Comparative analyses of short- and long-term outcomes between endoscopic submucosal dissection and endoscopic laryngo-pharyngeal surgery for superficial pharyngeal carcinomas.

Objectives: Endoscopic treatment of superficial pharyngeal carcinomas includes endoscopic submucosal dissection (ESD; usually performed by endoscopists), and endoscopic laryngo-pharyngeal surgery (ELPS; primarily performed by otolaryngologists). Few studies have compared the efficacy of the two techniques in treating superficial pharyngeal carcinomas. In this study, we compared the outcomes of these two techniques to determine the advantages. Methods: We retrospectively examined the short- and long-term outcomes of 93 consecutive patients with superficial pharyngeal carcinoma who either underwent an ESD or ELPS between August 2008 and December 2021. Results: There were 35 lesions among 29 patients and 93 lesions among 71 patients in the ESD and ELPS groups, respectively. The ELPS group had a significantly shorter procedure time (121.2 ± 97.4 min vs. 54.7 ± 40.2 min, p<0.01), greater procedure speed (0.10 ± 0.06 min/min vs. 0.30 ± 0.23 min/min, p<0.01), and less laryngeal edema than that of the ESD group. There were no significant differences in the 3-year overall, relapse-free, or disease-specific survival rates between the two groups. Intervention with ESD during ELPS was most commonly required when it was difficult to secure the visual field. Conclusions: There were no differences in batch resection rates or long-term prognoses between the two groups; nevertheless, the ELPS group had a shorter treatment time and less laryngeal edema than the ESD group. However, the treatment of narrow areas, such as the esophageal inlet patch, is a technical limitation of ELPS; thus, ELPS should be combined with ESD techniques.

Mild hyperthermia upregulates PD-L1 in the tumor microenvironment and enhances antitumor efficacy of PD-L1 blockade in murine squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) has a low five-year survival rate because of its high rate of recurrence and metastasis. After surgical resection or radiation, the main treatments for HNSCC, patients sometimes experience functional or aesthetic disorders. Therefore, there is a great demand for the development of non-surgical treatment strategies to improve clinical outcomes and patients' quality of life. One such non-surgical treatment is mild hyperthermia (mHT). Many studies have investigated combination treatments with mHT and immune checkpoint inhibitors in preclinical settings. However, there have been no detailed reports on the effects of mHT on immune checkpoint molecules. Here, we investigated the effects of mHT on the tumor microenvironment (TME), particularly on programmed cell death receptor-1 (PD-1)/programmed cell death ligand-1 (PD-L1), in SCCVII cells and a squamous cell carcinoma mouse model. First, we found that PD-L1 mRNA levels and surface PD-L1 expression significantly increased after mHT. Second, a single tumor model was used to determine the effect of HT on the TME. mHT enhanced the accumulation of CD4+ and CD8+ T cells, elevated PD-L1 expression in the TME, and decreased the PD-1 positive rate of CD4+ T cells. Finally, using a bilateral tumor model, we found that anti-PD-L1 monotherapy and combination therapy resulted in longer survival than the isotype control or mHT monotherapy. Moreover, the combination therapy resulted in a significantly higher survival rate than anti-PD-L1 monotherapy. In conclusion, our findings elucidate changes in PD-L1 expression in the TME and strengthen the rationale for mHT and PD-L1 blockade combination therapy.

Retrospective analysis of treatment-positioning accuracy and dose error in boron neutron capture therapy using a sitting-position treatment system for head and neck cancer.

The neutron beam in boron neutron capture therapy (BNCT) exhibits poor directionality and significantly decreasing neutron flux with increasing distance. Therefore, the treatment site must be close to the irradiation aperture. Some patients with head and neck cancer may benefit from a sitting-position setup. The study aim was to evaluate the treatment-positioning accuracy and dose error in sitting patients receiving BNCT. Thirty-two patients with head and neck cancer who underwent sitting-position BNCT at Southern Tohoku BNCT Research Center were included in the study. Horizontal (ΔX) and vertical (ΔY) errors were defined as the displacement between the treatment planning system (TPS) digital reconstructed radiograph and the pre-treatment X-ray image. Using in-house software, image matching was performed. The beam-axial directional (ΔZ) error was compared with the parameters entered into the TPS and the actual pre-treatment measured values. The translational-position error was reflected in the TPS's patient coordinate system with respect to the reference plan. Re-dose calculations were performed to evaluate the effect of positional error on tumor and normal-tissue doses. The [ΔX, ΔY, ΔZ] DRR-CR mean ± 1SD were - 0.40 ± 2.0, 0.30 ± 2.3, and - 1.4 ± 1.5 mm, respectively. The Dmean and D98% tumor-dose errors were 1.22 % ± 1.44 % and 0.99 % ± 1.63 %, respectively. The D2% pharyngeal and oral mucosal-dose errors were 0.98 % ± 1.91 % and 1.21 % ± 1.78 %, respectively. The tumor- and normal-tissue dose errors were typically < 5 %. High-precision treatment was feasible in sitting-positioned BNCT.

Loss of MACROD2 drives radioresistance but not cisplatin resistance in HPV-positive head and neck cancer.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer type worldwide. In recent years, there has been an increase in the rate of HNSCC cases attributed to the infection of the oropharynx by the human papillomavirus (HPV). Given the significant treatment-related toxicities of the current standard of care for HPV-positive HNSCC, there is an urgent need for the development of precision patient stratification and treatment strategies to improve patients' quality of life while maintaining excellent survival rates. We have previously carried out whole genome sequencing of HPV+ HNSCC tumors that failed concurrent cisplatin and radiation treatment and discovered that MACROD2 deletion is enriched among these tumors. In the current study, we sought to investigate the mechanistic role of MACROD2 in HPV+ HNSCC treatment resistance. Our results indicate that MACROD2 depletion in HNSCC cell lines leads to increased cell viability and colony formation capacity. Interestingly, MACROD2 depletion did not alter cisplatin sensitivity but led to an increase in radiation resistance of HPV+ HNSCC cell lines. RNA sequencing and immunofluorescence microscopy demonstrated that MACROD2-depleted HPV+ HNSCC cells displayed elevated levels of hypoxia and an altered DNA damage response. Taken together, this study establishes and characterizes the role of MACROD2 in HPV+ HNSCC radioresistance. Further work is needed to validate MACROD2 as a biomarker of treatment failure and to understand how to overcome the identified molecular mechanisms of resistance.

Cancer cell-specific PD-L1 expression is a predictor of poor outcome in patients with locally advanced oral cavity squamous cell carcinoma.

BACKGROUND: Locally advanced oral cavity squamous cell carcinoma (OCSCC) presents a significant clinical challenge despite being partially responsive to standard treatment modalities. This study investigates the prognostic implications of programmed death-ligand 1 (PD-L1) expression in these tumors, focusing on its association with treatment outcomes and the immune microenvironment. METHODS: We assessed tumor-infiltrating lymphocytes (TILs) in 132 patients with OCSCC to evaluate their impact on survival. Multiplex immunohistochemistry staining for CD3, CD68, CD11c, PD-L1, and P40 was used to explore correlations with clinical outcomes in patients with early-stage (n=22) and locally advanced (n=36) OCSCC. These initial findings were validated through differential gene expression analysis, gene set enrichment, and immune cell deconvolution in a The Cancer Genome Atlas cohort of 163 locally advanced OCSCC tumors. Additionally, single-cell RNA sequencing (scRNA-seq) on a smaller cohort (n=10) further characterized the PD-L1hi or PD-L1lo cancer cells in these tumors. RESULTS: Elevated PD-L1 expression was associated with poor outcomes in patients with locally advanced OCSCC undergoing standard adjuvant therapy, irrespective of "hot" or "cold" classification based on TILs assessment. PD-L1hi tumors exhibited an active immune response phenotype, enriched with M1 macrophages, CD8+ T cells and T regulatory cells in the tumor microenvironment. Notably, the negative impact of PD-L1 expression on outcomes was primarily attributed to its expression by cancer cells, rather than immune cells. Furthermore, scRNA-seq revealed that immune interactions were not essential for PD-L1 upregulation in cancer cells, instead, complex regulatory networks were involved. Additionally, PD-L1lo locally advanced tumors exhibited more complex pathway enrichment and diverse T-cell populations compared with those in the early-stage. CONCLUSION: Our findings underscore the prognostic significance of PD-L1 expression in locally advanced OCSCC, and unveil the complex interplay between PD-L1 expression, immune responses, and molecular pathways in the tumor microenvironment. This study provides insights that may inform future therapeutic strategies, including the possibility of tailored immunotherapeutic approaches for patients with PD-L1hi locally advanced OCSCC.

