Reducing repeat pleural biopsies in suspected cancer
| ISRCTN | ISRCTN15548114 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN15548114 |
| IRAS number | 329574 |
| Secondary identifying numbers | V1.0, IRAS 329574 |
- Submission date
- 07/02/2024
- Registration date
- 16/02/2024
- Last edited
- 08/07/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Plain English summary of protocol
Background and study aims
Pleural mesothelioma is a cancer that affects the lung lining, caused by asbestos. Despite recent treatment advances, the prognosis is often poor. Prompt diagnosis is vital. A biopsy can diagnose mesothelioma, guide treatment and support compensation claims. However, some people need multiple biopsies, increasing the risk of biopsy-related complications and prolonging the time to diagnosis. Doing additional tests on initial biopsies may increase the chance of diagnosing mesothelioma and avoid repeat biopsies. This would allow anti-cancer treatment to be started sooner and improve survival. The extra tests are not genetic but look for genetic changes in the cancer that allow it to grow and spread. The genetic markers in mesothelioma are called BAP1, p16 and MTAP. If they have disappeared on biopsy mesothelioma is diagnosed. Another study was previously conducted on people with suspected mesothelioma who required further biopsies as their first biopsy did not give a diagnosis (TARGET: https://www.isrctn.com/ISRCTN14024829). It took place in eight UK centres and recruited 59 patients. This study aims to perform these additional tests on their biopsy samples to see whether this would have made the diagnosis sooner and removed the need for further biopsies. It will investigate how many biopsies could have been avoided, how much time would have been saved, how this may have impacted survival and what cost-savings this would have offered the NHS.
Who can participate?
This study includes the 59 participants in the original TARGET study who were recruited between September 2015 and September 2018. No additional participants will be recruited. Should any participants of the original TARGET trial wish to opt-out, they can contact the main contact below.
What does the study involve?
Biopsy samples taken as part of the participants’ routine clinical care will be tested for the markers of genetic change in mesothelioma (BAP1, MTAP and p16). The ability to make a diagnosis using these tests will be compared with the original diagnostic pathway, which was before the use of these tests.
What are the possible benefits and risks of participating?
The benefits of enrolling are to future patients, whose diagnostic process could be improved, with no additional requirements of TARGET participants. As there are no additional interventions required of participants and this will not impact management, there are no risks identified.
Where is the study run from?
North Bristol NHS Trust (UK)
When is the study starting and how long is it expected to run for?
October 2022 to September 2025
Who is funding the study?
Southmead Hospital Charity
Who is the main contact?
Geraldine Lynch, Geraldine.lynch@nbt.nhs.uk
Contact information
Principal Investigator
Learning & Research (Level 3), Southmead Hospital
Westbury-On-Trym Bristol, Bristol
BS10 5NB
United Kingdom
 ORCID ID |
0000-0002-1276-6500 |
|---|---|
| Phone | +44 (0)1174149330 |
| nick.maskell@bristol.ac.uk |
Principal Investigator
2nd Floor Learning & Research Building
Southmead Hospital
Bristol
BS10 5NB
United Kingdom
| ORCID ID |
0000-0001-7386-7754 |
|---|---|
| Phone | +44 (0)1174146479 |
| anna.bibby@bristol.ac.uk |
Public, Scientific
North Bristol NHS Trust
Bristol
BS3 4PB
United Kingdom
| ORCID ID |
0009-0007-6591-2720 |
|---|---|
| Phone | +44 (0)1174148049 |
| geraldine.lynch@nbt.nhs.uk |
Study information
| Study design | Observational study using historical data and stored samples |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cohort study |
| Study setting(s) | Laboratory, Medical and other records |
| Study type | Diagnostic |
| Participant information sheet | No participant information sheet available |
| Scientific title | Reducing repeat pleural biopsies in suspected cancer – a study of the TARGET trial cohort comparing the diagnostic yield of standard histology vs additional tests in suspected pleural malignancy |
| Study acronym | REPLICA |
| Study objectives | Testing for BAP1, P16 FISH and MTAP IHC could remove the need for further invasive procedures in patients with suspected pleural malignancy and an initial non-diagnostic biopsy |
| Ethics approval(s) |
Approved 28/03/2024, East Midlands - Leicester South Research Ethics Committee (3 Piccadilly Place, London Road, Manchester, M1 3BN, United Kingdom; +44 (0)207 104 8079; Leicestersouth.rec@hra.nhs.uk), ref: 24/EM/0042 |
| Health condition(s) or problem(s) studied | Improving diagnosis in pleural mesothelioma |
| Intervention | Current interventions as of 06/06/2025: This is an observational study using historical data and stored samples from a multi-centre randomised controlled trial (TARGET; https://www.isrctn.com/ISRCTN14024829), where each participant will act as a case (additional tests applied to stored samples) and internal control (initial outcomes using standard testing only). Pleural biopsies of patients with a final diagnosis of mesothelioma will be tested for BAP1 and MTAP using immunohistochemistry (IHC) and in some samples for P16 using fluorescent in-situ hybridisation (FISH). Previous interventions: This is an observational study using historical data and stored samples from a multi-centre randomised controlled trial (TARGET; https://www.isrctn.com/ISRCTN14024829), where each participant will act as a case (additional tests applied to stored samples) and internal control (initial outcomes using standard testing only). Pleural biopsies will be tested for BAP1 and MTAP using immunohistochemistry (IHC) and in some samples for P16 using fluorescent in-situ hybridisation (FISH). |
| Intervention type | Other |
| Primary outcome measure | Identification of malignancy on biopsy measured using immunohistochemistry (IHC) and fluorescent in-situ hybridisation (FISH) in the laboratory at one timepoint |
| Secondary outcome measures | The total number of biopsies required, time to diagnosis, stage at diagnosis, number of multi-disciplinary team (MDT) discussions, biopsy-associated costs, biopsy-related adverse events and survival measured using data recorded in medical records at one timepoint |
| Overall study start date | 08/10/2022 |
| Completion date | 30/09/2025 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 59 |
| Total final enrolment | 59 |
| Key inclusion criteria | All patients who were included in the TARGET trial (ISRCTN14024829). TARGET eligibility required all of the following to apply: 1. Pleural thickening on CT suspicious for pleural malignancy 2. Have had any form of pleural biopsy in the last 12 months (either by thoracoscopy or under radiological guidance) which was non-diagnostic for cancer 3. Lung cancer/mesothelioma MDT decision to perform further CT-guided biopsy to pursue a diagnosis |
| Key exclusion criteria | Not eligible if not recruited to the TARGET trial |
| Date of first enrolment | 29/04/2024 |
| Date of final enrolment | 30/09/2025 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
- Wales
Study participating centres
Southmead Road
Westbury-on-trym
Bristol
BS10 5NB
United Kingdom
Gloucester
GL1 3NN
United Kingdom
Colney
Norwich
NR4 7UY
United Kingdom
C Floor, Huntsmnan Building
Herries Road
Sheffield
S5 7AU
United Kingdom
Stoke-on-trent
ST4 6QG
United Kingdom
Headley Way
Headington
Oxford
OX3 9DU
United Kingdom
Newport
NP20 2UB
United Kingdom
Glasgow
G51 4TF
United Kingdom
Sponsor information
Hospital/treatment centre
Learning & Research (Level 3), Southmead Hospital
Westbury-On-Trym, Bristol
BS10 5NB
England
United Kingdom
| Phone | +44 (0)1174149330 |
|---|---|
| researchsponsor@nbt.nhs.uk | |
| Website | https://www.nbt.nhs.uk/ |
"ROR" |
https://ror.org/036x6gt55 |
Funders
Funder type
Charity
No information available
Results and Publications
| Intention to publish date | 04/07/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | The results of this research will be disseminated to patients and carers, fellow mesothelioma researchers and clinicians. Patients will be informed via the local mesothelioma patient group and the annual mesothelioma patient and carer conference. Results will be disseminated to the public via the Bristol Academic Respiratory and UK Pleural Society Twitter feeds. Results will be presented to fellow academics at scientific conferences e.g. the British Thoracic Oncology Group or International Mesothelioma Interest Group meetings. Clinicians will be informed via the UK Pleural Society state-of-the-art meetings and annual update day. The final report will be written up for publication in a peer-reviewed scientific journal, published open-access. |
| IPD sharing plan | Deidentified data from this study will be made available by secure transfer from the corresponding author upon reasonable request from a qualified academic investigator for the sole purpose of replicating results presented in the article, under conditions of appropriate ethical oversight, upon investigator approval and execution of a data use agreement. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version 1.0 | 16/01/2024 | 07/02/2024 | No | No |
Additional files
Editorial Notes
08/07/2025: The following changes were made:
1. The date of final enrolment was changed from 31/07/2025 to 30/09/2025.
2. The completion date was changed from 31/07/2025 to 30/09/2025.
3. IPD sharing plan added.
10/06/2025: The following changes were made:
1. The overall study end date was changed from 04/07/2025 to 31/07/2025.
2. The recruitment end date was changed from 04/06/2025 to 31/07/2025.
06/06/2025: The interventions were updated. Study website added.
09/04/2024: The following changes were made:
1. The date of ethics approval was added.
2. The recruitment start date was changed from 23/02/2024 to 29/04/2024.
07/02/2024: Study's existence confirmed by Southmead Hospital Charity.
