes of an organ-preservation trial for advanced laryngeal cancer.

INTRODUCTION: Organ-preservation treatment approaches for advanced laryngeal cancer patients that use combination chemoradiotherapy result in cure rates similar to primary laryngectomy with postoperative radiotherapy. In the national VA Larynx Cancer Trial, successful organ preservation was associated with an overall improvement in quality of life but not in subjective speech compared with long-term laryngectomy survivors. As part of a Phase II clinical trial, a prospective study of speech and swallowing results was conducted to determine if larynx preservation is associated with improved voice and swallowing compared with results in patients who require salvage laryngectomy. SUBJECTS: A total of 97 patients with advanced laryngeal cancer (46 Stage III, 51 Stage IV) were given a single course of induction chemotherapy (cisplatin 100 mg/m2 on Day 1 and 5-FU 1,000 mg/m2/day x 5 days), followed by assessment of response. Patients with less than 50% response underwent early salvage laryngectomy, and patients with 50% or better response underwent concurrent chemoradiation (72 Gy and cisplatin 100 mg/m2 on Days 1, 22, and 43), followed by two cycles of adjuvant chemotherapy (DDP/5-FU). Direct laryngoscopy and biopsy were performed 8 weeks after radiation therapy to determine final tumor response. Late salvage surgery was performed on patients with persistent or recurrent disease. METHODS: Completed survey data on voice and swallowing utilizing the Voice-Related Quality of Life Measure (V-RQOL) and the List Performance Status Scale for Head and Neck Cancer Patients (PSS-HN) were obtained from 56 patients who were alive and free of disease at the time of survey, with a minimum follow-up of 8 months. Comparisons were made between patients with an intact larynx (n = 37) vs. laryngectomy (n = 19), as well as early (n = 12) vs. late salvage laryngectomy (n = 7). Multivariate analysis was performed to determine factors predictive of voice and swallowing outcomes. Overall 3-year determinant survival was 87%, with median follow-up of 40 months. RESULTS: Patients with an intact larynx demonstrated significantly higher (p = 0.02) mean V-RQOL scores (80.3) than did laryngectomy patients (65.4). This finding was consistent in the social-emotional (p = 0.007) and physical functioning domains (p = 0.03). No differences in V-RQOL scores were found in comparisons between early and late salvage laryngectomy. Multiple linear regression revealed that predictors of higher total V-RQOL scores include lower T stage (p = 0.03), organ preservation (p = 0.0007), and longer duration since treatment (p = 0.01). Understandability of speech was better in patients with an intact larynx (p = 0.001). Overall swallowing function was comparable between groups. Multiple logistic regression revealed that longer duration since treatment (p = 0.03, odds ratio = 1.1) and lower maximal mucositis grade (p = 0.03, odds ratio = 0.3) were predictive of higher likelihood of eating in public. Nutritional mode consisting of oral intake alone without nutritional supplements was achieved in 88.9% of patients with an intact larynx compared with 64.3% of laryngectomees (p = 0.09). CONCLUSIONS: Voice-related quality of life is better in patients after chemoradiation therapy compared with salvage laryngectomy. Earlier salvage, although known to be associated with fewer surgical complications, did not result in improved voice; however, the number of patients analyzed is small. Overall swallowing function is good in all patients; however, patients with an intact larynx are more likely to obtain nutrition with oral intake alone without supplements. Such measures of function and quality of life are important endpoints to help judge overall effectiveness as newer, more aggressive treatment protocols with added toxicities are developed and evaluated.

Objective assessment of swallowing dysfunction and aspiration after radiation concurrent with chemotherapy for head-and-neck cancer.

