Mary Dunne - Academia.edu (original) (raw)

Papers by Mary Dunne

International Journal of Molecular Sciences

The quest for the discovery and validation of radiosensitivity biomarkers is ongoing and while co... more The quest for the discovery and validation of radiosensitivity biomarkers is ongoing and while conventional bioassays are well established as biomarkers, molecular advances have unveiled new emerging biomarkers. Herein, we present the validation of a new 4-gene signature panel of CDKN1, FDXR, SESN1 and PCNA previously reported to be radiation-responsive genes, using the conventional G2 chromosomal radiosensitivity assay. Radiation-induced G2 chromosomal radiosensitivity at 0.05 Gy and 0.5 Gy IR is presented for a healthy control (n = 45) and a prostate cancer (n = 14) donor cohort. For the prostate cancer cohort, data from two sampling time points (baseline and Androgen Deprivation Therapy (ADT)) is provided, and a significant difference (p > 0.001) between 0.05 Gy and 0.5 Gy was evident for all donor cohorts. Selected donor samples from each cohort also exposed to 0.05 Gy and 0.5 Gy IR were analysed for relative gene expression of the 4-gene signature. In the healthy donor cohor...

Journal of Radiotherapy in Practice

Aim: This work compares dose-volume constraints (DVCs) and tumour control predictions based on th... more Aim: This work compares dose-volume constraints (DVCs) and tumour control predictions based on the average intensity projection (AVIP) to those on each phase of the four-dimensional computed tomography. Materials and methods: In this prospective study plans generated on an AVIP for nine patients with locally advanced non-small-cell lung cancer were recalculated on each phase. Dose-volume histogram (DVH) metrics extracted and tumour control probabilities (TCP) were calculated. These were evaluated by Bland–Altman analysis and Pearson Correlation. Results: The largest difference between clinical target volume (CTV) on the individual phases and the internal CTV (iCTV) on the AVIP was seen for the smallest volume. For the planning target volume, the mean of each metric across all phases is well represented by the AVIP value. For most patients, TCPs from individual phases are representative of that on the AVIP. Organ at risk metrics from the AVIP are similar to those seen across all phas...

Translational Biophotonics

Cancer Medicine

This is an open access article under the terms of the Creative Commons Attribution License, which... more This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Frontiers in Oncology

Background: The role of stereotactic radiosurgery (SRS) in the treatment of limited numbers of br... more Background: The role of stereotactic radiosurgery (SRS) in the treatment of limited numbers of brain metastases in selected breast cancer patients is well-established. Aims: To analyse outcome from a single institutional experience with SRS, to identify any significant prognostic factors and to assess the influence of Her-2, estrogen receptor status, and prescribed dose on outcome. Methods: The medical records of 56 patients treated at in a single institution between 2009 and 2014 were reviewed. Demographic, treatment related and outcome data were analyzed to identify prognostic factors in this patient population. The primary endpoints were overall survival and local control. Secondary endpoint was distant intra-cranial progression-free survival. Results: The median follow-up time for the entire cohort was 10.33 months (1.25-97.28). The overall median survival was 12.5months (95%CI= 5.8-19.2), with 53.3%, and 35.8% surviving at 1-and 2-years post-SRS. After adjustment for the effect of Her 2 status, uncontrolled extra-cranial disease at the time of SRS predicted for shorter survival (HR for death = 3.1, 95% CI= 1.4-6.9, p = 0.006). At the time of death, 75% of the patients had active, uncontrolled intra-cranial disease, with 56% these patients presenting intra-cranial disease only. Sustained local control was observed in 56 (59.6%) of 94 treated metastases. In univariate analysis, Her2 status, ERHer2 group status?, and prescribed SRS dose were highly significant for local progression free-survival (LPFS). After adjustment for the effect of Her 2 status, patients receiving 12-16 Gy can expect shorter LPFS than those receiving 18-20 Gy (HR = 1.7, 95% CI = 1.0-2.8, p = 0.043). After adjustment for the effect of dose group, patients with Her 2 negative cancer can expect shorter LPFS than those with Her 2 positive cancer (HR = 2.6, 95% CI = 1.5-4.4, p < 0.0005). Use of prior WBRT did not impact survival, local or distant intra-cranial progression-free survival. Armstrong et al. SRS Brain Metastases Breast Primary Conclusions: Survival outcome is similar to the published literature. Improved outcomes are observed in patients with Her 2-positive, controlled extracranial disease at the time of SRS and higher SRS dose delivered. Achieving intra-cranial control appears to be an important factor for the survival of the breast cancer patients in the era of targeted therapies.

