From doctors to ancillary staff: Regional and metropolitan cancer workforce perceptions and distress resulting from COVID-19 pandemic adaptations.

INTRODUCTION: The declaration of the COVID-19 pandemic has resulted in necessary and rapid changes to health service delivery. In the Australian context, it has been broadly identified that these impacts have been felt by health care workers (HCW) providing care. We aimed to capture oncology HCW perceptions of support, stress, personal ability to meet needs and institutional preparedness across longitudinal periods of COVID-19 response in the early stages of the pandemic. METHODS AND MATERIALS: An electronic survey was developed to measure the weekly impacts and distress experienced by HCW during the early phases of the pandemic. Hospital email communications relating to pandemic directives were noted. HCW included nursing, medical, ancillary staff and allied health team members at 2 study sites, 1 metropolitan and 1 regional center in Queensland, Australia. Descriptive statistics were applied to quantitative data, and a framework analysis for qualitative data. Key themes were synthesized using mixed methods approaches. RESULTS: A total of 176 HCW consented to participate. Four key themes were identified. Key theme 1 was strategies for protection, and included the subthemes of self-isolation, using personal protective equipment (PPE), protecting patients and families and each other. Key theme 2 was navigating rules and keeping up, and included the subthemes of compliance, exceptions, conflict and complex decision fatigue. Key theme 3 was tempered optimism, with subthemes including this is grief, pride in one's place and strategies for coping. Key theme 4 was framing the new normal, with subthemes including using technology, second wave and uncertainty. CONCLUSION: Staff groups reported the emotional impacts of rapid change across clinical areas and centers. Distress corresponded to rapid change amid uncertainty, rather than reported infection rates. These findings give insight into the experiences of patient facing oncology HCW during periods of uncertainty, potentially informing policy in the future.

Resilience and ongoing quality care for cancer clinical trials during COVID-19: Experience from a tertiary hospital in Australia.

BACKGROUND: The COVID-19 pandemic has forced rapid system-wide changes to be implemented within cancer care at an alarming pace. Clinical trials are a key element of comprehensive cancer care. Ensuring the continuing safe conduct of cancer clinical trials in the context of a pandemic is challenging. METHODS: We aimed to describe the COVID-19 pandemic response of a Cancer Care Clinical Research Unit (CRU) of a tertiary hospital in Queensland, Australia. We used a mixed methods approach for this case study. Emailed directives from CRU managers to all CRU staff sharing were qualitatively analysed and mapped against our unit activities over longitudinal time points. Data from patient recruitment and protocol deviations were analysed using descriptive statistics. RESULTS: Mapping activity from 11 March to 30 September 2020 revealed rapid change during the first 2 weeks. Four key strategies to accommodate change were identified: supporting patients and families, introduction of telehealth, accessing investigational product, and social distancing. Early in the pandemic we recognised that our core key stakeholders were integral to our response. When compared to the previous 12 months, our recruitment numbers dropped markedly in early phases of the response but recovered over time, as we accommodated internal and external impacts. CONCLUSION: Our experience of agility as a necessity, adapting to support patients, and managing both clinical research activity and sponsors during the height of the pandemic response is presented here in order to inform future disaster response planning by clinical trial organisations.

Semiqualitative research protocol to explore cancer care workforce perceptions of the health system response to COVID-19 preparations in Southeast Queensland, Australia.

INTRODUCTION: Sars-CoV-2 is a novel coronavirus responsible for COVID-19 officially declared pandemic in March 2020. Health systems worldwide responded with swift changes to increase workflow capacity while protecting the vulnerable, including those with cancer. This led to unprecedented and rapid restructuring of health service provision. Published data from the 2003 SARS pandemic focuses on medical and nursing staff, overlooking other departmental employees such as administration officers or food service workers. Our protocol aims to document directives and adjustments communicated to staff in two cancer care departments and correlate this with measures of distress and perceived preparedness across the spectrum of all staff involved in cancer care. METHODS AND ANALYSIS: We use a semiqualitative approach comprising weekly diarising of events and simultaneous staff surveys. Principal investigators will document changes at a metropolitan quaternary cancer centre and a regional cancer centre. Communications, directives and changes will be diarised in real time in four executional domains. Simultaneously, prospective voluntary self-administered online surveys will be conducted at regular intervals by staff. The survey assesses the perceived institutional preparedness and personal well-being, with a combination of Likert scaled and open response questions. A semiquantitative self-assessment of distress adapted from National Comprehensive Cancer Network distress thermometer is incorporated. Additionally, open-text personal reflections on themes including difficult decisions will be invited. Survey participants will be drawn from various work areas of the cancer care departments: administrative staff, health professionals, for example, allied health, ancillary workers, nursing and medical. ETHICS AND DISSEMINATION: The study has been reviewed and approved by the Human Research Ethics Committee (LNR/2020/QRBW/62982). Published literature on domains of distress neglects categories of healthcare worker who form an essential part of the care delivery team. Our study hopes to gather insights about psychosocial impact and adjustment which could direct responses in future emergencies.

Spatial profiling technologies and applications for brain cancers.

INTRODUCTION: Malignant primary and secondary brain tumors pose a major health challenge, and the incidence of these tumors is rising. The brain tumor microenvironment (TME) is highly complex and thought to impact treatment resistance and failure. To enable a greater understanding of the milieu of cells in the brain TME, advances in imaging and sequential profiling of proteins/mRNA have given rise to the field of spatial transcriptomics. These technologies provide a greater depth of understanding of the tissue architecture, cellular and spatial profiles, including cellular activation status, which may provide insights into effective therapies for brain cancers. AREAS COVERED: In this review, we provide an overview of spatial profiling technologies at the forefront in the field and describe the applications for brain cancer. EXPERT OPINION: Brain tumors are often resistant to treatment, and display both an immunosuppressive and heterogeneous tumor microenvironment. Next-generation imaging and multi-omics technologies are providing a tool for intricately characterizing their tissue biology. This information will aid in the design of effective therapies and begin to provide an understanding of therapy resistance.

Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small-Cell Lung Cancer (NSCLC).

Epidermal growth factor receptor (EGFR) mutations are the most common oncogenic drivers in non-small-cell lung cancer (NSCLC). Significant developments have taken place which highlight the differences in tumor biology that exist between the mutant and wild-type subtypes of NSCLC. Patients with advanced EGFR-mutant NSCLC have a variety of EGFR-targeting agents available proven to treat their disease. This has led to superior patient outcomes when used as a monotherapy over traditional cytotoxic systemic therapy. Attempts at combining EGFR agents with other anticancer systemic treatment options, such as chemotherapy, antiangiogenic agents, and immunotherapy, have shown varied outcomes. Currently, no specific combination stands out to cause a shift away from the use of single-agent EGFR inhibitors in the first-line setting. Similarly, adjuvant EGFR inhibitors, are yet to significantly add to patient overall survival if used at earlier timepoints in the disease course. Liquid biopsy is an evolving technology with potential promise of being incorporated into the management paradigm of this disease. Data are emerging to suggest that this technique may be capable of identifying early resistance mechanisms and consequential disease progression on the basis of the analysis of blood-based circulating tumor cells.

COVID-19 and the cancer care workforce: From doctors to ancillary staff.

The COVID-19 pandemic poses daily challenges to the entire oncology workforce. Staff members must absorb multiple executive briefings, adapt to escalating scenario modelling, and seamlessly execute ever-changing operational modes in real-time. The unique threat of looming re-deployment and rationing care add to the uncertainty. We highlight the need for qualitative research to understand the psychosocial impact of these challenges. We posit that the perspective of all team members should be explored: from doctors to ancillary staff.

Defining the Most Appropriate Primary End Point in Phase 2 Trials of Immune Checkpoint Inhibitors for Advanced Solid Cancers: A Systematic Review and Meta-analysis.

IMPORTANCE: Checkpoint inhibitors have a unique mechanism of action that differs from chemotherapy or targeted therapies. The validity of objective response rate (ORR) as a surrogate for progression-free survival (PFS) and overall survival (OS) in checkpoint-inhibitor trials is uncertain. OBJECTIVE: To determine the types of primary end points used in phase 2 checkpoint-inhibitor trials, and to assess the strength of associations for ORR with PFS and OS. DATA SOURCES: Trials listed in electronic databases from 2000 to 2017 (PREMEDLINE, MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials). STUDY SELECTION: Advanced solid cancers in phase 2 and phase 3 trials. DATA EXTRACTION AND SYNTHESIS: Correlations between ORR odds ratios and hazard ratios (HRs) for PFS and OS were examined for randomized comparisons. Within checkpoint-inhibitor treatment arms, correlations for ORR with 6-month PFS and 12-month OS rates were examined. All analyses were weighted by trial size. Multivariable models to predict 6-month PFS and 12-month OS rates from ORR were developed and their performance validated in an independent sample of trials. MAIN OUTCOMES AND MEASURES: Correlation coefficient (r) of ORR with PFS and OS. RESULTS: Of 87 phase 2 trials identified, ORR was the most common (52 [60%]) primary end point. Twenty randomized clinical trials with 25 treatment comparisons were identified. Checkpoint-inhibitor therapy was associated with pooled ORR of 24% (95% CI, 18%-31%). For randomized comparisons, r between ORR odds ratio and PFS HR was 0.63 (95% CI, 0.35-0.89), ORR odds ratio and OS HR was 0.57 (95% CI, 0.23-0.89), and between PFS HR and OS HR was 0.42 (95% CI, 0.04-0.81). Within the checkpoint-inhibitor arms, r correlation coefficients between ORR with 6-month PFS, ORR with 12-month OS, and 6-month PFS with 12-month OS were 0.37 (95% CI, -0.06 to 0.95), 0.08 (95% CI, -0.17 to 0.70), and 0.74 (95% CI, 0.57-0.92), respectively. In validation, when 6-month PFS was used to predict 12-month OS, there was a good calibration between actual and predicted 12-month OS. When ORR was used to predict 6-month PFS and 12-month OS rates, respectively, the actual vs predicted rates calibrated poorly. CONCLUSIONS AND RELEVANCE: In checkpoint-inhibitor trials, ORR correlated poorly with OS. For future phase 2 studies, 6-month PFS rate is recommended as an end point.