Prognostic and predictive role of soluble programmed death ligand-1 in head and neck cancer

Abstract Objectives The aim of the study was to investigate clinical significance of soluble PD-L1 (sPD-L1) serum level in head and neck cancer and to evaluate its role as a possible prognostic and predictive biomarker. Methods A prospective analysis of sPD-L1 levels in 60 patients diagnosed and treated due to malignant and non-malignant lesions in the region of head and neck was performed in peripheral blood by an ELISA test. Results The range of sPD-L1 in the study group was 0.16-1.63 ng/mL, mean 0.64 ± 0.32. There were no differences in the mean sPD-L1 regarding patients' age, sex, and the localization of the lesion. Statistically significant difference was revealed in the average sPD-L1 level (p = 0.006) depending on the histopathological advancement of the lesions, 0.704 ± 0.349 and 0.512 ± 0.177 respectively in the malignant and benign group. The separate analysis of laryngeal lesions confirmed statistical difference in sPD-L1 (p = 0.002) for the malignant lesions (0.741 ± 0.353) compared with the benign (0.489 ± 0.175). The sPD-L1 level of 0.765 ng/mL or higher, revealed 35% sensitivity and 95.5% specificity for the diagnosis of head and neck malignant lesions (AUC = 0.664, 95% CI 0.529‒0.8, p-value = 0.039). The 1-year DFS was 83.3% in the group of patients with low sPD-L1 levels (< 0.765 ng/mL) and 53.8% in patients with high sPD-L1 (≥0.765 ng/mL). The 2-year OS were 68% and 69.2% respectively in both groups. The log-rank test confirmed statistically significant prognostic value of sPD-L1 level for 1-year DFS (p-value = 0.035). Conclusions sPD-L1 is a promising prognostic and early recurrence predictive biomarker for head and neck cancers, most significantly for laryngeal lesions. Level of evidence 3.

Prognostic and predictive role of soluble programmed death ligand-1 in head and neck cancer.

OBJECTIVES: The aim of the study was to investigate clinical significance of soluble PD-L1 (sPD-L1) serum level in head and neck cancer and to evaluate its role as a possible prognostic and predictive biomarker. METHODS: A prospective analysis of sPD-L1 levels in 60 patients diagnosed and treated due to malignant and non-malignant lesions in the region of head and neck was performed in peripheral blood by an ELISA test. RESULTS: The range of sPD-L1 in the study group was 0.16-1.63ng/mL, mean 0.64±0.32. There were no differences in the mean sPD-L1 regarding patients' age, sex, and the localization of the lesion. Statistically significant difference was revealed in the average sPD-L1 level (p= 0.006) depending on the histopathological advancement of the lesions, 0.704 ± 0.349 and 0.512 ± 0.177 respectively in the malignant and benign group. The separate analysis of laryngeal lesions confirmed statistical difference in sPD-L1 (p= 0.002) for the malignant lesions (0.741 ± 0.353) compared with the benign (0.489 ± 0.175). The sPD-L1 level of 0.765 ng/mL or higher, revealed 35% sensitivity and 95.5% specificity for the diagnosis of head and neck malignant lesions (AUC=0.664, 95% CI 0.529‒0.8, p-value=0.039). The 1-year DFS was 83.3% in the group of patients with low sPD-L1 levels (< 0.765ng/mL) and 53.8% in patients with high sPD-L1 (≥0.765ng/mL). The 2-year OS were 68% and 69.2% respectively in both groups. The log-rank test confirmed statistically significant prognostic value of sPD-L1 level for 1-year DFS (p-value=0.035). CONCLUSIONS: sPD-L1 is a promising prognostic and early recurrence predictive biomarker for head and neck cancers, most significantly for laryngeal lesions.

Correlação de padrões vasculares na imagem de banda estreita com a densidade imuno-histológica de microvasos em lesões de pregas vocais / Correlation of narrow band imaging vascular patterns with immunohistological microvessel density in vocal fold lesions

