• Interval cancer audit and disclosure in breast screening programmes: An international survey.

      Fitzpatrick, Patricia; Byrne, Helen; Flanagan, Fidelma; O'Doherty, Ann; Connors, Alissa; Larke, Aideen; O'Laoide, Risteard; Williams, Yvonne; Mooney, Therese (2022-09-07)
    • The SARS-CoV-2 Pandemic and Cancer Trials Ireland: Impact, Resolution and Legacy.

      O'Reilly, Seamus; Murphy, Verena; Mulroe, Eibhlin; Tucker, Lisa; Carragher, Fiona; Marron, Jacinta; Shannon, Aoife M; Rogan, Ken; Connolly, Roisin M; Hennessy, Bryan T; et al. (2022-04-30)
    • Refining Glioblastoma Surgery through the Use of Intra-Operative Fluorescence Imaging Agents.

      Netufo, Oluwakanyinsolami; Connor, Kate; Shiels, Liam P; Sweeney, Kieron J; Wu, Dan; O'Shea, Donal F; Byrne, Annette T; Miller, Ian S (2022-04-29)
    • Association of treatment-emergent symptoms identified by patient-reported outcomes with adjuvant endocrine therapy discontinuation.

      Smith, Karen Lisa; Verma, Neha; Blackford, Amanda L; Lehman, Jennifer; Westbrook, Kelly; Lim, David; Fetting, John; Wolff, Antonio C; Jelovac, Daniela; Miller, Robert S; et al. (2022-04-21)
    • Genetic and RNA-related molecular markers of trastuzumab-chemotherapy-associated cardiotoxicity in HER2 positive breast cancer: a systematic review.

      Lunardi, Mattia; Al-Habbaa, Ahmed; Abdelshafy, Mahmoud; Davey, Matthew G; Elkoumy, Ahmed; Ganly, Sandra; Elzomor, Hesham; Cawley, Christian; Sharif, Faisal; Crowley, James; et al. (2022-04-12)
    • National Screening Service Key Performance Indicator Metadata 2022

      Health Service Executive (HSE) (Health Service Executive, 2022-04-11)
    • Colorectal microbiota after removal of colorectal cancer.

      Cronin, Peter; Murphy, Clodagh L; Barrett, Maurice; Ghosh, Tarini Shankar; Pellanda, Paola; O'Connor, Eibhlis M; Zulquernain, Syed Akbar; Kileen, Shane; McCourt, Morgan; Andrews, Emmet; et al. (2022-04-08)
      The colonic microbiome has been implicated in the pathogenesis of colorectal cancer (CRC) and intestinal microbiome alterations are not confined to the tumour. Since data on whether the microbiome normalises or remains altered after resection of CRC are conflicting, we studied the colonic microbiota of patients after resection of CRC. We profiled the microbiota using 16S rRNA gene amplicon sequencing in colonic biopsies from patients after resection of CRC (n = 63) in comparison with controls (n = 52), subjects with newly diagnosed CRC (n = 93) and polyps (i = 28). The colonic microbiota after surgical resection remained significantly different from that of controls in 65% of patients. Genus-level profiling and beta-diversity confirmed two distinct groups of patients after resection of CRC: one with an abnormal microbiota similar to that of patients with newly diagnosed CRC and another similar to non-CRC controls. Consumption levels of several dietary ingredients and cardiovascular drugs co-varied with differences in microbiota composition suggesting lifestyle factors may modulate differential microbiome trajectories after surgical resection. This study supports investigation of the colonic microbiota as a marker of risk for development of CRC.
    • Development and Validation of a Raman Spectroscopic Classification Model for Cervical Intraepithelial Neoplasia (CIN).

