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1.
J Cancer Res Clin Oncol ; 150(6): 288, 2024 Jun 04.
Article En | MEDLINE | ID: mdl-38834932

BACKGROUND: Neuroendocrine neoplasm is a rare cancer of head and neck. This study aimed to evaluate clinical features, treatment outcomes, and prognostic factors of neuroendocrine neoplasm of head and neck treated at a single institution. METHODS: Between Nov 2000 and Nov 2021, ninety-three patients diagnosed with neuroendocrine neoplasms of head and neck treated at our institution were reviewed retrospectively. The initial treatments included chemotherapy (induction, adjuvant, or concurrent) combined with radiotherapy in 40 patients (C + RT group), surgery followed by post-operative RT in 34 (S + RT group), and surgery plus salvage therapy in 19 patients (S + Sa group). RESULTS: The median follow-up time was 64.5 months. 5-year overall survival rate (OS), progression-free survival rate (PFS), loco-regional relapse-free survival free rate (LRRFS) and distant metastasis-free survival rate (DMFS) were 64.5%, 51.6%, 66.6%, and 62.1%, respectively. For stage I-II, the 5-year LRRFS for patients' treatment regimen with or without radiotherapy (C + RT and S + RT groups versus S + Sa group) was 75.0% versus 12.7% (p = 0.015) while for stage III-IV, the 5-year LRRFS was 77.8% versus 50.0% (p = 0.006). The 5-year DMFS values for patients with or without systemic therapy (C + RT group versus S + RT or S + Sa) were 71.2% and 51.5% (p = 0.075). 44 patients (47.3%) experienced treatment failure and distant metastasis was the main failure pattern. CONCLUSIONS: Radiotherapy improved local-regional control and played an important role in the management of HNNENs. The optimal treatment regimen for HNNENs remains the combination of local and systemic treatments.


Head and Neck Neoplasms , Neuroendocrine Tumors , Humans , Male , Female , Middle Aged , Head and Neck Neoplasms/therapy , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/mortality , Adult , Aged , Neuroendocrine Tumors/therapy , Neuroendocrine Tumors/pathology , Neuroendocrine Tumors/mortality , Retrospective Studies , Prognosis , Young Adult , Survival Rate , Treatment Outcome , Combined Modality Therapy , Follow-Up Studies , Adolescent
3.
Microsurgery ; 44(5): e31190, 2024 Jul.
Article En | MEDLINE | ID: mdl-38828550

BACKGROUND: Scalp defect reconstruction poses considerable challenges, with ongoing debates regarding the most effective strategies. While the latissimus dorsi (LD) flap has traditionally been favored, the anterolateral thigh (ALT) flap has been well described as a versatile alternative for addressing extensive scalp defects. This study underscores the success of scalp reconstruction using ALT flaps, notably pushing the boundaries of previously reported flap sizes. Our approach leverages the use of indocyanine green (ICG) perfusion to guide precise preoperative planning and vascular modification, contributing to improved outcomes in challenging cases. METHODS: We performed 43 ALT flap reconstructions for scalp defects between 2016 and 2023. We collected patients' demographic and clinical data and evaluated flap size and recipient vessels and additional surgical techniques. Detailed preoperative plans with ultrasound and ICG use for intraoperative plans were performed to find perforators location. The cohort was divided into two, with or without complications on flaps, and analyzed depending on its surgical details. RESULTS: This study involved 38 patients with extensive scalp defects (mean age: 69.4 ± 11 years) who underwent ALT perforator flap transfers (mean flap size: 230.88 ± 145.6 cm2). There was only one case of unsuccessful flap transfer, and four cases had a few complications. The characteristics of the complication group included a large flap size (303.1 ± 170.9 vs. 214.9 ± 136.6 cm2, P = .211), few perforator numbers without pedicle manipulation, lack of intraoperative indocyanine green administration (75% vs. 25%, P = .607), and the use of superficial temporal vessels as recipient vessels. CONCLUSIONS: Scalp reconstruction using large ALT free flaps with the aid of imaging modalities facilitates the optimization of surgical techniques, such as pedicle manipulation, perforator numbers, and vein considerations, thereby contributing to successful reconstruction.


