Oncological Engineering - A new concept in the treatment of bone metastases

Lead Research Organisation: University of Leeds
Department Name: Mechanical Engineering

Abstract

Approximately 2 million people are living with cancer in the UK and this number is set to rise considerably over the next decade to 3.2M. A significant complication of late stage (stage 4) cancer is metastases or secondary tumours which are caused by tumour cells spreading to different locations in the body. Metastases are particularly associated with breast cancer, which is the most common cancer in females and the leading cause of cancer deaths in this group. Figures vary but some studies put a figure of about 50-60 % of patients will have bone metastases in late stage cancer. The tumours weaken the bone and lead to a variety of problems for the patients at a time when quality of life is a paramount consideration, especially as the prognosis is usually terminal. Significant issues include severe pain and spinal fracture which made lead to spinal cord injury. These complications often require major surgery which encroaches, significantly, on the patients' quality of life, when life expectancy is a matter of months and may, in certain cases, provide a mechanism of further spread of the cancer. Currently, there are no implants for supporting the bones before fracture as we cannot identify which vertebrae are likely to fail.

OncoEng will deliver a paradigm shift in the current treatment technologies and stratification of care based on the application of core enabling engineering technologies. A more patient-friendly approach is realised in OncoEng in which we predict which vertebrae with tumours are likely to fail in the future enabling informed decision on care. Advanced computational modelling and imaging will be used to look at the growth of the tumour so that predictions of the strength of the vertebrae can be calculated a different points in time. These strengths can then be compared to spinal loads and an assessment of fracture risk undertaken. Those vertebrae at his risk would then receive special implant to support the weakened bone and prevent fracture. This implant would only require key-hole surgery and would not impinge on the patient's quality of life through a lengthy recuperation period or additional pain. The research proposed responds to the Cancer Strategy in the NHS Long Term Plan and the EU's Beating Cancer Plan.

Three Universities in the UK, University of Leeds, Imperial College and University College London, have come together to deliver this research so as to make a big change in the way these patients are treated. In addition we have formed an international network of academic, industrial and clinical collaborators from Europe, USA and Australia (OncoEng+ Network) with a focus on novel modelling, imaging, advanced materials and innovative medical devices to overcome the challenges of predicting fracture and producing a new implant. Impacts from the research include (1) new diagnostic tools for predicting bone failure using imaging and advanced computational modelling, which can be used in this and other disease such as osteoporosis, (2) a new patient-specific implant that can be inserted using minimally invasive surgery reducing the trauma to the patient and having a shorter recovery period (days rather than weeks or months); the implant would be inserted before the vertebrae is susceptible to fracture, (3) new manufacturing techniques for the delivery of the minimally invasive implant, which have wide ranging applications outside medicine including the aerospace and automotive sector, and (4) new test methodologies for spinal implants to ensure that these devices are tested under a range of activities including adverse conditions such as high patient loading. Importantly, the programme grant will train and up-skill a new generation engineers and scientists in a novel area of application-based research, that of devices for skeletal cancers and software for fracture prediction, and aims to bring together activities in the UK and internationally to form a holistic integrated activity.
 
Description Richard Hall, Chair of a Working Group within NCRI Bone Metastases Group - Engineering support, preventing fracture and treating skeletally related events in metastatic bone disease.
Geographic Reach Europe 
Policy Influence Type Participation in a guidance/advisory committee
URL https://www.ncri.org.uk/groups/bone-metastases-group/
 
Description BioTrib-AVN: The effect of avascular necrosis of the hip on articular function in natural and artificial joints
Amount £229,535 (GBP)
Funding ID EP/X023532/1 
Organisation University of Leeds 
Sector Academic/University
Country United Kingdom
Start 09/2022 
End 12/2024
 
Description Multiscale optimisation algorithm for the next generation of heat exchanger
Amount £226,488 (GBP)
Funding ID 10061301 
Organisation Innovate UK 
Sector Public
Country United Kingdom
Start 08/2023 
End 10/2024
 
Description Novel Ceramic Matrix Composite Integrated Thermal Protection System for Missiles
Amount £46,001 (GBP)
Organisation MBDA Missile Systems 
Department MBDA UK Ltd
Sector Private
Country United Kingdom
Start 04/2022 
End 08/2022
 
Description FractureFix - International Centre of Excellence in the Treatment of Pathological Fractures 
Organisation ETH Zurich
Department Department of Health Sciences and Technology
Country Switzerland 
Sector Academic/University 
PI Contribution Underpinning expertise and facilities in in vitro characterisation of bone and implant performance. Facilities are beyond the state of the art with recent developments through the OncoEng Programme grant - EP/W007096/1/. This new funded partnership is based on substantial previous research collaborations delivered through: EU funded SpineFX 2009-13 EU funded LifeLongJoints 2013-2018 EU funded Nu-Spine 2019-2023 EU funded BioTrib 2021-2024
Collaborator Contribution The contributions from the partners is based around two world leading activities: Uppsala University: Additive Manufacturing for the Life Sciences(VINNOVA funded Competence Centre) and Soft Bone (EIT Health funded) a new generation of low modulus materials designed to fix and prevent fractures in the vertebrae as well as augmentation of the disc. ETH Zurich: Advanced imaging and modelling for pathological fractures (FHT Singapore) and fracture modelling in metastatic disease (EU funded METASTRA).
Impact The grant to continue this collaboration has just been awarded: UKRI/EPSRC: The Funding Service ID - APP9995
Start Year 2024
 
