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Background: In Europe, induction chemotherapy (ICT) followed by radiotherapy is preferred to conventional chemoradiotherapy to avoid total laryngectomy in patients with laryngeal/hypopharyngeal cancer. In comparison with conventional radiotherapy, bioradiotherapy with cetuximab significantly improves locoregional control rates (LCRs) and overall survival (OS) without any increase in unmanageable toxicity., Methods: Patients included had untreated non-metastatic stage III-IV laryngeal/hypopharyngeal invasive squamous cell carcinoma. Good responders after three cycles of docetaxel-cisplatin-5-fluorouracil (TPF)-ICT (docetaxel and cisplatin, 75 mg/m 2 each on day 1, and 5-fluorouracil, 750 mg/m 2 /day on days 1-5) every 3 weeks were randomised to receive radiotherapy (70 Gy) with concurrent cisplatin (100 mg/m 2 /day on days 1, 22 and 43 of radiotherapy) or cetuximab (400 mg/m 2 of loading dose, 250 mg/m 2 /week during radiotherapy). The primary end-point was larynx preservation. The secondary end-points were laryngo-oesophageal dysfunction-free survival (LEDFS), LCR and OS., Results: A total of 153 patients were enrolled. Among 126 TPF-ICT responders, 116 were randomised to receive either cisplatin (n = 60) or cetuximab (n = 56). The median follow-up was 77.5 months. Five-year OS rates were 66.6% (95% confidence interval [CI]: 0.54-0.79) versus 66.9% (95% CI: 0.54-0.79) (p = 0.9), respectively. Five-year LCRs were 79.8% (95% CI: 69.5-90.0) versus 67.8% (95% CI: 55.1-80.5%) (p = 0.18). Five-year LEDFS was 62.2% (95% CI: 49.7-74.8%) versus 56.2% (95% CI: 43.0-69.4) (p = 0.38). Late grade III/IV salivary gland and laryngeal toxicity occurred in 10.3% versus 9.8% and 6.8% versus 11.8% of patients receiving cisplatin-radiotherapy versus cetuximab, respectively., Conclusions: No significant difference in LEDFS was observed between the two arms. TPF-ICT followed by conventional chemoradiotherapy or cetuximab was feasible, and long-term toxicity was not statistically different between the two arms. LEDFS appears as a relevant end-point., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: The purpose of this study is to determine the effects of various prognostic factors for early glottic cancer patients who underwent radiotherapy., Methods: We retrospectively reviewed the all patients who were treated at our hospital for early glottic squamous cell carcinoma from 2004 to 2016. Data included patient's age, sex, T classification, tumor size, pathological grade, anterior commissure involvement, subglottic extension, laryngeal ventricle involvement, and restriction of vocal cord movement., Results: There were 74 patients with T1 tumors and 31 with T2 tumors. Recurrence was found in four patients with T1 and eight patients with T2. There were 99 males and six females enrolled, and the mean age was 67.5 ± 9.2 years for T1a, 67.3 ± 11.2 years for T1b, and 67.4 ± 7.9 years for T2. One patient with recurrence after 1 month was thought to have a residual tumor. The 5-year overall survival (OS) rate and the 5-year disease-specific survival (DSS) rate for T1-T2 patients were both 100%. The rate of larynx preservation was 94.6% for T1 and 74.2% for T2. A univariate analysis showed that the effective factors were age, T, size, SE. A multivariate logistic regression analysis showed that age influenced the recurrence status. Size is also suspected to be a prognostic factor., Conclusions: This study revealed that the effective factors were age, T, size, and SE., Level of Evidence: 4 Laryngoscope, 130:1701-1706, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Introduction: The authors provide an updated, systematic and comprehensive summary of the literature concerning management of the N0 neck in patients for whom primary irradiation for squamous cell carcinoma of the larynx has been unsuccessful and salvage surgery in the form of total laryngectomy (TL) advocated., Methods: Bibliographic databases MEDLINE, Cochrane, PubMed and Embase were searched from inception to April 2019, with no language restrictions. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Risk of bias was defined using the Joanna Briggs Institute guidelines. Outcome measures were defined as the impact of END on locoregional control, complication rate, disease-specific and overall survival (DSS and OS)., Results: The primary search identified 19 eligible articles, comprising 1353 patients, (1552 ENDs). The overall risk of occult metastases was 14% (9% of ENDs). The relative risk (RR) of developing complications was 1.29 when END was performed, compared to observation of the neck (CI 0.86-1.92). Contrariwise, patients in whom the neck was managed with neck dissection had a decreased risk of developing regional recurrence (RR 0.62, CI 0.35-1.08). There was no statistically significant variation between DSS and OS between END and neck observation groups, respectively., Summary: END during salvage TL may reduce the rate of regional recurrence, but not at the expense of improving DSS or OS. Rates of occult metastases, regional recurrence and "cure" through salvage neck dissection are not equivalent. Significant bias in all collated manuscripts should encourage the reader to interpret conclusions with caution. Patients should be fully involved in the decision-making process and their performance status and co-morbidities taken carefully into account when deciding to increase the extent of surgery, which we believe should remain limited to TL in the majority of cases., (© 2020 John Wiley & Sons Ltd.)

Objective: The purpose of this study was to demonstrate the prognostic role of inflammatory biomarkers in patients with laryngeal squamous cell carcinoma., Methods: For this study, we enrolled 151 patients who had undergone surgery for laryngeal squamous cell carcinoma. We assessed the preoperative neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR), mean platelet volume, red cell distribution width, and alkaline phosphatase. The chi-square test, Kaplan-Meier survival analysis, and Cox proportional hazards model were conducted on overall survival, progression-free survival, locoregional recurrence-free survival, and distant metastasis-free survival of patients with laryngeal squamous cell carcinoma., Results: Both Kaplan-Meier analysis and univariate analysis showed significant prognostic differences with age, laryngectomy methods, Tumor Node Metastasis (TNM) staging, tumor location, NLR, PLR, MLR, and mean platelet volume. Multivariate analysis indicated that NLR (overall survival: hazard ratio [HR] = 3.02, 95% confidence interval [CI]: 1.28-7.10, P = .011), PLR (overall survival: HR = 0.33, 95% CI: 0.14-0.78, P = .011; progression-free survival: HR = 0.016,95% CI: 0.10-0.79, P = .016), and MLR (overall survival: HR = 0.29, 95% CI: 0.11-0.76, P = .012) were independent prognostic factors for 5-year survival. However, red cell distribution width and alkaline phosphatase had no significant difference in overall survival and progression-free survival., Conclusions: Preoperative high NLR, PLR, and MLR were associated with poor prognosis. They were found to be effective and reliable inflammatory biomarkers for patients with laryngeal squamous cell carcinoma.

Background: Open partial laryngeal surgery (OPLS) represents a wide array of procedures that can be fitted to treat different types of laryngeal cancer (LC). We would like to present our 30-years' institutional experience, to analyze survival outcomes and to critically discuss prognostic factors., Methods: We reviewed all cases of OPLS performed at our Institution from 1982 to 2016 for LC. Survival analysis by Kaplan-Meier estimate was performed and prognostic variables by multivariate analysis were identified., Results: Mean follow-up time was 68.3 months, 30-day mortality 0.2%, subsequent functional total laryngectomy (TL) was 1.01%. Over 80% of cases were stage I to II. We had 25 local, 62 regional and eight distant recurrences. Local control was 94.9%, overall survival (OS) was 83.4% and disease-specific survival (DSS) was 87.7%. The two major risk factors significantly associated with the risk of death were cT and cN stage. CONCLUSIONS: We have confirmed that OPLS represents an oncologically sound option in the treatment of LC despite the emergence of non-surgical strategies and new transoral mininvasive techniques. Our results highlight that accurate staging, correct selection of the patient and a strong surgical expertise are of paramount importance in this type of surgery.

