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In Australia, the COVID-19 pandemic has resulted in the exponential growth in the delivery of telehealth services. Medicare data indicates that the majority of telehealth consultations have used the telephone, despite the known benefits of using video. The aim of this study was to understand the perceived quality and effectiveness of in-person, telephone and videoconsultations for cancer care. Data was collected via online surveys with consumers ( n = 1162) and health professionals ( n = 59), followed by semi-structured interviews with telehealth experienced health professionals ( n = 22) and consumers ( n = 18). Data were analysed using descriptive statistics and significance was tested using the chi-square test. A framework analysis and thematic analysis were used for qualitative data. Results indicate telehealth is suitable for use across the cancer care pathway. However, consumers and health professionals perceived videoconsultations facilitated visual communication and improved patients’ quality of care. The telephone was appropriate for short transactional consultations such as repeat prescriptions. Consumers were rarely given the choice of consultation modality. The choice of modality depended on a range of factors such as the type of consultation and stage of cancer care. Hybrid models of care utilising in-person, video and telephone should be developed and requires further guidance to promote the adoption of telehealth in cancer care.

Cancer clinical trials have traditionally occurred in-person. However, the COVID-19 pandemic has forced adaptions of all aspects of cancer care (including clinical trials) so they can be delivered remotely. We aimed to quantify and qualify current use of telehealth and how it can be further improved and routinely integrated into cancer clinical trials in Australia.We used a mixed-method study design, involving surveys of 14 multi-site Collaborative Cancer Clinical Trial Groups members across Australia (n = 98) and qualitative interviews with trial administrators and clinicians (n = 21).The results of our study indicated a strong willingness to use telehealth for certain transactions of clinical trials because it was perceived as a way of increasing efficiency and reach of services. Hybrid models (including telehealth and in-person methods), which considered transaction, cancer type, and patient preferences were most favorable. Additionally, telehealth allowed for greater equity to access and reduced trial burden but interestingly had little effect on increased diversity and recruitment. Factors influencing telehealth service implementation and uptake included communication among trial stakeholders, training, and learning from the experience of others in the clinical trials community.Many but not all aspects of clinical trial care are appropriate to be delivered via telehealth. A hybrid approach provides flexibility to trial delivery and may support greater equity of access to trials in the future. Our findings and actionable recommendations support the need for greater planning, training, and guidelines to enable telehealth to be better integrated into clinical trials. Opportunities exist to expand the use of remote patient monitoring to enable more objective data collection from trial participants in the future.

Skeletal muscle has remarkable regeneration capabilities, mainly due to its resident muscle stem cells (MuSCs). In this review, we introduce recently developed technologies and the mechanistic insights they provide to the understanding of MuSC biology, including the re-definition of quiescence and Galert states. Additionally, we present recent studies that link MuSC function with cellular heterogeneity, highlighting the complex regulation of self-renewal in regeneration, muscle disorders and aging. Finally, we discuss MuSC metabolism and its role, as well as the multifaceted regulation of MuSCs by their niche. The presented conceptual advances in the MuSC field impact on our general understanding of stem cells and their therapeutic use in regenerative medicine., Skeletal muscle has a remarkable regenerative capacity, which can largely be attributed to resident muscle stem cells (MuSCs). Here, the authors review the molecular mechanisms regulating MuSC quiescence, activation and proliferation, how these processes are regulated by the stem cell niche, and the role of MuSCs in neuromuscular diseases.

Introduction Driven by the need to reduce risk of SARS‐CoV‐2 infection and optimise use of health system resources, while maximising patient outcomes, the COVID‐19 pandemic has prompted unprecedented changes in cancer care. Some new or modified health care practices adopted during the pandemic will be of long term value in improving the quality and resilience of cancer care in Australia and internationally. The Cancer Australia consensus statement is intended to guide and enhance the delivery of cancer care during the pandemic and in a post‐pandemic environment. This article summarises the full statement, which is available at https://www.canceraustralia.gov.au/covid‐19/covid‐19‐recovery‐implications‐cancer‐care. Main recommendations The statement is informed by a desktop literature review and input from cancer experts and consumers at a virtual roundtable, held in July 2020, on key elements of cancer care that changed during the pandemic. It describes targeted strategies (at system, service, practitioner and patient levels) to retain, enhance and embed high value changes in practice. Principal strategies include: implementing innovative models of care that are digitally enabled and underpinned by clear governance, policies and procedures to guide best practice cancer care;enabling health professionals to deliver evidence‐based best practice and coordinated, person‐centred cancer care; andempowering patients to improve health literacy and enhancing their ability to engage in informed, shared decision making. Changes in management as a result of this statement Widespread adoption of high value health care practices across all levels of the cancer control sector will be of considerable benefit to the delivery of optimal cancer care into the future.

