Assessment of endpoint definitions in curative-intent trials for mucosal head and neck squamous cell carcinomas: Head and Neck Cancer International Group consensus recommendations.

Robust time-to-event endpoint definitions are crucial for the assessment of treatment effect and the clinical value of trial interventions. Here, the Head and Neck Cancer International Group investigated endpoint use in phase 3 trials and trials considered potentially practice-changing published between 2008 and 2021 in the curative-intent setting for patients with mucosal head and neck squamous cell carcinoma. Of the 92 trials reviewed, we show that all core components of endpoint reporting were heterogeneous, including definitions of common terms, such as overall survival and progression-free survival. Our report highlights the urgent need for harmonisation of fundamental components of clinical trial endpoints and the engagement of all stakeholders to ensure the transparent reporting of endpoint details.

Assessment of endpoint definitions in recurrent and metastatic mucosal head and neck squamous cell carcinoma trials: Head and Neck Cancer International Group consensus recommendations.

Transparent and precise endpoint definitions are a crucial aspect of clinical trial conduct and reporting, and are used to communicate the benefit of an intervention. Previous studies have identified inconsistencies in endpoint definitions across oncological clinical trials. Here, the Head and Neck Cancer International Group assessed endpoint definitions from phase 3 trials or trials considered practice-changing for patients with recurrent or metastatic mucosal head and neck squamous cell carcinoma, published between 2008 and 2021. We identify considerable and global heterogeneity in endpoint definitions, which undermines the interpretation of results and development of future studies. We show how fundamental components of even incontrovertible endpoints such as overall survival vary widely, highlighting an urgent need for increased rigour in reporting and harmonisation of endpoints.

Challenges in the Assessment of Medullary Bone Invasion in Oral Cavity Cancers and Its Prognostic Significance.

BACKGROUND: As per AJCC 8th edition TNM staging system, bone invasion is a poor prognostic marker that upstages oral cavity squamous carcinoma (OSCC) to pT4a. Cortical erosion alone of bone or tooth socket by a gingival primary is not sufficient to upstage a tumour. The differentiation of cortical erosion from invasion through the cortical bone into the medulla is often challenging, limiting accurate staging. This review aims to assess the difficulties in differentiating cortical erosion from medullary invasion and evaluate the prognostic significance of different patterns of bone involvement. METHODS: A retrospective review of OSCC with primary curative surgery and bone resection treated at a single-center over 10 years, was performed to assess the prognostic significance of bone invasion. Hematoxylin-eosin stained slides of a subset of cases were re-reviewed in a planned manner to assess difficulties in precise categorization (no invasion/erosion/cortical invasion and medullary invasion), evaluate interobserver agreement, and correlate with clinical outcome. RESULTS: Five hundred and ninety patients were included, with a median follow-up of 28 months. On univariate analysis, the 3-year local, nodal and distant metastasis control were not significantly different in the 3 groups of no invasion, erosion, and invasion (p = 0.43, 0.47, and 0.47, respectively). Overall survival (OS) at 3 years was 78.1% and disease-free-survival(DFS) was 63.7% in the entire cohort. On univariate analysis, there was significant difference in OS and DFS based on these groups. This did not translate into independent prognostic benefit on multivariable analysis (p = 0.75 and 0.19, respectively). The independent prognostic factors were margin positivity, tumor differentiation, perineural invasion and pathological nodal involvement. Planned re-review of a subset of 202 cases resulted in a change in bone involvement category in 26/202 cases, which was mainly due to difficulty in assessing cortico-medullary junction near the tooth socket and bone fragmentation. The assessment showed moderate to near complete agreement (kappa 0.59-0.82) between 2 observers. CONCLUSION: Our study shows that bone involvement is not an independent prognostic marker and there is no specific correlation of medullary invasion with outcome over those that showed cortical erosion. Several factors contribute to difficulties and interobserver variability in assessing bone involvement.

