Royal Marsden Hospital Institute of Cancer Research

Sutton, United Kingdom

Royal Marsden Hospital Institute of Cancer Research

Sutton, United Kingdom
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Willowson K.P.,University of Sydney | Tapner M.,Sirtex | Bailey D.L.,Royal North Shore Hospital | Bailey D.L.,University of Sydney | And 101 more authors.
European Journal of Nuclear Medicine and Molecular Imaging | Year: 2015

Purpose: To investigate and compare the quantitative accuracy of 90Y imaging across different generation PET/CT scanners, for the purpose of dosimetry after radioembolization with resin microspheres. Methods: A strict experimental and imaging protocol was followed by 47 international sites using the NEMA 2007/IEC 2008 PET body phantom with an 8-to-1 sphere-to-background ratio of 90Y solution. The phantom was imaged over a 7-day period (activity ranging from 0.5 to 3.0 GBq) and all reconstructed data were analysed at a core laboratory for consistent processing. Quantitative accuracy was assessed through measures of total phantom activity, activity concentration in background and hot spheres, misplaced counts in a nonradioactive insert, and background variability. Results: Of the 69 scanners assessed, 37 had both time-of-flight (ToF) and resolution recovery (RR) capability. These current generation scanners from GE, Philips and Siemens could reconstruct background concentration measures to within 10 % of true values over the evaluated range, with greater deviations on the Philips systems at low count rates, and demonstrated typical partial volume effects on hot sphere recovery, which dominated spheres of diameter <20 mm. For spheres >20 mm in diameter, activity concentrations were consistently underestimated by about 20 %. Non-ToF scanners from GE Healthcare and Siemens were capable of producing accurate measures, but with inferior quantitative recovery compared with ToF systems. Conclusion: Current generation ToF scanners can consistently reconstruct 90Y activity concentrations, but they underestimate activity concentrations in small structures (≤37 mm diameter) within a warm background due to partial volume effects and constraints of the reconstruction algorithm. At the highest count rates investigated, measures of background concentration (about 300 kBq/ml) could be estimated on average to within 1 %, 5 % and 2 % for GE Healthcare (all-pass filter, RR + ToF), Philips (4i8s ToF) and Siemens (2i21s all-pass filter, RR + ToF) ToF systems, respectively. Over the range of activities investigated, comparable performance between GE Healthcare and Siemens ToF systems suggests suitability for quantitative analysis in a scenario analogous to that of postradioembolization imaging for treatment of liver cancer. © 2015, The Author(s).

De Bono J.S.,Royal Marsden Hospital Institute of Cancer Research | Molife L.R.,Royal Marsden Hospital Institute of Cancer Research | Sonpavde G.,Texas Oncology | Maroto J.P.,Santa Creu I Sant Pau Hospital | And 9 more authors.
Annals of Oncology | Year: 2012

Background: Treatment options remain limited for patients with castration-resistant prostate cancer (CRPC). We evaluated eribulin mesylate (E7389), a nontaxane halichondrin B analog microtubule inhibitor, in patients with metastatic CRPC with or without previous taxane exposure. Patients and methods: Men with histologically proven CRPC, with or without prior taxane exposure, were enrolled in an open-label, single-arm phase II trial. Patients received eribulin mesylate 1.4 mg/m. 2 as a 2- to 5-min i.v. bolus infusion on days 1 and 8 of a 21-day cycle. The primary efficacy end point was prostate-specific antigen (PSA) response rate. Results: In total, 108 patients were assessable for safety (50 were taxane-pretreated) and 105 for efficacy in the per-protocol population. The median age of patients was 71 years and median number of cycles was 4. PSA decreases of ≥50% were achieved in 22.4% and 8.5% of taxane-naive and taxane-pretreated patients, respectively. The most common grade 3/4 adverse event was neutropenia, seen in 22.4% of chemo-naive and 40% of taxane-pretreated men. Grade 3 peripheral neuropathy occurred in none of the taxane-naive patients and 6.0% of taxane-pretreated patients. Conclusion: Eribulin mesylate demonstrated activity and a relatively favorable toxicity profile in metastatic CRPC. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Ahmadi F.,Nanyang Technological University | McLoughlin I.V.,Nanyang Technological University | Chauhan S.,Nanyang Technological University | ter-Haar G.,Royal Marsden Hospital Institute of Cancer Research
Progress in Biophysics and Molecular Biology | Year: 2012

Low-frequency (LF) ultrasound (20-100. kHz) has a diverse set of industrial and medical applications. In fact, high power industrial applications of ultrasound mainly occupy this frequency range. This range is also used for various therapeutic medical applications including sonophoresis (ultrasonic transdermal drug delivery), dentistry, eye surgery, body contouring, the breaking of kidney stones and eliminating blood clots. While emerging LF applications such as ultrasonic drug delivery continue to be developed and undergo translation for human use, significant gaps exist in the coverage of safety standards for this frequency range. Accordingly, the need to understand the biological effects of LF ultrasound is becoming more important.This paper presents a broad overview of bio-effects and safety of LF ultrasound as an aid to minimize and control the risk of these effects. Its particular focus is at low intensities where bio-effects are initially observed. To generate a clear perspective of hazards in LF exposure, the mechanisms of bio-effects and the main differences in action at low and high frequencies are investigated and a survey of harmful effects of LF ultrasound at low intensities is presented.Mechanical and thermal indices are widely used in high frequency diagnostic applications as a means of indicating safety of ultrasonic exposure. The direct application of these indices at low frequencies needs careful investigation. In this work, using numerical simulations based on the mathematical and physical rationale behind the indices at high frequencies, it is observed that while thermal index (TI) can be used directly in the LF range, mechanical index (MI) seems to become less reliable at lower frequencies. Accordingly, an improved formulation for the MI is proposed for frequencies below 500. kHz. © 2012 Elsevier Ltd.

PubMed | Royal Marsden Hospital & Institute of Cancer Research
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

4577 Background: Prostate cancer (PCa) is the commonest male cancer in the Western world. Its biology and prognosis are heterogeneous and improved tools are needed to predict outcome more reliably. Here we studied the feasibility and clinical utility of whole blood mRNA expression array studies for this purpose.Whole blood samples were collected into PaxGene tubes between 08/2007 and 04/2008 from 100 PCa patients (pts): 31 good prognosis pts selected for active surveillance (AS) and 69 advanced castration resistant prostate cancer (CRPC) pts. RNA was extracted, amplified and biotinylated; unsupervised genome-wide expression profiles were analysed with HGU133plus2 (Affymetrix) microarrays and using Bayesian Latent Process Decomposition (LPD) analyses (Carrivick et al, 2006) in 94 patients; associations with outcome were studied.LPD analysis of the whole blood mRNA expression data divided the pts into 4 separate groups (LPD1 to 4, with 10 unclassifiable pts). LPD1 (n=14) and LPD2 (n=18) consisted almost entirely of CRPC pts (14/14; 17/18); the single active surveillance patient in LPD2 had a rapidly rising PSA and required a prostatectomy. All the 4 groups included CRPC pts (LPD3:15/31; LDP4: 12/21); LPD1 CRPC pts had poorer overall survival (median 10.7 months, CI-95% 4.2-17.2) than CRPC pts in LPD2 to 4 (median 26.5 months, CI-95% 18.1-34.9, p=0.00007). Other baseline characteristics associated with LPD1 were increased number of treatment lines, worse performance status, and a higher proportion of detectable TMPRSS2/ERG transcripts. Group 1 membership remained the strongest prognostic factor in a multivariate analysis (HR 5.0, CI-95% 2.1-11.9, p = 0.0002). Gene signatures in the poor prognosis LPD group 1 were associated with increased CD71+ early erythroid cells and a decreased B-cell and T-cell immune response. A 9-gene signature (TERF2IP, TMCC2, GABARAPL2, SNCA, RIOK3, TFDP1, SLC4A1, HMBS, STOM) classified samples as group LPD 1 with a very low misclassification rate (0.012).PCa patient outcome can be predicted using gene expression signatures from peripheral blood.

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