ISRCTN - ISRCTN86637908: Comparison of two methods of lymph node removal in patients suffering from lung cancer

Plain English Summary

Background and study aims
Lung cancer is the number 1 killer among all malignancies in both sexes. The most effective way to treat it is complete surgical resection (removal of part of the lung), which is possible in less advanced cases. Together with the diseased part of the lung, also lymph nodes are removed, as they often are cancer deposits. The standard systematic lymph node dissection (SLND) removes nodes but this only removes nodes from one side of the chest. Unfortunately, cancer deposits can develop also in the contralateral (opposite) side of the chest. This study is aimed at assessment of bilateral removal of the lymph nodes during lung cancer surgery.

Who can participate?
Adults aged 18 with non-small cell lung cancer.

What does the study involve?
Participants are randomly allocated to one of two groups. Those in the first group have their lung resection done with the standard procedure. Those in the second group receive the standard procedure as well as an additional lymph node dissection in the other side of their chest through a neck incision. Participants are followed for operative time, blood loss, number of lymph nodes removed and any other complication during the surgery. Participants are followed up after the surgery for their pain and survival.

What are the possible benefits and risks of participating?
The potential benefit is more complete resection achieved with bilateral removal of lymph nodes, resulting in better chance for cure. There is a possible increased risk of adverse effects as the procedure is more invasive.

Where is the study run from?
This study is being run by Jagiellonian University and takes place in hospitals in Poland, China, Germany, Austria, and Turkey.

When is the study starting and how long is it expected to run for?
January 2017 to December 2025

Who is funding the study?
1. Jagiellonian University in Krakow (Poland)
2. Sun Yat-sen University Cancer Center (China)
3. Catholic Hospital Koblenz (Germany)
4. Otto Wagner Hospital, Vienna (Austria)
5. ELK Berlin Chest Hospital, Berlin (Germany)
6. Istanbul University, Cerrahpasa Medical Faculty (Turkey)
7. Thoraxzentrum Ruhrgebiet (Germany)
8. University of Giessen (Germany)

Who is the main contact?
Professor Jaroslaw Kuzdzal

Study website

Contact information

Type

Scientific

Contact name

Prof Jaroslaw Kuzdzal

ORCID ID

Contact details

Department of Thoracic Surgery
Jagiellonian University
ul. Pradnicka 80
Cracow
31-202
Poland

Additional identifiers

EudraCT/CTIS number

IRAS number

ClinicalTrials.gov number

Protocol/serial number

1072.6120.91.2017

Study information

Scientific title

Comparison of unilateral and Bilateral Mediastinal Lymph node dissection in patients with non-small cell lung cancer

Acronym

BML-2

Study hypothesis

In patients operated on for non-small cell lung cancer, bilateral mediastinal lymph node dissection is associated with improved survival as compared with standard systematic lymph node dissection.

Ethics approval(s)

Bio-ethical Committee of the Jagiellonian University, 30/06/2017, ref: decision No 1072.6120.91.2017

Study design

Prospective multicentre study

Primary study design

Interventional

Secondary study design

Randomised parallel trial

Study setting(s)

Hospital

Study type

Treatment

Patient information sheet

See additional files

Condition

Non-small cell lung cancer

Intervention

Prospective multicentre study with 1:1 randomisation using computer-generated random numbers. The intervention group includes patients undergoes bilateral mediastinal lymph node dissection (BML), and the control group includes participants who undergo standard systematic lymph node dissection (SLND).

Randomisation in the ratio 1:1 using computer-based random digit generator. All participants receive anatomical lung resection with SLND is performed according to the ESTS guidelines. VATS and thoracotomy approaches are acceptable. In the BML group, additional contralateral lymph node dissection is performed during the same anaesthesia, via separate neck incision (using either the VAMLA technique,10 or modified TEMLA technique15).

The following intraoperative parameters are recorded: operative time, blood loss, number of lymph nodes removed from each nodal station, any complications.

The following postoperative parameters are recorded: volume of chest tube output, time of chest drainage, time of air leak, pain intensity measured using the visual analogue scale (VAS), any complications, tumour relapse and survival recorded at least every three months in the first three years, and at least every six months in the 4th and 5th year after surgery.

Patients with stage pII or pIII (according to the final pathological report) are referred for adjuvant platinum-based chemotherapy.

Intervention type

Procedure/Surgery

Primary outcome measure

1. Overall and cancer-specific 5-year survival rate is measured using the CRF data at 5-year survival is by definition measured 5 years after initiation of the treatment
2. DFS is measured using the CRF data at the time of closing the study 5 year after treatment of the last patient included

Secondary outcome measures

1. Operative time is measured using case report forms at the end of the procedure
2. Blood loss is measured using the scale of the suction device container at the end of the procedure
3. Pain intensity measured using VAS every 4 hours at the days 0, 1, 2, 3, 4, and 5
4. Complications is measured using the CRF data that include records of 45 categories of adverse effects at day of discharge
5. Length of hospital stay is measured using hospital records at the day of discharge
6. Number of removed lymph nodes in each station is counted by the pathologist during the final pathological examination of the surgical specimen

Overall study start date

15/01/2017

Overall study end date

31/12/2025

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Age ≥18
2. Proven or suspected NSCLC
3. Clinical stage I, II or minimal N2 IIIA, assessed on the basis of CT, PET-CT (except of T1a-b), bronchoscopy and EBUS/EUS (except of T1a-b)
4. General fitness enabling appropriate pulmonary resection (according to the ERS/ESTS guidelines) (both genders are included, this onfo has been given elsewhere in your on-line form)

Participant type(s)

Patient

Age group

Adult

Lower age limit

18 Years

Sex

Both

Target number of participants

500

Participant exclusion criteria

1. History of other malignance (except on non-melanoma skin cancer)
2. Final pathological report of tumour other than NSCLC
3. Final pathological report of carcinoid or salivary gland-type tumour
4. Intraoperative finding of M1 disease

Recruitment start date

30/11/2017

Recruitment end date

31/12/2021

Locations

Countries of recruitment

University of Giessen
Section of Thoracic Surgery, Department of General Surgery
Giesen
35385
Germany

Sponsor information

Organisation

Jagiellonian University

Sponsor details

Department of Thoracic Surgery
ul. Pradnicka 80
Cracow
31-202
Poland

Sponsor type

Hospital/treatment centre

Website

ROR

https://ror.org/03bqmcz70

Funders

Funder type

University/education

Funder name

Uniwersytet Jagielloński w Krakowie

Alternative name(s)

Universitas Jagellonica Cracoviensis, Jagiellonian University in Krakow, UJ

Funding Body Type

private sector organisation

Funding Body Subtype

Universities (academic only)

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

The study is planned to be presented during oncological and thoracic surgical conferences, and publication of its results is planned in high-impact peer-reviewed journals.

Intention to publish date

31/03/2020

Individual participant data (IPD) sharing plan

The datasets generated during and/or analysed during the current study are not expected to be made available due to the legal regulations of patients' data protection. The data will be stored at the John Paul II Hospital, Krakow, Poland.

IPD sharing plan summary

Not expected to be made available

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet		13/11/2017	02/04/2019	No	Yes

Additional files

ISRCTN86637908_PIS_13Nov17.doc Uploaded 02/04/2019

Editorial Notes

19/03/2020: The recruitment end date was changed from 31/12/2020 to 31/12/2021. 19/08/2019: The following changes were made to the trial record: 1. The recruitment end date was changed from 30/06/2019 to 31/12/2020. 2. The overall trial end date was changed from 31/12/2019 to 31/12/2025. 3. The intention to publish date was changed from 31/12/2020 to 31/03/2020. 02/04/2019: The participant information sheet has been uploaded.