Computed tomography/magnetic resonance imaging for mandibular boundary invasion of oral squamous cell carcinoma assessment.

BACKGROUND: The range of mandibular invasion by a tumour needs to be determined accurately to minimize unnecessary damage to the mandible. This study aimed to compare tumour boundary lines on computed tomography/magnetic resonance (CT/MR) images with those from pathological findings during the preoperative assessment of mandibular invasion by oral squamous cell carcinoma (OSCC). By comparing the methods, the potential of CT/MR for this application could be further elucidated. METHODS: Eight patients with OSCC were imaged with CT/MR, mandibular specimens were collected, and the material site was measured. Haematoxylin-eosin staining was used for histopathological assessment. The presence and boundaries of bone invasion were evaluated. The CT/MR and histopathological boundaries of bone invasion were delineated and merged to compare and calculate the deviation of CT/MR and histopathological boundaries using the Fréchet distance. RESULTS: The mean Fréchet distance between the CT and pathological tumour boundaries was 2.69 mm (standard error 0.46 mm), with a minimum of 1.18 mm, maximum of 3.64 mm, median of 3.10 mm, and 95% confidence interval of 1.40-3.97 mm. The mean Fréchet distance between the tumour boundaries on the MR and pathological images was 3.07 mm (standard error 0.56 mm), with a minimum of 1.53 mm, maximum of 4.74 mm, median of 2.90 mm, and 95% confidence interval of 1.53-4.61 mm. CONCLUSIONS: CT/MR imaging can provide an effective preoperative assessment of mandibular invasion of OSCC. Pathology images can be positioned on CT/MR scans with the help of computer software to improve the accuracy of the findings. The introduction of the Fréchet distance to compare tumour boundary lines is conducive to computer image diagnosis of tumour invasion of jaw boundaries.

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.

Qualitative Assessment of Collagen and Elastic Fibers in Oral Submucous Fibrosis (OSMF), OSMF with Dysplasia and Oral Squamous Cell Carcinoma Arising from OSMF: A Histochemical Study.

BACKGROUND: Oral submucous fibrosis (OSMF) is a habit related potentially malignant disorder seen mainly in South Asian people. The malignancy arising from OSMF has been regarded as low grade with better outcome. The present study was orchestrated to histochemically analyze collagen and elastic fibres in OSMF without dysplasia, OSMF with dysplasia and OSMF turning malignant. MATERIALS AND METHODS: 100 cases (80 cases and 20 healthy controls) were included after obtaining clearance from ethical committee. All cases were subjected to Van Gieson staining for collagen and a novel simple method for elastic fibres (Orcein staining). Data were analyzed using SPSS software. RESULTS: Controls showed haphazard arrangement of collagen and elastic fibres. The collagen bundles were parallelly arranged in OSMF without dysplasia and OSMF with dysplasia; the collagen was however haphazard in cases of OSMF turning malignant. As with collagen, elastic fibres were also haphazardly arranged in the control group; in contrast, the elastic fibres were predominantly arranged in a criss-cross pattern in the other study groups. The difference in orientation and density among the groups was statistically significant. CONCLUSION: With advancement of stage there is increased collagenization of OSMF, as the condition acquires dysplastic changes and turns malignant, microenvironment alters resulting in increased activity of collagenases. However, the arrangement of more resistant elastic fibres depicts the better outcome, once OSMF shows malignant transformation, limiting locoregional and distant spread.

Clinical significance of overall assessment of tumor-infiltrating lymphocytes in oropharyngeal cancer: A meta-analysis.

