Prognostic Immune Biomarkers in HNSCC

Evaluation of the Prognostic Potential of New Immune Biomarkers in Non-metastatic Squamous Cell Carcinoma of the Head and Neck

Evaluation of the prognostic potential of tumor-infiltrating lymphocytes and PD-L1 expression in non-metastatic squamous cell carcinoma of the head and neck

Study Overview

• Status: Completed
• Conditions: Head and Neck Cancer; Squamous Cell Carcinoma
• Intervention / Treatment: Diagnostic test: Tumour immunoprofile evaluation

Detailed Description

The role of the immune system in the process of tumor growth and progression in head and neck (HaN) cancer has become of increasing importance. In the last years, the concept of tumor immune microenvironment (TIME) with the presence of tumor cells (TC) and infiltrating immune cells (IC) has been intensively studied. The results of available clinical studies suggest a positive impact of tumor-infiltrating lymphocytes (TILs) on the prognosis of HNSCC patients and their overall (OS) and cancer specific survivals. Beside TILs, an integral component of TIME is the immunosuppressive activity represented by inhibitory signalling molecules expressed on tumor cells (TCs) and immune cells (ICs).

One of these molecules is programmed death-ligand 1 (PD-L1), which inhibits the cytotoxic immune response mediated by T-lymphocytes.

The aim of this observational cohort study is to assess the prognostic potential of novel immune biomarkers in patients with HNSCC tumors stage I-IVb treated with radical radiotherapy and radiochemotherapy. Specifically, the association between high and low TILs infiltration and OS and cancer specific survival parameters will be investigated. As well as the association between high and low PD-L1 expression and OS and cancer specific survival parameters will be investigated.

This is a non-interventional study conducted in one institution - Department of oncology, University hospital Ostrava. The tumor immunoprofile defined by the presence of immune biomarkers (TIL, PD-L1) will be evaluated in each patient from biopsy specimens in representative hematoxylin and eosin stained sections by immuno-histochemistry. The Cox proportional risk model will be used to estimate the prognostic potential of each of the biomarker.

• Study Type: Observational
• Enrollment (Actual): 55

Contacts and Locations

Study Locations

• Czechia
  • Moravian-Silesian Region
    • Ostrava, Moravian-Silesian Region, Czechia, 70852
      • University Hospital Ostrava

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Patients with stage I-IVb HNSCC indicated for radical treatment - radiotherapy or radiochemotherapy

Description

Inclusion Criteria:

• Patients with non-metastatic squamous-cell head and neck cancer (HNSCC) stage I-IVb indicated for curative/radical treatment
• Histologically verified squamous cell carcinoma including HPV-positive carcinomas
• Tumor site: oropharynx, larynx, hypopharynx, oral cavity, nasal cavity
• Treatment modality - radiotherapy or radiochemotherapy
• Presence of immune biomarkers in the tissue - tumor-infiltrating lymphocytes (TILs) and/or PD-L1 expression
• Sufficient data on patient follow-up

Exclusion Criteria:

• Histological type other than squamous cell carcinoma
• Paranasal sinus tumors, thyroid and nasopharyngeal carcinomas, salivary gland tumors, mucosal melanoma, skin carcinoma, lymphomas, and occult primary tumors
• Synchronous malignancies or recurrent disease
• The previous use of radiotherapy
• The presence of distant metastatic disease
• Missing or inadequate follow-up data
• The inability to evaluate biomarkers (TILs or PD-L1) in a histological tissue sample.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Head and neck carcinoma patients; Head and neck carcinoma patients will be enrolled in this study group.	Diagnostic test: Tumour immunoprofile evaluation; Tumour immunoprofile evaluation will be performed in patients with head and neck cancer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Overall survival measured in months - calculated from the date of initiation of radiotherapy to the date of death from any cause or the date of the last follow-up visit.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-specific survival (DSS)	Disease-specific survival calculated from the date of initiation of radiotherapy to the date of cancer death, or date of the last follow-up visit. Patients who died from causes other than HNSCC are censored at the time of death.	24 months
Disease-free survival (DFS)	Disease-free survival calculated from the date of initiation of radiotherapy to the date of detection of any recurrence, or date of death from any cause or date of the last follow-up visit. Patients without tumor recurrence are censored at the last follow-up contact.	24 months
Locoregional-free survival (LRFS)	Locoregional-free survival calculated from the date of initiation of radiotherapy to the date of detection of clinical, radiological and/or pathological evidence of recurrence or tumor progression at the primary site or in the regional nodal area, or date of death from any cause or date of the last follow-up visit. Patients without tumor recurrence are censored at the last follow-up contact.	24 months
Distant metastatic-free survival (DMFS)	Distant metastatic-free survival calculated from the date of initiation of radiotherapy to the date of detection of distant metastasis of the tumor, or date of death from any cause or date of the last follow-up visit. Patients without tumor recurrence were censored at the last follow-up contact.	24 months

Collaborators and Investigators

• Sponsor: University Hospital Ostrava

Publications and helpful links

General Publications

• Blazek T, Petras M, Knybel L, Cvek J, Soumarova R. Programmed Cell Death Ligand 1 Expression on Immune Cells and Survival in Patients With Nonmetastatic Head and Neck Cancer: A Systematic Review and Meta-analysis. JAMA Netw Open. 2023 Mar 1;6(3):e236324. doi: 10.1001/jamanetworkopen.2023.6324.

Helpful Links

• A Systematic Review and Meta-analysis

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Actual): August 30, 2022
• Study Completion (Actual): June 30, 2023

Study Registration Dates

• First Submitted: July 3, 2023
• First Submitted That Met QC Criteria: July 3, 2023
• First Posted (Actual): July 12, 2023

Study Record Updates

• Last Update Posted (Actual): July 12, 2023
• Last Update Submitted That Met QC Criteria: July 3, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: radiotherapy; prognosis; head and neck cancer; head and neck squamous cell carcinoma (HNSCC); immune biomarkers; tumor-infiltrating lymphocytes; PD-L1 (programmed death ligand-1) expression
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Head and Neck Neoplasms; Carcinoma; Carcinoma, Squamous Cell
• Other Study ID Numbers: ONKOL-01-Head and neck; RVO-FNOs/2021 (Other Grant/Funding Number: University Hospital Ostrava)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to make individual participant data available to other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No