Evaluating the Diagnostic Potential of Connected Speech for Benign Laryngeal Disease Using Deep Learning Analysis.

OBJECTIVES: This study aimed to evaluate the performance of artificial intelligence (AI) models using connected speech and vowel sounds in detecting benign laryngeal diseases. STUDY DESIGN: Retrospective. METHODS: Voice samples from 772 patients, including 502 with normal voices and 270 with vocal cord polyps, cysts, or nodules, were analyzed. We employed deep learning architectures, including convolutional neural networks (CNNs) and time series models, to process the speech data. The primary endpoint was the area under the receiver's operating characteristic curve for binary classification. RESULTS: CNN models analyzing speech segments significantly outperformed those using vowel sounds in distinguishing patients with and without benign laryngeal diseases. The best-performing CNN model achieved areas under the receiver operating characteristic curve of 0.895 and 0.845 for speech and vowel sounds, respectively. Correlations between AI-generated disease probabilities and perceptual assessments were more pronounced in the connected-speech analyses. However, the time series models performed worse than the CNNs. CONCLUSION: Connected speech analysis is more effective than traditional vowel sound analysis for the diagnosis of laryngeal voice disorders. This study highlights the potential of AI technologies in enhancing the diagnostic capabilities of speech, advocating further exploration, and validation in this field.

Adjuvant radiotherapy in node-negative salivary malignancies of the parotid gland: A multi-institutional analysis.

BACKGROUND AND PURPOSE: To determine the role of adjuvant radiotherapy (ART) in parotid gland cancer without nodal metastasis, we evaluated the survival outcomes, prognostic factors, and dose-response relationships in patients with node-negative parotid gland cancer patients. MATERIALS AND METHODS: Patients who underwent curative parotidectomy and were pathologically diagnosed with parotid gland cancer without regional or distant metastases between 2004 and 2019 were reviewed. The benefit of ART in terms of locoregional control (LRC) and progression-free survival (PFS) were evaluated. RESULTS: In total, 261 patients were included in the analysis. Of them, 45.2 % received ART. The median follow-up period was 66.8 months. Multivariate analysis revealed that histological grade and ART were independent prognostic factors for LRC and PFS (all p <.05). For patients with high-grade histology, ART was associated with a significant improvement in 5-year LRC (p =.005) and PFS (p =.009). Among patients with high-grade histology who completed RT, higher biologic effective dose (≥77 Gy10) significantly increased PFS (adjusted hazard ratio [HR], 0.10 per 1-Gy increase; 95 % confidence interval [CI], 0.02-0.58; p =.010). ART significantly improved LRC (p =.039) in patients with low-to-intermediate histological grade as well per multivariate analysis, and subgroup analyses revealed patients with T3-4 stage and close/positive resection margins (<1 mm) would benefit from ART. CONCLUSION: ART should be strongly recommended for patients with node-negative parotid gland cancer with high-grade histology in terms of disease control and survival. In patients with low-to-intermediate-grade disease, those with high T stage and incomplete resection margin benefit with ART.

The Expression of Defensin-Associated Genes May Be Correlated With Lymph Node Metastasis of Early-Stage Tongue Cancer.