BACKGROUND: The overall assessment of tumor-infiltrating lymphocytes (TILs) evaluated using hematoxylin and eosin (HE) staining has been recently studied in oropharyngeal squamous cell carcinoma (OPSCC). METHODS: We conducted a systematic review of Scopus, Ovid Medline, PubMed, Web of Science, and Cochrane Library to retrieve studies assessing TILs in HE-stained sections of OPSCC. We used fixed-effect models and random-effect models to estimate the pooled hazard ratios (HRs) and confidence intervals (CIs) for disease-free survival (DFS), overall survival (OS) and disease-specific survival (DSS). RESULTS: Eleven studies were identified that had analyzed the prognostic significance of TILs in OPSCC using HE-stained specimens. Our meta-analyses showed that a high infiltration of TILs was significantly associated with improved DFS (HR 0.39, 95%CI 0.24-0.65, P = 0.0003), OS (HR 0.38, 95%CI 0.29-0.50, P < 0.0001), and DSS (HR 0.32, 95%CI 0.19-0.53, P < 0.0001). CONCLUSION: Findings of our meta-analysis support a growing body of evidence indicating that assessment of TILs in OPSCC using HE-stained sections has reliable prognostic value. The clinical significance of such assessment of TILs has been reported repeatedly in many studies on OPSCC. The assessment is cost-effective, feasible, easy to transfer from lab to clinic, and therefore can be incorporated in daily practice.

Extranodal Extension Improves AJCC-8 Accuracy in HPV+ Oropharyngeal Cancer in a High-Risk Population.

OBJECTIVES: The American Joint Committee on Cancer's 8th edition (AJCC-8) separates oropharyngeal squamous cell carcinomas (OPSCCs) into human papillomavirus-positive (HPV+) tumors and HPV-negative tumors. Although AJCC-8 improves prognostic prediction for survival for the majority of HPV+ OPSCC, outliers are still encountered. The goal of this manuscript is to validate the AJCC-8 as a better metric of survivability than the AJCC-7 in an historically under-served rural population with confounding variables, such as tobacco use, alcohol consumption, and poor health care access and to analyze the role of extranodal extension (ENE) in this population. DESIGN: Retrospective cohort study. RESULTS: Compared to AJCC-7, AJCC-8 had a higher odds ratio (OR) for predicting mortality of stage IV HPV+ OPSCCs versus stages I-III. On multivariate analysis, HPV+ OPSCCs with ENE had a higher OR of mortality compared to ENE- OPSCCs. In addition, HPV+ OPSCC patients with a Charlson Comorbidity Index (CCI) > 3 had a higher OR of mortality compared to those with a CCI ≤ 3. Patients with Medicaid/self-pay status had a higher OR of mortality compared to those with private insurance/Medicare. Finally, patients from rural populations had a higher OR of presenting with stage IV disease, a CCI > 3, and Medicaid/self-pay status. CONCLUSIONS: Despite not being a discrete part of the AJCC-8 staging rubric, ENE was found to have a significant impact on mortality among this population, whereas tobacco use had no effect. Rural patients were more likely to present with stage IV disease, CCI > 3, and Medicaid/self-pay status. Stage IV disease was also associated with a higher OR of mortality. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2621-2626, 2023.

Treatment outcomes and cost comparisons for older adults with T4 laryngeal squamous cell cancer.

BACKGROUND: To evaluate treatment modalities of T4 larynx cancer in older adults using SEER-Medicare. METHODS: The database was queried for patients aged 66 and older with nonmetastatic T4 laryngeal squamous cell cancer from 2006 to 2015. Treatment modalities compared were surgery plus chemoradiation (SCR), surgery plus radiation (SR), chemoradiation (CR), surgery (S), and radiation (R). Multivariate analysis and Kaplan-Meier methods were used to explore the relationship of treatment modality and survival. Total cancer-related costs were calculated. RESULTS: A total of 438 patients met inclusion criteria. Patients receiving CR or SR had similar CSS to SCR (HR 1.36 and HR 1.24, respectively). Those receiving S (HR 2.00) or R (HR 2.41) had significantly worse CSS. Similar findings were observed for OS. Cancer care-related costs were not significantly different but highest in SCR ($162215) and lowest in R ($121421). CONCLUSION: Older patients with T4 larynx cancer had similar survival rates when treated with CR, SR, and SCR. Average total health care costs were not significantly different between modalities. Patients not eligible for triple-modality could consider these other treatment options.

