p-PHOTOLARYNX- ANTHEM: Photon-Counting CT in Laryngeal Cancer Staging (H&NRAD-2025-01)

May 19, 2026 updated by: Caterina Giannitto, Humanitas University

p-PHOTOLARYNX- ANTHEM: Pilot Photon-Counting CT Evaluation of the Paraglottic Space and Cartilage Involvement in Laryngeal Cancer

Laryngeal cancer can affect speaking, swallowing, and breathing. Treatment selection depends on accurately defining tumor spread within the larynx, particularly invasion of the paraglottic space, thyroid cartilage, and subglottic region. Understaging may lead to insufficient treatment and recurrence, whereas overstaging may result in unnecessarily aggressive surgery and impaired quality of life.

CT and MRI are routinely used for local staging, but both have limitations. Conventional CT may have limited soft-tissue and cartilage contrast, while MRI is more time-consuming, motion-sensitive, and not feasible in all patients. Photon-counting CT (PCCT) is a new CT technology offering higher spatial resolution, improved tissue contrast, and reconstructions at different energy levels.

This study evaluates whether PCCT performed during phonation, while the patient produces a sustained sound, can improve local staging of laryngeal cancer. Phonation may better separate and display laryngeal structures, improving detection of tumor extension.

The main hypothesis is that optimized phonation PCCT reconstructions can assess tumor spread more accurately than standard CT and may approach MRI performance. Participants undergo PCCT as part of routine preoperative imaging. Images are reconstructed using different settings and reviewed by radiologists for image quality and tumor extension. When surgery is performed, imaging findings are compared with surgical and histopathological results.

The study aims to identify the most accurate PCCT reconstruction strategy to support better treatment planning in laryngeal cancer.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Detailed Description

This is a prospective, single-center observational imaging study designed to evaluate the diagnostic performance of photon-counting computed tomography (PCCT) acquired during phonation for local staging of biopsy-proven laryngeal squamous cell carcinoma.

Study Overview and Imaging Workflow

Eligible adult patients with histologically confirmed laryngeal squamous cell carcinoma referred for preoperative imaging undergo contrast-enhanced PCCT as part of routine clinical work-up. PCCT examinations are performed on a dedicated photon-counting CT system using a standardized acquisition protocol optimized for ultra-high-resolution imaging of the larynx during phonation. Imaging is acquired in the venous phase under sustained vocalization to enhance functional and morphological assessment of glottic and subglottic structures.

For each acquisition, multiple reconstructions are generated, including ultra-high-resolution virtual monoenergetic images (VMIs) at predefined energy levels and different reconstruction kernels. A 70-keV reconstruction with standard slice thickness is included as an energy-integrating detector (EID)-CT-like reference. When available, previously acquired conventional CT and/or MRI performed as part of standard care are included for comparative analysis. Surgical histopathology serves as the reference standard for local tumor extension.

Qualitative Image Assessment

Qualitative analysis is restricted to phonation acquisitions to maximize clinical relevance and reduce reader burden. Four expert head and neck radiologists independently review anonymized and randomized datasets, blinded to reconstruction parameters. For each dataset, readers assign a qualitative diagnostic quality score using a five-point Likert scale and evaluate tumor extension into the paraglottic space, thyroid cartilage (with distinction between inner cortical erosion and full-thickness invasion), and subglottic space using predefined ordinal scoring systems. Multiplanar reformations aligned with the glottic plane and axis are mandatorily assessed as part of each dataset.

Quantitative Image Assessment

Quantitative analysis is performed by two independent observers on a dedicated workstation. Standardized regions of interest (ROIs) are placed in the primary tumor, adjacent non-tumoral laryngeal tissues, subcutaneous fat (for noise estimation), and the common carotid artery (vascular reference). ROIs are defined on a representative axial slice and propagated across all reconstructions to ensure measurement consistency. Quantitative metrics include attenuation values, image noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR).