Background: The choice of treatment in laryngeal cancer is mainly based on tumor stage, post-treatment morbidity and quality of life. Biological tumor markers might also be of potential clinical relevance., Objective of the Review: The aim was to systematically review the value of published biological tumor markers to predict local control in laryngeal cancer patients treated with definitive radiotherapy., Type of Review: Systematic review., Search Strategy: PubMed, Embase, Cochrane Library., Evaluation Method: A literature search was performed using multiple terms for laryngeal cancer, radiotherapy, biological markers, detection methods and local control or survival. Studies regarding the relation between biological tumor markers and local control or survival in laryngeal cancer patients primarily treated with radiotherapy were included. Markers were clustered on biological function. Quality of all studies was assessed. Study selection, data extraction and quality assessment was performed by two independent reviewers., Results: A total of 52 studies out of 618 manuscripts, concerning 118 markers, were included. EGFR and P53 showed consistent evidence for not being predictive of local control after primary radiotherapy, whereas proliferation markers (ie high Ki-67 expression) showed some, but no consistent, evidence for being predictive of better local control. Other clusters of markers (markers involved in angiogenesis and hypoxia, apoptosis markers, cell cycle, COX-2 and DNA characteristics) showed no consistent evidence towards being predictors of local control after primary radiotherapy., Conclusions: Cell proliferation could be of potential interest for predicting local control after primary radiotherapy in laryngeal cancer patients, whereas EGFR and p53 are not predictive in contrast to some previous analyses. Large diversity in research methods is found between studies, which results in contradictory outcomes. Future studies need to be more standardised and well described according to the REMARK criteria in order to have better insight into which biomarkers can be used as predictors of local control after primary radiotherapy., (© 2020 The Authors. Clinical Otolaryngology published by John Wiley & Sons Ltd.)

Purpose: The purpose of the study is to evaluate the expression of NRP-2 and explore its role in Laryngeal squamous cell carcinoma (LSCC)., Materials and Methods: NRP-2 expression in 70 primary LSCC tissue specimens were analyzed by immunohistochemistry and correlated with clinicopathological parameters and patients´ survival rate. Additionally, 9 paired LSCC tissues were evaluated for NRP-2 expression by Western blotting., Results: The Western blotting indicated that NRP-2 expression levels in LSCC were significantly higher than those in the paraneoplastic tissues (P < 0.05). Immunohistochemistry staining revealed that NRP-2 was detected in all primary tumor samples, moreover, high expression of NRP-2 was significantly correlated with TNM stage (P < 0.05), clinical stage (P < 0.05), histological classification (P < 0.05), lymph node metastasis (P < 0.05) and recurrence (P = 0.001). Survival curves determined by the Kaplan-Meier method showed that high expression of NRP-2 can reduce overall survival (both group P < 0.05). Then we combined the NRP-2 expression and lymph node status, and Kaplan-Meier survival showed patients with high expression of NRP-2 or lymph node metastasis (+) had both shorter disease-free and overall survival than others (both P < 0.05). Multivariate Cox proportional hazards model analysis confirmed that histological grade (P = 0.045), lymph node metastasis (P = 0.020) and high expression of NRP-2 (P = 0.033) were statistically significant, independent predictor of prognosis., Conclusions: NRP-2 may contribute to LSCC progression and represents as a novel prognostic indicator as well as a potential therapeutic target for LSCC., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Inflammatory bowel disease (IBD) patients are at increased risk for developing extra-intestinal malignancies, mainly due to immunosuppressive medication. The risk of developing head and neck cancer in immunosuppressed transplant patients is increased. The relation between IBD patients and laryngeal cancer (LC) remains unclear. We aimed (1) to identify risk factors in IBD patients for LC development and (2) to compare clinical characteristics, outcome, and survival of LC in IBD patients with the general population., Methods: All IBD patients with LC (1993-2011) were retrospectively identified using the Dutch Pathology Database. We performed 2 case-control studies: (1) to identify risk factors, we compared patients with IBD and LC (cases) with the general IBD population; (2) to analyze LC survival, we compared cases with controls from the general LC population., Results: We included 55 cases, 1800 IBD controls, and 2018 LC controls. Cases were more frequently male compared with IBD controls (P < 0.001). For ulcerative colitis (UC), cases were older at IBD diagnosis (P < 0.001). Crohn's disease (CD) cases were more frequently tobacco users (P < 0.001) and more often had stricturing (P = 0.006) and penetrating (P = 0.008) disease. We found no survival difference. Immunosuppressive medication had no impact on survival., Conclusions: Male sex was a risk factor for LC in IBD patients. Older age at IBD diagnosis was a risk factor for UC to develop LC. Tobacco use and stricturing and penetrating disease were risk factors for LC development in CD patients. Inflammatory bowel disease was not associated with impaired survival of LC. Immunosuppressive medication had no influence on survival., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

It is known that lymph node metastasis lowers the survival rates in laryngeal carcinoma. This study aimed to investigate the effect of extranodal extension in lymph node metastasis on survival. The demographic characteristics and histopathologic results of 81 patients who underwent total laryngectomy and neck dissection due to advanced larynx squamous cell carcinoma between 2011 and 2018 were reviewed retrospectively. The patients were divided into 3 groups by lymph node metastasis status as reactive lymph node (group 1), lymph node metastasis without detected extranodal extension (group 2), and lymph node metastasis with detected extranodal extension (group 3). Survival analysis was performed between these 3 groups. In the patient population with a mean age of 61.56 years consisting of 6 females and 75 males, demographic characteristics between groups were comparable. Overall survival (OS) rates were detected to be 81% in group 1, 69.2% in group 2, and 61.5% in group 3. Two-year OS rates were detected to be 66.7% in group 1, 46.2% in group 2, and 38.5% in group 3. Statistical difference was detected between group 1 and group 3 both for OS and 2-year OS ( P = .014, P = .008, respectively). No statistical difference was detected between group 2 and group 1, and between group 2 and group 3. In this study, we found a negative effect of detecting neck lymphadenopathy metastasis and extranodal extension on survival in patients who underwent total laryngectomy and neck dissection due to advanced laryngeal carcinoma.

Objective: Investigate the impact of medical comorbidities on treatment regimen and overall survival (OS) in patients with locally advanced laryngeal cancer., Study Design: Retrospective Review of the National Cancer Database (NCDB)., Methods: The NCDB was queried for patients with T3 and T4 laryngeal cancer. Comorbidity scores were calculated from the Charlson-Deyo comorbidity index (CDCI). Univariate and multivariate analyses explored the association of CDCI scores on treatment regimen and OS., Results: 14,053 patients were analyzed. 65% of patients had a CDCI score of 0, whereas 25%, 7%, and 3% had CDCI score of 1, 2, and ≥3, respectively. As patients' CDCI increased, they became more likely to receive treatment options other than a laryngectomy or chemoradiation therapy (CRT) (P < 0.0001). Patients with CDCI ≥1 were more likely have a laryngectomy than those with CDCI 0 (P < 0.0001). In patients with T3 tumors, OS did not differ between those receiving CRT versus laryngectomy with any CDCI score. In patients with T4 tumors, laryngectomy was associated with improved OS compared to CRT across all CDCI scores except CDCI ≥3., Conclusion: Our results support the current national guidelines with a recommendation for CRT or TL for T3 tumors and a preference for TL for T4 tumors. These outcomes are generally consistent in patients as their CDCI scores increases., Level of Evidence: NA Laryngoscope, 130:1459-1464, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Several recent studies have indicated that the lymph node ratio (LNR) is an independent prognostic factor for laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC). The purpose of this paper is to assess the prognostic value of LNR and explore appropriate cutoff values by conducting a systematic review and meta-analysis., Methods: Pubmed, Embase (via Ovid), and Cochrane library were systematically searched for studies on the prognostic value of LNR in LHSCC up to October 31, 2019. Then, Literature review, data extraction, and quality assessment of eligible studies were performed by two independent reviewers back-to-back. Lastly, Stata 14.0 software was hired to conduct a meta-analysis., Results: A total of 445 articles were retrieved, and 13 studies published in English between 2013 and 2019 were included after the title/abstract and full-text screening. Among the 13 studies contributed to 4197 patients, seven studies were about hypopharyngeal squamous cell carcinoma (HPSCC), four studies about laryngeal squamous cell carcinoma (LSCC), and the remaining two studies about LHSCC. The meta-analysis results showed that shorter overall survival (OS) (HR 1.49; 95%CI: 1.18 to 1.88), disease-specific survival (DSS) (HR 1.66; 95%CI: 1.32 to 2.07) and disease-free survival (DFS) (HR 2.04; 95%CI: 1.54 to 2.71) were significantly correlated with a higher LNR in a random-effect model. The cutoff values of eligible studies were varied from 0.03 to 0.14, and the lowest significant LNR was 0.044., Conclusion: LNR is a valuable prognostic factor in the survival of LHSCC and may be used to improve the tumor staging systems, which, however, requires the solid support of more high-quality studies.

Objective: To study if pre-treatment CT texture features in locally advanced squamous cell carcinoma of laryngo-pharynx can predict long-term local control and laryngectomy free survival (LFS)., Methods: Image texture features of 60 patients treated with chemoradiation (CTRT) within an ethically approved study were studied on contrast-enhanced images using a texture analysis research software (TexRad, UK). A filtration-histogram technique was used where the filtration step extracted and enhanced features of different sizes and intensity variations corresponding to a particular spatial scale filter (SSF): SSF = 0 (without filtration), SSF = 2 mm (fine texture), SSF = 3-5 mm (medium texture) and SSF = 6 mm (coarse texture). Quantification by statistical and histogram technique comprised mean intensity, standard-deviation, entropy, mean positive pixels, skewness and kurtosis. The ability of texture analysis to predict LFS or local control was determined using Kaplan-Meier analysis and multivariate cox model., Results: Median follow-up of patients was 24 months (95% CI:20-28). 39 (65%) patients were locally controlled at last follow-up. 10 (16%) had undergone salvage laryngectomy after CTRT. For both local control & LFS, threshold optimal cut-off values of texture features were analyzed. Medium filtered-texture feature that were associated with poorer laryngectomy free survival were entropy ≥4.54, ( p = 0.006), kurtosis ≥4.18; p = 0.019, skewness ≤-0.59, p = 0.001, and standard deviation ≥43.18; p = 0.009). Inferior local control was associated with medium filtered features entropy ≥4.54; p 0.01 and skewness ≤ - 0.12; p = 0.02. Using fine filters, entropy ≥4.29 and kurtosis ≥-0.27 were also associated with inferior local control ( p = 0.01 for both parameters). Multivariate analysis showed medium filter entropy as an independent predictor for LFS and local control ( p < 0.001 & p = 0.001)., Conclusion: Medium texture entropy is a predictor for inferior local control and laryngectomy free survival in locally advanced laryngo-pharyngeal cancer and this can complement clinico-radiological factors in predicting prognosticating these tumors., Advances in Knowledge: Texture features play an important role as a surrogate imaging biomarker for predicting local control and laryngectomy free survival in locally advanced laryngo-pharyngeal tumors treated with definitive chemoradiation.

Objectives/hypothesis: To characterize patients undergoing laryngeal transoral robotic surgery (TORS) and compare to open partial surgery and transoral laser microsurgery (TLM) in achieving negative margins, requiring adjuvant radiation, and overall survival., Study Design: Retrospective database analysis., Methods: Early-stage (T1/2) laryngeal squamous cell carcinoma patients from the National Cancer Database. Univariable and multivariable logistic and Cox regressions were used to identify predictors., Results: There were 1,780 patients included in the study (186 [10.4%] = TORS; 523 [29.4%] = open surgery; 1,071 [60.2%] = TLM). TORS was more commonly treated at academic centers (68.8% = open surgery, 53.9% = TLM, 71.0% = TORS; P < .001) and had more T2 (52.7% = TORS, 46.7% = open surgery, 20.5% = TLM; P < .001) and N-positive disease (26.9% = TORS, 19.5% = open surgery, 5.5% = TLM; P < .001). Surgical approach was significantly associated with margin status (positive margin rates: TORS = 17.4%, TLM = 20.0%, open surgery = 13.8%) between open surgery and TLM in multivariable analysis (compared to open surgery, TLM: 1.63 [1.12-2.38], TORS: 1.18 [0.72-1.94]; P = .04). Surgical approach was not associated with receipt of adjuvant radiation (compared to open surgery, TLM: 1.52 [1.04-2.24], TORS: 1.56 [0.97-2.49]; P = .05). It was not associated with margins or adjuvant radiation in supraglottic patients. TORS had the highest 5-year overall survival, although the survival for TLM was similar (68.7% and 64.8%, respectively), and both were higher than that of open surgery (59.1%; P = .01). In multivariable Cox regression for supraglottic patients, there was no observed difference between TORS and open surgery (compared to TORS, open surgery: 1.44 [0.93-2.24]; P = .25)., Conclusions: On multivariable analysis, there was no observed difference in margin status in TORS patients compared to TLM and open surgery (in both the total cohort and supraglottic subgroup). Similarly there was no observed difference in necessitating adjuvant radiation. In Cox regression, there was no observed difference between TORS and open surgery in overall survival for supraglottic patients. This study suggests that TORS may be a viable treatment option for early-stage laryngeal cancer., Level of Evidence: 4 Laryngoscope, 130:1195-1201, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Introduction: Human papilloma virus is an etiological risk factor for a subset of head and neck squamous cell carcinomas. HPV has been proven to be a powerful prognostic biomarker for oropharyngeal cancer, but its role in the larynx has not been explored in depth. The developmental mechanisms of laryngeal carcinomas are quite complex and controlled by various factors. Smoking and alcohol are most important risk factors. Recent studies indicate that HPV infection also plays an important role in larynx carcinomas. HPV related laryngeal carcinomas especially occur at the supraglottic region of larynx., Objective: We aimed to determine the frequency of HPV/protein16 positivity in patients with laryngeal carcinoma and association of HPV and/or p16 positivity with variables such as age, sex, smoking habits, tumor localization, lymph node metastasis, recurrence and survival in advanced stage laryngeal carcinoma in our study., Methods: This retrospective study included 90 patients with advanced laryngeal carcinoma. The Control group was 10 normal larynx mucosa specimens. The presence of HPV was investigated polyclonally by polymerase chain reaction, and protein16 with immunohistochemical method. In HPV positive cases, the presence of HPV types 16, 18 were evaluated by polymerase chain reaction. Demographic features of patients were noted. Patient survival and association with HPV/protein16 was determined., Results: Polyclonal HPV positivity was detected in 11 (12.2%) of 90 cases. Out of these 11 cases, HPV 16 was positive in 6, HPV 18 in 4, and both HPV 16 and 18 were positive in 1. In 18 (20%) of the cases, p16 was positive. Six of the cases (6.6%) had both HPV and protein16 positivity. In cases where protein16 alone or HPV and protein16 were co-positive, alcohol use was less and the tumor was found more likely to be localized in the supraglottic area. These ratios were statistically significant. Supraglottic localization of tumor was determined to be increased in protein16 positive cases. The correlation between protein16 positivity and supraglottic area location was determined to be statistically significant (p =  0.011). 55.6% of protein16 positive cases was located in the supraglottic region, 33.3% was glottic and 11.1% was transglottic. Although life expectancy over 5 years were numerically higher in HPV and protein16 positive cases, this was not found to be statistically significant. There was no statistically significant relationship between HPV positivity and mean age, differentiation, smoking and alcohol use, tumor progression, lymph node metastasis, localization, recurrence, cause of mortality and treatment methods in our study. The mean follow-up period of our patients was 6.7 years., Conclusion: The close relationship between HPV and oropharyngeal squamous cell carcinoma could not be shown in larynx malignancy in many studies, including our study. Our findings support a limited role of HPV in laryngeal carcinogenesis. Protein16 is not a reliable surrogate for HPV status in laryngeal cancers and is not a predictor of laryngeal cancer survival. Supraglottic localization of tumor was determined to be increased in protein16 positive cases. The correlation between protein16 positivity and supraglottic area location was determined to be statistically significant. There is a need for more populated clinical trials, where neoplastic proliferation is better demonstrated and the accuracy of the results obtained is supported by different techniques., (Copyright © 2019 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

Objectives/hypothesis: Prognostic variables upon presentation can assist in recommending the optimal treatment for patients and may help in management of patient's expectations and side effects. Our objective was to evaluate prognostic factors for survival and nonfunctional larynx in patients with laryngeal squamous cell carcinoma (SCC)., Study Design: Retrospective chart review., Methods: All patients diagnosed as having laryngeal SCC from January 2007 through December 2016 in a tertiary, university-affiliated medical center were reviewed. Main outcomes were survival and nonfunctional larynx rate., Results: Two hundred sixty-five patients were identified; the male:female ratio was 4.5:1. Mean age at diagnosis was 64 ± 11.8 years. Overall and disease-free survival were 7.9 and 6.7 years, respectively. A univariate analysis found that older age significantly affected survival. Alcohol abuse, diabetes mellitus, and advanced disease stage at presentation were also found to decrease survival but were not significant. A multivariate Cox regression found age, alcohol abuse, and advanced disease stage to significantly affect and lower survival (P < .05). Of the entire cohort 19% were defined as having a nonfunctional larynx (e.g., tracheostomy or feeding-tube dependent). A backward logistic regression found that male sex and advanced disease stage increased the risk, and anterior commissure involvement was found to lower the probability of nonfunctional larynx (P < .01)., Conclusions: Older age, history of alcohol use, and advanced disease stage at presentation negatively affect survival in larynx cancer patients. Male gender and advanced disease stage increased the risk, and anterior commissure involvement was found to lower the risk for tracheostomy or feeding-tube dependency., Level of Evidence: 4 Laryngoscope, 130:1202-1205, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: It has been demonstrated that miRNAs play critical roles in the tumorigenesis and progression of various tumors. Objective: The purpose of this research was to determine the serum miR-632 levels in patients with laryngeal squamous cell carcinoma (LSCC) and to investigate its diagnostic and prognostic value. Materials and methods: We detected serum miR-632 levels in 162 LSCC patients and 42 healthy volunteers. The ROC curve was carried out to determine diagnostic accuracy. Results: We observed that serum miR-632 levels were upregulated in LSCC patients compared with healthy volunteers ( p  < .01). Subsequent results from ROC indicated that high sensitivity and specificity of serum miR-632 for diagnosing LSCC (area under the curve 0.8828). In addition, it was found that high expressions of serum miR-632 were significantly associated with advanced N stage ( p  = .020), histological grade ( p  = .001), and TNM stage ( p  = .014). Furthermore, patients with higher serum miR-632 expression had a shorter OS and DFS time than those with lower serum miR-632 levels. Conclusion: Our data revealed that serum miR-632 may be a potential noninvasive biomarker which may become a potential diagnostic and prognostic biomarker for LSCC patients.

Objective: The value of adjuvant therapy in resected laryngeal cancer remains controversial. This large SEER-based cohort study aimed to investigate the existing parameters of lymph node status that could predict survival outcomes and the prognostic value of adjuvant treatment in resected laryngeal carcinoma., Methods: Population-based data from the US Surveillance, Epidemiology, and End Results (SEER-18) Program on patients after laryngectomy and lymphadenectomy (2004-2015) were analyzed. The optimal cut-off values for examined lymph nodes number (ELNs) and metastatic lymph nodes ratio (MLNR) were determined using the X-tile program. Associations of ELNs and MLNR with overall survival were investigated through Cox regression analysis. A survival-predicting model was then constructed to stratified patients. The prognostic value of adjuvant therapy was evaluated in different subgroups., Results: A total of 2122 patients with resected laryngeal cancer were analyzed. A novel survival-predicting model was proposed based on ELNs, MLNR, and other clinicopathological characteristics. Patients were stratified into three subgroups with the increasing risk of death. Only patients in the high-risk group who receiving adjuvant treatment had a significantly better survival outcome than those receiving surgery alone., Conclusion: A new survival-predicting model was established in this study, which was superior in assessing the survival outcomes of patients with resected laryngeal cancer. Notably, this model was also able to assist in the decision making of adjuvant therapy for patients and physicians., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: X inactivate-specific transcript (XIST) is an attractive long noncoding RNA (lncRNA) functioning as an indicator of various human tumors, including laryngeal squamous cell carcinoma (LSCC). The present study was conducted to explore a novel regulatory network of lncRNA XIST in LSCC cells., Materials and Methods: Quantitative real-time polymerase chain reaction (QRT-PCR) was used to detect the expression levels of XIST, miR-125b-5p and TRIB2 in LSCC cells and tissues. Cell proliferation, apoptosis, migration and invasion were detected by Cell Counting Kit-8 (CCK-8), flow cytometry and Transwell assays, separately. The relationship among XIST, miR-125b-5p and tribbles homolog 2 (TRIB2) was predicted by starBase v2.0 or TargetScan and confirmed by Dual-luciferase reporter assay. The TRIB2 protein expression was quantified by Western blot assay. Murine xenograft model was utilized to validate the role of XIST in vivo., Results: XIST was notably up-regulated in LSCC tissues and cells, and the high level of XIST was associated with the low survival rate of LSCC patients. XIST knockdown markedly repressed cell proliferation, migration and invasion and promoted the apoptosis of LSCC cells and the effects were antagonized by loss of miR-125b-5p. MiR-125b-5p was a target of XIST in LSCC cells, and it could bind to TRIB2 as well. Moreover, XIST-loss-induced down-regulation of TRIB2 could be significantly reversed by miR-125b-5p knockdown. XIST promoted the growth of LSCC tumor in vivo., Conclusion: LncRNA XIST promoted the malignance of LSCC cells partly through competitively binding to miR-125b-5p, which in turn increased TRIB2 expression., (© 2020 The Author(s).)

Background: The aim of this study was to evaluate the prognostic value of radiomics signature and nomogram based on contrast-enhanced computed tomography (CT) in patients after surgical resection of laryngeal squamous cell carcinoma (LSCC)., Methods: All patients (n = 136) were divided into the training cohort (n = 96) and validation cohort (n = 40). The LASSO regression method was performed to construct radiomics signature from CT texture features. Then a radiomics nomogram incorporating the radiomics signature and clinicopathologic factors was established to predict overall survival (OS). The validation of nomogram was evaluated by calibration curve, concordance index (C-index) and decision curve., Results: Based on three selected texture features, the radiomics signature showed high C-indexes of 0.782 (95%CI: 0.656-0.909) and 0.752 (95%CI, 0.614-0.891) in the two cohorts. The radiomics nomogram had significantly better discrimination capability than cancer staging in the training cohort (C-index, 0.817 vs. 0.682; P = 0.009) and validation cohort (C-index, 0.913 vs. 0.699; P = 0.019), as well as a good agreement between predicted and actual survival in calibration curves. Decision curve analysis also suggested improved clinical utility of radiomics nomogram., Conclusions: Radiomics signature and nomogram showed favorable prediction accuracy for OS, which might facilitate the individualized risk stratification and clinical decision-making in LSCC patients.

Objectives/hypothesis: We studied the influence of the neutrophil-to-lymphocyte ratio (NLR) and anemia on the response to induction chemotherapy (IC) and survival outcomes in laryngeal cancer patients treated with a preservation protocol., Study Design: Retrospective single-center case series., Methods: We analyzed patients with T3 laryngeal cancer treated with IC using a preservation protocol. The NLR and hemoglobin levels were assessed before treatment and after IC. The response to chemotherapy was assessed using Response Evaluation Criteria in Solid Tumours 1.1 and World Heath Organization standards. The oncological endpoints were overall survival (OS) and disease-free survival (DFS)., Results: Sixty-eight patients were analyzed. The median NLR and hemoglobin levels before and after IC were 2.76 and 14.5 g/dL, and 2.01 and 11.6 g/dL, respectively. The NLR and anemia before treatment were not correlated, and they were not associated with the response to chemotherapy. However, an NLR > 5 and anemia before treatment were both associated with shorter OS and DFS. Notably, they were the only factors found to be significantly associated with survival outcomes., Conclusions: In laryngeal cancer, patients treated with a preservation protocol, a high NLR ratio, and anemia before IC were associated with shorter survival, independently of the response to chemotherapy., Level of Evidence: 4 Laryngoscope, 130:E144-E150, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: This study was aimed to evaluate the involvement of lncRNA MALAT1 in modifying chemo-sensitivity of laryngeal squamous cell carcinoma (LSCC) cell lines., Methods: Totally 108 pairs of tumor tissues and matched para-tumor normal tissues were gathered from patients who were pathologically confirmed as LSCC. Meanwhile, LSCC cell lines, including TU686, TU177, AMC-HN-8, and LSC-1, were purchased to evaluate their tolerance to cisplatin, 5-fluorouracil, paclitaxel, and vincristine. Additionally, CCK-8 assay, flow cytometry, transwell assay, and wound healing assay were implemented to assess the part of MALAT1 in modulating viability, apoptosis, invasion, and migration of LSCC cell lines., Results: MALAT1 expression was higher in LSCC tissues than in adjacent normal tissues (P < .05), and LSCC patients who carried highly expressed MALAT1 demonstrated poorer 5-year survival than ones with low MALAT1 expression (P < .05). For another, expression of MALAT1 was also unusually elevated within TU686, TU177, AMC-HN-8, and LSC-1 cell lines as relative to NHBEC cell line (P < .05). The TU686 cell line therein excelled in resisting the growth-curbing effects of 5-fluorouracil (IC50 = 20.44 μmol/L), paclitaxel (IC50 = 35.86 μg/L), and vincristine (IC50 = 0.12 μmol/L), when compared with TU177, AMC-HN-8, and LSC-1 cell line (P < .05). Moreover, there seemed great potential for over-expressed MALAT1 to enhance the chemo-resistance of both TU686 and LSC-1 cell lines (P < .05). Not only that, silencing of MALAT1 tended to undermine the proliferative and metastatic power of TU686 and LSC-1 cell lines (P < .05)., Conclusion: LncRNA MALAT1 counted in triggering tolerance of LSCC against chemo-drugs by boosting metastasis and depressing apoptosis of tumor cells., (© 2019 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals, Inc.)

