• Glioblastoma Multiforme in the over 70's: "To treat or not to treat with radiotherapy?"

      O'Shea, Julianne; Dunne, Mary; Grogan, Roger; MacNally, Stephen; Fitzpatrick, David; Faul, Clare; Glynn, Am; Rangaswamy, Guhan (2019-07-04)
      BACKGROUND: The incidence of Glioblastoma Multiforme (GBM) is increasing among the older population and is associated with poor prognosis. Management guidelines are lacking in this group. The purpose of this study was to analyze survival data and determine predictors of survival in patients aged ≥70 years treated with radiotherapy (RT) and/or Temozolomide. MATERIALS AND METHODS: A retrospective analysis of all GBM patients treated at our institution between January 2011 and January 2017 was carried out. RESULTS: One-hundred and four patients were eligible. Median age was 73.8 years (70-87). Thirty-three patients received radical RT and 71 palliative RT. Overall median survival (MS) was 6 months. The MS was 10.6 months for radical patients and 4.9 months for palliative patients (P < 0.0005). The MS was 6.9 months in patients aged 70-75 years and 5.2 months in those aged 76-80 years (P = 0.004). The debulked group had a statistically significantly longer survival (8.0 months) than the biopsy only group (4.9 months). Biopsy only (hazard ratio [HR] 2.4), ECOG performance status 3 vs 0 (HR 6.4), and increasing age (HR 1.06) were associated with statistically significant shorter survival after adjustment for the effects of concurrent chemo, delay in starting RT, and RT dose. CONCLUSION: The MS for radical patients was favorable and approaching current literature for the under 70 age group. Radical treatment should be considered for good performance patients aged 70-75 years. Increasing age was associated with shorter MS in patients aged ≥76 years. Debulking and good performance status were associated with improved survival.
    • International Variation in Criteria for Internal Mammary Chain Radiotherapy.

      Duane, F K; McGale, P; Teoh, S; Mortimer, C; Broggio, J; Darby, S C; Dodwell, D; Lavery, B; Oliveros, S; Vallis, K A; et al. (2019-07-01)
      Aims; Evidence has emerged that internal mammary chain (IMC) radiotherapy reduces breast cancer mortality, leading to changes in treatment guidelines. This study investigated current IMC radiotherapy criteria and the percentages of patients irradiated for breast cancer in England who fulfilled them. Materials and methods; A systematic search was undertaken for national guidelines published in English during 2013–2018 presenting criteria for ‘consideration of’ or ‘recommendation for’ IMC radiotherapy. Patient and tumour variables were collected for patients who received breast cancer radiotherapy in England during 2012–2016. The percentages of patients fulfilling criteria stipulated in each set of guidelines were calculated. Results: In total, 111 729 women were recorded as receiving adjuvant breast cancer radiotherapy in England during 2012–2016 and full data were available on 48 095 of them. Percentages of patients fulfilling IMC radiotherapy criteria in various national guidelines were: UK Royal College of Radiologists 13% (6035/48 095), UK National Institute for Health and Care Excellence 18% (8816/48 095), Germany 32% (15 646/48 095), Ireland 56% (26 846/48 095) and USA 59% (28 373/48 095). Differences between countries occurred because in Ireland and the USA, treatment may be considered in some node-negative patients, whereas in the UK, treatment is considered if at least four axillary nodes are involved or for high-risk patients with one to three positive nodes. In Germany, treatment may be considered for all node-positive patients. Conclusions: There is substantial variability between countries in criteria for consideration of IMC radiotherapy, despite guidelines being based on the same evidence. This will probably lead to large variations in practice and resource needs worldwide.
    • Being “Mindful” of Dignity in Dying: Developing Awareness, Fostering a Psychological Understanding, and Supporting Dignified Endings-To-Life

      Hession, Natalie; Elmer, Nicola; O'Kane, Aifric; Cotter, Pádraig; Psycho-Oncology Department, St. Luke's Radiation Oncology Network (IJEPP, 2019)
      Experiencing a sense of dignity when nearing end-of-life has been shown to be very important. There are many things that hospice and palliative nurses can do to support dignified endings-to-life. This paper explores the different aspects of this process from both the perspective of the person dying and in particular the individual in the caring role. Consideration is given to the different components of experiencing dignity in dying, especially those aspects that nursing staff can influence most. The importance of a sense of dignity to people who are dying is explored using two psychological models that provide an intrapersonal and transpersonal perspective. These include the Abandonment of Self Model and the Surface-Depth Model respectively. The types of obstacles to nursing staff providing this type of care and support are reflected upon, with particular emphasis placed on the practitioner’s own personal fears and anxieties and how these may manifest within the patient-nurse relationship. The final section explores the use of mindfulness practises as a way of interacting more fully with people diagnosed with terminal illnesses to support their experience of a dignified ending-to-life. This process is termed “mindful engagement”.
    • 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.