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.

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.

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.

Microvascular cricoid cartilage reconstruction with the thoracodorsal artery scapular tip autogenous transplant.

Conservation laryngeal surgery has been limited by difficulties with partial resection of the cricoid. Numerous options have been suggested that include temporoparietal flaps, free cartilage grafts, radial forearm free tissue transfers, and tracheal autotransplantation with vascular carriers. The authors present a one-stage procedure for the reconstruction of the cricoid cartilage based on the thoracodorsal artery scapular tip (Tdast) autogenous transplant that uses the curved tip of the scapula and does not create a secondary tracheal defect. Because the Tdast is a vascularized graft it may withstand radiation treatment.

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.

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.

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.

Oropharyngoplasty with template-based reconstruction of oropharynx defects.

OBJECTIVE: To determine if oropharyngoplasty using a Gehanno technique of superior constrictor velopharyngoplasty, base of tongue mounding, and primary hypopharyngeal closure in combination with template-based revascularized free tissue transfer is effective for reconstruction of the oropharyngeal defect. DESIGN: Prospective case series. SETTING: Tertiary care academic medical center. PATIENTS: The study population comprised 25 patients (21 men and 4 women; mean age, 55.3 years) presenting from January 1998 to January 2001 with oropharyngeal squamous cell carcinoma. A comparison was performed based on the percentage of resection of the soft palate (group 1, < or =50% palate; group 2, >50% palate). INTERVENTIONS: Of the 25 patients, 24 (96%) received radiotherapy. The donor sites were radial forearm for 23 of 25 patients (92%) and lateral arm for 2 of 25 patients (8%). The mean area was 92 cm(2) (range, 25-150 cm(2)), and the mean length of the velopharyngoplasty component of the oropharyngoplasty was 2.15 cm (range, 1-3 cm). MAIN OUTCOME MEASURES: Gastrostomy tube dependence, major and minor complications, time to oral intake, speech and swallowing assessment, and quality-of-life assessment. RESULTS: Of the 25 patients, 2 (8%) remain gastrostomy dependent; 6 (24%) developed major complications; and 7 (28%) developed minor complications. Speech in both groups 1 and 2 was considered understandable most of the time, with occasional repetition. The group 1 patient with a median assessment score could eat a solid diet without restriction of place or person, whereas the group 2 patient with a median assessment score could eat a soft, moist diet with selected persons in selected places. CONCLUSION: Integration of oropharyngoplasty with template-based revascularized free tissue transfer produced speech results that were independent of palate defect size, and swallow function test results were similar to other published reconstructive techniques.

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.

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.

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.