Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Patients will undergo pEBUS with a regular size bronchoscope using the guide sheath technique and presence of ROSE

Patients will undergo pEBUS with a slim bronchoscope combined with a 1.7mm radial probe but no guide sheath and the presence of ROSE.

Patients will undergo pEBUS with a regular size bronchoscope using the guide sheath technique but without ROSE.

Patients will undergo pEBUS with a slim bronchoscope combined with a 1.7mm radial probe but no the guide sheath an without the presence of ROSE.

Pathologist on site for direct evaluation of specimen adequacy

Rapid on-site evaluation (ROSE)

peripheral endobronchial ultrasound performed with a slim bronchoscope (3.0 mm outer diameter with a 1.7mm channel) combined with a radial ultrasound probe but without the use of a guide sheath.

Slim bronchoscope without a guide sheath

Using a flexible bronchoscope with minimal outer diameter of 4.2mm.

Standard pEBUS with guide sheath

Alain Tremblay, MDCM

Peripheral pulmonary lesions (PPL) are defined as nodules or masses that are located in the lung periphery; hence cannot be seen via regular bronchoscopy. Due to their location, establishing a pathological diagnosis can be challenging. Investigations of PPL has significantly evolved in the last decade with the development of new technologies such as peripheral endobronchial ultrasound (pEBUS), virtual bronchoscopy and electromagnetic navigational bronchoscopy (ENB). Although these technologies have allowed physicians to safely biopsy previously difficult to access nodules, their sensitivity have been lower than trans-thoracic needle aspiration (TTNA). In fact, the largest registry to date has found a diagnostic yield of pEBUS of 57% compared to 93% for TTNA. However, TTNA caries substantially more procedural risk than pEBUS with a 25% rate of complication vs 2.8% for pEBUS (1, 2). With increased sensitivity, pEBUS could become the procedure of choice for PPL investigation in view of its safety profile. Rapid on-site evaluation of biopsy samples by a cytopathologist (ROSE) allows for direct evaluation of specimen adequacy. By offering real-time feedback to the bronchoscopist about specimen adequacy, the adding of ROSE to pEBUS could lead to an increase in diagnostic yield, allowing for a faster diagnosis of lung cancer and avoiding the need for further diagnostic procedures. Minitiazuration of broncoscopes can also allow navigation to more distal areas of the lung closer to the PPL. While this may also improve diagnostic yield, other technical modification such as the need for smaller sampling instruments and inability to use a guide sheath may have drawbacks.

This study will use a 2 x 2 factorial design to compare diagnostic yield of pEBUS bronchoscopic PPL sampling with vs. without ROSE as well as with a novel "slim" bronchoscope vs. standard bronchoscope. The investigators aim to randomize 208 patients to independently test each hypothesis.

Peripheral EBUS With ROSE vs no ROSE; Slim Bronchoscope Without Guide Sheath vs Standard Bronchoscope With Guide Sheath

Rapid On-site Evaluation and Use of a Slim Bronchoscope During Peripheral Endobronchial Ultrasonography for the Investigation of Peripheral Pulmonary Lesion - A Randomized Controlled Factorial Trial

Individual deidentified participant data that underlie the results reported in this article (text, tables, figures and appendices) will be shared with researchers who provide a methodologically sound proposal. Other accessible documents will include the study protocol. Beginning 9 months and ending 36 months following article publications, proposals may be submitted to alain.tremblay@ucalgary.ca. To gain access, data requestors will need to sign a data access agreement.

Sample adequacy for EGFR mutation analysis, ALK and PDL1 immunohistochemistry.

Combination of endpoints following chart review, including but not limited to unplanned hospitalization or emergency room visit, hemoptysis, pneumothorax, chest infection, fever or exacerbation of lung disease.

McGill University

Laval University

University of Calgary

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

In patients allocated to this arm a CT guided core biopsy will be performed

If the patient is randomised to this arm, the lesion will be located via R-EBUS.

Each patient will have 3 cryo biopsies and 3 forceps biopsies. The order of the cryo biopsy and forcep biopsy will be randomly allocated at the time of initial randomisation.

CT guided biopsy will be performed by a trained interventional radiologist using core biopsy.

CT guided core biopsy

Cryo-biopsy will be performed via R-EBUS guidance. Cryo biopsy probe will be applied for 4 seconds for each biopsy and a minimum of 3 biopsies will be performed . Each patient will also have 3 forceps biopsies. The order of forceps biopsy or cryo biopsy will be randomly allocated.

Cryo-biopsy via Radial EBUS navigation

Samantha Herath, MBBS, MPhil, FRACP

Andrew Veale, FRACP

Samantha Herath, MBBS, FRACP

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.

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%.

Use of a new biopsy method called cryo-biopsy may bridge the gap and increase the diagnostic yield of PPL.

Cryotherapy is the use of a compressed gas released at a high flow that rapidly expands and creates very low temperatures up to -89C. These very low temperatures then cause tissue to get stuck to the end of the cryo-probe. Due to the rapid cooling the microvasculature around the biopsy site go into vasospasm and reduces bleeding despite a large biopsy sample being acquired.

Cryotherapy has been used in the airway since 1968. The ability to use this method while the patient is using high flow oxygen as well as being a cheap equipment to use makes it very affordable and useful equipment in any interventional bronchoscopy unit. Most bronchoscopists will be trained and familiar with cryo biopsy technique.

The cryo-biopsies were compared against forceps biopsies in this study and demonstrated larger sample size and less crush artefact favouring cryo- biopsy use.

The most encouraging results published recently was looking at cryo-biopsy for PPL using R-EBUS guidance, which demonstrated a yield of 74% and the ability to obtain 3 times larger tissue biopsies when compared to traditional forceps biopsies. There were no pneumothorax in this cohort and only minor bleeding was recorded requiring bronchoscopy suction alone and no other intervention recorded.

However, there had been no head to head trials comparing Cryo-probe vs. the gold standard: CT-guided biopsy.

As cryo-biopsy has very favourable side effect profile without any pneumothorax occurrence if the yield were to be non-inferior this would certainly be the preferred choice of biopsy for PPL in the future.

With regards to cost analysis it has been shown that R-EBUS guided biopsy Vs. CT guided biopsy has similar cost profiles for the procedure alone. However the final cost of the procedure depends on the side effects experienced using each procedure, making CT guided biopsy the costlier of the 2 methods.

However, cryo-biopsy and CT guided biopsy had not been compared in an economic analysis before.

Methodology All patients with a PPL requiring a diagnosis will be eligible for the trial.

Prior to the procedure: (Either CT guided biopsy or cryo biopsy)

1. The size of the lesion will be recorded (volume assessment and maximum diameter on the axial scan) from the CT scan prior to procedure. .

If the patient is randomised to the cryo biopsy arm:

1. The bronchoscopist will plan the pathway to the PPL based on the CT scans. The sub segments from which the lesions could be biopsied will be pre-determined and documented. If available, virtual bronchoscopy will be used to confirm this navigational path to the lesion.
2. Maximum time allowed to locate the lesion via R-EBUS would be 20 mins.
3. The procedure will be done under the usual guidelines and practice of the centre as for a flexible bronchoscopy procedure. As this is a multi-centre trial centre variation on the usual practice of bronchoscopy may vary.
4. Some centres may use fluoroscopy, in addition, to localise the lesion. This is also acceptable in the protocol.
5. If an endobronchial lesion is found then the patient is excluded.
6. Once flexible bronchoscopy is introduced the pre-determined desired segment, the R-EBUS is inserted covered by the GS.
7. Once the R EBUS locates the lesion, the GS is left in situ and the USS probe is retracted.
8. The cryo probe is then inserted through the GS to the desired location. Flexible Cryo probe (outer diameter 1.9 mm) will be applied for 4 seconds for each biopsy.
9. The probe will be retracted together with the GS and the bronchoscope en masse after each biopsy.
10. A minimum of 1 and maximum of 3 samples will be taken.
11. A CXR is taken within 1-hour post procedure to access for pneumothorax.
12. Adverse events during the procedure will be recorded as: Minor bleeding (requiring cold saline or adrenalin), moderate bleeding (requiring a bronchial blocker or APC) and a large bleed (requiring blood transfusion, FFP, cardiothoracic support) etc.
13. 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:

1. The interventional radiologist will decide on the best position for the patient to stay during the procedure.
2. A core biopsy will be performed as per usual practice of that centre. In CMDHB all CT guided biopsies are performed as core biopsies.
3. The patient will have 2-6 biopsies from the PPL.
4. Patient lies on the side of the biopsy for 1 hour post procedure. Post procedure monitoring will be performed as per usual practice.
5. A CXR 1 hour post procedure will be performed to assess for pneumothorax or procedure related bleeding.
6. 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 area of specimen to assess the size. The ability to perform molecular typing will be documented.

An independent pathologist will assess samples

Economic analysis:

For both procedures: Both direct costs (From the hospital records) and indirect cost (by administering a patient questionnaire) will be recorded.

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.

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

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)

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.

The CT guided biopsy has good efficacy rates but a high risk of pneumothorax (up to 30%) and pulmonary haemorrhage (4-27%), which requires further management adding to the cost of the intervention. The cryobiopsy method had been proven in pilot studies to have a better safety profile with \<1% pneumothorax risk. Hence comparing the side effect profile and if cryo biopsy is far safer alternative would make this the first option for the patient.

Cryo biopsy gives a larger sample size and hypothesized to give a better molecular analysis for EGFR mutation and ALK mutation analysis

Middlemore Hospital, New Zealand

Respiratory Physician, Intervetional bronchoscopist

Endobronchial ultrasound miniprobe is used to identify solid mass in lung parenchyma.

Endobronchial ultrasound miniprobe

Jon A Hardie, MD/PhD

Bronchoscopy of non visible lesions in the lung, have a low diagnostic yield. The use of endoscopic ultrasound might increase the diagnostic yield. This prospective study randomises between bronchoscopy with the use of a ultrasound miniprobe and bronchoscopy without the use of a miniprobe in clinical practice at Haukeland University Hospital.

The study hypothesis:

The use of the ultrasound miniprobe will increase the diagnostic yield of bronchoscopy in non visible lesions.

Bronchoscopy is usually the primary investigation of lesions in the lung. X-ray fluorescence guides the sampling with brushing, biopsy or trans bronchial needle aspiration (TBNA) if the lesion not is visible. Ct guided trans-thoracic sampling will be performed if a the sample is non representative. This will delay the diagnosis, and trans-thoracic sampling has a higher risk of pneumothorax. The use of a ultrasound miniprobe might increase the diagnostic yield of bronchoscopy in non visible lesions. The ultrasound probe in a guide sheath is advanced to the lesion with use of X-ray fluorescence. When the lesion is visualised the miniprobe is removed and sampling is performed with TBNA, biopsy and brushing through the guide sheath. If rapid on site cytoevaluation is negative, new TBNA is performed. Previous trials have shown a diagnostic yield without ultrasound between 40-50% and with ultrasound between 60-80%. The studies with ultrasound have been performed by "super specialists". This study will evaluate bronchoscopy with the use of ultrasound miniprobe in clinical practice without "super specialists". It is a prospective randomised trial.

Utility of Endobronchial Ultrasound in the Investigation of Suspected Lung Cancer.

Diagnostic Utility of Endobronchial Ultrasound in the Investigation of Suspected Malignant Lung Lesions Where the Lesions Are Not Visible During Bronchoscopy.

Helse Sunnmore, 6026 Ålesund

Haukeland University Hospital

Jon Andrew Hardie, MD/PhD

Fluoroscopy are not used in this group. EBUS and GS are inserted into bronchi in the assistance of VBN. The EBUS probe and GS are confirmed to reach the lesion by EBUS images alone, cytologic and pathologic specimens are obtained without fluoroscopic guidance.

EBUS and GS are inserted into bronchi in the assistance of VBN. The EBUS probe and GS are confirmed to reach the lesion by EBUS images and radiograph fluoroscopy, cytologic and pathologic specimens are obtained with fluoroscopic guidance.