Spindle cell carcinoma (SpCC) is a rare tumor, which occurs in upper respiratory tract, mainly in larynx. This study aimed to review the clinical and pathological characteristics for diagnosis and prognosis. Retrospective cohort study. All patients with SpCC in upper respiratory tract treated for curative intent was included. All patients were reviewed in search of epithelial component and immunohistochemistry when not found. It was evaluated rate of recurrence and disease-free survival with univariate and multivariate analysis with Kaplan Meier and Cox Regression model adjusted to propensity score indexes (PSI) according to age, gender, site of tumor, stage, surgical treatment, status of margins of surgical resection, lymphatic invasion. There were 16 cases of SpCC.31% were diagnosed with light microscopy and others with immunohistochemistry for epithelial marker. Disease-free survival was higher in early stage disease in univariate and multivariate analysis, as the main prognostic factor. Surgical treatment increases in 2.54 the rate of survival. The SpCC is a rare tumor considered a highly malignant variant of squamous cell carcinoma. It has male predominance and tobacco use as risk factors. Its treatment should follow the same recommendations for squamous cell carcinoma, with surgery as the maintain treatment. Immunohistochemistry is an adjuvant important tool for diagnosis of SpCC.

Objective: To analyse the oncological results of a salvage total laryngectomy in patients with a laryngeal carcinoma., Material and Methods: Retrospective review of a cohort of 241 patients treated with a salvage laryngectomy after a local recurrence. The initial treatment received by these patients was radiotherapy (n=201, 83.4%), chemoradiotherapy (n=19, 7.9%), and partial surgery (n=21, 8.7%), RESULTS: Total laryngectomy as salvage treatment achieved local control of the disease in 81.3% of cases, with a 5-year specific survival of 65.3%. The variables related with specific survival in a univariate analysis were the location of the primary tumour, the local extension of the initial tumour and of the recurrence, the resection margins, and the pathological status of the neck dissections. According to the results of a multivariate analysis, the variables related to specific survival were the status of the resection margins, the presence of simultaneous regional recurrence, and the local extension of the recurrence., Conclusion: The 5-year specific survival of patients treated with a salvage laryngectomy was 65.3%. The variables related with the control of the disease were the status of the resection margins, the presence of simultaneous regional recurrence and the local extension of the recurrence., (Copyright © 2019 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objectives/hypothesis: To examine associations between survival and adherence to National Comprehensive Cancer Network (NCCN) treatment guidelines using an observed-to-expected (O/E) ratio for greater adherence as a risk-adjusted hospital measure of quality care in elderly patients treated for larynx cancer., Study Design: Retrospective analysis of Surveillance, Epidemiology, and End Results (SEER)-Medicare data., Methods: Patients diagnosed with larynx cancer from 2004 to 2007 were evaluated using multivariate regression and survival analysis. A fit logistic regression model was used to calculate an O/E ratio for guideline adherence for each hospital using quality indicators derived from NCCN guidelines for recommended treatment and stratified by hospital volume., Results: Of 1,721 patients treated at 395 hospitals, 43.0% of patients received NCCN guideline-adherent care. Low-volume hospitals (N = 295) treating six or fewer cases treated 765 patients (44.5%), with a mean O/E of 0.96 ± 0.45. Hospitals treating more then six cases with an O/E <1 (N = 32) treated 284 patients (16.5%), with a mean O/E of 0.77 ± 0.18. Hospitals treating more than six cases with an O/E ≥1 (N = 68) treated 672 patients (39.1%), with a mean O/E of 1.17 ± 0.11. Treatment at hospitals with an O/E ≥1 was associated with improved survival (hazard ratio [HR] = 0.83 [95% confidence interval [CI]: 0.70 to 0.98]) and lower mean incremental treatment-related costs (-$3,009 [-$5,226 to -$791]) compared with hospitals with an O/E <1 (HR = 1.00 [0.80 to 1.24]) and the reference group of low-volume hospitals., Conclusions: A hospital-specific O/E for NCCN treatment guideline adherence, combined with a minimum case volume criterion, is associated with survival and treatment-related costs in elderly patients with larynx cancer, and may be a feasible measure of larynx cancer quality of care., Level of Evidence: NA Laryngoscope, 130:672-678, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Purpose: To evaluate the prognostic significance of DNA excision repair gene polymorphisms, excision repair cross-complementation group 1 (ERCC1) and X-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1) polymorphisms were investigated in Japanese patients with head and neck squamous cell carcinoma (HNSCC)., Methods: A total of 225 consecutive patients with HNSCC who underwent surgery or chemoradiotherapy/radiotherapy (CRT/RT) with curative intent as primary treatment from 2006 to 2017 were recruited. ERCC1 C8092A and XRCC1 Arg399Gln polymorphisms in DNA extracted from individual blood samples were determined by the polymerase chain reaction-restriction fragment length polymorphism method. Cumulative survival was estimated by Kaplan-Meier analysis with a log-rank test and Cox proportional hazards model stratified by treatment arm, adjusting for clinical prognostic factors., Results: Multivariate analysis showed that carriers with the ERCC1 8092 (C/A+A/A) genotype (hazard ratio, 3.56; 95% confidence interval, 1.22-7.39; p = 0.02) had significantly worse survival than those with ERCC1 8092 C/C who received CRT/RT. Conversely, the XRCC1 Arg399Gln polymorphism did not influence survival in patients who received CRT/RT as well as surgery., Conclusion: The ERCC1 C8092A polymorphism might be an independent predictor of response to CRT and survival outcome in patients with HNSCC. This is the first report to investigate the role of DNA excision repair gene polymorphisms in patients with head and neck cancer in a Japanese population.

Aim: To evaluate the impact of preoperative platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), derived NLR (dNLR) and lymphocyte-monocyte ratio (LMR) on the prognosis of laryngeal squamous cell carcinoma. Materials & methods: Overall survival and recurrence-free survival (RFS) were analyzed using Kaplan-Meier estimates. Multivariable Cox regression model was used to evaluate the independent prognostic significance of variables. Results: High PLR (>103.96), NLR (>1.96) and dNLR (>1.70) predicted lower RFS according to Kaplan-Meier method. In COX regression model, patients with high PLR had poor RFS estimates compared with those with lower PLR (p < 0.001). Conclusion: Preoperative PLR was a more valuable prognostic factor than NLR, dNLR and LMR for the recurrence of laryngeal squamous cell carcinoma.

Background: The various pathological types of non-squamous cell carcinomas (nSCCs) of the larynx accounted for about 5% laryngeal malignancies, but the knowledge regarding these pathological behaviors, therapeutic models and prognostic factors was limited. Objectives: To investigate the clinical characteristics and the survival outcomes of nSCCs of the larynx. Material and methods: A total of 106 patients diagnosed with laryngeal nSCC between 2003 and 2014 were retrospectively investigated from a cohort of 4,796 patients with laryngeal malignancies. Results: Spindle cell carcinoma, malignant salivary gland carcinoma, neuroendocrine carcinoma, non-Hodgkin's lymphomas, and carcinosarcoma accounted for the majority of the nSCCs of the larynx. In laryngeal nSCCs (excluding non-Hodgkin lymphomas), there was no significant difference in overall survival (OS) by tumor subsite ( p  = .818), clinical-stage ( p  = .051) or T stage ( p  = .412), but the difference in OS by N stage was statistically significant ( p  = .001). Upon comparison of propensity score-matched groups, the OS was longer in SCCs of the larynx ( p  = .0004). Conclusions and significance: Primary nSCC of the larynx is rare, and its diagnosis depends on comprehensive immunohistochemical examination, as the clinical characteristics are non-specific compared with SCC. The overall prognosis of nSCC is relatively poor compared with that of SCC in the larynx.

Objectives: Ambiguous results have been reported on the predictive value of the Ki-67 proliferation index (Ki-67 PI) regarding local control (LC) and survival after primary radiotherapy (RT) in early-stage laryngeal squamous cell cancer (LSCC). Small study size, heterogenic inclusion, variations in immunostaining and cut-off values are attributing factors. Our aim was to elucidate the predictive value of the Ki-67 PI for LC and disease-specific survival (DSS) using a well-defined series of T1-T2 LSCC, standardised automatic immunostaining and digital image analysis (DIA)., Methods: A consecutive and well-defined cohort of 208 patients with T1-T2 LSCC treated with primary RT was selected. The Ki-67 PI was determined using DIA. Mann-Whitney U-tests, logistic and Cox regression analyses were performed to assess associations between Ki-67 PI, clinicopathological variables, LC and DSS., Results: In multivariate Cox regression analysis, poor tumour differentiation (HR 2.20; 95% CI 1.06-4.59, P = .04) and alcohol use (HR 2.84, 95% CI 1.20-6.71; P = .02) were independent predictors for LC. Lymph node positivity was an independent predictor for DSS (HR 3.16, 95% CI 1.16-8.64; P = .03). Ki-67 PI was not associated with LC (HR 1.59; 95% CI 0.89-2.81; P = .11) or DSS (HR 0.98; 95% CI 0.57-1.66; P = .97). In addition, continuous Ki-67 PI was not associated with LC (HR 2.03; 95% CI 0.37-11.14, P = .42) or DSS (HR 0.62; 95% CI 0.05-8.28; P = .72)., Conclusion: The Ki-67 PI was not found to be a predictor for LC or DSS and therefore should not be incorporated in treatment-related decision-making for LSCC., (© 2019 The Authors. Clinical Otolaryngology published by John Wiley & Sons Ltd.)

