Personalising gastro-intestinal cancers radiotherapy: the ultimate aim of the research of my group is to maximise clinical benefit in terms of better tumour control and reduction in toxicity after radiotherapy to enhance life expectancy of the patients.
Despite several advances in techniques of radiotherapy planning (intensity modulated radiotherapy), tumour imaging (PET, MRI); radiation delivery (rotational arc therapy) the techniques and doses used for radiotherapy treatments of gastro-intestinal malignant cancers have remained unchanged. Chemoradiation remains the main treatment for inoperable patients and the outcomes for tumours such as oesophagus or pancreas have not improved over the last decades. The causes of local failure are due to several aspects: inadequate radiation dose, low oxygen levels (hypoxia), and failure to target areas that have an unfavourable micro-environment. The advances in technology, imaging and understanding of biological processes offer an opportunity to explore novel approaches.
The aim of my research has three main themes with the ultimate aim of maximising clinical benefit in terms of better tumour control and reduction in toxicity.
1. Strategies of modulating radiotherapy (SMART). 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. The dose escalation is being tested in the phase 3 clinical trial SCOPE2 for oesophageal cancer in collaboration with Dr Crosby in Cardiff.
2. Margin targeted radiotherapy concept. 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. This is tested in a phase 1 trial in the preoperative setting for tumours that are difficult to clear due to proximity to critical organs.
3. Refining normal tissue toxicity modelling in thoracic malignancies. The objective of this work is to characterise and corroborate lung, heart and oesophagus radiotherapy toxicity parameters and develop individualised radiotherapy delivery techniques to minimise dose to susceptible heart, oesophagus and lung substructures. This would allow selection of the best radiotherapy dose delivery technique in patients receiving combined chemoradiation and surgery.
Caption Figure 1a
Standard dose radiotherapy treatment plan for a mid-oesophagus cancer patient. The dose scale is from 6 Gy (blue) to 50 Gy (orange) to 65 Gy (red), and is identical for both images.
Caption Fig 1b
Increased radiotherapy dose may be delivered using SMART techniques to the central high risk volume with no increase in dose to the surrounding tissues.
Maria Hawkins is an Associate Professor and has been an MRC Clinical Group Leader in Advanced Radiation Technology at the CRUK/MRC Oxford Institute for Radiation Oncology and an Honorary Consultant Clinical Oncologist at the Oxford University Hospitals NHS Trust since 2013. Following a research Fellowship at Princess Margaret Hospital in Toronto Canada, she was a consultant in Clinical Oncology at the Royal Marsden Hospital and The Institute of Cancer Research, conducting research on integrating new technological developments in radiotherapy for gastrointestinal cancers. She was awarded the 2008 Dr Karol Sicher Fellowship by The Royal College of Radiologists and the 2009 Sylvia Lawler Prize by the Oncology Section of the Royal Society of Medicine.
Sharma, R. A., Plummer, R., Stock, J. K., Greenhalgh, T. A., Ataman, O., Kelly, S., Clay, R., Adams, R. A., Baird, R. D., Billingham, L., Brown, S. R., Buckland, S., Bulbeck, H., Chalmers, A. J., Clack, G., Cranston, A. N., Damstrup, L., Ferraldeschi, R., Forster, M. D., Golec, J., Hagan, R. M., Hall, E., Hanauske, A. R., Harrington, K. J., Haswell, T., Hawkins, M. A., Illidge, T., Jones, H., Kennedy, A. S., McDonald, F., Melcher, T., O'Connor, J. P., Pollard, J. R., Saunders, M. P., Sebag-Montefiore, D., Smitt, M., Staffurth, J., Stratford, I. J.,Wedge, S. R. (2016). Clinical development of new drug-radiotherapy combinations. Nature reviews. Clinical oncology, 13(10), 627-642. doi: 10.1038/nrclinonc.2016.79
Holyoake, D. L., Ward, E., Grose, D., McIntosh, D., Sebag-Montefiore, D., Radhakrishna, G., Patel, N., Silva, M., Mukherjee, S., Strauss, V. Y., Odondi, L., Fokas, E., Melcher, A., Hawkins, M. A. (2016). A phase-I trial of pre-operative, margin intensive, stereotactic body radiation therapy for pancreatic cancer: the 'SPARC' trial protocol. BMC cancer, 16(1), 728. doi: 10.1186/s12885-016-2765-4
Witztum, A., George, B., Warren, S., Partridge, M., and Hawkins, M. A. (2016). Unwrapping 3D complex hollow organs for spatial dose surface analysis. Medical Physics, 43(11), 6009-6016. doi:10.1118/1.4964790
Warren, S., Partridge, M., Bolsi, A., Lomax, A. J., Hurt, C., Crosby, T., and Hawkins, M. A. (2016). An Analysis of Plan Robustness for Esophageal Tumors: Comparing Volumetric Modulated Arc Therapy Plans and Spot Scanning Proton Planning. International journal of radiation oncology, biology, physics, 95(1), 199-207. doi: 10.1016/j.ijrobp.2016.01.044
Wilson, J. M., Fokas, E., Dutton, S. J., Patel, N., Hawkins, M. A., Eccles, C., Chu, K. Y., Durrant, L., Abraham, A. G., Partridge, M., Woodward, M., O'Neill, E., Maughan, T., McKenna, W. G., Mukherjee, S., Brunner, T. B. (2016). ARCII: A phase II trial of the HIV protease inhibitor Nelfinavir in combination with chemoradiation for locally advanced inoperable pancreatic cancer. Radiotherapy and oncology, 119(2), 306-311. doi: 10.1016/j.radonc.2016.03.021
Holyoake, D. L., Robinson, M., Grose, D., McIntosh, D., Sebag-Montefiore, D., Radhakrishna, G., Patel, N., Partridge, M., Mukherjee, S., Hawkins, M. A. (2016). Conformity analysis to demonstrate reproducibility of target volumes for Margin-Intense Stereotactic Radiotherapy for borderline-resectable pancreatic cancer. Radiotherapy and oncology, 121(1):86-91. doi: 10.1016/j.radonc.2016.08.001
Warren S, Partridge M, Carrington R, Hurt C, Crosby T, Hawkins MA. Radiobiological determination of dose escalation and normal tissue toxicity in definitive chemoradiation therapy for esophageal cancer Int J Radiat Oncol Biol Phys. 2014 Oct 1;90(2):423-9. doi: 10.1016/j.ijrobp.2014.06.028
Wilson JM, Mukherjee S, Chu KY, Brunner TB, Partridge M, Hawkins M. Challenges in using ¹⁸F-fluorodeoxyglucose-PET-CT to define a biological radiotherapy boost volume in locally advanced pancreatic cancer Radiat Oncol. 2014 Jun 24;9:146. doi: 10.1186/1748-717X-9-146
Tree AC, Khoo VS, Eeles RA, Ahmed M, Dearnaley DP, Hawkins MA, Huddart RA, Nutting CM, Ostler PJ, van As NJ. Stereotactic body radiotherapy for oligometastases Lancet Oncol. 2013 Jan;14(1):e28-37.
Louise Bendell, DPhil student
Daniel Holyoake, Clinical Researcher Training Fellow
Rebecca Muirhead, Career Development Fellow
Sean O'Cathail, Clinical Research Training Fellow
Sindu Vivekanandan, Clinical Researcher Training Fellow
Alon Witztum, DPhil Student