Free Tissue Flaps , Indocyanine Green , Plastic Surgery Procedures , Scalp , Thigh , Humans , Scalp/surgery , Scalp/blood supply , Male , Aged , Female , Free Tissue Flaps/blood supply , Plastic Surgery Procedures/methods , Thigh/surgery , Thigh/blood supply , Thigh/diagnostic imaging , Middle Aged , Aged, 80 and over , Retrospective Studies , Head and Neck Neoplasms/surgery , Head and Neck Neoplasms/diagnostic imaging , Perforator Flap/blood supply , Ultrasonography/methods , Coloring Agents , Skin Neoplasms/surgery , Skin Neoplasms/diagnostic imaging
4.
J Chin Med Assoc ; 87(6): 643-652, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38838200

BACKGROUND: Early palliative care (EPC) benefits some cancers, but its clinical outcomes differ depending on patients' racial and ethnic disparities, and customs. To determine whether EPC improves symptoms, emotional distress, and quality of life among Taiwanese patients with early or advanced-stage head and neck cancer (HNC). METHODS: Based on participants' pathological stages, they were categorized as having early and advanced-stage HNC. Those willing and unwilling to undergo EPC were assigned to the EPC and standard groups, respectively. Their daily cancer-related symptoms were assessed using the Distress Thermometer (DT) and MD Anderson Symptom Inventory (MDASI), whose scores' concurrent validity was evaluated using the European Organization for Research and Treatment of Core Quality of Life (EORTC-QLQ-C30) and Head and Neck 35 (EORTC-QLQ-H&N35) questionnaires. RESULTS: Patients (n = 93) diagnosed with HNC at Taiwan's Chia-Yi Christian Hospital from November 2020 to October 2022 were recruited. The patients voluntarily split into two groups: EPC groups and standard groups (23 and 11 in early-stage; 46 and 13 in advanced-stage, respectively). DT assessment showed significant emotional distress improvements for all patients with HNC who received EPC. The EORTC-QLQ-C30 questionnaire indicated that, compared to standard interventions, EPC groups significantly improved the quality of life and some symptoms for both early and advanced-stage HNC patients. However, the EORTC-QLQ-H&N35 questionnaire found no significant difference between the two groups. Furthermore, advanced-stage patients' anticancer treatment completion rates with EPC and standard interventions were 95.35% and 75%, respectively. CONCLUSION: EPC improves symptoms, emotional distress, quality of life, and treatment completion rates in Taiwanese patients with early or advanced-stage HNC. Nonetheless, further extensive clinical studies are required for validation.


Head and Neck Neoplasms , Palliative Care , Quality of Life , Humans , Head and Neck Neoplasms/therapy , Head and Neck Neoplasms/psychology , Male , Female , Middle Aged , Aged , Taiwan , Adult , Surveys and Questionnaires
5.
Mayo Clin Proc ; 99(6): 1006-1012, 2024 Jun.
Article En | MEDLINE | ID: mdl-38839179

This case report describes the safety and utility of a noninvasive therapy, Purified Exosome Product (PEP), for poorly healing scalp wounds in the setting of prior chemoradiation and surgery. A man in his 60s with a history of high-grade angiosarcoma of the right temporoparietal scalp reconstruction had a 1-year history of 2 nonhealing scalp wounds after neoadjuvant chemotherapy followed by concurrent chemoradiation therapy, wide local excision, and latissimus dorsi free flap and split-thickness skin graft. The patient underwent débridement followed by 4 collagen (Bellafill)-PEP and 4 fibrin (Tisseel)-PEP applications during 7 months in 2022. Photographs of the area of exposed bone of the temporoparietal wound were measured and standardized by ImageJ open-source software. The frontal wound was not routinely measured and therefore was qualitatively assessed by reviewing photographs over time. The frontal wound completely healed, and the temporoparietal wound showed a 96% decrease in overall size. The patient had no adverse effects of treatment and continues to demonstrate ongoing healing. This case exhibits the safety and utility of topical PEP therapy for noninvasive treatment of poorly healing scalp wounds and offers the potential for an alternative treatment of patients who are poor candidates for additional surgical intervention.


Exosomes , Scalp , Wound Healing , Humans , Male , Middle Aged , Skin Neoplasms/therapy , Chemoradiotherapy/methods , Chemoradiotherapy/adverse effects , Hemangiosarcoma/therapy , Head and Neck Neoplasms/therapy , Debridement/methods
6.
J Cardiothorac Surg ; 19(1): 318, 2024 Jun 04.
Article En | MEDLINE | ID: mdl-38835049

Thymoma is a rare malignancy with usual location in the antero-superior mediastinum. Ectopic cervical thymoma (ECT) is an extremely rare tumor that originates from ectopic tissue, and is caused by the aberrant migration of the embryonic thymus. Our patient was a 56-year-old man who had a nodular lesion in the neck for several years. Computed tomography and Enhanced magnetic resonance imaging were performed. He underwent surgery, and a histological examination resulted in a diagnosis of type AB thymoma.


