Stage Squamous Cell Carcinoma Research Articles

COMPARISON OF FEATURES AND OUTCOMES OF VERMILION LIP SCC WITH ORAL AND HEAD AND NECK CUTANEOUS SCC

<h3>Objectives</h3> Comparing features and outcomes of patients with skin, lip, and oral squamous cell carcinoma (SCC) and evaluating restaging lip cancer as skin cancer. <h3>Study Design</h3> All patients surgically treated at our center for vermilion lip SCC, oral SCC, and cutaneous head and neck (HN) SCC between January 2011 and December 2019 were retrospectively reviewed. <h3>Results</h3> 79, 125, and 620 cases were respectively included. Lip and oral SCC were similar regarding tumor diameter (<i>P</i> < .001), depth of invasion (<i>P</i> < .001), surgical margins (<i>P</i> = .01), T stage (<i>P</i> < .001), N stage (<i>P</i> < .001), AJCC stage (<i>P</i> < .001), perineural invasion (<i>P</i> < .001), and vascular invasion (<i>P</i> < .001). In total, 31 lip SCC cases were restaged applying cutaneous HN SCC staging system criteria, with a shift from stages I/II and T1/2 to stages III and T3, respectively. In Kaplan-Meier curves, there was a good distinction among staging curves for oral SCC and cutaneous SCC but not for lip SCC, in both staging models. <h3>Conclusions</h3> There are more similarities between lip SCC and cutaneous HN SCC than oral SCC, although both staging systems failed to distinguish categories in Kaplan-Meier curves.

IDO1 is highly expressed in macrophages of patients in advanced tumour stages of oral squamous cell carcinoma

PurposeStrategies for Indolamine-2,3-dioxygenase 1 (IDO1) inhibition in cancer immunotherapy once produced encouraging results, but failed in clinical trials. Recent evidence indicates that immune cells in the tumour microenvironment, especially macrophages, contribute to immune dysregulation and therefore might play a critical role in drug resistance.MethodsIn this study, we investigated the significance of IDO1 expressing immune cells in primary tumours and corresponding lymph node metastases (LNMs) in oral squamous cell carcinoma (OSCC) by immunohistochemistry. The link between IDO1 and macrophages was investigated by flow cytometry in tumour tissue, healthy adjacent tissue and peripheral blood mononuclear cells (PBMCs). IDO1 activity (measured as Kynurenine/Tryptophan ratio) was assessed by ELISAs.ResultsHigh IDO1 expression in tumour-infiltrating immune cells was significantly correlated with advanced stages [Spearman’s rank correlation (SRC), p = 0.027] and reduced progression-free survival (multivariate Cox regression, p = 0.034). IDO1 was significantly higher expressed in PBMCs of patients in advanced stages than in healthy controls (ANOVA, p < 0.05) and IDO1+ macrophages were more abundant in intratumoural areas than peritumoural (t test, p < 0.001). IDO1 expression in PBMCs was significantly correlated with IDO1 activity in serum (SRC, p < 0.05). IDO1 activity was significantly higher in patients with LNMs (t test, p < 0.01).ConclusionAll in all, IDO1 expressing immune cells, especially macrophages, are more abundant in advanced stages of OSCC and are associated with reduced progression-free survival. Further investigations are needed to explore their role in local and systemic immune response. The IDO1 activity might be a suitable biomarker of metastasis in OSCC patients.

Association of Stathmin (Op18) with TNM Staging and Grading of Oral Squamous Cell Carcinoma and Its Role in Tumor Progression

