Clinical & Translational Research > Radiotherapy Physics > Professor Alan Nahum

We are investigating new methodologies for delivering, analysing, optimising and quantifying external-beam radiotherapy. The group is led by Professor Alan Nahum with Drs John Fenwick (Oxford) and Colin Baker (Liverpool) as senior partners. Dr. Philip Mayles plays a key supporting role as head of CCO Physics. We have developed a delay-differential model of stem cell number variation with time during radiation treatments, which we are using to study the effects of different schedule adaptation and individualisation strategies (Dr. John Fenwick). The model links compensatory proliferation kinetics in early reacting tissues to the degree of tissue damage, and addresses radiation and chemoradiation schedule effects not analysable using simpler approaches.

Complementary to this work we are carrying out sequential PET-FLT imaging studies to determine NSCLC and HNSCC tumour kinetics throughout radiotherapy, in collaboration with St Thomas’ Hospital, London.

Software has been developed (by Dr. Uzan) for the radiobiological optimisation of treatment planning: BioSuite  enables isotoxic customisation of both the prescription dose and the number of fractions (especially powerful for NSCLC) and our modifications to the Pinnacle Research Interface (PRI) enable biologically optimised “inverse planning” of intensity-modulated treatments, e.g. by maximising tumour local control at a fixed complication risk (a new protocol for prostate radiotherapy, BIOPROP – under development - exploits directly this capability and has been extended to use functional MR images of clonogen concentration, thus enabling radiobiologically guided dose-painting). Software developed in-house (Dr. Uzan) is deployed in the computer lab which is an important component of our 4-day international-level course “Radiobiology & Radiobiological Modelling in Radiotherapy” which was given for  the 5th time in May 2010.

We are using the “dose accumulator” of the PRI together with 4DCT images to examine the effects of tumour motion (e.g. due to respiration) on conformal dose distributions, including the novel strategy of a deliberate reduction of field sizes under an isotoxic constraint (with Dr. Popescu, Vancouver BC – our sabbatical visitor during 2008-9); A BioSuite–based analysis indicates that the highest therapeutic ratio is obtained with a 5 mm margin outside the GTV thus involving a highly non-uniform dose distribution in the tumour.  An alternative device to enable “gating” of moving lung tumours has been investigated (PhD project); it works by detecting the change in temperature between inhalation and exhalation.

A related PhD project involves building a flexible computer model of a moving tumour, which can be displaced in an arbitrary fashion both within and between fractions (Jothy Basu). The relationship between various types of movement and tumour local control is obtained through an extension (to individual tumour voxels) of the “Marsden” TCP model, developed by one of us (Nahum). Preliminary results show very clearly that random tumour displacements (from fraction to fraction, for large nos. of fractions) result in much smaller reductions in TCP than a constant shift on every fraction.  

Conventional ideas on the radiobiology of fractionation have been re-examined and found to be inadequate when considering so-called “parallel” organs such as (normal) lung tissue. New theoretical insights have been gained, which demonstrate that much larger fraction sizes can be used for cases where ‘organs at risk’ respond in a “parallel” fashion (Prof. Alan Nahum).  A more sophisticated approach to normal-tissue complication modelling has been undertaken (PhD project; Eva Rutkowska): a radiobiologically-based, mechanistic computer simulation of the response of normal tissues to irradiation has been constructed, which, through “virtual irradiation” of the voxelised organ, is yielding valuable insight into the validity of several much simpler, analytical models of complication probability (NTCP) in common use: Rutkowska et al Physics in Medicine and Biology vol. 55, 2121-36, 2010.

We are playing a pivotal role in the design and quality assurance of UK multicentre phase I/II trials of dose-escalated intensified radiation and chemoirradiation treatments for NSCLC (Dr. John Fenwick, Prof. Alan Nahum) and late stage prostate cancer (involving functional MR imaging – Dr. Isabel Syndikus; Dr. Julien Uzan) as well the biological-model based analysis of the treatment outcomes (using the VODCA-BIO database; Aisyah Yusof Azuddin; Dr. Stefano Gianolini, Zurich).

Additionally, we are developing fast multi-objective Pareto-based optimisation of arc-based intensity-modulated treatments (IMAT), potentially opening the way to more interactive and effective treatment planning (Juan Pardo Montero); an external project (Mauro Iori, Reggio Emilia, Italy) revolves around the dosimetric quality assurance of various clinical IMAT techniques, and is currently being extended to radiobiological “dose painting” of tumours with heterogeneous clonogen density.

We have implemented the Vancouver system of Monte-Carlo based dose computation (MCTP) for the QA of treatment plans (including RapidArc  rotational IMRT) through a collaboration with Dr. Popescu (Vancouver) and the Liverpool University Computing Department (Dr. Ian Smith); through the latter we are able to run our CPU-intensive simulations on the NW grid, a powerful multi-node distributed system.  The clinical impact of MCTP and other more or less approximate dose computation methods (aka algorithms) is being critically examined (in a PhD study – Mekala Chadrasekaran, Vanessa Panettieri) by evaluating dose differences in a number of tumour sites in terms of TCP and NTCP. Initial results indicate that pencil-beam based treatment plans for NSCLC seriously overestimate tumour coverage and hence TCP.   

