Australian Cancer Research Articles

Comparing spiritual wellbeing and illness perceptions between cancer patients from culturally and linguistically diverse and those from mainstream backgrounds in Australia.

Cancer presents a significant health challenge, particularly within culturally and linguistically diverse (CALD) populations. Religious, spiritual, and personal beliefs regarding illness may mitigate its psychological and physical impacts, varying with CALD status. This study aims to assess illness perceptions in Australian cancer patients from both CALD and Anglo-Australian backgrounds and to explore the associations between spiritual wellbeing and illness perceptions within these groups. Cross-sectional study, involving 119 cancer patients from CALD backgrounds (Arabic, Chinese, and Greek) and 50 Anglo-Australians. Spiritual wellbeing and cancer perception were assessed using the World Health Organization Quality of Life-Spirituality, Religiousness, and Personal Beliefs questionnaire and the revised Illness Perception Questionnaire, respectively. Linear regression models analyzed associations. CALD patients perceived their cancer as less enduring (β - 4.74, 95%CI - 6.16, - 3.31) and symptoms as less predictable (- 4.96, 95%CI - 6.12, - 3.86) compared to Anglo-Australians. They had lower confidence in medical interventions (- 2.96, 95%CI - 3.36, - 1.22) and poorer illness understanding (- 4.66, 95%CI - 5.83, - 3.49). In Greek-speaking patients, an increase in spiritual wellbeing was associated with less favourable perceptions of treatment controllability (β - 2.25, 95%CI - 4.39, - 0.09). Conversely, for Chinese-speaking patients, an increase in spiritual wellbeing was associated with improved illness perception across all domains except for consequences and emotional representation. However, no significant association was observed for Arabic patients. Differences in illness perceptions exist among CALD and Anglo-Australians. Spiritual wellbeing appears linked to more favourable perceptions; however, differential effects emerged among groups, emphasizing the need for culturally tailored interventions to improve outcomes.

Real-world patient experience with medicinal cannabis use for symptom management in an Australian advanced cancer setting: a mixed method, cohort study using the theory of planned behaviour framework

PurposePatient hesitancy to use MC due to the fear of negative social implications leads to intentional non-adherence and compromises therapeutic outcomes. Hence, we aimed to determine the rate of patient adherence to MC and explore factors influencing patient MC use.MethodsDemographic and quantitative data related to MC usage were extracted from medical records for patients prescribed MC at a single cancer centre in metropolitan Sydney. Qualitative data was generated from semi-structured interviews. Interview guides were developed based on the Theory of Planned Behaviour (TBP) domains (i.e. Attitudes, Subjective Norms, Behavioural Intention and Perceived Behavioural Control) to elucidate themes influencing MC use. A mixed method approach involving triangulation of quantitative and qualitative methods was used for data analysis.ResultsTwenty patients were included in the study, and the majority of patients showed adherence (n = 14, 70%). The MC formulation used (p = .018), symptom relief (p = .001) and side effects experienced (p = .007) significantly influenced MC adherence. In addition to side effects experienced, findings for barriers to adherence were convergent or complementary for other medication-related factors, including the inconvenience of MC co-administration with food, cost and unpleasant taste.ConclusionsMC adherence is influenced by its effectiveness for symptom relief whereby appropriate MC formulation selection is crucial and should be determined by the indication (or symptom clusters). Social factors such as the views and experiences of close others had little bearing on MC adherence.

A05 - HPB Interrogating the spatial biology of pancreatic cancer-associated fibroblasts