      Traynor, Damien; Duraipandian, Shiyamala; Bhatia, Ramya; Cuschieri, Kate; Tewari, Prerna; Kearney, Padraig; D'Arcy, Tom; O'Leary, John J; Martin, Cara M; Lyng, Fiona M (2022-04-06)
      The mortality associated with cervical cancer can be reduced if detected at the precancer stage, but current methods are limited in terms of subjectivity, cost and time. Optical spectroscopic methods such as Raman spectroscopy can provide a rapid, label-free and nondestructive measurement of the biochemical fingerprint of a cell, tissue or biofluid. Previous studies have shown the potential of Raman spectroscopy for cervical cancer diagnosis, but most were pilot studies with small sample sizes. The aim of this study is to show the clinical utility of Raman spectroscopy for identifying cervical precancer in a large sample set with validation in an independent test set. Liquid-based cervical cytology samples (n = 662) (326 negative, 200 cervical intraepithelial neoplasia (CIN)1 and 136 CIN2+) were obtained as a training set. Raman spectra were recorded from single-cell nuclei and subjected to a partial least squares discriminant analysis (PLSDA). In addition, the PLSDA classification model was validated using a blinded independent test set (n = 69). A classification accuracy of 91.3% was achieved with only six of the blinded samples misclassified. This study showed the potential clinical utility of Raman spectroscopy with a good classification of negative, CIN1 and CIN2+ achieved in an independent test set.
    • Survival and prognostic factors of isolated pulmonary metastases originating from colorectal cancer: An 8-year single-center experience.

      Balhareth, Ameera S; AlQattan, Abdullah S; Alshaqaq, Hassan M; Alkhalifa, Abdullah M; Al Abdrabalnabi, Alaa A; Alnamlah, Muna S; MacNamara, Deborah (2022-04-04)
    • Mitochondrial complex IV defects induce metabolic and signaling perturbations that expose potential vulnerabilities in HCT116 cells.

      Uchenunu, Oro; Zhdanov, Alexander V; Hutton, Phillipe; Jovanovic, Predrag; Wang, Ye; Andreev, Dmitry E; Hulea, Laura; Papadopoli, David J; Avizonis, Daina; Baranov, Pavel V; et al. (2022-04-01)
      Mutations in genes encoding cytochrome c oxidase (mitochondrial complex IV) subunits and assembly factors [e.g., synthesis of cytochrome c oxidase 2 (SCO2)] are linked to severe metabolic syndromes. Notwithstanding that SCO2 is under transcriptional control of tumor suppressor p53, the role of mitochondrial complex IV dysfunction in cancer metabolism remains obscure. Herein, we demonstrate that the loss of SCO2 in HCT116 colorectal cancer cells leads to significant metabolic and signaling perturbations. Specifically, abrogation of SCO2 increased NAD+ regenerating reactions and decreased glucose oxidation through citric acid cycle while enhancing pyruvate carboxylation. This was accompanied by a reduction in amino acid levels and the accumulation of lipid droplets. In addition, SCO2 loss resulted in hyperactivation of the insulin-like growth factor 1 receptor (IGF1R)/AKT axis with paradoxical downregulation of mTOR signaling, which was accompanied by increased AMP-activated kinase activity. Accordingly, abrogation of SCO2 expression appears to increase the sensitivity of cells to IGF1R and AKT, but not mTOR inhibitors. Finally, the loss of SCO2 was associated with reduced proliferation and enhanced migration of HCT116 cells. Collectively, herein we describe potential adaptive signaling and metabolic perturbations triggered by mitochondrial complex IV dysfunction.
    • IL-36 signalling enhances a pro-tumorigenic phenotype in colon cancer cells with cancer cell growth restricted by administration of the IL-36R antagonist.

