Comprehensive investigation into the influence of glycosylation on head and neck squamous cell carcinoma and development of a prognostic model for risk assessment and anticipating immunotherapy.

Background: It has been well established that glycosylation plays a pivotal role in initiation, progression, and therapy resistance of several cancers. However, the correlations between glycosylation and head and neck squamous cell carcinoma (HNSCC) have not been elucidated in detail. Methods: The paramount genes governing glycosylation were discerned via the utilization of the Protein-Protein Interaction (PPI) network and correlation analysis, coupled with single-cell RNA sequencing (scRNA-seq) analysis. To construct risk models exhibiting heightened predictive efficacy, cox- and lasso-regression methodologies were employed, and the veracity of these models was substantiated across both internal and external datasets. Subsequently, an exploration into the distinctions within the tumor microenvironment (TME), immunotherapy responses, and enriched pathways among disparate risk cohorts ensued. Ultimately, cell experiments were conducted to validate the consequential impact of SMS in Head and Neck Squamous Cell Carcinoma (HNSCC). Results: A total of 184 genes orchestrating glycosylation were delineated for subsequent scrutiny. Employing cox- and lasso-regression methodologies, we fashioned a 3-gene signature, proficient in prognosticating the outcomes for patients afflicted with HNSCC. Noteworthy observations encompassed distinctions in the Tumor Microenvironment (TME), levels of immune cell infiltration, and the presence of immune checkpoint markers among divergent risk cohorts, holding potentially consequential implications for the clinical management of HNSCC patients. Conclusion: The prognosis of HNSCC can be proficiently anticipated through risk signatures based on Glycosylation-related genes (GRGs). A thorough delineation of the GRGs signature in HNSCC holds the potential to facilitate the interpretation of HNSCC's responsiveness to immunotherapy and provide innovative strategies for cancer treatment.

Insurance Status is Associated With Recurrence in Cutaneous Head and Neck Squamous Cell Carcinoma.

OBJECTIVE: To identify socioeconomic factors influencing the presentation and outcomes of cutaneous head and neck squamous cell carcinoma (cHNSCC). STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary academic medical center with comprehensive cancer center. METHODS: Patients treated for cHNSCC at a single institution between 2008 and 2022 were included. Demographic, socioeconomic data and disease characteristics were obtained from medical record abstraction. Outcome measures included tumor stage, number of distinct primaries, recurrence, and disease-related death. χ2 and Mann-Whitney tests were implemented to evaluate clinicopathologic distributions across disease stages. Survival analyses were performed using Cox regression and Kaplan-Meier analysis. RESULTS: A total of 346 patients met the inclusion criteria. The median age at presentation and length of follow-up was 70.8 and 3.1 years, respectively. The majority of the cohort was white, male, and English-speaking. 13.3% of patients were underinsured and 27.5% were immunosuppressed. Patients who presented with advanced disease were more likely to be underinsured (21.7% vs 9.6%, P = .006) and have a history of homelessness (8.5% vs 2.1%, P = .014). Immunosuppressed patients were more likely to be underinsured (P = .009). Insurance status (1.97 [1.06-3.66], P = .032) and immune status (2.35 [1.30-4.26], P = .005) were independently associated with worse recurrence-free survival. CONCLUSION: Socioeconomic factors that influence access to care, such as insurance status, are associated with cHNSCC disease stage and disease recurrence. These factors may impose barriers that delay diagnosis and treatment. This may result in worse disease-related outcomes and greater treatment-associated morbidity for certain patients.

Costs of oropharyngeal squamous cell cancer treatment in Finland.

