Advanced Head And Neck Cancer Research Articles

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.

Phase II Trial of Enfortumab Vedotin in Patients With Previously Treated Advanced Head and Neck Cancer.

Despite advances in immunotherapy, unresectable recurrent/metastatic head and neck cancer (HNC) carries a poor prognosis, and effective treatments are needed. As nectin-4 is widely expressed in HNC, enfortumab vedotin (EV), a nectin-4-directed antibody-drug conjugate, was explored in HNC in EV-202 (ClinicalTrials.gov identifier: NCT04225117). This open-label, multicohort, phase II study evaluated intravenous EV 1.25 mg/kg on days 1, 8, and 15 of each 28-day cycle. In the HNC cohort, eligible patients had recurrent/metastatic HNC and had received platinum-based therapy for locally advanced/metastatic disease and a PD-1/PD-L1 inhibitor. The primary end point was investigator-assessed confirmed objective response rate (ORR) per RECIST version 1.1. Secondary end points were investigator-assessed duration of response (DOR), disease control rate (DCR), and progression-free survival (PFS); overall survival (OS); and safety. The primary analysis included 46 patients; all received EV (median follow-up, 9.3 months). Most patients (52.2%) had ≥3 previous lines of systemic therapy in the metastatic setting. Confirmed ORR was 23.9%, DCR was 56.5%, and median DOR was not reached (median DOR was 9.4 months at a later data cutoff [median follow-up, 11.3 months]). Median PFS and OS were 3.9 and 6.0 months, respectively. Treatment-related adverse events (TRAEs) occurring in >20% of patients were alopecia (28.3%), fatigue (26.1%), and peripheral sensory neuropathy (23.9%). Sixteen patients (34.8%) experienced grade ≥3 TRAEs; anemia and decreased neutrophil count occurred in ≥1 patient (both n = 2; 4.3%). EV demonstrated antitumor activity in heavily pretreated HNC. Safety was consistent with the known safety profile of EV; no new safety signals were identified. These data support further evaluation of EV for advanced HNC not amenable to definitive local therapy.

The association between the mental health disorders, substance abuse, and tobacco use with head & neck cancer stage at diagnosis.

Mental health disorders, substance abuse, and tobacco use are prevalent in the US population. However, the association between these conditions and head and neck cancer (HNC) stage is poorly understood. This research aims to uncover the relationship between pre-existing mental health disorders, substance abuse, and tobacco use and HNC stage at diagnosis in patients receiving care in an integrated, public safety-net healthcare system. This study was a secondary data analysis of linked hospital tumor registries and electronic health record (EHR) data. The study's primary independent variables were the comorbidities of mental health disorders, substance abuse, and tobacco use. The dependent variable was HNC stage at diagnosis, operationalized as early stage (i.e., stages I, II, and III) and advanced stage (stage IV, IVA, IVB, or IVC). The analysis included multivariable logistic regression adjusted for covariates of demographic variables, tumor anato RESULTS: The study population consisted of 357 patients with median age of 59years, and was primarily male (77%), diverse (Black or African American 41%; Hispanic 22%), and from neighborhoods with low income (median average annual household income $39,785). Patients with a history of mental health disorders with or without tobacco use had significantly lower odds of advanced stage HNC at diagnosis (adjusted OR = 0.35, 95% Confidence Interval [CI]: 0.17-0.72.) while patients with a history of substance abuse with or without tobacco use had significantly higher odds of advanced stage HNC at diagnosis (adjusted OR 1.41, 95% CI: 1.01-1.98) than patients with no history of mental health disorders, substance abuse, or tobacco use. The relationship between HNC stage at diagnosis and the comorbidities of mental health disorders, substance abuse, or tobacco differs depending on the type and co-occurrence of these comorbidities. These findings demonstrate the need for innovative care delivery models and education initiatives tailored to meet the needs of patients with mental health disorders, substance abuse, and tobacco use that facilitate early detection of HNC.

Sepsis surveillance in patients with head-and-neck cancer undergoing chemo-radiation.