Objective: The objective of the study was to analyze the results of endoscopic laser microsurgery for early glottic carcinoma treatment (Stages I and II) at a Tertiary Center in Mexico City., Materials and Methods: Descriptive, retrospective review of 40 patients with early glottic carcinoma who were treated with endoscopic laser microsurgery with curative intent at our institution from November 2003 to December 2013., Results: The study yielded 4 pTis, 19 pT1a, 8 pT1b, and 9 pT2 patients. Mean patient follow-up time was 7.4 years (range 3-12.9 years). Post-operative bleeding requiring surgical intervention occurred in 1 (2.5%) patient. Kaplan-Meier results at 3 and 5-year estimates were as follows: overall survival was 92.5 and 87%, respectively; laser only local control was 94.9 and 91.6%, respectively; and disease specific survival and ultimate local control rate were 97.5% for both time periods. We found a 97.5% (39/40) organ preservation rate., Conclusions: Laser microsurgery for glottic carcinoma treatment is an emerging technique in Mexico. Our results are promising as reported by other authors in Europe and United States of America, which support the replicability of the surgical technique refined by Dr. Wolfgang Steiner., (Copyright: © 2020 Permanyer.)

Purpose: Due to a potential exposure to several definite or probable carcinogens, the IARC classified manufacturing of art glass, glass containers, and pressed ware as probably carcinogenic to humans in 1993 (Group 2A). Purpose of this study was to update the evidence from recently published scientific reports., Methods: We searched for peer-reviewed articles published between 1993 and 2018 and combined result in terms of a meta-analysis. Overall, we considered twelve articles for a meta-analytic approach published after 1992., Results: From a meta-analysis we derived a standardized incidence ratio (mSIR) and a standardized mortality ratio (mSMR) for lung cancer in men of 1.25 (95% CI 0.97-1.59) and 1.41 (95% CI 1.11-1.77), respectively. The estimated odds ratio (mOR) from five case-control studies was 1.25 (95% CI 0.90-1.73). Associated with an employment in glass factories, the estimated mSMR for larynx cancer was 2.38 (95% CI 1.23-4.16) based on two cohort studies; the mOR from four case-control studies was 1.35 (95% CI 0.73-2.52). Reports on elevated cancer risks at other sites were not consistent., Conclusions: Only few studies assessed cancer risk solely in glass workers. Gained evidence from more recent reports supports the IARC rating from 1993. Our combined results add limited evidence to a moderately elevated risk for cancer of the airways.

Background: In laryngeal cancer, multidisciplinary treatment improves the patient's quality of life and the possibility of preserving the larynx. Most cases occur in a locally advanced stage. The aim is to present the results according to the stage., Method: A retrospective study which analyzed the clinical stage, type of primary treatment, outcomes, and survival were analyzed., Results: 451 patients were included. The median age was 66 years. The majority of the tumors presented in advanced stage (72%) and the most affected subsite was the glottis (84.5%). In the early stage the most frequent treatment was radiotherapy as the only treatment modality. In stages III and IVA, 65% were resectable. In stage IVB the management was non-surgical, with control in 26% of the cases. Survival at 10 years was related to the clinical stage: 81.7% for stage I and 0% for stages IVB and IVC., Conclusions: Patients with laryngeal cancer should be treated according to the clinical stage, through a multidisciplinary approach. Long-term follow-up showed a worse prognosis for advanced clinical stages., (Copyright: © 2020 Permanyer.)

Aims: To investigate the clinical features, treatment, and outcomes of laryngeal spindle cell carcinoma (SpCC)., Methods: Between 2005 and 2014, patients from our hospital with SpCC of the larynx were retrospectively analyzed alongside patient data from the SEER database of America., Results: A total of 11 patients with SpCC of the larynx were diagnosed and underwent surgery in our hospital. All patients were male and all tumors were located in the glottis. The 3- and 5-year OS rates were both 54.5%. In the SEER database, 148 patients were diagnosed with SpCC of the larynx. The 3- and 5-year OS rates were 72.8 and 63.2%, respectively. According to the comparison of propensity score-matched analysis, the OS was longer in squamous cell carcinoma (SCC) of the larynx (p < 0.0001)., Conclusion: SpCC of the larynx is rare and typically originates in the glottis. Its prognosis is worse than that of laryngeal SCC, and surgery is a reasonable treatment strategy., (© 2020 S. Karger AG, Basel.)

Objective: To evaluate the association of human papilloma virus (HPV) infection with prognosis, specifically overall survival (OS) and disease-free survival (DFS), in laryngeal squamous cell carcinoma (LSCC) patients., Method: A systematic review and meta-analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. LSCC was confirmed on the basis of histopathology, whereas HPV status was confirmed by polymerase chain reaction., Results: A total of 6539 articles were initially searched from 8 databases, of which 11 studies were eligible for our review. A total of 1442 LSCC cases were included in this analysis. Eight studies examined 3-year OS for LSCC. The pooled hazard ratio (HR) from the 8 studies was 0.29 (95% CI: 0.25-0.33). There was a statistically significant difference in 3-year OS between the HPV-negative and -positive groups, with the latter having a better survival. There was no statistically significant differences in 5- and 10-year OS. Five studies examined 3- and 5-year DFS for LSCC, whereas only 3 studies examined 10-year DFS. There was no statistically significant difference in 3-, 5-, and 10-year DFS between the HPV groups., Conclusion: This study evaluated the survival impact of HPV infection in LSCC patients. The OS of the HPV-positive group was better than that of the HPV-negative group in terms of short-term survival. Compared with the HPV-negative group, the HPV-positive group had a better trend of DFS, suggesting that a larger sample size and further exploration of the pathology and local control of HPV-positive tumors are needed., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Definitive radiotherapy is an effective single-modality in T1 glottic cancer. Hypofractionated schemes could offer excellent results in a shorter treatment period. We aimed to evaluate the clinical outcomes and toxicity comparing conventional vs. hypofractionated radiotherapy treatment in T1N0M0-glottic cancer., Patients and Methods: Between Jan-1st, 2005 and August-1st, 2017, in a prospective cohort study, with 10-year follow-up, 138 patients were treated with conventional schedule 2 Gy/day, total dose 70 Gy/7 weeks (N = 71) or hypofractionated schedule 2, 2-2, 25 Gy/day, total dose 63, 8-63 Gy/5, 5 weeks (N = 67). Endpoints were clinical-response rate, local relapse-free survival (LRFS), laryngectomy-free survival (LFS), toxicity rates, relapse-free survival (RFS), metastasis-free survival (MFS), second tumour-free survival (2TFS), and overall survival (OS)., Results: All patients showed a complete clinical response. No differences were found for LRFS (p = 0.869), LFS (p = 0.975), RFS (p = 0.767), MFS (p = 0.601), 2TFS (p = 0.293), or OS (p = 0.685). Acute toxicity for skin and mucosae was similar (p = 0.550 and p = 0.698). Acute laryngeal toxicity was higher in the hypofractionation group (p = 0.004), due to an increase in slight moderate grade. No differences in late laryngeal edema were found (p = 0.989)., Conclusion: Radiotherapy offers high rate survival, local control, and larynx preservation after 5-10-year follow-up. A hypofractionation could be preferable, since it offers the same results as conventional with fewer treatment sessions.

The aim is to estimate the prognostic value of lactate dehydrogenase (LDH) in patients undergoing surgical resection for laryngeal squamous cell carcinoma (LSCC). A total of 640 resected LSCC patients were included. Preoperative lactate dehydrogenase (LDH) was assessed. Kaplan-Meier survival analysis and Cox regression analysis were conducted for overall survival (OS) and recurrence-free survival (RFS). Kaplan-Meier analysis, univariate analysis and multivariate analysis demonstrated significant prognostic value for preoperative LDH. Although LDH was predictor of OS, it failed to be a predictor of RFS. The univariate HR and 95% CI of LDH were 0.484 and 0.357-0.658 (P < 0.0001). The multivariate analysis showed that LDH (HR = 0.518, 95% CI: 0.380-0.705, p < 0.0001) was related to OS. Elevated preoperative LDH >132 IU/L was significantly associated with better survival. Preoperative LDH might be an independent prognostic marker of OS in LSCC patients undergoing surgical resection.

