Effectiveness of early palliative care in patients with head and neck cancer in Taiwan.

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.

Exosome Therapy for a Nonhealing Scalp Wound Following Chemoradiation and Surgical Therapy.

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.

[Research progress in the anatomy and surgical approach of the parapharyngeal space].

The parapharyngeal space, a complex fascial compartment within the head and neck region, encompasses crucial anatomical structures including blood vessels and nerves. Tumors occurring within this space are rare, with the majority being benign in nature. Surgical intervention remains the primary treatment modality; however, managing parapharyngeal space tumors poses significant challenges due to their intricate anatomical configuration. Conventional open surgical approaches have been associated with significant tissue damage and a high prevalence of postoperative complications. Recently, advancements in anatomical studies and surgical techniques have led to significant progress in understanding parapharyngeal space anatomy and improving surgical management. This article aims to provide a comprehensive overview of these developments.

Basaloid squamous cell carcinoma clinically and radiologically masquerading as a head and neck paraganglioma: a case report and review of the literature.

BACKGROUND: This paper reports the first case of basaloid squamous cell carcinoma clinically and radiologically masquerading as a head and neck paraganglioma. CASE PRESENTATION: A 66-year-old Sinhalese male with unilateral hearing impairment and 7th-12th (excluding 11th) cranial nerve palsies was diagnosed radiologically with a head and neck paraganglioma by magnetic resonance imaging of the brain, which revealed a hypointense and hyperintense punctate mass centered at the jugular fossa with intracranial extension. The ascending pharyngeal artery, recognized as the major feeder, was embolized by percutaneous embolization following digital subtraction angiography. Gross total resection of the tumor was followed by an uneventful postoperative recovery. Combined immunohistochemistry and histopathological morphology revealed a basaloid squamous cell carcinoma, following which the patient completed radiotherapy and is at 3-month follow-up currently. CONCLUSION: This case report discusses the diagnostic pitfalls and management challenges of this rare entity on the basis of prior evidence, as well as a literature review and clinical and surgical analysis.

The Combined Effects of Alcohol Consumption and Smoking on Cancer Risk by Exposure Level: A Systematic Review and Meta-Analysis.

BACKGROUND: Alcohol consumption is a major risk factor for cancer, and when combined with smoking, the risk increases. Nevertheless, few studies have comprehensively evaluated the combined effects of alcohol consumption and smoking on the risk of various cancer types. Therefore, to assess these effects, we conducted a systematic review and meta-analysis. METHODS: We performed a systematic search of five literature databases, focusing on cohort and case-control studies. Considering exposure levels, we quantified the combined effects of alcohol consumption and smoking on cancer risk and assessed multiplicative interaction effects. RESULTS: Of 4,452 studies identified, 24 (4 cohort studies and 20 case-control studies) were included in the meta-analysis. We detected interaction effect of light alcohol and moderate smoking on head and neck cancer risk (relative risk [RR], 4.26; 95% confidence interval [CI], 2.50-7.26; I² = 65%). A synergistic interaction was observed in heavy alcohol and heavy smoking group (RR, 35.24; 95% CI, 23.17-53.58; I² = 69%). In more detailed cancer types, the interaction effect of heavy alcohol and heavy smoking was noticeable on oral (RR, 36.42; 95% CI, 24.62-53.87; I² = 46%) and laryngeal (RR, 38.75; 95% CI, 19.25-78.01; I² = 69%) cancer risk. CONCLUSION: Our study provided a comprehensive summary of the combined effects of alcohol consumption and smoking on cancers. As their consumption increased, the synergy effect became more pronounced, and the synergy effect was evident especially for head and neck cancer. These findings provide additional evidence for the combined effect of alcohol and smoking in alcohol guidelines for cancer prevention.

The potential therapeutic targets of glutamine metabolism in head and neck squamous cell carcinoma.

Targeting metabolic reprogramming may be an effective strategy to enhance cancer treatment efficacy. Glutamine serves as a vital nutrient for cancer cells. Inhibiting glutamine metabolism has shown promise in preventing tumor growth both in vivo and in vitro through various mechanisms. Therefore, this review collates recent scientific literature concerning the correlation between glutamine metabolism and cancer treatment. Novel treatment modalities based on amino acid transporters, metabolites, and glutaminase are discussed. Moreover, we demonstrate the relationship between glutamine metabolism and tumor proliferation, drug resistance, and the tumor immune microenvironment, offering new perspectives for the clinical treatment of head and neck squamous cell carcinoma, particularly for combined therapies. Identifying innovative approaches for enhancing the efficacy of glutamine-based metabolic therapy is crucial to improving HNSCC treatment.

Longitudinal study of the role of salivary proteins on radiation-related caries onset in head and neck cancer patients using 5000 ppm fluoride dentifrice up to one-year post-intensity modulated radiotherapy.

OBJECTIVES: Longitudinal assessment of the role of specific proteins on radiotherapy caries (RC) onset in head and neck cancer patients(HNC) up to one-year post-IMRT using a 5000ppm fluoride paste daily. MATERIALS AND METHODS: Dental status/salivary protein data were obtained from 40 HNC patients pre-IMRT, six months (T1) and 12 months (T2) post-IMRT (ethical approval/consent). DMFT/salivary parameters were quantified, including flow rate, mucin 5B/7, Immunoglobulin A (IgA), cystatin S and α-amylase. RESULTS: 45% patients had at least one carious lesion at T2, a significant reduction in the number of remaining teeth (65% <21), salivary flow rate (< 50%) and, protein secretion (< 0.05) post-IMRT. T1 IgA concentration/secretion rate was associated with RC (p < 0.05). Finally, IgA and total protein concentration obtained at T1 could provide a predictive pattern (AUC 82.3%) for the patients more predisposed to developing RC at T2. CONCLUSIONS: This study demonstrated the significant association of RC with salivary proteins in HNC patients treated with IMRT, revealing the potential role of salivary proteins in the early diagnosis of RC. CLINICAL RELEVANCE: This research contributes to revealing salivary proteins association with RC, and its role in early diagnosis. Therefore, this could be the first step towards personalized medicine approaches to improve this group quality-of-life.

[A rapidly enlarging neck mass]. / Een snelgroeiende zwelling in de hals.

The differential diagnosis of a rapidly enlarging neck mass consists of many different benign ((haemorrhagic) cyst) and malignant (anaplastic thyroid cancer (ATC) and lymphoma) causes. ATC is a rare disease with a median survival of 6 months. As early diagnosis and management are key for fast-growing cancers, in our centre we have implemented a dedicated short-stay in-hospital fast-track diagnostic work-up for patients with a rapid growing mass in the neck. The goal of this track is to have a fast diagnostic and therapeutic plan for this disease. Based on three clinical cases we discuss our experience with this fast-track diagnostic work-up for rapidly growing mass in the neck and illustrate the additional value in this clinical entity.

Autophagy is the main driver of radioresistance of HNSCC cells in mild hypoxia.

Hypoxia poses a significant challenge to the effectiveness of radiotherapy in head and neck squamous cell carcinoma (HNSCC) patients, and it is imperative to discover novel approaches to overcome this. In this study, we investigated the underlying mechanisms contributing to x-ray radioresistance in HPV-negative HNSCC cells under mild hypoxic conditions (1% oxygen) and explored the potential for autophagy modulation as a promising therapeutic strategy. Our findings show that HNSCC cells exposed to mild hypoxic conditions exhibit increased radioresistance, which is largely mediated by the hypoxia-inducible factor (HIF) pathway. We demonstrate that siRNA knockdown of HIF-1α and HIF-1ß leads to increased radiosensitivity in HNSCC cells under hypoxia. Hypoxia-induced radioresistance was not attributed to differences in DNA double strand break repair kinetics, as these remain largely unchanged under normoxic and hypoxic conditions. Rather, we identify autophagy as a critical protective mechanism in HNSCC cells following irradiation under mild hypoxia conditions. Targeting key autophagy genes, such as BECLIN1 and BNIP3/3L, using siRNA sensitizes these cells to irradiation. Whilst autophagy's role in hypoxic radioresistance remains controversial, this study highlights the importance of autophagy modulation as a potential therapeutic approach to enhance the effectiveness of radiotherapy in HNSCC.

Coenzyme Q0 inhibited the NLRP3 inflammasome, metastasis/EMT, and Warburg effect by suppressing hypoxia-induced HIF-1α expression in HNSCC cells.

Coenzyme Q0 (CoQ0), a quinone derivative from Antrodia camphorata, has antitumor capabilities. This study investigated the antitumor effect of noncytotoxic CoQ0, which included NLRP3 inflammasome inhibition, anti-EMT/metastasis, and metabolic reprogramming via HIF-1α inhibition, in HNSCC cells under normoxia and hypoxia. CoQ0 suppressed hypoxia-induced ROS-mediated HIF-1α expression in OECM-1 and SAS cells. Under normoxia and hypoxia, the inflammatory NLRP3, ASC/caspase-1, NFκB, and IL-1ß expression was reduced by CoQ0. CoQ0 reduced migration/invasion by enhancing epithelial marker E-cadherin and suppressing mesenchymal markers Twist, N-cadherin, Snail, and MMP-9, and MMP-2 expression. CoQ0 inhibited glucose uptake, lactate accumulation, GLUT1 levels, and HIF-1α-target gene (HK-2, PFK-1, and LDH-A) expressions that are involved in aerobic glycolysis. Notably, CoQ0 reduced ECAR as well as glycolysis, glycolytic capability, and glycolytic reserve and enhanced OCR, basal respiration, ATP generation, maximal respiration, and spare capacity in OECM-1 cells. Metabolomic analysis using LC-ESI-MS showed that CoQ0 treatment decreased the levels of glycolytic intermediates, including lactate, 2/3-phosphoglycerate, fructose 1,6-bisphosphate, and phosphoenolpyruvate, and increased the levels of TCA cycle metabolites, including citrate, isocitrate, and succinate. HIF-1α silencing reversed CoQ0-mediated anti-metastasis (N-Cadherin, Snail, and MMP-9) and metabolic reprogramming (GLUT1, HK-2, and PKM-2) under hypoxia. CoQ0 prevents cancer stem-like characteristics (upregulated CD24 expression and downregulated CD44, ALDH1, and OCT4) under normoxia and/or hypoxia. Further, in IL-6-treated SG cells, CoQ0 attenuated fibrosis by inhibiting TGF-ß and Collagen I expression and suppressed EMT by downregulating Slug and upregulating E-cadherin expression. Interesting, CoQ0 inhibited the growth of OECM-1 tumors in xenografted mice. Our results advocate CoQ0 for the therapeutic application against HNSCC.

Is thermography an effective screening tool for differentiating benign and malignant skin lesions in the head and neck? A systematic review.

The aim of this study was to assess, through a systematic review, the status of infrared thermography (IRT) as a diagnostic tool for skin neoplasms of the head and neck region and in order to validate its effectiveness in differentiating benign and malignant lesions. A search was carried out in the LILACS, PubMed/MEDLINE, SCOPUS, Web of Science and EMBASE databases including studies published between 2004 and 2024, written in the Latin-Roman alphabet. Accuracy studies with patients aged 18 years or over presenting benign and malignant lesions in the head and neck region that evaluated the performance of IRT in differentiating these lesions were included. Lesions of mesenchymal origin and studies that did not mention histopathological diagnosis were excluded. The systematic review protocol was registered in the PROSPERO database (CRD42023416079). Reviewers independently analyzed titles, abstracts, and full-texts. After extracting data, the risk of bias of the selected studies was assessed using the QUADAS - 2 tool. Results were narratively synthesized and the certainty of evidence was measured using the GRADE approach. The search resulted in 1,587 records and three studies were included. Only one of the assessed studies used static IRT, while the other two studies used cold thermal stress. All studies had an uncertain risk of bias. In general, studies have shown wide variation in the accuracy of IRT for differentiating between malignant and benign lesions, with a low level of certainty in the evidence for both specificity and sensitivity.

A druggable cascade links methionine metabolism to epigenomic reprogramming in squamous cell carcinoma.

Upper aerodigestive squamous cell carcinoma (UASCC) is a common and aggressive malignancy with few effective therapeutic options. Here, we investigate amino acid metabolism in this cancer, surprisingly noting that UASCC exhibits the highest methionine level across all human cancers, driven by its transporter LAT1. We show that LAT1 is also expressed at the highest level in UASCC, transcriptionally activated by UASCC-specific promoter and enhancers, which are directly coregulated by SCC master regulators TP63/KLF5/SREBF1. Unexpectedly, unbiased bioinformatic screen identifies EZH2 as the most significant target downstream of the LAT1-methionine pathway, directly linking methionine metabolism to epigenomic reprogramming. Importantly, this cascade is indispensable for the survival and proliferation of UASCC patient-derived tumor organoids. In addition, LAT1 expression is closely associated with cellular sensitivity to inhibition of the LAT1-methionine-EZH2 axis. Notably, this unique LAT1-methionine-EZH2 cascade can be targeted effectively by either pharmacological approaches or dietary intervention in vivo. In summary, this work maps a unique mechanistic cross talk between epigenomic reprogramming with methionine metabolism, establishes its biological significance in the biology of UASCC, and identifies a unique tumor-specific vulnerability which can be exploited both pharmacologically and dietarily.

Effects of early nutritional intervention on oral mucositis and basic conditions in patients receiving radiotherapy for head and neck cancer: Randomized controlled trial (ChiCTR2000031418).

BACKGROUND & AIMS: This study aims to observe the effects of early nutritional intervention on radiation-induced oral mucositis (OM) and the nutritional status of patients with head and neck cancer (HNC) receiving radiotherapy. METHODS: Eligible patients receiving radiotherapy for HNC were randomly divided into an early nutritional intervention group (enteral nutritional intervention was administered at the beginning of radiotherapy) and a late nutritional intervention group (enteral nutritional intervention was administered at the beginning of eating restriction) in a 1:1 ratio. The primary endpoint was radiation-induced OM. Secondary endpoints included nutrition-related indicators, immune function, overall survival (OS), progression-free survival (PFS), quality of life, and other radiotherapy-induced adverse effects. RESULTS: A total of 100 patients were enrolled between 2020 and 2021, including 50 each in the early nutritional intervention group and in the late group. The incidence of Grade-III/IV OM was lower in the early treatment group than in the late treatment group (2% vs 14%, P = 0.059). By week 7 weight loss was significantly lower in the early group than in the late group (1.08 kg, 95% CI: 0.08-2.09, P = 0.035). Regarding the PG-SGA scores after receiving radiotherapy, the early group comprised more well-nourished and fewer malnourished patients than those in the late group (P = 0.002). The scores of the immune function indices of T cell CD3+, CD4+/CD8+, and B cell CD19+ were slightly higher in the early group than in the late group; however, the difference was not statistically significant (all P > 0.05). PFS and OS were better in the early group than in the late group; however, the differences were not statistically significant (P > 0.05). CONCLUSIONS: Early nutritional intervention can effectively improve the nutritional status and reduce the incidence of high-grade OM in patients with HNC receiving radiotherapy. TRIAL REGISTRATION: Chinese Clinical Trials Registry (http://www.chictr.org.cn). CHICTR-ID: ChiCTR2000031418.

Safety of nivolumab monotherapy in five cancer types: pooled analysis of post-marketing surveillance in Japan.

BACKGROUND: Nivolumab has been approved for treating ≥ 10 cancer types. However, there is limited information on the incidence of rare, but potentially serious, treatment-related adverse events (TRAEs), as well as notable TRAEs in patients with certain medical disorders or older patients in Japan. METHODS: We performed pooled analyses of data from published post-marketing surveillance in Japan of nivolumab monotherapy for patients with malignant melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck cancer, and gastric cancer to determine the frequencies of 20 categories of TRAEs of special interest overall and in patient groups with higher perceived safety risks (history of autoimmune disease, interstitial lung disease, tuberculosis, or hepatitis B/C; patients vaccinated during nivolumab treatment; and older patients [≥ 75 years]). RESULTS: The overall population comprised 7421 patients treated with nivolumab. TRAEs were reported in 49.1% of patients, with grade ≥ 3 TRAEs in 16.7%. Endocrine disorders (14.4%), hepatobiliary disorders (10.9%), and interstitial lung disease (7.0%) were the three most common categories (any grade). The incidences of rare TRAEs with high risk of becoming serious, which occurred in < 1% of patients, were consistent with those in previous reports. The frequencies of TRAEs were not markedly increased in the specified patient groups relative to the overall population. CONCLUSION: To our knowledge, this is the largest study examining the safety of nivolumab-treated patients in real-world clinical practice including rare but potentially serious TRAEs. We found no new signals in the safety of nivolumab among the patient groups relative to the overall population, and no additional safety measures are required in these groups. Trial registration UMIN000048892 (overall analysis), JapicCTI-163272 (melanoma), Japic-163271 (non-small cell lung cancer), JapicCTI-184071 (head and neck cancer), JapicCTI-184070 (gastric cancer), and JapicCTI-184069 (renal cell cancer).

Pushing boundaries: Anterolateral thigh free flaps for extensive scalp defects beyond previous limits, leveraging imaging modalities with ultrasound and indocyanine green.

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.

Rebamipide gargle and benzydamine gargle in prevention and management of chemo-radiotherapy and radiotherapy-induced oral mucositis in head and neck cancer patients (randomized clinical trial).

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.

FAP Serves as a Prognostic Biomarker in Head and Neck Squamous Cell Carcinoma.

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.