Comparing Diagnostic Yield Between R-EBUS Guided Cryo Biopsy Vs. CT Guided Biopsy for PPL

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.

Sex

All

Minimum age

18 Years

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:

1. Patients with mediastinal adenopathy amenable to liner EBUS should have this procedure first and enrolled only if it fails to derive a diagnosis.
2. Endobronchial tumour on flexible bronchoscopy
3. Platelet count\>150
4. International Normalised Ratio \>=1.5
5. Haemoglobin\>100
6. Neutrophils \>1.0
7. Glomerular Filtration Rate\>30
8. Liver Function Test\< 2 times upper limit of normal
9. Unable to give consent/intellectually impaired

• RESULTNational Lung Screening Trial Research Team; Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, Fagerstrom RM, Gareen IF, Gatsonis C, Marcus PM, Sicks JD. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011 Aug 4;365(5):395-409. doi: 10.1056/NEJMoa1102873. Epub 2011 Jun 29. PMID 21714641
• RESULTProsch H, Stadler A, Schilling M, Burklin S, Eisenhuber E, Schober E, Mostbeck G. CT fluoroscopy-guided vs. multislice CT biopsy mode-guided lung biopsies: accuracy, complications and radiation dose. Eur J Radiol. 2012 May;81(5):1029-33. doi: 10.1016/j.ejrad.2011.01.064. Epub 2011 Jul 12. PMID 21752567
• RESULTLoh SE, Wu DD, Venkatesh SK, Ong CK, Liu E, Seto KY, Gopinathan A, Tan LK. CT-guided thoracic biopsy: evaluating diagnostic yield and complications. Ann Acad Med Singap. 2013 Jun;42(6):285-90. PMID 23842769
• RESULTMontaudon M, Latrabe V, Pariente A, Corneloup O, Begueret H, Laurent F. Factors influencing accuracy of CT-guided percutaneous biopsies of pulmonary lesions. Eur Radiol. 2004 Jul;14(7):1234-40. doi: 10.1007/s00330-004-2250-3. Epub 2004 Feb 13. PMID 14963689
• RESULTArslan S, Yilmaz A, Bayramgurler B, Uzman O, Nver E, Akkaya E. CT- guided transthoracic fine needle aspiration of pulmonary lesions: accuracy and complications in 294 patients. Med Sci Monit. 2002 Jul;8(7):CR493-7. PMID 12118196
• RESULTWu CC, Maher MM, Shepard JA. Complications of CT-guided percutaneous needle biopsy of the chest: prevention and management. AJR Am J Roentgenol. 2011 Jun;196(6):W678-82. doi: 10.2214/AJR.10.4659. PMID 21606253
• RESULTGrasso RF, Cazzato RL, Luppi G, D'Agostino F, Schena E, Del Vescovo R, Giurazza F, Faiella E, Beomonte Zobel B. Percutaneous lung biopsies: performance of an optical CT-based navigation system with a low-dose protocol. Eur Radiol. 2013 Nov;23(11):3071-6. doi: 10.1007/s00330-013-2932-9. Epub 2013 Jun 20.