Feasibility Study Testing Transcriptional Responses as an Indicator of Individualised Responses to Radiation Effects

NCT02780375 | Completed

• 1 other identifier: CCR4553
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Peripheral blood samples will be taken with informed consent from radiotherapy patients undergoing standard radiotherapy at The Royal Marsden before and during treatment for breast, lung, gastrointestinal and genitourinary tumours. Responses from panels of up to 800 coding and non-coding RNAs will be assessed in the samples using the nCounter system. Candidate genes identified by Public Health England, Columbia University and/or in the literature as being specific to radiation responses will be included, together with genes relevant to systemic inflammatory responses, to identify transcriptional responses for a range of doses and exposures on an inter-individual basis. Data will be analysed using existing and new statistical tools focused on count data modelling. The intended outcome is identification of a radiation specific panel of genes to inform individual radiation responses and if the results are favourable, a large scale follow up to this proposed pilot is expected in due course.

Conditions

Cancer

Keywords

Transcriptional Responses; Radiation

Outcome Measures

Primary Outcomes (1)

• Transcriptional responses as measured by nCounter molecular profiling as biomarker of individual radiation exposure

  3 months after all volunteers have finished radiotherapy and donated blood samples

Study Arms (1)

Blood donation during radiotherapy

Participants will be asked to donate a blood sample at 5 time points before and during their radiotherapy

Procedure: Blood donation during radiotherapy

Interventions

Blood donation during radiotherapy PROCEDURE

Participants will be asked to donate a blood sample at 5 time points before and during their radiotherapy

Blood donation during radiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients undergoing radiotherapy for cancer

You may qualify if:

• Age ≥18 years
• Requirement for external beam radiotherapy for breast, lung, gastrointestinal or genitourinary tumours
• Written informed consent

You may not qualify if:

• Previous radiotherapy
• Concurrent chemotherapy or chemotherapy preceding radiotherapy by less than 4 weeks
• Concurrent hormone therapy or hormone therapy preceding radiotherapy by less than 4 weeks

Sponsors & Collaborators

• Institute of Cancer Research, United Kingdom: lead
• Public Health England: collaborator

Study Sites (1)

The Royal Marsden

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (15)

• Lloyd, D.C. and A.A. Edwards, Biological dosimetry after radiation accidents. In: G. Obe et al.,(eds). Chromosomal Aberrations. Springer-Verlag, Berlin, Heidelberg. 1990.

  BACKGROUND

• Maznik, N.A., et al., Chromosomal dosimetry for some groups of evacuees from Prypiat and Ukrainian liquidators at Chernobyl. Radiation Protection Dosimetry, 1997. 74(1-2): p. 5-11.

  BACKGROUND

• Kabacik S, Mackay A, Tamber N, Manning G, Finnon P, Paillier F, Ashworth A, Bouffler S, Badie C. Gene expression following ionising radiation: identification of biomarkers for dose estimation and prediction of individual response. Int J Radiat Biol. 2011 Feb;87(2):115-29. doi: 10.3109/09553002.2010.519424. Epub 2010 Nov 10.

  PMID: 21067298 BACKGROUND

• Manning G, Kabacik S, Finnon P, Bouffler S, Badie C. High and low dose responses of transcriptional biomarkers in ex vivo X-irradiated human blood. Int J Radiat Biol. 2013 Jul;89(7):512-22. doi: 10.3109/09553002.2013.769694. Epub 2013 Feb 27.

  PMID: 23362884 BACKGROUND

• Kabacik S, Ortega-Molina A, Efeyan A, Finnon P, Bouffler S, Serrano M, Badie C. A minimally invasive assay for individual assessment of the ATM/CHEK2/p53 pathway activity. Cell Cycle. 2011 Apr 1;10(7):1152-61. doi: 10.4161/cc.10.7.15231. Epub 2011 Apr 1.

  PMID: 21389785 BACKGROUND

• Badie C, Kabacik S, Balagurunathan Y, Bernard N, Brengues M, Faggioni G, Greither R, Lista F, Peinnequin A, Poyot T, Herodin F, Missel A, Terbrueggen B, Zenhausern F, Rothkamm K, Meineke V, Braselmann H, Beinke C, Abend M. Laboratory intercomparison of gene expression assays. Radiat Res. 2013 Aug;180(2):138-48. doi: 10.1667/RR3236.1. Epub 2013 Jul 25.

