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Conclusions: Nuclear nm23-H1 expression may be useful in identifying elderly patients operated for laryngeal squamous cell carcinoma (LSCC) at higher risk of recurrence. Further studies are needed to clarify the biological role of nm23-H1 in elderly patients with LSCC and to determine how to restore nm23-H1 loss of expression/function. Objectives: Nowadays more than 50% of cancer cases are elderly patients and this percentage is expected to be 70% by 2030. Despite advances in LSCC diagnosis and treatment, patient survival has not improved in the last two decades. Novel, effective strategies should rely also on receptor-mediated LSCC-targeted therapy. nm23-H1 protein is related to the tumor cells' metastatic potential, and low nm23-H1 expression in carcinomas often correlates with a poor prognosis. Methods: Immunohistochemistry and image analysis were used to investigate the prognostic value of nm23-H1 expression and subcellular localization in a series of 54 elderly patients consecutively undergoing primary surgery for LSCC. Results: On univariate analysis, the disease recurrence rate correlated inversely with nuclear nm23-H1 expression ( p = 0.014), and disease-free survival (DFS) was longer in patients whose nuclear nm23-H1 levels were ≥2.0% ( p = 0.022). On multivariate analysis, nuclear nm23-H1 expression (hazard ratio (HR) 2.77, p = 0.022) and N stage (HR 3.49, p = 0.007) were prognostically significant in terms of DFS. [ABSTRACT FROM AUTHOR]

Objective: Tumor-associated tissue eosinophilia (TATE) has been noted in human cancers, sometimes with different results regarding their association with clinical outcome. In this study, the association between TATE and prognostic parameters of supraglottic laryngeal cancer was analyzed. Materials and methods: Sixty-two patients with diagnosis of supraglottic laryngeal squamous cell carcinoma and who treated surgically in our center were evaluated. The cases were divided into 3 categories according to the average number of eosinophils per high-power field (400x): 0 (negative), 1-5 (grade 1+), more than 5 (grade 2+). Results: We found 24 TATE-negative (38.7%) and 38 TATE-positive (61.3%) cases. There was not any statistically significant correlation between TATE and tumor differentiation, vascular invasion, perineural invasion, lymph node metastasis, patients' ages, T stages (p>0.05). As expected, vascular invasion correlated with lymph node metastasis (p=0.001). Conclusion: The results of this study showed that TATE has no correlation with prognostic parameters such as histologic differentiation, vascular invasion, perineural invasion, lymph node metastasis, patients' ages and T stages in supraglottic laryngeal squamous cell carcinoma. The data suggest that stromal eosinophilic infiltration is not useful for determining biological aggressiveness in supraglottic laryngeal cancer. [ABSTRACT FROM AUTHOR]

Abstract: Aims: To evaluate the prognostic significance of potential tumour markers of hypoxia and apoptosis in early squamous cell carcinoma of the glottic larynx managed with radiotherapy. Materials and methods: In total, 382 patients with T1 and T2 squamous cell carcinoma of the glottic larynx (vocal cords) received radical radiotherapy (50–55 Gy, in 16 fractions in 98% of cases). Pre-treatment haemoglobin was available for 328 patients; biopsy samples were available for 286. Immunohistochemistry was carried out for carbonic anhydrase-9 (CA-9), hypoxia inducible factor-1α (HIF-1α) and Bcl-2. Results: At 5 years, locoregional control was achieved in 88.2%, cancer-specific survival in 95.0% and overall survival in 78.7%. Adverse prognostic factors for locoregional tumour recurrence were pre-treatment haemoglobin <13.0 g/dl (P = 0.035, Log rank test; sensitivity 0.28, specificity 0.84) and stage T2 rather than T1 (P = 0.002). The effect of haemoglobin level on locoregional control was not significant when stratified by the median of 14.2 g/dl (P = 0.43) or as a continuous variable (P = 0.59). High CA-9 (P = 0.11), HIF-1α (P = 0.67) and Bcl-2 (P = 0.77) expression had no prognostic significance. Conclusions: High CA-9, HIF-1α and Bcl-2 do not add to the prognostic significance of tumour stage and lower haemoglobin in predicting failure of local control in early glottic larynx squamous cell carcinoma managed with radiotherapy. The effect of haemoglobin was not strong enough to be useful as a prognostic biomarker. [Copyright &y& Elsevier]

