Research

Prof Chris NuttingI firmly believe that the future of improving outcomes in cancer treatment is through well designed clinical research programmes. During my Intercalated BSc (1989) I worked in the cell biology laboratory and gained experience of cell culture and basic laboratory techniques such as clonogenic cell survival assays. The project studied growth factor and retinoid interactions in bladder cancer cell lines.

Over the last 10 years I have been involved in the evaluation of conformal and intensity-modulated radiotherapy techniques for a number of tumour sites. During my MD (ICR 1998-2000; Supervisors Prof Webb and Prof Dearnaley) I was able to show the ability of conformal radiotherapy techniques to allow normal-tissue sparing and escalation of radiation dose. I described class solutions for IMRT in the treatment of tumours of the paranasal sinuses, larynx, hypopharynx, thyroid, parotid, oesophagus, prostate and pelvic lymph node irradiation.

This period of research culminated in the clinical implementation of the IMRT programme at the RMT/ICR that treated the first patients with inverse-planned IMRT in September 2000 in the context of a Phase I/II pelvic node dose escalation study in prostate cancer patients.

Since my appointment at the RMH in 2001 I have developed a number of academic collaborations with colleagues at the ICR in sections of Clinical Trials, Radiotherapy, Joint Department of Physics, MRI research, and Cell and Molecular Biology. I have developed my research areas with clinical trial protocols and radiotherapy technical development concentrating on head and neck cancer as detailed below:

Clinical Research Protocols:

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Radiotherapy:

Randomised Phase III clinical trials:
I am the Principal Investigator of several clinical trials in head and neck IMRT. PARSPORT and COSTAR are both National phase III randomised trials funded by CRUK and trial grants are held within CTSU at ICR (Prof Judith Bliss).

The PARSPORT trial is designed to evaluate the ability of parotid gland-sparing IMRT to reduce xerostomia (dry mouth), the most common long term side effect of head and neck radiotherapy. This is the first randomised study of IMRT against conventional radiotherapy in head and neck cancer, and involved several UK radiotherapy centres. PARSPORT completed recruitment in autumn 2007, and we anticipate analysis of the primary endpoint will be complete in January 2009.

Twenty UK radiotherapy departments completed the quality assurance requirements for PARSPORT, which accelerated the National implementation of head and neck IMRT. Head and neck IMRT guidelines produced for this trial, and published in Clinical Oncology in 2007 form the basis of UK head and neck IMRT practice.

COSTAR is the second randomised head and neck IMRT trial. It aims to evaluate the role of IMRT in preventing radiation-induced hearing loss in patients with parotid gland tumours. It follows preclinical modelling work with radiotherapy physics (Prof Steve Webb). This trial opened to recruitment in spring 2008.

Phase I and II Trials of radiation dose escalation with IMRT
The use of more conformal radiotherapy techniques such as IMRT may allow safe increased radiation dose delivery to maximise tumour control. Two Phase I/II dose escalation studies in patients with thyroid and larynx/ hypopharynx cancer have been performed. Both studies aim to determine the maximum safe dose of chemo-radiotherapy which can be delivered with IMRT to these tumour sites. These trials are supported by the CRUK-funded Radiotherapy Program Grant held by Prof Alan Horwich.

The early results of the Phase I component of both trials were published in Radiotherapy and Oncology in 2008, and were presented at ECCO in 2007 during a plenary session.

Novel Radiotherapy indications for IMRT
In 2007 we designed and published a new technique for total mucosal IMRT for patients with unknown primary squamous cell carcinoma of the head and neck region. The preclinical project led to a phase II clinical trial which is currently recruiting patients at RMH. New optimisation algorithms for salivary gland sparing are being evaluated in Phase II studies of difficult-to-treat midline tumour sites (nasopharynx and tongue base).

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Mucousitis

I have been the Local Principal Investigator on three pharmaceutical trials aimed at reducing this radiotherapy complication. The latest study using a keratinocyte growth factor is currently recruiting patients.

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Image guided RT

The use of conformal radiotherapy techniques requires improvements in tumour and normal tissue imaging. I have performed studies in collaboration with Prof Martin Leach, to investigate the benefits of adding MRI to treatment planning for skull base tumours. These showed improved accuracy of both tumour and neurological structure localisation. These techniques have now been incorporated into clinical protocols at RMH.

Through a clinical grant from the Royal College of Radiologists and RMH CRD, I developed this area further and have been investigating the integration of PET/CT, dceMRI and dceCT into radiotherapy treatment planning for advanced head and neck cancers.

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Chemotherapy

Over the last seven years I have been involved with trials of cytotoxic and biological chemotherapy agents and viruses in head and neck cancer.

Lapatinib (GSK): I have been co-investigator on a series of chemoradiation trials with this multi-targeted tyrosine kinase inhibitor. Phase I and II trials are completed, and two randomised Phase III trials are recruiting.

Zalutumamab (GenMab): I am the UK PI on a trial of this anti EGFR antibody in palliative chemotherapy for patients with relapsed or metastatic head and neck cancer, a new trial of this agent in combination with radiotherapy is due to open in 2008.

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Thyroid Cancer

Radio-iodine resistant thyroid cancer is my main area of research in this tumour type. I am the Principal Investigator of an investigator-led phase II trial of Sorafinib, a multi-targeted tyrosine kinase inhibitor sponsored by a clinical trial grant from Bayer. A biomarker study in this trial has been performed in conjunction with Prof Richard Marais. The trial has recently been completed, and has been selected for oral presentation at ASCO 2008.

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Research Grants

I currently hold a number of clinical research grants:

CTAAC Clinical Trial Grant: COSTAR: A randomised trial of IMRT vs. Conventional radiotherapy in parotid gland tumours
Role: Principal Investigator
£280,000 2007-2011

Clinical Trial Grant from HTA: PET/NECK: A randomised trial to investigate the role of PET/CT in the evaluation of nodal metastases after chemoradiation in head and neck cancer
Role: Co-investigator and radiotherapy lead
HTA grant £2,100,000 2007-2011

CTAAC Clinical Trial Grant: PARSPORT: A randomised trial of IMRT vs. Conventional radiotherapy in head and neck cancer
Role: Principal Investigator
£250,000 2003-2007 Extension of this grant to December 2008 £70,000

Investigator lead clinical trial grant (Bayer): MATISSE – a Phase II trial of Sorafinib in differentiated and medullary thyroid cancer
Role: Principal Investigator
£200,000 2006-2009

Head and Neck Research programme funded from Biomedical Research Grant from Department of Health Proportion of total grant of £10M
Role: Co-investigator

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Previous Grants and Research Awards:

Royal Marsden Hospital Clinical Research and Development Award 2005-2006
Role: Principal Investigator
£45,000 to support MD student

RCR/BUPA Fellowship to study PET/CT in head and neck cancer RT 2004-2005. Role: Principal Investigator
£50,000 to support MD student

CRUK Research Registrar to conduct IMRT studies in head and neck cancer. From CRUK programme grant led by Prof A Horwich 2005-2006 £100,000

Head and Neck Cancer Research Trust Research Fellowship program 2004-2007 (£50,000 pa)

Royal Marsden Head and Neck Research Trust. Salary for the support of two Research Nurses. £90,000

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