• 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”.
    • 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.
    • Challenges in the Management of Pediatric Central Venous Access Devices in the Community.

      Wallace, Elaine; Twomey, Marie; O'Reilly, Maeve; Department of Palliative Medicine, Our Lady's Hospital for Sick Children , Crumlin, Dublin , Ireland. (2012-05-25)
      Central venous access devices (CVADs) play an essential role in the care of critically ill children. Significant challenges exist for teams in managing CVADs particularly in a community setting. The authors aimed to assess the experience of general practitioners (GPs) caring for children with CVADs. From 200 CVADs inserted in a pediatric hospital in 2009, 50 patients were randomly selected and 44 GPs were forwarded a questionnaire. Twenty (46%) GPs responded. The main reasons (n = 22) for using CVADs were medication administration (n = 11), nutrition (n = 6), and blood sampling (n = 5). Thirteen (65%) GPs had no education in CVAD management and 14 (70%) were unaware of existing guidelines. Those identified by GPs as having primary responsibility for care of CVADs in the community included hospital/pediatric teams (n = 9), parents (n = 3), GPs (n = 2), public health nurses (n = 1), and palliative care ("home care") teams (n = 1). The main challenges (n = 15) identified by GPs were lack of education (n = 4), line management difficulties (n = 3), infection risk (n = 3), infrequent exposure to CVADs (n = 3), and poor communication (n = 1). GPs felt that these challenges could be addressed through: education (n = 8), increased manpower and community support (n = 1), and improved communication (n = 1). This study highlights the inconsistency and challenges for GPs surrounding CVAD use in children. Further education and support is necessary to assist GPs in their use particularly when providing end-of-life care for children in the community.
    • Chromosomal radiosensitivity in breast cancer patients with a known or putative genetic predisposition.

      Baeyens, A; Thierens, H; Claes, K; Poppe, B; Messiaen, L; De Ridder, L; Vral, A (London, Lewis, 2002-12-02)
      The chromosomal radiosensitivity of breast cancer patients with a known or putative genetic predisposition was investigated and compared to a group of healthy women. The chromosomal radiosensitivity was assessed with the G2 and the G0-micronucleus assay. For the G2 assay lymphocytes were irradiated in vitro with a dose of 0.4 Gy (60)Co gamma-rays after 71 h incubation, and chromatid breaks were scored in 50 metaphases. For the micronucleus assay lymphocytes were exposed in vitro to 3.5 Gy (60)Co gamma-rays at a high dose rate or low dose rate. 70 h post-irradiation cultures were arrested and micronuclei were scored in 1000 binucleate cells. The results demonstrated that the group of breast cancer patients with a known or putative genetic predisposition was on the average more radiosensitive than a population of healthy women, and this with the G2 as well as with the high dose rate and low dose rate micronucleus assay. With the G2 assay 43% of the patients were found to be radiosensitive. A higher proportion of the patients were radiosensitive with the micronucleus assay (45% with high dose rate and 61% with low dose rate). No correlation was found between the G2 and the G0-micronucleus chromosomal radiosensitivity. Out of the different subgroups considered, the group of the young breast cancer patients without family history showed the highest percentage of radiosensitive cases in the G2 (50%) as well as in the micronucleus assay (75-78%).
    • A clinical review of treatment outcomes in glioblastoma multiforme - the validation in a non-trial population of the results of a randomised Phase III clinical trial: has a more radical approach improved survival?