The infection rate among patients with head-and-neck cancer (HNC) undergoing chemoradiotherapy (CRT) is approximately 19%, with sepsis-related death ranging from 3-9%. A previous study at our institute found a 12%sepsis-related death rate in HNC patients during CRT. The objective of this study is to investigate the utilization of sepsis surveillance and early intervention in reducing the occurrence of sepsis-related deaths in locally advanced HNC patients receiving CRT. This retrospective analysis examined 54 patients with locally advanced HNC undergoing CRT who underwent sepsis surveillance between January 2018 and December 2021. The study recorded the utilization of oral and intravenous antibiotics, G-CSF, early admissions and their reasons, and the incidence of early mortality. Data analysis was conducted using SPSS v.24 software. Twenty-one (38.9%) patients were prescribed oral antibiotics, and 14 (25.9%) received G-CSF on an outpatient basis. Twenty-nine (54%) patients required hospital admission. Among the admitted patients, 28 (96%) received intravenous antibiotics, and G-CSF was administered in 18 (62%) patients. In 8 cases, antibiotic treatment was intensified due to persistent fever and deteriorating neutropenia. The median time for receiving antibiotics and G-CSF after starting CRT was 5th week (range: 3-8weeks). Five patients required readmission. Only one patient succumbed to sepsis. Among the 54 patients, 48 (89%) completed the scheduled RT, while 14 (25.9%) received all 6 cycles of chemotherapy. Sepsis surveillance and the prompt use of antibiotics and G-CSF, along with early hospitalization, when necessary, reduces the occurrence of sepsis-related early deaths in HNC patients undergoing CRT.

Assessing Postoperative Quality of Life and Psychological Impact of Free Flap Reconstruction in Advanced Head and Neck Cancer Patients.

Introduction Head and neck cancer (HNC) significantly affects patients worldwide, often resulting in physical disfigurement, functional impairment, and diminished quality of life (QoL). Advanced HNC may necessitate reconstructive surgeries using free tissue transfer, which, despite improving survival, can exacerbate emotional and social challenges such as anxiety, depression, and social isolation. This study aims to evaluate the well-being of patients undergoing free flap surgery for advanced HNC using validated tools. Methods We conducted a prospective longitudinal study of 30 patients with advanced HNC (≥T3, stage ΙΙΙ-IV) who underwent free flap reconstructive surgery at the General Oncological Anticancer Hospital of Athens 'Agios Savvas' between January 2018 and January 2024. Patient-reported outcomes were assessed using three validated questionnaires in Greek: the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module (EORTC QLQ-H&N35), the Hospital Anxiety and Depression Scale (HADS), and the Brief Pain Inventory (BPI). Statistical analysis was performed using IBM SPSS Statistics for Windows, version 26.0 (IBM Corp., Armonk, NY), with statistical significance set at p < 0.05. Results Among the 30 patients (10 women and 20 men; mean age = 56.6 years), post-surgical assessments indicated significant worsening of symptoms, including increased pain (p < 0.001), swallowing difficulties (p < 0.001), and speech impairments (p < 0.001). Nearly all patients reported increased analgesic use post surgery (p = 0.003), and a significant correlation was found between pain severity and diminished daily functioning, particularly life enjoyment (correlation coefficient = 0.788, p < 0.001). Additionally, 63% of patients (n = 19) were diagnosed with depression and 67% with anxiety (n = 20), with men showing a higher prevalence of depression (p = 0.001). No significant differences in anxiety rates were found between the sexes. Overall, pain severity had a broad impact on both physical and psychological status, contributing to social withdrawal and isolation. Conclusions Patients with HNC who undergo free flap reconstructive surgery face significant challenges in emotional, social, and physical well-being. Depression and anxiety are common but often undetected, especially in men. Pain remains a significant factor affecting QoL and social engagement. Comprehensive care models, including standardized pre- and post-treatment assessments, early mental health screenings, and personalized rehabilitation strategies, are essential to improve outcomes and enhance QoL for HNC patients.

Early circulating tumor DNA changes predict outcomes in head and neck cancer patients under re-radiotherapy.

Local recurrence after radiotherapy is common in locally advanced head and neck cancer (HNC) patients. Re-irradiation can improve local disease control, but disease progression remains frequent. Hence, predictive biomarkers are needed to adapt treatment intensity to the patient's individual risk. We quantified circulating tumor DNA (ctDNA) in sequential plasma samples and correlated ctDNA levels with disease outcome. Ninety four longitudinal plasma samples from 16 locally advanced HNC patients and 57 healthy donors were collected at re-radiotherapy baseline, after 5 and 10 radiation fractions, at irradiation end, and at routine follow-up visits. Plasma DNA was subjected to low coverage whole genome sequencing for copy number variation (CNV) profiling to quantify ctDNA burden. CNV-based ctDNA burden was detected in 8/16 patients and 25/94 plasma samples. Ten additional ctDNA-positive samples were identified by tracking patient-specific CNVs found in earlier sequential plasma samples. ctDNA-positivity after 5 and 10 radiation fractions (both: log-rank, p = .050) as well as at the end of irradiation correlated with short progression-free survival (log-rank, p = .006). Moreover, a pronounced decrease of ctDNA toward re-radiotherapy termination was associated with worse treatment outcome (log-rank, p = .005). Dynamic ctDNA tracking in serial plasma beyond re-radiotherapy reflected treatment response and imminent disease progression. In five patients, molecular progression was detected prior to tumor progression based on clinical imaging. Our findings emphasize that quantifying ctDNA during re-radiotherapy may contribute to disease monitoring and personalization of adjuvant treatment, follow-up intervals, and dose prescription.

Local Control, Survival, and Toxicity Outcomes with High-Dose-Rate Peri-Operative Interventional Radiotherapy (Brachytherapy) in Head and Neck Cancers: A Systematic Review.

Background. Peri-operative interventional radiotherapy (POIRT) entails tumor resection, catheter implantation in the same surgery, and irradiation within the peri-operative period. It allows for maximal tumor burden reduction, better tumor bed identification, more flexible implant geometry, highly conformal irradiation, and treatment delay minimization. We reviewed the published local control, survival, toxicity, and quality of life (QOL) outcomes with POIRT for head and neck cancers (HNCs) in primary and re-irradiation settings. Materials and Methods. A systematic search of PubMed, Scopus, Science Direct, and other databases, supplemented by bibliography scanning and hand-searching, yielded 107 titles. Fifteen unique articles were eligible, five of which were merged with more updated studies. Of the ten remaining studies, four reported on primary POIRT, and seven reported on reirradiation POIRT. Given data heterogeneity, only qualitative synthesis was performed. Results. Primary POIRT in early tongue cancer results in 6-year recurrence-free (RFS) and overall survival (OS) of 92% for both; in advanced HNCs, the 9-year RFS and OS rates are 52% and 55%. Grade 1-2 toxicity is very common; grade 3-4 toxicity is rare, but grade 5 toxicity has been reported. POIRT re-irradiation for recurrent HNCs results in 5y RFS and OS rates of 37-55% and 17-50%; better outcomes are achieved with gross total resection (GTR). QOL data are lacking. Conclusions. Primary POIRT is safe and effective in early tongue cancers; its use in other HNC sites, especially in advanced disease, requires careful consideration. Re-irradiation POIRT is most effective and safe when combined with GTR; toxicity is significant and may be limited by careful case selection, implant planning and execution, use of smaller fraction sizes, and adherence to homogeneity constraints. Study Registration Number. PROSPERO Registry Number CRD42024548294.

Role of Mesenchymal Stem/Stromal Cells in Head and Neck Cancer-Regulatory Mechanisms of Tumorigenic and Immune Activity, Chemotherapy Resistance, and Therapeutic Benefits of Stromal Cell-Based Pharmacological Strategies.

Head and neck cancer (HNC) entails a heterogenous neoplastic disease that arises from the mucosal epithelium of the upper respiratory system and the gastrointestinal tract. It is characterized by high morbidity and mortality, being the eighth most common cancer worldwide. It is believed that the mesenchymal/stem stromal cells (MSCs) present in the tumour milieu play a key role in the modulation of tumour initiation, development and patient outcomes; they also influence the resistance to cisplatin-based chemotherapy, the gold standard for advanced HNC. MSCs are multipotent, heterogeneous and mobile cells. Although no MSC-specific markers exist, they can be recognized based on several others, such as CD73, CD90 and CD105, while lacking the presence of CD45, CD34, CD14 or CD11b, CD79α, or CD19 and HLA-DR antigens; they share phenotypic similarity with stromal cells and their capacity to differentiate into other cell types. In the tumour niche, MSC populations are characterized by cell quiescence, self-renewal capacity, low reactive oxygen species production and the acquisition of epithelial-to-mesenchymal transition properties. They may play a key role in the process of acquiring drug resistance and thus in treatment failure. The present narrative review examines the links between MSCs and HNC, as well as the different mechanisms involved in the development of resistance to current chemo-radiotherapies in HNC. It also examines the possibilities of pharmacological targeting of stemness-related chemoresistance in HNSCC. It describes promising new strategies to optimize chemoradiotherapy, with the potential to personalize patient treatment approaches, and highlights future therapeutic perspectives in HNC.

Real world effectiveness and safety of low dose nivolumab with metronomic chemotherapy in patients with advanced platinum-resistant head and neck cancer: An Indian institutional experience.

6050 Background: Triple Metronomic chemotherapy (TMC) regimen of low-dose methotrexate, erlotinib, and celecoxib has been proven to improve overall survival (OS) of advanced platinum-resistant head and neck cancer (HNC) patients. The addition of low-dose nivolumab to metronomic chemotherapy is an alternative standard of care for those patients, who cannot access full-dose checkpoint inhibitors. In the present study, we aimed to assess the real world effectiveness and safety of low-dose nivolumab along with TMC. Methods: We performed a prospective analysis of advanced platinum-resistant HNC patients treated at our institute from June 2021 to June 2023 with TMC and low-dose immunotherapy consisting of capsule celecoxib (200 mg twice daily), tablet methotrexate (9 mg/m2/week), and erlotinib (150 mg once daily), along with intravenous nivolumab 20 mg (once every 2 weeks). Data was analysed descriptively and the Kaplan-Meier method was used to estimate OS, progression-free survival (PFS), and duration of response (DOR). Results: Overall, 85 patients of advanced platinum-resistant HNC were enrolled in this study. The median age of the patients was 54 years with male predominance. The most common primary sites were buccal mucosa (54%) and tongue (32%). The median follow-up was 6.5 months with 5 months of DOR to therapy. Median number of nivolumab doses received were 8 (IQR 2–48). The termination of therapy in the majority of patients was due to disease progression (55%). Most common adverse events reported were acneiform rash (62%), mucositis (52%), and fatigue (34%). Dose reduction for triple metronomic chemotherapy was required in 42% of patients for grade 3 and above adverse events. No grade 3/4 immune-related adverse events were reported throughout the study period. The median PFS and OS of the study population were observed to be 4.3 months and 8.8 months, respectively. Overall, 8 of 85 patients survived for ≥30 months and 20 (24%) patients were on treatment at the time of data analysis. Conclusions: Low-dose immunotherapy along with triple metronomic chemotherapy is a safe treatment option in real world advanced platinum-resistant HNC patients with acceptable outcomes.

Genetic Risk For Depression and Quality of Life in Patients With Head and Neck Cancer

Although patients with head and neck cancer (HNC) have been shown to experience high distress, few longitudinal studies include a comprehensive evaluation of biopsychosocial factors affecting quality of life (QoL), including genetic risk for depression. To identify factors at the time of cancer diagnosis associated with QoL scores at 3 months after treatment in patients newly diagnosed with a first occurrence of HNC. This prospective longitudinal study of 1464 participants with a 3-month follow-up, including structured clinical interviews and self-administered measures was carried out at the Department of Otolaryngology Head and Neck Surgery at 2 tertiary care McGill University Affiliated Hospitals, McGill University Health Centre, and Jewish General Hospital. Eligible patients were adults newly diagnosed within 2 weeks with a primary first occurrence of HNC, had a Karnofsky Performance Scale score higher than 60, and an expected survival of more than 6 months. Two hundred and twenty-three patients (72%) consented to participate and completed the baseline questionnaire, and 71% completed the 3-month follow-up measures. An a priori conceptual model including sociodemographics, medical variables, psychosocial risk factors, and a polygenic risk score for depression (PRS-D) was tested. The Functional Assessment of Cancer Therapy-Head and Neck measured QoL at baseline and at 3 months. Participants were mostly men (68.7%), with a mean (range) age of 62.9 (31-92) years, 36.6% having a university degree, 35.6% living alone, and 71.4% diagnosed with advanced HNC with mostly cancers being of the oropharynx (42.2%), oral cavity (17%), and larynx (16.3%). QoL at 3 months after HNC diagnosis was associated with higher PRS-D (B = -4.71; 95% CI, -9.18 to -0.23), and a diagnosis of major depressive disorder within 2 weeks of an HNC diagnosis (B = -32.24; 95% CI, -51.47 to 13.02), lifetime suicidal ideation (B = -22.39; 95% CI, -36.14 to -8.65), living with someone (B = 12.48; 95% CI, 3.43-21.52), having smoked cigarettes in the past 30 days pre-HNC diagnosis (B = -15.50; 95% CI, -26.07 to -4.93), chemotherapy type (B = -11.13; 95% CI, -21.23 to -1.02), and total radiotherapy dose (Gy) (B = -0.008; 95% CI, -0.01 to -0.002). This study identified the predictive value of a genetic predisposition to depression on QoL and function immediately after oncologic treatments. These findings highlight the potential importance of genetic profiling pretreatment to identify those most susceptible to experience QoL and functional compromise. Depression is a clear area of public health concern and should be a central focus in the treatment of patients with HNC.

Abstract 2408: Comprehensive genomic profiling of ctDNA reveals distinct genomic signatures and therapeutic implications for immunotherapy response in advanced head and neck cancer

Abstract Background: Head and Neck Cancer (HNC) is highly prevalent malignancy in Southeast Asia. We investigated comprehensive genomic profiling (CGP) of ctDNA, aimed to compare genomic landscapes between responders (R) and non-responders (NR) to immunotherapy among advanced HNC patients. Methods: An observational study, ctDNA was evaluated in 69 advanced HNC patients both at the baseline (BL) and during follow up (FL). OncoIndx® CGP was used to identify patient-specific genomic alterations in the ctDNA cohort. Raw sequence alignment and variant calling were performed using iCare® software. Progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier statistics. Results: Total 250 mutations, encompassing pathogenic (P), likely pathogenic (LP), and variants of unknown significance (VUS), were identified at BL. In FL samples a slight decrease in the overall number of mutations was observed. Loss-of-function (LOF) KMT2C, MSH6 mutations, and activating HNF1α mutations were consistently present at comparable frequencies in BL and FL samples, exhibiting ubiquity across immunotherapy R and NR populations (F test, P 0.00063, OR 13). The variants did not demonstrate statistically significant association with PFS and OS. Most prevalent variants at follow-up emerged from tumor suppressor genes TP53, BRIP1, STAT5B, NF1, suggesting their potential role as therapy-resistant variants. PFS and OS were notably lower for patients with TP53 + BRCA pathway variants compared to their wild-type counterparts (median PFS TP53 + BRCA pathway mutated 2.7 months vs wt 9.1 months, HR = 4.1; median OS TP53 + BRCA pathway mutated 4.7 months vs 12.8 months for wt, HR 7.7). Similarly STAT5B carriers compared to the wild-type STAT5B-bearing population. Multivariate analysis further confirmed the independent role of TP53 + BRCA pathway and STAT5B variants as determinants for worst outcome (P 0.006, HR2.5). Population with prevalent TP53 and STAT5B LOF variants exhibited a strong negative correlation with the PD-L1 score compared to the population with their wild-type counterparts (P 0.03). Average scores for genome-wide homologous recombination deficiency (HRD), bTMB, and loss of LOH were low at BL and FL and did not correlate with the PD-L1 score. Interestingly, bTMB was low for the cohort, Tumor fraction (TF) emerged as an independent prognosticator for OS and PFS. Conclusions: ctDNA revealed distinct genomic signatures in R and NR populations at BL and FL. Significant prevalence of TP53, BRIP1, STAT5B, and NF1 in the NR population suggest a potential role in conferring immunotherapy resistance. Genomic signatures, TMB and TF impacted survival of immunotherapy responders. Integrating CGP into SOC protocol may help in identifying therapy resistance in advanced HNC patients who did not respond to initial treatment. Citation Format: Atul Bharde, Vanita Noronha, Mrunal Ratnaparkhi, Vijay Patil, Bhagwat Jadhav, Sangeeta Prajapati, Anuradha Choughule, Pratik Chandrani, Sumit Haldar, Fauzul Moubeen, Nandini Menon, Kanchan Hariramani, Madhura Basavalingegowda, Aarthi Ramesh, Jayant Khandare, Pankaj Chaturvedi, Gowhar Shafi, Kumar Prabhash. Comprehensive genomic profiling of ctDNA reveals distinct genomic signatures and therapeutic implications for immunotherapy response in advanced head and neck cancer [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 2408.

Prevalence of obstructive sleep apnea after treatment for advanced T-stage head and neck cancer

PurposeTreatment of head and neck cancer (HNC) may lead to obstructive sleep apnea (OSA), but conclusive results on the prevalence of OSA are lacking. The objective of this study is to investigate the prevalence of OSA in a cohort of patients treated for advanced T-stage HNC.MethodsA cross-sectional study was conducted in two tertiary cancer care centers including patients at least 1 year after treatment with curative intent with surgery and/or (chemo)radiotherapy ((C)RT) for advanced T-staged (T3-4) cancer of the oral cavity, oropharynx, hypopharynx, or larynx. A polysomnography (PSG) was performed in all participants. OSA was defined as an apnea–hypopnea index (AHI) of 15 events/h or higher or an AHI of 5 events/h and higher with OSA related symptoms, such as sleeping problems, daytime dysfunction and/or cardiac/metabolic comorbidities collected through file review and questionnaires.ResultsOf the 67 participants, 48 (72%, 95% CI 59–82%) were diagnosed with OSA. Possible risk factors are male gender, higher BMI, greater neck circumference, more nicotine pack years, cardiometabolic comorbidities, use of medication with sleepiness as side effect, present tonsils, lower T-stage (T3 vs. T4 stage), higher AJCC stage and a HPV-negative tumor.ConclusionIn this population of advanced T-stage HNC patients, the prevalence of OSA was 72%, which is considerably higher than in the general population (2–50%). Given the high prevalence, screening of this entire subgroup for OSA may be indicated. Future studies to identify high risk factors and develop an OSA screening protocol are needed.

Outcome of Hypofractionated Palliative Radiotherapy Regimens for Patients With Advanced Head and Neck Cancer in Tikur Anbessa Hospital, Ethiopia: A Prospective Cohort Study.

