4 results on '"Galazi, Myria"'
Search Results
2. The potential of using circulating tumour cells and their gene expression to predict docetaxel response in metastatic prostate cancer.
- Author
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Davies, Caitlin R., Tianyu Guo, Burke, Edwina, Stankiewicz, Elzbieta, Lei Xu, Mao, Xueying, Scandura, Glenda, Rajan, Prabhakar, Tipples, Karen, Alifrangis, Constantine, Wimalasingham, Akhila Ganeshi, Galazi, Myria, Crusz, Shanthini, Powles, Thomas, Grey, Alistair, Oliver, Tim, Kudahetti, Sakunthala, Shaw, Greg, Berney, Daniel, and Shamash, Jonathan
- Subjects
PROSTATE cancer ,DOCETAXEL ,GENE expression ,METASTASIS ,CASTRATION-resistant prostate cancer ,PROGRESSION-free survival - Abstract
Background: Docetaxel improves overall survival (OS) in castration-resistant prostate cancer (PCa) (CRPC) and metastatic hormone-sensitive PCa (mHSPC). However, not all patients respond due to inherent and/or acquired resistance. There remains an unmet clinical need for a robust predictive test to stratify patients for treatment. Liquid biopsy of circulating tumour cell (CTCs) is minimally invasive, can provide real-time information of the heterogeneous tumour and therefore may be a potentially ideal docetaxel response prediction biomarker. Objective: In this study we investigate the potential of using CTCs and their gene expression to predict post-docetaxel tumour response, OS and progression free survival (PFS). Methods: Peripheral blood was sampled from 18 mCRPC and 43 mHSPC patients, pre-docetaxel treatment, for CTC investigation. CTCs were isolated ® using the epitope independent Parsortix system and gene expression was determined by multiplex RT-qPCR. We evaluated CTC measurements for post-docetaxel outcome prediction using receiver operating characteristics and Kaplan Meier analysis. Results: Detection of CTCs pre-docetaxel was associated with poor patient outcome post-docetaxel treatment. Combining total-CTC number with PSA and ALP predicted lack of partial response (PR) with an AUC of 0.90, p= 0.037 in mCRPC. A significantly shorter median OS was seen in mCRPC patients with positive CTC-score (12.80 vs. 37.33 months, HR= 5.08, p= 0.0005), ≥3 total-CTCs/7.5mL (12.80 vs. 37.33 months, HR= 3.84, p= 0.0053), ≥1 epithelial-CTCs/7.5mL (14.30 vs. 37.33 months, HR= 3.89, p= 0.0041) or epithelial to mesenchymal transitioning (EMTing)-CTCs/7.5mL (11.32 vs. 32.37 months, HR= 6.73, p= 0.0001). Significantly shorter PFS was observed in patients with ≥2 epithelial-CTCs/7.5mL (7.52 vs. 18.83 months, HR= 3.93, p= 0.0058). mHSPC patients with ≥5 CTCs/7.5mL had significantly shorter median OS (24.57 vs undefined months, HR= 4.14, p= 0.0097). In mHSPC patients, expression of KLK2, KLK4, ADAMTS1, ZEB1 and SNAI1 was significantly associated with shorter OS and/or PFS. Importantly, combining CTC measurements with clinical biomarkers increased sensitivity and specificity for prediction of patient outcome. Conclusion: While it is clear that CTC numbers and gene expression were prognostic for PCa post-docetaxel treatment, and CTC subtype analysis may have additional value, their potential predictive value for docetaxel chemotherapy response needs to be further investigated in large patient cohorts. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
3. INNOVATE: A prospective cohort study combining serum and urinary biomarkers with novel diffusion-weighted magnetic resonance imaging for the prediction and characterization of prostate cancer.
