Role of systemic inflammatory markers (biomarkers) as important prognostic factors for survival in head and neck cancer

Introduction and Aim: Cancer related inflammation is recognized as a critical multifaceted player in tumour initiation and progression. The neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are important markers of systemic inflammatory burden in malignancy. The present retrospective study aimed to evaluate the prognostic value of pre-treatment baseline (NLR) and (PLR) for survival in HNC patients. Materials and Methods: Analysis of data of 257 patients with head and neck cancer treated with definitive therapy over 3.5 yrs. Neutrophil, lymphocyte and platelet counts before treatment of all patients were collected and NLR and PLR were calculated. Results: Median value of NLR and PLR were 3.7 and 170.63 respectively. Receiver operator characteristics (ROC) curve analysis showed the predictive cut-off value of NLR and PLR as 3.9 and 158.3. Univariate analysis using Cox-regression model showed NLR (p < 0.001) and PLR (p = 0.001) significantly influenced the locoregional recurrence free survival (LRRFS) and overall survival (OS). The multivariate analysis showed NLR is the independent prognostic factors influencing LRRFS (p = 0.007) and OS (p = 0.002). Kaplan-Meier survival curve (Log rank test; Chi-square (?2) value) showed OS is significantly influenced by NLR group (LRRFS; ?2 = 23.9 and OS; ?2 = 33.7) and PLR group (LRRFS; ?2 = 11.2 and OS; ?2 = 19.3) in contrast to LRRFS. Conclusion: NLR can be strongly used as biomarker for prognostication for outcome and survival in head neck cancer. However, a well-designed, larger studies with longer follow-up is warranted.

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Venous Thromboembolism Risk in Head and Neck Cancer: Significance of the Preoperative Platelet-to-Lymphocyte Ratio

10.1101/217042 ◽

2017 ◽

Author(s):

Tristan Tham ◽

Lauren Rahman ◽

Christina Persaud ◽

Peter Costantino

Keyword(s):

Risk Factors ◽

Head And Neck Cancer ◽

Venous Thromboembolism ◽

Head And Neck ◽

Neck Cancer ◽

Oral Presentation ◽

Univariate Analysis ◽

Major Surgery ◽

Platelet To Lymphocyte Ratio ◽

Lymphocyte Ratio

Abstract (250 limit)ObjectiveWe aimed to investigate the association between the preoperative platelet-to-lymphocyte ratio (PLR) and venous thromboembolism (VTE) in head and neck cancer (HNC) patients undergoing major surgery.Study DesignRetrospective cohort studySettingAcademic tertiary hospital from 2011 to 2017Subjects and MethodsPatients with confirmed HNC undergoing major surgery were included in this study. The preoperative PLR was recorded for all patients. Known VTE risk factors, including age, sex, smoking, BMI, prior VTE, and anticoagulation were also recorded. Risk factors were screened in univariate analysis using Wilcoxon’s rank sum test and χ2 test (Bonferroni corrected). Significant covariates were subsequently included in a multivariate regression model. Bootstrap techniques were used to obtain credible confidence intervals (CI).ResultsThere were 306 patients enrolled with 7 cases of VTE (6 DVTs and 1 PE). On univariate analysis, length of stay (p = 0.0026), length of surgery (p = 0.0029), and PLR (p = 0.0002) were founded to have significant associations with VTE. A Receiver Operator Characteristic (ROC) curve was constructed, that yielded an AUROC of 0.905 (95% CI: 0.82 - 0.98). Using an optimized cutoff, the multivariate model showed that length of surgery (β 95% CI: 0.0001 - 0.0006; p = 0.0056), and PLR (β 95% CI: 5.3256 - 5.3868; p < 0.0001) were significant independent predictors of VTE.ConclusionThis exploratory pilot study has shown that PLR offers a potentially accurate risk stratification measure as an adjunct to current tools in VTE risk prediction, without additional cost to health systems.Oral PresentationThis data was presented as an oral presentation at the Annual American Academy of Otolaryngology – Head and Neck Surgery (AAO-HNSF) Meeting, 13th September 2017

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Aberrant Epigenetic Regulation in Head and Neck Cancer Due to Distinct EZH2 Overexpression and DNA Hypermethylation

10.20944/preprints201810.0565.v1 ◽

2018 ◽

Author(s):

Daiki Mochizuki ◽

Yuki Misawa ◽

Hideya Kawasaki ◽

Atsushi Imai ◽

Shiori Endo ◽

...

Keyword(s):

Head And Neck Cancer ◽

Rna Interference ◽

Head And Neck ◽

Neck Cancer ◽

Univariate Analysis ◽

Disease Free Survival ◽

Rank Test ◽

Dna Hypermethylation ◽

Free Survival ◽

Disease Free

EZH2 overexpression is associated with tumor proliferation, metastasis, and poor prognosis. Targeting and inhibiting EZH2 may be an effective therapeutic strategy for head and neck squamous cell carcinoma (HNSCC). We previously analyzed EZH2 mRNA expression in a well-characterized dataset of 230 (110 original and 120 validation cohorts) human head and neck cancer samples. This study aimed to investigate the effects of inhibiting EZH2, either via RNA interference or via pharmacotherapy, on HNSCC growth. EZH2 upregulation was significantly correlated with recurrence (P < 0.001) and the methylation index of tumor suppressor genes (P < 0.05). DNMT3A was significantly upregulated upon EZH2 upregulation (P = 0.043). Univariate analysis revealed that EZH2 upregulation was associated with poor disease-free survival (log-rank test, P < 0.001). In multivariate analysis, EZH2 upregulation was evaluated as a significant independent prognostic factor of disease-free survival (hazard ratio: 2.085, 95% confidence interval: 1.390–3.127; P < 0.001). Cells treated with RNA interference and DZNep, an EZH2 inhibitor, showed the most dramatic changes in expression, accompanied with a reduction in the growth and survival of FaDu cells. These findings suggest that EZH2 upregulation is correlated with tumor aggressiveness and adverse patient outcomes in HNSCC. Evaluation of EZH2 expression might help predict the prognosis of HNSCC patients.

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Immunoscore Combining CD8, FoxP3 and CD68 Expression and Distribution Predicts the Prognosis of Head and Neck Cancer Patients

10.21203/rs.3.rs-176581/v1 ◽

2021 ◽

Author(s):

Sonia Furgiuele ◽

Géraldine Descamps ◽

Jérôme R. Lechien ◽

Didier Dequanter ◽

Fabrice Journe ◽

...

Keyword(s):

Multivariate Analysis ◽

Head And Neck Cancer ◽

Head And Neck ◽

Cancer Patients ◽

Neck Cancer ◽

Immune Cell ◽

Cox Regression ◽

Histological Grade ◽

Univariate Analysis ◽

Kaplan Meier

Abstract Purpose: The objective of this study was to assess immune cell infiltrates to develop an immunoscore for prognosis and to investigate its correlation with clinical data of patients with head and neck squamous cell carcinomaMethods: CD8, FoxP3 and CD68 were evaluated by immunohistochemistry in 258 carcinoma samples and counted in stromal and intra-tumoral compartments. Optimal cut-offs were assessed to divide population regarding to survival while the prognostic value was established by using Kaplan-Meier curves and Cox regression models for each immune marker alone and in combination.Results: We found with univariate analysis that infiltration of immune cells in both compartments was predictive for RFS and OS. Multivariate analysis revealed that CD8+ number influenced independently patient prognosis. Additionally, the combination of CD8, FoxP3 and CD68 in an immunoscore provided a significant association with OS (p=0.002, HR=9.87). Such immunoscore stayed significant (p=0.018, HR=11.17) in a multivariate analysis in comparison to tumour stage and histological grade which had lower prognostic values.Conclusion: Altogether, our analysis indicated that an immunoscore including CD8, FoxP3 and CD68 immunostaining was a strong, independent, and significant prognostic marker which could be introduced into the landscape of current tools to improve the clinical management of head and neck cancer patients.

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Aberrant Epigenetic Regulation in Head and Neck Cancer Due to Distinct EZH2 Overexpression and DNA Hypermethylation

International Journal of Molecular Sciences ◽

10.3390/ijms19123707 ◽

2018 ◽

Vol 19 (12) ◽

pp. 3707 ◽

Cited By ~ 8

Author(s):

Daiki Mochizuki ◽

Yuki Misawa ◽

Hideya Kawasaki ◽

Atsushi Imai ◽

Shiori Endo ◽

...

Keyword(s):