Background: Early laryngeal cancer treated with definitive radiotherapy or surgery has a high cure rate. This study evaluated the patterns of treatment failure and long-term results of early laryngeal cancers treated with definitive radiotherapy., Method: From January 2002 to December 2014, a total of 242 patients with early-stage laryngeal cancers were treated with radical radiotherapy., Results: All patients had squamous cell carcinoma of the larynx (92 per cent male and 8 per cent female). Median follow-up was 4.5 years. The majority of patients were smokers (57.4 per cent). Local failure was seen in 12.5 per cent of stage I patients and 22.8 per cent of stage II patients. The 5-year overall survival and disease specific survival were 84 per cent and 91 per cent, respectively., Conclusion: In summary, radiotherapy is a suitable treatment modality for patients with early-stage laryngeal cancer, with an overall locoregional control rate of 84 per cent. Patients who fail radiotherapy may still undergo salvage laryngectomy.

Background and Objectives: Controversial prognostic factors of primary CO 2 laser cordectomy are anterior commissure involvement (ACI) and status of margin., Study Design/materials and Methods: Retrospective analysis of oncological outcomes in 102 patients with early glottic cancer undergoing laser cordectomy between 2013 and 2015., Results: The T stages distribution included: 72.6% T1a, 14.7% T1b, and 12.7% T2. The ACI was diagnosed in 26 patients. The primary cordectomy was radical in 72 patients. The 2- and 5-year disease free survival (DFS) for all patients were, respectively, 83.3% and 77.3%.The 2-year DFS rates for T1a, T1b, T2 were, respectively, 91.7%, 66.7%, and 53.9% and the differences were statistically significant (P < 0.001). The 2-year DFS rates according to the ACI and free anterior commissure tumors were, respectively, 65.4% and 89.2%, and the ACI indicated worse prognosis (P = 0.057). The 2-year DFS rates according to margins status were higher for patients with close or positive margins, who had second resection (88.9%) compared with those of negative margins (80.9%) (P = 0.340). Lasers Surg. Med. © 2019 Wiley Periodicals, Inc., (© 2019 Wiley Periodicals, Inc.)

Objectives: This multicenter retrospective cohort study aimed to evaluate the significance of adding S-1 to radiotherapy (RT) for the treatment of T2N0 glottic cancer using a propensity score matched analysis in Japan., Materials and Methods: This study was conducted on 287 patients with T2N0 glottic cancer who were treated with definitive RT or chemoradiotherapy with S-1 (S-1 RT) between April 2007 and March 2017. Propensity score matched analysis was performed to ensure the well-balanced characteristics of the groups of patients who received RT alone and S-1 RT. Overall, progression-free and laryngectomy-free survivals and local control and laryngeal preservation rates were compared., Results: Fifty-four pairs of patients were selected after performing propensity score matched analysis. Clinical characteristics were well-balanced between the two groups. The overall survival of patients in the S-1 RT group was significantly better than those in the RT alone group (P = 0.008). The progression-free and laryngectomy-free survivals of patients in the S-1 RT group were also better than those in the RT alone group; however, the differences were not significant. In contrast, patients in the S-1 RT group had slightly lower local control and laryngeal preservation rates compared with those in the RT alone group. The incidence of dermatitis in the S-1 RT group was significantly higher than that in the RT alone group in the matched population (P = 0.013)., Conclusions: The addition of S-1 to RT for the treatment of T2N0 glottic cancer was not associated with better local control and laryngeal preservation rates in this study., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The purpose of this study was to investigate significance of HPV16 DNA/p16 for survival of patients with laryngeal squamous cell carcinoma (LSCC)., Methods: HPV16 DNA and p16 status in 812 LSCC patients were determined. The survival was performed using Kaplan-Meier estimates and Cox model., Results: Compared with HPV negativity, adjusted HRs for HPV16 positivity were 0.57, 95% CI, 0.38 to 0.87; 0.60, 0.40 to 0.88; and 0.65, 0.46 to 0.94 for disease-specific survival (DSS), recurrence-free survival (RFS), and overall survival (OS), respectively. Additionally, for p16 expression, aHRs were 0.68, 95% CI, 0.48 to 0.96; 0.72, 0.52 to 0.98; and 0.73, 0.54 to 0.99 for DSS, RFS, and OS, respectively. Finally, for combined analysis, patients with both HPV16-positivity/p16-positivity had much better prognosis than those with either negativity. Such above survivals are more significantly better in never smokers., Conclusion: Our findings suggest that HPV16/p16 may affect survival outcomes of LSCC patients, particularly in never smokers., (© 2019 Wiley Periodicals, Inc.)

Background: Transoral surgery (TOS) has been widely applied for early T-stage head and neck cancer (HNC). The resection is performed with a minimum safety margin for function preservation under a limited surgical field; therefore, it is difficult to have a strong conviction about the complete resection. This study aims to evaluate the completeness of the initial TOS procedure; possibility of primary control by TOS alone; and predictive factors in patients with early T-stage laryngeal, oropharyngeal, and hypopharyngeal cancer., Methods: Patients were treated by TOS at the primary site with or without neck dissection. The patients were divided into two groups based on the pathological evaluation of their surgical specimens: the control (observation) group, in that the resection was considered complete and the intervention (second-look procedure) group, in that incomplete tumor resection was suspected. The predictive factors for the possibility and/or limitations of complete resection by TOS were then analyzed., Results: The study enrolled 26 and 25 patients in the control and intervention group, respectively. The success rate for single resection was 66% and the predictive factor was tumor depth obtained by enhanced computed tomography (CT) examination (odds ratio, 7.870, P = .0243). The success rate for definitive therapy by TOS alone was 83% and the predictive factor was poor differentiation observed on pathological examination (odds ratio, 6.800, P = .0248)., Conclusions: TOS has the potential for both definitive resection and function preservation with minimal invasiveness. Identification of the risk factors for TOS is advantageous for accurate treatment selection in patients with early T-stage HNC., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Long noncoding RNAs (lncRNAs), which have little or no ability to encode proteins, have attracted special attention due to their potential role in cancer disease. We aimed to establish a lncRNA signature and a nomogram incorporating the genomic and clinicopathologic factors to improve the accuracy of survival prediction for laryngeal squamous cell carcinoma (LSCC)., Methods: A LSCC RNA-sequencing (RNA-seq) dataset and the matched clinicopathologic information were downloaded from The Cancer Genome Atlas (TCGA). Using univariable Cox regression and least absolute shrinkage and selection operator (LASSO) analysis, we developed a thirteen-lncRNA signature related to prognosis. On the basis of multivariable Cox regression analysis results, a nomogram integrating the genomic and clinicopathologic predictors was built. The predictive accuracy and discriminative ability of the inclusive nomogram were confirmed by calibration curve and a concordance index (C-index), and compared with the TNM staging system by C-index and receiver operating characteristic (ROC) analysis. Decision curve analysis (DCA) was conducted to evaluate the clinical value of our nomogram., Results: Thirteen overall survival- (OS-) related lncRNAs were identified, and the signature consisting of the selected thirteen lncRNAs could effectively divide patients into high-risk and low-risk subgroups, with area under curves (AUC) of 0.89 (3-year OS) and 0.885 (5-year OS). Independent factors derived from multivariable analysis to predict survival were margin status, tumor status, and lncRNA signature, which were all assembled into the nomogram. The calibration curve for the survival probability showed that the predictions based on the nomogram coincided well with actual observations. The C-index of the nomogram was 0.82 (0.77-0.87), and the area under curve (AUC) of the nomogram in predicting overall survival (OS) was 0.938, both of which were significantly higher than the traditional TNM stage. Decision curve analysis further demonstrated that our nomogram had larger net benefit than TNM stage., Conclusion: An inclusive nomogram for patients with LSCC, comprising genomic and clinicopathologic variables, generates more accurate estimations of the survival probability when compared with TNM stage alone, but more data are needed before the nomogram is used in clinical practice., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2019 Jie Cui et al.)

Aim: Treatment strategies in laryngeal squamous cell cancer (LSCC) straddle the need for long term survival and tumor control as well as preservation of laryngeal function as far as possible. We sought to identify prognostic factors affecting LSCC outcomes in our population., Methods: Clinical characteristics, treatments and survival outcomes of patients with LSCC were analysed. Baseline comorbidity data was collected and age-adjusted Charlson Comorbidity Index (aCCI) was calculated. Outcomes of overall survival (OS), progression-free survival (PFS) and laryngectomy-free survival (LFS) were evaluated., Results: Two hundred and fifteen patients were included, 170 (79%) underwent primary radiation/ chemoradiation and the remainder upfront surgery with adjuvant therapy where indicated. The majority of patients were male, Chinese and current/ex-smokers. Presence of comorbidity was common with median aCCI of 3. Median OS was 5.8 years. On multivariable analyses, high aCCI and advanced nodal status were associated with inferior OS (HR 1.24 per one point increase in aCCI, P<0.001 and HR 3.52; p<0.001 respectively), inferior PFS (HR 1.14; p = 0.007 and HR 3.23; p<0.001 respectively) and poorer LFS (HR 1.19; p = 0.001 and HR 2.95; p<0.001 respectively). Higher tumor (T) stage was associated with inferior OS and LFS (HR 1.61; p = 0.02 and HR 1.91; p = 0.01 respectively)., Conclusion: In our Asian population, the presence of comorbidities and high nodal status were associated with inferior OS, PFS and LFS whilst high T stage was associated with inferior LFS and OS., Competing Interests: The authors have declared that no competing interests exist.

Background: Despite advances in treatment, the recurrence rates for laryngeal cancer range from 16% to 40%., Methods: Patients with recurrent laryngeal cancer treated at Memorial Sloan Kettering (MSK) from 1999 to 2016 were reviewed. Survival outcomes were analyzed., Results: Of 241 patients, 88% were male; the median age was 67 years; 71% had primary glottic tumors. At initial treatment, 72% of patients were seen with early stage disease; primary treatment was radiation (68%), chemoradiation (29%), and surgery (3%). The most common salvage surgery was total laryngectomy (74%). Forty-seven percentage were upstaged at salvage surgery. The 2- and 5-year disease-specific survival (DSS) was 74% and 57%, respectively. Patients with cT4 disease treated with nonsurgical primary management had a 0% 5-year DSS. Independent predictors of DSS were tumor location, perineural invasion, margin, and stage., Conclusions: Salvage surgery results in acceptable oncologic outcomes. Stage, disease site, perineural invasion, and margins are associated with inferior DSS., (© 2019 Wiley Periodicals, Inc.)

Objectives: To analyze the incidence and clinical profile of nonsquamous cell (non-SCC) laryngeal carcinomas and to analyze the effect of surgery on survival., Study Design: A retrospective analysis of the National Cancer Database (2004-2014)., Methods: Adult patients with non-SCC laryngeal cancers were divided into six major histological subtypes. A descriptive clinical profile was obtained for non-SCC patients, and multivariate regressions were performed to analyze the effect of surgery on survival within the non-SCC cohort., Results: We identified 878 cases of non-SCC laryngeal cancers, representing 1.02% of all malignant laryngeal cancers. Neuroendocrine tumors and bone/cartilage sarcomas made up the largest groups (37.02% and 32.35%, respectively). Metastasis (M) was higher in neuroendocrine tumors, representing 19.1% of those with known clinical M stages. Of those treated, the majority of patients with bone/cartilage sarcomas (80.9%) and minor salivary gland tumors (82.6%) received surgery as part of their treatment. Survival varied significantly based upon histology, with bone/cartilage sarcomas having the highest 5-year survival at 90.4%, and neuroendocrine tumors exhibiting the poorest 5-year survival at 25.7%. Multivariate analyses found surgery to be significantly associated with improved survival (hazard ratio: 0.679; 95% confidence interval: 0.472-0.976; P = 0.036). The specific surgical method (i.e., local excision vs. partial vs. total laryngectomy) did not have any effect on survival., Conclusion: Approximately 1% of all malignant laryngeal cancers are non-SCC in origin. At presentation, neuroendocrine tumors have the highest rate of distant metastasis and have the worst prognosis of the non-SCC cancers. Most non-SCC patients received surgery as part of their treatment regimen., Level of Evidence: NA. Laryngoscope, 129:2496-2505, 2019., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Salvage total laryngectomy (TL) and laryngopharyngectomy (LP) after chemoradiotherapy may produce disfiguring defects with severe complications that require complex reconstructions., Methods: Between January 2012 and December 2018, we enrolled 25 patients who underwent internal mammary artery perforator (IMAP) flap reconstruction after salvage TL or LP. We performed retrospective review of clinical charts to collect information such as history, timing of reconstruction, type of defect, follow-up, donor and recipient site complications, and overall flap survival (OFS) rate. Three years overall survival (OS), relapse-free survival (RFS), and disease-specific survival (DSS) were calculated., Results: The OFS rate was 95%. One partial flap necrosis was recorded. No donor-site complications were found. The mean follow-up was 18 months. Three years OS was 44%, RFS was 47%, and DSS was 54%., Conclusions: IMAP flap appears to be safe, versatile, and easy to harvest, with minimal donor site morbidity. It is a reliable option in Head&Neck reconstruction, in salvage surgery as well., (© 2019 Wiley Periodicals, Inc.)

Background: To evaluate the differences in treatment modality and outcomes between male and female patients with laryngeal squamous cell carcinoma (SCC) in the United States., Methods: Data were extracted from the Surveillance, Epidemiology, and End Results Database for patients with laryngeal SCC (2004-2013). Overall survival (OS), disease specific survival (DSS), and multivariate analyses were conducted., Results: Among women, supraglottic cancers were the most prevalent (61.2%); whereas the majority of men developed glottic cancers (64.2%; P < .001). Women with T4 disease were more likely to undergo primary radiation (56.8% vs 45.3%; P < .001) and less likely to undergo open surgery were than men (37.1% vs 48.2%; P < .001). Women had significantly better OS in glottic and supraglottic cancers, and comparable survival in subglottic cancer. Sex remained an independent prognostic factor for both DSS and OS., Conclusion: Sex is an independent prognostic factor for DSS and OS in patients with laryngeal SCC., (© 2019 Wiley Periodicals, Inc.)

Background: Primary hematologic malignancies of the larynx are rare diagnoses, accounting for less than 1% of all laryngeal tumors. They most commonly present as submucosal masses of the supraglottis, with symptoms including hoarseness, dysphagia, dyspnea and rarely cervical lymphadenopathy., Purpose: METHODS: Retrospective case series of patients in a tertiary academic laryngeal practice with hematologic malignancy of the larynx presenting over a 10 year period; charts were reviewed for diagnosis, symptoms, treatment, and outcomes., Results: 12 patients were found to have primary presentation of a hematologic malignancy within the larynx between 2009 and 2019. A submucosal mass was the most common finding, and hoarseness was the most common symptom. Local control of disease was high. Airway obstruction was managed with tracheostomy. Several patients required tube feeding prior to disease control. Most patients underwent radiation therapy and chemotherapy, although surgery alone was effective in patients with isolated disease., Conclusions: Hematologic malignancies of the larynx are rare but treatable. Biopsy is the mainstay of diagnosis, and imaging may be helpful to exclude diseases with a similar physical presentation (i.e., laryngocele). Prognosis depends on diagnosis but is generally favorable., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Larynx preservation with chemoradiotherapy (CRT) is used frequently in the treatment of locally advanced hypopharyngeal/laryngeal squamous cell carcinoma (LSCC). Multiple large retrospective analyses have shown that CRT is associated with worse overall survival (OS) compared to total laryngectomy (TL) in patients with T4a disease. Burgeoning evidence suggests HPV status may play a prognostic role in patients with LSCC. We aimed to determine if HPV status influences OS among patients with T4a LSCC, and, if so, if it may be useful in selecting patients for CRT., Methods: Using the National Cancer Database (NCDB), we identified 810 patients with T4a N0-3 M0 squamous cell carcinoma of the larynx or hypopharynx with known HPV status who received either definitive CRT (to 66-81.6 Gy with any chemotherapy) or definitive TL (with the addition of 60-70 Gy of adjuvant RT). We evaluated differences in OS using the Kaplan-Meier method and Cox proportional hazards analyses., Results: On multivariate analysis, HPV-negative status (HR = 1.42, p = 0.02) and receipt of CRT (HR = 1.34, p = 0.01) were associated with worse OS when compared to HPV-positive patients and patients receiving TL, respectively. Among patients receiving CRT, 5-year OS was lower among HPV-negative patients (33.4%) when compared to HPV-positive patients (50.6%)., Conclusions: These data suggest that HPV status may be a prognostic factor in patients with T4a LSCC. Further, it supports further investigation into the usefulness of HPV status as a selection factor for larynx preservation with CRT in these patients., (Copyright © 2019 Elsevier B.V. All rights reserved.)