Prospective randomised phase II trial evaluating adjuvant pelvic radiotherapy using either IMRT or 3-Dimensional planning for endometrial cancer.

Objective: To compare the incidence of grade ≥2 gastrointestinal (GI) or genitourinary (GU) toxicity for patients undergoing 3DRT versus IMRT in the postoperative setting for endometrial cancer.

Methods: Eligible patients were post-operatively randomly assigned to one of two parallel groups in a 1:1 ratio, to have their RT delivered using either a 3DRT technique or using IMRT. The prescription dose was 45 Gy in 25 fractions over 5 weeks followed by vaginal vault brachytherapy.

Efficacy and toxicity of primary re-irradiation for malignant spinal cord compression based on radiobiological modelling: a phase II clinical trial.

Background: The efficacy and safety of primary re-irradiation for MSCC are not known. Our aim was to establish the efficacy and safety of biologically effective dose-based re-irradiation.

Methods: Patients presenting with MSCC at a previously irradiated spine segment, and not proceeding with surgical decompression, were eligible.

The SARS-CoV-2 Pandemic and Cancer Trials Ireland: Impact, Resolution and Legacy.

Background: Cancer Trials Ireland (CTI) is the national cooperative group in Ireland. The SARS-CoV-2 pandemic led to significant ongoing disruptive change in healthcare from March 2020 to the present day. Its impact and legacy on a national clinical trials organisation was assessed.

A 4-Gene Signature of CDKN1, FDXR, SESN1 and PCNA Radiation Biomarkers for Prediction of Patient Radiosensitivity.

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.

Perinatal social work during the Covid-19 pandemic: Reflecting on concepts of time and liminality.

This article reflects upon the experiences of two perinatal, hospital social workers during the unprecedented time of the Covid-19 in Ireland, as discussed with their academic colleague. This encounter revealed the complexity of service delivery that emerged, when managing the needs of vulnerable clients whilst being mindful of personal safety. One of the social workers was pregnant so was conscious of possible risks to her unborn child, as well as her young family at home.

Vibrational spectroscopy of liquid biopsies for prostate cancer diagnosis.

Background: Screening for prostate cancer with prostate specific antigen and digital rectal examination allows early diagnosis of prostate malignancy but has been associated with poor sensitivity and specificity. There is also a considerable risk of over-diagnosis and over-treatment, which highlights the need for better tools for diagnosis of prostate cancer. This study investigates the potential of high throughput Raman and Fourier Transform Infrared (FTIR) spectroscopy of liquid biopsies for rapid and accurate diagnosis of prostate cancer.

Effect of hemolysis on Fourier transform infrared and Raman spectra of blood plasma.

Hemolysis is a very common phenomenon and is referred as the release of intracellular components from red blood cells to the extracellular fluid. Hemolyzed samples are often rejected in clinics due to the interference of hemoglobin and intracellular components in laboratory measurements. Plasma and serum based vibrational spectroscopy studies are extensively applied to generate spectral biomarkers for various diseases.

Non-inferiority randomised phase 3 trial comparing two radiation schedules (single vs. five fractions) in malignant spinal cord compression.

Background: The optimal EBRT schedule for MSCC is undetermined. Our aim was to determine whether a single fraction (SF) was non-inferior to five daily fractions (5Fx), for functional motor outcome.

Methods: Patients not proceeding with surgical decompression in this multicentre non-inferiority, Phase 3 trial were randomised to 10 Gy/SF or 20 Gy/5Fx.

Monitoring Radiotherapeutic Response in Prostate Cancer Patients Using High Throughput FTIR Spectroscopy of Liquid Biopsies.

Radiation therapy (RT) is used to treat approximately 50% of all cancer patients. However, RT causes a wide range of adverse late effects that can affect a patient's quality of life. There are currently no predictive assays in clinical use to identify patients at risk of normal tissue radiation toxicity.

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.

Title: 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.

Background & Purpose: 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.

Prediction of DNA damage and G2 chromosomal radio-sensitivity ex vivo in peripheral blood mononuclear cells with label-free Raman micro-spectroscopy.

Purpose: 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 not only for the biochemical profiling of the individual, but also, being living cells, can provide insights into the individuals response to ionizing radiation exposure.

Materials And Methods: 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.

Discovery and Longitudinal Evaluation of Candidate Protein Biomarkers for Disease Recurrence in Prostate Cancer.

