Neck Carcinoma Research Articles

Current Applications of PET/MR: Part I: Technical Basics and Preclinical/Clinical Applications.

Positron emission tomography/magnetic resonance (PET/MR) imaging has gone through major hardware improvements in recent years, making it a reliable state-of-the-art hybrid modality in clinical practice. At the same time, image reconstruction, attenuation correction, and motion correction algorithms have significantly evolved to provide high-quality images. Part I of the current review discusses technical basics, pre-clinical applications, and clinical applications of PET/MR in radiation oncology and head and neck imaging. PET/MR offers a broad range of advantages in preclinical and clinical imaging. In the preclinic, small and large animal-dedicated devices were developed, making PET/MR capable of delivering new insight into animal models in diseases and facilitating the development of methods that inform clinical PET/MR. Regarding PET/MR's clinical applications in radiation medicine, PET and MR already play crucial roles in the radiotherapy process. Their combination is particularly significant as it can provide molecular and morphological characteristics that are not achievable with other modalities. In addition, the integration of PET/MR information for therapy planning with linear accelerators is expected to provide potentially unique biomarkers for treatment guidance. Furthermore, in clinical applications in the head and neck region, it has been shown that PET/MR can be an accurate modality in head and neck malignancies for staging and resectability assessment. Also, it can play a crucial role in diagnosing residual or recurrent diseases, reliably distinguishing from oedema and fibrosis. PET/MR can furthermore help with tumour characterization and patient prognostication. Lastly, in head and neck carcinoma of unknown origin, PET/MR, with its diagnostic potential, may obviate multiple imaging sessions in the near future.

CSE1L as a prognostic biomarker associated with pan cancer immune infiltration and drug sensitivity

ABSTRACT Background Rising cancer-related mortality underscores the importance of biomarkers for treatment and prognosis, with Chromosome Segregation 1 Like (CSE1L) linked to various cancers yet its roles remain partially understood. This study investigates CSE1L’s expression and oncogenic mechanisms in solid tumors. Research design and methods We analyzed multi-omics data from 31 solid tumors, measured CSE1L in 41 head and neck carcinoma patients post-chemotherapy via qRT-PCR, and evaluated the impact of CSE1L knockdown on cell proliferation in A549 and HepG2 cells. Results In this study, we observed significantly elevated levels of CSE1L RNA in 13 tumor tissues and protein levels in 8 tumor tissues compared to their corresponding adjacent normal tissues. Additionally, our investigation unveiled a correlation between heightened CSE1L expression in tumor tissues and worsened patient prognosis, poor response to immunotherapy, and diminished effectiveness of neoadjuvant chemotherapy. Through an analysis of CSE1L mechanisms, we discovered its potential involvement in promoting tumor cell proliferation, enhancing drug resistance, and influencing immune infiltration, thereby impacting patient prognosis and treatment outcomes. Finally, we delved into the potential mechanisms underlying upregulation of CSE1L in tumor tissues. Conclusion Our findings demonstrate that CSE1L promotes tumor development in various malignancies, highlighting its potential as both a therapeutic target and prognostic indicator.

Maxillary Sinus NUT Carcinoma: A Case Report.

Nuclear protein in testis (NUT) carcinoma is extremely rare, occurs in the midline of the body, progresses rapidly and is refractory to treatment; most patients die within a year. Here, we describe a case of maxillary sinus NUT carcinoma presenting with epistaxis and nasal obstruction that was treated as a standard head and neck carcinoma. The patient was a 41-year-old male with a left buccal swelling; the diagnosis was made of primary NUT carcinoma of the left maxillary sinus and bone metastasis in the cervical spine. After induction chemotherapy with docetaxel plus cisplatin and 5-fluorouracil, the tumor decreased in size, and the patient was further treated with cisplatin and radiation therapy. One month after that, the tumor remained small, however, lung metastasis was observed. Therefore, nivolumab was administered. Cetuximab and paclitaxel were administered after the lung metastasis worsened, but the patient developed progressive disease and died 11 months after diagnosis. Effective treatments for NUT carcinoma have not yet been established. However, early testing to establish the diagnosis may provide useful insights to guide clinical decisions to improve patient outcomes.

Combined approach for predicting the efficacy of nivolumab in head and neck carcinoma by tissue and soluble expressions of PD-L1 and PD-L2.