Shared breast cancer follow-up care involving a breast cancer specialist and a general practitioner (GP) has been demonstrated to be effective, yet barriers to participation in this model by women remain. This study explores the responses of women who recently finished active treatment for early breast cancer (EBC) to a proposed model of shared follow-up care to understand the type of information needed to support participation.Qualitative study based on focus groups with women with EBC in the early stage of follow-up care from across metropolitan, regional and rural settings in Australia. Discussions were transcribed and thematic analysis is undertaken.Four focus groups were conducted, involving 31 women aged between 32 and 78 years. The discussion focused on two topics. In the first topic 'Current experiences of follow-up care', two themes emerged: (i) follow-up as a continuation of active treatment; (ii) GPs involvement in care during active treatment influence attitudes to shared follow-up care. In the second topic area 'Perceptions of shared follow-up care' four themes emerged: (i) a need for evidence regarding model effectiveness; (ii) choice; (iii) concerns regarding capacity and capability of GPs to deliver care and (iv) the need for clear communication between GPs, specialists and women.Women need information regarding the evidence for the effectiveness of shared follow-up care to assure them it does not pose a risk to their health outcomes. Clear descriptions of GP and specialist roles and the opportunity to jointly decide participation is essential for the model to be adopted.

BACKGROUND Shared breast cancer follow-up care involving a breast cancer specialist and a general practitioner (GP) has been demonstrated to be effective, yet barriers to participation in this model by women remain. This study explores the responses of women who recently finished active treatment for early breast cancer (EBC) to a proposed model of shared follow-up care to understand the type of information needed to support participation. METHODS Qualitative study based on focus groups with women with EBC in the early stage of follow-up care from across metropolitan, regional and rural settings in Australia. Discussions were transcribed and thematic analysis is undertaken. RESULTS Four focus groups were conducted, involving 31 women aged between 32 and 78 years. The discussion focused on two topics. In the first topic 'Current experiences of follow-up care', two themes emerged: (i) follow-up as a continuation of active treatment; (ii) GPs involvement in care during active treatment influence attitudes to shared follow-up care. In the second topic area 'Perceptions of shared follow-up care' four themes emerged: (i) a need for evidence regarding model effectiveness; (ii) choice; (iii) concerns regarding capacity and capability of GPs to deliver care and (iv) the need for clear communication between GPs, specialists and women. CONCLUSIONS Women need information regarding the evidence for the effectiveness of shared follow-up care to assure them it does not pose a risk to their health outcomes. Clear descriptions of GP and specialist roles and the opportunity to jointly decide participation is essential for the model to be adopted.