Novel bispecific antibody-drug conjugate targeting PD-L1 and B7-H3 enhances antitumor efficacy and promotes immune-mediated antitumor responses.

BACKGROUND: Antibody-drug conjugates (ADCs) offer a promising approach, combining monoclonal antibodies with chemotherapeutic drugs to target cancer cells effectively while minimizing toxicity. METHODS: This study examined the therapeutic efficacy and potential mechanisms of a bispecific ADC (BsADC) in laryngeal squamous cell carcinoma. This BsADC selectively targets the immune checkpoints programmed cell death ligand-1 (PD-L1) and B7-H3, and the precise delivery of the small-molecule toxin monomethyl auristatin E. RESULTS: Our findings demonstrated that the BsADC outperformed its bispecific antibody and PD-L1 or B7-H3 ADC counterparts, particularly in terms of in vitro/in vivo tumor cytotoxicity, demonstrating remarkable immune cytotoxicity. Additionally, we observed potent activation of tumor-specific immunity and significant induction of markers of immunogenic cell death (ICD) and potential endoplasmic reticulum stress. CONCLUSION: In conclusion, this novel BsADC, through immune checkpoint inhibition and promotion of ICD, amplified durable tumor immune cytotoxicity, providing novel insights and potential avenues for future cancer treatments and overcoming resistance.

Squamous cell carcinoma involving the midline of the dorsum of the tongue: a case report.

Introduction: Most cases of squamous cell carcinoma (SCC) of the tongue occur on the lateral surface; however, SCC of the dorsum is extremely rare. Case presentation: The authors describe the case of a 79-year-old man with SCC involving the midline of the dorsum of the tongue. The lesion was surgically resected. The patient was followed up for 1 year and 6 months, and no recurrence was noted. Discussion: SCC of the dorsal midline is even rarer and accounts for less than 1% of tongue carcinomas. SCC involving the dorsum may have a worse prognosis than SCC of the lateral or ventral surface. This report is the first to use submental flap reconstruction to treat cancer of the midline dorsum of the tongue. Conclusion: The authors encountered a case of SCC involving the midline of the dorsum of the tongue, which has rarely been reported in the literature. The authors attained a favorable outcome through surgical intervention.

Probiotics in the management of radiation-induced oral mucositis.

Oral mucositis is a common and debilitating oral complication in head and neck cancer patients undergoing radiotherapy, resulting in diminished quality of life and potential treatment disruptions. Oral microbiota has long been recognized as a contributing factor in the initiation and progression of radiation-induced oral mucositis (RIOM). Numerous studies have indicated that the radiation-induced oral microbial dysbiosis promotes the occurrence and severity of oral mucositis. Therefore, approaches that modulate oral microbial ecology are promising for the management of RIOM. Probiotics as a relatively predicable and safe measure that modulates microecology have garnered significant interest. In this review, we discussed the correlation between RIOM and oral microbiota, with a particular focus on the efficacy of probiotics in the control of RIOM, in order to provide novel paradigm for the management of this disease.

Unveiling therapeutic avenues targeting xCT in head and neck cancer.

Head and neck cancer (HNC) remains a major global health burden, prompting the need for innovative therapeutic strategies. This review examines the role of the cystine/glutamate antiporter (xCT) in HNC, specifically focusing on how xCT contributes to cancer progression through mechanisms such as redox imbalance, ferroptosis, and treatment resistance. The central questions addressed include how xCT dysregulation affects tumor biology and the potential for targeting xCT to enhance treatment outcomes. We explore recent developments in xCT-targeted current and emerging therapies, including xCT inhibitors and novel treatment modalities, and their role in addressing therapeutic challenges. This review aims to provide a comprehensive analysis of xCT as a therapeutic target and to outline future directions for research and clinical application.

Enhanced computed tomography radiomics predicts solute carrier family 7, member 11 in head and neck squamous cell carcinoma.

Introduction: Traditional prognostic indicators for head and neck squamous cell carcinoma (HNSCC), such as clinicopathological features, human papillomavirus status, and imaging examinations, often lack precision in guiding medical therapy. Therefore, discovering novel tumor biomarkers that can accurately assess prognosis and aid in personalized medical treatment for HNSCC is critical. Solute carrier family 7, member 11 (SLC7A11), is implicated in ferroptosis, and various malignant tumor therapies regulate its expression. However, the mechanisms regulating SLC7A11 expression, the transporter activity, and its specific role in controlling ferroptosis in cancer cells remain unknown. Thus, in this study, we aimed to develop an improved computed tomography (CT) radiomics model that could predict SLC7A11 expression in patients with HNSCC. Methods: We used patient genomic data and corresponding augmented CT images for prognostic analysis and building models. Further, we investigated the potential molecular mechanisms underlying SLC7A11 expression in the immune microenvironment. Our radiomics model successfully predicted SLC7A11 mRNA expression in HNSCC tissues and elucidated its association with relevant genes and prognostic outcomes. Results: SLC7A11 expression level was high within tumor tissues and was connected to the infiltration of eosinophil, CD8+ T-cell, and macrophages, which was associated with poor overall survival. Our models demonstrated robust predictive power. The distribution of radiomics scores (RAD scores) within the training and validation sets was markedly different between the high- and low-expression groups of SLC7A11. Conclusion: SLC7A11 is likely an important factor in the prognosis of HNSCC. SLC7A11 expression can be predicted effectively and reliably by radiomics models based on enhanced CT.

A bioengineered tumor matrix-based scaffold for the evaluation of melatonin efficacy on head and neck squamous cancer stem cells.

Head and neck squamous cell carcinoma (HNSCC) presents a significant challenge worldwide due to its aggressiveness and high recurrence rates post-treatment, often linked to cancer stem cells (CSCs). Melatonin shows promise as a potent tumor suppressor; however, the effects of melatonin on CSCs remain unclear, and the development of models that closely resemble tumor heterogeneity could help to better understand the effects of this molecule. This study developed a tumor scaffold based on patient fibroblast-derived decellularized extracellular matrix that mimics the HNSCC microenvironment. Our study investigates the antitumoral effects of melatonin within this context. We validated its strong antiproliferative effect on HNSCC CSCs and the reduction of tumor invasion and migration markers, even in a strongly chemoprotective environment, as it is required to increase the minimum doses necessary to impact tumor viability compared to the non-scaffolded tumorspheres culture. Moreover, melatonin exhibited no cytotoxic effects on healthy cells co-cultured in the tumor hydrogel. This scaffold-based platform allows an in vitro study closer to HNSCC tumor reality, including CSCs, stromal component, and a biomimetic matrix, providing a new valuable research tool in precision oncology.

Assessing Long-Term Quality of Life Concerns Through Survivorship Clinic in Head and Neck Cancer Patients.

