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

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.

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.

Publications

10 25 50
 
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 10/2018 
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 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
 
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...