The chromosome translocations generating PAX3-FOXO1 and PAX7-FOXO1 chimeric proteins are the primary hallmarks of the paediatric fusion-positive alveolar subtype of Rhabdomyosarcoma (FP-RMS). Despite the ability of these transcription factors to remodel chromatin landscapes and promote the expression of tumour driver genes, they only inefficiently promote malignant transformation in vivo. The reason for this is unclear. To address this, we developed an in ovo model to follow the response of spinal cord progenitors to PAX-FOXO1s. Our data demonstrate that PAX-FOXO1s, but not wild-type PAX3 or PAX7, trigger the trans-differentiation of neural cells into FP-RMS-like cells with myogenic characteristics. In parallel, PAX-FOXO1s remodel the neural pseudo-stratified epithelium into a cohesive mesenchyme capable of tissue invasion. Surprisingly, expression of PAX-FOXO1s, similar to wild-type PAX3/7, reduce the levels of CDK-CYCLIN activity and increase the fraction of cells in G1. Introduction of CYCLIN D1 or MYCN overcomes this PAX-FOXO1-mediated cell cycle inhibition and promotes tumour growth. Together, our findings reveal a mechanism that can explain the apparent limited oncogenicity of PAX-FOXO1 fusion transcription factors. They are also consistent with certain clinical reports indicative of a neural origin of FP-RMS., Author summary The fusion-positive subtype of rhabdomyosarcoma (FP-RMS) is a rare malignant paediatric cancer, whose induction and evolution still remain to be deciphered. Out of the gross genetic aberrations found in these cancers, t(2:13) and t(1,13) chromosome translocations are the first to appear and lead to the expression of fusion proteins made of the DNA binding domains of either PAX3 or PAX7 and the transactivation domain of FOXO1. Both PAX3-FOXO1 and PAX7-FOXO1 have a strong impact on gene transcription, yet they only inefficiently promote the transformation of healthy cells into tumorigenic cells. To address this issue, we have used chick embryos to monitor in vivo the early response of cells to PAX-FOXO1 chimeric proteins. We showed that both proteins, but not the normal PAX3 and PAX7, transform neural cells into cells with FP-RMS molecular features. The PAX-FOXO1s also force polarized epithelial neural cells to adopt a mesenchymal phenotype with tissue invasive properties. However, the PAX-FOXO1s inhibit cell division and hence tumour growth. Genetically re-activating core cell cycle regulators rescues PAX-FOXO1 mediated cell cycle inhibition. Together, our findings bring further support to the idea that the PAX-FOXO1s are stricto sensu oncoproteins, whose oncogenicity is limited by negative effects on cell cycle.

The chromosome translocations generating PAX3FOXO1 and PAX7FOXO1 chimeric proteins are the primary hallmarks of the paediatric cancer, Alveolar Rhabdomyosarcoma (ARMS). Despite the ability of these transcription factors to remodel chromatin landscapes and promote the expression of tumour driver genes, they only inefficiently promote malignant transformationin vivo. The reason for this is unclear. To address this, we developed anin ovomodel to follow the response of spinal cord progenitors to PAXFOXO1s. Our data demonstrate that PAXFOXO1s, but not wild-type PAX3 and PAX7, trigger the trans-differentiation of neural cells into ARMS-like cells with myogenic characteristics. In parallel expression of PAXFOXO1s remodels the neural pseudo-stratified epithelium into a cohesive mesenchyme capable of tissue invasion. Surprisingly, gain for PAXFOXO1s, as for wild-type PAX3/7, reduces the levels of CDK-CYCLIN activity and arrests cells in G1. Introduction of CYCLIN D1 or MYCN overcomes PAXFOXO1s mediated cell cycle inhibition and promotes tumour growth. Together, our findings reveal a mechanism underpinning the apparent limited oncogenicity of PAXFOXO1 fusion transcription factors and support a neural origin for ARMS.

The protein O-glucosyltransferase 1 (Poglut1) links O-glucose to epidermal growth factor-like repeats harboring the C1XSX(P/A)C2 consensus sequence. Poglut1 is a ubiquitous endoplasmic reticulum-resident protein largely found in metazoans, but only about 50 proteins possess this consensus sequence. Among them, Notch receptors have multiple O-glucosylation sites and their activation depends on this status. In adult skeletal muscle, Notch signaling contributes to the maintenance of satellite cell (SC) quiescence and the proliferation of myoblasts after SC activation. To address the role of Poglut1 in myogenesis, we created two stable C2C12 cell lines where Poglut1 was downexpressed by 42% and 81%, and assessed their ability to differentiate. We showed that Poglut1 knockdown reduced Notch signaling and largely affected the key regulators of myogenic differentiation, with PAX7 decrease and MYOD increase. This perturbed Pax7/MyoD expression balance led to a premature myogenic differentiation and an increase in myotube size, accentuated in case of strong Poglut1 downexpression. Differences observed between myotubes of the two Poglut1 knockdown cell lines could reflect dissimilar fusion defects. We concluded that Poglut1 contributes to myogenesis by regulating Notch signaling and defining, directly or indirectly, the proportion of cells that commit differentiation.