OBJECTIVES: We aimed to assess the genetic differences between cases of early-stage tongue cancer that were positive or negative for lymph node metastasis. METHODS: In total, 35 cases of tongue cancer with RNA sequencing data were enrolled in this study. The gene expression profile of the following two groups was compared: N0 group (T stage 1 or 2 with N0 stage) and N+ group (T stage 1 or 2 with N+ stage). Using the R and limma packages in the Bioconductor program, we extracted the differentially expressed genes (DEGs). Gene ontology and pathway enrichment analysis were performed using the Database for Annotation, Visualization and Integration Discovery (DAVID) online tool. Immune cell infiltration was analyzed using the CIBERSORT online program. Immunochemical staining of the cancer tissue was evaluated and The Cancer Genome Atlas (TCGA) data were analyzed to validate the identified DEGs. RESULTS: No significant differences were found in the infiltration of 22 types of immune cells. Among a total of 51 identified DEGs, 14 genes were significantly upregulated, while 37 genes were significantly downregulated (P<0.01; fold change >2). Pathway analysis revealed significant associations with the arachidonic acid metabolism-related pathway, calcium signaling, and the muscle contraction pathway. The following DEGs were the most significantly different between the two groups: DEFB4A, SPRR2B, DEFB103B, SPRR2G, DEFB4B, and FAM25A. TCGA data showed that DEFB4A and DEFB103B were more highly expressed in the N0 group than in the N+ group, although the difference did not achieve statistical significance. Immunochemical staining of cancer tissue revealed significantly higher expression of defensin in the N0 group. CONCLUSION: . Defensin (DEFB4A, DEFB103B, DEFB4B) may be a novel biomarker for early regional metastasis in T1/2 tongue cancer.

Cumulative Sum Analysis of the Learning Curve of Free Flap Reconstruction in Head and Neck Cancer Patients.

OBJECTIVES: Owing to the functional and structural complexity of the head and neck area, the reconstruction of defects in these areas is challenging. Free flap surgery has become standard for the reconstruction of the head and neck with improvements in microvascular surgery. The aim of this study was to use the cumulative sum (CUSUM) method to evaluate the learning curve for free-flap head and neck reconstruction performed by a single surgeon. METHODS: We retrospectively reviewed the medical records of 47 patients who underwent free-flap reconstruction from 2017 to 2021. The clinical demographics and surgical outcomes were analyzed. The total operation time was analyzed using the CUSUM method, which is an analytical approach for visualizing patterns in data by converting raw data into an accumulation of deviations from the average value. RESULTS: CUSUM analysis showed two phases of the learning curve: phase 1 (cases 1-22) and phase 2 (cases 23-47). The operative time in phase 1 (579.9±128.2 minutes) was significantly longer than that in phase 2 (418.6±80.9 minutes) (P<0.001). The re-exploration rate was higher in phase 1 (31.8%) than in phase 1 (4%) (P=0.018). The flap failure rate was higher in phase 1 (9.1%) than in phase 1 (4%), but this difference was not statistically significant (P=0.593). CONCLUSION: The learning curve of free-flap head and neck reconstruction seems to stabilize after approximately 20 cases.

Radiotherapy versus Surgery in Early-Stage HPV-Positive Oropharyngeal Cancer.

PURPOSE: This study aimed to compare the outcomes of primary radiotherapy (RT) versus surgery in early-stage human papilloma virus-positive oropharyngeal squamous cell carcinoma (hpv+OPC), and investigate the preoperative clinical factors that can predict the requirement for postoperative adjuvant treatment. MATERIALS AND METHODS: This multicenter study included 166 patients with American Joint Committee on Cancer 8th edition-Stages I-II hpv+OPC. Sixty (36.1%) and 106 (63.9%) patients underwent primary (concurrent chemo)radiotherapy [(CC)RT] and surgery, respectively. Seventy-eight patients (73.6%) in the surgery group received postoperative (CC)RT. RESULTS: With a median follow-up of 45.6 months for survivors, the 2-year overall survival (OS), progression-free survival (PFS), and locoregional control (LC) for RT/surgery were 97.8%/96.4%, 91.1%/92.0%, and 92.9%/93.3%, respectively. In multivariate analyses, patients with synchronous radiologic extranodal extension and conglomeration (ENEcong) of metastatic lymph nodes (LNs) showed significantly poorer OS (p=0.047), PFS (p=0.001), and LC (p=0.003). In patients undergoing primary surgery, two or more clinically positive LN metastases (odds ratio [OR], 5.15; p=0.004) and LN metastases with ENEcong (OR, 3.75; p=0.009) were predictors of postoperative chemoradiotherapy. No patient in the primary RT group demonstrated late severe toxicity whereas three (2.8%), one (0.9%), and one (0.9%) patient in the surgery group showed grade 3 dysphagia, grade 3 xerostomia, and fatal oral cavity bleeding. CONCLUSION: We found no differences in OS, PFS, and LC between upfront RT and surgery in stage I-II hpv+OPC which warrants comparison through a prospective trial in the treatment de-escalation era. However, most early-stage hpv+OPC patients undergoing surgery received adjuvant (CC)RT. Pretreatment LN findings were prognostic and predictive for adjuvant treatment.

Primary versus modified secondary closure techniques for persistent tracheocutaneous fistula in pediatric patients.

PURPOSE: This study aimed at compating two closure techniques for tracheocutaneous fistulas (TCFs) in pediatric patients. METHODS: A total of 106 consecutive pediatric patients who underwent closure of a persistent TCF between April 2007 and February 2021 at a tertiary pediatric hospital were evaluated, and 103 pediatric patients aged between 12 months and 18 years were included. The clinical characteristics, perioperative outcomes, and postoperative outcomes were compared between TCF closure by primary closure (Group 1) and a modified secondary healing technique (Group 2). RESULTS: Of the 103 patients, 58 were classified into Group 1, and 45 into Group 2. The mean age at tracheostomy and TCF closure was significantly younger in Group 2, and the interval between decannulation to TCF closure was significantly shorter in Group 2. Procedural time and hospital stay were significantly shorter in Group 2 than Group 1. Group 2 had a significantly lower complication rate, need for revision surgery, and recannulation rate than Group 1. CONCLUSIONS: Modified secondary healing was more efficient in terms of procedural time and hospital stay, and safer (i.e., fewer complications). It is an effective surgical technique for closing a persistent TCF in younger patients more quickly after decannulation compared to primary closure.

Long-term impact of smoking cessation on new glottic cancer events in patients with early glottic cancer.

Objective: Patients with early glottic cancer sometimes exhibit new glottic cancer events after 5 years. This study aimed to analyse the patterns and risk factors of new glottic cancer events in patients with early glottic cancer 5 years after initial treatment. Methods: In total, 209 patients were included in this study. Age, sex, T stage, anterior commissure involvement, smoking pattern and treatment modality were retrospectively analysed. Results: The median follow-up was 91 (range, 60-266) months. The median time for the occurrence of new glottic cancer events was 97 (range, 61-199) months. New glottic cancer events occurred 5 years after initial treatment in 16 (7.6%) patients, among whom 12 (75.0%) had new glottic cancer event lesions overlapping with initial lesions. Smoking cessation after treatment was significantly correlated with fewer new glottic cancer events after 5 years. Conclusions: New glottic cancer events occurring 5 years after initial treatment in patients with early glottic cancer are not negligible. In particular, if smoking is continued after treatment, these patients can experience new glottic cancer events even after 5 years.

Prediction of Malignancy in Salivary Gland Tumors by a New Cytology Reporting System.

OBJECTIVES: The aim of this study was to analyze the risk of malignancy in salivary gland tumors on the basis of the Milan System for Reporting Salivary Gland Cytopathology. METHODS: A retrospective review was performed of the charts of patients with salivary gland tumors in whom the final diagnosis was confirmed by surgical excision. Preoperative fine needle aspiration results were categorized according to the Milan System for Reporting Salivary Gland Cytopathology: non-diagnostic (category I), nonneoplastic (category II), atypia of undetermined significance (category III), neoplasm (category IV), suspicious for malignancy (category V), and malignant (category VI). Fine needle aspiration and final diagnosis were compared, and the risk of malignancy and operative/oncological outcomes were analyzed. RESULTS: A total of 288 patients were enrolled in this study. Postoperative histopathologic salivary gland malignancies were found in 30 (10.4%) patients. Risk of malignancy was 7.1%, 0%, 48.0%, 4.8%, 88.7%, and 100% in categories I, II, III, IV, V, and VI, respectively. The most common malignant tumor in category III was salivary duct carcinoma (37.5%), followed by acinic cell carcinoma (25.0%), mucoepidermoid carcinoma (25.0%), and squamous cell carcinoma (12.5%). The 5-year survival rate of patients with malignant tumors showed no statistical difference between category III and category V/VI (P = .140). Risk of malignancy was 88.9% and 100% in category V and VI, respectively. CONCLUSIONS: A half of atypia of undetermined significance (category III) cases were malignant. Once diagnosed, the prognosis of malignant tumor in category III was similar with that in category V/VI.

