Research by staff affiliated to St. Luke's Radiation Oncology Network

Recent Submissions

  • Inter-clinician delineation variation for a new highly-conformal flank target volume in children with renal tumors: A SIOP-Renal Tumor Study Group international multicenter exercise.

    Mul, Joeri; Melchior, Patrick; Seravalli, Enrica; Saunders, Daniel; Bolle, Stephanie; Cameron, Alison L; Gurtner, Kristin; Harrabi, Semi; Lassen-Ramshad, Yasmin; Lavan, Naomi; et al. (2021-03-11)
    Background and purpose: Recently, the SIOP-RTSG developed a highly-conformal flank target volume definition for children with renal tumors. The aims of this study were to evaluate the inter-clinician delineation variation of this new target volume definition in an international multicenter setting and to explore the necessity of quality assurance. Materials and methods: Six pediatric renal cancer cases were transferred to ten radiation oncologists from seven European countries ('participants'). These participants delineated the pre- and postoperative Gross Tumor Volume (GTVpre/post), and Clinical Target Volume (CTV) during two test phases (case 1-2 and 3-4), followed by guideline refinement and a quality assurance phase (case 5-6). Reference target volumes (TVref) were established by three experienced radiation oncologists. The Dice Similarity Coefficient between the reference and participants (DSCref/part) was calculated per case. Delineations of case 5-6 were graded by four independent reviewers as 'per protocol' (0-4 mm), 'minor deviation' (5-9 mm) or 'major deviation' (≥10 mm) from the delineation guideline using 18 standardized criteria. Also, a major deviation resulting in underestimation of the CTVref was regarded as an unacceptable variation. Results: A total of 57/60 delineation sets were completed. The median DSCref/part for the CTV was 0.55 without improvement after sequential cases (case 3-4 vs. case 5-6: p = 0.15). For case 5-6, a major deviation was found for 5/18, 12/17, 18/18 and 4/9 collected delineations of the GTVpre, GTVpost, CTV-T and CTV-N, respectively. An unacceptable variation from the CTVref was found for 7/9 participants for case 5 and 6/9 participants for case 6. Conclusion: This international multicenter delineation exercise demonstrates that the new consensus for highly-conformal postoperative flank target volume delineation leads to geometrical variation among participants. Moreover, standardized review showed an unacceptable delineation variation in the majority of the participants. These findings strongly suggest the need for additional training and centralized pre-treatment review when this target volume delineation approach is implemented on a larger scale.
  • Clinical supervision in oncology: A narrative review.

    Hession, Natalie; Habenicht, Andrea (2020-05-26)
    The aim of this narrative literature review is to (a) review all empirical studies of clinical supervision (CS) in oncology and to (b) highlight some CS practice issues distinctive to cancer care. This review identified empirical studies related to qualified professionals and published in English since 1995 that connected to CS and oncology. A total of 15 studies were identified with the majority as small scale, exploratory and qualitative. Psychologists were predominantly utilised as facilitators of the CS with varied sample sizes ranging from 5-230 participants. The studies were grouped into three main categories; the impact of supervision on staff, impact of supervision on professional care/development and impact of supervision in existential exploration. This review highlighted the positive impact of CS while demonstrating the need for more methodologically sound programmes of research into CS in cancer settings so detailed models of effective supervision can develop and thereby inform practice.
  • PORTEC-4a: international randomized trial of molecular profile-based adjuvant treatment for women with high-intermediate risk endometrial cancer.

    van den Heerik, Anne Sophie V M; Horeweg, Nanda; Nout, Remi A; Lutgens, Ludy C H W; van der Steen-Banasik, Elzbieta M; Westerveld, G Henrike; van den Berg, Hetty A; Slot, Annerie; Koppe, Friederike L A; Kommoss, Stefan; et al. (2020-10-12)
    Background: Vaginal brachytherapy is currently recommended as adjuvant treatment in patients with high-intermediate risk endometrial cancer to maximize local control and has only mild side effects and no or limited impact on quality of life. However, there is still considerable overtreatment and also some undertreatment, which may be reduced by tailoring adjuvant treatment to the patients' risk of recurrence based on molecular tumor characteristics. Primary objectives: To compare the rates of vaginal recurrence in women with high-intermediate risk endometrial cancer, treated after surgery with molecular-integrated risk profile-based recommendations for either observation, vaginal brachytherapy or external pelvic beam radiotherapy or with standard adjuvant vaginal brachytherapy STUDY HYPOTHESIS: Adjuvant treatment based on a molecular-integrated risk profile provides similar local control and recurrence-free survival as current standard adjuvant brachytherapy in patients with high-intermediate risk endometrial cancer, while sparing many patients the morbidity of adjuvant treatment and reducing healthcare costs. Trial design: A multicenter, international phase III randomized trial (2:1) of molecular-integrated risk profile-based adjuvant treatment (experimental arm) or adjuvant vaginal brachytherapy (standard arm). Major inclusion/exclusion criteria: Women aged 18 years and over with a histological diagnosis of high-intermediate risk endometrioid endometrial cancer after total abdominal or laparoscopic hysterectomy and bilateral salpingo-oophorectomy. High-intermediate risk factors are defined as: (i) International Federation of Gynecology and Obstetrics stage IA (with invasion) and grade 3; (ii) stage IB grade 1 or 2 with age ≥60 and/or lymph-vascular space invasion; (iii) stage IB, grade 3 without lymph-vascular space invasion; or (iv) stage II (microscopic and grade 1). Endpoints: The primary endpoint is vaginal recurrence. Secondary endpoints are recurrence-free and overall survival; pelvic and distant recurrence; 5-year vaginal control (including treatment for relapse); adverse events and patient-reported symptoms and quality of life; and endometrial cancer-related healthcare costs. Sample size: 500 eligible and evaluable patients. Estimated dates for completing accrual and presenting results: Estimated date for completing accrual will be late 2021. Estimated date for presentation of (first) results is expected in 2023. Trial registration: The trial is registered at clinicaltrials.gov (NCT03469674) and ISRCTN (11659025). Keywords: endometrium; radiation oncology.
  • Involving Clients to Inform Development and Implementation of Combined Type 2 Diabetes and Chronic Kidney Disease Care Using Discovery Interview Technique.

    Blanchfield, Denise; O'Connor, Laserina (Innovational Publishers, 2020-10)
    The development of chronic kidney disease in persons with Type 2 diabetes has been described as an epidemic. Standard outpatient care for these associated conditions is routinely provided separately, resulting in missed opportunities to implement preventative and early management strategies. Historically, care delivery for these combined conditions has fallen within the remit of medical professionals, evidenced by a dearth of information pertaining to the contribution of advanced practice nursing for this cohort. Clients report an uncoordinated impersonal approach to care delivery for associated conditions, however incorporating their experience is vital to the delivery of patient centered care and will be included in this study through their stories. The primary aim of this participatory action research (PAR) study is to utilize the client care stories and health-care professional perspectives to inform development and implementation of a new combined Type 2 diabetes and chronic kidney disease service in the context of advanced practice nursing. Methodology: This study adopted a PAR approach informed by patient discovery interviews and key stakeholders focus groups. Transcripts will be developed from discovery interviews and focus groups and analyzed using thematic analysis. Results: The PAR will utilize thematic analysis outcomes to inform the primary aim and clinical outcomes from combined care will be evaluated after 9 months by retrospective chart review. Conclusion: The approach adopted in this study represents a departure from traditional medically led care strategies. Outcomes may elucidate potential challenges to the development and delivery of innovative care delivery for underserved patient cohorts in the context of advanced practice nursing.
  • 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”.
  • 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.
  • 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.
  • 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).
  • 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.
  • MR vs CT imaging: low rectal cancer tumour delineation for three-dimensional conformal radiotherapy.

    O'Neill, B D P; Salerno, G; Thomas, K; Tait, D M; Brown, G (British Institute of Radiology, 2009-06)
    Modern three-dimentional radiotherapy is based upon CT. For rectal cancer, this relies upon target definition on CT, which is not the optimal imaging modality. The major limitation of CT is its low inherent contrast resolution. Targets defined by MRI could facilitate smaller, more accurate, tumour volumes than CT. Our study reviewed imaging and planning data for 10 patients with locally advanced low rectal cancer (defined as < 6 cm from the anal verge on digital examination). Tumour volume and location were compared for sagittal pre-treatment MRI and planning CT. CT consistently overestimated all tumour radiological parameters. Estimates of tumour volume, tumour length and height of proximal tumour from the anal verge were larger on planning CT than on MRI (p < 0.05). Tumour volumes defined on MRI are smaller, shorter and more distal from the anal sphincter than CT-based volumes. For radiotherapy planning, this may result in smaller treatment volumes, which could lead to a reduction in dose to organs at risk and facilitate dose escalation.
  • Monoamine oxidase inhibitors l-deprenyl and clorgyline protect nonmalignant human cells from ionising radiation and chemotherapy toxicity.