The purpose of the study was to evaluate the expression of stathmin in different histological grades and tumor, node, metastasis (TNM) staging of Oral carcinoma and various grades of oral dysplasia. The study also aims at observing the stathmin expression with respect to lymph node metastasis. A total of 90 histopathologically confirmed tissue sections were acquired, of which 30 sections of oral dysplasia, 30 oral squamous cell carcinoma (OSCC) and 30 normal tissue sections were stained immunohistochemically with stathmin. The tissue sections, were categorized into different grades of oral dysplasia and OSCC based on histopathological examination. For estimation of stathmin expression, manual examination of 300 cells was done in a minimum of five different areas of tissue section and a mean proportion of positive-stained cells were determined. The statistical analysis of the results was done using ANOVA test. A statistically significant increase in mean staining scores of stathmin in OSCC group compared to dysplasia and control groups. A statistically significant difference was observed in different grades of dysplasia and OSCC groups. Stage III and stage IV OSCC tissue sections showed high intensity staining scores of stathmin expression. An increased expression of stathmin was detected in various grades of OSCC and also with respect to staging of oral cancer. Half the cases of OSCC with lymph node metastasis showed high intensity scores of stathmin. Based on the above facts, stathmin expression was indicated as a potential tool for predicting the outcome of oral cancer patients with lymph node metastasis and its expression was increased in the group with poor prognosis. Any damage/mutation to stathmin can result in defects in cell division resulting in aneuploidy and in turn cancers. In this study, the results showed that there is a differential expression of stathmin in the early and the advanced grades and different TNM stages of OSCC. A high expression of stathmin was observed in all the cases with lymph node metastasis. These observations prove that stathmin has an important role in the progression, tumorigenicity, and prognosis of the oral cancer.

Clinical practicality of reporting cutaneous squamous cell carcinoma risk factors at the time of Mohs surgery.

Multiple high-risk factors have been associated with poor outcomes in cutaneous squamous cell carcinoma, including immunosuppression, poor differentiation, depth, diameter, and perineural invasion. While many of these are included in major staging systems, their measurement and reporting vary considerably in clinical practice. We performed a survey study of fellowship-trained Mohs surgeons to explore their attitudes and practices related to recording squamous cell carcinoma high-risk factors and staging information at the time of Mohs. An anonymous Qualtrics survey of 25 questions was distributed to the American College of Mohs Surgery membership listserv. There were 107 complete surveys (response rate 7.1%), with over 95% of subjects from the United States. Fifty-five percent had been practicing 10years or less, 28% between 11 and 20years, and the remainder greater than 20years. Fifty-seven percent were in private or group practices, and 43% were in academia. Nearly all respondents consistently report tumor recurrence (100%), location (100%), immunosuppression (94%), and diameter (93%). Only 70% grade differentiation for every squamous cell carcinoma case. Sixty-six percent of participants consistently record anatomic depth, while only 2% always or almost always record Breslow depth. Although 96% of respondents almost always or always record perineural invasion, only 34% consistently record nerve diameter. Forty-three percent reported that they never or rarely stage cutaneous squamous cell carcinomas, whereas 43% often, almost always, or always stage. In conclusion, certain high-risk factors, such as differentiation, Breslow depth, and stage, are recorded inconsistently by Mohs surgeons. Several participants commented that they prefer to send a central debulk to dermatopathology to assess staging parameters in all tumors with high-risk features. While this strategy may be useful in some practice settings, Mohs surgeons possess the skills necessary to perform a central debulk analysis themselves at the time of Mohs. Whether performed at the time of Mohs or by dermatopathology, assessing high-risk features and accurately staging cutaneous squamous cell carcinoma is paramount to detecting tumors at higher risk of poor outcomes.

Prognostic factors in oropharyngeal squamous cell carcinoma in the state of São Paulo, Brazil: 10-year follow-up

ObjectiveTo descriptively analyze the epidemiological data, clinical stage, and outcomes of oropharyngeal squamous cell carcinoma in the state of São Paulo, Brazil, and to estimate the influence of clinical stage and treatment type on overall and disease-free survival. MethodsWe retrospectively analyzed epidemiological data from the São Paulo Cancer Center Foundation database relative to patients with oropharyngeal squamous cell carcinoma diagnosed between 2004 and 2014 in the state of São Paulo. Univariate and multivariate Cox regression analyses were performed to assess factors associated with the outcomes. A forward stepwise selection procedure was used. Survival curves were estimated by the Kaplan-Meier method and compared by the Gehan-Breslow-Wilcoxon test. ResultsA total of 8075 individuals with oropharyngeal squamous cell carcinoma were identified. Of these, 86.3% were diagnosed at an advanced stage and 13.7% at an early stage. Only 27.2% of patients were treated surgically, whereas 57.5% were treated medically. Patients undergoing surgery had longer overall survival than those receiving medical treatment in both early- and advanced-stage oropharyngeal squamous cell carcinoma. However, there was no significant difference in disease-free survival between surgical and medical treatment. ConclusionNo significant difference in disease-free survival between medical and surgical treatment suggests similar complete remission rates with both approaches. Patients receiving medical treatment had shorter overall survival, which may be due to complications from chemotherapy and radiotherapy. However, we cannot confirm this relationship based on the data provided by the São Paulo Cancer Center Foundation. Prospective studies are warranted to assess whether the lower overall survival rate in patients receiving medical treatment is secondary to complications from chemotherapy and radiotherapy. Level of evidence2C.

Immunotherapy for the Treatment of Squamous Cell Carcinoma: Potential Benefits and Challenges.

Melanoma and nonmelanoma skin cancers (NMSCs) are recognized as among the most common neoplasms, mostly in white people, with an increasing incidence rate. Among the NMSCs, squamous cell carcinoma (SCC) is the most prevalent malignancy known to affect people with a fair complexion who are exposed to extreme ultraviolet radiation (UVR), have a hereditary predisposition, or are immunosuppressed. There are several extrinsic and intrinsic determinants that contribute to the pathophysiology of the SCC. The therapeutic modalities depend on the SCC stages, from actinic keratosis to late-stage multiple metastases. Standard treatments include surgical excision, radiotherapy, and chemotherapy. As SCC represents a favorable tumor microenvironment with high tumor mutational burden, infiltration of immune cells, and expression of immune checkpoints, the SCC tumors are highly responsive to immunotherapies. Until now, there are three checkpoint inhibitors, cemiplimab, pembrolizumab, and nivolumab, that are approved for the treatment of advanced, recurrent, or metastatic SCC patients in the United States. Immunotherapy possesses significant therapeutic benefits for patients with metastatic or locally advanced tumors not eligible for surgery or radiotherapy to avoid the potential toxicity caused by the chemotherapies. Despite the high tolerability and efficiency, the existence of some challenges has been revealed such as, resistance to immunotherapy, less availability of the biomarkers, and difficulty in appropriate patient selection. This review aims to accumulate evidence regarding the genetic alterations related to SCC, the factors that contribute to the potential benefits of immunotherapy, and the challenges to follow this treatment regime.

Histopathologic Evaluation of Cutaneous Squamous Cell Carcinoma Debulk Specimens Before Mohs Micrographic Surgery and Its Influence on Squamous Cell Carcinoma Staging.

Weinhammer, Annika MD*; Bennett, Daniel D. MD*; Eickhoff, Jens PhD†; Xu, Yaohui G. MD, PhD* Author Information

Real-world data analysis of immune checkpoint inhibitors in stage III-IV adenocarcinoma and squamous cell carcinoma

BackgroundThis study was designed to investigate the clinical application, efficacy, and safety of immune checkpoint inhibitors (ICIs) in the treatment of lung cancer in the real world.MethodsA retrospective, observational analysis was conducted on patients treated with ICIs in four tertiary hospitals in the region from January 2015 to March 2021, to evaluate the clinical efficacy of ICIs single-agent or combined chemotherapy and anti-vascular drugs in the first-line or second-line treatment of patients with lung cancer.ResultsThree hundred and fifteen patients were enrolled in this study. In patients with stage III-IV adenocarcinoma and Squamous cell carcinoma, the objective response rate (ORR) and disease control rate (DCR) were 35.5% (87/245) and 93.5% (229/245), respectively, the median progression-free survival (PFS) was 10.8 months, and the median overall survival (OS) was not reached. A total of 132 patients received ICIs as the first-line treatment, the median treatment cycle was 8 cycles (2–20 cycles), the short-term efficacy ORR was 38.6%, DCR was 93.9%, and the median PFS was 11.4 months. One hundred thirteen patients received ICIs treatment as second-line treatment, the median treatment cycle was five cycles (2–10 cycles), the short-term efficacy ORR was 31.9%, DCR was 92.9%, and the median PFS was 10.0 months. There were no statistically significant differences in ORR, DCR, or median PFS with ICIs as the first-line treatment compared with the second-line treatment(P > 0.05). The results of subgroup analysis showed that Eastern Cooperative Oncology Group performance status (ECOG PS), epidermal growth factor receptor (EGFR) mutation status, pathological type and number of treatment lines were not correlated with median PFS(P > 0.05). However, there were statistically significant differences in programmed death-ligand 1(PD-L1) expression, corticosteroid interference, and antibiotic (Abx) treatment among all groups (P < 0.05). In terms of safety, the overall incidence of adverse reactions in 315 patients was 62.5%, and the incidence of immune-related adverse events (irAEs) was 13.7%. Grade 1–2 and 3–4 incidence of adverse events were 34.9 and 27.65%, respectively. There were four patients who experienced fatal irAEs, two cases were liver damage leading to liver failure, one case was immune related pneumonia, and one case was immune related myocarditis.ConclusionIn the real world, ICIs has a good effect on patients with lung cancer and significantly improves ORR and PFS.

Comparison Between Preoperative Inflammation Based Scores and TNM Staging in Patients with Oral Cancer

Abstract Background: India, one of the countries with the highest incidence of oral cancer, accounting for 30% of all new oral cancer cases in the world. Therefore, strong diagnostic markers are critical for the diagnosis and survival of patients suffering from oral cancer. Based on this relationship between inflammation and cancer progression, several inflammation-based scores have been demonstrated to have diagnostic and prognostic value in many types of malignant solid tumours. Objective: To compare the correlation between systemic inflammation based prognostic scores and tumour node metastasis (TNM) stage in patients undergoing oral cancer treatment. Methods: The inflammation-based scores were calculated for 120 patients with oral squamous cell carcinoma divided into four groups based on TNM staging. Neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), tumour size, nodes involved were analysed. Statistics were performed to compare the diagnostic value of the selected scores and TNM stage. Results: This current study compares 30 patients in each stage of TNM stages 1,2,3 and 4. The mean tumour size is 1.8 x 1.41, 3.23x2.28, 2.85x2.43 and 3.78x 3.06 in stage 1,2,3 and 4 respectively. The largest lymph node measurable was 1.33x1.36 in stage 3 and 1.84x 1.38 in stage 4. The number of lymph nodes involved in stage 3 are 1.1 and 2.82 in stage 4. The mean NLR in stage 1,2,3 and 4 were 2.68, 2.72, 3.17 and 3.68 respectively. The mean PLR in stage 1, 2,3 and 4 were 106.4, 117.8, 108.2 and 182.2 respectively. Conclusion: The present study indicates that elevated NLR and PLR values are associated with advanced stages of TNM staging for Oral squamous cell carcinoma.

The minimum number of examined lymph nodes for accurate nodal staging and optimal survival of stage T1-2 esophageal squamous cell carcinoma: A retrospective multicenter cohort with SEER database validation

BackgroundThe extent of lymphadenectomy during esophagectomy remains controversial for patients with T1-2 ESCC. The aim of this study was to identify the minimum number of examined lymph node (ELN) for accurate nodal staging and overall survival (OS) of patients with T1-2 esophageal squamous cell carcinoma (ESCC). Materials and methodsPatients with T1-2 ESCC from three institutes between January 2011 and December 2020 were retrospectively reviewed. The associations of ELN count with nodal migration and OS were evaluated using multivariable models, and visualized by using locally weighted scatterplot smoothing (LOWESS). Chow test was used to determine the structural breakpoints of ELN count. External validation in the SEER database was performed. ResultsIn total, 1537 patients were included. Increased ELNs was associated with an increased likelihood of having positive nodal disease and incremental OS. The minimum numbers of ELNs for accurate nodal staging and optimal survival were 14 and 18 with validation in the SEER database (n = 519), respectively. The prognostic prediction ability of N stage was improved in the group with ≥14 ELNs compared with those with fewer ELNs (iAUC, 0.70 (95%CI 0.66–0.74) versus 0.61(95%CI 0.57–0.65)). The higher prognostic value was found for patients with ≥18 ELNs than those with <18 ELNs (iAUC, 0.78 (95%CI 0.74–0.82) versus 0.73 (95%CI 0.7–0.77)). ConclusionThe minimum numbers of ELNs for accurate nodal staging and optimal survival of stage T1-2 ESCC patients were 14 and 18, respectively.

To analyse the mitotic and keratinisation correlation with bcl-2 expression in varying grades of oral epithelial dysplasia and squamous cell carcinoma.

The bcl-2 proto-oncogene was discovered at the chromosomal breakpoint of t (14;18) found in follicular lymphoma. Histological changes in dysplasia are considered the earliest signs preceding the progression into squamous cell carcinoma. Serving as critical regulators of apoptotic pathways, bcl-2 prohibits programmed cell death and subsequently assists in uncontrolled neoplastic growth. This study included 48 cases, eight each of epithelial dysplasia and squamous cell carcinoma. Immunohistochemical staining using bcl-2 antibody was performed and different histological parameters were correlated with bcl-2 positive cells in all the cases. All 3 μm thick sections were stained with bcl-2 antibody. After identifying four representative fields at 40x, their images were obtained for assessment of bcl-2 labelled cells and their intensity along with different histological parameters in all the cases. The differences between different histological parameters were analysed using the Anova test, post hoc test and Bonferroni test. Pearson's Chi-square test was carried out to determine the level of correlation between the bcl-2 positive cells in both epithelial dysplasia and oral squamous cell carcinoma cases. Sequential increase in the bcl-2 expression was observed in increasing grades of epithelial dysplasia, whereas bcl-2 expression was significantly decreased in ascending stages of squamous cell carcinoma thus, suggesting a possible role of bcl-2 in disease progression from premalignancy to malignancy.

The predictive value of depth of invasion and tumor size on risk of neck node metastasis in squamous cell carcinoma of the oral cavity: A prospective study.

Tumor depth is a reliable parameter to predict nodal metastasis in oral cancers; therefore, the authors embarked upon a prospective observational study to define the relationship between the tumor depth and the risk of cervical lymph node involvement as well to determine the optimal tumor depth cutoff point for nodal metastasis. The aim was to study the predictive value of depth of invasion (DOI) and tumor size on risk of cervical node metastasis in squamous cell carcinoma of the oral cavity. Biopsy-proven Stage I-Stage III oral cavity squamous cell carcinoma patients were included in this prospective, observational study. Various histopathological characteristics (DOI, tumor size, lympho-vascular invasion [LVI], perineural spread, and grade of differentiation) were analyzed to predict the cervical node metastasis. The impact of the clinical and histopathological parameters of primary tumor on cervical lymph node metastasis was analyzed by univariate as well as multivariate logistic regression analyses using NCSS 12 version 12.0.5 statistical software. The independent predictors of cervical lymph node metastasis were DOI (P = 0.0014) and LVI (P = 0.0414). The incidence of cervical metastasis increased markedly when the DOI was over 5 mm, and it was a statistically significant (P < 0001) association. DOI is a significant predictor of cervical nodal metastasis and tumor depth 5 mm can be considered as a cutoff value in staging and management of early oral squamous cell carcinoma.

P49: A comparative analysis of cutaneous squamous cell carcinoma staging before and during the COVID‐19 pandemic.

P49: A comparative analysis of cutaneous squamous cell carcinoma staging before and during the COVID‐19 pandemic.

Outcomes of Oral and Oropharyngeal Squamous Cell Carcinoma Related to Healthcare Coverage: A Retrospective Cohort Study in Brazil

We investigated the differences in prognosis according to the type of healthcare coverage of patients with oral and oropharyngeal squamous cell carcinoma (OOSCC). This study included 875 medical records. Patients covered by the publicly funded Unified Health System (SUS) had a low educational level, with advanced T stage and delayed treatment initiation. Multivariate analyses revealed an association between T stage (p = .035) and poor prognosis in oral squamous cell carcinoma, and age (p = .029) in oropharyngeal squamous cell carcinoma. Surgical treatment (p = .036) and marital status (p = .015) were considered predictors of better prognosis in OOSCC. Exclusive SUS-dependency can be considered an indirect prognostic factor for OOSCC.

The Apoptotic and Antiproliferative Effects of Capsaicin in the Developmental Stages of Oral Squamous Cell Carcinoma Induced in Hamsters.