PURPOSE: To objectively assess swallowing function after an intensive chemoradiation regimen for locally advanced head-and-neck cancer and to assess the clinical implications of swallowing dysfunction. PATIENTS AND METHODS: Twenty-nine patients with nonresectable Stage IV head-and-neck cancer participated in a Phase I study of radiation, 70 Gy/7 weeks, concurrent with weekly gemcitabine. Because of a high rate of mucosal toxicity, reduced drug doses were delivered to subsequent patient groups: 300, 150, 50, and 10 mg/m(2)/week. Twenty-six of these patients underwent prospective evaluation of swallowing function with videofluoroscopy and esophagogram. Studies were performed pretherapy, early post-therapy (1-3 months), and late post-therapy (6-12 months). RESULTS: Complete tests were performed pretherapy in 22 patients, early post-therapy in 20, and late post-therapy in 13. Twenty-five patients had at least one post-therapy study. Post-therapy dysfunction was characterized by reduced inversion of the epiglottis, delayed swallow initiation and uncoordinated timing of the propulsion of the bolus, opening of the cricopharyngeal muscle, and closure of the larynx, all of which promoted aspiration during and after the swallow. In addition, reduced base-of-tongue retraction with reduced contact to the posterior pharyngeal wall and incomplete cricopharyngeal relaxation resulted in pooling in the pyriform sinuses and vallecula of residue, which was frequently aspirated after the swallow. Post-therapy aspirations were typically "silent," eliciting no cough reflex, or the cough was delayed and noneffective in expelling the residue. Aspiration was observed in 3 patients (14%) in the pretherapy studies, in 13 (65%) in the early post-therapy studies, and in 8 (62%) in the late post-therapy studies (aspiration rates post-therapy vs. pretherapy: p = 0.0002). Six patients had pneumonia requiring hospitalization 1-14 months after therapy (median: 2.5 months), being the likely cause of death in 2 patients. Five cases of pneumonia occurred among 17 patients who had demonstrated aspiration in the post-therapy studies, compared with no cases of pneumonia among 8 patients who had not demonstrated aspiration (p = 0.1). Of the 4 patients who had not undergone any post-therapy study, 1 developed pneumonia. Mucositis scores, prolonged tube feeding, presence of tracheostomy tube, and gemcitabine doses were not found to be related to aspiration or pneumonia risk. CONCLUSIONS: After intensive chemoradiotherapy, significant objective swallowing dysfunction is prevalent. It promotes aspiration, which may not elicit a cough reflex and may be associated with pneumonia. Aspiration pneumonia may be an underdocumented complication of chemoradiotherapy for head-and-neck cancer. Future studies should examine whether routine post-therapy videofluoroscopy and training aspirating patients in safe swallowing strategies can reduce this risk.

Aspiration pneumonia after chemo-intensity-modulated radiation therapy of oropharyngeal carcinoma and its clinical and dysphagia-related predictors.

BACKGROUND: The purpose of this study was to assess aspiration pneumonia (AsPn) rates and predictors after chemo-irradiation for head and neck cancer. METHODS: The was a prospective study of 72 patients with stage III to IV oropharyngeal cancer treated definitively with intensity-modulated radiotherapy (IMRT) concurrent with weekly carboplatin and paclitaxel. AsPn was recorded prospectively and dysphagia was evaluated longitudinally through 2 years posttherapy by observer-rated (Common Toxicity Criteria version [CTCAE]) scores, patient-reported scores, and videofluoroscopy. RESULTS: Sixteen patients (20%) developed AsPn. Predictive factors included T classification (p = .01), aspiration detected on videofluoroscopy (videofluoroscopy-asp; p = .0007), and patient-reported dysphagia (p = .02-.0003), but not observer-rated dysphagia (p = .4). Combining T classification, patient reported dysphagia, and videofluoroscopy-asp, provided the best predictive model. CONCLUSION: AsPn continues to be an under-reported consequence of chemo-irradiation for head and neck cancer. These data support using patient-reported dysphagia to identify high-risk patients requiring videofluoroscopy evaluation for preventive measures. Reducing videofluoroscopy-asp rates, by reducing swallowing structures radiation doses and by trials reducing treatment intensity in patients predicted to do well, are likely to reduce AsPn rates.

Toxicities affecting quality of life after chemo-IMRT of oropharyngeal cancer: prospective study of patient-reported, observer-rated, and objective outcomes.