      Baker, Kevin; O'Donnell, Charlotte; Bendix, Maura; Keogh, Samuel; Byrne, James; O'Riordain, Michael; Neary, Peter; Houston, Aileen; Brint, Elizabeth (2022-04-01)
      The IL-36 cytokines are a recently described subset of the IL-1 family of cytokines, shown to play a role in the pathogenesis of intestinal diseases such as Inflammatory Bowel Disease (IBD). Given the link between IBD and colitis -associated cancer, as well as the involvement of other IL-1 family members in intestinal tumorigenesis, the aim of this work was to investigate whether IL-36 cytokines play a role in the pathogenesis of colon cancer. Whilst research to date has focused on the role of IL-36 family members in augmenting the immune response to induce tumour rejection, very little remains known about IL-36R signalling in tumour cells in this context. In this study we demonstrate that expression of IL-36 family member mRNA and protein are significantly increased in colorectal cancer tissue compared to adjacent non-tumour. In vitro assays showed stimulation of colon cancer cell lines with IL-36R agonists resulted in the activation of the pro-tumorigenic phenotypes of increased cellular migration, invasion and proliferation in both 2D and 3D models. In addition, the IL-36 cytokines induced strong expression of pro-inflammatory chemokines in both human and murine cell lines. Intraperitoneal injection of IL-36Ra significantly reduced tumour burden using the subcutaneous CT26 tumour model in syngeneic Balb/mice, and this was associated with a decrease in Ki-67 expression by tumour cells in the IL-36Ra- treated group relative to untreated, suggesting the inhibition of the pro-proliferative signalling of IL-36 agonists resulted in the decreased tumour size. Moreover, colon cancer cells lacking the IL-36R also showed reduced tumour growth and reduced Ki-67 expression in vivo. Taken together, this data suggests that targeting IL-36R signalling may be a useful targeted therapy for colorectal cancer patients with IL-36R+ tumour cells.
    • Framework for the Care and Support of Adolescents and Young Adults (AYA) with Cancer in Ireland 2021-2026

      National Cancer Control Programme (NCCP) (National Cancer Control Programme (NCCP), 2022-04)
    • NCCP Child, Adolescent and Young Adult (CAYA) Cancer Annual Report 2021

      National Cancer Control Programme (NCCP) (National Cancer Control Programme (NCCP), 2022-04)
    • Using administrative health data for palliative and end of life care research in Ireland: potential and challenges.

      Kelly, Maria; O'Brien, Katie M; Hannigan, Ailish (2021-05-26)
      Background: This study aims to examine the potential of currently available administrative health and social care data for palliative and end-of-life care (PEoLC) research in Ireland. Objectives include to i) identify data sources for PEoLC research ii) describe the challenges and opportunities of using these and iii) evaluate the impact of recent health system reforms and changes to data protection laws. Methods: The 2017 Health Information and Quality Authority catalogue of health and social care datasets was cross-referenced with a recognised list of diseases with associated palliative care needs. Criteria to assess the datasets included population coverage, data collected, data dictionary and data model availability, and mechanisms for data access. Results: Nine datasets with potential for PEoLC research were identified, including death certificate data, hospital episode data, pharmacy claims data,  one national survey, four disease registries (cancer, cystic fibrosis, motor neurone and interstitial lung disease) and a national renal transplant registry.  The ad hoc development of the health system in Ireland has resulted in i) a fragmented information infrastructure resulting in gaps in data collections particularly in the primary and community care sector where much palliative care is delivered, ii) ill-defined data governance arrangements across service providers, many of whom are not part of the publically funded health service and iii) systemic and temporal issues that affect data quality. Initiatives to improve data collections include introduction of i) patient unique identifiers, ii) health entity identifiers and iii) integration of the Eircode postcodes. Recently enacted general data protection and health research regulations will clarify legal and ethical requirements for data use. Conclusions: Ongoing reform initiatives and recent changes to data privacy laws combined with detailed knowledge of the datasets, appropriate permissions, and good study design will facilitate future use of administrative health and social care data for PEoLC research in Ireland.
    • NRG Oncology/NSABP B-47 menstrual history study: impact of adjuvant chemotherapy with and without trastuzumab.

