Stromal Desmoplastic Reaction as a Predictive Factor for Lymph Node Metastasis in Medullary Thyroid Cancer (DESMED)

September 25, 2026 updated by: Papavramidis Theodossis, Aristotle University Of Thessaloniki

This is a prospective multicenter observational study on medullary thyroid cancer , aiming to investigate the correlation of stromal desmoplastic reaction with tumor aggressiveness.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Research hypothesis

Negative Desmoplastic stromal reaction is correlated to negative nodal disease in medullary thyroid cancer.

Introduction

Medullary thyroid cancer is a rare but aggressive subtype of thyroid cancer, counting for 5-10% of thyroid cancers with a 1-2% incidence in nodular thyroid diseases. The aggressiveness of this tumor has been correlated with certain factors in the international literature. These are the tumor size, carcinoembryonic antigen (CEA) and calcitonin levels pre- and postoperatively, patient age and sex, TNM stage, type of surgery and time interval to relapse. Recently, desmoplastic stromal reaction is considered a major risk factor for nodal metastases, but is still a debatable topic in the literature(1-6). Our study aims to assess desmoplastic stromal reaction as an independent risk factor for lymph node metastasis in medullary thyroid cancer.

Study Description

This study is designed as a prospective multicenter cohort study. Five centers will take part in this study:

  1. 1st Propaedeutic Department of Surgery, AHEPA University Hospital, Aristotle University Hospital, Thessaloniki, Greece
  2. General Surgery Unit, Cagliari University Hospital, Monserrato, Italy
  3. Endocrine Surgery Unit, University Hospital of Pisa, Pisa, Italy
  4. Endocrine Surgery Unit, Verona University Hospital, Verona, Italy
  5. Endocrine Surgery Unit, University Hospital Agostino Gemelli IRCCS, Rome, Italy

The aim of this study is to evaluate desmoplastic stromal reaction as an independent factor of lymph node metastasis (central and lateral neck compartment) in medullary thyroid cancer.

Sample size calculation Each research question-whether primary or secondary-will be evaluated individually to determine whether the null or the alternative hypothesis holds true. Theoretically, each hypothesis carries a 50% probability of being correct. To ensure a robust study design that aligns with globally accepted research standards, the statistical power was set at 80% with a margin of error (significance level) of 0.05. Based on sample size calculations conducted via G*power application, the required sample size was determined to be 74 patients.

Materials and Methods

Inclusion criteria:

  • Patients who underwent thyroidectomy for medullary thyroid cancer (total thyroidectomy) +/- central/lateral neck dissection
  • Sporadic medullary thyroid cancer

Exclusion criteria

  • Age < 18 years
  • Hereditary medullary thyroid cancer cases
  • Patients that do not undergo central or lateral lymph node dissection
  • Patient unwillingness to participate in this study
  • Incomplete follow-up
  • Patient is participating in another clinical trial which may affect this study's outcomes

Study period

September 2026- September 2027

Data collection

Data will be collected prospectively in this study, by each participating center. This data include: age, gender, tumor diameter, Body Mass Index (BMI), preoperative basal calcitonin and CEA (carcinoembryonic antigen) levels, Fine-needle Aspiration (FNA) (conduction preoperatively or not and time period before operation), type of operation underwent, presence of lymph node and distant metastasis preoperatively, TNM stage in the pathology report, presence of extrathyroidal extension, lymphovascular invasion, capsular invasion, multifocality, postoperative levels of calcitonin and CEA.

Evaluation of stromal desmoplastic reaction

Two independent and experienced pathologists from each center will evaluate the stromal desmoplastic reaction (DSR) around tumor according to international guidelines. Stromal desmoplastic reaction is defined by the fibrotic response in the tumor microenvironment. It is evaluated under a standard hematoxylin and eosin (H&E) microscope review. Masson's Trichrome staining is a specialized histological stain, highlighting the architecture, density, and distribution of collagen, allowing pathologists to accurately visualize the extent of fibrosis and the structural maturity of the tumor stroma. DSR will be categorized into three distinct categories: (a) negative (<1%), (b) low-intermediate (1-10%), (c) intermediate-high (11-50%) and (d) high (>50%).

Database

The database will be held on Microsoft Excel, where all centers included in this study will add the parameters needed.

Outcomes

Primary outcome: Absence of Desmoplastic stromal reaction and lymph node status.

Secondary outcome: Multivariable analysis of several factors including desmoplastic reaction related to lymph node metastasis.

Statistical analysis

Statistical analysis will be applied in Statistical Package for the Social Sciences 25.0 (SPSS Inc., Chicago, IL, USA). Continuous variables will be demonstrated as mean with standard deviation (SD) or as median with interquartile range (IQR), depending on normality having been assumed or not, respectively, while categorical variables will be presented as frequencies with percentages (%). Univariate and multivariate analysis will be applied to assess the correlation of these parameters with tumor aggressiveness. In case of data heterogeneity, we will conduct propensity score matching analysis in order to eliminate the risk of bias (Selection bias, extrapolation bias).

Data monitoring plan

We are going to monitor all data accrual. Furthermore, we will review the progress of the clinical trial including safety data and ensure as possible that it is conducted, recorded and reported in accordance with the protocol, good clinical practice and the applicable regulatory requirements.

Data confidentiality

Each patient- sample will be identified by his/her initials and a unique patient identification number. Source data will be stored with source documents. Only personnel responsible for collecting data and transcribing it into the case report forms will have access to the data. Records will remain on site in secure areas.

Funding

No additional funding for the execution of the present protocol is necessary. The investigators are willing to execute the present study without any additional reimbursement.

Ethics

The aim of this study is to evaluate stromal desmoplastic reaction as an independent risk factor for nodal metastasis in medullary thyroid cancer. Information regarding desmoplasia will be collected postoperatively and this will not interfere with the therapeutic decisions for the patients. Therapeutic strategy will NOT be altered and patients will receive the treatment of choice regarding their disease stage according to the international guidelines.

Prior to study institution review board (IRB) approval should be obtained. Any changes in the study protocol, informed consent forms, or investigator must be re-approved by the IRB. All patients enrolled in the study will provide their consent prior to entering the study. An informed consent form shall be signed and dated by the patient. The investigator will retain the forms as part of the study records.

This study will be executed in accordance with the Declaration of Helsinki, in agreement with the guidelines for conducting a clinical investigation in accordance with the principles of ICH GCP outlined in the E6 document. By signing the present protocol, participants in the study commit themselves to carry it out in accordance with local legal requirements.

Informed consent

All eligible patients should have the capacity to provide an informed consent. The above described inclusion and exclusion criteria were designed to ensure the entry of the appropriate population of patients to this study and will be approved by the local IRB. Screening for these criteria will be conducted by the coordinator. Eligible patients will be educated about the research proposal by a study investigator. To determine whether the patient has understood the issues, he/she will be asked to describe what the research entails and whether they have any questions. All questions will be addressed prior to enrollment. The patient can refuse participation in the study at any time. A written informed consent form will be generated. For each patient, a case report form (CRF) will be completed, providing general medical information and history.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
74

Contacts and Locations

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

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Patients with medullary thyroid cancer that will undergo surgery as curative method

Description

Inclusion Criteria:

  • Patients who underwent thyroidectomy for medullary thyroid cancer (total thyroidectomy) +/- central/lateral neck dissection
  • Sporadic medullary thyroid cancer

Exclusion Criteria:

  • Age < 18 years
  • Hereditary medullary thyroid cancer cases
  • Patients that do not undergo central or lateral lymph node dissection
  • Patient unwillingness to participate in this study
  • Incomplete follow-up
  • Patient is participating in another clinical trial which may affect this study's outcomes

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

  • Observational Models: COHORT
  • Time Perspectives: PROSPECTIVE

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of patients with absence of Desmoplastic stromal reaction and metastatic lymph node in central and lateral compartment
Time Frame: Perioperative/ From the end of the surgery to the pathology report results that characterizes this outcome

Number of patients with absence of Desmoplastic stromal reaction and metastatic lymph node in central and lateral compartment
Perioperative/ From the end of the surgery to the pathology report results that characterizes this outcome

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Factors like baseline calcitonin levels, extrathyroidal extension, lymphovascular and capsular invasion that correlate with lymph node metastasis in medullary thyroid cancer
Time Frame: From baseline to up to 3 months postoperatively

Factors like baseline calcitonin levels, extrathyroidal extension, lymphovascular and capsular invasion that correlate with lymph node metastasis in medullary thyroid cancer
From baseline to up to 3 months postoperatively

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Aristotle University Of Thessaloniki

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of Pisa
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Universita di Verona
University of Cagliari

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 (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 30, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 20, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 25, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 1, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 1, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 25, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • DESMED study
  • DESMED (Other Identifier: Aristotle University of Thessaloniki)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings