MesobanK (ODR1516_410)

The Royal Papworth NHS Foundation Trust MesobanK study has a remit to collect, process and despatch human tissue, pleural fluid and blood samples from NHS patients with clinically proven mesothelioma to support asbestos-related research.

Tissue, pleural fluid and blood samples are procured from NHS patients who either have a clinically proven diagnosis of mesothelioma or are suspected of having the disease.

The patient's name and NHS number are entered onto the database by staff at the donor centre so that follow-up information can be collected about that patient's disease progression, treatment and other outcomes at a later date - information will be pulled from the NHS Cancer Registries.

Clinically annotated biospecimens will be inwardly shared to support applications from researchers undertaking biomedical research directly concerned with asbestos-related disease diagnosis and treatment.

Royal Papworth Hospital NHS Foundation Trust requires access to NHS England data for the purpose of the following research project: Mesobank.

Mesobank has two cohorts of patients.

1) A prospective cohort of recruited patients via consent.

2) A retrospective cohort of around 100 deceased patients which is covered by s251 CAG (no further data will be requested for the retrospective cohort).

The following datasets are required:

NDRS Cancer registrations

NDRS Anti-Cancer Therapy (SACT) data

NDRS Radiotherapy Data Set (RTDS) data

NDRS HES admitted care

NDRS HES outpatient data

The level of the data will be pseudonymised

The data will be minimised as follows:

Limited to data for a study cohort identified by Royal Papworth Hospital NHS Foundation Trust

• Mesobank participants where extant consent remains in place (or s251 approval for the retrospective deceased cohort).

• Limited to conditions relevant to the study identified by specific ICD and OPCS codes

• Treatment data provided will be for the 3 months prior to and 24 months post diagnosis

Royal Papworth Hospital NHS Foundation Trust is the research sponsor and the data controller and the organisation responsible for ensuring that the data will only be processed for the purpose described above.

The lawful basis for processing personal data under the UK GDPR is:

Article 6 (1) (e): processing is necessary for the performance of a task carried out in the public interest or in the exercise of official authority vested in the controller.

The lawful basis for processing special category data under the UK GDPR is:

Article 9 (2) (j): processing is necessary for archiving purposes in the public interest, scientific or historical research purposes or statistical purposes in accordance with Article 89(1) based on Union or Member State law which shall be proportionate to the aim pursued, respect the essence of the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject.

The processing is in the public interest because it aims to produce clinically annotated biospecimens that researchers can use when undertaking biomedical research directly concerned with asbestos-related disease diagnosis and treatment. Mesothelioma is a rare cancer that arises from the pleura and peritoneum often following exposure to asbestos. Whilst there is a long latency between exposure to asbestos and the development of disease, an individual’s prognosis following diagnosis is generally poor with a median survival of 9-12 months. Owing to its historically high levels of asbestos use, the UK has the world’s highest incidence of mesothelioma per head of population.

Mesobank operates on a cost recovery basis and has also received research grants from several charities including:

Mick Knighton Mesothelioma Research Fund

Asthma and Lung UK (formerly the British Lung Foundation

The Victor Dahdaleh Foundation

The June Hancock Mesothelioma Research Fund

None of the listed funders have been involved in any decision making processes or development in the scope of the research undertaken by MesobanK.

A number of groups were involved in setting up Mesobank:

Mesothelioma UK

Greater Manchester Asbestos Victims Support Group

Papworth Hospital Mesothelioma Support Group

The national data opt-out does not apply where explicit consent has been obtained from the patient for the specific purpose.

Where individuals have opted out of disease registration by the National Disease Registration Service (NDRS), their data has been permanently removed from the registry and therefore will not be disseminated under this Data Sharing Agreement (DSA). https://digital.nhs.uk/ndrs/patients/opting-out

Data Recipient will transfer direct identifiers to enable tumour level linkage to data held by the NCRAS. Where there is an unambiguous match, NCRAS will provide the Data Recipient with pseudonymised clinical data for each matched data subject.

Data processing is only carried out by substantive employees of Royal Papworth Hospital NHS Foundation Trust who have been appropriately trained in data protection and confidentiality.

Pseudonymised NCRAS clinical data is stored on secure network drives and access to folders is restricted

Royal Papworth Hospital NHS Foundation Trust will transfer the data below to NHS England for the cohort to be linked with NHS England data.

NHS number

Surname

Forename

Date of birth

Postcode of residence

Trust of diagnosis of mesothelioma

Date of diagnosis of mesothelioma

Primary diagnosis (ICD 10)

MesobanK ID

NHS England will provide the relevant records from the datasets below. The data will contain no direct identifying data items but will contain a unique person ID which can be used to link the data with other record level data already held by the recipient:

AV_patient data

MesobanK ID

ETHNICITY

VITALSTATUS (patientstatus)

VITALSTATUSDATE Split into two, date if dead (deathdate

and lastalivedate)

DEATHCAUSECODE_1A

DEATHCAUSECODE_1B

DEATHCAUSECODE_1C

DEATHCAUSECODE_2

AV_tumour data

MesobanK ID

Tumour ID (pseudonymised)

SITE_ICD10_O2

LATERALITY

BASISOFDIAGNOSIS

MORPH_ICD10_O2

BEHAVIOUR_ICD10_O2

T_BEST

N_BEST

M_BEST

DIAGNOSISDATEBEST

Previouscancers Derived field

AV_treatment data

Tumour ID (pseudonymised)

CHEMO_ALL_DRUGS

CHEMO_DRUG_GROUP

OPCS4_CODE

EVENTDATE

EVENTDESC

AV_Systematic Anti-Cancer Therapy (SACT) data

MESOBANK ID (pseudonymised)

Analysis_Group

Start_Date_of Regimen

Number_of_Cycles_Delivered Derived field

AV_National Radiotherapy Data Set (RTDS) data

MESOBANK ID (pseudonymised)

Treatmentstartdate

rttreatmentanatomicalsite

RTDS_PRESCRIPTIONS.RTTREATMENTM

ODALITY

AV_linked HES admitted care and outpatient data

MESOBANK ID (pseudonymised)

Opertn OPCS codes:

'E391','E398','E399','E441','E461','E541',

'E542','E543',

'E544','E545','E548','E549','E552','E559','T0

13','T023','E554','E551'

'T01','T02','T03','T05','T07','T08','T09',

'T10','T11','T12','T13','T14','T15','T16','T17'

Opdate

The data will be stored on servers at Royal Papworth Hospital NHS Foundation Trust

The data will not be transferred to any other location, except when the servers are backed up and the data is copied to tape and encrypted. Royal Papworth Hospital NHS Foundation Trust uses offsite back-up storage services. Data is copied to tape, encrypted and stored offsite at Iron Mountain. Iron Mountain only provide the physical storage location for backup purposes and have no access to/nor process the Mesobank data.

The data will be accessed onsite at the premises of Royal Papworth Hospital and by authorised personnel via remote access. The data will remain on the servers at Royal Papworth Hospital at all times except when backed up and sent to the offsite storage facility at Iron Mountain.

Access is restricted to individuals within the Research and Development Department of Royal Papworth Hospital who have authorisation from the Head of Department to access certain project specific (Mesobank) folders. All such individuals are substantive employees of Royal Papworth Hospital.

All personnel accessing the data have been appropriately trained in data protection and confidentiality.

The identifying details will be stored in a separate database to the linked dataset used for analysis. All analyses will use the pseudonymised dataset. There will be no requirement and no attempt to reidentify individuals when using the pseudonymised dataset.

Staff that work on MesobanK from Royal Papworth Hospital will process the data for the purposes described above.

Data will not leave England or Wales at any time.

Clinically annotated biospecimens that will be used by researchers undertaking biomedical research directly concerned with asbestos-related disease diagnosis and treatment.

The data will mostly be used to identify appropriate samples for particular research projects e.g. samples that are chemo naïve or samples from patients that have survived for a certain time period from the point of diagnosis

The outputs will be communicated to relevant recipients through the following dissemination channels:

• Journals

• Website / Social Media

• Posters displayed at Conferences

• Presentations given at Conferences

There are no target dates, Mesobank has been operating for 10 years

Below are a list of the Scientific Publications utilising Mesobank samples and data

The amino-acid stress sensing eIF2α kinase GCN2 is a survival biomarker for malignant mesothelioma

Gold, L.T., Bray, S.E., Kernohan, N.M. et al.

BJC Rep 1, 4 (2022). https://doi.org/10.1038/s44276-023-00004-y

BAP1 loss is associated with higher ASS1 expression in epithelioid mesothelioma: implications for therapeutic stratification.

Barnett SE, Kenyani J, Tripari M, Butt Z, Grosman R, Querques F, Shaw L, Silva LC, Goate Z, Marciniak SJ, Rassl DM, Jackson R, Lian LY, Szlosarek PW, Sacco JJ, Coulson JM.

Mol Cancer Res. 2023 Jan 20:MCR-22-0635. doi: 10.1158/1541-7786.MCR-22-0635. Epub ahead of print. PMID: 36669126.

The Chick Embryo Xenograft Model for Malignant Pleural Mesothelioma: A Cost and Time Efficient 3Rs Model for Drug Target Evaluation.

Barnett, S.E.; Herrmann, A.; Shaw, L.; Gash, E.N.; Poptani, H.; Sacco, J.J.; Coulson, J.M.

Cancers 2022, 14, 5836. https://doi.org/ 10.3390/cancers14235836.

Surface-fill hydrogel attenuates the oncogenic signature of complex anatomical surface cancer in a single application.

Majumder P, Singh A, Wang Z, Dutta K, Pahwa R, Liang C, Andrews C, Patel NL, Shi J, de Val N, Walsh STR, Jeon AB, Karim B, Hoang CD, Schneider JP.

Nat Nanotechnol. 2021 Nov;16(11):1251-1259. doi: 10.1038/s41565-021-00961-w. Epub 2021 Sep 23. PMID: 34556833; PMCID: PMC8595541.

BAP1 and YY1 regulate expression of death receptors in malignant pleural mesothelioma.

Ishii Y, Kolluri KK, Pennycuick A, Zhang X, Nigro E, Alrifai D, Borg E, Falzon M, Shah K, Kumar N, Janes SM.

J Biol Chem. 2021 Nov;297(5):101223. doi: 10.1016/j.jbc.2021.101223. Epub 2021 Sep 29. PMID: 34597666; PMCID: PMC8545693.

MicroRNA-206 suppresses mesothelioma progression via the Ras signaling axis.

Singh A, Pruett N, Pahwa R, Mahajan AP, Schrump DS, Hoang CD.

Mol Ther Nucleic Acids. 2021 Apr 3;24:669-681. doi: 10.1016/j.omtn.2021.04.001. PMID: 33996251; PMCID: PMC8093312.

Integrated genomics point to immune vulnerabilities in pleural mesothelioma.

Nastase A, Mandal A, Lu SK, Anbunathan H, Morris-Rosendahl D, Zhang YZ, Sun XM, Gennatas S, Rintoul RC, Edwards M, Bowman A, Chernova T, Benepal T, Lim E, Taylor AN, Nicholson AG, Popat S, Willis AE, MacFarlane M, Lathrop M, Bowcock AM, Moffatt MF, Cookson WOCM.

Sci Rep. 2021 Sep 27;11(1):19138. doi: 10.1038/s41598-021-98414-w. PMID: 34580349; PMCID: PMC8476593.

Biological basis for novel mesothelioma therapies.

Obacz J, Yung H, Shamseddin M, Linnane E, Liu X, Azad AA, Rassl DM, Fairen-Jimenez D, Rintoul RC, Nikolić MZ, Marciniak SJ.

Br J Cancer. 2021 Oct;125(8):1039-1055. doi: 10.1038/s41416-021-01462-2. Epub 2021 Jul 5. PMID: 34226685; PMCID: PMC8505556.

Use of preclinical models for malignant pleural mesothelioma.

Shamseddin M, Obacz J, Garnett MJ, Rintoul RC, Francies HE, Marciniak SJ.

Thorax. 2021 Nov;76(11):1154-1162. doi: 10.1136/thoraxjnl-2020-216602. Epub 2021 Mar 10. PMID: 33692175; PMCID: PMC8526879.

Normal mesothelial cell lines newly derived from human pleural biopsy explants.

Pruett N, Singh A, Shankar A, Schrump DS, Hoang CD

Am J Physiol Lung Cell Mol Physiol. 2020 Oct 1;319(4):L652-L660. doi: 10.1152/ajplung.00141.2020. Epub 2020 Jul 29. PMID: 32726133; PMCID: PMC764289

Exploring High Aspect Ratio Gold Nanotubes as Cytosolic Agents: Structural Engineering and Uptake into Mesothelioma Cells.

Ye S, Azad AA, Chambers JE, Beckett AJ, Roach L, Moorcroft SCT, Aslam Z, Prior IA, Markham AF, Coletta PL, Marciniak SJ, Evans SD.

Small. 2020 Nov;16(46):e2003793. doi: 10.1002/smll.202003793. Epub 2020 Oct 25. PMID: 33103323.

Integrative Molecular Characterization of Malignant Pleural Mesothelioma.

Hmeljak J, Sanchez-Vega F, Hoadley KA, Shih J, Stewart C, Heiman D, Tarpey P, Danilova L, Drill E, Gibb EA, Bowlby R, Kanchi R, Osmanbeyoglu HU, Sekido Y, Takeshita J, Newton Y, Graim K, Gupta M, Gay CM, Diao L, Gibbs DL, Thorsson V, Iype L, Kantheti H, Severson DT, Ravegnini G, Desmeules P, Jungbluth AA, Travis WD, Dacic S, Chirieac LR, Galateau-Sallé F, Fujimoto J, Husain AN, Silveira HC, Rusch VW, Rintoul RC, Pass H, Kindler H, Zauderer MG, Kwiatkowski DJ, Bueno R, Tsao AS, Creaney J, Lichtenberg T, Leraas K, Bowen J; TCGA Research Network, Felau I, Zenklusen JC, Akbani R, Cherniack AD, Byers LA, Noble MS, Fletcher JA, Robertson AG, Shen R, Aburatani H, Robinson BW, Campbell P, Ladanyi M.

Cancer Discov. 2018 Dec;8(12):1548-1565. doi: 10.1158/2159-8290.CD-18-0804. Epub 2018 Oct 15.

Loss of functional BAP1 augments sensitivity to TRAIL in cancer cells.

Kolluri KK, Alifrangis C, Kumar N, Ishii Y, Price S, Michaut M, Williams S, Barthorpe S, Lightfoot H, Busacca S, Sharkey A, Yuan Z, Sage EK, Vallath S, Le Quesne J, Tice DA, Alrifai D, von Karstedt S, Montinaro A, Guppy N, Waller DA, Nakas A, Good R, Holmes A, Walczak H, Fennell DA, Garnett M, Iorio F, Wessels L, McDermott U, Janes SM.

Elife. 2018 Jan 18;7. pii: e30224. doi: 10.7554/eLife.30224.

MesobanK UK: an international mesothelioma bioresource.

Rintoul RC, Rassl DM, Gittins J, Marciniak SJ; MesobanK collaborators.

Thorax. 2016 Apr;71(4):380-2. doi: 10.1136/thoraxjnl-2015-207496.

Mesothelioma is a rare incurable cancer that arises from the pleura and peritoneum often following exposure to asbestos. Whilst there is a long latency between exposure to asbestos and the development of disease, an individual’s prognosis following diagnosis is generally poor with a median survival of 9-12 months. Owing to its historically high levels of asbestos use, the UK has the world’s highest incidence of mesothelioma per head of population. The data will be used to produce clinically annotated biospecimens that will be made available to researchers undertaking biomedical research directly concerned with the prevention, diagnosis and treatment of mesothelioma. It is hoped that these clinically annotated biospecimens will enable us to better understand how mesothelioma develops from its early stages and translate this into more effective diagnosis and treatment for patients.

To date, Mesobank have supplied samples for use in over 50 different research projects. It usually takes many years for laboratory research to produce advances in the way diseases are diagnosed, treated or prevented.