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Prognostic Factors of Recurrence in Squamous Cell Carcinoma of the Head and Neck


Vital, Domenic. Prognostic Factors of Recurrence in Squamous Cell Carcinoma of the Head and Neck. 2021, University of Zurich, Faculty of Medicine.

Abstract

Head and neck squamous cell carcinomas have a good chance of cure if diagnosed and treated early. Unfortunately, many head and neck cancer patients present late and with advanced disease. Despite “state of the art” treatment, these patients have a high risk of loco-regional recurrence and most often, salvage surgery has to be considered. Salvage surgery is at times not only disfiguring, but also shows relatively low cure rates.
This thesis highlights the importance of a comprehensive understanding of “classical” prognostic parameters like tumor stage, surgical margins, perineural invasion or immunosuppression, but also relevant molecular markers, which might enable a future patient-tailored treatment according to the predicted patterns of aggressiveness.
To reach these goals, it is not only necessary to continuously monitor and analyze the patients clinical and clinicopathologic features, but also to conduct translational research projects on patient’s tumor tissue. In this thesis, six original publications with focus on loco-regional recurrence or disease-free/recurrence-free survival are presented. The first three publications focused on the role of “classical” clinicopathologic risk factors:
1. An analysis of “classical” clinicopathologic factors in patients with squamous cell carcinoma of the nasal vestibule demonstrated that a locally advanced tumor stage and positive surgical margins are the main “classical” predictors of loco-regional recurrence.
2. A further study on “classical” clinicopathologic factors in squamous cell carcinoma, which focused on solid organ transplant recipients, suggested that anatomical site, differentiation pattern, tumor diameter, depth of infiltration and perineural invasion are important predictors of aggressive behavior.
3. A survey of the role of the two patterns of perineural invasion on outcome demonstrated that both patterns are associated with a worse recurrence-free survival. The latter three publications included molecular tumor markers into the analysis. Aim was to focus on the prognostic relevance of three commonly used markers in routine diagnostics (p16INK4a, p53 and Ki-67) and PD-L1, which is not routinely analyzed, but becomes more and more relevant with respect to systemic treatments with immune checkpoint inhibitors.
4. An analysis of p16INK4a and HPV in squamous cell carcinoma of the nasal vestibule revealed that about one fifth of the patients were p16INK4a positive as a surrogate marker of high risk HPV association. This was without impact on survival.
5. A study on the “aberrant p53 patterns” as a potential surrogate marker of the TP53 mutation showed that it was associated with a poor disease-free survival.
6. A survey on the expression of PD-L1 in squamous cell carcinoma of the nasal vestibule demonstrated PD-L1 positivity in about 50% of the patients, which was associated with a favorable disease-free survival.
These findings not only confirm the importance of “classical” clinical and clinicopathological risk factors, but also propose potential useful prognostic or predictive molecular markers. Especially the latter ones merit further investigation in larger and eventually prospective studies as well as regarding their predictive value. It seems unlikely that prognostic molecular markers will replace classical clinical and clinicopathological parameters, but might be of pivotal importance when combined with the latter.

Abstract

Head and neck squamous cell carcinomas have a good chance of cure if diagnosed and treated early. Unfortunately, many head and neck cancer patients present late and with advanced disease. Despite “state of the art” treatment, these patients have a high risk of loco-regional recurrence and most often, salvage surgery has to be considered. Salvage surgery is at times not only disfiguring, but also shows relatively low cure rates.
This thesis highlights the importance of a comprehensive understanding of “classical” prognostic parameters like tumor stage, surgical margins, perineural invasion or immunosuppression, but also relevant molecular markers, which might enable a future patient-tailored treatment according to the predicted patterns of aggressiveness.
To reach these goals, it is not only necessary to continuously monitor and analyze the patients clinical and clinicopathologic features, but also to conduct translational research projects on patient’s tumor tissue. In this thesis, six original publications with focus on loco-regional recurrence or disease-free/recurrence-free survival are presented. The first three publications focused on the role of “classical” clinicopathologic risk factors:
1. An analysis of “classical” clinicopathologic factors in patients with squamous cell carcinoma of the nasal vestibule demonstrated that a locally advanced tumor stage and positive surgical margins are the main “classical” predictors of loco-regional recurrence.
2. A further study on “classical” clinicopathologic factors in squamous cell carcinoma, which focused on solid organ transplant recipients, suggested that anatomical site, differentiation pattern, tumor diameter, depth of infiltration and perineural invasion are important predictors of aggressive behavior.
3. A survey of the role of the two patterns of perineural invasion on outcome demonstrated that both patterns are associated with a worse recurrence-free survival. The latter three publications included molecular tumor markers into the analysis. Aim was to focus on the prognostic relevance of three commonly used markers in routine diagnostics (p16INK4a, p53 and Ki-67) and PD-L1, which is not routinely analyzed, but becomes more and more relevant with respect to systemic treatments with immune checkpoint inhibitors.
4. An analysis of p16INK4a and HPV in squamous cell carcinoma of the nasal vestibule revealed that about one fifth of the patients were p16INK4a positive as a surrogate marker of high risk HPV association. This was without impact on survival.
5. A study on the “aberrant p53 patterns” as a potential surrogate marker of the TP53 mutation showed that it was associated with a poor disease-free survival.
6. A survey on the expression of PD-L1 in squamous cell carcinoma of the nasal vestibule demonstrated PD-L1 positivity in about 50% of the patients, which was associated with a favorable disease-free survival.
These findings not only confirm the importance of “classical” clinical and clinicopathological risk factors, but also propose potential useful prognostic or predictive molecular markers. Especially the latter ones merit further investigation in larger and eventually prospective studies as well as regarding their predictive value. It seems unlikely that prognostic molecular markers will replace classical clinical and clinicopathological parameters, but might be of pivotal importance when combined with the latter.

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Additional indexing

Item Type:Habilitation (monographical)
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Otorhinolaryngology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:6 January 2021
Deposited On:16 Feb 2021 08:41
Last Modified:16 Feb 2021 08:43
OA Status:Closed

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