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1. Comparison of actionable events detected in cancer genomes by whole-genome sequencing, in silico whole-exome and mutation panels

Author

Ramarao-Milne, P., Kondrashova, O., Patch, A.-M., Nones, K., Koufariotis, L.T., Newell, F., Addala, V., Lakis, V., Holmes, O., Leonard, C., Wood, S., Xu, Q., Mukhopadhyay, P., Naeini, M.M., Steinfort, D., Williamson, J.P., Bint, M., Pahoff, C., Nguyen, P.T., Twaddell, S., Arnold, D., Grainge, C., Basirzadeh, F., Fielding, D., Dalley, A.J., Chittoory, H., Simpson, P.T., Aoude, L.G., Bonazzi, V.F., Patel, K., Barbour, A.P., Fennell, D.A., Robinson, B.W., Creaney, J., Hollway, G., Pearson, J.V., and Waddell, N.

Published
2022
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2. Impact of Synoptic Reporting on Completeness of Systematic Endoscopic Lymph Node Sampling in Non-small Cell Lung Cancer Patients: A Post-hoc Analysis From the SEISMIC Study

Author

Steinfort, D., primary, Watson, J.M., additional, Kothari, G., additional, Wallace, N., additional, Hardcastle, N., additional, Rangamuwa, K., additional, Curran, J., additional, Yo, S., additional, Bashirdazeh, F., additional, Nguyen, P., additional, Jennings, B.R., additional, Fielding, D.I., additional, Irving, L., additional, Siva, S., additional, Crombag, L., additional, Annema, J., additional, Yasufuku, K., additional, and Ost, D.E., additional

Published
2024
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4. Systematic Endoscopic Staging of Mediastinum to Determine Impact on Radiotherapy for Locally Advanced Lung Cancer (seismic): An International Multicentre Single-arm Clinical Trial

Author

Steinfort, D., primary, Kothari, G., additional, Wallace, N., additional, Hardcastle, N., additional, Rangamuwa, K., additional, Lee, P., additional, Yo, S., additional, Bashirzadeh, F., additional, Nguyen, P., additional, Jennings, B.R., additional, Fielding, D.I., additional, Crombag, L., additional, Irving, L., additional, Yasufuku, K., additional, Annema, J., additional, Ost, D.E., additional, and Siva, S., additional

Published
2024
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5. Reduction of COPD Hyperinflation by Endobronchial Valves Improves Intercostal Muscle Morphology on Ultrasound

Author

Wallbridge P, Hew M, Parry SM, Irving L, and Steinfort D

Subjects
endobronchial valve, copd, ultrasound, respiratory muscle, measurement, Diseases of the respiratory system, RC705-779
Abstract

Peter Wallbridge,1,2 Mark Hew,1,3,4 Selina M Parry,5 Louis Irving,1,2 Daniel Steinfort1,2 1Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC, Australia; 2Department of Respiratory and Sleep Medicine, Royal Melbourne Hospital, Parkville, VIC, Australia; 3Public Health and Preventive Medicine, Monash University, Clayton, VIC, Australia; 4Allergy, Asthma & Clinical Immunology, Alfred Health, Prahran, VIC, Australia; 5Department of Physiotherapy, The University of Melbourne, Parkville, VIC, AustraliaCorrespondence: Peter WallbridgeDepartment of Respiratory Medicine, Level 5 East, Royal Melbourne Hospital, Grattan St, Parkville, VIC 3050, AustraliaTel +61 3 9342 7000Fax +61 3 9342 3141Email peter.wallbridge@mh.org.auBackground and Objectives: Parasternal intercostal ultrasound morphology reflects spirometric COPD severity. Whether this relates to the systemic nature of COPD or occurs in response to hyperinflation is unknown. We aimed to assess changes in ultrasound parasternal intercostal muscle quantity and quality (echogenicity) in response to relief of hyperinflation. We hypothesised that reduction in hyperinflation following endobronchial valve (EBV) insertion would increase ultrasound parasternal thickness and decrease echogenicity.Methods: In this prospective cohort study, eight patients with severe COPD underwent evaluation of health-related quality of life, lung function, and sonographic thickness of 2nd parasternal intercostal muscles and diaphragm thickness, both before and after EBV insertion. Relationships between physiological and radiographic lung volumes, quality of life and ultrasound parameters were determined.Results: Baseline FEV1 was 1.02L (SD 0.37) and residual volume (RV) was 202% predicted (SD 41%). Median SGRQ was 63.26 (range 20– 70.6). Change in RV (− 0.51 ± 0.9L) following EBV-insertion showed a strong negative correlation with change in parasternal thickness (r = − 0.883) ipsilateral to EBV insertion, as did change in target lobe volume (− 0.89 ± 0.6L) (r = − 0.771). Parasternal muscle echogenicity, diaphragm thickness and diaphragm excursion did not significantly change.Conclusions: Dynamic changes in intercostal muscle thickness on ultrasound measurement occur in response to relief of hyperinflation. We demonstrate linear relationships between intercostal thickness and change in hyperinflation following endobronchial valve insertion. This demonstrates the deleterious effect of hyperinflation on intrinsic inspiratory muscles and provides an additional mechanism for symptomatic response to EBVs.Keywords: endobronchial valve, COPD, ultrasound, respiratory muscle, measurement

Published
2020

7. EP08.02-20 A Prospective Study of Gallium-68 Ventilation and Perfusion PET/CT Before, During, and After Radiotherapy in Patients with NSCLC

Author

Wallace, N.D., primary, Hardcastle, N., additional, Bressel, M., additional, Bucknell, N., additional, McIntosh, L., additional, Callahan, J., additional, MacManus, M., additional, Shaw, M., additional, Plumridge, N., additional, Ball, D., additional, Selbie, L., additional, Hofman, M., additional, Kron, T., additional, Steinfort, D., additional, and Siva, S., additional

Published
2023
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8. Dosimetric Impact of Systematic Mediastinal Staging via Endobronchial Ultrasound for Patients with Locally Advanced Lung Cancer: The SEISMIC Trial

Author

Siva, S., primary, Wallace, N., additional, Hardcastle, N., additional, Kothari, G., additional, Crombag, L., additional, Rangamuwa, K., additional, Annema, J., additional, Lee, P., additional, Dieleman, E.M., additional, Jennings, B., additional, Yo, S., additional, Nguyen, P., additional, Bashirzadeh, F., additional, Fielding, D., additional, Yasufuku, K., additional, Ost, D., additional, Irving, L., additional, and Steinfort, D., additional

Published
2023
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10. Systematic Endoscopic Staging of Mediastinum to Determine Impact on Radiotherapy for Locally Advanced Lung Cancer (SEISMIC): Initial Findings of a Prospective Multicentre Interventional Study

Author

Steinfort, D., primary, Siva, S., additional, Yasufuku, K., additional, Annema, J., additional, Irving, L., additional, Crombag, L., additional, Jennings, B.R., additional, Fielding, D.I., additional, Bashirzadeh, F., additional, Nguyen, P., additional, Yo, S., additional, Rangamuwa, K., additional, Lee, P., additional, Kothari, G., additional, Hardcastle, N., additional, and Ost, D.E., additional

Published
2023
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11. Early immune pressure initiated by tissue-resident memory T cells sculpts tumor evolution in non-small cell lung cancer

Author

Weeden, CE, Gayevskiy, V, Marceaux, C, Batey, D, Tan, T, Yokote, K, Ribera, NT, Clatch, A, Christo, S, Teh, CE, Mitchell, AJ, Trussart, M, Rankin, LC, Obers, A, McDonald, JA, Sutherland, KD, Sharma, VJ, Starkey, G, D'Costa, R, Antippa, P, Leong, T, Steinfort, D, Irviing, L, Swanton, C, Gordon, CL, Mackay, LK, Speed, TP, Gray, DHD, Asselin-Labat, M-L, Weeden, CE, Gayevskiy, V, Marceaux, C, Batey, D, Tan, T, Yokote, K, Ribera, NT, Clatch, A, Christo, S, Teh, CE, Mitchell, AJ, Trussart, M, Rankin, LC, Obers, A, McDonald, JA, Sutherland, KD, Sharma, VJ, Starkey, G, D'Costa, R, Antippa, P, Leong, T, Steinfort, D, Irviing, L, Swanton, C, Gordon, CL, Mackay, LK, Speed, TP, Gray, DHD, and Asselin-Labat, M-L

Abstract

Tissue-resident memory T (TRM) cells provide immune defense against local infection and can inhibit cancer progression. However, it is unclear to what extent chronic inflammation impacts TRM activation and whether TRM cells existing in tissues before tumor onset influence cancer evolution in humans. We performed deep profiling of healthy lungs and lung cancers in never-smokers (NSs) and ever-smokers (ESs), finding evidence of enhanced immunosurveillance by cells with a TRM-like phenotype in ES lungs. In preclinical models, tumor-specific or bystander TRM-like cells present prior to tumor onset boosted immune cell recruitment, causing tumor immune evasion through loss of MHC class I protein expression and resistance to immune checkpoint inhibitors. In humans, only tumors arising in ES patients underwent clonal immune evasion, unrelated to tobacco-associated mutagenic signatures or oncogenic drivers. These data demonstrate that enhanced TRM-like activity prior to tumor development shapes the evolution of tumor immunogenicity and can impact immunotherapy outcomes.