Objective:This study aimed to investigate the relationship between focal adhesion kinase expression and clinicopathological factors, cell apoptosis and proliferation, and overall survival, in laryngeal squamous cell carcinoma.Methods:Immunohistochemical staining was used to detect the expression of focal adhesion kinase and proliferating cell nuclear antigen in tissue samples. Apoptotic cells were assessed using the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labelling (‘TUNEL’) method.Results:The proportion of focal adhesion kinase expression was 73.26 per cent in tumour tissues, significantly greater than in normal tissues (p < 0.05), and was significantly related to laryngeal cancer clinical stage, lymph node metastasis and overall survival (p < 0.05). In the tumour cases assessed, up-regulation of focal adhesion kinase expression was significantly associated with decreased cell apoptosis and increased proliferation (p < 0.05).Conclusion:These findings suggest that focal adhesion kinase may affect laryngeal squamous cell carcinoma progression through regulation of cell apoptosis and proliferation. Focal adhesion kinase expression is a major prognostic factor in laryngeal cancer patients. [ABSTRACT FROM PUBLISHER]

Angiogenesis is a hallmark of cancer, fundamental to its growth. The 'angiogenic switch' occurs when pro-angiogenic factors are not balanced by anti-angiogenic factors. A correlation between angiogenic properties and oncological prognosis (for laryngeal squamous cell carcinoma (LSCC) too) was first hypothesized in the 1990s. An exhaustive literature review was performed to investigate available data on angiogenesis markers and their biological role and therapeutic potential in LSCC. The prognostic significance of microvascular density in LSCC was investigated with endothelial targets, e.g. CD105, CD34, and CD31. Epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), VEGF receptor 2, angiogenin, hypoxia-inducible factor 1, and other biological markers were also studied. Only anti-EGFR therapy has been approved by the USFood and Drug Administration (FDA) for head and neck carcinoma in recent years, while several agents interfering with VEGF and its receptors are being studied. Experimental findings indicate that anti-CD105 monoclonal antibodies efficiently inhibit tumor angiogenesis. There are two main ways to approach the vascular profile of solid malignancies: by inhibiting new vessel formation (anti-angiogenic therapy) or selectively damaging neoplastic vessels (vascular targeting therapy). In advanced LSCC, both these strategies seem promising and warrant further preclinical and clinical investigation. [ABSTRACT FROM AUTHOR]

An international consensus panel was convened to develop guidelines for the conduct of phase III clinical trials of larynx preservation in patients with locally advanced laryngeal and hypopharyngeal cancer. According to their recommendations, future trial populations should include patients with T2 or T3 laryngeal or hypopharyngeal squamous cell carcinoma not considered for partial laryngectomy and should exclude those with laryngeal dysfunction or aged >70 years. Baseline and post-treatment functional assessments should include speech and swallowing evaluations. Furthermore, voice should be routinely assessed with a simple, validated instrument. Regarding endpoints, the primary endpoint should capture survival and function. As a result, the panel created a new endpoint of laryngoesophageal dysfunction (LED)-free survival, which includes the events of death, local relapse, total or partial laryngectomy, tracheotomy at ≥2 years, or feeding tube at ≥2 years. Recommended secondary endpoints are freedom from LED, overall survival, progression-free survival, locoregional control, time to tracheotomy, time to laryngectomy, time to discontinuation of feeding tube, and quality of life/patient-reported outcomes. Future exploratory correlative biomarker studies should include epidermal growth factor receptor, excision repair cross-complementation group 1 gene, E-cadherin and β-catenin, epiregulin and amphiregulin, and TP53 mutation. Revised trial designs in several key areas are needed to advance the study of larynx preservation. With consistent methodologies, clinical trials can more effectively evaluate and quantify the therapeutic benefit of novel treatment options for patients with locally advanced laryngeal and hypopharyngeal cancer. [ABSTRACT FROM AUTHOR]

