Neck Cancer Research Articles

Characterizing Physiologic Swallowing Impairment Profiles: A Large-Scale Exploratory Study of Head and Neck Cancer, Stroke, Chronic Obstructive Pulmonary Disease, Dementia, and Parkinson's Disease

Purpose: The purpose of the present study was to use a large swallowing database to explore and compare the swallow-physiology impairment profiles of five dysphagia-associated diagnoses: chronic obstructive pulmonary disease (COPD), dementia, head and neck cancer (HNC), Parkinson's disease (PD), and stroke. Method: A total of 8,190 patients across five diagnoses were extracted from a de-identified swallowing database, that is, the Modified Barium Swallow Impairment Profile Swallowing Data Registry, for the present exploratory cross-sectional analysis. To identify the impairment profiles of the five diagnoses, we fit 18 partial proportional odds models, one for each of the 17 Modified Barium Swallow Impairment Profile components and the Penetration–Aspiration Scale, with impairment score as the dependent variable and diagnoses, age, sex, and race as the independent variables with interactions between age and diagnoses and between PD and dementia (in effect creating a PD with dementia [PDwDem] group). For components with > 5% missingness, we applied inverse probability weighting to correct for bias. Results: PD and COPD did not significantly differ on 13 of the 18 outcome variables (all p s > .02). Dementia, stroke, and PDwDem all showed worse impairments than COPD or PD on five of six oral components (all p s < .007). HNC had worse impairment than all diagnoses except PDwDem for nine of 10 pharyngeal components (all p s < .006). Stroke and HNC had worse penetration/aspiration than all other diagnoses (all p s < .003). Conclusions: The present results show that there are both common and differing impairment profiles among these five diagnoses. These commonalities and differences in profiles provide a basis for the generation of hypotheses about the nature and severity of dysphagia in these populations. These results are also likely highly generalizable given the size and representativeness of the data set. Supplemental Material: https://doi.org/10.23641/asha.27478245

Hardware Complication Risks in Head and Neck Cancer Patients Undergoing Reconstructive Surgery With Segmental Mandibulectomy

ABSTRACTBackgroundThe primary objective of this study was to ascertain the risk factors associated with hardware complications following segmental mandibular reconstruction in head and neck cancer patients. Additionally, we sought to develop a nomogram model that enables accurate risk prediction.MethodsPatients who underwent segmental mandibulectomy with immediate free or local regional tissue transfer between January 2016 and December 2020 were reviewed. Hardware complications were defined. Patient demographics and perioperative parameters were analyzed.ResultsA total of 510 patients were analyzed. Postoperative radiation therapy (OR = 2.296, 95% CI = 1.339–3.938, p = 0.003), postoperative wound infection (OR = 2.367, 95% CI = 1.472–3.806, p < 0.001), and debridement for flap‐related complications (OR = 5.484, 95% CI = 3.269–9.199, p < 0.001) were identified as independent risk factors. The nomogram model demonstrated good discriminatory ability.ConclusionThis comprehensive analysis identified three independent risk factors, and the nomogram provides a valuable tool for predicting the risks. Further research is needed to validate these findings and explore preventive strategies.

Abstract B034: Engineering the tumor microenvironment: Patient-specific microphysiological systems of the head and neck cancer tumor microenvironment