Background and aimSeveral epidemiological and experimental studies have approve that the vegetarian diet has an anticancer effect. Capsaicin is the active botanical ingredient found in red chili peppers. While the data strongly argue for the significant anticancer benefits of capsaicin, nevertheless, much information is required to shed light on the anticancer molecular mechanisms to improve knowledge and suggest potential therapeutic mechanisms for the use of capsaicin against cancer. This study aimed to investigate the effect of capsaicin on the rate of cell division and apoptosis in the development of oral squamous cell carcinoma induced in the buccal pouch of hamsters.Materials and methodsThe sample consisted of two groups; the first group consisted of 20 hamsters with the application of carcinogenic 7,12-dimethylbenz(a)anthracene (DMBA) in the buccal pouch (the control group) and the second group (the study group) also consisted of 20 hamsters with the application of DMBA in alternatively with capsaicin. Tissue biopsies were taken from experimental animals after sacrificing. The samples were immunostained for the detection of Ki-67 and Bcl-2 proteins.ResultsImmunohistochemical staining by monoclonal antibody to Ki-67 and Bcl-2 in the study group showed lower expression at all stages of oral cancer development compared with their expression in the control group. After performing the one-way (ANOVA) test, we found statistically significant differences by comparing the expression degree of Ki-67 and Bcl-2 proteins in both study groups, where the p-value was less than 0.05.ConclusionWe conclude from the data of our study that capsaicin has an anti-cancer role in oral squamous cell carcinoma if applied in the digestive tract of experimental animals by inhibiting the proliferation of cancer cells and activating apoptosis in them.

Comprehensive analysis reveals COPB2 and RYK associated with tumor stages of larynx squamous cell carcinoma

BackgroundLaryngeal squamous cell carcinoma (LSCC) is one of the highly aggressive malignancy types of head and neck squamous cell carcinomas; genes involved in the development of LSCC still need exploration.MethodsWe downloaded expression profiles of 96 (85 in advanced stage and 11 in early stage) LSCC patients from TCGA-HNSC. Function enrichment and protein-protein interactions of genes in significant modules were conducted. Univariate and multivariate Cox regression analyses were performed to explore potential prognostic biomarkers for LSCC. The expression levels of genes at different stages were compared and visualized via boxplots. Immune infiltration was examined by the CIBERSORTx web-based tool and depicted with ggplot2. Gene set enrichment analysis (GSEA) was utilized to analyze functional enrichment terms and pathways. Immunohistochemical staining (IHC) was used to verify the expression of genes in the LSCC samples.ResultsWe identified 25 modules, including 3 modules significantly related to tumor stages of LSCC via weighted gene co-expression network analysis (WGCNA). UIMC1, NPM1, and DCTN4 in the module ‘cyan’, TARS in the module ‘darkorange’, and COPB2 and RYK in the module ‘lightyellow’ showed statistically significant relation to overall survival. The expression of COPB2, DCTN4, RYK, TARS, and UIMC1 indicated association with the change of fraction of immune cells in LSCC patients; two genes, COPB2 and RYK, indicated different expression in various tumor stages of LSCC. Finally, COPB2 and RYK showed high-expression in tumor tissues of advanced LSCC patients.ConclusionsOur study provided a potential perceptive in analyzing progression of LSCC cells and exploring prognostic genes.

18F]FDG-PET/CT improves the detection of synchronous malignancies at primary staging of oral squamous cell carcinoma – A retrospective study

The purpose of this study was to show the non-inferiority of [18F]FDG-PET/CT compared with panendoscopy with regards to secondary malignancies of the UADT, and to evaluate the diagnostic performance of PET/CT for detecting synchronous malignancies.Patients with newly diagnosed OSCC and both panendoscopy and [18F]FDG-PET/CT at primary staging were enrolled in this retrospective study. The accuracy in detecting synchronous malignancies was assessed for both modalities, and their diagnostic measures for the detection of malignancies within the UADT were compared. Histopathological analysis and clinical follow-up served as reference standards.In total, 182 patients were enrolled in this study. Eighteen patients (9.9%) had in total 22 synchronous malignancies, of which eight were located within the UADT. [18F]FDG-PET/CT detected all malignancies within the whole body (sensitivity: 100%) and yielded false-positive results in four cases (specificity: 97.6%). Sensitivity ([18F]FDG-PET/CT: 100% vs panendoscopy: 87.5%), specificity (99.4% vs 100%), negative predictive value (100% vs 99.4%), and positive predictive value (88.9% vs 100%) for detecting secondary UADT malignancies did not differ between modalities (all p = 0.32).Within the limitations of the study it seems that [18F]FDG-PET/CT detects synchronous malignancies of the UADT with an accuracy comparable to panendoscopy, and enables highly sensitive whole-body tumor screening in patients with newly diagnosed OSCC. This could be a relevant factor for therapeutic decision making in clinical routine.

