163 results on '"Gavin M. Wright"'
Search Results
2. Attitudes and Perceptions to Prehabilitation in Lung Cancer
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Anna Shukla BAppSc, Catherine L. Granger B Physio(Hons), PhD, Gavin M. Wright MBBS, FRACS, PhD, Lara Edbrooke BAppSc, PhD, and Linda Denehy BAppSc, PhD
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: Prehabilitation to maximize exercise capacity before lung cancer surgery has the potential to improve operative tolerability and patient outcomes. However, translation of this evidence into clinical practice is limited. Aims: To determine the acceptability and perceived benefit of prehabilitation in lung cancer among thoracic surgeons. Procedure: 198 cardiothoracic surgeons within Australia and New Zealand were surveyed to evaluate their attitudes and perceived benefits of prehabilitation in lung cancer. Results: Response rate was 14%. A moderate proportion of respondents reported that there is a need to refer lung resection patients to preoperative physiotherapy/prehabilitation, particularly high-risk patients or those with borderline fitness for surgery. 91% of surgeons were willing to delay surgery (as indicated by cancer stage/type) to optimize patients via prehabilitation. The main barriers to prehabilitation reported were patient comorbidities and access to allied health professionals, with 33% stating that they were unsure who to refer to for prehabilitation in thoracic surgery. This is despite 60% of the cohort reporting that pulmonary rehabilitation is available as a preoperative resource. 92% of respondents believe that further research into prehabilitation in lung cancer is warranted. Conclusion: The benefits of prehabilitation for the oncology population have been well documented in the literature over recent years and this is reflected in the perceptions surgeons had on the benefits of prehabilitation for their patients. This survey demonstrates an interest among cardiothoracic surgeons in favor of prehabilitation, and therefore further research and demonstration of its benefit is needed in lung cancer to facilitate implementation into practice.
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- 2020
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3. Phase 1, open-label, dose-escalation study on the safety, pharmacokinetics, and preliminary efficacy of intravenous Coxsackievirus A21 (V937), with or without pembrolizumab, in patients with advanced solid tumors
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Christy Ralph, Sumati Gupta, Matthew Zibelman, Brendan D Curti, Kevin J Harrington, Steven J O'Day, Andrew G Hill, David C Campbell, Gavin M Wright, David E Gerber, Jonathan E Rosenberg, Jaime R Merchan, Charles M Rudin, Hardev S Pandha, Wallace L Akerley, Daphne Day, Timothy D Clay, Ross R Jennens, Yixin Ren, Emmett V Schmidt, and Lisa Guttman
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background Oncolytic virus V937 showed activity and safety with intratumoral administration. This phase 1 study evaluated intravenous V937±pembrolizumab in patients with advanced solid tumors.Methods Patients had advanced non-small cell lung cancer (NSCLC), urothelial cancer, metastatic castration-resistant prostate cancer, or melanoma in part A (V937 monotherapy), and metastatic NSCLC or urothelial cancer in part B (V937+pembrolizumab). Prior immunotherapy was permitted >28 days before study treatment. Patients received intravenous V937 on days 1, 3, and 5 (also on day 8 in part B) of the first 21-day cycle and on day 1 of subsequent cycles for eight cycles. Three ascending dose-escalation cohorts were studied. Dose-escalation proceeded if no dose-limiting toxicities (DLTs) occurred in cycle 1 of the previous cohort. In part B, patients also received pembrolizumab 200 mg every 3 weeks from day 8 for 2 years; dose-expansion occurred at the highest-dose cohort. Serial biopsies were performed.Results No DLTs occurred in parts A (n=18) or B (n=85). Grade 3–5 treatment-related adverse events (AEs) were not observed in part A and were experienced by 10 (12%) patients in part B. The most frequent treatment-related AEs (any grade) in part B were fatigue (36%), pruritus (18%), myalgia (14%), diarrhea (13%), pyrexia (13%), influenza-like illness (12%), and nausea (12%). At the highest tested dose, median intratumoral V937 concentrations were 117,631 copies/mL on day 8, cycle 1 in part A (n=6) and below the detection limit for most patients (86% (19/22)) on day 15, cycle 1 in part B. Objective response rates were 6% (part A), 9% in the NSCLC dose-expansion cohort (n=43), and 20% in the urothelial cancer dose-expansion cohort (n=35).Conclusions Intravenous V937+pembrolizumab had a manageable safety profile. Although V937 was detected in tumor tissue, in NSCLC and urothelial cancer, efficacy was not greater than that observed in previous studies with pembrolizumab monotherapy.Trial registration number NCT02043665.
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- 2023
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4. Development of an Australia and New Zealand Lung Cancer Clinical Quality Registry: a protocol paper
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Fraser Brims, John Zalcberg, Sue Evans, Nick Pavlakis, Jennifer Philip, Ross Lawrenson, Susan Harden, Henry Marshall, Gavin M Wright, Paul Dawkins, Emily Stone, Shantelle Smith, Margaret Brand, Lisa Briggs, Lillian Leigh, Mark Brooke, Vanessa N Brunelli, Collin Chia, Mary Duffy, Tracy Leong, Dainik Patel, Nicole Rankin, Nimit Singhal, Rebecca Tay, Shalini Vinod, Morgan Windsor, David Leong, and Rob G Stirling
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Medicine - Abstract
Introduction Lung cancer is the leading cause of cancer mortality, comprising the largest national cancer disease burden in Australia and New Zealand. Regional reports identify substantial evidence-practice gaps, unwarranted variation from best practice, and variation in processes and outcomes of care between treating centres. The Australia and New Zealand Lung Cancer Registry (ANZLCR) will be developed as a Clinical Quality Registry to monitor the safety, quality and effectiveness of lung cancer care in Australia and New Zealand.Methods and analysis Patient participants will include all adults >18 years of age with a new diagnosis of non-small-cell lung cancer (NSCLC), SCLC, thymoma or mesothelioma. The ANZLCR will register confirmed diagnoses using opt-out consent. Data will address key patient, disease, management processes and outcomes reported as clinical quality indicators. Electronic data collection facilitated by local data collectors and local, state and federal data linkage will enhance completeness and accuracy. Data will be stored and maintained in a secure web-based data platform overseen by registry management. Central governance with binational representation from consumers, patients and carers, governance, administration, health department, health policy bodies, university research and healthcare workers will provide project oversight.Ethics and dissemination The ANZLCR has received national ethics approval under the National Mutual Acceptance scheme. Data will be routinely reported to participating sites describing performance against measures of agreed best practice and nationally to stakeholders including federal, state and territory departments of health. Local, regional and (bi)national benchmarks, augmented with online dashboard indicator reporting will enable local targeting of quality improvement efforts.
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- 2022
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5. Use of Indocyanine Green Fluorescence Imaging in Thoracic and Esophageal Surgery
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Calvin Sze-Hang Ng, Boon-Hean Ong, Yin Kai Chao, Gavin M. Wright, Yasuo Sekine, Ian Wong, Zhexue Hao, Guangjian Zhang, Harit Chaturvedi, Subramanyeshwar Rao Thammineedi, Simon Law, and Hyun Koo Kim
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Pulmonary and Respiratory Medicine ,Surgery ,Cardiology and Cardiovascular Medicine - Abstract
Fluorescence imaging using indocyanine green in thoracic and esophageal surgery is gaining popularity because of the potential to facilitate surgical planning, to stage disease, and to reduce postoperative complications. To optimize use of fluorescence imaging in thoracic and esophageal surgery, an expert panel sought to establish a set of recommendations at a consensus meeting.The panel included 12 experts in thoracic and upper gastrointestinal surgery from Asia-Pacific countries. Before meeting, 7 focus areas were defined: intersegmental plane identification for sublobar resections; pulmonary nodule localization; lung tumor detection; bullous lesion detection; lymphatic mapping of lung tumors; evaluation of gastric conduit perfusion; and lymphatic mapping in esophageal surgical procedures. A literature search of the PubMed database was conducted using keywords indocyanine green, fluorescence, thoracic, surgery, and esophagectomy. At the meeting, panelists addressed each focus area by discussing the most relevant evidence and their clinical experiences. Consensus statements were derived from the proceedings, followed by further discussions, revisions, finalization, and unanimous agreement. Each statement was assigned a level of evidence and a grade of recommendation.A total of 9 consensus recommendations were established. Identification of the intersegmental plane for sublobar resections, localization of pulmonary nodules, lymphatic mapping in lung tumors, and assessment of gastric conduit perfusion were applications of fluorescence imaging that have the most robust current evidence.Based on best available evidence and expert opinions, these consensus recommendations may facilitate thoracic and esophageal surgery using fluorescence imaging.
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- 2023
6. Lung neuroendocrine neoplasms: a single centre surgical series and analysis of staging
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Reece A. Davies, Naveed Z. Alam, and Gavin M. Wright
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Surgery ,General Medicine - Published
- 2023
7. Table 2 from Cisplatin Increases Sensitivity to FGFR Inhibition in Patient-Derived Xenograft Models of Lung Squamous Cell Carcinoma
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Marie-Liesse Asselin-Labat, Benjamin Solomon, Christopher J. Burns, Matthew E. Ritchie, Prudence A. Russell, Gavin M. Wright, Daniel P. Steinfort, Louis B. Irving, Phillip Antippa, Stephen B. Fox, Jean-Marc Garnier, Stephen B. Ma, Richard J. Young, Aliaksei Z. Holik, and Clare E. Weeden
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Supplementary Table S2: GO term enrichment analysis of differentially expressed genes between t1 and t0, overlapping in PDX 788, 926, 792
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- 2023
8. Supplementary Tables from CD74–NRG1 Fusions in Lung Adenocarcinoma
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Roman K. Thomas, Yasushi Yatabe, Stefan A. Haas, Sascha Ansén, Sven Perner, Jürgen Wolf, Thomas Zander, Reinhard Buettner, Lukas C. Heukamp, Martin Vingron, Dirk Brehmer, Marc Parade, Souichi Ogata, Timothy Perera, Idoya Lahortiga, Vito M. Fazio, Annamaria la Torre, Lucia A. Muscarella, Jörg Sänger, Joachim H. Clement, Iver Petersen, Erich Stoelben, Johannes M. Heuckmann, Peter Nürnberg, Christian Becker, Janine Altmüller, Sylvie Lantuejoul, Christian G. Brambilla, Denis Moro-Sibilot, Hélène Nagy-Mignotte, Elisabeth Brambilla, Benjamin Solomon, Zoe Wainer, Prudence A. Russell, Gavin M. Wright, Roland T. Ullrich, Mirjam Koker, Ilona Dahmen, Wenzel Vogel, Jakob Schöttle, Florian Malchers, Juliane Daßler, Marc Bos, Martin Peifer, Sandra Ortiz-Cuaran, Frauke Leenders, Roopika Menon, Ruping Sun, Hirotaka Osada, Dennis Plenker, and Lynnette Fernandez-Cuesta
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XLSX file 75K, This is an excel file containing 9 sheets, one for each of the 9 supplementary tables (S1 to S9) mentioned in the main text
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- 2023
9. Supplementary Tables S1, S3-S7, Supplementary Material and Methods, and Supplementary Figure Legends from Cisplatin Increases Sensitivity to FGFR Inhibition in Patient-Derived Xenograft Models of Lung Squamous Cell Carcinoma
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Marie-Liesse Asselin-Labat, Benjamin Solomon, Christopher J. Burns, Matthew E. Ritchie, Prudence A. Russell, Gavin M. Wright, Daniel P. Steinfort, Louis B. Irving, Phillip Antippa, Stephen B. Fox, Jean-Marc Garnier, Stephen B. Ma, Richard J. Young, Aliaksei Z. Holik, and Clare E. Weeden
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Supplementary Table 1. Engraftment rates of lung cancer patient-derived xenografts vary according to histology and specimen type; Supplementary Table 3. TP53 mutations in primary lung cancer and corresponding PDX, as detected by exome sequencing; Supplementary Table 4. FGFR1 FISH scores are conserved for successive passages of squamous cell carcinoma PDXs 792, 406, 788, and 926; Supplementary Table 5. FGFR1 gene amplification does not always correlate with FGFR1 RNA expression in a tissue microarray patient cohort; Supplementary Table 6. FGFR1 gene amplification does not always correlate with FGFR1 RNA expression in squamous cell carcinoma patients from a tissue microarray cohort; Supplementary Table 7. FGFR1 gene amplification does not always correlate with RNA expression in a squamous cell carcinoma PDX cohort; Supplementary Material and Methods, and Supplementary Figure Legends
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- 2023
10. Supplementary Figures from CD74–NRG1 Fusions in Lung Adenocarcinoma
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Roman K. Thomas, Yasushi Yatabe, Stefan A. Haas, Sascha Ansén, Sven Perner, Jürgen Wolf, Thomas Zander, Reinhard Buettner, Lukas C. Heukamp, Martin Vingron, Dirk Brehmer, Marc Parade, Souichi Ogata, Timothy Perera, Idoya Lahortiga, Vito M. Fazio, Annamaria la Torre, Lucia A. Muscarella, Jörg Sänger, Joachim H. Clement, Iver Petersen, Erich Stoelben, Johannes M. Heuckmann, Peter Nürnberg, Christian Becker, Janine Altmüller, Sylvie Lantuejoul, Christian G. Brambilla, Denis Moro-Sibilot, Hélène Nagy-Mignotte, Elisabeth Brambilla, Benjamin Solomon, Zoe Wainer, Prudence A. Russell, Gavin M. Wright, Roland T. Ullrich, Mirjam Koker, Ilona Dahmen, Wenzel Vogel, Jakob Schöttle, Florian Malchers, Juliane Daßler, Marc Bos, Martin Peifer, Sandra Ortiz-Cuaran, Frauke Leenders, Roopika Menon, Ruping Sun, Hirotaka Osada, Dennis Plenker, and Lynnette Fernandez-Cuesta
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PDF file 234K, This is a file containing the list of supplementary tables, the list of supplementary figures, as well as the 7 supplementary figures (S1 to S7) and their correspondent legends, mentioned in the main text
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- 2023
11. Data from CD74–NRG1 Fusions in Lung Adenocarcinoma
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Roman K. Thomas, Yasushi Yatabe, Stefan A. Haas, Sascha Ansén, Sven Perner, Jürgen Wolf, Thomas Zander, Reinhard Buettner, Lukas C. Heukamp, Martin Vingron, Dirk Brehmer, Marc Parade, Souichi Ogata, Timothy Perera, Idoya Lahortiga, Vito M. Fazio, Annamaria la Torre, Lucia A. Muscarella, Jörg Sänger, Joachim H. Clement, Iver Petersen, Erich Stoelben, Johannes M. Heuckmann, Peter Nürnberg, Christian Becker, Janine Altmüller, Sylvie Lantuejoul, Christian G. Brambilla, Denis Moro-Sibilot, Hélène Nagy-Mignotte, Elisabeth Brambilla, Benjamin Solomon, Zoe Wainer, Prudence A. Russell, Gavin M. Wright, Roland T. Ullrich, Mirjam Koker, Ilona Dahmen, Wenzel Vogel, Jakob Schöttle, Florian Malchers, Juliane Daßler, Marc Bos, Martin Peifer, Sandra Ortiz-Cuaran, Frauke Leenders, Roopika Menon, Ruping Sun, Hirotaka Osada, Dennis Plenker, and Lynnette Fernandez-Cuesta
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We discovered a novel somatic gene fusion, CD74–NRG1, by transcriptome sequencing of 25 lung adenocarcinomas of never smokers. By screening 102 lung adenocarcinomas negative for known oncogenic alterations, we found four additional fusion-positive tumors, all of which were of the invasive mucinous subtype. Mechanistically, CD74–NRG1 leads to extracellular expression of the EGF-like domain of NRG1 III-β3, thereby providing the ligand for ERBB2–ERBB3 receptor complexes. Accordingly, ERBB2 and ERBB3 expression was high in the index case, and expression of phospho-ERBB3 was specifically found in tumors bearing the fusion (P < 0.0001). Ectopic expression of CD74–NRG1 in lung cancer cell lines expressing ERBB2 and ERBB3 activated ERBB3 and the PI3K–AKT pathway, and led to increased colony formation in soft agar. Thus, CD74–NRG1 gene fusions are activating genomic alterations in invasive mucinous adenocarcinomas and may offer a therapeutic opportunity for a lung tumor subtype with, so far, no effective treatment.Significance: CD74–NRG1 fusions may represent a therapeutic opportunity for invasive mucinous lung adenocarcinomas, a tumor with no effective treatment that frequently presents with multifocal unresectable disease. Cancer Discov; 4(4); 415–22. ©2014 AACR.This article is highlighted in the In This Issue feature, p. 377
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- 2023
12. Figure S1-S6 from Cisplatin Increases Sensitivity to FGFR Inhibition in Patient-Derived Xenograft Models of Lung Squamous Cell Carcinoma
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Marie-Liesse Asselin-Labat, Benjamin Solomon, Christopher J. Burns, Matthew E. Ritchie, Prudence A. Russell, Gavin M. Wright, Daniel P. Steinfort, Louis B. Irving, Phillip Antippa, Stephen B. Fox, Jean-Marc Garnier, Stephen B. Ma, Richard J. Young, Aliaksei Z. Holik, and Clare E. Weeden
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Supplementary Fig. S1. Generation of patient-derived xenografts from surgery and biopsy specimens of non small cell lung cancer Supplementary Fig. S2. Squamous cell carcinoma patient-derived xenografts recapitulate the genomic phenotype of patients'' tumors Supplementary Fig. S3. Analysis of biomarkers of response to FGFR inhibition Supplementary Fig. S4. High FGFR1 RNA expression does not predict patient outcome Supplementary Fig. S5. PIK3CA amplification does not predict response to PI3K inhibitors Supplementary Fig. S6. FGFR targeted therapy in FGFR inhibitor resistant tumors does not increase cisplatin sensitivity
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- 2023
13. Promoter hypomethylation of NY-ESO-1, association with clinicopathological features and PD-L1 expression in non-small cell lung cancer
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John M. Mariadason, Paul C. Boutros, Gavin M. Wright, Mun Sem Liew, Thomas John, Aparna Jayachandran, Anderly C. Chueh, Maud H.W. Starmans, Stephen Barnett, Prudence A. Russell, and Marzena Walkiewicz
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PD-L1 ,0301 basic medicine ,medicine.medical_treatment ,Oncology and Carcinogenesis ,Cell ,promoter methylation ,03 medical and health sciences ,0302 clinical medicine ,medicine ,NY-ESO-1 ,Lung cancer ,Uncategorized ,biology ,business.industry ,Immunotherapy ,Methylation ,medicine.disease ,Immune checkpoint ,3. Good health ,lung cancer ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Immunology ,Cancer research ,biology.protein ,biomarker ,Nivolumab ,business ,Research Paper - Abstract
Cancer-Testis antigens (CTA) are immunogenic molecules with normal tissue expression restricted to testes but with aberrant expression in up to 30% of non-small cell lung cancers (NSCLCs). Regulation of CTA expression is mediated in part through promoter DNA methylation. Recently, immunotherapy has altered treatment paradigms in NSCLC. Given its immunogenicity and ability to be re-expressed through demethylation, NY-ESO-1 promoter methylation, protein expression and its association with programmed death receptor ligand-1 (PD-L1) expression and clinicopathological features were investigated. Lung cancer cell line demethylation resulting from 5-Aza-2'-deoxycytidine treatment was associated with both NY-ESO-1 and PD-L1 re-expression in vitro but not increased chemosensitivity. NY-ESO-1 hypomethylation was observed in 15/94 (16%) of patient samples and associated with positive protein expression (P < 0.0001). In contrast, PD-L1 expression was observed in 50/91 (55%) but strong expression in only 12/91 (13%) cases. There was no association between NY-ESO-1 and PD-L1 expression, despite resultant re-expression of both by 5-Aza-2'-deoxycytidine. Importantly, NY-ESO-1 hypomethylation was found to be an independent marker of poor prognosis in patients not treated with chemotherapy (HR 3.59, P = 0.003) in multivariate analysis. In patients treated with chemotherapy there were no differences in survival associated with NY-ESO-1 hypomethylation. Collectively, these results provided supporting evidence for the potential use of NY-ESO-1 hypomethylation as a prognostic biomarker in stage 3 NSCLCs. In addition, these data highlight the potential to incorporate demethylating agents to enhance immune activation, in tumours currently devoid of immune infiltrates and expression of immune checkpoint genes.
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- 2023
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14. A comparison of outcomes and survival between Victoria and Denmark in lung cancer surgery: opportunities for international benchmarking
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Michael Stenger, Robert G Stirling, Gavin M. Wright, Erik Jakobsen, and John Zalcberg
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medicine.medical_specialty ,Lung Neoplasms ,Victoria ,Denmark ,Concordance ,Population ,Danish ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Humans ,Medicine ,Registries ,Stage (cooking) ,education ,Lung cancer ,Lung cancer surgery ,education.field_of_study ,business.industry ,Mortality rate ,General Medicine ,medicine.disease ,language.human_language ,Benchmarking ,language ,Surgery ,business ,Wedge resection (lung) - Abstract
Backgrounds Victoria (Australia) and Denmark have comparable population sizes and high-quality healthcare systems. Lung cancer surgery, however, is performed in more than 20 Victorian hospitals compared to four in Denmark. Such differences in centralization may influence outcomes. We engaged clinical quality registries to enable international benchmarking by exploring patterns of lung cancer surgery including mortality and survival. Methods All patients undergoing lung cancer surgery between 2015 and 2018 registered in the Victorian Lung Cancer Registry and the Danish Lung Cancer Registry were included. Analyses on stage concordance, 30 and 90-day mortality, and overall survival were restricted to a selected subgroup with NSCLC and no neo-adjuvant therapy or metastatic disease and only one operation. Results We included 1554 Victorian and 4319 Danish patients. The resection rate was 26.3% in Victoria and 28% in Denmark, but a higher proportion of Victorian patients underwent wedge resection (19.1% versus 8.8%). Stage concordance was 59.6% and 54.9% in Victoria and Denmark, respectively. The 30- and 90-day mortality was 1.3% and 2.6% in Victoria, compared to 1.4% and 2.8% in Denmark with no difference in overall survival (p = 0.28) or risk-adjusted survival (HR: 1.10 (95% CI: 0.89-1.37); p = 0.38). Conclusion High-quality surgical lung cancer care was confirmed by similar high resection and low mortality rates including no overall survival difference. The drivers and consequences of stage discordance and differences in patterns of resection deserve further exploration. This study provides a model for international benchmarking using clinical quality registries, although caution remains in the interpretation given disparities in data completeness.