      Rock, K; McArdle, O; Forde, P; Dunne, M; Fitzpatrick, D; O'Neill, B; Faul, C; St. Luke's Radiation Oncology Network, Dublin, Ireland, and Beaumont Hospital, Dublin, Ireland. (2012-01-03)
      Objective: Glioblastoma multiforme (GBM) accounts for up to 60% of all malignant primary brain tumours in adults, occurring in 2-3 cases per 100 000 in Europe and North America. In 2005, a Phase III clinical trial demonstrated a significant improvement in survival over 2, and subsequently, 5 years with the addition of concurrent and adjuvant temozolomide (TMZ) to radical radiotherapy (RT) (Stupp R, Hegi M, van den Bent M, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 2009:10:459-66). The aim of this study was to investigate if the demonstrated improved survival in the literature translated to clinical practice.Methods: This was a retrospective study including all patients with histologically proven GBM diagnosed from 1999 to 2008 and treated with adjuvant RT at our institution. A total of 273 patients were identified. Statistical analysis was carried out using SPSS v18.Results: The median survival for the whole group (n = 273) over the 10-year period was 7.6 months (95% confidence interval 6.7-8.4 months). Overall, the cumulative probability of survival at 1 and 2 years was 31.5 and 9.4%, respectively. In total, 146 patients received radical RT. 103 patients were treated with radical RT and TMZ and 43 patients received radical RT alone. The median survival for patients receiving radical RT with TMZ was 13.4 months (95% CI 10.9-15.8 months) vs 8.8 months for radical RT alone (95% CI 6.9 - 10.7 months, p = 0.006). 2-year survival figures were 21.2 vs 4.7%, respectively. On multivariate analysis, independent predictors of survival included KPS, RT dose, TMZ and extent of surgery. The strongest predictors of poorer outcome based on the hazard ratio were palliative RT, followed by not receiving TMZ chemotherapy, then KPS <90 and a biopsy only surgical approach.Conclusion: This paper demonstrates improved survival outcomes consistent with those published in the literature for the addition of concurrent and adjuvant TMZ to radical RT for the treatment of GBM. Although 63% of patients seen in the clinic were suitable for a combined modality approach, the prognosis for the lower Radiation Therapy Oncology Group classes still remains poor.
    • A comparison of multimodal therapy and surgery for esophageal adenocarcinoma.

      Walsh, T N; Noonan, N; Hollywood, D; Kelly, A; Keeling, N; Hennessy, T P (1996-08-15)
      Uncontrolled studies suggest that a combination of chemotherapy and radiotherapy improves the survival of patients with esophageal adenocarcinoma. We conducted a prospective, randomized trial comparing surgery alone with combined chemotherapy, radiotherapy, and surgery.
    • 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.
    • 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.
    • Duration of short-course androgen suppression therapy and the risk of death as a result of prostate cancer.

      D'Amico, Anthony V; Chen, Ming-Hui; Crook, Juanita; Armstrong, John G; Malone, Shawn; Steigler, Allison; Dunne, Mary; Kantoff, Philip W; Denham, James W; Brigham and Women's Hospital, Boston, MA 02115, USA. adamico@partners.org (2011-12-10)
      We evaluated whether the duration of androgen suppression therapy (AST) had an impact on the risk of prostate cancer-specific mortality (PCSM) in men with unfavorable-risk prostate cancer (PC) within established Gleason score (GS) categories.
    • The effect of short term neo-adjuvant androgen deprivation on erectile function in patients treated with external beam radiotherapy for localised prostate cancer: an analysis of the 4- versus 8-month randomised trial (Irish Clinical Oncology Research Group 97-01).

      Daly, Patricia E; Dunne, Mary T; O'Shea, Carmel M; Finn, Marie A; Armstrong, John G; Department of Radiation Oncology, St. Luke's Hospital, Dublin, Ireland. trish_daly@eircom.net (Elsevier, 2012-07)
      Erectile dysfunction is a common consequence of external beam radiotherapy (EBRT) for prostate cancer. The addition of neo-adjuvant androgen deprivation (NAD) has an indeterminate additive effect. We examined the long-term effect on erectile function (EF) of two durations (4 months: arm 1 and 8 months: arm 2) of NAD prior to radiation (RT) for patients with localised prostate cancer from the Irish Clinical Oncology Research Group (ICORG 97-01) 4- versus 8-month trial. In this study we aimed to (1) analyse the overall effect on EF of NAD in an EBRT population, (2) compare the probability of retained EF over time in an EBRT population treated with either 4 or 8 months of NAD and (3) identify any variables such as risk group and age which may have an additive detrimental effect. This analysis provides unique long term follow up data.
    • 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.
    • Escalated dose for non-small cell lung cancer with accelerated hypofractionated three-dimensional conformal radiation therapy. [ICORG 99-09]

      Thirion, P.; Brennan, S.; Fitzpatrick, D.; Armstrong, J.; Dunne, M.; O'Shea, C.; McElroy, A.; St. Luke's Radiation Oncology Network (2009-09)
      Radiother Oncol 2009;S48 (Oral presentation, Abstr, 10th Biennial ESTRO Conference, Maastricht, Sept. 2009)
    • A European survey relating to cancer therapy and neutropenic infections: Nurse and patient viewpoints.

