scholarly journals Evaluation Challenges in the Validation of B7-H3 as Oral Tongue Cancer Prognosticator

2020 ◽  
Author(s):  
Meri Sieviläinen ◽  
Anna Maria Wirsing ◽  
Aini Hyytiäinen ◽  
Rabeia Almahmoudi ◽  
Priscila Rodrigues ◽  
...  
Keyword(s):  
Tongue Cancer ◽  
Univariate Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Immune Checkpoints ◽  
Oral Tongue ◽  
Scoring Method ◽  
Full Cohort ◽  
Kaplan Meier ◽  
Tumor Immunogenicity ◽  
Disease Specific

Abstract B7-H3 was the only molecule identified with prognostic potential from a recent systematic review of the prognostic value of immune checkpoints in oral cancer. We aimed to validate this finding in a multicenter international cohort. We retrospectively retrieved 323 oral tongue squamous cell carcinoma (OTSCC) samples from three different countries (Brazil, Finland, and Norway) for immunostaining and scoring for B7-H3. We evaluated tumor immunogenicity by analyzing the amount of tumor-infiltrating lymphocytes and divided the tumors into immune hot and cold. To increase the reliability of the results, both digital and manual visual scoring were used. Survival curves were constructed based on the Kaplan-Meier method, and the Cox proportional hazard model was utilized for univariate and multivariate survival analysis. B7-H3 expression was not significantly associated with overall or disease-specific survival in the whole OTSCC cohort. When divided into immune hot and cold tumors, high B7-H3 expression was significantly associated with poor disease-specific and overall survival in the immune hot group, depending on the scoring method and the country of the cohort. This was achieved only in the univariate analysis. In conclusion, B7-H3 was a negative prognosticator for OTSCC patient survival in the subgroup of immune hot tumors, and was not validated as a prognosticator in the full cohort. Our findings suggest that the immune activity of the tumor should be considered when testing immune checkpoints as biomarkers.

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

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3235
Author(s):  
Alhadi Almangush ◽  
Ibrahim O. Bello ◽  
Ilkka Heikkinen ◽  
Jaana Hagström ◽  
Caj Haglund ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tongue Cancer ◽  
Early Stage ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Staging System ◽  
Oral Tongue ◽  
Oral Tongue Cancer ◽  
Important Player ◽  
Infiltrating Lymphocytes

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.

scholarly journals Stromal categorization in early oral tongue cancer

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.

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

2019 ◽  
Vol 43 (10) ◽  
pp. 1392-1396 ◽  
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

scholarly journals Biopsy Quality is Essential for Preoperative Prognostication in Oral Tongue Cancer

2020 ◽  
Author(s):  
Ibrahim O Bello ◽  
Pia M. Wennerstrand ◽  
Ilida Suleymanova ◽  
Maria Siponen ◽  
Ahmed Qannam ◽  
...  
Keyword(s):  
Light Microscopy ◽  
Tongue Cancer ◽  
Saudi Arabian ◽  
Tumor Infiltrating Lymphocytes ◽  
Tumor Stroma ◽  
Depth Of Invasion ◽  
Oral Tongue ◽  
Prognostic Information ◽  
Prognostic Features ◽  
Digital Assessment

Abstract Background: A role for incisional biopsy in preoperative prognostication is increasingly being advocated in oral tongue squamous cell carcinomas (OTSCC). Biopsies at two locations were compared and prognostic factors in biopsies and their corresponding resections were evaluated. Methods: A total of 138 OTSCC biopsy slides from Finland and Saudi-Arabia were compared for size (horizontal and vertical) and invasive front. The Finnish cases were assessed for tumor stroma ratio (TSR) and tumor-infiltrating lymphocytes (TILs) using light microscopy and digital image analysis assessment and compared. Furthermore, TSR, TILs, and previously analyzed budding and depth of invasion (BD) score in biopsies were compared with their evaluation in the corresponding resections. Results: Finnish biopsies were deeper than Saudi-Arabian biopsies (59% versus 42%) while Saudi-Arabian biopsies were wider (98% versus 76%). Invasion fronts were more readily assessable in Finnish biopsies (72% versus 40%). There was 86.8% agreement between TSR and 75% agreement between TIL evaluation using light microscopy and digital assessment. Significant agreement was obtained on comparing the TSR (P=0.04) and BD (P<0.001) values in biopsies and resections. Conclusions: Biopsies of ≥5 mm depth from representative OTSCC areas are essential for prognostic information. Clinical pathologists are advised to assess BD score and TSR for prognostic features in such biopsies.