      Ganz, Patricia A; Cecchini, Reena S; Fehrenbacher, Louis; Geyer, Charles E; Rastogi, Priya; Crown, John P; Thirlwell, Michael P; Ellison, David M; Boileau, Jean-Francois; Flynn, Patrick J; et al. (2021-05-20)
    • Recommendations from the European Commission Initiative on Breast Cancer for multigene testing to guide the use of adjuvant chemotherapy in patients with early breast cancer, hormone receptor positive, HER-2 negative.

      Giorgi Rossi, Paolo; Lebeau, Annette; Canelo-Aybar, Carlos; Saz-Parkinson, Zuleika; Quinn, Cecily; Langendam, Miranda; McGarrigle, Helen; Warman, Sue; Rigau, David; Alonso-Coello, Pablo; et al. (2021-02-18)
    • Cross-species identification of PIP5K1-, splicing- and ubiquitin-related pathways as potential targets for RB1-deficient cells.

      Parkhitko, Andrey A; Singh, Arashdeep; Hsieh, Sharon; Hu, Yanhui; Binari, Richard; Lord, Christopher J; Hannenhalli, Sridhar; Ryan, Colm J; Perrimon, Norbert; University College Dublin (2021-02-16)
    • Possible modification of BRSK1 on the risk of alkylating chemotherapy-related reduced ovarian function.

      van der Kooi, Anne-Lotte L F; van Dijk, Marloes; Broer, Linda; van den Berg, Marleen H; Laven, Joop S E; van Leeuwen, Flora E; Lambalk, Cornelis B; Overbeek, Annelies; Loonen, Jacqueline J; van der Pal, Helena J; et al. (2021-02-14)
    • National Screening Service Key Performance Indicator Metadata 2020

      Health Service Executive (HSE) (Health Service Executive (HSE), 2020-07-09)
    • Weekly platinum-based chemotherapy versus 3-weekly platinum-based chemotherapy for newly diagnosed ovarian cancer (ICON8): quality-of-life results of a phase 3, randomised, controlled trial.

      Blagden, Sarah P; Cook, Adrian D; Poole, Christopher; Howells, Lesley; McNeish, Ian A; Dean, Andrew; Kim, Jae-Weon; O'Donnell, Dearbhaile M; Hook, Jane; James, Elizabeth C; et al. (2020-07-01)
      In this open-label, randomised, controlled, phase 3, three-arm, Gynecologic Cancer Intergroup (GCIG) trial done at 117 hospital sites in the UK, Australia, New Zealand, Mexico, South Korea, and Republic of Ireland, women (aged at least 18 years) with newly diagnosed, histologically confirmed International Federation of Gynecology and Obstetrics stage IC-IV ovarian cancer and an Eastern Cooperative Oncology Group performance status of 0-2 were randomly assigned (1:1:1) centrally using minimisation to group 1 (intravenous carboplatin area under the curve [AUC]5 or AUC6 and 175 mg/m2 intravenous paclitaxel every 3 weeks), group 2 (carboplatin AUC5 or AUC6 every 3 weeks and 80 mg/m2 paclitaxel weekly), or group 3 (carboplatin AUC2 weekly and 80 mg/m2 paclitaxel weekly). Randomisation was stratified by GCIG group, disease stage, and outcome and timing of surgery. Patients and clinicians were not masked to treatment assignment. Patients underwent immediate or delayed primary surgery according to clinicians' choice. Patients were asked to complete European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-OV28 questionnaires at enrolment, before each chemotherapy cycle, then 6-weekly up to 9 months, 3-monthly up to 2 years, and 6-monthly up to 5 years. Quality of life was a prespecified secondary outcome of the ICON8 study. Within the quality-of-life study, the co-primary endpoints were QLQ-C30 global health score at 9 months (cross-sectional analysis) and mean QLQ-C30 global health score from randomisation to 9 months (longitudinal analysis). Data analyses were done on an intention-to-treat basis. The trial is registered on ClinicalTrials.gov, NCT01654146 and ISRCTN Registry, ISRCTN10356387, and is currently in long-term follow up.