OBJECTIVE: To characterize the concerns of head and neck cancer (HNC) patients and discern changes in quality-of-life (QoL) during long-term follow-up. STUDY DESIGN: Retrospective review. SETTING: Survivorship clinic at a tertiary academic center. METHODS: A retrospective review was conducted on HNC patients seen in our survivorship clinic between 1/2020 and 1/2024 using the University of Washington Quality of Life (UW-QOL) Questionnaire. RESULTS: Three hundred and forty-two patients were seen for 914 encounters. Patients were divided into 4 groups: pretreatment (n = 326), 0 to 12 months posttreatment (n = 247), 1 to 3 years posttreatment (n = 248), and more than 3 years posttreatment (n = 64). The average follow-up after treatment was 459 days (range: 0-5.2 years). Multivariable analysis revealed significant improvements in overall QoL, health-related QoL, social-emotional composite scores, activity, anxiety, appearance, chewing, mood, pain, speech, and recreation at more than 1-year posttreatment compared to less than 1-year posttreatment. However, declines were noted in saliva and taste scores. No differences in scores were observed between patients 1 to 3 years posttreatment and those >3 years posttreatment. At all timepoints before and after treatment, top concerns were pain, activity, and swallowing. Patients with oral cancer followed for more than 1-year posttreatment had worse scores in appearance, chewing, pain, and speech compared to those with oropharyngeal cancer. CONCLUSIONS: Understanding the evolving concerns of HNC patients is imperative for enhancing care. Most QoL domains improve at 1-year posttreatment except for saliva, taste, swallowing, and shoulder function. QoL scores stabilize after 1-year post-treatment. Pain, activity, and swallowing remain the top concerns at all time points.

A multicentre observational study of paediatric head and neck abscesses.

INTRODUCTION: In winter of 2022/3 paediatric ENT surgeons across the UK observed that the incidence of severe abscesses in the head and neck and associated complications was higher than seen in previous years. We aimed to collate and evaluate data from across the UK to establish if this was a true rise in cases, and to describe the factors associated. METHODS: A multicentre retrospective data collection was undertaken from 13 units across the UK. Patients admitted between September 2022-February 2023 with a head and neck abscess including sinogenic, otogenic, deep and superficial neck abscesses were included. Demographic, disease specific, management and outcome data were collected. Hospital episode statistic data were also requested and analysed to allow for comparison with previous 10 years of head and neck abscesses. RESULTS: 262 patients with abscesses of the head and neck were admitted during the study period, 100 between September and November and 163 between December and February. Mastoid abscesses were the most common abscess across both groups. The rate of group A streptococcus + culture results rose significantly from 12 % in autumn group to 30 % in winter (p = 0.02). The rate of intracranial complications rose from 10 % to 18 % (p = 0.11) and the rate of venous thrombosis rose over the same timeframe from 3 % to 14 % (p = 0.01). DISCUSSION: This study demonstrated a statistically significant rise in the rate of group A streptococcus associated abscesses when comparing Autumn and Winter 2022/2023. Over the same timeframe a statistically significant rise in the proportion of patients with venous thromboses associated with H&N abscesses was noted. Interestingly, despite perceived national consensus regarding a spike in abscess incidence, the number of abscesses seen in winter 2022/2023 was in keeping with expected rates of paediatric H&N abscesses, based on pre covid year-on-year rise in incidence.

Supervised deep learning-based synthetic computed tomography from kilovoltage cone-beam computed tomography images for adaptive radiation therapy in head and neck cancer.

PURPOSE: To generate and investigate a supervised deep learning algorithm for creating synthetic computed tomography (sCT) images from kilovoltage cone-beam computed tomography (kV-CBCT) images for adaptive radiation therapy (ART) in head and neck cancer (HNC). MATERIALS AND METHODS: This study generated the supervised U-Net deep learning model using 3,491 image pairs from planning computed tomography (pCT) and kV-CBCT datasets obtained from 40 HNC patients. The dataset was split into 80% for training and 20% for testing. The evaluation of the sCT images compared to pCT images focused on three aspects: Hounsfield units accuracy, assessed using mean absolute error (MAE) and root mean square error (RMSE); image quality, evaluated using the peak signal-to-noise ratio (PSNR) and structural similarity index (SSIM) between sCT and pCT images; and dosimetric accuracy, encompassing 3D gamma passing rates for dose distribution and percentage dose difference. RESULTS: MAE, RMSE, PSNR, and SSIM showed improvements from their initial values of 53.15 ± 40.09, 153.99 ± 79.78, 47.91 ± 4.98 dB, and 0.97 ± 0.02 to 41.47 ± 30.59, 130.39 ± 78.06, 49.93 ± 6.00 dB, and 0.98 ± 0.02, respectively. Regarding dose evaluation, 3D gamma passing rates for dose distribution within sCT images under 2%/2 mm, 3%/2 mm, and 3%/3 mm criteria, yielded passing rates of 92.1% ± 3.8%, 93.8% ± 3.0%, and 96.9% ± 2.0%, respectively. The sCT images exhibited minor variations in the percentage dose distribution of the investigated target and structure volumes. However, it is worth noting that the sCT images exhibited anatomical variations when compared to the pCT images. CONCLUSION: These findings highlight the potential of the supervised U-Net deep learningmodel in generating kV-CBCT-based sCT images for ART in patients with HNC.

Head and Neck Paragangliomas: 16-year Single-center Experience and Mini Review on Diagnosis, Treatment, and Follow-up.

Objective: To investigate head and neck paraganglioma cases treated at a tertiary center from 2007 to 2023. The research includes a thorough examination of published studies that have focused on long-term outcomes. The additional goal is to contribute to the existing knowledge on head and neck paraganglioma, with a particular emphasis on refining diagnostic algorithms, treatment selection, and follow-up procedures. Methods: A total of 44 patients were retrospectively analyzed, and 39 were included. Demographic information, symptoms, radiological examination results, types, stages, and postoperative complications were recorded. A review was conducted to select articles that reported single-center experiences with large cohorts, long follow-ups, and different treatment modalities since 2010. Results: The mean age of the patients was 54 years, and the female/male ratio was 3.55:1. Among the 39 cases examined, 18 and 19 were identified as cervical paraganglioma and 19 as temporal bone paraganglioma. All patients initially underwent surgical resection. The mean follow-up duration was 5.42 years. Four residual cases and two recurrences were identified postoperatively, and a Gamma Knife was used as additional treatment. Subsequently, 17 articles were selected and summarized, and then a flowchart was prepared showing the possible options for diagnosis, treatment, and follow-up. Conclusions: Preoperative staging is essential for surgical planning and predicting potential intraoperative complications. Based on our findings and review of the articles, we have prepared a flowchart that includes all possibilities depending on the tumor stage to help in the diagnosis, treatment, and follow-up of head and neck paragangliomas.

Juvenile xanthogranuloma manifesting in the forehead: A case report.

A 3 -year-old boy presented with a forehead nodular mass, which was excised and confirmed histologically as Juvenile Xanthogranulomma (JXG). It affects children with a predilection for the head and neck region. A relatively rare, benign, histiocytic proliferative cutaneous disorder with a potential for malignancy. A prompt and wide resection is recommended.

Enhanced head and neck radiotherapy target definition through multidisciplinary delineation and peer review: A prospective single-center study.

This study evaluates the benefit of weekly delineation and peer review by a multidisciplinary team (MDT) of radiation oncologists (ROs), radiologists (RXs), and nuclear medicine (NM) physicians in defining primary and lymph node tumor volumes (GTVp and GTVn) for head and neck cancer (HNC) radiotherapy. This study includes 30 consecutive HNC patients referred for definitive curative (chemo)-radiotherapy. Imaging data including head and neck MRI, [18F]-FDG-PET and CT scan were evaluated by the MDT. The RO identified the 'undeniable' tumor as GTVp_core and determined GTVp_max, representing the maximum tumoral volume. The MDT delineation (MDT-D) by RX and NM physicians outlined their respective primary GTVs (GTVp_RX and GTVp_NM). During the MDT meeting (MDT-M), these contours were discussed to reach a consensus on the final primary GTV (GTVp_final). In the comparative analysis of various GTVp delineations, we performed descriptive statistics and assessed two MDT-M factors: 1) the added value of MDT-M, which includes the section of GTVp_final outside GTVp_core but within GTVp_RX or GTVp_NM, and 2) the part of GTVp_final that deviates from GTVp_max, representing the area missed by the RO. For GTVn, discussions evaluated lymph node extent and malignancy, documenting findings and the frequency of disagreements. The average GTVp core and max volumes were 19.5 cc (range: 0.4-90.1) and 22.1 cc (range: 0.8-106.2), respectively. Compared to GTVp_core, MDT-D to GTVp_final added an average of 3.3 cc (range: 0-25.6) and spared an average of 1.3 cc (0-15.6). Compared to GTVp_max, MDT-D and -M added an average of 2.7 cc (range: 0-20.3) and removed 2.3 cc (0-21.3). The most frequent GTVn discussions included morphologically suspicious nodes not fixing on [18F]-FDG-PET and small [18F]-FDG-PET negative retropharyngeal lymph nodes. Multidisciplinary review of target contours in HNC is essential for accurate treatment planning, ensuring precise tumor and lymph node delineation, potentially improving local control and reducing toxicity.

De-intensification of postoperative radiotherapy in head and neck cancer irrespective of human papillomavirus status-results of a prospective multicenter phase II trial (DIREKHT Trial).

Background: Current standard treatment concepts in head and neck squamous cell carcinoma (HNSCC) are based on former studies using 2D and 3D treatment plans. However, modern radiation techniques allow for a more precise and individual dose application. Therefore, in a clearly defined patient population, de-intensified risk-adapted radiation is investigated. Methods: Patients with newly diagnosed HNSCC after surgery (with resection margins ≥1 mm and cM0) with the following tumor stages (TNM 7th Edition) were eligible for the study: oral cavity, oropharynx, or larynx: pT1-3, pN0-pN2b; hypopharynx: pT1-2, pN1. The patients should have either a low risk of local recurrence [≤pT2, resection margin ≥5 mm, no peritumoral lymphangiosis (L0), and no perineural invasion] or contralateral lymph node metastasis (≤3 ipsilateral lymph node metastases, in case of well-lateralized oropharyngeal or oral cavity cancer contralateral cN0, otherwise pN0). Patients were assigned to three different treatment regimes with reduction of the treated volume, radiation dose, or both, according to tumor stage and results of surgery performed. The primary objective was to show an LRR of <10% after 2 years. Findings: A total of 150 patients were enrolled. Tumor localizations were as follows: n = 53 (35.3%), oral cavity; n = 94 (62.7%), oropharynx (82% HPV-positive); n = 2 (1.3%), hypopharynx; and n = 1 (0.7%), larynx. A total of 61 patients (41.0%) were stage IVA, 81 (54.0%) were stage III, and 8 (5.3%) were stage II. Median follow-up was 36 months. Cumulative incidence of 2y-LRR was 5.6% (95% CI: 1.7%-9.2%) in the whole study population and 14.1% (95% CI: 3.8%-23.2%) in patients with oral cavity cancer. Cumulative incidence of 2y-LRR in non-irradiated or dose-reduced regions was 3.5% (95% CI: 0.4%-6.5%). After 2 years, disease-free survival was 92% (95% CI: 87%-96%) and overall survival was 94% (95% CI: 90%-98%) for the complete study cohort. Acute III° toxicity was as follows: dysphagia, 30%; xerostomia, 7%; mucositis, 19%; and dermatitis, 4%. Dysphagia and xerostomia decrease over time. After 27 months, late dysphagia III° and xerostomia II° were 1% and 9%, respectively. Interpretation: The study met its primary objective. De-intensification of postoperative radiotherapy irrespective of HPV status in a predefined patient population is associated with a favorable toxicity profile without compromising LRR. In an unplanned subgroup analysis, a significantly increased risk of LRR was observed in patients with oral cavity cancer. In these patients, de-intensified radiotherapy should be applied with caution.