Published
2023

13. PL02.14 Triaging ILST Screening Participants at Program Entry: Comparative Performance of PanCan versus LungRADSv1.1 Protocol

Author

McWilliams, A.M., Tammemagi, M., Atkar-Khattra, S., Mayo, J., Meyers, R., Yee, J., English, J., Marshall, H., Passmore, L., Bowman, R., Yang, I., Brims, F., Logan, J., Lim, K.P., Mo, L., Melsom, S., Saffar, B., Kwok, Y., Sheehan, R., Teh, M., Dormer, S., Stone, E., Hsu, E., Hu, X., Milner, B., Nguyen, D., Rofe, C., Silverstone, E., Manser, R., Pascoe, D., McCusker, M., Steinfort, D., Irving, L., Bonney, A., Lam, D., Lam, M.-Y., Vardhanabhuti, V., Fogarty, P., Rosell, A., Baeza, S., Fong, K., and Lam, S.

Published
2024
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15. USPSTF2013 versus PLCOm2012 lung cancer screening eligibility criteria (International Lung Screening Trial): interim analysis of a prospective cohort study

Author

Tammemagi, MC, Ruparel, M, Tremblay, A, Myers, R, Mayo, J, Yee, J, Atkar-Khattra, S, Yuan, R, Cressman, S, English, J, Bedard, E, MacEachern, P, Burrowes, P, Quaife, SL, Marshall, H, Yang, I, Bowman, R, Passmore, L, McWilliams, A, Brims, F, Lim, KP, Mo, L, Melsom, S, Saffar, B, Teh, M, Sheehan, R, Kuok, Y, Manser, R, Irving, L, Steinfort, D, McCusker, M, Pascoe, D, Fogarty, P, Stone, E, Lam, DCL, Ng, M-Y, Vardhanabhuti, V, Berg, CD, Hung, RJ, Janes, SM, Fong, K, Lam, S, Tammemagi, MC, Ruparel, M, Tremblay, A, Myers, R, Mayo, J, Yee, J, Atkar-Khattra, S, Yuan, R, Cressman, S, English, J, Bedard, E, MacEachern, P, Burrowes, P, Quaife, SL, Marshall, H, Yang, I, Bowman, R, Passmore, L, McWilliams, A, Brims, F, Lim, KP, Mo, L, Melsom, S, Saffar, B, Teh, M, Sheehan, R, Kuok, Y, Manser, R, Irving, L, Steinfort, D, McCusker, M, Pascoe, D, Fogarty, P, Stone, E, Lam, DCL, Ng, M-Y, Vardhanabhuti, V, Berg, CD, Hung, RJ, Janes, SM, Fong, K, and Lam, S

Abstract

BACKGROUND: Lung cancer is a major health problem. CT lung screening can reduce lung cancer mortality through early diagnosis by at least 20%. Screening high-risk individuals is most effective. Retrospective analyses suggest that identifying individuals for screening by accurate prediction models is more efficient than using categorical age-smoking criteria, such as the US Preventive Services Task Force (USPSTF) criteria. This study prospectively compared the effectiveness of the USPSTF2013 and PLCOm2012 model eligibility criteria. METHODS: In this prospective cohort study, participants from the International Lung Screening Trial (ILST), aged 55-80 years, who were current or former smokers (ie, had ≥30 pack-years smoking history or ≤15 quit-years since last permanently quitting), and who met USPSTF2013 criteria or a PLCOm2012 risk threshold of at least 1·51% within 6 years of screening, were recruited from nine screening sites in Canada, Australia, Hong Kong, and the UK. After enrolment, patients were assessed with the USPSTF2013 criteria and the PLCOm2012 risk model with a threshold of at least 1·70% at 6 years. Data were collected locally and centralised. Main outcomes were the comparison of lung cancer detection rates and cumulative life expectancies in patients with lung cancer between USPSTF2013 criteria and the PLCOm2012 model. In this Article, we present data from an interim analysis. To estimate the incidence of lung cancers in individuals who were USPSTF2013-negative and had PLCOm2012 of less than 1·51% at 6 years, ever-smokers in the Prostate Lung Colorectal and Ovarian Cancer Screening Trial (PLCO) who met these criteria and their lung cancer incidence were applied to the ILST sample size for the mean follow-up occurring in the ILST. This trial is registered at ClinicalTrials.gov, NCT02871856. Study enrolment is almost complete. FINDINGS: Between June 17, 2015, and Dec 29, 2020, 5819 participants from the International Lung Screening Trial (ILST) were enr

Published
2022

16. Comparison of actionable events detected in cancer genomes by whole-genome sequencing, in silico whole-exome and mutation panels

Author

Ramarao-Milne, P, Kondrashova, O, Patch, A-M, Nones, K, Koufariotis, LT, Newell, F, Addala, V, Lakis, V, Holmes, O, Leonard, C, Wood, S, Xu, Q, Mukhopadhyay, P, Naeini, MM, Steinfort, D, Williamson, JP, Bint, M, Pahoff, C, Nguyen, PT, Twaddell, S, Arnold, D, Grainge, C, Basirzadeh, F, Fielding, D, Dalley, AJ, Chittoory, H, Simpson, PT, Aoude, LG, Bonazzi, VF, Patel, K, Barbour, AP, Fennell, DA, Robinson, BW, Creaney, J, Hollway, G, Pearson, JV, Waddell, N, Ramarao-Milne, P, Kondrashova, O, Patch, A-M, Nones, K, Koufariotis, LT, Newell, F, Addala, V, Lakis, V, Holmes, O, Leonard, C, Wood, S, Xu, Q, Mukhopadhyay, P, Naeini, MM, Steinfort, D, Williamson, JP, Bint, M, Pahoff, C, Nguyen, PT, Twaddell, S, Arnold, D, Grainge, C, Basirzadeh, F, Fielding, D, Dalley, AJ, Chittoory, H, Simpson, PT, Aoude, LG, Bonazzi, VF, Patel, K, Barbour, AP, Fennell, DA, Robinson, BW, Creaney, J, Hollway, G, Pearson, JV, and Waddell, N

Abstract

BACKGROUND: Next-generation sequencing is used in cancer research to identify somatic and germline mutations, which can predict sensitivity or resistance to therapies, and may be a useful tool to reveal drug repurposing opportunities between tumour types. Multigene panels are used in clinical practice for detecting targetable mutations. However, the value of clinical whole-exome sequencing (WES) and whole-genome sequencing (WGS) for cancer care is less defined, specifically as the majority of variants found using these technologies are of uncertain significance. PATIENTS AND METHODS: We used the Cancer Genome Interpreter and WGS in 726 tumours spanning 10 cancer types to identify drug repurposing opportunities. We compare the ability of WGS to detect actionable variants, tumour mutation burden (TMB) and microsatellite instability (MSI) by using in silico down-sampled data to mimic WES, a comprehensive sequencing panel and a hotspot mutation panel. RESULTS: We reveal drug repurposing opportunities as numerous biomarkers are shared across many solid tumour types. Comprehensive panels identify the majority of approved actionable mutations, with WGS detecting more candidate actionable mutations for biomarkers currently in clinical trials. Moreover, estimated values for TMB and MSI vary when calculated from WGS, WES and panel data, and are dependent on whether all mutations or only non-synonymous mutations were used. Our results suggest that TMB and MSI thresholds should not only be tumour-dependent, but also be sequencing platform-dependent. CONCLUSIONS: There is a large opportunity to repurpose cancer drugs, and these data suggest that comprehensive sequencing is an invaluable source of information to guide clinical decisions by facilitating precision medicine and may provide a wealth of information for future studies. Furthermore, the sequencing and analysis approach used to estimate TMB may have clinical implications if a hard threshold is used to indicate which pati

Published
2022

17. ImmunoPET: IMaging of cancer imMUNOtherapy targets with positron Emission Tomography: a phase 0/1 study characterising PD-L1 with 89Zr-durvalumab (MEDI4736) PET/CT in stage III NSCLC patients receiving chemoradiation study protocol.