Description FractureFix - International Centre of Excellence in the Treatment of Pathological Fractures 
Organisation Uppsala University
Department Department of Engineering Sciences
Country Sweden 
Sector Academic/University 
PI Contribution Underpinning expertise and facilities in in vitro characterisation of bone and implant performance. Facilities are beyond the state of the art with recent developments through the OncoEng Programme grant - EP/W007096/1/. This new funded partnership is based on substantial previous research collaborations delivered through: EU funded SpineFX 2009-13 EU funded LifeLongJoints 2013-2018 EU funded Nu-Spine 2019-2023 EU funded BioTrib 2021-2024
Collaborator Contribution The contributions from the partners is based around two world leading activities: Uppsala University: Additive Manufacturing for the Life Sciences(VINNOVA funded Competence Centre) and Soft Bone (EIT Health funded) a new generation of low modulus materials designed to fix and prevent fractures in the vertebrae as well as augmentation of the disc. ETH Zurich: Advanced imaging and modelling for pathological fractures (FHT Singapore) and fracture modelling in metastatic disease (EU funded METASTRA).
Impact The grant to continue this collaboration has just been awarded: UKRI/EPSRC: The Funding Service ID - APP9995
Start Year 2024
 
Description Surgery and Biomechanics in Metastatic Bone Disease 
Organisation Royal National Orthopaedic Hospital
Country United Kingdom 
Sector Hospitals 
PI Contribution We facilitated a stakeholder meeting in Leeds in January 2023 as part of a designated activity within OncoEng. The meeting also included new partners from Leeds Beckett University (high-end biomechanics) and Faculty of Biological Sciences, University of Leeds (community orientated biomechanics and interventional biomechanics). Two grant applications are currently been prepared in the areas of Surgical Oncology and Biomechanics of People living with metastatic bone disease. The grants are being prepared as a collaborative activity between RNOH and the UoL.
Collaborator Contribution RNOH acted as hosts to a meeting in October 2022 in which both the patient experience and surgical/clinical need were explored. The meeting emphasised the needs of the patients and how varied their needs are. It also provided an enhancement for target product profile for the minimally invasive implant being developed within OncoEng.
Impact Clinical - revised and enhanced target product profile for the MMI. Engineering - New constraints/requirements to the device.
Start Year 2022
 
Description British Orthopaedic Oncology Society and National Cancer Research Institute - Metastatic Bone Clinical Leaders Group meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The event comprised approximately 60 members of the community of which 45 were orthopaedic surgeons with a professional interest in the growing incidence of metastatic bone disease. The meeting was designed to allow the identification of urgent clinical need in terms of surgical inventions, allow exchange of ideas, networking and raising the profile of research in this area. Prof Mike bryant and Mr Vishal Borse (both OncoEng Co-Is) provided presentations at the meeting. The event was co-sponsored and co-organised by OncoEng.

Importantly several urgent clinical needs were identified and discussed which are currently being worked on as future grant submissions.
Year(s) Of Engagement Activity 2023
 
Description Chair of a National Cancer Research Institute working group on Engineering Aspects of Bone Metastases 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The activity part of an overall NCRI activity on metastatic bone cancer which is becoming a significant challenge clinically. The NCRI WG was formed in 2022 but was curtailed in 2023 due to budgetary constraints at Cancer Research UK. A more ad hoc group has now formed around Bone Metastases with a wider remit.
Year(s) Of Engagement Activity 2023
 
Description Invited public lecture, Institute of Physics and Engineering in Medicine, Hiding in Plain Sight: The Unseen Impact of Engineering in Healthcare 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Invited talk for flagship event through IPEM, reaching ~150 people from diverse backgrounds - school children, healthcare professionals, engineering.
Year(s) Of Engagement Activity 2023
 
Description Keynote lecture, 32nd Annual Meeting of the Seddon Society 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Invited lecture to healthcare professionals from the Sedan Society (medics) as part of regional event.
Year(s) Of Engagement Activity 2022
 
Description OncoEng LinkedIn Activity 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact The LinkedIn OncoEng page disseminates activities of interest to persons in the medical device, oncology and imaging sectors. It has over 500 followers.
Year(s) Of Engagement Activity 2022,2023
URL https://www.linkedin.com/company/oncoeng/
 
