Head And Neck Research Articles

Myxoid Solitary Fibrous Tumor of the Nasal Vestibule: An Unusual Histological Subtype in the Head and Neck Region.

Solitary fibrous tumors (SFTs) are mesenchymal neoplasms associated with the characteristic NAB2::STAT6 gene fusion. They frequently occur in extra-thoracic sites and are not uncommon in the head and neck (HN) region. Myxoid SFT is a rare morphological subtype of SFT, the features of which overlap with those of other myxoid-appearing tumors, making the diagnosis challenging. We describe the distinctive histopathological and immunohistochemical features of myxoid SFT that occurred in a 32-year-old man with a recurrent swelling in the nasal vestibule. Histological examination showed a nodular tumor composed of short spindle-shaped cells in an abundant myxoid stroma. Nuclei were ovoid, with minimal pleomorphism. Occasional intervening slender vascular channels were present; staghorn vasculature was absent. Tumor cells were diffusely immunopositive for STAT6, CD34, and BCL2, while S100, SOX10, EMA, ER, and CD10 were negative, confirming the diagnosis of myxoid SFT. Thus, myxoid SFTs are unusual in the HN, with potential for misdiagnosis. Due to their propensity for local recurrence if incompletely excised, a high index of suspicion is required to include them in differential diagnosis of myxoid mesenchymal neoplasms occurring at this location. STAT6 is a reliable immunohistochemical marker that aids in diagnosis, reducing the necessity for molecular testing.

Stroma-and Tumor-Associated Predictive Features inSalivary Gland Adenoid Cystic Carcinoma of the Headand Neck.

There is lack of knowledge on the utility of prognostic histopathologic characteristics in adenoid cystic carcinoma (ACC) of the head and neck. We evaluated the prognostic value of tumor and stroma-related histopathologic features in ACC. A total of 65 cases of ACC from minor and major salivary glands were included in this study. We evaluated tumor budding, tumor-infiltrating lymphocytes (TILs), and tumor-stroma ratio (TSR) in hematoxylin and eosin (HE) stained sections. Stroma-rich ACCs recurred more frequently (p = 0.029) during follow-up and associated with distant metastasis (p = 0.038). In multivariable analysis, stroma-rich tumors associated with poorer disease-specific survival with a hazard ratio of 3.76 (95% CI 1.10-12.83, p = 0.034). ACCs commonly showed a low infiltration of TILs as 89% of the tumors was characterized by an immune desert pattern. Low infiltration of TILs associated significantly with increased tumor budding (p = 0.039). Adverse features of TSR and tumor budding are widely expressed in ACC, and stroma-rich tumors are associated with poor prognosis. Low number of TILs in ACC tissue indicates a weak immune response by the host and illustrates the nature of ACC as a relentless malignancy.

Effects of spot size errors in DynamicARC pencil beam scanning proton therapy planning.

Spot size stability is crucial in pencil beam scanning (PBS) proton therapy, and variations in spot size can disrupt dose distributions. Recently, a novel proton beam delivery method known as DynamicARC PBS scanning has been introduced. The current study investigates the dosimetric impact of spot size errors in DynamicARC proton therapy for head and neck (HNC), prostate, and lung cancers.
Approach: Robustly optimized DynamicARC proton therapy plans were created for HNC (n=4), prostate (n=4), and lung (n=4) cancer patients. Spot size errors of ±10%, ±15%, and ±20% were introduced, and their effects on target coverage (D95% and D99%), homogeneity index (HI), and organ-at-risk (OAR) doses were analyzed across different cancer sites.
Main Results: HNC and lung cancer plans showed greater vulnerability to spot size errors, with reductions in target coverage of up to 4.8% under -20% spot size errors. Dose homogeneity was also more affected in these cases, with HI degrading by 0.12 in lung cancer. Prostate cancer demonstrated greater resilience to spot size variations, even under errors of ±20%. For spot size errors ±10%, the oral cavity, parotid glands, and constrictor muscles experienced Dmean deviations within ±1.2%, while deviations were limited to ±0.5% for D10% of the bladder and rectum and ±0.3% for V20Gy(RBE) of the lungs. The robustness analysis indicated that lung cancer plans were most susceptible to robustness reductions caused by spot size errors, while HNC plans demonstrated moderate sensitivity. Conversely, prostate cancer plans demonstrated high robustness, experiencing only minimal reductions in target coverage.
Significance: While the ±10% spot size tolerance is appropriate in the majority of the cases, lung cancer plans may require more stringent criteria. As DynamicARC becomes clinically available, measuring spot size errors in practice will be essential to validate these findings and refine tolerance thresholds for clinical use.