  PMID: 23886340 BACKGROUND

• Ainsbury EA, Bakhanova E, Barquinero JF, Brai M, Chumak V, Correcher V, Darroudi F, Fattibene P, Gruel G, Guclu I, Horn S, Jaworska A, Kulka U, Lindholm C, Lloyd D, Longo A, Marrale M, Monteiro Gil O, Oestreicher U, Pajic J, Rakic B, Romm H, Trompier F, Veronese I, Voisin P, Vral A, Whitehouse CA, Wieser A, Woda C, Wojcik A, Rothkamm K. Review of retrospective dosimetry techniques for external ionising radiation exposures. Radiat Prot Dosimetry. 2011 Nov;147(4):573-92. doi: 10.1093/rpd/ncq499. Epub 2010 Dec 23.

  PMID: 21183550 BACKGROUND

• Kabacik S, Manning G, Raffy C, Bouffler S, Badie C. Time, dose and ataxia telangiectasia mutated (ATM) status dependency of coding and noncoding RNA expression after ionizing radiation exposure. Radiat Res. 2015 Mar;183(3):325-37. doi: 10.1667/RR13876.1. Epub 2015 Mar 4.

  PMID: 25738893 BACKGROUND

• Manning, G., et al., Assessing a new gene expression analysis technique for radiation biodosimetry applications. Radiation Measurements, 2011. 46(9): p. 1014-1018.

  BACKGROUND

• Finnon P, Kabacik S, MacKay A, Raffy C, A'Hern R, Owen R, Badie C, Yarnold J, Bouffler S. Correlation of in vitro lymphocyte radiosensitivity and gene expression with late normal tissue reactions following curative radiotherapy for breast cancer. Radiother Oncol. 2012 Dec;105(3):329-36. doi: 10.1016/j.radonc.2012.10.007. Epub 2012 Nov 15.

  PMID: 23157981 BACKGROUND

• Krenn-Pilko S, Langsenlehner U, Stojakovic T, Pichler M, Gerger A, Kapp KS, Langsenlehner T. The elevated preoperative derived neutrophil-to-lymphocyte ratio predicts poor clinical outcome in breast cancer patients. Tumour Biol. 2016 Jan;37(1):361-8. doi: 10.1007/s13277-015-3805-4. Epub 2015 Jul 29.

  PMID: 26219894 BACKGROUND

• Chua ML, Horn S, Somaiah N, Davies S, Gothard L, A'Hern R, Yarnold J, Rothkamm K. DNA double-strand break repair and induction of apoptosis in ex vivo irradiated blood lymphocytes in relation to late normal tissue reactions following breast radiotherapy. Radiat Environ Biophys. 2014 May;53(2):355-64. doi: 10.1007/s00411-014-0531-z. Epub 2014 Mar 13.

  PMID: 24622963 BACKGROUND

• Chua ML, Somaiah N, A'Hern R, Davies S, Gothard L, Yarnold J, Rothkamm K. Residual DNA and chromosomal damage in ex vivo irradiated blood lymphocytes correlated with late normal tissue response to breast radiotherapy. Radiother Oncol. 2011 Jun;99(3):362-6. doi: 10.1016/j.radonc.2011.05.071. Epub 2011 Jun 23.

  PMID: 21704405 BACKGROUND

• Chua ML, Somaiah N, Bourne S, Daley F, A'hern R, Nuta O, Davies S, Herskind C, Pearson A, Warrington J, Helyer S, Owen R, Yarnold J, Rothkamm K. Inter-individual and inter-cell type variation in residual DNA damage after in vivo irradiation of human skin. Radiother Oncol. 2011 May;99(2):225-30. doi: 10.1016/j.radonc.2011.04.009. Epub 2011 May 26.

  PMID: 21620495 BACKGROUND

• Prise KM, O'Sullivan JM. Radiation-induced bystander signalling in cancer therapy. Nat Rev Cancer. 2009 May;9(5):351-60. doi: 10.1038/nrc2603. Epub 2009 Apr 20.

  PMID: 19377507 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples

MeSH Terms

Conditions

Neoplasms

Study Officials

• Navita Somaiah

  Institute of Cancer Research, United Kingdom

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2016
• First Posted: May 23, 2016
• Study Start: September 12, 2016
• Primary Completion: July 17, 2018
• Study Completion: July 17, 2018
• Last Updated: October 31, 2018

Record last verified: 2018-10

Locations

GB (1)