Description OncoEng Patient Outreach Day 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact Patients, as the ultimate end-users of any healthcare intervention, offer insights into the relevance of research questions, the impact of treatments on daily life, and the prioritisation of outcomes that matter most to them. Their contributions ensure that the results of research are not only theoretically sound but are also pragmatically tuned to the real-world experiences of those affected by metastatic bone disease. Together we can build social capital, enriches transparency, and nurtures a collective trust. Contributing to a heightened sense of participant ownership, which is instrumental in driving research forward in a manner that yields tangible benefits for both individual patients and the broader society. OncoEng's ethos is deeply rooted in the active involvement of patients and the public throughout the research continuum. By co-creating research questions and directions with patient input, OncoEng ensures that the patient voice is not just heard but is also a determinative force in guiding research. The commitment to this collaborative approach is evident in the alignment of research outputs with the real-life experiences of individuals grappling with metastatic bone disease.

Impact:
* Enhanced trust between patients and researchers
* Increased knowledge exchange between patients and researchers. Important that patients understand the research process, particularly the length of time it takes to deliver research and its translation. Euqally it is important that the researchers understand the challenges patients face in their everyday life.
* Increased visibility for the research itself and the broader theme of metastatic breast cancer in the bone.
* Plans for future engagement and related activities.
* Increased willingness to participate in research.
Year(s) Of Engagement Activity 2023
URL https://oncoeng.org/patient-day/
 
Description OncoEng website 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The Website was launched in April 2022 to coincide with the start of OncoEng. It contains information about OncoEng including profiles, dissemination activities and the scientific rationale for OncoEng.
Year(s) Of Engagement Activity 2022,2023
URL https://oncoeng.org/
 
Description OncoEng: Cancer for Physical Scientists and Engineers 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The events consisted of series of lectures delivered by world leading authorities on cancer and cancer research. The lectures were delivered to enable engineers and physical scientists to have an underpinning grasp of the concepts, language and challenges faced at the interface between cancer and engineering. The lectures were delivered between 11th January 2023 and 15th February 2023 on a weekly basis. Recordings of the meetings are currently being edited and made publically available as part of an online resource.
Year(s) Of Engagement Activity 2023
URL https://oncoeng.org/events/
 
Description Presentations and future funding development with Surgical Oncologists at the Royal National Orthopaedic Hospitals 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact A workshop was arranged with surgical team dealing with metastatic bone disease (spinal and non-spinal) at the Royal National Orthopaedic Hospital, Stanmore, UK. Date: 7-10-22; Host Mr Craig Gerrard and Dr Sherron Furtado. The meeting was employed to:
(1) Develop a new partnership with a major centre for surgical interventions for metastatic bone disease for the purposes of accessing additional patients for the OncoEng study and widen the investigation through the skills developed at the RNOH.
(2) Refine the target product profile for the Minimally Invasive Implant for metastatic bone disease (MBD) in the spine.
(3) Refine the target product profile for the fracture prediction software.
(4) Seek a wider collaboration for future funding opportunities.

Follow-up workshop held at the University of Leeds 12-01-23. This also included biomechanics experts from Leeds Beckett University (Dr David Lunn) and Faculty of Biological Sciences, University of Leeds (Dr Sarah Astill). Outputs from this workshop included the formation of two groups to develop further grant applications for (1) Biomechanical Interventions for Improving the Quality of Life for person living with MBD and (2) the Utilisation of robotic technologies for MBD surgery. A follow-up meeting was held on 10th February to report on progress.
Year(s) Of Engagement Activity 2022,2023
URL https://www.linkedin.com/feed/update/urn:li:activity:7019461214116175873
 
Description The OncoEng+ Network Seminar Series 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The OncoEng+ Network Seminar Series are bi-monthly on-line lectures provided by researchers of an international standing. The inaugural lecture was delivered in September 2022 by Prof W Greg Sawyer (University of Florida), followed by Prof Alex Frangi (University of Leeds), Prof Emad Moeendarbary for the Christmas Lecture (UCL), and Dr Alvaro Köhn-Luque (University of Oslo). The Seminar Series has continued in 2023/4 with a presentation being delivered every second month.
Year(s) Of Engagement Activity 2022,2023
URL https://oncoeng.org/
 
Description Workshop - OncoEng Metamaterial and Additive Manufacturing Workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Course on the Optimisation of Structural Metamaterials and Additive Manufacturing as part of the EPSRC OncoEng Programme Grant. The workshop comprised three day's which broadly alignedto the following subject areas:

Day 1: A general introduction to design optimisation with a focus on topology optimisation. - Attendees - Academic: 28, Industry: 5
Day 2: Multiscale design optimisation. Attendees - Academic: 27, Industry: 12
Day 3: Printing technologies to be developed in the programme grant, especially those with small print details. Attendees - Academic: 22, Industry :5

Impact:
(1) Developing further relationships with end-users and strengthening existing ones.
(2) Developing a relationships with DSTL for further funded metamaterial work.
Year(s) Of Engagement Activity 2023