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Johnston, Edward, Hayley Pye, Bonet-Carne, Elisenda, Panagiotaki, Eleftheria, Patel, Dominic, Galazi, Myria, Heavey, Susan, Carmona, Lina, Freeman, Alexander, Trevisan, Giorgia, Allen, Clare, Kirkham, Alexander, Burling, Keith, Stevens, Nicola, Hawkes, David, Emberton, Mark, Moore, Caroline, Ahmed, Hashim U., Atkinson, David, and Rodriguez-Justo, Manuel
- Subjects
BIOMARKERS ,DIFFUSION magnetic resonance imaging ,BLOOD serum analysis ,URINALYSIS ,DIAGNOSIS ,PROSTATE cancer ,COHORT analysis - Abstract
Background: Whilst multi-parametric magnetic resonance imaging (mp-MRI) has been a significant advance in the diagnosis of prostate cancer, scanning all patients with elevated prostate specific antigen (PSA) levels is considered too costly for widespread National Health Service (NHS) use, as the predictive value of PSA levels for significant disease is poor. Despite the fact that novel blood and urine tests are available which may predict aggressive disease better than PSA, they are not routinely employed due to a lack of clinical validity studies. Furthermore approximately 40 % of mp-MRI studies are reported as indeterminate, which can lead to repeat examinations or unnecessary biopsy with associated patient anxiety, discomfort, risk and additional costs. Methods/Design: We aim to clinically validate a panel of minimally invasive promising blood and urine biomarkers, to better select patients that will benefit from a multiparametric prostate MRI. We will then test whether the performance of the mp-MRI can be improved by the addition of an advanced diffusion-weighted MRI technique, which uses a biophysical model to characterise tissue microstructure called VERDICT; Vascular and Extracellular Restricted Diffusion for Cytometry in Tumours. INNOVATE is a prospective single centre cohort study in 365 patients. mp-MRI will act as the reference standard for the biomarker panel. A clinical outcome based reference standard based on biopsy, mp-MRI and follow-up will be used for VERDICT MRI. Discussion: We expect the combined effect of biomarkers and VERDICT MRI will improve care by better detecting aggressive prostate cancer early and make mp-MRI before biopsy economically viable for universal NHS adoption. [ABSTRACT FROM AUTHOR]
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- 2016
- Full Text
- View/download PDF
4. Localising occult prostate cancer metastasis with advanced imaging techniques (LOCATE trial): a prospective cohort, observational diagnostic accuracy trial investigating whole-body magnetic resonance imaging in radio-recurrent prostate cancer
- Author
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Adeleke, Sola, Latifoltojar, Arash, Sidhu, Harbir, Galazi, Myria, Shah, Taimur T, Clemente, Joey, Davda, Reena, Payne, Heather Ann, Chouhan, Manil D, Lioumi, Maria, Chua, Sue, Freeman, Alex, Rodriguez-Justo, Manuel, Coolen, Anthony, Vadgama, Sachin, Morris, Steve, Cook, Gary J, Bomanji, Jamshed, Arya, Manit, Chowdhury, Simon, Wan, Simon, Haroon, Athar, Ng, Tony, Ahmed, Hashim Uddin, and Punwani, Shonit
- Subjects
Male ,Positron emission tomography ,Prostate cancer ,Radiotherapy ,Cost-Benefit Analysis ,Brachytherapy ,Prostatic Neoplasms ,Exosomes ,Magnetic Resonance Imaging ,Sensitivity and Specificity ,Economic evaluation ,3. Good health ,Cost comparison ,ErbB Receptors ,Recurrence ,Humans ,Cost-effectiveness ,Whole Body Imaging ,Prospective Studies ,Neoplasm Metastasis ,Neoplasm Recurrence, Local - Abstract
BACKGROUND: Accurate whole-body staging following biochemical relapse in prostate cancer is vital in determining the optimum disease management. Current imaging guidelines recommend various imaging platforms such as computed tomography (CT), Technetium 99 m (99mTc) bone scan and 18F-choline and recently 68Ga-PSMA positron emission tomography (PET) for the evaluation of the extent of disease. Such approach requires multiple hospital attendances and can be time and resource intensive. Recently, whole-body magnetic resonance imaging (WB-MRI) has been used in a single visit scanning session for several malignancies, including prostate cancer, with promising results, providing similar accuracy compared to the combined conventional imaging techniques. The LOCATE trial aims to investigate the application of WB-MRI for re-staging of patients with biochemical relapse (BCR) following external beam radiotherapy and brachytherapy in patients with prostate cancer. METHODS/DESIGN: The LOCATE trial is a prospective cohort, multi-centre, non-randomised, diagnostic accuracy study comparing WB-MRI and conventional imaging. Eligible patients will undergo WB-MRI in addition to conventional imaging investigations at the time of BCR and will be asked to attend a second WB-MRI exam, 12-months following the initial scan. WB-MRI results will be compared to an enhanced reference standard comprising all the initial, follow-up imaging and non-imaging investigations. The diagnostic performance (sensitivity and specificity analysis) of WB-MRI for re-staging of BCR will be investigated against the enhanced reference standard on a per-patient basis. An economic analysis of WB-MRI compared to conventional imaging pathways will be performed to inform the cost-effectiveness of the WB-MRI imaging pathway. Additionally, an exploratory sub-study will be performed on blood samples and exosome-derived human epidermal growth factor receptor (HER) dimer measurements will be taken to investigate its significance in this cohort. DISCUSSION: The LOCATE trial will compare WB-MRI versus the conventional imaging pathway including its cost-effectiveness, therefore informing the most accurate and efficient imaging pathway. TRIAL REGISTRATION: LOCATE trial was registered on ClinicalTrial.gov on 18th of October 2016 with registration reference number NCT02935816.
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