MiR-125a-5p regulates the radiosensitivity of laryngeal squamous cell carcinoma via HK2 targeting through the DDR pathway.

Objective: To determine the function of miR-125a-5p in laryngeal squamous cell carcinoma (LSCC), its correlation with radiation sensitivity, and the underlying regulatory mechanism. Materials and methods: We conducted the analysis on the correlation between miR-125a-5p and head and neck squamous cell carcinoma (HNSCC) using data obtained from The Cancer Genome Atlas (TCGA). The putative gene targeted by miR-125a-5p has been identified as HK2, while the expression levels of miR-125a-5p and HK2 were measured in laryngeal cancer tissues and cells using RT-PCR. MiR-125a-5p and HK2 were introduced into the lentiviral vector and the vector was used to transfect AMC-HN-8 cells. The roles of miR-125a-5p and HK2 in LSCC and on radiosensitivity were determined by evaluating cell growth, examining colony formation, analyzing flow cytometry, and utilizing the single hit multi-target model. Western blotting was used to measure H2AX and rH2AX levels in the DNA damage response (DDR) pathway. The validation of the interaction between miR-125a-5p and HK2 was conducted through the dual-luciferase assay. To further confirm the association between miR-125a-5p and HK2, as well as its influence on radiosensitivity, rescue experiments were performed. Results: The expression of miR-125a-5p is downregulated in LSCC, while upregulating its expression could suppress cell growth, induce apoptosis, and enhance radiosensitivity. Additionally, HK2 exhibited high expression in LSCC and the biological function was opposite to miR-125a-5p. Western blotting analysis revealed that miR-125a-5p increased rH2AX levels and decreased H2AX levels, conversely, HK2 had the opposite effect on miR-125a-5p. These findings suggested that HK2 may serve as the target gene of miR-125a-5p. The double luciferase assay confirmed the binding of HK2 to miR-125a-5p, and rescue trials confirmed the role of miR-125a-5p in regulating the effects and radiation sensitivity of LSCC by targeting HK2 via the DDR pathway. Conclusion: By targeting HK2 and impacting the DDR pathway, miR-125a-5p has been found to inhibit cellular proliferation, enhance apoptosis, and heighten radiosensitivity in LSCC.

Intravenous lipomas of head and neck: an exceptional entity and its clinical implications.

Intravenous lipomas (IVLs) of the head and neck are uncommon benign tumors that develop within the venous walls, often detected incidentally during imaging for unrelated issues. While usually asymptomatic, these IVLs can cause congestive venous symptoms like swelling, paresthesia or pain in the head and neck and upper limbs, or even venous thromboembolism. The precise diagnosis of IVLs is predominantly achieved through computed tomography (CT) and magnetic resonance imaging (MRI), with CT being the most frequently used method. Symptomatic patients generally undergo open surgery with excision of the IVL followed by venous reconstruction, which has shown safe and effective outcomes. However, the management of asymptomatic IVLs remains controversial due to the limited number of reported cases. Despite this, there is a notable trend toward recommending surgical removal of IVLs to prevent complications and rule out malignancy, driven by the challenges of differentiating IVLs from malignant tumors using imaging alone. This review highlights the key differential imaging characteristics of IVLs and the main surgical techniques to remove the tumor and repair the vascular defect. Further research is necessary to establish a robust, evidence-based approach for treating asymptomatic IVLs, balancing the risks of surgery against the potential for future complications.