• Heterogeneity in high-risk prostate cancer treated with high-dose radiation therapy and androgen deprivation therapy.

      Cagney, Daniel N; Dunne, Mary; O'Shea, Carmel; Finn, Marie; Noone, Emma; Sheehan, Martina; McDonagh, Lesley; O'Sullivan, Lydia; Thirion, Pierre; Armstrong, John (2017-08-01)
      Our aim was to assess the heterogeneity of high-risk (HR) prostate cancer managed with high-dose external beam radiotherapy (EBRT) with androgen deprivation therapy (ADT).
    • Stereotactic Radiosurgery (SRS) / Stereotactic body radiotherapy (SBRT): Benefit to Irish patients and Irish Healthcare Economy

      Cagney, DN; Armstrong, JG (Irish Medical Journal, 2017-01)
      Cancer incidence across Europe is projected to rise rapidly over the next decade. This rising cancer incidence is mirrored by increasing use of and indications for stereotactic radiation. This paper seeks to summarize the exponential increase in indications for stereotactic radiotherapy as well as the evolving economic advantages of stereotactic radiosurgery and stereotactic body radiotherapy
    • Nodular fasciitis: A pseudomalignant clonal neoplasm characterized by USP gene rearrangements and spontaneous regression

      Hennebry, Jennifer; Mulholland, Douglas; Tchrakian, Nairi; Martin Gillham, Charles; Julian Beddy, Peter; Mai O'Donnell, Dearbhaile; Eibhlín McMenamin, Máirín (Edorium Journals, 2017-01)
      Introduction: Nodular fasciitis (NF) is a rapidly growing, self-limited, myofibroblastic neoplasm that typically arises in subcutaneous tissues of young adults and regresses spontaneously. Nodular fasciitis mimics sarcoma on clinical, radiological, and histological grounds and is usually, diagnosed following excision. Case Report: A 26-year-old female presented at surveillance computed tomography (CT) scan one year post-treatment for stage 1c ovarian dysgerminoma with a 4 cm axillary soft tissue mass, radiologically suspicious for metastasis with subclavian vein invasion. Histopathology of core biopsies favored NF, confirmed by detection of USP6 gene rearrangements by FISH analysis. This case describes an unusual relatively deep NF, suspicious for metastasis on CT scan with confirmed spontaneous regression over two years. Conclusion: Nodular fasciitis should be considered in the differential diagnosis of rapidly growing enhancing soft tissue masses. Molecular cytogenetic testing of USP6 gene rearrangements allows definitive diagnosis on core biopsies in challenging cases, permitting a conservative approach and avoiding potentially radical and unnecessary surgery.
    • The Role of Proteomics in Biomarker Development for Improved Patient Diagnosis and Clinical Decision Making in Prostate Cancer.

      Tonry, Claire L; Leacy, Emma; Raso, Cinzia; Finn, Stephen P; Armstrong, John; Pennington, Stephen R (2016-07-18)
      Prostate Cancer (PCa) is the second most commonly diagnosed cancer in men worldwide. Although increased expression of prostate-specific antigen (PSA) is an effective indicator for the recurrence of PCa, its intended use as a screening marker for PCa is of considerable controversy. Recent research efforts in the field of PCa biomarkers have focused on the identification of tissue and fluid-based biomarkers that would be better able to stratify those individuals diagnosed with PCa who (i) might best receive no treatment (active surveillance of the disease); (ii) would benefit from existing treatments; or (iii) those who are likely to succumb to disease recurrence and/or have aggressive disease. The growing demand for better prostate cancer biomarkers has coincided with the development of improved discovery and evaluation technologies for multiplexed measurement of proteins in bio-fluids and tissues. This review aims to (i) provide an overview of these technologies as well as describe some of the candidate PCa protein biomarkers that have been discovered using them; (ii) address some of the general limitations in the clinical evaluation and validation of protein biomarkers; and (iii) make recommendations for strategies that could be adopted to improve the successful development of protein biomarkers to deliver improvements in personalized PCa patient decision making.
    • Impact of delineation uncertainties on dose to organs at risk in CT-guided intracavitary brachytherapy.

