The Method ISET (Insulation by Size of Epithelial Tumor Cells)

Evaluation of the Value Forecasts of the Identification of the Circulating Tumoral Cells (CTC) in the Broncho-lung Carcinomas Not in Small Cells of Stages I and II by the Method ISET (Insulation by Size of Epithelial Tumor Cells)

The aim of this study is, i) to assess the presence and the frequency of CTC in NSCLC patients undergoing surgery by using cytopathological analysis after their isolation by size (ISET method), and, ii) to correlate the presence of CNHC with pTNM stage, histological subtype, and percentage of tumor cells present into the primary tumors.

Study Overview

• Status: Unknown
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Biological: ISET Methode

Detailed Description

Lung cancer is the most prevalent neoplasm and the major cause of tumor-related mortality worldwide. Despite recent advances in the management of resected lung cancers (i.e., the use of adjuvant therapy) and more effective treatments of metastatic tumors (i.e., molecular targeted agents), the cure rate of patients with lung cancer remains low (. Histological classification of lung tumors distinguishes small (SCLC) and non-small cell lung cancers (NSCLC). Most NSCLC display three histological subtypes: adenocarcinoma, squamous cell carcinoma and large cell carcinoma. The prognosis of these three NSCLC subtypes is quite similar. In this regard, development and validation of new prognostic/predictive biomarkers from tumor tissues and biological fluids is one of the more promising domain in translational cancer research. However, the clinical impact of new biomarkers has to be carefully validated, including for NSCLC. While pTNM staging is currently the only validated prognostic factor used in NSCLC patients follow up and treatment, 25% to 50% of patients with early-stage I NSCLC show tumor recurrence following extensive tumor resection, indicating the urgent need of more sensitive prognostic markers. Furthermore, it has been reported that the presence of occult metastatic disease correlates with disease recurrence in stage I NSCLC patients. There is now a sizable body of evidence that metastases could develop from circulating tumor cells (CTC) spread in blood before or during surgery . Thus, sensitive and specific detection of CTC in blood is considered as a potentially relevant predictive biomarker for patients with NSCLC. Indeed, the main goal for preoperative detection of CTC is to identify patients with high risk of recurrence after surgery, in order to perform more adapted therapeutic strategy. Despite several studies reported about CTC detection, methodological aspects concerning sensitivity, specificity and reproducibility have prevented a clear appraisal of their clinical impact. While RT-PCR and immune-mediated methods can be very sensitive, specificity remains a critical issue for these approaches as no transcript or antigen is known at present specifically recognizing tumor cells from solid tumors . In this setting, cytopathological analysis of circulating non hematological cells (CNHC), of epithelial (CEC) and endothelial (CEN-C) origin, isolated according to their size (ISET, Isolation by Size of Epithelial Tumor cells) is considered a promising approach, as CNHC enrichment is very sensitive and cell morphology is not damaged allowing to apply classical cytopathological criteria to identify tumor cells. In this regard, ISET technology has been previously reported to allow identification of CTC in patients with liver and breast tumors. However, ISET method has never been used to detect CTC in patients with NSCLC. The aim of this study is to determine the diagnostic potential of ISET method for preoperative detection of CTC in NSCLC patients. For this purpose cytomorphological criteria have been established by a group of 10 cytologists to classify CNHC in 3 groups : i) CNHC with malignant features (CNHC-MF) , ii) CNHC with uncertain features (CNHC-UMF), and, iii) CNHC with benign features (CNHC-BF). The presence and number of these circulating cells are then correlated with pTNM, histological subtype, and percentage of tumor cells into the primary tumors.

• Study Type: Interventional
• Enrollment (Anticipated): 520
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Nice, France
    • Recruiting
    • Pr Paul HOFMAN
    • Contact: Paul Pr Hofman, PU-PH; Phone Number: 04 92 03 87 49; Email: hofman.p@chu-nice.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

For the patients:

• patient having been operated for a strong suspicion or a suspicion of a malignant tumoral hurt corresponding to a primitive carcinoma not in small cell of the lung

For the control subjects:

• Tabagical patients (between 10 and 30 packages years)
• unhurt of any malignant or mild tumoral pathology or patients that must benefit from a surgical operation for an extract of a hurt lung parenchymateuse for a not tumoral hurt

Exclusion Criteria:

• Patient with histories of cancer or the other synchronous cancer
• Patient with carcinomas with small cells, bronchiolo-alveolar carcinomas, the other types of tumors (lymphomes, sarcomas, etc.).
• Patient with neoadditives treatments
• Patient according to treatments additives others than protocols codified (in particular, platinum navelbine or gemcitabine platinum) for stages II

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; stade IA [pT1 N0M0]	Biological: ISET Methode; Sampling of blood - ISET Methode
Experimental: 2; stade IB [pT2 N0M0]	Biological: ISET Methode; Sampling of blood - ISET Methode
Experimental: 3; stade IIA [pTI N1M0]	Biological: ISET Methode; Sampling of blood - ISET Methode
Experimental: 4; stade IIB [pT2 N1 et T3N0M0]	Biological: ISET Methode; Sampling of blood - ISET Methode
Experimental: 5; control groupe [tabagic subject]	Biological: ISET Methode; Sampling of blood - ISET Methode
Experimental: 6; Control group B [intervention for a pulmonaire non tumoral pulmonary lesion]	Biological: ISET Methode; Sampling of blood - ISET Methode

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Presence or absence of circulating tumoral Cells(Units) according to: 1) The pTNM stage 2) the histological type	immediately

Secondary Outcome Measures

Outcome Measure	Time Frame
Specific survival and global survival, recurrence and metastasis	in 2 years, 3 years and 5 years

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nice
• Investigators: Principal Investigator: Paul Pr Hofman, PU-PH, Centre Hospitalier Universitaire de Nice

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Anticipated): October 1, 2012
• Study Completion (Anticipated): October 1, 2012

Study Registration Dates

• First Submitted: January 5, 2009
• First Submitted That Met QC Criteria: January 6, 2009
• First Posted (Estimate): January 7, 2009

Study Record Updates

• Last Update Posted (Estimate): December 8, 2011
• Last Update Submitted That Met QC Criteria: December 7, 2011
• Last Verified: December 1, 2011

More Information

Terms related to this study

• Keywords: non small cell lung cancer
• 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: 04-APN-08