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Eve Denton,1 Matthew Conron2 1Allergy, Immunology and Respiratory Department, Alfred Hospital, 2Department of Respiratory and Sleep Medicine, St Vincent's Hospital, Melbourne, VIC, Australia Abstract: Lung cancer is a major worldwide health burden, with high disease-related morbidity and mortality. Unlike other major cancers, there has been little improvement in lung cancer outcomes over the past few decades, and survival remains disturbingly low. Multidisciplinary care is the cornerstone of lung cancer treatment in the developed world, despite a relative lack of evidence that this model of care improves outcomes. In this article, the available literature concerning the impact of multidisciplinary care on key measures of lung cancer outcomes is reviewed. This includes the limited observational data supporting improved survival with multidisciplinary care. The impact of multidisciplinary care on other benchmark measures of quality lung cancer treatment is also examined, including staging accuracy, access to diagnostic investigations, improvements in clinical decision making, better utilization of radiotherapy and palliative care services, and improved quality of life for patients. Health service research suggests that multidisciplinary care improves care coordination, leading to a better patient experience, and reduces variation in care, a problem in lung cancer management that has been identified worldwide. Furthermore, evidence suggests that the multidisciplinary model of care overcomes barriers to treatment, promotes standardized treatment through adherence to guidelines, and allows audit of clinical services and for these reasons is more likely to provide quality care for lung cancer patients. While there is strengthening evidence suggesting that the multidisciplinary model of care contributes to improvements in lung cancer outcomes, more quality studies are needed. Keywords: lung cancer, multidisciplinary care, mortality, tumor board, quality of life

Background Lung cancer remains a major disease burden in Victoria (Australia) and requires a complex and multidisciplinary approach to ensure optimal care and outcomes. To date, no uniform mechanism is available to capture standardized population-based outcomes and thereby provide benchmarking. The establishment of such a data platform is, therefore, a primary requisite to enable description of process and outcome in lung cancer care and to drive improvement in the quality of care provided to individuals with lung cancer. Materials and Methods A disease quality registry pilot has been established to capture prospective data on all adult patients with clinical or tissue diagnoses of small cell and non-small cell lung cancer. Steering and management committees provide clinical governance and supervise quality indicator selection. Quality indicators were selected following extensive literature review and evaluation of established clinical practice guidelines. A minimum dataset has been established and training and data capture by data collectors is facilitated using a web-based portal. Case ascertainment is established by regular institutional reporting of ICD-10 discharge coding. Recruitment is optimized by provision of opt-out consent. Results The collection of a standardized minimum data set optimizes capacity for harmonized population-based data capture. Data collection has commenced in a variety of settings reflecting metropolitan and rural, and public, and private health care institutions. The data set provides scope for the construction of a risk-adjusted model for outcomes. A data access policy and a mechanism for escalation policy for outcome outliers has been established. Conclusions The Victorian Lung Cancer Registry provides a unique capacity to provide and confirm quality assessment in lung cancer and to drive improvement in quality of care across multidisciplinary stakeholders., Author(s): Rob G. Stirling[sup.1] [sup.2] , S. M. Evans[sup.2] , P. McLaughlin[sup.2] , M. Senthuren[sup.2] , J. Millar[sup.3] , J. Gooi[sup.4] , L. Irving[sup.5] , P. Mitchell[sup.6] , A. Haydon[sup.7] [...]

Background Lung cancer accounts for significant morbidity and mortality worldwide. The effect of recent changes in demographics and management on outcomes in Australia has not been clearly defined. Aims To compare three consecutive lung cancer cohorts to evaluate emergent differences in diagnosis, management and mortality. Methods For comparative analysis, 2119 lung cancer patients were divided into three successive cohorts. Current death data were sought from the Victorian Cancer Registry. Results Age at diagnosis, mode of presentation and pathology did not significantly differ between the groups. Significantly more females were diagnosed with lung cancer in the most recent cohort ( P = 0.04). Amongst non-small-cell lung cancer patients, there were more adenocarcinomas and less large cell carcinomas in the latest cohort ( P = <0.01). More patients from the most recent cohort were staged pathologically and via positron emission tomography and fewer were clinically staged ( P = <0.01). The most recent cohort had a greater proportion of Stage IV disease ( P = <0.01) and more curative surgical or combined modality radiotherapy and chemotherapy versus palliative radiotherapy or supportive care ( P = <0.01). Overall 5-year survival improved significantly in the most recent cohort, even after adjustment for age, gender and stage ( P = <0.01). Conclusion Comparison of three lung cancer patient cohorts diagnosed between 2001 and 2013 highlights emergent changes in lung cancer demographics, management and outcomes. These include recent increases in proportion of females, pathological and positron emission tomography staging, and Stage IV disease, as well as improved survival despite later stage disease. [ABSTRACT FROM AUTHOR]

