Feasibility of Radioisotope-guided Excision of Mediastinal Lymph Nodes in Patients With Non-small Cells Lung Carcinoma (SLN_NSCLC)

Non-small cells lung carcinoma (NSCLC) represents one of the most common and lethal neoplasms. NSCLC is characterized by an early asymptomatic phase, which hinders the disease identification in its earliest stages. As a consequence, NSCLC is often diagnosed at a clinical stage when the potentially curative surgical approach is challenging. In general, NSCLC up to the TNM stage cT3N2M0 are considered operable; in particular, nodal localizations in the homolateral hilus (N1) and underneath the carina (N2) are considered surgically manageable. Identification of nodal disease on the pre-operative PET/CT does not guarantee that all disease-bearing lymph node will be retrieved in the course of the open operative procedure. Smaller nodes might be challenging to identify; moreover, the co-existence of macroscopic and microscopic disease might hinder the radicality of the surgical intervention. This process can be tracked using specific radioactive radiopharmaceuticals, such as radioisotope-labelled colloids, which can be injected in the immediate proximity of the primary and then travel toward the closest cluster of mediastinal lymph nodes. There, they are incorporated in the nodal structure and progress no farther. By employing a radioisotope probe during surgery, all of the first-line nodes (so-called sentinel lymph node, SLN), which receive the lymphatic flow from the tumor region directly, can be identified.

The hypothesis of the investigators is that, by performing a radioisotope SLN mapping intraoperatively, the surgeons will be able to detect the metastatization process more accurately than relying on pre-operative imaging alone.

The present study will be a prospective and monocentric trial. Clinical, histological, and imaging data collected from examinations performed according to the good clinical practice will be analyzed. The estimated duration of the study is 12 months. It will include the prospective inclusion of patients with a diagnosis of operable NSCLC, who will receive a surgical treatment with curative intent at the investigators' institution (ICH).

Study Overview

• Status: Recruiting
• Conditions: Lung Cancer
• Intervention / Treatment: Diagnostic test: Sentinel lymph node scintigraphy

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Arturo Chiti, Professor; Phone Number: +390282246621; Email: arturo.chiti@hunimed.eu
• Study Contact Backup: Name: Lidija Antunovic, MD; Phone Number: +390282247545; Email: lidija.antunovic@humanitas.it

Study Locations

• Italy
  • Milano
    • Rozzano, Milano, Italy, 20089
      • Recruiting
      • Istituto Clinico Humanitas
      • Contact: Arturo Chiti, Professor; Phone Number: +390282246621; Email: arturo.chiti@hunimed.eu
      • Contact: Lidija Antunovic, MD; Phone Number: +390282247545; Email: lidija.antunovic@humanitas.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18 years
• Newly diagnosis of stage I-IIIa NSCLC (higher stage could be considered, pending a multidisciplinary evaluation and approval).
• Baseline 18FFDG-PET-CT and ceCT
• Treatment according to good clinical practice

Exclusion criteria:

• Unavailability of baseline images
• Diagnosis other than NSCLC at definitive pathology
• Surgery carried without complete resection or with no curative intent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Experimental

Diagnostic test: Sentinel lymph node scintigraphy; During the surgery, right after the identification of the primary, 18-37 MBq of 99mTc-Nanocolloids in two ml will be injected at four peritumoral locations. After a brief waiting time (5-10'), the thoracic surgeon will perform the clinical intervention, including the lobectomy (the injection sites will be resected alongside the tumour) and lymphadenectomy, according to the best clinical practice. All the excised lymph nodes will be ex vivo counted using a gamma probe: those with a detectable activity (at least 10% of the "hottest" lymph node) will be considered as SLN. Thereafter, the mediastinum will be scanned using the gamma probe and a handheld gamma-camera (the latter will not be employed in case of robotic-assisted surgery); any further source of radioactivity will be investigated and, should further lymph nodes be identified, these will be also resected and classified in SLN or non-SLN, based on ex vivo activity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detection rate (DR) of the SLN technique.	The DR is defined as the capability of the SLN of identifying the mediastinal lymph nodes receiving the lymphatic flow, i.e., the presence and the number of lymph nodes, which can be identified with the gamma probe intraoperatively. This parameter will be measured as the ratio between the number of removed lymph nodes that will show a signifcant uptake of the radiotracer (>10 counts per minute) and the total number of removed lymph nodes.	12 months
Sensitivity (Se) of the SLN technique.	The Se will be defined as the ratio between the number of identified nodal disease foci that will show a signifcant uptake of the radiotracer (>10 counts per minute) and the total number of identified nodal disease foci.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of the efficiency of a portable gamma camera	the measurement of the efficiency of a portable gamma camera, when compared with the standard gamma probe, in terms of DR. This parameter will be measured as the ratio between the number of removed lymph nodes that will show a signifcant uptake at the examination with the portable gamma camera (as evaluated by an expert operator) and the number of removed lymph nodes that will show a signifcant uptake of the radiotracer (>10 counts per minute) with the standard gamma probe	12 months
Comparison between the lower (I-II) and the higher (III and above) disease stages	The comparison of DR and Se between the lower (I-II) and the higher (III and above) disease stages. The analysis will be performed using the ROC curves for these parameters.	12 months

Collaborators and Investigators

• Sponsor: Istituto Clinico Humanitas

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2021
• Primary Completion (Anticipated): May 1, 2022
• Study Completion (Anticipated): July 1, 2022

Study Registration Dates

• First Submitted: May 24, 2021
• First Submitted That Met QC Criteria: October 8, 2021
• First Posted (Actual): October 11, 2021

Study Record Updates

• Last Update Posted (Actual): December 8, 2021
• Last Update Submitted That Met QC Criteria: November 24, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: 1957 (NRICP)

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