Association between postoperative complications and long-term oncologic outcomes following total laryngectomy: 10-year experience at MD Anderson Cancer Center.

BACKGROUND: Postoperative complications are an independent predictor of poor survival across several tumors. However, there is limited literature on the association between postoperative morbidity and long-term survival following total laryngectomy (TL) for cancer. METHODS: We conducted a retrospective review of all TL patients at a single institution from 2008 to 2013. Demographic and clinical data were collected and analyzed, including postsurgical outcomes, which were classified using the Clavien-Dindo system. Multivariable Cox regression analyses were performed to identify factors associated with overall survival (OS) and disease-free survival (DFS). RESULTS: A total of 362 patients were identified. The mean age was 64 years, and the majority of patients were male (81%). The median follow-up interval was 21 months. Fifty-seven percent of patients had received preoperative radiation, and 40% had received preoperative chemotherapy. Fifty-seven percent of patients underwent salvage TL, and 60% underwent advanced reconstruction (45% free flap and 15% pedicled flap). A total of 136 patients (37.6%) developed postoperative complications, 92 (25.4%) of which were major. Multivariable modeling demonstrated that postoperative complications independently predicted shorter OS (hazard ratio [HR], 1.50; 95% CI, 1.16-1.96; P = .002) and DFS (HR, 1.36; 95% CI, 1.05-1.76; P = .021). Other independent negative predictors of OS and DFS included positive lymph node status, preoperative chemotherapy, comorbidity grade, and delayed adjuvant therapy. Severity of complication and reason for TL (salvage vs primary) were not shown to be predictive of OS or DFS. CONCLUSION: Postoperative complications are associated with worse long-term OS and DFS relative to uncomplicated cases. Patient optimization and timely management of postoperative complications may play a critical role in long-term survival.

Outcomes after radiation therapy for T2N0/stage II glottic squamous cell carcinoma.

BACKGROUND: We report outcomes for patients with T2N0M0 glottic squamous cell carcinoma (SCC) treated with radiation therapy (RT). METHODS: Patients who received definitive RT for T2 glottic SCC from 2000 through 2013 were retrospectively reviewed. RESULTS: One hundred and thirteen patients were analyzed (median follow-up time 91 months; 85 patients received three-dimensional conformal radiotherapy [3D-CRT] and 28 received intensity-modulated radiation therapy [IMRT]). Fractionation was conventional (58%) or altered (42%); 20 patients (18%) received concurrent chemotherapy. Five-year local control was 83% for the 3D-CRT vs 81% for the IMRT group (P = .76). The ultimate locoregional control at 5 years was 100% for IMRT vs 91% for 3D-CRT (P = .1). The 5-year overall survival (OS) was 78% for 3D-CRT vs 81% for IMRT (P = .83). On multivariate analysis, younger age was the only independent predictor of improved OS (P = .0002). CONCLUSIONS: Oncologic and survival outcomes were excellent for patients with T2N0 glottic cancer. Patients treated with IMRT and 3D-CRT had no statistically significant differences in all investigated endpoints.

Prospective longitudinal patient-reported outcomes of swallowing following intensity modulated proton therapy for oropharyngeal cancer.

BACKGROUND AND PURPOSE: With an enlarging population of long-term oropharyngeal cancer survivors, dysphagia is an increasingly important toxicity following oropharynx cancer treatment. While lower doses to normal surrounding structures may be achieved with intensity modulated proton therapy (IMPT) compared to photon-based radiation, the clinical benefit is uncertain. METHODS AND MATERIALS: Seventy-one patients with stage III/IV oropharyngeal cancer (AJCC 7th edition) undergoing definitive IMPT on a longitudinal prospective cohort study who had completed the MD Anderson Dysphagia Inventory (MDADI) at pre-specified time points were included. RESULTS: The majority of patients had HPV-positive tumors (85.9%) and received bilateral neck radiation (81.4%) with concurrent systemic therapy (61.8%). Mean composite MDADI scores decreased from 88.2 at baseline to 59.6 at treatment week 6, and then increased to 74.4 by follow up week 10, 77.0 by 6 months follow up, 80.5 by 12 months follow up, and 80.1 by 24 months follow up. At baseline, only 5.6% of patients recording a poor composite score (lower than 60), compared to 61.2% at treatment week 6, 19.1% at follow up week 10, 13.0% at 6 months follow up, 13.5% at 1 year follow up, and 11.1% at 2 years follow up. CONCLUSIONS: Patient reported outcomes following IMPT for oropharyngeal cancer demonstrates decreased swallowing function at completion of treatment with relatively rapid recovery by 10 weeks follow up and steady improvement through 2 years. The results are comparable to similar longitudinal studies of photon-based radiotherapy for oropharynx cancer, and suggest that IMPT confers no additional excess toxicity related to swallowing.

Neurologic sequelae following radiation with and without chemotherapy for oropharyngeal cancer: Patient reported outcomes study.

BACKGROUND: There is little data describing neurocognitive late sequelae in patients treated for oropharyngeal cancer. METHODS: Using PROs, scores for "numbness/tingling" and "difficulty remembering" were assessed. Wilcoxon testing was utilized to compare mean assessment scores (1-10) between treatment subgroups. RESULTS: Four-hundred ninety-seven patients were evaluated and 267 (54%) received chemotherapy. The mean score for numbness/tingling for patients receiving radiation alone was 0.99 and for each chemotherapy subgroup were: Induction chemotherapy (IC), 1.35 (n = 99); concurrent chemotherapy (CCRT), 1.04 (n = 111) and IC + CCRT, 2.48 (n = 57); 30% of patients who received IC + CCRT had scores ≥5. The mean scores for difficulty remembering were XRT: 1.44, chemotherapy: 1.45, and IC + CCRT subgroup: 2.42. CONCLUSIONS: The symptom burden related to peripheral neuropathy and cognitive complaints was minimal. A minority of patients reported high burdens. Particularly, 30% of patients receiving IC + CCRT described moderate to severe numbness/tingling.

Pembrolizumab-induced mucositis in a patient with recurrent hypopharynx squamous cell cancer.

Pembrolizumab, an anti-PD-1 checkpoint inhibitor, is used in patients with recurrent or metastatic squamous cell carcinoma of the head and neck who have received prior therapy with a platinum-based regimen. As a monotherapy, it is generally well tolerated, but a small percentage of patients may develop immune-mediated inflammatory reactions. We report a case of mucositis and laryngeal edema in a patient on pembrolizumab and review the literature. Laryngoscope, 130:E140-E143, 2020.

Outcomes of carotid-sparing IMRT for T1 glottic cancer: Comparison with conventional radiation.

OBJECTIVES: We aim to report oncologic outcomes after conventional radiotherapy (ConRT) using opposed lateral beams and intensity-modulated radiation therapy (IMRT) for tumor (T)1 nodal (N)0 T1 N0 glottic squamous cell carcinoma. STUDY DESIGN: Retrospective case-control study. METHODS: We retrospectively reviewed demographic, disease, and treatment characteristics for patients treated at our institution during 2000 to 2013. RESULTS: One hundred fifty-three patients (71%) were treated using ConRT and 62 (29%) using IMRT. The median follow-up for all patients was 68 months. There was no statistically significant difference in 5-year local control between patients with T1a versus T1b disease (94% vs. 89%, respectively, P = 0.5). Three-year locoregional control for patients treated with ConRT was 94% compared to 97% with IMRT (P = 0.4). Three-year overall survival (OS) for patients treated with ConRT was 92.5% compared with 100% with IMRT (P = 0.1). Twelve of 14 patients with local recurrence underwent salvage surgery with 5-year ultimate locoregional control of 98.5% and 97.1% in the ConRT and IMRT cohorts, respectively (P = 0.7). Multivariate analysis showed age < 60 years (P < 0.0001) and pretreatment Eastern Cooperative Oncology Group performance status <2 (P = 0.0022) to be independent correlates of improved OS. Postradiation cerebrovascular events were in four patients in the ConRT cohort (3%), whereas no patients in the IMRT cohort suffered any events. CONCLUSION: Because the oncologic outcomes for patients treated with IMRT were excellent and IMRT allows for carotid sparing, we have transitioned to IMRT as our standard for most patients with T1 glottic cancer. LEVEL OF EVIDENCE: 3b Laryngoscope, 130:146-153, 2020.

Dysphagia After Primary Transoral Robotic Surgery With Neck Dissection vs Nonsurgical Therapy in Patients With Low- to Intermediate-Risk Oropharyngeal Cancer.

IMPORTANCE: A major goal of primary transoral robotic surgery (TORS) for oropharyngeal cancer is to optimize swallowing outcomes by personalized treatment based on pathologic staging. However, swallowing outcomes after TORS are uncertain, as are the outcomes compared with nonsurgical options. OBJECTIVES: To estimate rates of acute dysphagia and recovery after TORS and to compare swallowing outcomes by primary treatment modality (TORS or radiotherapy). DESIGN, SETTING, AND PARTICIPANTS: This case series study was a secondary analysis of prospective registry data from 257 patients enrolled from March 1, 2015, to February 28, 2018, at a single academic institution who, according to the AJCC Staging Manual, 7th edition TNM classification, had low- to intermediate-risk human papillomavirus-related oropharyngeal squamous cell carcinoma possibly resectable by TORS. EXPOSURE: Patients were stratified by primary treatment (75 underwent TORS and 182 received radiotherapy). MAIN OUTCOMES AND MEASURES: Modified barium swallow (MBS) studies graded per Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) and the MD Anderson Symptom Inventory-Head and Neck Module (MDASI-HN) questionnaires were administered at standard intervals. Prevalence and severity of dysphagia were estimated per DIGEST before and after TORS and 3 to 6 months after treatment. Moderate-severe dysphagia (DIGEST grade ≥2) was assessed using logistic regression and compared by primary treatment group. The MDASI swallowing symptom severity item scores during and after radiotherapy were compared using generalized estimating equations by treatment status at the start of radiotherapy, after induction, and after TORS. RESULTS: A total of 257 patients (mean [SD] age, 59.54 [9.07] years; 222 [86.4%] male) were included in the study. Dysphagia severity (per DIGEST) was significantly worse after TORS (r = -0.63; 95% CI, -0.78 to -0.44): 17 patients (22.7%; 95% CI, 13.8%-33.8%) had moderate-severe (DIGEST grade ≥2) acute post-TORS dysphagia significantly associated with primary tumor volume (odds ratio, 1.43; 95% CI, 1.11-1.84). DIGEST improved by 3 to 6 months but remained worse than that at baseline; at 3 to 6 months, the number of patients with DIGEST grade 2 or higher dysphagia was 5 (6.7%; 95% CI, 2.2%-14.9%) after primary TORS and 29 (15.9%; 95% CI, 10.9%-22.1%) after radiotherapy. At the start of radiotherapy, MDASI swallowing symptom severity item scores were significantly worse in the post-TORS group compared with postinduction (mean [SD] change, 2.6 [1.1]) and treatment-naive (mean [SD] change, 1.7 [0.3]) patients. This result inverted at radiotherapy end, and all groups converged at 3 to 6 months. CONCLUSIONS AND RELEVANCE: Subacute swallowing outcomes were similar regardless of primary treatment modality among patients with low- to intermediate-risk oropharyngeal squamous cell carcinoma.

Swallowing-related outcomes associated with late lower cranial neuropathy in long-term oropharyngeal cancer survivors: cross-sectional survey analysis.

BACKGROUND: The purpose of this study was to quantify the association of late lower cranial neuropathy (late LCNP) with swallowing-related quality of life (QOL) and functional status among long-term oropharyngeal cancer (OPC) survivors. METHODS: Eight hundred eighty-nine OPC survivors (median survival time: 7 years) who received primary treatment at a single institution between January 2000 and December 2013 completed a cross-sectional survey (56% response rate) that included the MD Anderson Dysphagia Inventory (MDADI) and self-report of functional status. Late LCNP events ≥3 months after cancer therapy were abstracted from medical records. Multivariate models regressed MDADI scores on late LCNP status adjusting for clinical covariates. RESULTS: Overall, 4.0% (n = 36) of respondents developed late LCNP with median time to onset of 5.25 years post-treatment. LCNP cases reported significantly worse mean composite MDADI (LCNP: 68.0 vs no LCNP: 80.2; P < .001). Late LCNP independently associated with worse mean composite MDADI (ß = -6.7, P = .02; 95% confidence interval [CI], -12.0 to -1.3) as well as all MDADI domains after multivariate adjustment. LCNP cases were more likely to have a feeding tube at time of survey (odds ratio [OR] = 20.5; 95% CI, 8.6-48.9), history of aspiration pneumonia (OR = 23.5; 95% CI, 9.6-57.6), and tracheostomy (OR = 26.9; 95% CI, 6.0-121.7). CONCLUSIONS: In this large survey study, OPC survivors with late LCNP reported significantly poorer swallowing-related QOL and had significantly higher likelihood of poor functional status. Further efforts are necessary to optimize swallowing outcomes to improve QOL in this subgroup of survivors.

