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Salivary Glands Tumors, Head and Neck Tumors and Thymoma: Current Understanding and Future Personalized Therapeutic Approach

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (15 January 2024) | Viewed by 16202

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Special Issue Editors

Dr. Nikhil Patel

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Guest Editor

Medical College of Georgia, Augusta University, Augusta, GA, USA
Interests: oncology; hematology; oncologic pathology

Dr. Saleh Heneidi

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Guest Editor

Cedars Sinai Medical Center, Los Angeles, CA, USA
Interests: head and neck cancers

Dr. Asad Ullah

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Guest Editor

Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX, USA
Interests: cancer epidemiology; cancer diagnosis; genomic profiling of cancer; emerging therapies in cancer, neuroendocrine neoplasm; melanoma
Special Issues, Collections and Topics in MDPI journals

Dr. Jaffar Khan

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Guest Editor

Indiana School of Medicine, Indiana University, Indianapolis, IN, USA
Interests: neuroblastoma; ganglioneuroblastoma; pediatric neck mass; malignancy; neoplasm; pancreas; malignant neoplasm; biphasic; Carcinosarcoma; Pancreatic Ductal Carcinoma; seer; mesothelioma; peritoneal; hipec; radiation; Surgery; Parathyroid carcinoma; seer program; Cancer Staging; incidence; survival; mortality; gist; metastatic gists; MOLECULAR; sdh; dog1; spindle cell tumors; programmed death-ligand; immunosuppression; Autoimmunity; adenocarcinoma
Special Issues, Collections and Topics in MDPI journals

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Dear Colleagues,

Head and neck tumors include the oral cavity, paranasal sinuses, salivary glands, pharynx, larynx, cervical esophagus, thyroid, associated lymph nodes, soft tissues, and bone. About 6% of head and neck tumors arise from salivary glands. Salivary gland tumors (SGTs) represent a heterogeneous group of neoplasms that vary considerably in their anatomic site of origin, histology, and biological behavior, making the entity both uncommon but commonly challenging. The diverse tissues in this anatomic region give rise to a broad spectrum of neoplasms with differing morphologies, molecular alterations, risk factors, and treatment options. Thymomas and thymic carcinomas typically present in one of three major ways: as an incidental finding, or due to local (thoracic) symptoms or paraneoplastic syndrome symptoms. Despite the increasing incidence of these tumors, the awareness and development of personalized approach therapies in these patients are lacking. The current management of these tumors along with immunotherapy towards a personalized therapeutic approach is an area which requires further attention. Increased knowledge of genetic mutations and novel therapies is also needed.

Dr. Nikhil Patel
Dr. Saleh Heneidi
Dr. Asad Ullah
Dr. Jaffar Khan
Guest Editors

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Keywords

head and neck tumors
salivary glands tumors
thymoma
personalized therapeutic
SGTs
immunotherapy
genetic mutations

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Published Papers (6 papers)

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Research

27 pages, 2714 KiB

Open AccessArticle

Segmentation of 71 Anatomical Structures Necessary for the Evaluation of Guideline-Conforming Clinical Target Volumes in Head and Neck Cancers

by Alexandra Walter, Philipp Hoegen-Saßmannshausen, Goran Stanic, Joao Pedro Rodrigues, Sebastian Adeberg, Oliver Jäkel, Martin Frank and Kristina Giske

Cancers 2024, 16(2), 415; https://doi.org/10.3390/cancers16020415 - 18 Jan 2024

Cited by 1 | Viewed by 2167

Abstract

The delineation of the clinical target volumes (CTVs) for radiation therapy is time-consuming, requires intensive training and shows high inter-observer variability. Supervised deep-learning methods depend heavily on consistent training data; thus, State-of-the-Art research focuses on making CTV labels more homogeneous and strictly bounding them to current standards. International consensus expert guidelines standardize CTV delineation by conditioning the extension of the clinical target volume on the surrounding anatomical structures. Training strategies that directly follow the construction rules given in the expert guidelines or the possibility of quantifying the conformance of manually drawn contours to the guidelines are still missing. Seventy-one anatomical structures that are relevant to CTV delineation in head- and neck-cancer patients, according to the expert guidelines, were segmented on 104 computed tomography scans, to assess the possibility of automating their segmentation by State-of-the-Art deep learning methods. All 71 anatomical structures were subdivided into three subsets of non-overlapping structures, and a 3D nnU-Net model with five-fold cross-validation was trained for each subset, to automatically segment the structures on planning computed tomography scans. We report the DICE, Hausdorff distance and surface DICE for 71 + 5 anatomical structures, for most of which no previous segmentation accuracies have been reported. For those structures for which prediction values have been reported, our segmentation accuracy matched or exceeded the reported values. The predictions from our models were always better than those predicted by the TotalSegmentator. The sDICE with 2 mm margin was larger than 80% for almost all the structures. Individual structures with decreased segmentation accuracy are analyzed and discussed with respect to their impact on the CTV delineation following the expert guidelines. No deviation is expected to affect the rule-based automation of the CTV delineation. Full article

