Randomised Controlled Trial Comparing the Diagnostic Yield of Radial Endo-Bronchial Ultra-Sound (R-EBUS) Guided Cryo-biopsy Vs. CT-guided Transthoracic Biopsy in Patients With Parenchymal Lung Lesion, Suspected of Lung Cancer (CT-CROP)
Trial Snapshot
- Phase
- Phase 3
- Sponsor
- Enrollment
- 158
- Locations
- 2
- Primary Endpoint
- Diagnostic yield of cryo biopsy Vs. CT guided biopsy as measured by final histological diagnosis
Study Overview
Brief Summary
Obtaining a tissue sample to diagnose a PPL suspected of cancerous origin is of utmost importance. The current gold standard; Transthoracic CT guided needle biopsy approach with a success rate of >90% comes at the expense of an increased side effect profile.
Given that most lung cancers originate in the bronchus, hence named "bronchogenic carcinoma", it would be rational to think that endobronchial route should provide the best route of sampling with the least amount of side effects. Radial EBUS has become popular during the last decade as an endobronchial modality in diagnosing PPL with minimal side effects. However, the yield is still not satisfactory in comparison to CT guided biopsy with only 73% success rate in a meta-analysis. There is also with wide variation in different centres.
Use of a new biopsy method called cryo-biopsy using the R-EBUS guide sheath may bridge the gap and increase the diagnostic yield of PPL.
Cryo biopsy had been proven to give larger sample sizes and reduced crush artefact compared to the conventional radial EBUS biopsies.
However, there have been no head to head trials comparing Cryo-probe biopsy vs. the gold standard: CT guided biopsy.
Cryo-biopsy has very favourable side effect profile without any pneumothorax occurrence. If the yield were to be non-inferior to CT guided biopsy this would certainly be the preferred choice of biopsy for PPL in the future.
Methodology All patients with a PPL requiring a diagnostic biopsy will be eligible for recruitment to the trial. The recruited patients will be randomly allocated to either CT guided core biopsy or radial EBUS guided cryobiopsy.
Study design Multi centre intervetional,randomised control trial.
Study population:
Patients diagnosed with a PPL that requires a biopsy.
If the patient is randomised to the cryo biopsy arm:
The procedure will be done under the usual guidelines and practice of the centre as for a flexible bronchoscopy procedure.
Once flexible bronchoscopy is introduced the pre-determined desired segment, the R-EBUS is inserted covered by the GS.
Once the R EBUS locates the lesion, the GS is left in situ and the USS probe is retracted.
The cryoprobe is then inserted through the GS to the desired location. Flexible Cryoprobe (outer diameter 1.9mm) will be applied for 4 seconds for each biopsy. The cryogen gas used will be Co2.
The probe will be retracted together with the GS and the bronchoscope en masse after each biopsy. A minimum of 1 and maximum of 3 samples will be taken.
A CXR is taken within 1 hour post procedure to access for pneumothorax. Adverse events during the procedure will be recorded. If a chest tube placement, other investigations due to side effects or overnight hospital stay were to be required; all costs will be calculated retrospectively. Minor bleeding will not be considered an additional cost as this occurs with routine bronchoscopy.
If the patient is randomised to the CT biopsy arm:
A CT guided core biopsy will be performed as per usual practice of that centre. 2-6 passes will be performed for each PPL.
A CXR 1hour post procedure will be performed to assess for pneumothorax or procedure related bleeding.
If a chest tube placement, other investigations due to side effects or overnight hospital stay were to be required all costs will be calculated retrospectively.
At the pathology:
All samples will be assessed for the size of the sample and the suitability for molecular testing. An independent pathologist will assess samples.
Economic analysis:
For both procedures: Both direct and indirect costs will be calculated. The main aim of cost analysis is to calculate the cost of side effect management in each arm to determine the most cost-effective method of sampling a PPL.
Detailed Description
Obtaining a tissue sample to diagnose PPL suspected of cancerous origin is of utmost importance. Sampling of PPL can be done either through the chest wall (transthoracic) or through the airways that lead to the PPL (endobronchial).
The current gold slandered is Transthoracic Needle Aspiration (TTNA) approach is done by using CT guided biopsy with a success rate of >90%. However, this success in diagnostic yield comes at the expense of increased side effect profile including a very high risk of pneumothorax (up to 30%). Half of these patients require chest drain insertion.
Given that most lung cancers originate in the bronchus, hence named "bronchogenic carcinoma", it would be rational to think that endobronchial route should provide the best way of sampling with least amount of side effects. However, the yield is still not satisfactory and has a wide confidence interval.
When diagnosing a PPL endobronchially, accurate visualisation of the lesion is the main issue. To overcome this issue various navigation methods have been used to accurately locate the PPL to improve the diagnostic yield.
The use of Radial Endo Bronchial USS (R-EBUS) is one such navigational modality. The conventional R-EBUS guided biopsies are carried out using cytology brushes and forceps biopsy. These methods had been extremely safe with <1% pneumothorax rate however, the diagnostic yield in a meta-analysis of 14 studies is only 73%.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Diagnostic
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •All patients aged >18 years with a peripheral pulmonary lesion, suspected of lung cancer, requiring a biopsy
- •The lesion will be included irrespective of the relationship to the bronchus or ground glass appearance.
Exclusion Criteria
- •Patients with mediastinal adenopathy amenable to liner EBUS should have this procedure first and enrolled only if it fails to derive a diagnosis.
- •Endobronchial tumour on flexible bronchoscopy
- •Platelet count>150
- •International Normalised Ratio >=1.5
- •Haemoglobin>100
- •Neutrophils >1.0
- •Glomerular Filtration Rate>30
- •Liver Function Test< 2 times upper limit of normal
- •Unable to give consent/intellectually impaired
Outcomes
Primary Outcomes
Diagnostic yield of cryo biopsy Vs. CT guided biopsy as measured by final histological diagnosis
Time Frame: 2 years
This outcome measures the efficacy of CT guided biopsy (The current Gold standard) against the new biopsy method called cryo-biopsy which has better safety profile from previous pilot studies.
Secondary Outcomes
- Safety profile as measured by the rate of pneumothorax and bleeding(2 years)
- Ability to sub type and molecular type the biopsy sample over and above the conventional radial EBUS samples(2 years)
Investigators
Samantha Herath
Respiratory Physician, Intervetional bronchoscopist
Middlemore Hospital, New Zealand