Abstract Introduction: Survival rates in advanced head and neck cancer (HNC) remain poor with no clinically approved biomarkers to predict treatment efficacy. HNC is a highly heterogenous disease and the lack of available models that capture patient heterogeneity and the complexity of the tumor microenvironment (TME) contributes to these poor patient outcomes. Microphysiological systems (MPS) are complex multicellular in vitro models that can recapitulate three-dimensional organ structure and function. The low cell number requirements for MPS permits the creation of patient-specific TME models, where all the cell types can be isolated from a single piece of tumor tissue. These patient-specific MPS represent a promising strategy for elucidating the contribution of the TME to treatment resistance, predicting the best treatment for each patient and improving patient outcomes in HNC. Here, we report a patient-specific MPS that contains multiple TME compartments and recapitulates patient heterogeneity. Methods: Tumor tissue was collected from patients with oral cavity carcinoma undergoing standard of care surgery followed by radiation or chemoradiation. Tissue from each patient was digested and tumor infiltrating leukocytes (TIL) were isolated using CD45 magnetic beads, while epithelial cells and fibroblasts were expanded in culture using specific media formulations. Tissue was also snap frozen for single cell RNA sequencing analysis. To build the MPS, a custom designed microfluidic device was filled with a hydrogel matrix containing patient-matched TIL, fibroblasts and epithelial spheroids to mimic the solid tumor. Lumens molded from the hydrogel were seeded with blood or lymphatic endothelial cells to create vasculature. Multiple replicate MPS can be built from each patient, which are cultured in an optimized media formulation to support the multiple primary cell types. Patient-specific MPS were treated with radiation or cisplatin + radiation to mimic the treatment the patient received. Multiple orthogonal endpoints were measured including tumor cell migration and viability, cytokine secretion and angiogenesis. Single cell sequencing was also performed on the original tumor tissue and matched MPS. Results: We have successfully created patient-specific models of the HNC TME. Single cell RNA sequencing analysis of the MPS suggests that cellular heterogeneity is being retained. Patient characteristics varied between MPS with some patient TME MPS showing highly migratory tumor cells or angiogenic responses. Treatment responses were measured for each patient-specific MPS and ongoing work will characterize the contributions of the TME to treatment resistance. These data demonstrate the feasibility of using patient-specific MPS to investigate the contribution of the TME to treatment response and resistance and lays important groundwork for using MPS to identify patient treatment responses. Citation Format: Adeel Ahmed, Marcos Lares, Fauzan Ahmed, Adam R. Burr, Paul M. Harari, David J. Beebe, Sheena C. Kerr. Engineering the tumor microenvironment: Patient-specific microphysiological systems of the head and neck cancer tumor microenvironment [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr B034.

Abstract PR008: Cross-talk between metastatic cells and host systems: Neutrophil metabolic adaptation, immune profiling, and systemic metabolic shifts in tumor progression and cachexia

Abstract Oral squamous cell carcinoma (OSCC) is a prevalent type of head and neck cancer with a high mortality rate, partly due to late diagnosis often accompanied by metastasis. Cachexia, a complex syndrome marked by severe weight loss and muscle wasting, frequently accompanies advanced cancers including OSCC. Notably, 50-70% of OSCC patients exhibit cachexia at diagnosis, which persists post-treatment, hinting at a metastatic contribution to this syndrome. One significant challenge in studying cancer cachexia is the lack of well-characterized pre-clinical models that accurately reflect human disease. Traditional mouse models often involve subcutaneously transplanted cells, which fail to mimic the natural tumor-host interactions and metastatic progression seen in patients. These models do not typically exhibit metastasis and differ significantly from the genetic and molecular landscape of human cancers. To address these limitations, we developed a syngeneic mouse model by orthotopically transplanting MOC2 murine OSCC cells into the tongues of B6J mice, thereby closely mimicking the tumor microenvironment and metastatic behavior of human OSCC. By enhancing metastasis with a palm-enriched high-fat diet, we observed progressive tumor growth, metastasis, and body weight loss, independent of food intake reduction, indicating metabolic dysregulation rather than anorexia. Comprehensive analyses, including single-cell RNA sequencing (scRNAseq) of immune cells and transcriptomic and metabolomic profiling of tumor and host tissues, identified significant gene expression changes associated with metastasis and cachexia. Enhanced metastasis correlated with lipid metabolism changes in lung metastases, suggesting that metastatic cells exploit lipids for growth. Further, immune profiling revealed neutrophils' metabolic adaptation in metastasis, with implications for both tumor progression and cachexia. Targeting key metabolic and inflammatory pathways in tumor and immune cells holds potential for mitigating metastasis and cachexia. Early-stage serum metabolomics indicated systemic metabolic shifts, emphasizing the need to understand the interplay between tumor metastasis and host metabolism. These findings underscore the complex mechanisms underlying OSCC-induced cachexia, and the need for new targeted therapeutic strategies to disrupt this lethal synergy between cancer progression and metabolic deterioration of the host. Citation Format: Blanca Majem, Josefina Martin, Liudmila Shevkova, Claudia Bigas, Gloria Pascual, Salvador Aznar-Benitah. Cross-talk between metastatic cells and host systems: Neutrophil metabolic adaptation, immune profiling, and systemic metabolic shifts in tumor progression and cachexia [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr PR008.