Patient-reported outcomes of symptom burden in patients receiving surgical or nonsurgical treatment for low-intermediate risk oropharyngeal squamous cell carcinoma: A comparative analysis of a prospective registry.

PURPOSE: To explore treatment-related changes in symptom burden and quality of life (QOL) in oropharyngeal squamous cell cancer (OPSCC) patients treated surgically and non-surgically. PATIENTS AND METHODS: Eighty-six patients with human papillomavirus-associated OPSCC treated at the Head and Neck Center at The University of Texas MD Anderson Cancer Center were recruited to a prospective registry study between 2014 and 2016 and completed the core, head and neck-specific, and symptom interference sections of the MD Anderson symptom inventory (MDASI) multi-symptom questionnaire and the EQ-5D health status assessment as a measure of QOL at four time points. RESULTS: Longitudinal improvements from post-treatment nadir were observed across all groups. For patients treated with single modality, symptom interference, but not core and head and neck specific, MDASI scores were significantly better at 6 months in patients treated with surgery than radiation (P = 0.04). For patients treated with multiple modalities, scores for each of the three domains (i.e., core, head and neck -specific, and interference MDASI) were significantly better in the surgical group than the nonsurgical group at treatment completion (P = 0.0003, P = 0.0006 and P = 0.02) and 6 weeks (P = 0.001, P = 0.05 and P = 0.04), but not 6 months (P = 0.11, P = 0.16 and P = 0.040). No significant differences in EQ5D health status were observed between groups at any time point, reflecting similar overall QOL in all groups. CONCLUSION: Symptom burden and QOL improves after treatment in OPSCC survivors over time regardless of whether primary surgical or nonsurgical treatment is used, although acute symptom profiles may differ.

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.

Two-year prevalence of dysphagia and related outcomes in head and neck cancer survivors: An updated SEER-Medicare analysis.

BACKGROUND: The aim of the study was to examine prevalence of dysphagia at the population level in head and neck cancer (HNC) survivors. METHODS: Surveillance, Epidemiology, and End Results-Medicare claims among 16 194 patients with HNC (2002-2011) were analyzed to estimate 2-year prevalence of dysphagia, stricture, and aspiration pneumonia, and derive treatment- and site-specific estimates. RESULTS: Prevalence of dysphagia, stricture, pneumonia, and aspiration pneumonia was 45.3% (95% confidence interval [CI]: 44.5-46.1), 10.2% (95% CI: 9.7-10.7), 26.3% (95% CI: 25.6-26.9), and 8.6% (95% CI: 8.2-9.1), respectively. Dysphagia increased by 11.7% over the 10-year period (P < .001). Prevalence was highest after chemoradiation and multimodality therapy. CONCLUSION: Comparing to published rates using similar methodology the preceding decade (1992-1999), prevalence of dysphagia based on claims data was similar in 2002-2011 in this study. These results suggest persistence of dysphagia as a highly prevalent morbidity, even in the decade in which highly conformal radiotherapy and minimally invasive surgeries were popularized.

Symptom Burden Associated With Late Lower Cranial Neuropathy in Long-term Oropharyngeal Cancer Survivors.

