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Emerging Concepts in Treatment of Laryngeal Cancer
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Emerging Concepts in Treatment of Laryngeal Cancer

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (31 March 2020) | Viewed by 94606

Special Issue Editors

Dr. Cesare Piazza

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Guest Editor
Department of Otorhinolaryngology, Maxillofacial and Thyroid Surgery, Fondazione IRCCS, National Cancer Institute of Milan, Via Giacomo Venezian 1, 20133 Milan, Italy
Interests: head and neck surgery; radiotherapy; medical oncology
Dr. Ester Orlandi

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Guest Editor
Department of Radiation Oncology, Fondazione IRCCS, National Cancer Institute of Milan, Milan, Italy
Interests: head and neck surgery; radiotherapy; medical oncology
Dr. Laura Locati

E-Mail Website
Guest Editor
Department of Medical Oncology; Head and Neck Unit, Fondazione IRCCS, National Cancer Institute of Milan, Milan, Italy
Interests: head and neck surgery; radiotherapy; medical oncology

Special Issue Information

Dear Colleague,

This Special Issue will focus on emerging concepts in the multimodal treatment approach to laryngeal squamous cell carcinoma, starting from its precise pre- and intraoperative bio-endoscopic assessment and radiologic evaluation by magnetic resonance with surface coils (that allows a level of detail far superior to that obtainable by previous imaging techniques). Radiomics is making its way also in this field, and promising nuances are already at hands. In-depth analysis of different surgical as well as non-surgical organ preservation strategies will be carried out, with special emphasis given to how to reduce the number of wrong therapeutic planning decisions in a multidisciplinary team setting. Modern oncology is rapidly going towards an always more focused and fine-tuned personalized therapeutic strategy. Big data, genomics, and proteomics are promising aids in such a direction and could be soon used to implement the existing TNM staging system (as has already happened for thyroid, nasopharynx, and oropharynx). At a minimum, however, there is already multiple evidence that such an essential prognostic tool can be greatly improved by introducing just some of the new anatomic and therapeutic concepts developed in the last 5–10 years.

Prof. Cesare Piazza
Dr. Ester Orlandi
Dr. Laura Locati
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • laryngeal cancer
  • transoral laser microsurgery
  • open partial surgery
  • robotic surgery
  • radiotherapy
  • IMRT
  • VMAT
  • chemotherapy
  • immunotherapy
  • omics

Published Papers (20 papers)

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18 pages, 3160 KiB  
Article
Laryngeal Compartmentalization Does Not Affect the Prognosis of T3-T4 Laryngeal Cancer Treated by Upfront Total Laryngectomy
by Filippo Marchi, Francesco Missale, Claudio Sampieri, Marta Filauro, Andrea Iandelli, Giampiero Parrinello, Fabiola Incandela, Ludwig E. Smeele, Michiel W. M. van den Brekel, Francesca Del Bon, Piero Nicolai, Cesare Piazza and Giorgio Peretti
Cancers 2020, 12(8), 2241; https://doi.org/10.3390/cancers12082241 - 11 Aug 2020
Cited by 12 | Viewed by 2606
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Emerging Concepts in Treatment of Laryngeal Cancer)
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10 pages, 784 KiB  
Article
Laryngeal Mid-Cord Erythroleukoplakias: How to Modulate the Transoral CO2 Laser Excisional Biopsy
by Francesco Mora, Filippo Carta, Francesco Missale, Andrea Laborai, Giampiero Parrinello, Cesare Piazza, Roberto Puxeddu and Giorgio Peretti
Cancers 2020, 12(8), 2165; https://doi.org/10.3390/cancers12082165 - 4 Aug 2020
Cited by 4 | Viewed by 2003
Abstract
Background: The endoscopic appearance of glottic erythroleukoplakias is non-predictive of their histopathology, potentially ranging from keratosis to invasive squamous cell carcinoma (SCC). The aim of this study was to assess a comprehensive workup for the one-step diagnosis and treatment of mid-cord erythroleukoplakias, using [...] Read more.
Background: The endoscopic appearance of glottic erythroleukoplakias is non-predictive of their histopathology, potentially ranging from keratosis to invasive squamous cell carcinoma (SCC). The aim of this study was to assess a comprehensive workup for the one-step diagnosis and treatment of mid-cord erythroleukoplakias, using CO2 laser excisional biopsy. Methods: We evaluated 147 untreated patients affected by 155 mid-cord erythroleukoplakias submitted to excisional biopsy by subepithelial (Type I) or subligamental cordectomy (Type II), across two academic institutions. Patients were evaluated by preoperative videolaryngostroboscopy, pre- and intraoperative videoendoscopy with biologic endoscopy (narrow band imaging, NBI, or the Storz professional image enhancement system, SPIES), either with or without intraoperative saline infusion into the Reinke’s space. Adequacy of treatment was the primary outcome. Results: The histopathologic diagnosis was keratosis in 26 (17%) cases, squamous intraepithelial neoplasia (SIN1-2) in 47 (30%), carcinoma in situ in 21 (14%), and SCC in 61 (39%) patients. The adequacy of treatment across the entire cohort was 89%. The intraoperative saline infusion procedure, facing not clearly suspicious lesions, raised the adequacy of treatment from 60% to 90% (p = 0.006). Conclusions: Excisional biopsy by Type I–II cordectomies, after a comprehensive diagnostic workup, should be accepted as an adequate and cost-effective treatment of unilateral mid-cord glottic erythroleukoplakias. Full article
(This article belongs to the Special Issue Emerging Concepts in Treatment of Laryngeal Cancer)
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12 pages, 1970 KiB  
Article
T1 Glottic Cancer: Does Anterior Commissure Involvement Worsen Prognosis?
by Giuditta Mannelli, Lara Valentina Comini, Roberto Santoro, Alessandra Bettiol, Alfredo Vannacci, Isacco Desideri, Pierluigi Bonomo and Cesare Piazza
Cancers 2020, 12(6), 1485; https://doi.org/10.3390/cancers12061485 - 6 Jun 2020
Cited by 9 | Viewed by 4449
Abstract
Radiotherapy (RT) and transoral laser microsurgery (TLM) represent the main treatment modalities for early glottic carcinoma. Local failure is notoriously more frequent in T1b glottic cancer in comparison to T1a and T2 tumors. In this scenario, the role of anterior commissure (AC) involvement [...] Read more.