Author

Hegi-Johnson, F, Rudd, SE, Wichmann, C, Akhurst, T, Roselt, P, Trinh, J, John, T, Devereux, L, Donnelly, PS, Hicks, R, Scott, AM, Steinfort, D, Fox, S, Blyth, B, Parakh, S, Hanna, GG, Callahan, J, Burbury, K, MacManus, M, Hegi-Johnson, F, Rudd, SE, Wichmann, C, Akhurst, T, Roselt, P, Trinh, J, John, T, Devereux, L, Donnelly, PS, Hicks, R, Scott, AM, Steinfort, D, Fox, S, Blyth, B, Parakh, S, Hanna, GG, Callahan, J, Burbury, K, and MacManus, M

Abstract

BACKGROUND: ImmunoPET is a multicentre, single arm, phase 0-1 study that aims to establish if 89Zr-durvalumab PET/CT can be used to interrogate the expression of PD-L1 in larger, multicentre clinical trials. METHODS: The phase 0 study recruited 5 PD-L1+ patients with metastatic non-small cell lung cancer (NSCLC). Patients received 60MBq/70 kg 89Zr-durva up to a maximum of 74 MBq, with scan acquisition at days 0, 1, 3 or 5±1 day. Data on (1) Percentage of injected 89Zr-durva dose found in organs of interest (2) Absorbed organ doses (µSv/MBq of administered 89Zr-durva) and (3) whole-body dose expressed as mSv/100MBq of administered dose was collected to characterise biodistribution.The phase 1 study will recruit 20 patients undergoing concurrent chemoradiotherapy for stage III NSCLC. Patients will have 89Zr-durva and FDG-PET/CT before, during and after chemoradiation. In order to establish the feasibility of 89Zr-durva PET/CT for larger multicentre trials, we will collect both imaging and toxicity data. Feasibility will be deemed to have been met if more than 80% of patients are able complete all trial requirements with no significant toxicity. ETHICS AND DISSEMINATION: This phase 0 study has ethics approval (HREC/65450/PMCC 20/100) and is registered on the Australian Clinical Trials Network (ACTRN12621000171819). The protocol, technical and clinical data will be disseminated by conference presentations and publications. Any modifications to the protocol will be formally documented by administrative letters and must be submitted to the approving HREC for review and approval. TRIAL REGISTRATION NUMBER: Australian Clinical Trials Network ACTRN12621000171819.

Published
2022

21. Aspirin-triggered resolvin d1 reduces proliferation and the neutrophil to lymphocyte ratio in a mutant kras-driven lung adenocarcinoma model.

Author

Vannitamby A., Saad M.I., Aloe C., Wang H., Kumar B., Vlahos R., Selemidis S., Irving L., Steinfort D., Jenkins B.J., Bozinovski S., Vannitamby A., Saad M.I., Aloe C., Wang H., Kumar B., Vlahos R., Selemidis S., Irving L., Steinfort D., Jenkins B.J., and Bozinovski S.

Abstract

Tumour-associated neutrophils (TANs) can support tumour growth by suppressing cyto-toxic lymphocytes. AT-RvD1 is an eicosanoid that can antagonise neutrophil trafficking instigated by ALX/FPR2 ligands such as serum amyloid A (SAA). We aimed to establish whether SAA and ALOX5 expression associates with TANs and investigate the immunomodulatory actions of AT-RvD1 in vivo. MPO-positive neutrophils were quantified in tumour blocks from lung adenocarcinoma (n = 48) and control tissue (n = 20) by IHC. Tumour expression of SAA and ALOX5 were analysed by RTqPCR and an oncogenic KrasG12D lung adenocarcinoma mouse model was used to investigate the in vivo efficacy of AT-RvD1 treatment. ALOX5 expression was markedly reduced in lung adenocarcinoma tumours. The SAA/ALOX5 ratio strongly correlated with TANs and was significantly increased in tumours harbouring an oncogenic KRAS mutation. AT-RvD1 treatment reduced tumour growth in KrasG12D mice, which was accompanied by suppressed cellular proliferation within parenchymal lesions. In addition, AT-RvD1 significantly reduced the neutrophil to lymphocyte ratio (NLR), an established prognostic marker of poor survival in adenocarcinoma. This study identifies a novel molecular signature whereby elevated levels of SAA relative to ALOX5 favour accumulation of TANs. Furthermore, the ALOX5/5-LO enzymatic product, AT-RvD1, markedly reduced the NLR and suppressed tumour growth in KrasG12D mice.Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Published
2021

24. Feasibility of pulse oximetry after water immersion

Author

Holbery-Morgan, L, Carew, J, Angel, C, Simpson, N, Steinfort, D, Radford, S, Murphy, M, Douglas, N, Johnson, D, Holbery-Morgan, L, Carew, J, Angel, C, Simpson, N, Steinfort, D, Radford, S, Murphy, M, Douglas, N, and Johnson, D

Abstract

OBJECTIVE: This study aimed to determine if pulse oximetry could reliably be used after immersion in water, and if so, which of the finger, earlobe or nose most reliably produced a functional waveform. METHOD: Pulse oximetry data was recorded from the ear, nose and finger before and after 30 min of immersion in water. The primary outcome was the ability to measure pulse oximetry at any of the sites. RESULTS: A total of 119 participants were enrolled (with a median age of 16 years, 55% male). A useful pulse oximetry waveform was obtained after immersion from at least one of the measurement sites in 118 (99.2%) participants. Waveforms were usable after immersion in 96% of participants at the nostril, compared to 92% at the finger, and 41% at the ear lobe. The likelihood of success at the ear was significantly lower than either the finger or the nose (41% vs 92% and 96% respectively, p < 0.0001 for both comparisons). The finger and nostril were similar. Oxygen saturations were not significantly different after immersion at the nostril (100% vs 100%, p = 0.537) and finger (100% vs 100%, p = 0.032) sites but were different at the ear (100% vs 96%, p < 0.0001). CONCLUSION: This study demonstrates that pulse oximetry is feasible and reliable in a large cohort of participants who have been immersed in water for 30 min. The results support the nostril as the most reliable location. Only pulse oximeters registered for clinical use should be employed for patient care.

Published
2021

25. Emerging and multifaceted role of neutrophils in lung cancer

Author

Aloe, C, Wang, H, Vlahos, R, Irving, L, Steinfort, D, Bozinovski, S, Aloe, C, Wang, H, Vlahos, R, Irving, L, Steinfort, D, and Bozinovski, S

Abstract

It has long been recognized that cigarette smoking is a shared risk factor for lung cancer and the debilitating lung disease, chronic obstructive pulmonary disease (COPD). As the severity of COPD increases, so does the risk for developing lung cancer, independently of pack years smoked. Neutrophilic inflammation increases with COPD severity and anti-inflammatories such as non-steroidal anti-inflammatory drugs (NSAIDs) can modulate neutrophil function and cancer risk. This review discusses the biology of tumour associated neutrophils (TANs) in lung cancer, which increase in density with tumour progression, particularly in smokers with non-small cell lung cancer (NSCLC). It is now increasingly recognized that neutrophils are responsive to the tumour microenvironment (TME) and polarize into distinct phenotypes that operate in an anti- (N1) or pro-tumorigenic (N2) manner. Intriguingly, the emergence of the pro-tumorigenic N2 phenotype increases with tumour growth, to suggest that cancer cells and the surrounding stroma can re-educate neutrophils. The neutrophil itself is a potent source of reactive oxygen species (ROS), arginase, proteases and cytokines that paradoxically can exert a potent immunosuppressive effect on lymphocytes including cytotoxic T cells (CTLs). Indeed, the neutrophil to lymphocyte ratio (NLR) is a systemic biomarker that is elevated in lung cancer patients and prognostic for poor survival outcomes. Herein, we review the molecular mechanisms by which neutrophil derived mediators can suppress CTL function. Selective therapeutic strategies designed to suppress pathogenic neutrophils in NSCLC may cooperate with immune checkpoint inhibitors (ICI) to increase CTL killing of cancer cells in the TME.

