Is Desmoplastic Stromal Reaction Useful to Modulate Lymph Node Dissection in Sporadic Medullary Thyroid Carcinoma? (DSR-MTC)

The oncologic benefit of lateral neck dissection (LND) during index operation for sporadic medullary thyroid carcinoma (MTC) basing on basal calcitonin (bCT) levels has been questioned due to the potential post-operative complications. This study aims to evaluate desmoplastic reaction (DSR), as predictor of nodal metastases, for definition of surgical strategy.

Data from pathological report of MTC after operations between 1997 and 2022 were collected. The primary endpoint of the study was evaluating the risk factors for nodal metastases. The secondary endpoints analyzed the correlations between DSR and nodal metastases and the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of DSR for nodal metastases.

Study Overview

• Status: Completed
• Conditions: Medullary Thyroid Cancer; Lymph Node Disease; Lymph Node Metastasis; Medullary Carcinoma; Medullary Tumor; Medullary Neoplasms; Desmoplasia; Desmoplastic; Desmoplastic Reaction

Detailed Description

Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor associated with aggressive biological behavior and a tendency for earlier lymphatic spread compared with differentiated thyroid carcinoma. Most MTCs are sporadic (75%), although some (25%) are hereditary, either familial or occurring in association with multiple endocrine neoplasia type 2 (MEN 2) syndrome. In contrast to hereditary MTC, sporadic MTC presents as multifocal disease only in 10% of patients.

As the most common clinical presentation is an asymptomatic solitary thyroid nodule, sporadic MTC detection is often late. Consequently, it is usually diagnosed as advanced disease, with cervical node involvement in most patients (70%) and compressive symptoms of the upper aerodigestive tract (15% of cases). Indeed, at the time of diagnosis, MTC presents with nodal involvement of central and lateral compartment in 50-81% and 34-81% of patients, respectively. Approximately 5% to 10% of patients with sporadic MTC even present with distant metastasis to the liver, lung, bones, brain and skin.

Complete surgical resection of the primary tumor and regional metastases is the cornerstone for locoregional disease control, since adjuvant therapy remains ineffective for the treatment of sporadic MTC. Moreover, as the number of positive lymph nodes and involved anatomical compartments are cancer-specific prognostic factors, early and accurate diagnosis of regional lymph nodes involvement is crucial for determining the surgical strategy. However, pre-operative diagnosis of MTC-related nodal disease is challenging due to the low sensitivity of imaging studies on detecting regional spread. Therefore, clinical decisions are often based upon biomarkers, mainly basal calcitonin levels, to predict nodal involvement and plan the surgical extent. Several associations have advocated in favor of this approach, although not with a strong recommendation, by suggesting prophylactic neck dissections based on basal calcitonin levels, especially for the lateral compartments. However, recent studies challenge this approach since a significant portion of patients were exposed to operations with increased morbidity without nodal spread on final histology or obvious survival benefits. As a consequence, the need to develop new predictive tools to tailor the surgical extent to each patient is paramount.

Desmoplasia, defined as the newly paraneoplastic formed stromal reaction surrounding the invasive epithelial tumor cells, has recently resurfaced as a morphological parameter with distinct clinical relevance in MTC. Significant correlation of desmoplasia with lymph node metastasis has been described in literature, with a higher specificity in predicting the nodal metastasizing pattern when compared with other morphological features. More specifically, the absence of desmoplasia on frozen section and definitive histopathology has been strongly associated with the absence of nodal metastases. As such, desmoplasia may have a crucial role in guiding surgical extent in the future.

The aim of this study is to evaluate the correlation between desmoplasia and nodal involvement in unifocal sporadic MTC in our experience.

• Study Type: Observational
• Enrollment (Actual): 246

Contacts and Locations

Study Locations

• Italy
  • Rome, Italy, 00168
    • Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

All adults patients who underwent index procedure between January 1997 and December 2022 in our center for sporadic unifocal MTC whose specimens were retrospectively re-evaluated by an expert endocrine pathologist (E.D.R.) for DSR were candidates for inclusion.

Description

Inclusion Criteria:

• All adults patients who underwent index procedure for sporadic unifocal MTC whose specimens were retrospectively re-evaluated by an expert endocrine pathologist (E.D.R.) for DSR were candidates for inclusion.

Exclusion Criteria:

• hereditary MTC
• sporadic multifocal MTC
• index operation in another center
• incidental diagnosis of MCT after less than total thyroidectomy and bilateral central neck dissection
• less than 6-months-follow-up
• patients < 18 years old

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Risk factors for nodal metastases	The primary endpoint of the study consists in the evaluation of risk factors for nodal metastases in patients with histopathologic report of medullary thryoid carcinoma	January 1997-December 2022

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlations between desmoplastic stromal reaction and nodal metastases	The secondary endpoints consist in the evaluation of correlations between desmoplastic stromal reaction and nodal metastases and in the sensitivity, specificity, PPV and PNV of desmoplastic stromal reaction for nodal metastases in patients with histopathologic report of medullary thyroid carcinoma	January 1997-December 2022

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 1997
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): August 31, 2023

Study Registration Dates

• First Submitted: January 15, 2024
• First Submitted That Met QC Criteria: February 5, 2024
• First Posted (Estimated): February 6, 2024

Study Record Updates

• Last Update Posted (Estimated): February 6, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: medullary thryoid carcinoma; desmoplasia; lateral neck dissection
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neoplastic Processes; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neuroendocrine Tumors; Neoplasm Metastasis; Carcinoma, Neuroendocrine; Infratentorial Neoplasms; Neoplasms, Ductal, Lobular, and Medullary; Fibrosis; Carcinoma; Thyroid Diseases; Lymphatic Metastasis; Thyroid Neoplasms; Carcinoma, Medullary; Brain Stem Neoplasms
• Other Study ID Numbers: 5547

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Reasonable requests will be evaluated by the Principal Investigator of our study

Drug and device information, study documents

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