Radiotherapy (RT) and transoral laser microsurgery (TLM) represent the main treatment modalities for early glottic carcinoma. Local failure is notoriously more frequent in T1b glottic cancer in comparison to T1a and T2 tumors. In this scenario, the role of anterior commissure (AC) involvement is still controversial. The aim of the present study was therefore to determine its potential prognostic power in worsening patients’ survival and outcomes. We categorized different tumor glottic fold locations with respect to the involvement of one (T1a) or both vocal cords, with or without AC involvement. We analyzed a retrospective cohort of 74 patients affected by Stage I glottic cancer, treated between 2011 and 2018 by TLM or RT at a single academic institution. There were 22 T1a (30%) and 52 T1b (70%) cases. The median follow-up period was 30 months (mean, 32.09 ± 18.738 months; range, 12–79). Three-year overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), and laryngectomy-free survival (LFS) were compared according to tumor location, extension, and cT category. According to both uni- and multivariate analyses, an increased risk for recurrence in T1b with AC involvement and T1a tumors was 7.31 and 9.45 times, respectively (p-values of 0.054 and 0.030, respectively). Among the 17 recurrences, T1b with AC involvement experienced 15 tumor relapses (88.2%), thus significantly affecting both the RFS and LFS in comparison to the other two tumor subcategories (T1a, p = 0.028 and T1b without AC involvement, p = 0.043). The deteriorating prognosis in the presence of AC involvement likely reflects the need to power the hazard consistency and discrimination of the T1b category when associated with such a risk factor, thus deserving an independent T category. Full article
(This article belongs to the Special Issue Emerging Concepts in Treatment of Laryngeal Cancer)
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13 pages, 2697 KiB  
Article
Imaging Accuracy in Preoperative Staging of T3-T4 Laryngeal Cancers
by Marco Benazzo, Fabio Sovardi, Lorenzo Preda, Simone Mauramati, Sergio Carnevale, Giulia Bertino, Francesca Berton, Matteo Meroni, Irene Herman, Giuseppe Trisolini and Patrizia Morbini
Cancers 2020, 12(5), 1074; https://doi.org/10.3390/cancers12051074 - 26 Apr 2020
Cited by 6 | Viewed by 4028
Abstract
Background: Preoperative imaging impacts treatment planning and prognosis in laryngeal cancers. We investigated the accuracy of standard computed tomography (CT) in evaluating tumor invasions at critical glottic areas. Methods: CT scans of glottic cancers treated by partial or total laryngectomy between Jan 2015 [...] Read more.
Background: Preoperative imaging impacts treatment planning and prognosis in laryngeal cancers. We investigated the accuracy of standard computed tomography (CT) in evaluating tumor invasions at critical glottic areas. Methods: CT scans of glottic cancers treated by partial or total laryngectomy between Jan 2015 and Aug 2019 were reviewed to assess levels of tumor invasion at critical glottic subsites. CT accuracy in the identification of tumor extensions was determined against the gold standard of histopathological analysis of surgical samples. Results: This study included 64 patients. In the anterior commissure, CT showed high rates of false positives at all levels (sensitivity 56.2–70%, specificity 87.8–92.3%); in the anterior vocal fold, it overestimated the deep invasion (19.5% specificity, 90.3% sensitivity), while it underestimated the extralaryngeal spread (63.6% sensitivity, 98.1% specificity). In the posterior paraglottic space (pPGS), false negative results were more frequent for superficial extensions (25% sensitivity, 95.8% specificity) and deep invasions (58.8% sensitivity, 82.3% specificity). Shorter disease-specific and disease-free survivals were associated with pStage IV (p: 0.045 and 0.008) and with the pathological involvement of pPGS (p: 0.045 and 0.015). Conclusions: Negative prognostic correlation of pPGS involvement was confirmed on histopathological data. CT staging did not provide a satisfactory prognostic stratification and should be complemented with magnetic resonance imaging. Full article
(This article belongs to the Special Issue Emerging Concepts in Treatment of Laryngeal Cancer)
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14 pages, 2426 KiB  
Article
Transcriptome Analysis Identifies ALCAM Overexpression as a Prognosis Biomarker in Laryngeal Squamous Cell Carcinoma
by Pedro Nicolau-Neto, Paulo Thiago de Souza-Santos, Mariana Severo Ramundo, Priscila Valverde, Ivanir Martins, Izabella Costa Santos, Fernando Dias, Tatiana de Almeida Simão and Luis Felipe Ribeiro Pinto
Cancers 2020, 12(2), 470; https://doi.org/10.3390/cancers12020470 - 18 Feb 2020
Cited by 17 | Viewed by 2831
Abstract
Background: Laryngeal squamous cell carcinoma (LSCC) is one of the most incident tumors in the world, especially in developing countries, such as Brazil. Different from other tumors, LSCC prognosis did not improve during the past four decades. Therefore, the objective of this study [...] Read more.