Head and neck cancers (HNCs) are the third most commonly treated cancer with radiation in Ethiopia. Most patients present with advanced stage and are not candidates for curative treatment. The objective of our study is to assess the outcome of hypofractionated palliative radiotherapy (RT) for advanced HNCs in a resource-limited setting. Patients with histology-proven advanced HNC candidates for hypofractionated palliative RT were enrolled. Three regimens were allowed: 44.4 Gy in 12 fractions, 30 Gy in 10 fractions, and 20 Gy in five fractions. Response to treatment was assessed at baseline and at 4 weeks after treatment completion. The Kaplan-Meier curve was used to measure the survival. Between January 2022 and January 2023, 52 patients were enrolled and 25 patients were eligible for outcome assessment. Index symptoms include pain, bleeding, dysphagia, respiratory distress, and others in 25, 13, 10, 6, and 17 patients, respectively. Complete relief of the top three symptoms include pain in 52% of patients, hemostasis in 84% of patients, and dysphagia in 30% of patients. Objectively, 64% of patients attained partial response. For 48% of patients, their quality of life (QoL) improved in one parameter of the physical scores. Moreover, 64% of patients showed improvement in three parameters. The global functional score improved in 80% of patients. One patient had grade 3 xerostomia. At the end of the study period, 44% of patients died. The median survival after radiation was 9 months (95% CI, 7.2 to 10.8). All palliative hypofractionated regimens used were effective in terms of symptom control, tumor response rate, and QoL, and were well tolerated. This makes it appropriate for our setup because the majority of patients require palliation.

Frailty is an independent factor for health-related quality of life in patients with head and neck cancer receiving definitive concurrent chemoradiotherapy.

Health-related quality of life (HRQoL) is associated with treatment-related complications and poor survival in patients with head and neck cancer (HNC). We investigated the effects of frailty on HRQoL in patients with HNC receiving definitive concurrent chemoradiotherapy (CCRT). A total of 461 consecutive patients with locally advanced HNC who received CCRT between 2017 and 2018 at three medical centers in Taiwan were included. Frailty and HRQoL were assessed using the Comprehensive Geriatric Assessment and QLQ-H&N35 before CCRT. The sum score was calculated based on the first 30 questions of QLQ-H&N35. Multivariate analysis was performed to evaluate the impact of frailty on HRQoL. The overall sum score was 39 (34-49). The sum scores of patients with impairments in 0, 1, 2, 3, and ≥ 4 frailty domains were 34 (32-38), 40 (34-47), 46 (36-55), 48 (41-64), and 56 (50-60), respectively. Patients with impairments in more frailty domains had a higher symptom burden (p for trend < 0.001). Frail patients tended to experience symptoms across all QLQ-H&N35 subscales. Sex, body mass index, tumor type, tumor stage, Eastern Cooperative Oncology Group performance status, and frailty were determinants of HRQoL in the univariate analysis. Frailty was an independent determinant of HRQoL in the multivariate analysis. Routine frailty assessment may serve as a surrogate for the selection of patients with HNC with poor HRQoL before CCRT. Further studies are needed to determine whether appropriate interventions in frail patients would improve their HRQoL during CCRT.

Head and Neck Cancer Incidence in the United States Before and During the COVID-19 Pandemic

Research about population-level changes in the incidence and stage of head and neck cancer (HNC) associated with the COVID-19 pandemic is sparse. To examine the change in localized vs advanced HNC incidence rates before and during the first year of the pandemic. In this cross-sectional study of patients in the US diagnosed with HNC from 2017 to 2020, the estimated number with cancer of the oral cavity and pharynx (floor of mouth; gum and other mouth; lip; oropharynx and tonsil; and tongue) and larynx were identified from the SEER cancer registry. Subgroup analyses were stratified by race and ethnicity, age, and sex. Data were analyzed after the latest update in April 2023. The COVID-19 pandemic in 2020. The primary outcomes were the annual incidence rates per 100 000 people for localized HNC (includes both localized and regional stages) and advanced HNC (distant stage) and weighted average annual percentage change from 2019 to 2020. Secondary outcomes included annual percentage change for 2017 to 2018 and 2018 to 2019, which provided context for comparison. An estimated 21 664 patients (15 341 [71%] male; 10 726 [50%] ≥65 years) were diagnosed with oral cavity and pharynx cancer in 2019 in the US, compared with 20 390 (4355 [70%] male; 10 393 [51%] ≥65 years) in 2020. Overall, the HNC incidence rate per 100 000 people declined from 11.6 cases in 2019 to 10.8 in 2020. The incidence rate of localized cancer declined to 8.8 cases (-7.9% [95% CI, -7.5 to -8.2]) from 2019 to 2020. The localized cancer incidence during the first year of the pandemic decreased the most among male patients (-9.3% [95% CI, -9.2 to -9.5]), Hispanic patients (-12.9% [95% CI, -12.9 to -13.0]), and individuals with larynx cancer (-14.3% [95% CI, -13.6 to -15.0]). No change in the overall incidence rate was found for advanced HNC. In this cross-sectional study, the incidence of localized HNC declined during the first year of the pandemic. A subsequent increase in advanced-stage diagnoses may be observed in later years.