A separate strand of work concerns the metrology of very small radiation fields delivered in the course of certain intensity-modulated and stereotactic treatments, where we have used the power of Monte-Carlo simulation to unpick the response of small detectors in non-equilibrium conditions and to predict highly accurately the dependence of absolute dose on field size down to a few mm in diameter (Alison Scott, John Fenwick). We have shown, for the first time, that in these very special non-equilibrium photon fields the density of the detector material plays a crucial role in its response, with high-density detectors (diodes, diamonds) over-reading compared to water.

 

Education and qualifications

1976: Postgraduate Certificate of Education (Physics), Nottingham University.

1975: PhD, Dept. of Medical Physics, Edinburgh University.

1971: BA (2:1 Hons), Oxford University.

Appointments

2004: Head of Physics Research, Clatterbridge Centre for Oncology, Wirral, Merseyside

2003: Hospital Physicist, Dept. of Radiation Physics, Copenhagen University Hospital

1993: Senior Researcher, Institute of Cancer Research, Sutton, UK

1985: Postdoctoral Research Fellow, Institute of Cancer Research/Royal Marsden Hospital, Sutton, UK

1980: Postdoctoral Research Fellow, Umea University, Sweden.

1979: Research Assistant, Umea University, Sweden.

1978: Physics/Mathematics school teacher, UK and Sweden.

1976: Hospital Physicist, Nottingham General Hospital.

Membership of Professional Bodies

2009: IPEM Fellowship

1997-2004: American Association of Medical Physics

1985-2002:The Institute of Physics and Engineering in Medicine (IPEM)

1984: European Society for Therapeutic Radiology and Oncology (ESTRO).

Academic Research Journals

1997-2004: Associate Editor of Medical Physics (journal of the American Association of Physicists in Medicine - AAPM)

1991-1992: Deputy Editor of Physics in Medicine and Biology

1989-1992 Member of the Editorial Board of Physics in Medicine and Biology (Institute of Physics Publishing, Bristol, UK)

I act as referee for the following journals:
Physics in Medicine and Biology
Medical Physics
Physica Medica
Radiotherapy and Oncology
International Journal of Radiation Oncology, Biology, Physics
International Journal of Radiation Biology
Acta Oncologica
British Journal of Radiology

Fenwick J D, Lawrence G P, Malik Z, Nahum A E and Mayles W P M
Early mucosal reactions during and following head and neck radiotherapy: Dependence of treatment tolerance on radiation dose and schedule duration
Int. J. Radiat. Oncol. Biol. Phys. 71 625-34 2008

Iori M, Cattaneo G M, Cagni E, Fiorino C, Borasi G, Calandrino R, Iotti C, Fazio F and Nahum A E
Dose-volume and biological-model based comparison between helical tomotherapy and (inverse-planned) IMAT for prostate tumours
Radiotherapy & Oncology, 88 34-45 2008

Scott A J D, Nahum A E and Fenwick J D,
Using a Monte Carlo model to predict dosimetric properties of small radiotherapy photon fields.
Medical Physics, 35 4671-84 2008

Aarup L R, Nahum A E, Zacharatou Jarlskog C, Juhler-Nøttrup T, Knöös T, Nyström H, Specht L, Wieslander E, and Korreman S S.
The effect of different lung densities on the accuracy of various radiotherapy dose calculation methods: Implications for tumour coverage
Radiotherapy & Oncology 91 405-14 2009.

Iori M, Paiusco M, Cagni E, Riccardi S, Lambertini D, Bizzocchi N, Borasi G, Iotti C, D’Abbiero N, Nahum A E,
The Intensity Modulated Arc Therapy (IMMA) technique: forward & inverse planned procedures to deliver hypo-fractionated IMAT treatments.
Current Radiopharmaceuticals 2 149–159 2009

Fenwick J D, Nahum A E, Malik Z I, Eswar C V, Hatton M Q, Lawrence V, Lester J F and Landau D B,
Escalation and intensification of radiotherapy for stage III non-small cell lung cancer: Opportunities for treatment improvement.
Clinical Oncology. 21 343-60 2009.

Scott A J D, Nahum A E and Fenwick J D.
Monte Carlo modeling of small photon fields: quantifying the impact of focal spot size on source occlusion and output factors, and exploring miniphantom design for small-field measurements
Medical Physics 36 3132-3144 2009.

Iori M, Cagni E, Paiusco M, Munro P, Nahum A E
Dosimetric verifications of IMAT delivery with a conventional EPID system and a commercial portal dose image prediction tool.
Medical Physics 37 377-90 2010.