      Duane, Frances K; Langan, Brian; Gillham, Charles; Walsh, Lorraine; Rangaswamy, Guhan; Lyons, Ciara; Dunne, Mary; Walker, Christopher; McArdle, Orla; Department of Radiation Oncology, St. Luke's Radiation Oncology Network, Rathgar, Dublin, Republic of Ireland. Electronic address: fran.duane@ctsu.ox.ac.uk. (2014-08-07)
      This study quantifies the inter- and intraobserver variations in contouring the organs at risk (OARs) in CT-guided brachytherapy (BT) for the treatment of cervical carcinoma. The dosimetric consequences are reported in accordance with the current Gynecological Groupe Européen de Curiethérapie/European Society for Therapeutic Radiology and Oncology guidelines.
    • Exposure to low dose ionising radiation: Molecular and clinical consequences.

      Martin, Lynn M; Marples, Brian; Lynch, Thomas H; Hollywood, Donal; Marignol, Laure (2014-07-10)
      This review article provides a comprehensive overview of the experimental data detailing the incidence, mechanism and significance of low dose hyper-radiosensitivity (HRS). Important discoveries gained from past and present studies are mapped and highlighted to illustrate the pathway to our current understanding of HRS and the impact of HRS on the cellular response to radiation in mammalian cells. Particular attention is paid to the balance of evidence suggesting a role for DNA repair processes in the response, evidence suggesting a role for the cell cycle checkpoint processes, and evidence investigating the clinical implications/relevance of the effect.
    • Endobronchial cryotherapy facilitates end-stage treatment options in patients with bronchial stenosis: A case series.

      Fitzmaurice, Gerard J; Redmond, Karen C; Fitzpatrick, David A; Bartosik, Waldemar; Department of Cardiothoracic Surgery, The Mater Misericordiae University Hospital, Dublin 7, Ireland. (2014-04)
      In keeping with international trends, lung cancer incidence and mortality are increasing among the Irish population with many patients presenting with advanced disease that excludes the potential for curative management. Consequently palliative treatment options for this patient group are being increasingly explored with various degrees of success. Endobronchial stenosis represents a particularly challenging area of management among these patients and a number of techniques have been described without the identification of a single gold standard. We report our experience of the first time use of endobronchial cryotherapy in Ireland with reference to a case series, including an example of its use in the management of benign disease, in order to support patients with borderline lung function and enable definitive palliative treatment.
    • Magnetic resonance imaging appearances in primary and secondary angiosarcoma of the breast.

      O'Neill, Ailbhe C; D'Arcy, Clare; McDermott, Enda; O'Doherty, Ann; Quinn, Cecily; McNally, Sorcha; Department of Breast Radiology, St. Vincent's University Hospital, Dublin, Ireland. (2014-04)
      Angiosarcomas are malignant tumours of endovascular origin. They are rare tumours accounting for 0.04-1% of all breast malignancies. Two different forms are described: primary, occurring in young women, and secondary angiosarcoma, which occurs in older women with a history of breast-conserving surgery and radiation therapy. Imaging findings on mammography and ultrasound are non-specific, but magnetic resonance imaging with dynamic contrast enhancement is more informative. We present two cases - one of primary and one of secondary angiosarcoma - and review the imaging findings.
    • Active surveillance for low-risk prostate cancer: diversity of practice across Europe.

      Azmi, A; Dillon, R A; Borghesi, S; Dunne, M; Power, R E; Marignol, L; O'Neill, B D P; St. Luke's Radiation Oncology Centre, Beaumont Hospital, Dublin, Ireland, aini.azmi@slh.ie. (2014-03-21)
      Active surveillance (AS) is a recognised treatment option for low-risk prostate cancer (PCa).
    • A randomized trial comparing bladder volume consistency during fractionated prostate radiation therapy

      Mullaney, L.; O'Shea, E.; Dunne, M.; Finn, M.; Thirion, P.; Cleary, L. A.; McGarry, M.; O'Neill, L.; Armstrong, J.G. (2014-01-10)
      Organ motion is a contributory factor to the variation in location of the prostate and organs at risk during a course of fractionated prostate radiation therapy (RT). A prospective randomized controlled trial was designed with the primary endpoint to provide evidence-based bladder-filling instructions to achieve a consistent bladder volume (BV) and thus reduce the bladder-related organ motion. The secondary endpoints were to assess the incidence of acute and late genitourinary (GU) and gastrointestinal (GI) toxicity for patients and patients’ satisfaction with the bladder-filling instructions.
    • Head and neck cancer of unknown primary site

      McArdle, Orla; McDermott, Ronan (2013-11-21)
    • Sensitivity of volumetric modulated arc therapy patient specific QA results to multileaf collimator errors and correlation to dose volume histogram based metrics.