We report the case of a 58-year-old man who presented with a squamous cell carcinoma pT1a G2 of the left vocal cord. Six months after histologically verified complete resection, the patient experienced an endolaryngeal and extralaryngeal local recurrence pT4 pN2b G2. We applied DNA flow cytometry (FCM) and comparative genomic hybridization (CGH) on both primary and recurrent tumor. The primary tumor and the endolaryngeal compartment of the relapse was an aneuploid cell clone with a FCM DNA index of 1.42 and 1.44, respectively. The extralaryngeal compartment showed a shift featuring a DNA index of 2.78. In the primary tumor and in both compartments of the recurrence there was an identical pattern of complex chromosomal imbalances as detected in CGH (CGH karyotype: rev ish enh [8q24.2-q24.3, 10q26.1-q26.3, 11q24-q25, 12q24.2-q23.33,X], dim [4q, 13q14.3-q31], amp[1p36.1-p36.2]). Hence, the recurrence was not associated with further gains and losses of chromosomal material. However, in the anterior part of the recurrence, the aneuploid tumor cell genome had completely doubled, obviously due to endoreduplication. Immunohistochemical analysis of several cell-cycle regulators revealed altered expression of checkpoint proteins, pointing to a complex disturbance in cell-cycle regulation. [ABSTRACT FROM AUTHOR]

: PurposeTo study locoregional tumor control in postoperative radiotherapy (PRT) for head-and-neck cancer in relation to the position and duration of treatment gaps, duration of the interval surgery-radiotherapy, and to the other potentially prognostic variables.: Methods and materialsThe retrospective study included 868 patients with cancer of the larynx, oral cavity, oropharynx, and hypopharynx treated in Gliwice between 1980 and 1997. Mean total radiation dose, dose per fraction, overall radiation treatment time (OTT), and the interval surgery-PRT were 62.8 Gy, 2.1 Gy, 45 days, and 63 days, respectively. No interruptions during PRT (except for weekend breaks) appeared in 30% of patients, whereas 19% had more than 5 days of gap. The actuarial locoregional recurrence-free survival (RFS) has been examined using multivariate Cox regression model, and the ultimate locoregional tumor control probability using a logistic model.: ResultsIncreased duration of treatment gaps, positive resection margins, pathologically proven metastases to the neck nodes, and extralaryngeal site of cancer were significantly related to a decrease in RFS. The duration of time interval surgery-PRT appeared, by contrast, only borderline significant for RFS. The relative risk of locoregional recurrence was approximately the same for the gaps in days 1–21 as for the “late” gaps (days >21), except in a subgroup of patients with positive clinical margins. The logistic analysis revealed a significant time-related displacement of the dose–response curves for PRT. The detriment from the protraction of OTT appeared to be larger than the benefit from the equivalent shortening of OTT.: ConclusionsAlthough the conclusions from this study must be regarded as only hypothesis-generating, we assume that a highly significant adverse influence of radiation treatment gaps on the rate of tumor control is consistent with rapid repopulation of cancer clonogenes during PRT. Lack of significant effect of the position of gaps on locoregional tumor control after radical surgery may suggest that a lag time for the onset of repopulation in PRT is short. A less likely explanation is that the total amount of regeneration during OTT is the same, regardless of the timing of the gap, even if all the repopulation occurred late. The magnitude of the detriment in tumor control from prolonged interval surgery-PRT indicates that repopulation of cancer cells between surgery and radiotherapy is not as fast as between the fractions of radiotherapy. [Copyright &y& Elsevier]

Molecular prognostic and predictive factors have extensively been studied in different cancers during the past decades, some of which were found to be useful in diagnosis, follow up or even treatment of some malignant tumors. To assess the significance of c-erbB-1, c-erbB-2 and p53 expression in head and neck tumors among Iranian patients and their correlation with known prognostic factors, samples from 53 patients with squamous cell carcinomas of larynx and tongue were studied immunohistochemically. Strong immunoreactivity of c-erbB-1, c-erbB-2 and p53 was observed in 37 (70%), 40 (76%) and 37 (70%) of cases, respectively. The coexpression of these molecules was detected in 27 (50.9%) samples. Neither histological grading nor nodal involvement revealed correlation with c-erbB-1 and/or c-erbB-2 expression. No correlation was found between p53 expression and histological grade. However, a significant positive association was observed between p53 expression and nodal involvement. This data, which is the first report on head and neck squamous cell carcinomas (HNSCC) in Iran, indicates the significance of p53 protein expression which may result from p53 tumor suppressor gene inactivation in lymph node metastasis of HNSCC among Iranian patients. [Copyright &y& Elsevier]

Purpose: In a series of consecutive patients with squamous cell carcinoma of the supraglottic larynx, in which almost all were treated by primary radiotherapy, the study describes the path from diagnosis to cure or death, and evaluates the patterns of failure and the treatment of recurrences.Methods and Materials: The analysis included 410 patients, 104 females and 306 males, treated between 1963 and 1991. Most patients were in Stage I (33%), and the remaining were in Stage II (18%), III (23%), and IV (26%). Primary intended curative treatment was delivered in 398 (radiotherapy, 394; surgery, 4) of 410 cases (98%).Results: Initial radical treatment resulted in 173 cured patients and 225 patients with a recurrence. Curatively intended salvage could be applied in 158 patients: surgery in 154 patients (74 cured) and radiotherapy in 4 (none cured). Overall, 247 patients (60%) obtained tumor control, 179 (44%) without a laryngectomy. Sixty-three patients had a total laryngectomy, and five had a partial laryngectomy. The 5-year locoregional tumor control, disease-specific survival, and overall survival rates were 43%, 61%, and 47%, respectively. With a follow-up of 20 years posttreatment, 91 new primary malignant tumors were detected.Conclusions: Radiotherapy is effective in the treatment of supraglottic laryngeal carcinoma, and the patients have a relatively good prognosis. Many patients retained their larynx intact. Recurrence after primary radiotherapy can be treated by surgery, with a high success rate even in advanced stages. Development of second primary cancer is a growing problem. [Copyright &y& Elsevier]

Tumour oxygenation and vasculature are determinants for radiation treatment outcome and prognosis in patients with squamous cell carcinomas of the head and neck. In this study we visualized and quantified these factors which may provide a predictive tool for new treatments. Twenty-one patients with stage III-IV squamous cell carcinomas of the head and neck were intravenously injected with pimonidazole, a bioreductive hypoxic marker. Tumour biopsies were taken 2 h later. Frozen tissue sections were stained for vessels and hypoxia by fluorescent immunohistochemistry. Twenty-two sections of biopsies of different head and neck sites were scanned and analysed with a computerized image analysis system. The hypoxic fractions varied from 0.02 to 0.29 and were independent from T- and N-classification, localization and differentiation grade. No significant correlation between hypoxic fraction and vascular density was observed. As a first attempt to categorize tumours based on their hypoxic profile, three different hypoxia patterns are described. The first category comprised tumours with large hypoxic, but viable, areas at distances even greater than 200 micrometer from the vessels. The second category showed a typical band-like distribution of hypoxia at an intermediate distance (50-200 micrometer) from the vessels with necrosis at greater distances. The third category demonstrated hypoxia already within 50 micrometer from the vessels, suggestive for acute hypoxia. This method of multiparameter analysis proved to be clinically feasible. The information on architectural patterns and the differences that exist between tumours can improve our understanding of the tumour micro-environment and may in the future be of assistance with the selection of (oxygenation modifying) treatment strategies. [ABSTRACT FROM AUTHOR]

Basaloid squamous cell carcinoma (BSC) is regarded as a variant of squamous cell carcinoma, but displays distinct morphological and biological features as well as a different clinical course. The tumor is frequently seen in the head and neck and is preferentially located in the larynx, especially in supraglottic sites. Ten patients with BSC of the supraglottic larynx were treated from 1991 to 1995 at the Medical Faculty of the University of Istanbul. Results of treatment were compared retrospectively with a control group consisting of 44 patients with well-differentiated squamous cell carcinomas. Ages, ¶localizations, stages and treatment procedures were similar. In both groups mean survival, nodal involvement and distant metastases were comparable although the local ¶(laryngeal) recurrence rate in patients with early supraglottic (T2) disease in the BSC group after conservative partial surgery was distinct compared to the control group (P < 0.05). These results indicate that conservative surgery should be assessed with caution in patients with BSC, and postoperative irradiation be taken into consideration. [ABSTRACT FROM AUTHOR]

