Predictive modelling of response to neoadjuvant therapy in HER2+ breast cancer.

HER2-positive (HER2+) breast cancer accounts for 20-25% of all breast cancers. Predictive biomarkers of neoadjuvant therapy response are needed to better identify patients with early stage disease who may benefit from tailored treatments in the adjuvant setting. As part of the TCHL phase-II clinical trial (ICORG10-05/NCT01485926) whole exome DNA sequencing was carried out on normal-tumour pairs collected from 22 patients.

An observational study of dose dense chemotherapy with lipegfilgrastim support in early breast cancer.

Purpose: Breast cancer is one of the most prevalent malignant diseases in women. The development of dose dense chemotherapy regimens has improved clinical outcomes but has been associated with increased hematological toxicity. Currently there is a paucity of data on the use of lipegfilgrastim in dose dense AC treatment in early breast cancer.

Oesophageal cancer metastases: An observational study of a more aggressive approach.

Background: The prognosis for oesophageal carcinoma is poor, but once distant metastases emerge the prognosis is considered hopeless. There is no consistent protocol for the early identification and aggressive management of metastases.

Aim: To examine the outcome of a policy of active postoperative surveillance with aggressive treatment of confirmed metastases.

Exhaled Breath Condensate (EBC) analysis of circulating tumour DNA (ctDNA) using a lung cancer specific UltraSEEK oncogene panel.

Introduction: Small diagnostic tissue samples can be inadequate in testing an expanding list of validated oncogenic driver alterations and fail to reflect intratumour heterogeneity (ITGH) in lung cancer. Liquid biopsies are non-invasive and may better reflect ITGH. Most liquid biopsies are performed in the context of circulating tumour DNA (ctDNA) in plasma but Exhaled Breath Condensate (EBC) shows promise as a lung-specific liquid biopsy.

BRCA mutations lead to XIAP overexpression and sensitise ovarian cancer to inhibitor of apoptosis (IAP) family inhibitors.

Background: We tested the hypothesis that inhibitor of apoptosis family (IAP) proteins may be altered in BRCA1-mutated ovarian cancers and that could affect the sensitivity to IAP inhibitors.

Methods: The levels of IAP proteins were evaluated in human cancers and cell lines. Cell lines were used to determine the effects of IAP inhibitors.

Trauma Assessment Clinic: A virtual fracture clinic model that delivers on its PROMise!

Background: The use of virtual fracture clinics across the United Kingdom and Ireland is growing and have been shown in an increasing number of studies to be safe, cost-effective and associated with good functional outcomes and patient satisfaction rates for certain fracture types. Initially pioneered at Glasgow Royal Infirmary, many centres have adopted similar templates, or variations of, and the overall aim of this study was to assess functional outcomes and injury recovery satisfaction rates of patients discharged directly following review in a specific virtual fracture clinic model known as the Trauma Assessment Clinic (TAC).

Methods: A prospective observational study was carried out of paediatric (aged <17 years) and adult (aged >17 years) patients, with the five most commonly observed fracture types, who were discharged directly following review at the TAC in a single hospital centre over a 12 month period from January to December 2018.

The cost of cancer care: how far would you go for a trial?

Background: Clinical trials are often considered the gold standard in cancer care. However, patients face barriers in trial participation including distances to cancer centres and personal costs including changing employment status, cost of medications, inpatient admissions, and parking tariffs.

Aim: Our aim was to compare the distances patients travelled for clinical trials compared to those receiving standard systemic anticancer therapy (SACT).

COVID-19-related mortality in cancer patients in an Irish setting.

Background: The COVID-19 pandemic has impacted significantly on healthcare across the globe. It has been reported to have higher incidence and be associated with worse outcomes in patients with cancer.

Aim: To examine the characteristics of patients with cancer who were diagnosed with COVID-19 and to identify factors which may predict a poorer outcome.

Tumour Genome Characterization of a Rare Case of Pulmonary Enteric Adenocarcinoma and Prior Colon Adenocarcinoma.

Pulmonary enteric adenocarcinoma (PEAC) is a rare variant of lung adenocarcinoma first described in the early 1990s in a lung tumour with overlapping lung and small intestine features. It is a rare tumour with fewer than 300 cases described in the published literature and was only formally classified in 2011. Given these characteristics the diagnosis is challenging, but even more so in a patient with prior gastrointestinal malignancy.

Pregnancy-associated breast cancer: evaluating maternal and foetal outcomes. A national study.

Purpose: Pregnancy-associated breast cancer (PABC) is defined as breast cancer diagnosed during the gestational period (gp-PABC) or in the first postpartum year (pp-PABC). Despite its infrequent occurrence, the incidence of PABC appears to be rising due to the increasing propensity for women to delay childbirth. We have established the first retrospective registry study of PABC in Ireland to examine specific clinicopathological characteristics, treatments, and maternal and foetal outcomes.

The role of infiltrating lymphocytes in the neo-adjuvant treatment of women with HER2-positive breast cancer.

Background: Pre-treatment tumour-associated lymphocytes (TILs) and stromal lymphocytes (SLs) are independent predictive markers of future pathological complete response (pCR) in HER2-positive breast cancer. Whilst studies have correlated baseline lymphocyte levels with subsequent pCR, few have studied the impact of neoadjuvant therapy on the immune environment.

Methods: We performed TIL analysis and T-cell analysis by IHC on the pretreatment and 'On-treatment' samples from patients recruited on the Phase-II TCHL (NCT01485926) clinical trial.

Delivery of systemic anti-cancer therapy during the COVID-19 pandemic.

Background: The first confirmed case of COVID-19 in Ireland was on February 29th 2020. From March until late April, the number of cases increased exponentially. The delivery of anti-cancer therapy during the COVID-19 pandemic was extremely challenging.

An exploration of the impact of ethanol diluent on breath alcohol concentration in patients receiving paclitaxel chemotherapy.

Purpose: This study aimed to provide a better understanding of the impact of paclitaxel chemotherapy on breath alcohol in an Irish population.

Methods: Patients attending the Oncology Day Unit at Beaumont Hospital were invited to participate on the day of their treatment. The brand of paclitaxel used was Actavis Pharma Inc and contained 6 mg/mL paclitaxel in 50% Ethanol/ 50% Cremophor EL.

Targeting the PI3K and MAPK pathways to improve response to HER2-targeted therapies in HER2-positive gastric cancer.

Background: Aberrant PI3K signalling is implicated in trastuzumab resistance in HER2-positive gastric cancer (GC). The role of PI3K or MEK inhibitors in sensitising HER2-positive GCs to trastuzumab or in overcoming trastuzumab resistance is unclear.

Methods: Using mass spectrometry-based genotyping we analysed 105 hotspot, non-synonymous somatic mutations in PIK3CA and ERBB-family (EGFR, ERBB2, ERBB3 and ERBB4) genes in gastric tumour samples from 69 patients.

Phase Ib Trial of Copanlisib, A Phosphoinositide-3 Kinase (PI3K) Inhibitor, with Trastuzumab in Advanced Pre-Treated HER2-Positive Breast Cancer "PantHER".

Background: Activation of the phosphoinositide-3 kinase (PI3K) pathway is a resistance mechanism to anti-human epidermal growth factor receptor 2 (HER2) therapy. This phase Ib trial was conducted to determine the maximum tolerated dose (MTD) of copanlisib, an intravenous (IV) pan-class I PI3K inhibitor, combined with trastuzumab.

Methods: Patients with advanced HER2-positive breast cancer and disease progression following at least one prior line of HER2 therapy in the metastatic setting were treated with copanlisib (45 or 60 mg) IV on days 1, 8 and 15 of a 28-day cycle with a fixed dose of trastuzumab 2 mg/kg weekly.

One year of procarbazine lomustine and vincristine is poorly tolerated in low grade glioma: a real world experience in a national neuro-oncology centre.

Background: Following optimal local therapy, adjuvant Procarbazine, Lomustine and Vincristine (PCV) improves overall survival (OS) in low-grade glioma (LGG). However, 1 year of PCV is associated with significant toxicities. In the pivotal RTOG 9802 randomised control trial, approximately half of the patients discontinued treatment after 6 months.

Chemotherapy in the Covid-19 era: the patient's perception.

Background: The Covid-19 pandemic poses significant challenges for the management of patients with cancer. In our institution, we adapted our delivery of outpatient systemic anti-cancer therapy (SACT) by introducing a number of 'risk-reducing' measures including pre-assessment screening.

Aims: We sought to evaluate the experience and perceptions of patients with cancer undergoing SACT during the Covid-19 pandemic.

Use of exhaled breath condensate (EBC) in the diagnosis of SARS-COV-2 (COVID-19).

False negatives from nasopharyngeal swabs (NPS) using reverse transcriptase PCR (RT-PCR) in SARS-CoV-2 are high. Exhaled breath condensate (EBC) contains lower respiratory droplets that may improve detection. We performed EBC RT-PCR for SARS-CoV-2 genes (E, S, N, ORF1ab) on NPS-positive (n=16) and NPS-negative/clinically positive COVID-19 patients (n=15) using two commercial assays.

Prevalence of tumor BRCA1 and BRCA2 dysfunction in unselected patients with ovarian cancer.

Objective: The therapeutic benefits of poly(ADP-ribose) polymerase inhibitors highlight the need to evaluate BRCA1/2 defects in tubal/ovarian cancer (OC). We sought to determine the pattern and disease characteristics associated with tumor BRCA1/2 mutations and BRCA1 methylation in women with OC.

Methods: We obtained 111 OC specimens from 2 university hospitals and assessed BRCA1/2 mutations and BRCA1 methylation in tumor DNA.

Challenges associated with systemic therapy for older patients with inoperable non-small cell lung cancer.

Introduction: Lung cancer is the most common cancer diagnosed worldwide. Data from several studies fall short to make appropriate conclusions on the management for elderly patients. The discovery of targeted therapy and immunotherapy has allowed these patients access to a wider array of options.

Lack of familiarity with genetic testing among patients in Ireland with Cancer.

Background: Cancer gene panel testing is available in Ireland. The need for a clear strategy to deal with patient information generated from tumour genomic testing is recognised as a challenge in the National Cancer Strategy. However, the public's attitude and opinions regarding these results is not known in Ireland.

Genomic and Transcriptomic Characterisation of Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer.

Standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (NACRT), followed by surgical resection. However, >70% of patients do not achieve a complete pathological response and have higher rates of relapse and death. There are no validated pre- or on-treatment factors that predict response to NACRT besides tumour stage and size.