Ocular Oncology and Pathology

Purpose: To report the clinical features and epidemiology of uveal melanoma in Ireland. Methods: ... more Purpose: To report the clinical features and epidemiology of uveal melanoma in Ireland. Methods: This was an observational study of 253 patients with a new diagnosis of uveal melanoma between June 2010 and December 2015. Main outcome measures included demographics, clinical features, age-adjusted incidence, relative survival, overall survival, and distant metastases-free survival. Results: The mean patient age was 61.7 years. Tumour location was choroidal in 82%, ciliochoroidal in 9%, iridociliary in 2%, and iris in 7%. Treatment modalities included brachytherapy (ruthenium-106 and iodine-125 [64%]), enucleation (27%), and proton beam radiation (8%). The mean age-adjusted incidence of uveal melanoma in Ireland from 2010 to 2015 was 9.5 per million of the population (95% confidence interval [CI]: 8.4–10.7). Four-year relative survival was 81.3% (95% CI: 72.8–87.3). Four-year overall survival was 84% (95% CI: 78–90) and 4-year distant metastases-free survival was 79% (95% CI: 73–86). ...

Journal of Medical Imaging and Radiation Oncology

The British journal of radiology, Jan 27, 2018

The aim of this study is to investigate if a handheld ultrasound device (BladderScan® BVI 6100)... more The aim of this study is to investigate if a handheld ultrasound device (BladderScan® BVI 6100) can accurately measure bladder volumes in prostate radiotherapy (RT) patients. A comparison was made of contoured bladder volumes based on treatment planning CT (TPCT) and BladderScan® BVI 6100 ultrasound device in a large prostate RT population. Three bladder volume (BV) measurements were taken using the bladder volume instrument (BVI) device on prostate RT patients immediately prior to TPCT (n = 190). The CT delineation bladder volumes were also recorded. The mean of the three BVI readings (BVI) and the maximum (BVI) of the readings were considered for a comparative analysis. There was a strong positive correlation between the BVI and CT delineated bladder volumes (BVI r = 0.825; BVI r = 0.830). The mean difference [± standard deviation (SD)] was an underestimation of BV for both BVI and BVI (44.8 ± 88.2 ml and 32.9 ± 87.5 ml, respectively). This is the largest study to date (n = 190)...

$Research paper thumbnail of The potential for increased tumor control probability in non-small cell lung cancer with a hypofractionated integrated boost to the gross tumor volume$

Medical dosimetry : official journal of the American Association of Medical Dosimetrists, Jan 27, 2017

Treatment outcomes in locally advanced non-small cell lung cancer (NSCLC) to date have been poor,... more Treatment outcomes in locally advanced non-small cell lung cancer (NSCLC) to date have been poor, with normal tissue toxicity often limiting the dose that can be delivered to the tumor. Treatment intensification in NSCLC via targeted dose escalation with modern delivery techniques may offer the potential for a significant increase in tumor control probability (TCP) without a clinically significant increase in organ-at-risk (OAR) toxicity. In this planning study, 20 patients were re-planned with a volumetric modulated arc therapy (VMAT) and an inhomogeneous dose distribution with iteratively escalated doses to the gross tumor volume (iGTV) (composite GTV across multiple 4-dimensional computed tomography [4DCT] phases) in a series of 20 fraction regimes. For each plan OAR doses, target coverage and predicted TCPs were collected and compared with homogenous 3-dimensional (3D) and VMAT plans, as well as with each other. In 70% of patients, it was possible to escalate to 75 Gy in 20 frac...

Journal of radiosurgery and SBRT, 2017

To evaluate the clinical outcomes of patients with OMD from a CRC primary, who underwent SABR eit... more To evaluate the clinical outcomes of patients with OMD from a CRC primary, who underwent SABR either as first treatment at diagnosis of metachronous oligometastatic disease to lung or at progression in lung after prior treatments for metastatic disease. This is a retrospective review of 60 patients with 85 lung oligometastases treated by SABR at two institutions, between May 2009 and September 2014. Local control (LC), overall survival (OS), progression - free survival (PFS), and toxicity were evaluated. Median follow-up was 22.9±15.5 months (range: 2.6-68.6). For the entire cohort, LC was observed for 76.6% of the target lesions; the 2- year OS and PFS were 77% and 28 % respectively. After a median of 7.9 months from SABR, 39 patients presented a first progression. In univariate analysis, patients with multiple recurrences prior to SABR (p=0.001) and those who received chemotherapy for metastatic progression (p=0.014) had poorer PFS from time of SABR. Median PFS for patients with n...

International journal of radiation biology, Jan 12, 2018

Liquid biopsies are a potentially rich store of biochemical information that can be linked to an ... more Liquid biopsies are a potentially rich store of biochemical information that can be linked to an individual's response to therapeutic treatments, including radiotherapy, and which may ultimately play a role in the individualization of treatment regimens. Peripheral blood mononuclear cells (PBMCs) can be used for the biochemical profiling of the individual, but also, being living cells, can provide insights into the individuals response to ionizing radiation exposure. The present study attempts to link the biochemical profile of lymphocytes within PBMCs obtained through Raman spectroscopy, to in-vitro measures of low-dose (< 0.5Gy) DNA damage response and cytogenetic metrics of radiosensitivity in a cohort of healthy controls and prostate cancer patients (from CTRIAL-IE(ICORG) 08-17, NCT00951535). All parallel metrics to the Raman spectra of the cells were obtained ex-vivo in cycling peripheral blood lymphocytes, with radiosensitivity estimated using the G2 chromosomal assay a...