Past work has shown that the protein O-fucosyltransferase 1 (POFUT1) is involved in mammal myogenic differentiation program. Pofut1 knockdown (Po &ndash, ) in murine C2C12 cells leads to numerous elongated and thin myotubes, suggesting significant defects in secondary fusion. Among the few pathways involved in this process, NFATc2/IL-4 is described as the major one. To unravel the impact of POFUT1 on secondary fusion, we used wild-type (WT) C2C12 and Po &ndash, cell lines to follow Myf6, Nfatc2, Il-4 and Il-4r&alpha, expressions during a 120 h myogenic differentiation time course. Secreted IL-4 was quantified by ELISA. IL-4R&alpha, expression and its labeling on myogenic cell types were investigated by Western blot and immunofluorescence, respectively. Phenotypic observations of cells treated with IL-4R&alpha, blocking antibody were performed. In Po &ndash, we found a decrease in nuclei number per myotube and a downexpression of Myf6. The observed downregulation of Nfatc2 is correlated to a diminution of secreted IL-4 and to the low level of IL-4R&alpha, for reserve cells. Neutralization of IL-4R&alpha, on WT C2C12 promotes myonuclear accretion defects, similarly to those identified in Po &ndash, Thus, POFUT1 could be a new controller of myotube growth during myogenesis, especially through NFATc2/IL-4 signaling pathway.

e18685 Background: Health systems pressures during the COVID-19 pandemic have driven adoption of innovative models of cancer care which optimise resources and protect patients and staff. High-value changes should be identified and retained to improve resilience of cancer care. Methods: Cancer Australia reviewed the literature and consulted with oncology health professionals, cancer control experts and consumers to examine elements of cancer care that changed during the pandemic. Strategies that support high-value care and improve cancer outcomes were identified. Results: The pandemic highlighted models of care which minimise risk of infection for cancer patients, whilst optimising outcomes. Of the numerous cancer care elements that we examined, this abstract focuses on key enhancements in digital health and treatment practices. Digital health helped maintain quality and continuity of cancer care during the pandemic. Use of telehealth (for clinical and supportive care), e-prescribing, and e-ordering of investigations increased, supported by national health system funding. Shared care between care settings was facilitated by rapid uptake of telehealth, e-health records, virtual multidisciplinary team meetings and secure messaging. Treatment modifications included hypofractionated radiotherapy, transitioning to oral chemotherapy where possible, and home-based palliative care. Lower thresholds adopted for use of G-CSF with chemotherapy to reduce risk of febrile neutropenia, aimed to decrease hospital admission rates. It is important to address barriers to uptake of these high value changes. For digital health, variations in patient access to telehealth and digital health literacy can be reduced through technical and coordination support (tailored to people with diverse needs and backgrounds), with telehealth consultations offered in safe, accessible clinical or community settings. Administrative and technical burdens in health service settings can be mitigated through sustainable IT infrastructure, standardised processes for appointments, and improving staff digital health capabilities. Patient anxiety regarding changes in care plans can be mitigated through transparent, accessible, and culturally appropriate communication, documentation and shared decision-making. Clinician uncertainty in calculating risks and benefits in treatment modifications can be addressed through evidence-based standardised care procedures and risk-stratification protocols. Conclusions: Many modifications to cancer care made during the pandemic can have long-term benefits and should become standard care, including enhancements in digital health and treatment practices. Strategies have been identified which enable these changes and address barriers to uptake at the system-, service-, practitioner-, and patient-level. Efforts to embed high value changes are required across the cancer control sector.