The Clinical Utility and Cost of Routine Staging Exam under Anesthesia for Oral Cavity Squamous Cell Carcinoma.

INTRODUCTION: The standard complete evaluation of patients with head and neck squamous cell carcinoma (HNSCC) has included a staging exam under anesthesia (EUA) since the 1970s. The EUA for all sites of HNSCC has historically consisted of panendoscopy for the purpose of diagnostic biopsy, accurate staging of primary disease, and identification of second primary tumors. However, due to the accessibility of the oral cavity, the sole purpose of EUA for tumors of this site is to identify second primary tumors. Since the EUA became the gold standard for evaluation of HNSCC, there have been significant advancements in less invasive technologies such as CT, PET-CT, MRI, and fiberoptic examination. In this study, we sought to determine the value to patient care and cost-effectiveness of EUA in patients with oral cavity squamous cell carcinoma (OCSCC). METHODS: A retrospective chart review identified 77 patients who underwent EUA for OCSCC. RESULTS: The most common subsites were the oral tongue and floor of mouth (59.7% and 24.7% respectively). All underwent direct laryngoscopy, 94.8% underwent esophagoscopy, and 20.8% underwent flexible transnasal examination in clinic prior to EUA. For 90.9% of patients, the EUA did not change initial T-staging based on clinical examination and imaging. The remaining 9.1% of patients were upstaged after EUA, however this change did not impact the treatment plan. Second primary tumors were identified in 3.9% of patients, all were found in either the oral cavity or oropharynx, and were also identified with clinical examination or imaging. Analysis of patient charges determined an average cost of $8,022.93 per patient under the current paradigm involving EUA, however with a new algorithm eliminating mandatory EUA average cost decreases to $1,448.44. CONCLUSION: Formal EUA has historically been the gold standard for all HNSCC tumors. However, when performed for cases of oral cavity carcinoma, it is safe and cost effective to limit its use to select clinical scenarios.

Sentinel lymph node biopsy for head and neck cutaneous squamous cell carcinoma using the Brigham and Women's staging system: a cost analysis.

The objective is to determine the cost-effectiveness of sentinel lymph node biopsy (SLNB) for cutaneous squamous cell carcinoma (CSCC) according to the Brigham and Women's Hospital (BWH) Tumor Staging system. A decision analysis was utilized to examine costs and outcomes associated with the use of SLNB in patients with high-risk head and neck CSCC. Decision tree outcome probabilities were obtained from published literature. Costs were derived from Medicare reimbursement rates (US$) and effectiveness was represented by quality-adjusted life-years (QALYs). The primary outcome was the incremental cost-effectiveness ratio (ICER), with a willingness-to-pay set at $100,000 per QALY gained. SLNB was found to be a cost-effective tool for patients with T3 tumors, with an ICER of $18,110.57. Withholding SLNB was the dominant strategy for both T2a and T2b lesions, with ICERs of - $2468.99 and - $16,694.00, respectively. Withholding SLNB remained the dominant strategy when examining immunosuppressed patients with T2a or T2b lesions. In patients with head and neck CSCC, those with T3 or T2b lesions with additional risk factors not accounted for in the staging system alone, may be considered for SLNB, while in other tumor stages it may be impractical. SLNB should only be offered on an individual patient basis.

Comparative Assessment of E-cadherin's Expression between the Metastatic and Non-metastatic Oral Squamous Cell Carcinoma: An Immunohistochemical Study

ABSTRACT Objective: To identify the clinicopathological correlation of E-cadherin expression in metastatic and non-metastatic oral squamous cell carcinoma (OSCC). Material and Methods: A total of 90 paraffin-embedded tissue sections of OSCC were retrieved from the registry. The total selected samples were 45 cases each from the primary lesions of metastatic and non-metastatic OSCC. One section was subjected to routine Hematoxylin and eosin stain and another to immunohistochemical analysis for E-cadherin expression. Results: A non-significant (p˃0.05) increased expression is seen in the non-metastatic group compared to the metastatic group, with predominantly membrane as the staining site in either group. However, the expression of E-cadherin did not reveal any statistically significant association with independent variables such as age, gender, and adverse habits of the patients (p>0.05). On the other hand, with respect to the histological differentiation of OSCC, a significant association (p<0.001) was observed with the well-differentiated type of metastatic OSCC. Conclusion: E-cadherin was useful to some extent in predicting regional metastasis. However, further studies using a panel of biomarkers with increased sample size may help us understand the process involved in metastasis.

Serum lactate dehydrogenase in the prognostic assessment of patients with oral squamous cell carcinoma.

Background: Lactate dehydrogenase (LDH) has been proven to be a diagnostic marker in oral squamous cell carcinoma (OSCC). However, the prognostic value of serum LDH in OSCC is yet to be explored. The purpose of this study is to correlate the level of serum LDH with the degree of OSCC and to evaluate the role of serum LDH as a prognostic marker in OSCC. Methods: The investigators designed and implemented a prospective cohort study composed of patients with OSCC (n = 66) sub-grouped as follows: 2A-well-differentiated (n = 22), 2B-moderately differentiated (n = 22), 2C-poorly differentiated OSCC (n = 22), and normal healthy controls (n = 40). The primary outcome variable was the serum LDH measured at baseline (pre-treatment) and 2 and 12 months post-treatment in OSCC patients. The statistical analysis was performed using the student t-test and analysis of variance, and the P value was set at 0.05. Results: The habit of alcohol consumption alone as a single habit was found only in males (17.5%) (P = 0.3343), whereas betel quid chewing was more common among females (P = 0.0182). A significant difference was observed in the mean serum LDH between OSCC subjects (pre-treatment) (831.56 ± 93.43 IU/L) and controls (188.82 ± 25.53 IU/L), P < 0.00001. The baseline serum LDH was significantly higher in subgroup 2C (933.41 ± 46.1969 IU/L) than in the 2A (742.59 ± 46.5676 IU/L) and 2B (818.68 ± 58.1643 IU/L) subgroups (P = 0). There was a significant decline in the serum LDH within 2 months after treatment, and a further decrement was observed during a 12-month follow-up among the survivors of all three subgroups; P < 0.00001. Conclusion: Serum LDH can play a dual role as a reliable indicator of the degree of OSCC for decision-making in treatment modalities and as a prognostic marker of response to therapy.

Comparison of CT, MRI, and F-18 FDG PET/CT for initial N-staging of oral squamous cell carcinoma: a cost-effectiveness analysis.

BACKGROUND AND PURPOSE: Treatment of oral squamous cell carcinoma (OSCC) is based on clinical exam, biopsy, and a precise imaging-based TNM-evaluation. A high sensitivity and specificity for magnetic resonance imaging (MRI) and F-18 FDG PET/CT are reported for N-staging. Nevertheless, staging of oral squamous cell carcinoma is most often based on computed tomography (CT) scans. This study aims to evaluate cost-effectiveness of MRI and PET/CT compared to standard of care imaging in initial staging of OSCC within the US Healthcare System. METHODS: A decision model was constructed using quality-adjusted life years (QALYs) and overall costs of different imaging strategies including a CT of the head, neck, and the thorax, MRI of the neck with CT of the thorax, and whole body F-18 FDG PET/CT using Markov transition simulations for different disease states. Input parameters were derived from literature and willingness to pay (WTP) was set to US $100,000/QALY. Deterministic sensitivity analysis of diagnostic parameters and costs was performed. Monte Carlo modeling was used for probabilistic sensitivity analysis. RESULTS: In the base-case scenario, total costs were at US $239,628 for CT, US $240,001 for MRI, and US $239,131 for F-18 FDG PET/CT whereas the model yielded an effectiveness of 5.29 QALYs for CT, 5.30 QALYs for MRI, and 5.32 QALYs for F-18 FDG PET/CT respectively. F-18 FDG PET/CT was the most cost-effective strategy over MRI as well as CT, and MRI was the cost-effective strategy over CT. Deterministic and probabilistic sensitivity analysis showed high robustness of the model with incremental cost effectiveness ratio remaining below US $100,000/QALY for a wide range of variability of input parameters. CONCLUSION: F-18 FDG PET/CT is the most cost-effective strategy in the initial N-staging of OSCC when compared to MRI and CT. Despite less routine use, both whole body PET/CT and MRI are cost-effective modalities in the N-staging of OSCC. Based on these findings, the implementation of PET/CT for initial staging could be suggested to help reduce costs while increasing effectiveness in OSCC.

Ultrasonography for masses of the pharynx and larynx and assessment of laryngeal squamous cell carcinoma.

OBJECTIVE: To evaluate the ultrasonography (US) characteristics of pharyngeal/laryngeal masses and the role of US in the assessment of laryngeal squamous cell carcinoma (LSCC). METHODS: This study enrolled patients who underwent US for evaluation of pharyngeal/laryngeal masses between 2018 and 2021. Characteristics of pharyngeal/laryngeal masses and subsite invasion in cases of LSCC were evaluated using US. RESULTS: Forty-six patients with pharyngeal (n = 22) /laryngeal (n = 24) masses were enrolled. The pathological results were benign and malignant in 7 (15.2%) and 39 (84.8%) patients, respectively. Malignant masses were significantly associated with US characteristics of heterogeneity (P = 0.002), irregular/speculated margin (P < 0.001), and increased internal vascularity (P = 0.014) compared with benign masses. In patients with LSCC, the detection rate of US for subsites invasion, including that of the anterior commissure, paraglottic space, outer cortex of the thyroid cartilage, cricoid cartilage, and extralaryngeal soft tissue, was similar to that of computed tomography (CT). Although the difference was not statistically significant, US more frequently demonstrated invasion of the inner cortex of the thyroid cartilage than CT (40.9% vs. 22.7%; P = 0.195). US and CT had a concordance rate of 81% (18 of 22 patients) in determining the tumour stage of the lesions. CONCLUSION: US could facilitate differentiation between benign and malignant masses of the pharynx and larynx in selective patients and has a possible role in the assessment of LSCC.

The impact of socioeconomic and geographic factors on access to transoral robotic/endoscopic surgery for early stage oropharyngeal malignancy.

OBJECTIVE: To evaluate the role of social and geographic factors on the likelihood of receiving transoral robotic surgery (TORS) or non-robotic transoral endoscopic surgery treatment in early stage oropharyngeal squamous cell carcinoma (OPSCC). MATERIALS AND METHODS: The National Cancer Database was queried to form a cohort of patients with T1-T2 N0-N1 M0 OPSCC (AJCC v.7) who underwent treatment from 2010 to 2016. Demographics, tumor characteristics, treatment type, social, and geographic factors were all collected. Univariate analysis and multivariate logistic regression were then performed. RESULTS: Among 9267 identified patients, 1774 (19.1%) received transoral robotic surgery (TORS), 1191 (12.9%) received transoral endoscopic surgery, and 6302 (68%) received radiation therapy. We found that lower cancer stage, lower comorbidity burden and HPV- positive status predicted a statistically significant increased likelihood of receiving surgery. Patients who reside in suburban or small urban areas (>1 million population), were low-to- middle income, or rely on Medicaid were less likely to receive surgery. Patients that reside in Medicaid-expansion states were more likely to receive TORS (p > .0001). Patients that reside in states that expanded Medicaid January 2014 and after were more likely to receive non-robotic transoral endoscopic surgery (p > .0001). CONCLUSIONS: Poorer baseline health, lower socioeconomic status and residence in small urban areas may act as barriers to accessing minimally invasive transoral surgery while residence in a Medicaid-expansion state may improve access. Barriers to accessing robotic surgery may be greater than accessing non-robotic surgery.

Assessment of immune status of laryngeal squamous cell carcinoma can predict prognosis and guide treatment.

BACKGROUND: In the past few years, immunotherapy has changed the way we treat solid tumors. People pay more and more attention to the immune microenvironment of laryngeal squamous cell carcinoma (LSCC). In this study, our immunotherapy research took advantage of the clinical database and focused our in-depth analysis on the tumor microenvironment (TME). METHODS: This study evaluated the relationship between the clinical outcome and the local tissue and overall immune status in 412 patients with primary LSCC. We constructed and validated a risk model that could predict prognosis, assess immune status, identify high-risk patients, and develop personalized treatment plans through bioinformatics. In addition, through immunohistochemical analysis, we verified the differential expression of CTSL and KDM5D genes with the largest weight coefficients in the model in LSCC tissues and their influence on the prognosis and tumor-infiltrating lymphocytes (TILs). RESULTS: We found that interstitial tumor-infiltrating lymphocytes, tumor parenchymal-infiltrating lymphocyte volume, tumor infiltrates lymphocytes of frontier invasion, and the platelet-to-lymphocyte ratio (PLR) were independent factors affecting the prognosis of patients with LSCC. A novel risk model can guide clinicians to accurately predict prognosis, identify high-risk patients, and formulate personalized treatment plans. The differential expression of genes such as CTSL and KDM5D has a significant correlation with the TILs of LSCC and the prognosis of patients. CONCLUSION: Local and systemic inflammatory markers in patients with laryngeal squamous cell carcinoma are reliable prognostic factors. The risk model and CTSL, KDM5D gene have important potential research value.

Cancer Stem Cell Markers, CD44 and ALDH1, for Assessment of Cancer Risk in OPMDs and Lymph Node Metastasis in Oral Squamous Cell Carcinoma.

Tumour heterogeneity in oral cancer is attributed to the presence of cancer stem cells (CSCs). CSCs are the most migratory and metastatic cellular subpopulation within tumours. Assessment of CSC markers as significant predictors of lymph node metastasis may prove valuable in the clinical setting. Furthermore, analysis of this panel of putative stem cell markers in oral dysplasia may additionally inform of the likelihood for oral potentially malignant disorders (OPMDs) to progress to oral squamous cell carcinoma (OSCC). The present study aims to assess the significance of CSC markers in the progression of OPMDs to OSCC and assessment of lymph node metastasis in OSCC. CD44 and ALDH1 were assessed immunohistochemically in 25 normal, 30 OPMDs, and 24 OSCCs. CD44 is a membranous marker and ALDH1 is a cytoplasmic marker. The immunohistochemical expression of these markers were compared between OPMDs with and without dysplasia, as well as between low-risk and high-risk dysplasias. Similarly, expression was compared between OSCC with and without lymph node metastasis and among grades of OSCC. Positive CD44 expression was seen in all normal mucosal tissues. The expression decreased from normal epithelium to OPMDs but increased in OSCC. CD44 expression was positive in 21 cases of OSCC (87.5%) and reduced from well-differentiated to poorly differentiated OSCC. CD44 staining index was higher in OSCC without lymph node metastasis (3.59) when compared with OSCC with lymph node metastasis (1.33). There was a statistically significant difference observed in the ALDH1 staining index among three groups (p < 0.05), with highest expression seen in OSCC. Within OPMDs, the ALDH1 staining index was statistically higher in OPMDs with dysplasia as compared to OPMDs without dysplasia. Furthermore, the expression was higher in OPMDs with high-risk dysplasia when compared with low-risk dysplasia, but this was not statistically significant (p = 0.82). In conclusion, The CD44 positive population possesses properties of CSCs in head and neck carcinoma, and continuous shedding could be found after CD44 down-regulation. The present study reports differences in ALDH1 expression between OPMDs with and without dysplasia, dysplastic and non-dysplastic epithelia, and low-risk and high-risk dysplasia. These findings may suggest ALDH1 as a specific marker for dysplasia. CD44 demonstrated a difference in staining index in OSCC without lymph node metastasis versus OSCC with lymph node metastasis. These findings may suggest CD44 as a marker for lymph node metastasis. Both proteins may play key roles in the tumorigenicity of CSCs in OPMDs and OSCC.

Assessment of the Diagnostic Accuracy of Baseline Clinical Examination and Ultrasonographic Imaging for the Detection of Lymph Node Metastasis in Patients With High-risk Cutaneous Squamous Cell Carcinoma of the Head and Neck.

IMPORTANCE: Patients with cutaneous squamous cell carcinoma (SCC) of the head and neck may develop lymph node metastasis; therefore, additional workup of the regional lymph nodes in these patients should be considered. However, there is uncertainty regarding the value of baseline ultrasonographic imaging in addition to clinical examination for the detection of metastasis. OBJECTIVE: To assess the diagnostic accuracy of clinical examination and baseline ultrasonography for the detection of metastasis among patients with high-risk cutaneous SCC of the head and neck and to assess the accuracy of ultrasonography when baseline clinical examination produces negative results. DESIGN, SETTING, AND PARTICIPANTS: This diagnostic study was conducted among a retrospective cohort of 233 patients with 246 high-risk cutaneous SCC tumors of the head and neck. The study included all patients with high-risk cutaneous SCC of the head and neck who received clinical examination and baseline ultrasonographic imaging of their lymph nodes at the Erasmus Medical Center Cancer Institute, a tertiary referral hospital for patients with skin cancer in Rotterdam, the Netherlands, between January 1, 2015, and December 31, 2017. Data were analyzed from October 13, 2020, to September 29, 2021. MAIN OUTCOMES AND MEASURES: Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Fine-needle aspiration cytologic biopsy and 6 months of follow-up per patient were used as the reference standards. RESULTS: Among 233 patients (176 men [75.5%]; median age, 79.1 years [IQR, 71.5-83.7 years]; data on race and ethnicity were not collected) with 246 high-risk cutaneous SCC tumors of the head and neck, 20 metastases were cytologically confirmed at baseline, and 2 metastases were detected during 6 months of follow-up, yielding a 9% metastasis rate. The sensitivity of clinical examination was 50% (95% CI, 28%-72%), and the specificity was 96% (95% CI, 93%-98%). The PPV and NPV were 55% (95% CI, 36%-72%) and 95% (95% CI, 93%-97%), respectively. In the total cohort, ultrasonography had a sensitivity of 91% (95% CI, 71%-99%) and a specificity of 78% (95% CI, 72%-83%), with a PPV of 29% (95% CI, 23%-35%) and an NPV of 99% (95% CI, 96%-100%). In the group of patients with negative results at baseline clinical examination, 9 of 11 metastases were detected by ultrasonography, with 82% sensitivity (95% CI, 48%-98%); specificity was 79% (95% CI, 73%-84%), PPV was 17% (95% CI, 12%-23%), and NPV was 99% (95% CI, 96%-100%). CONCLUSIONS AND RELEVANCE: In this diagnostic study, among a cohort of patients with high-risk cutaneous SCC of the head and neck, baseline ultrasonography was more sensitive than clinical examination alone for the detection of lymph node metastasis. In the setting of a negative result at baseline clinical examination, ultrasonography had high sensitivity for detecting nodal metastases, but this sensitivity should be evaluated against the high rate of false-positive findings.

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.