Abstract PR002: Lymph node colonization reprograms lymphocyte responses to generate systemic tolerance and promote distant metastasis

Abstract The majority of cancer-associated deaths result from distant organ metastasis, yet the mechanisms that enable this process remain poorly understood. Colonization of locoregional or distant lymph nodes (LNs) typically precedes the formation of distant organ metastases, yet it has been unclear whether LN metastasis plays a functional role in disease progression. LNs are major sites of anti-tumor lymphocyte education, including in the context of immunotherapy, yet LN metastasis frequently correlates with further disease progression. By leveraging our mouse models of LN metastasis, we find that LN colonization represents a critical step in tumor progression by inducing tumor-specific immune tolerance in a manner that promotes further dissemination of tumors to distant organs. This promotion of distant seeding by LN metastases is reliant upon adaptive immunity and is tumor specific. Using flow cytometry and single-cell sequencing to perform comprehensive immune profiling, we identify multiple cellular mediators of tolerance. LN metastases evade NK cells, induce shifts in DC and B cell populations, and promote CD8 T cell exhaustion, but of particular importance, we find that regulatory T cells (Tregs) are enriched in the LNs of mice and patients with LN metastases. LN metastatic cells exhibit an enhanced capacity to induce Treg differentiation from naïve CD4 T cells, and ablation of Tregs using FoxP3-DTR mice eliminates the ability of LN metastases to promote distant metastasis. Furthermore, adoptive transfer of Tregs from the LNs of mice bearing LN metastases to naïve mice facilitates lung metastasis in a manner that Tregs from mice without LN metastases cannot. These Tregs are induced in a tumor antigen-specific manner and TCR recognition of tumors is required for the metastasis-promoting tolerance. Using photoconvertible mice, we track the trafficking dynamics of Tregs from tumor involved LNs and demonstrate their elevated trafficking to sites of distant metastasis prior to the formation of detectable metastases in those sites. Through bulk and single-cell TCR sequencing of the Treg repertoire we reveal how LN colonization alters the clonal architecture of the Treg compartment and demonstrate how the evolution of metastatic traits coincides with shifts in the Treg repertoire. Parallel analyses in patients with melanoma and head and neck cancer reveal similar CD4 T cell dynamics in the context of LN involvement. Together, these findings demonstrate a critical role for LN metastasis in promoting tumor-specific immune tolerance and metastatic progression. Citation Format: Cort B. Breuer, Norma A. Gutierrez, Zhewen Xiong, Amanda R. Kirane, John B. Sunwoo, Nathan E. Reticker-Flynn. Lymph node colonization reprograms lymphocyte responses to generate systemic tolerance and promote distant metastasis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr PR002.

Pretreatment neutrophil-lymphocyte ratio as a prognostic factor in recurrent/metastatic head and neck cancer treated with pembrolizumab.

Pembrolizumab-containing regimens are the standard first-line treatment for recurrent/metastatic squamous cell carcinoma of the head and neck (R/M HNSCC). The neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein-to-albumin ratio (CAR) have been reported to be important prognostic factors in a variety of carcinomas, but none have been investigated in combination with pembrolizumab and chemotherapy or in first-line treatment. Seventy-four patients with R/M HNSCC received pembrolizumab-containing regimens at Tohoku University Hospital, Sendai, Japan, from April 2020 to March 2023. Patient characteristics, tumor response, overall survival (OS), progression-free survival (PFS), and laboratory findings were reviewed. Associations between NLR, CAR, and survival outcomes were analyzed. The 1-year OS and 1-year PFS rates were 60.4% and 18.1%, respectively. The disease control rate was 66.2%. In multivariate analysis, low NLR (< 5) was significantly associated with better OS and PFS. NLR may be a predictive factor for OS and PFS in patients with R/M HNSCC treated with a pembrolizumab-containing regimen.

Microorganisms isolated from thermoplastic masks and storage racks in head and neck cancer patients with radiation dermatitis.

