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      Posttreatment Non-Improved Vocal Cord Mobility Indicates the Need of Salvage Surgery for Hypopharyngeal Carcinomas

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          Abstract

          Introduction

          We aimed to analyze the relationship between the changed status of vocal cord mobility and survival outcomes.

          Methods

          Seventy-eight patients with dysfunctional vocal cords and hypopharyngeal carcinomas accepted non-surgical treatment as the initial therapy between May 2009 and December 2016. Vocal cord mobility was assessed before and after the initial non-surgical treatment. The cord mobility status was classified as normal, impaired, and fixed. Patients with improved mobility (IM) (n =56) were retrospectively analyzed for disease-free survival (DFS), recurrence-free survival (RFS), and overall survival (OS) and compared with 22 patients with non-improved mobility (non-IM).

          Results

          Fifty-six (71.8%) patients had improved cord mobility after the initial non-surgical treatment. The non-improved cord mobility was significantly associated with shortened DFS ( P=0.005), RFS ( P=0.002), and OS ( P<0.001). If non-improved cord mobility was regarded as an indicator for local-regional recurrence within 1 year, the sensitivity and the specificity were 60.9%, 87.5% respectively. The multivariate analysis showed that improved cord mobility ( P=0.006) and salvage surgery ( P=0.015) were both independent protective factors for OS.

          Conclusion

          Changes in cord mobility are a key marker for predicting prognosis. Non-improved cord mobility may indicate a high possibility of a residual tumor, therefore, patients whose cord mobility remains dysfunctional or worsens after non-surgical treatment might need an aggressive salvage strategy.

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          Most cited references20

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          Current trends in initial management of hypopharyngeal cancer: the declining use of open surgery.

          Squamous cell carcinoma of the hypopharynx represents a distinct clinical entity. Most patients present with significant comorbidities and advanced-stage disease. The overall survival is relatively poor because of high rates of regional and distant metastasis at presentation or early in the course of the disease. A multidisciplinary approach is crucial in the overall management of these patients to achieve the best results and maintain or improve functional results. Traditionally, operable hypopharyngeal cancer has been treated by total (occasionally partial) laryngectomy and partial or circumferential pharyngectomy, followed by reconstruction and postoperative radiotherapy in most cases. Efforts to preserve speech and swallowing function in the surgical treatment of hypopharyngeal (and laryngeal) cancer have resulted in a declining use of total laryngopharyngectomy and improved reconstructive efforts, including microvascular free tissue transfer. There are many surgical, as well as nonsurgical, options available for organ and function preservation, which report equally effective tumor control and survival. The selection of appropriate treatment is of crucial importance in the achievement of optimal results for these patients. In this article, several aspects of surgical and nonsurgical approaches in the treatment of hypopharyngeal cancer are discussed. Future studies must be carefully designed within clearly defined populations and use uniform terminology and standardized functional assessment and declare appropriate patient or disease endpoints. These studies should focus on improvement of results, without increasing patient morbidity. In this respect, technical improvements in radiotherapy such as intensity-modulated radiotherapy, advances in supportive care, and incorporation of newer systemic agents such as targeted therapy, are relevant developments. Copyright © 2010 Wiley Periodicals, Inc.
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            Association of Quantitative Metastatic Lymph Node Burden With Survival in Hypopharyngeal and Laryngeal Cancer

            Question What is the independent impact of quantitative metastatic nodal burden in hypopharyngeal and laryngeal malignancies? Findings This study of 8351 cases identified continuously escalating mortality risk with increasing number of metastatic lymph nodes, eclipsing conventional nodal staging factors such as node size and contralaterality. A simplified nodal staging system based on metastatic node number exhibited improved prognostic value and discrimination compared with the TNM staging system outlined in the American Joint Committee on Cancer’s AJCC Staging Manual , 8th edition. Meaning Greater incorporation of numerical metastatic nodal burden into nodal classification for hypopharyngeal and laryngeal cancers may streamline staging, refine patient prognosis, and triage patients who may benefit from adjuvant treatment. This analysis examines the association between metastatic lymph node burden and overall survival in patients with laryngohypopharyngeal cancers. Importance Nodal staging for laryngohypopharyngeal cancers is based primarily on size and laterality, with less value placed on absolute number of metastatic lymph nodes (LNs). We are aware of no studies to date that have specifically addressed the prognostic effect of quantitative nodal burden in larynx or hypopharynx malignancies. Objective To assess the independent impact of quantitative metastatic LN burden on mortality risk. Design, Setting, and Participants Univariate and multivariable models were constructed to evaluate the association between patients’ number of metastatic LNs and their survival, adjusting for factors such as nodal size, laterality, extranodal extension, margin status, and adjuvant treatment. Participants were patients with squamous cell carcinoma of the larynx or hypopharynx undergoing upfront surgical resection for curative intent at a US hospital between 2004 and 2013, as identified in the National Cancer Database. A neck dissection of a minimum of 10 LNs was required. Main Outcomes and Measures Overall survival. Results Overall, 8351 cases were included (mean [SD] age, 61 [10.1] years; 6499 men [77.8%]; 4710 patients with metastatic LNs and 3641 with no metastatic LNs). Mortality risk escalated continuously without plateau as number of metastatic nodes increased, with the hazard per node (hazard ratio [HR], 1.19; 95% CI, 1.16-1.23; P  < .001) most pronounced up to 5 positive LNs. Extranodal extension was also associated with increased mortality (HR, 1.34; 95% CI, 1.13-1.59; P  < .001). Increasing number of nodes examined was associated with improved survival, albeit to a lesser degree (per 10 LNs: HR, 0.97; 95% CI, 0.96-0.98; P  < .001) and without a detectable change point. Other nodal factors, including nodal size, contralateral LN involvement (TNM stage N2c), and lower LN involvement (levels 4-5), were not associated with mortality in multivariable models when accounting for number of positive LNs. A novel, parsimonious nodal staging system derived by recursive partitioning analysis exhibited greater concordance with survival than the TNM staging system outlined in the American Joint Committee on Cancer’s AJCC Staging Manual , 8th edition. Conclusions and Relevance The number of metastatic nodes is a predominant independent factor associated with mortality in hypopharyngeal and laryngeal cancers. Moreover, standard nodal staging factors like LN size and contralaterality have no independent prognostic value when accounting for positive LN number. Deeper integration of quantitative metastatic nodal disease may simplify staging and better triage the need for adjuvant therapy.
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              Trends in treatment, incidence and survival of hypopharynx cancer: a 20-year population-based study in the Netherlands

              Hypopharynx cancer has the worst prognosis of all head and neck squamous cell cancers. Since the 1990s, a treatment shift has appeared from a total laryngectomy towards organ preservation therapies. Large randomized trials evaluating treatment strategies for hypopharynx cancer, however, remain scarce, and frequently this malignancy is evaluated together with larynx cancer. Therefore, our aim was to determine trends in incidence, treatment and survival of hypopharynx cancer. We performed a population-based cohort study including all patients diagnosed with T1–T4 hypopharynx cancer between 1991 and 2010 in the Netherlands. Patients were recorded by the national cancer registry database and verified by a national pathology database. 2999 patients were identified. The incidence increased significantly with 4.1% per year until 1997 and decreased non-significantly afterwards. For women, the incidence increased with 1.7% per year during the entire study period. Total laryngectomy as primary treatment significantly decreased, whereas radiotherapy and chemoradiation increased. The 5-year overall survival significantly increased from 28% in 1991–2000 to 34% in 2001–2010. Overall survival for T3 was equal for total laryngectomy and (chemo)radiotherapy, but for T4-patients the survival was significantly better after primary total laryngectomy (± adjuvant radiotherapy). This large population-based study demonstrates a shift in treatment preference towards organ preservation therapies. The 5-year overall survival increased significantly in the second decade. The assumed equivalence of organ preservation and laryngectomy may require reconsideration for T4 disease. Electronic supplementary material The online version of this article (doi:10.1007/s00405-017-4766-6) contains supplementary material, which is available to authorized users.
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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                08 January 2021
                2020
                : 10
                : 600599
                Affiliations
                [1] 1 Department of Head and Neck Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College , Beijing, China
                [2] 2 Department of Endoscopy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College , Beijing, China
                [3] 3 Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College , Beijing, China
                Author notes

                Edited by: Alan Jay Katz, St. Francis Hospital, United States

                Reviewed by: Ruijie Yang, Peking University Third Hospital, China; Jung Sun Yoo, Hong Kong Polytechnic University, Hong Kong

                *Correspondence: Shao-yan Liu, shaoyan_liu@ 123456sina.com ; Jun-lin Yi, yijunlin1969@ 123456163.com

                This article was submitted to Radiation Oncology, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2020.600599
                7821786
                784215a5-984d-4478-a41d-e0ff0801a306
                Copyright © 2021 He, Zhang, Zhu, Ni, Huang, An, Yi and Liu

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 30 August 2020
                : 23 November 2020
                Page count
                Figures: 4, Tables: 3, Equations: 0, References: 20, Pages: 9, Words: 4148
                Categories
                Oncology
                Original Research

                Oncology & Radiotherapy
                salvage therapy,radiotherapy,hypopharyngeal neoplasms,prognosis,vocal fold paralysis

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