Impact of Artificial Intelligence-Based Autosegmentation of Organs at Risk in Low- and Middle-Income Countries

Radiation therapy (RT) processes require significant human resources and expertise, creating a barrier to rapid RT deployment in low- and middle-income countries (LMICs). Accurate segmentation of tumor targets and organs at risk (OARs) is crucial for optimal RT. This study assessed the impact of artificial intelligence (AI)-based autosegmentation of OARs in 2 LMICs. Ten patients, comprising 5 head and neck (HN) cancer patients and 5 prostate cancer patients, were randomly selected. Planning computed tomography images were subjected to autosegmentation using an Food and Drug Administration-approved AI software tool and manual segmentation by experienced radiation oncologists from 2 LMIC RT clinics. The control data, obtained from a large academic institution in the United States, consisted of contours obtained by an experienced radiation oncologist. The segmentation time, DICE similarity coefficient (DSC), Hausdorff distance, and mean surface distance were evaluated. AI significantly reduced segmentation time, averaging 2 minutes per patient, compared with 57 to 84 minutes for manual contouring in LMICs. Compared with the control data, the AI pelvic contours provided better agreement than did the LMIC manual contours (mean DSC of 0.834 vs 0.807 in LMIC1 and 0.844 vs 0.801 in LMIC2). For HN contours, AI provided better agreement for the majority of OAR contours than manual contours in LMIC1 (mean DSC: 0.823 vs 0.821) or LMIC2 (mean DSC: 0.792 vs 0.748). Neither the AI nor LMIC manual contours had good agreement with the control data (DSC < 0.600) for the optic nerves, chiasm, and cochlea. AI-based autosegmentation generates OAR contours of comparable quality to manual segmentation for both pelvic and HN cancer patients in LMICs, with substantial time savings.

Ganglioneuroma in Head and Neck: A Case Report of a Laryngeal Ganglioneuroma and a Systematic Review of the Literature.

Introduction: Ganglioneuroma (GN) is a rare, benign tumor of the autonomic nervous system. It is seldom located in the head and neck (HN) region. GN typically presents as a slow-growing, painless mass, often leading to delayed diagnosis. Case report: We report a unique case of laryngeal-originating GN in a 43-year-old female who presented with worsening dysphonia and dyspnea. Imaging revealed a large mass originating from the larynx. Histological examination confirmed the diagnosis. The tumor was surgically excised with preservation of key structures in the neck. At the follow-up, the patient experienced a significant improvement in symptoms. Material and methods: A systematic literature review following PRISMA guidelines was conducted in January 2024 to investigate the common sites of GN in the HN region and the complications associated with its treatment. Results: In a total of 58 articles, we studied 65 patients, mostly under 30 years old. Surgical excision remains the primary treatment, and post-operative complications were mostly neurological. Discussion: GNs are generally slow-growing and asymptomatic, but they can reveal themselves when compressing nearby structures, especially in the HN region. In symptomatic cases or when the tumor exhibits significant growth or hormonal activity, surgical resection is required. The lateral cervical approach is the most common one. The risk of postoperative complications and recurrence underscores the need for careful surgical planning and long-term follow-up. Conclusion: This unique laryngeal GN case highlights the importance of considering GN in the differential diagnosis of HN masses. Further large-scale studies are warranted to establish evidence-based protocols for their management, especially in the HN region.