PURPOSE: To test the hypothesis that intensity modulated radiation therapy (IMRT) aiming to spare the salivary glands and swallowing structures would reduce or eliminate the effects of xerostomia and dysphagia on quality of life (QOL). METHODS AND MATERIALS: In this prospective, longitudinal study, 72 patients with stage III-IV oropharyngeal cancer were treated uniformly with definitive chemo-IMRT sparing the salivary glands and swallowing structures. Overall QOL was assessed by summary scores of the Head Neck QOL (HNQOL) and University of Washington QOL (UWQOL) questionnaires, as well as the HNQOL "Overall Bother" question. Quality of life, observer-rated toxicities (Common Toxicity Criteria Adverse Effects scale, version 2), and objective evaluations (videofluoroscopy assessing dysphagia and saliva flow rates assessing xerostomia) were recorded from before therapy through 2 years after therapy. Correlations between toxicities/objective evaluations and overall QOL were assessed using longitudinal repeated measures of analysis and Pearson correlations. RESULTS: All observer-rated toxicities and QOL scores worsened 1-3 months after therapy and improved through 12 months, with minor further improvements through 24 months. At 12 months, dysphagia grades 0-1, 2, and 3, were observed in 95%, 4%, and 1% of patients, respectively. Using all posttherapy observations, observer-rated dysphagia was highly correlated with all overall QOL measures (P<.0001), whereas xerostomia and mucosal and voice toxicities were significantly correlated with some, but not all, overall QOL measures, with lower correlation coefficients than dysphagia. Late overall QOL (≥6 or ≥12 months after therapy) was primarily associated with observer-rated dysphagia, and to a lesser extent with xerostomia. Videofluoroscopy scores, but not salivary flows, were significantly correlated with some of the overall QOL measures. CONCLUSION: After chemo-IMRT, although late dysphagia was on average mild, it was still the major correlate of QOL. Further efforts to reduce swallowing dysfunction are likely to yield additional gains in QOL.

Chemo-IMRT of oropharyngeal cancer aiming to reduce dysphagia: swallowing organs late complication probabilities and dosimetric correlates.

PURPOSE: Assess dosimetric correlates of long-term dysphagia after chemo-intensity-modulated radiotherapy (IMRT) of oropharyngeal cancer (OPC) sparing parts of the swallowing organs. PATIENTS AND METHODS: Prospective longitudinal study: weekly chemotherapy concurrent with IMRT for Stages III/IV OPC, aiming to reduce dysphagia by sparing noninvolved parts of swallowing-related organs: pharyngeal constrictors (PC), glottic and supraglottic larynx (GSL), and esophagus, as well as oral cavity and major salivary glands. Dysphagia outcomes included patient-reported Swallowing and Eating Domain scores, Observer-based (CTCAEv.2) dysphagia, and videofluoroscopy (VF), before and periodically after therapy through 2 years. Relationships between dosimetric factors and worsening (from baseline) of dysphagia through 2 years were assessed by linear mixed-effects model. RESULTS: Seventy-three patients participated. Observer-based dysphagia was not modeled because at >6 months there were only four Grade ≥2 cases (one of whom was feeding-tube dependent). PC, GSL, and esophagus mean doses, as well as their partial volume doses (V(D)s), were each significantly correlated with all dysphagia outcomes. However, the V(D)s for each organ intercorrelated and also highly correlated with the mean doses, leaving only mean doses significant. Mean doses to each of the parts of the PCs (superior, middle, and inferior) were also significantly correlated with all dysphagia measures, with superior PCs demonstrating highest correlations. For VF-based strictures, most significant predictor was esophageal mean doses (48±17 Gy in patients with, vs 27±12 in patients without strictures, p = 0.004). Normal tissue complication probabilities (NTCPs) increased moderately with mean doses without any threshold. For increased VF-based aspirations or worsened VF summary scores, toxic doses (TDs)(50) and TD(25) were 63 Gy and 56 Gy for PC, and 56 Gy and 39 Gy for GSL, respectively. For both PC and GSL, patient-reported swallowing TDs were substantially higher than VF-based TDs. CONCLUSIONS: Swallowing organs mean doses correlated significantly with long-term worsening of swallowing. Different methods assessing dysphagia resulted in different NTCPs, and none demonstrated a threshold.