Head And Neck Cancer ◽

Rna Interference ◽

Head And Neck ◽

Neck Cancer ◽

Univariate Analysis ◽

Disease Free Survival ◽

Rank Test ◽

Dna Hypermethylation ◽

Free Survival ◽

Disease Free

Enhancer of Zeste homologue 2 (EZH2) overexpression is associated with tumor proliferation, metastasis, and poor prognosis. Targeting and inhibition of EZH2 is a potentially effective therapeutic strategy for head and neck squamous cell carcinoma (HNSCC). We analyzed EZH2 mRNA expression in a well-characterized dataset of 230 (110 original and 120 validation cohorts) human head and neck cancer samples. This study aimed to investigate the effects of inhibiting EZH2, either via RNA interference or via pharmacotherapy, on HNSCC growth. EZH2 upregulation was significantly correlated with recurrence (p < 0.001) and the methylation index of tumor suppressor genes (p < 0.05). DNMT3A was significantly upregulated upon EZH2 upregulation (p = 0.043). Univariate analysis revealed that EZH2 upregulation was associated with poor disease-free survival (log-rank test, p < 0.001). In multivariate analysis, EZH2 upregulation was evaluated as a significant independent prognostic factor of disease-free survival (hazard ratio: 2.085, 95% confidence interval: 1.390–3.127; p < 0.001). Cells treated with RNA interference and DZNep, an EZH2 inhibitor, showed the most dramatic changes in expression, accompanied with a reduction in the growth and survival of FaDu cells. These findings suggest that EZH2 upregulation is correlated with tumor aggressiveness and adverse patient outcomes in HNSCC. Evaluation of EZH2 expression might help predict the prognosis of HNSCC patients.

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Swedish National Multicenter Study on Head and Neck Cancer of Unknown Primary: Prognostic Factors and Impact of Treatment on Survival

International Archives of Otorhinolaryngology ◽

10.1055/s-0040-1712106 ◽

2020 ◽

Author(s):

Lars Axelsson ◽

Erik Holmberg ◽

Jan Nyman ◽

Anders Högmo ◽

Helena Sjödin ◽

...

Keyword(s):

Head And Neck Cancer ◽

Prognostic Factors ◽

Head And Neck ◽

Neck Dissection ◽

Neck Cancer ◽

Multicenter Study ◽

Performance Status ◽

Cancer Of Unknown Primary ◽

Unknown Primary ◽

N Stage

Abstract Introduction Head and neck cancer of unknown primary (HNCUP) is a rare condition whose prognostic factors that are significant for survival vary between studies. No randomized treatment study has been performed thus far, and the optimal treatment is not established. Objective The present study aimed to explore various prognostic factors and compare the two main treatments for HNCUP: neck dissection and (chemo) radiation vs primary (chemo) radiation. Methods A national multicenter study was performed with data from the Swedish Head and Neck Cancer Register (SweHNCR) and from the patients' medical records from 2008 to 2012. Results Two-hundred and sixty HNCUP patients were included. The tumors were HPV-positive in 80%. The overall 5-year survival rate of patients treated with curative intent was 71%. Age (p < 0.001), performance status (p= 0.036), and N stage (p= 0.046) were significant factors for overall survival according to the multivariable analysis. Treatment with neck dissection and (chemo) radiation (122 patients) gave an overall 5-year survival of 73%, and treatment with primary (chemo) radiation (87 patients) gave an overall 5-year survival of 71%, with no significant difference in overall or disease-free survival between the 2 groups. Conclusions Age, performance status, and N stage were significant prognostic factors. Treatment with neck dissection and (chemo) radiation and primary (chemo) radiation gave similar survival outcomes. A randomized treatment study that includes quality of life is needed to establish the optimal treatment.

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Prognosis in Head and Neck Cancer: Importance of Nutritional and Biological Inflammatory Status

Otolaryngology ◽

10.1177/01945998211004592 ◽

2021 ◽

pp. 019459982110045

Author(s):

Nicolas Saroul ◽

Mathilde Puechmaille ◽

Céline Lambert ◽

Achraf Sayed Hassan ◽

Julian Biau ◽

...

Keyword(s):

Head And Neck Cancer ◽

Prognostic Factors ◽

Inflammatory Response ◽

Nutritional Status ◽

Head And Neck ◽

Neck Cancer ◽

Risk Index ◽

Nutritional Risk ◽

Inflammatory Status ◽

Nutritional Risk Index

Objectives To determine the importance of nutritional status, social status, and inflammatory status in the prognosis of head and neck cancer. Study Design Single-center retrospective study of prospectively collected data. Setting Tertiary referral center. Methods Ninety-two consecutive patients newly diagnosed for cancer of the upper aerodigestive tract without metastases were assessed at time of diagnosis for several prognostic factors. Nutritional status was assessed by the nutritional risk index, social status by the EPICES score, and inflammatory status by the systemic inflammatory response index. The primary endpoint was overall survival. Results In multivariable analysis, the main prognostic factors were the TNM classification (hazard ratio [HR] = 3.34, P = .002, for stage T3-4), malnutrition as assessed by the nutritional risk index (HR = 3.64, P = .008, for severe malnutrition), and a systemic inflammatory response index score ≥1.6 (HR = 3.32, P = .02). Social deprivation was not a prognostic factor. Conclusion Prognosis in head and neck cancer is multifactorial; however, malnutrition and inflammation are important factors that are potentially reversible by early intervention.

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