A Review of Immunotherapy for Head and Neck Cancer

The introduction of immune checkpoint inhibitors (ICIs) to oncological care has transformed the management of various malignancies, including head and neck squamous cell carcinoma (HNSCC), offering improved outcomes. The first-line treatment of recurrent and malignant HNSCC for many years was combined platinum, 5-fluorouracil, and cetuximab. Recently, the ICI pembrolizumab was approved as a first-line treatment, with or without chemotherapy, based on tumor and immune cell percentage of programmed-death ligand 1 (PD-L1). Multiple head and neck (HN) cancer trials have subsequently explored immunotherapies in combination with surgery, chemotherapy, and/or radiation. Immunotherapy regimens may be personalized by tumor biomarker, including PD-L1 content, tumor mutational burden, and microsatellite instability. However, further clinical trials are needed to refine biomarker-driven protocols and standardize pathological methods to guide combined regimen timing, sequencing, and deescalation. Gaps remain for protocols using immunotherapy to reverse oral premalignant lesions, particularly high-risk leukoplakias. A phase II nonrandomized controlled trial, using the ICI nivolumab, showed a 2-y cancer-free survival of 73%, although larger trials are needed. Guidelines are also needed to standardize the role of dental evaluation and care before, during, and after immunotherapy, specifically in regard to oral immune-related adverse events and their impact on cancer recurrence. Standardized diagnostic and oral care coordination strategies to close these gaps are needed to ensure continued success of HN cancer immunotherapy.

Development of a Preclinical Double Model of MandibularIrradiated Bone and Osteoradionecrosis in NewZealand Rabbits.

Radiotherapy (RT) plays a crucial role in head and neck (HN) cancer treatment. Nevertheless, it can lead to serious and challenging adverse events such as osteoradionecrosis (ORN). A preclinical rabbit model of irradiated bone and ORN is herein proposed, with the aim to develop a viable model to be exploited for investigating new therapeutic approaches. Nine New Zealand white rabbits were irradiated using a single beam positioned to the left of the mandible and directed perpendicular to the left mandible. A 10 × 10 mm2 region of interest (ROI) located below the first molar tooth on the left side was identified and irradiated with 7 Gy each fraction, once every 2 days, for five fractions. Dose distributions demonstrated that the corresponding ROI on the contralateral (right) mandibular side received approximately 5 Gy each fraction, thus bilateral irradiation of the mandible was achieved. ROIs were categorized as ROIH on the left side receiving the high dose and ROIL on the right side receiving the low dose. Rabbits were followed up clinically and imaged monthly. After 4 months, the irradiated bone was excised, and histological examination of ROIs was performed. Radiological signs suggestive for ORN were detected in the entire population (100%) 16 weeks after irradiation on ROIH, which consisted of cortical erosion and loss of trabeculae. ROIL did not show any radiological evidence of bone damage. Histologically, both sides showed comparable signs of injury, with marked reduction in osteocyte count and increase in empty lacunae count. A preclinical double model was successfully developed. The side receiving the higher dose showed radiological and histological signs of bone damage, resulting in an ORN model. Whereas the contralateral side, receiving the lower dose, presented with histological damage only and a normal radiological appearance. This work describes the creation of a double model, an ORN and irradiated bone model, for further study using this animal species.

The impact of oncology nutrition services on weight change among patients with head and neck or pancreatic cancers.