Simple summary: The mechanism of epithelial–mesenchymal transition is fundamental for carcinogenesis, tumor progression, cancer cell invasion, metastasis, recurrence, and therapy resistance, resulting in cellular junction degradation and increased cellular motility. The same factors that drive epithelial cells toward a mesenchymal phenotype may also drive endothelial cells toward a proangiogenic phenotype. This study aimed to investigate a potential interplay between epithelial–mesenchymal transition and angiogenesis in laryngeal carcinoma. In our study, univariate Cox regression identified pN+ status and Slug expression as predictive of disease-free survival, while a trend toward significance emerged for CD105-assessed microvessel density and N-cadherin expression. In the multivariate Cox regression model, pN-status, Slug, and N-cadherin expressions retained their significant values in predicting disease-free survival. Data from our study support the hypothesis of a mutual concurrence of epithelial–mesenchymal transition and angiogenesis in the development of an aggressive phenotype in laryngeal squamous cell carcinoma. The mechanism of epithelial–mesenchymal transition (EMT) is fundamental for carcinogenesis, tumor progression, cancer cell invasion, metastasis, recurrence, and therapy resistance, comprising important events, such as cellular junction degradation, downregulation of epithelial phenotype markers, overexpression of mesenchymal markers, and increase in cellular motility. The same factors that drive epithelial cells toward a mesenchymal phenotype may also drive endothelial cells toward a proangiogenic phenotype. The aim of this exploratory study was to investigate a potential interplay between EMT and angiogenesis (quantified through CD105 expression) in laryngeal carcinoma (LSCC). CD105-assessed microvessel density (MVD) and EMT markers (E-cadherin, N-cadherin, Snail, Slug, Zeb1, and Zeb2) were assessed on 37 consecutive LSCC cases. The univariate Cox regression model identified pN+ status (p = 0.0343) and Slug expression (p = 0.0268) as predictive of disease-free survival (DFS). A trend toward significance emerged for CD105-assessed MVD (p = 0.0869) and N-cadherin expression (p = 0.0911). In the multivariate Cox model, pN-status, Slug, and N-cadherin expressions retained their significant values in predicting DFS (p = 0.0346, p = 0.0430, and p = 0.0214, respectively). Our data support the hypothesis of a mutual concurrence of EMT and angiogenesis in driving LSCC cells toward an aggressive phenotype. To better characterize the predictive performance of prognostic models based on EMT and angiogenesis, further large-scale prospective studies are required. [ABSTRACT FROM AUTHOR]

Purpose: In the treatment of laryngeal carcinoma definitive radiotherapy results in a similar outcome as surgical treatment in the early stages with a lower morbidity rate and good functional results. In fact no randomized studies exist, so far, and the optimal treatment concept for the different stages is not well defined. The following study analyses retrospectively the treatment results and the recurrence data in patients with a squamous cell carcinoma of the larynx treated with definitive radiotherapy.Patients and Method: Two hundreds and eighty-three patients with carcinoma of the larynx were treated with radiation therapy in the department of radiology of the LMU München between September 1971 and June 1986. Twenty-six patients (9.2%) were female and 257 (73.1%) male. The median age was 68.5 years, respectively 70 years. All patients had a histologically confirmed squamous cell carcinoma of the larynx. No true subglottic cases were observed. Forty-one (14.5%) tumors were localized supraglottically, 207 (73.1%) glottically. Thirty-five patients had a T4 tumor with glottic and supraglottic involvement. In 147 patients the histopathological grading was evaluable: 32 tumors were classified as G1, 95 as G2, 15 as G3 and 5 as G4. According to the UICC classification of 1979 25 patients had a carcinoma in situ (Tis), 93 patients had a stage T1, 90 stage T2, 40 stage T3 and 35 stage T4. Two hundreds and thirty-three of 283 (82.3%) had no lymph node involvement. In 50 patients clinically a lymph node involvement was observed. 22 patients had a stage N1, 5 patients stage N2 and 23 patients stage N3. An external beam radiation mostly with cobalt-60 was performed with a mean dose of 61.9 Gy.Results: The 5-years relapse-free survival for the whole group was 61.7%. The probability for "no evidence of disease" (NED) depended on tumor stage and localisation (glottic tumors: Tis/T1 90.5%: T2 59.4%: T3 39.6%: [5-year NED]; supraglottic tumors T1 64.2%: T2/3 28.6%: T4/N3 24.7% [3-year NED]). Other significant prognostic factors besides T-stage were N-stage (NO vs. N1-3: 3-year recurrence-free survival 68% vs. 37.2%, p < 0.001) and histopathologic grading (G1 vs. G3/4: 3-year recurrence-free survival 74% vs. 37.1%, p < 0.01). One hundred and twenty-two (43.1%) patients had a recurrence, which occurred in 75.4% local, in 12.3% loco regional, in 8.2%, with distant metastases and 4.1% combined. In 50 patients with a recurrent disease a salvage therapy was carried out. Thereby 17 patients achieved a complete response.Conclusion: Even for the here described negatively selected patient group with a high median age and multimorbidity, good local control rates could be achieved especially in early stages with definitive radiation therapy. In more advanced stages even in elderly patients a combined surgical-radiotherapeutic treatment should be performed. [ABSTRACT FROM AUTHOR]