(This article belongs to the Special Issue Salivary Glands Tumors, Head and Neck Tumors and Thymoma: Current Understanding and Future Personalized Therapeutic Approach)

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22 pages, 5623 KiB

Open AccessArticle

Inhibition of EIF2α Dephosphorylation Decreases Cell Viability and Synergizes with Standard-of-Care Chemotherapeutics in Head and Neck Squamous Cell Carcinoma

by Anna M. Cyran, Florian Kleinegger, Norbert Nass, Michael Naumann, Johannes Haybaeck and Christoph Arens

Cancers 2023, 15(22), 5350; https://doi.org/10.3390/cancers15225350 - 9 Nov 2023

Viewed by 1665

Abstract

Drug resistance is a common cause of therapy failure in head and neck squamous cell carcinoma (HNSCC). One approach to tackling it is by targeting fundamental cellular processes, such as translation. The eukaryotic translation initiation factor 2α (EIF2α) is a key player in canonical translation initiation and integrates diverse stress signals; when phosphorylated, it curbs global protein synthesis. This study evaluates EIF2α expression and phosphorylation in HNSCC. A small-molecule inhibitor of EIF2α dephosphorylation, salubrinal, was tested in vitro, followed by viability assays, flow cytometry, and immunoblot analyses. Patient-derived 3D tumor spheres (PD3DS) were cultured with salubrinal and their viability assessed. Lastly, salubrinal was evaluated with standard-of-care chemotherapeutics. Our analysis of RNA and proteomics data shows elevated EIF2α expression in HNSCC. Immunohistochemical staining reveals increasing EIF2α abundance from premalignant lesions to invasive and metastatic carcinoma. In immunoblots from intraoperative samples, EIF2α expression and steady-state phosphorylation are higher in HNSCC than in neighboring normal tissue. Inhibition of EIF2α dephosphorylation decreases HNSCC cell viability and clonogenic survival and impairs the G₁/S transition. Salubrinal also decreases the viability of PD3DS and acts synergistically with cisplatin, 5-fluorouracil, bleomycin, and proteasome inhibitors. Our results indicate that pharmacological inhibition of EIF2α dephosphorylation is a potential therapeutic strategy for HNSCC. Full article

(This article belongs to the Special Issue Salivary Glands Tumors, Head and Neck Tumors and Thymoma: Current Understanding and Future Personalized Therapeutic Approach)

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23 pages, 2806 KiB

Open AccessArticle

Depth of Invasion: Influence of the Latest TNM Classification on the Prognosis of Clinical Early Stages of Oral Tongue Squamous Cell Carcinoma and Its Association with Other Histological Risk Factors

by Ignacio Navarro Cuéllar, Samuel Espías Alonso, Francisco Alijo Serrano, Isabel Herrera Herrera, José Javier Zamorano León, José Luis Del Castillo Pardo de Vera, Ana María López López, Cristina Maza Muela, Gema Arenas de Frutos, Santiago Ochandiano Caicoya, Manuel Tousidonis Rial, Alba García Sevilla, Raúl Antúnez-Conde, José Luis Cebrián Carretero, María Isabel García-Hidalgo Alonso, José Ignacio Salmerón Escobar, Miguel Burgueño García, Carlos Navarro Vila and Carlos Navarro Cuéllar

Cancers 2023, 15(19), 4882; https://doi.org/10.3390/cancers15194882 - 8 Oct 2023

Cited by 1 | Viewed by 2608

Abstract

Background: The American Joint Committee on Cancer (AJCC), in its 8th edition, introduces modifications to the previous TNM classification, incorporating tumour depth of invasion (DOI). The aim of this research is to analyse the prognosis (in terms of disease-free survival and overall survival) of clinical early stage (I and II) squamous cell carcinomas of the oral tongue according to the DOI levels established by the AJCC in its latest TNM classification to assess changes to the T category and global staging system and to evaluate the association between DOI and other histological risk factors. Methods: A retrospective longitudinal observational study of a series of cases was designed. All patients were treated with upfront surgery at our institution between 2010 and 2019. The variables of interest were defined and classified into four groups: demographic, clinical, histological and evolutive control. Univariate and multivariate analyses were carried out and survival functions were calculated using the Kaplan–Meier method. Statistical significance was established for p values below 0.05. Results: Sixty-one patients were included. The average follow-up time was 47.42 months. Fifteen patients presented a loco-regional relapse (24.59%) and five developed distant disease (8.19%). Twelve patients died (19.67%). Statistically significant differences were observed, with respect to disease-free survival (p = 0.043), but not with respect to overall survival (p = 0.139). A total of 49.1% of the sample upstaged their T category and 29.5% underwent modifications of their global stage. The analysis of the relationship between DOI with other histological variables showed a significant association with the presence of pathological cervical nodes (p = 0.012), perineural invasion (p = 0.004) and tumour differentiation grade (p = 0.034). Multivariate analysis showed association between depth of invasion and perineural invasion. Conclusions: Depth of invasion is a histological risk factor in early clinical stages of oral tongue squamous cell carcinoma. Depth of invasion impacts negatively on patient prognosis, is capable per se of modifying the T category and the global tumour staging, and is associated with the presence of cervical metastatic disease, perineural invasion and tumoural differentiation grade. Full article

(This article belongs to the Special Issue Salivary Glands Tumors, Head and Neck Tumors and Thymoma: Current Understanding and Future Personalized Therapeutic Approach)

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18 pages, 2790 KiB

Open AccessArticle

High-Multiplex Aptamer-Based Serum Proteomics to Identify Candidate Serum Biomarkers of Oral Squamous Cell Carcinoma

by Sebastian Blatt, Peer W. Kämmerer, Maximilian Krüger, Rambabu Surabattula, Daniel G. E. Thiem, Simon T. Dillon, Bilal Al-Nawas, Towia A. Libermann and Detlef Schuppan

Cancers 2023, 15(7), 2071; https://doi.org/10.3390/cancers15072071 - 30 Mar 2023

Cited by 3 | Viewed by 2665

Abstract

Improved serological biomarkers are needed for the early detection, risk stratification and treatment surveillance of patients with oral squamous cell carcinoma (OSCC). We performed an exploratory study using advanced, highly specific, DNA-aptamer-based serum proteomics (SOMAscan, 1305-plex) to identify distinct proteomic changes in patients with OSCC pre- vs. post-resection and compared to healthy controls. A total of 63 significantly differentially expressed serum proteins (each p < 0.05) were found that could discriminate between OSCC and healthy controls with 100% accuracy. Furthermore, 121 proteins were detected that were significantly altered between pre- and post-resection sera, and 12 OSCC-associated proteins reversed to levels equivalent to healthy controls after resection. Of these, 6 were increased and 6 were decreased relative to healthy controls, highlighting the potential relevance of these proteins as OSCC tumor markers. Pathway analyses revealed potential pathophysiological mechanisms associated with OSCC. Hence, quantitative proteome analysis using SOMAscan technology is promising and may aid in the development of defined serum marker assays to predict tumor occurrence, progression and recurrence in OSCC, and to guide personalized therapies. Full article

(This article belongs to the Special Issue Salivary Glands Tumors, Head and Neck Tumors and Thymoma: Current Understanding and Future Personalized Therapeutic Approach)

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15 pages, 3950 KiB

Open AccessArticle

The Value of Multiparametric Magnetic Resonance Imaging in the Preoperative Differential Diagnosis of Parotid Gland Tumors

by Sebastian Stoia, Manuela Lenghel, Cristian Dinu, Tiberiu Tamaș, Simion Bran, Mihaela Băciuț, Emil Boțan, Daniel Leucuța, Gabriel Armencea, Florin Onișor and Grigore Băciuț

