Exploring novel solutions of radiotherapy delivery and using biology, imaging, new fractionations and radiobiological models to improve TCP/NTCP ratio
Lead Research Organisation:
University of Oxford
Department Name: UNLISTED
Abstract
Cancers of the upper gastro-intestinal tract (oesophagus, pancreas) have a poor outcome if surgery cannot be undertaken. Radical radiotherapy combined with chemotherapy are the standard of care, however a significant number of patients have tumour recurrence in the radiotherapy field. In the past increasing radiotherapy dose caused severe toxicity. There are now several technological advances in radiotherapy that permits further individualization of treatment using either functional imaging such as MRI and PET to guide the areas that need more radiotherapy or focused radiotherapy (such as Stereotactic ablative radiotherapy) to areas of tumour that cannot be removed by surgery.
The aim of the research is to further personalise the way radiotherapy is delivered using characteristics specific to an individual patient and/or tumour. Novel drugs that have been shown in laboratory to enhance radiation will be combined with the radiation to further enhance tumour kill. The ultimate impact in clinical practice would be improvement in local tumour control and reduction in toxicity caused by radiation.
The aim of the research is to further personalise the way radiotherapy is delivered using characteristics specific to an individual patient and/or tumour. Novel drugs that have been shown in laboratory to enhance radiation will be combined with the radiation to further enhance tumour kill. The ultimate impact in clinical practice would be improvement in local tumour control and reduction in toxicity caused by radiation.
Technical Summary
To develop and optimise novel radiotherapy delivery strategies, additionally incorporating novel agents, with the goal of maximising tumour control and minimising toxicity with a specific focus in gastro-intestinal malignancies.
The ultimate aim is to personalize radiotherapeutic management using molecular and imaging biomarkers to select a patient /cancer specific radiation treatment with individualised dose, fractionation and choice of radiation sensitizer.
The aim of my research has three main themes
1. Strategies of modulating radiotherapy (SMART) with drugs or new modalities of delivering radiation. Radiotherapy dose escalation techniques using ‘Simultaneous Integrated Boost’ permit intensification of radiotherapy dose to predetermined volumes within the tumour, derived from biological imaging such as PET or functional MRI. Tumour control probability and normal tissue control probability models can then be used to refine the dose escalation within the tumour further and spare normal tissue exposure. Continue to understand this concepts wich are now tested in phase III trials in oesophageal and anal cancer. In parallel we are testing DNA damage response modifiers ( e.g. ATR-i) in combination with radiation to optimise the therapeutic window.
2. Advanced radiotherapy as a bridge to radical surgery. The use of stereotactic ablative radiotherapy to areas at risk of not being completely cleared with surgery; with the aim of achieving complete tumour resection. Continue to test this concept in the preoperative setting for tumours such as pancreatic cancers that are difficult to clear due to proximity to critical organs.
3. Refining normal tissue toxicity modelling in gastro-intestinal malignancies receiving radiotherapy. We have identified that substructures of heart receiving a specific radiation dose could adversely affect radiation outcomes. The aim is to study mechanisms of damage and how to minimise radiation to certain substructures. This would allow selection of the best radiotherapy dose delivery technique in patients receiving combined chemoradiation and surgery.
The ultimate aim is to personalize radiotherapeutic management using molecular and imaging biomarkers to select a patient /cancer specific radiation treatment with individualised dose, fractionation and choice of radiation sensitizer.
The aim of my research has three main themes
1. Strategies of modulating radiotherapy (SMART) with drugs or new modalities of delivering radiation. Radiotherapy dose escalation techniques using ‘Simultaneous Integrated Boost’ permit intensification of radiotherapy dose to predetermined volumes within the tumour, derived from biological imaging such as PET or functional MRI. Tumour control probability and normal tissue control probability models can then be used to refine the dose escalation within the tumour further and spare normal tissue exposure. Continue to understand this concepts wich are now tested in phase III trials in oesophageal and anal cancer. In parallel we are testing DNA damage response modifiers ( e.g. ATR-i) in combination with radiation to optimise the therapeutic window.
2. Advanced radiotherapy as a bridge to radical surgery. The use of stereotactic ablative radiotherapy to areas at risk of not being completely cleared with surgery; with the aim of achieving complete tumour resection. Continue to test this concept in the preoperative setting for tumours such as pancreatic cancers that are difficult to clear due to proximity to critical organs.
3. Refining normal tissue toxicity modelling in gastro-intestinal malignancies receiving radiotherapy. We have identified that substructures of heart receiving a specific radiation dose could adversely affect radiation outcomes. The aim is to study mechanisms of damage and how to minimise radiation to certain substructures. This would allow selection of the best radiotherapy dose delivery technique in patients receiving combined chemoradiation and surgery.
Organisations
Publications
Gwynne S
(2019)
Driving developments in UK oesophageal radiotherapy through the SCOPE trials.
in Radiation oncology (London, England)
Bluemke E
(2020)
Oxygen-enhanced MRI MOLLI T1 mapping during chemoradiotherapy in anal squamous cell carcinoma.
in Clinical and translational radiation oncology
Bluemke E
(2020)
Oxygen-enhanced MRI MOLLI T1 mapping during chemoradiotherapy in anal squamous cell carcinoma
in Clinical and Translational Radiation Oncology
Chalmers AJ
(2020)
CTRad 10 Years On: From 10-point Plan to Top 10 Achievements.
in Clinical oncology (Royal College of Radiologists (Great Britain))
O'Cathail SM
(2020)
NRF2 metagene signature is a novel prognostic biomarker in colorectal cancer.
in Cancer genetics
O'Cathail SM
(2020)
Superior outcomes of nodal metastases compared to visceral sites in oligometastatic colorectal cancer treated with stereotactic ablative radiotherapy.
in Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
Jones D
(2020)
A systematic review of health economic evaluations of proton beam therapy for adult cancer: Appraising methodology and quality
in Clinical and Translational Radiation Oncology
Gilbert A
(2020)
UK national cohort of anal cancer treated with intensity-modulated radiotherapy: One-year oncological and patient-reported outcomes.
in European journal of cancer (Oxford, England : 1990)
Nix MG
(2020)
Chemoradiotherapy of locally-advanced non-small cell lung cancer: Analysis of radiation dose-response, chemotherapy and survival-limiting toxicity effects indicates a low a/ß ratio.
in Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
Van Werkhoven E
(2020)
Practicalities in running early-phase trials using the time-to-event continual reassessment method (TiTE-CRM) for interventions with long toxicity periods using two radiotherapy oncology trials as examples.
in BMC medical research methodology
Muirhead R
(2020)
A Prospective Study of Diffusion-weighted Magnetic Resonance Imaging as an Early Prognostic Biomarker in Chemoradiotherapy in Squamous Cell Carcinomas of the Anus.
in Clinical oncology (Royal College of Radiologists (Great Britain))
Robinson M
(2020)
Response of FDG avid pelvic bone marrow to concurrent chemoradiation for anal cancer.
in Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
Cooke R
(2020)
Stereotactic body radiotherapy for moderately central and ultra-central oligometastatic disease: Initial outcomes.
in Technical innovations & patient support in radiation oncology
Holyoake DLP
(2021)
SPARC, a phase-I trial of pre-operative, margin intensified, stereotactic body radiation therapy for pancreatic cancer.
in Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
Jin H
(2021)
Cost-Effectiveness Analysis of Stereotactic Ablative Body Radiation Therapy Compared With Surgery and Radiofrequency Ablation in Two Patient Cohorts: Metastatic Liver Cancer and Hepatocellular Carcinoma.
in Clinical oncology (Royal College of Radiologists (Great Britain))
Related Projects
Project Reference | Relationship | Related To | Start | End | Award Value |
---|---|---|---|---|---|
MC_UU_00001/1 | 31/03/2017 | 30/03/2022 | £2,508,000 | ||
MC_UU_00001/2 | Transfer | MC_UU_00001/1 | 31/03/2017 | 30/03/2022 | £2,488,000 |
MC_UU_00001/3 | Transfer | MC_UU_00001/2 | 31/03/2017 | 30/05/2018 | £349,000 |
MC_UU_00001/4 | Transfer | MC_UU_00001/3 | 31/03/2017 | 30/03/2022 | £2,486,000 |
MC_UU_00001/5 | Transfer | MC_UU_00001/4 | 31/03/2017 | 29/09/2019 | £1,732,000 |
MC_UU_00001/6 | Transfer | MC_UU_00001/5 | 31/03/2017 | 30/03/2022 | £2,525,000 |
MC_UU_00001/7 | Transfer | MC_UU_00001/6 | 31/03/2017 | 30/03/2022 | £1,773,000 |
MC_UU_00001/8 | Transfer | MC_UU_00001/7 | 03/01/2019 | 30/03/2023 | £2,682,000 |
MC_UU_00001/9 | Transfer | MC_UU_00001/8 | 30/09/2019 | 30/03/2022 | £1,492,800 |
MC_UU_00001/10 | Transfer | MC_UU_00001/9 | 07/12/2020 | 30/03/2023 | £888,708 |
MC_UU_00001/11 | Transfer | MC_UU_00001/10 | 08/01/2021 | 30/03/2023 | £874,512 |
Description | Human Immune Discovery Initiative (HIDI |
Amount | £12,500 (GBP) |
Funding ID | Initial assessment of circulating immune cell populations in response to stereotactic body radiotherapy in patients with borderline resectable pancreatic cancer Reference Number: 0005924 |
Organisation | University College Oxford |
Sector | Academic/University |
Country | United Kingdom |
Start | 09/2018 |
End | 10/2020 |
Title | A phase I dose escalation safety study combining the ATR inhibitor M6620 with chemoradiotherapy in oesophageal cancer & other solid cancers using time to event continual reassessment method |
Description | To determine the best tolerated M6620 treatment schedule (or phase II recommended dose (RPTD)) administered concomitantly with radiotherapy (RT) only in the palliative treatment of oesophageaL cancer. trail activated and recruiting patients |
Type | Therapeutic Intervention - Drug |
Current Stage Of Development | Early clinical assessment |
Year Development Stage Completed | 2018 |
Development Status | Under active development/distribution |
Impact | this is a phase I trial |
URL | https://www.oncology.ox.ac.uk/trial/chariot |
Description | Ben George_Talk about radiotherapy to Sixth Form students at a local secondary school in January. |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | TBC |
Year(s) Of Engagement Activity | 2018 |
Description | Louise Bendall_Volunteering with a summer school (UNIQ), |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Louise did some volunteering with a summer school (UNIQ), teaching year 12 students about Radiotherapy physics. (two 1.5 hour sessions) on 24-27th July. |
Year(s) Of Engagement Activity | 2017 |
Description | Maria Hawkins_SABR talk for Royal Berkshire Hospital |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | TBA |
Year(s) Of Engagement Activity | 2018 |
Description | WEBINAR |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Other audiences |
Results and Impact | webinar to promote the trial to professionals and patients |
Year(s) Of Engagement Activity | 2018 |
URL | https://www.rcr.ac.uk/clinical-oncology/event/webinar-hpb-webinar-series-1-precision-radiation-techn... |
Description | presented poster with trial update at patients meeting during AMMF Conference May 2018 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | discussion about potential benefits to patients if they would consider participation int he trial |
Year(s) Of Engagement Activity | 2018 |