Evaluating and reporting dysphagia in trials of chemoirradiation for head-and-neck cancer.

PURPOSE: Reporting long-term toxicities in trials of chemoirradiation (CRT) of head-and-neck cancer (HNC) has mostly been limited to observer-rated maximal Grades >or=3. We evaluated this reporting approach for dysphagia by assessing patient-reported dysphagia (PRD) and objective swallowing dysfunction through videofluoroscopy (VF) in patients with various grades of maximal observer-reported dysphagia (ORD). METHODS AND MATERIALS: A total of 62 HNC patients completed quality-of-life questionnaires periodically through 12 months post-CRT. Five PRD items were selected: three dysphagia-specific questions, an Eating-Domain, and "Overall Bother." They underwent VF at 3 and 12 months, and ORD (Common Terminology Criteria for Adverse Events) scoring every 2 months. We classified patients into four groups (0-3) according to maximal ORD scores documented 3-12 months post-CRT, and assessed PRD and VF summary scores in each group. RESULTS: Differences in ORD scores among the groups were considerable throughout the observation period. In contrast, PRD scores were similar between Groups 2 and 3, and variable in Group 1. VF scores were worse in Group 3 compared with 2 at 3 months but similar at 12 months. In Group 1, PRD and VF scores from 3 through 12 months were close to Groups 2 and 3 if ORD score 1 persisted, but were similar to Group 0 in patients whose ORD scores improved by 12 months. CONCLUSIONS: Patients with lower maximal ORD grades, especially if persistent, had similar rates of PRD and objective dysphagia as patients with highest grades. Lower ORD grades should therefore be reported. These findings may have implications for reporting additional toxicities besides dysphagia.

Intensity-modulated chemoradiotherapy aiming to reduce dysphagia in patients with oropharyngeal cancer: clinical and functional results.

PURPOSE: To assess clinical and functional results of chemoradiotherapy for oropharyngeal cancer (OPC), utilizing intensity-modulated radiotherapy (IMRT) to spare the important swallowing structures to reduce post-therapy dysphagia. PATIENTS AND METHODS: This was a prospective study of weekly chemotherapy (carboplatin dosed at one times the area under the curve [AUC, AUC 1] and paclitaxel 30 mg/m(2)) concurrent with IMRT aiming to spare noninvolved parts of the swallowing structures: pharyngeal constrictors, glottic and supraglottic larynx, and esophagus as well as the oral cavity and major salivary glands. Swallowing was assessed by patient-reported Swallowing and Eating Domain scores, observer-rated scores, and videofluoroscopy (VF) before therapy and periodically after therapy through 2 years. RESULTS: Overall, 73 patients with stages III to IV OPC participated. At a median follow-up of 36 months, 3-year disease-free and locoregional recurrence-free survivals were 88% and 96%, respectively. All measures of dysphagia worsened soon after therapy; observer-rated and patient-reported scores recovered over time, but VF scores did not. At 1 year after therapy, observer-rated dysphagia was absent or minimal (scores 0 to 1) in all patients except four: one who was feeding-tube dependent and three who required soft diet. From pretherapy to 12 months post-therapy, the Swallowing and Eating Domain scores worsened on average (+/- standard deviation) by 10 +/- 21 and 13 +/- 19, respectively (on scales of 0 to 100), and VF scores (on scale of 1 to 7) worsened from 2.9 +/- 1.5 (mild dysphagia) to 4.1 +/- 0.9 (mild/moderate dysphagia). CONCLUSION: Chemoradiotherapy with IMRT aiming to reduce dysphagia can be performed safely for OPC and has high locoregional tumor control rates. On average, long-term patient-reported, observer-rated, and objective measures of swallowing were only slightly worse than pretherapy measures, representing potential improvement compared with previous studies.