The impact of COVID-19 pandemic on head and neck cancer diagnosis and treatment

Background/purposeFollowing the COVID-19 pandemic, there were reports of diagnostic delays and a surge in the prevalence of advanced head and neck cancer (HNC). We conducted a retrospective study on the impact of COVID-19 on the number of newly diagnosed HNC among patients who underwent screening at our center to understand the temporal changes. Materials and methodsWe investigated the Union for International Cancer Control guidelines-TNM classification, presence of subjective symptoms at the time of consultation, and initial treatment from the medical records of first-time patients with HNC who visited our head and neck surgery department during 2019–2021 and compared them with those before (2019) and after (2020–2021) the pandemic. ResultsA total of 1245 patients were included in the study. The number of patients were 437, 417, and 391 in 2019, 2020, and 2021, respectively, indicating a downward trend following the pandemic. When the incidence of early (stage 0–II) and advanced (stage III–IV) HNC cancers was compared, the proportion of patients with early-stage cancer declined. Among them, significant primary tumor progression was observed in T classification. The number of patients with no subjective symptoms at initial diagnosis was decreasing significantly. ConclusionA decrease in the proportion of HNC patients with early-stage cancer and primary tumor progression was observed after the pandemic in 2020 and 2021. The number of early-stage malignancies may have dropped due to patients’ unwillingness to visit a doctor.

CTLA-4 Blockade Results in the Enrichment of Proliferative CD56 dimCD16 + NK Cells Following Infusion of Haploidentical Donor Memory-like Natural Killer Cells Plus IL-15 Superagonist in a Phase 1 Trial

Introduction Regulatory T cells (Tregs) blunt anti-tumor responses of major immune effector cells including CD8 T cells and natural killer (NK) cells. Tregs constitutively express CTLA-4 and thus the use of ipilimumab, a CTLA-4 blocker can potentially overcome the Treg-mediated immune suppression. We (and others) have shown that a brief activation of conventional NK cells with the cytokine combination IL-12, IL-15, and IL-18 generates cytokine-induced memory-like (CIML) NK cells which exhibit enhanced anti-tumor responses, have a longer half-life (up to 90 vs ~12 days of conventional NK cells), and show promising activity in several early phase clinical trials. N-803 is an IL-15 super-agonist with a long half-life that preferentially activates and expands NK and CD8+ T cells without affecting Tregs, making it an ideal cytokine for combining with adoptive immunotherapy. In the current study, we hypothesized the use of ipilimumab (IPI) will abrogate Treg-mediated inhibition and thus allow enhanced proliferation, activation, and anti-tumor responses of the adoptively transferred CIML NK cells.To address this, we conducted a phase 1 trial of HLA-haploidentical CIML NK cells in combination with IPI and N-803 in patients with advanced head and neck cancer (HNC). Using flow cytometry and CITE-Seq on the banked peripheral blood samples, we performed an in-depth characterization of NK cells expanded following IPI pre-exposure and compared it to those who did not receive IPI. Methods We enrolled 10 patients with refractory HNC regardless of human papillomavirus (HPV) status who had prior platinum and immunotherapy (NCT04290546). All patients received lymphodepletion with fludarabine (25 mg/m 2 x 5 days) and cyclophosphamide (60 mg/kg x 2 days) during days -6 to -2 prior to haploidentical CIML NK cell infusion on day 0 (5-10 x 10 6 cells/kg=dose level 0) followed by N-803 (15 mcg/kg subcutaneously) starting on day +1 every 21-days for 4-doses. In cohort 2, patients received IPI (3 mg/kg) on day -7, no ipilimumab was given to the first 6 patients treated on the lead-in safety cohort 1. Flow cytometry using a custom NK cell panel was performed on samples collected on days +7, +14, +21, +28, +42, and +60 after CIML NK cell infusion. FlowSOM clustering was performed on NK cell markers. UMAP clustering was applied to CITE sequencing data acquired from samples collected on day +7 and day +28, and well-defined markers genes for each cluster were used to identify cell populations. NK cell function (cytotoxicity, IFNg, and CD107a) was assessed using flow-cytometry based assays. Results The median age of the patients was 58, 90% were men and 80% had oropharyngeal primaries. Mild CRS (grade 2 or lower) was observed in 60% of patients. No neurotoxicity or graft-versus-host disease was observed. Maximal expansion of NK cells occurred on day +7 following CIML NK cell infusion in 9/10 of patients. The single patient without NK cell expansion was found to have a donor-specific anti-HLA antibody. Day +7 NK cells exhibited upregulation of IFNg expression following cytokine restimulation as compared to resting NK cells. Tumor regression was observed in 50% of treated patients at day +30 based on RECIST v1.1 criteria. Patients who had tumor regression had an expansion of CD56 dimCD16 + NK cell clusters by day +14. IPI treated patients were noted to have a relative enrichment of CD16 + NK cell metaclusters at day +14 compared to no IPI patients (Figure 1A). At the time of maximal NK cell expansion, CITEseq defined NK cell clusters were dominant in both IPI and no IPI patients, but the proliferative gene sets were enriched in the IPI treated patient (Figure 1B). IPI exposure had no effect on the distribution of regulatory T cells or CD8 + T cell populations at day +28 compared to the no IPI patients. Conclusions The use of donor-derived CIML NK cells is safe and associated with tumor regression in patients with advanced HNC. The use of IPI was associated with the preferential expansion of CD16 + NK cell clusters that had enrichment of proliferative gene sets. Tumor regression was associated with CD56 dimCD16 + NK cell expansion. Further work is required to elucidate the mechanism by which IPI exposure is associated with the expansion of specific subsets of CIML NK cells.