Resumo Introdução: A microarquitetura dos vasos mucosos e submucosos é crucial para o diagnóstico. A neoangiogênese é um parâmetro biológico confirmado que implica progressão e metástase no câncer de laringe. Objetivo: Investigar a correlação entre as classificações de padrões vasculares por imagem de banda estreita e densidade imuno-histológica de microvasos em diferentes tipos de lesões intraepiteliais da prega vocal. Método: A análise da densidade imuno-histológica de microvasos com o uso de anticorpos CD31 e CD34 foi feita em 77 lesões, inclusive: 20 lesões não displásicas, 20 com displasia de baixo grau, 17 com displasia de alto grau e 20 com câncer invasivo. A avaliação dos padrões vasculares com a imagem de banda estreita, de acordo com as diretrizes de classificação de Ni e da European Laryngological Society, foi feita antes da ressecção cirúrgica. Resultados: O valor médio da densidade imuno-histológica de microvasos com CD31 foi o mais alto para as lesões do Tipo IV de Ni (20,55), enquanto para o padrão longitudinal e perpendicular, de acordo com a classificação da European Laryngological Society, foi de 12,50 e 19,45, respectivamente. O maior valor médio da densidade imuno-histológica de microvasos com CD34 foi identificado nas lesões de Ni Tipo Va (35,43) e nos padrões longitudinal e perpendicular de acordo com a classificação da European Laryngological Society foi de 15,12 e 30,40, respectivamente. Conclusões: As alterações morfológicas microvasculares das lesões laríngeas intraepiteliais observadas na endoscopia por imagem de banda estreita foram positivamente correlacionadas com os índices de angiogênese da avaliação imuno-histológica.

Correlation of narrow band imaging vascular patterns with immunohistological microvessel density in vocal fold lesions.

INTRODUCTION: The microarchitecture of the mucosal and submucosal vessels is crucial for diagnosis of vocal fold lesions. Neo-angiogenesis is a confirmed biological parameter that implicates progression and metastasis in laryngeal cancer. OBJECTIVE: This study investigates the correlation between vascular pattern classifications by narrow band imaging and immunohistological microvessel density in different types of intraepithelial vocal fold lesions. METHODS: Analysis of immunohistological microvessel density using CD31 and CD34 antibodies was performed in 77 lesions including: 20 non-dysplastic lesions, 20 with low-grade dysplasia, 17 with high-grade dysplasia and 20 invasive cancers. The evaluation of vascular patterns with narrow band imaging according to the Ni classification and European Laryngological Society guidelines was performed prior to surgical resection. RESULTS: The mean value of CD31 microvessel density was the highest for Ni Type IV lesions (20.55), whereas for the longitudinal and perpendicular patterns according to the European Laryngological Society classification it was 12.50 and 19.45 respectively. The highest mean value of microvessel density with CD 34 was identified in Ni Type Va (35.43) lesions and in the longitudinal and perpendicular patterns according to the European Laryngological Society classification was 15.12 and 30.40 respectively. CONCLUSIONS: The microvascular morphological changes of intraepithelial laryngeal lesions observed under narrow band imaging endoscopy are positively correlated with angiogenesis indexes of immunohistological evaluation.

Learning curve for endoscopic evaluation of vocal folds lesions with narrow band imaging / Curva de aprendizado para avaliação endoscópica de lesões de pregas vocais com imagem de banda estreita

Abstract Introduction: The endoscopic methods are progressing and becoming more common in routine clinical diagnosis in the field of otorhinolaryngology. Relatively large amount of researches have proved high accuracy of narrow band imaging endoscopy in differentiating benign and malignant lesions within vocal folds. However, little is known about learning curve in narrow band imaging evaluation of laryngeal lesions. Objective: The aim of this study was to determine the learning curve for the narrow band imaging evaluation of vocal folds pathologies depending on the duration of the procedure. Methods: Records of 134 narrow band imaging that were analyzed in terms of the duration of the procedure and the accuracy of diagnosis confirmed by histopathological diagnosis were enrolled in the study. The narrow band imaging examinations were performed sequentially by one investigator over a period of 18 months. Results: The average duration of narrow band imaging recordings was 127.82 s. All 134 studies were divided into subsequent series of several elements. An evident decrease in time of investigation was noticed between 13th and 14th series, when the examinations were divided into 5 elements series, which corresponds to the difference between 65th and 70th subsequent narrow band imaging examination. Parallel groups of 67 examinations were created. Group 1 included 1st to 67th subsequent narrow band imaging examination; Group 2 - 68th to 134th narrow band imaging examinations. The non-parametric U Mann-Whitney test confirmed statistically significant difference between the mean duration of narrow band imaging examination in both groups 160.5 s and 95.1 s, respectively (p < 10−7). Sensitivity and specificity of narrow band imaging examination in the first group were respectively: 83.7% and 76.7%. In the second group, these indicators amounted 98.1% and 80% respectively. Conclusions: A minimum of 65th-70th narrow band imaging examinations are required to reach a plateau phase of the learning process in assessment of glottis lesions. Analysis of learning curves is useful for the development of training programs and determination of a mastery level.

Resumo Introdução: Os métodos endoscópicos estão progredindo e se tornando comuns no diagnóstico clínico de rotina também na otorrinolaringologia. Um número relativamente grande de pesquisas demonstrou alta precisão na endoscopia com imagem de banda estreita na diferenciação de lesões benignas e malignas nas pregas vocais. Entretanto, pouco se sabe sobre a curva de aprendizado na avaliação da de banda estreita de lesões laríngeas. Objetivo: Determinar a curva de aprendizado para a avaliação por imagem de banda estreita das afecções das pregas vocais, de acordo com a duração do procedimento. Método: Foram incluídos no estudo 134 registros de imagens de banda estreita analisadas em termos da duração do procedimento e da acurácia do diagnóstico confirmado pelo diagnóstico histopatológico. Os exames com imagem de banda estreita foram feitos sequencialmente por um investigador por 18 meses. Resultados: A duração média dos registros de imagem de banda estreita foi de 127,82s. Todos os 134 estudos foram divididos em séries subsequentes de vários elementos. Uma evidente diminuição no tempo de investigação foi observada entre as séries 13 e 14, quando os exames foram divididos em séries de cinco elementos, o que corresponde à diferença entre o 65° e 70° exames de imagem de banda estreita subsequentes. Foram criados grupos paralelos de 67 exames. O grupo 1 incluiu o 1° ao 67° exame de imagem de banda estreita subsequente; Grupo 2 - o 68° ao 134° exame de imagem de banda estreita. O teste não paramétrico U de Mann-Whitney confirmou uma diferença estatisticamente significante entre a duração média do exame de imagem de banda estreita em ambos os grupos de 160,5s e 95,1s, respectivamente (p < 10-7). A sensibilidade e especificidade do exame de imagem de banda estreita no primeiro grupo foram, respectivamente: 83,7% e 76,7%. No segundo grupo, esses indicadores foram 98,1% e 80%, respectivamente. Conclusões: Um mínimo de 65 a 70 exames de imagem de banda estreita é necessário para se atingir a fase de estabilização (plateau) do processo de aprendizado na avaliação de lesões de glote. A análise das curvas de aprendizado é útil para o desenvolvimento de programas de treinamento e determinar o n.

Learning curve for endoscopic evaluation of vocal folds lesions with narrow band imaging.

INTRODUCTION: The endoscopic methods are progressing and becoming more common in routine clinical diagnosis in the field of otorhinolaryngology. Relatively large amount of researches have proved high accuracy of narrow band imaging endoscopy in differentiating benign and malignant lesions within vocal folds. However, little is known about learning curve in narrow band imaging evaluation of laryngeal lesions. OBJECTIVE: The aim of this study was to determine the learning curve for the narrow band imaging evaluation of vocal folds pathologies depending on the duration of the procedure. METHODS: Records of 134 narrow band imaging that were analyzed in terms of the duration of the procedure and the accuracy of diagnosis confirmed by histopathological diagnosis were enrolled in the study. The narrow band imaging examinations were performed sequentially by one investigator over a period of 18 months. RESULTS: The average duration of narrow band imaging recordings was 127.82s. All 134 studies were divided into subsequent series of several elements. An evident decrease in time of investigation was noticed between 13th and 14th series, when the examinations were divided into 5 elements series, which corresponds to the difference between 65th and 70th subsequent narrow band imaging examination. Parallel groups of 67 examinations were created. Group 1 included 1st to 67th subsequent narrow band imaging examination; Group 2 - 68th to 134th narrow band imaging examinations. The non-parametric U Mann-Whitney test confirmed statistically significant difference between the mean duration of narrow band imaging examination in both groups 160.5s and 95.1s, respectively (p<10-7). Sensitivity and specificity of narrow band imaging examination in the first group were respectively: 83.7% and 76.7%. In the second group, these indicators amounted 98.1% and 80% respectively. CONCLUSIONS: A minimum of 65th-70th narrow band imaging examinations are required to reach a plateau phase of the learning process in assessment of glottis lesions. Analysis of learning curves is useful for the development of training programs and determination of a mastery level.