Healthcare-associated infections (HAIs) remain a critical public health issue, as they contribute to prolonged treatment duration, increased healthcare costs, and heightened risks of morbidity and mortality. In head and neck cancer patients undergoing radiotherapy, thermoplastic masks (TMs), which come into direct contact with the skin, represent a potential vector for infection. Additionally, the storage racks where these masks are kept may also facilitate microorganism transmission. Our study aimed to isolate and identify microorganisms from infective skin lesions secondary to radiation dermatitis in head and neck cancer patients, as well as from the TMs and storage racks, and to evaluate the antibiotic resistance profiles of the isolated microorganisms. The study included 71 locally advanced head and neck cancer patients who underwent radiotherapy between August 2022 and November 2023. Patients were monitored daily, and their skin evaluations were made according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Grade 2 and 3 radiodermatitis was observed in 29 of these 71 patients. Samples were collected using sterile swabs from the skin lesions on the head and neck area, the inner surfaces of the TM, and the storage rack from 29 patients. Samples were inoculated into enrichment and selective media. After the growing microorganisms were identified, antimicrobial susceptibility was evaluated using conventional methods and automated systems according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. At least one type of microorganism was isolated from the skin samples of infected patients, and double growth was detected in two patients. Among the samples, 2 were methicillin-resistant coagulase-negative Staphylococcus (MRCNS), 1 was methicillin-resistant Staphylococcus aureus (MRSA), 1 was Candida albicans (C. albicans), 15 were methicillin-sensitive coagulase-negative Staphylococcus (MSCNS), 1 was methicillin-sensitive Staphylococcus aureus (MSSA), 1 was Bacillus subspecies (Bacillus spp.) and 3 were Corynebacterium diphtheriae (C. diphtheriae). Coagulase-negative Staphylococcus strains were isolated from the skin of 14 of 19 patients with grade 2 radiation dermatitis, whereas CNS strains were isolated from only 2 of 10 patients with grade 3 radiation dermatitis. Among the gram-negative bacteria, 3 Pseudomonas aeruginosa (P. aeruginosa), 2 Enterobacter cloacae (E. cloacae), 1 Klebsiella pneumoniae (K. pneumoniae) and 1 Moraxella catarrhalis (M. catarrhalis) strain were isolated. Sixteen (55.1%) of the TMs used in 29 patients and 20 (68.9%) of the storage racks harbored microorganisms, including HAI agents and flora bacteria. Bacteria colonize TMs and storage racks where they are risk factors for secondary skin infections in radiation dermatitis lesions that develop on the skin of head and neck cancer patients. Decontamination procedures should be meticulously applied to surfaces such as TMs and their storage racks during the course of radiotherapy.

Assessment of oral disease burden among head and neck cancer patients in the Merseyside region.

Introduction Head and neck cancer (HANC) significantly impacts the oral cavity and dental health issues may complicate cancer treatment and post-treatment quality of life. Pre-treatment dental evaluation is critical for identifying and managing existing oral health problems. However, limited literature exists on the dental health status of patients at the time of HANC diagnosis. This study aims to address this gap and emphasise the importance of dental care in the management of HANC.Methods A retrospective analysis of medical records was conducted on patients scheduled for radiotherapy for HANC. Data on demographic characteristics, tumour characteristics and dental exam findings were extracted from the patient record.Results Of the 191 included patients, the average age was 62.9 years (SD: 10.09), with 80% being men. The prevalence of dental disease revealed 59% of cases presenting with unstable periodontal disease and an average decayed, missing, and filled teeth score of 19.9. Two-thirds of patients exhibited one or more carious lesions.Conclusion This retrospective study sheds light on the dental health status of patients with HANC at their pre-treatment evaluation. The high prevalence rates of dental caries and unstable periodontal disease highlight the importance of dental evaluation and intervention as part of the overall management of HANC patients.

MiR-22-3p as a promising predictor of nutritional deficiencies in patients with head and neck cancer subjected to intensity-modulated radiation therapy.

Head and neck cancer (HNC) is the seventh most common cancer globally, with 20-60% of patients experiencing nutritional deficiencies. Recent studies indicate that microRNAs (miRNAs) may serve as molecular markers for malnutrition. This study evaluated miR-22-3p as a potential predictor of nutritional deficiencies and a prognostic factor in HNC patients undergoing intensity-modulated radiation therapy (IMRT). From 2014 to 2017, fifty-six advanced HNC patients at the Medical University of Lublin received IMRT, with miR-22-3p levels measured from peripheral blood before treatment. Statistical analysis using MedCalc 15.8 revealed that underweight patients had significantly lower miR-22-3p expression compared to non-underweight patients (0.89 vs. 2.47; p = 0.0233). Moderately or severely malnourished patients also showed reduced miR-22-3p levels compared to well-nourished individuals (1.42 vs. 11.04; p = 0.026). Additionally, patients with critical weight loss (CWL) had significantly lower miR-22-3p levels than those without CWL (0.96 vs. 4.91; p = 0.0015). Weak correlations were found between miR-22-3p levels, cancer stage, body mass index (BMI), and C-reactive protein (CRP), with lower miR-22-3p levels linked to advanced tumor stages and higher CRP levels. This study suggests miR-22-3p as a biomarker for nutritional deficiency risk in HNC patients, though further research is needed to validate its predictive capacity.

Technical note: Optimizing spot-scanning proton arc therapy with a novel spot sparsity approach.

One of the main challenges of utilizing spot-scanning proton arc therapy (SPArc) in routine clinics is treatment delivery efficiency. Spot reduction, which relies on spot sparsity optimization (SSO), is crucial for achieving high delivery efficiency inSPArc. This study aims to develop a novel SSO approach based on the alternating directions method of multipliers (ADMM) for SPArc to achieve high treatment delivery efficiency and maintain optimal dosimetric planquality. In this study, SSO for SPArc is based on the least-square dose fidelity term with L0-norm regularization. The novel optimization approach is based on the ADMM framework, in which the minimum monitor unit constraint was considered to improve the plan quality. A state-of-the-art SSO method, the primal-dual active set with continuation (PDASC) algorithm published previously, was utilized as a benchmark. Two SPArc plan groups with the same beam assignment and clinical constraint were generated, in which the former group was SPArc plan with SSO utilizing ADMM, denoted as , and the later group was SPArc with SSO utilizing PDASC, denoted as . Nine clinical cases included five different cancer sites (brain, lung, liver, prostate, and head&neck cancer) were used. The SSO method's performance was evaluated in terms of spot sparsity level (the number of zero-valued elements divided by the total number of elements), beam delivery time, dosimetric plan quality, and plan robustness. Compared to the plan, the plan exhibits superior sparsity and higher delivery efficiency while maintaining good planquality. This study introduces a novel spot sparsity optimization approach using the ADMM framework to improve the delivery efficiency of SPArc. Compared to the existing state-of-the-art SSO method, such an approach could further enhance delivery efficiency while maintaining good plan quality, which could promote the implementation of SPArc in theclinic's.

Electronic Health in the Palliative Care Pathway for Patients With Head and Neck Cancer.

The Expert Center of Palliative Care for head and neck cancer offers structural attention to patients' complex physical and psychosocial care needs. Patients are offered remote care, including digital monitoring using patient-reported outcome measures, to enable them to stay as long as possible in their trusted home environment. There is limited literature on qualitative feedback and patient-reported experiences with palliative head and neck cancer care, especially for remote care. To provide optimal palliative care, more information on this is needed. To provide insight into the experiences of patients with head and neck cancer and their next of kin with a hybrid palliative care pathway. A mixed-methods quality improvement study was conducted at a tertiary cancer center. The experiences of patients with head and neck cancer in the palliative phase as of June 2022 and next of kin of patients who had died between June 2021 and March 2022 were evaluated using a patient-reported experience measure that included open-ended questions. Hybrid palliative care pathway. Experiences of patients and next of kin. Of 105 included participants, 54 (51.4%) were male, and the mean (SD) age was 67.2 (12.7) years. A total of 56 participants were patients and 49 were next of kin. The face-to-face consultations on the day of the palliative diagnosis were positively experienced by most patients and next of kin. A total of 42 of 102 participants (41%) and 24 of 79 participants (30%) missed at least 1 topic during consultations with their physician and oncology nurse, respectively, such as discussing life expectancy. During the remote follow-up, 71 of 92 (77%) felt safe with this care: they were able to sufficiently clarify their problems, and if necessary, timely action was taken. However, 17 of 48 patients (35%) and 21 of 46 next of kin (46%) considered the provided psychosocial support to be insufficient. In this quality improvement study, patients and next of kin were satisfied with most aspects of the hybrid palliative care pathway, and remote care seemed to be a promising means of delivery. Key areas needing attention are discussing life expectancy and providing psychosocial support. These insights represent the initial steps toward gaining a deeper understanding of patients' needs during specific moments in a hybrid palliative trajectory. They may support health care professionals in optimizing personalized and value-based palliative care delivery.

Phenotypical differences of neutrophils patrolling tumour-draining lymph nodes in head and neck cancer.