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- 2021
15. Genomic and Clinical Significance of Multiple Primary Lung Cancers as Determined by Next-Generation Sequencing
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Gavin M. Wright, Matthew Conron, Vivek Rathi, and Daryn Goodwin
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0301 basic medicine ,Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,Lung Neoplasms ,DNA Mutational Analysis ,Disease ,DNA sequencing ,Neoplasms, Multiple Primary ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Clinical significance ,In patient ,Lung ,business.industry ,High-Throughput Nucleotide Sequencing ,Genomics ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Mutation ,Cohort ,Histopathology ,business ,Personal genomics - Abstract
Introduction Marked variations in survival rates have brought into question whether standard clinicopathologic classification should be applied to patients presenting with multiple primary lung cancers (MPLCs). This study investigated the genetic profiles of MPLCs in a cohort of patients using next-generation sequencing and correlated results to clinicopathologic data and patient outcome. Methods Patients treated surgically with curative intent for two putative primaries of similar histopathology from January 2000 to December 2019 at St Vincent’s Hospital Melbourne. DNA and RNA was extracted from formalin-fixed, paraffin-embedded tumor tissue and sequenced on an Ion Torrent Personal Genome Machine system. Patient outcome was determined by overall survival and disease-free survival. Results A total of 40 cases fulfilled the inclusion criteria. Mutational profiling was concordant with clinicopathologic diagnosis in most cases; however, seven cases (17.5%) revealed shared mutations suggesting metastatic disease and this was associated with a substantial reduction in overall survival (p Conclusions Our results suggest that gene sequencing technologies are potentially a more accurate diagnostic and prognostic tool compared with traditional histopathologic evaluation in patients presenting with suspected MPLCs, which could better guide management and predict outcomes.
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- 2021
16. Long‐term outcomes of pulmonary metastasectomy: a multicentre analysis
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Phillip Antippa, Francis Cheung, Nima Yaftian, Benjamin Dunne, and Gavin M. Wright
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medicine.medical_specialty ,Lung Neoplasms ,medicine.medical_treatment ,Disease-Free Survival ,03 medical and health sciences ,Pneumonectomy ,0302 clinical medicine ,Renal cell carcinoma ,medicine ,Humans ,Survival rate ,Retrospective Studies ,business.industry ,Metastasectomy ,Sarcoma ,General Medicine ,Neoplasms, Germ Cell and Embryonal ,Prognosis ,medicine.disease ,Confidence interval ,Surgery ,Survival Rate ,Treatment Outcome ,Cardiothoracic surgery ,030220 oncology & carcinogenesis ,Video-assisted thoracoscopic surgery ,030211 gastroenterology & hepatology ,Colorectal Neoplasms ,business ,Wedge resection (lung) - Abstract
BACKGROUND: Many extrapulmonary neoplasms metastasize to the lungs. We conducted a retrospective review of all patients who underwent pulmonary metastasectomy for oligometastatic disease at two centres in order to determine long-term outcomes. METHODS: The study institutions' thoracic surgery databases were searched for all patients who underwent pulmonary metastasectomy from 2000 to 2017. RESULTS: There were a total of 476 patients who underwent pulmonary metastasectomy. Mean age at time of surgery was 57.2 ± 15.9 years. Mean number of pulmonary lesions was 1.9 ± 1.6. Mean disease-free interval (DFI) was 3.6 ± 4.3 years. The most common primary neoplasms were colorectal cancer (CRC) in 35.1% (167/476), sarcoma in 23.9% (114/476), melanoma in 16.2% (77/478), renal cell carcinoma (RCC) in 7.3% (35/476) and germ cell tumour (GCT) in 4.4% (21/476). Hospital mortality was 0.4% (2/476). Mean follow-up time was 3.8 ± 2.9 years. Survival was 88.9% (95% confidence interval 85.77-91.5) at 1 year and 49.6% (95% confidence interval 44.4-54.6) at 5 years. On multivariate Cox-regression analysis GCT (P = 0.004), CRC (P = 0.03), DFI of 36+ months (P = 0.007), R0 resection (P = 0.002) and non-anatomical, sub-lobar (wedge) resection (P = 0.002) were protective against mortality. CONCLUSION: Pulmonary metastasectomy is associated with survival of 50% at 5-year follow-up. DFI of over 36 months, R0 resections, lesions resectable by wedge resection rather than anatomic resection and GCT and CRC primary cancers were associated with improved survival.
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- 2021
17. Pulmonary carcinoid tumours: A multi-centre analysis of survival and predictors of outcome following sublobar, lobar, and extended pulmonary resections
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Daniel Florisson, Siven Seevanayagam, Nima Yaftian, Naveed Z. Alam, Jean Lee, Stacy Telianidis, Sameer Thakur, Stephen Barnett, Phillip Antippa, Simon Knight, and Gavin M. Wright
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Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Lung Neoplasms ,Carcinoid Tumor ,Disease-Free Survival ,medicine ,Long term outcomes ,Retrospective analysis ,Humans ,Carcinoid tumour ,Multi centre ,Lung cancer ,Retrospective Studies ,Lung ,business.industry ,Cancer ,General Medicine ,Middle Aged ,Prognosis ,medicine.disease ,medicine.anatomical_structure ,Cardiothoracic surgery ,Lymphatic Metastasis ,Female ,Surgery ,Radiology ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background Pulmonary carcinoids are rare neoplasms, accounting for approximately 1%–2% of all lung malignancies. A retrospective analysis was undertaken of all patients who underwent surgical resection of pulmonary carcinoid tumours across multiple institutions in Melbourne, Australia. Methods From May 2000 through April 2020, 241 patients who underwent surgical resection of pulmonary carcinoid tumours were retrospectively reviewed. Patient demographics, pathologic data, and long-term outcomes were recorded. Results Median age was 57.7 years and the majority of patients were female (58.9% vs. 41.1%). Typical carcinoid was present in 77.1%. Histological subtype was associated with several factors. Atypical carcinoid was more likely to have larger tumour size and nodal involvement. Overall survival for typical carcinoid at 5, 10, and 15 years was 98%, 95%, and 84%, and for atypical carcinoid was 88%, 82%, and 62%, respectively. Histological subtype and age were found to be independent predictors of overall survival, with worse outcomes for atypical and those above 60 years of age. Disease-free survival was related to sublobar resection (p Conclusion Excellent long-term outcomes can be achieved following surgical resection of pulmonary carcinoids. Atypical histology and lymph node involvement are significant prognostic factors, and sublobar resection should not be considered in patients with either of the above features. Typical carcinoid tumour without nodal involvement may be appropriate for sublobar resection. Typical and atypical carcinoid tumours should be considered distinct disease entities, and as such treated accordingly.
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- 2021
18. Excess mortality and undertreatment in elderly lung cancer patients: treatment nihilism in the modern era?
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Matthew Conron, Paul Mitchell, Jennifer Philip, Margaret Brand, Robert G Stirling, John Zalcberg, Gavin M. Wright, Jonathan Pham, and David Ball
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Performance status ,business.industry ,Lung Cancer ,Cancer ,Original Articles ,Disease ,medicine.disease ,Comorbidity ,Clinical trial ,03 medical and health sciences ,0302 clinical medicine ,Tolerability ,030220 oncology & carcinogenesis ,Internal medicine ,Risk of mortality ,medicine ,Medicine ,030212 general & internal medicine ,Lung cancer ,business - Abstract
Treatment of elderly patients with lung cancer is significantly hindered by concerns about treatment tolerability, toxicity and limited clinical trial data in the elderly; potentially giving rise to treatment nihilism amongst clinicians. This study aims to describe survival in elderly patients with lung cancer and explore potential causes for excess mortality. Patients diagnosed with lung cancer in the Victorian Lung Cancer Registry between 2011–2018 were analysed (n=3481). Patients were age-categorised and compared using Cox-regression modelling to determine mortality risk, after adjusting for confounding. Probability of being offered cancer treatments was also determined, further stratified by disease stage. The eldest patients (≥80 years old) had significantly shorter median survival compared with younger age groups (, Treatment strongly determines lung cancer survival, yet nihilism may threaten treatment provision and survival outcomes. Older patients in this cohort had reduced multidisciplinary presentation, less treatment (OR 0.24) and 28% increased mortality risk. https://bit.ly/2ZGotj0
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- 2021
19. Phase 1, open-label, dose-escalation study on the safety, pharmacokinetics, and preliminary efficacy of intravenous Coxsackievirus A21 (V937), with or without pembrolizumab, in patients with advanced solid tumors
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Charles M Rudin, Hardev S Pandha, Matthew Zibelman, Wallace L Akerley, Kevin J Harrington, Daphne Day, Andrew G Hill, Steven J O'Day, Timothy D Clay, Gavin M Wright, Ross R Jennens, David E Gerber, Jonathan E Rosenberg, Christy Ralph, David C Campbell, Brendan D Curti, Jaime R Merchan, Yixin Ren, Emmett V Schmidt, Lisa Guttman, and Sumati Gupta
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Pharmacology ,Cancer Research ,Oncology ,Immunology ,Molecular Medicine ,Immunology and Allergy - Abstract
BackgroundOncolytic virus V937 showed activity and safety with intratumoral administration. This phase 1 study evaluated intravenous V937±pembrolizumab in patients with advanced solid tumors.MethodsPatients had advanced non-small cell lung cancer (NSCLC), urothelial cancer, metastatic castration-resistant prostate cancer, or melanoma in part A (V937 monotherapy), and metastatic NSCLC or urothelial cancer in part B (V937+pembrolizumab). Prior immunotherapy was permitted >28 days before study treatment. Patients received intravenous V937 on days 1, 3, and 5 (also on day 8 in part B) of the first 21-day cycle and on day 1 of subsequent cycles for eight cycles. Three ascending dose-escalation cohorts were studied. Dose-escalation proceeded if no dose-limiting toxicities (DLTs) occurred in cycle 1 of the previous cohort. In part B, patients also received pembrolizumab 200 mg every 3 weeks from day 8 for 2 years; dose-expansion occurred at the highest-dose cohort. Serial biopsies were performed.ResultsNo DLTs occurred in parts A (n=18) or B (n=85). Grade 3–5 treatment-related adverse events (AEs) were not observed in part A and were experienced by 10 (12%) patients in part B. The most frequent treatment-related AEs (any grade) in part B were fatigue (36%), pruritus (18%), myalgia (14%), diarrhea (13%), pyrexia (13%), influenza-like illness (12%), and nausea (12%). At the highest tested dose, median intratumoral V937 concentrations were 117,631 copies/mL on day 8, cycle 1 in part A (n=6) and below the detection limit for most patients (86% (19/22)) on day 15, cycle 1 in part B. Objective response rates were 6% (part A), 9% in the NSCLC dose-expansion cohort (n=43), and 20% in the urothelial cancer dose-expansion cohort (n=35).ConclusionsIntravenous V937+pembrolizumab had a manageable safety profile. Although V937 was detected in tumor tissue, in NSCLC and urothelial cancer, efficacy was not greater than that observed in previous studies with pembrolizumab monotherapy.Trial registration numberNCT02043665.
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- 2023
20. Lung Cancer in Australia
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Benjamin J. Solomon, Wendy A Cooper, Thomas John, Kwun M. Fong, Henry M. Marshall, Shankar Siva, and Gavin M. Wright
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Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,Lung Neoplasms ,business.industry ,medicine.medical_treatment ,Australia ,MEDLINE ,medicine.disease ,Radiation therapy ,Text mining ,Internal medicine ,medicine ,Humans ,business ,Lung cancer - Published
- 2020
21. Thoracic surgery in Australia
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Gavin M. Wright
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Pulmonary and Respiratory Medicine ,Editorial Commentary on Thoracic Surgery Worldwide ,medicine.medical_specialty ,Cardiothoracic surgery ,business.industry ,General surgery ,medicine ,business - Published
- 2022
22. Impact of COVID-19 on cancer service delivery: a follow-up international survey of oncology clinicians
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Robert Zielinski, Florian Lordick, Benjamin Solomon, Solange Peters, Fanny Franchini, Susana Banerjee, David Ball, Grace Chazan, Deme Karikios, Marliese Alexander, Nick Pavlakis, Linda Mileshkin, Gavin M. Wright, Prunella Blinman, Maarten Joost IJzerman, TechMed Centre, Health Technology & Services Research, and Orthopedics and Sports Medicine
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Service delivery framework ,telehealth ,service delivery ,Telehealth ,1117 Public Health and Health Services ,SDG 3 - Good Health and Well-being ,Internal medicine ,Neoplasms ,Surveys and Questionnaires ,Pandemic ,medicine ,Advanced disease ,Humans ,1112 Oncology and Carcinogenesis ,Pandemics ,11 Medical and Health Sciences ,Original Research ,business.industry ,SARS-CoV-2 ,International survey ,Cancer ,COVID-19 ,medicine.disease ,Coronavirus ,oncology ,Professional association ,Follow-Up Studies ,Neoplasms/epidemiology ,Neoplasms/therapy ,business - Abstract
Background The COVID-19 pandemic has had a vast impact on cancer service delivery around the world. Previously reported results from our international survey of oncology clinicians, conducted through March-April 2020, found that clinicians reported altering management in both the curative and palliative settings and not in proportion to the COVID-19 case burden in their region of practice. This follow-up survey, conducted from 27th September to 7th November 2020, aimed to explore how attitudes and practices evolved over the 2020 pandemic period. Participants and methods Participants were medical, radiation and surgical oncologist and trainees. Surveys were distributed electronically via ESMO and other collaborating professional societies. Participants were asked to compare their practice prior to the pandemic to both the period of March-April 2020, referred to as the ‘early’ period, and the current survey period, referred to as the ‘later’ period. Results One hundred and seventy-two oncology clinicians completed the survey. The majority of respondents were medical oncologists (n = 136, 79%) and many were from Europe (n = 82, 48%). In the ‘early’ period, 88% (n = 133) of clinicians reported altering their practice compared to 63% (n = 96) in the ‘later’ period. Compared to prior to the pandemic, clinicians reported fewer new patient presentations in the ‘early’ period and a trend towards more patients presenting with advanced disease in the ‘later’ period. Conclusions Results indicate a swing back towards pre-COVID-19 practices despite an increase in the rate of cumulative COVID-19 cases across 2020. The impact of these changes on cancer associated morbidity and mortality remains to be measured over the months and years to come., Highlights • This collaborative international survey of oncology clinicians was conducted in October/November of 2020. • Findings indicate a swing back towards ‘pre-coronavirus disease’ practice. • Fewer clinicians altered practice compared to the ‘early’ period of the pandemic in 2020 (63% versus 88%). • Clinicians reported seeing more new patients and a greater proportion of patients presenting with advanced disease.
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- 2021
23. Development of an Australia and New Zealand Lung Cancer Clinical Quality Registry: a protocol paper
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Shantelle Smith, Margaret Brand, Susan Harden, Lisa Briggs, Lillian Leigh, Fraser Brims, Mark Brooke, Vanessa N Brunelli, Collin Chia, Paul Dawkins, Ross Lawrenson, Mary Duffy, Sue Evans, Tracy Leong, Henry Marshall, Dainik Patel, Nick Pavlakis, Jennifer Philip, Nicole Rankin, Nimit Singhal, Emily Stone, Rebecca Tay, Shalini Vinod, Morgan Windsor, Gavin M Wright, David Leong, John Zalcberg, and Rob G Stirling
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Adult ,Lung Neoplasms ,Carcinoma, Non-Small-Cell Lung ,Australia ,Humans ,Registries ,General Medicine ,New Zealand - Abstract
IntroductionLung cancer is the leading cause of cancer mortality, comprising the largest national cancer disease burden in Australia and New Zealand. Regional reports identify substantial evidence-practice gaps, unwarranted variation from best practice, and variation in processes and outcomes of care between treating centres. The Australia and New Zealand Lung Cancer Registry (ANZLCR) will be developed as a Clinical Quality Registry to monitor the safety, quality and effectiveness of lung cancer care in Australia and New Zealand.Methods and analysisPatient participants will include all adults >18 years of age with a new diagnosis of non-small-cell lung cancer (NSCLC), SCLC, thymoma or mesothelioma. The ANZLCR will register confirmed diagnoses using opt-out consent. Data will address key patient, disease, management processes and outcomes reported as clinical quality indicators. Electronic data collection facilitated by local data collectors and local, state and federal data linkage will enhance completeness and accuracy. Data will be stored and maintained in a secure web-based data platform overseen by registry management. Central governance with binational representation from consumers, patients and carers, governance, administration, health department, health policy bodies, university research and healthcare workers will provide project oversight.Ethics and disseminationThe ANZLCR has received national ethics approval under the National Mutual Acceptance scheme. Data will be routinely reported to participating sites describing performance against measures of agreed best practice and nationally to stakeholders including federal, state and territory departments of health. Local, regional and (bi)national benchmarks, augmented with online dashboard indicator reporting will enable local targeting of quality improvement efforts.
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- 2022
24. Endobronchial metastases from hepatocellular carcinoma: a case report
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Naveed Z. Alam, Francis Cheung, Prudence A. Russell, and Gavin M. Wright
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Palliative care ,medicine.diagnostic_test ,business.industry ,Treatment outcome ,General Medicine ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Bronchoscopy ,Laser therapy ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,medicine ,Carcinoma ,Bronchial neoplasm ,030211 gastroenterology & hepatology ,Surgery ,Neoplasm staging ,Radiology ,Cardiology and Cardiovascular Medicine ,business - Abstract
Advanced-stage hepatocellular carcinoma presenting with endobronchial metastases is an extremely rare phenomenon, with only a few cases reported to date. Despite endobronchial metastases being a rare occurrence, the clinically significant sequelae require prompt diagnosis and management. Therapeutic bronchoscopy represents an effective palliative treatment for malignant airway obstruction. This case report describes a 62-year-old man who presented with bilateral endobronchial metastases from advanced-stage hepatocellular carcinoma, requiring symptom palliation with laser bronchoscopy.
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- 2019
25. Mesenchyme to epithelial transition protein expression, gene copy number and clinical outcome in a large non-small cell lung cancer surgical cohort
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Benjamin Solomon, Paul Mitchell, Adrienne Morey, Marzena Walkiewicz, Paul C. Boutros, Thomas John, Carmel Murone, Maud H.W. Starmans, Gavin M. Wright, Khashayer Asadi, Simon R. Knight, Gareth Rivalland, and RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy
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0301 basic medicine ,in situ hybridisation ,mesenchyme to epithelial transition receptor ,Mesenchyme ,Clinical Sciences ,Oncology and Carcinogenesis ,non-small cell lung cancer (NSCLC) ,ERLOTINIB ,medicine.disease_cause ,ACTIVATION ,03 medical and health sciences ,0302 clinical medicine ,medicine ,mesenchyme to epithelial transition amplification ,Lung cancer ,non-small cell lung cancer ,Polysomy ,business.industry ,ONARTUZUMAB ,MUTATIONS ,medicine.disease ,Immunohistochemistry ,PROGNOSTIC VALUE ,030104 developmental biology ,medicine.anatomical_structure ,mesenchyme to epithelial transition amplification (MET amplification) ,TARGET ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,MET ,Original Article ,Erlotinib ,KRAS ,mesenchyme to epithelial transition receptor (MET receptor) ,business ,Tyrosine kinase ,PHASE-II TRIAL ,medicine.drug - Abstract
Author(s): Rivalland, Gareth; Mitchell, Paul; Murone, Carmel; Asadi, Khashayer; Morey, Adrienne L; Starmans, Maud; Boutros, Paul C; Walkiewicz, Marzena; Solomon, Benjamin; Wright, Gavin; Knight, Simon; John, Thomas | Abstract: BackgroundIn non-small cell lung cancer (NSCLC), mesenchyme to epithelial transition (MET) protein abundance increases with disease stage and is implicated in resistance to tyrosine kinase inhibitors. To better clarify the impact of MET overexpression on tumor behavior, we investigated a large cohort of patients who underwent curative surgical resection to determine whether MET gene amplification or protein abundance was prognostic.MethodsTissue microarrays (TMAs) were constructed using triplicate 1 mm cores of FFPE primary NSCLC specimens. TMAs underwent immunohistochemical (IHC) staining with the SP44 clone (Ventana) and cores were considered positive if g50% of tumor exhibited 2+ staining. The highest of triplicate values was used. MET gene amplification was detected using either SISH using Ventana's MET DNP probe or FISH using the D7S486/CEP 7 Abbott Probe. DNA was subjected to mutational profiling using Sequenom's LungCarta panel.ResultsData from two institutions comprising 763 patients (516; 68%) male were generated, including 360 stage I, 226 stage II, 160 stage III and 18 resected stage IV. High MET protein expression was detected in 25% (193/763), and was significantly more common in adenocarcinomas than squamous cell carcinoma (Pl0.01). MET gene copy number (GCN) correlated with high MET protein expression by IHC (P=0.01). Increased MET protein expression was associated with EGFR and KRAS mutations (Pl0.01 for both). Once polysomy was excluded, true MET gene amplification was detected in only 8/763 (1%) of samples. In multivariate analysis, neither MET protein abundance nor GCN were correlated to overall patient survival.ConclusionsMET expression by IHC and GCN amplification was not prognostic in this large Caucasian surgical series. MET's primary role remains as a therapeutic target.
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- 2019
26. Sex-Dependent Staging in Non–Small-Cell Lung Cancer; Analysis of the Effect of Sex Differences in the Eighth Edition of the Tumor, Node, Metastases Staging System
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Benjamin Solomon, Gavin M. Wright, Peter F. M. Choong, Matthew Conron, Prudence A. Russell, Zoe Wainer, Marissa Daniels, Karla Gough, and David Ball
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Adult ,Male ,0301 basic medicine ,Pulmonary and Respiratory Medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Databases, Factual ,Population ,TNM staging system ,Cohort Studies ,Young Adult ,03 medical and health sciences ,Sex Factors ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,medicine ,Humans ,Neoplasm Metastasis ,Lung cancer ,education ,Survival analysis ,Aged ,Neoplasm Staging ,Proportional Hazards Models ,Aged, 80 and over ,education.field_of_study ,business.industry ,Proportional hazards model ,Hazard ratio ,Australia ,Middle Aged ,Prognosis ,medicine.disease ,Survival Analysis ,United States ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cohort ,Female ,business ,Cohort study - Abstract
Introduction: Non–small-cell lung cancer (NSCLC) has disproportionately negative outcomes in men compared with women. The importance of the relationship between sex and tumor, node, metastases (TNM) staging system remains unknown. The objective of this study was to investigate the effect of sex on NSCLC survival for each stage in the eighth edition of the TNM staging system in NSCLC. Patients and Methods: Two cohorts treated surgically with curative intent between 2000 and 2010 were analyzed. The primary cohort was from Australia with a second population set from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate analyses of putative and validated prognostic factors were undertaken to investigate sex-dependent prognostication with detailed analyses of sex differences in each TNM stage. The primary outcome was disease-specific survival (DSS) at 5 years. Results: Inclusion criteria were met by 555 patients in the Australian cohort, 335 men (60.4%) and 220 (39.6%) women; and 47,706 patients from the SEER cohort, 24,671 men (51.7%) and 23,035 women (48.3%). Five-year DSS was significantly worse for men in multivariate analyses for the Australian (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.04-1.98; P =.026) and SEER (HR, 1.24; 95% CI, 1.20-1.28; P
- Published
- 2018
27. EGFR Exon 20 Insertion Mutations: Clinicopathological Characteristics and Treatment Outcomes in Advanced Non-Small Cell Lung Cancer
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Jose Luis Leal, Thomas John, Nick Pavlakis, Gavin M. Wright, Stephen Clarke, Benjamin Solomon, Marliese Alexander, Malinda Itchins, Anthony J. Gill, Brett G.M. Hughes, Steven Kao, and Hannah Ainsworth
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0301 basic medicine ,Pulmonary and Respiratory Medicine ,Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Disease ,Polymerase Chain Reaction ,03 medical and health sciences ,Exon ,T790M ,Young Adult ,0302 clinical medicine ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,medicine ,Humans ,Epidermal growth factor receptor ,Genetic Testing ,Lung cancer ,Aged ,Aged, 80 and over ,Chemotherapy ,Lung ,biology ,business.industry ,Exons ,Middle Aged ,medicine.disease ,Confidence interval ,ErbB Receptors ,Mutagenesis, Insertional ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,biology.protein ,Female ,business - Abstract
Background Epidermal growth factor receptor gene (EGFR) exon 20 insertion (ex20-ins) mutations are an uncommon and heterogeneous group of non–small cell lung cancers (NSCLCs), resistant to conventional EGFR tyrosine kinase inhibitors (TKIs). Characteristics and outcomes of patients with EGFR ex20-ins have not been fully established; we sought to clarify them using a multinational patient database. Patients and Methods Patients with NSCLC from six Australian institutions with EGFR exon 20 mutations (ex20-mut), excluding T790M, were retrospectively reviewed. Clinical characteristics and outcomes with systemic treatments were collected and analyzed using comparative statistics. Results Among 109 patients with ex20-mut, 61% were females and 75% were Caucasians. More males presented with de novo metastatic disease (84% vs. 51%; P = .002). Central nervous system (48%) and liver (24%) metastases were common within metastatic patients (n = 86). Thirty-nine patients received platinum-based chemotherapy (PBC) and achieved a 43% objective response rate (ORR), median progression-free survival (mPFS) of 6.9 months, and median overall survival (mOS) of 31.0 months. Twenty-three of the patients with ex20-ins received conventional TKIs, resulting in an ORR of 13%, mPFS of 3.4 months (95% confidence interval [CI], 1.91-6.25), and mOS of 31.0 months (95% CI, 15.09-not reached). Nine patients with S786I mutations received TKIs, resulting in an ORR of 50%, mPFS of 18.2 months (2.79-not reached), and mOS of 33.4 months (95% CI, 16.14-not reached). Twenty-three patients received immune checkpoint inhibitor monotherapy (ICIm), resulting in an ORR of 4%, mPFS of 2.6 months (95% CI, 1.91-4.83), and mOS of 30.8 months (95% CI, 17.62-41.62). Conclusion Although phenotypically similar to patients with common EGFR mutations, patients with EGFR ex20-mut had worse survival, perhaps due to the lack of targeted therapies. Chemotherapy was superior to conventional EGFR TKIs in patients with EGFR ex20-ins, although there was moderate activity of TKIs in S768I mutations. ICIm was ineffective.
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- 2021
28. A predictive model for identifying candidates for adjuvant chemotherapy based on recurrence risk profile of resected, node-negative (N0) non-small cell lung cancer
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Gavin M. Wright, Muteb Al Zaidi, and Timur A Krivitsky
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Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,business.industry ,Hazard ratio ,non-small cell lung cancer (NSCLC) ,Retrospective cohort study ,030204 cardiovascular system & hematology ,medicine.disease ,Confidence interval ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Adenocarcinoma ,Original Article ,Stage (cooking) ,business ,Lung cancer - Abstract
Background The decision for administering adjuvant chemotherapy (AC) in completely resected node-negative non-small cell lung cancer (NSCLC) is guided by likelihood of disease recurrence or death based on tumor, node, metastasis (TNM) stage. However, within each TNM stage are sub-groups of patients that are more or less likely to relapse than stage alone predicts. Methods In this retrospective cohort study, prospective data from 394 consecutive patients who underwent complete resection of node-negative NSCLC without adjuvant therapies, between 2002 and 2019 was retrospectively analyzed. Independent tumor and host risk factors for recurrence were subjected to multivariate analysis to develop a predictive risk model distributing patients into low-risk or high-risk categories. Results Recurrence risk was independently predicted by a neutrophil:lymphocyte ratio (NLR) of ≥3.5 [hazard ratio (HR), 1.9; 95% confidence interval (CI), 1.1-3.5], visceral pleural invasion (HR, 2.2; 95% CI, 1.3-3.8), histopathology other than adenocarcinoma or squamous cell (HR, 2.6; 95% CI, 1.2-5.5) and tumor size >33 mm (HR, 3.9; 95% CI, 2.3-6.7). The specific combination of risk factors contributed to a score for a risk model which classified 9% of Stage I and 69% of Stage ≥II patients as high-risk. The predicted 5-year disease-free survival (DFS) for high-risk and low-risk patients as scored by the predictive model was 30% and 85%, respectively. Conclusions Our readily reproducible, low-technology model, developed from individually validated tumor/host risk factors, identified sub-groups of resected node-negative NSCLC patients at significantly discordant risk of recurrence to their TNM stage category.
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- 2021
29. Towards Routine Implementation of Liquid Biopsies in Cancer Management: It Is Always Too Early, until Suddenly It Is Too Late
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Maarten Joost IJzerman, Jeanne Tie, Koen Degeling, Joel Geoghegan, Belinda Lee, Chelsee A. Hewitt, Arun Azad, Jasper de Boer, Frédéric Hollande, Yat Ho To, Sarah-Jane Dawson, Richard W. Tothill, Gavin M. Wright, Erasmus School of Health Policy & Management, Health Services Management & Organisation (HSMO), and Medical Microbiology & Infectious Diseases
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Clinical Biochemistry ,Article ,03 medical and health sciences ,0302 clinical medicine ,SDG 3 - Good Health and Well-being ,medicine ,genomics ,cancer ,health economics ,Medical physics ,Liquid biopsy ,early detection ,Genotyping ,lcsh:R5-920 ,Health economics ,liquid biopsy ,business.industry ,Health services research ,biomarkers ,Evidence-based medicine ,ctDNA ,Molecular diagnostics ,CTC ,health services research ,030104 developmental biology ,Clinical research ,030220 oncology & carcinogenesis ,Cancer management ,minimal residual disease ,cancer surveillance ,business ,lcsh:Medicine (General) - Abstract
Blood-based liquid biopsies are considered a new and promising diagnostic and monitoring tool for cancer. As liquid biopsies only require a blood draw, they are non-invasive, potentially more rapid and assumed to be a less costly alternative to genomic analysis of tissue biopsies. A multi-disciplinary workshop (n = 98 registrations) was organized to discuss routine implementation of liquid biopsies in cancer management. Real-time polls were used to engage with experts&rsquo, about the current evidence of clinical utility and the barriers to implementation of liquid biopsies. Clinical, laboratory and health economics presentations were given to illustrate the opportunities and current levels of evidence, followed by three moderated break-out sessions to discuss applications. The workshop concluded that tumor-informed assays using next-generation sequencing (NGS) or PCR-based genotyping assays will most likely provide better clinical utility than tumor-agnostic assays, yet at a higher cost. For routine application, it will be essential to determine clinical utility, to define the minimum quality standards and performance of testing platforms and to ensure their use is integrated into current clinical workflows including how they complement tissue biopsies and imaging. Early health economic models may help identifying the most viable application of liquid biopsies. Alternative funding models for the translation of complex molecular diagnostics, such as liquid biopsies, may also be explored if clinical utility has been demonstrated and when their use is recommended in multi-disciplinary consensus guidelines.
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- 2021
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30. Surgical Management of Pulmonary Metastases from Sarcoma
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Gavin M. Wright
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medicine.medical_specialty ,business.industry ,Clinical evidence ,medicine ,In patient ,Radiology ,Disease ,Sarcoma ,Primary sarcoma ,business ,medicine.disease ,Complete resection - Abstract
Sarcomas, despite being a disparate group of malignant diseases, share a common propensity to metastasise to the lungs, regardless of origin of the primary. This risk correlates with location, size, grade and histological subtype [1]. Often this is the only clinical evidence of disease in patients after appropriate complete resection of their primary sarcoma. They may appear at the time of local recurrence in an incompletely resected or inappropriately treated primary sarcoma.
- Published
- 2020
31. Impact of COVID-19 on cancer service delivery: Results from an international survey of oncology clinicians
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Gavin M. Wright, Florian Lordick, Robert Zielinski, David Ball, Deme Karikios, Benjamin Solomon, Susana Banerjee, Linda Mileshkin, Nick Pavlakis, Fanny Franchini, Marliese Alexander, Maarten Joost IJzerman, Prunella Blinman, Grace Chazan, Solange Peters, Erasmus School of Health Policy & Management, and Health Services Management & Organisation (HSMO)
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Cancer Research ,Asia ,Coronavirus disease 2019 (COVID-19) ,Service delivery framework ,service delivery ,Telehealth ,Medical Oncology ,lcsh:RC254-282 ,Objective assessment ,SDG 3 - Good Health and Well-being ,Neoplasms ,Surveys and Questionnaires ,Internal medicine ,Pandemic ,Humans ,Medicine ,Pandemics ,Original Research ,Oncologists ,SARS-CoV-2 ,business.industry ,Australia ,International survey ,COVID-19 ,Cancer ,Asia/epidemiology ,Australia/epidemiology ,COVID-19/epidemiology ,COVID-19/virology ,Europe/epidemiology ,Female ,Medical Oncology/methods ,Medical Oncology/statistics & numerical data ,Neoplasms/epidemiology ,Neoplasms/therapy ,Oncologists/statistics & numerical data ,SARS-CoV-2/isolation & purification ,oncology ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Mental health ,Europe ,business - Abstract
Objectives: To report clinician-perceived changes to cancer service delivery in response to COVID-19. Design: Multidisciplinary Australasian cancer clinician survey in collaboration with the European Society of Medical Oncology. Setting: Between May and June 2020 clinicians from 70 countries were surveyed; majority from Europe (n=196; 39%) with 1846 COVID-19 cases per million people, Australia (AUS)/New Zealand (NZ) (n=188; 38%) with 267/236 per million and Asia (n=75; 15%) with 121 per million at time of survey distribution. Participants Medical oncologists (n=372; 74%), radiation oncologists (n=91; 18%) and surgical oncologists (n=38; 8%). Results: Eighty-nine per cent of clinicians reported altering clinical practices; more commonly among those with versus without patients diagnosed with COVID-19 (n=142; 93% vs n=225; 86%, p=0.03) but regardless of community transmission levels (p=0.26). More European clinicians (n=111; 66.1%) had treated patients diagnosed with COVID-19 compared with Asia (n=20; 27.8%) and AUS/NZ (n=8; 4.8%), pConclusion: Clinicians reported widespread changes to oncology services, in regions of both high and low COVID-19 case numbers. Clinician concerns of potential negative impacts on patient outcomes warrant objective assessment, with system and policy implications for healthcare delivery at large.
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- 2020
32. Locally advanced non-small cell lung cancer: the place of specialist thoracic surgery in the multidisciplinary team
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Gavin M. Wright and Muteb Al Zaidi
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medicine.medical_specialty ,Thoracic Surgical Procedure ,Modalities ,Referral ,business.industry ,General surgery ,Locally advanced ,medicine.disease ,Review Article on Lung Cancer Multidisciplinary Care ,Oncology ,Quality of life ,Multidisciplinary approach ,Cardiothoracic surgery ,medicine ,Lung cancer ,business - Abstract
One reason that lung cancer is the leading cause of cancer mortality worldwide, is that surgical intervention is highly dependent on earlier tumor stage and good patient condition. As large proportion of cases are already metastatic at presentation and many are locally advanced, curative surgery is only possible in a minority of fit patients. Increasing the number of patients achieving complete resection is one of the avenues to increase overall survival using our existing technology. In the past, complex cases may have been sporadically discussed between various specialists in order to achieve better outcomes. More recently, the idea of discussing those cases on a routine basis, rather than an accident of geography or referral pattern, gave rise to the multidisciplinary team. Lung cancer management is now increasingly complex, especially with novel modalities such as targeted therapies, immune checkpoint inhibitors and stereotactic body radiotherapy delivery. Likewise, in thoracic surgery, minimally invasive techniques, early recovery after surgery protocols and complex techniques for resecting locally advanced tumours or preserving lung parenchyma must all be deployed appropriately to continue our incremental gains in survival and quality of life. To highlight the role of specialist thoracic surgeon in the multidisciplinary care of locally advanced non-small cell lung cancer, we conducted a search of English language publications for its multidisciplinary-based surgical management. We limited our search to the last decade, then hand-searched relevant references. In addition, we used our large prospective database as a team-oriented specialized thoracic surgical service to benchmark and demonstrate the benefits of specialist surgeons in the modern multidisciplinary team. In conclusion, patients with locally advanced non-small cell lung cancer should have any surgical option withheld without a specialist thoracic surgical opinion as part of the multidisciplinary team discussion.
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- 2020
33. TP53 Status, Patient Sex, and the Immune Response as Determinants of Lung Cancer Patient Survival
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Paul J Neeson, Simon P. Keam, David Ball, Cassandra Litchfield, Sue Haupt, Benjamin Solomon, Franco Caramia, Gavin M. Wright, Donald Freudenstein, and Ygal Haupt
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0301 basic medicine ,Oncology ,LUAD ,Cancer Research ,medicine.medical_specialty ,Tumor suppressor gene ,Population ,Gene mutation ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Internal medicine ,medicine ,LUSC ,sex disparity ,TP53 ,Lung cancer ,education ,TP53 Gene Mutation ,immune signatures ,education.field_of_study ,business.industry ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Immune checkpoint ,lung cancer ,030104 developmental biology ,030220 oncology & carcinogenesis ,Adenocarcinoma ,business - Abstract
Lung cancer poses the greatest cancer-related death risk and males have poorer outcomes than females, for unknown reasons. Patient sex is not a biological variable considered in lung cancer standard of care. Correlating patient genetics with outcomes is predicted to open avenues for improved management. Using a bioinformatics approach across non-small cell lung cancer (NSCLC) subtypes, we identified where patient sex, mutation of the major tumor suppressor gene, Tumour protein P53 (TP53), and immune signatures stratified outcomes in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), among datasets of The Cancer Genome Atlas (TCGA). We exposed sex and TP53 gene mutations as prognostic for LUAD survival. Longest survival in LUAD occurred among females with wild-type (wt) TP53 genes, high levels of immune infiltration and enrichment for pathway signatures of Interferon Gamma (INF-&gamma, ), Tumour Necrosis Factor (TNF) and macrophages-monocytes. In contrast, poor survival in men with LUAD and wt TP53 genes corresponded with enrichment of Transforming Growth Factor Beta 1 (TGFB1, hereafter TGF-&beta, ) and wound healing signatures. In LUAD with wt TP53 genes, elevated gene expression of immune checkpoint CD274 (hereafter: PD-L1) and also protein 53 (p53) negative-regulators of the Mouse Double Minute (MDM)-family predict novel avenues for combined immunotherapies. LUSC is dominated by male smokers with TP53 gene mutations, while a minor population of TCGA LC patients with wt TP53 genes unexpectedly had the poorest survival, suggestive of a separate etiology. We conclude that advanced approaches to LUAD and LUSC therapy lie in the consideration of patient sex, TP53 gene mutation status and immune signatures.
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- 2020
34. Tubeless video-assisted thoracic surgery for lung cancer: is it ready for prime time?
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Jianrong Zhang, Zhihua Guo, Lei Chen, Qintai Yang, Long Jiang, Jianfei Shen, Haibo Sun, Hengrui Liang, Jian Zhang, Gavin M. Wright, Yu Jiang, Jianxing He, Yaokai Wen, Shengyi Zhong, Chenglin Yang, Jiaxi He, Shuben Li, Clive Musonza, Wenhua Liang, and R. Lucas Thomas
- Subjects
Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,business.industry ,Spontaneous ventilation ,Thoracic Surgery, Video-Assisted ,medicine.medical_treatment ,Clinical Decision-Making ,MEDLINE ,Disease Management ,General Medicine ,medicine.disease ,Surgery ,Chest tube ,Locoregional anaesthesia ,Treatment Outcome ,Oncology ,Video assisted thoracic surgery ,Medicine ,Humans ,business ,Lung cancer ,Pneumonectomy - Published
- 2020
35. SASH1 is a prognostic indicator and potential therapeutic target in non-small cell lung cancer
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Pascal H.G. Duijf, Gavin M. Wright, Shu-Dong Zhang, Emma Bolderson, Steven G. Gray, Joshua T. Burgess, Mark N. Adams, Derek J. Richard, Kenneth J. O'Byrne, Burgess, Joshua T, Bolderson, Emma, Adams, Mark N, Duijf, Pascal HG, Zhang, Shu‑Dong, Gray, Steven G, Wright, Gavin, Richard, Derek J, and O'Byrne, Kenneth J
- Subjects
0301 basic medicine ,Cell death ,Cell biology ,Lung Neoplasms ,Cancer therapy ,Cell ,lcsh:Medicine ,Apoptosis ,Treatment of lung cancer ,Article ,03 medical and health sciences ,Cell growth ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,Medicine ,Humans ,RNA, Messenger ,SASH1 ,lcsh:Science ,Lung cancer ,Cancer ,Cell Proliferation ,tumor suppressor protein ,Cisplatin ,Multidisciplinary ,business.industry ,Tumor Suppressor Proteins ,lcsh:R ,Chloropyramine ,apoptosis ,mRNA expression ,medicine.disease ,Prognosis ,Gene Expression Regulation, Neoplastic ,non‑small cell lung cancer ,030104 developmental biology ,medicine.anatomical_structure ,A549 Cells ,030220 oncology & carcinogenesis ,Cancer research ,Adenocarcinoma ,lcsh:Q ,business ,medicine.drug - Abstract
SASH1 (SAM and SH3 domain-containing protein 1) is a tumor suppressor protein that has roles in key cellular processes including apoptosis and cellular proliferation. As these cellular processes are frequently disrupted in human tumours and little is known about the role of SASH1 in the pathogenesis of the disease, we analysed the prognostic value of SASH1 in non-small cell lung cancers using publicly available datasets. Here, we show that low SASH1 mRNA expression is associated with poor survival in adenocarcinoma. Supporting this, modulation of SASH1 levels in a panel of lung cancer cell lines mediated changes in cellular proliferation and sensitivity to cisplatin. The treatment of lung cancer cells with chloropyramine, a compound that increases SASH1 protein concentrations, reduced cellular proliferation and increased sensitivity to cisplatin in a SASH1-dependent manner. In summary, compounds that increase SASH1 protein levels could represent a novel approach to treat NSCLC and warrant further study.
- Published
- 2020
36. Pulmonary metastasectomy: analysis of survival and prognostic factors in 243 patients
- Author
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Gavin M. Wright, Naveed Z. Alam, and Francis Cheung
- Subjects
Oncology ,Subset Analysis ,medicine.medical_specialty ,Univariate analysis ,Proportional hazards model ,business.industry ,Cancer ,Retrospective cohort study ,General Medicine ,030204 cardiovascular system & hematology ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Surgery ,Sarcoma ,Metastasectomy ,business ,Survival rate - Abstract
BACKGROUND Pulmonary metastases are a sign of advanced malignant disease. Interdisciplinary management of metastatic cancer mandates the consideration of all treatment options, and in selected patients pulmonary metastasectomy can be performed with curative intent. This study aims to analyze the prognostic factors associated with survival and optimize the selection of surgical candidates. The sarcoma subset analysis aims to examine the role of multiple repeat resections for pulmonary metastatic recurrence. METHODS A total of 243 patients were analyzed in this retrospective cohort study. Overall survival was estimated using Kaplan-Meier analysis. Univariate analyses with log-rank tests and multivariate analysis with Cox proportional hazards model were undertaken to determine the independent prognostic factors for survival. RESULTS Multivariate analyses identified germ cell cancer (P = 0.01) and a disease-free interval of >36 months (P = 0.006) as significant independent prognostic factors for improved survival, whilst synchronous metastases (P = 0.04), multiple metastases (P = 0.005) and incomplete resection (P
- Published
- 2018
37. Integrative and comparative genomic analyses identify clinically relevant pulmonary carcinoid groups and unveil the supra-carcinoids
- Author
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F. Le Calvez-Kelm, John K. Field, Nicolas Girard, Ernst-Jan M. Speel, Marie Brevet, Lynnette Fernandez-Cuesta, Jean-François Deleuze, Nicolas Lemaitre, Noémie Leblay, Sandrine Boyault, Marius Lund-Iversen, Gabriella Sozzi, Véronique Hofman, Sylvie Lantuejoul, Lucia Anna Muscarella, Paolo Graziano, Alex Soltermann, Matthieu Foll, Amelie Chabrier, Robert Olaso, A. Ferrari, Anne Boland, Paul Hofman, Luca Roz, Behnoush Abedi-Ardekani, Janine Altmüller, Tiffany M. Delhomme, Akram Ghantous, Christophe Caux, Jules L. Derks, Giuseppe Pelosi, Vincent Meyer, Anne-Marie C. Dingemans, Juan Sandoval, Jean-Michel Vignaud, Jelena Stojsic, Catherine Voegele, Geoffroy Durand, James D. McKay, Peter Nuernberg, Cyrille Cuenin, Nicolas Alcala, L. Moonen, Hector Hernandez-Vargas, Ugo Pastorino, Theo Giffon, O.T. Brustugun, L. Mangiante, Mauro Papotti, Philippe Lorimier, Anne-Claire Toffart, Prudence A. Russell, Aurélie A G Gabriel, Zdenko Herceg, A. S. Sertier, Joachim H. Clement, M. Milione, Joerg Saenger, Luka Brcic, Stéphanie Lacomme, V. Thomas de Montpreville, A. Viari, Marco Volante, Elisabeth Brambilla, Gavin M. Wright, Cécile Blanc-Fournier, David Hervás, N. Le Stang, H. Popper, Françoise Galateau-Sallé, Centre international de Recherche sur le Cancer (CIRC), Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Fondation Synergie Lyon Cancer [Lyon], Centre Léon Bérard [Lyon], Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Cologne Center for Genomics [Cologne] (CCG), University of Cologne, Centre for Molecular Medicine Cologne [Cologne] (CMMC), University Hospital of Cologne [Cologne], School for Oncology and Developmental Biology [Maastricht] (GROW), Maastricht University [Maastricht]-Maastricht University Medical Centre (MUMC), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service de pneumologie [Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Institute of Pathology and Molecular Pathology [Zurich], Department Hematology and Medical Oncology [Jena], Jena University Hospital [Jena], Central Clinic Bad Berka, Department of Molecular and Clinical Cancer Medicine [Liverpool], University of Liverpool, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), University of Melbourne, IRCCS Istituto Nazionale dei Tumori [Milano], Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Oslo University Hospital [Oslo], Centre Chirurgical Marie Lannelongue (CCML), Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Casa Sollievo della Sofferenza [San Giovanni Rotondo] (IRCCS), University Hospital Graz, Clinical Center of Serbia (KCS), Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale (ERABLE), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Università degli Studi di Milano = University of Milan (UNIMI), Università degli studi di Torino = University of Turin (UNITO), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospital Universitari i Politècnic La Fe, Synergie Lyon Cancer [Lyon], UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Université Nice Sophia Antipolis (... - 2019) (UNS), Centre chirurgical Marie Lannelongue, University of Milan, University of Turin, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Promovendi ODB, Pulmonologie, RS: GROW - R2 - Basic and Translational Cancer Biology, MUMC+: MA Med Staf Spec Longziekten (9), and Pathologie
- Subjects
0301 basic medicine ,Oncology ,Male ,Lung Neoplasms ,[SDV]Life Sciences [q-bio] ,General Physics and Astronomy ,Datasets as Topic ,02 engineering and technology ,Neuroendocrine tumors ,Machine Learning ,PATHWAY ,Cancer genomics ,lcsh:Science ,Lung ,Aged, 80 and over ,Comparative Genomic Hybridization ,Multidisciplinary ,Intracellular Signaling Peptides and Proteins ,Genomics ,Middle Aged ,021001 nanoscience & nanotechnology ,Prognosis ,3. Good health ,Neuroendocrine Carcinomas ,Survival Rate ,medicine.anatomical_structure ,Female ,Non small cell ,HEALTH ,Technology Platforms ,0210 nano-technology ,Adult ,EXPRESSION ,medicine.medical_specialty ,Adolescent ,Science ,CELL LUNG-CANCER ,Nerve Tissue Proteins ,Carcinoid Tumor ,DENDRITIC CELLS ,General Biochemistry, Genetics and Molecular Biology ,Article ,Small-cell lung cancer ,CLASSIFICATION ,03 medical and health sciences ,Young Adult ,Internal medicine ,Overall survival ,medicine ,Carcinoma ,Biomarkers, Tumor ,Humans ,Survival rate ,Aged ,Homeodomain Proteins ,IDENTIFICATION ,business.industry ,MUTATIONS ,Membrane Proteins ,General Chemistry ,medicine.disease ,Small Cell Lung Carcinoma ,030104 developmental biology ,DISCOVERY ,Carcinoma, Large Cell ,lcsh:Q ,business ,NEUROENDOCRINE TUMORS ,Comparative genomic hybridization - Abstract
The worldwide incidence of pulmonary carcinoids is increasing, but little is known about their molecular characteristics. Through machine learning and multi-omics factor analysis, we compare and contrast the genomic profiles of 116 pulmonary carcinoids (including 35 atypical), 75 large-cell neuroendocrine carcinomas (LCNEC), and 66 small-cell lung cancers. Here we report that the integrative analyses on 257 lung neuroendocrine neoplasms stratify atypical carcinoids into two prognostic groups with a 10-year overall survival of 88% and 27%, respectively. We identify therapeutically relevant molecular groups of pulmonary carcinoids, suggesting DLL3 and the immune system as candidate therapeutic targets; we confirm the value of OTP expression levels for the prognosis and diagnosis of these diseases, and we unveil the group of supra-carcinoids. This group comprises samples with carcinoid-like morphology yet the molecular and clinical features of the deadly LCNEC, further supporting the previously proposed molecular link between the low- and high-grade lung neuroendocrine neoplasms., The worldwide incidence of pulmonary carcinoids is increasing, but little is known about their molecular characteristics. Here, Alcala and colleagues present a multi-omics analysis of these tumours, revealing distinct molecular and prognostic subgroups.
- Published
- 2019
38. Comparison of Four PD-L1 Immunohistochemical Assays in Lung Cancer
- Author
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Shona Hendry, David J Byrne, Sue Sturrock, Gavin M. Wright, Wendy A Cooper, Stephen B. Fox, and Richard J. Young
- Subjects
0301 basic medicine ,Pulmonary and Respiratory Medicine ,Pathology ,medicine.medical_specialty ,Tissue microarray ,biology ,business.industry ,Pembrolizumab ,medicine.disease ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,medicine ,Carcinoma ,biology.protein ,Adenocarcinoma ,Immunohistochemistry ,Nivolumab ,Antibody ,business ,Lung cancer - Abstract
Introduction Four different programmed death ligand 1 immunohistochemical assays are approved or in development as companion or complementary diagnostics to different immunotherapeutic agents in lung carcinoma. We sought to determine whether these assays are technically equivalent and whether one antibody can be used on an alternate staining platform. Methods Serial sections of tissue microarrays constructed from 368 cases of resected lung cancer were stained for 22C3 and 28-8 on the Dako Link 48 platform (Dako, Carpinteria, Ca) and for SP142 and SP263 on the Ventana Benchmark Ultra platform (Ventana Medical Systems, Tucson, AZ) strictly as per product insert. A protocol was developed to use the 22C3 antibody on the Ventana Benchmark Ultra platform. Results Differences in mean tumor cell and immune cell staining were observed between the four assays ( p Conclusions Concordance between the four programmed death ligand 1 immunohistochemical assays when performed and scored as intended show that apart from 28-8 and 22C3, they cannot be used interchangeably in clinical practice. A protocol was successfully developed to use 22C3 on an alternate platform, which may help to overcome some barriers to implementation.
- Published
- 2018
39. Correlation between molecular analysis, diagnosis according to the 2015 WHO classification of unresected lung tumours and TTF1 expression in small biopsies and cytology specimens from 344 non-small cell lung carcinoma patients
- Author
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Vivek Rathi, Gavin M. Wright, Stephen Barnett, Toni-Maree Rogers, Richard A. Williams, Prudence A. Russell, Naveed Z. Alam, Benjamin Solomon, and Matthew Conron
- Subjects
Adult ,Male ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Lung Neoplasms ,Biopsy ,Adenocarcinoma ,Biology ,World Health Organization ,medicine.disease_cause ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Unresected ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Cytology ,medicine ,Carcinoma ,Humans ,neoplasms ,Aged ,Aged, 80 and over ,medicine.diagnostic_test ,Australia ,Cancer ,Middle Aged ,Molecular Abnormality ,medicine.disease ,Immunohistochemistry ,digestive system diseases ,respiratory tract diseases ,DNA-Binding Proteins ,030104 developmental biology ,030220 oncology & carcinogenesis ,Mutation ,Female ,KRAS ,Transcription Factors - Abstract
We investigated correlations between diagnosis according to the 2015 World Health Organization (WHO) classification of unresected lung tumours, molecular analysis and TTF1 expression in small biopsy and cytology specimens from 344 non-small cell lung carcinoma (NSCLC) patients. One case failed testing for EGFR, KRAS and ALK abnormalities and six had insufficient tumour for ALK testing. Overall mutation rate in 343 cases was 48% for the genes tested, with 19% EGFR, 33% KRAS and 4% BRAF mutations, and 5% ALK rearrangements detected. More EGFR-mutant (78%) and ALK-rearranged (75%) tumours had morphologic adenocarcinoma than KRAS-mutant (56%) tumours. Despite no significant difference in the overall rate of any molecular abnormality between morphologic adenocarcinoma (52%) and NSCLC, favour adenocarcinoma (47%) (p = 0.18), KRAS mutations were detected more frequently in the latter group. No significant difference in the overall rate of any molecular abnormality between TTF1 positive (49%) and TTF1 negative tumours (44%) (p = 0.92) was detected, but more EGFR-mutant (97%) and ALK-rearranged tumours (92%) were TTF1 positive than KRAS-mutant tumours (68%). Rates of EGFR, KRAS and BRAF mutations and ALK rearrangements in this Australian NSCLC patient population are consistent with the published international literature. Our findings suggest that 2015 WHO classification of unresected tumours may assist in identifying molecular subsets of advanced NSCLC.
- Published
- 2017
40. MA04.09 Impacts of Multidisciplinary Meeting Presentation: Drivers and Outcomes from a Population Registry Retrospective Cohort study
- Author
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Susan Harden, John Zalcberg, T. Lin, Robert G Stirling, Philip B. Mitchell, Jonathan Pham, Matthew Conron, N. Atkin, Gavin M. Wright, E. Paul, David Ball, and Margaret Brand
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,education.field_of_study ,Oncology ,business.industry ,Multidisciplinary approach ,Family medicine ,Population ,medicine ,Retrospective cohort study ,Presentation (obstetrics) ,education ,business - Published
- 2021
41. Lung cancer and socio-economic status: inextricably linked to place of residence
- Author
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David Hart, Matthew Conron, Eve Denton, Gavin M. Wright, and Prue Russell
- Subjects
Gerontology ,education.field_of_study ,Multivariate analysis ,Referral ,business.industry ,Population ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Cohort ,Internal Medicine ,medicine ,030212 general & internal medicine ,education ,Lung cancer ,Prospective cohort study ,business ,Socioeconomic status ,Cohort study ,Demography - Abstract
Background The association between socioeconomic status (SES) and lung cancer is internationally established but in Australia this relationship remains ill defined. Aims To examine the association between SES, place of residence and lung cancer outcomes in a large Australian cohort. Methods 2369 consecutive lung cancer patients managed by St Vincent's Hospital lung multidisciplinary meeting between 2001–2014 were included. Postcode data stratified participants by Socio-Economic Indexes for Areas, a validated measure of SES, and by geographical location, an important socioeconomic factor in Australia. Results There was no difference between socioeconomic groups in age (68 years), sex (63% males) or presentation (75% symptomatic). Low socioeconomic patients had increased smoking rates and a trend towards less adenocarcinoma. More low SES patients were from rural locations, had a greater frequency of earlier stage disease and curative treatment with higher overall survival even after multivariate analysis. When stratified for socioeconomic status, overall 5-year survival was significantly better in the low SES group (33% vs 24%, n = 2275, p = 0.02), although stage-stratified survival was similar in all socioeconomic groups. Conclusions Low SES patients were more frequently from rural locations and unexpectedly had earlier stage disease and higher overall survival. The excellent outcomes in rural and lower SES patients is reassuring but suggests that there is a population of these patients with advanced lung cancer who are not referred for multidisciplinary care. Further studies are required to better define this group and determine the barriers to referral to improve overall lung cancer outcomes.
- Published
- 2017
42. Clinical validation of the 50 gene AmpliSeq Cancer Panel V2 for use on a next generation sequencing platform using formalin fixed, paraffin embedded and fine needle aspiration tumour specimens
- Author
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Atha Palios, Sue-Anne McLachlan, Richard A. Williams, Gavin M. Wright, Vivek Rathi, Kerryn Jones, Huong Pham, Siok Chang, Penny McKelvie, Matthew Conron, and Diana Constantin
- Subjects
0301 basic medicine ,Tissue Fixation ,Formalin fixed paraffin embedded ,Biopsy, Fine-Needle ,DNA Mutational Analysis ,Medical laboratory ,Diagnostic tools ,Bioinformatics ,DNA sequencing ,Pathology and Forensic Medicine ,03 medical and health sciences ,symbols.namesake ,Neoplasms ,Humans ,Medicine ,Genetic Predisposition to Disease ,Sanger sequencing ,Massive parallel sequencing ,medicine.diagnostic_test ,business.industry ,Australia ,High-Throughput Nucleotide Sequencing ,DNA, Neoplasm ,Mutational analysis ,030104 developmental biology ,Fine-needle aspiration ,Mutation ,symbols ,business ,Software engineering - Abstract
The advent of massively parallel sequencing has caused a paradigm shift in the ways cancer is treated, as personalised therapy becomes a reality. More and more laboratories are looking to introduce next generation sequencing (NGS) as a tool for mutational analysis, as this technology has many advantages compared to conventional platforms like Sanger sequencing. In Australia all massively parallel sequencing platforms are still considered in-house in vitro diagnostic tools by the National Association of Testing Authorities (NATA) and a comprehensive analytical validation of all assays, and not just mere verification, is a strict requirement before accreditation can be granted for clinical testing on these platforms. Analytical validation of assays on NGS platforms can prove to be extremely challenging for pathology laboratories. Although there are many affordable and easily accessible NGS instruments available, there are no standardised guidelines as yet for clinical validation of NGS assays. We present an accreditation development procedure that was both comprehensive and applicable in a setting of hospital laboratory for NGS services. This approach may also be applied to other NGS applications in service laboratories.
- Published
- 2017
43. Reply
- Author
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Louisa Jorm, Gavin M. Wright, and Art Sedrakyan
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Lung Neoplasms ,business.industry ,Australia ,Humans ,Medicine ,Surgery ,Pulmonary Surgical Procedures ,Lung resection ,Cardiology and Cardiovascular Medicine ,business - Published
- 2020
44. Distinct initiating events underpin the immune and metabolic heterogeneity of KRAS-mutant lung adenocarcinoma
- Author
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Kate D. Sutherland, Sarah A. Best, Gavin M. Wright, Ariena Kersbergen, Sheryl Ding, James E Vince, Yi Xie, Kaiming Li, Ji-Ying Song, Vivek Rathi, Matthew E. Ritchie, Xueyi Dong, and Boris Reljic
- Subjects
Male ,0301 basic medicine ,Lung Neoplasms ,endocrine system diseases ,General Physics and Astronomy ,medicine.disease_cause ,Mice ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,lcsh:Science ,Kelch-Like ECH-Associated Protein 1 ,Multidisciplinary ,respiratory system ,Flow Cytometry ,Cancer metabolism ,Immunohistochemistry ,3. Good health ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Adenocarcinoma ,Female ,KRAS ,Cancer microenvironment ,NF-E2-Related Factor 2 ,Science ,Blotting, Western ,Adenocarcinoma of Lung ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,Proto-Oncogene Proteins p21(ras) ,Alveolar cells ,03 medical and health sciences ,Immune system ,Cell Line, Tumor ,medicine ,Animals ,Cancer models ,Lung cancer ,neoplasms ,Transcription factor ,Cancer ,General Chemistry ,medicine.disease ,digestive system diseases ,NFE2L2 ,respiratory tract diseases ,Mice, Inbred C57BL ,030104 developmental biology ,Cancer research ,lcsh:Q ,Reactive Oxygen Species ,Non-small-cell lung cancer - Abstract
The KRAS oncoprotein, a critical driver in 33% of lung adenocarcinoma (LUAD), has remained an elusive clinical target due to its perceived undruggable nature. The identification of dependencies borne through common co-occurring mutations are sought to more effectively target KRAS-mutant lung cancer. Approximately 20% of KRAS-mutant LUAD carry loss-of-function mutations in KEAP1, a negative regulator of the antioxidant response transcription factor NFE2L2/NRF2. We demonstrate that Keap1-deficient KrasG12D lung tumors arise from a bronchiolar cell-of-origin, lacking pro-tumorigenic macrophages observed in tumors originating from alveolar cells. Keap1 loss activates the pentose phosphate pathway, inhibition of which, using 6-AN, abrogated tumor growth. These studies highlight alternative therapeutic approaches to specifically target this unique subset of KRAS-mutant LUAD cancers., Lung adenocarcinomas frequently harbour KRAS mutations, of which a subset are characterized by co-mutation of KEAP1. Here the authors show, in mice, that KrasG12D mutant tumours are metabolically distinct, with a bronchiolar cell-of-origin.
- Published
- 2019
45. The Past, Present and Future of Pulmonary Metastasectomy: A Review Article
- Author
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Gavin M. Wright, Francis Cheung, and Naveed Z. Alam
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Lung Neoplasms ,lung metastasectomy ,medicine.medical_treatment ,Review Article ,030204 cardiovascular system & hematology ,Malignancy ,History, 21st Century ,survival ,Disease-Free Survival ,03 medical and health sciences ,Pneumonectomy ,0302 clinical medicine ,Breast cancer ,Risk Factors ,medicine ,Humans ,metastases ,pulmonary metastasectomy ,Lung ,business.industry ,General surgery ,Gastroenterology ,Metastasectomy ,Combination chemotherapy ,General Medicine ,History, 20th Century ,medicine.disease ,Review article ,Radiation therapy ,medicine.anatomical_structure ,030228 respiratory system ,lung resection ,Disease Progression ,Surgery ,Cardiology and Cardiovascular Medicine ,business ,Forecasting - Abstract
Pulmonary metastases are a sign of advanced malignancy and an omen of poor prognosis. Once primary tumors metastasize, they become notoriously difficult to treat and interdisciplinary management often involves a combination of chemotherapy, radiotherapy, and surgery. Over the last 25 years, the emerging body of evidence has recognized the curative potential of pulmonary metastasectomy. Surgical resection of pulmonary metastases is now commonly considered for patients with controlled primary disease, absence of widely disseminated extrapulmonary disease, completely resectable lung metastases, sufficient cardiopulmonary reserve, and lack of a better alternative systemic therapy. Since the development of these selection criteria, other prognostic factors have been proposed to better predict survival and optimize the selection of surgical candidates. Disease-free interval (DFI), completeness of resection, surgical approach, number and laterality of lung metastases, and lymph node metastases all play a dynamic role in determining patient outcomes. There is a definite need to continue reviewing these prognosticators to identify patients who will benefit most from pulmonary metastasectomy and those who should avoid unnecessary loss of lung parenchyma. This literature review aims to explore and synthesize the last 25 years of evidence on the long-term survival, prognostic factors, and patient selection process for pulmonary metastasectomy.
- Published
- 2019
46. Excision of Giant Schwannoma in a Nonagenarian—operative techniques for enhanced recovery after thoracotomy in the high-risk patient
- Author
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Tali Lior, Gavin M. Wright, and Rajeev Shukla
- Subjects
medicine.medical_specialty ,High risk patients ,Evidence-based practice ,business.industry ,medicine.medical_treatment ,MEDLINE ,Soft tissue ,Schwannoma ,Nerve injury ,medicine.disease ,Surgery ,03 medical and health sciences ,0302 clinical medicine ,Enhanced recovery ,030202 anesthesiology ,medicine ,Thoracotomy ,medicine.symptom ,Innovation ,business ,030217 neurology & neurosurgery - Abstract
Thoracotomy is acknowledged as one of the most painful procedures in surgical practice, with the potential to result in significant acute and chronic sequelae, which become especially relevant in high-risk patient populations. Certain pathologies necessitate this surgical approach, and in those circumstances we must aim to mitigate postoperative complications by employing surgical techniques that decrease the risk of nerve injury, rib fracture, and unnecessary soft tissue trauma. We describe an approach to thoracotomy that incorporates evidence-based strategies to lessen the risk of these potential complications, which resulted in rapid postoperative recovery in a nonagenarian.
- Published
- 2019
47. Novel technique for parietal pleural dissection using a laparoscopic hernia balloon
- Author
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Gavin M. Wright, Rajeev Shukla, Daniel Florisson, and Naveed Z. Alam
- Subjects
Pulmonary and Respiratory Medicine ,Extrapleural Pneumonectomy ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Pleural Neoplasms ,030204 cardiovascular system & hematology ,Balloon ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Medicine ,Humans ,Hernia ,Thoracotomy ,Pleural Neoplasm ,Osteosarcoma ,business.industry ,Thoracic Surgery, Video-Assisted ,Dissection ,General Medicine ,respiratory system ,medicine.disease ,respiratory tract diseases ,Surgery ,body regions ,030228 respiratory system ,Video-assisted thoracoscopic surgery ,Pleura ,Cardiology and Cardiovascular Medicine ,business ,Pleurectomy ,Pleurodesis - Abstract
We describe a novel technique for the creation of a pleural tent and pleurectomy via the use of a laparoscopic hernia balloon. In this method a Spacemaker™ Structural Balloon Trocar (Covidien, USA) is tunnelled under the pleura at the site of thoracotomy or video assisted thoracoscopic surgery port and incrementally inflated under vision. This method is less traumatic than traditional methods, is more likely to provide an intact pleural tent, and allows the surgeon to operate in a near bloodless operative field.
- Published
- 2019
48. P62.05 Identifying Therapeutic Approaches to Treat KEAP1-Mutant Lung Adenocarcinoma
- Author
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Matthew E. Ritchie, Ariena Kersbergen, Vivek Rathi, D. Desouza, Sheryl Ding, Malcolm J. McConville, Gavin M. Wright, Kate D. Sutherland, Boris Reljic, and Sarah A. Best
- Subjects
Pulmonary and Respiratory Medicine ,Lung ,medicine.anatomical_structure ,Oncology ,business.industry ,Mutant ,medicine ,Cancer research ,Adenocarcinoma ,medicine.disease ,business ,KEAP1 - Published
- 2021
49. OA05.06 Lessons Learned from the Victorian Lung Cancer Registry: Opportunities for Quality Improvement in Lung Cancer Management and Outcomes
- Author
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B. Jennings, Phillip Parente, L. Briggs, D. Langton, Robert Blum, Margaret Brand, John Zalcberg, Javier Torres, Phillip Antippa, Jeremy Millar, Craig Underhill, M. Caldecott, I. Olesen, Philip B. Mitchell, Arul Earnest, Gavin M. Wright, David Ball, K. See, Gary Richardson, Matthew Conron, Michael Stenger, John J McNeil, James Bartlett, and Robert G Stirling
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Quality management ,Oncology ,business.industry ,medicine ,Lung cancer ,medicine.disease ,Intensive care medicine ,business - Published
- 2021
50. Prognostic utility of inflammation-based biomarkers, neutrophil–lymphocyte ratio and change in neutrophil–lymphocyte ratio, in surgically resected lung cancers
- Author
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Jahan Dimiri, Adele Hwee Hong Lee, Daniel Thompson, Gavin M. Wright, Domagoj Vodanovich, Jesse Renouf, and Luke A Perry
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,Multivariate analysis ,Lymphocyte ,neutrophil–lymphocyte ratio ,Inflammation ,Diseases of the respiratory system ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Epidemiology ,Overall survival ,medicine ,Diseases of the circulatory (Cardiovascular) system ,030212 general & internal medicine ,Lung cancer ,Prospective cohort study ,Lung ,RC705-779 ,business.industry ,Cancer prognostication ,medicine.disease ,lung cancer ,medicine.anatomical_structure ,030228 respiratory system ,RC666-701 ,Original Article ,Surgery ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - Abstract
BACKGROUND/OBJECTIVE: Given the poor overall survival (OR) and progression-free survival (PFS) rates for lung cancers managed with surgical resection, there is a need to identify the prognostic markers that would improve the risk stratification of patients with operable lung cancer to inform treatment decisions. We investigate the prognostic utility of two established inflammation-based scores, the neutrophil–lymphocyte ratio (NLR) and the change in neutrophil–lymphocyte ratio (ΔNLR), throughout the operative period in a prospective cohort of patients with lung cancer who underwent surgical resection. METHODS: Demographic, clinical, and treatment details for 345 patients with lung cancer who underwent surgical resection between 2000 and 2019 at multiple centers across Melbourne, Victoria (Australia), were prospectively collected. Preoperative NLR and ΔNLR were calculated after which Cox univariate and multivariate analyses were conducted for OS and PFS against the known prognostic factors. RESULTS: Both univariate and multivariate analyses showed that preoperative NLR >4.54, as well as day 1 and day 2 postoperative NLR (P < 0.01), was associated with increased risk for postoperative mortality (hazard ratio 1.8; P < 0.01) and PFS (P < 0.05), whereas ΔNLR was not a significant predictor of OS or PFS. CONCLUSION: Elevated NLR among patients with lung cancer who underwent surgical resection was prognostic for poor OS and PFS, whereas ΔNLR was not found to be prognostic for either OS or PFS. Further research may yet reveal a prognostic value for ΔNLR when compared across a greater time period.
- Published
- 2021
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