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      Laryngeal Compartmentalization Does Not Affect the Prognosis of T3-T4 Laryngeal Cancer Treated by Upfront Total Laryngectomy

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          Abstract

          A picture is emerging in which advanced laryngeal cancers (LCs) are potentially not homogeneous and may be characterized by subpopulations which, if identified, could allow selection of patients amenable to organ preservation treatments in contrast to those to be treated with total laryngectomy (TL). This work aims to analyze a multicentric cohort of T3-T4a LCs treated by upfront TL, investigating the clinical and pathological features that can best predict oncologic outcomes. A total of 149 previously untreated patients who underwent TL for T3-T4a LC at four institutions were analyzed. Survival and disease-control were considered as the main outcomes. A secondary end-point was the identification of covariates associated with nodal status, investigating also the tumor thickness. T and N categories were significantly associated with both overall and disease-specific survival. The number of positive nodes and tracheal involvement were associated with loco-regional failure; post-cricoid area invasion and extra-nodal extension with distant failure. Posterior laryngeal compartment involvement was not a significant prognostic feature, by either univariable and multivariable analyses. These results support the conclusion that laryngeal compartmentalization has no impact on survival in patients treated by upfront TL and the current TNM staging system remains a robust prognosticator in advanced LC.

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          Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. The Department of Veterans Affairs Laryngeal Cancer Study Group.

          Gregory Wolf, Susan Gross Fisher, Waun Hong … (1991)
          We performed a prospective, randomized study in patients with previously untreated advanced (Stage III or IV) laryngeal squamous carcinoma to compare the results of induction chemotherapy followed by definitive radiation therapy with those of conventional laryngectomy and postoperative radiation. Three hundred thirty-two patients were randomly assigned to receive either three cycles of chemotherapy (cisplatin and fluorouracil) and radiation therapy or surgery and radiation therapy. The clinical tumor response was assessed after two cycles of chemotherapy, and patients with a response received a third cycle followed by definitive radiation therapy (6600 to 7600 cGy). Patients in whom ther was no tumor response or who had locally recurrent cancers after chemotherapy and radiation therapy underwent salvage laryngectomy. After two cycles of chemotherapy, the clinical tumor response was complete in 31 percent of the patients and partial in 54 percent. After a median follow-up of 33 months, the estimated 2-year survival was 68 percent (95 percent confidence interval, 60 to 76 percent) for both treatment groups (P = 0.9846). Patterns of recurrence differed significantly between the two groups, with more local recurrences (P = 0.0005) and fewer distant metastases (P = 0.016) in the chemotherapy group than in the surgery group. A total of 59 patients in the chemotherapy group (36 percent) required total laryngectomy. The larynx was preserved in 64 percent of the patients overall and 64 percent of the patients who were alive and free of disease. These preliminary results suggest a new role for chemotherapy in patients with advanced laryngeal cancer and indicate that a treatment strategy involving induction chemotherapy and definitive radiation therapy can be effective in preserving the larynx in a high percentage of patients, without compromising overall survival.
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            NCCN Guidelines Insights: Head and Neck Cancers, Version 1.2018

            Susan D. Darlow, Antonio Jimeno, Debra S Leizman … (2018)
            The NCCN Guidelines for Head and Neck (H&N) Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the H&N, and separate algorithms have been developed by the panel for very advanced H&N cancers. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding evaluation and treatment of nasopharyngeal carcinoma.
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              Laryngeal cancer in the United States: changes in demographics, patterns of care, and survival.

              Andrew Stewart, Kie-Kian Ang, Max Langer … (2006)
              Survival has decreased among patients with laryngeal cancer during the past 2 decades in the United States. During this same period, there has been an increase in the nonsurgical treatment of laryngeal cancer. The objectives of this study were to identify trends in the demographics, management, and outcome of laryngeal cancer in the United States and to analyze factors contributing to the decreased survival. The authors conducted a retrospective, longitudinal study of laryngeal cancer cases. Review of the National Cancer Data Base (NCDB) revealed 158,426 cases of laryngeal squamous cell carcinoma (excluding verrucous carcinoma) diagnosed between the years 1985 and 2001. Analysis of these case records addressed demographics, management, and survival for cases grouped according to stage, site, and specific TNM classifications. This review of data from the NCDB analysis confirms the previously identified trend toward decreasing survival among patients with laryngeal cancer from the mid-1980s to mid-1990s. Patterns of initial management across this same period indicated an increase in the use of chemoradiation with a decrease in the use of surgery despite an increase in the use of endoscopic resection. The most notable decline in the 5-year relative survival between the 1985 to 1990 period and the 1994 to 1996 period occurred among advanced-stage glottic cancer, early-stage supraglottic cancers, and supraglottic cancers classified as T3N0M0. Initial treatment of T3N0M0 laryngeal cancer (all sites) in the 1994 to 1996 period resulted in poor 5-year relative survival for those receiving either chemoradiation (59.2%) or irradiation alone (42.7%) when compared with that of patients after surgery with irradiation (65.2%) and surgery alone (63.3%). In contrast, identical 5-year relative survival (65.6%) rates were observed during this same period for the subset of T3N0M0 glottic cancers initially treated with either chemoradiation or surgery with irradiation. The decreased survival recorded for patients with laryngeal cancer in the mid-1990s may be related to changes in patterns of management. Future studies are warranted to further evaluate these associations.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Cancers (Basel)
                Journal ID (iso-abbrev): Cancers (Basel)
                Journal ID (publisher-id): cancers
                Title: Cancers
                Publisher: MDPI
                ISSN (Electronic): 2072-6694
                Publication date (Electronic): 11 August 2020
                Publication date Collection: August 2020
                Volume: 12
                Issue: 8
                Electronic Location Identifier: 2241
                Affiliations
                [1 ]IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy; filippomarchi@ 123456hotmail.it (F.M.); missale.francesco@ 123456gmail.com (F.M.); mfilauro@ 123456yahoo.com (M.F.); iandelliandrea@ 123456gmail.com (A.I.); giampiero.parrinello@ 123456gmail.com (G.P.); giorgioperetti18@ 123456gmail.com (G.P.)
                [2 ]Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, 16132 Genoa, Italy
                [3 ]Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Taipei 33305, Taiwan
                [4 ]Department of Molecular and Translational Medicine, University of Brescia, 25100 Brescia, Italy
                [5 ]Department of Experimental Medicine (DIMES), University of Genoa, 16132 Genoa, Italy
                [6 ]Department of Head and Neck Surgery, Chang Gung Memorial Hospital, Chang Gung University and Medical College, Taoyuan 33305, Taiwan
                [7 ]Department of Otorhinolaryngology, Maxillofacial and Thyroid Surgery, Fondazione IRCCS, National Cancer Institute of Milan, 20133 Milan, Italy; Fabiola.Incandela@ 123456istitutotumori.mi.it (F.I.); ceceplaza@ 123456libero.it (C.P.)
                [8 ]Department of Head & Neck Oncology & Surgery Otorhinolaryngology, Antoni Van Leeuwenhoek, Nederlands Kanker Instituut, 1066 Amsterdam, The Netherlands; l.smeele@ 123456nki.nl (L.E.S.); m.vd.brekel@ 123456nki.nl (M.W.M.v.d.B.)
                [9 ]Department of Otorhinolaryngology—Head and Neck Surgery, University of Brescia, 25123 Brescia, Italy; delbonfrancesca@ 123456gmail.com
                [10 ]Section of Otorhinolaryngology—Head and Neck Surgery, Department of Neurosciences, University of Padua, Via Giustiniani, 2-35128 Padua, Italy; pieronicolai@ 123456icloud.com
                [11 ]Department of Oncology and Oncohematology, University of Milan, 20122 Milan, Italy
                Author notes
                [†]

                These authors equally contributed to the work.

                Author information
                https://orcid.org/0000-0002-7997-964X
                https://orcid.org/0000-0002-5357-5348
                https://orcid.org/0000-0002-7699-2291
                https://orcid.org/0000-0002-6000-3006
                https://orcid.org/0000-0002-6338-6743
                Article
                Publisher ID: cancers-12-02241
                DOI: 10.3390/cancers12082241
                PMC ID: 7463701
                PubMed ID: 32796540
                SO-VID: 254d1cb5-3876-450f-ac82-7011e5be6442
                Copyright © © 2020 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 07 July 2020
                Date accepted : 07 August 2020
                Categories
                Subject: Article

                Keywords: laryngeal neoplasms,total laryngectomy,paraglottic space,tumor thickness,prognosis,multicentric study
                Data availability:
                Keywords: laryngeal neoplasms, total laryngectomy, paraglottic space, tumor thickness, prognosis, multicentric study

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