Actin-Associated Gene Expression is Associated with Early Regional Metastasis of Tongue Cancer.

OBJECTIVES: We aimed to analyze gene expression profile of tongue cancer associated with early lymph node metastasis using the cancer genome atlas (TCGA) data. STUDY DESIGN: Basic research. METHODS: A total of 515 patients with matched RNAseq data of primary tumor and clinical data from TCGA data were extracted. To compare gene expression profile between early T-stage tongue cancer with cervical lymph node metastasis and late T-stage tongue cancer without cervical metastasis, genomic data of following two groups was assessed; 1) group 1: T1/2 and N2/3 (n = 41), 2) group 2: T4 and N0 (n = 65). Using R and limma package in bioconductor program, differentially expressed genes (DEGs) were extracted. Gene ontology and pathway enrichment analysis were performed using the DAVID online tool. FFPE tissue of 285 patients were evaluated for the validation of relevant genes by imunofluorescence (IF) and immunohistochemical (IHC) stain. RESULTS: A total of 225 DEGs were found, and 50 genes were highly significant with absolute fold change over eight. Gene ontology and pathway enrichment analysis revealed that most of the upregulated genes were associated with actin cytoskeleton and included following genes: ANKRD23, NO3, PDLIM3, MUSTN1, TNNT3, MYBPC1, MB, MYH3, TTN, ACTA1, and ACTC1. When comparing tongue cancer with cN0pN0 vs. pN0pN+ using the total tongue cancer cohort of TCGA, ACTA1 was the only parameter which was associated with hidden lymph node metastasis in T1/2 (P = .019). Perineural invasion was significantly associated with high expression of ACTA1 (P < .001). IF and IHC analysis revealed that actin was overexpressed, while E-cadherin and N-cadherin were not significantly different. CONCLUSIONS: Actin associated genes, especially overexpression of ACTA1 may be associated with early regional metastasis of tongue cancer. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:813-819, 2021.

Guidelines for the Management of Unilateral Vocal Fold Paralysis From the Korean Society of Laryngology, Phoniatrics and Logopedics.

The Korean Society of Laryngology, Phoniatrics and Logopedics appointed a task force to establish clinical practice guidelines for the management of unilateral vocal fold paralysis (UVFP). These guidelines cover a comprehensive range of management-related factors, including the diagnosis and treatment of UVFP, and provide in-depth information based on current, up-to-date knowledge. Detailed evidence profiles are provided for each recommendation. The CORE databases, including OVID Medline, Embase, the Cochrane Library, and KoreaMed, were searched to identify all relevant papers, using a predefined search strategy. When insufficient evidence existed, expert opinions and Delphi questionnaires were used to fill the evidence gap. The committee developed 16 evidence-based recommendations in six categories: initial evaluation (R1-4), spontaneous recovery (R5), medical treatment (R6), surgical treatment (R7-14), voice therapy (R15), and aspiration prevention (R16). The goal of these guidelines is to assist general otolaryngologists and speech-language pathologists who are primarily responsible for treating patients with UVFP. These guidelines are also intended to facilitate understanding of the condition among other health-care providers, including primary care physicians, nurses, and policy-makers.

Continuous pressure measurement and serial micro-computed tomography analysis during injection laryngoplasty: A preliminary canine cadaveric study.

Injection laryngoplasty (IL) has been used to treat various types of glottal insufficiency. The precise volume and location of the injected materials impact the outcomes. However, exactly how increasing volumes of material are distributed is unknown. In fact, the amount of IL material required to medialize a vocal cord tends to be determined empirically. Thus, the goal of this study was to investigate the pattern of IL material distribution by checking serial micro-computed tomography (MCT) and pressure changes during ILs. This experimental study used 10 excised canine larynges. Experimental devices included the IL syringe, pressure sensor, infusion pump, fixed frame, and monitoring system. We injected calcium hydroxyapatite in the thyroarytenoid muscle; whenever 0.1 mL of material was injected, we obtained an MCT scan while simultaneously measuring the pressure. After the experiments, we performed histologic analyses. MCT analyses showed that materials initially expanded centrifugally and then expanded in all directions within the muscle. The pressure initially increased rapidly but then remained relatively constant until the point at which the materials expanded in multiple directions. Histologic analyses showed that the IL material tended to expand within the epimysium of the thyroarytenoid muscle. However, in some cases, the MCT revealed that there were leakages to the surrounding space with a corresponding pressure drop. If the IL material passes through the epimysium, leakage can occur in the surrounding space, which can account for the reduction in resistance during ILs.

Functional Voice and Swallowing Outcome Analysis After Thyroid Lobectomy: Transoral Endoscopic Vestibular Versus Open Approach.

BACKGROUND: The transoral endoscopic thyroidectomy vestibular approach (TOETVA) is a scarless remote-access thyroidectomy technique. This study compared subjective and objective voice outcomes and swallowing outcomes of patients who underwent thyroid lobectomy using the TOETVA versus conventional open thyroidectomy (OT). METHODS: In addition to questionnaires, acoustic and aerodynamic analyses were performed to compare subjective and objective voice outcomes of the two groups. Swallowing outcome analyses were conducted using Swallowing Impairment Index-6 (SIS-6) scores. Assessments were performed preoperatively and 3 and 6 months after surgery. Propensity score matching was performed to compare the outcomes of the two groups. RESULTS: One hundred and two patients were included in this study (52 TOETVA and 50 OT). Excluding two patients who had vocal cord palsy and open conversion in the TOETVA group, 100 patients completed 3-month postoperative surveys. There were no significant differences between the groups in VAS, GRBAS, or VHI-10 scores at the preoperative and 3- and 6-month assessments. For both groups, there were no significant changes in acoustic or aerodynamic parameters during the 3-6-month postoperative period. The TOETVA group had lower SIS-6 scores at the postoperative 6-month assessment, but the SIS-6 scores after 12 months were similar between groups before and after propensity score matching. CONCLUSIONS: Following TOETVA lobectomy, there were no significant changes in voice outcomes 3 and 6 months after surgery, and the outcomes were comparable with those of OT. The TOETVA group also had swallowing outcomes that were comparable with the OT group.

Prognostic value of the posterior cricoarytenoid muscle atrophy in computerized tomography scans for unilateral vocal fold paralysis recovery.

OBJECTIVES: To evaluate the prognostic value of the posterior cricoarytenoid (PCA) muscle atrophy observed on neck computed tomography (CT) in patients with unilateral vocal fold paralysis. METHODS: CT images of 87 subjects with unilateral vocal fold paralysis (UVFP) were evaluated to analyze the PCA muscle atrophy and to measure the severity of the PCA muscle atrophy in semi-quantitative manner. The grading of the PCA muscle atrophy was compared with the recruitment pattern of laryngeal electromyography (LEMG) and restoration of vocal fold movement. RESULTS: The PCA muscle was identifiable on CT in 73 subjects. Using the PCA muscle atrophy as an indicator of UVFP, we correctly predicted the paralysis in 69 (94.5%). Grade of the PCA muscle atrophy is significantly correlated with recruitment pattern of LEMG. If the positive result is defined as the PCA muscle showed moderate to severe degree of atrophy, we could predict the persistent UVFP in 88% of patients. CONCLUSIONS: PCA muscle atrophy identified on CT scan in patients with UVFP, is associated with low rates of return of mobility in the affected vocal fold.

Natural Course of Unilateral Vocal Fold Paralysis and Optimal Timing of Permanent Treatment.