The complexity and heterogeneity of neutrophils are recognized, especially their roles in modulating inflammation and cancer immune responses. The detailed functions of neutrophils in human tumour-draining lymph nodes (TDLNs), specifically in the context of head and neck cancer, remain inadequately characterized. This study aims to delineate the phenotypic diversity of neutrophils in TDLNs, non-tumour-draining lymph nodes (nTDLNs) from patients with oral squamous cell carcinoma (OSCC), and to evaluate their correlation with clinical outcomes. A flow cytometry-based investigation. Neutrophils manifest a tissue-specific heterogeneity with significant phenotypic differences between compartments. A substantial fraction of neutrophils displayed an activated CD16highCD62Ldim profile in TDLNs, more prominent in patients with advanced T stages, implicating their involvement in the disease's progression. Notably, the presence of this activated neutrophil phenotype in TDLNs was strongly associated with poorer patient prognosis. The study confirms the heterogeneity of neutrophils in human TDLNs, aligning with findings from animal models but extending them to show clinical relevance in human disease. The correlation of neutrophil phenotypes with cancer progression and prognosis emphasizes the importance of these cells in the tumour-microenvironment. The data suggests a future possibility to develop targeted therapies that modulate the neutrophilic response in OSCC.

FOXA1 enhances antitumor immunity via repressing interferon-induced PD-L1 expression in nasopharyngeal carcinoma

BackgroundNasopharyngeal carcinoma (NPC) is a distinct subtype of head and neck cancer which is prevalent in south of China and southeastern of Asia. Consistent activation of interferon (IFN) signaling, and...

Lyophilized particles and ethanolic extracts of Antrodia cinnamomea mycelia suppress the tumorigenicity of head and neck cancer cells in vivo

Lyophilized particles and ethanolic extracts of Antrodia cinnamomea mycelia suppress the tumorigenicity of head and neck cancer cells in vivo

Time to Onset of Dysphagia Following Head and Neck Radiation.

To evaluate the time of onset of dysphagia in a cohort of head and neck cancer patients treated with radiation or chemoradiation. Retrospective chart review of adult patients. 237 patients met inclusion criteria for the study. The average age at cancer diagnosis was 62 years (± 12.6) in a predominantly male cohort (n = 198, 83.5%). The most common subsite was oropharyngeal (n = 146, 60.8%) and squamous cell carcinoma in origin (n = 232, 97.9%). Of head and neck cancer patients diagnosed with new onset dysphagia or a dysphagia related diagnosis, nine (3.8%) were diagnosed at six months to 1 year, 12 (5.1%) at 1-2 years, and 17 (7.1%) at greater than 2 years. The mean radiation dose to the larynx was 43.8Gy (Gy) (± 14.5) and statistically significant across time the periods (p = 0.018, η2 = 0.161). No difference was found between age, HPV status, T stage, smoking history, or tumor site. The majority of head and neck cancer patients treated with chemoradiation who developed dysphagia did so within the acute time period (during treatment and up to 6 months post treatment). However, a substantial proportion of patients also developed dysphagia in later time periods (16%). The incidence of dysphagia in certain time periods may be impacted by laryngeal radiation dose. Therefore, we recommend long term monitoring/screening of these patients so early intervention can occur.

Integrating Palliative Care Into Routine Head and Neck Cancer Care-Separate Is Inherently Unequal.

Integrating Palliative Care Into Routine Head and Neck Cancer Care-Separate Is Inherently Unequal.

Abstract PR004: Biological insights into tissue-agnostic plasma cfDNA methylation signature for surveillance of head and neck tumor recurrence