BACKGROUND: Oropharyngeal squamous cell carcinoma (OPSCC) can be treated with definitive (chemo)radiotherapy ((C)RT) or primary surgical treatment (PST) with or without postoperative oncologic treatment. The prognosis of OPSCC does not essentially depend on the treatment modality, which allows to consider secondary decision-making aspects such as treatment costs when recommending an individual treatment modality. We attempted to analyze the costs associated with definitive (C)RT and PST in the treatment of OPSCC in Finland. MATERIALS AND METHODS: We included 73 patients diagnosed with OPSCC at the Helsinki University Hospital (HUS) (Helsinki, Finland) in 2019 and 2020. Treatment costs were defined as the costs incurred in the specialized medical care during the first 12 months after the diagnosis was established. RESULTS: Definitive RT and definitive CRT were on a 1-year horizon associated with median costs of approximately 10 700€ and 13 300€, respectively; while, the median costs of PST equaled about 40 600€. The costs of definitive (C)RT mostly consisted of the costs of (chemo)radiotherapy sessions; while, the operating room costs and the costs of intensive care and stay on a ward drove the costs of PST. CONCLUSIONS: PST is associated with 2-3 times higher median costs than definitive (C)RT in Finland. The finding differs from the results previously reported in North America, which is related, e.g., to differences in the treatment practices as well as in the regulation of the health care systems.

Treatment of supraglottic squamous cell carcinoma with advanced technologies: observational prospective evaluation of oncological outcomes, functional outcomes, quality of life and cost-effectiveness (SUPRA-QoL).

BACKGROUND: Over the past decade, therapeutic options in head and neck supraglottic squamous cell carcinoma have constantly evolved. The classical total laryngectomy has been partially replaced by alternative organ- and function-sparing techniques with the same prognosis but less morbidity, such as Radiotherapy, Transoral Laser Microsurgery (TLM) and Trans-Oral Robotic Surgery (TORS). Up to now, a prospective comparison of these innovant techniques has not been conducted. METHODS/DESIGN: We will conduct an original international multicentric prospective nonrandomized clinical trial to compare the efficacy between these treatments (Arm 1: Radiotherapy ± chemotherapy; Arm 2: TLM and Arm 3: TORS) with 4 classes of outcomes: quality of life (QoL), oncological outcomes, functional outcomes and economic resources. The population will include cT1-T2 /cN0-N1/M0 supraglottic squamous cell carcinoma. The primary outcome is a Clinical Dysphagia QoL evaluation assessed by the MD Anderson Dysphagia questionnaire. Secondary outcomes include others QoL evaluation, oncological and functional measures and cost parameters. The sample size needs to reach 36 patients per arm (total 108). DISCUSSION: In the current literature, no prospective head-to-head trials are available to compare objectively these different treatments. With the increase of highly efficient treatments and the increase of oncological survival, it is imperative also to develop management strategies that optimize QoL and functional results. We will conduct this innovate prospective trial in order to obtain objective data in these two main issues. TRIAL REGISTRATION: NCT05611515 posted on 10/11/2022 (clinicaltrial.fgov).

Diagnostic Performance of Response Assessment FDG-PET/CECT in HNSCC Treated With Definitive Radio(chemo)therapy Using NI-RADS.

OBJECTIVE: To assess the diagnostic performance of response assessment 18F-fluorodeoxyglucose positron emission tomography/contrast-enhanced computed tomography (FDG-PET/CECT) following definitive radio(chemo)therapy in head and neck squamous cell carcinoma (HNSCC) using Neck Imaging Reporting and Data System (NI-RADS). STUDY DESIGN: A retrospective analysis from a prospectively maintained dataset. SETTING: Tertiary-care comprehensive cancer center in a low-middle-income country. METHODS: Adults with newly diagnosed, biopsy-proven, nonmetastatic HNSCC treated with definitive radio(chemo)therapy were included. Posttreatment response assessment FDG-PET/CECT scans were retrospectively assigned NI-RADS categories (1-3) for the primary site, neck, and both sites combined. Locoregional recurrence occurring within 2-years was defined as the event of interest. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy were calculated. Locoregional control stratified by NI-RADS categories was computed with the Kaplan-Meier method and compared using the log-rank test. RESULTS: Posttreatment FDG-PET/CECT scans were available in 190 patients constituting the present study cohort. Sensitivity, specificity, PPV, NPV, and overall accuracy of the NI-RADS template for the primary site was 73.5%, 81.4%, 46.3%, 93.4%, and 80.0%, respectively. Similar metrics for the neck were 72.7%, 87.5%, 43.2%, 96.1%, and 85.8%, respectively. Combining primary site and neck, the corresponding metrics of diagnostic accuracy were 84.4%, 69.7%, 46.3%, 93.5%, and 73.2%, respectively. At a median follow-up of 40 months, Kaplan-Meier estimates of 2-year locoregional control were significantly higher for NI-RADS category 1 (94.2%) compared to NI-RADS category 2 (69.4%) and category 3 (20.4%), respectively (stratified log-rank p < .0001). CONCLUSION: FDG-PET/CECT using the NI-RADS template is associated with good diagnostic performance and prognostic utility in HNSCC treated with definitive radio(chemo)therapy.

An ion-channel-gene-based prediction model for head and neck squamous cell carcinoma: Prognostic assessment and treatment guidance.

Purpose: Head and neck squamous cell carcinoma (HNSCC) is a very diverse malignancy with a poor prognosis. The purpose of this study was to develop a new signature based on 12 ion channel genes to predict the outcome and immune status of HNSCC patients. Methods: Clinicopathological information and gene sequencing data of HNSCC patients were generated from the Cancer Genome Atlas and Gene Expression Omnibus databases. A set of 323 ion channel genes was obtained from the HUGO Gene Nomenclature Committee database and literature review. Using univariate Cox regression analysis, the ion channel genes related to HNSCC prognosis were identified. A prognostic signature and nomogram were then created using machine learning methods. Kaplan-Meier analysis was used to explore the relevance of the risk scores and overall survival (OS). We also investigated the association between risk scores, tumor immune infiltration, and gene mutational status. Finally, we detected the expression levels of the signature genes by quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry. Results: We separated the patients into high- and low-risk groups according to the risk scores computed based on these 12 ion channel genes, and the OS of the low-risk group was significantly longer (p<0.001). The area under the curve for predicting 3-year survival was 0.729. Univariate and multivariate analyses showed that the 12-ion-channel-gene risk model was an independent prognostic factor. We also developed a nomogram model based on risk scores and clinicopathological variables to forecast outcomes. Furthermore, immune cell infiltration, gene mutation status, immunotherapy response, and chemotherapeutic treatment sensitivity were all linked to risk scores. Moreover, high expression levels of ANO1, AQP9, and BEST2 were detected in HNSCC tissues, whereas AQP5, SCNN1G, and SCN4A expression was low in HNSCC tissues, as determined by experiments. Conclusion: The 12-ion-channel-gene prognostic signatures have been demonstrated to be highly efficient in predicting the prognosis, immune microenvironment, gene mutation status, immunotherapy response, and chemotherapeutic sensitivity of HNSCC patients.

The Impact of the Affordable Care Act on Insurance Coverage and Stage Among Head and Neck Squamous Cell Carcinoma Patients.

The purpose was to examine the change in percent uninsured and if there is change in T-stage, N-stage and overall-stage among nonelderly patients with newly diagnosed head and neck squamous cell carcinoma after the Affordable Care Act (ACA). The National Cancer Database was used for this study. Patients were divided between pre-ACA and post-ACA implementation with stratification between areas of ACA expansion versus non-expansion. A quasi-experimental difference-in-difference study design was undertaken. A total of 15,037 patients met the inclusion criteria. Between the pre-ACA and post-ACA periods, there was increase in proportion of percent insured with Medicaid coverage in patients residing in expansion region. There was a decrease in the proportion of patients who had advanced Tumor stage and Nodal stage decreased after implementation of ACA. With the implementation of ACA expansion, there is increased Medicaid coverage, corresponding to a decreased proportion of patients presenting with advanced T-stage and N-stage.

Assessment of gene expressions from squamous cell carcinoma of the head and neck to predict radiochemotherapy-related xerostomia and dysphagia.