86 Background: Weight loss is prevalent among cancer patients and correlates with lower health-related quality of life and overall survival rates. Individuals diagnosed with head and neck (HN) and pancreatic cancers face a heightened risk of weight loss due to tumor location and treatment-related side effects. Although guidelines advocate early interventions such as referral to a dietitian for tailored nutritional support, the precise impact of oncology nutrition services (ONS) on weight loss remains unclear. In this study, we investigated the longitudinal association between weight change and ONS among patients diagnosed with HN or pancreatic cancers. Methods: A retrospective chart review was conducted for patients diagnosed with HN or pancreatic cancers visited between January 2019 and December 2023. Inclusion criteria encompassed patients who had weight measurements taken within 30 days of their cancer diagnosis. Patient demographics, clinical characteristics, all recorded body weights, and receipt of ONS were extracted from electronic health records. Weight change (%) from the baseline was calculated at each measurement by subtracting the initial weight value. A mixed-effects model was employed to evaluate the impact of ONS on weight change, with time to weight measurement and ONS serving as interaction terms, after adjusting for demographics and clinical characteristics. Results: A cohort of 1305 patients was identified, predominantly comprising males (n=1014, 63%) and individuals of White race (n=1358, 85%), with a diverse ethnic distribution (Hispanic: n=620, 39%). Of these patients, 947 (73%) received ONS at any point following cancer diagnosis. Significant weight loss over time was noted among all patients (-0.53% per 6 months, p&lt;0.001). Baseline weight, sex, ethnicity, receipt of percutaneous endoscopic gastrostomy, total parenteral nutrition, radiation, chemotherapy, and ONS were significantly associated with weight loss. Following adjustment for the covariates, patients receiving ONS showed significantly less weight loss compared to those without ONS (-0.06% [95% confidence interval (CI): -0.10, -0.03] vs. -0.04% [95% CI: -0.38, -0.23] per 6 months, p&lt;0.001). Conclusions: The findings indicate that ONS plays a significant role in attenuating weight loss among patients diagnosed with HN or pancreatic cancer, irrespective of baseline demographics or clinical status. While the magnitude of weight change may appear modest, its implications are substantial long term. Early referrals to ONS should be recommended for HN or pancreatic cancer patients to mitigate weight loss.

Proton Radiation Therapy for Head and Neck Cancers.

Head and neck (HnN) cancers are among the most common cancers in the world. Proton therapy (PT) is one of the latest advancements in the treatment modalities of cancers. Proton therapy is specifically used to treat HnN cancer patients due to its less toxic effects on the surrounding critical structures. Keeping in view the opportunities for further advancements, there is a lot of literature covering PT in HnN cancer patients. However, few compiled studies are not enough to compare the toxicities, overall survival (OS), local control (LC), and quality of life (QoL) of PT with that of intensity-modulated radiation therapy (IMRT). The objective of this review is to compile and summarize the literature available on the toxicities, OS, LC, and QoL in HnN cancer patients post PT. We have gathered and summarized the literature found under the keyword "proton therapy for head and neck cancers". Proton therapy is a preferable option over IMRT because it isolates tumors of the HnN, reduces exposure of healthy cells to radiation, and allows accurate tumor scanning using the pencil beam technique. In view of this article, we can say that PT is a preferable mode of radiotherapy for HnN cancer patients in view of its accuracy and lower incidents of acute and late toxicities.

Head and neck automatic multi-organ segmentation on Dual-Energy Computed Tomography

Background and purposeDeep-learning-based automatic segmentation is widely used in radiation oncology to delineate organs-at-risk. Dual-energy CT (DECT) allows the reconstruction of enhanced contrast images that could help with manual and auto-delineation. This paper presents a performance evaluation of a commercial auto-segmentation software on image series generated by a DECT. Material and methodsDifferent types of DECT images from seventy four head-and-neck (HN) patients were retrieved, including polyenergetic images at different voltages [80 kV reconstructed with a kernel corresponding to the commercial algorithm DirectDensity™ (PEI80-DD), 80 kV (PEI80), 120 kV-mixed (PEI120)] and a virtual-monoenergetic image at 40 keV (VMI40). Delineations used for treatment planning were considered as ground truth (GT) and were compared with the auto-segmentations performed on the 4 DECT images. A blinded qualitative evaluation of 3 structures (thyroid, left parotid, left nodes level II) was carried out. Performance metrics were calculated for thirteen HN structures to evaluate the auto-contours including dice similarity coefficient (DSC), 95th percentile Hausdorff distance (95HD) and mean surface distance (MSD). ResultsWe observed a high rate of low scores for PEI80-DD and VMI40 auto-segmentations on the thyroid and for GT and VMI40 contours on the nodes level II. All images received excellent scores for the parotid glands. The metrics comparison between GT and auto-segmented contours revealed that PEI80-DD had the highest DSC scores, significantly outperforming other reconstructed images for all organs (p < 0.05). ConclusionsThe results indicate that the auto-contouring system cannot generalize to images derived from DECT acquisition. It is therefore crucial to identify which organs benefit from these acquisitions to adapt the training datasets accordingly.