e24028 Background: Given the impact of COVID-19 on Indigenous and ethnic minority populations observed globally, keeping COVID-19 out of vulnerable Aboriginal and Torres Strait Islander (Indigenous Australian) communities remains a priority. Compared to non-Indigenous Australians, Indigenous Australians experience disparities in cancer incidence and outcomes due to social disadvantage, increased cancer-related modifiable risk factors, poorer access to health services and lower participation in screening. During the pandemic, cancer-related investigations and treatment reduced significantly in Australia, leading to potential decreases in cancer diagnoses and consequences for future survival outcomes. Concerned about the risk of morbidity and mortality due to COVID-19 for Indigenous Australians, as well as worsening cancer outcomes, Cancer Australia undertook strategic health promotion initiatives, to inform and support optimal cancer care. Methods: In consultation with respected Indigenous colleagues to ensure cultural appropriateness of language and information, we published a dedicated webpage titled ‘ Cancer and COVID-19 – what it means for our Mob*’ with tailored information, advice, and links to key resources and support services for Indigenous Australians. We also released a video titled ‘ Act early for our Mob’s Health’, providing targeted, culturally appropriate, consumer-friendly information to encourage Indigenous Australians to see their doctor or Aboriginal Health Worker with symptoms that may be due to cancer. Results: The information hub has been well-received among the Indigenous Australian community, receiving over 3,200 visits, and the social media campaigns have received over 1.4 million impressions and 46,000 video views between mid-March 2020 to mid-February 2021. This campaign has supported proactivity among the Indigenous population in keeping their communities safe during the pandemic, maintaining a population rate of COVID-19 of less than one percent of all confirmed cases in Australia. Conclusions: Culturally appropriate information and resources developed through the process of co-design can help to influence positive health behaviour change in Indigenous populations. We predict that our strategic, multi-channel health promotion campaign is contributing to keeping the Indigenous Australian community safe and informed during the pandemic, with additional work needed to monitor cancer rates and outcomes and address the ongoing information needs of the community. *Mob is a colloquial term to identify a group of Indigenous Australians associated with a family or community from a certain place.

e18628 Background: At the start of the COVID-19 pandemic, a plan for cancer management during a pandemic did not exist. It soon became clear that without proper planning, cancer outcomes would worsen. Cancer patients are at increased risk of COVID-19 infection, morbidity, and mortality. Health sectors internationally reduced or paused non-urgent cancer care to protect cancer patients from COVID-19. However, disproportionate delays in screening, diagnosis, and treatment can unduly impact cancer outcomes, and backlogs can further burden a strained health system. Tailored approaches to cancer management are required which balance health resource availability along with the risks of exposure and benefits of treatment. Australia’s relatively low COVID-19 case numbers afforded Cancer Australia an opportunity to proactively plan for optimal cancer management during this, and future, pandemics. Methods: Cancer Australia’s Cancer care in the time of COVID-19: A conceptual framework for the management of cancer during a pandemic (the framework) maps evidence-based cancer care considerations in relation to a health system’s capacity across acute and recovery pandemic phases, in relation to steps of the cancer care pathway. The framework promotes infection control and resource prioritisation in the context of innovative care models, triaging approaches and individualised treatment plans, underpinned by effective communication and shared decision-making. Results: The framework supports health system planning and risk-stratified approaches to guide decision-making and improve cancer outcomes. Many aspects of cancer care are recommended to continue (to varying degrees) in most pandemic phases, with modifications or pauses in some aspects of care as the pandemic curve approaches or exceeds health system capacity. Principles of the framework were employed during the second wave of COVID-19 in the Australian state of Victoria, with continuation of cancer screening programs, diagnostic investigations, and treatments wherever it was safe to do so. This resulted in reductions in cancer services and treatment being relatively smaller than in the first wave. Conclusions: Cancer management in a pandemic is not a one-size-fits-all. Countries and jurisdictions need to tailor cancer care according to the risk of the health system becoming overwhelmed. The framework guides optimal cancer care to improve outcomes for people with cancer, while minimising COVID-19 infection. As further evidence becomes available from this pandemic or in future pandemics, this framework can be refined to inform ongoing and future pandemic health system planning.

Introduction: Air pollution (AP) represents the largest environmental risk for health. Such considerations however rely on the static quantification of only a few individual components of AP, without considering their interactions, chemical reactivity and synergistic toxicity. We therefore developed an innovative approach to analyze the health effects of “real life” model atmospheres at the preclinical level. Here, we report the first results of the feasibility study. Methods: A realistic atmosphere, representative of a 2017 pollution event in Paris, was generated (CESAM atmospheric simulation chamber - cesam.cnrs.fr). The chamber was connected to stalling cabinets where mice were exposed during 6 or 48 hours. Lungs, spleen, adipose tissue, heart, mesenteric ganglions were then harvested to address the expression of detoxification and antioxidant genes, as well as total cell count (TCC) and inflammatory cytokines expression in BAL fluid Results: The atmosphere contained 57.3 µg/m3 particulate matter, 114±11 ppb NO2 and 242±101 ppb O3. No mortality and no weight loss was observed. Increased expression of Ahr, Cyp1a1, Hmox1 and NQO1 was detected in the lungs, and increased TCC and KC concentrations in the BAL. Interestingly, we found extra pulmonary modifications; increased expression of Ahr, Cyp1a1, Hmox1 and NQO1 in the spleen, Hmox1, Cyp1a1 and Cyp1b1 in ganglions, and Hmox1 in the adipose tissue and heart. Limited modifications were detected after 6h. Conclusion: These preliminary results demonstrate the feasibility of our innovative experimental approach, which represents a versatile tool to get a better understanding of AP impacts on health.

Background Obesity is associated with oxidative stress, a major factor in carcinogenesis, and with high leptin concentration. The aim of this study was to determine the effects of leptin on the antioxidant response in three human mammary epithelial cells each presenting a different neoplastic status: healthy human mammary epithelial cells (HMEC), oestrogen-receptor positive MCF-7 cells and triple-negative MDA-MB-231 cells. Methods This in vitro kinetic study characterized the cell antioxidant response after 1, 6 and 24 h in the presence of leptin (10 or 100 ng/ml).The antioxidant response was defined in terms of cell glutathione content, gene expression and catalytic activity of antioxidant enzymes (i.e. glutathione peroxidase 1 (Gpx1), glutathione reductase (GR), glutathione S transferase (GST), heme-oxygenase 1 (HO-1) and cyclooxygenase-2 (COX-2)). Oxidative stress occurrence was assessed by lipid hydro peroxide (HPLIP) and isoprostane concentrations in culture media at 24 h. Results At both concentrations used, leptin induced ROS production in all cell models, contributing to various antioxidant responses linked to neoplastic cell status. HMEC developed a highly inducible antioxidant response based on antioxidant enzyme activation and an increase in cell GSH content at 10 ng/ml of leptin. However, at 100 ng/ml of leptin, activation of antioxidant response was lower. Conversely, in tumour cells, MCF-7 and MDA-MB-231, leptin did not induce an efficient antioxidant response, at either concentration, resulting in an increase of lipid peroxidation products. Conclusions Leptin can modulate the oxidative status of mammary epithelial cells differently according to their neoplastic state. These novel results shed light on oxidative status changes in mammary cells in the presence of leptin.

NADPH oxidase (NOX) complexes (a family of seven isoforms) drive cellular ROS production in patho-logical processes such as cancer. NOX-driven ROS production is involved in cell mechanisms from signalling to oxidative stress. Leptin, an adipokine overexpressed in obese patients, has been investigated in studies on breast carcinogenesis, but its effects on oxidative stress remain largely unexplored, especially in breast cancer. The study used three human mammary epithelial cell models presenting different neoplastic status (healthy primary HMECs, neoplastic MCF-7 cells and neoplastic MDA-MB-231 cells) to determine the effects of leptin on short-term ROS production and to characterize the enzymes involved. All three cell models significantly expressed NADPH oxidase isoform 5 (NOX5) in our culture conditions. All models showed induced ROS production regardless of leptin concentration (10 ng/ml mimicking good health, 100 ng/ml mimicking obesity). Cell treatment with either siRNA against NOX5, NOX inhibitor DPI or a calcium channel blocker (verapamil) confirmed the putative involvement of the NOX5 isoenzyme in ROS production. Moreover, cell treatments suppressed ROS production under leptin at both concentrations. Neoplastic cells appeared unable to downregulate NOX5 mRNA expression under leptin. Leptin emerged as a potential activator of ROS production in human epithelial mammary cells, where the ROS production was apparently linked to NOX5 activation. This novel finding could shed light on the potential role of obesity-associated hyperleptinemia in mammary cells via the activation of NOX enzymes.