Objectives: The tumor secretome deconvolution is a promising strategy to identify diagnostic and prognostic biomarkers. Here, transcriptomic-based secretome analysis was performed aiming to discover laryngeal squamous cell carcinomas (LSCC) biomarkers from potentially secreted proteins (PSPs).Material and Methods: The tumor expression profile (35 LSCC biopsies compared with surrounding normal tissues - SN) revealed 589 overexpressed genes. This gene list was used for secretome analysis based on laryngeal tumors and related secretome databases.Results: Forty-nine (Laryngeal tumor secretome database) and 50 (Human Protein Atlas and Cancer Secretome Database) PSPs presented an association with worse overall survival. Specifically, DSG2 overexpression was strongly correlated with poor survival and distant metastasis. DSG2 increased expression was confirmed in the LSCC dataset (LSCC = 111; SN = 12) from TCGA. A significant association between shorter survival and DSG2 overexpression was also detected. In an independent cohort of cases, we analyzed and confirmed high protein levels of DSG2 in plasma from LSCC patients.Conclusion: A set of PSPs including the circulating DSG2, were associated with shorter overall survival in LSCC. DSG2 overexpression was also correlated with distant metastasis. The high plasmatic protein levels of DSG2 suggest its potential to be tested in liquid biopsies and applied as prognostic biomarker of LSCC. [ABSTRACT FROM AUTHOR]

Aberrant SRC expression and activation is frequently detected in multiple cancers, and hence, targeting SRC has emerged as a promising therapeutic strategy. Different SRC inhibitors have demonstrated potent anti-tumor activity in preclinical models, although they largely lack clinical efficacy as monotherapy in late-stage solid tumors, including head and neck squamous cell carcinomas (HNSCC). Adequate selection and stratification of patients who may respond to and benefit from anti-SRC therapies is therefore needed to guide clinical trials and treatment efficacy. This study investigates the prognostic significance of active SRC expression in a homogeneous cohort of 122 human papillomavirus (HPV)-negative, surgically treated HNSCC patients. Immunohistochemical evaluation of the active form of SRC by means of anti-SRC Clone 28 monoclonal antibody was specifically performed and subsequently correlated with clinical data. The expression of p-SRC (Tyr419), total SRC, and downstream SRC effectors was also analyzed. Our results uncovered striking differences in the prognostic relevance of SRC expression in HNSCC patients depending on the tumor site. Active SRC expression was found to significantly associate with advanced disease stages, presence of lymph node metastasis, and tumor recurrences in patients with laryngeal tumors, but not in the pharyngeal subgroup. Multivariate Cox analysis further revealed active SRC expression as an independent predictor of cancer-specific mortality in patients with laryngeal carcinomas. Concordantly, expression of p-SRC (Tyr419) and the SRC substrates focal adhesion kinase (FAK) and the Arf GTPase-activating protein ASAP1 also showed specific associations with poor prognosis in the larynx. These findings could have important implications in ongoing Src family kinase (SFK)-based clinical trials, as these new criteria could help to improve patient selection and develop biomarker-stratified trials. [ABSTRACT FROM AUTHOR]

