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Article ; Online: Clinical significance of overall assessment of tumor-infiltrating lymphocytes in oropharyngeal cancer: A meta-analysis.

Almangush, Alhadi / Alabi, Rasheed Omobolaji / De Keukeleire, Stijn / Mäkitie, Antti A / Pirinen, Matti / Leivo, Ilmo

2023 Volume 243, Page(s) 154342

Abstract: Background: The overall assessment of tumor-infiltrating lymphocytes (TILs) evaluated using hematoxylin and eosin (HE) staining has been recently studied in oropharyngeal squamous cell carcinoma (OPSCC).: Methods: We conducted a systematic review of ... ...

Abstract	Background: The overall assessment of tumor-infiltrating lymphocytes (TILs) evaluated using hematoxylin and eosin (HE) staining has been recently studied in oropharyngeal squamous cell carcinoma (OPSCC). Methods: We conducted a systematic review of Scopus, Ovid Medline, PubMed, Web of Science, and Cochrane Library to retrieve studies assessing TILs in HE-stained sections of OPSCC. We used fixed-effect models and random-effect models to estimate the pooled hazard ratios (HRs) and confidence intervals (CIs) for disease-free survival (DFS), overall survival (OS) and disease-specific survival (DSS). Results: Eleven studies were identified that had analyzed the prognostic significance of TILs in OPSCC using HE-stained specimens. Our meta-analyses showed that a high infiltration of TILs was significantly associated with improved DFS (HR 0.39, 95%CI 0.24-0.65, P = 0.0003), OS (HR 0.38, 95%CI 0.29-0.50, P < 0.0001), and DSS (HR 0.32, 95%CI 0.19-0.53, P < 0.0001). Conclusion: Findings of our meta-analysis support a growing body of evidence indicating that assessment of TILs in OPSCC using HE-stained sections has reliable prognostic value. The clinical significance of such assessment of TILs has been reported repeatedly in many studies on OPSCC. The assessment is cost-effective, feasible, easy to transfer from lab to clinic, and therefore can be incorporated in daily practice.
MeSH term(s)	Humans ; Clinical Relevance ; Head and Neck Neoplasms/pathology ; Lymphocytes, Tumor-Infiltrating/pathology ; Oropharyngeal Neoplasms/pathology ; Prognosis ; Squamous Cell Carcinoma of Head and Neck/pathology
Language	English
Publishing date	2023-01-25
Publishing country	Germany
Document type	Journal Article ; Meta-Analysis
ZDB-ID	391889-0
ISSN	1618-0631 ; 0344-0338
ISSN (online)	1618-0631
ISSN	0344-0338
DOI	10.1016/j.prp.2023.154342
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Article ; Online: The Therapeutic Landscape of Salivary Gland Malignancies-Where Are We Now?

Cleymaet, Robbert / Vermassen, Tijl / Coopman, Renaat / Vermeersch, Hubert / De Keukeleire, Stijn / Rottey, Sylvie

International journal of molecular sciences

2022 Volume 23, Issue 23

Abstract: Salivary gland malignancies (SGMs) account for less than 5% of new diagnoses in head and neck tumors. If feasible, surgery is the preferred treatment modality. Nevertheless, some malignancies have a tendency of recurrence, with possible distant ... ...

Abstract	Salivary gland malignancies (SGMs) account for less than 5% of new diagnoses in head and neck tumors. If feasible, surgery is the preferred treatment modality. Nevertheless, some malignancies have a tendency of recurrence, with possible distant metastasis. Alternative treatment strategies, such as primary radiation or chemotherapeutics, often present low response rates. As a result, there is an unmet need for novel therapeutic approaches. Nowadays, target-based therapies (e.g., small inhibitors and immunotherapy) are used by the medical oncologist for possible treatment of advanced SGMs. Based on recent published trials, some novel treatments may provide additional disease control for some patients. However, sample sizes are small, the general findings are unsatisfactory, and a lot of uncertainties remain to be elucidated. Nevertheless, research shows that patients do not benefit from blind administration of systemic treatments and therefore a more personalized approach is highly needed. The aim of this review paper is to summarize the most recent advances in the biological understanding and molecular pathways of salivary gland cancers, the association of these pathways with the current treatments used and their implications for more personalized targeted-based therapies.
Language	English
Publishing date	2022-11-28
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms232314891
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Article ; Online: Choice of surgery in intestinal-type adenocarcinoma of the sinonasal tract: a long-term comparative study.

Vermassen, Tijl / De Keukeleire, Stijn / Saerens, Michael / Heerwegh, Sylvester / Debacker, Jens M / Huvenne, Wouter / Deron, Philippe / Creytens, David / Ferdinande, Liesbeth / Rottey, Sylvie / Bachert, Claus / Duprez, Fréderic / Van Zele, Thibaut

European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery

2024 Volume 281, Issue 6, Page(s) 2993–3004

Abstract: Purpose: Intestinal-type adenocarcinoma (ITAC) is a rare sinonasal malignancy. Curative treatment requires multidisciplinary approach, with surgical options consist of the endonasal endoscopic approach (EEA) and external surgery (EXTS). Here, we provide ...

Abstract	Purpose: Intestinal-type adenocarcinoma (ITAC) is a rare sinonasal malignancy. Curative treatment requires multidisciplinary approach, with surgical options consist of the endonasal endoscopic approach (EEA) and external surgery (EXTS). Here, we provide the post-operative and survival results from a single-center long-term follow-up. Methods: We report long-term follow-up of 92 ITAC cases treated between 1998 and 2018, treated with EEA (n = 40) or EXTS (n = 52). Survival estimates, post-operative complications and duration of hospitalization were compared between surgical modalities. Results: Baseline characteristics were similar. A higher number of T4b tumors (16%), and subsequently more tumoral invasion (39%), was present in patients undergoing EXTS compared to EEA (3% and 18%, respectively). No difference in Barnes histology subtypes was noticed. Patients undergoing EEA had a shorter post-operative hospitalization stay versus EXTS (4 versus 7 days). Use of EEA was associated to improved disease-specific survival (DSS; 11.4 versus 4.4 years; HR Conclusions: Long-term follow-up in locally advanced ITAC demonstrates that resection by EEA is correlated with improved DSS compared to EXTS, especially for T3-4 tumors. No significant differences between both treatment modalities was observed regarding per- and post-operative complications, although hospitalization in patients undergoing EEA was shorter than for patients treated with EXTS. These results confirm that EEA should remain the preferred surgical procedure in operable cases of sinonasal ITAC.
MeSH term(s)	Humans ; Male ; Female ; Paranasal Sinus Neoplasms/surgery ; Paranasal Sinus Neoplasms/pathology ; Paranasal Sinus Neoplasms/mortality ; Adenocarcinoma/surgery ; Adenocarcinoma/pathology ; Adenocarcinoma/mortality ; Middle Aged ; Aged ; Follow-Up Studies ; Postoperative Complications/epidemiology ; Retrospective Studies ; Length of Stay/statistics & numerical data ; Adult ; Endoscopy/methods ; Survival Rate ; Neoplasm Staging
Language	English
Publishing date	2024-01-16
Publishing country	Germany
Document type	Journal Article ; Comparative Study
ZDB-ID	1017359-6
ISSN	1434-4726 ; 0937-4477
ISSN (online)	1434-4726
ISSN	0937-4477
DOI	10.1007/s00405-024-08447-w
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Article: Immuno-Oncological Biomarkers for Squamous Cell Cancer of the Head and Neck: Current State of the Art and Future Perspectives.

De Keukeleire, Stijn J / Vermassen, Tijl / Hilgert, Elien / Creytens, David / Ferdinande, Liesbeth / Rottey, Sylvie

Cancers

2021 Volume 13, Issue 7

Abstract: The era of immune checkpoint inhibitors has altered the therapeutic landscape in squamous cell cancer of the head and neck (SCCHN). Our knowledge about the tumor microenvironment has fueled the research in SCCHN, leading to several well-known and less- ... ...

Abstract	The era of immune checkpoint inhibitors has altered the therapeutic landscape in squamous cell cancer of the head and neck (SCCHN). Our knowledge about the tumor microenvironment has fueled the research in SCCHN, leading to several well-known and less-known prognostic and predictive biomarkers. The clinical staging, p16/HPV status, and PD-L1 expression are currently the main tools for assessing the patients' diagnosis and prognosis. However, several novel biomarkers have been thoroughly investigated, some reaching actual significant clinical contributions. The untangling of the immune infiltrate with the subtyping of tissue-associated tumor infiltrating lymphocytes, tumor-associated macrophages, and circulating blood-based biomarkers are an interesting avenue to be further explored and prospectively assessed. Although PD-L1 expression remains the most important response predictor for immune checkpoint inhibitors, several flaws impede proper assessment such as technical issues, different scoring protocol, and intra-, inter-, and temporal heterogeneity. In addition, the construction of an immune-related gene panel has been proposed as a prognostic and predictive stratification but lacks consensus. Recently, the role of microbioma have also been explored regarding its systemic and antitumor immunity. This review gives a comprehensive overview of the aforementioned topics in SCCHN. To this end, the integration of these clinically advantageous biomarkers via construction of an immunogram or nomogram could be an invaluable tool for SCCHN in future prospects.
Language	English
Publishing date	2021-04-04
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13071714
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Article: Tumor-Infiltrating Lymphocytes in Head and Neck Cancer: Ready for Prime Time?

Almangush, Alhadi / De Keukeleire, Stijn / Rottey, Sylvie / Ferdinande, Liesbeth / Vermassen, Tijl / Leivo, Ilmo / Mäkitie, Antti A

Cancers

2022 Volume 14, Issue 6

Abstract: The evaluation of tumor-infiltrating lymphocytes (TILs) has received global attention as a promising prognostic cancer biomarker that can aid in clinical decision making. Proof of their significance was first shown in breast cancer, where TILs are now ... ...

Abstract	The evaluation of tumor-infiltrating lymphocytes (TILs) has received global attention as a promising prognostic cancer biomarker that can aid in clinical decision making. Proof of their significance was first shown in breast cancer, where TILs are now recommended in the classification of breast tumors. Emerging evidence indicates that the significance of TILs extends to other cancer types, including head and neck cancer. In the era of immunotherapy as a treatment choice for head and neck cancer, assessment of TILs and immune checkpoints is of high clinical relevance. The availability of the standardized method from the International Immuno-oncology Biomarker Working Group (IIBWG) is an important cornerstone toward standardized assessment. The aim of the current article is to summarize the accumulated evidence and to establish a clear premise for future research toward the implementation of TILs in the personalized management of head and neck squamous cell carcinoma patients.
Language	English
Publishing date	2022-03-18
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14061558
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Article ; Online: Targeting FGFR in bladder cancer: ready for clinical practice?

De Keukeleire, Stijn / De Maeseneer, Daan / Jacobs, Celine / Rottey, Sylvie

Acta clinica Belgica

2019 Volume 75, Issue 1, Page(s) 49–56

Abstract: ... ...

Abstract	Objective
MeSH term(s)	Anticarcinogenic Agents/therapeutic use ; Biomarkers, Tumor/analysis ; Carcinoma, Transitional Cell/diagnosis ; Carcinoma, Transitional Cell/genetics ; Carcinoma, Transitional Cell/therapy ; Humans ; Immunotherapy/methods ; Molecular Targeted Therapy/methods ; Mutation ; Predictive Value of Tests ; Protein Kinase Inhibitors/therapeutic use ; Receptors, Fibroblast Growth Factor/antagonists & inhibitors ; Receptors, Fibroblast Growth Factor/genetics ; Urinary Bladder Neoplasms/diagnosis ; Urinary Bladder Neoplasms/genetics ; Urinary Bladder Neoplasms/therapy
Chemical Substances	Anticarcinogenic Agents ; Biomarkers, Tumor ; Protein Kinase Inhibitors ; Receptors, Fibroblast Growth Factor
Language	English
Publishing date	2019-10-31
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	390201-8
ISSN	2295-3337 ; 0001-5512 ; 1784-3286
ISSN (online)	2295-3337
ISSN	0001-5512 ; 1784-3286
DOI	10.1080/17843286.2019.1685738
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Article ; Online: Managing viral hepatitis in cancer patients under immune checkpoint inhibitors: should we take the risk?

De Keukeleire, Stijn J / Vermassen, Tijl / Nezhad, Zahra M / Kerre, Tessa / Kruse, Vibeke / Vlierberghe, Hans Van / Vermaelen, Karim / Rottey, Sylvie

Immunotherapy

2021 Volume 13, Issue 5, Page(s) 409–418

Abstract: More patients with chronic hepatitis B and C infection are being exposed to immune checkpoint inhibitors (ICIs), but the safety and efficacy of ICIs in patients with chronic viral hepatitis are still poorly described. To explore this interaction, we ... ...

Abstract	More patients with chronic hepatitis B and C infection are being exposed to immune checkpoint inhibitors (ICIs), but the safety and efficacy of ICIs in patients with chronic viral hepatitis are still poorly described. To explore this interaction, we identified eight studies of cancer patients with viral hepatitis treated with one or more ICIs, formally assessed tumor responses and safety by grading liver dysfunction. ICIs appear to be relatively safe in HBV/HCV-infected patients, and hepatitis related to viral reactivation is rare. In some patients, viral load regressed during ICI treatment, so immune checkpoints may play a role in viral clearance. HBV/HCV do not appear to be a contraindication to ICIs, although careful clinical and biochemical follow-up is recommended and, whenever necessary, antiviral therapy commenced.
MeSH term(s)	Chronic Disease ; Hepacivirus/drug effects ; Hepacivirus/physiology ; Hepatitis B virus/drug effects ; Hepatitis B virus/physiology ; Hepatitis, Viral, Human/complications ; Hepatitis, Viral, Human/drug therapy ; Hepatitis, Viral, Human/immunology ; Hepatitis, Viral, Human/virology ; Humans ; Immune Checkpoint Inhibitors/therapeutic use ; Liver/drug effects ; Liver/immunology ; Neoplasms/complications ; Neoplasms/drug therapy ; Neoplasms/immunology ; Neoplasms/virology ; Review Literature as Topic ; Viral Load/drug effects ; Virus Activation/drug effects
Chemical Substances	Immune Checkpoint Inhibitors
Language	English
Publishing date	2021-01-25
Publishing country	England
Document type	Journal Article
ZDB-ID	2495964-9
ISSN	1750-7448 ; 1750-743X
ISSN (online)	1750-7448
ISSN	1750-743X
DOI	10.2217/imt-2020-0273
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Article ; Online: To treat or not to treat? Managing comorbidities in cancer patients under immune checkpoint inhibition.

De Keukeleire, Stijn / Vermassen, Tijl / De Schoenmakere, Gert / Kruse, Vibeke / Vermaelen, Karim / Rottey, Sylvie

Acta clinica Belgica

2019 Volume 75, Issue 6, Page(s) 434–441

Abstract: ... ...

Abstract	Objectives
MeSH term(s)	Age Factors ; Autoimmune Diseases/epidemiology ; Brain Neoplasms/secondary ; Comorbidity ; Functional Status ; Humans ; Immune Checkpoint Inhibitors/therapeutic use ; Immunocompromised Host ; Kidney Failure, Chronic/epidemiology ; Kidney Failure, Chronic/therapy ; Liver Diseases/epidemiology ; Neoplasms/drug therapy ; Neoplasms/epidemiology ; Organ Transplantation ; Renal Dialysis ; Renal Insufficiency/epidemiology ; Ventricular Dysfunction, Left/epidemiology
Chemical Substances	Immune Checkpoint Inhibitors
Language	English
Publishing date	2019-07-29
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	390201-8
ISSN	2295-3337 ; 0001-5512 ; 1784-3286
ISSN (online)	2295-3337
ISSN	0001-5512 ; 1784-3286
DOI	10.1080/17843286.2019.1646516
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Article: Concordance, Correlation, and Clinical Impact of Standardized PD-L1 and TIL Scoring in SCCHN.

De Keukeleire, Stijn Jeroen / Vermassen, Tijl / Deron, Philippe / Huvenne, Wouter / Duprez, Fréderic / Creytens, David / Van Dorpe, Jo / Ferdinande, Liesbeth / Rottey, Sylvie

Cancers

2022 Volume 14, Issue 10

Abstract: Background: The clinical significance of tumor-infiltrating lymphocytes (TILs) and programmed cell death-ligand 1 (PD-L1) expression has been thoroughly researched in squamous cell carcinoma of the head and neck (SCCHN). To address the impact of intra- ... ...

Abstract	Background: The clinical significance of tumor-infiltrating lymphocytes (TILs) and programmed cell death-ligand 1 (PD-L1) expression has been thoroughly researched in squamous cell carcinoma of the head and neck (SCCHN). To address the impact of intra- and intertumoral heterogeneity in these biomarkers, we explored the concordance of PD-L1 combined positive score (CPS) and stromal TILs in different paired tissue sample types, while evaluating their internal relationship and prognostic impact. Methods: A total of 165 tissue blocks from 80 SCCHN patients were reviewed for TILs and PD-L1 CPS. Concordance between paired tissue samples was evaluated, and their association with several clinicopathological variables, overall survival (OS), and disease-free survival (DFS) was determined. Results: Biopsies and paired resection material were severely discordant in 39% and 34% of samples for CPS and TIL count, respectively, of which CPS was underscored in 27% of biopsies. In paired primary tumor-metastatic lesions, the disagreement was lower for CPS (19%) but not for TIL count (44%). PD-L1 CPS was correlated with prolonged OS when calculated from tissue acquirement, while extended OS and DFS were observed for high TIL density. Conclusion: Intertumoral and, especially, intratumoral heterogeneity were confounding factors when determining PD-L1 CPS and TIL count on paired tissue samples, indicating the increasing necessity of assessing both biomarkers on representative tissue material. Although TILs hold valuable prognostic information in SCCHN, the robustness of PD-L1 as a biomarker in SCCHN remains ambiguous.
Language	English
Publishing date	2022-05-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14102431
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Article ; Online: Verrucous hyperplasia and verrucous carcinoma in head and neck: use and benefit of methotrexate.

De Keukeleire, Stijn / De Meulenaere, Astrid / Deron, Philippe / Huvenne, Wouter / Fréderic, Duprez / Bouckenooghe, Olivier / Ferdinande, Liesbeth / Creytens, David / Rottey, Sylvie

Acta clinica Belgica

2020 Volume 76, Issue 6, Page(s) 487–491

Abstract: Background and ... ...

Abstract	Background and aim
MeSH term(s)	Carcinoma, Verrucous/drug therapy ; Head and Neck Neoplasms/drug therapy ; Humans ; Hyperplasia/drug therapy ; Methotrexate/therapeutic use ; Neoplasm Recurrence, Local ; Quality of Life
Chemical Substances	Methotrexate (YL5FZ2Y5U1)
Language	English
Publishing date	2020-04-11
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	390201-8
ISSN	2295-3337 ; 0001-5512 ; 1784-3286
ISSN (online)	2295-3337
ISSN	0001-5512 ; 1784-3286
DOI	10.1080/17843286.2020.1752455
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