Choristoma , Magnetic Resonance Imaging , Thymoma , Thymus Neoplasms , Tomography, X-Ray Computed , Humans , Male , Middle Aged , Thymoma/surgery , Thymoma/diagnosis , Thymoma/diagnostic imaging , Thymoma/pathology , Thymus Neoplasms/surgery , Thymus Neoplasms/diagnosis , Thymus Neoplasms/diagnostic imaging , Thymus Neoplasms/pathology , Choristoma/surgery , Choristoma/diagnosis , Choristoma/pathology , Choristoma/diagnostic imaging , Neck/diagnostic imaging , Head and Neck Neoplasms/surgery , Head and Neck Neoplasms/diagnosis , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/diagnostic imaging
7.
BMC Oral Health ; 24(1): 645, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38824583

OBJECTIVES: This study aimed to evaluate the preventive and therapeutic effects of rebamipide gargle in comparison with benzydamine in head and neck cancer patients undergoing radiotherapy with or without chemotherapy. MATERIALS AND METHODS: Phase III randomized clinical trial was conducted from January 2021 till August 2022 on one hundred patients with head and neck cancer receiving high doses of radiotherapy. These patients were equally allocated into either rebamipide group or benzydamine group, The measured outcomes were the incidence of oral mucositis ≥ grade1, according to the WHO mucositis scale, in addition to the duration, and the onset of oral mucositis. RESULTS: There was no statistically significant difference between the two groups, regarding the incidence of a severe grade of oral mucositis (WHO grades 3), as well as the onset and duration of oral mucositis. Both gargles succeeded to prevent the development of WHO grade 4 oral mucositis. Side effects reported were mainly burning sensation in benzydamine group and nausea in rebamipide group. CONCLUSION: Rebamipide mouthwash was as beneficial as benzydamine mouthwash in minimizing the incidence of severe oral mucositis induced by treatment of head and neck cancer. However, rebamipide gargle proved to be superior to benzydamine in terms of reduction in the severity of the radiation-induced oral mucositis. TRIAL REGISTRATION: The trial was registered in the protocol Registration and Result system of Clinical Trials (Registration ID: NCT04685395)0.28-12-2020.


Alanine , Benzydamine , Head and Neck Neoplasms , Mouthwashes , Quinolones , Stomatitis , Humans , Stomatitis/prevention & control , Stomatitis/etiology , Head and Neck Neoplasms/radiotherapy , Benzydamine/therapeutic use , Male , Middle Aged , Female , Quinolones/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Mouthwashes/therapeutic use , Chemoradiotherapy/adverse effects , Radiation Injuries/prevention & control , Aged , Adult
8.
Anal Cell Pathol (Amst) ; 2024: 8810804, 2024.
Article En | MEDLINE | ID: mdl-38826849

Head and neck squamous cell carcinoma (HNSCC) poses significant challenges with poor survival rates and limited therapeutic strategies. Our study, using The Cancer Genome Atlas (TCGA) data, assesses cancer-associated fibroblast (CAF) gene signatures' clinical relevance. In our analysis across TCGA tumor types, differential gene expression analysis revealed that fibroblast activation protein (FAP) is upregulated in tumor tissues and associated with poorer survival rates in HNSCC. Furthermore, mechanistic studies employing gene-silencing techniques substantiated that FAP knockout led to a significant decrease in cellular proliferation, invasion, and migration in HNSCC cell lines. Through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, we established that high FAP expression correlates with vital biological processes such as extracellular matrix organization, angiogenesis, and cellular motility. Importantly, FAP was found to regulate these processes by promoting the expression of key proteins involved in epithelial-mesenchymal transition-related pathways. Additionally, our analysis revealed a significant correlation between FAP expression and the expression profiles of immune checkpoint molecules, underscoring its potential role in immune modulation. Collectively, our findings illuminate FAP's pivotal role in HNSCC pathogenesis and its potential as a prognostic biomarker and therapeutic target. This research lays the groundwork for understanding the multifaceted roles and regulatory mechanisms of CAFs in HNSCC, thereby offering valuable perspectives for the development of targeted therapeutic strategies aimed at improving patient outcomes.


