Complete Endosonographic Intrathoracic Nodal Staging of Lung Cancer Patients in Whom SABR is Considered

Complete Endosonographic Intrathoracic Nodal Staging of Lung Cancer Patients in Whom Stereotactic Ablative Radiotherapy (SABR), is Considered

Rationale: Accurate staging of lung cancer is important because it directs treatment and determines prognosis. The development of Stereotactic Ablative Radiotherapy (SABR), has revolutionized radiation therapy for early stage lung cancer and results demonstrate similar outcomes in comparison to surgical resection of the lung tumor. The staging work-up program for patients with a potentially resectable Non-Small-Cell Lung Cancer (NSCLC) includes at least a computed tomography (CT) scan of the chest and integrated Positron Emission Tomography - Computed Tomography (PET/CT) scans, and when indicated, invasive mediastinal staging. However, patients who are treated with SABR do not routinely undergo the same nodal staging work-up as do surgical candidates. As both surgery and SABR appear to achieve comparable rates of local and regional tumor control, it appears only logical to perform a similar staging work-up in all patients with early stage lung cancer who will be treated with either of the two curative local modalities. In the past, a lack of invasive nodal sampling before SABR was considered acceptable as invasive surgical staging (mediastinoscopy) was widely considered the preferred procedure. However, with minimally invasive and safe endosonography procedures now available, improved pre-treatment staging has become possible for patient groups who are eligible for SABR, including those with significant comorbidities.

Hypothesis: Complete endosonographic (combined endobronchial and esophageal) staging of hilar and mediastinal lymph nodes in patients with (suspected) non-small cell lung cancer (NSCLC) will result in change of loco-regional nodal status in 20% of patients, in comparison to staging by PET-CT alone.

Study population: Patients with either established or suspected early-stage NSCLC who are medically inoperable, or who refuse surgery but are potential candidates for SABR with curative intent (provided no intrathoracic metastases are present). Patients will undergo a single scope complete mediastinal and hilar staging procedure (combined EndoBronchial UltraSound (EBUS) and Transesophageal Endoscopic Ultrasound with EBUS scope (EUS-B)).

Study Overview

• Status: Unknown
• Conditions: Non Small Cell Lung Cancer (NSCLC); Intrathoracic Nodal Staging

• Study Type: Observational
• Enrollment (Anticipated): 102

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Recruiting
    • NKI-AvL
    • Contact: W Buikhuisen, MD
    • Contact: Wieneke Buikhuisen; Phone Number: +31-20-512 2958
  • Amsterdam, Netherlands
    • Recruiting
    • VUmc
    • Contact: Johannes Daniels, MD PhD
    • Contact: Johannes Daniels, MD PhD; Phone Number: +31-20-4444444
  • Nijmegen, Netherlands
    • Recruiting
    • UMCN
    • Contact: O Schuurbiers, MD PhD; Phone Number: +31(0)243613648
    • Principal Investigator: Olga Schuurbiers, MD
• Poland
  • Krakow, Poland
    • Recruiting
    • Independent Endoscopy Unit, John Paul II Specialist Hospital
    • Contact: Artur Szlubowski, MD

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

Patients with either established or suspected early-stage NSCLC who are medically inoperable, or who refuse surgery but are potential candidates for stereotactic ablative radiotherapy (SABR) with curative intent (provided no intrathoracic metastases are present)

Description

Inclusion Criteria:

• Proven, or highly suspected, non-small cell lung cancer (NSCLC)
• Absence of distant metastases based on PET-CT
• Stereotactic ablative radiotherapy (SABR) with curative intent is contemplated
• One of the following features based on PET-CT:
• Centrally located clinical T1-T2 N0 tumor
• Peripheral located clinical T2 N0 tumor
• Suspicion of N1- N2 disease based on either size (short axis > 10mm CT) or FDG uptake
• Non-FDG avid primary lung tumor and lymph nodes

Exclusion Criteria:

• Medically operable patients with a resectable lung tumor (unless SABR is the explicit preference of the patients or treating physicians preference).
• Bulky nodal disease based on PET-CT
• Contra-indications for endosonography and / or bronchoscopy
• Pregnancy
• Age under 18
• No informed consent

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

NSCLC, SABR, nodal staging; Patients with a clinical or pathological diagnosis of Non-Small Cell Lung Cancer (NSCLC), and who are medically inoperable or refuse surgery, are eligible if Stereotactic ablative radiotherapy (SABR) is recommended by a multi-disciplinary tumor board. All patients undergo complete mediastinal and hilar staging procedure (EBUS+EUS-B). Pre endoscopy imaging data will be compared with endosonography data.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with change in nodal status based on imaging compared to nodal status based on endosonography.	Prior to endoscopy the nodal status (single outcome measure either N0,N1,N2,N3) will be defined based on (PET) CT imaging. After complete endosonographic staging (EBUS+EUS-B) of the hilus and mediastinum again the nodal status will be defined (single outcome measure either N0,N1,N2,N3) based on endosonography findings. The sensitivities, negative predictive values (NPV) and positive predictive values (PPV) for endosonography and PET-CT imaging will be calculated.	0-6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiotherapy plan based on imaging (prior to endosonography) compared to the radiotherapy plan based on endosonography outcomes.	The radiotherapist will make a radiation plan (Gross Tumor Volume (GTV) primary tumor, internal target volume (ITV) primary tumor and planning target volume (PTV) primary tumor) based on (PET) CT imaging prior to endosonography. After endosonography the radiotherapist will make another radiotherapy plan based on endosonography staging results. The proportions of changed radiotherapy plans per patient basis will be calculated.	1 month
Incremental pathological confirmation of the diagnosis of lung cancer in patients with only a clinical diagnosis, following endosonographic staging.		1 month
Complication rate of a complete endosonographic procedure in this patients group		1 month

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Investigators: Principal Investigator: Jouke T Annema, MD PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Anticipated): June 1, 2017

Study Registration Dates

• First Submitted: October 17, 2014
• First Submitted That Met QC Criteria: December 15, 2016
• First Posted (Estimate): December 20, 2016

Study Record Updates

• Last Update Posted (Estimate): December 20, 2016
• Last Update Submitted That Met QC Criteria: December 15, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Stereotactic ablative radiotherapy (SABR); Non-Small Cell Lung Cancer (NSCLC); Intrathoracic nodal staging
• 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: STAGE; 2013_196 (Other Identifier: Medical Ethics Review Committee Academic Medical Center)