Importance: Lower cranial neuropathy (LCNP) is a rare but potentially disabling result of radiotherapy and other head and neck cancer therapies. Survivors who develop late LCNP may experience profound functional impairment, with deficits in swallowing, speech, and voice. Objective: To investigate the association of late LCNP with severity of cancer treatment-related symptoms and subsequent general functional impairment among oropharyngeal cancer (OPC) survivors. Design, Setting, and Participants: This cross-sectional survey study analyzed 889 OPC survivors nested within a retrospective cohort of OPC survivors treated at MD Anderson Cancer Center from January 1, 2000, to December 31, 2013. Eligible survey participants were disease free and completed OPC treatment 1 year or more before the survey. Data analysis was performed from October 10, 2017, to March 15, 2018. Exposures: Late LCNP defined by onset 3 months or more after cancer therapy. Main Outcomes and Measures: The primary outcome variable was the mean of the top 5 most severely scored symptoms of all 22 core and head and neck cancer-specific symptoms from the MD Anderson Symptom Inventory Head and Neck Cancer Module (MDASI-HN). Secondary outcomes included mean MDASI-HN interference scores and single-item scores of the most severe symptoms. Multivariate models regressed MDASI-HN scores on late LCNP status, adjusting for clinical covariates. Results: Overall, 36 of 889 OPC survivors (4.0%) (753 [84.7%] male; 821 [92.4%] white; median [range] age, 56 [32-84] years; median [range] survival time, 7 [1-16] years) developed late LCNP. Late LCNP was significantly associated with worse mean top 5 MDASI-HN symptom scores (coefficient, 1.54; 95% CI, 0.82-2.26), adjusting for age, survival time, sex, therapeutic modality, T stage, subsite, type of radiotherapy, smoking, and normal diet before treatment. Late LCNP was also significantly associated with single-item scores for difficulty swallowing or chewing (coefficient, 2.25; 95% CI, 1.33-3.18), mucus (coefficient, 1.97; 95% CI, 1.03-2.91), fatigue (coefficient, 1.35; 95% CI, 0.40-2.21), choking (coefficient, 1.53; 95% CI, 0.65-2.41), and voice or speech symptoms (coefficient, 2.30; 95% CI, 1.60-3.03) in multivariable models. Late LCNP was not significantly associated with mean interference scores after correction for multiple comparisons (mean interference coefficient, 0.72; 95% CI, 0.09-1.35). Conclusions and Relevance: In this large survey study, OPC survivors with late LCNP reported worse cancer treatment-related symptoms, a finding suggesting an association between late LCNP and symptom burden. This research may inform the development and implementation of strategies for LCNP surveillance and management.

Decreased gastrostomy tube incidence and weight loss after transoral robotic surgery for low- to intermediate-risk oropharyngeal squamous cell carcinoma.

BACKGROUND: Functional outcomes after treatment for oropharyngeal squamous cell carcinoma (SCC) are increasingly prioritized. The purpose of this study was to investigate the incidence of gastrostomy tube placement and weight loss in patients with oropharyngeal SCC who may be eligible for either transoral robotic surgery (TORS) or nonsurgical management. METHODS: We conducted a retrospective review of previously untreated T1 to T2 and N0 to N2b oropharyngeal SCC to determine the rates of gastrostomy tube placement and weight loss according to Common Terminology Criteria for Adverse Events (CTCAE) criteria. Multivariate regression models were fit to compare these end points between groups. RESULTS: Two hundred twenty-three patients were included, comprised of 66 patients who underwent TORS and 157 patients who underwent (chemo)radiation. Thirty-two (48.5%) of the TORS patients received adjuvant radiation. On multivariate analysis, patients treated nonsurgically were 10.6 times and 8.1 times more likely to receive a gastrostomy tube and experience greater than CTCAE grade 1 weight loss, respectively. CONCLUSION: In selected patients with oropharyngeal SCC, TORS may help avoid critical weight loss and gastrostomy tube placement in the acute treatment period.

Radiotherapy dose-volume parameters predict videofluoroscopy-detected dysphagia per DIGEST after IMRT for oropharyngeal cancer: Results of a prospective registry.

PURPOSE: Our primary aim was to prospectively validate retrospective dose-response models of chronic radiation-associated dysphagia (RAD) after intensity modulated radiotherapy (IMRT) for oropharyngeal cancer (OPC). The secondary aim was to validate a grade ≥2 cut-point of the published videofluoroscopic dysphagia severity (Dynamic Imaging Grade for Swallowing Toxicity, DIGEST) as radiation dose-dependent. MATERIAL AND METHODS: Ninety-seven patients enrolled on an IRB-approved prospective registry protocol with stage I-IV OPC underwent pre- and 3-6 month post-RT videofluoroscopy. Dose-volume histograms (DVH) for swallowing regions of interest (ROI) were calculated. Dysphagia severity was graded per DIGEST criteria (dichotomized with grade ≥2 as moderate/severe RAD). Recursive partitioning analysis (RPA) and Bayesian Information Criteria (BIC) were used to identify dose-volume effects associated with moderate/severe RAD. RESULTS: 31% developed moderate/severe RAD (i.e. DIGEST grade ≥2) at 3-6 months after RT. RPA found DVH-derived dosimetric parameters of geniohyoid/mylohyoid (GHM), superior pharyngeal constrictor (SPC), and supraglottic region were associated with DIGEST grade ≥2 RAD. V61 ≥ 18.57% of GHM demonstrated optimal model performance for prediction of DIGEST grade ≥2. CONCLUSION: The findings from this prospective longitudinal registry validate prior observations that dose to submental musculature predicts for increased burden of dysphagia after oropharyngeal IMRT. Findings also support dichotomization of DIGEST grade ≥2 as a dose-dependent split for use as an endpoint in trials or predictive dose-response analysis of videofluoroscopy results.