Biomarkers, Tumor , Endopeptidases , Gelatinases , Gene Expression Regulation, Neoplastic , Head and Neck Neoplasms , Membrane Proteins , Serine Endopeptidases , Squamous Cell Carcinoma of Head and Neck , Humans , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , Prognosis , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/metabolism , Squamous Cell Carcinoma of Head and Neck/pathology , Endopeptidases/metabolism , Endopeptidases/genetics , Serine Endopeptidases/metabolism , Serine Endopeptidases/genetics , Membrane Proteins/metabolism , Membrane Proteins/genetics , Cell Line, Tumor , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/metabolism , Head and Neck Neoplasms/pathology , Gelatinases/metabolism , Gelatinases/genetics , Epithelial-Mesenchymal Transition/genetics , Cell Proliferation/genetics , Cell Movement/genetics
11.
Cancer Med ; 13(11): e7250, 2024 Jun.
Article En | MEDLINE | ID: mdl-38826090

PURPOSE: Since June 2020, boron neutron capture therapy (BNCT) has been a health care service covered by health insurance in Japan to treat locally advanced or recurrent unresectable head and neck cancers. Therefore, we aimed to assess the clinical outcomes of BNCT as a health insurance treatment and explore its role among the standard treatment modalities for head and neck cancers. MATERIALS AND METHODS: We retrospectively analyzed data from patients who were treated using BNCT at Kansai BNCT Medical Center, Osaka Medical and Pharmaceutical University, between June 2020 and May 2022. We assessed objective response rates based on the Response Evaluation Criteria in Solid Tumors version 1.1, and adverse events based on the Common Terminology Criteria for Adverse Events, version 5.0. Additionally, we conducted a survival analysis and explored the factors that contributed to the treatment results. RESULTS: Sixty-nine patients (72 treatments) were included in the study, with a median observation period of 15 months. The objective response rate was 80.5%, and the 1-year locoregional control, progression-free survival, and overall survival rates were 57.1% (95% confidence interval [CI]: 43.9%-68.3%), 42.2% (95% CI: 30.1%-53.8%), and 75.4% (95% CI: 62.5%-84.5%), respectively. Locoregional control was significantly longer in patients with earlier TNM staging and no history of chemotherapy. CONCLUSIONS: BNCT may be an effective treatment option for locally advanced or recurrent unresectable head and neck cancers with no other definitive therapies. If definitive surgery or radiation therapy are not feasible, BNCT should be considered at early disease stages.


Boron Neutron Capture Therapy , Head and Neck Neoplasms , Humans , Boron Neutron Capture Therapy/methods , Male , Female , Head and Neck Neoplasms/radiotherapy , Head and Neck Neoplasms/therapy , Head and Neck Neoplasms/mortality , Japan , Middle Aged , Aged , Retrospective Studies , Adult , Aged, 80 and over , Treatment Outcome , Insurance, Health , Survival Rate
12.
JAMA Netw Open ; 7(6): e2413004, 2024 Jun 03.
Article En | MEDLINE | ID: mdl-38833253

Importance: It is essential to identify inequitable cancer care for ethnic minority groups, which may allow policy change associated with improved survival and decreased mortality and morbidity. Objective: To investigate ethnic disparities in survival and mortality among New Zealand (NZ) patients with head and neck cancer (HNC) and the association of other variables, including socioeconomic status, tumor stage, and age at diagnosis, with survival rates. Design, Setting, and Participants: This retrospective cohort study was conducted among NZ patients diagnosed with specific HNCs from 2010 to 2020. Anonymized data were obtained from the NZ Cancer Registry, including patients diagnosed from International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes C00-C14 and C30-C32. Data were analyzed from July 2020 through January 2024. Main Outcomes and Measures: Censored Kaplan-Meier estimates were used to analyze survival distribution. Cox regression models were used to estimate the association of age, tumor stage at diagnosis, and socioeconomic status with survival rates. Age-standardized mortality rates were assessed. Results: Among 6593 patients with HNCs (4590 males [69.6%]; 4187 patients aged 51-75 years [63.5%]), there were 706 Maori individuals (10.7%) and 5887 individuals with other ethnicity (89.3%), including 4327 NZ European individuals (65.6%; defined as New Zealanders of European descent). Maori individuals had a decreased survival proportion at all years after diagnosis compared with individuals with other ethnicity (eg, 66.1% [95% CI, 62.6%% to 69.8%] vs 71.2% [95% CI, 70.0% to 72.4%] at 2 years). At 1 year after diagnosis, Maori individuals did not have a significantly increased mortality rate compared with 5795 individuals with other ethnicity with data (193 deaths [27.3%] vs 1400 deaths [24.2%]; P = .06), but the rate was significantly increased at 5 years after diagnosis (277 deaths [39.3%] vs 2034 deaths [35.1%]; P = .03); there was greater disparity compared with NZ European individuals (1 year: 969 deaths [22.4%]; P = .003; 5 years: 1441 deaths [33.3%]; P = .002). There were persistent age-adjusted mortality rate disparities: 40.1% (95% CI, -25.9% to 71.2%) for Maori individuals and 18.8% (95% CI, -15.4% to 24.4%) for individuals with other ethnicity. Maori individuals were diagnosed at a mean age of 58.0 years (95% CI, 57.1-59.1 years) vs 64.3 years. (95% CI, 64.0-64.7 years) for individuals with other ethnicity, or 5 to 7 years younger, and died at mean age of 63.5 years (95% CI, 62.0-64.9 years) compared with 72.3 years (95% CI, 71.8-72.9 years) for individuals with other ethnicity, or 7 to 10 years earlier. Maori individuals presented with proportionally more advanced disease (only localized disease, 102 patients [14.5%; 95% CI, 12.0%-17.4%] vs 1413 patients [24.0%; 95% CI, 22.9%-25.1%]; P < .001) and showed an increase in regional lymph nodes (276 patients [39.1%; 95% CI, 35.5%-42.9%] vs 1796 patients [30.5%; 95% CI, 29.3%-31.8%]; P < .001) at diagnosis compared with individuals with other ethnicity. Socioeconomic status was not associated with survival. Conclusions and Relevance: This study found that Maori individuals experienced worse survival outcomes and greater mortality rates from HNC in NZ and presented with more advanced disease at a younger age. These findings suggest the need for further research to alleviate these disparities, highlight the importance of research into minority populations with HNC globally, and may encourage equity research for all cancers.


