Variations in patterns of prescribing durvalumab in stage III lung cancer: a survey of Australian Medical Oncologists.

BACKGROUND: Local Australian guidelines for the optimal management of stage III unresectable NSCLC are lacking. The American Society of Clinical Oncology (ASCO) guidelines recommend consolidation durvalumab for all patients with unresectable stage III NSCLC irrespective of their PD-L1 expression or driver mutation status. The European Society of Medical Oncology (ESMO) differs, with consolidation durvalumab only recommended in those patients whose tumours express PD-L1. METHODS: Due to differing global guidelines we conducted an Australia and New Zealand wide survey of medical oncologists specialising in thoracic cancer to determine the variations in patterns of prescribing durvalumab in stage III unresectable NSCLC. This survey was done electronically and sponsored by the Thoracic Oncology Group of Australia (TOGA). RESULTS: Thirty-two medical oncologists completed the survey. In patients with EGFR¬-mutated stage III unresectable NSCLC, 6% of respondents stated that they prescribed durvalumab for all patients, whilst an additional 6% strongly recommended treatment. Fourty-four percent suggested little benefit of consolidation durvalumab in this cohort, with an additional 19% advocating for observation only. In patients with PD-L1 negative (0%) stage III unresectable NSCLC, 13% of respondents prescribed durvalumab for all patients, whilst an additional 56% strongly recommended treatment. Interestingly, 18%, 10% and 10% of prescribers discussed self-funded oral tyrosine kinase inhibitor (TKI) therapy in patients with EGFR, ALK or ROS-1 mutated NSCLC respectively as a substitute for consolidation durvalumab. CONCLUSION: Overall, the clinical practice of Australian and New Zealand Medical Oncologists is variable, but remains consistent with either the ASCO or ESMO guidelines. Local practice guidelines are required to ensure consistency in prescribing patterns across Australia, as well as providing evidence for self-funded treatments outside standard of care.

Out-of-pocket health care expenses for people with and without cancer, New South Wales, 2020: a cross-sectional study.

OBJECTIVES: To investigate self-reported out-of-pocket health care expenses, both overall and by cost type, for a large population-based sample of Australians, by cancer status and socio-demographic and medical characteristics. STUDY DESIGN: Cross-sectional study. SETTING, PARTICIPANTS: New South Wales residents participating in the 45 and Up Study (recruited aged 45 years or older during 2005-2009) who completed the 2020 follow-up questionnaire; survey responses linked with New South Wales Cancer Registry data. MAIN OUTCOME MEASURES: Proportions of respondents who reported that out-of-pocket health care expenses during the preceding twelve months exceeded $1000 or $10 000; adjusted odds ratios (aORs) for associations with socio-demographic and medical characteristics. RESULTS: Of the 267 357 recruited 45 and Up Study participants, 45 061 completed the 2020 survey (response rate, 53%); 42.7% (95% confidence interval [CI], 42.2-43.1%) reported that overall out-of-pocket health care expenses during the previous year exceeded $1000, including 55.4% (52.1-58.7%) of participants diagnosed in the preceding two years and 44.9% (43.7-46.1%) of participants diagnosed with cancer more than two years ago. After adjustment for socio-demographic factors, out-of-pocket expenses greater than $1000 were more likely to be reported by participants with cancer than by those without cancer (diagnosis in past two years: aOR, 2.06 [95% CI, 1.77-2.40]; diagnosis more than two years ago: aOR, 1.22 [95% CI, 1.15-1.29]). The odds of out-of-pocket expenses exceeding $1000 increased with area-based socio-economic advantage and household income, and were higher for people with private health insurance (v people with Medicare coverage only: aOR, 1.64; 95% CI, 1.53-1.75). Out-of-pocket expenses exceeding $10 000 were also more likely for participants diagnosed with cancer during the past two years (v no cancer: aOR, 3.30; 95% CI, 2.56-4.26). CONCLUSIONS: People diagnosed with cancer during the past two years were much more likely than people without cancer to report twelve-month out-of-pocket health care expenses that exceeded $1000. Out-of-pocket expenses for people with cancer can exacerbate financial strain at a time of vulnerability, and affect health care equity because some people cannot pay for all available treatments.

Oncology and intensive care doctors' perception of intensive care admission of cancer patients: A cross-sectional national survey.

INTRODUCTION: Prognosis in oncology has improved with early diagnosis and novel therapies. However, critical illness continues to trigger clinical and ethical dilemmas for the treating oncology and intensive care unit (ICU) doctors. OBJECTIVES: The objective of this study was to investigate the perceptions of oncology and ICU doctors in managing critically ill cancer patients. METHODS: A cross-sectional web-based survey exploring the management of a fictitious acutely deteriorating case vignette with solid-organ malignancy. The survey weblink was distributed between May and July 2022 to all Australian oncology and ICU doctors via newsletters to the members of the Medical Oncology Group of Australia, the Australian and New Zealand Intensive Care Society, and the College of Intensive Care Medicine inviting them to participate. The weblink was active till August 2022. The six domains included patient prognostication, advanced care plan, collaborative management, legal/ethical/moral challenges, ICU referral, and protocol-based ICU admission. The outcomes were reported as the level of agreement between oncology and ICU doctors for each domain/question. RESULTS: 184 responses (64 oncology and 120 ICU doctors) were analysed. Most respondents were specialists (78.1% [n = 50] oncology, 78.3% [n = 94] ICU doctors). Oncology doctors more commonly reported managing cancer patients with poor prognosis than ICU doctors (p < 0.001). Oncology doctors less commonly referred such patients for ICU admission (29.7% [n = 19] vs. 80.8% [n = 97], p < 0.001; odds ratio [OR] = 0.07; 95% confidence interval [CI]: 0.03-0.16) and infrequently encountered patients with prior goals of care (GOC) in medical emergency team escalations (40.6% [n = 26] vs. 86.7% [n = 104]; p < 0.001; OR = 0.06; 95% CI: 0.02-0.15; p < 0.001). Oncology doctors were less likely to discuss GOC during medical emergency team calls or within 24 h of ICU admission. More oncology doctors than ICU doctors thought that training rotation in the corresponding speciality group was beneficial (56.3% [n = 36] vs. 31.7% [n = 38]; p = 0.012; OR = 2.07; 95% CI: 1.02-4.23; p = 0.045). CONCLUSION: Oncology doctors were less likely to encounter acute patient deterioration or establish timely GOC for such patients. Oncology doctors believed that an ICU rotation during their training may have helped manage challenging situations.

Health technology assessment for cancer medicines across the G7 countries and Oceania: an international, cross-sectional study.

BACKGROUND: Criticisms have emerged that cancer medicines offer modest benefits at increasingly high prices. Reimbursement decisions made by health technology assessment (HTA) agencies have become a complex endeavour for cancer medicines. Most high-income countries (HICs) use HTA criteria to identify high-value medicines for reimbursement under public drug coverage plans. We compared HTA criteria specific for cancer medicines in economically similar HICs, to understand how these criteria contribute to reimbursement decisions. METHODS: We did an international, cross-sectional analysis in collaboration with author investigators across eight HICs, from the Group of Seven (known as G7; Canada, England, France, Germany, Italy, and Japan) and Oceania (Australia and New Zealand). Publicly available data from HTA agency reports and official documentation were extracted and analysed between Aug 15, 2021, and July 31, 2022. We collected data pertaining to the decision-making criteria used by the national HTA agency; HTA reimbursement status for 34 medicine-indication pairs corresponding to 15 unique US top-selling cancer medicines; and HTA reimbursement status for 18 cancer medicine-indication pairs (13 unique medicines) with minimal clinical benefit (score of 1 on the European Society of Medical Oncology Magnitude of Clinical Benefit Scale). Descriptive statistics were used to compare HTA decision criteria and drug reimbursement recommendations (or for Germany and Japan, final reimbursement status) across the eight countries. FINDINGS: Therapeutic impact related to clinical outcomes of the new medicine was a uniform criterion across the eight countries, whereas quality of evidence (under the remit of therapeutic impact assessment) and equity were infrequently cited criteria. Only the German HTA agency mandated that surrogate endpoints be validated in therapeutic impact assessment. All countries except Germany included formal cost-effectiveness analyses within HTA reports. England and Japan were the only countries that specified a cost-effectiveness threshold. Of the 34 medicine-indication pairs corresponding to US top-selling cancer medicines, Germany reimbursed the maximum (34 [100%]), followed by Italy (32 [94%] recommended for reimbursement), Japan (28 [82%] reimbursed), Australia, Canada, England, and France (27 [79%] recommended for reimbursement), and New Zealand (12 [35%] recommended for reimbursement). Of the 18 cancer medicine-indication pairs with marginal clinical benefit, Germany reimbursed 15 (83%) and Japan reimbursed 12 (67%). France recommended nine (50%) for reimbursement, followed by Italy (seven [39%]), Canada (five [28%]), and Australia and England (three [17%] each). New Zealand did not recommend any medicine-indications with marginal clinical benefit for reimbursement. Considering the overall cumulative proportion across the eight countries, 58 (21%) of 272 indications for the US top-selling medicines and 90 (63%) of 144 marginally beneficial medicine-indications were not recommended for reimbursement or reimbursed. INTERPRETATION: Our findings indicate discordance in public reimbursement decisions across economically similar countries, despite overlapping HTA decision criteria. This suggests a need for improved transparency around the nuances of the criteria to ensure improved access to high-value cancer medicines, and deprioritisation of low-value cancer medicines. Health systems have opportunities to improve their HTA decision-making processes by learning from the systems in other countries. FUNDING: None.

Challenges and solutions to cancer-related financial toxicity according to Australian health professionals: qualitative results from a national survey.

PURPOSE: To qualitatively explore Australian healthcare professionals' perspectives on how to improve the care and management of cancer-related financial toxicity, including relevant practices, services, and unmet needs. METHODS: We invited healthcare professionals (HCP) who currently provide care to people with cancer within their role to complete an online survey, which was distributed via the networks of Australian clinical oncology professional associations/organisations. The survey was developed by the Clinical Oncology Society of Australia's Financial Toxicity Working Group and contained 12 open-ended items which we analysed using descriptive content analysis and NVivo software. RESULTS: HCPs (n = 277) believed that identifying and addressing financial concerns within routine cancer care was important and most believed this to be the responsibility of all HCP involved in the patient's care. However, financial toxicity was viewed as a "blind spot" within a medical model of healthcare, with a lack of services, resources, and training identified as barriers to care. Social workers reported assessment and advocacy were part of their role, but many reported lacking formal training and understanding of financial complexities/laws. HCPs reported positive attitudes towards transparent discussions of costs and actioning cost-reduction strategies within their control, but feelings of helplessness when they perceived no solution was available. CONCLUSION: Identifying financial needs and providing transparent information about cancer-related costs was viewed as a cross-disciplinary responsibility, however, a lack of training and services limited the provision of support. Increased cancer-specific financial counselling and advocacy, via dedicated roles or developing HCPs' skills, is urgently needed within the healthcare system.

Large-Scale Population-Based Surveys Linked to Administrative Health Databases as a Source of Data on Health Utilities in Australia.

OBJECTIVES: Large-scale health surveys that contain quality-of-life instruments are a rich source of health utility data for health economic evaluations, especially when linked to routinely collected, administrative health databases. We derived health utility values for a wide range of health conditions using a large Australian cohort study linked to population-wide health databases. METHODS: Short-Form 6-Dimension utility values were calculated for 56 094 adults, aged 47+ years, in the New South Wales 45 and Up Study who completed the Social, Economic, and Environmental Factors survey (2010-2011). Mean utilities were summarized for major health conditions identified through self-report, hospital records, primary cancer notifications, and claims for government-subsidized prescription medicines and medical services. To identify unique associations between health conditions and utilities, beta regression was performed. Utility values were analyzed by time to death using linked death records. RESULTS: Mean Short-Form 6-Dimension utility was 0.810 (95% confidence interval [CI] 0.809-0.811), was age dependent, and was higher in men than women. Utilities for serious health conditions ranged from 0.685 (95% CI 0.652-0.718) for lung cancer to 0.800 (95% CI 0.787-0.812) for melanoma whereas disease-free respondents had a mean of 0.859 (95% CI 0.858-0.861). Most health conditions were independently associated with poorer quality of life. Utility values also declined by proximity to death where participants sampled 6 months before death had a mean score of 0.637 (95% CI 0.613-0.662). CONCLUSIONS: Our data offer a snapshot of the health status of an older Australian population and show that record linkage can enable comprehensive ascertainment of utility values for use in health economic modeling.

Physician-patient communication of costs and financial burden of cancer and its treatment: a systematic review of clinical guidelines.

BACKGROUND: Optimising the care of individuals with cancer without imposing significant financial burden related to their anticancer treatment is becoming increasingly difficult. The American Society of Clinical Oncology (ASCO) has recommended clinicians discuss costs of cancer care with patients to enhance shared decision-making. We sought information to guide oncologists' discussions with patients about these costs. METHODS: We searched Medline, EMBASE and clinical practice guideline databases from January 2009 to 1 June 2019 for recommendations about discussing the costs of care and financial burden. Guideline quality was assessed with the AGREE-II instrument. RESULTS: Twenty-seven guidelines met our eligibility criteria, including 16 from ASCO (59%). 21 of 27 (78%) guidelines included recommendations about discussion or consideration of treatment costs when prescribing, with information about actual costs in four (15%). Recognition of the risk of financial burden or financial toxicity was described in 81% (22/27) of guidelines. However, only nine guidelines (33%) included information about managing the financial burden. CONCLUSIONS: Current clinical practice guidelines have little information to guide physician-patient discussions about costs of anticancer treatment and management of financial burden. This limits patients' ability to control costs of treatment, and for the healthcare team to reduce the incidence and severity of financial burden. Current guidelines recommend clinician awareness of price variability and high costs of treatment. Clinicians are recommended to explore cost concerns and address financial worries, especially in high risk groups. Future guidelines should include advice on facilitating cost transparency discussions, with provision of cost information and resources.

Medical Oncology Group of Australia position statement: COVID-19 vaccination in patients with solid tumours.

People with cancer are vulnerable to increased morbidity and mortality from the coronavirus disease 2019 (COVID-19). COVID-19 vaccination is key to protecting the population of people with cancer from adverse outcomes of SARS-CoV-2 infection. The Medical Oncology Group of Australia aimed to address the considerations around COVID-19 vaccination in people with cancer, in particular, safety and efficacy of vaccination. The assessment of patients with generalised allergic reaction to anti-cancer therapy containing vaccine components and practical implementation of vaccination of people on active anti-cancer therapy are also discussed.

Durvalumab with first-line chemotherapy in previously untreated malignant pleural mesothelioma (DREAM): a multicentre, single-arm, phase 2 trial with a safety run-in.

BACKGROUND: There is a strong unmet need to improve systemic therapy in mesothelioma. Chemotherapy with cisplatin and pemetrexed improves survival in malignant pleural mesothelioma, and immune checkpoint inhibitors are an emerging treatment in this disease. We aimed to evaluate the activity of durvalumab, an anti-PD-L1 antibody, given during and after first-line chemotherapy with cisplatin and pemetrexed in patients with advanced malignant pleural mesothelioma. METHODS: DREAM was a multicentre, single-arm, open-label, phase 2 trial done in nine hospitals in Australia. Eligible patients were aged 18 years or older and had histologically confirmed malignant pleural mesothelioma considered unsuitable for cancer-directed surgery, an Eastern Cooperative Oncology Group performance status of 0 or 1, and measurable disease as per the modified Response Evaluation Criteria in Solid Tumors version 1.0 (mRECIST) for mesothelioma that was previously untreated with systemic therapy. All histological subtypes were eligible. The first six participants were treated for two cycles in a safety run-in. All participants received cisplatin 75 mg/m2, pemetrexed 500 mg/m2, and durvalumab 1125 mg intravenously on day 1 of a 3-weekly schedule for a maximum of six cycles. Change from cisplatin to carboplatin with an area under the curve of 5 was permitted. Durvalumab was continued for a maximum of 12 months. The primary endpoint was progression-free survival at 6 months, measured according to mRECIST for malignant pleural mesothelioma and analysed in the intention-to-treat population. Safety analyses included all participants who receive at least one dose of any study drug. This study is registered with the Australia New Zealand Clinical Trials Registry, ACTRN12616001170415. FINDINGS: Between Dec 28, 2016, and Sept 27, 2017, 55 participants were enrolled. 54 patients were eligible and were followed up for a median of 28·2 months (IQR 26·5-30·2). 31 (57%; 95% CI 44-70) of 54 patients were alive and progression-free at 6 months. The most common grade 3-4 adverse events were neutropenia (seven [13%] patients), nausea (six [11%]), and anaemia (four [7%]). A total of 60 serious adverse events occurred in 29 participants, five of which were considered possibly related to durvalumab. Five patients died during the study treatment; none of these five deaths were attributed to study treatment. INTERPRETATION: The combination of durvalumab, cisplatin, and pemetrexed has promising activity and an acceptable safety profile that warrants further investigation in a randomised phase 3 trial. FUNDING: AstraZeneca.

Is it all about price? Why requests for government subsidy of anticancer drugs were rejected in Australia.

BACKGROUND: Australians access anticancer drugs predominantly through the Pharmaceutical Benefits Scheme (PBS). AIM: To determine why the Pharmaceutical Benefits Advisory Committee (PBAC) rejects submissions to list anticancer drugs on the PBS. METHODS: We reviewed publicly available information about submissions made to the PBAC for PBS listing of anticancer drugs from 2005 to 2014. Submission characteristics, including clinical and economic evidence, PBAC recommendations, and the reasons offered for rejection were recorded. Two reviewers independently categorised the reason for rejection offered by the PBAC. Logistic regression was used to determine submission characteristics associated with rejection. RESULTS: We identified 213 submissions for 110 unique indications of 60 anticancer drugs. The overall rejection rate was 56% (119/213). Of the 110 indications assessed, 69% (76/110) were rejected at least once. The annual rejection rate ranged from 50 to 73% with little evidence of a trend over time (P = 0.2). Submission characteristics strongly associated with rejection in multivariable analysis included: PBAC judged the clinical evidence to be problematic or uncertain (P < 0.001); PBAC judged the economic evidence to be problematic or uncertain (P < 0.001); and, inactive comparator used (P < 0.001). The most frequent reasons for rejection offered by the PBAC was 'inadequate cost-effectiveness or drug price too high' (75/109, 69%). CONCLUSIONS: Inadequate cost-effectiveness and PBAC uncertainty about the clinical and economic evidence were the most frequent reasons for rejection. Clarity of information about PBAC deliberations and their reasons for rejection are important for patients and doctors grappling with decisions about the use of expensive unfunded anticancer drugs.

Treatment patterns and long-term survival outcomes for patients with stage III non-small cell lung cancer: A retrospective study.

AIM: Lung cancer is the leading cause of cancer-related deaths in Australia with poor long-term survival outcomes. Stage III non-small cell lung cancer (NSCLC) is a highly heterogenous group with diverse tumor characteristics and multiple, possible treatment options. We present retrospective data on patient characteristics, treatment patterns, and long-term outcomes in stage III NSCLC patients treated at a single cancer center in New South Wales, Australia. METHODS: Stage III NSCLC patients were identified from the 'Nepean Cancer Research Biobank'. Patient demographics, cancer-related information, and long-term follow-up data were collected and analyzed. RESULTS: A total of 88 patients were eligible for analysis with 61% of them diagnosed as stage IIIA, 35% IIIB, and 4% IIIC. Induction chemotherapy was administered in 20% of the patients. Overall, 48% of the study population underwent surgery, and 38% underwent concurrent chemoradiotherapy (CCRT). Both median progression-free survival and overall survival (OS) were superior in stage IIIA patients in comparison to stage IIIB (and IIIC) patients (22 vs. 11 months, p = .018; and 58 vs. 19 months, p = .048, respectively). Patients who were younger (<65 years old), good Eastern Cooperative Oncology Group performance status (ECOG PS <2), and females had better prognosis on univariate analysis. There was a nonstatistically significant trend toward better median OS with CCRT in comparison to surgery (58 vs. 37 months, p = .87). CONCLUSIONS: Long-term outcomes remain poor, and hence better treatment strategies are urgently needed in stage III NSCLC. Equally, more robust, prospective studies would help delineate the optimal treatment modality in these patients.

Evaluating Systemic Burnout in Medical Oncology Through a National Oncology Mentorship Program.

PURPOSE: Mentorship has a positive influence on trainee skills and well-being. A 2022 Pilot Mentorship Program in New South Wales involving 40 participants revealed high burnout rates in Medical Oncology trainees. As part of an Australia-wide inaugural National Oncology Mentorship Program in 2023 (NOMP23), a national survey was undertaken to assess the prevalence of burnout, anxiety, depression, professional fulfilment, and drivers of distress in the Australian medical oncology workforce. METHODS: NOMP23 is a 1-year prospective cohort study that recruited medical oncology trainees and consultants using e-mail correspondence between February and March 2023. Each participant completed a baseline survey which included the Maslach Burnout Index (MBI), Stanford Professional Fulfilment Index, and Patient Health Questionnaire-4 for anxiety and depression. RESULTS: One hundred and twelve participants (56 mentors, 56 mentees) were enrolled in NOMP23, of which 86 (77%) completed the baseline survey. MBI results at baseline demonstrated that 77% of consultants and 82% of trainees experienced burnout in the past 12 months. Professional fulfilment was noted to be <5% in our cohort. Screening rates of anxiety and depression in trainees were 32% and 16%, respectively, compared with 7% and 2% for consultants. When assessing reasons for workplace stress, two thirds stated that heavy patient load contributed to stress, while almost three quarters attributed a heavy administrative load. Lack of supervision was a key stressor for trainees (39%), as was lack of support from the training college (58%). CONCLUSION: Trainees and consultant medical oncologists demonstrate high rates of burnout and low professional fulfilment. The NOMP23 program has identified a number of key stress factors driving burnout and demonstrated concerning levels of anxiety and depression. Ongoing mentorship and other well-being initiatives are needed to address these issues.

Nurse-led supportive care management: a 6-month review of the role of a nurse practitioner in a chemotherapy unit.

OBJECTIVES: This case study evaluates the oncology nurse practitioner (NP) role in a chemotherapy unit. BACKGROUND: The NP works in the cancer centre of a major metropolitan public hospital. The NP role was established in the chemotherapy unit in 2007. The NP reviews all patients that have an unscheduled presentation to the unit, with symptoms relating either to their disease or treatment. METHODS: All unscheduled occasions of service provided by the NP in the chemotherapy unit over 6 months were recorded. Data were collected on patient demographic characteristics, medical problems and reason for presentation. Data on duration of care, interventions and outcomes administered by the NP were captured. RESULTS: There were 87 occasions of service (72 patients) during the study period. Nausea, vomiting or dehydration were the most common presenting problems and most presenting problems were moderate or severe (n = 73, 84%). The median time to review for the NP was 5 min and nearly all consultations (n = 83, 96%) took 30 min or less. Following NP consultation, most occasions of service did not require subsequent hospital admission (n = 52, 60%), medical advice (n = 61, 70%) or medical review (n = 75, 86%). CONCLUSIONS: The NP is a valuable asset to a busy department, increasing access to timely and appropriate healthcare for patients on chemotherapy.

Improving Access to Cancer Clinical Trials for Patients From Culturally and Linguistically Diverse Backgrounds in Australia: A Survey of Clinical and Research Professionals.

PURPOSE: Patients with cancer from racial and ethnic minorities, referred to as culturally and linguistically diverse (CALD) in Australia, are significantly under-represented in cancer clinical trials. We performed a national survey of the Australian cancer clinical trials workforce to determine barriers and preferred solutions to address this inequity. METHODS: A 15-item online survey containing both closed- and open-ended purpose-designed questions was created using REDCap. The survey was emailed to members of the Clinical Oncology Society of Australia, Medical Oncology Group of Australia, and Australian cancer cooperative trial groups, and promoted via Twitter. Descriptive analyses summarized quantitative data, and free-text entries underwent thematic analysis with NVivo Version 12. RESULTS: Ninety one respondents completed the survey-with representation across Australia. Eighty-seven percent were directly involved in clinical trial recruitment. Sixty-eight percent were clinicians. Seventy-four percent of respondents did not collect routine data on CALD patient enrollment to cancer clinical trials. Communication (eg, lack of translated materials) and opportunity-related barriers (eg, exclusionary trial protocols) were the most frequently perceived barriers to recruitment. Additionally, qualitative analysis indicated that insufficient consultation time and difficulties accessing interpreters for patients with non-English language preference were significant barriers. Trial navigators and a generic cancer trial pamphlet available in multiple languages were judged the most likely solutions to improve recruitment. CONCLUSION: This study articulates the Australian clinical trials workforce's perspective on current barriers and potential solutions to the under-representation of patients from CALD backgrounds on cancer clinical trials. The insights and solutions from this survey provide steps toward achieving equity in Australian cancer clinical trials.

Haematological and nutritional prognostic biomarkers for patients receiving CROSS or FLOT.

Background: Neoadjuvant carboplatin and paclitaxel with radiotherapy (CROSS) and perioperative docetaxel, oxaliplatin, calcium folinate and fluorouracil (FLOT) are widely used for gastric (GC), gastro-oesophageal junction (GOJ) and oesophageal cancers (OC). Prognostic and predictive markers for response and survival outcomes are lacking. This study evaluates dynamic neutrophil-lymphocyte ratios (NLR), platelet-lymphocyte ratios (PLR), albumin and body mass index (BMI) as predictors of survival, response and toxicity. Methods: This multi-centre retrospective observational study across 5 Sydney hospitals included patients receiving CROSS or FLOT from 2015 to 2021. Haematological results and BMI were recorded at baseline and pre-operatively, and after adjuvant treatment for FLOT. Toxicities were also recorded. An NLR ≥2 and PLR ≥200 was used to stratify patients. Univariate and multivariate analyses were performed to determine predictors of overall survival (OS), disease free survival (DFS), rates of pathological complete response (pCR) and toxicity. Results: One hundred sixty-eight patients were included (95 FLOT, 73 FLOT). A baseline NLR ≥2 was predictive for worse DFS (HR 2.78, 95% CI: 1.41-5.50, P<0.01) and OS (HR 2.90, 95% CI: 1.48-5.67, P<0.01). Sustained elevation in NLR was predictive for DFS (HR 1.54, 95% CI: 1.08-2.17, P=0.01) and OS (HR 1.65, 95% CI: 1.17-2.33, P<0.01). An NLR ≥2 correlated with worse pCR rates (16% for NLR ≥2, 48% for NLR <2, P=0.04). A baseline serum albumin <33 was predictive of worse DFS and OS with a HR of 6.17 (P=0.01) and 4.66 (P=0.01) respectively. Baseline PLR, BMI, and dynamic changes in these markers were not associated with DFS, OS or pCR rates. There was no association of the aforementioned variables with toxicity. Conclusions: This demonstrates that a high inflammatory state represented by an NLR ≥2, both at baseline and sustained, is prognostic and predictive of response in patients receiving FLOT or CROSS. Baseline hypoalbuminaemia is predictive of poorer outcomes.

Real-World Outcomes of FLOT versus CROSS Regimens for Patients with Oesophagogastric Cancers.

Introduction: Treatment of oesophageal (OC), gastro-oesophageal junction (GOJ), and gastric cancer (GC) includes either neoadjuvant Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) for OC or GOJ or perioperative 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) for OC, GOJ, and GC adenocarcinomas. This study aims to describe the real-world outcomes of patients with GC, GOJ, and OC treated with FLOT or CROSS and identify variables associated with efficacy through exploratory analysis. We also aimed to evaluate the comparison of FLOT and CROSS for the treatment of OC and GOJ adenocarcinomas. Methods: This is a retrospective observational study of patients with locally advanced OC, GOJ, or GC treated with FLOT or CROSS between January 2015 and June 2021 in 5 cancer centres across Sydney, Australia. Long-rank test was used to compare survival estimated between subgroups. Hazard ratios for univariate and multivariate analyses were estimated with Cox proportional regression. Results: The study included 168 patients. The 24-month relapse-free survival (RFS) and overall survival (OS) for FLOT were 59% and 69%, respectively. The median RFS was 29.6 months and median OS was not reached. For CROSS, the 24-month RFS and OS were 55% and 63% with a median RFS and OS of 28.5 and 40.2 months, respectively. There was no difference in OS and RFS between the treatments. FLOT was less tolerable than CROSS with more dose reductions, treatment discontinuation, and clinically relevant grade 3 and 4 toxicity. Neutrophil lymphocyte ratio was associated with survival for both treatments. Conclusion: Similar efficacy outcomes were seen in this real-world population compared to the clinical trials for FLOT and CROSS.

Interactions between Australian cancer physicians and the pharmaceutical industry: a qualitative study.

OBJECTIVES: To understand how and why Australian cancer physicians interact with the pharmaceutical industry. DESIGN: Qualitative study using semistructured interviews, performed by a medical oncologist. Thematic analysis using a combination of deductive and inductive codes. SETTING: Given the evidence on industry influences on clinical practice and the importance to the market of oncology drugs, we sought to better understand cancer physicians' experiences. Practising consultant medical oncologists and clinical haematologists from four Australian states were interviewed over Zoom. PARTICIPANTS: 16 cancer physicians were interviewed between November 2021 and March 2022, from 37 invited (response rate 43%). Most were medical oncologists (n=12 of 16, 75%) and male (n=9 of 16, 56%). OUTCOME MEASURES: The analysis of all interviews was based on grounded theory. Transcripts were coded and then codes formed into themes with supporting quotes. The themes were then placed into categories, used to describe the broad areas into which the themes could be grouped. RESULTS: Six themes were identified that fell within two broad categories: cancer physicians' views and experiences of interactions and management of these interactions. Views and experiences included: the transactional nature of relationships, risks of research dependence, ethical challenges and varied attitudes based on interaction type. Management themes included: lack of useful guidance and reduced interactions during the COVID-19 pandemic. These led to an overarching seventh theme, on the desire for a 'middle road'. Cancer physicians identified the transactional nature of industry relationships and felt uncomfortable with several types of interactions, including those with sales representatives. Most wanted less contact with industry, and the forced separation that occurred with the COVID-19 pandemic was generally welcome. CONCLUSIONS: Cancer physicians may have difficulty balancing the perceived need to interact with industry in modern cancer care while maintaining distance to minimise conflicts of interest. Further research is needed to assess management strategies in this area.

Development and Validation of txSim: A Model of Advanced Lung Cancer Treatment in Australia.

BACKGROUND AND OBJECTIVE: Since 2016, new therapies have transformed the standard of care for lung cancer, creating a need for up-to-date evidence for health economic modelling. We developed a discrete event simulation of advanced lung cancer treatment to provide estimates of survival outcomes and healthcare costs in the Australian setting that can be updated as new therapies are introduced. METHODS: Treatment for advanced lung cancer was modelled under a clinician-specified treatment algorithm for Australia in 2022. Prevalence of lung cancer subpopulations was extracted from cBioPortal and the Sax Institute's 45 and Up Study, a large prospective cohort linked to cancer registrations. All costs were from the health system perspective for the year 2020. Pharmaceutical and molecular diagnostic costs were obtained from public reimbursement fees, while other healthcare costs were obtained from health system costs in the 45 and Up Study. Treatment efficacy was obtained from clinical trials and observational study data. Costs and survival were modelled over a 10-year horizon. Uncertainty intervals were generated with probabilistic sensitivity analyses. Overall survival predictions were validated against real-world studies. RESULTS: Under the 2022 treatment algorithm, estimated mean survival and costs for advanced lung cancer 10 years post-diagnosis were 16.4 months (95% uncertainty interval [UI]: 14.7-18.1) and AU$116,069 (95% UI: $107,378-$124,933). Survival and costs were higher assuming optimal treatment utilisation rates (20.5 months, 95% UI: 19.1-22.5; $154,299, 95% UI: $146,499-$161,591). The model performed well in validation, with good agreement between predicted and observed survival in real-world studies. CONCLUSIONS: Survival improvements for advanced lung cancer have been accompanied by growing treatment costs. The estimates reported here can be used for budget planning and economic evaluations of interventions across the spectrum of cancer control.

Case series: Immune checkpoint inhibitor-induced transverse myelitis.

Introduction: Increasing implementation of the highly efficacious immune checkpoint inhibitors (ICIs) has raised awareness of their various complications in the form of immune-related adverse events (irAEs). Transverse myelitis following ICIs is thought to be a rare but serious neurologic irAE and knowledge is limited about this distinct clinical entity. Cases: We describe four patients across three tertiary centers in Australia with ICI-induced transverse myelitis. Three patients had a diagnosis of stage III-IV melanoma treated with nivolumab and one patient had stage IV non-small cell lung cancer treated with pembrolizumab. All patients had longitudinally extensive transverse myelitis on magnetic resonance imaging (MRI) spine and clinical presentation was accompanied by inflammatory cerebrospinal fluid (CSF) findings. Half of our cohort had received spinal radiotherapy, with the areas of transverse myelitis extending beyond the level of previous radiation field. Inflammatory changes on neuroimaging did not extend to the brain parenchyma or caudal nerve roots, except for one case involving the conus medullaris. All patients received high dose glucocorticoids as first-line therapy, however the majority relapsed or had a refractory state (3/4) despite this, requiring escalation of their immunomodulation, with either induction intravenous immunoglobulin (IVIg) or plasmapheresis. Patients in our cohort who relapsed had a poorer outcome with more severe disability and reduced functional independence following resolution of their myelitis. Two patients had no progression of their malignancy and two patients had malignancy progression. Of the three patients who survived, two had resolution of their neurological symptoms and one remained symptomatic. Conclusion: We propose that prompt intensive immunomodulation is favored for patients with ICI-transverse myelitis in an attempt to reduce associated significant morbidity and mortality. Furthermore, there is a significant risk of relapse following cessation of immunomodulatory therapy. We suggest one treatment approach of IVMP and induction IVIg for all patients presenting with ICI-induced transverse myelitis based on such findings. With the increasing use of ICIs across oncology, further studies are required to explore this neurological phenomenon in greater detail to help establish management consensus guidelines.