(BRC) Identification of novel risk factors associated with the development of pelvic radiotherapy-induced insufficiency fractures (Non-Clinical)


   Faculty of Biology, Medicine and Health

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  Dr Azadeh Abravan, Dr Alan McWilliam, Dr Marianne Aznar, Prof Peter Hoskin, Dr Joe Swift, Dr Claire Higham  No more applications being accepted  Competition Funded PhD Project (UK Students Only)

About the Project

The overarching goal of this project is to enhance our understanding of the risk factors predicting Radiotherapy-Related Insufficiency Fractures (RRIFs). RRIFs, occurring in 15-20% of patients undergoing pelvic radiotherapy, significantly impact on patients' quality of life [1]. Current knowledge gaps underscore the need for research to address patient concerns and guide clinical management. Moreover, patients expressed a desire for pre-radiotherapy risk information during a Patient and Public Involvement and Engagement event and a previously published qualitative interview study  [2]. The project aligns with broader initiatives, including the completion of the RadBone Feasibility study [7] and the development of a care program to enhance post-pelvic radiotherapy outcomes.

In this project, the aim is to identify predictive factors and biomarkers for development of RRIFs; utilizing routine imaging, novel finite element modelling, in addition to DXA bone mineral density and proteomic samples collected during the RadBone study. Additionally, the project aims to develop protocols for assessing local bone mineral density and RRIF risk using baseline CT scans, with the ambition to be able to manipulate radiotherapy dose to high risk areas.

The project will leverage patient cohorts, including data from the Christie Metabolic Bone clinic and the RadBone clinic trial, to conduct a comprehensive study. This PhD project, with a multidisciplinary approach, aims to fill crucial knowledge gaps surrounding RRIFs. By leveraging advanced imaging, proteomics, and patient data, the project seeks to develop risk prediction tools, addressing both patient concerns and the lack of intervention studies in this critical area of research. Ongoing patient and public involvement ensures the project remains patient-centric and contributes to wider initiatives improving radiotherapy outcomes.

Eligibility 

Applicants must have obtained or be about to obtain a First or Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in a relevant discipline or in Physics, data science, engineering.

Before you Apply 

Applicants must make direct contact with the primary supervisor before applying to discuss their interest in the project. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.  

How to Apply 

To be considered for this project you MUST submit a formal online application form - full details on how to apply can be found on the BRC website https://www.bmh.manchester.ac.uk/study/research/funded-programmes/manchester-brc-phd-studentships/ 

Your application form must be accompanied by a number of supporting documents by the advertised deadlines. Without all the required documents submitted at the time of application, your application will not be processed and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered. If you have any queries regarding making an application please contact our admissions team.

Equality, Diversity and Inclusion  

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/  

Biological Sciences (4) Computer Science (8) Mathematics (25)

Funding Notes

This studentship covers tuition fees and stipend for home candidates only.

References

1. Higham CE, Faithfull S: Bone Health and Pelvic Radiotherapy. Clin Oncol (R Coll Radiol) 2015, 27(11):668-678.
2. Taylor S, Chaudhary P, McCartin F, Higham C: Understanding the impact of radiotherapy related insufficiency fractures and exploring satisfaction with two existing patient reported outcome measures: A qualitative interview study. Technical innovations & patient support in radiation oncology 2023, 27:100210.
3. Razavian N, Laucis A, Sun Y, Spratt DE, Owen D, Schonewolf C, Uppal S, Maturen KE, Jolly S: Radiation-Induced Insufficiency Fractures After Pelvic Irradiation for Gynecologic Malignancies: A Systematic Review. Int J Radiat Oncol Biol Phys 2020, 108(3):620-634.
4. Sapienza LG, Salcedo MP, Ning MS, Jhingran A, Klopp AH, Calsavara VF, Schmeler KM, Leite Gomes MJ, de Freitas Carvalho E, Baiocchi G: Pelvic Insufficiency Fractures After External Beam Radiation Therapy for Gynecologic Cancers: A Meta-analysis and Meta-regression of 3929 Patients. Int J Radiat Oncol Biol Phys 2020, 106(3):475-484.
5. Mir R, Dragan AD, Mistry HB, Tsang YM, Padhani AR, Hoskin P: Sacral Insufficiency Fracture Following Pelvic Radiotherapy in Gynaecological Malignancies: Development of a Predictive Model. Clin Oncol (R Coll Radiol) 2021, 33(3):e101-e109.
6. Chatzimavridou-Grigoriadou V, Barraclough LH, Kochhar R, Buckley L, Alam N, Higham CE: Radiotherapy-related insufficiency fractures and bone mineral density: what is the connection? Endocr Connect 2023, 12(7).
7. Chatzimavridou Grigoriadou V, Barraclough LH, Baricevic-Jones I, Bristow RG, Eden M, Haslett K, Johnson K, Kochhar R, Merchant Z, Moore J, O'Connell S, Taylor S, Westwood T, Whetton AD, Yorke J, Higham CE: RadBone: bone toxicity following pelvic radiotherapy - a prospective randomised controlled feasibility study evaluating a musculoskeletal health package in women with gynaecological cancers undergoing pelvic radiotherapy. In: BMJ open. vol. 12; 2022: e056600.
8. Recknell C, Saatchi R: A Finite Element Study to Assess Fracture Risk in Humans with Low Bone Density. In: Advances in Asset Management and Condition Monitoring: 2020// 2020; Cham: Springer International Publishing; 2020: 1143-1150.