Head and Neck Neoplasms , Humans , New Zealand/epidemiology , Male , Female , Middle Aged , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/ethnology , Head and Neck Neoplasms/therapy , Aged , Retrospective Studies , Ethnicity/statistics & numerical data , Adult , Survival Rate , Health Status Disparities , Healthcare Disparities/statistics & numerical data , Healthcare Disparities/ethnology
13.
Cancer Med ; 13(11): e7370, 2024 Jun.
Article En | MEDLINE | ID: mdl-38847087

OBJECTIVES: Certain low-level immune-related adverse events (irAEs) have been associated with survival benefits in patients with various solid tumors on immune checkpoint inhibitors (ICIs). We aimed to investigate the association between irAEs and response to neoadjuvant ICIs in patients with head and neck squamous cell carcinoma (HNSCC) and to identify differences in circulating cytokine levels based on irAE status. METHODS: This was a retrospective cohort study including three neoadjuvant clinical trials from July 2017 to January 2022: NCT03238365 (nivolumab ± tadalafil), NCT03854032 (nivolumab ± BMS986205), NCT03618654 (durvalumab ± metformin). The presence and type of irAEs, pathologic treatment response, and survival were compared. Canonical linear discriminant analysis (LDA) was performed to identify combinations of circulating cytokines predictive of irAEs using plasma sample multiplex assay. RESULTS: Of 113 participants meeting inclusion criteria, 32 (28.3%) developed irAEs during treatment or follow-up. Positive p16 status was associated with irAEs (odds ratio [OR] 2.489; 95% CI 1.069-6.119; p = 0.043). irAEs were associated with pathologic treatment response (OR 3.73; 95% CI 1.34-10.35; p = 0.011) and with higher OS in the combined cohort (HR 0.319; 95% CI 0.113-0.906; p = 0.032). Patients with irAEs within the nivolumab cohort had significant elevations of select cytokines pre-treatment. Canonical LDA identified key drivers of irAEs among all trials, which were highly predictive of future irAE status. CONCLUSIONS: irAEs are associated with response to neoadjuvant ICI therapy in HNSCC and can serve as clinical indicators for improved clinical outcomes. irAEs can be predicted by concentrations of several circulating cytokines prior to treatment.


Cytokines , Head and Neck Neoplasms , Immune Checkpoint Inhibitors , Neoadjuvant Therapy , Squamous Cell Carcinoma of Head and Neck , Humans , Squamous Cell Carcinoma of Head and Neck/drug therapy , Squamous Cell Carcinoma of Head and Neck/blood , Squamous Cell Carcinoma of Head and Neck/immunology , Immune Checkpoint Inhibitors/adverse effects , Immune Checkpoint Inhibitors/therapeutic use , Male , Neoadjuvant Therapy/adverse effects , Neoadjuvant Therapy/methods , Female , Middle Aged , Retrospective Studies , Cytokines/blood , Aged , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/blood , Head and Neck Neoplasms/immunology , Nivolumab/adverse effects , Nivolumab/therapeutic use
14.
Int J Biol Sci ; 20(7): 2576-2591, 2024.
Article En | MEDLINE | ID: mdl-38725862

