Clinical trial NCT04743583: Prevalence and Malignant Involvement of Calcified Intrathoracic Lymph Nodes in Patients Undergoing Endosonography
Official title: Prevalence of Intrathoracic Lymph Node Calcifications and Metastatic Involvement in Patients Undergoing Endosonography for Diagnosis and/or Mediastinal Staging of Intrathoracic Malignancy: a Cross-sectional Pilot Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Lymphadenopathy
Lung Cancer
Sarcoidosis
Tuberculosis
Lead sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Sponsor class: OTHER
First posted: 2021-02-08
Enrollment: 362
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_CROSSOVER
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with known or suspected lung cancer or other intrathoracic malignancy with indication to endosonography for diagnosis or staging of intrathoracic lymph nodes according to currently accepted international guidelines

Brief summary: The presence of calcifications, which is a relatively common feature in intrathoracic lymph nodes, typically contributes to confer them a heterogeneous aspect during endosonographic B-mode examination, but their prevalence and a possible association between calcifications and metastatic involvement has never been systematically evaluated. We hypothesize that, in patients undergoing mediastinal diagnosis or staging of suspected/known lung cancer/intrathoracic malignancies, the prevalence of lymph node metastases is similar in calcified and non-calcified lymph nodes.

Detailed description: The presence of calcifications, which is a relatively common feature in intrathoracic lymph nodes, typically contributes to confer them a heterogeneous aspect during endosonographic B-mode examination, but a possible association between calcifications and metastatic involvement has never been systematically evaluated. The most likely reason why this possible association has been overlooked up to now is that the presence of calcifications in intrathoracic lymph nodes has long been thought to be the consequence of the prior involvement from granulomatous diseases (i.e., tuberculosis or sarcoidosis), and as such has been considered a sign of benignity. However, the presence of lymph node calcifications at ultrasound examination is a known predictor of lymph node metastasis in patients with some specific tumours, such as the papillary thyroid carcinoma or the squamous cell carcinoma of head or neck. Furthermore, recent radiological-pathological studies have shown that metastatic foci from lung cancer are observed in up to 19% calcified mediastinal lymph nodes identified at CT in surgical candidates. Finally, a recently published EBUS study has reported, for the first time, a very strong association between a very specific pattern of mediastinal lymph node calcification, known as "starry sky sign", and metastasis from pulmonary, colonic and breast adenocarcinoma. Interestingly, the starry sky sign is characterized by the presence of few to countless dot-like calcifications which are too small to be seen at CT and can be identified only during EBUS B-mode examination.

To the best of our knowledge, no studies have been carried out to assess the correlation between the presence and the ultrasound pattern of lymph node calcifications and lymph node metastasis from lung cancer or other intrathoracic malignancies.

Eligibility criteria: Inclusion Criteria:

* Age \>18 years at the time of the procedure
* Known or suspected lung cancer or other intrathoracic malignancy based on imaging (CT and/or PET/CT)
* Endosonography (EBUS and/or EUS) indicated for intrathoracic lymph node assessment/sampling according to national and international guidelines: 1) enlarged (\> 1 cm on its short axis at CT) and/or PET positive lymph node; and/or 2) conditions at risk for occult mediastinal metastases, such as: i) central primary tumor; ii) primary tumor \> 3 cm; iii) PET negative primary tumor; iv) ipsilateral hilar metastasis (cN1 status).

Exclusion Criteria:

* Inability or unwillingness to consent
* Compromised upper airway (i.e., concomitant head and neck cancer with upper airway obstruction; critical central airway obstruction from any cause)
* Contraindication for temporary interruption of the use of antiplatelet (excluded aspirin) or anticoagulant drugs
* American Society of Anesthesiologists grade 4

Primary outcomes:
measure: prevalence of metastatic involvement in intrathoracic lymph nodes featuring calcifications of any type
timeFrame: 6 months
Secondary outcomes:
measure: The prevalence of metastatic involvement from lung cancer linked to 5 predefined patterns of lymph node calcification at B-mode ultrasound examination carried out during endosonography
timeFrame: 6 months
measure: The interobserver agreement for the identification of 5 predefined patterns of lymph node calcification at endosonographic B-mode ultrasound examination
timeFrame: 1 month
measure: The prevalence of actionable mutations in the overall cohort of calcified lymph nodes identified with endosonography
timeFrame: 1 month
Other outcomes:
Locations:
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A. Gemelli IRCCS
Study officials:
affiliation: Catholic University of the Sacred Hearth
name: Rocco Trisolini, MD
role: PRINCIPAL_INVESTIGATOR
References: