Comparison of the Diagnostic Accuracy Between US-guided Percutaneous Lung Biopsies vs CT-guided in Peripheral Lung Lesions (SULTAN)

A Prospective, Randomized, Multicentric and Single-blinded Study on Accuracy and Safety of Ultrasound (US) Guided Percutaneous Needle Biopsy of Peripheral Lung Lesion Compared With Computed TomogrAphy (CT) Guided Needle Biopsy

A non-sponsored prospective randomized single-blind national multicenter interventional study which aims to compare the diagnostic accuracy between US-guided percutaneous lung needle biopsies and CT-guided in peripheral lung lesions. Secondary endpoints are:

• onset of number and type of complications during and after the procedure, within the first three hour;
• exposition to ionizing radiation, in mGy;
• patient comfort during the procedure;
• duration of the procedure,

Study Overview

• Status: Recruiting
• Conditions: Peripheral Lung Lesions
• Intervention / Treatment: Diagnostic test: US-GUIDED PERCUTANEOUS LUNG NEEDLE BIOPSY; Diagnostic test: CT-GUIDED PERCUTANEOUS LUNG NEEDLE BIOPSY

Detailed Description

Peripherical pulmonary lesions without endobronchial lesions (LPP) are nowadays more and more frequently found in clinical practice, and it's only assumable that this tendency will keep growing in the future, alongside the increasing use of thoracic CT scanning and the proven efficacy in lung cancer screening. Even though most of these lesions are benign, it's still important to be able to identify neoplastic lesions in an early stage.

The gold standard for diagnosis definition is biopsy, which can be performed by four paths: surgery, transbronchial endoscopy (TBB), endobronchial endoscopy (EBB) or percutaneous (TTNA).

Surgical option is the most reliable one in terms of diagnostic yield, at the expense of an increased risk of complications, post-operative recovery in hospital staying and costs, compared with the other three procedures; due to the safety and diagnostic yield of TBB, EBB and TTNA, the surgical approach, just for the purpose of diagnosis, resulted in a secondary choice in the diagnostic flowchart of LPP. In addiction, given the high probability of the benign nature of the LPP, the choice of a less invasive approach in the diagnostic phase is even more reasonable. Even though technology really improved the diagnostic yield of LPP, overall sensibility is around 70-80%, influenced by many factors such as: localization and extension of the lesion, presence of bronchus sign, sampling techniques and procedural errors. The incidence of complications for this type of sampling, mostly presented by pneumothorax, is around 4%.

The TTNA is a largely used procedure for diagnosing LPP and it can be conducted using both a CT guided and an ultrasound guided approach, as long as the lesion is located in direct contact with the thoracic wall. CT scan guide has the perk of giving a more precise view of: densitometric feature of the lesions, their location and the connections with the anatomical structures surrounding them. LPP CT guided TTNA (tTTNA) can reach a diagnostic yield of 98% in case of an experienced operator, where ultrasound guided reaches about 93.4%, only slightly inferior to the prior one. Both tTTNA and ultrasound guided percutaneous transthoracic biopsy (eTTNA) are useful techniques not only for pulmonary parenchymal diseases but also in case of pleural lesions, allowing simultaneous sampling and visualization of the lesions in exam.

Peripheric pleural lesions can also be approached via thoracoscopy (both medical and surgical) with a diagnostic efficiency between 91-95% for malignant lesions and 100% for TBC-related lesions. However, the high risk of complications after the procedure, the duration of hospitalization post-surgery and the costs, suggest choosing between eTTNA and tTTNA as the very first diagnostic step in pleural lesions as well. Moreover, the diagnostic yield of tTTNA and eTTNA is respectively of 89% and 90%.

Both eTTNA and tTTNA demonstrated a good ability in distinguishing between benign and malignant lesions. In the latter case, collecting a representative enough sample allows the appropriate immunohistochemical phenotyping and genetic sequencing of it, enabling to make targeted therapeutical choices according to the current Guidelines.

Literature suggests that the number of bioptic steps necessary to obtain an adequate diagnostic sample is of three steps, where an upper number of them would increase the risk of complications despite an almost equal diagnostic efficiency. Principal complications of percutaneous sampling, common to both the approaches, are pneumothorax and minor bleeding (not requiring blood transfusion) In literature there are no clear indications about which of these two methods is better in case of lesions touching the pleural surface, therefore approachable with both tTTNA and eTTNA; in everyday clinical practice the choice is mostly driven by the availability of each technique in the Center of expertise. Also, from the literature that could be gathered, there is no prospective comparison between ultrasound-guided and CT-guided needle biopsy of peripheric pulmonary lesion touching the thoracic wall.

Nonetheless, a trial retrospectively analyzed both ultrasound-guided and CT-guided sampling of thoracic lesions touching the wall and it enlighted that the complications rate was minor for the ultrasound-guided approach: respectively 3.3% and 24%. Even more, differently from the tTTNA, eTTNA doesn't expose the patients to any ionizing radiation and it allows to avoid artefacts deriving from respiratory movements and the ribs' interposition.

On this ground of observations, we present the following trial, which would be the first prospective one to compare the diagnostic accuracy between the two approaches (tTTNA and eTTNA) for diagnosing peripheric pulmonary lesions touching the thoracic wall.

The trial's goal is comparing the diagnostic yield of ultrasound-guided vs CT-guided histological sampling of peripheric pulmonary lesions touching the thoracic wall.

All patients must, therefore, have carried out recent blood tests (within one month before the procedure) routine including: complete blood count, INR, aPTT, PT.

When taking charge of the patient, the inclusion and exclusion criteria will be verified. The patient candidate for the procedure signs the informed consent to the study in the presence of the local coordinator or co-investigator. The coordinator or co-investigator will proceed with the randomization (through random numbers generated by a computer) to perform ultrasound-guided or CT-guided sampling, which will be scheduled with the usual technical times of each individual participating Center.

Each patient will be assigned a progressive number/code for anonymization purposes to be used in the eCRF. The diagnostic procedures will be carried out in the Respiratory Endoscopy and Radiology rooms where TTNAs are usually carried out. The ultrasound investigation will be conducted usings the ultrasound machine supplied to the Center involved in the trial and usually used in eTTNA procedures.

The CT scan will be performed using the CT machinery equipped by the Center involved in the trial and usually used for the tTTNA procedures.

Before the procedure, the vital signs of the patient will be noted and each operator will choose the most appropriate position for the sampling, based on the location of the lesion. The thoracic area to biopsy will then be defined and then there will be the setting of the sterile field. In accordance to the guide-lines the patient should not be sedated if possible. At this point, local anesthesia with a maximum of 20ml of 2% lidocaine will be administrated, marking down this time as the time of the beginning of the procedure.

18G needles will be used to collect the samples, since this size allows a good balancing between risk of complication and diagnostic yield. For each patient, there will be collected a minumum number of one and a maximum number of three bioptic sampling. The sample will be stored and preserved inside specific containers to allow optimal transfer to the Pathology laboratories, based on the directions of the laboratory itself and the usual procedure of the involved Center.

Once the procedure is done, the patient will remain in the involved Center for a period of observation of at least three hours. During this time, the patient will be monitored through vital signs and the occurrence of any complication. After one hour from the procedure, a thoracic X-Ray examination will be taken, preferably in orthostatism, in both inhale and exhale. The management of any possible complication will be carried out as part the singular Center's practice, in agreement with the latest Guide Lines regarding the matter.

In the case of the impossibility of the technical use of the procedure assign to the singular patient by the randomization, the patient will be excluded from the trial and will carry on the diagnostic iter according to the usual clinical practices.

The onset of complications will be registered during the patients' monitoring process, which will last for the three hours following the procedure. All the participant patients will be informed about the possible late-onset complications after the procedure and about the necessity of coming back to the hospital in case of the occurrence of any symptoms, such as dyspnea, chest pain, hemoptysis/hemosputum.

The anatomopathologist will receive the samples without the indication of the methodic used for the biopsy. The pathologist will, then, pronounce judgment un: 1) adequacy of the samples for the purpose of the diagnosis 2) where indicated, the suitability for a full histological molecular analysis. Once the diagnosis is given, the local coordinator or the co-investigators will communicate the result to the patient as soon as possible, in order to address the patient to the currently most appropriated diagnostic-therapeutic pathway.

The tissue sample will be submitted to the pathologist along with a form containing personal data, anamnesis, clinical suspicion, the sample topography and the trial code. In order to preserve the double-blind criteria in the anatomopathological reporting, all the requests coming from a center will submitted after the name of the local coordinator. The pathologist will report the resulting diagnosis to his center's the coordinator via email and only then it will be possible to move forward to the unblinding. Enrolled patients will be entered in an eCRF file, shared exclusively between the interventional operators. Therefore, the patients will be addressed to the best diagnostic-therapeutic program available at the time, according to the most recent guidelines.

• Study Type: Interventional
• Enrollment (Estimated): 236
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mario Tamburrini, Dr; Phone Number: 3490091667; Email: mario.tamburrini@ospfe.it
• Study Contact Backup: Name: Ludovica Rizzo, Dr; Phone Number: 3337944389; Email: ludovica01.rizzo@edu.unife.it

Study Locations

• Italy
  • Ferrara, Italy, 44124
    • Recruiting
    • UO Pneumologia AOSP-AUSL
    • Contact: Mario Tamburrini, Dr; Phone Number: 3490091667; Email: mario.tamburrini@ospfe.it
    • Contact: Ludovica Rizzo, Dr; Phone Number: 3337944389; Email: ludovica01.rizzo@edu.unife.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Willingness and ability to provide free and informed consent. Age older then 18 years old.
• Peripheric pulmonary lesions adherent to the thoracic wall in CT scans with indication to typing

Exclusion Criteria:

• Inability to provide free and informed consent, in the absence of an available legal guardian.
• Age younger then 18 years old.
• Terminal neoplastic diseases/ palliative care patients.
• Patients with one lung, anatomical of functional.
• Severe non-treatable blood clothing disfunctions.
• Severe organ failure (pulmonary, renal, hepatic or cardiac).
• Women in state of pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: US-guided percutaneous needle biopsy	Diagnostic test: US-GUIDED PERCUTANEOUS LUNG NEEDLE BIOPSY; The ultrasound investigation will be conducted using the ultrasound machine supplied to the Center involved in the trial and usually used in eTTNA procedures. Before the procedure, the vital signs of the patient will be noted and each operator will choose the most appropriate position for the sampling, based on the location of the lesion. The thoracic area to biopsy will then be defined and then there will be the setting of the sterile field. At this point, local anesthesia with a maximum of 20ml of 2% lidocaine will be administrated, marking down this time as the time of the beginning of the procedure. 18G needles will be used to collect the sample. For each patient, there will be collected a minumum number of one and a maximum number of three bioptic sampling .
Experimental: CT-guided percutaneous needle biopsy	Diagnostic test: CT-GUIDED PERCUTANEOUS LUNG NEEDLE BIOPSY; The CT scan will be performed using the CT machinery equipped by the Center involved in the trial and usually used for the tTTNA procedures. Before the procedure, the vital signs of the patient will be noted and each operator will choose the most appropriate position for the sampling, based on the location of the lesion. The thoracic area to biopsy will then be defined and then there will be the setting of the sterile field. At this point, local anesthesia with a maximum of 20ml of 2% lidocaine will be administrated, marking down this time as the time of the beginning of the procedure. 18G needles will be used to collect the sample. For each patient, there will be collected a minumum number of one and a maximum number of three bioptic sampling .

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of diagnostic samples vs rate of non diagnostic samples assessed by the histological reports, detecting the ones positive for malignant neoplasm or specific benign process out of the totality of procedures for both US-guided and CT-guided biopsy	For diagnostic sampling is meant the ability to diagnose a malignant neoplasm or a specific benign process (such as benignant neoplasia, granulomatous inflammation). For nondiagnostic sample is meant the finding of a non-specific benign process or that the sample is not adequate/sufficient. For benign non-specific is meant a histological diagnosis suggesting a benign process without any evidence of malignancy but that does not give the specific information to achieve a definitive diagnosis. In any case that does not include a diagnostic confirmation of a non-specific benign lesion by a surgical approach, TTNA will be considered a true negative only after a follow-up documenting a downsizing of at least 20% in the major axial diameter or a stability in sizing for at least one year from the lesion itself.	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of complications that can be occur during the procedures assessed by physiological parameter, VAS scale, radiography	The data about number and the type of complications during and after the procedure will be collected to calculate the rate of complications for both US-guided and CT-guided biopsies. The investigator will evaluate the pain by VAS scale which goes from 0 (no pain) to 10 (worst pain possible). The physiological parameters will be checked during the procedure and within three hours after the procedure. The patient will undergo radiography to check one hour after the procedure.	3 hours
Amount of Ionizing radiation to which the patient is exposed calculated in mGy	During each procedure of CT-guided biopsy the investigators will obtain information about the amount of ionizing radiation to which the patient is exposed and this will be reported in mGy.	1 hour
Comfort of the patient during the procedure assessed by VAS scale	The patient will be asked about the discomfort related to the procedure by VAS scale, which goes from 0 (extreme discomfort-absence of comfort) to 100 (extreme comfort-absence of discomfort)	1 hour
Duration of the procedure in seconds	The duration of each procedure (from the time of the local anesthesia for the time of the extraction of the last biopsy)will be calculated and reported in seconds	1 hour
Rate of sample suitable for NGS analysis based on percentage of neoplastic cell in samples	Regarding malignant lesions, for those eligible to molecular target therapy, samples will be divided based on the percentage of neoplastic cells in the sample (T%) in T% >20% (suitable for NGS analysis) and T% <20% (non-suitable for NGS analysis)	1 month

Collaborators and Investigators

• Sponsor: University Hospital of Ferrara

Publications and helpful links

General Publications

• DiBardino DM, Yarmus LB, Semaan RW. Transthoracic needle biopsy of the lung. J Thorac Dis. 2015 Dec;7(Suppl 4):S304-16. doi: 10.3978/j.issn.2072-1439.2015.12.16.
• Koegelenberg CF, Irusen EM, von Groote-Bidlingmaier F, Bruwer JW, Batubara EM, Diacon AH. The utility of ultrasound-guided thoracentesis and pleural biopsy in undiagnosed pleural exudates. Thorax. 2015 Oct;70(10):995-7. doi: 10.1136/thoraxjnl-2014-206567. Epub 2015 May 21.
• Criner GJ, Eberhardt R, Fernandez-Bussy S, Gompelmann D, Maldonado F, Patel N, Shah PL, Slebos DJ, Valipour A, Wahidi MM, Weir M, Herth FJ. Interventional Bronchoscopy. Am J Respir Crit Care Med. 2020 Jul 1;202(1):29-50. doi: 10.1164/rccm.201907-1292SO.
• Asano F. Advanced bronchoscopy for the diagnosis of peripheral pulmonary lesions. Respir Investig. 2016 Jul;54(4):224-9. doi: 10.1016/j.resinv.2015.11.008. Epub 2016 Mar 2.
• Wang B, Zhong F, An W, Liao M. The diagnostic value of CT-guided percutaneous puncture biopsy of pulmonary ground-glass nodules: a meta-analysis. Acta Radiol. 2023 Apr;64(4):1431-1438. doi: 10.1177/02841851221137693. Epub 2022 Nov 15.
• Baratella E, Cernic S, Minelli P, Furlan G, Crimi F, Rocco S, Ruaro B, Cova MA. Accuracy of CT-Guided Core-Needle Biopsy in Diagnosis of Thoracic Lesions Suspicious for Primitive Malignancy of the Lung: A Five-Year Retrospective Analysis. Tomography. 2022 Nov 25;8(6):2828-2838. doi: 10.3390/tomography8060236.
• Yamamoto N, Watanabe T, Yamada K, Nakai T, Suzumura T, Sakagami K, Yoshimoto N, Sato K, Tanaka H, Mitsuoka S, Asai K, Kimura T, Kanazawa H, Hirata K, Kawaguchi T. Efficacy and safety of ultrasound (US) guided percutaneous needle biopsy for peripheral lung or pleural lesion: comparison with computed tomography (CT) guided needle biopsy. J Thorac Dis. 2019 Mar;11(3):936-943. doi: 10.21037/jtd.2019.01.88.
• Ikezoe J, Sone S, Higashihara T, Morimoto S, Arisawa J, Kuriyama K. Sonographically guided needle biopsy for diagnosis of thoracic lesions. AJR Am J Roentgenol. 1984 Aug;143(2):229-34. doi: 10.2214/ajr.143.2.229.
• Niu XK, Bhetuwal A, Yang HF. CT-guided core needle biopsy of pleural lesions: evaluating diagnostic yield and associated complications. Korean J Radiol. 2015 Jan-Feb;16(1):206-12. doi: 10.3348/kjr.2015.16.1.206. Epub 2015 Jan 9.
• Knox D, Halligan K. Case series of trans-thoracic nodule aspirate performed by interventional pulmonologists. Respir Med Case Rep. 2021 Feb 2;32:101362. doi: 10.1016/j.rmcr.2021.101362. eCollection 2021.
• Lim C, Lee KY, Kim YK, Ko JM, Han DH. CT-guided core biopsy of malignant lung lesions: how many needle passes are needed? J Med Imaging Radiat Oncol. 2013 Dec;57(6):652-6. doi: 10.1111/1754-9485.12054. Epub 2013 Apr 1.
• Manhire A, Charig M, Clelland C, Gleeson F, Miller R, Moss H, Pointon K, Richardson C, Sawicka E; BTS. Guidelines for radiologically guided lung biopsy. Thorax. 2003 Nov;58(11):920-36. doi: 10.1136/thorax.58.11.920. No abstract available.
• Moore W, Sawas A,Lee C,Ferretti J,
• Kim D, Han JY, Baek JW, Lee HY, Cho HJ, Heo YJ, Shin GW. Effect of the respiratory motion of pulmonary nodules on CT-guided percutaneous transthoracic needle biopsy. Acta Radiol. 2023 Jul;64(7):2245-2252. doi: 10.1177/02841851221144616. Epub 2022 Dec 27. Erratum In: Acta Radiol. 2023 Feb 14;:2841851231156905.

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2024
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): October 31, 2026

Study Registration Dates

• First Submitted: April 29, 2024
• First Submitted That Met QC Criteria: May 8, 2024
• First Posted (Actual): May 14, 2024

Study Record Updates

• Last Update Posted (Actual): May 14, 2024
• Last Update Submitted That Met QC Criteria: May 8, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: 648/2023/Sper/AOUFe

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No