We showed that microtubule-associated tumor suppressor gene (MTUS1/ATIP) downregulation correlated with poor survival in head and neck squamous cell carcinoma (HNSCC) patients and that MTUS1/ATIP1 was the most abundant isoform in HNSCC tissue. However, the location and function of MTUS1/ATIP1 have remain unclear. In this study, we confirmed that MTUS1/ATIP1 inhibited proliferation, growth and metastasis in HNSCC in cell- and patient-derived xenograft models in vitro and in vivo. MTUS1/ATIP1 localized in the outer mitochondrial membrane, influence the morphology, movement and metabolism of mitochondria and stimulated oxidative stress in HNSCC cells by directly interacting with MFN2. MTUS1/ATIP1 activated ROS, recruiting Bax to mitochondria, facilitating cytochrome c release to the cytosol to activate caspase-3, and inducing GSDME-dependent pyroptotic death in HNSCC cells. Our findings showed that MTUS1/ATIP1 localized in the outer mitochondrial membrane in HNSCC cells and mediated anticancer effects through ROS-induced pyroptosis, which may provide a novel therapeutic strategy for HNSCC treatment.


Head and Neck Neoplasms , Mitochondria , Pyroptosis , Reactive Oxygen Species , Squamous Cell Carcinoma of Head and Neck , Humans , Reactive Oxygen Species/metabolism , Head and Neck Neoplasms/metabolism , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/genetics , Animals , Cell Line, Tumor , Mitochondria/metabolism , Squamous Cell Carcinoma of Head and Neck/metabolism , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/genetics , Mice , Mitochondrial Proteins/metabolism , Mitochondrial Proteins/genetics , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/genetics , Mice, Nude , Tumor Suppressor Proteins/metabolism , Tumor Suppressor Proteins/genetics , Mitochondrial Membranes/metabolism , Cell Proliferation
15.
Cancer Biol Ther ; 25(1): 2350249, 2024 Dec 31.
Article En | MEDLINE | ID: mdl-38722731

Head and Neck Squamous Cell Carcinoma (HNSCC) comprises a diverse group of tumors with variable treatment response and prognosis. The tumor microenvironment (TME), which includes microbiome and immune cells, can impact outcomes. Here, we sought to relate the presence of specific microbes, gene expression, and tumor immune infiltration using tumor transcriptomics from The Cancer Genome Atlas (TCGA) and associate these with overall survival (OS). RNA sequencing (RNAseq) from HNSCC tumors in TCGA was processed through the exogenous sequences in tumors and immune cells (exotic) pipeline to identify and quantify low-abundance microbes. The detection of the Papillomaviridae family of viruses assessed HPV status. All statistical analyses were performed using R. A total of 499 RNAseq samples from TCGA were analyzed. HPV was detected in 111 samples (22%), most commonly Alphapapillomavirus 9 (90.1%). The presence of Alphapapillomavirus 9 was associated with improved OS [HR = 0.60 (95%CI: 0.40-0.89, p = .01)]. Among other microbes, Yersinia pseudotuberculosis was associated with the worst survival (HR = 3.88; p = .008), while Pseudomonas viridiflava had the best survival (HR = 0.05; p = .036). Microbial species found more abundant in HPV- tumors included several gram-negative anaerobes. HPV- tumors had a significantly higher abundance of M0 (p < .001) and M2 macrophages (p = .035), while HPV+ tumors had more T regulatory cells (p < .001) and CD8+ T-cells (p < .001). We identified microbes in HNSCC tumor samples significantly associated with survival. A greater abundance of certain anaerobic microbes was seen in HPV tumors and pro-tumorigenic macrophages. These findings suggest that TME can be used to predict patient outcomes and may help identify mechanisms of resistance to systemic therapies.


Head and Neck Neoplasms , Microbiota , Papillomavirus Infections , Squamous Cell Carcinoma of Head and Neck , Tumor Microenvironment , Humans , Head and Neck Neoplasms/virology , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/immunology , Head and Neck Neoplasms/microbiology , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/genetics , Female , Papillomavirus Infections/virology , Papillomavirus Infections/immunology , Papillomavirus Infections/complications , Male , Microbiota/genetics , Tumor Microenvironment/immunology , Squamous Cell Carcinoma of Head and Neck/virology , Squamous Cell Carcinoma of Head and Neck/microbiology , Squamous Cell Carcinoma of Head and Neck/immunology , Squamous Cell Carcinoma of Head and Neck/mortality , Prognosis , Middle Aged , Papillomaviridae/genetics , Aged
16.
Biomed Phys Eng Express ; 10(4)2024 May 10.
Article En | MEDLINE | ID: mdl-38697044