VBN is carried out by a VBN software（DirectPath; Olympus, Japan) which can automatically create virtual bronchoscopic images.

EBUS is performed using an endoscope ultrasound system , which is equipped with a 20-MHz mechanical radial-type probe (UM-S20-17S;Olympus) with an external diameter of 1.4 mm and a GS (K-201; Olympus).

EBUS-GS

The radiograph fluoroscopy are performed when the probe and GS are confirmed to reach the lesion by EBUS images ,cytologic and pathologic specimens are obtained under fluoroscopic guidance.

X-ray

Sun Jiayuan, MD

The purpose of this study is to evaluate the feasibility, efficacy and safety of transbronchial lung biopsy (TBLB) and bronchial brushing by using virtual bronchoscopic navigation (VBN) combined with endobronchial ultrasound (EBUS) and a Guide Sheath (GS) for the diagnosis of peripheral pulmonary lesions (PPLs) without radiographic fluoroscopy.

The investigators evaluate the feasibility, efficacy and safety of transbronchial lung biopsy (TBLB) and bronchial brushing by using virtual bronchoscopic navigation (VBN) combined with endobronchial ultrasound (EBUS) and a Guide Sheath (GS) as a guide for diagnosing peripheral pulmonary lesions (PPLs) without radiographic fluoroscopy.The study is designed as a three centers prospective randomized controlled trial.The participating centers are Department of endoscopy , Shanghai chest Hospital, Shanghai JiaoTong University, China. Department of endoscopy, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, China. Department of Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, China. Patients are divided into two groups, VBN-EBUS-GS-X-ray group and VBN-EBUS-GS group. Each subject will be randomized to each group. The study is expected to enroll 436 patients at 3 centers.

VBN-EBUS-GS-TBLB With or Without Fluoroscopy for the Diagnosis of PPLs

Diagnostic Value of Virtual Bronchoscopic Navigation (VBN) Combined With Endobronchial Ultrasound (EBUS) With a Guide Sheath (GS) for Peripheral Pulmonary Lesions (PPLs) Without Fluoroscopy: a Randomized Controlled Trial

The diagnostic value means sensitivity and specificity in two groups

The operation time includes total operation time,total GS time and total EBUS time

Complications mean a composite of operation-related serious adverse events (pneumothorax, bleeding, etc.) during and after the operation

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Peripheral EBUS With ROSE vs no ROSE; Slim Bronchoscope Without Guide Sheath vs Standard Bronchoscope With Guide Sheath	NCT03809169	Peripheral Pulm... Lung Cancer	Rapid on-site e... Slim bronchosco... Standard pEBUS ...	18 Years -	University of Calgary
Comparing Diagnostic Yield Between R-EBUS Guided Cryo Biopsy Vs. CT Guided Biopsy for PPL	NCT02395939	Lung Cancer	CT guided core ... Cryo-biopsy via...	18 Years -	Middlemore Hospital, New Zealand
Comparing Diagnostic Yield Between R-EBUS Guided Cryo Biopsy Vs. CT Guided Biopsy for PPL	NCT02395939	Lung Cancer	CT guided core ... Cryo-biopsy via...	18 Years -	Middlemore Hospital, New Zealand
Utility of Endobronchial Ultrasound in the Investigation of Suspected Lung Cancer.	NCT00398970	Lung Cancer	Endobronchial u...	-	Haukeland University Hospital
VBN-EBUS-GS-TBLB With or Without Fluoroscopy for the Diagnosis of PPLs	NCT02484066	Lung Cancer	VBN EBUS-GS X-ray	18 Years -	Shanghai Chest Hospital
Comparing Diagnostic Yield Between R-EBUS Guided Cryo Biopsy Vs. CT Guided Biopsy for PPL	NCT02395939	Lung Cancer	CT guided core ... Cryo-biopsy via...	18 Years -	Middlemore Hospital, New Zealand
Utility of Endobronchial Ultrasound in the Investigation of Suspected Lung Cancer.	NCT00398970	Lung Cancer	Endobronchial u...	-	Haukeland University Hospital

Spots Global Cancer Trial Database for guide sheath

Every month we try and update this database with for guide sheath cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.