scholarly journals Clinical Significance of Tumor Microenvironment in Acral Melanoma: A Large Single-Institution Study of Caucasians

2021 ◽  
Vol 10 (7) ◽  
pp. 1452
Author(s):  
Aneta Maria Borkowska ◽  
Anna Szumera-Ciećkiewicz ◽  
Maria Chraszczewska ◽  
Kamil Sokół ◽  
Tomasz Goryń ◽  
...  
Keyword(s):  
Univariate Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Lymph Node Status ◽  
Survival Outcomes ◽  
Acral Melanoma ◽  
Kaplan Meier ◽  
Programmed Death ◽  
Impact On Survival ◽  
Melanoma Patients ◽  
Infiltrating Lymphocytes

Background: The presence of tumor-infiltrating lymphocytes (TILs) in many studies is associated with a better prognosis in melanoma patients. Programmed death-ligand 1 (PD-L1) expression has a significant value in predicting several cancers, but its role in melanoma remains ambiguous. The study aims to report a comprehensive analysis of TILs characteristics and their impact on survival in primary acral melanoma (AM). Methods: Clinical and pathological features and survival outcomes were investigated in 70 patients with AM. Immunohistochemical quantitative analysis of TILs, including expression of CD4, CD8, FOXP3, PD-1, and PD-L1, on melanoma cells was performed. Results: Kaplan-Meier analysis showed significant differences in overall survival (OS) for CD4+ (p = 0.021), CD8+ (p = 0.037), FOXP3+ (p = 0.007), and TILs density (p = 0.043). In univariate analysis of immunohistochemical features, FOXP3, CD4, CD8, PD-1, and Melanoma Institute of Australia (MIA) grading TILs (grade, density, and distribution) were correlated with survival. The higher density of FOXP3-positive cells was an independent factor associated with better survival. Conclusions: High TILs content (classed as brisk Clark scale and marked/diffuse TILs MIA grade) regardless of its immunophenotype was associated with better survival outcomes in AM. PD-L1 expression on tumor cells did not influence OS and was independent of clinical and pathological characteristics. We demonstrated that TILs are significant biomarkers in sentinel lymph node status prediction.

scholarly journals Confirmed Angiosarcoma: Prognostic Factors and Outcome in 50 Prospectively Followed Patients

Sarcoma ◽  
2000 ◽  
Vol 4 (4) ◽  
pp. 173-177 ◽  
Author(s):  
N. J. Espat ◽  
J. J. Lewis ◽  
J. M. Woodruff ◽  
C. Antonescu ◽  
J. Xia ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Metastatic Disease ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Rank Test ◽  
Disease Specific Survival ◽  
Kaplan Meier ◽  
Endothelial Cell Differentiation ◽  
Disease Specific

Purpose.Angiosarcoma is a rare tumor with endothelial cell differentiation that may arise in any anatomic location.The purpose of this report was to identify prognostic factors on outcome in a group of prospectively followed patients with confirmed angiosarcoma.Subjects.Adult patients (>16 years old) with angiosarcoma treated between July 1982 and February 1998 were identified from a prospective database.Methods.Pathologic confirmation of all cases was performed prior to inclusion in this analysis. Various prognostic factors were evaluated for disease-specific survival. Survival was determined by the Kaplan– Meier method. Statistical significance was evaluated by log-rank test for univariate analysis and Cox stepwise regression for multivariate analysis (p<0.05).Results.Fifty patients were identified; at the initial evaluation, this group included 32 patients with a primary tumor, three with local recurrence and 15 with metastatic disease. Tumor sites included 16 head and neck and skin of head, eight extremity, seven trunk, six breast, five pelvis, four viscera and four thoracic. Median follow-up among survivors was 71 months (range, 38–191 months).Two- and 5-year disease-specific survival was 50 and 30%, respectively, with a median of 24 months. The factor predictive of tumor-related mortality was presentation status (p=0.001; relative risk, 5). Two-year disease-specific survival for patients presenting with recurrent or metastatic disease was 13%, compared with 70% for those with primary disease.

scholarly journals Primary Surgical Therapy for Locally Limited Oral Tongue Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Konstantinos Mantsopoulos ◽  
Georgios Psychogios ◽  
Julian Künzel ◽  
Frank Waldfahrer ◽  
Johannes Zenk ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
Tongue Cancer ◽  
Occult Metastasis ◽  
Tongue Carcinoma ◽  
Disease Specific Survival ◽  
Oral Tongue ◽  
Tertiary Referral Center ◽  
Primary Surgery ◽  
Neck Disease ◽  
Disease Specific

Objectives. The aim of this study was to assess the efficacy of primary surgical treatment in the management of locally limited oral tongue carcinoma.Methods. A retrospective evaluation was carried out for all patients treated with primary surgery for pT1-pT2 oral tongue carcinomas at a tertiary referral center between 1980 and 2005. All cases were assessed for disease-specific survival and local control rates in relation to T classification, N classification, infiltration depth of the primary tumor, and decision making on neck management and adjuvant therapy. The cases were additionally evaluated for the incidence of major complications and tracheotomies.Results. 263 cases were assessed. The 5-year disease-specific survival rate was 75.2%. Positive neck disease was shown to be a significant negative prognostic factor. The occult metastasis rate was 20.2%.Conclusions. Primary surgical treatment is a very effective modality against T1-T2 oral tongue carcinoma, and a low rate of complications can be anticipated.

scholarly journals Cohort study of the overall survival of patients with pancreatic cancer in a hospital of specialties of Quito-Ecuador in the period 2007–2017

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Andrés Moreno Roca ◽  
Luciana Armijos Acurio ◽  
Ruth Jimbo Sotomayor ◽  
Carlos Céspedes Rivadeneira ◽  
Carlos Rosero Reyes ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cohort Study ◽  
Survival Time ◽  
Univariate Analysis ◽  
Rank Test ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Icd 10 ◽  
The Difference ◽  
Clinical Records

Abstract Objectives Pancreatic cancers in most patients in Ecuador are diagnosed at an advanced stage of the disease, which is associated with lower survival. To determine the characteristics and global survival of pancreatic cancer patients in a social security hospital in Ecuador between 2007 and 2017. Methods A retrospective cohort study and a survival analysis were performed using all the available data in the electronic clinical records of patients with a diagnosis of pancreatic cancer in a Hospital of Specialties of Quito-Ecuador between 2007 and 2017. The included patients were those coded according to the ICD 10 between C25.0 and C25.9. Our univariate analysis calculated frequencies, measures of central tendency and dispersion. Through the Kaplan-Meier method we estimated the median time of survival and analyzed the difference in survival time among the different categories of our included variables. These differences were shown through the log rank test. Results A total of 357 patients diagnosed with pancreatic cancer between 2007 and 2017 were included in the study. More than two-thirds (69.9%) of the patients were diagnosed in late stages of the disease. The median survival time for all patients was of 4 months (P25: 2, P75: 8). Conclusions The statistically significant difference of survival time between types of treatment is the most relevant finding in this study, when comparing to all other types of treatments.

scholarly journals Predictors of Central Compartment Involvement in Patients with Positive Lateral Cervical Lymph Nodes according to Clinical and/or Ultrasound Evaluation

2021 ◽  
Vol 10 (15) ◽  
pp. 3407
Author(s):  
Giuseppa Graceffa ◽  
Giuseppina Orlando ◽  
Gianfranco Cocorullo ◽  
Sergio Mazzola ◽  
Irene Vitale ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Univariate Analysis ◽  
Roc Curves ◽  
Central Compartment ◽  
Central Neck Dissection ◽  
Level Of Evidence ◽  
Cervical Lymph Nodes ◽  
Kaplan Meier ◽  
Ultrasound Evaluation ◽  
Central Lymph

Lymph node neck metastases are frequent in papillary thyroid carcinoma (PTC). Current guidelines state, on a weak level of evidence, that level VI dissection is mandatory in the presence of latero-cervical metastases. The aim of our study is to evaluate predictive factors for the absence of level VI involvement despite the presence of metastases to the lateral cervical stations in PTC. Eighty-eight patients operated for PTC with level II–V metastases were retrospectively enrolled in the study. Demographics, thyroid function, autoimmunity, nodule size and site, cancer variant, multifocality, Bethesda and EU-TIRADS, number of central and lateral lymph nodes removed, number of positive lymph nodes and outcome were recorded. At univariate analysis, PTC location and number of positive lateral lymph nodes were risk criteria for failure to cure. ROC curves demonstrated the association of the number of positive lateral lymph nodes and failure to cure. On multivariate analysis, the protective factors were PTC located in lobe center and number of positive lateral lymph nodes < 4. Kaplan–Meier curves confirmed the absence of central lymph nodes as a positive prognostic factor. In the selected cases, Central Neck Dissection (CND) could be avoided even in the presence of positive Lateralcervical Lymph Nodes (LLN+).

Tumor-Infiltrating Lymphocytes in Patients With Advanced Laryngeal Cancer Undergoing Bioselection

2021 ◽  
pp. 019459982110137
Author(s):  
Molly E. Heft Neal ◽  
Joshua D. Smith ◽  
Andrew C. Birkeland ◽  
Catherine T. Haring ◽  
Steven B. Chinn ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Induction Chemotherapy ◽  
Neck Cancer ◽  
Tertiary Care ◽  
Tumor Infiltrating Lymphocytes ◽  
Care Hospital ◽  
Disease Specific Survival ◽  
Infiltrating Lymphocytes ◽  
Disease Specific

Objective Bioselection to assess tumor response after induction chemotherapy has been introduced as an alternative treatment strategy to total laryngectomy for patients with advanced larynx squamous cell carcinoma (LSCC). Tumor-infiltrating lymphocytes (TILs) have proven to serve as prognostic biomarkers in head and neck cancer but have not been evaluated as a way to select patients for treatment paradigms. The aim of this study is to evaluate the role of pretreatment TILs in patients with advanced LSCC undergoing the bioselection paradigm. Study Design Retrospective study. Setting Tertiary care hospital. Methods Patients with advanced LSCC treated with bioselection and available tissue were included (N = 76). Patients were stratified into CD8-low and CD8-high cohorts by using the median TIL count. Kaplan-Meier survival analysis and multivariate cox regression were performed with SPSS version 26 (IBM). Results After controlling for tobacco use, tumor site, and stage, a high CD8 TIL count was an independent predictor of improved 5-year disease-specific survival (hazard ratio, 0.17 [95% CI, 0.03-0.84]; P = .03). CD8 TIL counts did not predict response to induction chemotherapy; however, subgroup analysis of patients treated with chemoradiation therapy revealed that CD8 TIL count was significantly associated with degree of response ( P = .012). Conclusion These findings support prior data published by our group showing that TILs are predictive of disease-specific survival in patients with head and neck cancer. CD8 TIL counts were significantly associated with degree of clinical response after induction chemotherapy. These results suggest that pretreatment assessment of tumor-infiltrating CD8 cells could be useful in selecting patients.

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