PURPOSE: We tested the hypothesis that gene expressions from biopsies of locally advanced head and neck squamous cell carcinoma (HNSCC) patients can supplement dose-volume parameters to predict dysphagia and xerostomia following primary radiochemotherapy (RCTx). MATERIAL AND METHODS: A panel of 178 genes previously related to radiochemosensitivity of HNSCC was considered for nanoString analysis based on tumour biopsies of 90 patients with locally advanced HNSCC treated by primary RCTx. Dose-volume parameters were extracted from the parotid, submandibular glands, oral cavity, larynx, buccal mucosa, and lips. Normal tissue complication probability (NTCP) models were developed for acute, late, and for the improvement of xerostomia grade ≥2 and dysphagia grade ≥3 using a cross-validation-based least absolute shrinkage and selection operator (LASSO) approach combined with stepwise logistic regression for feature selection. The final signatures were included in a logistic regression model with optimism correction. Performance was assessed by the area under the receiver operating characteristic curve (AUC). RESULTS: NTCP models for acute and late xerostomia and the improvement of dysphagia resulted in optimism-corrected AUC values of 0.84, 0.76, and 0.70, respectively. The minimum dose to the contralateral parotid was selected for both acute and late xerostomia and the minimum dose to the larynx was selected for dysphagia improvement. For the xerostomia endpoints, the following gene expressions were selected: RPA2 (cellular response to DNA damage), TCF3 (salivary gland cells development), GBE1 (glycogen storage and regulation), and MAPK3 (regulation of cellular processes). No gene expression features were selected for the prediction of dysphagia. CONCLUSION: This hypothesis-generating study showed the potential of improving NTCP models using gene expression data for HNSCC patients. The presented models require independent validation before potential application in clinical practice.

Assessment of Toxic Effects and Survival in Treatment Deescalation With Radiotherapy vs Transoral Surgery for HPV-Associated Oropharyngeal Squamous Cell Carcinoma: The ORATOR2 Phase 2 Randomized Clinical Trial.

Importance: The optimal approach for treatment deescalation in human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCCs) is unknown. Objective: To assess a primary radiotherapy (RT) approach vs a primary transoral surgical (TOS) approach in treatment deescalation for HPV-related OPSCC. Design, Setting, and Participants: This international, multicenter, open-label parallel-group phase 2 randomized clinical trial was conducted at 9 tertiary academic cancer centers in Canada and Australia and enrolled patients with T1-T2N0-2 p16-positive OPSCC between February 13, 2018, and November 17, 2020. Patients had up to 3 years of follow-up. Interventions: Primary RT (consisting of 60 Gy of RT with concurrent weekly cisplatin in node-positive patients) vs TOS and neck dissection (ND) (with adjuvant reduced-dose RT depending on pathologic findings). Main Outcomes and Measures: The primary end point was overall survival (OS) compared with a historical control. Secondary end points included progression-free survival (PFS), quality of life, and toxic effects. Results: Overall, 61 patients were randomized (30 [49.2%] in the RT arm and 31 [50.8%] in the TOS and ND arm; median [IQR] age, 61.9 [57.2-67.9] years; 8 women [13.6%] and 51 men [86.4%]; 31 [50.8%] never smoked). The trial began in February 2018, and accrual was halted in November 2020 because of excessive toxic effects in the TOS and ND arm. Median follow-up was 17 months (IQR, 15-20 months). For the OS end point, there were 3 death events, all in the TOS and ND arm, including the 2 treatment-related deaths (0.7 and 4.3 months after randomization, respectively) and 1 of myocardial infarction at 8.5 months. There were 4 events for the PFS end point, also all in the TOS and ND arm, which included the 3 mortality events and 1 local recurrence. Thus, the OS and PFS data remained immature. Grade 2 to 5 toxic effects occurred in 20 patients (67%) in the RT arm and 22 (71%) in the TOS and ND arm. Mean (SD) MD Anderson Dysphagia Inventory scores at 1 year were similar between arms (85.7 [15.6] and 84.7 [14.5], respectively). Conclusions and Relevance: In this randomized clinical trial, TOS was associated with an unacceptable risk of grade 5 toxic effects, but patients in both trial arms achieved good swallowing outcomes at 1 year. Long-term follow-up is required to assess OS and PFS outcomes. Trial Registration: Clinicaltrials.gov Identifier: NCT03210103.

Tumor molecular differences associated with outcome disparities of Black patients with head and neck cancer.