      Coleman, Linda; Skourou, Christina; University Hospital Galway, Newcastle Road, Galway, Ireland. (2013-11)
      This study investigates the impact of systematic multileaf collimator (MLC) positional errors on gamma analysis results used for quality assurance (QA) of Rapidarc treatments. In addition, this study evaluates the relationship of these gamma analysis results and clinical dose volume histogram metrics (DVH) for Rapidarc treatment plans.
    • The use of complementary and alternative medicine by Irish pediatric cancer patients.

      O'Connor, Niamh; Graham, Donna; O'Meara, Anne; Devins, Mary; Jennings, Valerie; O'Leary, Denise; O'Reilly, Maeve; The Departments of Palliative Medicine and Oncology, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland. (2013-10)
      The use of complementary and alternative medicine (CAM) in the Irish pediatric cancer setting has not previously been established.
    • Prostate cancer in a male with Holt-Oram syndrome: first clinical association of the TBX5 mutation.

      Aherne, Noel J; Rangaswamy, Guhan; Thirion, Pierre; Department of Radiation Oncology, North Coast Cancer Institute, Coffs Harbour, NSW 2450, Australia. (Hindawi Publishing Corp., 2013-08-05)
      Holt-Oram syndrome is an autosomal dominant disorder which is caused by mutations of TBX5 and is characterised by cardiac and skeletal abnormalities. TBX5 is part of the T-box gene family and is thought to upregulate tumour cell proliferation and metastasis when mutated. We report the first clinical case of prostate cancer in an individual with Holt Oram syndrome.
    • DNA mismatch repair protein MSH2 dictates cellular survival in response to low dose radiation in endometrial carcinoma cells.

      Martin, Lynn M; Marples, Brian; Davies, Anthony M; Atzberger, Ann; Edwards, Connla; Lynch, Thomas H; Hollywood, Donal; Marignol, Laure; Radiation and Urologic Oncology, Prostate Molecular Oncology Research Group, Academic Unit of Clinical and Molecular Oncology, Institute of Molecular Medicine, Trinity College Dublin, Dublin 8, Ireland. (Elsevier Ireland Ltd, 2013-07-10)
      DNA repair and G2-phase cell cycle checkpoint responses are involved in the manifestation of hyper-radiosensitivity (HRS). The low-dose radioresponse of MSH2 isogenic endometrial carcinoma cell lines was examined. Defects in cell cycle checkpoint activation and the DNA damage response in irradiated cells (0.2 Gy) were evaluated. HRS was expressed solely in MSH2+ cells and was associated with efficient activation of the early G2-phase cell cycle checkpoint. Maintenance of the arrest was associated with persistent MRE11, γH2AX, RAD51 foci at 2 h after irradiation. Persistent MRE11 and RAD51 foci were also evident 24 h after 0.2 Gy. MSH2 significantly enhances cell radiosensitivity to low dose IR.
    • Development of a label-free LC-MS/MS strategy to approach the identification of candidate protein biomarkers of disease recurrence in prostate cancer patients in a clinical trial of combined hormone and radiation therapy.

      Morrissey, Brian; O'Shea, Carmel; Armstrong, John; Rooney, Cathy; Staunton, Lisa; Sheehan, Martina; Shannon, Aoife M; Pennington, Stephen R; Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland. (2013-06)
      Combined hormone and radiation therapy (CHRT) is one of the principle curative regimes for localised prostate cancer (PCa). Following treatment, many patients subsequently experience disease recurrence however; current diagnostics tests fail to predict the onset of disease recurrence. Biomarkers that address this issue would be of significant advantage.
    • Manipulating the epigenome for the treatment of urological malignancies.

      O'Rourke, Colm J; Knabben, Vinicius; Bolton, Eva; Moran, Diarmaid; Lynch, Thomas; Hollywood, Donal; Perry, Antoinette S; Prostate Molecular Oncology, Institute of Molecular Medicine, Trinity College, Dublin, Ireland. (2013-05)
      Urological malignancies (cancers of the prostate, bladder, kidney and testes) account for 15% of all human cancers and more than 500,000 deaths worldwide each year. This group of malignancies is spread across multiple generations, affecting the young (testicular) through middle and old-age (kidney, prostate and bladder). Like most human cancers, urological cancers are characterized by widespread epigenetic insult, causing changes in DNA hypermethylation and histone modifications leading to silencing of tumor suppressor genes and genomic instability. The inherent stability yet dynamic plasticity of the epigenome lends itself well to therapeutic manipulation. Epigenetic changes are amongst the earliest lesions to occur during carcinogenesis and are essentially reversible (unlike mutations). For this reason, much attention has been placed over the past two decades on deriving pharmacological compounds that can specifically target and reverse such epi-mutations, either halting cancer on its developmental trajectory or reverting fully formed cancers to a more clinically manageable state. This review discusses DNA methyltransferase and histone deacetylase inhibitors that have been extensively studied in preclinical models and clinical trials for advanced and metastatic urological cancers.
    • Gene expression and epigenetic discovery screen reveal methylation of SFRP2 in prostate cancer.