Published
2021

26. Aspirin-Triggered Resolvin D1 Reduces Proliferation and the Neutrophil to Lymphocyte Ratio in a Mutant KRAS-Driven Lung Adenocarcinoma Model

Author

Vannitamby, A, Saad, MI, Aloe, C, Wang, H, Kumar, B, Vlahos, R, Selemidis, S, Irving, L, Steinfort, D, Jenkins, BJ, Bozinovski, S, Vannitamby, A, Saad, MI, Aloe, C, Wang, H, Kumar, B, Vlahos, R, Selemidis, S, Irving, L, Steinfort, D, Jenkins, BJ, and Bozinovski, S

Abstract

Tumour-associated neutrophils (TANs) can support tumour growth by suppressing cytotoxic lymphocytes. AT-RvD1 is an eicosanoid that can antagonise neutrophil trafficking instigated by ALX/FPR2 ligands such as serum amyloid A (SAA). We aimed to establish whether SAA and ALOX5 expression associates with TANs and investigate the immunomodulatory actions of AT-RvD1 in vivo. MPO-positive neutrophils were quantified in tumour blocks from lung adenocarcinoma (n = 48) and control tissue (n = 20) by IHC. Tumour expression of SAA and ALOX5 were analysed by RTqPCR and an oncogenic KrasG12D lung adenocarcinoma mouse model was used to investigate the in vivo efficacy of AT-RvD1 treatment. ALOX5 expression was markedly reduced in lung adenocarcinoma tumours. The SAA/ALOX5 ratio strongly correlated with TANs and was significantly increased in tumours harbouring an oncogenic KRAS mutation. AT-RvD1 treatment reduced tumour growth in KrasG12D mice, which was accompanied by suppressed cellular proliferation within parenchymal lesions. In addition, AT-RvD1 significantly reduced the neutrophil to lymphocyte ratio (NLR), an established prognostic marker of poor survival in adenocarcinoma. This study identifies a novel molecular signature whereby elevated levels of SAA relative to ALOX5 favour accumulation of TANs. Furthermore, the ALOX5/5-LO enzymatic product, AT-RvD1, markedly reduced the NLR and suppressed tumour growth in KrasG12D mice.

Published
2021

27. Automated assessment of functional lung imaging with 68Ga-ventilation/perfusion PET/CT using iterative histogram analysis

Author

McIntosh, L, Jackson, P, Hardcastle, N, Bressel, M, Kron, T, Callahan, JW, Steinfort, D, Bucknell, N, Hofman, MS, Siva, S, McIntosh, L, Jackson, P, Hardcastle, N, Bressel, M, Kron, T, Callahan, JW, Steinfort, D, Bucknell, N, Hofman, MS, and Siva, S

Abstract

PURPOSE: Functional lung mapping from Ga68-ventilation/perfusion (V/Q) PET/CT, which has been shown to correlate with pulmonary function tests (PFTs), may be beneficial in a number of clinical applications where sparing regions of high lung function is of interest. Regions of clumping in the proximal airways in patients with airways disease can result in areas of focal intense activity and artefact in ventilation imaging. These artefacts may even shine through to subsequent perfusion images and create a challenge for quantitative analysis of PET imaging. We aimed to develop an automated algorithm that interprets the uptake histogram of PET images to calculate a peak uptake value more representative of the global lung volume. METHODS: Sixty-six patients recruited from a prospective clinical trial underwent both V/Q PET/CT imaging and PFT analysis before treatment. PET images were normalised using an iterative histogram analysis technique to account for tracer hotspots prior to the threshold-based delineation of varying values. Pearson's correlation between fractional lung function and PFT score was calculated for ventilation, perfusion, and matched imaging volumes at varying threshold values. RESULTS: For all functional imaging thresholds, only FEV1/FVC PFT yielded reasonable correlations to image-based functional volume. For ventilation, a range of 10-30% of adapted peak uptake value provided a reasonable threshold to define a volume that correlated with FEV1/FVC (r = 0.54-0.61). For perfusion imaging, a similar correlation was observed (r = 0.51-0.56) in the range of 20-60% adapted peak threshold. Matched volumes were closely linked to ventilation with a threshold range of 15-35% yielding a similar correlation (r = 0.55-0.58). CONCLUSIONS: Histogram normalisation may be implemented to determine the presence of tracer clumping hotspots in Ga-68 V/Q PET imaging allowing for automated delineation of functional lung and standardisation of functional volume reporting.

Published
2021

29. Increase in tumour PD-L1 expression in non-small cell lung cancer following bronchoscopic thermal vapour ablation

Author

Rangamuwa, K, Leong, T, Bozinovski, S, Christie, M, John, T, Antippa, P, Irving, L, Steinfort, D, Rangamuwa, K, Leong, T, Bozinovski, S, Christie, M, John, T, Antippa, P, Irving, L, and Steinfort, D

Abstract

Limited early evidence indicates thermal ablation of non-small cell lung cancer (NSCLC) may induce alterations to the immune response that could enhance the efficacy of immunotherapy with immune checkpoint inhibitor therapy. This study reports pilot data demonstrating increased programmed death-ligand 1 (PD-L1) expression on tumour cells in response to bronchoscopic thermal vapour ablation. Five patients underwent bronchoscopic thermal vapour ablation under a treat-and-resect protocol, as part of a clinical safety and feasibility study, with lobectomy performed five days after thermal vapour ablation. PD-L1 (clone SP263) immunohistochemistry (IHC) tumour proportion score (TPS) was assessed on both baseline diagnostic biopsy specimens, and post-ablation resection specimens in five patients with stage I NSCLC. Two areas of the resection sample defined as viable tumour and injured tumour were examined. All tumours demonstrated 0% PD-L1 TPS at baseline. Three of five (60%) patients demonstrated an increase in PD-L1 TPS in areas of injured tumour to 20%, 30% and 50%. One patient demonstrated an increase in PD-L1 expression in an area of viable tumour to 5%. Changes in PD-L1 expression did not correlate with measures of systemic inflammation. Our findings comprise the first evidence that thermal ablation of NSCLC may induce PD-L1 expression. Further investigation is required to determine the extent of an adaptive immune response, and confirm the potential for augmentation of clinical response to immune check point inhibitor therapy in NSCLC.

Published
2021

30. Thermal ablation in non-small cell lung cancer: a review of treatment modalities and the evidence for combination with immune checkpoint inhibitors

Author

Rangamuwa, K, Leong, T, Weeden, C, Asselin-Labat, M-L, Bozinovski, S, Christie, M, John, T, Antippa, P, Irving, L, Steinfort, D, Rangamuwa, K, Leong, T, Weeden, C, Asselin-Labat, M-L, Bozinovski, S, Christie, M, John, T, Antippa, P, Irving, L, and Steinfort, D

Abstract

Lung cancer is the leading cause of cancer death worldwide, with approximately 1.6 million cancer related deaths each year. Prognosis is best in patients with early stage disease, though even then five-year survival is only 55% in some groups. Median survival for advanced non-small cell lung cancer (NSCLC) is 8-12 months with conventional treatment. Immune checkpoint inhibitor (ICI) therapy has revolutionised the treatment of NSCLC with significant long-term improvements in survival demonstrated in some patients with advanced NSCLC. However, only a small proportion of patients respond to ICI, suggesting the need for further techniques to harness the potential of ICI therapy. Thermal ablation utilizes the extremes of temperature to cause tumour destruction. Commonly used modalities are radiofrequency ablation (RFA), cryoablation and microwave ablation (MWA). At present thermal ablation is reserved for curative-intent therapy in patients with localized NSCLC who are unable to undergo surgical resection or stereotactic ablative body radiotherapy (SABR). Limited evidence suggests that thermal ablative modalities can upregulate an anticancer immune response in NSCLC. It is postulated that thermal ablation can increase tumour antigen release, which would initiate and upregulated steps in the cancer immunity cycle required to elicit an anticancer immune response. This article will review the current thermal ablative techniques and their ability to modulate an anti-cancer immune response with a view of using thermal ablation in conjunction with ICI therapy.