    Seymour, C B; Mothersill, C; Mooney, R; Moriarty, M; Tipton, K F (London, Lewis, 2003-11-17)
    l-Deprenyl (R-(-)-deprenyl, selegiline) is an inhibitor of monoamine oxidase-B (MAO-B) that is known to protect nerve cells from a variety of chemical and physical insults. As apoptosis is a common mechanism of radiation-induced cell death, the effect of l-deprenyl on the survival of cultured cells and tissue explants was studied following exposure to gamma radiation. The results obtained were compared with the effects of the less-selective MAO-B inhibitor pargyline and the MAO-A inhibitor clorgyline. l-Deprenyl at a concentration of 10(-9) M protected the nontumorigenic cell line (HaCaT) and normal human urothelial explants from the effects of cobalt-60 gamma radiation, but did not protect tumorigenic human cell lines HaCaT-ras, HPV-transfected human keratinocytes (HPV-G cells), or PC3. Human bladder carcinoma explants were not protected. Clorgyline showed a smaller protective effect of normal cells, whereas pargyline had no effect. Radiation-induced delayed effects (genomic instability measured as delayed cell death) were prevented in normal cells by l-deprenyl but, interestingly, deprenyl appeared to increase the amount of delayed death in the tumorigenic cell lines. Studies using l-deprenyl prior to the exposure of nonmalignant cells to cisplatin showed that cell death due to this agent was also reduced. Treatment of cultures of nontumorigenic cells with l-deprenyl or clorgyline significantly increased the levels of the protein Bcl-2 following irradiation, but there was no such effect on the already-elevated levels of this protein in the tumour samples. Since the Bcl-2 has been shown to be an inhibitor of apoptosis or programmed cell death, this would imply that the protective effects of l-deprenyl and clorgyline involve activation of antiapoptotic pathways within the normal cell. This hypothesis is supported by data showing reduced levels of apoptosis in HaCAT cells and in normal bladder explant cultures following treatment with l-deprenyl.
  • 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%).
  • Primary thromboprophylaxis for cancer patients with central venous catheters--a reappraisal of the evidence.

    Cunningham, M S; White, B; Hollywood, D; O'Donnell, J (2006-01-30)
    Venous thromboembolism (VTE) is responsible for an estimated 25 000 deaths per annum in UK hospital practice. It is well established that many of these deaths could be prevented through the use of appropriate thromboprophylaxis. This issue is of particular relevance in oncology practice, where the risks of VTE and bleeding are both significantly higher than those observed in general medical patients. Cancer patients with in-dwelling central venous catheters (CVCs) are at particularly high risk of developing thrombotic complications. However, the literature has produced conflicting conclusions regarding the efficacy of using routine primary thromboprophylaxis in these patients. Indeed such is the level of confusion around this topic, that the most recent version of the American College of Chest Physicians (ACCP) guidelines published in 2004 actually reversed their previous recommendation (published in 2001). Nevertheless, minidose warfarin continues to be routinely used in many oncology centres in the UK. In this article, we have performed a systematic review of the published literature regarding the efficacy and the risks, associated with using thromboprophylaxis (either minidose warfarin or low-dose LMWH) in cancer patients with CVC. On the basis of this evidence, we conclude that there is no proven role for using such thromboprophylaxis. However, asymptomatic CVC-related venous thrombosis remains common, and further more highly powered studies of better design are needed in order to define whether specific subgroups of cancer patients might benefit from receiving thromboprophylaxis.
  • 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.
  • Preventing treatment errors in radiotherapy by identifying and evaluating near misses and actual incidents

    Holmberg, Ola; McClean, Brendan (Cambridge University Press, 2002-06)
    When preparing radiation treatment, the prescribed dose and irradiation geometry must be translated into physical machine parameters. An error in the calculations or machine settings can negatively affect the intended treatment outcome. Analysing incidents originating in the treatment preparation chain makes it possible to find weak links and prevent treatment errors. The aim of this work is to study the effectiveness of a multilayered error prevention system by analysing both near misses and actual treatment errors.
  • The involvement of calcium and MAP kinase signaling pathways in the production of radiation-induced bystander effects.