Objective.The aim of this work was to develop a Phase I control chart framework for the recently proposed multivariate risk-adjusted Hotelling'sT2chart. Although this control chart alone can identify most patients receiving extreme organ-at-risk (OAR) dose, it is restricted by underlying distributional assumptions, making it sensitive to extreme observations in the sample, as is typically found in radiotherapy plan quality data such as dose-volume histogram (DVH) points. This can lead to slightly poor-quality plans that should have been identified as out-of-control (OC) to be signaled in-control (IC).Approach. We develop a robust iterative control chart framework to identify all OC patients with abnormally high OAR dose and improve them via re-optimization to achieve an IC sample prior to establishing the Phase I control chart, which can be used to monitor future treatment plans.Main Results. Eighty head-and-neck patients were used in this study. After the first iteration, P14, P67, and P68 were detected as OC for high brainstem dose, warranting re-optimization aimed to reduce brainstem dose without worsening other planning criteria. The DVH and control chart were updated after re-optimization. On the second iteration, P14, P67, and P68 were IC, but P40 was identified as OC. After re-optimizing P40's plan and updating the DVH and control chart, P40 was IC, but P14* (P14's re-optimized plan) and P62 were flagged as OC. P14* could not be re-optimized without worsening target coverage, so only P62 was re-optimized. Ultimately, a fully IC sample was achieved. Multiple iterations were needed to identify and improve all OC patients, and to establish a more robust control limit to monitor future treatment plans.Significance. The iterative procedure resulted in a fully IC sample of patients. With this sample, a more robust Phase I control chart that can monitor OAR doses of new plans was established.


Organs at Risk , Quality Control , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted , Humans , Organs at Risk/radiation effects , Radiotherapy Planning, Computer-Assisted/methods , Head and Neck Neoplasms/radiotherapy , Algorithms
17.
J Cancer Res Clin Oncol ; 150(5): 240, 2024 May 07.
Article En | MEDLINE | ID: mdl-38713284

PURPOSE: Head and neck cancer is the sixth most common type of cancer worldwide, wherein the immune responses are closely associated with disease occurrence, development, and prognosis. Investigation of the role of immunogenic cell death-related genes (ICDGs) in adaptive immune response activation may provide cues into the mechanism underlying the outcome of HNSCC immunotherapy. METHODS: ICDGs expression patterns in HNSCC were analyzed, after which consensus clustering in HNSCC cohort conducted. A 4-gene prognostic model was constructed through LASSO and Cox regression analyses to analyze the prognostic index using the TCGA dataset, followed by validation with two GEO datasets. The distribution of immune cells and the response to immunotherapy were compared between different risk subtypes through multiple algorithms. Moreover, immunohistochemical (IHC) analyses were conducted to validate the prognostic value of HSP90AA1 as a predictor of HNSCC patient prognosis. In vitro assays were performed to further detect the effect of HSP90AA1 in the development of HNSCC. RESULTS: A novel prognostic index based on four ICDGs was constructed and proved to be useful as an independent factor of HNSCC prognosis. The risk score derived from this model grouped patients into high- and low-risk subtypes, wherein the high-risk subtype had worse survival outcomes and poorer immunotherapy response. IHC analysis validated the applicability of HSP90AA1 as a predictor of prognosis of HNSCC patients. HSP90AA1 expression in tumor cells promotes the progression of HNSCC. CONCLUSIONS: Together, these results highlight a novel four-gene prognostic signature as a valuable tool to assess survival status and prognosis of HNSCC patients.


HSP90 Heat-Shock Proteins , Head and Neck Neoplasms , Squamous Cell Carcinoma of Head and Neck , Humans , Squamous Cell Carcinoma of Head and Neck/immunology , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/metabolism , Prognosis , HSP90 Heat-Shock Proteins/genetics , HSP90 Heat-Shock Proteins/metabolism , Head and Neck Neoplasms/immunology , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/metabolism , Female , Male , Immunogenic Cell Death , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Middle Aged , Immunotherapy/methods , Gene Expression Regulation, Neoplastic
18.
Arch Microbiol ; 206(6): 248, 2024 May 07.
Article En | MEDLINE | ID: mdl-38713383

Describing the microbial community within the tumour has been a key aspect in understanding the pathophysiology of the tumour microenvironment. In head and neck cancer (HNC), most studies on tissue samples have only performed 16S rRNA short-read sequencing (SRS) on V3-V5 region. SRS is mostly limited to genus level identification. In this study, we compared full-length 16S rRNA long-read sequencing (FL-ONT) from Oxford Nanopore Technology (ONT) to V3-V4 Illumina SRS (V3V4-Illumina) in 26 HNC tumour tissues. Further validation was also performed using culture-based methods in 16 bacterial isolates obtained from 4 patients using MALDI-TOF MS. We observed similar alpha diversity indexes between FL-ONT and V3V4-Illumina. However, beta-diversity was significantly different between techniques (PERMANOVA - R2 = 0.131, p < 0.0001). At higher taxonomic levels (Phylum to Family), all metrics were more similar among sequencing techniques, while lower taxonomy displayed more discrepancies. At higher taxonomic levels, correlation in relative abundance from FL-ONT and V3V4-Illumina were higher, while this correlation decreased at lower levels. Finally, FL-ONT was able to identify more isolates at the species level that were identified using MALDI-TOF MS (75% vs. 18.8%). FL-ONT was able to identify lower taxonomic levels at a better resolution as compared to V3V4-Illumina 16S rRNA sequencing.