Published
2021

33. FP10.02 Investigating the Immunophenotype of Small Cell Lung Cancer to Improve Immunotherapeutic Targeting

Author

Best, S., primary, Hess, J., additional, Souza-Fonseca Guimaraes, F., additional, Cursons, J., additional, Kersbergen, A., additional, You, Y., additional, Ng, J., additional, Davis, M., additional, Leong, T., additional, Irving, L., additional, Ritchie, M., additional, Steinfort, D., additional, Huntington, N., additional, and Sutherland, K., additional

Published
2021
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34. P09.18 COVID-19 Outcomes in Patients With Thoracic Malignancies According to Gender and Ethnicity (TERAVOLT)

Author

Whisenant, J., primary, Wong, S., additional, Torri, V., additional, Revuelta, J., additional, Halmos, B., additional, Ceresoli, G., additional, Monnet, I., additional, Popat, S., additional, Arrieta, O., additional, Azab, M., additional, Dingemans, A., additional, Spasic, J., additional, Van Meerbeeck, J., additional, Recondo, G., additional, Reinmuth, N., additional, Valter, A., additional, Unk, M., additional, Ghalehtaki, R., additional, Steinfort, D., additional, Chorostowska-Wynimko, J., additional, Viola, L., additional, Horn, L., additional, Peters, S., additional, Wakelee, H.A., additional, Garassino, M.C., additional, and Tapan, U., additional

Published
2021
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35. Poster abstracts

Author

Ferrie, J., Shipley, M., Cappuccio, F., Brunner, E., Miller, M., Kumari, M., Marmot, M., Coenen, A., Castillo, J. L., Araya, F., Bustamante, G., Montecino, L., Torres, C., Oporto, S., Gronli, J., Fiske, E., Murison, R., Bjorvatn, B., Sorensen, E., Ursin, R., Portas, C. M., Rajaraman, S., Gribok, A., Wesensten, N., Balkin, T., Reifman, J., Dursunoglu, N., Ozkurt, S., Baser, S., Delen, O., Sarikaya, S., Sadler, P., Mitchell, P., Françon, D., Decobert, M., Herve, B., Richard, A., Griebel, G., Avenet, P., Scatton, B., Fur, G. L., Eckert, D., Jordan, A., Wellman, A., Smith, S., Malhotra, A., White, D., Bruck, D., Thomas, I., Kritikos, A., Oertel, W., Stiasny-Kolster, K., Garcia-Borreguero, D., Poewe, W., Hoegl, B., Kohnen, R., Schollmayer, E., Keffel, J., Trenkwalder, C., Valle, A., Roizenblatt, S., Fregni, F., Boggio, P., Tufik, S., Ward, K., Robertson, L., Palmer, L., Eastwood, P., Hillman, D., Lee, J., Mukherjee, S., de Padova, V., Barbato, G., Ficca, G., Zilli, I., Salzarulo, P., Veldi, M., Hion, T., Vasar, V., Kull, M., Nowak, L., Davis, J., Latzer, Y., Tzischinsky, O., Crowley, S., Carskadon, M., Anca-Herschkovitsch, M., Frey, D., Ortega, J., Wiseman, C., Farley, C., Wright, K., Campbell, A., Neill, A., Spiegel, K., Leproult, R., Tasali, E., Scherberg, N., van Cauter, E., Noradina, A. T., Karim, N. A., Norlinah, I., Raymond, A. A., Sahathevan, R., Hamidon, B., Werth, E., Poryazova, R., Khatami, R., Bassetti, C., Beran, R. G., Ainley, L., Holand, G., Duncan, J., Kinney, H., Davis, B., Hood, B., Frey, S., Schmidt, C., Hofstetter, M., Peigneux, P., Cajochen, C., Hu, W.-P., Li, J.-D., Zhang, C., Boehmer, L., Siegel, J., Zhou, Q.-Y., Sagawa, Y., Kondo, H., Takemura, T., Kanayama, H., Kaneko, Y., Sato, M., Kanbayashi, T., Hishikawa, Y., Shimizu, T., Viola, A., James, L., Schlangen, L., Dijk, D.-J., Andretic, R., Kim, Y.-C., Han, K.-A., Jones, F., Greenspan, R., Sanford, L., Yang, L., Tang, X., Dieter, K., Uta, E., Sven, H., Richard, M., Oyane, N., Pallesen, S., Holsten, F., Inoue, Y., Fujita, M., Emura, N., Kuroda, K., Uchimura, N., Johnston, A., Astbury, J., Kennedy, G., Hoedlmoser, K., Schabus, M., Pecherstorfer, T., Moser, S., Gruber, G., Anderer, P., Klimesch, W., Naidoo, N., Ferber, M., Pack, A., Neu, D., Mairesse, O., Hoffmann, G., Dris, A., Lambrecht, L., Linkowski, P., Verbanck, P., Le Bon, O., Matsuura, N., Yamao, M., Adachi, N., Aritomi, R., Komada, Y., Tanaka, H., Shirakawa, S., Kondoh, H., Takemura, F., Ohnuma, S., Suzuki, M., Uemura, S., Iskra-Golec, I., Smith, L., Thanh, D.-V., Boly, M., Phillips, C., Steven, L., Luxen, A., Maquet, M., Jay, S., Dawson, D., Lamond, N., Basner, M., Fomberstein, K., Dinges, D., Ogawa, K., Nittono, H., Yamazaki, K., Hori, T., Glamann, C., Hornung, O., Hansen, M.-L, Danker-Hopfe, H., Jung, C., Kecklund, G., Anund, A., Peters, B., Åkerstedt, T., Verster, J., Roehrs, T., Mets, M., de Senerpont Domis, L., Olivier, B., Volkerts, E., Knutson, K., Lauderdale, D., Rathouz, P., Christie, M., Chen, L., Bolortuya, Y., Lee, E., Mckenna, J., Mccarley, R., Strecker, R., Tamaki, M., Matsuoka, T., Aritake, S., Suzuki, H., Kuriyama, K., Ozaki, A., Abe, Y., Enomoto, M., Tagaya, H., Mishima, K., Matsuura, M., Uchiyama, M., Lima-Pacheco, E., Davis, K., Sabourin, C., Lortie-Lussier, M., de Koninck, J., van Der Werf, Y., van Der Helm, E., Schoonheim, M., van Someren, E., Tokley, M., Ball, M., Sato, T., Ghilardi, M. F., Moisello, C., Bove, M., Busi, M., Pelosin, E., Tononi, G., Eguchi, N., Sakata, M., Urade, Y., Doe, N., Yoshihara, K., Abe, K., Manabe, Y., Iwatsuki, K., Hayashi, T., Shoji, M., Kamiya, T., Gooley, J., Brainard, G., Rajaratnam, S., Kronauer, R., Czeisler, C., Lockley, S., Phillips, A., Robinson, P., Burgess, H., Revell, V., Eastman, C., Bihari, S., Ramakrishnan, N., Camerino, D., Conway, P. M., Costa, G., Vandewalle, G., Albouy, G., Sterpenich, V., Darsaud, A., Rauchs, G., Berken, P.-Y, Balteau, E., Maquet, P., Tendero, J. A., Domenech, M. P., Isern, F. S., Martínez, C., Roure, N., Sancho, E. E., Moreno, C. R., Silva, M., Marqueze, E. C., Waage, S., Bobko, N., Chernyuk, V., Yavorskiy, Y., Saxvig, I., Sørensen, E., de Mello, M. T., Esteves, A., Teixeira, C., Bittencourt, L. R., Silva, R., Pires, M. L., Mottram, V., Middelton, B., Arendt, J., Amaral, O., Rodrigues, M., Pereira, C., Tavares, I., Baba, K., Honma, S., Honma, K.-I., Yamanaka, Y., Hashimoto, S., Tanahashi, Y., Nishide, S.-Y, Honma, K.-I, Sletten, T., Middleton, B., Lederle, K., Skene, D., Roth, T., Walsh, J., Hogben, A., Ellis, J., Archer, S., von Schantz, M., Chen, N.-H., Wang, P.-C., Chen, C.-W., Lin, Y., Shih, T.-S., Armstrong, S., Redman, J., Stephan, E., David, M., Delanaud, S., Chardon, K., Libert, J.-P., Bach, V., Telliez, F., Reid, K., Jaksa, A., Eisengart, J., Kane, P., Naylor, E., Zee, P., Viola, A. U., de Valck, E., Hofmans, J., Theuns, P., Cluydts, R., Alexander, G., Karel, M., Christina, R., Sohn, I.-K., Cho, I. H., Kim, S. J., Yu, S.-H., Kim, H., Yoo, S. Y., Koh, S.-H., Cho, S.-J., Rotenberg, L., Silva-Costa, A., Griep, R. H., Amely, T., Kennedy, G. A., Pavlis, A., Thompson, B., Pierce, R., Howard, M., Briellmann, R., Venkateswaran, S., Blunden, S., Krawczyk, E., Blake, J., Gururajan, R., Kerr, D., Matuisi, T., Iwasaki, M., Yamasita, N., Iemura, A., Ohya, T., Yanagawa, T., Misa, R., Coleman, G., Conduit, R., Duce, B., Hukins, C., Nyandaiti, Y. W., Bamaki, S., Mohammed, A., Kwajarfa, S., Veeramachaneni, S. P., Murthy, A., Wilson, A., Maul, J., Hall, G., Stick, S., Moseley, L., Gradisar, M., Kurihara, T., Yamamoto, M., Yamamoto, S., Kuranari, M., Sparks, C. B., Bartle, A., Beckert, L., Latham-Smith, F. B., Hilton, J., Whitehead, B., Gulliver, T., Salvini, A., Grahame, S., Swift, M., Laybutt, N., Sharon, D., Mack, C., Hymell, B., Perrine, B., Ideshita, K., Taira, M., Matuo, A., Furutani, M., van Dongen, H., Mott, C., Huang, J.-K., Mollicone, D. J., Mckenzie, F., Dinges, David, Barnes, M., Rochford, P., Churchward, T., O’Donoghue, F., Penzel, T., Fietze, I., Canisius, S., Bekiaris, E., Terrill, P. I., Wilson, S., Suresh, S., Cooper, D., Suzuki, T., Ouchi, K., Moriya, A., Kameyama, K., Takahashi, M., Büttner, A., Rühle, K.-H., Wang, D., Wong, K., Dungan, II, G., Grunstein, R., Davidson, P., Jones, R., Gergely, V., Mashima, K., Miyazaki, S., Tanaka, T., Okawa, M., Yamada, N., Wyner, A., Raizen, D., Galante, R., Ng, A. K., Koh, T. S., Lim, L. L., Puvanendran, K., Peiris, M., Bones, P., Roebuck, T., Ho, S., Szollosi, I., Naughton, M., Williams, G., Parsley, C., Harris, M.-A., Thornton, A., Ruehland, W., Banks, S., Arroyo, S., Carroll, K., Pilmore, J., Stewart, C., Hamilton, G., van Acker, F., Cvetkovic, D., Holland, G., Cosic, I., Tolson, J., Worsnop, C., Cresswell, P., Hart, I., Bouarab, M., Delechelle, E., Drouot, X., Acebo, C., Singh, P., Lakey, T., Schachter, L., Rand, J., Collin, H., Snyder, E., Ma, J., Svetnick, V., Deacon, S., Dana, B., Konstanze, D., Uwe, M., Ingo, F., Thomas, P., Ivar, R., Mackiewicz, M., Shockley, K., Romer, M., Zimmerman, J., Baldwin, D., Jensen, S., Churchill, G., Paigen, B., Imeri, L., Ferrari, L., Bianchi, S., Dossena, S., Garofoli, A., Mangieri, M., Tagliavini, F., Forloni, G., Chiesa, R., Pedrazzoli, M., Pereira, D., Veauny, M., Bodenmann, S., Hohoff, C., Freitag, C., Deckert, J., Rétey, J., Landolt, H.-P., Strohl, K., Price, E., Yamauchi, M., Dostal, J., Feng, P., Han, F., Havekes, R., Novati, A., Hagewoud, R., Barf, P., van Der Borght, K., van Der Zee, E., Meerlo, P., Ruby, P., Caclin, A., Boulet, S., Delpuech, C., Morlet, D., Veasey, S., Aton, S., Jha, S., Coleman, T., Seibt, J., Frank, M., Lack, L., Churches, O., Feng, S. Y. S., Cassaglia, P., Yu, V. Y. H., Walker, A. M., Kohler, M., Kennedy, D., Martin, J., van Den Heuvel, C., Lushington, K., Herron, K., Khurana, C., Sterr, A., Olivadoti, M., Toth, L., Opp, M., Dang-Vu, T., Degueldre, C., Gais, S., Dang-Vu, T. T., Desseilles, M., Philips, C., Chijavadze, E., Babilodze, M., Chkhartishvili, E., Nachkebia, N., Mchedlidze, O., Dzadzamia, S., Griffiths, R., Walker, A., Horovitz, S., Fukunaga, M., Carr, W., Picchioni, D., de Zwart, J., van Gelderen, P., Braun, A., Duyn, J., Hanlon, E. H., Faraguna, U., Vyazovskiy, V., Cirelli, C., Ocampo-Garcés, A., Ibáñez, F., López, S., Vivaldi, E., Torrealba, F., Romanowski, C. P. N., Fenzl, T., Flachskamm, C., Deussing, J., Kimura, M., Tarokh, L., van Reen, E., Dorn, H., Velluti, R., Qu, W.-M., Huang, Z.-L., Hayaishi, O., Pedemonte, M., Drexler, D., Pol-Fernández, D., Bernhardt, V., Lopez, C., Rodriguez-Servetti, Z., Romanowski, C., Polta, S., Yassouridis, A., Abe, T., Takahashi, K., Koyama, Y., Kayama, Y., Lin, J.-S., Sakai, K., Gulia, K., Karashima, A., Shimazaki, M., Katayama, N., Nakao, M., Winsky-Sommerer, R., Knapman, A., Tobler, I., Altena, E., Sanz-Arigita, E., Chang, F.-C., Lu, C.-Y., Yi, P.-L., Hsiao, Y.-Z., Lowden, A., Nilsson, J., Hillert, L., Wiholm, C., Kuster, N., Arnetz, B., Szameitat, A., Shen, S., Daurat, A., Tiberge, M., Sok, N., D’Ortho, M. P. I. A., Karasinsky, P., Kohlmeier, K., Wess, J., Leonard, C., Kristensen, M., Kalinchuk, A., Porkka-Heiskanen, T., Mccarley, R. W., Basheer, R., Aizawa, R., Sunahara, H., Abe, S.-I., Iwaki, S., Houjyou, M., Satoh, M., Suda, H., Kheirandish-Gozal, L., Gozal, D., Walker, P., Noa, A., O’Driscoll, D., Ng, M., Yang, J., Davey, M., Anderson, V., Trinder, J., Horne, R., Sands, S., Kelly, V., Sia, K., Edwards, B., Skuza, E., Davidson, M., Berger, P. H. I. L. I. P., Wilkinson, M., Sánchez-Narváez, F., Gutiérrez, R., Camacho, L., Anaya, E., García-Campos, E., Labra, A., Domínguez, G., García-Polo, L., Haro, R., Verginis, N., Nixon, G., Baumert, M., Pamula, Y., Mihai, R., Wawurszak, M., Smith, N., Yiallourou, S., Andrew Ramsden, C., Williamson, B., Blecher, G., Teng, A., Dakin, C. Y. N., Yuil, M., Harris, M., Sadasivam, S., Bennison, J., Galland, B., Dawes, P., Taylor, B., Norman, M., Edwards, N., Harrison, H., Kol, C., Sullivan, C., Valladares, E., Macey, P., Kumar, R., Woo, M., Harper, R., Alger, J., Mcnamara, D., Tang, J., Goh, A., Teoh, O. H., Chiang, W. C., Chay, O. M., Marie Salvini, A., Riben, C., Blanck, A.-S., Marklund, M., Tourneux, P., Cardot, V., Leke, A., Iqbal, S. M., (Gus) Cooper, D., Witmans, M., Rodger, K., Thevasagayam, R., El-Hakim, H., Hill, C. M., Baya, A., Bucks, R., Kirkham, F., Virues-Ortega, J., Baldeweg, T., Paul, A., Hogan, A., Goodwin, J., Silva, G., Kaemingk, K., Sherrill, D., Morgan, W., Fregosi, R., Quan, S., Evans, C., Maclean, J., Waters, K., Fitzsimmons, D., Hayward, P., Fitzgerald, D., Terrill, G., O’Connell, A., Vannan, K., Richardson, H., Poluektov, M., Levin, I., Snegodskaya, M., Kolosova, N., Geppe, N., Nixon, G. Michelle, Thompson, J., Yhan, D., Becroft, D., Clark, P., Robinson, E., Waldie, K., Wild, C., Black, P., Stone, K., Britton, W., Chaves, Claudia, Tinoco, C., Goncalves, C., Ferreira, E., Santos, H., Boloto, J., Duarte, L., Paine, S., Wright, H., Slater, A., Rosen, G., Telliez, Frédéric, Djeddi, D., Kongolo, G., Degrugilliers, L., Horton, J., Buscemi, N., Vandermeer, B., Owens, J., Klassen, T., Gordon, J., King, N., Tripp, G., Oka, Y., Suzuki, S., de Lemos, M. C., Gonzaga, F. G., Shah, M. L., Bittencourt, L., Oliveira, L. V. Franco, Elshoff, J.-P., Braun, M., Andreas, J.-O., Strauss, B., Horstmann, R., Ahrweiler, S., Goldammer, N., Wada, M., Matsumoto, N., Rahman, M. D., Xu, X.-H., Makino, Y., Hashimoto, K., Zhang, M., Sastre, J.-P., Buda, C., Anaclet, C., Ohtsu, H., Danober, L., Desos, P., Cordi, A., Roger, A., Jacquet, A., Rogez, N., Thomas, J.-Y., Krentner, M., Boutin, J., Audinot-Bouchez, V., Baumann, C., Valko, P., Uhl, M., Hersberger, M., Rupp, T., Uchiyama, N., Nakamura, N., Konishi, T., Mcgrath, P., Fujiki, N., Tokunaga, J., Iijima, S., Nishino, S., Catherine, B.-R., Lely, F., Ralf, K., Oliver, N., François, J., Francois, J., Cedric, F., Changbin, Q., Patrick, H., Homanics, G., Heussler, H., Norris, R., Pache, D., Charles, B., Mcguire, T., Shelton, J., Bonaventure, P., Kelly, L., Aluisio, L., Lovenberg, T., Atack, J., Dugovic, C., Shapiro, C., Shen, J., Trajanovic, N., Chien, J., Verma, M., Fish, V., Wheatley, J., Amis, T., Alexiou, T., Wild, J., Bjursell, A., Solin, P., Sato, S., Matsubuchi, N., Gingras, M.-A., Labrosse, M., Chevrier, É, Lageix, P., Guay, M.-C., Braun, C., Godbout, R., Fatim, E. H., Loic, D., Stephane, D., Nathalie, L., Stéphane, D., Alain, G., Wiâm, R., Koabyashi, T., Tomita, S., Ishikawa, T., Manadai, O., Arakawa, K., Siato, Y., Bassi, A., Ocampo, A., Estrada, J., Blyton, D., O’Keeffe, K., Galletly, D., Larsen, P., Amatoury, J., Bilston, L., Kairaitis, K., Stephenson, R., Chu, K., Sekiguchi, Y., Suzuki, N., Yasuda, Y., Kodama, T., Honda, Y., Hsieh, K.-C., Lai, Y.-Y., Bannai, M., Kawai, N., Amici, R., Baracchi, F., Cerri, M., Del Sindaco, E., Dentico, D., Jones, C. A., Luppi, M., Martelli, D., Perez, E., Tazaki, M., Katayose, Y., Yasuda, K., Tokuyama, K., Maddison, K., Platt, P., Kirkness, J., Ware, J. C., May, J., Rosenthal, T., Park, G., Guibert, M., Allen, R. W., Cetin, T., Roman, V., Mollicone, D., Crummy, F., Cameron, P., Swann, P., Kossman, T., Taggart, F., Kandala, N.-B., Currie, A., Peile, E., Stranges, S., Marshall, N., Peltonen, M., Stenlof, K., Hedner, J., Sjostrom, L., Anderson, C., Platten, C., Jordan, K., Horne, J., Bjorkum, A., Kluge, B., Braseth, T., Gurvin, I., Kristensen, T., Nybo, R., Rosendahl, K., Nygaard, I., Biggs, S., Dollman, J., Kennedy, J. D., Martin, A. J., Haghighi, K. S., Bakht, N., Hyde, M., Harris, E., Zerouali, Y., Hosein, A., Jemel, B., Dodd, M., Rogers, N., Andersen, M., Martins, R., Alvarenga, T., Antunes, I., Papale, L., Killgore, W. S., Axelsson, J., Lekander, M., Ingre, M., Brismar, K., Dorrian, J., Ferguson, S., Jones, C., Buxton, O., Marcelli, E., Phipps-Nelson, J. O., Teixeira, L. R., de Castro Moreno, C., Turte, S. L., Nagai, R., do Rosário Dias De Oliveira Latorre, M., Marina, F., Paterson, J., Jackson, M., Johnston, P., Papafotiou, K., Croft, R., Dawson, S., Leenaars, C., Sandberg, H., Joosten, R., Dematteis, M., Feenstra, M., Wehrle, R., Rieger, M., Widmann, A., Dietl, T., Philipp, S., Wetter, T., Drummond, S., Czisch, M., Cairns, A., Lebourgeois, M., Harsh, J., Baulk, S., Vakulin, A., Catcheside, P., Antic, N., Mcevoy, D., Orff, H., Salamat, J., Meloy, M. J., Caron, A., Kostela, J., Purnell, M., Feyer, A.-M., Herbison, P., Saaresranta, T., Aittokallio, J., Karppinen, N., Toikka, J., Polo, O., Sallinen, M., Haavisto, M.-L., Hublin, C., Kiti, M., Jussi, V., Mikko, H., Chuah, L., Chee, M., Borges, F., Fischer, F., Moreno, C., Soares, N., Fonseca, M., Smolensky, M., Sackett-Lundeen, L., Haus, E., Nagata, N., Michael, N., Siccoli, M., Rogers, A., Hwang, W.-T., Scott, L., Dean, G., Geissler, E., Ametamey, S., Treyer, V., Wyss, M., Achermann, P., Schubiger, P., Theorell-Haglöw, J., Berne, C., Janson, C., Svensson, M., Lindberg, E., Caruso, H., Avinash, D., Minkel, J., Thompson, C., Wisor, J., Gerashchenko, D., Smith, K., Kuan, L., Pathak, S., Hawrylycz, M., Jones, A., Kilduff, T., Bergamo, C., Ecker, A., William, J., Niyogi, S., Coble, M., Goel, N., Lakhtman, L., Horswill, M., Whetton, M., Chambers, B., Signal, L., van Den Berg, M., Gander, P., Polotsky, V., Savransky, V., Bevans, S., Nanayakkara, A., Li, J.-G., Smith, P., Torbenson, M., Stockx, E., Brodecky, V., Berger, P., Chung-Mei Lam, J., Rial, R., Roca, C., Garau, C., Akaarir, M., Mccoy, J., Ward, C., Connolly, N., Tartar, J., Brown, R., Carberry, J., Bradford, A., O’Halloran, K., Mcguire, M., Nacher, M., Serrano-Mollar, A., Navajas, D., Farre, R., Montserrat, J., Fenik, V., Rukhadze, I., Kubin, L., Sivertsen, B., Overland, S., Mykletun, A., Czira, M., Fornádi, K., Lindner, A., Szeifert, L., Szentkirályi, A., Mucsi, I., Molnár, M., Novák, M., Zoller, R., Chin, K., Takegami, M., Oga, T., Nakayama-Asida, Y., Wakamura, T., Mishima, M., Fukuhara, S., Shepherd, K., Keir, G., Rixon, K., Makarie-Rofail, L., Unger, G., Svanborg, E., Harder, L., Sarberg, M., Broström, A., Josefsson, A., Herrera, A., Aguilera, L., Diaz, M., Fedson, A., Hung, J., Williams, C., Love, G., Middleton, S., Vermeulen, W., Middleton, P., Steinfort, D., Goldin, J., Eritaia, J., Dionysopoulos, P., Irving, L., Ciftci, T. U., Kokturk, O., Demirtas, S., Kanbay, A., Tavil, Y., Bukan, N., Demritas, S., Olsen, S., Douglas, J., Oei, T., Williams, S., Leung, S., Starmer, G., Lee, R., Chan, A., Dungan, G., Cistulli, P., Zeng, B., Bansal, A., Patial, K., Vijayan, V. K., Sonka, K., Fialova, L., Svarcova, J., Volna, J., Jiroutek, P., Pretl, M., Bartos, A., Hasegawa, R. A., Sasanabe, R., Nomura, A., Morita, M., Hori, R., Ohkura, Y., Shiomi, T. 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P., Boldt, C., Geyh, S., Stucki, A., Dahlberg, A., Michel, F., Savard, M.-H., Savard, J., Quesnel, C., Hirose, K., Takahara, M., Mizuno, K., Sadachi, H., Nagashima, Y., Yada, Y., Cheung, C.-F., Lau, C., Lai, W., Sin, K., Tam, C., Hellgren, J., Omenaas, E., Gíslason, T., Jögi, R., Franklin, K., Torén, K., Wang, F., Kadono, M., Shigeta, M., Nakazawa, A., Ueda, M., Fukui, M., Hasegawa, G., Yoshikawa, T., de Niet, G., Tiemens, B., Lendemeijer, B., Hutschemaekers, G., Gauthier, A.-K., Chevrette, T., Chevrier, E., Bouvier, H., Parry, B., Meliska, C., Nowakowski, S., Lopez, A., Martinez, F., Sorenson, D., Lien, M. L., Lattova, Z., Maurovich-Horvat, E., Nia, S., Pollmächer, T., Poulin, J., Chouinard, S., Stip, E., Guillem, F., Venne, D., Caouette, M., Lamont, M.-E., Lázár, A., Lázár, Z., Bíró, A., Gyõri, M., Tárnok, Z., Prekop, C., Gádoros, J., Halász, P., Bódizs, R., Okun, M., Hanusa, B., Hall, M., Wisner, K., Pereira, M., Kumar, R. A. J. E. S. H., Macey, P. A. U. L., Woo, M. A. R. Y., Serber, S. T. A. C. Y., Valladares, E. D. W. I. N., Harper, R. E. B. E. C. C. A., Harper, R. O. N. A. L. D., Puttonen, S., Härmä, M., Vahtera, J., Kivimäki, M., Lamarche, L., Hemmeter, U. M., Thum, A., Rocamora, R., Giesler, M., Haag, A., Dodel, R., Krieg, J. C., Shechter, A., L’Esperance, P., Boivin, D. B., Vu, M.-T., and Richards, H.

Published
2007
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37. Don't forget shared decision-making in theCOVID-19 crisis

Author

Simpson, N, Milnes, S, Steinfort, D, Simpson, N, Milnes, S, and Steinfort, D

Abstract

Mechanical ventilation as a resource is limited and may lead to poor outcomes in at-risk populations. Critical care supports may not be preferred by those at risk of deterioration in the COVID-19 setting. Patient-centred communication and shared decision-making should continue to remain central to clinical practice.

Published
2020

38. Single-arm prospective interventional study assessing feasibility of using gallium-68 ventilation and perfusion PET/CT to avoid functional lung in patients with stage III non-small cell lung cancer

Author

Bucknell, N, Hardcastle, N, Jackson, P, Hofman, M, Callahan, J, Eu, P, Iravani, A, Lawrence, R, Martin, O, Bressel, M, Woon, B, Blyth, B, MacManus, M, Byrne, K, Steinfort, D, Kron, T, Hanna, G, Ball, D, Siva, S, Bucknell, N, Hardcastle, N, Jackson, P, Hofman, M, Callahan, J, Eu, P, Iravani, A, Lawrence, R, Martin, O, Bressel, M, Woon, B, Blyth, B, MacManus, M, Byrne, K, Steinfort, D, Kron, T, Hanna, G, Ball, D, and Siva, S

Abstract

BACKGROUND: In the curative-intent treatment of locally advanced lung cancer, significant morbidity and mortality can result from thoracic radiation therapy. Symptomatic radiation pneumonitis occurs in one in three patients and can lead to radiation-induced fibrosis. Local failure occurs in one in three patients due to the lungs being a dose-limiting organ, conventionally restricting tumour doses to around 60 Gy. Functional lung imaging using positron emission tomography (PET)/CT provides a geographic map of regional lung function and preclinical studies suggest this enables personalised lung radiotherapy. This map of lung function can be integrated into Volumetric Modulated Arc Therapy (VMAT) radiotherapy planning systems, enabling conformal avoidance of highly functioning regions of lung, thereby facilitating increased doses to tumour while reducing normal tissue doses. METHODS AND ANALYSIS: This prospective interventional study will investigate the use of ventilation and perfusion PET/CT to identify highly functioning lung volumes and avoidance of these using VMAT planning. This single-arm trial will be conducted across two large public teaching hospitals in Australia. Twenty patients with stage III non-small cell lung cancer will be recruited. All patients enrolled will receive dose-escalated (69 Gy) functional avoidance radiation therapy. The primary endpoint is feasibility with this achieved if ≥15 out of 20 patients meet pre-defined feasibility criteria. Patients will be followed for 12 months post-treatment with serial imaging, biomarkers, toxicity assessment and quality of life assessment. DISCUSSION: Using advanced techniques such as VMAT functionally adapted radiation therapy may enable safe moderate dose escalation with an aim of improving local control and concurrently decreasing treatment related toxicity. If this technique is proven feasible, it will inform the design of a prospective randomised trial to assess the clinical benefits of functional lung

Published
2020

39. Reduction of COPD Hyperinflation by Endobronchial Valves Improves Intercostal Muscle Morphology on Ultrasound

Author

Wallbridge, P, Hew, M, Parry, SM, Irving, L, Steinfort, D, Wallbridge, P, Hew, M, Parry, SM, Irving, L, and Steinfort, D

Abstract

BACKGROUND AND OBJECTIVES: Parasternal intercostal ultrasound morphology reflects spirometric COPD severity. Whether this relates to the systemic nature of COPD or occurs in response to hyperinflation is unknown. We aimed to assess changes in ultrasound parasternal intercostal muscle quantity and quality (echogenicity) in response to relief of hyperinflation. We hypothesised that reduction in hyperinflation following endobronchial valve (EBV) insertion would increase ultrasound parasternal thickness and decrease echogenicity. METHODS: In this prospective cohort study, eight patients with severe COPD underwent evaluation of health-related quality of life, lung function, and sonographic thickness of 2nd parasternal intercostal muscles and diaphragm thickness, both before and after EBV insertion. Relationships between physiological and radiographic lung volumes, quality of life and ultrasound parameters were determined. RESULTS: Baseline FEV1 was 1.02L (SD 0.37) and residual volume (RV) was 202% predicted (SD 41%). Median SGRQ was 63.26 (range 20-70.6). Change in RV (-0.51 ± 0.9L) following EBV-insertion showed a strong negative correlation with change in parasternal thickness (r = -0.883) ipsilateral to EBV insertion, as did change in target lobe volume (-0.89 ± 0.6L) (r = -0.771). Parasternal muscle echogenicity, diaphragm thickness and diaphragm excursion did not significantly change. CONCLUSIONS: Dynamic changes in intercostal muscle thickness on ultrasound measurement occur in response to relief of hyperinflation. We demonstrate linear relationships between intercostal thickness and change in hyperinflation following endobronchial valve insertion. This demonstrates the deleterious effect of hyperinflation on intrinsic inspiratory muscles and provides an additional mechanism for symptomatic response to EBVs.

Published
2020

40. The impact of perceived risk, screening eligibility and worry on preference for lung cancer screening: a cross-sectional survey

Author

See, K, Manser, R, Park, ER, Steinfort, D, King, B, Piccolo, F, Manners, D, See, K, Manser, R, Park, ER, Steinfort, D, King, B, Piccolo, F, and Manners, D

Abstract

Lung cancer screening is effective at reducing lung cancer deaths when individuals at greatest risk are screened. Recruitment initiatives target all current and former smokers, of whom only some are eligible for screening, potentially leading to discordance between screening preference and eligibility in ineligible individuals. The objective of the present study was to identify factors associated with preference for screening among ever-smokers. Ever-smokers aged 55-80 years attending outpatient clinics at three Australian hospitals were invited. The survey recorded: 1) demographics; 2) objective lung cancer risk and screening eligibility using the Prostate Lung Colon Ovarian 2012 risk model; and 3) perceived lung cancer risk, worry about and seriousness of lung cancer using a validated questionnaire. Multivariable ordinal logistic regression identified predictors of screening preference. The survey was completed by 283 individuals (response rate 27%). Preference for screening was high (72%) with no significant difference between low-dose computed tomography screening-eligible and -ineligible individuals (77% versus 68%, p=0.11). Worry about lung cancer (adjusted-proportional odds ratio (adj-OR) 1.31, 95% CI 1.08-1.58; p=0.007) and perceived seriousness of lung cancer (adj-OR 1.31, 95% CI 1.05-1.64; p=0.02) were associated with higher preference for lung cancer screening while screening eligibility was not. The concept of "early detection" was the most important driver to have screening while practical obstacles like difficulty travelling to the scan or taking time off work were the least important barriers to screening. Most current or former smokers prefer to undergo screening. Worry about lung cancer and perceived seriousness of the diagnosis are more important drivers for screening preference than eligibility status.

Published
2020

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