Background: Laryngeal squamous cell carcinoma (LSCC) is one of the most incident tumors in the world, especially in developing countries, such as Brazil. Different from other tumors, LSCC prognosis did not improve during the past four decades. Therefore, the objective of this study was to develop biomarkers that can predict LSCC patient’s prognosis. Results: Transcriptome analysis pointed out 287 overexpressed genes in LSCC in comparison to adjacent mucosa. Among these, a gene-pattern signature was created with 24 genes associated with prognosis. The Bayesian clustering of both Brazil and The Cancer Genome Atlas (TCGA) data pointed out clusters of samples possessing significative differences in the prognosis, and the expression panel of three genes (ALCAM, GBP6, and ME1) was capable to distinguish patients with worse prognosis with an accuracy of 97%. Survival analyses with TCGA data highlighted ALCAM gene expression as an independent prognostic factor for LSCC. This was further confirmed through immunohistochemistry, using a validation set of Brazilian patients. ALCAM expression was not associated with prognosis for other head and neck tumor sites. Conclusion: ALCAM overexpression seems to be an independent prognosis biomarker for LSCC patients. Full article
(This article belongs to the Special Issue Emerging Concepts in Treatment of Laryngeal Cancer)
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9 pages, 1031 KiB  
Article
Evaluation of Vascular Patterns Using Contact Endoscopy and Narrow-Band Imaging (CE-NBI) for the Diagnosis of Vocal Fold Malignancy
by Nikolaos Davaris, Anke Lux, Nazila Esmaeili, Alfredo Illanes, Axel Boese, Michael Friebe and Christoph Arens
Cancers 2020, 12(1), 248; https://doi.org/10.3390/cancers12010248 - 20 Jan 2020
Cited by 14 | Viewed by 3975
Abstract
The endoscopic detection of perpendicular vascular changes (PVC) of the vocal folds has been associated with vocal fold cancer, dysplastic lesions, and papillomatosis, according to a classification proposed by the European Laryngological Society (ELS). The combination of contact endoscopy with narrow-band imaging (NBI-CE) [...] Read more.
The endoscopic detection of perpendicular vascular changes (PVC) of the vocal folds has been associated with vocal fold cancer, dysplastic lesions, and papillomatosis, according to a classification proposed by the European Laryngological Society (ELS). The combination of contact endoscopy with narrow-band imaging (NBI-CE) allows intraoperatively a highly contrasted, real-time visualization of vascular changes of the vocal folds. Aim of the present study was to determine the association of PVC to specific histological diagnoses, the level of interobserver agreement in the detection of PVC, and their diagnostic effectiveness in diagnosing laryngeal malignancy. The evaluation of our data confirmed the association of PVC to vocal fold cancer, dysplastic lesions, and papillomatosis. The level of agreement between the observers in the identification of PVC was moderate for the less-experienced observers and almost perfect for the experienced observers. The identification of PVC during NBI-CE proved to be a valuable indicator for diagnosing malignant and premalignant lesions. Full article
(This article belongs to the Special Issue Emerging Concepts in Treatment of Laryngeal Cancer)
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15 pages, 1130 KiB  
Article
Patterns of Care and Outcomes of Intensity-Modulated Radiotherapy and 3D Conformal Radiotherapy for Early Stage Glottic Cancer: A National Cancer Database Analysis
by Mark C. Korpics, W. Tyler Turchan, Michael K. Rooney, Matthew Koshy and Michael T. Spiotto
Cancers 2019, 11(12), 1996; https://doi.org/10.3390/cancers11121996 - 12 Dec 2019
Cited by 14 | Viewed by 2458
Abstract
Early stage glottic cancer has traditionally been treated with 3D conformal radiotherapy (3DCRT). However, intensity-modulated radiotherapy (IMRT) has been recently adopted as an alternative to decrease toxicity. Here, we compared the usage and outcomes of IMRT and 3DCRT for patients with early stage [...] Read more.
Early stage glottic cancer has traditionally been treated with 3D conformal radiotherapy (3DCRT). However, intensity-modulated radiotherapy (IMRT) has been recently adopted as an alternative to decrease toxicity. Here, we compared the usage and outcomes of IMRT and 3DCRT for patients with early stage squamous cell carcinoma (SCC) of the glottic larynx. Using the National Cancer Database, we identified patients with Stage I–II SCC of the glottis who received 55–75 Gy using IMRT (n = 1623) or 3DCRT (n = 2696). Median follow up was 42 months with a 5-year overall survival (OS) of 72%. Using a nominal logistic regression, race, ethnicity, year of diagnosis and fraction size were associated with the receipt of IMRT (p < 0.05). Using Kaplan–Meier methods and Cox proportional hazards models as well as a propensity matched cohort, there was no difference in OS for patients who received IMRT versus 3DCRT (hazard ratio (HR), 1.08; 95% confidence interval (95% CI), 0.93–1.26; p = 0.302). However, there was a survival benefit for patients receiving slight hypofractionation as compared to conventional fractionation (HR, 0.78; 95% CI, 0.69–0.92; p = 0.003). IMRT was associated with similar survival as 3DCRT, supporting the implementation of this potentially less toxic modality without compromising survival. Full article
(This article belongs to the Special Issue Emerging Concepts in Treatment of Laryngeal Cancer)
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12 pages, 568 KiB  
Article
Survival and Prognostic Factors for Outcome after Radiotherapy for T2 Glottic Carcinoma
by Martine Hendriksma, Marc A.P. van Ruler, Berit M. Verbist, Martin A. de Jong, Ton P.M Langeveld, Peter Paul G. van Benthem and Elisabeth V. Sjögren
Cancers 2019, 11(9), 1319; https://doi.org/10.3390/cancers11091319 - 6 Sep 2019
Cited by 7 | Viewed by 2757
Abstract
Background: Local recurrence after radiotherapy for T2 glottic carcinoma remains an issue and identifying patients at risk for relapse is, therefore, important. This study aimed to assess the oncological outcomes and prognostic factors in a consecutive series of patients treated with radiotherapy for [...] Read more.