Abstract BACKGROUND: We recently described a clinical validation of a tissue-agnostic genome-wide methylome enrichment molecular residual disease (MRD) assay for head and neck cancers (HNC) (Liu, ESMO 2024). Herein, we investigate the cfDNA methylation signature utilized by this test to demonstrate the biological relevance with respect to the tissue of origin and epigenetic mechanisms of dysregulation that alter normal cellular activity. We evaluate the signature to gain insights and to characterize the biology of this biomarker and to investigate the application of cfMeDIP-seq assay as a diagnostic tool. METHODS: From unblinded training set of 163 HNC patients, including HPV+ (n = 76), HPV- (n = 43), and HPV-unknown (n = 44) individuals, a cfDNA methylation classifier signature was developed to detect recurrence (n MRD+ = 62, n MRD- = 101) in samples from blood draws approximately at 3, 12, and 24 months post curative intent treatment using cfMeDIP-seq assay. Clinical performance of the signature was then successfully validated in a blinded HNC validation cohort (n = 162), including HPV+ and HPV- patients (Liu, ESMO 2024). Here, the signature’s ability to detect ctDNA was assessed using HNC tumor tissue (n = 523), adjacent normal tissue (n = 45), and healthy peripheral blood leukocytes (n = 93) DNA methylation data from TCGA. The signature’s ability to provide biological insights was assessed by evaluating enrichment in CpG elements, epigenetic regulators, regulatory pathways, and other biological pathways. RESULTS: Identified differentially methylated regions (DMRs) were significantly hypermethylated in HNC tumor tissue samples when compared to adjacent normal and healthy peripheral blood leukocytes (P = 1.3e-131), and the mean signature signal within tumor tissue samples correlated with tumor purity (P = 2.47e-21). These DMRs were also significantly enriched in CpG islands, shores, and shelves and could classify HNC patients into identifiable molecular subtypes. Further analysis of the DMRs, based on their genomic coordinates, shows association with known cancer genes and significant enrichment in pathways known to be associated with HNC, for example, epithelial to mesenchymal transition (P = 1.76e-4), and multiple functional pathways involved in DNA and transcription factor binding, transcriptional regulation, and chromatin remodeling. CONCLUSIONS: These results, along with the previous clinical validation, provide strong evidence that the cfDNA methylation signature developed in HNC detects ctDNA shed from residual tumor and provide insights into relevant tumor biology and epigenetic mechanisms, including CpG island hypermethylation and epithelial to mesenchymal transition. Furthermore, these data support the generalization of biomarker detection utilizing cfMeDIP-seq to a broad spectrum of indications. Citation Format: Yulia Newton, Justin Burgener, Margaret Gruca, Collin Melton, Jun Min, Abel Licon, Scott Bratman, Alan Williams, Daniel D De Carvalho. Biological insights into tissue-agnostic plasma cfDNA methylation signature for surveillance of head and neck tumor recurrence [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr PR004.

Abstract IA018: Liquid biopsy in head and neck cancers: A model for tissue-agnostic MRD detection

Abstract Head and neck cancer (HNC) is a molecularly heterogenous disease with a variable clinical course. Current treatment decisions rely primarily on pre-treatment prognostic factors without consideration of treatment response. This presentation will introduce liquid biopsy biomarkers that can be repeated in HNC patients for the purpose of dynamic risk stratification, treatment adaptation, and post-treatment surveillance. Novel approaches to measuring circulating tumor DNA (ctDNA) will be described, with particular attention to viral-associated and non-viral- associated subtypes of HNC. Detection of molecular residual disease (MRD) using ctDNA will be discussed. As HNC is often treated by non-surgical means, there is a pressing need for tissue- agnostic methods for ctDNA-based MRD detection. Analysis of tumor-specific genetic and epigenetic aberrations within ctDNA each present distinct opportunities and challenges for tissue-agnostic characterization of ctDNA. Viral ctDNA has emerged as a convenient target for MRD detection in viral-associated HNC, while ctDNA methylome profiling offers a versatile approach for tissue-agnostic MRD detection across HNC subtypes. Future applications of these methods may improve individualized management of HNC patients without requiring access to precious tumor tissue samples. Citation Format: Scott V Bratman. Liquid biopsy in head and neck cancers: A model for tissue-agnostic MRD detection [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr IA018.

Dual-encoder architecture for metal artifact reduction for kV-cone-beam CT images in head and neck cancer radiotherapy.

During a radiotherapy(RT) course, geometrical variations of target volumes, organs at risk, weight changes (loss/gain), tumor regression and/or progression can significantly affect the treatment outcome. Adaptive RT has become the effective methods along with technical advancements in imaging modalities including cone-beam computed tomography (CBCT). Planning CT (pCT) can be modified via deformable image registration (DIR), which is applied to the pair of pCT and CBCT. However, the artifact existed in both pCT and CBCT is a vulnerable factor in DIR. The dose calculation on CBCT is also suggested. Missing information due to the artifacts hinders the accurate dose calculation on CBCT. In this study, we aim to develop a deep learning-based metal artifact reduction(MAR) model to reduce the metal artifacts in CBCT for head and neck cancer RT. To train the proposed MAR model, we synthesized the kV-CBCT images including metallic implants, with and without metal artifacts (simulated image data pairs) through sinogram image handling process. We propose the deep learning architecture which focuses on both artifact removal and reconstruction of anatomic structure using a dual-encoder architecture. We designed four single-encoder models and three dual-encoder models based on UNet (for an artifact removal) and FusionNet (for a tissue restoration). Each single-encoder model contains either UNet or FusionNet, while the dual-encoder models have both UNet and FusionNet architectures. In the dual-encoder models, we implemented different feature fusion methods, including simple addition, spatial attention, and spatial/channel wise attention. Among the models, a dual-encoder model with spatial/channel wise attention showed the highest scores in terms of peak signal-to-noise ratio, mean squared error, structural similarity index, and Pearson correlation coefficient. CBCT images from 34 head and neck cancer patients were used to test the developed models. The dual-encoder model with spatial/channel wise attention showed the best results in terms of artifact index. By using the proposed model to CBCT, one can achieve more accurate synthetic pCT for head and neck patients as well as better tissue recognition and structure delineation for CBCT image itself.

Abstract A010: Biofluid-Ensemble Analysis through Multi-modal Spectroscopy (BEAMS): A deep learning architecture for rapid early-stage liquid biopsy cancer diagnostics

Abstract Introduction: Head and neck cancer (HNC) is one of the most common cancer types globally without an accessible rapid screening method. Conventional screening occurs at the clinician’s office, where grading and staging of the tumors are physically performed, and the clinician’s preliminary diagnosis is usually confirmed through laborious procedures of histology and CT/PET/MR scans. Patient’s quality of life and expected outcomes can be improved through early-stage screening, yet there is no existing technology on the market that tackles this dire need. As such, we propose a rapid liquid biopsy diagnostic platform empowered by deep learning algorithms that makes early-stage non-invasive screening possible. The platform utilizes the complementary vibrational spectral biomarkers information from Fourier Transform Infrared Spectroscopy (FTIR) and Raman spectroscopy. We coupled the techniques with two biofluids: saliva and plasma, which offered information on circulating and localized metabolites. Materials and Methods: The patient’s biofluid is first drop-casted on top of a substrate and air-dried at room temperature. Using an FTIR microscope or a Raman microscope, 25 spot measurements are made in a 5 by 5 grid pattern to produce a comprehensive scan of the sample. The measured spectra are subsequently fed into the deep learning framework to perform classification. The deep machine learning framework is composed of spectrum and subject-level models. Specifically, the spectrum-level model employs cascading convolutional layers to identify the prominent features within the spectrum. This is followed by a sequence of linear layers that further extract features from the convolutional layers and carry out binary classification. For each patient, preliminary classification results of the spectral level model are then evaluated on a per- modality basis across our four modalities (FTIR/Raman measurements made on saliva/plasma) where the patient is classified as positive if any of the modality models deem it so. This framework is applied to a cohort of 96 patients, with 36 non-cancerous patients, 28 early-stage patients, and 32 late-stage patients. Results and Discussion: Our model optimized for general cancer detection has a sensitivity of 91.7%, specificity of 77.8%, and accuracy of 86.5%. Late- stage cancer has proven to be less challenging to detect since our model optimized for late-stage cancer diagnosis has a sensitivity of 93.8%, a specificity of 83.3%, and an accuracy of 88.2%. Our best early-stage model has a sensitivity of 89.3%, a specificity of 69.4%, and an accuracy of 78.1%. Conclusions: Our proposed framework has demonstrated promising capability as the preliminary screening method for high-risk patients (e.g. tobacco users) while providing further interpretability of the deep learning model that is often characterized as a “black box”. The modular nature of our model structure offers substantial flexibility, enabling effective performance even when specific biofluids or spectroscopy modalities are unavailable. Citation Format: Kwan Lun Chiu, Antonio Guillen-Perez, Rebecca Mayer, Wesley Viner, Hanna Koster, Matthew Benson, Jeremy Rowe, Maria Navas-Moreno, Andrew Birkeland, Maria-Dolores Cano, J. Sebastián Gomez-Diaz, Randy Carney. Biofluid-Ensemble Analysis through Multi-modal Spectroscopy (BEAMS): A deep learning architecture for rapid early-stage liquid biopsy cancer diagnostics [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A010.