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, May 13, 2018

Cancer Trials Ireland (ICORG) 06-34: A multi-centre clinical trial using three-dimensional confor... more Cancer Trials Ireland (ICORG) 06-34: A multi-centre clinical trial using three-dimensional conformal radiation therapy to reduce the toxicity of palliative radiation for lung cancer. NCT01176487. Trials of radiation therapy for the palliation of intra-thoracic symptoms from locally advanced non-small cell lung cancer (NSCLC) have concentrated on optimising fractionation and dose schedules. In these trials, the rates of oesophagitis induced by this "palliative" therapy have been unacceptably high. In contrast, this non-randomised, single-arm trial was designed to assess if more technically advanced treatment techniques would result in equivalent symptom relief and reduce the side-effect of symptomatic oesophagitis. Thirty-five evaluable patients with symptomatic locally advanced or metastatic NSCLC were treated using a three-dimensional conformal technique (3-DCRT) and standardised dose regimens of 39 Gy in 13 fractions, 20 Gy in 5 fractions or 17 Gy in 2 fractions. Treatme...

BMC Urology

Background: Our aim was to assess the heterogeneity of high-risk (HR) prostate cancer managed wit... more Background: 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). Methods: We identified 547 patients who were treated with modern EBRT from 1997 to 2013, of whom 98% received ADT. We analyzed biochemical relapse-free survival (bRFS) and distant metastases-free survival (DMFS). Results: Median EBRT dose was 74 Gy, and median ADT duration was 8 months. At 5 years, the DMFS was 85%. On multivariate analysis, significant predictors of shorter bRFS were biopsy Gleason score (bGS) of 8 to 10, higher prostate-specific antigen (PSA) level, shorter duration of ADT and lower radiation dose while predictors of shorter DMFS were bGS of 8 to 10, higher PSA level, and lower radiation dose. We identified an unfavorable high-risk (UHR) group of with 2-3 HR factors based on 2015 National Comprehensive Cancer Network (NCCN) criteria and a favorable high-risk (FHR) group, with 1 HR feature. Comparing very-HR prostate cancer, UHR & FHR, 5 year bRFS rates were 58.2%, 66.2%, and 69.2%, and 5 year DMFS rates were 78.4%, 81.2%, and 88.0%. Conclusion: Patients with multiple HR factors have worse outcome than patients with 1 HR factor. Future studies should account for this heterogeneity in HR prostate cancer.

Radiotherapy and Oncology

$Research paper thumbnail of Hypofractionated accelerated high-dose radiotherapy (RT) in non-small cell lung cancer (NSCLC)$

Journal of Clinical Oncology

Background: Dose escalation and RT intensification may improve local control in NSCLC but may pot... more Background: Dose escalation and RT intensification may improve local control in NSCLC but may potentially increase late toxicity. We postulated that accelerated hypofractionated RT is safe and efficacious with use of 3D-CRT and application of strict dose volume constraints (DVC). Methods: 50 patients with stage 1-3 medically inoperable/unresectable NSCLC, with weight loss less than 10% and KPS &amp;amp;amp;amp;amp;amp;gt;70% were enrolled

Journal of geriatric oncology, Jan 23, 2016

In this study we evaluate the usefulness of the Edmonton Frail Scale (EFS) in predicting which ol... more In this study we evaluate the usefulness of the Edmonton Frail Scale (EFS) in predicting which older patients are at risk of developing serious toxicities during radiotherapy. This prospective study was carried out over an 18month period. Our primary aim was to examine the Edmonton Frail Scale (EFS) as a predictor of toxicity in patients over 70years undergoing radical radiotherapy for any malignant diagnosis. 63 patients were recruited: 29% experienced grade 3 or greater toxicities, with very few having multiple grade 3 or greater toxicities. The majority of patients experienced multiple grade 1 or 2 toxicities. Patients were often admitted: either electively due to geographical reasons, or due to toxicities. All patients completed their courses of radiotherapy. All grade 3 or 4 toxicities occurred within five radiotherapy sites; upper GI, gynaecological, lung, prostate and head & neck. There was no statistical correlation between EFS score and the presence of grade 3 or 4 toxiciti...

The Analyst, Jan 21, 2016

Extensive research has been undertaken on the examination of tissue biopsies using vibrational sp... more Extensive research has been undertaken on the examination of tissue biopsies using vibrational spectroscopic techniques. However, fewer studies have focused on less invasive and commonly acquired blood samples. Recent studies have shown the ability of Raman and Fourier transform infrared (FTIR) spectroscopy to discriminate between non-cancer controls and cancer cases using blood serum or plasma. Even though many studies have proposed Raman spectroscopy as a potential diagnostic tool in various cancers, the Raman spectroscopic technique has not been introduced as a routine clinical technology. This is due to multiple drawbacks with the application of the technique, including sample preparation, the requirement for expensive substrates and long acquisition times. The current study aims to overcome these limitations and focuses on the translation of Raman spectroscopy into a high throughput clinical diagnostic tool for prostate cancer. In this study, the effect of different instrumenta...

Dunne Mary T a Modified Mathematical Model For Hiv Transmission Aids and Intervention Strategies in Ireland Master of Science Thesis Dublin City University, 1995