When compared with hormonal therapy alone, treatment with combined hormone and radiation therapy (CHRT) gives improved disease-specific survival outcomes for patients with prostate cancer; however, a significant number of CHRT patients still succumb to recurrent disease. The purpose of this study was to use longitudinal patient samples obtained as part of an ongoing noninterventional clinical trial (ICORG06-15) to identify and evaluate a potential serum protein signature of disease recurrence. Label-free LC-MS/MS based protein discovery was undertaken on depleted serum samples from CHRT patients who showed evidence of disease recurrence (n = 3) and time-matched patient controls (n = 3).

Examining changes in [18 F]FDG and [18 F]FLT uptake in U87-MG glioma xenografts as early response biomarkers to treatment with the dual mTOR1/2 inhibitor AZD8055.

Purpose: The mTOR kinase inhibitor AZD8055 inhibits both mTORC1 and mTORC2 leading to disruption of glucose metabolism and proliferation pathways. This study assessed the impact of single and multiple doses of AZD8055 on the uptake of the glucose metabolism marker 2-deoxy-2-[(18) F]fluoro-D-glucose ([(18) F]FDG) and the proliferation marker 3'-deoxy-3'-[(18) F]fluorothymidine ([(18) F]FLT) in U87-MG glioma xenografts.

Procedures: Mice bearing U87-MG tumours received either vehicle or AZD8055 (20 mg/kg) once daily p.

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.

Purpose: 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.

An evaluation of 2-deoxy-2-[18F]fluoro-D-glucose and 3'-deoxy-3'-[18F]-fluorothymidine uptake in human tumor xenograft models.

Purpose: The aim of this study is to assess the variability of 2-deoxy-2-[(18)F]fluoro-D: -glucose ([(18)F]-FDG) and 3'-deoxy-3'-[(18)F]-fluorothymidine ([(18)F]-FLT) uptake in pre-clinical tumor models and examine the relationship between imaging data and related histological biomarkers.

Procedures: [(18)F]-FDG and [(18)F]-FLT studies were carried out in nine human tumor xenograft models in mice. A selection of the models underwent histological analysis for endpoints relevant to radiotracer uptake.

The mitogen-activated protein/extracellular signal-regulated kinase kinase 1/2 inhibitor AZD6244 (ARRY-142886) enhances the radiation responsiveness of lung and colorectal tumor xenografts.

Purpose: Novel molecularly targeted agents, given in combination with radiotherapy, have the potential to increase tumor response rates and the survival of patients with lung cancer. AZD6244 is a potent and selective inhibitor of mitogen-activated protein kinase (MAPK) kinase 1/2 (MEK1/2), a critical enzyme within the MAPK/extracellular signal-regulated kinase (ERK) signaling pathway that regulates the proliferation and survival of tumor cells.

Experimental Design: This study examined the potential benefit of combining AZD6244 with fractionated radiotherapy using human lung and colon carcinoma xenograft models.

Antiangiogenics and radiotherapy.

Antiangiogenic therapies are one of the fore-runners of the new generation of anticancer drugs aimed at tumour-specific molecular targets. Up until the beginning of this century, the general opinion was that targeted agents should show antitumour activity when used as single agents. However, it has now become clear that much greater improvements in therapeutic activity may be achieved by combining the novel agents with conventional cytotoxic therapies already in use in the clinic.

Combining radiotherapy with AZD2171, a potent inhibitor of vascular endothelial growth factor signaling: pathophysiologic effects and therapeutic benefit.

AZD2171 is a highly potent, orally active inhibitor of vascular endothelial growth factor receptor signaling. The potential for AZD2171 to enhance the antitumor effects of radiotherapy was investigated in lung (Calu-6) and colon (LoVo) human tumor xenograft models. Combined treatment resulted in a significantly enhanced growth delay compared with either modality alone.

Oncological implications of hypoxia inducible factor-1alpha (HIF-1alpha) expression.

Solid tumours contain regions of hypoxia, which may be a prognostic indicator and determinant of malignant progression, metastatic development and chemoradio-resistance. The degree of intra-tumoural hypoxia has been shown to be positively correlated with the expression of the transcription factor hypoxia-inducible factor 1. HIF-1 is composed of 2 sub-units, namely HIF-1alpha and HIF-1beta.

Tumour hypoxia, chemotherapeutic resistance and hypoxia-related therapies.

Tissue hypoxia occurs where there is an imbalance between oxygen supply and consumption. Hypoxia occurs in solid tumours as a result of an inadequate supply of oxygen, due to exponential cellular proliferation and an inefficient vascular supply. It is an adverse prognostic indicator in cancer as it is associated with tumour progression and resistance to therapy.