Background: Local recurrence after radiotherapy for T2 glottic carcinoma remains an issue and identifying patients at risk for relapse is, therefore, important. This study aimed to assess the oncological outcomes and prognostic factors in a consecutive series of patients treated with radiotherapy for T2N0 glottic carcinoma. Methods: Patients with T2N0 glottic carcinoma treated with radiotherapy were included in this retrospective study. Five- and ten-year local control (LC), overall survival (OS), disease-specific survival (DSS), and laryngeal preservation (LP) rates were calculated with the Kaplan–Meier method. The impact of prognostic variables was evaluated with the log-rank test. Results: Ninety-four patients were included for analysis. LC, OS, DSS, and LP rates were 70.5, 63.7, 86.0, and 74.7%, respectively at five years and 65.8, 41.0, 75.6, and 72.4% at 10 years. In total, 46 scans were included in the analyses. Vertical involvement of the anterior commissure on imaging showed a significant impact on LC. Conclusions: In accordance with previously described surgical risk factors, we identified vertical involvement of the anterior commissure on imaging as a prognostic factor for radiation failure. Full article
(This article belongs to the Special Issue Emerging Concepts in Treatment of Laryngeal Cancer)
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15 pages, 989 KiB  
Article
A Multidisciplinary Team Guided Approach to the Management of cT3 Laryngeal Cancer: A Retrospective Analysis of 104 Cases
by Filippo Marchi, Marta Filauro, Francesco Missale, Giampiero Parrinello, Fabiola Incandela, Almalina Bacigalupo, Stefania Vecchio, Cesare Piazza and Giorgio Peretti
Cancers 2019, 11(5), 717; https://doi.org/10.3390/cancers11050717 - 24 May 2019
Cited by 11 | Viewed by 3769
Abstract
The optimal treatment for T3 laryngeal carcinoma (LC) is still a matter of debate. Different therapeutic options are available: Transoral laser microsurgery (TLM), open partial horizontal laryngectomies (OPHLs), total laryngectomy (TL), and organ preservation protocols (radiation therapy (RT) or chemo-radiation (CRT)). This study [...] Read more.
The optimal treatment for T3 laryngeal carcinoma (LC) is still a matter of debate. Different therapeutic options are available: Transoral laser microsurgery (TLM), open partial horizontal laryngectomies (OPHLs), total laryngectomy (TL), and organ preservation protocols (radiation therapy (RT) or chemo-radiation (CRT)). This study aimed to retrospectively evaluate oncologic outcomes of 104 T3 LCs treated by surgery or non-surgical approaches from January 2011 to December 2016 at a single academic tertiary referral center. Each case was evaluated by a multidisciplinary team (MDT) devoted to the management of head and neck cancers. We divided the cohort into two subgroups: Group A, surgical treatment (TLM, OPHLs, TL) and Group B, non-surgical treatment (RT, CRT). For the entire cohort, two- and five-year overall survival (OS) rates were 83% and 56%, respectively. The two- and five-year disease-free survival (DFS) rates were 75% and 65%, and disease-specific survival rates were 93% and 70%, respectively. The N category was a significant independent prognosticator for OS (p = 0.02), whereas Group B was significantly and independently associated with DFS (HR 4.10, p = 0.006). Analyzing laryngo-esophageal dysfunction-free survival as an outcome, it was found that this was significantly lower in higher N categories (p = 0.04) and in cases that underwent non-surgical treatments (p = 0.002). Optimization of oncologic outcomes in T3 LCs may be obtained only by a comprehensive MDT approach, considering that different treatment options have heterogenous toxicity profiles and indications. Full article
(This article belongs to the Special Issue Emerging Concepts in Treatment of Laryngeal Cancer)
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13 pages, 715 KiB  
Article
Swallowing Safety and Efficiency after Open Partial Horizontal Laryngectomy: A Videofluoroscopic Study
by Nicole Pizzorni, Antonio Schindler, Micol Castellari, Marco Fantini, Erika Crosetti and Giovanni Succo
Cancers 2019, 11(4), 549; https://doi.org/10.3390/cancers11040549 - 17 Apr 2019
Cited by 13 | Viewed by 3465
Abstract
Dysphagia is common after an open partial horizontal laryngectomy (OPHL). The mechanisms causing lower airways’ invasion and pharyngeal residue are unclear. The study aims to examine physio-pathological mechanisms affecting swallowing safety and efficiency after OPHL. Fifteen patients who underwent an OPHL type IIa [...] Read more.