Predictive biomarkers for nivolumab in recurrent or metastatic head and neck squamous cell carcinoma (RMHNSCC) have not yet been established. The tumor proportion score (TPS), combined positive score (CPS), and soluble forms of programmed cell death ligand-1 (PD-L1) and programmed cell death ligand-2 (PD-L2) were retrospectively analyzed in patients with RMHNSCC treated with nivolumab. The positivity rates for TPS (PD-L1), CPS (PD-L1), TPS (PD-L2), and CPS (PD-L2) were 73.8%, 78.2%, 56.4%, and 78.2%, respectively. Patients with high TPS (PD-L1), CPS (PD-L1), or CPS (PD-L1 and PD-L2) showed significantly prolonged progression-free survival. Favorable overall survival was associated with high CPS (PD-L1 and PD-L2) and low soluble PD-L1 and PD-L2 levels. The expressions of tissue and soluble PD-L1/2 were not correlated. Our study revealed that compared to PD-L1 expression alone, dual expression of PD-L1 and PD-L2 in tissue or soluble form could be feasible biomarkers in patients with RMHNSCC who received nivolumab.

Accuracy of Narrow-Band Imaging-Guided Histopathology and Ki-67 Index in Head and Neck Carcinoma.

All patients were first examined under white light and then under NBI endoscopy, and a biopsy was obtained from suspected lesions and sent for histopathological examination (HPE) and Ki-67 index. Eighty patients were examined out of which, 68 patients having lesions in the oral cavity, oropharynx, larynx, and hypopharynx were examined. The rate of detecting cancerous lesion by white light and NBI were respectively 92% and 100% for oral cavity lesions, 69% and 100% for oropharyngeal lesions, 38% and 100% for hypopharyngeal lesions, and 37% and 100% for laryngeal carcinoma. However, we have found no significant difference in detecting T2-T4 tumors. Hence, we concluded that NBI mode can be a significantly better diagnostic tool than white light mode in detecting early mucosal cancer in head and neck cancer. We have concluded that NBI combined with Ki-67 estimation is a very promising tool that helps in the early diagnosis of mucosal lesions in head and and neck cancer.

Evaluating the Response of Hypofractionated Radiotherapy verses Conventional Radiotherapy with Concurrent Cisplatin in Advanced Fixed Node Head and Neck Carcinoma

Background: The evolution of radiotherapy over recent decades has reintroduced the hypofractionation for many tumour sites with similar outcomes to those of conventional fractionated radiotherapy. The use of hypofractionation in locally advanced head and neck cancer (LAHNC) has been already used, however, its use has been restricted to only a few countries. The aim of this trial was to evaluate the safety and feasibility of moderate hypofractionated radiotherapy (HYP-RT) with concomitant cisplatin (CDDP). Objectives: To evaluate the efficacy of hypofractionated radiotherapy in advanced unresectable head neck cancer, in terms of response rate and evaluate the local and systemic toxicities of hypofractionated regimen with symptomatic improvement of radiotherapy and treatment compliance. Methods: A total of 50 cases of locally advanced head and neck cancer (stage cT4b and/or N3) without any evidence of distant metastasis were included in this study. These 50 cases were randomly distributed into study and control group containing 25 each. Radiotherapy consists of a single fraction of 6 Gy Per week for a total of 6 weeks. If the patient received less than 6weeks of treatment, he/she was excluded from study. Total dose given was 36 Gy in 6 fractions. All the patients were treated by unilateral or bilateral portal till 24 Gy and then off cord planning was done. Patients with complete disease regression after initially planned 36 Gy (BED-57.6Gy, considering alpha/beta of 10 and corresponding EQD2-48Gy) were offered further dose escalation depending upon tumour regression status, tolerability and toxicity according to institutional guidelines. Partial responders are given no treatment up to end of treatment period. Results: Among the study and control group, incidence of carcinoma of tonsil was 12% and 20%, carcinoma of base of tongue was 24% and 16%, carcinoma larynx 16% and 24%, respectively and Hematological toxicities (reference to blood hemoglobin level), Renal (reference to blood urea) were assessed according to WHO toxicity criteria in all cases weekly up to six weeks Among the study and control group, 8% and 12% had no acute hematologic reactions (χ2 = 0.22, p > 0.05), 56% and 48% had grade I hematologic reactions (χ2 = 0.32 p > 0.05,), 28% and 36% had grade II hematologic reactions (χ2 = 0.36, p > 0.05) and 8% and 4% had grade III hematologic reactions (χ2 = 0.35, p > 0.05) respectively. No patient had had grade IV hematological toxicity. Among the study and control group, 80% and76% had no acute renal toxicity. (χ2 = 0.11, p > 0.05), 20% and 24% had grade I hematologic reactions (χ2= 0.11 p > 0.05). No patients from either group develop grade II, III and IV renal toxicity. Conclusions: HYP-RT with concomitant CDDP was considered feasible for LAHNC, and the rate of acute toxicity was comparable to that of standard concomitant chemoradiation. A feeding tube was necessary for most patients during treatment. Further investigation of this strategy is warranted.

