Publications
310 results found
Price P, Heap G, 2008, Implementing image-guided radiotherapy in the UK: plans for a co-ordinated UK research and development strategy, Br J Radiol, Vol: 81, Pages: 379-382
Rembielak A, Price P, 2008, The role of PET in target localization for radiotherapy treatment planning, Onkologie, Vol: 31, Pages: 57-62
Positron emission tomography (PET) is currently accepted as an important tool in oncology, mostly for diagnosis, staging and restaging purposes. It provides a new type of information in radiotherapy, functional rather than anatomical. PET imaging can also be used for target volume definition in radiotherapy treatment planning. The need for very precise target volume delineation has arisen with the increasing use of sophisticated three-dimensional conformal radiotherapy techniques and intensity modulated radiation therapy. It is expected that better delineation of the target volume may lead to a significant reduction in the irradiated volume, thus lowering the risk of treatment complications (smaller safety margins). Better tumour visualisation also allows a higher dose of radiation to be applied to the tumour, which may lead to better tumour control. The aim of this article is to review the possible use of PET imaging in the radiotherapy of various cancers. We focus mainly on non-small cell lung cancer, lymphoma and oesophageal cancer, but also include current opinion on the use of PET-based planning in other tumours including brain, uterine cervix, rectum and prostate.
Silva P, Slevin NJ, Sloan P, et al., 2008, Prognostic significance of tumor hypoxia inducible factor-1alpha expression for outcome after radiotherapy in oropharyngeal cancer, Int J Radiat Oncol Biol Phys, Vol: 72, Pages: 1551-1559, ISSN: 1879-355X
PURPOSE: Head-and-neck squamous cell carcinoma (HNSCC) represents a heterogeneous group of patients in terms of subsite, treatment, and biology. Currently most management decisions are based on clinical parameters with little appreciation of patient differences in underlying tumor biology. We investigated the prognostic significance of clinicopathologic features and tumor hypoxia-inducible factor-1alpha (HIF-1alpha) expression in a homogeneous series of patients who underwent radiotherapy. METHODS AND MATERIALS: An audit identified 133 consecutive patients with histologically proven squamous cell carcinoma of the tonsil or tongue base. All patients received primary radiotherapy between 1996 and 2001. Tumor HIF-1alpha expression was examined in 79 patients. RESULTS: Features associated with poor locoregional control were low Hb level (p = 0.05) and advancing T (p = 0.008), N (p = 0.03), and disease (p = 0.008) stage. HIF-1alpha expression was a more significant adverse prognostic factor in the tonsil (hazard ratio [HR], 23.1; 95% confidence interval [CI]. 3.04-176.7) than the tongue-base tumor (HR, 2.86; 95% CI, 1.14-7.19) group (p = 0.03, test for interaction). High tumor HIF-1alpha expression was associated with low blood Hb levels (p = 0.03). In a multivariate analysis HIF-1alpha expression retained prognostic significance for locoregional control (HR, 7.10; 95% CI, 3.07-16.43) and cancer-specific survival (HR, 9.19; 95% CI, 3.90-21.6). CONCLUSIONS: There are significant differences in radiation therapy outcome within a homogeneous subsite of the oropharynx related to molecular marker expression. The work highlights the importance of studying homogeneous groups of patients in HNSCC, and the complex interrelationships between tumor biology and clinicopathologic factors. The establishment of tumor-type specific markers would represent a major advance in this area.
Whitfield GA, Jackson A, Moore C, et al., 2008, Radical chemoradiotherapy for adenocarcinoma of the distal oesophagus and oesophagogastric junction: what planning margins should we use?, Br J Radiol, Vol: 81, Pages: 921-934, ISSN: 1748-880X
Distal oesophageal and Type I-II oesophagogastric junctional adenocarcinomas have a poor prognosis. In radical chemoradiotherapy, consensus is lacking on radiotherapy margins. Here, we review the effect of common imaging modalities on the extent of the gross tumour volume (GTV) and the evidence for margins. To do this, papers were identified from PubMed, and geometric uncertainties were combined using the British Institute of Radiology formula. CT and endoscopic ultrasound were best for GTV delineation, but the role of positron emission tomography is uncertain. Evidence suggests 3 cm proximal and 5 cm distal GTV-CTV (clinical target volume) margins (along the mucosa) for advanced tumours, but is lacking for early tumours and radial margins. Nodal spread, present in most pT2 tumours, is strongly prognostic and is initially to regional nodes (not wholly covered by typical radiotherapy). Calculated CTV-PTV (planning target volume) margins for three-dimensional conformal radiotherapy using literature estimates of tumour motion and set-up errors with bony online set-up correction, ignoring delineation errors, are 2.2 cm superiorly (sup) and inferiorly (inf) and 1.2-1.3 cm radially (1.3 cm sup-inf; 0.8 cm radially if the tumour's mid-position is known). As these margins may risk excessive toxicity, we propose treating microscopic disease for potentially curable tumours (cT2N0, some cT3N0), but gross disease only for advanced tumours. Recommended GTV-CTV margins are a maximum of 3 cm proximally and 5 cm distally up to cT2N0; 3 cm proximally and 5 cm distally for cT3N0 if anticipated toxicity allows; and 0 cm for cT4 and most node-positive tumours. The CTV-PTV margins above must be added to this for all stages. Methods of including elective nodal areas close to the GTV should be researched, e.g. nodal maps and intensity-modulated radiotherapy.
Charnley N, Airley R, Du Plessis D, et al., 2008, No relationship between 18F-fluorodeoxyglucose positron emission tomography and expression of Glut-1 and -3 and hexokinase I and II in high-grade glioma, Oncol Rep, Vol: 20, Pages: 537-542, ISSN: 1021-335X
The purpose of this study was to compare glucose metabolism, measured using 18F-fluorodeoxyglucose positron emission tomography ([18F]FDG-PET), with the expression of Glut-1 and -3 and hexokinase I (Hex I) and II in high-grade glioma. The retrospective study involved 27 patients with WHO classification grade III and IV glioma, with either newly diagnosed or recurrent tumours. Patients underwent dynamic and static [18F]FDG-PET to glucose metabolic rate (MRGlu) and standardised uptake value (SUV), respectively. Tumour biopsies were obtained and stained using immunohistochemistry for the expression of Glut-1, -3, Hex I and II. Relationships between variables were studied using Spearman's rank correlation test. Results showed that the expression of Glut-1, Glut-3, Hex I and Hex II varied between and within the tumour samples. The mean of MRGlu was 0.2 (range 0.09-0.25) micromol/min/ml and that of SUV was 4.2 (range 3.2-5.2). There were no significant relationships among the tumour expression of any of the proteins studied with either MRGlu or SUV (p>0.21 for all). In conclusion, the lack of relationship between the immunohistochemical expression of Glut-1, -3, Hex I or II and glucose metabolism measured using [18F]FDG-PET in patients with high-grade glioma may be due to the tissue heterogeneity and presence of necrosis in high-grade tumours.
Jain P, Amer A, Stratford J, et al., 2007, X-ray volumetric imaging (XVI) to redefine radiotherapy margins for locally advanced pancreatic cancer (LAPC), CLINICAL ONCOLOGY, Vol: 19, Pages: S33-S33, ISSN: 0936-6555
Saleem A, Price P, 2007, PET measurement of drug kinetics, In Vivo Imaging in Cancer Therapy, Editors: Shlelds, Price, Publisher: Humana Press, ISBN: 1588296334
Jain P, Saleem A, Price P, 2007, Principles of Adjuvant Radiotherapy, Textbook of Surgical Oncology, Editors: Poston, London and New York, Publisher: Taylor Francis
Griffiths EA, Pritchard SA, McGrath SM, et al., 2007, Increasing expression of hypoxia-inducible proteins in the Barrett's metaplasia-dysplasia-adenocarcinoma sequence, Br J Cancer, Vol: 96, Pages: 1377-1383
Hypoxia-associated markers are involved in the progression of several malignancies, but are relatively unstudied in Barrett's carcinogenesis. Our aim was to assess the immunohistochemical expression of hypoxia-inducible factor (HIF)-1alpha, HIF-2alpha, erythropoietin (Epo), Epo receptor (Epo-R), Glut-1 and vascular endothelial growth factor (VEGF) along with Ki67/MIB-1 in the Barrett's metaplasia-dysplasia-adenocarcinoma sequence. Endoscopic biopsies of normal squamous epithelium (NSE) (n=20), columnar-lined oesophagus (CLO) (n=15), CLO with intestinal metaplasia (n=20), dysplasia (n=17) and Barrett's type adenocarcinoma (n=20) were obtained. Immunohistochemistry was performed on the paraffin-embedded tissue. A score was calculated for each marker (range 0-300) by multiplying intensity (none 0, weak 1, moderate 2, strong 3) by percentage of expression (range 0-100). Significant increases in the expression of HIF-2alpha (P=0.014), VEGF (P<0.0001), Epo-R (P<0.0001) and Ki67 (P<0.0001) were found as tissue progressed from NSE to adenocarcinoma. HIF-2alpha was expressed late in the sequence and was only seen in dysplasia and adenocarcinoma. High HIF-2alpha expression was seen in 12 out of 20 Barrett's type adenocarcinoma. The late expression of HIF-2alpha in the Barrett's carcinogenesis sequence and its high expression in adenocarcinoma suggest that it is worth further investigation as a marker of disease progression and therapeutic target.
Griffiths EA, Pritchard SA, Valentine HR, et al., 2007, Hypoxia-inducible factor-1alpha expression in the gastric carcinogenesis sequence and its prognostic role in gastric and gastro-oesophageal adenocarcinomas, Br J Cancer, Vol: 96, Pages: 95-103
Hypoxia-inducible factor-1 (HIF-1)alpha expression was studied in the gastric carcinogenesis sequence and as a prognostic factor in surgically resected gastric and gastro-oesophageal junction tumours. Protein expression was examined using immunohistochemistry on formalin-fixed biopsies of normal mucosa (n=20), Helicobacter pylori associated gastritis (n=24), intestinal metaplasia (n=24), dysplasia (n=12) and intestinal (n=19) and diffuse (n=21) adenocarcinoma. The relationship between HIF-1alpha expression and prognosis was assessed in resection specimens from 177 patients with gastric and gastro-oesophageal junction adenocarcinoma. Hypoxia-inducible factor-1alpha expression was not observed in normal gastric mucosa but increased in density (P<0.01) and intensity (P<0.01) with progression from H. pylori-associated gastritis, intestinal metaplasia, dysplasia to adenocarcinoma. The pattern of staining in the resection specimens was focally positive in 49 (28%) and at the invasive tumour edge in 41 (23%). Invasive edge expression was associated with lymph node metastases (P=0.034), advanced TNM stage (P=0.001) and was an adverse prognostic factor for cancer-specific survival (P=0.019). In univariate analysis and in comparison with tumours not expressing HIF-1alpha, invasive edge staining was associated with a hazard ratio of 1.6 (95% CI 1.0-2.5) and focally positive staining a hazard ratio of 0.7 (95% CI 0.5-1.2). Hypoxia-inducible factor-1alpha lost prognostic significance in multivariate analysis. The results suggest HIF-1alpha is involved in gastric carcinogenesis and disease progression, but is only a weak prognostic factor for survival.
Price P, 2007, Advancing radiotherapy: international networking might be the way forward, Lancet Oncol, Vol: 8, Pages: 364-365, ISSN: 1470-2045
Price P, 2007, The Role of PET Scanning in Determining Pharmacoselective Doses in Oncology Drug Development, Pages: 185-193
Silva P, Homer JJ, Slevin NJ, et al., 2007, Clinical and biological factors affecting response to radiotherapy in patients with head and neck cancer: a review, Clin Otolaryngol, Vol: 32, Pages: 337-345, ISSN: 1749-4478
OBJECTIVE: The main aim of this article was to review the clinical and biological factors that have been shown to influence the response of the head and neck squamous cell carcinoma (HNSCC) to primary radiotherapy and briefly discuss how some of these factors could be exploited to improve outcome. DESIGN: Medline based search covering 1982-2006 to identify the HNSCC literature where the effect of clinical and biological factors on locoregional control and overall survival were investigated. RESULTS: Clinical factors are routinely used in management decisions. Nevertheless, identically staged tumours receiving the same treatment may have different outcomes. Biological factors such as hypoxia, proliferation and radio-sensitivity play an important role in radiation response. However, these are not currently used in practise because tests that are clinically reliable and feasible are not available. CONCLUSION: High-quality translational research will allow us to develop biological tests that can be used in routine clinical practise to tailor individual treatment, with the ability to improve patient outcome further by modifying the underlying tumour biology.
Price P, Sikora K, Illidge T, 2007, Treatment of Cancer, 5th Edition, London, Publisher: Arnold
Sripadam R, Amer A, Marchant T, et al., 2007, Optimal Planning and Delivery of Radiotherapy for Oesophago-gastric Junction (OGJ) Cancers, Clin Oncol (R Coll Radiol), Vol: 19
Wells P, Price P, 2007, Tumor Proliferation 2-[11C]-Thymidine Positron Emission Tomography, Cancer Imaging, Editors: Hayat, Publisher: Elsevier
Coope D, Herholz K, Price P, 2007, Brain tumours: planning and monitoring therapy with PET, Cancer Imaging, Editors: Hayat, Publisher: Elsevier Science/Academic Press
Charnley N, Jones T, Price P, 2007, Principles of PET in cancer treatment: for the assessment of chemotherapy and radiotherapy response, and for radiotherapy treatment planning., Clinical PET-CT, Editors: Shreve, Townsend, Publisher: Springer-Verlag New York Inc, ISBN: 0387489002
Price P, 2007, The Potential of Molecular Imaging with PET to Improve the Radiotherapy Treatment Process, Clin Oncol (R Coll Radiol), Vol: 19
Price P, 2007, ACCORN - Revitalising Radiotherapy in England, Clin Oncol (R Coll Radiol), Vol: 19
Jain P, Amer A, Stratford J, et al., 2007, X-ray Volumetric Imaging (XVI) to Redefine Radiotherapy Margins for Locally Advanced Pancreatic Cancer (LAPC), Clin Oncol (R Coll Radiol), Vol: 19
Quasar Collaborative G, Gray R, Barnwell J, et al., 2007, Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study, Lancet, Vol: 370, Pages: 2020-2029, ISSN: 1474-547X
BACKGROUND: The aim of the QUASAR trial was to determine the size and duration of any survival benefit from adjuvant chemotherapy for patients with colorectal cancer at low risk of recurrence, for whom the indication for such treatment is unclear. METHODS: After apparently curative resections of colon or rectal cancer, 3239 patients (2963 [91%] with stage II [node negative] disease, 2291 [71%] with colon cancer, median age 63 [IQR 56-68] years) enrolled between May, 1994, and December, 2003, from 150 centres in 19 countries were randomly assigned to receive chemotherapy with fluorouracil and folinic acid (n=1622) or to observation (with chemotherapy considered on recurrence; n=1617). Chemotherapy was delivered as six 5-day courses every 4 weeks or as 30 once-weekly courses of intravenous fluorouracil (370 mg/m2) with high-dose (175 mg) L-folinic acid or low-dose (25 mg) L-folinic acid. Until 1997, levamisole (12 courses of 450 mg over 3 days repeated every 2 weeks) or placebo was added. After 1997, patients who were assigned to receive chemotherapy were given fluorouracil and low-dose folinic acid only. The primary outcome was all-cause mortality. Analyses were done by intention to treat. This trial is registered with the International Clinical Trial Registry, number ISRCTN82375386. FINDINGS: At the time of analysis, 61 (3.8%) patients in the chemotherapy group and 50 (3.1%) in the observation group had missing follow-up. After a median follow-up of 5.5 (range 0-10.6) years, there were 311 deaths in the chemotherapy group and 370 in the observation group; the relative risk of death from any cause with chemotherapy versus observation alone was 0.82 (95% CI 0.70-0.95; p=0.008). There were 293 recurrences in the chemotherapy group and 359 in the observation group; the relative risk of recurrence with chemotherapy versus observation alone was 0.78 (0.67-0.91; p=0.001). Treatment efficacy did not differ significantly by tumour site, stage, sex, age, or chemotherapy sched
Jain P, Marchant T, Duffy M, et al., 2007, X-ray volumetric imaging (XVI) to quantitate the dosimetric impact of the uncertainties during radical radiotherapy (RT) of non small cell lung cancers, Lung Cancer, Vol: 57, Pages: S7-S8
Winter SC, Buffa FM, Silva P, et al., 2007, Relation of a hypoxia metagene derived from head and neck cancer to prognosis of multiple cancers, Cancer Res, Vol: 67, Pages: 3441-3449
Affymetrix U133plus2 GeneChips were used to profile 59 head and neck squamous cell cancers. A hypoxia metagene was obtained by analysis of genes whose in vivo expression clustered with the expression of 10 well-known hypoxia-regulated genes (e.g., CA9, GLUT1, and VEGF). To minimize random aggregation, strongly correlated up-regulated genes appearing in >50% of clusters defined a signature comprising 99 genes, of which 27% were previously known to be hypoxia associated. The median RNA expression of the 99 genes in the signature was an independent prognostic factor for recurrence-free survival in a publicly available head and neck cancer data set, outdoing the original intrinsic classifier. In a published breast cancer series, the hypoxia signature was a significant prognostic factor for overall survival independent of clinicopathologic risk factors and a trained profile. The work highlights the validity and potential of using data from analysis of in vitro stress pathways for deriving a biological metagene/gene signature in vivo.
Amer A, Jain P, Stratford J, et al., 2006, A method for utilising cone-beam CT projection images to determine intra and inter fraction organ motion, 25th Congress of the European-Society-for-Therapeutic-Radiology-and-Oncology, Publisher: ELSEVIER IRELAND LTD, Pages: S316-S317, ISSN: 0167-8140
Gupta N, Saleem A, Kotz B, et al., 2006, Carbogen and nicotinamide increase blood flow and 5-fluorouracil delivery but not 5-fluorouracil retention in colorectal cancer metastases in patients, Clin Cancer Res, Vol: 12, Pages: 3115-3123
PURPOSE: To examine whether carbogen and nicotinamide increases 5-fluorouracil (5-FU) delivery to colorectal cancer metastases. EXPERIMENTAL DESIGN: Six patients were scanned using positron emission tomography. Two scans were done to coincide with the start of separate chemotherapy cycles. At the second positron emission tomography session, 60 mg/kg nicotinamide was given orally 2 to 3 hours before 10-minute carbogen inhalation. In the middle of carbogen treatment, [15O]H2O (to measure regional tissue perfusion) and then [18F]5-FU (to measure 5-FU tissue pharmacokinetics) were administered. RESULTS: Regions of interest were drawn in 12 liver metastases, 6 spleens, 6 livers, and 12 kidneys. Nicotinamide and carbogen administration increased mean blood pO2 from 93 mm Hg (95% confidence interval, 79-198) to 278 mm Hg (95% confidence interval, 241-316; P = 0.031). Regional perfusion (mL(blood)/min/mL(tissue)) increased in metastases (mean change = 52%, range -32% to +261%, P = 0.024), but decreased in kidney (mean change = -42%, range -82% to -11%, P = 0.0005) and liver (mean change = -34%, range -43% to -26%, P = 0.031). 5-FU uptake at 3.75 minutes (m(2)/mL) increased in tumor (mean change = 40%, range -39% to +196%, P = 0.06) and decreased in kidney (mean change = -25%, range -71% to 12%, P = 0.043). 5-FU delivery measured as K1 increased in tumor (mean change = 74%, range -23% to +293%, P = 0.0039). No differences were seen in [18F]5-FU tumor exposure (net area under curve) and retention. CONCLUSION: Nicotinamide and carbogen administration can increase 5-FU delivery to colorectal cancer liver metastases. Despite an increase in perfusion and 5-FU delivery, the effects were not directly related and did not increase 5-FU retention or tissue exposure.
Workman P, Aboagye EO, Chung YL, et al., 2006, Minimally invasive pharmacokinetic and pharmacodynamic technologies in hypothesis-testing clinical trials of innovative therapies, J Natl Cancer Inst, Vol: 98, Pages: 580-598
Clinical trials of new cancer drugs should ideally include measurements of parameters such as molecular target expression, pharmacokinetic (PK) behavior, and pharmacodynamic (PD) endpoints that can be linked to measures of clinical effect. Appropriate PK/PD biomarkers facilitate proof-of-concept demonstrations for target modulation; enhance the rational selection of an optimal drug dose and schedule; aid decision-making, such as whether to continue or close a drug development project; and may explain or predict clinical outcomes. In addition, measurement of PK/PD biomarkers can minimize uncertainty associated with predicting drug safety and efficacy, reduce the high levels of drug attrition during development, accelerate drug approval, and decrease the overall costs of drug development. However, there are many challenges in the development and implementation of biomarkers that probably explain their disappointingly low implementation in phase I trials. The Pharmacodynamic/Pharmacokinetic Technologies Advisory committee of Cancer Research UK has found that submissions for phase I trials of new cancer drugs in the United Kingdom often lack detailed information about PK and/or PD endpoints, which leads to suboptimal information being obtained in those trials or to delays in starting the trials while PK/PD methods are developed and validated. Minimally invasive PK/PD technologies have logistic and ethical advantages over more invasive technologies. Here we review these technologies, emphasizing magnetic resonance spectroscopy and positron emission tomography, which provide detailed functional and metabolic information. Assays that measure effects of drugs on important biologic pathways and processes are likely to be more cost-effective than those that measure specific molecular targets. Development, validation, and implementation of minimally invasive PK/PD methods are encouraged.
Stratford J, Ball K, Henry AM, et al., 2006, Radiotherapy treatment verification in the UK: an audit of practice in 2004, Clin Oncol (R Coll Radiol), Vol: 18, Pages: 15-22
AIMS: To audit current practice related to treatment verification undertaken in radiotherapy departments throughout the UK. MATERIALS AND METHODS: A questionnaire was circulated to the radiotherapy service managers of 62 radiotherapy centres in the UK. This looked in detail at the department demographics, imaging equipment, site-specific verification protocols, and training and competency assessment of staff responsible for verification. RESULTS: The response rate was 48% (30/62). All departments were using megavoltage imaging equipment in routine clinical practice. Twenty-four out of 29 (83%) departments that had electronic portal imaging capability were using image analysis software for verification. Twenty-nine out of 30 (97%) departments had site-specific written verification protocols. Twenty out of 30 (67%) treatment centres audited set-up errors within their department. Forty-three per cent of centres were using simulator image as the reference image of choice across all sites. Electronic portal imaging, alone or in combination with portal film, was being used for verification in 75% of the centres. Fifty-three per cent of centres used off-line correction strategies for measuring set-up errors across all sites. Radiographer-led interventions were primarily in the pelvis. CONCLUSION: Presently in the UK, verification strategies vary widely at individual treatment sites and between departments. Dedicated departmental verification teams, with input from radiographers, physicists and clinicians, may assist in the effective implementation of evidence-based verification. The inclusion of comprehensive verification protocols within multicentre radiotherapy trials encourages standardisation across treatment centres.
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