Bacteria , Head and Neck Neoplasms , Nanopore Sequencing , RNA, Ribosomal, 16S , Humans , RNA, Ribosomal, 16S/genetics , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/microbiology , Nanopore Sequencing/methods , Bacteria/genetics , Bacteria/classification , Bacteria/isolation & purification , Microbiota/genetics , High-Throughput Nucleotide Sequencing , Middle Aged , Sequence Analysis, DNA , Male , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Female , Aged , Adult , Phylogeny
19.
Laryngorhinootologie ; 103(5): 371-382, 2024 May.
Article De | MEDLINE | ID: mdl-38697084

In CUP syndrome (CUP = cancer of unknown primary) there are 1 or more metastases of a primary tumor that cannot be localized despite extensive diagnostics. CUP syndrome accounts for 5% of all human malignancies, making it one of the 10 most common forms of cancer. In addition to inflammatory lymph node enlargement and benign changes such as cervical cysts, lymph node metastases are among the most common cervical masses. Cervical CUP syndrome is a histologically confirmed cervical lymph node metastasis with an unknown primary tumor. In addition to anamnesis, clinical examination and histological confirmation, diagnostics include radiological imaging using PET-CT and panendoscopy with histological primary tumor search. Treatment options include surgical therapy with neck dissection and chemoradiotherapy.


Lymphatic Metastasis , Neoplasms, Unknown Primary , Humans , Neoplasms, Unknown Primary/therapy , Neoplasms, Unknown Primary/diagnosis , Neoplasms, Unknown Primary/pathology , Lymphatic Metastasis/pathology , Neck Dissection , Head and Neck Neoplasms/therapy , Head and Neck Neoplasms/diagnosis , Head and Neck Neoplasms/pathology , Syndrome , Combined Modality Therapy , Positron Emission Tomography Computed Tomography , Diagnosis, Differential , Chemoradiotherapy
20.
Laryngorhinootologie ; 103(S 01): S3-S27, 2024 May.
Article En, De | MEDLINE | ID: mdl-38697141

Squamous cell carcinomas are the most common malignancies in the oral cavity, pharynx, and larynx. Even in the age of the most modern drug treatment methods, radical resection of these tumors is and currently remains the therapeutic gold standard. The loss of anatomical structures associated with surgery inevitably increases the functional deficits caused by the tumor itself. In this context, the extent of functional deficits is largely determined by the extent of resection. Complete organ resections, such as glossectomy, complete palate resection, laryngectomy, or transverse pharyngo-laryngectomy, lead to severe functional deficits, such as swallowing disturbances with life-threatening aspiration and articulation disorders up to the inability to speak. With the help of plastic reconstructive surgery, the lost tissue can be replaced and the specific functions of the upper aerodigestive tract can be preserved or restored.In recent decades, reconstructive surgical procedures have developed enormously in the treatment of malignant tumors of the head and neck. In order to make optimal use of them, a comprehensive, interdisciplinary therapy concept is a prerequisite for positive oncological and functional outcome. In addition to general medical and social parameters, surgical parameters play a crucial role in the choice of the reconstruction method. The extent to which the surgical measures must be interdisciplinary depends on the localization of the defects in the head and neck region and on the type of replacement tissue required. Here, the expertise of plastic surgery, oral and maxillofacial surgery, and abdominal surgery comes into play in particular. The use of different tissues, the combination of different grafts and flaps, or the preforming of donor regions allow reconstructions far beyond the level of simply restoring surface integrity. The functional results and thus the quality of life of patients after surgical therapy of extensive tumors of the mentioned localizations depend decisively on the type of reconstruction. Therefore, in the following review, special emphasis 1 be placed on the choice of reconstruction method and reconstruction technique for tissue loss after resections of HNSCC.


Plastic Surgery Procedures , Humans , Plastic Surgery Procedures/methods , Carcinoma, Squamous Cell/surgery , Carcinoma, Squamous Cell/pathology , Interdisciplinary Communication , Head and Neck Neoplasms/surgery , Head and Neck Neoplasms/pathology , Patient Care Team , Squamous Cell Carcinoma of Head and Neck/surgery , Squamous Cell Carcinoma of Head and Neck/pathology , Intersectoral Collaboration
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