Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT06243965 |
| Other study ID # |
5547 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 1, 1997 |
| Est. completion date |
August 31, 2023 |
Study information
| Verified date |
January 2024 |
| Source |
Fondazione Policlinico Universitario Agostino Gemelli IRCCS |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
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.
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.
