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ISMO Travel Bursary Awards 2021

The ISMO meeting featured some of the best cancer research currently being undertaken in Ireland

This year’s Irish Society of Medical Oncology (ISMO) annual meeting took place on Friday, 29 January 2021. As a result of Covid-19, the meeting was held virtually, streaming live from the Fintan Gunne Theatre, Catherine McAuley Centre, Mater Misericordiae University Hospital (MMUH), and only featured presentations relating to the Travel Bursary Awards (though there were also poster presentations). As usual, however, the meeting featured some of the best cancer research currently being undertaken in Ireland.

Breast cancer and pregnancy

The presentation of Dr Claire Foran, Cork University Hospital (CUH), was based on a case report, and was entitled ‘Pregnancy, pneumonia and PCP’.
A 36-year-old woman presented to the acute oncology service complaining of grade 3 mucositis and grade 2 fatigue on a background of oestrogen receptor positive (ER)/progesterone receptor (PR) positive/HER2-negative pregnancy-associated breast cancer (PABC). She was 33 weeks’ gestation at this time and four months post-mastectomy and axillary lymph node dissection for a P2N0 tumour. At the time of review, she was D11 post C6 AC (doxorubicin/cyclophosphamide).

On admission, she was noted to be tachycardic (110bpm). Laboratory tests demonstrated neutropaenia with an ANC of 0.47×109/L, an elevated CRP of 63.3mg/L and a raised lactate of 4mmol/L. She was admitted and empirically treated with intravenous Tazocin. Overnight, she clinically deteriorated with persistent pyrexia, worsening dyspnoea and increasing oxygen requirements.

Two SARS-CoV-2 tests did not detect the virus. Despite expanded antibiotic therapy, she continued to deteriorate over the coming days, with increasing oxygen requirements via high flow humidified oxygen (requiring up to 85 per cent Fi02).

A multidisciplinary approach to care included: Medical oncology, obstetrics, respiratory and infectious diseases physicians, microbiology, and anaesthetics. Chest imaging demonstrated a worsening atypical pneumonia, bronchoscopy and bronchoalveolar lavage was unremarkable. On day four of admission, a broader differential diagnosis was investigated including an extended respiratory viral panel. Despite this, cultures were negative, and on day seven of admission further pulmonary specimens were sent for microbiology analysis including pneumocystis pneumonia (PCP) PCR testing from bronchoscopy.

Post-bronchoscopy, antibiotics were escalated to include meropenem, antifungal and PCP cover with co-trimoxazole. Following urgent multidisciplinary discussion, an elective Caesarean section under general anaesthesia and intubation was performed. This was followed by transfer to intensive care for ventilation due to worsening respiratory failure despite escalation of treatment.

The neonate was transferred to a neonatal intensive care unit (NICU) for 34 weeks’ gestation prematurity and supportive management for transient tachypnoea of the newborn and no acute complications.

Despite a high incidence of brain metastases in those with NSCLC, little is known about the potential use of combined immune checkpoint inhibitors and chemotherapy

The woman improved significantly post Caesarean section and was extubated two days later. PCP-PCR testing confirmed the presence of PCP and a full 21-day treatment plan was implemented. She was transferred to the co-located maternity hospital high-dependency unit once stable for ongoing treatment after three days in ICU.

She made continued daily improvement and was discharged 19 days after her initial admission and her newborn son was subsequently discharged from NICU two weeks later.

According to Dr Foran, this case highlights “a rare complication of adjuvant breast cancer chemotherapy, the complexities and clinical volatility of its management in association with pregnancy and the lifesaving benefits of co-located maternity and medical services”.

Non-small cell lung cancer

The presentation of Dr Jennifer McGarry, Beacon Hospital, was entitled ‘Pembrolizumab-induced myasthenia gravis in a patient with metastatic non-small cell lung cancer to brain’.

She described the case of a 59-year-old male with stage IV non-small cell lung cancer (NSCLC) with metastases to brain, with no actionable mutations such as EGFR or ALK, but PDL1 positivity of >90 per cent, who underwent 10 fractions whole brain radiotherapy followed by two cycles of combined chemotherapy and immunotherapy (carboplatin, pembrolizumab and pemetrexed).

Three weeks after his second cycle of pembrolizumab he presented with a four-day history of eye drooping and neck weakness. Positive examination findings included ptosis bilaterally, limitation of right eye lateral abduction, severe limitation of upgaze, marked weakness of neck extension, and gait ataxia.

MRI B at admission demonstrated interval reduction in size and perilesional oedema within multiple brain metastases in the left frontal, right parietal, inferior left temporal, right occipital lobes and cerebellar vermis. No new intracranial metastases and no cause of symptoms were identified. CT thorax with contrast showed significant interval reduction in size of a large primary left upper lobe pulmonary mass and left hilar lymphadenopathy since previous imaging.

The patient deteriorated rapidly during the course of his stay, with profound neck weakness, ongoing ptosis as well as marked type 1 respiratory failure. Initial investigations revealed a CK of 2200. Pembrolizumab-induced myasthenia gravis with diaphragmatic crisis as well as immunotherapy-related myositis were hypothesised and the patient was commenced on 2mg/kg prednisolone, 40g per day IVIG, pyridostigmine 30mg three times daily. Peak flow monitoring was commenced hourly, with averages of 150mL at day one.

The patient required high flow oxygen and AIRVO to maintain oxygen saturations. He completed five days of IVIG, pyridostigmine was tapered up to 180 four times daily and steroids were tapered slowly. The patient demonstrated a marked improvement on these treatments, with complete resolution of oxygen requirement and normalised peak flows over the following week. Later investigations revealed elevated anti-striatal antibody of 320.

According to Dr McGarry, despite a high incidence of brain metastases in those with NSCLC, little is known about the potential use of combined immune checkpoint inhibitors and chemotherapy. In this case, the patient’s percentage of tumour cells expressing PDL1 ligand was 90 per cent.
“The use of pembrolizumab combined with whole brain radiotherapy and systemic chemotherapy led to a substantial reduction in tumour size both at the primary left upper lobe, but also in his numerous brain metastases,” according to the authors of the study.

“The alteration of the immune system may predispose to serious autoimmune conditions such as myasthenia gravis. In this case, despite developing this complication our patient responded well to steroids, IVIG and pyridostigmine.”

Multiplicities of malignancy

Dr Niamh Ryan, Bon Secours Hospital, Cork, delivered a presentation based on case studies she was involved in, which was entitled ‘The multiplicities of malignancy’.

Patient X had a long history of psoriasis when he presented in 2017 with a diagnosis of chronic lymphocytic leukaemia (CLL), confirmed with flow cytometry. He had an excellent response to RCVP (rituximab/cyclophosphamide/vincristine/prednisolone). Patient X remained well until 2020 when he presented with a right medial malleolus raised necrotic lesion and lymphadenopathy. His psoriasis was poorly controlled and symptomatic. CT scans confirmed progression of CLL and a biopsy from the leg lesion again confirmed CLL.

The patient was commenced on ibrutinib, a Bruton’s tyrosine kinase inhibitor. However, the patient’s skin began to deteriorate and he was readmitted to hospital, where deep biopsies were taken from the right malleolar tumour and from a newly developing left thigh lesion. Deeper biopsies confirmed the presence of both CLL and a new diagnosis of mycosis fungoides, a T-cell non-Hodgkin’s lymphoma.

PCR confirmed clonal immunoglobulin gene and clonal T-cell receptor gene rearrangements, consistent with separate monoclonal B and T-cell malignancies. He commenced on single agent gemcitabine and continues ibrutinib and after just two cycles, a significant improvement was seen in the condition of his skin.

Patient Y has a history of treated prostate and resected NSCLC in 2015. He also had a past medical history of psoriasis. In 2020 he began to develop widespread cutaneous erythema. He had skin biopsies which confirmed psoriasis and commenced anti IL-17 therapy without effect. He developed axillary adenopathy and complained of personality change and memory problems. A core biopsy of lymph nodes was felt to be reactive. He was admitted for investigation and skin biopsies and flow cytometry of peripheral blood confirmed the presence of Sézary syndrome, the haematological variant of mycosis fungoides.

This was confirmed in T-cell receptor studies of a resected axillary node. An MRI brain was carried out, demonstrating a space-occupying lesion which was biopsied and was found to be a metastasis from his EGFR mutated NSCLC, resected five years previously. He responded well in skin and brain to high-dose steroids and will start gemcitabine post brain irradiation. Targeted lung cancer therapy (osimertinib) is being kept in reserve.

According to Dr Ryan’s study, these cases underline the importance of suspecting dual malignant pathology when there is a discordant response to treatment, especially in the setting of a previously treated cancer. The diagnosis of cutaneous T-cell malignancies may be drawn out and require repeated investigation over time especially in the setting of refractory psoriasis. Both these patients have oral TKI available for their non T-cell malignancies, highlighting the importance of molecular pathology.

Access and value of innovative medicines

The title of the presentation by Dr David O’Reilly, CUH, was ‘Access and value of innovative cancer medicines in Europe: How bad is the problem?’. The study investigated patient access, cost and value of new systemic anti-cancer therapies (SACT) in the US, UK, and Europe (Republic of Ireland [ROI]).

The study highlighted the significant disparities between regimens approved by the US FDA/EMA and those that are reimbursed in the UK and ROI. Dr Orla Fitzpatrick, Beaumont Hospital, Dublin, spoke about a study she was involved in entitled ‘The cost of cancer care: How far would you go for a trial?’. This was a retrospective review of electronic medical records conducted in Beaumont Hospital.

A total of 271 patients receiving standard SACT and 111 patients enrolled on clinical trials were included. The median age was 58 years old for clinical trials patients and 59 years old for patients receiving standard SACT. The majority of patients enrolled on clinical trials were women (67 per cent female vs 33 per cent male) compared to standard of care (51 per cent female vs 49 per cent male).

The median distance travelled by patients enrolled in clinical trials was 56.3km, compared to 26.4km in those patients receiving standard SACT. This difference was seen throughout all cancer groups. The most significant difference was seen in patients with lung cancer (53km vs 9.8km for clinical trials patients versus those receiving standard of care, respectively).

The majority of patients enrolled on clinical trials lived between 50-100km away from Beaumont Hospital (43.2 per cent), compared to patients receiving standard SACT where the majority of patients lived within a 10km distance (39.4 per cent). Mirroring the distance discrepancy between clinical trials and standard of care journeys, the cost of journeys are estimated to be higher for those enrolled on clinical trials (€22.4 vs €4.2).

When the cost for those enrolled on clinical trials was adjusted to allow for mileage allowance, this resulted in no cost to these patients.
The study concluded that patients enrolled on clinical trials often travel twice as far to receive their anti-cancer treatment compared to those receiving standard of care treatments.

Covid-19 research

The research of a number of award winners focused on Covid-19. The impact of the Covid-19 pandemic on the levels of psychological distress among patients with cancer was examined in one study. A survey was undertaken in Beaumont Hospital and the results were presented by Dr Nicole Anne Pierce, who is based in the hospital.

A total of 122 patients participated, of whom 51 per cent were male. The most common cancer types were breast (25 per cent), followed by lung (17 per cent) and colorectal (12 per cent). In total, 31 per cent were aged 50-to-59 years and 20 per cent were approximately 70 years. Only one participant had previously been diagnosed with Covid-19.

As a result of the pandemic, a high number of patients expressed increased levels of anxiety (55 per cent), 47 per cent felt frustrated and 42 per cent felt they had lost their independence. The most common effect on daily living was missing important family occasions and gatherings (55 per cent).

The vast majority (80 per cent) reported feeling frustrated by the lack of compliance of others to public health guidelines; 61 per cent felt significantly more vulnerable in society and 34 per cent were concerned that their cancer care would be affected. Using the DT, 57 per cent reported increased concern about their health, and 88 per cent reported a new baseline of moderate or high anxiety.

Of those, 79 per cent also reported heightened levels of anxiety for their families, with 25 per cent moderate and 67 per cent high distress levels among family. Distress appeared highest among patients who were female, had breast cancer and were aged 50-to-59 years.

Overall, 21 per cent expressed a need for additional psychological resources but only 47 per cent felt these were available. Of those, 27 per cent (n=4) were started on medications during the pandemic for mood and sleep, with 17 per cent (n=12) reporting a previous history of mental illness. Overall, the most commonly cited resources that participants stated they would use for future support were family and friends (76 per cent), followed by GPs (22 per cent) and oncology nursing staff (15 per cent).

Interestingly, 62 per cent of patients experienced some benefit due to the Covid-19 pandemic, including infection avoidance (44 per cent), life appreciation (35 per cent) and quality time with family (32 per cent). In fact, seven participants (5 per cent) reported a measurable decrease in anxiety when compared to their lives pre-Covid.

Dr Richard O’Dwyer, Beaumont Hospital, made a presentation entitled ‘Attitudes towards the Covid-19 vaccine in oncology patients: An Irish Hospital Experience’. An anonymised questionnaire was distributed among patients attending the oncology day ward in Beaumont for systemic SACT over a three-week period from November 2020 to December 2020. Statistical analyses were performed using SPSS v23 (IBM, Armonk, NY, USA).
In total, 115 patients completed the survey. Of these, 30 (26 per cent) patients were aged over 65, 50 (44 per cent) were male and 54 (47 per cent) patients were being treated for metastatic disease.

Overall, 68 (59 per cent) patients were receiving cytotoxic chemotherapy and 15 (13 per cent) were receiving immunotherapy. The most common cancer was breast (29 per cent), followed by colorectal (18 per cent) and lung (10 per cent). The vast majority (72 per cent) of patients had received or were intending to receive the influenza vaccine.

While 17 per cent reported having friends or family who had been diagnosed with Covid-19, only three (2.6 per cent) of the patients surveyed had been diagnosed with Covid-19 themselves. In total, 83 per cent patients agreed that Covid-19 was more dangerous than influenza and 74 per cent described themselves as being very concerned about the Covid-19 pandemic. The majority (81 per cent) of patients were in favour of receiving a Covid-19 vaccine if it was recommended for them.

However, six (5.2 per cent) patients were against receiving a vaccine. Patients appeared equivocal as to whether they worried that a Covid-19 vaccine could be unsafe, with 40 (35 per cent) patients neither agreeing nor disagreeing. In addition, 48 (42 per cent) patients stated that if a Covid-19 vaccine was to be made available, they would prefer to wait rather than get it right away.

Patients who had received or intended to receive the influenza vaccine were less likely to want to delay receiving a Covid-19 vaccine (p=0.018). Age group, education level and whether treatment was palliative were not associated with a significant difference in vaccine acceptance.

Patient and staff views on the introduction of virtual clinics was also examined in new research. A presentation on the subject was delivered by Dr Ruth Kiernan, MMUH. Data on clinic duration, outcomes and doctor satisfaction was prospectively gathered for virtual oncology outpatients clinics, April – July 2020 (n=53, 89 per cent ‘attendance’ rate). Patients (n=21) were subsequently contacted for a follow-up survey (January 2021, median interval since appointment 8.4 months (range 6.3-8.7)).

A total of 15 completed the survey. Oncology doctors and administration staff also completed a survey assessing their views on virtual clinics (January 2021). Patient satisfaction was very high: 69 per cent preferred the phone clinic to in-person visits, and 87 per cent would like to have future virtual appointments. The mean Short Assessment of Patient Satisfaction score was 27.8 (maximum possible score 28).

A third (33 per cent) of the surveyed patients have a travel time of more than one hour to in-person clinics, 67 per cent feel they wait a very long time in the waiting room for in-person clinics, while 67 per cent and 47 per cent saved significant time and money during virtual clinics, respectively. No patient objected to future virtual appointments. No concerns were reported regarding ability to hear/understand the doctor or regarding privacy/distractibility.

The majority (73 per cent) of the patients would not want to receive bad news over the phone, but 13 per cent would prefer this. While 60 per cent had access to video calling; only 20 per cent feel this would enhance the interaction.

Dr Ronan McLaughlin, University Hospital Limerick, presented the findings of one study that investigated the prevalence of SARS-CoV-2 antibodies, using commercially available SARS-CoV-2 antibody tests with paired serological testing, in high-risk asymptomatic haematology/oncology (H/O) patient and associated healthcare worker cohorts.

A single centre prospective cohort study was carried out at MMUH identifying 221 eligible participants, of which 157 individuals underwent SARS-CoV-2 rapid antibody testing (RDT) in combination with three commercially available validated laboratory serology tests.

Asymptomatic participants with no previous confirmation of Covid-19 were recruited. Participants were recruited over three days in total; a single day in H/O directorate including all healthcare workers (HCWs), inpatients and day-ward patients. Patients on haemodialysis (HD) requiring more frequent hospital visitations also have recorded high infection rates. This study included testing of these patients over two days in the haemodialysis unit.
In total, 5.1 per cent (eight/157) of study participants were positive for SARS-CoV-2 IgG antibody in two or more tests. These were deemed to be true positives.

None of these positive IgG cases were among H/O patients, however, seven of the eight cases were among H/O staff, indicating a prevalence of 9.9 per cent of asymptomatic infection. A single (2.7 per cent) HD patient was positive. Five patients were IgM positive on the RDT, all were negative on subsequent SARS-CoV-2 PCR testing from nasopharyngeal swabs.

“In conclusion we found asymptomatic seroprevalence in high-risk hospital-associated cohorts to be 5.1 per cent (n=8),” according to the authors.

“Highest seroprevalence was in HCWs (9.9 per cent), illustrating the risk to patients posed by HCWs. The low prevalence of positivity amongst H/O patients is likely attributed to several measures implemented by the cancer directorate at the Mater Misericordiae University Hospital to protect its high-risk patient cohort. Ultimately, with low seroprevalence amongst H/O patients these results are reassuring with regards to the safety of SACT administration in this patient cohort and reinforce the need for adherence to strict Covid-19 social distancing measures.”

Rest of the ISMO winners

The presentations of the other winners were on the following subjects:

Dr Ross Matthews, CUH, ‘Predictive and prognostic implications of BRAF mutation in coloretal cancer.’

Dr Catherine Weadick, MMUH, ‘The incidence of Epstein-Barr virus-associated gastric cancer in an Irish population.’

Dr Tim O’Brien, MMUH, ‘Research in progress: Exploring the tumour and intestinal microbiome of patients with advanced ovarian cancer – pilot study.’

Dr Rachel Keogh, Beaumont Hospital, ‘A prospective observational study investigating the impact of immune checkpoint inhibitors for cancer on fertility.’

Dr Kate McKendry, MMUH, ‘Pseudoprogression and cancer immunotherapy: A seven-year retrospective audit of rate, temporal course and patient outcomes in an Irish tertiary referral centre.’

Dr Maeve Hennessy, University Hospital Waterford, ‘Metastatic gastroesophageal cancer in older patients – Are these patients represented in clinical trials?’

Dr Karine Ronan, Beacon Hospital, ‘Improved patient outcomes associated with an updated laboratory monitoring schedule for immunotherapy regimes.’

Dr Mary O’Reilly, St Vincent’s University Hospital, ‘Colorectal cancer in an Irish population – What’s age got to do with it.’

Dr Kate Johnstone, Beacon Hospital, ‘Fusobacterium nucleatum and rectal cancer treatment response.’

Dr Pranshul Chauhan, Beaumont Hospital, ‘Circulating tumour cells (CTCs) and total cell free DNA (cfDNA) levels as predictive biomarkers of
response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer.’

Dr Hailey Carroll, MMUH, ‘Trial in progress: A pilot study of combined immune checkpoint inhibition in combination with ablative therapies in subjects with hepatocellular carcinoma (HCC).’

The winner for best poster was Dr Iseult Browne, the Mater Hospital, for ‘Assessing the impact of anti PD-1/PD-L1 inhibitors on cancer care health
and budget in Ireland’.

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