Palliative care interventions for patients with head and neck cancer: protocol for a scoping review

IntroductionA head and neck cancer (HNC) diagnosis significantly impacts a patient’s quality of life (QOL). Palliative care potentially improves their QOL. We will conduct a scoping review to identify existing...

Assessment of Neutrophil-to-Lymphocyte Ratio as A Prognostic Marker in Locally Advanced Head and Neck Cancer Treated with Concomitant Chemoradiation

Abstract Background Various experimental and epidemiological studies have been conducted to find the relationship between hematologic parameters like neutrophil-to-lymphocyte ratio (NLR) and prognosis in numerous solid malignancies. We conducted a similar study to assess the role of NLR as a prognostic marker in locally advanced head and neck cancer (HNC) treated with chemoradiation. Patients and methods A total of 60 patients of histopathologically proven, previously untreated, locally advanced HNC were included in this randomized, prospective study. They were stratified into five groups according to their NLR values (&lt;2, 2–3, 3–4, 4–5, and &gt;5). All 60 patients received the same concurrent chemoradiation with a radiation dose of 66 Gy in 33 fractions over 6.5 weeks with injection cisplatin 40 mg/m2 weekly. Treatment-related toxicities were assessed weekly. Association of NLR was assessed with the outcomes as per the World Health Organization (WHO) response criteria. Informed consent was taken from all patients, and approval of institutional ethical committee was obtained. Results Complete response was observed to be maximum in patients with low NLR value of &lt;2 (73% of patients). Higher percentage of treatment-related toxicities was also observed in groups with higher NLR values, that is, NLR 4–5 and &gt;5. The association of NLR with treatment response was statistically significant on Pearson's chi-square test (P = 0.019). Conclusion Our study was able to establish the relationship between NLR and treatment outcome in HNC patients treated by concurrent chemoradiation. Higher pretreatment NLR values were associated with poorer survival outcomes and increased treatment-induced toxicities.

Initial Clinical Experience Using Daily Artificial Intelligence-Assisted Adaptive Radiotherapy on Cone-Beam CT for Cancer of the Head and Neck

Adaptive radiation therapy (ART) has emerged as a promising method to modify treatment plans in response to structural and spatial changes that occur during a treatment course. In particular, patients with locally advanced Head and Neck (HN) Cancers often experience changes in target volumes and organs-at risk requiring replanning throughout treatment. The implementation of daily ART using daily cone-beam Cone-Beam CT (CBCT) imaging is a solution that may improve the therapeutic ratio by accounting for intra-fractional changes throughout the patient's treatment course. We evaluated the initial clinical experience of daily ART for patients with locally advanced HN cancer using a commercially available, online adaptive platform with AI-assisted workflows on daily CBCT. For treatment, AI-based auto-contour and structure deformation of OARs and Targets were reviewed and edited by the treating physician. Two plans were generated including, a CT sim-based plan with deformed structures (scheduled) and a re-optimized plan (adaptive) of which both plans evaluated and the best one approved and delivered. Clinical outcomes and dosimetric parameters were reviewed. A total of 23 patients with locally advanced HN cancers (7 Nasopharynx, 6 Oropharynx, 2 oral cavity, 8 larynx) were treated with daily ART from December 2020 until November 2022. 655 adaptive and scheduled radiotherapy plans were generated of which 95.7% of the adaptive plans were chosen. Adaptive plans demonstrated superior V95 PTV70, PTV60, PTV56 mean coverage by 1.02%, 8.14%, and 7.2%, respectively. At a median follow up of 10.1 months, the local control was 91.3%. The 1-year actuarial PFS was 86.9% and 1 year actuarial OS was 82.6%. Two patients required prophylactic g-tube. 30% and 21% of patients had acute grade 3 dysphagia and odynophagia, respectively; 13% with chronic grade 2 xerostomia. There were no grade 4 or grade 5 toxicities. These findings provide evidence for the feasibility and potential clinical benefit of incorporating daily adaptive AI radiotherapy on CBCT in the treatment of locally advanced HN cancer. Further prospective studies are needed to confirm these findings and determine the optimal clinical applications of this approach.