Importance: Permanent surgical treatment for unilateral vocal fold paralysis (UVFP) should be performed when further neural recovery is improbable. Conservative delay of the surgical procedure may cause unnecessary deterioration of the patient's quality of life. Knowledge of the natural course of UVFP is important for better management and counseling. Objective: To evaluate the natural course of UVFP, focusing on the recovery time according to the injury level to assess the optimal timing for permanent surgical intervention. Design, Setting, and Participants: This retrospective case series enrolled 1264 patients with UVFP who visited the voice clinic of Seoul National University Hospital, Seoul, Korea, from November 1, 2005, through December 31, 2016. Medical records and stroboscopic video images were reviewed to obtain data on demographic characteristics, vocal fold movement, onset and recovery time, follow-up duration, and cause. Cases of UVFP were classified into 5 groups based on the location of injury: distal to the thyroid level, thyroid level, esophagus and mediastinum level, heart and lung level, and proximal to the thorax level. Data analysis was performed from January 23, 2018, to May 21, 2018. Main Outcomes and Measures: Recovery of vocal fold movement defined as more than vocal fold twitching confirmed by stroboscopy video images, estimated injury level, and start time of recovery. The recovery time was analyzed according to age, sex, paralytic side, and 5 injury levels. Results: Of 1264 eligible patients with UVFP (655 [51.8%] male; median age, 56 years [range, 1-90 years]), 208 had evidence of recovery with the recovery time relatively accurate. The maximum recovery time for the group with distal to the thyroid-level injury was 120 days; the group with thyroid-level injury, 157 days; the group with esophagus and mediastinum-level injury, 244 days; the group with heart and lung-level injury, 328 days; and the group with proximal to the thorax-level injury, 333 days with the exception of 1 outlier value (482 days). Recovery time did not differ according to age, sex, or paralytic side. As distance between the vocal fold and injury level increased, the maximum recovery time increased, plateauing at 1 year. Among the patients who showed recovery of the vocal fold movement, most patients with injuries distal to or at the level of the thyroid recovered within 6 months, whereas those with injury more distant from the vocal fold recovered within approximately 1 year. Conclusions and Relevance: A linear association between injury level and maximum recovery time was observed. The findings suggest that the decision to proceed with permanent phonosurgical treatment should be based on the level of injury associated with UVFP.

Lung metastasis in adenoid cystic carcinoma of the head and neck.

BACKGROUND: Distant metastasis of adenoid cystic carcinoma (ACC) is most commonly identified in the lung, but risk factors are still on debate. METHODS: Risk factors for lung metastasis were evaluated by using Cox proportional hazards model and Kaplan-Meier curves. RESULTS: Of 112 patients, 48% had distant metastasis; 94.4% of whom had lung metastasis. Univariable analysis revealed sublingual or minor salivary gland, tumor size ≥2.5 cm, and perineural invasion as risk factors (hazard ratio [HR]: 1.99 [1.02-3.91], 2.57 [1.19-5.58], and 2.46 [1.28-4.74], respectively), whereas size, perineural invasion, and local recurrence were risk factors in multivariable analysis (HR: 2.29 [1.05-4.96], 2.32 [1.09-4.96], and 2.68 [1.24-5.79], respectively). CONCLUSION: Sublingual gland or minor salivary glands ACC has a higher risk of lung metastasis. If the site is not considered, the following factors increased the risk of lung metastasis; (a) size ≥2.5 cm, (b) perineural invasion, and (c) local recurrence.

Safety of office-based percutaneous injection laryngoplasty with calcium hydroxylapatite.