Dysphagia is common after an open partial horizontal laryngectomy (OPHL). The mechanisms causing lower airways’ invasion and pharyngeal residue are unclear. The study aims to examine physio-pathological mechanisms affecting swallowing safety and efficiency after OPHL. Fifteen patients who underwent an OPHL type IIa with arytenoid resection were recruited. Videofluoroscopic examination of swallowing was performed. Ten spatial, temporal, and scalar parameters were analyzed. Swallowing safety and efficiency were assessed through the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) scale. Swallowing was considered unsafe or inefficient for a DIGEST safety or efficiency grade ≥2, respectively. Videofluoroscopic measurements were compared between safe vs. unsafe swallowers, and efficient vs. inefficient swallowers. Seven patients (46.7%) showed unsafe swallowing and 6 patients (40%) inefficient swallowing. Unsafe swallowers had worse laryngeal closure (p = 0.021). Inefficient swallowers presented a longer pharyngeal transit time (p = 0.008), a reduced pharyngoesophageal segment opening lateral (p = 0.008), and a worse tongue base retraction (p = 0.018 with solids and p = 0.049 with semisolids). In conclusion, swallowing safety was affected by incomplete laryngeal closure, while swallowing efficiency was affected by increased pharyngeal transit time, reduced upper esophageal sphincter opening, and incomplete tongue base retraction. The identified physio-pathological mechanisms could represent targets for rehabilitative and surgical approaches in patients with dysphagia after OPHL. Full article
(This article belongs to the Special Issue Emerging Concepts in Treatment of Laryngeal Cancer)
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17 pages, 3775 KiB  
Article
Arytenoid Fixation in Laryngeal Cancer: Radiological Pictures and Clinical Correlations with Respect to Conservative Treatments
by Giovanni Succo, Stefano Cirillo, Ilaria Bertotto, Elena Maldi, Davide Balmativola, Massimo Petracchini, Dario Gned, Alessandro Fornari, Gian Marco Motatto, Andrea E. Sprio, Andrea Manca and Erika Crosetti
Cancers 2019, 11(3), 360; https://doi.org/10.3390/cancers11030360 - 13 Mar 2019
Cited by 11 | Viewed by 5445
Abstract
Background: The aim of this retrospective study was to identify different radiological features in intermediate–advanced laryngeal cancer (LC) associated with arytenoid fixation, in order to differentiate cases still safely amenable to conservative treatment by partial laryngectomy or chemoradiotherapy. Methods: 29 consecutive patients [...] Read more.
Background: The aim of this retrospective study was to identify different radiological features in intermediate–advanced laryngeal cancer (LC) associated with arytenoid fixation, in order to differentiate cases still safely amenable to conservative treatment by partial laryngectomy or chemoradiotherapy. Methods: 29 consecutive patients who underwent open partial horizontal laryngectomies (OPHLs), induction chemotherapy followed by radiotherapy in the case of >50% response (IC + RT) or total laryngectomy were classified as: pattern I (supraglottic LC fixing the arytenoid due to weight effect), pattern II (glottic LC involving the posterior paraglottic space and spreading toward the crico-arytenoid joint and infraglottic extension <10 mm), pattern III (glottic—infraglottic LC involving the crico-arytenoid joint and infraglottic extension >10 mm) and pattern IV (transglottic and infraglottic LC with massive crico-arytenoid unit involvement, reaching the hypopharyngeal submucosa). All glottic cancers treated with surgery were studied by a cross sectional approach. Results: A substantial agreement between the work-up and the pathology results has been obtained in each of the subcategories. Three-year disease-free survivals, local control and freedom from laryngectomy were significantly better in pattern II compared to pattern III–IV. Conclusions: LC showing fixed arytenoid due to weight effect or posterior paraglottic space involvement with infraglottic extension <10 mm assessed at the true vocal cord midline are still safely manageable by OPHL or IC + RT. Full article
(This article belongs to the Special Issue Emerging Concepts in Treatment of Laryngeal Cancer)
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12 pages, 1984 KiB  
Article
Open Partial Horizontal Laryngectomies for T3–T4 Laryngeal Cancer: Prognostic Impact of Anterior vs. Posterior Laryngeal Compartmentalization
by Francesca Del Bon, Cesare Piazza, Davide Lancini, Alberto Paderno, Paolo Bosio, Stefano Taboni, Riccardo Morello, Nausica Montalto, Francesco Missale, Fabiola Incandela, Filippo Marchi, Marta Filauro, Alberto Deganello, Giorgio Peretti and Piero Nicolai
Cancers 2019, 11(3), 289; https://doi.org/10.3390/cancers11030289 - 1 Mar 2019
Cited by 28 | Viewed by 3909
Abstract
Open partial horizontal laryngectomies (OPHLs) are well-established and oncologically safe procedures for intermediate–advanced laryngeal cancers (LC). T–N categories are well-known prognosticators: herein we tested if “anterior” vs. “posterior” tumor location (as defined in respect to the paraglottic space divided according to a plane [...] Read more.
Open partial horizontal laryngectomies (OPHLs) are well-established and oncologically safe procedures for intermediate–advanced laryngeal cancers (LC). T–N categories are well-known prognosticators: herein we tested if “anterior” vs. “posterior” tumor location (as defined in respect to the paraglottic space divided according to a plane passing through the arytenoid vocal process, perpendicular to the ipsilateral thyroid lamina) may represent an additional prognostic factor. We analyzed a retrospective cohort of 85 T3–4a glottic LCs, treated by Type II or III OPHL (according to the European Laryngological Society classification) from 2005 to 2017 at two academic institutions. Five-year overall survival (OS), disease-specific survivals (DSS), and recurrence-free survivals (RFS) were compared according to tumor location and pT category. Anterior and posterior tumors were 43.5% and 56.5%, respectively, 78.8% of lesions were T3 and 21.2% were T4a. Five-year OS, DSS, and RFS for T3 were 74.1%, 80.5%, and 63.4%, respectively, and for T4a 71.8%, 71.8%, and 43%, respectively (p not significant). In relation to tumor location, the survival outcomes were 91%, 94.1%, and 72.6%, respectively, for anterior tumors, and 60.3%, 66.3%, and 49.1%, respectively, for posterior lesions (statistically significant differences). These data provide evidence that laryngeal compartmentalization is a valid prognosticator, even more powerful than the pT category. Full article
(This article belongs to the Special Issue Emerging Concepts in Treatment of Laryngeal Cancer)
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11 pages, 4586 KiB  
Article
Prediction of Posterior Paraglottic Space and Cricoarytenoid Unit Involvement in Endoscopically T3 Glottic Cancer with Arytenoid Fixation by Magnetic Resonance with Surface Coils
by Marco Ravanelli, Alberto Paderno, Francesca Del Bon, Nausica Montalto, Carlotta Pessina, Simonetta Battocchio, Davide Farina, Piero Nicolai, Roberto Maroldi and Cesare Piazza
Cancers 2019, 11(1), 67; https://doi.org/10.3390/cancers11010067 - 10 Jan 2019
Cited by 20 | Viewed by 7523
Abstract
Discrimination of the etiology of arytenoid fixation in cT3 laryngeal squamous cell carcinoma (SCC) is crucial for treatment planning. The aim of this retrospective study was to differentiate among possible causes of arytenoid fixation (edema, inflammation, mass effect, or tumor invasion) by analyzing [...] Read more.
Discrimination of the etiology of arytenoid fixation in cT3 laryngeal squamous cell carcinoma (SCC) is crucial for treatment planning. The aim of this retrospective study was to differentiate among possible causes of arytenoid fixation (edema, inflammation, mass effect, or tumor invasion) by analyzing related signal patterns of magnetic resonance (MR) in the posterior laryngeal compartment (PLC) and crico-arytenoid unit (CAU). Seventeen patients affected by cT3 glottic SCC with arytenoid fixation were preoperatively studied by state-of-the-art MR with surface coils. Different signal patterns were assessed in PLC subsites. Three MR signal patterns were identified: A, normal; B, T2 hyperintensity and absence of restriction on diffusion-weighted imaging (DWI); and C, intermediate T2 signal and restriction on DWI. Signal patterns were correlated with the presence or absence of CAU and PLC neoplastic invasion. Patients were submitted to open partial horizontal or total laryngectomy and surgical specimens were analyzed. Pattern A and B did not correlate with neoplastic invasion, while Pattern C strongly did (Spearman’s coefficient = 0.779, p < 0.0001; sensitivity: 100%; specificity: 78%). In conclusion, MR with surface coils is able to assess PLC/CAU involvement with satisfactory accuracy. In absence of Pattern C, arytenoid fixation is likely related to mass effect and/or inflammatory reaction and is not associated with neoplastic invasion. Full article
(This article belongs to the Special Issue Emerging Concepts in Treatment of Laryngeal Cancer)
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Review

Jump to: Research

26 pages, 2762 KiB  
Review
New Developments in Imaging for Sentinel Lymph Node Biopsy in Early-Stage Oral Cavity Squamous Cell Carcinoma
by Rutger Mahieu, Josanne S. de Maar, Eliane R. Nieuwenhuis, Roel Deckers, Chrit Moonen, Lejla Alic, Bennie ten Haken, Bart de Keizer and Remco de Bree
Cancers 2020, 12(10), 3055; https://doi.org/10.3390/cancers12103055 - 20 Oct 2020
Cited by 29 | Viewed by 6884
Abstract
Sentinel lymph node biopsy (SLNB) is a diagnostic staging procedure that aims to identify the first draining lymph node(s) from the primary tumor, the sentinel lymph nodes (SLN), as their histopathological status reflects the histopathological status of the rest of the nodal basin. [...] Read more.
Sentinel lymph node biopsy (SLNB) is a diagnostic staging procedure that aims to identify the first draining lymph node(s) from the primary tumor, the sentinel lymph nodes (SLN), as their histopathological status reflects the histopathological status of the rest of the nodal basin. The routine SLNB procedure consists of peritumoral injections with a technetium-99m [99mTc]-labelled radiotracer followed by lymphoscintigraphy and SPECT-CT imaging. Based on these imaging results, the identified SLNs are marked for surgical extirpation and are subjected to histopathological assessment. The routine SLNB procedure has proven to reliably stage the clinically negative neck in early-stage oral squamous cell carcinoma (OSCC). However, an infamous limitation arises in situations where SLNs are located in close vicinity of the tracer injection site. In these cases, the hotspot of the injection site can hide adjacent SLNs and hamper the discrimination between tracer injection site and SLNs (shine-through phenomenon). Therefore, technical developments are needed to bring the diagnostic accuracy of SLNB for early-stage OSCC to a higher level. This review evaluates novel SLNB imaging techniques for early-stage OSCC: MR lymphography, CT lymphography, PET lymphoscintigraphy and contrast-enhanced lymphosonography. Furthermore, their reported diagnostic accuracy is described and their relative merits, disadvantages and potential applications are outlined. Full article
(This article belongs to the Special Issue Emerging Concepts in Treatment of Laryngeal Cancer)
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21 pages, 3502 KiB  
Review
Emerging Concepts and Novel Strategies in Radiation Therapy for Laryngeal Cancer Management
by Mauricio E. Gamez, Adriana Blakaj, Wesley Zoller, Marcelo Bonomi and Dukagjin M. Blakaj
Cancers 2020, 12(6), 1651; https://doi.org/10.3390/cancers12061651 - 22 Jun 2020
Cited by 26 | Viewed by 5115
Abstract
Laryngeal squamous cell carcinoma is the second most common head and neck cancer. Its pathogenesis is strongly associated with smoking. The management of this disease is challenging and mandates multidisciplinary care. Currently, accepted treatment modalities include surgery, radiation therapy, and chemotherapy—all focused on [...] Read more.
Laryngeal squamous cell carcinoma is the second most common head and neck cancer. Its pathogenesis is strongly associated with smoking. The management of this disease is challenging and mandates multidisciplinary care. Currently, accepted treatment modalities include surgery, radiation therapy, and chemotherapy—all focused on improving survival while preserving organ function. Despite changes in smoking patterns resulting in a declining incidence of laryngeal cancer, the overall outcomes for this disease have not improved in the recent past, likely due to changes in treatment patterns and treatment-related toxicities. Here, we review emerging concepts and novel strategies in the use of radiation therapy in the management of laryngeal squamous cell carcinoma that could improve the relationship between tumor control and normal tissue damage (therapeutic ratio). Full article
(This article belongs to the Special Issue Emerging Concepts in Treatment of Laryngeal Cancer)
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16 pages, 957 KiB  
Review
Incidence of Occult Lymph Node Metastasis in Primary Larynx Squamous Cell Carcinoma, by Subsite, T Classification and Neck Level: A Systematic Review
by Alvaro Sanabria, Jatin P. Shah, Jesus E. Medina, Kerry D. Olsen, K. Thomas Robbins, Carl E. Silver, Juan P. Rodrigo, Carlos Suárez, Andrés Coca-Pelaz, Ashok R. Shaha, Antti A. Mäkitie, Alessandra Rinaldo, Remco de Bree, Primož Strojan, Marc Hamoir, Robert P. Takes, Elisabeth V. Sjögren, Trinitia Cannon, Luiz P. Kowalski and Alfio Ferlito
Cancers 2020, 12(4), 1059; https://doi.org/10.3390/cancers12041059 - 24 Apr 2020
Cited by 27 | Viewed by 5848
Abstract
Background: Larynx cancer is a common site for tumors of the upper aerodigestive tract. In cases with a clinically negative neck, the indications for an elective neck treatment are still debated. The objective is to define the prevalence of occult metastasis based on [...] Read more.
Background: Larynx cancer is a common site for tumors of the upper aerodigestive tract. In cases with a clinically negative neck, the indications for an elective neck treatment are still debated. The objective is to define the prevalence of occult metastasis based on the subsite of the primary tumor, T classification and neck node levels involved. Methods: All studies included provided the rate of occult metastases in cN0 larynx squamous cell carcinoma patients. The main outcome was the incidence of occult metastasis. The pooled incidence was calculated with random effects analysis. Results: 36 studies with 3803 patients fulfilled the criteria. The incidence of lymph node metastases for supraglottic and glottic tumors was 19.9% (95% CI 16.4–23.4) and 8.0% (95% CI 2.7–13.3), respectively. The incidence of occult metastasis for level I, level IV and level V was 2.4% (95% CI 0–6.1%), 2.0% (95% CI 0.9–3.1) and 0.4% (95% CI 0–1.0%), respectively. For all tumors, the incidence for sublevel IIB was 0.5% (95% CI 0–1.3). Conclusions: The incidence of occult lymph node metastasis is higher in supraglottic and T3–4 tumors. Level I and V and sublevel IIB should not be routinely included in the elective neck treatment of cN0 laryngeal cancer and, in addition, level IV should not be routinely included in cases of supraglottic tumors. Full article
(This article belongs to the Special Issue Emerging Concepts in Treatment of Laryngeal Cancer)
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20 pages, 292 KiB  
Review
Comparison of Current Surgical and Non-Surgical Treatment Strategies for Early and Locally Advanced Stage Glottic Laryngeal Cancer and Their Outcome
by Olgun Elicin and Roland Giger
Cancers 2020, 12(3), 732; https://doi.org/10.3390/cancers12030732 - 20 Mar 2020
Cited by 37 | Viewed by 5017
Abstract
For the treatment of early and locally advanced glottic laryngeal cancer, multiple strategies are available. These are pursued and supported by different levels of evidence, but also by national and institutional traditions. The purpose of this review article is to compare and discuss [...] Read more.
For the treatment of early and locally advanced glottic laryngeal cancer, multiple strategies are available. These are pursued and supported by different levels of evidence, but also by national and institutional traditions. The purpose of this review article is to compare and discuss the current evidence supporting different loco-regional treatment approaches in early and locally advanced glottic laryngeal cancer. The focus is kept on randomized controlled trials, meta-analyses, and comparative retrospective studies including the treatment period within the last twenty years (≥ 1999) with at least one reported five-year oncologic and/or functional outcome measure. Based on the equipoise in oncologic and functional outcome after transoral laser surgery and radiotherapy, informed and shared decision-making with and not just about the patient poses a paramount importance for T1-2N0M0 glottic laryngeal cancer. For T3-4aN0-3M0 glottic laryngeal cancer, there is an equipoise regarding the partial/total laryngectomy and non-surgical modalities for T3 glottic laryngeal cancer. Patients with extensive and/or poorly functioning T4a laryngeal cancer should not be offered organ-preserving chemoradiotherapy with salvage surgery as a back-up plan, but total laryngectomy and adjuvant (chemo) radiation. The lack of high-level evidence comparing contemporary open or transoral robotic organ-preserving surgical and non-surgical modalities does not allow any concrete conclusions in terms of oncological and functional outcome. Unnecessary tri-modality treatments should be avoided. Instead of offering one-size-fits-all approaches and over-standardized rigid institutional strategies, patient-centered informed and shared decision-making should be favored. Full article
(This article belongs to the Special Issue Emerging Concepts in Treatment of Laryngeal Cancer)
14 pages, 2071 KiB  
Review
Current Role of Total Laryngectomy in the Era of Organ Preservation
by Alexandre Bozec, Dorian Culié, Gilles Poissonnet and Olivier Dassonville
Cancers 2020, 12(3), 584; https://doi.org/10.3390/cancers12030584 - 3 Mar 2020
Cited by 34 | Viewed by 8225
Abstract
In this article, we aimed to discuss the role of total laryngectomy (TL) in the management of patients with larynx cancer (LC) in the era of organ preservation. Before the 1990s, TL followed by radiotherapy (RT) was the standard treatment for patients with [...] Read more.
In this article, we aimed to discuss the role of total laryngectomy (TL) in the management of patients with larynx cancer (LC) in the era of organ preservation. Before the 1990s, TL followed by radiotherapy (RT) was the standard treatment for patients with locally advanced LC. Over the last 30 years, various types of larynx preservation (LP) programs associating induction or concurrent chemotherapy (CT) with RT have been developed, with the aim of treating locally advanced LC patients while preserving the larynx and its functions. Overall, more than two-thirds of patients included in a LP program will not require total laryngectomy (TL) and will preserve a functional larynx. However, despite these advances, the larynx is the only tumor site in the upper aero-digestive tract for which prognosis has not improved during recent decades. Indeed, none of these LP protocols have shown any survival advantage compared to primary radical surgery, and it appears that certain LC patients do not benefit from an LP program. This is the case for patients with T4a LC (extra-laryngeal tumor extension through the thyroid cartilage) or with poor pretreatment laryngeal function and for whom primary TL is still the preferred therapeutic option. Moreover, TL is the standard salvage therapy for patients with recurrent tumor after an LP protocol. Full article
(This article belongs to the Special Issue Emerging Concepts in Treatment of Laryngeal Cancer)
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14 pages, 967 KiB  
Review
Radiomics and Texture Analysis in Laryngeal Cancer. Looking for New Frontiers in Precision Medicine through Imaging Analysis
by Carlos Miguel Chiesa-Estomba, Oier Echaniz, Ekhiñe Larruscain, Jose Angel Gonzalez-Garcia, Jon Alexander Sistiaga-Suarez and Manuel Graña
Cancers 2019, 11(10), 1409; https://doi.org/10.3390/cancers11101409 - 20 Sep 2019
Cited by 19 | Viewed by 5866
Abstract
Radiomics and texture analysis represent a new option in our biomarkers arsenal. These techniques extract a large number of quantitative features, analyzing their properties to incorporate them in clinical decision-making. Laryngeal cancer represents one of the most frequent cancers in the head and [...] Read more.
Radiomics and texture analysis represent a new option in our biomarkers arsenal. These techniques extract a large number of quantitative features, analyzing their properties to incorporate them in clinical decision-making. Laryngeal cancer represents one of the most frequent cancers in the head and neck area. We hypothesized that radiomics features can be included as a laryngeal cancer precision medicine tool, as it is able to non-invasively characterize the overall tumor accounting for heterogeneity, being a prognostic and/or predictive biomarker derived from routine, standard of care, imaging data, and providing support during the follow up of the patient, in some cases avoiding the need for biopsies. The larynx represents a unique diagnostic and therapeutic challenge for clinicians due to its complex tridimensional anatomical structure. Its complex regional and functional anatomy makes it necessary to enhance our diagnostic tools in order to improve decision-making protocols, aimed at better survival and functional results. For this reason, this technique can be an option for monitoring the evolution of the disease, especially in surgical and non-surgical organ preservation treatments. This concise review article will explain basic concepts about radiomics and discuss recent progress and results related to laryngeal cancer. Full article
(This article belongs to the Special Issue Emerging Concepts in Treatment of Laryngeal Cancer)
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15 pages, 811 KiB  
Review
Involvement of the Anterior Commissure in Early Glottic Cancer (Tis-T2): A Review of the Literature
by Martine Hendriksma and Elisabeth V. Sjögren
Cancers 2019, 11(9), 1234; https://doi.org/10.3390/cancers11091234 - 23 Aug 2019
Cited by 17 | Viewed by 6252
Abstract
Background: The impact of the anterior commissure (AC) involvement on prognosis in laryngeal cancer remains a topic of discussion with inconsistent results in the literature. This review examines AC involvement as a prognostic factor in patients with early glottic cancer (Tis–T2) treated with [...] Read more.
Background: The impact of the anterior commissure (AC) involvement on prognosis in laryngeal cancer remains a topic of discussion with inconsistent results in the literature. This review examines AC involvement as a prognostic factor in patients with early glottic cancer (Tis–T2) treated with radiotherapy or transoral laser microsurgery (TLM). Methods: A systematic literature search was performed. Due to the heterogeneity of the data, no meta-analysis was implemented. Weighted averages were calculated if the appropriate data were extractable. Results: Thirty-four studies on radiotherapy and 23 on TLM fit the inclusion criteria. The majority of studies for both radiotherapy (67.7%) and TLM (75.0%) did not report a significant impact on oncological outcomes. Weighted averages were slightly lower in patients with AC involvement. The two studies that applied a more detailed classification showed a significant impact on the amount of AC involvement. Conclusions: Binary variables (yes/no) for AC involvement lead to inconsistent results. Studies that use more detailed classifications of the AC show that there is a significant impact on the outcome. To further elucidate the role of the AC, detailed stratification of tumors involving the AC need to be investigated in further studies for both treatment modalities. Full article
(This article belongs to the Special Issue Emerging Concepts in Treatment of Laryngeal Cancer)
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