Validation of the Histologic Risk Model in a New Cohort of Patients With Head and Neck Squamous Cell Carcinoma

Brandwein-Gensler, Margaret; Smith, Richard V.; Wang, Beverly; Penner, Carla; Theilken, Andrea; Broughel, Darcy; Schiff, Bradley A.; Owen, Randall P.; Smith, Jonathan G.; Sarta, Catherine; Hébert, Tiffany; Nason, Richard W.; Ramer, Marie; DeLacure, Mark D.; Hirsch, David L.; Myssiorek, David; Heller, Keith S.; Prystowsky, Michael B.; Schlecht, Nicolas F.; Negassa, Abdissa

doi:10.1097/pas.0b013e3181d95c37

Cited by 196 publications

(209 citation statements)

References 19 publications

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“…Earlier models by Bryne et al [5,6], Bundgaard et al [18] involved multiparameter histopathological grading system based on pattern of tumor invasion (POI), degree of keratinisation, nuclear pleomorphism and lymphocytic host response for prognosis of oral cancer. Similarly later a novel histologic risk scoring scheme was developed and validated by BrandweinGensler [7,8] which included perineural invasion in addition to Bryne's parameters for decision making and adjuvant treatment in head and neck cancer. Although several such histopathological parameters, grading systems and risk models have been described in literature, none is universally accepted because their clinical utility and reproducibility have not been demonstrated.…”

Section: Discussionmentioning

confidence: 99%

“…Bryne et al had developed a multiparameter histopathological grading system based on pattern of tumor invasion (POI), degree of keratinisation, nuclear pleomorphism and host response for prognosis of oral cancer [5,6]. Similar histologic risk scoring scheme for decision making and adjuvant treatment in head and neck cancer has been developed and validated by Brandwein-Gensler [7,8]. Although several such histopathological parameters and grading systems have been developed and refined in literature, none is universally accepted.…”

Section: Introductionmentioning

confidence: 99%

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Prognostic and Predictive Factors in Gingivo Buccal Complex Squamous Cell Carcinoma: Role of Tumor Budding and Pattern of Invasion

Manjula

Augustine

Selvam³

et al. 2014

Indian J Otolaryngol Head Neck Surg

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Invasive tumor front (ITF) is the deepest three to six cell layers or detached tumor cell groups at the advancing edge of the tumor. Tumor budding is defined as presence of isolated single cells or small cell clusters scattered in the stroma ahead of the ITF and is characteristic of aggressive cancer. It is recognized as an adverse prognostic factor in several human cancers like colorectal, oesophageal, laryngeal cancers and more recently tongue cancers. However, the prognostic value of tumor budding has not been reported in GBCSCC. The aim of our study was to evaluate the role of pattern of invasion (POI) at the ITF, Tumor budding and other clinicopathological parameters in predicting nodal metastases and prognosis in GBCSCC. 33 patients with primary GBCSCC were prospectively evaluated at a tertiary care referral centre. Tumor budding and type of POI was examined in detail and data documented. Statistical analyses were carried out to assess the correlation of tumor budding, POI, and other clinicopathologic parameters (stage, grade of the tumor, tumor thickness, PNI, LVI) with nodal metastases and predict prognosis. Cox regression was used for both Univariate and multivariate analysis. Significant predictors of nodal metastases on Univariate analysis were male gender (p = 0.021), smoking (p = 0.046), Tumor budding (p = 0.014) and diffuse infiltrative/worst POI (p = 0.004), where as on multivariate analysis only worst POI was significantly associated with positive lymph nodes (p = 0.004). Presence of nodal metastases (p = 0.01) and tumor thickness [5 mm (p = 0.009) were independent negative prognostic factors on multivariate analysis. Significant single risk factor predictive of positive lymph nodes is worst POI in GBCSCC. Nodal metastases and [5 mm tumor thickness are independent risk factors for disease free survival.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prognostic and Predictive Factors in Gingivo Buccal Complex Squamous Cell Carcinoma: Role of Tumor Budding and Pattern of Invasion

Manjula

Augustine

Selvam³

et al. 2014

Indian J Otolaryngol Head Neck Surg

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“…It is also significantly associated with poorer outcome as compared to small nerve involvement or no perineural invasion. We have recently completed the first validation study on a cohort of 305 patients with primary HNSCC of the oral cavity, oropharynx, and larynx, from three different institutions [26]. The median follow-up period for all patients was 27 months.…”

Section: Predictors Of Occult Metastases: Tumor Depth Of Invasionmentioning

confidence: 99%

Prognostic Indicators in Head and Neck Oncology Including the New 7th Edition of the AJCC Staging System

Brandwein-Gensler

Smith

2010

Head and Neck Pathol

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“…Weak LHR was assigned for limited response that lacks any lymphoid nodules. We have demonstrated that strong LHR at the interface is associated with improved outcome [1], which is consistent with the concept that enhanced immune surveillance and adaptive immunity have protective impact for cancer patients [3]. Similarly, light microscopic assessment of tumor-infiltrating lymphocytes (categorized as either brisk, non-brisk, or absent) has been demonstrated to be a valuable prognosticator for patients with stage I/II cutaneous melanoma and vertical growth, as it significantly directly correlates with survival [4].…”

Section: Introductionmentioning

confidence: 98%

“…The histological Risk Model significantly correlates with disease progression and survival for patients with primary head and neck squamous cell carcinoma (HNSCC) when adjusted for clinical confounders [1,2]. The model is based on the histological examination of resection specimens for oral and oropharyngeal squamous carcinomas, with the classification of three histological variables: worst pattern of invasion, perineural invasion and lymphocytic host response (LHR).…”

Section: Introductionmentioning

confidence: 99%

Lymphocytic Host Response to Oral Squamous Cell Carcinoma: An Adaptive T-Cell Response at the Tumor Interface

Maleki

Keller

Diaz

et al. 2011

Head and Neck Pathol

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Lymphocytic host response (LHR) in the RiskModel is histologically quantified as the density of lymphocytes at the tumor interface (Brandwein-Gensler in Am J Surg Pathol, 34:676-688, 1; in, Am J Surg Pathol 29:167-178, 2). It is classified as strong, intermediate or weak, and is inversely associated with the risk of decreased time to disease progression. In this study, we test the hypothesis that strong LHR corresponds to a greater degree of adaptive cytotoxic T cell response as compared to moderate LHR. We studied resection specimens of primary oral squamous carcinoma classified as having either strong (n = 16), intermediate (n = 20) or weak (n = 4) LHR. CD20?, CD4?, & CD8? cells were detected by immunohistochemistry and quantified at 409 with a grid; counting the 10 fields with the most lymphocytes at the tumor interface and within tumors. Mean counts/tumor were analyzed by the 2-sided T-test. Statistically significant differences were observed for interface CD8 cells with respect to strong versus moderate LHR, strong versus weak LHR, and moderate versus weak LHR, and tumor infiltrating CD8 cells with respect to strong versus weak LHR. Statistically significant differences were also observed for interface CD4 cells with respect to strong versus weak LHR, and moderate versus weak LHR. Statistically significant differences in interface B cell counts were seen with respect to strong versus weak LHR, and moderate versus weak LHR. Decreased CD8? T cells were significantly associated with higher stage at presentation (P = 0.005); a direct, but nonsignificant correlation was seen between decreased CD8? T cells and decreased survival time.Immune response at the tumor interface correlates with an adaptive T cell response; the degree of cytotoxic CD8? cells infiltrate can distinguish between strong and intermediate LHR at the interface of oral carcinomas.

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Validation of the Histologic Risk Model in a New Cohort of Patients With Head and Neck Squamous Cell Carcinoma

Abstract: We demonstrate significant predictive performance of the risk model in a new cohort of patients with primary HNSCC, adjusted for confounders. Our training experience also supports the feasibility of adapting the risk model in clinical practice.

Cited by 196 publications

References 19 publications

Prognostic and Predictive Factors in Gingivo Buccal Complex Squamous Cell Carcinoma: Role of Tumor Budding and Pattern of Invasion

Prognostic and Predictive Factors in Gingivo Buccal Complex Squamous Cell Carcinoma: Role of Tumor Budding and Pattern of Invasion

Prognostic Indicators in Head and Neck Oncology Including the New 7th Edition of the AJCC Staging System

Lymphocytic Host Response to Oral Squamous Cell Carcinoma: An Adaptive T-Cell Response at the Tumor Interface

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