Three-dimensional imaging assessment of anatomic invasion and volumetric considerations for chemo/radiotherapy-based laryngeal preservation in T3 larynx cancer.

OBJECTIVES: To investigate the impact of 3-Diminsional (3D) tumor volume (TV) and extent of involvement of primary tumor on treatment outcomes in a large uniform cohort of T3 laryngeal carcinoma patients treated with nonsurgical laryngeal preservation strategies. MATERIALS AND METHODS: The pretreatment contrast-enhanced computed tomography images of 90 patients with T3 laryngeal carcinoma were reviewed. Primary gross tumor volume (GTVp) was delineated to calculate the 3D TV and define the extent of invasion. Cartilage and soft tissue involvement was coded. The extent of invasion was dichotomized into non/limited invasion versus multiple invasion extension (MIE), and was subsequently correlated with survival outcomes. RESULTS: The median TV was 6.6 cm3. Sixty-five patients had non/limited invasion, and 25 had MIE. Median follow-up for surviving patients was 52 months. The 5-year local control and overall survival rates for the whole cohort were 88% and 68%, respectively. There was no correlation between TV and survival outcomes. However, patients with non/limited invasion had better 5-year local control (LC) than those with MIE (95% vs 72%, p = .009) but did not have a significantly higher rate of overall survival (OS) (74% vs 67%, p = .327). In multivariate correlates of LC, MIE maintained statistical significance whereas baseline airway status showed a statistically significance trend with poor LC (p = .0087 and 0.06, respectively). Baseline good performance status was an independent predictor of improved OS (p = .03) in multivariate analysis. CONCLUSION: The extent of primary tumor invasion is an independent prognostic factor of LC of the disease after definitive radiotherapy in T3 larynx cancer.

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.

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.

Use of Larynx-Preservation Strategies in the Treatment of Laryngeal Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update.

Purpose To update the guideline recommendations on the use of larynx-preservation strategies in the treatment of laryngeal cancer. Methods An Expert Panel updated the systematic review of the literature for the period from January 2005 to May 2017. Results The panel confirmed that the use of a larynx-preservation approach for appropriately selected patients does not compromise survival. No larynx-preservation approach offered a survival advantage compared with total laryngectomy and adjuvant therapy as indicated. Changes were supported for the use of endoscopic surgical resection in patients with limited disease (T1, T2) and for initial total laryngectomy in patients with T4a disease or with severe pretreatment laryngeal dysfunction. New recommendations for positron emission tomography imaging for the evaluation of regional nodes after treatment and best measures for evaluating voice and swallowing function were added. Recommendations Patients with T1, T2 laryngeal cancer should be treated initially with intent to preserve the larynx by using endoscopic resection or radiation therapy, with either leading to similar outcomes. For patients with locally advanced (T3, T4) disease, organ-preservation surgery, combined chemotherapy and radiation, or radiation alone offer the potential for larynx preservation without compromising overall survival. For selected patients with extensive T3 or large T4a lesions and/or poor pretreatment laryngeal function, better survival rates and quality of life may be achieved with total laryngectomy. Patients with clinically involved regional cervical nodes (N+) who have a complete clinical and radiologic imaging response after chemoradiation do not require elective neck dissection. All patients should undergo a pretreatment baseline assessment of voice and swallowing function and receive counseling with regard to the potential impact of treatment options on voice, swallowing, and quality of life. Additional information is available at www.asco.org/head-neck-cancer-guidelines and www.asco.org/guidelineswiki .

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.