BACKGROUND: Numerous studies of head and neck squamous cell carcinoma (HNSCC) have demonstrated disparate outcomes by race and ethnicity. Beyond known associations with socioeconomic variables, whether these are also associated with differences in tumor molecular composition has thus far been poorly explored. METHODS: We downloaded clinical and multiplatform molecular data from The Cancer Genome Atlas and other published studies. These were compared between non-Hispanic Black (n = 43) and White (n = 354) patients with non-HPV-related tumors, using multivariable models. Publicly available validation cohorts were used. RESULTS: Black patients had poorer progression-free survival than White patients. Tumors of Black patients had greater copy number aberrations, and increased SFRP1 methylation and miRNA-mediated PRG4 silencing associated with poor survival. PI3K/AkT/mTOR pathway proteins were differentially expressed. CONCLUSIONS: There are molecular differences between tumors of Black and White patients that may partially account for differences in survival. These may inform targeted treatment decisions to achieve equitable outcomes.

Comparison of efficacy and toxicity of chemoradiation regimens for head and neck squamous cell carcinoma primary treatment.

BACKGROUND: The best chemoradiation regimen to treat locally and regionally advanced head and neck squamous cell carcinoma (HNSCC) is yet to be established. METHODS: We compared overall survival (OS) and adverse events following chemoradiation regimens (high-dose [HDC] or low-dose [LDC] cisplatin, or carboplatin [CB]) in HNSCC cases selected from SEER-Medicare linked database. RESULTS: Of the 1335 cases who underwent radiotherapy, 264 received HDC, 259 received LDC, and 353 received CB, concurrently. Compared to chemoradiation with HDC, using LDC or CB, or radiotherapy alone were associated with an increasingly worse OS; hazard ratios were 1.33, p = 0.03; 1.35, p = 0.02; and 2.12, p < 0.001; respectively. There were no differences in the rates of adverse events between the three chemoradiation regimens. CONCLUSION: Chemoradiation regimen using HDC appears to be the best primary treatment for locally and regionally advanced HNSCC. Nonetheless, prospective large studies are warranted to further determine its absolute benefit.

Treatment modalities, adverse events, and survival outcomes in older patients with head and neck squamous cell carcinoma.

BACKGROUND: Chemoradiation with curative intent in older adults with locally advanced head and neck squamous cell carcinoma (HNSCC) has been a challenge, because of its potential toxicities. METHODS: We selected primary HNSCC cases from the SEER-Medicare linked database, assessed overall survival (OS) and adverse events and their associations with different treatments, across four age groups including the youngest (66-69 years) and the oldest (≥80 years). RESULTS: Better OS was associated with chemoradiation compared to radiation alone, not only in all patients (N = 5879) (hazard ratio [HR] = 0.82, p < 0.001), but also in the oldest group (N = 1380) (HR = 0.77, p = 0.006) in whom the adverse events rates were not higher than those in the youngest (N = 1562); more of the latter (26%-30%) than the former (14%-19%) received chemoradiation, regardless of their comorbidity indices. CONCLUSIONS: Our findings provide evidence that patients' characteristics, other than chronological age, should be equally considered in selecting the best therapy for older patients with HNSCC.

Assessment of the perceived stress and burden of family caregivers of the head-and-neck cancer patients at a tertiary care cancer center: A cross-sectional study.

INTRODUCTION: Cancer is a major life-threatening disease and has an impact on both patients and their family members. Caring for cancer patients may lead to several levels of stress which may affect their own health as well as their quality of life. AIM: To assess the perceived stress and burden of family caregivers of head and neck cancer patients (HNC) attending cancer care centre at a tertiary care centre, Tamil Nadu. OBJECTIVES: To assess the perceived stress and the burden among caregivers of patients with head and neck cancer using the Perceived Stress Scale (PSS) and Caregiver Strain Index (CSI) respectively. MATERIALS AND METHOD: A Cross-sectional study was carried out for a period of three months among the caregivers of head and neck cancer patients at a cancer care centre, Madurai. A total of 200 caregivers were selected by Convenience sampling method. Data was collected using a pretested, self-structured, closed-ended questionnaire by face to face interview method. RESULTS: The study population consisted of Caregivers aged 21-60 years, mostly females (80%), spouses (54%), employed (57%) and uneducated (66%). Most of the caregivers were from lower socioeconomic status (66%) and those who are providing care for 1 to 6 months were more in number. In this study, 82% of caregivers reported high caregiver burden (CSI ≥7) and 67% of caregivers reported high stress (PSS ≥ 26 - 40). CONCLUSION: Caregivers are experiencing significant burden, particularly with respect to their physical and psychological well-being, economic circumstances, social and personal relationships.

Real-world study of the impact of recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) on quality of life and productivity in Europe.

BACKGROUND: Although current therapy for patients with early-stage squamous cell carcinoma of the head and neck (SCCHN) is potentially curative, the recurrence rate is high. Patients with recurrent or metastatic (R/M) SCCHN have a poor prognosis and substantial disease burden, including impaired health-related quality of life (HRQoL), productivity loss and indirect costs, such as need for caregiver support. The aim of this study was to characterize the impact of R/M SCCHN and its first-line treatment on patient and caregiver quality of life, daily activities and work productivity using real-world evidence from Europe. METHODS: This was a multicentre retrospective study of patients with R/M SCCHN in France, Germany, Italy, Spain and the United Kingdom incorporating patient and caregiver surveys, and a physician-reported medical chart review, conducted between January and May 2019. Patients aged 18 or over with a physician confirmed diagnosis R/M SCCHN completed four validated measures of disease activity and its impact on quality of life and work productivity, while caregivers also completed questionnaire to assess the burden of providing care. Physicians provided data for clinical characteristics, patient management, testing history and treatment patterns. RESULTS: A total of 195 medical/clinical oncologists provided data for 937, predominantly male (72%) patients, with almost half of patients aged over 65 years. The most frequently reported symptoms were fatigue (43%), weight loss (40%), pain (35%) and difficulty swallowing (32%). The EXTREME regimen was the most common first line therapy in over half of patients, who reported moderate or extreme pain/discomfort, and anxiety/depression, and problems with self-care resulting in a diminished health status compared with the general population. Only 14% were employed with high absenteeism or presenteeism, and over half of patients had a caregiver for whom the burden of care was substantial. CONCLUSION: Our results provide real-world insight into the multi-faceted burden associated with R/M SCCHN. The combination of poor HRQoL and the impairment in daily activities, social life and employment illustrates the wider impact of R/M SCCHN on patients and their caregivers, and highlights a need for novel 1 L treatment regimens to improve the humanistic and productivity burdens of this cancer.

A hidden Markov model for lymphatic tumor progression in the head and neck.

Currently, elective clinical target volume (CTV-N) definition for head and neck squamous cell carcinoma (HNSCC) is mostly based on the prevalence of nodal involvement for a given tumor location. In this work, we propose a probabilistic model for lymphatic metastatic spread that can quantify the risk of microscopic involvement in lymph node levels (LNL) given the location of macroscopic metastases and T-category. This may allow for further personalized CTV-N definition based on an individual patient's state of disease. We model the patient's state of metastatic lymphatic progression as a collection of hidden binary random variables that indicate the involvement of LNLs. In addition, each LNL is associated with observed binary random variables that indicate whether macroscopic metastases are detected. A hidden Markov model (HMM) is used to compute the probabilities of transitions between states over time. The underlying graph of the HMM represents the anatomy of the lymphatic drainage system. Learning of the transition probabilities is done via Markov chain Monte Carlo sampling and is based on a dataset of HNSCC patients in whom involvement of individual LNLs was reported. The model is demonstrated for ipsilateral metastatic spread in oropharyngeal HNSCC patients. We demonstrate the model's capability to quantify the risk of microscopic involvement in levels III and IV, depending on whether macroscopic metastases are observed in the upstream levels II and III, and depending on T-category. In conclusion, the statistical model of lymphatic progression may inform future, more personalized, guidelines on which LNL to include in the elective CTV. However, larger multi-institutional datasets for model parameter learning are required for that.

