Ascertaining the Radiologic Prognostic Importance of Extranodal Extension on Imaging (iENE) in Head and Neck Cancer (EPIC-iENE DATA)

Ascertaining the Radiologic Prognostic Importance of Extranodal Extension on Imaging (iENE) in Head and Neck Cancer Part of the Evaluation Prognostic and Predictive Indicators in Head and Neck Cancer (EPIC) Programme, Run Under the Auspices of the Head and Neck Inter Group (HNCIG, Www.Hncig.Org)

Extranodal extension (ENE) refers to the spread of head and neck squamous cell carcinoma (HNSCC) outside the lymph nodes. It is a well-known factor that indicates a poorer prognosis and outcome for patients who have undergone surgical removal of the cancer. In such cases, it is recommended to combine chemotherapy with radiation therapy after surgery.

As the number of cases of HNSCC related to the human papillomavirus (HPV) is increasing, treatment approaches have shifted towards using radiation therapy as the primary treatment method instead of surgery. This raises an important question about the significance of ENE observed through imaging tests (referred to as iENE) and its impact on the prognosis. Unfortunately, this question remains unanswered.

The objective of this project is to conduct a comprehensive study across multiple medical institutions. The investigators will gather data including scan results, histopathology reports, and data from patient charts from individuals who have been treated for head and neck cancer. The aim is to analyze and correlate the findings between the pathological evidence of ENE and the imaging results, while also assessing the prognostic value of iENE. Additionally, the investigators will explore the influence of HPV status on these factors.

By collecting and analyzing this data, the investigators hope to establish standardized criteria that can assist radiologists in accurately identifying ENE through imaging tests. This research is essential for enhancing our understanding of HNSCC and improving the effectiveness of diagnostic procedures and treatment planning.

Study Overview

• Status: Completed
• Conditions: Head and Neck Squamous Cell Carcinoma; Extranodal Extension; Human Papilloma Virus Related Carcinoma
• Intervention / Treatment: Other: Extranodal extension

• Study Type: Observational
• Enrollment (Actual): 3500

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia
    • Royal Adelaide Hospital
• Denmark
  • Copenhagen, Denmark
    • Copenhagen University Hospitals
• France
  • Paris, France
    • Georges Pompidou European hospital
• Germany
  • Cologne, Germany
    • University of Cologne
  • Munich, Germany
    • Technical University of Munich
• Spain
  • Barcelona, Spain
    • Catalan Institute of Oncology
• Switzerland
  • Zürich, Switzerland
    • University Hospital Zurich
• United Kingdom
  • Birmingham, United Kingdom
    • University Hospitals Birmingham
  • Leeds, United Kingdom
    • Leeds Teaching Hospitals NHS Trust
• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Methodist Estabrook Cancer Center
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Health System
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients presented and treated for Head and neck squamous cell carcinoma

Description

Inclusion Criteria:

The investigators will examine data from consecutive patients at each site treated between 1/1/1999 and 12/31/2020. Patients must fulfil all these criteria:

i. Been treated for oral cavity, oropharyngeal, carcinoma of unknown primary, laryngeal, or hypopharyngeal squamous cell carcinoma and be over the age of 18.

ii. The participants must have been treated with curative intent via surgery, radiotherapy, or chemoradiotherapy or a combination within the study inclusion period.

iii. The participants must have had CT or/and MRI scans of the neck, performed within 12 weeks before the start of treatment.

iv. Results for the presence or absence of extranodal extension on CT or/and MRI scans, or ability to report them within the deadline period.

v. For surgically-treated patients: Results for the presence or absence of both extranodal extension on histopathology and on radiology, or ability to report them within the deadline period.

vi. Must have had at least two years of follow-up, or death. vii. Data on staging must be available at least in TNM 7th edition or later editions.

Exclusion Criteria:

i. Patients who were diagnosed with distant metastasis at presentation. ii. Patients treated palliatively at first presentation iii. Patients presenting with recurrent disease who don't meet all the eligibility criteria above

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Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the accuracy of the identification of iENE by radiologists in real world situations by correlating with histopathology (pENE)	Endpoints: Accuracy of a radiologic "call" of iENE (with pENE being the gold standard comparator) by radiologists not trained for any standardized diagnostic classification systems for iENE.	31 December 2023
To evaluate the prognostic significance (overall survival rates) of iENE.	Endpoints: Overall survival rates based on presence of iENE and pENE	31 December 2023
To evaluate the prognostic significance (recurrence rates) of iENE	Endpoints: Recurrence rates based on presence of iENE and pENE	31 December 2023
To evaluate the prognostic significance (overall survival rates) of iENE: Risk stratify HNSCC patients based on presence of radiographic ENE, according to their HPV status and N stage	Endpoints: Overall survival rates based on presence of various degrees of iENE and pENE	31 December 2023
To evaluate the prognostic significance (recurrence rates) of iENE: Risk stratify HNSCC patients based on presence of radiographic ENE, according to their HPV status and N stage	Endpoints: Recurrence rates based on presence of various degrees of iENE and pENE	31 December 2023

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improve the diagnosis of iENE: Determine radiological features of iENE that best correlate with pENE (the gold standard comparator)	Endpoints: Diagnostic accuracy of various radiographic features of iENE with pENE.	31 December 2023
Assess the utility of various existing standardized diagnostic classification systems in accurately diagnosing iENE	Endpoints: Diagnostic accuracy of published standardized classification systems with pENE	31 December 2023
Measure interobserver variability amongst radiologists in grading radiographic ENE and to measure impact of standardized criteria on this variability	Endpoints: Interobserver variability measured by Cohen's kappa	31 December 2023

Collaborators and Investigators

• Sponsor: Head and Neck Cancer International Group
• Investigators: Principal Investigator: Hisham Mehanna, PhD, University of Birmingham; Principal Investigator: Christina Henson, MD, The University of Oklahoma Health Sciences Center; Principal Investigator: Ahmad K. Abou-Foul, MD, University of Birmingham; Principal Investigator: Paul C Nankivell, PhD, University of Birmingham

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2022
• Primary Completion (Actual): August 15, 2023
• Study Completion (Actual): September 30, 2023

Study Registration Dates

• First Submitted: May 24, 2023
• First Submitted That Met QC Criteria: July 6, 2023
• First Posted (Actual): July 7, 2023

Study Record Updates

• Last Update Posted (Actual): February 1, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Neoplastic Processes; Neoplasm Metastasis; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Carcinoma; Squamous Cell Carcinoma of Head and Neck; Papilloma; Extranodal Extension
• Other Study ID Numbers: EPIC-iENE DATA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The data will bill kept in the HNCIG database, and might be shared with other researchers following a reasonable request (and following agreement by the HNCIG board)

Drug and device information, study documents

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