Data Management and Quality Assurance

Data are collected using structured electronic case report forms (eCRFs) derived from hospital source documents. All imaging data are anonymized prior to analysis. Quality assurance procedures are based on written standard operating procedures at the sponsor site and include verification of data completeness, internal consistency checks, and cross-validation of imaging assessments with source data (radiology reports, surgical and pathology records). Access to source data is permitted for authorized personnel in accordance with Good Clinical Practice and data protection regulations.

Statistical Analysis Plan

Given the exploratory, pilot nature of the study, the planned sample size of 60 patients is based on feasibility and the need to support descriptive and comparative multi-dataset, multi-reader analyses rather than formal hypothesis testing. Quantitative variables are summarized using appropriate descriptive statistics based on data distribution. Interobserver agreement is assessed using intraclass correlation coefficients for quantitative measures and Fleiss' kappa for ordinal qualitative scores.

The effects of VMI energy level and reconstruction kernel on quantitative and qualitative outcomes are evaluated using mixed-effects models accounting for repeated measures within patients and readers. Diagnostic performance of PCCT, and where available conventional CT and MRI, is assessed using sensitivity, specificity, predictive values, and receiver operating characteristic analysis with histopathology as the reference standard. Adjustment for multiple comparisons is applied when appropriate.

Handling of Missing Data

Missing or non-evaluable data (e.g., due to severe artifacts or unavailable histopathology) are documented explicitly. Analyses are primarily conducted on available data without imputation, and sensitivity analyses may be performed to assess the impact of missing values.

Ethical and Operational Considerations

The study does not modify standard clinical management. No study-specific adverse events are anticipated. All procedures comply with the Declaration of Helsinki, Good Clinical Practice, and applicable regulatory requirements. Written informed consent is obtained prior to participation.

Study Type

Observational

Enrollment (Estimated)

60

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Rozzano, Italy, 20089
        • Humanitas Research Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

A total of sixty patients, with biopsy-proven laryngeal squamous cell carcinoma will be enrolled in the study.

Description

1. SELECTION CRITERIA

Inclusion Criteria

  • Adults (≥18 years)
  • Biopsy-proven laryngeal cancer squamous cell carcinoma
  • Candidate for surgical staging able to undergo PCCT

Exclusion criteria

  • Renal failure
  • Allergy to contrast medium
  • Refusal of informed consent
  • Lack of histopathologic confirmation
  • Histopathologic diagnosis of non laryngeal tumors
  • Poor image quality due to severe artifacts

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Biopsy-Proven Laryngeal Squamous Cell Carcinoma Patients
A total of sixty patients, with biopsy-proven and clinical laryngeal squamous cell carcinoma
Diagnostic test: Photon Counting Computed Tomography
Photon-Counting CT (PCCT) will be performed using the Siemens Healthineers NAEOTOM Alpha, the latest generation of CT technology and the first system to apply photon-counting detector technology to laryngeal imaging. Its CdTe detectors count individual photons and measure their energy, enabling true spectral imaging with ultra-high spatial resolution (voxel size down to 0.2 mm). Multi-energy maps significantly improve tissue differentiation, allowing clearer distinction between paraglottic fat, non-ossified thyroid cartilage, and tumor tissue. The technology also reduces artifacts and enhances contrast, enabling detailed evaluation of the laryngeal cartilages and paraglottic space.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Diagnostic Accuracy of Phonation Photon-Counting CT (PCCT) for Local Tumor Extension
Time Frame: From completion of baseline phonation PCCT imaging to histopathological correlation, assessed up to 12 weeks.

