Office-Based Structural Autologous Fat Injection Laryngoplasty for Unilateral Vocal Fold Paralysis.

Unilateral vocal fold paralysis (UVFP) is a common cause of incomplete glottic closure, leading to significant somatic and social disabilities. Office-based autologous fat injection laryngoplasty (AFIL) has been proposed as an effective treatment for glottic insufficiency but has not been well-studied for UVFP. We enrolled 23 patients who underwent office-based structural AFIL due to unilateral vocal paralysis at our institution between February 2021 and January 2022. In the procedure, autologous fat was harvested and injected into the vocal fold under the guidance of flexible digital endoscopy for structural fat grafting. The voice handicap index-10 (VHI-10) score and perceptual voice measurements were collected before the operation, 2 weeks postoperatively, and 3 months postoperatively. Twenty-two patients were followed-up for at least 3 months. The VHI-10 score improved significantly from 29.65 ± 8.52 preoperatively to 11.74 ± 7.42 at 2 weeks (p < 0.0001) and 5.36 ± 6.67 at 3 months (p < 0.0001). Significant improvements in grades of dysphonia (p < 0.0001), breathiness (p < 0.0001), and asthenia (p = 0.004) were also noted at 3 months postoperatively when perceptual measurements were investigated. Office-based structural AFIL is an effective treatment for improving voice-related disability for UVFP patients.

Deep Learning Application for Vocal Fold Disease Prediction Through Voice Recognition: Preliminary Development Study.

BACKGROUND: Dysphonia influences the quality of life by interfering with communication. However, a laryngoscopic examination is expensive and not readily accessible in primary care units. Experienced laryngologists are required to achieve an accurate diagnosis. OBJECTIVE: This study sought to detect various vocal fold diseases through pathological voice recognition using artificial intelligence. METHODS: We collected 189 normal voice samples and 552 samples of individuals with voice disorders, including vocal atrophy (n=224), unilateral vocal paralysis (n=50), organic vocal fold lesions (n=248), and adductor spasmodic dysphonia (n=30). The 741 samples were divided into 2 sets: 593 samples as the training set and 148 samples as the testing set. A convolutional neural network approach was applied to train the model, and findings were compared with those of human specialists. RESULTS: The convolutional neural network model achieved a sensitivity of 0.66, a specificity of 0.91, and an overall accuracy of 66.9% for distinguishing normal voice, vocal atrophy, unilateral vocal paralysis, organic vocal fold lesions, and adductor spasmodic dysphonia. Compared with the accuracy of human specialists, the overall accuracy rates were 60.1% and 56.1% for the 2 laryngologists and 51.4% and 43.2% for the 2 general ear, nose, and throat doctors. CONCLUSIONS: Voice alone could be used for common vocal fold disease recognition through a deep learning approach after training with our Mandarin pathological voice database. This approach involving artificial intelligence could be clinically useful for screening general vocal fold disease using the voice. The approach includes a quick survey and a general health examination. It can be applied during telemedicine in areas with primary care units lacking laryngoscopic abilities. It could support physicians when prescreening cases by allowing for invasive examinations to be performed only for cases involving problems with automatic recognition or listening and for professional analyses of other clinical examination results that reveal doubts about the presence of pathologies.

Author Correction: Bmi1 is essential in Twist1-induced epithelial-mesenchymal transition.

In the version of Supplementary Fig. 3c originally published with this Article, the authors mistakenly duplicated a blot from Supplementary Fig. 3b. The correct versions of these figures are shown below. In addition, two independent repeats of the experiments presented in Supplementary Figs. 3b and 3c, showing results consistent with those originally reported, have been deposited in Figshare ( 10.6084/m9.figshare.7545263 ).

Office-Based Autologous Fat Injection Laryngoplasty for Glottic Insufficiency in Patients Under 50 Years Old.

OBJECTIVE: We sought to determine the outcomes of office-based autologous fat injection laryngoplasty in the treatment of patients under 50 years old with glottic insufficiency but without neurological problems or acquired organic lesions in the vocal fold. METHODS: We conducted a retrospective chart review of consecutive patients under 50 years of age who underwent office-based autologous fat injection laryngoplasty for glottic insufficiency. None of the patients presented neurological problems or acquired organic lesions in the vocal fold. Videolaryngostroboscopic data, objective voice assessment, perceptual measurements of vocal quality, and subjective ratings of voice quality were evaluated before and after treatment. RESULTS: The 23 patients (7 men and 16 women) in this study presented significant improvements in phonatory function in terms of maximum phonation time, jitter, grade, asthenia, and Voice Handicap Index-10 (VHI-10) values at 3 months. Significant improvements in terms of jitter, noise-to-harmonic ratio, grade, roughness, breathiness, asthenia, and the VHI-10 values were also observed at 6 months. CONCLUSIONS: Glottic insufficiency in younger patients without neurological problems or acquired organic lesions in the vocal fold can be treated effectively using office-based autologous fat injection laryngoplasty. Significant improvements in phonatory function were observed even 6 months after surgery.

Feasibility and Associated Limitations of Office-Based Laryngeal Surgery Using Carbon Dioxide Lasers.

Importance: There are few reports evaluating awake, office-based carbon dioxide (CO2) laser surgery for laryngeal lesions. To date, this study was the largest reported case series of office-based laryngeal surgery by fiber delivery CO2 laser. Office-based laryngeal surgical procedures have become increasingly popular. Technical problems and treatment outcomes associated with the use of a CO2 laser for office-based laryngeal surgery have yet to be fully addressed. Objectives: To discuss a single institution's clinical experience with office-based CO2 laser laryngeal surgery and the feasibility and limitations associated with this procedure. Design, Setting, and Participants: This retrospective study evaluated 49 laryngeal surgical procedures performed using a CO2 laser in 40 consecutive adult patients at a single institution in Taiwan from July 1, 2014, through September 30, 2015. Laryngeal lesions treated included vocal fold leukoplakia (n = 13), benign vocal fold lesions (n = 10), Reinke edema (n = 4), recurrent respiratory papillomatosis (n = 6), and lesions outside the vocal folds (n = 7). Interventions: Office-based laryngeal surgery performed using a CO2 laser under topical anesthesia. Main Outcomes and Measures: Videolaryngoscopy was performed on all patients at each follow-up point. Among patients with benign vocal lesions and Reinke edema, videolaryngostroboscopy, voice laboratory measurements, perceptual measurements of vocal quality, and subjective evaluations were conducted before and after surgery. Results: Among the 40 patients included in this study (28 men [70%] and 12 women [30%]; median [range] age, 56 [29-83] years), median follow-up time was 6.5 months (range, 1-21 months). Among the 49 procedures, 2 (4%) could not be tolerated by patients owing to severe gag reflex and laryngeal hypersensitivity, 6 (12%) could not completely evaporate lesions owing to an inadequate surgical field or laryngeal instability, and 1 (2%) led to a complication (ie, mild vocal fold wound stiffness). In addition, 2 patients with premalignant vocal fold leukoplakia showed lesion recurrence in the subglottic area. Among patients with benign vocal lesions and Reinke edema, postoperative phonatory function showed large improvements in jitter (effect size, 0.61; median difference, -0.98%; 95% CI, -1.57% to -0.11%), noise to harmonic ratio (effect size, 0.63; median difference, -0.02; 95% CI, -0.07 to -0.01), maximal phonation time (effect size, 0.61; median difference, 3.6 seconds; 95% CI, 1.9 to 8.8 seconds), and Voice Handicap Index-10 score (effect size, 0.60; median difference, -7; 95% CI, -12 to -2). Conclusions and Relevance: Office-based laryngeal surgery performed using a CO2 laser was shown to be a feasible treatment option for various types of vocal lesions. However, patients should not undergo this procedure if they have multiple bulky lesions or lesions involving the subglottic area, the laryngeal ventricle, or (in cases of inadequate laryngeal stability) the free edge of a vocal fold.

Office-based Autologous Fat Injection Laryngoplasty for Vocal Process Granuloma.

OBJECTIVE: To present the outcomes of office-based autologous fat injection laryngoplasty for the treatment of vocal process granuloma in conjunction with glottic insufficiency. STUDY DESIGN: Retrospective chart review. METHODS: This study included nine patients with vocal process granuloma in conjunction with glottic insufficiency who received autologous fat injection laryngoplasty. Videolaryngostroboscopic data, objective voice assessment, perceptual measurements of vocal quality, and subjective ratings of voice quality were examined before and after treatment. RESULTS: Of the nine patients, seven (78%) exhibited complete remission. The other two patients (22%) exhibited a partial response following the injection. In a subgroup of five patients who were refractory to antireflux and voice therapies, the resolution rate was 60%. Phonatory function presented significant improvements in jitter, noise-to-harmonic ratio, maximal phonation time, and asthenia. Videolaryngostroboscopic rating revealed significant improvements in closure phase ratio in the vibratory cycle. CONCLUSIONS: Autologous fat injection laryngoplasty can ameliorate glottic insufficiency and the resulting hyperfunctional behavior of the larynx. This therapy also encourages remission of vocal process granuloma and may represent an alternative treatment strategy.

NM23-H1 expression of head and neck squamous cell carcinoma in association with the response to cisplatin treatment.

We recently reported that low NM23-H1 expression of head and neck squamous cell carcinoma (HNSCC) correlated with poor patients' prognosis. Growing evidence has indicated that high tumor NM23-H1 expression contributes to a good response to chemotherapy. Therefore, we investigated the role of NM23-H1 in susceptibility of HNSCC cells to cisplatin and its clinical significance, as well as the in vitro study for validation was performed. Using immunohistochemistry, we analyzed NM23-H1 expression in surgical specimens from 46 HNSCC patients with cervical metastases receiving surgery and adjuvant chemoradiotherapy. Low tumor NM23-H1 expression correlated with locoregional recurrence of HNSCC following postoperative cisplatin-based therapy (p = 0.056) and poor patient prognosis (p = 0.001). To validate the clinical observation and the effect of NM23-H1 on cisplatin cytotoxicity, we established several stable clones derived from a human HNSCC cell line (SAS) by knockdown and overexpression. Knockdown of NM23-H1 attenuated the chemosensitivity of SAS cells to cisplatin, which was associated with reduced cisplatin-induced S-phase accumulation and downregulation of cyclin E1 and A. Overexpression of NM23-H1 reversed these results, indicating the essential role of NM23-H1 in treatment response to cisplatin. NM23-H1 may participate in HNSCC cell responses to cisplatin and be considered a potential therapeutic target.

Treatment selection for tonsillar squamous cell carcinoma.

BACKGROUND: The optimal treatment for tonsillar squamous cell carcinoma (SCC) remains controversial. The purpose of this study was to evaluate long-term treatment outcomes of patients with tonsillar SCC, in order to aid in appropriate treatment selection. METHODS: We conducted a retrospective chart review of 105 patients with curatively treated tonsillar SCC between January 1996 and December 2005. Forty-three patients (41.0%) underwent primary surgery with or without adjuvant therapy (primary surgery group), and 62 patients (59.0%) were treated with radiotherapy/chemoradiotherapy (RT/CRT, organ preservation group). Twenty patients (19%) received tumor tonsillectomy before definitive RT/CRT and were grouped into the organ preservation group. RESULTS: No significant differences were observed between the primary surgery and organ preservation groups in terms of local control (p = 0.212), regional control (p = 0.684), distant metastasis (p = 0.627), 5-year disease-specific survival (DSS, p = 0.774), and overall survival rates (OS, p = 0.667). The rates of major complication (p = 0.216), long-term dependency on feeding tubes (p = 0.876), and tracheostomy (p = 0.401) were also similar. Advanced T classification (T3-4) was the only factor associated with significantly worse DSS (p = 0.007) and OS (p = 0.012). However, there was also no difference in final treatment outcomes in T3-4 patients regardless of whether they were treated with primary surgery or RT/CRT. In the organ preservation group, tumor tonsillectomy before RT/CRT did not improve local control (p = 0.520) or other treatment outcomes, including 5-year DSS (p = 0.707) and OS (p = 0.745). CONCLUSION: Both primary surgery and RT/CRT organ preservation are effective treatments for tonsillar SCC. Single modality treatment, either surgery or RT/CRT, can typically be provided for stage I-II diseases. Although RT/CRT organ preservation is used more frequently for stage III-IV tonsillar SCC in recent years, primary surgery combined with adjuvant therapy still achieves equivalent outcomes. Multidisciplinary pretreatment counseling and the facilities and personnel available are therefore important for decision-making. In addition, if RT/CRT organ preservation is selected as the primary treatment, tumor tonsillectomy is not indicated.