The current status and future perspectives of clinical boron neutron capture therapy trials

PurposeSeveral hundreds of patients have been so far treated in clinical trials with boron neutron capture therapy (BNCT).MethodsThis is a non-systematic review of clinical trials with BNCT, with special emphasis on the more recent trials.ResultsThe conducted trials have been relatively small single-arm studies and included mostly the patients with head and neck carcinomas resistant to traditional treatment modalities and glioblastomas. In general, the efficacy results have been promising and BNCT has been relatively well tolerated, even in the patients who have already been treated with conventional radiotherapy or chemoradiation. The most frequent adverse events have been similar to those associated with the conventional radiotherapy. At present, there is no evidence how the efficacy of BNCT would compare to the standard treatment modalities in earlier treatment lines.ConclusionsMost of the existing studies have been performed with reactor-based facilities, but there is now a rapidly increasing number of linear accelerator-based BNCT sites, and the clinical research is apparently activating again. This, combined with the increased knowledge on cancer biology and novel types of oncological therapies, opens possibilities to study innovative boron carriers and to combine BNCT with modern oncological therapies in the future clinical trials. To conduct larger phase III trials, multicenter approaches are encouraged to be applied, keeping in mind the importance of joint instructions and quality control measurements.

IP3R1 dysregulation via mir-200c-3p/SSFA2 axis contributes to taxol resistance in head and neck cancer

Head and neck cancer (HNC) is the sixth most common malignancy worldwide. Although current modalities offer a wide variety of therapy choices, head and neck carcinoma has poor prognosis due to its diagnosis at later stages and development of resistance to current therapeutic tools. In the current study, we aimed at exploring the roles of miR-200c-3p during head and neck carcinogenesis and acquisition of taxol resistance. We analyzed miR-200c-3p levels in HNC clinical samples and cell lines using quantitative real-time polymerase chain reaction and evaluated the effects of differential miR-200c-3p expression on cancer-related cellular phenotypes using in-vitro tools. We identified and characterized a direct target of miR-200c-3p using in-silico tools, luciferase and various in-vitro assays. We investigated potential involvement of miR-200c-3p/SSFA2 axis in taxol resistance in-vitro. We found miR-200c-3p expression as significantly downregulated in both HNC tissues and cells compared to corresponding controls. Ectopic miR-200c-3p expression in HNC cells significantly inhibited cancer-related phenotypes such as viability, clonogenicity, migration, and invasion. We, then, identified SSFA2 as a direct target of miR-200c-3p and demonstrated that overexpression of SSFA2 induced malignant phenotypes in HNC cells. Furthermore, we found reduced miR-200c-3p expression in parallel with overexpression of SSFA2 in taxol resistant HNC cells compared to parental sensitive cells. Both involved in intracellular cytoskeleton remodeling, we found that SSFA2 works collaboratively with IP3R1 to modulate resistance to taxol in HNC cells. When considered collectively, our results showed that miR-200c-3p acts as a tumor suppressor microRNA and targets SSFA2/IP3R1 axis to sensitize HNC cells to taxol.

Enhancing quality of life in head and neck cancer patients: a comparative analysis of 3D exoscope-assisted surgery vs. traditional approaches.

The increasing population of survivors of head and neck carcinomas is becoming more conspicuous. Consequently, the pivotal role of quality of life, particularly elucidated through the assessment of dysphagia and dysphonia, is progressively influencing the decision-making process. The current study aims to assess whether VITOM 3D could offer a comparable post-treatment quality of life to traditional approaches for patients with laryngeal cancer and oro-hypopharyngeal cancer. A case series of laryngeal cancer and oro-hypopharyngeal cancer patients treated either with an exoscopic-assisted surgical setup and with conventional treatments (transoral microsurgery and radio-chemotherapy) at the Otolaryngology Unit of IRCCS San Martino Hospital, Genoa, is presented. The post-treatment quality of life of the two cohorts were compared through the administration of the University of Washington Quality of Life Questionnaire, Voiceik Handicap Index-10, M.D. Anderson Dysphagia Inventory were administrated to both cohorts of patients. In the laryngeal cancer group, a total of 79 patients were included. Of these, 50.1% underwent transoral exoscope-assisted surgery, while 49.9% underwent primary transoral microscopic-assisted surgical approach. No significant differences were observed in terms of the University of Washington Quality of Life Questionnaire and Voice Handicap Index-10 between the two subgroups. Conversely, in the oro-hypopharyngeal cancer group, 43 patients were included. Of these, 37.2% underwent primary transoral exoscope-assisted surgery, while 62.8% received (chemo)radiotherapy. No notable differences were reported in terms of the University of Washington Quality of Life Questionnaire and M.D. Anderson Dysphagia Inventory between the transoral exoscope-assisted surgery and (chemo)radiotherapy subgroups. Assessments of quality of life, conducted through the University of Washington Quality of Life Questionnaire questionnaire, dysphonia evaluations using the Voice Handicap Index-10, and dysphagia assessments employing the M.D. Anderson Dysphagia Inventory questionnaire, demonstrate analogous outcomes between conventional treatment modalities and transoral interventions utilizing the 3D exoscope.

Sentinel lymph node biopsy versus observation in high risk cutaneous squamous cell carcinoma of head and neck: a propensity score matching analysis.

Sentinel lymph node biopsy (SLNB) has gained considerable attention in the management of head and neck cutaneous squamous cell carcinoma (HNcSCC). The aim of this study was to compare the oncologic outcomes between observation and SLNB in cN0 high-risk HNcSCC patients. We retrospectively enrolled patients from the SEER database and evaluated the impact of observation versus SLNB on disease-specific survival (DSS) and overall survival (OS) using a Propensity Score Matching (PSM) analysis. A total of 9804 patients were included, with 1169 cases treated by SLNB. Successful retrieval of the sentinel lymph node was achieved in 1130 procedures. After PSM and subsequent multivariate analysis, SLNB was found to be an independent predictor for improved DSS, with a hazard ratio of 0.70 (95% confidence interval: 0.56-0.86). In patients presenting with two or three high-risk factors, SLNB was associated with better DSS (p = 0.021 and p = 0.044), but similar OS (p = 0.506 and p = 0.801) when compared to observation. However, in patients exhibiting four high-risk factors, SLNB demonstrated significantly improved DSS (p = 0.040) and OS (p = 0.028) compared to observation. Our findings suggest that SLNB is a highly feasible technique in HNcSCC and provides significant survival benefits. It is strongly recommended in patients with two or more high-risk factors, as it can help guide treatment decisions and improve patient outcomes.

Intraoperative Assessment of Margin Accuracy in Patients Diagnosed With Oral Squamous Cell Carcinoma in a Tertiary Hospital of Jharkhand: Frozen Section Versus Histopathology.

Background The incidence of head and neck carcinoma is increasing. The use of an intraoperative frozen section plays a vital role in the evaluation of margin status in patients undergoing surgery for oral squamous cell carcinoma. A negative margin is not only an indication of successful surgery but also decreases the recurrence of disease and improves the overall survival of patients. Aims and objective The aim of this study is to assess the accuracy of margin in patients undergoing surgery for oral squamous cell carcinoma by intraoperative frozen section and compare it with conventional histopathological examination. Methodology The approach of our study was a hospital-based prospective study conducted on 28 patients diagnosed with oral squamous cell carcinoma. A frozen section was done on all patients undergoing surgery and compared with histopathological examination. Results Out of 28 patients undergoing surgery, the incidence of males was more than females, with a ratio of 6:1. The most common site of the tumor was left buccal mucosa comprising 28.57%, followed by gingivobuccal sulcus comprising 17.85%. In our study, the frozen assessed margin showed a sensitivity of 58.33%, specificity of 98.76%, and accuracy of 95.25%. Conclusion Frozen section is a reliable method for confirmation of margin accuracy and thus reduces the chance of re-surgery and recurrence of disease and increases overall patient survival.

Impact of Radiation on Dysphagia-Related Structures: A Dosimetric and Clinical Comparative Analysis of Three-Dimensional Conformal Radiotherapy (3D-CRT) and Intensity-Modulated Radiation Therapy (IMRT) Techniques in Patients With Head and Neck Cancer.

Introduction Head and neck squamous cell carcinoma (HNSCC)is a significant health concern in India, with around one million new cases annually. The prevalence of HNSCC is notably high in Asia, especially in India, due to habitslike tobacco chewing, betel nut usage, and alcohol consumption. Treatment typically involves a combination of surgery, radiation, chemotherapy, and biological therapy, aiming for tumor control while preserving function and quality of life. However, survivors often face long-term side effectslike difficulty swallowing, leading to complicationssuch as aspiration pneumonia. Intensity-modulated radiotherapy (IMRT) has shown promise in improving outcomes by sparing critical swallowing structures. Efforts to minimize radiation-related dysphagia are crucial for enhancing patients' quality of life post-treatment. Our study focuses on examining dosimetric parameters associated with dysphagia aspiration, alongside evaluating dysphagia grades in both treatment groups using the RTOGscale. Material and methods Patients with histologically confirmed non-metastatic head and neck carcinomas were included in our study in November 2018-April 2020. A total of 56 patients were taken into our study with 28 in each arm. They underwent radical radiotherapy (RT) with a total dose of 66-70 Gy, with or without concurrent chemotherapy, meeting specific inclusion criteria and excluding those receiving reirradiation or with distant metastasis. Patients were divided into two groups: Group I received three-dimensional conformal radiotherapy (3D-CRT), and Group II received IMRT. Treatment planning involved immobilization, CT imaging, delineation of target volumes and organs at risk, and contouring of swallowing structures. Dose-volume histogram parameters (mean dose, maximum dose, V30, V70, V80, D50, and D80) were used to assess mean dose to swallowing structures outside the planning target volume (PTV), with a mean dose constraint of 50 Gy. Dysphagia was evaluated using the RTOGcriteria at baseline, during treatment, and six months post-treatment. Statistical analysis was performed using SPSS, with significance set at p < 0.05. Results In our study, the mean age at presentation differed slightly between the IMRT and 3D-CRT arms: 58 years versus 55 years, respectively. A higher proportion of patients in both arms experienced symptoms for three to six months, with 53.6% in 3D-CRT and 42.9% in IMRT. Stage distribution varied, with IV being most common in 3D-CRT and stage II in IMRT. Approximately 56% of patients in both groups had a history of smoking. Significant differences were observed in spinal cord dose between 3DCRT and IMRT techniques (p < 0.001). Similarly, a significant difference was found in the mean dose received by dysphagia aspiration-related structures (DARSs) between the 3D-CRT and IMRT arms (p = 0.04). Patients in the IMRT arm exhibited superior dysphagia grades compared to those in the 3D-CRT arm, with statistical significance observed in the third month (p = 0.008) and sixth month (p = 0.048). Conclusion Our study found a notable decrease in the mean DARS dose and reduced dysphagia severity at three and six months in the IMRT group compared to the 3D-CRT group. However, due to the diverse study population, establishing a definitive correlation between the DARS dose and dysphagia severity was challenging. Future large-scale studies are needed to validate these findings for improved preservation of DARS structures.

P16 and HPV status in head and neck sarcomas and sarcomatoid carcinomas

Human papillomavirus (HPV)-positive oropharyngeal carcinoma is a distinct type of head and neck carcinoma with improved prognosis. p16 immunostaining is often used as a surrogate marker for HPV infection in this particular setting. The aim of this study is to estimate the prevalence of p16 staining and HPV infection in head and neck sarcomatoid carcinomas as well as head and neck sarcomas. 21 sarcomatoid carcinomas and 28 head and neck sarcomas were tested for p16 positivity using immunohistochemical staining, and for high-risk HPV infection using In situ hybridization (ISH). 24 % of sarcomatoid carcinomas and 21 % of sarcomas were positive for p16 staining. All 49 cases were negative for HPV ISH. The results confirm that p16 staining is not specific and may not be associated with HPV infection in non-oropharyngeal head and neck sites. They also indicate that non-oropharyngeal head and neck sarcomatoid carcinomas are not likely to be HPV related.

Macrophage-Capturing Self-Assembly Photosensitizer Nanoparticles Induces Immune Microenvironment Re-Programming and Golgi-Responsive Immunogenic Cell Death in Head and Neck Carcinoma.