Description:

To evaluate the diagnostic accuracy of phonation PCCT in identifying paraglottic space invasion, thyroid cartilage invasion (including distinction between inner cortical erosion and full-thickness invasion), and subglottic extension, using surgical and histopathological findings as the reference standard.
From completion of baseline phonation PCCT imaging to histopathological correlation, assessed up to 12 weeks.
Identification of the Optimal PCCT Reconstruction for Local Staging
Time Frame: From completion of baseline phonation PCCT imaging to histopathological correlation, assessed up to 12 weeks.
To identify the best-performing phonation PCCT reconstruction (defined by VMI energy level and reconstruction kernel) for each anatomical target (paraglottic space, thyroid cartilage, subglottic space), based on diagnostic accuracy relative to histopathology.
From completion of baseline phonation PCCT imaging to histopathological correlation, assessed up to 12 weeks.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Robustness of Local Staging Across PCCT Reconstructions
Time Frame: From completion of baseline phonation PCCT imaging to histopathological correlation, assessed up to 12 weeks.
To assess variability in local staging classification (paraglottic space invasion, cartilage involvement, subglottic extension) across different phonation PCCT reconstructions, including staging upgrades or downgrades between datasets.
From completion of baseline phonation PCCT imaging to histopathological correlation, assessed up to 12 weeks.
Interobserver Agreement for Qualitative and Staging Assessments
Time Frame: From completion of baseline phonation PCCT imaging to histopathological correlation, assessed up to 12 weeks.

To evaluate interobserver reproducibility among readers for qualitative diagnostic quality scores and ordinal staging assessments of paraglottic space invasion, cartilage involvement, and subglottic extension.

.
From completion of baseline phonation PCCT imaging to histopathological correlation, assessed up to 12 weeks.
Tumor attenuation
Time Frame: At baseline imaging, before surgery.
Mean attenuation measured in Hounsfield Units (HU) within tumor regions of interest.
At baseline imaging, before surgery.
Image noise
Time Frame: At baseline imaging, before surgery.
Image noise defined as the standard deviation of attenuation measured in a homogeneous region (e.g., subcutaneous fat).
At baseline imaging, before surgery.
Signal-to-noise ratio (SNR)
Time Frame: At baseline imaging, before surgery.
Signal-to-noise ratio calculated as mean tumor attenuation divided by image noise.
At baseline imaging, before surgery.
Contrast-to-noise ratio (CNR)
Time Frame: At baseline imaging, before surgery.
Contrast-to-noise ratio calculated as the difference in attenuation between tumor and reference tissue divided by image noise.
At baseline imaging, before surgery.
CT dose index volume (CTDIvol)
Time Frame: At baseline imaging, before surgery.
Volume CT dose index measured in milligray (mGy)
At baseline imaging, before surgery.
Dose-length product (DLP)
Time Frame: At baseline imaging, before surgery.
Dose-length product measured in milligray-centimeters (mGy·cm).
At baseline imaging, before surgery.
Effective dose
Time Frame: At baseline imaging, before surgery.
Estimated effective radiation dose expressed in millisieverts (mSv).
At baseline imaging, before surgery.
Comparison of PCCT with Conventional CT and MRI
Time Frame: From completion of phonation PCCT imaging to completion of multimodality image review and histopathological correlation, assessed up to 12 weeks.
To compare the diagnostic performance of phonation PCCT with conventional energy-integrating detector CT and MRI, when available, using histopathology as the reference standard.
From completion of phonation PCCT imaging to completion of multimodality image review and histopathological correlation, assessed up to 12 weeks.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Humanitas University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 16, 2025

Primary Completion (Estimated)

May 31, 2026

Study Completion (Estimated)

May 31, 2027

Study Registration Dates

First Submitted

December 27, 2025

First Submitted That Met QC Criteria

May 19, 2026

First Posted (Actual)

May 22, 2026

Study Record Updates

Last Update Posted (Actual)

May 22, 2026

Last Update Submitted That Met QC Criteria

May 19, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 4981

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

At the time of registration, no final decision has been made regarding sharing of individual participant data. Any future data sharing would be subject to ethical approval, data protection regulations, and appropriate data use agreements.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Laryngeal Cancer

Clinical Trials on Photon Counting Computed Tomography

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Kenya

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe