Publications
310 results found
Jackson AS, Jain P, Watkins GR, et al., 2010, Efficacy and tolerability of limited field radiotherapy with concurrent capecitabine in locally advanced pancreatic cancer, Clin Oncol, Vol: 22, Pages: 570-577, ISSN: 1433-2981
AIMS: Patients with locally advanced pancreatic cancer (LAPC) are most commonly managed with chemotherapy or concurrent chemoradiotherapy (CRT), which may or may not include non-involved regional lymph nodes in the clinical target volume. We present our results of CRT for LAPC using capecitabine and delivering radiotherapy to a limited radiation field that excluded non-involved regional lymph nodes from the clinical target volume. MATERIALS AND METHODS: Thirty patients were studied. Patients received 50.4 Gy external beam radiotherapy in 28 fractions, delivered to a planning target volume expanded from the primary tumour and involved nodes only. Capecitabine (500-600 mg/m2) was given twice daily continuously during radiotherapy. Toxicity and efficacy data were prospectively collected. RESULTS: Nausea, vomiting and tumour pain were the most common grade 2 toxicities. One patient developed grade 3 nausea. The median time to progression was 8.8 months, with 20% remaining progression free at 1 year. The median overall survival was 9.7 months with a 1 year survival of 30%. Of 21 patients with imaged progression, 13 (62%) progressed systemically, three (14%) had local progression, two (10%) had locoregional progression and three (14%) progressed with both local/locoregional and systemic disease. CONCLUSION: CRT using capecitabine and limited field radiotherapy is a well-tolerated, relatively efficacious treatment for LAPC. The low toxicity and low regional progression rates support the use of limited field radiotherapy, allowing evaluation of this regimen with other anti-cancer agents.
Sillah K, Williams LR, Laasch H, et al., 2010, Computed tomography overestimation of esophageal tumour length: implications for radiotherapy planning, World J Gastrointest Oncol, Vol: 2, Pages: 197-204
Laking G, Price P, 2010, Radionuclide imaging of perfusion and hypoxia, Eur J Nucl Med Mol Imaging, Vol: 37 Suppl 1, Pages: S20-S29, ISSN: 1619-7089
PURPOSE: We present a review of radionuclide imaging of tumour vascular physiology as it relates to angiogenesis. We focus on clinical trials in human subjects using PET and SPECT to evaluate tumour physiology, in particular blood flow and hypoxia. METHODS: A systematic review of literature based on MEDLINE searches updated in February 2010 was performed. RESULTS: Twenty-nine studies were identified for review: 14 dealt with (15)O-water PET perfusion imaging, while 8 dealt with (18)F-fluoromisonidazole PET hypoxia imaging. Five used SPECT methods. The studies varied widely in technical quality and reporting of methods. CONCLUSIONS: A subset of radionuclide methods offers accurate quantitative scientific observations on tumour vascular physiology of relevance to angiogenesis and its treatment. The relationship between cellular processes of angiogenesis and changing physiological function remains poorly defined. The promise of quantitative functional imaging at high specificity and low administered dose sustains interest in radionuclide methods.
Lunt SJ, Cawthorne C, Ali M, et al., 2010, The hypoxia-selective cytotoxin NLCQ-1 (NSC 709257) controls metastatic disease when used as an adjuvant to radiotherapy, Br J Cancer, Vol: 103, Pages: 201-208, ISSN: 1532-1827
BACKGROUND: Metastases cause most cancer-related deaths. We investigated the use of hypoxia-selective cytotoxins as adjuvants to radiotherapy in the control of metastatic tumour growth. METHODS: The NLCQ-1, RB6145 and tirapazamine were assessed against the spontaneously metastasising KHT model. Subcutaneous KHT tumours (250 mm(3)) were irradiated with 25 Gy (single fraction) to control primary growth. Equitoxic drug treatments (NLCQ-1 (10 mg kg(-1)) once daily; RB6145 (75 mg kg(-1)) and tirapazamine (13 mg kg(-1)) twice daily) were administered 3-6 days post-radiotherapy when hypoxic cells were evident in lung micrometastases. Mice were culled when 50% of controls exhibited detrimental signs of lung metastases. RESULTS: In total, 95% of control mice presented with lung disease. This was significantly reduced by NLCQ-1 (33%; P=0.0002) and RB6145 (60%; P=0.02). Semi-quantitative grading of lung disease revealed a significant improvement with all treatments, with NLCQ-1 proving most efficacious (median grades: control, 4; NLCQ, 0 (P<0.0001); RB6145, 1 (P<0.001), tirapazamine, 3 (P=0.007)). Positron emission tomography (PET) was evaluated as a non-invasive means of assessing metastatic development. Primary and metastatic KHT tumours showed robust uptake of [(18)F]fluorodeoxyglucose ([(18)F]FDG). Metastatic burden discernable by [(18)F]FDG PET correlated well with macroscopic and histological lung analysis. CONCLUSION: The hypoxia-selective cytotoxin NLCQ-1 controls metastatic disease and may be a successful adjuvant to radiotherapy in the clinical setting.
Mayles WP, Radiotherapy Development B, 2010, Survey of the availability and use of advanced radiotherapy technology in the UK, Clin Oncol (R Coll Radiol), Vol: 22, Pages: 636-642, ISSN: 1433-2981
AIMS: To determine the availability of intensity-modulated radiotherapy (IMRT) treatment in the UK and to assess the magnitude of the shortfall in terms of patient treatments. In addition, the availability of image-guided radiotherapy (IGRT) was also reviewed. MATERIALS AND METHODS: A survey was carried out between July and September 2008 of the use of advanced technology in radiotherapy. RESULTS: In total, 50 centres responded out of the 58 National Health Service centres canvassed, representing about 89% of patients treated in the UK. Forty-six centres had at least two machines capable of IMRT and 26 centres had at least one machine capable of IGRT. Thirty-two centres were carrying out forward-planned IMRT and 18 centres were carrying out the more complex inverse-planned IMRT. In all, 38 centres (76% of respondents) were offering either forward- or inverse-planned IMRT to some of their patients. All the centres with IGRT capability were using IGRT for at least some of their patients. Respondents were asked to list the total number of radical and palliative patients being treated according to the treatment site. Forty-two per cent of respondents took the option to list the total number of radical and palliative patients only. Based on these data, 10.7% of radical patients are currently being given forward-planned IMRT, mainly for breast cancer (18.6% of such patients) and 2.2% of radical patients are being given inverse-planned IMRT, mainly for prostate (7.5% of such patients) and head and neck cancer (6.7% of such patients). Whereas at present only 18 centres are able to treat with inverse-planned IMRT, 45 centres expected to be able to do so by 2010. Respondents were asked to estimate the percentage of patients who should be given IMRT for each site and this was used to estimate the shortfall in IMRT provision. CONCLUSIONS: Based on the consensus of opinion, 32% of radically treated patients should receive inverse-planned IMRT and 22% forward-planned IMRT, making
Pettit GR, Minardi MD, Hogan F, et al., 2010, An efficient synthetic strategy for obtaining 4-methoxy carbon isotope labeled combretastatin A-4 phosphate and other Z-combretastatins, J Nat Prod, Vol: 73, Pages: 399-403, ISSN: 1520-6025
Human cancer and other clinical trials under development employing combretastatin A-4 phosphate (1b, CA4P) should benefit from the availability of a [(11)C]-labeled derivative for positron emission tomography (PET). In order to obtain a suitable precursor for addition of a [(11)C]methyl group at the penultimate step, several new synthetic pathways to CA4P were evaluated. Geometrical isomerization (Z to E) proved to be a challenge, but it was overcome by development of a new CA4P synthesis suitable for 4-methoxy isotope labeling.
Routsis D, Staffurth J, Beardmore C, et al., 2010, Education and training for intensity-modulated radiotherapy in the UK, Clin Oncol (R Coll Radiol), Vol: 22, Pages: 675-680, ISSN: 1433-2981
A growing body of evidence as to the benefits of intensity-modulated radiotherapy (IMRT) has led to the recommendation for its adoption as a treatment option for cancer patients within the UK. Routine clinical implementation of this technology has been slow. One of the causal factors was identified as being the need to improve confidence by improving the understanding and technical skills for IMRT of clinical oncology staff. This report determines and describes the additional knowledge and skills required for IMRT practice for clinical oncologists, clinical scientists (radiotherapy physicists) and radiographers, derived from reviewing evidence from other nations' IMRT practices and adapting them to UK needs. This knowledge and skills specification can be used to inform IMRT educational curricula. Novel educational methods to maintain the required understanding and skills are also described.
Silva P, Slevin NJ, Sloan P, et al., 2010, Use of multiple biological markers in radiotherapy-treated head and neck cancer, J Laryngol Otol, Vol: 124, Pages: 650-658, ISSN: 1748-5460
OBJECTIVE: Management of patients with head and neck squamous cell carcinoma is often based on clinical parameters, with little appreciation of the underlying tumour biology. Single biological marker studies fail to acknowledge the complexity of these tumours. Our aim was to define a profile of biological markers associated with outcome. DESIGN: This retrospective study involved consecutive patients with oropharyngeal squamous cell carcinoma treated with primary radiotherapy between 1996 and 2001. Pre-treatment biopsies were used to study the immunohistochemical expression of nine biological markers. Markers were chosen to reflect biologically relevant pathways. RESULTS: Following analysis of nine markers, a profile of two markers was derived (carbonic anhydrase 9 and major vault protein), the co-expression of which conferred a significantly poor probability of locoregional control. The prognostic effect of these biomarkers in combination was greater than their effect individually. CONCLUSION: Biomarker profiles can be established which highlight large differences in locoregional control. Identifying tumours that express both carbonic anhydrase 9 and major vault protein may facilitate patient selection for more aggressive treatment.
Staffurth J, Price OBORDBIP, 2010, A review of the clinical evidence for intensity-modulated radiotherapy, Clin Oncol, Vol: 22, Pages: 643-657, ISSN: 1433-2981
AIMS: Intensity-modulated radiotherapy (IMRT) is a development of three-dimensional conformal radiotherapy that offers improvements in dosimetry in many clinical scenarios. Here we review the clinical evidence for IMRT and present ongoing or unpublished randomised controlled trials (RCTs). METHODS: We identified randomised and non-randomised comparative studies of IMRT and conventional radiotherapy using MEDLINE, hand-searching Radiotherapy and Oncology and the International Journal of Radiation Oncology, Biology and Physics and the proceedings of the American Society for Therapeutic Radiology and Oncology and the European Society for Therapeutic Radiology and Oncology annual meetings. The metaRegister of Controlled Trials was searched to identify completed-unpublished, ongoing and planned RCTs. RESULTS: Sixty-one studies comparing IMRT and conventional radiotherapy were identified. These included three RCTs in head and neck cancer (205 patients) and three in breast cancer (664 patients) that had reported clinical outcomes; these were all powered for toxicity-related end points, which were significantly better with IMRT in each trial. There were 27 additional non-randomised studies in head and neck (1119 patients), 26 in prostate cancer (>5000 patients), four in breast cancer (875 patients) and nine in other tumour sites. The results of these studies supported those of the RCTs with benefits reported in acute and late toxicity, health-related quality of life and tumour control end points. Twenty-eight completed-unpublished, ongoing or planned RCTs incorporating IMRT were identified, including at least 12,310 patients, of which 15 compared conventional radiotherapy within IMRT as a randomisation or pre-planned stratification. DISCUSSION: Inverse-planned IMRT maintains parotid saliva production and reduces acute and late xerostomia during radiotherapy for locally advanced head and neck cancer, reduces late rectal toxicity in prostate cancer patients allowing safe d
Saleem A, Jackson A, Mukherjee S, et al., 2010, Radiotherapy in the management of unresectable locally advanced pancreatic cancer: a survey of the current UK practice of clinical oncologists, Clin Oncol (R Coll Radiol), Vol: 22, Pages: 257-260, ISSN: 1433-2981
A survey was conducted by the Academic Clinical Oncology and Radiobiology Research Network (ACORRN) to evaluate current radiotherapy practice and to inform future research needs in patients with locally advanced pancreatic cancer. A clear need for a co-ordinated multicentre approach, given the limited number of patients who may qualify for such UK trials, was identified. Such trials should incorporate evidence-based treatment protocols and appropriate quality assurance procedures to ensure delivery of the highest standards of radiation-based therapy within, and without, clinical trials.
Langley R, Price P, Pollock P, et al., 2010, Osteoporosis in patients with prostate cancer on long-term androgen deprivation therapy: an increasing but under-recognised problem, BJUI, Vol: 106, Pages: 726-727
Saleem A, Ranson M, Callies S, et al., 2009, Microdosing imaging pharmacokinetic (PK) study of the antisense oligonucleotide (ASO) to survivin (LY2181308) using positron emission tomography (PET): A novel paradigm in clinical drug development, 45th Annual Meeting of the American-Society-of-Clinical-Oncology, Publisher: AMER SOC CLINICAL ONCOLOGY, ISSN: 0732-183X
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Price PM, Asselin M, Koetz B, et al., 2009, A PET imaging study of the vascular disruptive agent OXi4503 to confirm in vivo mechanism of action in a phase I trial, 45th Annual Meeting of the American-Society-of-Clinical-Oncology, Publisher: AMER SOC CLINICAL ONCOLOGY, ISSN: 0732-183X
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Jackson A, Jain P, Watkins G, et al., 2009, Capecitabine-based Chemoradiotherapy (CRT) for Locally Advanced Pancreatic Cancer (LAPC): Efficacy and Toxicity, CLINICAL ONCOLOGY, Vol: 21, Pages: 270-270, ISSN: 0936-6555
Rembielak A, Saleem A, Valle J, et al., 2009, Phase II Study of Cetuximab and Radiotherapy in Patients with Locally Advanced Pancreatic Cancer (PACER Study), CLINICAL ONCOLOGY, Vol: 21, Pages: 254-255, ISSN: 0936-6555
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Rosso L, Brock CS, Gallo JM, et al., 2009, A new model for prediction of drug distribution in tumor and normal tissues: pharmacokinetics of temozolomide in glioma patients, Cancer Res, Vol: 69, Pages: 120-127, ISSN: 1538-7445
Difficulties in direct measurement of drug concentrations in human tissues have hampered the understanding of drug accumulation in tumors and normal tissues. We propose a new system analysis modeling approach to characterize drug distribution in tissues based on human positron emission tomography (PET) data. The PET system analysis method was applied to temozolomide, an important alkylating agent used in the treatment of brain tumors, as part of standard temozolomide treatment regimens in patients. The system analysis technique, embodied in the convolution integral, generated an impulse response function that, when convolved with temozolomide plasma concentration input functions, yielded predicted normal brain and brain tumor temozolomide concentration profiles for different temozolomide dosing regimens (75-200 mg/m(2)/d). Predicted peak concentrations of temozolomide ranged from 2.9 to 6.7 microg/mL in human glioma tumors and from 1.8 to 3.7 microg/mL in normal brain, with the total drug exposure, as indicated by the tissue/plasma area under the curve ratio, being about 1.3 in tumor compared with 0.9 in normal brain. The higher temozolomide exposures in brain tumor relative to normal brain were attributed to breakdown of the blood-brain barrier and possibly secondary to increased intratumoral angiogenesis. Overall, the method is considered a robust tool to analyze and predict tissue drug concentrations to help select the most rational dosing schedules.
McBain CA, Khoo VS, Buckley DL, et al., 2009, Assessment of bladder motion for clinical radiotherapy practice using cine-magnetic resonance imaging, Int J Radiat Oncol Biol Phys, Vol: 75, Pages: 664-671, ISSN: 1879-355X
PURPOSE: Organ motion is recognized as the principal source of inaccuracy in bladder radiotherapy (RT), but there is currently little information on intrafraction bladder motion. METHODS AND MATERIALS: We used cine-magnetic resonance imaging (cine-MRI) to study bladder motion relevant to intrafraction RT delivery. On two occasions, a 28 minute cine-MRI sequence was acquired from 10 bladder cancer patients and 5 control participants immediately after bladder emptying, after abstinence from drinking for the preceding hour. From the resulting cine sequences, bladder motion was subjectively assessed. To quantify bladder motion, the bladder was contoured in imaging volume sets at 0, 14, and 28 min to measure changes to bladder volumes, wall displacements, and center of gravity (COG) over time. RESULTS: The dominant source of bladder motion during imaging was bladder filling (up to 101% volume increase); rectal and small bowel movements were transient, with minimal impact. Bladder volume changes were similar for all participants. However for bladder cancer patients, wall displacements were larger (up to 58 mm), less symmetrical, and more variable compared with nondiseased control bladders. CONCLUSIONS: Significant and individualized intrafraction bladder wall displacements may occur during bladder RT delivery. This important source of inaccuracy should be incorporated into treatment planning and verification.
Walker MD, Matthews JC, Asselin MC, et al., 2009, Optimization of the injected activity in dynamic 3D PET: a generalized approach using patient-specific NECs as demonstrated by a series of 15O-H2O scans, J Nucl Med, Vol: 50, Pages: 1409-1417, ISSN: 0161-5505
The magnitude of the injected activity (A(0)) has a direct impact on the statistical quality of PET images. This study aimed to develop a generalized method for maximizing the statistical quality of dynamic PET images by optimizing A(0). METHODS: Patient-specific noise-equivalent counts (PS-NECs) were used as a metric of the statistical quality of each time frame of a dynamic PET image. Previous methodology developed to extrapolate the NEC as a function of A(0) was extended to dynamic PET, enabling the NEC to be extrapolated as a function of both A(0) and the time after injection. This method allowed A(0) to be optimized after a single scan (at a single A(0)), by maximizing the NEC within the time interval for which the parameter estimation is most sensitive. The extrapolation method was validated by a series of (15)O-H(2)O scans of the body acquired in 3-dimensional mode. Each patient (n = 6) underwent between 3 and 6 scans at 1 bed position. The injected activities were varied over a wide range (140-840 MBq). Noise-equivalent counting rate (NECR) versus A(0) curves and the optimal injected activities were calculated from each injection. RESULTS: PS-NECR versus A(0) curves as extrapolated from different injected activities were consistent (coefficient of variation, typically <5%). The optimal injected activities for an individual, as derived from these curves, were also consistent (maximum coefficient of variation, 4.3%). For abdominal (n = 4) and chest (n = 1) scans, we found optimal injected activities of (15)O-H(2)O in the range of 220-350 MBq for estimating blood perfusion (F) and 660-1,070 MBq for estimating the volume of distribution (V(T)). Higher optimal injected activities were found in the case of a pelvic scan (n = 1; 570 MBq for F and 1,530 MBq for V(T)). CONCLUSION: PS-NECs are a valid and generic method for optimizing the injected activity in PET, allowing scanning protocols to be improved after the collection of an initial, single dynamic dataset.
Kotz B, West C, Saleem A, et al., 2009, Blood flow and Vd (water): both biomarkers required for interpreting the effects of vascular targeting agents on tumor and normal tissue, Mol Cancer Ther, Vol: 8, Pages: 303-309, ISSN: 1535-7163
Positron emission tomography studies with oxygen-15-labeled water provide in vivo quantitative tissue perfusion variables-blood flow and fractional volume of distribution of water [V(d) (water)]. To investigate the relationship between perfusion variables and the effect of vascular-targeting agents on vasculature, we measured tissue perfusion in tumors, spleen, kidney, and liver before and after treatment with combretastatin-A4-phosphate, a combination of nicotinamide and carbogen (N/C), and interferon (IFN). We observed that mean tumor blood flow and V(d) (water) was lower than in kidney, liver, and spleen at baseline. Blood flow and V(d) (water) were related in tumor (r = 0.62; P = 0.004) at baseline, but not in other normal tissues evaluated, where minimal variations in V(d) (water) were observed over a wide range of blood flow. Despite the relationship between blood flow and V(d) (water) in tumors before intervention, vascular-targeting agent-induced changes in these perfusion variables were not correlated. In contrast, changes in blood flow and V(d) (water) correlated in kidney and spleen after N/C and in kidney after combretastatin-A4-phosphate. The close relation between blood flow and V(d) (water) in tumors but not normal tissue may reflect barriers to fluid exchange in tumors because of necrosis and/or increased interstitial fluid pressure and underlies the importance and interdependence of these positron emission tomography perfusion variables under these conditions. As blood flow and V(d) (water) signify different aspects of tissue perfusion, the differential effects of interventions on both variables, flow and V(d) (water), should therefore be reported in future studies.
Price GJ, Sharrock PJ, Marchant TE, et al., 2009, An analysis of breast motion using high-frequency, dense surface points captured by an optical sensor during radiotherapy treatment delivery, Phys Med Biol, Vol: 54, Pages: 6515-6533, ISSN: 0031-9155
Patient motion is an important factor affecting the quality of external beam radiotherapy in breast patients. We analyse the motion of a dense set of surface points on breast patients throughout their treatment schedule to assess the magnitude and stability of motion, in particular, with respect to breast volume. We use an optical sensor to measure the surface motion of 13 breast cancer patients. Patients were divided into two cohorts dependent upon breast volume. Measurements were made during radiotherapy treatment beam delivery for an average of 12 fractions per patient (total 158 datasets). The motion of each surface point is parameterized in terms of its period, amplitude and relative phase. Inter-comparison of the motion parameters across treatment schedules and between patients is made through the creation of corresponding regions on the breast surfaces. The motion period is spatially uniform and is similar in both patient groups (mean 4 s), with the small volume cohort exhibiting greater inter-fraction period variability. The mean motion amplitude is also similar in both groups with a range between 2 mm and 4 mm and an inter-fraction variability generally less than 1 mm. There is a phase lag of up to 0.4 s across the breast, led by the sternum. Breast patient motion is reasonably stable between and during treatment fractions, with the large volume cohort exhibiting greater repeatability than the small volume one.
Jain P, Marchant T, Green M, et al., 2009, Inter-fraction motion and dosimetric consequences during breast intensity-modulated radiotherapy (IMRT), Radiother Oncol, Vol: 90, Pages: 93-98, ISSN: 0167-8140
BACKGROUND AND PURPOSE: Intensity-modulated radiotherapy (IMRT) can improve dose homogeneity within the breast planned target volume (PTV), but may be more susceptible to patient/organ motion than standard tangential radiotherapy (RT). We used daily cone-beam CT (CBCT) imaging to assess inter-fraction motion during breast IMRT and its subsequent impact on IMRT and standard RT dose homogeneity. MATERIALS AND METHODS: Ten breast cancer patients selected for IMRT were studied. CBCT images were acquired immediately after daily treatment. Automatic image co-registration was used to determine patient positioning variations. Daily PTV contours were used to calculate PTV variations and daily delivered IMRT and theoretically planned tangential RT dose. RESULTS: Group systematic (and random) setup errors detected by CBCT were 5.7 (3.9)mm laterally, 2.8 (3.5)mm vertically and 2.3 (3.2)mm longitudinally. Rotations >2 degrees in any axis occurred on 53/106 (50%) occasions. Daily PTV volume varied up to 23%. IMRT dose homogeneity was superior at planning and throughout the treatment compared with standard RT (1.8% vs. 15.8% PTV received >105% planned mean dose), despite increased motion sensitivity. CONCLUSIONS: CBCT revealed inadequacies of current patient positioning and verification procedures during breast RT and confirmed improved dose homogeneity using IMRT for the patients studied.
Sripadam R, Stratford J, Henry AM, et al., 2009, Rectal motion can reduce CTV coverage and increase rectal dose during prostate radiotherapy: A daily cone-beam CT study, Radiother Oncol, Vol: 90, Pages: 312-317, ISSN: 0167-8140
BACKGROUND AND PURPOSE: Daily on-treatment verification cone-beam CT (CBCT) was used to study the effect of rectal motion on clinical target volume (CTV) coverage during prostate radiotherapy. MATERIAL AND METHODS: CBCT scans were acquired from 15 patients immediately after daily treatment. From these images, the rectum was contoured allowing the analysis of rectal volume cross-sectional area (CSA) and the determination of rectal dose. Rectal wall motion was quantified as a surrogate measure of prostate displacement and CTV coverage was subjectively assessed. RESULTS: Rectal volume decreased over the treatment course in 13 patients (P<0.001). Rectal wall regions corresponding to the prostate base displayed the greatest motion; larger displacements were seen in patients with larger rectal planning volumes. CTV coverage was inadequate, at the prostate base only, in 38% of the fractions delivered to 4/7 patients with a large rectum at planning (>100 cm(3)). In patients with small rectum at planning (<50 cm(3)) up to 25% more rectal volume than predicted was included in the high-dose region. CONCLUSIONS: Rectal motion during treatment in prostate cancer patients has implications for CTV coverage and rectal dose. Measures to ensure consistency in daily rectal volume or image-guided strategies should be considered.
McBain CA, Green MM, Stratford J, et al., 2009, Ultrasound imaging to assess inter- and intra-fraction motion during bladder radiotherapy and its potential as a verification tool, Clin Oncol (R Coll Radiol), Vol: 21, Pages: 385-393, ISSN: 0936-6555
AIMS: Organ motion is the principle source of error in bladder cancer radiotherapy. The aim of this study was to evaluate ultrasound bladder volume measurement as a surrogate measure of organ motion during radiotherapy: (1) to assess inter- and intra-fraction bladder variation and (2) as a potential treatment verification tool. MATERIALS AND METHODS: Twenty patients receiving radical radiotherapy for bladder cancer underwent post-void ultrasound bladder volume measurement at the time of radiotherapy treatment planning (RTP), and immediately before (post-void) and after receiving daily fractions. RESULTS: Ultrasound bladder volume measurement was found to be a simple and acceptable method to estimate relative bladder volume changes. Six patients showed significant changes to post-void bladder volume over the treatment course (P<0.05). The mean inter-fraction post-void bladder volume of five patients exceeded their RTP ultrasound bladder volume by more than 50%. Intra-fraction bladder volume increased on 275/308 (89%) assessed fractions, with the mean intra-fraction volume increases of seven patients exceeding their RTP ultrasound bladder volume by more than 50%. CONCLUSIONS: Both day-to-day bladder volume variation and bladder filling during treatment should be considered in RTP and delivery. Ultrasound may provide a practical daily verification tool by: supporting volume limitation as a method of treatment margin reduction; allowing detection of patients who may require interventions to promote bladder reproducibility; and identifying patients with prominent volume changes for the selective application of more advanced adaptive/image-guided radiotherapy techniques.
Rembielak A, Cullen J, Saleem A, et al., 2008, Imaging in cancer, Medicine, Vol: 36, Pages: 5-8, ISSN: 1357-3039
Medical imaging techniques are an important element in early detection for many cancers. They are also important for determining the stage and extension of the lesion, assessing tumour response during and after treatment, and locating cancer to aid surgery and other treatments. Imaging methods range from anatomical-based methods (ultrasound, conventional plain X-rays with mammography, computed tomography) to the more functional-based methods (magnetic resonance imaging with a spectroscopy option, single-photon emission computed tomography and positron emission tomography). The principles of image acquisition methods with examples of clinical indications are described in the article. Advances in medical imaging have also been widely applied in the field of radiation oncology. Technical development has lead to more accurate treatment plan calculations and more precise administration of the radiation. The range of imaging applications in radiation oncology is very wide and often called ‘therapeutic imaging’. Medical imaging is employed at almost every step of the radiation treatment process from diagnosis, treatment planning, dose calculations, and simulation of real treatment, to irradiation on the linear accelerator.
Saleem A, Aboagye EO, Matthews JC, et al., 2008, Plasma pharmacokinetic evaluation of cytotoxic agents radiolabelled with positron emitting radioisotopes, Cancer Chemother Pharmacol, Vol: 61, Pages: 865-873
PURPOSE: This study aimed to evaluate the utility of plasma pharmacokinetic analyses of anti-cancer agents from data obtained during positron emission tomography (PET) oncology studies of radiolabelled anti-cancer agents. PATIENTS AND METHODS: Thirteen patients were administered fluorine-18 radiolabelled 5-FU ([(18)F]5-FU) admixed with 5-FU, corresponding to a total 5-FU dose of 380-407 mg/m(2) (eight patients) and 1 mg/m(2) (five patients). Nine patients received 2.2-19.2 mug/m(2) of carbon-11 radiolabelled N-[2-(dimethylamino)ethyl]acridine-4-carboxamide ([(11)C]DACA) at 1/1,000th of phase I dose, as part of phase 0 microdosing study. Radioactivity of parent drug obtained from arterial blood samples, the injected activity of the radiolabelled drug, and the total dose of injected drug were used to obtain plasma drug concentrations. Plasma pharmacokinetic parameters were estimated using model-dependent and model-independent methods. RESULTS: 5-FU plasma concentrations at therapeutic doses were above the Km and a single compartment kinetic model was best used to fit the kinetics, with a mean half-life of 8.6 min. Clearance and volumes of distribution (V (d)) obtained using both model-dependent and model-independent methods were similar. Mean (SE) clearance was 1,421(144), ml min(-1) and 1,319 (119) ml min(-1) and the mean (SE) V (d) was 17.3 (1.8) l and 16.3 (1.9) l by the model-independent method and model-dependent methods, respectively. In contrast, with 1 mg/m(2), plasma concentrations of 5-FU were less than the Km and a two-compartment model was used to best fit the kinetics, with the mean 5-FU half-life of 6.5 min. The mean (SE) clearances obtained by the model-independent method and model-dependent methods were 3,089 (314) ml min(-1) and 2,225 (200) ml min(-1), respectively and the mean (SE) V (d) were 27.9 (7.0) l and 2.3 (0.4) l, by the model independent and dependent methods, respectively. Extrapolation of AUC(0-Clast) to AUC(0-infinity) was less than 3% in
Henry AM, Ryder WD, Moore C, et al., 2008, Chemoradiotherapy for locally advanced pancreatic cancer: a radiotherapy dose escalation and organ motion study, Clin Oncol (R Coll Radiol), Vol: 20, Pages: 541-547, ISSN: 0936-6555
AIMS: To determine the efficacy of radiation dose escalation and to examine organ motion during conformal radiotherapy for locally advanced pancreatic cancer. MATERIALS AND METHODS: Thirty-nine patients who were consecutively treated with chemoradiotherapy were studied. Fifteen patients, treated from 1993 to 1997, received 50Gy in 20 fractions (group I). Twenty-four patients, treated from 1997 to 2003, received an escalated dose of 55Gy in 25 fractions (group II). Intra-fraction pancreatic tumour motion was assessed in three patients using megavoltage movies during radiation delivery to track implanted radio-opaque markers. RESULTS: Improved survival rates were seen in latterly treated group II patients (P=0.083), who received escalated radiotherapy to smaller treatment volumes due to advances in verification. Worse toxicity effects (World Health Organization grade 3-4) were reported by some patients (<10%), but treatment compliance was similar in both groups, indicating equivalent tolerance. Substantial intra-fraction tumour displacement due to respiratory motion was observed: this was greatest in the superior/inferior (mean=6.6mm) and anterior/posterior (mean=4.75mm) directions. Lateral displacements were small (<2mm). CONCLUSIONS: Dose escalation is feasible in pancreatic cancer, particularly when combined with a reduction in irradiated volume, and enhanced efficacy is indicated. Large, globally applied margins to compensate for pancreatic tumour motion during radiotherapy may be inappropriate. Strategies to reduce respiratory motion, and/or the application of image-guided techniques that incorporate individual patients' respiratory motion into radiotherapy planning and delivery, will probably improve pancreatic radiotherapy.
Kim S, Russell W, Price P, et al., 2008, Suboptimal use of intravenous contrast during radiotherapy planning in the UK, Br J Radiol, Vol: 81, Pages: 963-969, ISSN: 1748-880X
We aimed to evaluate the use of intravenous (IV) contrast during acquisition of radiotherapy planning (RTP) scans and to compare current usage with the Royal College of Radiologists' (RCR) recommendations. Questionnaires were circulated via the Academic Clinical Oncology and Radiobiology Research Network (ACORRN) website, email and post to 60 UK radiotherapy centre managers. Questions were asked regarding the (i) tumour sites where IV contrast was used, (ii) person administering the contrast, (iii) availability of dynamic pump, (iv) tumour sites that centres wished to use contrast, (v) reasons for not using contrast and (vi) awareness of RCR recommendations. 50 (83%) centres responded to the questionnaire, of which 27 responded via the ACCORN website and 18 by e-mail. Despite 38 out of 50 responding centres using IV contrast, and accessibility to dynamic pumps existing in 39 centres, IV contrast usage was suboptimal, with more than half of the centres (27/50; 54%) wishing to use it at more tumour sites. IV contrast was most often used during RTP of the brain, with suboptimal usage in lung tumours. None of the 50 centres administered IV contrast during RTP scan acquisition in all of the 8 RCR recommended tumour sites. Radiographers were mainly responsible for contrast administration, and a lack of staff was cited as the main reason for suboptimal contrast usage. Disappointingly, only 35 of the 50 radiotherapy managers (70%) were aware of the RCR recommendations. Redress of the underlying reasons for suboptimal IV contrast administration during RTP, including acquisition of the necessary skill mix by staff and implementation of RCR recommendations, would help standardize UK practice.
Saleem A, Price PM, 2008, Early tumor drug pharmacokinetics is influenced by tumor perfusion but not plasma drug exposure, Clin Cancer Res, Vol: 14, Pages: 8184-8190, ISSN: 1078-0432
PURPOSE: Pharmacokinetic parameters derived from plasma sampling are used as a surrogate of tumor pharmacokinetics. However, pharmacokinetics-modulating strategies do not always result in increased therapeutic efficacy. Nonsurrogacy of plasma kinetics may be due to tissue-specific factors such as tumor perfusion. EXPERIMENTAL DESIGN: To assess the impact of tumor perfusion and plasma drug exposure on tumor pharmacokinetics, positron emission tomography studies were done with oxygen-15 radiolabeled water in 12 patients, with 6 patients undergoing positron emission tomography studies with carbon-11 radiolabeled N-[2-(dimethylamino)ethyl]acridine-4-carboxamide and the other 6 with fluorine-18 radiolabeled 5-fluorouracil. RESULTS: We found that tumor blood flow (mL blood/mL tissue/minute) was significantly correlated to early tumor radiotracer uptake between 4 and 6 minutes [standard uptake value (SUV)4-6; rho = 0.79; P = 0.002], tumor radiotracer exposure over 10 minutes [area under the time-activity curve (AUC)0-10; predominantly parent drug; rho = 0.86; P < 0.001], and tumor radiotracer exposure over 60 minutes (AUC0-60; predominantly radiolabeled metabolites; rho = 0.80; P = 0.002). Similarly, fractional volume of distribution of radiolabeled water in tumor (Vd) was significantly correlated with SUV4-6 (rho = 0.80; P = 0.002), AUC0-10 (rho = 0.85; P < 0.001), and AUC0-60 (rho = 0.66; P = 0.02). In contrast, no correlation was observed between plasma drug or total radiotracer exposure over 60 minutes and tumor drug uptake or exposure. Tumor blood flow was significantly correlated to Vd (rho = 0.69; P = 0.014), underlying the interdependence of tumor perfusion and Vd. CONCLUSIONS: Tumor perfusion is a key factor that influences tumor drug uptake/exposure. Tumor vasculature-targeting strategies may thus result in improved tumor drug exposure and therefore drug efficacy.
Griffiths EA, Pritchard SA, McGrath SM, et al., 2008, Hypoxia-associated markers in gastric carcinogenesis and HIF-2alpha in gastric and gastro-oesophageal cancer prognosis, Br J Cancer, Vol: 98, Pages: 965-973
The study investigated hypoxia-associated markers (HIF-2alpha, Epo, Epo-R, Glut-1 and VEGF) along with Ki-67 in a gastric carcinogenesis model, and the prognostic significance of hypoxia-inducible factor (HIF)-2alpha in surgically treated gastro-oesophageal cancer. Protein expression was examined using immunohistochemistry on formalin-fixed, paraffin-embedded 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. Relationships between HIF-2alpha expression and prognosis were assessed in resection specimens from 177 patients with gastric and gastro-oesophageal junction adenocarcinoma. Expression of all markers increased with progression along the gastric carcinogenesis sequence (P=0.0001). Hypoxia-inducible factor-2alpha was expressed in 63% of 177 resection specimens and at a high level in 44%. The median overall survival in patients with HIF-2alpha-expressing tumours was 22 (95% CI 18-26) months, whereas those with HIF-2alpha-negative tumours had a median survival of 37 (95% CI 29-44) months (P=0.015). Hypoxia-inducible factor-2alpha had no independent prognostic significance in multivariate analysis. In view of the lack of independent prognostic significance, HIF-2alpha has no role as a routine prognostic indicator. However, the high expression of HIF-2alpha suggests that it may be of value as a potential therapeutic target.British Journal of Cancer (2008) 98, 965-973. doi:10.1038/sj.bjc.6604210 www.bjcancer.com Published online 19 February 2008.
McBain CA, Moore CJ, Green MM, et al., 2008, Early clinical evaluation of a novel three-dimensional structure delineation software tool (SCULPTER) for radiotherapy treatment planning, Br J Radiol, Vol: 81, Pages: 643-652, ISSN: 1748-880X
Modern radiotherapy treatment planning (RTP) necessitates increased delineation of target volumes and organs at risk. Conventional manual delineation is a laborious, time-consuming and subjective process. It is prone to inconsistency and variability, but has the potential to be improved using automated segmentation algorithms. We carried out a pilot clinical evaluation of SCULPTER (Structure Creation Using Limited Point Topology Evidence in Radiotherapy) - a novel prototype software tool designed to improve structure delineation for RTP. Anonymized MR and CT image datasets from patients who underwent radiotherapy for bladder or prostate cancer were studied. An experienced radiation oncologist used manual and SCULPTER-assisted methods to create clinically acceptable organ delineations. SCULPTER was also tested by four other RTP professionals. Resulting contours were compared by qualitative inspection and quantitatively by using the volumes of the structures delineated and the time taken for completion. The SCULPTER tool was easy to apply to both MR and CT images and diverse anatomical sites. SCULPTER delineations closely reproduced manual contours with no significant volume differences detected, but SCULPTER delineations were significantly quicker (p<0.05) in most cases. In conclusion, clinical application of SCULPTER resulted in rapid and simple organ delineations with equivalent accuracy to manual methods, demonstrating proof-of-principle of the SCULPTER system and supporting its potential utility in RTP.
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