Cancers 2023, 15(4), 1325; https://doi.org/10.3390/cancers15041325 - 19 Feb 2023

Cited by 6 | Viewed by 2401

Abstract

Background: The aim of the present study was to determine the value of multiparametric MRI in the preoperative differential diagnosis of parotid tumors, which is essential for therapeutic strategy selection. Methods: A three-year prospective study was conducted with 65 patients. Each patient was investigated preoperatively with multiparametric MRI and surgical excision of the tumor was performed. The preoperative imaging diagnosis was compared with the histopathological report. Several MRI parameters were analyzed, including T1 and T2 weighted image (WI), apparent diffusion coefficient (ADC), time to peak (TTP), and the time intensity curve (TIC). Results: In the differential diagnosis of benign from malignant tumors, T2WI and ADC showed statistically significant differences. Multiparametric MRI had a sensitivity, specificity, and accuracy of 81.8%, 88.6% and 92.3%, respectively. All of the studied parameters (T1, T2, TIC, TTP, ADC) were significantly different in the comparison between pleomorphic adenomas and Warthin tumors. With reference to the scope of this study, the conjunction of multiparametric and conventional MRI demonstrated a sensitivity, specificity, and accuracy of 94.1%, 100%, and 97.8%, respectively. Conclusions: Morphological analysis using conventional MRI combined with diffusion-weighted imaging (DW) and dynamic contrast–enhanced (DCE) multiparametric MRI improved the preoperative differential diagnosis of parotid gland tumors. Full article

(This article belongs to the Special Issue Salivary Glands Tumors, Head and Neck Tumors and Thymoma: Current Understanding and Future Personalized Therapeutic Approach)

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17 pages, 2458 KiB

Open AccessArticle

Mucoepidermoid Carcinoma of the Salivary Gland: Demographics and Comparative Analysis in U.S. Children and Adults with Future Perspective of Management

by Asad Ullah, Jaffar Khan, Abdul Waheed, Nabin Raj Karki, Mya Goodbee, Abdul Qahar Khan Yasinzai, Bisma Tareen, Agha Wali, Khaleel Ahmad Khan, Muhammad Samsoor Zarak, Israr Khan, Andrea Agualimpia Garcia, Adil Khan, Marjan Khan, Sana Jogezai, Junaid Ahmad, Luis Velasquez Zarate, Nikhil Patel, Nagla Abdel Karim and Saleh Heneidi

Cancers 2023, 15(1), 250; https://doi.org/10.3390/cancers15010250 - 30 Dec 2022

Cited by 5 | Viewed by 3944

Abstract

Background: Salivary gland neoplasms are uncommon in both pediatric and adult populations. Mucoepidermoid carcinoma (MEC) is one of the most common salivary gland tumors and usually presents with atypical clinical features. This study sought to evaluate the demographic and clinical factors affecting outcomes in adults and pediatric populations with MEC that could be used to risk stratification for treatment selection and clinical trial enrollment. Methods: Data on 4507 MEC patients were extracted from the Surveillance Epidemiology and End Result (SEER) database (2000–2018). Patients aged ≤ 18 years were classified into the pediatric population, and those older than 18 years were placed in the adult group. Kaplan–Meier survival curves were created to analyze survival probabilities for various independent factors. Results: The pediatric population comprised 3.7% of the entire cohort, with a predominance of females (51.5%), while the adult population constituted 96.3% of the cohort, with a predominance of female patients (52.2%). Caucasians were the predominant race overall (75.3%), while more African Americans were seen in the pediatric group. In tumor size of <2 cm overall, poorly differentiated tumors with higher metastasis rates were observed more in adults (11.3% and 9.3%) than in the pediatric population (3.0% and 4.8%, p < 0.05). Surgical resection was the most common treatment option (53.9%), making up 63.6% of the pediatric and 53.5% of the adult groups. A combination of surgical resection and radiation was used in 29.8% of the entire cohort while a combination of surgical resection, radiation, and chemotherapy made up only 3.2%. The pediatric group had a lower overall mortality rate (5.5%) than the adult group (28.6%). Females had a higher 5-year survival rate in comparison to males (86.5%, and 73.7%, respectively). Surgical resection led to a more prolonged overall survival and 5-year cancer-specific survival (98.4% (C.I, 93.7–99.6) in the pediatric group and 88.8% (C.I, 87.5–90.0) in the adult group), respectively. Metastasis to the lung, bone, brain, and/or liver was found to have significantly lower survival rates. Multivariate analysis demonstrated that adults (hazard ratio [HR] = 7.4), Asian or Pacific Islander (HR = 0.5), male (HR = 0.8), poorly differentiated histology (HR = 3.8), undifferentiated histology (HR = 4.5), regional spread (HR = 2.1), and distant spread (HR = 3.2) were associated with increased mortality (p < 0.05). Conclusions: Mucoepidermoid carcinoma of the salivary glands primarily affects Whites and is more aggressive in adults than in the pediatric population. Even with surgical resection, the overall survival is poor in the adult population as compared to its pediatric counterparts. Advanced age, larger tumor size, male sex, and lymph node invasion are associated with increased mortality. Full article

(This article belongs to the Special Issue Salivary Glands Tumors, Head and Neck Tumors and Thymoma: Current Understanding and Future Personalized Therapeutic Approach)

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