      Leonard, Kay; Saint Luke's Radiation Oncology Centre, St James's Hospital, St James's Street, Dublin 8, Ireland. (2011-09-25)
      PURPOSE: Severe neutropenia and febrile neutropenia (FN) are the major causes of morbidity, treatment interruptions and dose reductions in patients undergoing chemotherapy. The European Oncology Nursing Society (EONS) conducted an European survey to evaluate nurse perspectives on prevention of infection and FN in this setting, and how much they educate their patients about this. A separate survey explored these issues in patients receiving chemotherapy. METHODS: 217 nurse participants were identified by EONS from the membership database and 473 cancer patients who were receiving/had received chemotherapy were identified through patient advocacy groups. Questionnaires were completed anonymously online for both surveys. RESULTS: More than 90% of the nurses agreed that preventing infections including FN is extremely/very important for a successful chemotherapy outcome and said that they, or other health professionals in their practice, advised patients about these issues. Most (90%) indicated that they favoured giving treatment to protect against FN and infections in chemotherapy patients at risk, rather than treating infection after it develops, but 82% expressed concern over patient concordance with measures employed. A substantial proportion of patients reported emergency room visits, hospitalization and/or chemotherapy delays or changes as a result of neutropenia, infection or FN. However, only 44% said that their infection risk was discussed with them before starting chemotherapy. CONCLUSIONS: Our findings indicate that nurses recognise the importance of reducing the risk of infection and FN in patients undergoing chemotherapy, as well as the need to educate patients. However, results of the patient survey suggest a need for better patient education.
    • Evolving progress in oncologic and operative outcomes for esophageal and junctional cancer: lessons from the experience of a high-volume center.

      Reynolds, John V; Donohoe, Claire L; McGillycuddy, Erin; Ravi, Naraymasamy; O'Toole, Dermot; O'Byrne, Ken; Hollywood, Donal; Department of Surgery, St James's Hospital and Trinity College, Dublin, Ireland. reynoljv@tcd.ie (Elsevier, 2012-05)
      Modern series from high-volume esophageal centers report an approximate 40% 5-year survival in patients treated with curative intent and postoperative mortality rates of less than 4%. An objective analysis of factors that underpin current benchmarks within high-volume centers has not been performed.
    • 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.
    • Factors influencing conformity index in radiotherapy for non-small cell lung cancer.

      Brennan, Sinead M; Thirion, Pierre; Buckney, Steve; Shea, Carmel O; Armstrong, John; Department of Radiation Oncology, St. Lukes Hospital, Dublin, Ireland. sinead.brennan09@gmail.com (2010)
      The radiotherapy conformity index (CI) is a useful tool to quantitatively assess the quality of radiotherapy treatment plans, and represents the relationship between isodose distributions and target volume. A conformity index of unity implies high planning target volume (PTV) coverage and minimal unnecessary irradiation of surrounding tissues. We performed this analysis to describe the CI for lung cancer 3-dimensional conformal radiotherapy (3DCRT) and to identify clinical and technical determinants of CI, as it is not known which factors are associated with good quality 3D conformal radiotherapy treatment planning. Radiotherapy treatment plans from a database of 52 patients with inoperable Stage 1 to 3b lung cancer, on a hypofractionated 3DCRT trial were evaluated. A CI was calculated for all plans using the definition of the ICRU 62:CI = (TV/PTV), which is the quotient of the treated volume (TV) and the PTV. Data on patient, tumor, and planning variables, which could influence CI, were recorded and analyzed. Mean CI was 2.01 (range = 1.06-3.8). On univariate analysis, PTV (p = 0.023), number of beams (p = 0.036), medial vs. lateral tumor location (p = 0.016), and increasing tumor stage (p = 0.041) were associated with improved conformity. On multiple regression analysis, factors found to be associated with CI included central vs. peripheral tumor location (p = 0.041) and PTV size (p = 0.058). The term 3DCRT is used routinely in the literature, without any indication of the degree of conformality. We recommend routine reporting of conformity indices. Conformity indices may be affected by both planning variables and tumor factors.
    • Functional outcomes of patients impending cord compression treated by palliative RT alone [ICORG 05-03]

      O'Sullivan, L.; Clayton-Lea, A.; McArdle, O.; McGarry, M.; Kenny, J.; Dunne, M.; O'Shea, E.; St. Luke's Radiation Oncology Network (2011-03)
      Oral presentation- 11th All Ireland Radiation Therapists Study Day, March 2011.
    • 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.
    • 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; et al. (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.
    • 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.