Neuromagnetic index of hemispheric asymmetry prognosticating the outcome of sudden hearing loss.

The longitudinal relationship between central plastic changes and clinical presentations of peripheral hearing impairment remains unknown. Previously, we reported a unique plastic pattern of "healthy-side dominance" in acute unilateral idiopathic sudden sensorineural hearing loss (ISSNHL). This study aimed to explore whether such hemispheric asymmetry bears any prognostic relevance to ISSNHL along the disease course. Using magnetoencephalography (MEG), inter-hemispheric differences in peak dipole amplitude and latency of N100m to monaural tones were evaluated in 21 controls and 21 ISSNHL patients at two stages: initial and fixed stage (1 month later). Dynamics/Prognostication of hemispheric asymmetry were assessed by the interplay between hearing level/hearing gain and ipsilateral/contralateral ratio (I/C) of N100m latency and amplitude. Healthy-side dominance of N100m amplitude was observed in ISSNHL initially. The pattern changed with disease process. There is a strong correlation between the hearing level at the fixed stage and initial I/C(amplitude) on affected-ear stimulation in ISSNHL. The optimal cut-off value with the best prognostication effect for the hearing improvement at the fixed stage was an initial I/C(latency) on affected-ear stimulation of 1.34 (between subgroups of complete and partial recovery) and an initial I/C(latency) on healthy-ear stimulation of 0.76 (between subgroups of partial and no recovery), respectively. This study suggested that a dynamic process of central auditory plasticity can be induced by peripheral lesions. The hemispheric asymmetry at the initial stage bears an excellent prognostic potential for the treatment outcomes and hearing level at the fixed stage in ISSNHL. Our study demonstrated that such brain signature of central auditory plasticity in terms of both N100m latency and amplitude at defined time can serve as a prognostication predictor for ISSNHL. Further studies are needed to explore the long-term temporal scenario of auditory hemispheric asymmetry and to get better psychoacoustic correlates of pathological hemispheric asymmetry in ISSNHL.

Expression of hedgehog signaling molecules as a prognostic indicator of oral squamous cell carcinoma.

BACKGROUND: Recent studies have indicated hedgehog pathway plays a role in carcinogenesis of certain cancers. We investigated the clinical significance of its signaling components, including Sonic hedgehog (Shh), Patched (Ptch), and Gli-1, in oral squamous cell carcinoma (OSCC). METHODS: By immunohistochemistry, we determined Shh, Ptch, and Gli-1 expression in surgical specimens from 40 patients with OSCC. The relationship between expression of these molecules and clinicopathologic variables were assessed by chi-square analysis. Statistical difference of survival was compared using log-rank test. RESULTS: Ptch overexpression was associated with lymphatic metastasis (p = .028). Nuclear Gli-1 overexpression correlated with primary tumor size (p = .001), lymphatic metastasis (p = .011), and tumor recurrence (p = .008). Overexpression of Ptch (p = .020) or Gli-1 (p = .002) in OSCC indicated poor prognosis in the univariate survival analysis. CONCLUSION: Our results suggest sonic hedgehog (Shh) pathway plays an important role in OSCC progression and should be considered a potential therapeutic target.

Risks and clinical implications of perineural invasion in T1-2 oral tongue squamous cell carcinoma.

BACKGROUND: Risks of perineural invasion (PNI) in T1-2 oral tongue squamous cell carcinoma (SCC) have not been specifically elucidated. METHODS: Pathological features, including PNI, were re-reviewed under regular hematoxylin-eosin staining in 190 patients with T1-2 oral tongue SCC. RESULTS: Tumor thickness >5 mm, PNI(+), and lymphovascular invasion (+) independently predicted lymph node involvement. PNI(+) and neck observation also independently predicted neck recurrence, but only PNI(+) was associated with a poor disease-specific survival (DSS; p = .003). In patients who were clinically node negative (cN0), elective neck dissection contributed to a better DSS in patients with PNI(+) tumors (p = .046), but not in patients with PNI (-) tumors (p = .809). Additionally, increased tumor thickness predicted the presence of PNI. CONCLUSION: PNI is a crucial pathological feature for T1-2 oral tongue SCC. Elective neck dissection should be performed in patients who were cN0 with PNI. Careful evaluation for PNI should be advocated in regular pathological diagnosis.

Treatment for T1-2 oral squamous cell carcinoma with or without perineural invasion: neck dissection and postoperative adjuvant therapy.

BACKGROUND: Although perineural invasion (PNI) has been a poor prognostic factor for head and neck cancers, few studies have focused on oral squamous cell carcinoma (OSCC). The independent significance of PNI in early T1-2 OSCC and the benefit of treatment modification based on PNI status have not been assessed. This study investigated the role of PNI in T1-2 OSCC patients, with focus on the controversial issues of neck management and postoperative adjuvant therapy. METHODS: PNI status was re-reviewed under hematoxylin and eosin staining in tumors of 307 consecutive T1-2 OSCC patients. Oncologic and survival outcomes were analyzed by univariate and multivariate analyses. RESULTS: PNI was identified in 84 (27.4%) patients, correlating with several established poor prognostic factors. In multivariate analysis, PNI remained an independent predictor for neck metastasis, neck recurrence, and a worse 5-year disease-specific survival. Elective neck dissection contributed to a significantly better 5-year disease-specific survival only in cN0 patients with PNI-positive tumors (P = 0.0071) but not in those with PNI-negative tumors (P = 0.3566). In low-risk patients who were treated by surgery alone, including neck dissection, the 5-year disease-specific survival rates were almost the same in those with PNI-positive tumors and those with PNI-negative tumors (92.0 vs. 92.9%; P = 0.9104). CONCLUSIONS: Elective neck dissection is indicated for cN0 patients with PNI-positive tumors for the efficacy of improving disease-specific survival as well as neck control. However, low-risk PNI-positive patients who undergo neck dissection do not need postoperative adjuvant therapy, because the residual risk from PNI is minimal.

Effectiveness of narrow band imaging in patients with oral squamous cell carcinoma after treatment.

BACKGROUND: We evaluated the effectiveness of narrow band imaging (NBI) in patients with oral squamous cell carcinoma (OSCC) after treatment. METHODS: In all, 101 consecutive OSCC patients underwent NBI examination for posttreatment follow-up. Four patients had local recurrence. Twenty-six second primary malignancies were found in 18 patients; 6 patients (33%) had more than 1 lesion. Seventeen lesions (65%) were carcinoma in situ or severe dysplasia. Most of them occurred in the oral cavity (77%). RESULTS: A higher incidence (18% vs 9%, p = .037) and less-advanced stage (4% vs 37%, p = .0005) of second primary malignancies were found among the NBI group compared with a previous cohort without NBI examination, and fewer patients needed postoperative adjuvant therapy (12% vs 50%, p = .0005). CONCLUSIONS: NBI is an effective method to identify early lesions in the head and neck area, especially the oral cavity, among patients with OSCC after treatment.

Pretreatment risk stratification for non-metastatic head and neck squamous cell carcinoma in a high-prevalence area.

BACKGROUND: This retrospective study was to establish a prognostic scoring system for patients with non-metastatic head and neck squamous cell carcinoma (HNSCC). METHODS: The medical records of 151 patients with HNSCC were evaluated. Clinical data were collected and statistical analyses were performed to determine the prognostic value of pretreatment variables and to build a risk stratification system. Analysis of the data for 94 additional patients validated the risk stratification system. RESULTS: Three independent adverse prognostic factors were identified: Age <65 years, LDH ≥ upper normal limit and performance status. The risk stratification was defined as two or more adverse factors presented at diagnosis versus one adverse factor or no adverse factors. Patients with two or more adverse factors had a shorter survival regardless of treatment. This was confirmed in both the training set and the validation set. CONCLUSION: This risk stratification provides additional information to the current tumor staging system, which could be useful in making decisions for individual patients and selecting more homogenous patients when designing clinical trials.

Interplay between HDAC3 and WDR5 is essential for hypoxia-induced epithelial-mesenchymal transition.

Epithelial-mesenchymal transition (EMT) is important for organ development, metastasis, cancer stemness, and organ fibrosis. Molecular mechanisms to coordinately regulate hypoxia-induced EMT remain elusive. Here, we show that HIF-1α-induced histone deacetylase 3 (hdac3) is essential for hypoxia-induced EMT and metastatic phenotypes. Change of specific chromatin states is associated with hypoxia-induced EMT. Under hypoxia, HDAC3 interacts with hypoxia-induced WDR5, recruits the histone methyltransferase (HMT) complex to increase histone H3 lysine 4 (H3K4)-specific HMT activity, and activates mesenchymal gene expression. HDAC3 also serves as an essential corepressor to repress epithelial gene expression. Knockdown of WDR5 abolishes mesenchymal gene activation but not epithelial gene repression during hypoxia. These results indicate that hypoxia induces different chromatin modifiers to coordinately regulate EMT through distinct mechanisms.

Promising long-term results with attenuated adverse effects by methotrexate-containing sequential chemoradiation therapy in locally advanced head and neck squamous cell carcinoma.

OBJECTIVE: To reduce severe acute and late toxicities without compromising organ preservation survival in patients with locoregionally advanced head and neck squamous cell carcinoma, we performed three-drug induction methotrexate-cisplatin-fluorouracil with weekly cisplatin-fluorouracil concurrent chemoradiation. METHODS: Two induction courses of methotrexate (40 mg/m(2)/day, days 1, 8 and 15), cisplatin and 5-fluorouracil (25 and 750 mg/m(2)/day, days 1-4) were given in new diagnoses of patients with non-nasopharyngeal locoregionally advanced head and neck squamous cell carcinoma. Responders received concurrent chemoradiation with weekly cisplatin (20 mg/m(2)/day) and 5-fluorouracil (400 mg/m(2)/day) on day 1. RESULTS: Among 57 patients (58% with Stage IV and hypopharyngeal cancer), the rates of Grade 3-4 toxicity were 30 and 74% during induction and CCRT, respectively. A total of 49 patients completed induction and began concurrent chemoradiation; 47 (96%) completed all planned treatment. With a median follow-up of 62 months (range 19-83 months) for the current survivors, the 3-year overall and disease-specific survival estimates were 50 and 58%, respectively. The 3-year organ preservation survival was 74% in patients who achieved complete remission after concurrent chemoradiation, and 96% of current survivors are tracheotomy and feeding tube-free. No patient without local/regional failure suffered from distant metastasis. CONCLUSIONS: Methotrexate-cisplatin-fluorouracil induction chemotherapy followed by weekly cisplatin-fluorouracil concurrent chemoradiation is an acute and late toxicity-acceptable protocol without attenuating organ preservation survival in patients with locoregionally advanced head and neck squamous cell carcinoma. In this patient cohort with advanced head and neck squamous cell carcinoma, overall and organ preservation survivals were encouraging, and provided promising long-term benefits of this approach.

Management of base of tongue squamous cell carcinoma: experience with 85 patients in Taipei Veterans General Hospital.

BACKGROUND: The optimal treatment of base of tongue squamous cell carcinoma (BOTSCC) remains controversial. To optimize treatment planning, this study analyzed the outcomes of patients with BOTSCC treated in Taipei Veterans General Hospital. METHODS: Retrospective chart reviews were performed for 107 patients with BOTSCC from January 1990 to December 2004, and 85 patients were included, with a mean follow-up interval of 38 months. Patients were divided into surgical and radiotherapy/chemoradiation therapy (RT/CRT) groups. Potentially significant variables for survival were analyzed. RESULTS: The 3-year overall survival (OS) and disease-free survival rates were 40% and 37.1%, respectively. No significant differences in the patient and disease characteristics between the surgical (n = 39) and RT/CRT groups (n = 46) were found. Advanced overall stage (p = 0.034), cervical lymph node metastasis (p = 0.007), and regional recurrence (p = 0.024) were poor prognostic factors for OS. In early-stage disease (Stages I and II), the 3-year OS was higher in the surgical group (68.6%) than in the RT/CRT group (37.5%), but the significance was only borderline (p = 0.071). There was no significant difference in the 3-year OS between the patients in the surgical and CT/CRT groups with advanced-stage disease. In the surgical group, lymphovascular permeation (p = 0.015) and soft-tissue involvement (p = 0.01), determined by pathologic examination, were poor prognostic factors for OS. Recurrence occurred in 35 patients (41.2%), with no significant difference in local, regional, or distant control between the surgical and RT/CRT groups. CONCLUSION: These findings emphasize the importance of neck disease control in the treatment of BOTSCC. Although currently, RT/CRT is used more frequently, surgery may still have a role in the treatment of early-stage disease. Both surgery with adjuvant therapy and RT/CRT produced equivalent survival rates in the treatment of advanced-stage disease, but the recurrence rate was unsatisfactory. A more effective treatment modality with less early and late toxicity is needed.

Triweekly reduced-dose docetaxel combined with cisplatin in recurrent/metastatic head and neck squamous cell carcinoma: a multicenter phase II study.

PURPOSE: To test the efficacy and safety of a triweekly reduced-dose docetaxel (60 mg/m(2)) regimen combined with a standard dose of cisplatin in patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: Patients with R/M HNSCC were enrolled. All eligible patients received intravenous docetaxel 60 mg/m(2) combined with cisplatin 75 mg/m(2) on day 1 and then every 3 weeks thereafter. Treatment was continued until disease progression, patient intolerance, or death. RESULTS: In total, 58 patients were enrolled and 41 patients were evaluated. Among the evaluated population, one patient achieved a complete response (2.4%) and nine patients achieved a partial response (22%), resulting in an overall response rate of 24.4%. Furthermore, 17 patients had stable disease (41.5%), which corresponds to a disease control rate of 65.9%. With a median follow-up of 24 months (1-43 months), progression-free survival was 170 days (95% confidence interval 97.9-242.1) and the median overall survival was 265 days (95% confidence interval 89.0-441.0) in evaluable population. The most common toxicities (≥ grade III) were leucopenia (66.7%) and anemia (33.3%). CONCLUSIONS: Triweekly reduced-dose docetaxel 60 mg/m(2) combined with cisplatin is effective and feasible for Taiwanese patients with R/M HNSCC. However, the hematologic toxicity of this regimen should be carefully monitored and managed.

A study using ifosfamide and etoposide in patients with cisplatin-refractory recurrent or metastatic head and neck squamous cell carcinoma.

OBJECTIVE: To investigate the efficacy and safety of combination therapy with ifosfamide and etoposide in cisplatin-refractory recurrent/metastatic squamous cell carcinoma of the head and neck. METHODS: Thirty patients with cisplatin-refractory recurrent/metastatic squamous cell carcinoma of the head and neck were treated with ifosfamide (1000 mg/m(2)/day) as a continuous 24 h infusion for 3 days and etoposide (100 mg/m(2)/day) as a bolus 1 h infusion on the same 3 days. The treatment was repeated every 4 weeks until disease progression. RESULTS: The overall rate of response was 27% (8/30), and 20% (6/30) of the patients achieved stable disease status. Median overall survival was 7.7 months. Subgroup analysis demonstrated significant improvement in overall survival in the group that achieved control of disease. Thirteen (43.3%) patients developed grade 3-4 neutropenia, and five (16.6%) developed grade 3-4 non-hematologic mucositis. CONCLUSIONS: This combination chemotherapy had an effective and safe profile and improved survival in patients with cisplatin-refractory recurrent/metastatic squamous cell carcinoma of the head and neck who achieved disease control.

Persistent Krüppel-like factor 4 expression predicts progression and poor prognosis of head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is one prevalent human cancer worldwide. No molecular markers are presently used for predicting prognosis in HNSCC. Krüppel-like factor 4 (KLF4) is a transcription factor with diverse physiological functions, and possesses opposing roles in different human cancers. The expression and roles of KLF4 in HNSCC remain to be elucidated. In this study, immunohistochemical (IHC) analysis of KLF4 in 62 HNSCC was firstly performed. IHC results demonstrated that 42 (67.7%) had decreased KLF4 expression compared with surrounding normal epithelium, while persistent KLF4 expression was demonstrated in 20 (32.3%). The IHC results were further verified by Western blot and real-time PCR analyses to confirm the robustness of staining and interpretation. Interestingly, persistent KLF4 expression independently correlated with a worse disease-specific survival (P = 0.005), especially in patients with advanced disease. In consistent with clinical observation, all five HNSCC cell lines tested revealed a low level of baseline KLF4 expression. Moreover, enforced KLF4 expression in cell line SAS significantly increased in vitro migration/invasion abilities, multi-drug resistance, and in vivo tumorigenicity. These results clearly illustrate that persistent KLF4 expression predicts poor prognosis and confers aggressiveness in HNSCC. Our data therefore provides valuable information that HNSCC with persistent KLF4 expression might require intensified combination treatment in future practice.