Improved quality of life in head and neck cancer patients treated with modern arc radiotherapy techniques - A prospective longitudinal analysis.

The present longitudinal study aimed to evaluate the potential impact of modern radiotherapy (RT) techniques on quality of life (QOL) in patients with head and neck (HNC) cancer. In this single-center prospective study, participants were asked to complete QOL questionnaires that included the EORTC QLQ-C30, QLQ-H&N 35 and utility score by time trade-off (TTO) at three time points (2 weeks, 3 months and 6 months) after completion of RT. All patients were treated by modern RT techniques [volumetric modulated arc therapy (VMAT) or helical tomotherapy (HT)]. Patients who developed recurrence or died before the 6-month follow-up were excluded. Linear mixed models with random intercepts for participants and restricted maximum likelihood estimates were used to assess the effect of our study variables (age, sex, primary site, cancer stage, treatment, radiation dose and radiation method). Overall changes in QOL, utility scores and symptom burdens at different time points were tested using paired t tests. A total of 45 patients were recruited from 2022 to 2023. Those who completed the surveys at 2 weeks with at least 1 follow-up (30 patients, 67%) were enrolled in the final analysis. The majority of these 30 patients were men (76.7%), had oral cancer (40%), had stage III or IV disease (60%), received surgical intervention (63%) and were treated with chemoradiation (80%). A curative total dose of 66 to 70 Gy was delivered to 23 (76.7%) patients, half of whom received HT. Patients who received chemotherapy had significantly lower global QoL scales (mean difference, 27.94; 95% CI, 9.33-46.55; p=0.005). Global QOL, physical function, symptoms of sticky saliva, cough, feelings of illness and weight loss improved significantly between 2 weeks and 3 months. There was no significant difference between 3 and 6 months. Interestingly, improvements in social function, social contact, pain and nutrition reached significance at 6 months. Subgroup analysis revealed greater pain relief over time for patients who underwent HT (p=0.030). Moreover, patients who participated in swallowing rehabilitation programs had a greater decrease in nausea and vomiting (p=0.036). HNC patients treated with modern RT techniques experience improved QOL and physical function over time. The most significant improvement occurs between 2 weeks and 3 months, after which the improvement plateaus. However, social function, social contact, pain and nutrition may require longer recovery intervals after treatment. HT with daily image guidance could provide a therapeutic opportunity for improving pain relief in patients with HNC.

Effects of Neck Radiation Therapy on Carotid Arteries in Patients with Head and Neck Carcinoma

Background: Radiotherapy is a main treatment modality for cancers of the head and neck (HNC). However, it can cause a number of complications, including carotid artery damage.This study aimed to determine the effect of head and neck radiotherapy on carotid Doppler ultrasound findings in patients with HNC treated at Imam Hossein University Hospital. Materials and Methods: This research is a descriptive-longitudinal and prospective study conducted in 2022 on patients with HNC undergoing neck radiotherapy. In this study, before the initiation of radiotherapy, the patients underwent neck carotid artery Doppler ultrasound and various parameters including peak systolic velocity (PSV), end-diastolic velocity (EDV), internal carotid artery/common carotid artery (ICA/CCA) PSV, the number of plaques, intimal thickness, and percentage of carotid diameter stenosis, were recorded. The Doppler ultrasound was repeated six months later, addressing the same characteristics, and the collected data were compared. Results: Of 49 investigated patients, 32 (65.3%) were male (mean age=59.46 years). PSV, EDV, and ICA/CCA ratios showed no statistically significant difference 6 months following the completion of radiotherapy compared to the initial investigation. On the other hand, the percentage of carotid artery stenosis, the middle intimal membrane thickness, and the number of vascular plaques increased significantly (P&lt;0.05). Conclusion: Carotid artery stenosis due to radiotherapy seems to be a common complication; however, radiotherapy probably has minimal effects on other ultrasound parameters of carotid arteries including EDV, PSV, and ICA/CCA ratio.

Reduced-distortion diffusion weighted imaging for head and neck radiotherapy

Background and purposeQuantitative Diffusion Weighted Imaging (DWI) has potential value in guiding head and neck (HN) cancer radiotherapy. However, clinical translation has been hindered by severe distortions in standard single-shot Echo-Planar-Imaging (ssEPI) and prolonged scan time and low SNR in Turbo-Spin-Echo (ssTSE) sequences. In this study, we evaluate “multi-shot” (ms) msEPI and msTSE acquisitions in the context of HN radiotherapy. Materials and methodsssEPI, ssTSE, msEPI with 2 and 3 shots (2sEPI, 3sEPI), and msTSE DWI were acquired in a phantom, healthy volunteers (N=10), and patients with HN cancer (N=5) on a 3-Tesla wide-bore MRI in radiotherapy simulation RF coil setup, with matched spatial resolution (2x2x5mm) and b = 0, 200, 800 s/mm2.Geometric distortions measured with deformable vector field (DVF) and contour analysis, apparent diffusion coefficient (ADC) values, and signal-to-noise-ratio efficiency (SNReff) were quantified for all scans. ResultsAll techniques significantly (P<1x10-3) reduced distortions compared with ssEPI (DVFmean = 3.1 ± 1.3 mm). Distortions were marginally lower for msTSE (DVFmean = 1.5 ± 0.6 mm) than ssTSE (1.8 ± 0.9 mm), but were slightly higher with 2sEPI and 3sEPI (2.6 ± 1.0 mm, 2.2 ± 1.0 mm). SNReff reduced with decreasing distortion with ssEPI=21.9 ± 7.9, 2sEPI=15.1 ± 5.0, 3sEPI=12.1 ± 4.5, ssTSE=6.0 ± 1.6, and msTSE=5.7 ± 1.9 for b = 0 images. Phantom ADC values were consistent across all protocols (errors ≤ 0.03x10-3mm2/s), but in vivo ADC values were ∼ 4 % lower with msEPI and ∼ 12 % lower with ssTSE/msTSE compared with ssEPI. ConclusionsmsEPI and TSE acquisitions exhibited improved geometric distortion at the cost of SNReff and scan time. While msTSE exhibited the least distortion, 3sEPI may offer an appealing middle-ground with improved geometric fidelity but superior efficiency and in vivo ADC quantification.

Nutritional status and primary tumour site in incurable cancer

ObjectivesWe aimed (1) to assess the nutritional status (NS) using different methods, according to the primary tumour site and (2) to evaluate the performance of these methods in patients with...

-KIDS: A novel feature evaluation in the ultrahigh-dimensional right-censored setting, with application to Head and Neck Cancer.

Recent advances in sequencing technologies have allowed collection of massive genome-wide information that substantially enhances the diagnosis and prognosis of head and neck cancer. Identifying predictive markers for survival time is crucial for devising prognostic systems, and learning the underlying molecular driver of the cancer course. In this paper, we introduce -KIDS, a model-free feature screening procedure with false discovery rate (FDR) control for ultrahigh dimensional right-censored data, which is robust against unknown censoring mechanisms. Specifically, our two-stage procedure initially selects a set of important features with a dual screening mechanism using nonparametric reproducing-kernel-based ANOVA statistics, followed by identifying a refined set (of features) under directional FDR control through a unified knockoff procedure. The finite sample properties of our method, and its novelty (in light of existing alternatives) are evaluated via simulation studies. Furthermore, we illustrate our methodology via application to a motivating right-censored head and neck (HN) cancer survival data derived from The Cancer Genome Atlas, with further validation on a similar HN cancer data from the Gene Expression Omnibus database. The methodology can be implemented via the R package DSFDRC, available in GitHub.

An operator-independent quality assurance system for automatically generated structure sets

Objective. This study describes geometry-based and intensity-based tools for quality assurance (QA) of automatically generated structures for online adaptive radiotherapy, and designs an operator-independent traffic light system that identifies erroneous structure sets. Approach. A cohort of eight head and neck (HN) patients with daily CBCTs was selected for test development. Radiotherapy contours were propagated from planning computed tomography (CT) to daily cone beam CT (CBCT) using deformable image registration. These propagated structures were visually verified for acceptability. For each CBCT, several error scenarios were used to generate what were judged unacceptable structures. Ten additional HN patients with daily CBCTs and different error scenarios were selected for validation. A suite of tests based on image intensity, intensity gradient, and structure geometry was developed using acceptable and unacceptable HN planning structures. Combinations of one test applied to one structure, referred to as structure-test combinations, were selected for inclusion in the QA system based on their discriminatory power. A traffic light system was used to aggregate the structure-test combinations, and the system was evaluated on all fractions of the ten validation HN patients. Results. The QA system distinguished between acceptable and unacceptable fractions with high accuracy, labeling 294/324 acceptable fractions as green or yellow and 19/20 unacceptable fractions as yellow or red. Significance. This study demonstrates a system to supplement manual review of radiotherapy planning structures. Automated QA is performed by aggregating results from multiple intensity- and geometry-based tests.

Analysis of heterochromatin remodeling as a mechanism of radiotherapy (RT) resistance through molecular profiling of radioresistant (RR) head and neck (HNC) and prostate cancers (PCa).

137 Background: Resistance to RT remains a clinical challenge, given our limited understanding of the molecular pathways underpinning radioresistance. Here, we investigated for mechanisms linked to RR using paired experimental and clinico-molecular HNC and PCa datasets for discovery and validation of novel pathways that may be enriched in RR cancers. Methods: For experimental data, we generated RR HNC (FaDu, HK1) and PCa (22Rv1, DU145) cell lines following high-dose X-irradiation (90 Gy in 45 fr). Genotypic characterization of RR and wildtype (WT) cells was performed by genomic and transcriptomic sequencing using WES (100X) and RNAseq (Illumina, CA), respectively, followed by functional characterization by western blot (WB) and immunofluorescence (IF). For clinico-molecular data, we utilized two prospectively recruited RT cohorts, consisting of 311 patients with HNC (n=158) and PCa (n=153). Tumor transcriptomes were profiled using RNAseq and Affymetrix ST array (ThermoFisher, CA), respectively. Comparative analyses of molecular profiles were first performed between RR and WT in vitro models to identify dysregulated pathways that were linked to radioresistance, and subsequently tested for association with disease-free survival (DFS) in the clinical cohorts. Results: Comparative genomic analyses between RR and WT HNC and PCa models revealed an abundance of acquired mutations in the RR compared with WT models, with a higher mutation count observed in PCa than HNC cells (SNV counts: 2,158 [DU145-RR] and 1,387 [22Rv1-RR] vs 396 [FaDu-RR] and 25 [HK1-RR], P&lt;0.0001). Mutational signature analyses indicated a common enrichment of DNA mismatch repair-related mutational signatures (SBS3, SBS14, and SBS21) across the RR HNC and PCa models. Transcriptomic profiling revealed an upregulation of the BAHD1 gene, which is involved in heterochromatin formation, across the 4 RR cell lines, corroborated by an enrichment of heterochromatin-related genesets. These results were consistent with functional characterization of RR versus WT cells by WB and IF indicating increased DNA repair capacity and heterochromatin response post-4 Gy irradiation. We further confirmed the dependency of the RR phenotype on the heterochromatin response with BAHD1 knockdown, resulting in reversal of these cellular responses. Finally, our results were supported by survival analyses indicating an inferior DFS post-RT in patients with HNC and PCa harboring a higher expression of heterochromatin-related geneset (HNC: HRhigh vs low 1.51 ; PCa: HRhigh vs low 1.37 ). Conclusions: Herein, by leveraging on paired experimental and clinico-molecular datasets, we have uncovered a novel BAHD1-dependent heterochromatin response that underpins resistance to RT in HNC and PCa, which may be amendable to systemic agents targeting chromatin remodeling.

CT-based synthetic contrast-enhanced dual-energy CT generation using conditional denoising diffusion probabilistic model

Objective. The study aimed to generate synthetic contrast-enhanced Dual-energy CT (CE-DECT) images from non-contrast single-energy CT (SECT) scans, addressing the limitations posed by the scarcity of DECT scanners and the health risks associated with iodinated contrast agents, particularly for high-risk patients. Approach. A conditional denoising diffusion probabilistic model (C-DDPM) was utilized to create synthetic images. Imaging data were collected from 130 head-and-neck (HN) cancer patients who had undergone both non-contrast SECT and CE-DECT scans. Main Results. The performance of the C-DDPM was evaluated using Mean Absolute Error (MAE), Structural Similarity Index (SSIM), and Peak Signal-to-Noise Ratio (PSNR). The results showed MAE values of 27.37±3.35 Hounsfield Units (HU) for high-energy CT (H-CT) and 24.57±3.35HU for low-energy CT (L-CT), SSIM values of 0.74±0.22 for H-CT and 0.78±0.22 for L-CT, and PSNR values of 18.51±4.55 decibels (dB) for H-CT and 18.91±4.55 dB for L-CT. Significance. The study demonstrates the efficacy of the deep learning model in producing high-quality synthetic CE-DECT images, which significantly benefits radiation therapy planning. This approach provides a valuable alternative imaging solution for facilities lacking DECT scanners and for patients who are unsuitable for iodine contrast imaging, thereby enhancing the reach and effectiveness of advanced imaging in cancer treatment planning.

Pediatric head and neck trauma in the United States: Trends, risk factors and outcomes using the National Trauma Data Bank.

Pediatric head and neck (HN) trauma is an important contributor to pediatric morbidity, resulting in significant downstream consequences. Few studies provide epidemiological predictors of pediatric HN trauma on a national scale. The present study aims to identify risk factors of HN injury and mortality in the pediatric population. A retrospective cohort study was conducted for patients (age <18 years) using the US National Trauma Data Bank (NTDB 2007-2019). Demographic, injury, and physiologic outcome data were analyzed. HN injury was defined as a head or neck Abbreviated Injury Scale (AIS) >0. Logistic regression identified independent predictors of mortality following HN trauma. Of the 1.42 million pediatric patients analyzed, 44.05% had HN injury. In patients aged 0-4, the most common mechanism was falls (47.67% in this age group) while in ages 14-17, motor vehicle/transport accidents (MVTs) were the most common mechanism (56.06%). Controlling for demographics, comorbidities, and injury severity, HN injury was associated with increased odds of mortality (OR 2.404, 95% CI 1.530-3.778). HN injury mortality was strongly predicted by firearm exposure (OR 11.28, 95% CI 6.074-20.95), age <4 (OR 1.179, 95% CI 1.071-1.299), and self-insured status (OR 1.977, 95% CI 1.811-2.157). NTDB data demonstrate that the percentage of pediatric patients with HN trauma has decreased over the past 12 years although is associated with increased odds of mortality. Age and insurance status predicted mortality from HN trauma, with falls and MVTs being the most common mechanisms of injury. These data have implications for future public health efforts in this patient population. 3.

Rare Case of Klippel Feil Syndrome Associated with Mirror Movements

Klippel Feil Syndrome (KFS) is a multisystem disorder with the typical clinical trial of short neck, restriction of headand neck movements and low posterior hairline and associated with anomalies of the urogenital, musculoskeletal, neurological andcardiovascular systems. Here is a case report of a young boy with history of abnormal head and upper limbs movements alongwith repeated bowing of head since the age of 6 months. He also had frequent falls with repeated minor trauma to the face.Antenatal and peripartum period was uneventful and child had no neonatal complications with normal development. Onexamination the child had abnormal head position with bowing, short neck and low hair line. Musculoskeletal system examinationrevealed decreased range of passive movements at cervical spine extension and lateral flexion with no focal neurological deficits.Further examination revealed Mirror movements (synkinesis) in the upper limbs. Mirror movements are the involuntarymovements of one body part that mirror intentional movements on the opposite side. Other Systemic examinations were normal.CT Cervical spine showed fusion of the upper three cervical vertebrae and the child was diagnosed as a case of klippel feil syndrometype 2 presenting with mirror movements. This rare case of klippel feil syndrome is being presented with the aim that such casesshould be detected and treated at an early stage to reduce the cosmetic &amp; social stigma to the patient and parents. This casereport also gives a brief overview of associated features of KFS along with its management.