Abstract Background Cancer-associated fibroblasts (CAFs) are key players in the fibrotic tumour microenvironment (TME) of pancreatic cancer. Recent evidence has demonstrated the existence of multiple CAF subtypes, however there is relatively little evidence validating and corroborating these CAF subtypes in resected human pancreatic cancer. Furthermore, the spatial interactions between CAF subtypes and the epithelial and immune compartments of the pancreatic cancer TME is not well understood. Method We designed and optimised a bespoke 8-plex immunofluorescence panel for the purposes of CAF subtype profiling and elucidation of CAF spatial biology: panCK, FAP, SMA, CTGF, S100A4, IL6, LIF, PDGFR. This was applied to a cohort of n=215 resected pancreatic cancer, well characterised with highly granular clinico-pathological and transcriptomic data through the Australian Pancreatic Cancer Genome Initiative. Spatial analysis was performed with novel computational biology techniques. Results We demonstrate seven CAF subtypes which cluster to form distinct, highly prognostic “enrichment profiles” (EPs). The cold EP represents quiescent CAFs in close proximity to immune cells (multivariate HR 0.45, 95% CI 0.30-0.68, p<0.001), and the fibrotic EP represents activated CAFs in close proximity to epithelial cells (multivariate HR 2.22, 95% CI 1.48-3.35, p<0.001). We also demonstrate the prognostic power of high spatial entropy (loss of tissue architecture, correlating with the fibrotic EP) vs low spatial entropy (preservation of tissue architecture, correlating with the cold EP) (HR 2.22, 95% CI 1.47-3.35, p<0.001). Conclusion We begin to unravel the elusive spatial biology of pancreatic CAFs in a large resected human cohort. We see changes in immune cell infiltrate, modulation of cellular relationships, and greater tissue disorganisation as a result of CAF activation. These features are highly prognostic and we hypothesise they are driven by changes in crosstalk between TME compartments. Current work focuses on application of these techniques to a large resected neoadjuvantly-treated cohort, allowing further interrogation of the notorious fibrotic post-neoadjuvant pancreatic cancer TME. If accepted for presentation we look forward to presenting both cohorts simultaneously.

General practice utilisation by Australian cancer patients in the last year of life.

General practice plays a key role in end-of-life care, yet the extent of this remains largely unknown due to a lack of detailed clinical data. This study aims to describe the care provided by General Practitioners (GPs) for people with cancer in their last year of life. Retrospective cohort study using linked routine primary care and death certificate data in Victoria, Australia. Patients were included who died from cancer between 2008 and 2017. In total 7025 cancer patients were included, mean age of 74.8 yrs. 95% of patients visited their GP in the last 6 months of life, with a median of 11 general practice contacts in this period. 72% of patients visited their GP in the second-last month prior to death, and 74% in the last month of life. The majority of patients (58%) were prescribed opioids, 19% anticipatory medications, 24% received a home visit, and a small proportion had imaging (6%) in the last month and pathology (6%) in the last fortnight. Patients in regional areas had more contact with general practices in the last year of life compared to metropolitan patients (median metropolitan = 16, inner regional = 25, and outer regional = 23, P < .001). The use of GP services did not differ by cancer type. GP's play a central role in end-of-life care provision for cancer patients, which intensifies in the last months of life. There is room for improvement, with a proportion having little or no engagement, and low rates of home visits and anticipatory medication prescribing.

DPYD genotype-guided dose personalisation for fluoropyrimidine-based chemotherapy prescribing in solid organ cancer patients in Australia: GeneScreen 5-FU study protocol

BackgroundFluoropyrimidine (FP) chemotherapies are commonly prescribed for upper and lower gastrointestinal, breast and head and neck malignancies. Over 16,000 people with cancer require FP chemotherapies per annum in Australia. Between 10 and 40% patients experience grade 3–4 (≥ G3) toxicities that require hospital-based management ± intensive care admission. Approximately 1% of patients die secondary to FP toxicities. Prospective screening for DPYD gene variants (encoding the key enzyme for FP catabolism) can identify patients at risk of ≥ G3 toxicity and allow for dose adjustment prior to first FP exposure. Evidence supports this as a cost-effective method of improving patient safety and reducing healthcare burden internationally; however, no Australian data confirms its feasibility on a large scale.MethodThis investigator-led, single-arm study will determine large scale feasibility of prospective DPYD genotyping, confirming patient safety and cost-effectiveness within the Australian health care system. 5000 patients aged 18 years and older with solid organ cancers requiring FP chemotherapy will be consented and genotyped prior to commencing treatment, and early toxicity (within 60 days) post-FP exposure will be determined. Toxicity data for DPYD variant carriers who have dose adjustments will be compared to the wild-type cohort and historical cohorts of carriers who did not undergo genotyping prior to FP exposure, and prospective variant carriers who do not undergo dose-adjustment. Prevalence of the four standard DPYD gene variants will be confirmed in an Australian population. Additionally, health economic analysis, implementation research via semi-structured interviews of patients and clinicians, and feasibility of UGT1A1 genotyping will be conducted.DiscussionThis study will determine the prevalence of DPYD gene variant status in Australia and its impact on FP-induced toxicity among Australians with cancer. Feasibility and cost-effectiveness for Australian health care system will be estimated to support national roll-out of prospective DPYD genotyping prior to FP administration. Additionally, feasibility will be confirmed with the intention of including UGT1A1 in future pharmacogenomic panels to aid chemotherapy prescribing.Trial registrationThis trial was registered with the Australian and New Zealand Cancer Trials Registry on 13th Dec 2023, ACTRN12623001301651.

Improving communication skills in caregivers: an adaptation and pilot test of a brief training module for caregivers of people with cancer in Australia.

Informal caregivers play a pivotal role in providing support to cancer survivors, yet have reported challenges with communicating with health providers to get all the information they need to provide optimal care. We aimed to adapt and pilot test a brief communication skills training program (COMFORT) to improve caregiver-provider communication in an Australian cancer setting. Module adaptation was guided by the cultural adaptation model. A working group completed the module and provided feedback for adaptation. The adapted module underwent pilot testing with cancer caregivers to examine module impact on communication confidence, preparedness for caregiving, health literacy, and psychological outcomes. Semi-structured interviews and survey data provided evidence of acceptability, usability, and preliminary efficacy. Eight working group members provided mostly positive feedback on module language, content, and images. Module modifications reflected Australian services and terminology. Nineteen caregivers provided pre-post-pilot data and participated in semi-structured interviews. Following module exposure, repeated measures t-test analyses showed significant improvements in communication confidence, preparedness for caregiving, health literacy, and depressive symptoms (p < 0.05). Survey and interview data supported the acceptability and utility of the program. The findings support the feasibility and preliminary efficacy of the brief module in improving communication confidence, caregiving preparedness, health literacy, and depressive symptoms in Australian cancer caregivers.

Expectations for gynaecological cancer nursing guidance development: A qualitative exploration: Part 1 – Creating foundational support

PurposeNurses are acknowledged as essential in the delivery of best practice gynaecological cancer care however previous studies have identified challenges in these nursing roles. Recommendations include the development of nursing guidance focused on supporting people with a gynaecological cancer. This study aimed to explore perceptions and expectations for the development of a gynaecological cancer nursing guidance resource in Australia and investigate preferred design and content inclusion. This paper presents the findings on expectations for the resource purpose. MethodsUtilising an exploratory qualitative descriptive design, 20 nurses and seven people with lived experience of gynaecological cancer participated in focus groups or interviews following a semi-structured interview guide. Transcripts underwent inductive content analysis. ResultsAll 27 participants identified as female, lived in one of 5 Australian states, included representation from regional locations (n=9, 33%), and mostly identified as Australian or mixed Australian ethnicity (n=25, 93%). The major theme, “Foundational support resource for nurses”, described how participants require a resource to support the delivery of gynaecological cancer nursing care. Participants articulated their goals for the resource through four subthemes: reducing variation in care; acknowledging diversity in nursing roles; addressing barriers; supporting development. ConclusionThe development of a guidance resource for gynaecological cancer nursing is supported by Australian gynaecological cancer nurses and people with cancer lived experience. It is expected its implementation will assist to improve cancer outcomes, equitable access to quality care and support the development and sustainability of the gynaecological cancer nursing workforce.

Medicine Access Programmes: what do patients think - a patient-reported outcome study on ribociclib in metastatic breast cancer in Australia.

This study evaluated patient-reported outcomes (PROs) of Medicine Access Programmes (MAPs) for Australian metastatic breast cancer patients on ribociclib. Limited patient awareness of MAP enrolment was identified, emphasising the need for improved education and consent processes. Most patients expressed gratitude for accessing non-funded medications and perceived enhanced medication adherence as a key benefit. Integrating PRO data with real-world registry data provides comprehensive insight for future MAP development.

A retrospective audit of audiology encounters in patients undergoing Cisplatin treatment at a large Australian tertiary cancer care centre.