OBJECTIVE: To evaluate the safety of office-based calcium hydroxylapatite (CaHA) injection laryngoplasty via the cricothyroid approach through an analysis of all procedures performed over a period of 10 years at a single institution. METHODS: In total, 962 office-based CaHA injection laryngoplasty via the cricothyroid approach procedures were performed by a single physician at our institution between 2007 and 2016. From these, 955 procedures performed in 617 patients were included in our analysis. The medical records of all 617 patients were retrospectively reviewed. We classified all procedure-related complications according to the time of onset. Complications that occurred during the procedure were considered intraprocedural complications, whereas complications that developed within 1 week after injection and those that developed after 1 week and were recorded more than twice in the medical records were considered acute and delayed complications, respectively. Failed cases were categorized separately as failure. RESULTS: Five cases were failed (0.5%). Intraprocedural complications included superficial injection in eight cases (0.8%). Acute and delayed onset of dyspnea was observed in three (0.3%) and two (0.2%) cases, respectively. The incidence of failures and major complications requiring active intervention was 1.6%. CONCLUSION: Our findings suggest that office-based CaHA injection laryngoplasty via the cricothyroid approach is as safe as conventional transoral injection laryngoplasty. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:2361-2365, 2019.

Long-term oncological and functional outcomes of induction chemotherapy followed by (chemo)radiotherapy vs definitive chemoradiotherapy vs surgery-based therapy in locally advanced stage III/IV hypopharyngeal cancer: Multicenter review of 266 cases.

OBJECTIVE: The aim of this study was to evaluate the treatment outcomes for stage III/IV locally advanced hypopharyngeal squamous cell carcinoma (SCC), comparing induction chemotherapy followed by (chemo)radiotherapy (ICT), definitive chemoradiotherapy (CRT) and surgery-based therapy (SRT). SUBJECTS AND METHODS: Two hundred sixty-six patients with stage III/IV locally advanced hypopharyngeal squamous cell carcinoma (SCC) who underwent ICT (n = 74), CRT (n = 53) or SRT (n = 139) from 1997 through 2014 at the Seoul National University Hospital (n = 127) and the Hallym University Medical Center (n = 139) were enrolled in the study. All surgical procedures in the SRT group were performed by a single surgeon to eliminate surgeon bias. RESULTS: The 5-year disease-free survival (DFS) and overall survival (OS) of all patients (n = 266) were 59.4% and 44%, respectively. The 5-year DFS rates after salvage treatment were 52.7% for ICT, 52.8% for CRT and 65.5% for SRT (p = 0.194). The OS rates were 44.6% for ICT, 39.6% for CRT and 45.3% for SRT group (p = 0.106). The salvage rates were 12.5% for ICT, 15.6% for CRT and 3.8% for SRT group. The final laryngeal preservation rate was significantly lower in the SRT group (44.6%) than in the ICT (71.6%) or CRT (71.7%) groups. All major postoperative complications were significantly higher in the salvage surgery group. CONCLUSION: Treatment outcomes in the ICT and CRT groups were comparable to that of the SRT group for stage III/IV hypopharyngeal SCC. However, the relatively low chance of cure and high risk of complications should be taken into account when considering salvage surgery.

Poor prognostic factors in human papillomavirus-positive head and neck cancer: who might not be candidates for de-escalation treatment?

BACKGROUND/AIMS: Since patients with human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) have favorable outcomes after treatment, treatment de-escalation for these patients is being actively investigated. However, not all HPV-positive HNSCCs are curable, and some patients have a poor prognosis. The purpose of this study was to identify poor prognostic factors in patients with HPV-positive HNSCC. METHODS: Patients who received a diagnosis of HNSCC and tested positive for HPV from 2000 to 2015 at a single hospital site (n = 152) were included in this retrospective analysis. HPV typing was conducted using the HPV DNA chip assay or liquid bead microarray system. Expression of p16 in the tumors was assessed by immunohistochemistry. To determine candidate factors associated with overall survival (OS), univariate and multivariable Cox regression analyses were performed. RESULTS: A total of 152 patients with HPV-positive HNSCC were included in this study; 82.2% were male, 43.4% were current or former smokers, and 84.2% had oropharyngeal cancer. By univariate analysis, old age, performance status ≥ 1, non-oropharyngeal location, advanced T classification (T3-4), and HPV genotype 18 were significantly associated with poor OS. By multivariable analysis, performance status ≥ 1 and non-oropharyngeal location were independently associated with shorter OS (hazard ratio [HR], 4.36, p = 0.015; HR, 11.83, p = 0.002, respectively). Furthermore, HPV genotype 18 positivity was also an independent poor prognostic factor of OS (HR, 10.87, p < 0.001). CONCLUSION: Non-oropharyngeal cancer, poor performance status, and HPV genotype 18 were independent poor prognostic factors in patients with HPV-positive HNSCC. Patients with these risk factors might not be candidates for de-escalation treatment.

Association of FOXP3 Single Nucleotide Polymorphisms With Clinical Outcomes After Allogenic Hematopoietic Stem Cell Transplantation.

BACKGROUND: Forkhead box P3 (FOXP3) is an important marker of regulatory T cells. FOXP3 polymorphisms are associated with autoimmune diseases, cancers, and allograft outcomes. We examined whether single nucleotide polymorphisms (SNPs) at the FOXP3 locus are associated with clinical outcomes after allogenic hematopoietic stem cell transplantation (HSCT). METHODS: Five FOXP3 SNPs (rs5902434, rs3761549, rs3761548, rs2232365, and rs2280883) were analyzed by PCR-sequencing of 172 DNA samples from allogenic HSCT patients. We examined the relationship between each SNP and the occurrence of graft-versus-host disease (GVHD), post-HSCT infection, relapse, and patient survival. RESULTS: Patients with acute GVHD (grades II-IV) showed higher frequencies of the rs3761549 T/T genotype, rs5902434 ATT/ATT genotype, and rs2232365 G/G genotype than did patients without acute GVHD (P=0.017, odds ratio [OR]=5.3; P=0.031, OR=2.4; and P=0.023, OR=2.6, respectively). Multivariate analysis showed that the TT genotype of rs3761549 was an independent risk factor for occurrence of acute GVHD (P=0.032, hazard ratio=5.6). In contrast, the genotype frequencies of rs3761549 T/T, rs5902434 ATT/ATT, and rs2232365 G/G were lower in patients with post-HSCT infection than in patients without infection (P=0.026, P=0.046, and P=0.031, respectively). CONCLUSIONS: rs3761549, rs5902434, and rs2232365 are associated with an increased risk of acute GVHD and decreased risk of post-HSCT infection.

Study design and early result of a phase I study of SABR for early-stage glottic cancer.

OBJECTIVE: Avoidance of organs at risk has become possible with advances in image-guided volumetric-modulated arc therapy (VMAT) techniques. This study was designed to evaluate the safety and feasibility of stereotactic ablative radiotherapy (SABR) for early stage glottic cancer. This report presents the preliminary result of the first and second dose level. METHODS: Fraction size was increased from 3.5 gray (Gy) (total dose 59.5 Gy) to 9 Gy (total dose 45 Gy). Dose-limiting toxicities were defined as grade 3 or higher treatment-related toxicities. Voice outcome was assessed with electroglottography, and quality of life (QoL) was measured with the Head and Neck Cancer Inventory (HNCI). RESULTS: Seven patients received 59.5 Gy at 3.5 Gy per fraction as the first dose level, and five patients received 55 Gy at 5 Gy per fraction as the second dose level. None of the patients developed grade 3+ toxicity throughout a median follow-up of 17.5 months (range, 1.7-30.6 months). One patient in the second dose level recurred in the primary site at 4 months after radiotherapy (RT) and received total laryngectomy. The rest of participants were disease-free at locoregional and distant sites. Jitter, shimmer, mean phonation time, and noise-to-harmony ratio did not change significantly at 6 months after RT. HNCI scores between pretreatment and posttreatment were not significantly different (P = 0.221). CONCLUSION: This study revealed acceptable toxicity, voice outcome, and QoL in patients treated with hypofractionated VMAT of 3.5 Gy and 5 Gy per fraction. This phase I study is currently ongoing with a dose of 55 Gy in 11 fractions and 45 Gy in five fractions. LEVEL OF EVIDENCE: 2b. Laryngoscope, 2560-2565, 2018.