      Perry, Antoinette S; O'Hurley, Gillian; Raheem, Omer A; Brennan, Kevin; Wong, Simon; O'Grady, Anthony; Kennedy, Anne-Marie; Marignol, Laure; Murphy, Therese M; Sullivan, Linda; Barrett, Ciara; Loftus, Barbara; Thornhill, John; Hewitt, Stephen M; Lawler, Mark; Kay, Elaine; Lynch, Thomas; Hollywood, Donal; Prostate Molecular Oncology, Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, Ireland. aperry@tcd.ie (2013-04-15)
      Aberrant activation of Wnts is common in human cancers, including prostate. Hypermethylation associated transcriptional silencing of Wnt antagonist genes SFRPs (Secreted Frizzled-Related Proteins) is a frequent oncogenic event. The significance of this is not known in prostate cancer. The objectives of our study were to (i) profile Wnt signaling related gene expression and (ii) investigate methylation of Wnt antagonist genes in prostate cancer. Using TaqMan Low Density Arrays, we identified 15 Wnt signaling related genes with significantly altered expression in prostate cancer; the majority of which were upregulated in tumors. Notably, histologically benign tissue from men with prostate cancer appeared more similar to tumor (r = 0.76) than to benign prostatic hyperplasia (BPH; r = 0.57, p < 0.001). Overall, the expression profile was highly similar between tumors of high (≥ 7) and low (≤ 6) Gleason scores. Pharmacological demethylation of PC-3 cells with 5-Aza-CdR reactivated 39 genes (≥ 2-fold); 40% of which inhibit Wnt signaling. Methylation frequencies in prostate cancer were 10% (2/20) (SFRP1), 64.86% (48/74) (SFRP2), 0% (0/20) (SFRP4) and 60% (12/20) (SFRP5). SFRP2 methylation was detected at significantly lower frequencies in high-grade prostatic intraepithelial neoplasia (HGPIN; 30%, (6/20), p = 0.0096), tumor adjacent benign areas (8.82%, (7/69), p < 0.0001) and BPH (11.43% (4/35), p < 0.0001). The quantitative level of SFRP2 methylation (normalized index of methylation) was also significantly higher in tumors (116) than in the other samples (HGPIN = 7.45, HB = 0.47, and BPH = 0.12). We show that SFRP2 hypermethylation is a common event in prostate cancer. SFRP2 methylation in combination with other epigenetic markers may be a useful biomarker of prostate cancer.
    • Gene expression analysis in prostate cancer: the importance of the endogenous control.

      Vajda, Alice; Marignol, Laure; Barrett, Ciara; Madden, Stephen F; Lynch, Thomas H; Hollywood, Donal; Perry, Antoinette S; Prostate Molecular Oncology, Academic Unit of Clinical and Molecular Oncology, Institute of Molecular Medicine, Trinity College Dublin, Ireland. vajdaa@tcd.ie (2013-03)
      Aberrant gene expression is a hallmark of cancer. Quantitative reverse-transcription PCR (qRT-PCR) is the gold-standard for quantifying gene expression, and commonly employs a house-keeping gene (HKG) as an endogenous control to normalize results; the choice of which is critical for accurate data interpretation. Many factors, including sample type, pathological state, and oxygen levels influence gene expression including putative HKGs. The aim of this study was to determine the suitability of commonly used HKGs for qRT-PCR in prostate cancer.
    • Cell death pathways in directly irradiated cells and cells exposed to medium from irradiated cells.

      Jella, Kishore Kumar; Garcia, Amaya; McClean, Brendan; Byrne, Hugh J; Lyng, Fiona M; Radiation and Environmental Science Centre, Focas Research Institute, Dublin Institute of Technology, Dublin. (2013-03)
      The aim of this study was to compare levels of apoptosis, necrosis, mitotic cell death and senescence after treatment with both direct radiation and irradiated cell conditioned medium.