Determinants of delay and association with outcome in head and neck cancer: A systematic review.

INTRODUCTION: Head and neck cancers (HNC) are relatively fast-growing tumours, and delay in treatment initiation is associated with tumour progression and adverse outcome. An overview of factors contributing to delay can provide critical insights on necessary adjustments to optimize care pathways. This systematic review aims to identify factors associated with delay and summarize the effect of delay on oncological outcome measures. METHODS: A search strategy was conducted according to PRISMA guidelines to search electronic databases for studies assessing the carepathway interval (days between first visit in head and neck oncology center and treatment initiation) and/or time-to-treatment-initiation interval (days between histological diagnosis and treatment initiation) and 1) determinants of delay and/or 2) effect of delay on outcome within these timeframes. Due to heterogeneity between included studies, a meta-analysis was not possible. RESULTS: Fifty-two studies were eligible for quantitative analysis. Non-Caucasian race, academic setting, Medicaid/no insurance and radiotherapy as primary treatment were associated with delay. Advanced tumour stage was related to increased time-to-treatment initiation in the four common sites combined (oral cavity, oropharynx, hypopharynx, larynx). Separate determinants for delay in different tumour locations were identified. In laryngeal, oral cavity cancer and the four common HNC sites combined, delay in start of treatment is associated with decreased overall survival, although no cut-off time point could be determined. CONCLUSION: Race, facility type, type of insurance and radiotherapy as primary treatment were associated with delay and subsequent inferior survival in the four common sites combined.

Cost-utility analysis of stereotactic body radiotherapy plus cetuximab in previously irradiated recurrent squamous cell carcinoma of the head and neck.

BACKGROUND: This study aimed to estimate the cost-utility of stereotactic body radiotherapy (SBRT) plus cetuximab for patients with previously irradiated recurrent squamous cell carcinoma of the head and neck. METHODS: We constructed a Markov health-state transition model to simulate costs and clinical outcomes of recurrent squamous cell carcinoma of the head and neck. Model parameters were derived from the published literature and the National Health Insurance Administration reimbursement price list. Incremental cost-effectiveness ratio and the net monetary benefit were calculated from a health payer perspective. The impact of uncertainty was modeled with one-way and probabilistic sensitivity analyses. RESULTS: In the base-case, SBRT plus cetuximab compared to SBRT alone resulted in an ICER of NT$ 840,455 per QALY gained. In the one-way sensitivity analysis, the utility of progression-free state for patients treated with SBRT plus cetuximab or SBRT alone and the cost of progression-free survival for SBRT+Cet were the most sensitive parameters in the model. Probabilistic sensitivity analysis showed that the probability of cost-effectiveness at a willingness-to-pay threshold of NT$ 2,252,340 per QALY was 100% for SBRT plus cetuximab but 0% for SBRT alone. CONCLUSIONS: This study showed that SBRT+Cet was cost-effective and benefited patients with previously irradiated rSCCHN.

Determinants of delay in the head and neck oncology care pathway: The next step in value-based health care.

OBJECTIVE: Head and neck squamous cell carcinomas (HNSCC) are relatively fast-growing tumours, and delay of treatment is associated with tumour progression and adverse outcomes. The aim of this study is to identify determinants of delay in a head and neck oncology centre. METHODS: This cohort study with prospectively collected data investigated associations between patient (including geriatric assessment at first consultation), tumour and treatment characteristics and treatment delay. Two quality indicator intervals assessing value-based healthcare were studied: care pathway interval (CPI, interval between first visit in an HNOC and treatment initiation) and time-to-treatment initiation (TTI, interval between histopathological confirmation of HNSCC and treatment initiation), using regression analyses. RESULTS: Stage-IV tumours and initial radiotherapy were independent predictors of delay in CPI. Initial radiotherapy was associated with delay in TTI. Overall, 37% of the patients started treatment within 30 days after first consultation (67% in case of initial surgical treatment and 11.5% if treated with (chemo)radiation, p < 0.001). Geriatric assessment outcomes were not associated with delay. Indicators for delay in initial surgery patients were stage-IV tumours (CPI). CONCLUSION: The majority of HNSCC patients encounter delay in treatment initiation, specifically in patients with advanced-stage tumours or when radiotherapy is indicated.

Mono-institutional retrospective cohort analysis of the insurance status dependent access to ENT-professionals and survival in head and neck squamous cell carcinoma.

BACKGROUND: To access the influence of insurance status on time of diagnosis, quality of treatment and survival in head and neck squamous cell carcinoma (HNSCC). METHODS: This mono-institutional retrospective cohort analysis included all HNSCC patients (n = 1,054) treated between 2001 and 2011, and subdivided the cohort according to the insurance status. Differences between the groups were analyzed using the Chi square and the unpaired student's t-test. Survival rates were calculated by Kaplan-Meier and Cox regression for forward selection. RESULTS: Nine hundred twenty-five patients showed general, 129 private insurance. The 2 groups were equal regarding age, gender, tumor localization, therapy, and N/M/G/R-status. The T-status differed significantly between the groups showing more advanced tumors in patients with general insurance (p = 0.002). While recurrence-free survival was comparable in both groups, overall survival was significantly better in private patients (p = 0.009). The time frame between first symptom and diagnosis was equal in both groups. CONCLUSIONS: The time frame between subjective percipience of first symptom and final therapy did not differ between the groups. In our cohort, access to otorhinolaryngological specialists is favorable in both, patients with general and private insurance. Recurrence-free survival was comparable in both groups, indicating successful HNSCC treatment both groups. However, overall survival was significantly better in patients with private insurance suggesting other socioeconomic factors influencing survival.

Costs of Definitive Chemoradiation, Surgery, and Adjuvant Radiation Versus De-Escalated Adjuvant Radiation per MC1273 in HPV+ Cancer of the Oropharynx.

PURPOSE: De-escalated treatment for human papillomavirus (HPV)+ oropharynx squamous cell carcinoma (OPSCC) has shown promising initial results. Health-care policy is increasingly focusing on high-value care. This analysis compares the cost of care for HPV+ OPSCC treated with definitive chemoradiation (CRT), surgery and adjuvant radiation (RT), and surgery and de-escalated CRT on MC1273. METHODS AND MATERIALS: MC1273 is a prospective, phase 2 study evaluating adjuvant CRT to 30 to 36 Gy plus docetaxel for HPV+ OPSCC after surgery for high-risk patients. Matched standard-of-care control groups were retrospectively identified for patients treated with definitive CRT or adjuvant RT. Standardized costs were evaluated before radiation, during treatment (during RT), and at short-term (6 month) and long-term (7-24 month) follow-up periods. RESULTS: A total of 56 definitive CRT, 101 adjuvant RT, and 66 MC1273 patients were included. The CRT arm had more T3-4 disease (63% vs 17-21%) and higher N2c-N3 disease (52% vs 20-24%) vs both other groups. The total treatment costs in the CRT, adjuvant RT, and MC1273 groups were $47,763 (standard deviation [SD], $19,060], $57,845 (SD, $17,480), and $46,007 (SD, $9019), respectively, and the chemotherapy and/or RT costs were $39,936 (SD, $18,480), $26,603 (SD, $12,542), and $17,864 (SD, $3288), respectively. The per-patient, per-month, average short-term follow-up costs were $3860 (SD, $10,525), $1072 (SD, $996), and $972 (SD, $833), respectively, and the long-term costs were $978 (SD, $2294), $485 (SD, $1156), and $653 (SD, $1107), respectively. After adjustment for age, T-stage, and N-stage, treatment costs remained lower for CRT and MC1273 versus adjuvant RT ($45,450 and $47,114 vs $58,590, respectively; P < .001), whereas the total per-patient, per-month follow-up costs were lower in the MC1273 study group and adjuvant RT versus CRT ($853 and $866 vs $2030, respectively; P = .03). CONCLUSIONS: MC1273 resulted in 10% and 20% reductions in global costs compared with standard-of-care adjuvant RT and definitive CRT treatments. Substantial cost savings may be an added benefit to the already noted low toxicity and maintained quality of life of treatment per MC1273.