To identify the number and timing of audiology encounters for adult oncology patients in a tertiary care setting in Australia. A retrospective case review was completed for 149 patients who received Cisplatin chemotherapy (CT) at a large, publicly funded tertiary hospital in Brisbane, Queensland, Australia between 1st January and 31st December 2019. Patient data was extracted from the Queensland Oncology Repository (QOR) provided by Cancer Alliance Queensland (CAQ). The number of audiology encounters was low overall with a median of 0 and interquartile range (IQR) of 0-1. Of the entire patient cohort, there was a mean of 1.2 encounters with 56% of patients not engaging with audiology. Where audiology did occur, encounters were most likely before or early in the CT treatment period. This study has demonstrated engagement with audiology services for patients undergoing CT treatment was limited with the few audiology engagements occurring before or early in the CT treatment period. Further research is needed to identify the barriers and facilitators to accessing audiological ototoxic monitoring (OtoM) during chemotherapy treatment in hospitals in Australia. Early identification of ototoxic hearing loss offers the opportunity to minimise further exposure to the ototoxic agent, minimise functional and communication impacts for the patient and provide early opportunity for discussion, education and counselling with patients, carers and their treating team. This, in turn, is expected to improve health related quality of life.

Australian males and females have similar rates of presentation for symptomatic and advanced thyroid cancer: Retrospective analysis of the Australian New Zealand Thyroid Cancer Registry.

Thyroid cancer is more commonly diagnosed in females, however recent research has challenged whether this finding is due to a true difference in biology or rates of diagnosis, with concerns that over-diagnosis may be a factor in differences. The rates of symptomatic versus incidental diagnosis by males and females is not well known. This study used the Australian and New Zealand Thyroid Cancer Registry (ANZTCR) to explore whether symptomatic presentation varies between sexes. Retrospective analysis on ANZTCR data between 2017 and 2022 was performed. Symptomatic cases were those with thyroid compressing symptoms, toxic goiter, Graves' disease, or abnormal laryngoscopy. Cases with asymptomatic goiter or surgeries for a thyroid nodule were classified as incidental. Among 1082 patients with differentiated thyroid cancer, 32% of males and 38% of females presented with symptomatic thyroid disease (p=0.06). A similar rate of presentation of advanced thyroid cancer (T3/4) was seen with male and female patients (n=70, 47% vs. n=79, 53%). Females exhibited a higher prevalence of low-risk relapse cancers according to American Thyroid Association stratification (66.3% vs. 50.4%), whereas males exhibited a higher prevalence of high-risk relapse cancers compared to females (27.3% vs. 15.3%, p<0.001). Regression showed symptoms were associated with more advanced T stage (OR=1.62, p=0.02). Symptomatic presentation was similar between males and females, but symptomatic presentation was associated with larger cancers. This study highlights comparable rates of symptomatic detection between males and females with DTCs and symptomatic presentations were responsible for less than 40% of presentations.

Cancer genetic counseling via telegenetics and telephone: A qualitative study exploring the experience of patients and genetic counselors in an Australian cancer genetics context.

The demand for direct-to-patient (DTP) telegenetics (genetics services delivered via videoconferencing) in genetic counseling practice has rapidly increased, particularly since the COVID-19 pandemic. Recent telegenetics literature is mostly quantitative and not in the Australian context. A qualitative interview study was conducted to address this gap. This research investigated the experiences of patients and genetic counselors (GCs), enrolled in a randomized controlled trial, using telegenetics and telephone for cancer genetic counseling appointments. Twenty-eight semi-structured interviews with patients (n = 22) and GCs (n = 6) were conducted following patient randomization to either a telephone or telegenetics genetic counseling appointment. The interviews explored participant's experiences of telegenetics and compared DTP telegenetics with telephone and in-person delivery. Codebook thematic analysis was used to develop topic summaries from the data. Patient and GC participants noted positive experiences of telegenetics; with key benefits reported as reduced travel time, time and cost saving, ease, convenience, efficiency, and comfortability. Technical issues and privacy concerns were highlighted as potential disadvantages of telegenetics. All but one patient felt sufficiently emotionally supported while using telegenetics. Telegenetics has both benefits and limitations; however, generally, this cohort found telegenetics to be a suitable and acceptable mode of delivery for genetic counseling with many advantages over in-person or telephone appointments. Further studies should be conducted to provide evidence for the long-term implementation of telegenetics, regardless of any future COVID-19 pandemic lockdown restrictions.

Priorities for multimorbidity management and research in cancer: a Delphi study of Australian cancer survivors, clinicians, and researchers.

Multimorbidity is common in people with cancer and associated with increased complexity of care, symptoms, mortality, and costs. This study aimed to identify priorities for care and research for cancer survivors with multimorbidity. A Delphi consensus process was conducted. Elements of care and research were based on Australia's National Strategic Framework for Chronic Conditions, a literature review, and expert input. In Round 1, health professionals, cancer survivors, and researchers rated the importance of 18 principles, 9 enablers, and 4 objectives. In Round 2, new elements were rated and all elements were ranked. In Round 1, all elements reached consensus for care delivery; three principles and one enabler did not reach consensus for research and were eliminated. One principle and two enablers were added, reaching consensus. In the final list, 19 principles, 10 enablers, and 4 objectives were included under care delivery; 14 principles, 9 enablers, and 4 objectives were included under research. For care delivery, principles of 'survivorship' and 'self-management' were ranked highest, and 'peer support' and 'technology' were the most important enablers. For research, 'survivorship' and 'coordinated care' were the highest-ranked principles, with 'peer support' and 'education' the most important enablers. Most elements apply to the general population and cancer survivors; however, additional elements relevant to survivorship need consideration when managing multimorbidity in cancer survivors. Chronic disease frameworks should be more inclusive of issues prioritised by people with, managing, or researching cancer through interdisciplinary approaches including acute and primary care.

Coronary artery calcification detected on low-dose computed tomography in high-risk participants of an Australian lung cancer screening program: A prospective observational study.

Coronary artery calcification (CAC) is a frequent additional finding on lung cancer screening (LCS) low-dose computed tomography (LDCT). Cardiovascular disease (CVD) is a major cause of death in LCS participants. We aimed to describe prevalence of incidental CAC detected on LDCT in LCS participants without prior history of coronary artery disease (CAD), evaluate their CVD risk and describe subsequent investigation and management. Prospective observational nested cohort study including all participants enrolled at a single Australian site of the International Lung Screen Trial. Baseline LDCTs were reviewed for CAC, and subsequent information collected regarding cardiovascular health. 5-year CVD risk was calculated using the AusCVD risk calculator. 55% (226/408) of participants had CAC on LDCT and no prior history of CAD, including 23% with moderate-severe CAC. Mean age of participants with CAC was 65 years, 68% were male. 53% were currently smoking. Majority were high risk (51%) or intermediate risk (32%) of a cardiovascular event in 5 years. 21% of participants were re-stratified to a higher CVD risk group when CAC detected on LCS was incorporated. Only 10% of participants with CAC received lifestyle advice (only 3% currently smoking received smoking cessation advice). 80% of participants at high-risk did not meet guideline recommendations, with 47% of this group remaining without cholesterol lowering therapy. LCS with LDCT offers the potential to identify and communicate CVD risk in this population. This may improve health outcomes for high-risk LCS participants and further personalize management once screening results are known.

Abstract A067: Identifying and targeting FOLFIRINOX resistance mechanisms to improve outcomes in pancreatic cancer

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a 5-year survival rate of only 12%. More than 80% of PDAC patients cannot undergo potentially curative surgical resection due to the presentation of advanced, metastatic disease, and are instead offered systemic chemotherapy regimens to which resistance is rapidly acquired. FOLFIRINOX chemotherapy offers an 11.1-month median survival compared to 6.8 months with Gemcitabine. Rapid onset of resistance to FOLFIRINOX, coupled with the lack of alternative targeted therapies, ultimately results in patients succumbing to the disease. My project aims to identify mechanisms by which PDAC cells acquire resistance to FOLFIRINOX treatment and investigate interventions aimed at enhancing and/or reinstating FOLFIRINOX sensitivity. Our lab has propagated distinct patient derived xenografts (PDXs) from the Avner Australian Pancreatic Cancer Matrix Atlas (APMA) and I have exposed them to 11 - 15 rounds of FOLFIRINOX (or vehicle control) in vivo to reflect the clinical management of PDAC. Additionally, intrapancreatic orthotopic tumors derived from cells from the KPC mouse model (LSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-Cre) have received 5 - 6 rounds of FOLFIRINOX (or vehicle control). These tumors will undergo quantitative data-independent acquisition mass spectrometry proteomic analysis and RNA sequencing transcriptomic analysis (RNAseq) to reveal resistance pathways and/or proteins operating in the chronically treated tumors and the surrounding pancreatic tumor microenvironment. Additionally, we have developed and cultured matched treatment naïve and FOLFIRINOX-treated patient-derived cell lines (PDCLs) and mouse cell lines from the PDX and KPC-derived tumors. These lines will allow us to validate future targets via gene knockdown and/or pharmacological intervention. 3D assays, such as our organotypic matrix models, will be performed to assess the metastatic potential of cancer cells and their response to FOLFIRINOX in vitro. Furthermore, subcutaneous and orthotopic (intrapancreatic) models coupled with intravital (in vivo) imaging and biosensor technology will allow us to assess targeting in live tumors and metastatic sites in real time. It is the hope that this research will lead to the identification of proteins or protein pathways which can be manipulated in order to re-sensitize tumors to FOLFIRINOX chemotherapy. Citation Format: Victoria Tyma, Ying-Fei Liew, Alice Tran, Anna Howell, Shona Ritchie, Avner Australian Pancreatic Cancer Matrix Atlas, Australian Pancreatic Genome Initiative, Thomas Cox, Marina Pajic, David Herrmann, Brooke Pereira, Paul Timpson, Katie Gordon. Identifying and targeting FOLFIRINOX resistance mechanisms to improve outcomes in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr A067.

Abstract A053: Interrogating the spatial biology of pancreatic cancer-associated fibroblasts in resected human pancreatic cancer

Abstract Introduction Cancer-associated fibroblasts (CAFs) are key players in the fibrotic tumour microenvironment (TME) of pancreatic cancer. Recent evidence has demonstrated the existence of multiple CAF subtypes, however there is relatively little evidence validating and corroborating these CAF subtypes in resected human pancreatic cancer. Furthermore, the spatial interactions between CAF subtypes and the epithelial and immune compartments of the pancreatic cancer TME is not well understood. Methods We designed and optimised a bespoke 8-plex immunofluorescence panel for the purposes of CAF subtype profiling and elucidation of CAF spatial biology: panCK, FAP, SMA, CTGF, S100A4, IL6, LIF, PDGFR. This was applied to a cohort of n=215 resected pancreatic cancer, well characterised with highly granular clinico-pathological and transcriptomic data through the Australian Pancreatic Cancer Genome Initiative. Spatial analysis was performed with novel computational biology techniques. Results We demonstrate seven CAF subtypes which cluster to form distinct, highly prognostic “enrichment profiles” (EPs). The cold EP represents quiescent CAFs in close proximity to immune cells (multivariate HR 0.45, 95% CI 0.30-0.68, p&amp;lt;0.001), and the fibrotic EP represents activated CAFs in close proximity to epithelial cells (multivariate HR 2.22, 95% CI 1.48-3.35, p&amp;lt;0.001). We also demonstrate the prognostic power of high spatial entropy (loss of tissue architecture, correlating with the fibrotic EP) vs low spatial entropy (preservation of tissue architecture, correlating with the cold EP) (HR 2.22, 95% CI 1.47-3.35, p&amp;lt;0.001). Conclusion We begin to unravel the elusive spatial biology of pancreatic CAFs in a large resected human cohort. We see changes in immune cell infiltrate, modulation of cellular relationships, and greater tissue disorganisation as a result of CAF activation. These features are highly prognostic and we hypothesise they are driven by changes in crosstalk between TME compartments. Current work focuses on application of these techniques to a large resected neoadjuvantly-treated cohort, allowing further interrogation of the notorious fibrotic post-neoadjuvant pancreatic cancer TME. If accepted for presentation we look forward to presenting both cohorts simultaneously. Citation Format: Adam Bryce, Stephan Dreyer, Fieke Froeling, Silvia Martinelli, Rachel Pennie, Leah Officer-Jones, John Le Quesne, David Chang. Interrogating the spatial biology of pancreatic cancer-associated fibroblasts in resected human pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr A053.

Bauxite mine and alumina refinery workers: mortality and cancer risk.

Aluminium industry workers are at risk of long-term health consequences. To investigate mortality and cancer incidence in bauxite mine and alumina refinery workers. A pre-existing cohort of workers was re-linked with the Australian National Death Index, and the Australian Cancer Database to provide additional death (7 years) and cancer (9 years) data. Standardized mortality ratios (SMRs) and standardized incidence rates (SIRs) were estimated by job category, duration of employment and time since first employment. Linkage was performed for 6935 (6207 male) workers. Compared with the general population, there was a reduced or similar risk of death for mine/refinery workers for all causes except mesothelioma which was increased amongst male production workers [SMR 2.42, 95% CI 1.11-4.60]. Mesothelioma incidence was also increased amongst males [SIR 2.50, 95% CI 1.60-3.71]. Male office workers had a greater incidence of prostate cancer [SIR 1.30, 95% CI 1.06-1.57] and thyroid cancer [SIR 3.47, 95% CI 1.66-6.38]. Melanoma incidence was increased in female office workers [SIR 2.27, 95% CI 1.36-3.54]. Lip cancer incidence was increased in male maintenance/production workers [SIR 2.04, 95% CI 1.02-3.65]. Overall cancer incidence was otherwise similar to the general Australian population. Overall risk of death and incidence of cancer for bauxite mine and alumina refinery workers was similar to the general population. Incidence and risk of death from mesothelioma were higher, likely due to historic asbestos exposure in this and other industries. The increased risk of melanoma, lip, prostate and thyroid cancers requires further investigation.

Safety of Rituximab biosimilar (Riximyo®) following a single switch from the reference product in patients with Non-Hodgkin’s lymphoma: a retrospective study

Unlike small molecule drugs and generic products, the active component of biologics and biosimilars are not identical chemical entities. Despite bioequivalence, there is limited evidence in clinical practice (i.e. Phase IV post-marketing surveillance) regarding the safety of biosimilar rituximab and even less so for “switching therapy” with respect to safety. Drug substitution by switching aims to realise cost savings by changing therapy involving a reference (biologic) product to a biosimilar. A retrospective analysis of safety outcomes including treatment-emergent adverse effects (TEAEs), rates of death and discontinuation of therapy, for all patients that received switching therapy (from reference to biosimilar rituximab, n = 33) was compared to patients who did not did not switch therapy (received biosimilar rituximab only, n = 18) at an Australian metropolitan cancer centre, over a six-month period. There was no statistical significant differences for any safety outcomes examined. Switching therapy for patients receiving rituximab does not lead to poorer safety outcomes.

Real-World Implementation of Simulation-Free Radiation Therapy (SFRT-1000): A Propensity Score-Matched Analysis of 1000 Consecutive Palliative Courses Delivered in Routine Care.

The feasibility of simulation-free radiation therapy (SFRT) has been demonstrated but information regarding its routine care impact and scalability is lacking. In this single-institution, retrospective cohort study, all patients receiving palliative radiation therapy at an Australian tertiary cancer center were eligible for consideration of SFRT unless mask immobilization, a stereotactic technique, or a definitive dose was indicated. Coprimary endpoints were SFRT utilization, impact on consultation-to-RT time, and on-couch treatment duration. Timing metrics were compared with a contemporary local cohort that received simulation-based palliative radiation therapy using unadjusted Wilcoxon rank-sum tests and a propensity score-matched regression. Electronic patient-reported outcomes captured 2-week toxicity and pain response. Between April 2018 and February 2024, 2849 palliative radiation courses were delivered, of which 1904 were eligible. Of the 1904 courses, 1000 (52.5% SFRT utilization) received SFRT, including 668 using intensity-modulated radiation therapy/volumetric-modulated arc therapy. A total of 788 individual patients received SFRT and the median age was 71 years (IQR, 61-80) with 59% being male and 42% being Eastern Collaborative Oncology Group 2-4. SFRT utilization increased from 41% to 54% between years 2018-2019 and 2022-2024. SFRT reduced median consultation-to-RT time from 7.0 to 5.1 days (P < .0001) corresponding to an adjusted average treatment effect in the treated of -2.1 days (95% CI, -2.8 to -1.3). SFRT increased median on-couch treatment duration from 17.8 to 20.5 minutes (P < .0001; adjusted average treatment effect in the treated 2.6 minutes, 95% CI, 1.3-3.9). Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events grade 3 acute toxicity was 9% and at 4 weeks after RT, patients with moderate/severe pain at baseline (≥5/10) had a mean pain reduction of 3.5 points (7.1-3.6; P < .0001). Using widely available technologies, the SFRT-1000 cohort demonstrates routine care scalability with patient-centered and workflow benefits. SFRT is an attractive new paradigm implementable in most settings following adaptation to local requirements. Thus, SFRT opens new avenues to potentially improve access to palliative RT, which remains a global area of need.

Melanoma overdiagnosis: What do we know and what do we do?

Melanoma overdiagnosis occurs when melanomas, not destined to cause morbidity or death in a patient's lifetime, are identified and treated. This study considers the causes and magnitude of melanoma overdiagnosis in Australia. We also speculate about a possible benefit of overdiagnosis in Australia; namely, a reduction in excess deaths in the geographical areas where melanoma is diagnosed most frequently. Overdiagnosis can arguably be mitigated by factors that reduce the number of lesions treated for each melanoma identified. Data from the Australian Cancer Atlas show that there is a reduction in excess deaths from melanoma in geographical areas where diagnostic rates are higher (Pearson correlation coefficient r=-0.5978, 95% CI: -0.6243 to -0.5699, P<0.0001); this being the strongest inverse correlation observed among the 20 cancer types in the Atlas. Is early diagnosis of actual life-threatening melanomas in these geographical regions impacting survival? Further research is planned.

Factors influencing fidelity to guideline implementation strategies for improving pain care at cancer centres: a qualitative sub-study of the Stop Cancer PAIN Trial

BackgroundThe Stop Cancer PAIN Trial was a phase III pragmatic stepped wedge cluster randomised controlled trial which compared effectiveness of screening and guidelines with or without implementation strategies for improving pain in adults with cancer attending six Australian outpatient comprehensive cancer centres (n = 688). A system for pain screening was introduced before observation of a ‘control’ phase. Implementation strategies introduced in the ‘intervention’ phase included: (1) audit of adherence to guideline recommendations, with feedback to clinical teams; (2) health professional education via an email-administered ‘spaced education’ module; and (3) a patient education booklet and self-management resource. Selection of strategies was informed by the Capability, Opportunity and Motivation Behaviour (COM-B) Model (Michie et al., 2011) and evidence for each strategy’s stand-alone effectiveness. A consultant physician at each centre supported the intervention as a ‘clinical champion’. However, fidelity to the intervention was limited, and the Trial did not demonstrate effectiveness. This paper reports a sub-study of the Trial which aimed to identify factors inhibiting or enabling fidelity to inform future guideline implementation initiatives.MethodsThe qualitative sub-study enabled in-depth exploration of factors from the perspectives of personnel at each centre. Clinical champions, clinicians and clinic receptionists were invited to participate in semi-structured interviews. Analysis used a framework method and a largely deductive approach based on the COM-B Model.ResultsTwenty-four people participated, including 15 physicians, 8 nurses and 1 clinic receptionist. Coding against the COM-B Model identified ‘capability’ to be the most influential component, with ‘opportunity’ and ‘motivation’ playing largely subsidiary roles. Findings suggest that fidelity could have been improved by: considering the readiness for change of each clinical setting; better articulating the intervention’s value proposition; defining clinician roles and responsibilities, addressing perceptions that pain care falls beyond oncology clinicians’ scopes of practice; integrating the intervention within existing systems and processes; promoting patient-clinician partnerships; investing in clinical champions among senior nursing and junior medical personnel, supported by medical leaders; and planning for slow incremental change rather than rapid uptake.ConclusionsFuture guideline implementation interventions may require a ‘meta-implementation’ approach based on complex systems theory to successfully integrate multiple strategies.Trial registrationRegistry: Australian New Zealand Clinical Trials Registry; number: ACTRN 12615000064505; data: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspxid=367236&isReview=true.