Patient knowledge, personal experience, and impact of the first wave of the COVD-19 pandemic in an Irish oncology cohort.

BACKGROUND: Oncology patients have had to make many changes to minimise their exposure to COVID-19, causing stress. Despite education, some patients still do not recognise potential COVID symptoms. AIMS: We assessed patient knowledge of COVID, and its impact on their behaviours, concerns, and healthcare experience. METHODS: A 16-page questionnaire was distributed to 120 oncology patients attending the day unit of a tertiary Irish cancer centre for systemic anti-cancer therapy (May/June 2020). The Irish 7-day COVID incidence during this period ranged from 2 to 11 cases/100,000 people. RESULTS: One hundred and one responses were received, 1% had tested positive for COVID, and 31% had undergone testing. Participant insight into their knowledge about COVID and their own behaviour was limited in some cases. Seventy-five percent reported total compliance with restrictions, but many were not fully compliant. Self-reported confidence in knowledge was high, but did not predict demonstrated knowledge. Sixty percent did not recognise two or more symptoms; 40% did not self-identify as high-risk. Patients reported more health-related worry (72%), loneliness (51%), and lower mood (42%) since the pandemic began. Financial toxicity worsened, with increased financial worry (78%), reductions in household income (40%), and increased costs due to lockdown (62%). Use of facemasks introduced new communications barriers for 67% of those with hearing loss. CONCLUSIONS: Despite self-reported confidence in knowledge, some patient's recognition of COVID symptoms and the preventative strategies they should use are not optimal, highlighting the need for further education in this regard. COVID has been a significant stressor for patients and more practical, financial, and psychological supports are needed.

Targeting MET amplification in Gastro-oesophageal (GO) malignancies and overcoming MET inhibitor resistance: challenges and opportunities.

INTRODUCTION: MET, the hepatocyte growth factor receptor is amplified in 8% of gastroesophageal (GO) malignancies and associated with poor prognosis. Therapeutic targeting of MET amplification and MET mutations has the potential to improve outcomes for patients with GO cancers (GOC). AREAS COVERED: The efficacy of MET inhibition (METi) in preclinical studies has yet to translate into meaningful improvements in the treatment paradigm for unselected GOC. MET amplification has been proposed as a superior modality for patient selection; however even if confirmed, frequency and duration of response to METi are limited by rapid activation of primary and secondary resistance pathways. These observations illustrate the challenges inherent in the application of precision oncology predicated on the theory of oncogenic addiction. EXPERT OPINION: A standardized definition of MET positivity is critical to enhance patient selection. Early successes targeting the METex14 skipping mutation demonstrate the potent therapeutic effects of METi in a clearly molecularly defined cohort. There is robust preclinical rationale and early-phase data supporting exploitation of immune system interaction with MET. Pragmatic investigation of rational therapeutic combinations based on molecular profiling of both primary and metastatic disease sites with sequential circulating tumor DNA analysis can inform successful clinical development of METi agents in GOC.

Metastatic gastroesophageal cancer in older patients - is this patient cohort represented in clinical trials?

BACKGROUND: Older patients are underrepresented in the clinical trials that determine the standards of care for oncological treatment. We conducted a review to identify whether there have been age-restrictive inclusion criteria in clinical trials over the last twenty five years, focusing on patients with metastatic gastroesophageal cancer. METHODS: A search strategy was developed encompassing Embase, PubMed and The Cochrane Library databases. Completed phase III randomised controlled trials evaluating systemic anti-cancer therapies in metastatic gastroesophageal malignancies from 1st January 1995 to 18th November 2020 were identified. These were screened for eligibility using reference management software (Covidence; Veritas Health Innovation Ltd). Data including age inclusion/exclusion criteria and median age of participants were recorded. The percentage of patients ≥ 65 enrolled was collected where available. The change over time in the proportion of studies using an upper age exclusion was estimated using a linear probability model. RESULTS: Three hundred sixty-three phase III studies were identified and screened, with 66 trials remaining for final analysis. The majority of trials were Asian (48%; n = 32) and predominantly evaluated gastric malignancies, (86%; n = 56). The median age of participants was 62 (range 18-94). Thirty-two percent (n = 21) of studies specified an upper age limit for inclusion and over half of these were Asian studies. The median age of exclusion was 75 (range 65-80). All studies prior to 2003 used an upper age exclusion (n = 12); whereas only 9 that started in 2003 or later did (17%). Among later studies, there was a very modest downward yearly-trend in the proportion of studies using an upper age exclusion (-0.02 per year; 95%CI -0.05 to 0.01; p = 0.31). Fifty-two percent (n = 34) of studies specified the proportion of their study population who were ≥ 65 years. Older patients represented only 36% of the trial populations in these studies (range 7-60%). CONCLUSIONS: Recent years have seen improvements in clinical trial protocols, with many no longer specifying restrictive age criteria. Reasons for poor representation of older patients are complex and ongoing efforts are needed to broaden eligibility criteria and prioritise the inclusion of older adults in clinical trials.

