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ISMO 2019 Fellowship and Bursary Awards

Paul Mulholland reports on the details of the 2019 Irish Society of Medical Oncology (ISMO) Fellowship and Bursary Awards in Dublin

The Irish Society of Medical Oncology (ISMO) Fellowship and Bursary Awards meeting took place in the Catherine McAuley Centre, the Mater Misericordiae University Hospital (MMUH), Dublin, on Friday, 25 January and Saturday, 26 January. As ever, the meeting featured the latest cutting edge research being carried about by young clinicians working in oncology in Ireland. The winners of the bursary awards were:
Dr Caitriona Goggin; Dr Colm Mac Eochagain; Dr Conor Moloney; Dr Dara Bracken-Clarke; Dr Eileen McMahon; Dr Fionnuala Crowley; Dr Iseult Browne; Dr Kate Coleman; Dr Lisa Prior; Dr Maeve Hennessy; Dr Michael Conroy; Dr Niamh Peters; Dr Paula Lynch; Dr Rachel Keogh; Dr Richard O’Dwyer; Dr Roshni Kalachand; Dr Sean Seltzer; Dr Veronica McSharry; Dr Wanyi Kee; and Dr Zac Coyne.
Dr Caitriona Goggin, St James’ Hospital, Dublin, spoke about education and engagement in cancer care by offering a patient perspective. Her study investigated patients’ experience and preferences regarding education on cancer diagnosis and treatment in St James’. This study showed that the majority of patients are happy with the education provided in the hospital. However given a reduced awareness of cancer type, stage and treatment, improved provision of education is required to tailor to individual patient needs.
The results of the study presented by Dr Colm Mac Eochagain, MMUH, concerned HPV vaccination among seropositive, DNA negative cohorts. A systematic review of double blinded RCTs of VLP-L1-based HPV vaccines was conducted between 2003 and 2018 with reported or derivable efficacy data, stratified by HrHPV strain (16/18), assesses across SCOPUS, EMBASE, PUBMED and CENTRAL databases. Of the 55,452 enrolled subjects, a total of 9,072 subjects were seropositive for prior HPV exposure by IgG and DNA negative at time of trial enrolment. Incident HPV-associated endpoints among the vaccine arm were 53/4470 as compared with 179/4602 in the placebo arm, corresponding to a HPV strain-specific vaccine efficacy of 73.3 per cent (95 per cent CI 65.5-85.0 per cent). According to Dr Mac Eochagain, this finding supports the expansion of vaccination programmes to include all subjects who currently test negative for HrHPV.
Dr Conor Moloney, Cork University Hospital (CUH), presented details about two cases of non-small cell to small cell transformation. He said these cases highlight the increasingly recognised subset of non-small-cell lung carcinoma (NSCLC) that undergo transformation to small-cell-lung carcinoma (SCLC). They also emphasise the importance of repeated biopsies in driver mutation-positive NSCLC progressing on treatment, and the role of continuing/restarting targeted therapy following treatment of the transformed SCLC.
The presentation by Dr Dara Bracken-Clarke, CUH, focused on the feasibility of and rationale for the introduction of an outpatient management of neutropaenic fever protocol in CUH. Febrile neutropaenia (FN) and neutropaenic sepsis represent some of the most common and, potentially, dangerous complications of cytotoxic chemotherapy. In an audit, the research team retrospectively assessed the risk scores for all patients admitted with FN to CUH during the period December 2017 to November 2018. In the cohort, total bed-days utilised for patients with FN were 438 with median length of stay (LoS) of six days and mean LoS of seven days. The most frequent cancer diagnoses were: Breast, lymphoma NSCLC and sarcoma.
“It is our hope, particularly given the present stresses to the Irish health system, that this may equate to a meaningful benefit in terms of bed-days required for treatment of FN cases,” said Dr Bracken-Clarke.
The presentation by Dr Eileen McMahon, CUH, concerned ‘Metronomic chemotherapy in advanced breast cancer: A single centre experience’. Patients who received at least one dose of metronomic chemotherapy in the form of capecitabine/cyclophosphamide for the treatment of advanced breast cancer from July 2013 and January 2019 were identified from the institutional database. Median overall survival for the group was 10 months (95 percent CI: 10.5-19.0), with a median follow-up of 12.5 months.
“An observational study of the utility of BRAF and MEK inhibitor targeted therapy in metastatic melanoma patients in a regional cancer centre” was the title of the paper presented by Dr Fionnuala Crowley, who is based in University College Cork (UCC). A retrospective chart review of all patients treated with dabrafenib alone or in combination with trametinib from May 2012 to September 2018 was carried out in CUH. Clinicopathologic variables were recorded. The clinical course of all patients was examined in detail. Treatment outcomes were measured using progression-free survival (PFS), overall survival (OS) and objective response rates (ORR).
“We had a very heterogeneous population in terms of baseline clinicopathological factors,” according to Dr Crowley.
The median OS of 18.19 months in patients without brain metastases was lower than the clinical trials median of 25.6 months.
“This is likely due to our heterogeneous population,” according to Dr Crowley. “Our overall response rate of 82 per cent was higher than the rate reported internationally. Our results highlight a statistically significant relationship between toxicity and PFS.”
Dr Iseult Browne, St Vincent’s University Hospital (SVUH), delivered a presentation focused on the ‘osimertinib experience in an Irish healthcare setting’. Osimertinib is a third generation EGFR inhibitor with activity against both standard activating EGFR mutations and T790M resistance mutations in patients with NSCLC. Although not yet reimbursed, osimertinib has been accessible to patients in Ireland via clinical trials and an expanded access programme. The aim of this project was to assess SVUH’s experience with osimertinib in an Irish population compared to the results observed in international clinical trials.
“We report a consistent safety profile with no new safety signals,” according to Dr Browne. “Osimertinib should be considered as a standard option for those with acquired T790M mutations post progression on first/second generation EGFR inhibitors in our patient population.”
Dr Kate Coleman, SVUH, Dublin, spoke about exploring the interface of oncology and palliative care (PC) in Ireland. The aim of her study was to explore the integration and delivery of oncology-led referrals to palliative care by examining oncologist attitudes and referral practices to help establish a comprehensive care model to match patient needs. The study (N=100) comprised 69 per cent oncologists (43 medical oncologists, 15 radiation oncologists and 11 haemato-oncologists) and 31 per cent PC physician participants.
“Our study demonstrated the willingness between oncologists and PC teams to work together to meet the needs of patients,” according to Dr Coleman.
“We highlighted the shared desire to provide PC in the acute hospital setting. The gulf between widely expressed positive attitudes and limited implementation suggests the need for more PC doctors, interdisciplinary and infrastructural change in clinical practice in Ireland. Our findings suggest service development is needed to make room in our current system to adopt initiatives such as those used in the Temel trial and to achieve the vision of the National Cancer Strategy by 2026.”
Patterns of treatment and outcomes of patients receiving palbociclib and endocrine therapy for metastatic ER+ breast cancer was the subject of the talk by Dr Lisa Prior, MMUH. A retrospective multicentre observational study of patients with metastatic ER+HER2- breast cancer who were treated with a combination of palbociclib and endocrine therapy between 2015 (introduction of compassionate access programme in Ireland) to October 2018 was conducted. Data extracted included information on patient demographics, disease characteristics, treatments received, toxicities, dose interruptions and delays, and survival outcomes. Standard biostatistical methods were used for analysis.
Dr Maeve Hennessy, Beaumont Hospital, Dublin, spoke about the survival of patients who have undergone re-resection for glioblastoma multiforme. A retrospective review of the BH Neuro-Oncology database was performed.
A total of 34 patients were eligible for inclusion into this study, of which 21 (61 per cent) were male. Median age was 52 years. A radiologically confirmed initial resection of >80 per cent was achieved in 52 per cent of patients. Median time from initial surgery to re-resection was 13.5 months. Median survival from initial surgery was 28.6 months and median survival after re-resection was 9.5 months.
“Our findings were in line with the current literature, overall survival in patients with glioblastoma is poor. Further studies into the benefit of re-resection in comparison to second-line chemotherapy and re-irradiation would be of value,” according to Dr Hennessy.
Dr Michael Conroy, St James’ Hospital, Dublin, spoke about prognostic factors in anaplastic thyroid carcinoma (ATC). For the study, a retrospective analysis of all ATCs identified in St James’ over 20 years was conducted. Demographic, pathologic, clinical and survival data were collected.
“Although the outlook for ATC patients is poor, some patients respond well to aggressive therapy and careful risk-stratification of patients is essential to guide appropriate treatment,” according to the study’s conclusion.
“A minority of ATCs harbour actionable molecular changes with BRAF mutations and NTRK fusions, and early testing is advised to help expedite treatment.”
Lung cancer in young people was the subject of a talk by Dr Niamh Peters, MMUH. All patients diagnosed with lung cancer between January 2015 and September 2018 and aged below 50 years were identified. Chart review to collect patient demographics, tumour characteristics and survival data was performed using electronic and paper medical records and an electronic prescribing system.
To allow for comparison of OS between young cancer patients and the standard population, a representative sample of patients diagnosed over the age of 50 years was generated. Kaplan Meier analysis was used to determine PFS and OS.
A total of 26 patients met study criteria, of which 58 per cent were men. The median age at diagnosis was 44 years (range 21-49 years). Almost one-in-five, 19 per cent, were diagnosed with small cell lung cancer and 81 per cent (21) with NSCLC. Of those with NSCLC, 66 per cent were of adenocarcinoma subtype and 15 per cent were of squamous cell subtype. Only 44 per cent of patients survived to receive more than one line of systemic treatment. At a median follow up of 10 months, 54 per cent of patients had died. Median time to progression was 6.5 months. Median OS of those under the age of 50 years was 9.36 months, compared to a survival of 9.2 months of those in the sample group. This was not statistically significant.
“Despite relatively good pre-morbid health and the frequent identification of an oncogenic driver mutation within their tumours, the clinical outcome for patients in our case series was poor, likely due to very late stage at presentation,” according to Dr Peters.
Cancer in young people was also the subject of Dr Paula Lynch’s presentation. Dr Lynch, MMUH, said it is well recognised that adolescents and young adults (AYAs) in medical oncology are an under-served group with complex medical needs. A database of patients attending the adult oncology services in MMUH aged 16-24 years from 2008-2018 was created. Patient records were used to collect patient demographics, pathological, radiological and clinical information.
A total of 81 AYA patients attended the adult medical oncology service in MMUH over the last 10 years for treatment or surveillance of their cancer. The majority of these patients were diagnosed and treated in MMUH. Only five patients were identified who graduated from paediatric services to adult oncology services. The majority of diagnoses are typical adolescent malignancies, with fewer adult malignancies and rarely paediatric tumour. Almost two-thirds, 62 per cent, of these patients are alive and the majority have ongoing follow-up.
The presentation of Dr Rachel Keogh, Beaumont Hospital, Dublin, concerned new drink legislation and chemotherapy drugs. As of 26 October 2018, ordinary fully licenced drivers detected with a blood alcohol level of 50-to-80mg will result in automatic disqualification from driving for three months and a fine of €200. Dr Keogh pointed out that alcohol is used in the formulation of several chemotherapy agents as a diluent. Paclitaxel appears to be the anti-cancer drug with the highest alcohol content. Macmillan recommends that any patients receiving paclitaxel do not drive for several hours after administration.
Currently, paclitaxel contains 391mg ethanol/ml with a drug concentration of 6mg/ml, so each patient receives approximately 65.1mg. In the case of breast cancer patients, they generally receive 80mg/m2. Therefore, patients with a BSA of 1.9m2 receive approximately 156mg (with dose banding). This would amount to about 10.1mg of ethanol. In Ireland, 10mg of pure ethanol is the equivalent of one standard drink. In the case of ovarian and occasionally lung cancer, patients receive the higher dose of 175mg/m2 three weekly. This would mean that the same patient would receive about a 342mg dose, which equals 22.2g of alcohol per dose, the equivalent to 2.2 standard drinks. Other chemotherapy agents that may be implicated include docetaxel, etoposide, cabazitaxel, melphalan, epirubicin, and temsirolimus, although these agents use lower amounts of alcohol.
The principal aim of the project discussed by Dr Keogh is to assess if patients in Beaumont Hospital on paclitaxel chemotherapy are over the legal limit to drive home when they have finished chemotherapy.
“The Road Traffic (Amendment) Act 2018 could have serious implications for oncology patients,” according to Dr Keogh.
‘Neutrophil to lymphocyte ratio (NLR): A prognostic marker in melanoma patients receiving immunotherapy?’ was the title of the talk by Dr Richard O’Dwyer, MMUH.
The records of patients with metastatic melanoma who had received immune checkpoint inhibitors between 2015 and 2018 in MMUH were examined. Continuous variables were expressed as a median. The NLR at baseline and at six weeks (+-two weeks) was checked. The research team also examined percentage change in NLR. These parameters were tested for association with PFS and OS using the log rank test.
Some 19 patients received immune checkpoint inhibitors in the form of ipilimumab, nivolumab, and pembrolizumab. The median age was 56 years (42.1 to 77.4 years). The median baseline NLR was 2.52 (1.3 to 15.8). The median NLR at six weeks (+-two weeks) was 2.63 (0.9 to 9.4). The median change in NLR was -22.3 per cent (-82 per cent to 119.6 per cent). There was no significant difference found in PFS in patients with higher baseline NLR (>2.5) (p=0.08), or higher NLR (>2.5) at six weeks (p=0.25).
“Our data suggests that in patients with metastatic melanoma undergoing immune checkpoint blockade, a lower baseline NLR and NLR at six weeks is not associated with a greater PFS,” according to the conclusion.
“Our study had a low number of patients and further work is warranted.”
Dr Roshni Kalachand, Beaumont Hospital, spoke about how targeting the PI3K pathway overcomes acquired resistance to platinum agents and PARP inhibitors in BRCA1-methylated ovarian cancer (BMOC). According to the results of the study, the addition of copanlisib to carboplatin or PARP inhibitors could represent a novel therapeutic strategy in BMOC that has acquired resistance to either carboplatin or PARP inhibitors.
Dr Sean Seltzer, CUH, examined expression signatures and clinical features of patients with de novo metastatic breast cancer. In this retrospective case-control study, gene expression and clinical data were accessed from the Cancer Genome Atlas (TCGA) for dnMBC cases (n=17) and relapsed control tumours (n=49).
“The work presented here demonstrates significant clinical and molecular differences between dnMBCs and relapse controls,” according to Dr Seltzer. “These differences translate into the gene ontology analysis where significant processes with known roles in cancer were observed and may contribute to the understanding of the molecular biology of these tumours as well as how they translate into the observed clinical presentation and patient outcomes.”
For her presentation, Dr Veronica McSharry, MMUH, spoke about the impact of nutritional intervention during chemotherapy for recurrent non-seminomatous germ cell cancer (GCC) on body composition. The report focused on the case of a 32-year-old man, who proceeded to left orchidectomy, which demonstrated a non-seminomatous germ cell tumour in July 2016.
“We report a case of recurrent GCC with treatment limiting obesity, which was improved with intensive nutritional counselling, making him eligible for oncological surgery,” according to Dr McSharry.
“This case demonstrates favourable body composition changes are achievable in patients with cancer following intensive nutritional support with a dietitian specialising in oncology. This outcome suggests beneficial changes for risk of CVD and type 2 diabetes in survivorship.”
‘Molecular targets in NSCLC: A real-world study on targetable and driver gene alterations, and PD-L1 expression levels in the Irish setting’ was the title of the talk given by Dr Wanyi Kee, School of Medicine, UCC. A retrospective medical record review of all NSCLC patients from CUH and Bon Secours Hospital, Cork, with samples sent for molecular testing between September 2009 and May 2018 was carried out. Targetable gene alterations were associated with a surrogate marker of higher socioeconomic status. Only 4.5 per cent of male smokers harboured a targetable gene alteration. KRAS mutations were more frequent in the Irish NSCLC population compared to other Caucasian populations. “Interestingly, patients with coexisting de novo resistance and sensitising EGFR alterations still exhibit sensitivity to erlotinib,” according to Dr Kee.
The presentation of Dr Zac Coyne, Beaumont Hospital, Dublin, examined the management challenges in an Irish symptomatic breast cancer unit. Patients who had undergone breast cancer surgery in Beaumont Hospital between 2014 and 2017 were identified from a prospectively maintained database.
“Beaumont Hospital symptomatic breast cancer unit sees a larger percentage of patients under 50 years compared to national statistics,” according to Dr Coyne. “As expected this patient population is enriched for HER2+ and triple negative breast cancer. Many of these patients require chemotherapy. In a subset analysis we have identified a high rate of documentation about important issues such as fertility, genetics and long-term complications.”

Keynote address
The keynote address of the ISMO meeting was delivered by Dr Victoria Makker, Consultant Medical Oncologist, Memorial Sloan Kettering Cancer Centre, New York, US. Dr Makker is a medical oncologist who focuses on the medical treatment of gynaecologic cancers and has a research interest in developing improved therapies for endometrial cancer. Her talk focused on endometrial cancer, which she described as a very “heterogeneous” disease. It is the sixth most common malignancy for females worldwide.
She said the prognosis for patients with early stage disease is “generally very good”; however, the prognosis for patients with advanced or recurrent disease is “poor”.
“When they present past frontline chemotherapy, the options are quite limited in terms of management.”
Currently in the US, there are only two FDA-approved agents for advanced endometrial cancer: Megestrol acetate for palliative treatment, and pembrolizumab for patients that are mismatch repair deficient (dMMR).
At last year’s ASCO meeting Dr Makker presented promising new data for the use of lenvatinib + pembrolizumab in patients with advanced endometrial cancer. The data came from Study 111/KEYNOTE-146, which was a multi-centre, open-label, single-arm phase 1b/2 basket trial evaluating the efficacy and safety of lenvatinib (20 mg/d) in combination with pembrolizumab (200mg intravenously every three weeks) in patients with selected solid tumours (renal cell carcinoma, endometrial carcinoma, NSCLC, urothelial cancer, squamous cell head and neck cancer, and melanoma).
The 53-patient endometrial cancer cohort had an objective response rate (ORR) at week 24 per independent radiology review of 45.3 per cent (95 per cent CI, 31.6-59.6). The overall ORR was 47.2 per cent (n=25; 95 per cent CI, 33.3-61.4), including three complete responses and 25 partial responses.
The combination of lenvatinib and pembrolizumab has been granted a breakthrough therapy designation by the FDA as a treatment for patients with advanced and/or metastatic non-microsatellite instability high (MSI-H)/proficient mismatch repair endometrial carcinoma who have progressed after ≥one prior systemic therapy.
Dr Makker said a phase 3 trial of the combination therapy was upcoming, adding it was a promising period for research into the disease.
“There are also a number of diet and exercise trials that are being launched or are in progress,” according to Dr Makker. “Chemotherapy in combination with immunotherapy drugs is being evaluated. Targeted therapy in combination with immunotherapy molecules are also being evaluated. So it is really a very exciting time to be an endometrial cancer researcher and I have to saw I feel truly privileged to work on this disease.”

Fellowship
Dr Makker helped select the two successful candidates for the ISMO Fellowship. This year’s winners are Dr Fergus Keane, Medical Oncology Specialist Registrar, Beaumont Hospital, Dublin, and Dr Jane Sui, Medical Oncology Higher Specialist, MMUH, Dublin. The Fellowship, which has been running since 2006, will be based in Memorial Sloan Kettering.

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