Background: There is a paucity of evidence comparing oncological and voice outcomes between T2a and T2b glottic squamous cell carcinoma (SCC) patients treated with transoral laser microsurgery (TLM). This study identified functional and oncological outcomes in this cohort. Methods: Retrospective review of prospectively collected data of patients treated with TLM for T2 glottic SCC from 2003 to 2017. Results: In total, 75 patients were included. Five-year local control rates were significantly different between T2a and T2b patients (75.2% vs 57.0%, p = 0.022). There was no difference in five-year survival between patients with T2a disease and T2b disease (69.5% vs 73.4%, p = 0.627). There was no significant difference in mean VHI-10 scores in the pre-operative period (18.3 vs 21.4, p = 0.409). However, patients with T2b disease had significantly worse perceived voice outcomes post-operatively (6.6 vs 21.3 p = 0.001). Patients with T2a disease saw significant improvements in mean VHI-10 scores following surgery (18.3 vs 6.6, p = 0.000), while T2b patients did not (21.4 vs 21.3, p = 0.979). The overall laryngeal preservation rate was 94.7%, with 11.5% of T2b patients requiring salvage organ sacrifice. Conclusions: This study highlights positive functional outcomes for T2a glottic SCC. Patients with T2b disease appear to have significantly worse oncological and functional outcomes, including worse voice quality following surgery and higher rates of salvage laryngectomy. [ABSTRACT FROM AUTHOR]

Background: We sought to expand upon preliminary data suggesting that metformin confers a survival benefit to patients with head and neck squamous cell carcinoma (HNSCC). Methods: A large-scale retrospective cohort study of all patients in Ontario diagnosed with squamous cancer of the larynx, hypopharynx, and nasopharynx between Dec 1st 2007 to Dec 1st 2012 was undertaken. The Institute for Clinical and Evaluative Sciences was accessed to obtain patient demographic, treatment and outcome information. We included patients on metformin at the time of diagnosis. Kaplan Meier methods and Cox Regression models were used. Results: Patients taking metformin at the time of diagnosis had a higher comorbid status but were otherwise similar to patients without metformin usage. Using multivariate analysis, neither overall survival nor disease specific survival was improved in patients on metformin (OS: HR 1.123, p =.338; DSS: HR 1.048, p =.792). Conclusions: No survival advantage was observed in patients with HNSCC taking metformin at the time of diagnosis. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to evaluate the benefit of induction chemotherapy followed by surgery in locally advanced unresectable stage IVb laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC). Methods: Data of patients with stage IVb LHSCC who received induction chemotherapy for the purpose of tumor resection between January 2007 and January 2016 were retrospectively collected. Definitive surgery with postoperative adjuvant therapy was performed in patients whose tumors became resectable (resectable group). Chemoradiotherapy, radiotherapy, or supportive care was considered in patients whose tumors remained unresectable (unresectable group). Results: Thirty-two patients were identified; the tumor resectability rate after induction chemotherapy was approximately 56%. The median overall survival (OS) rates of the resectable and unresectable groups were 20.0 months (range, 16.0–35.5 months) and 9.5 months (range, 6.0–15.0 months), respectively (p = 0.008). The estimated 2-year OS rates of the resectable and unresectable groups were 59.5% (95% confidence interval [CI], 33.2–78.3%) and 10.7% (95% CI, 1.1–35.4%), respectively (p = 0.008). The estimated 2-year disease-free survival (DFS) rates of the resectable and unresectable groups were 53.5% (95% CI, 27.9–73.6%), and 14.3% (95% CI, 2.3–36.6%), respectively (p = 0.009). On multivariate analysis, factors positively impacting OS and DFS in all patients were surgical resection, a laryngeal primary site, and induction chemotherapy with docetaxel, cisplatin, and fluorouracil. Conclusions: In advanced unresectable stage IVb LHSCC patients, surgical resection following induction chemotherapy appears to improve survival outcomes. [ABSTRACT FROM AUTHOR]