Ivosidenib for the treatment of isocitrate dehydrogenase-1 mutant cholangiocarcinoma.

Introduction: Cholangiocarcinomas (CCAs) are associated with poor survival outcomes, with limited treatment options in the unresectable or metastatic setting. A precision medicine approach to cancer treatment has revealed new therapeutic options that provide an alternative to traditional chemotherapeutic strategies. Isocitrate dehydrogenase 1 (IDH1) mutations are identified in approximately 10-15% of CCAs and may be targeted by ivosidenib, an oral selective inhibitor of mutant IDH1.Areas covered: This review will discuss the pathogenesis of IDH1 mutant CCA and the role of ivosidenib in patients with IDH1 mutant CCA. Topics to be covered include the pharmacology, safety and clinical efficacy of ivosidenib in this patient population.Expert opinion: Ivosidenib represents a promising treatment option for patients with IDH1 mutant CCA with a favorable side effect profile. Future studies will guide whether this targeted agent may be utilized in combination with other anticancer treatments to improve upon survival outcomes in advanced CCA.

Prevalence of Insomnia in an Oncology Patient Population: An Irish Tertiary Referral Center Experience.

BACKGROUND: The NCCN Guidelines for Survivorship recommend dedicated sleep assessment. Reported insomnia prevalence in the general Irish population is 6% to 15%. Reported insomnia prevalence internationally among new/recently diagnosed patients with cancer varies from 30.9% to 54.3%. Insomnia prevalence has not been previously quantified in an Irish oncology cohort. METHODS: A 40-item questionnaire was prospectively administered to ambulatory patients with cancer aged ≥18 years. Prespecified criteria to define insomnia syndrome combined those of the International Classification of Sleep Disorders, version 1, and the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). The Hospital Anxiety and Depression Scale-Depression/Anxiety (HADS-D/A) was used to screen for potential confounding variables. RESULTS: The response rate to the questionnaire was 87% (294/337). The predominant respondent age group was 55 to 64 years (26%; 77/294), 70.7% were female (208/294), and the most common cancer subtypes were breast (37.4%), colorectal (12.9%), and lung (12.2%). A total of 62% (183/294) of patients reported sleep disturbance after diagnosis, 63% (115/183) reported moderate/severe distress related to this disturbance, and 37% (61/183) reported a significant impact on physical function. Although 33% (98/294) met insomnia syndrome criteria, only 34% (33/98) of these patients had a preexisting history of sleep disturbance. Female sex, age <65 years, cancer subtype, alcohol consumption, and HADS-D/A ≥11 were associated with statistically significant higher odds ratios (OR) of insomnia syndrome. Multivariate analysis identified breast cancer (OR, 3.17; P=.01), age <65 years (OR, 1.8; P=.03), and alcohol consumption (OR, 2.3; P=.005) as independent predictors of insomnia syndrome. CONCLUSIONS: Insomnia syndrome prevalence in this cohort is comparable to that reported previously and supports dedicated sleep assessment. This study identifies potentially modifiable risk factors for insomnia and demonstrates additional utility of the HADS score in identifying patients at risk.

Professional burnout, work patterns and career satisfaction in medical oncologists in Ireland.

BACKGROUND: Burnout is an occupational syndrome frequently encountered within the healthcare profession. It is characterised by emotional exhaustion (EE), depersonalisation (DP) and a low sense of personal accomplishment (PA). Its negative impact extends to the physician, patient and overall service provision. AIMS: The aim of this study was to evaluate work patterns, the prevalence of burnout and its associations in medical oncology consultants and specialist registrars (SpRs) in Ireland. METHODS: Participants were invited to partake in an anonymised online survey. Burnout domains were measured using the validated Maslach Burnout Inventory. Associations between variables were evaluated using the Mann-Whitney U and Kruskal-Wallis tests (continuous), and chi-square and Fisher's exact testing (categorical). RESULTS: Seventy-four physicians were contacted to participate, 44 (59%) completed the survey. The majority (71%) work ≥ 50 h a week, with 57% having additional on-call commitments of ≥ 5 days/month. Burnout is defined by a high score in EE combined with a high DP and/or low PA was identified in 45% of consultants and 20% of SpRs. Longer working hours (≥ 60 h/ week) were found to be associated with both high EE (p = 0.049) and DP (p = 0.019). Higher EE scores were demonstrated in those ≥ 40 years (p = 0.04). The majority (86%) reported they would become an oncologist again. CONCLUSION: One or more of the symptoms of burnout is highly prevalent in medical oncologists in Ireland. With increasing pressure on resources, burnout is expected to increase. Attention to strategies for prevention needs to be prioritised within our healthcare system.

Epidermal growth factor receptor mutated oligometastatic adeno-squamous lung cancer transformation to small cell lung cancer.

A 66-year-old non-smoker was diagnosed with stage IIIB, epidermal growth factor receptor (EGFR) mutated, squamous cell lung carcinoma. Treatment included chemotherapy, 35 fractions of radiotherapy and later Gefitinib for 3.5 years. On progression he developed a solitary brain and liver lesion. The brain lesion was excised and histology revealed adenocarcinoma of a lung primary. Afatanib was commenced for 1 further year. At the second time of progression re-biopsy identified small cell carcinoma. He completed four cycles of Carboplatin and Etoposide however deteriorated on completion of chemotherapy. EGFR directed treatment is associated with improved patient outcomes. It has been suggested that EGFR mutated squamous cell carcinoma more likely represent mixed morphology or poorly differentiated adenocarcinoma. Patients with oligometastatic progression can be treated beyond progression however the addition of a local therapy may be required. Small cell transformation is described as a rare mechanism of resistance to EGFR treatment as in our case.

The challenge of treating older patients with pancreaticobiliary malignancies.

Pancreatic and biliary tract cancers are aggressive malignancies. They commonly present with metastatic or unresectable disease. Those that do present with resectable cancer have high rates of recurrence. Despite recent advances in surgical technique, chemotherapy, and radiotherapy regimens, they are associated with poor survival outcomes. These cancers represent an exception to the trend of improved overall survival evident in most malignancies in recent decades. Depending on the goal of treatment, active management of pancreatic and biliary cancers involves surgery, chemotherapy, and radiation therapy, either alone or in combination. Both pancreatic and biliary tract cancers have a preponderance in the older population. Older patients are a heterogeneous group; although tolerability of multimodality treatment may be a challenge for some, many fit older patients may be undertreated based on their age alone. The growing field of geriatric oncology has highlighted the importance of a comprehensive assessment of these patients, and not relying on age alone as a discriminating factor for treatment. Management of older patients with pancreaticobiliary cancers is particularly challenging owing to limited prospective data in this population. As such, there is uncertainty with regard to optimal treatment approaches for these patients. In this article, we outline the therapeutic options available to patients with localized or advanced pancreatic and biliary tract cancers, and the evidence for specified treatment options in the elderly. We examine the inclusion and outcomes of elderly patients in relevant clinical trials; the morbidity that may be encountered by elderly patients receiving specified treatments and the tools that may assist the physician in selecting elderly patients for particular treatments.