Head and neck carcinoma treatment is shifted toward the combination of therapy causing immune checkpoint blockade (ICB) and immunogenic cell death. In this study, a CSFRi-chimeric TAMCSFR+-targeting extracellular vesicle (EV@CSFRi) platform is developed and designed an intracellular protoporphyrin conjugated with RVRR peptide sequence for furin-cleavage to perform Golgi-targeting and generating ROS (GT-RG). The graphical abstract illustrates the self-assembly of GT-RG nanoparticles into nanofiber through the hydrophily of RVRR and hydrophobicity of RG, and the red line indicates the site of furin cleavage. As is shown in the Graphical abstract, the Golgi-targeting Protoporphyrin-RVRR platform is composed with CSFRi-chimeric extracellular vesicles and forms the tumor-responsive TAM-reprogramming bilayers (GT-RGEV@CSFRi). The GT-RGEV@CSFRi acted as a multifunctional theranostic platform, which can induce immunogenic cell death and further help modulate TAM, thus suppressing the HNC xenograft model by combination therapy with anti-PD-1.

Does Low-Level Laser Therapy affect Bcl-2 Gene Expression in Oral Squamous Cell Carcinoma; An invitro study

Objectives: Oral squamous cell carcinoma, which is known as the most common cancer of the oral cavity, is associated with high morbidity and mortality rate. To date, many efforts have been made to find effective methods to stop the growth of cancer cells. One of the emerging methods in this field is the application of low-level lasers.&#x0D; Material and Method: Human head and neck carcinoma cell lines were prepared and irradiated with four different wavelengths of low-level laser with a density of 1 j/cm2 and a power of 100 mW. The expression of the Bcl-2 and Bax genes and the Bax / Bcl-2 ratio were investigated by real-time PCR.&#x0D; Results: The highest percentage of Bcl-2 gene expression was related to 660 nm wavelength and the highest percentage of Bax gene expression was related to 810 nm infrared wavelength. The lowest level of expression of the Bcl-2 gene related to the 810 nm infrared wavelength and the Bax gene related to the 532 nm wavelength was obtained. The lowest Bax/Bcl-2 ratio was obtained at the wavelength of 660 nm and the highest ratio was obtained at the wavelength of 810 nm.&#x0D; Conclusion: Despite the extensive studies conducted in the field of low-level laser application in oncology, more studies are needed to investigate the effect of this technology on cancer cells.

Peritumor Mucosa in Advanced Laryngeal Carcinoma Exhibits an Aberrant Proangiogenic Signature Distinctive from the Expression Pattern in Adjacent Tumor Tissue.

The field cancerization theory is an important paradigm in head and neck carcinoma as its oncological repercussions affect treatment outcomes in diverse ways. The aim of this study is to assess the possible interconnection between peritumor mucosa and the process of tumor neoangiogenesis. Sixty patients with advanced laryngeal carcinoma were enrolled in this study. The majority of patients express a canonical HIF-upregulated proangiogenic signature with almost complete predominancy of HIF-1α overexpression and normal expression levels of the HIF-2α isoform. Remarkably, more than 60% of the whole cohort also exhibited an HIF-upregulated proangiogenic signature in the peritumoral benign mucosa. Additionally, the latter subgroup had a distinctly shifted phenotype towards HIF-2α upregulation compared to the one in tumor tissue, i.e., a tendency towards an HIF switch is observed in contrast to the dominated by HIF-1α tumor phenotype. ETS-1 displays stable and identical significant overexpression in both the proangiogenic phenotypes present in tumor and peritumoral mucosa. In the current study, we report for the first time the existence of an abnormal proangiogenic expression profile present in the peritumoral mucosa in advanced laryngeal carcinoma when compared to paired distant laryngeal mucosa. Moreover, we describe a specific phenotype of this proangiogenic signature that is significantly different from the one present in tumor tissue as we delineate both phenotypes, quantitively and qualitatively. This finding is cancer heterogeneity, per se, which extends beyond the "classical" borders of the malignancy, and it is proof of a strong interconnection between field cancerization and one of the classical hallmarks of cancer-the process of tumor neoangiogenesis.

Concurrent chemoradiation with low-dose and long-duration weekly infusion of gemcitabine in unresectable squamous cell carcinoma of head and neck (SCCHN).

Concurrent chemoradiotherapy now represents the standard of care in locally advanced unresectable squamous cell carcinoma of the head and neck, and the administration of cisplatin in triweekly or weekly schedules is the most commonly used chemotherapeutic agent. However, the chemotherapeutic agent and its scheduling with radiation is still an area of investigation with safer toxicity profile and better response rates. Gemcitabine is a potent radiosensitizer, and non-cytotoxic concentration results in decreased systemic toxicity while maintaining radiosensitization properties. Furthermore, data are emerging for low-dose and long-duration infusion where this strategy is found to be effective and a safe alternative to standard brief infusion. Based on these two strategies, that is, non-cytotoxic concentration with long duration, we have explored the unique possibility of further lowering the toxicity profile without compromising the efficacy. Eligible patients of locally advanced unresectable squamous cell carcinoma of the head and neck underwent radiation treatment with concurrent gemcitabine. A total dose of 70 Gy in 35 fractions over a period of seven weeks with conventional fractionation schedule was delivered with cord off after 44 Gy. Concurrent gemcitabine was administered intravenously for over two hours once a week, 1-2 h before radiation and for seven consecutive weeks at 50 mg/m2. Fifty-two patients was enrolled in this study, out of which 41 completed the treatment. Fifty-nine percent completed treatment within seven weeks. Sixty-four percent were found to have received more than five cycles. Mean follow-up of patients was found to be 4.9 months. Sixty-eight percent had complete response. Stage III patients achieved more complete response compared to stage IV. There was no site-wise difference in achieving complete response. Patients who have received less than five chemo cycles or completed the treatment in more than seven weeks had less complete response. Sixty-one percent had severe mucositis while 39% developed mild/moderate mucositis. Considering skin toxicity, 80% were found to have mild/moderate skin toxicity, while only 20% suffered from severe grades of skin toxicity. Gemcitabine in low-dose and long-duration infusion is a potent radiosensitizer with safer hematological toxicity and manageable local toxicities.

Assessment of collimator angle variation in volumetric-modulated arc therapy planning for head and neck carcinoma patients

Assessment of collimator angle variation in volumetric-modulated arc therapy planning for head and neck carcinoma patients

Abstract 2414: Feasibility and clinical utility of blood based NGS in head and neck carcinomas: A single center experience from precision medicine program

Abstract Background: While blood-based next-generation sequencing is increasingly integral to clinical practice across various malignancies, the routine assessment of circulating tumor DNA (ctDNA) in head and neck cancer remains underexplored, with limited supportive data. Methods: This study focused on head and neck cancer patients enrolled in the Gustave Roussy precision medicine program (STING, NCT04932525), undergoing liquid biopsy (LB) with the FoundationOne Liquid CDX panel. The Molecular Tumor Board discussed cases, calculating Tumor Fraction (TF) based on aneuploidy, categorizing it as high or low with a 10% cutoff. Results: The analysis encompassed 239 LBs from 214 patients with relapsed or metastatic head and neck cancers. Of these, 59 LBs were from 57 patients showing stability or positive response (SD/R), while 180 were from 167 patients at diagnosis or disease progression (BL/PD). Notably, 156 (73%) were male, with a median age of 61 years. Within the cohort, 65% of LBs were from patients with squamous cell carcinomas (SCC), 15% adenoid cystic carcinomas (ACC), and 20% other histologies mainly adenocarcinomas. The anatomical distribution included 59 LBs from salivary gland (SG) cancers, 49 oropharynx (OP), 48 oral cavity (OC), and others including larynx, hypopharynx, sinus and nasopharynx. Among LBs performed at BL/PD, 72% were informative, while only 36% were so at SD/R. The proportion of informative biopsies varied across anatomical sites. For SCC, TP53 mutations were most prevalent (71%), followed by TERT and PIK3CA variants, and FGF19 and FGF3 amplifications. ACCs showed NOTCH1 mutations (6/19, 32%) as the most common, followed by TP53 and various other variants. In the entire cohort, clonal hematopoiesis-related variants were identified, with 40% showing at least one of DNMT3A, CHEK2, or ASXL1. Patients with low TF at BL/PD exhibited significantly improved overall survival (21.6 vs. 7.6 months, HR 0.35, 95% CI 0.23 - 0.53, p &amp;lt; 0.0001), consistent across subgroups except for OP.Conclusion: This study demonstrates the feasibility of liquid biopsy in HNSCC and rare head and neck tumors, providing valuable therapeutic and prognostic insights. The findings underscore the potential of liquid biopsy as a valuable tool in clinical decision-making for head and neck cancer patients. Citation Format: Filippo Gustavo Dall'Olio, Damien Vasseur, Lea Loriguet, Francois Regis Ferrand, Antoine Moya-Plana, Yungan Tao, Mariana Iacob, Karim Benihoud, Odile CASIRAGHI, Catherine Brenner, Pierre Busson, Philippe Gorphe, Santiago Ponce, Pierre Blanchard, Etienne Rouleau, Yohann Loriot, Ludovic Lacroix, Antoine Italiano, Ingrid Breuskin, Caroline Even. Feasibility and clinical utility of blood based NGS in head and neck carcinomas: A single center experience from precision medicine program [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2414.

Abstract 7382: Artificial intelligence derived features of collagen architecture identify high risk HPV associated oropharyngeal squamous cell carcinoma patients

Abstract Introduction: Human papilloma virus (HPV) induced oropharyngeal squamous cell carcinoma (OPSCC) is a common subtype of head and neck carcinoma. Dysregulation of the extracellular matrix (ECM), an important part of the tumor microenvironment (TME), is shown in HPV related cancers. We studied collagen fibers (CF), the amplest component of the ECM, and evaluated whether their characteristics within the TME can offer a prognostic value in OPSCC. Methods: Whole slide images (WSIs) of OPSCC patients were obtained from Washington University (WU, n=107), Houston Veterans Administration Hospital (HV, n=94), Cleveland Clinic (CC, n=336), John Hopkins University (JH, n=121) and Vanderbilt Medical Centre (VM, n=158). For the identified CF in tumor-stroma regions of WSIs, the extracted CF features included: CF fragmentation measure, CF bundling percentage, CF rigidity measure, CF anisotropy index, and CF density index. For survival analysis using overall survival (OS) and Disease-Free Survival (DFS) as endpoints, the median risk score in the training set (WU) was applied for risk stratification in the validation sets (HV, CC, JH, VM) by means of a Least Absolute Shrinkage and Selection Operator-Cox regression model. Multivariable Cox Proportional Hazards Regression was done for both OS and DFS. Results: The patients defined as “high risk” had worse OS than those identified as “low risk” (HV(p=0.03), CC(p=0.03), JH(p=0.02), VM(p=0.04)). Multivariable analysis showed that CF features were prognostic independent of T/N stages, age, sex, and smoking status with HR=1.99 (95% CI=1.46-2.72, p=0.00001) for OS and HR=1.73 (95% CI=1.21-247, p=0.002) for DFS (Table 1). Table 1: Multivariable Survival Analysis for OS and DFS, HR=Hazard Ratio, CI=Confidence Interval Variable Overall Survival Disease Free Survival HR (95% CI) P value HR (95% CI) P value Age (&amp;lt;65 years vs. &amp;gt;=65 years) 0.99 (0.93-1.06) 0.78444 0.96 (0.82-1.12) 0.62864 Sex (Female vs. Male) 0.56 (0.29-1.10) 0.09042 0.50 (0.22-1.13) 0.09385 Smoking status (Yes vs. No) 1.85 (1.31-2.62) 0.00051 1.03 (0.72-1.47) 0.86871 T-stage (T3/4 vs T1/2) 1.86 (1.38-2.50) 0.00004 1.91 (1.36-2.69) 0.00018 N-stage (N+ vs N0) 1.76 (1.31-2.37) 0.00016 2.04 (1.46-2.86) 0.00003 Collagen fiber features (High risk vs low risk) 1.99 (1.46-2.72) 0.00001 1.73 (1.21-2.47) 0.00286 Conclusion: Artificial intelligence derived features of CF architecture can help identify high vs low risk patients in HPV related OPSCC. These findings deserve further confirmation in larger prospectively collected OPSCC data sets and could impact future treatment paradigms. Citation Format: Reetoja Nag, Haojia Li, Germán Corredor, Pingfu Fu, Nabil F. Saba, Mehmet A. Bilen, Tilak Pathak, Paula Toro, Mojgan Mokhtari, Krunal Pandav, Michael Gilkey, Shlomo Koyfman, Deborah Chute, Wade L. Thorstad, Mitra Mehrad, Patricia D. Castro, Andrew G. Sikora, Rebecca D. Chernock, Jingqin Luo, Mitchell Frederick, Vlad Sandulache, David J. Adelstein, James Lewis Jr., Anant Madabhushi. Artificial intelligence derived features of collagen architecture identify high risk HPV associated oropharyngeal squamous cell carcinoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7382.