Abstract 6322: Dynamic, stage-course protein interaction network using high power CpG sites in head and neck squamous cell carcinoma

Abstract Head and neck cancer is the most incident and prevalent cancer in men in South Asian countries, especially Pakistan. Prediction of pathological stages of cancer can play a critical role in early diagnosis and personalized medicine. This project ventures into the prediction of different stages of head and neck squamous cell carcinoma (HNSCC) using prioritized DNA methylation patterns. DNA methylation profiles for each HNSCC stage (stage-I-IV) were used to extensively analyze 485,577 methylation CpG sites and prioritize them on the basis of the highest predictive power using a wrapper-based feature selection method, along with different classification models. We identified 68 high-power methylation sites which predicted the pathological stage of HNSCC samples with 90.62% accuracy using a Random Forest classifier. We set out to construct a protein-protein interaction network for the proteins encoded by the 67 genes associated with these sites to study its network topology and also undertook enrichment analysis of nodes in their immediate neighborhood for GO and KEGG Pathway annotations revealing their role in cancer-related pathways, cell differentiation, signal transduction, metabolic and biosynthetic processes. With information on the predictive power of each of the 67 genes in each HNSCC stage, we unveil a dynamic stage-course network for HNSCC that evolves over the course of the four cancer stages. We intend to further study these genes in light of functional datasets from CRISPR, RNAi, drug screens for their putative role in HNSCC initiation and/or progression. Citation Format: Arsalan Riaz, Faisal Khan. Dynamic, stage-course protein interaction network using high power CpG sites in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6322.

18F-Fluorodeoxyglucose Positron Emission Tomography of Head and Neck Cancer: Location and HPV Specific Parameters for Potential Treatment Individualization.

Purpose18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is utilized for staging and treatment planning of head and neck squamous cell carcinomas (HNSCC). Some older publications on the prognostic relevance showed inconclusive results, most probably due to small study sizes. This study evaluates the prognostic and potentially predictive value of FDG-PET in a large multi-center analysis.MethodsOriginal analysis of individual FDG-PET and patient data from 16 international centers (8 institutional datasets, 8 public repositories) with 1104 patients. All patients received curative intent radiotherapy/chemoradiation (CRT) and pre-treatment FDG-PET imaging. Primary tumors were semi-automatically delineated for calculation of SUVmax, SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Cox regression analyses were performed for event-free survival (EFS), overall survival (OS), loco-regional control (LRC) and freedom from distant metastases (FFDM).ResultsFDG-PET parameters were associated with patient outcome in the whole cohort regarding clinical endpoints (EFS, OS, LRC, FFDM), in uni- and multivariate Cox regression analyses. Several previously published cut-off values were successfully validated. Subgroup analyses identified tumor- and human papillomavirus (HPV) specific parameters. In HPV positive oropharynx cancer (OPC) SUVmax was well suited to identify patients with excellent LRC for organ preservation. Patients with SUVmax of 14 or less were unlikely to develop loco-regional recurrence after definitive CRT. In contrast FDG PET parameters deliver only limited prognostic information in laryngeal cancer.ConclusionFDG-PET parameters bear considerable prognostic value in HNSCC and potential predictive value in subgroups of patients, especially regarding treatment de-intensification and organ-preservation. The potential predictive value needs further validation in appropriate control groups. Further research on advanced imaging approaches including radiomics or artificial intelligence methods should implement the identified cut-off values as benchmark routine imaging parameters.

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 purposeTreatment 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.MethodsA 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.ResultsIn 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.ConclusionF-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.