Ruggieri R, Naccarato S and Nahum A E
Severe hypofractionation: the usefulness of non-homogeneous tumour dose delivery in counteracting tumour hypoxia
Accepted for publication in Acta Oncologica, Special Issue on “Edmonton TCP workshop”

Uzan J and Nahum A E,
BioSuite, software for radiobiologically guided optimization of prescription dose and fractionation scheme in radiotherapy [To be submitted to Radiotherapy & Oncology (May 2010)]

Rutkowska Eva, Baker Colin and Nahum Alan
A mechanistic computer simulation of normal-tissue damage in radiotherapy – implications for dose-volume analyses
Phys. Med. Biol. 55 2121-36 2010

Nadia Stavreva, Pavel Stavrev, Ruggero Ruggieri and Alan Nahum
On Invariant Radiobiologically-based Radiation Therapy Plan Ranking.
Accepted for publication in Acta Oncologica, Special Issue on “Edmonton TCP workshop”, December 2009.

Nahum A.E., How robust are TCP models in preparation; to be submitted to Acta Oncologica, Special Issue on “Edmonton TCP workshop”.

Nahum A. E., How can a TCP model be used to increase local control? in preparation; to be submitted to Acta Oncologica, Special Issue on “Edmonton TCP workshop”

Book chapters

Nahum A.E.
“Cavity Theory, Stopping-Power Ratios, Correction Factors”, Chapter 3 in Clinical Dosimetry Measurements in Radiotherapy, Editors DWO Rogers and Joanna E Cygler, AAPM 2009 Summer School Proceedings, Medical Physics Publishing, Madison, WI. (ISBN 978-1-888340-84-6).

Invited talks at meetings

ESTRO pre-meeting teaching Course on DOSE-VOLUME RESPONSE RELATIONSHIPS IN NORMAL TISSUES, Gothenburg, 14 September 2008, invited lecture Hypofractionation in normal tissues – a fresh look.

ESTRO27, 27th Annual Congress of the European Society for Therapeutic Radiology and Oncology, September 14-18, 2008, Gothenburg, invited talk The Physics of the Dosimetry of Small Fields in Radiotherapy (also co-author on invited talk: Iori M, Cagni E, Paiusco M, Riccardi  S, Nahum AE “Verifying the dosimetry of intensity modulated arc therapy (IMAT)”.

ESTRO PREVENT (Prediction, Recognition, EValuation and Eradication of Normal Tissue Effects), January 11-12 2009, Brussels, invited talk MODELS FOR NORMAL TISSUE COMPLICATION PROBABILITY – HOW TO USE THEM IN CLINICAL RADIOTHERAPYi.

AAPM Summer School 2009, Topic: “Clinical dosimetry for radiotherapy”, 21-25 June 2009, Colorado College, Colorado Springs; invited lecture Cavity Theory, Stopping-Power Ratios, Correction Factors.

Irish Radiation Research Society Scientific Meeting 2009, 16-17 October 2009, Galway, Ireland, invited talk “Radiobiologically Optimised Radiotherapy”.

Swedish Oncology annual meeting, 23-24 March 2010, Kalmar; invited talks on “Tumour Control Probability” and “Radiobiological Optimisation”.

Talks at institutions

Velindre Cancer Centre, Cardiff, 5 November 2008,  “Use of radiobiological models to optimise radiotherapy treatment planning”.

MAASTRO clinic, Maastricht, The Netherlands, 20 July 2009, “Why we need radiobiology to optimise treatment plans”.

INSERM U650, Laboratoire de Traitment d’Information Medicale (LaTIM), Brest, France, 5 October 2009 « Radiobiologically guided, individualised Radiotherapy in the Conformal Era ».

3rd Modelling of Tumours (MOT) meeting, 27-29 May 2010, Adelaide; keynote speaker – “Tumour Control Probability Models: what do they tell us about tumour response to irradiation?”; “Treatment Plan Optimisation using Radiobiological Models”.

Potential New Trials

BioProp – Phase I-II trial on “Radiobiologically-guided dose-painting for advanced prostate radiotherapy”; CI – Dr. Isabel Syndikus, CCO.  This is being worked up at present as a CTAAC submission.

	Biography	Role	Email	Telephone	Location
	Professor Alan Nahum	Group Leader		+44 (0)151 482 7860	Clatterbridge Centre for Oncology (CCO)
	Dr Colin Baker	Senior Clinical Physicist		+44 (0)151 794 5754	Clatterbridge Centre for Oncology (CCO)
	Dr Julien Uzan	PostDoctoral Researcher		+44 (0)151 482 7860	Clatterbridge Centre for Oncology (CCO)
	Dr Alison Scott	Clinical Physicist		+44 (0)151 482 7860	Clatterbridge Centre for Oncology (CCO)
	Eva Rutkowska	PhD Student		+44 (0)151 482 7860	Clatterbridge Centre for Oncology (CCO)
	Mekala Chandrasekaran	PhD Student		+44 (0)151 482 7860	Clatterbridge Centre for Oncology (CCO)
	Jothy Basu	PhD Student		+44 (0)151 482 7860	Clatterbridge Centre for Oncology (CCO)
Administrative and Technical Staff
	Sue Nixon	Secretary		+44 (0)151 482 7860	Clatterbridge Centre for Oncology (CCO)