Improving Risk Stratification of Early Oral Tongue Cancer with TNM-Immune (TNM-I) Staging System

Although patients with early-stage oral tongue squamous cell carcinoma (OTSCC) show better survival than those with advanced disease, there is still a number of early-stage cases who will suffer from recurrence, cancer-related mortality and worse overall survival. Incorporation of an immune descriptive factor in the staging system can aid in improving risk assessment of early OTSCC. A total of 290 cases of early-stage OTSCC re-classified according to the American Joint Committee on Cancer (AJCC 8) staging were included in this study. Scores of tumor-infiltrating lymphocytes (TILs) were divided as low or high and incorporated in TNM AJCC 8 to form our proposed TNM-Immune system. Using AJCC 8, there were no significant differences in survival between T1 and T2 tumors (p > 0.05). Our proposed TNM-Immune staging system allowed for significant discrimination in risk between tumors of T1N0M0-Immune vs. T2N0M0-Immune. The latter associated with a worse overall survival with hazard ratio (HR) of 2.87 (95% CI 1.92–4.28; p < 0.001); HR of 2.41 (95% CI 1.26–4.60; p = 0.008) for disease-specific survival; and HR of 1.97 (95% CI 1.13–3.43; p = 0.017) for disease-free survival. The TNM-Immune staging system showed a powerful ability to identify cases with worse survival. The immune response is an important player which can be assessed by evaluating TILs, and it can be implemented in the staging criteria of early OTSCC. TNM-Immune staging forms a step towards a more personalized classification of early OTSCC.

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Assessment of Tumor-infiltrating Lymphocytes Predicts the Behavior of Early-stage Oral Tongue Cancer

The American Journal of Surgical Pathology ◽

10.1097/pas.0000000000001323 ◽

2019 ◽

Vol 43 (10) ◽

pp. 1392-1396 ◽

Cited By ~ 4

Author(s):

Ilkka Heikkinen ◽

Ibrahim O. Bello ◽

Awais Wahab ◽

Jaana Hagström ◽

Caj Haglund ◽

...

Keyword(s):

Tongue Cancer ◽

Early Stage ◽

Tumor Infiltrating Lymphocytes ◽

Oral Tongue ◽

Oral Tongue Cancer ◽

Infiltrating Lymphocytes

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Stromal categorization in early oral tongue cancer

Virchows Archiv ◽

10.1007/s00428-020-02930-5 ◽

2020 ◽

Author(s):

Alhadi Almangush ◽

Ibrahim O. Bello ◽

Ilkka Heikkinen ◽

Jaana Hagström ◽

Caj Haglund ◽

...

Keyword(s):

Prognostic Value ◽

Tongue Cancer ◽

Disease Free Survival ◽

Tumor Infiltrating Lymphocytes ◽

High Rate ◽

Cancer Center ◽

Oral Tongue ◽

University Hospitals ◽

Desmoplastic Reaction ◽

Infiltrating Lymphocytes

Abstract Stromal categorization has been used to classify many epithelial cancer types. We assessed the desmoplastic reaction and compared its significance with other stromal characteristics in early (cT1-2N0) oral tongue squamous cell carcinoma (OTSCC). In this multi-institutional study, we included 308 cases treated for early OTSCC at five Finnish university hospitals or at the A.C. Camargo Cancer Center in São Paulo, Brazil. The desmoplastic reaction was classified as immature, intermediate, or mature based on the amount of hyalinized keloid-like collagen and myxoid stroma. We compared the prognostic value of the desmoplastic reaction with a stromal grading system based on tumor-stroma ratio and stromal tumor-infiltrating lymphocytes. We found that a high amount of stroma with a weak infiltration of lymphocytes was associated statistically significantly with a worse disease-free survival with a hazard ratio (HR) of 2.68 (95% CI 1.26–5.69), worse overall survival (HR 2.95, 95% CI 1.69–5.15), and poor disease-specific survival (HR 2.66, 95% CI 1.11–6.33). Tumors having a high amount of stroma with a weak infiltration of lymphocytes were also significantly associated with a high rate of local recurrence (HR 4.13, 95% CI 1.67–10.24), but no significant association was found with lymph node metastasis (HR 1.27, 95% CI 0.37–4.35). Categorization of the stroma based on desmoplastic reaction (immature, intermediate, mature) showed a low prognostic value for early OTSCC in all survival analyses (P > 0.05). In conclusion, categorization of the stroma based on the amount of stroma and its infiltrating lymphocytes shows clinical relevance in early OTSCC superior to categorization based on the maturity of stroma.

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The updated AJCC/TNM staging system (8th edition) for oral tongue cancer

Translational Cancer Research ◽

10.21037/tcr.2019.01.02 ◽

2019 ◽

Vol 8 (S2) ◽

pp. S164-S166

Author(s):

Kyubo Kim ◽

Dong Jin Lee

Keyword(s):

Tongue Cancer ◽

Staging System ◽

Tnm Staging ◽

Oral Tongue ◽

Tnm Staging System ◽

Oral Tongue Cancer ◽

8Th Edition

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Tumor-Infiltrating Lymphocytes and Prognosis: A Pooled Individual Patient Analysis of Early-Stage Triple-Negative Breast Cancers

Journal of Clinical Oncology ◽

10.1200/jco.18.01010 ◽

2019 ◽

Vol 37 (7) ◽

pp. 559-569 ◽

Cited By ~ 122

Author(s):

Sherene Loi ◽

Damien Drubay ◽

Sylvia Adams ◽

Giancarlo Pruneri ◽

Prudence A. Francis ◽

...

Keyword(s):

Triple Negative ◽

Early Stage ◽

Disease Free Survival ◽

Tumor Infiltrating Lymphocytes ◽

Cox Proportional Hazards ◽

Prognostic Information ◽

Free Survival ◽

Node Negative ◽

Infiltrating Lymphocytes ◽

Disease Free

Purpose The aim of the current study was to conduct a pooled analysis of studies that have investigated the prognostic value of tumor-infiltrating lymphocytes (TILs) in early-stage triple negative breast cancer (TNBC). Methods Participating studies had evaluated the percentage infiltration of stromally located TILs (sTILs) that were quantified in the same manner in patient diagnostic samples of early-stage TNBC treated with anthracycline-based chemotherapy with or without taxanes. Cox proportional hazards regression models stratified by trial were used for invasive disease-free survival (iDFS; primary end point), distant disease-free survival (D-DFS), and overall survival (OS), fitting sTILs as a continuous variable adjusted for clinicopathologic factors. Results We collected individual data from 2,148 patients from nine studies. Average age was 50 years (range, 22 to 85 years), and 33% of patients were node negative. The average value of sTILs was 23% (standard deviation, 20%), and 77% of patients had 1% or more sTILs. sTILs were significantly lower with older age ( P = .001), larger tumor size ( P = .01), more nodal involvement ( P = .02), and lower histologic grade ( P = .001). A total of 736 iDFS and 548 D-DFS events and 533 deaths were observed. In the multivariable model, sTILs added significant independent prognostic information for all end points (likelihood ratio χ2, 48.9 iDFS; P < .001; χ2, 55.8 D-DFS; P < .001; χ2, 48.5 OS; P < .001). Each 10% increment in sTILs corresponded to an iDFS hazard ratio of 0.87 (95% CI, 0.83 to 0.91) for iDFS, 0.83 (95% CI, 0.79 to 0.88) for D-DFS, and 0.84 (95% CI, 0.79 to 0.89) for OS. In node-negative patients with sTILs ≥ 30%, 3-year iDFS was 92% (95% CI, 89% to 98%), D-DFS was 97% (95% CI, 95% to 99%), and OS was 99% (95% CI, 97% to 100%). Conclusion This pooled data analysis confirms the strong prognostic role of sTILs in early-stage TNBC and excellent survival of patients with high sTILs after adjuvant chemotherapy and supports the integration of sTILs in a clinicopathologic prognostic model for patients with TNBC. This model can be found at www.tilsinbreastcancer.org .

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