    Lyng, F M; Maguire, P; McClean, B; Seymour, C; Mothersill, C (2006-04)
    Much evidence now exists regarding radiation-induced bystander effects, but the mechanisms involved in the transduction of the signal are still unclear. The mitogen-activated protein kinase (MAPK) pathways have been linked to growth factor-mediated regulation of cellular events such as proliferation, senescence, differentiation and apoptosis. Activation of multiple MAPK pathways such as the ERK, JNK and p38 pathways have been shown to occur after exposure of cells to radiation and a variety of other toxic stresses. Previous studies have shown oxidative stress and calcium signaling to be important in radiation-induced bystander effects. The aim of the present study was to investigate MAPK signaling pathways in bystander cells exposed to irradiated cell conditioned medium (ICCM) and the role of oxidative metabolism and calcium signaling in the induction of bystander responses. Human keratinocytes (HPV-G cell line) were irradiated (0.005-5 Gy) using a cobalt-60 teletherapy unit. The medium was harvested 1 h postirradiation and transferred to recipient HPV-G cells. Phosphorylated forms of p38, JNK and ERK were studied by immunofluorescence 30 min-24 h after exposure to ICCM. Inhibitors of the ERK pathway (PD98059 and U0126), the JNK pathway (SP600125), and the p38 pathway (SB203580) were used to investigate whether bystander-induced cell death could be blocked. Cells were also incubated with ICCM in the presence of superoxide dismutase, catalase, EGTA, verapamil, nifedipine and thapsigargin to investigate whether bystander effects could be inhibited because of the known effects on calcium homeostasis. Activated forms of JNK and ERK proteins were observed after exposure to ICCM. Inhibition of the ERK pathway appeared to increase bystander-induced apoptosis, while inhibition of the JNK pathway appeared to decrease apoptosis. In addition, reactive oxygen species, such as superoxide and hydrogen peroxide, and calcium signaling were found to be important modulators of bystander responses. Further investigations of these signaling pathways may aid in the identification of novel therapeutic targets.
  • Modulation of Radiation responses by pre-exposure to irradiated Cell conditioned medium.

    Maguire, Paula; Mothersill, Carmel; McClean, Brendan; Seymour, Colin; Lyng, Fiona M (Radiation Research Society, 2007-04)
    The aim of this study was to investigate whether exposure of HPV-G cells to irradiated cell conditioned medium (ICCM) could induce an adaptive response if the cells were subsequently challenged with a higher ICCM dose. Clonogenic survival and major steps in the cascade leading to apoptosis, such as calcium influx and loss of mitochondrial membrane potential, were examined to determine whether these events could be modified by giving a priming dose of ICCM before the challenge dose. Clonogenic survival data indicated an ICCM-induced adaptive response in HPV-G cells "primed" with 5 mGy or 0.5 Gy ICCM for 24 h and then exposed to 0.5 Gy or 5 Gy ICCM. Reactive oxygen species (ROS) were found to be involved in the bystander-induced cell death. Calcium fluxes varied in magnitude across the exposed cell population, and a significant number of the primed HPV-G cells did not respond to the challenge ICCM dose. No significant loss of mitochondrial membrane potential was observed when HPV-G cells were exposed to 0.5 Gy ICCM for 24 h followed by exposure to 5 Gy ICCM for 6 h. Exposure of HPV-G cells to 5 mGy ICCM for 24 h followed by exposure to 0.5 Gy ICCM for 18 h caused a significant increase in mitochondrial mass and a change in mitochondrial location, events associated with the perpetuation of genomic instability. This study has shown that a priming dose of ICCM has the ability to induce an adaptive response in HPV-G cells subsequently exposed to a challenge dose of ICCM.
  • 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.
  • Review of surface dose detectors in radiotherapy

    O'Shea, E.; McCavana, P. (2006-11-20)
    Several instruments have been used to measure absorbed radiation dose under non-electronic equilibrium conditions, such as in the build-up region or near the interface between two different media, including the surface. Many of these detectors are discussed in this paper. A common method of measuring the absorbed dose distribution and electron contamination in the build-up region of high-energy beams for radiation therapy is by means of parallel-plate ionisation chambers. Thermoluminescent dosimeters (TLDs), diodes and radiographic film have also been used to obtain surface dose measurements. The diamond detector was used recently by the author in an investigation on the effects of beam-modifying devices on skin dose and it is also described in this report
  • 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.

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