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Lee C.D.,Clatterbridge Cancer Center
British Journal of Radiology | Year: 2014

Brachytherapy has evolved over many decades, but more recently, there have been significant changes in the way that brachytherapy is used for different treatment sites. This has been due to the development of new, technologically advanced computer planning systems and treatment delivery techniques. Modern, three-dimensional (3D) imaging modalities have been incorporated into treatment planning methods, allowing full 3D dose distributions to be computed. Treatment techniques involving online planning have emerged, allowing dose distributions to be calculated and updated in real time based on the actual clinical situation. In the case of early stage breast cancer treatment, for example, electronic brachytherapy treatment techniques are being used in which the radiation dose is delivered during the same procedure as the surgery. There have also been significant advances in treatment applicator design, which allow the use of modern 3D imaging techniques for planning, and manufacturers have begun to implement new dose calculation algorithms that will correct for applicator shielding and tissue inhomogeneities. This article aims to review the recent developments and best practice in brachytherapy techniques and treatments. It will look at how imaging developments have been incorporated into current brachytherapy treatment and how these developments have played an integral role in the modern brachytherapy era. The planning requirements for different treatments sites are reviewed as well as the future developments of brachytherapy in radiobiology and treatment planning dose calculation. © 2014 The Authors.

Thorp N.J.,Clatterbridge Cancer Center | Taylor R.E.,University of Swansea
Clinical Oncology | Year: 2014

This article reviews current approaches to management of central nervous system tumours of childhood, highlighting aspects particularly pertinent to the paediatric population. © 2014 The Royal College of Radiologists.

Nahum A.E.,Clatterbridge Cancer Center
Clinical Oncology | Year: 2015

If the α/β ratio is high (e.g. 10Gy) for tumour clonogen killing, but low (e.g. 3Gy) for late normal tissue complications, then delivering external beam radiotherapy in a large number (20-30) of small (≈2Gy) dose fractions should yield the highest 'therapeutic ratio'; this is demonstrated via the linear-quadratic model of cell killing. However, this 'conventional wisdom' is increasingly being challenged, partly by the success of stereotactic body radiotherapy (SBRT) or stereotactic ablative radiotherapy (SABR) extreme hypofractionation regimens of three to five large fractions for early stage non-small cell lung cancer and partly by indications that for certain tumours (prostate, breast) the α/β ratio may be of the same order or even lower than that characterising late complications. It is shown how highly conformal dose delivery combined with quasi-parallel normal tissue behaviour (n close to 1) enables 'safe' hypofractionation; this can be predicted by the (α/β)eff concept for normal tissues. Recent analyses of the clinical outcomes of non-small cell lung cancer radiotherapy covering 'conventional' hyper- to extreme hypofractionation (stereotactic ablative radiotherapy) regimens are consistent with linear-quadratic radiobiology, even at the largest fraction sizes, despite there being theoretical reasons to expect 'LQ violation' above a certain dose. Impairment of re-oxygenation between fractions and the very high (α/β) for hypoxic cells can complicate the picture regarding the analysis of clinical outcomes; it has also been suggested that vascular damage may play a role for very large dose fractions. Finally, the link between high values of (α/β)eff and normal-tissue sparing for quasi-parallel normal tissues, thereby favouring hypofractionation, may be particularly important for proton therapy, but more generally, improved conformality, achieved by whatever technique, can be translated into individualisation of both prescription dose and fraction number via the 'isotoxic' (iso-normal tissue complication probability) concept. © 2015 The Royal College of Radiologists.

Baldan V.,University of Manchester | Griffiths R.,University of Manchester | Griffiths R.,Clatterbridge Cancer Center | Hawkins R.E.,University of Manchester | Gilham D.E.,University of Manchester
British Journal of Cancer | Year: 2015

Background:Tumour-infiltrating lymphocyte (TIL) therapy is showing great promise in the treatment of patients with advanced malignant melanoma. However, the translation of TIL therapy to non-melanoma tumours such as renal cell carcinoma has been less successful with a major constraint being the inability to reproducibly generate TILs from primary and metastatic tumour tissue.Methods:Primary and metastatic renal cell carcinoma biopsies were subjected to differential tumour disaggregation methods and procedures that stimulate the specific expansion of TILs tested to determine which reliably generated TIL maintained antitumour specificity.Results:Enzymatic or combined enzymatic/mechanical disaggregation resulted in equivalent numbers of TILs being liberated from renal cell carcinoma biopsies. Following mitogenic activation of the isolated TILs with anti-CD3/anti-CD28-coated paramagnetic beads, successful TIL expansion was achieved in 90% of initiated cultures. The frequency of T-cell recognition of autologous tumours was enhanced when tumours were disaggregated using the GentleMACS enzymatic/mechanical system.Conclusion:TILs can be consistently produced from renal cell carcinoma biopsies maintaining autologous tumour recognition after expansion in vitro. While the method of disaggregation has little impact on the success of TIL growth, methods that preserve the cell surface architecture facilitate TIL recognition of an autologous tumour, which is important in terms of characterising the functionality of the expanded TIL population. © 2015 Cancer Research UK.

Palmer A.L.,University of Surrey | Lee C.,Clatterbridge Cancer Center | Ratcliffe A.J.,Coventry University | Bradley D.,University of Surrey | Nisbet A.,University of Surrey
Physics in Medicine and Biology | Year: 2013

A novel phantom is presented for 'full system' dosimetric audit comparing planned and delivered dose distributions in HDR gynaecological brachytherapy, using clinical treatment applicators. The brachytherapy applicator dosimetry test object consists of a near full-scatter water tank with applicator and film supports constructed of Solid Water, accommodating any typical cervix applicator. Film dosimeters are precisely held in four orthogonal planes bisecting the intrauterine tube, sampling dose distributions in the high risk clinical target volume, points A and B, bladder, rectum and sigmoid. The applicator position is fixed prior to CT scanning and through treatment planning and irradiation. The CT data is acquired with the applicator in a near clinical orientation to include applicator reconstruction in the system test. Gamma analysis is used to compare treatment planning system exported RTDose grid with measured multi-channel film dose maps. Results from two pilot audits are presented, using Ir-192 and Co-60 HDR sources, with a mean gamma passing rate of 98.6% using criteria of 3% local normalization and 3 mm distance to agreement (DTA). The mean DTA between prescribed dose and measured film dose at point A was 1.2 mm. The phantom was funded by IPEM and will be used for a UK national brachytherapy dosimetry audit. © 2013 Institute of Physics and Engineering in Medicine.

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