• 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.
    • Head and neck cancer of unknown primary site

      McArdle, Orla; McDermott, Ronan (2013-11-21)
    • 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).
    • How realistic are published dose-response models? [ICORG 99-09]

      Walsh, L.; Williams, I.; O'Shea, C.; Armstrong, J.; Thirion, P.; St. Luke's Radiation Oncology Network (2010-11)
      Poster presentation - Lorraine Walsh. ASTRO 52nd annual meeting, San Diego, Nov-2010. (Int. Journal Radiation Oncol. Biol. Physics 2010; 78(3), Supplement, 3148).
    • 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.
    • The impact of rectal and bladder preparation in prostate radiotherapy [ICORG 05-04]

      Mullaney, L.; Thirion, P.; Coffey, M.; St Lukes Radiation Oncology Network (2011-05)
      Oral presentation - ESTRO, London, May 2011.
    • In silico analysis and DHPLC screening strategy identifies novel apoptotic gene targets of aberrant promoter hypermethylation in prostate cancer.

      Murphy, Therese M; Sullivan, Linda; Lane, Caroline; O'Connor, Lisa; Barrett, Ciara; Hollywood, Donal; Lynch, Thomas; Lawler, Mark; Perry, Antoinette S; Prostate Molecular Oncology, Institute of Molecular Medicine, Trinity College, Dublin, Ireland. murphyth@tcd.ie (Wiley, 2011-01-01)
      Aberrant DNA methylation has been implicated as a key survival mechanism in cancer, whereby promoter hypermethylation silences genes essential for many cellular processes including apoptosis. Limited data is available on the methylation profile of apoptotic genes in prostate cancer (CaP). The aim of this study was to profile methylation of apoptotic-related genes in CaP using denaturing high performance liquid chromatography (DHPLC).
    • In silico mining identifies IGFBP3 as a novel target of methylation in prostate cancer.

      Perry, A S; Loftus, B; Moroose, R; Lynch, T H; Hollywood, D; Watson, R W G; Woodson, K; Lawler, M (2007-05-21)
      Promoter hypermethylation is central in deregulating gene expression in cancer. Identification of novel methylation targets in specific cancers provides a basis for their use as biomarkers of disease occurrence and progression. We developed an in silico strategy to globally identify potential targets of promoter hypermethylation in prostate cancer by screening for 5' CpG islands in 631 genes that were reported as downregulated in prostate cancer. A virtual archive of 338 potential targets of methylation was produced. One candidate, IGFBP3, was selected for investigation, along with glutathione-S-transferase pi (GSTP1), a well-known methylation target in prostate cancer. Methylation of IGFBP3 was detected by quantitative methylation-specific PCR in 49/79 primary prostate adenocarcinoma and 7/14 adjacent preinvasive high-grade prostatic intraepithelial neoplasia, but in only 5/37 benign prostatic hyperplasia (P < 0.0001) and in 0/39 histologically normal adjacent prostate tissue, which implies that methylation of IGFBP3 may be involved in the early stages of prostate cancer development. Hypermethylation of IGFBP3 was only detected in samples that also demonstrated methylation of GSTP1 and was also correlated with Gleason score > or =7 (P=0.01), indicating that it has potential as a prognostic marker. In addition, pharmacological demethylation induced strong expression of IGFBP3 in LNCaP prostate cancer cells. Our concept of a methylation candidate gene bank was successful in identifying a novel target of frequent hypermethylation in early-stage prostate cancer. Evaluation of further relevant genes could contribute towards a methylation signature of this disease.
    • Increased mitochondrial mass in cells with functionally compromised mitochondria after exposure to both direct gamma radiation and bystander factors.

      Nugent, Sharon M E; Mothersill, Carmel E; Seymour, Colin; McClean, Brendan; Lyng, Fiona M; Murphy, James E J (2007-07)
      The bystander effect describes radiation-like damage in unirradiated cells either in the vicinity of irradiated cells or exposed to medium from irradiated cells. This study aimed to further characterize the poorly understood mitochondrial response to both direct irradiation and bystander factor(s) in human keratinocytes (HPV-G) and Chinese hamster ovarian cells (CHO-K1). Oxygen consumption rates were determined during periods of state 4, state 3 and uncoupled respiration. Mitochondrial mass was determined using MitoTracker FM. CHO-K1 cells showed significantly reduced oxygen consumption rates 4 h after exposure to 5 Gy direct radiation and irradiated cell conditioned medium (ICCM) and an apparent recovery 12-24 h later. The apparent recovery was likely due to the substantial increase in mitochondrial mass observed in these cells as soon as 4 h after exposure. HPV-G cells, on the other hand, showed a sustained increase in oxygen consumption rates after ICCM exposure and a transient increase 4 h after exposure to 5 Gy direct radiation. A significant increase in mitochondrial mass per HPV-G cell was observed after exposure to both direct radiation and ICCM. These findings are indicative of a stress response to mitochondrial dysfunction that increases the number of mitochondria per cell.
    • 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.