Abstract Background The aim of this study was to identify critical genes involved in non-small cell lung cancer (NSCLC) pathogenesis that may lead to a more complete understanding of this disease and identify novel molecular targets for use in the development of more effective therapies. Methods Both transcriptional and genomic profiling were performed on 69 resected NSCLC specimens and results correlated with mutational analyses and clinical data to identify genetic alterations associated with groups of interest. Results Combined analyses identified specific patterns of genetic alteration associated with adenocarcinoma vs. squamous differentiation; KRAS mutation; TP53 mutation, metastatic potential and disease recurrence and survival. Amplification of 3q was associated with mutations in TP53 in adenocarcinoma. A prognostic signature for disease recurrence, reflecting KRAS pathway activation, was validated in an independent test set. Conclusions These results may provide the first steps in identifying new predictive biomarkers and targets for novel therapies, thus improving outcomes for patients with this deadly disease.

Abstract Background The development of targeted therapies has created a pressing clinical need for the rapid and robust molecular characterisation of cancers. We describe here the application of high-resolution melting analysis (HRM) to screen for KRAS mutations in clinical cancer samples. In non-small cell lung cancer, KRAS mutations have been shown to identify a group of patients that do not respond to EGFR targeted therapies and the identification of these mutations is thus clinically important. Methods We developed a high-resolution melting (HRM) assay to detect somatic mutations in exon 2, notably codons 12 and 13 of the KRAS gene using the intercalating dye SYTO 9. We tested 3 different cell lines with known KRAS mutations and then examined the sensitivity of mutation detection with the cell lines using 189 bp and 92 bp amplicons spanning codons 12 and 13. We then screened for KRAS mutations in 30 non-small cell lung cancer biopsies that had been previously sequenced for mutations in EGFR exons 18–21. Results Known KRAS mutations in cell lines (A549, HCT116 and RPMI8226) were readily detectable using HRM. The shorter 92 bp amplicon was more sensitive in detecting mutations than the 189 bp amplicon and was able to reliably detect as little as 5–6% of each cell line DNA diluted in normal DNA. Nine of the 30 non-small cell lung cancer biopsies had KRAS mutations detected by HRM analysis. The results were confirmed by standard sequencing. Mutations in KRAS and EGFR were mutually exclusive. Conclusion HRM is a sensitive in-tube methodology to screen for mutations in clinical samples. HRM will enable high-throughput screening of gene mutations to allow appropriate therapeutic choices for patients and accelerate research aimed at identifying novel mutations in human cancer.

Background: Lung cancer in Australia contributes 9% of all new cancer diagnoses and is the leading cause of cancer death and burden. Clinical practice guidelines provide evidence-based treatment recommendations for best practice management. We aimed to determine the extent of delivery of guideline-concordant treatment (GCT) and to identify modifiable variables influencing receipt of GCT and survival., Methods: Data was sourced from the Victorian Lung Cancer Registry (VLCR) in Victoria, Australia. Descriptive statistics were used to summarize patient and disease characteristics according to treatment type: GCT versus non-GCT versus no/declined treatment. Statistical analyses included multiple logistic regression, multiple COX regression and Kaplan-Meier survival estimates., Results: 52% of patients were treated with GCT, 32.8% non-GCT and 15.2% declined or received no treatment. GCT treated patients were younger, never smoked, had no comorbidities, had better performance status, had early stage cancer, were discussed at a multidisciplinary meeting or had treatment at a higher volume hospital. Overall, patients that received GCT had a 24% lower risk of mortality compared to patients that received non-GCT., Conclusion: Modifiable variables impacting likelihood of receiving GCT included age, smoking status and treating hospital characteristics. Several modifiable variables were identified with positive impacts on survival including increased treatment of the elderly, smoking cessation, delivery of GCT, and treatment in higher volume hospitals. The measurement and reporting of delivery of GCT has positive impacts on survival and therefore merits consideration as an evidence-based quality indicator in the reporting of lung cancer quality and safety outcomes., Competing Interests: Disclosure All other authors state that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Cardiopulmonary complications of connective tissue diseases (CTDs), particularly pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD), are major determinants of morbidity and mortality. Multidisciplinary meetings may improve diagnostic accuracy and optimise treatment. We review the literature regarding multidisciplinary meetings in CTD-ILD and PAH and describe our tertiary centre experience of the role of the multidisciplinary meeting in managing CTD-PAH., (© 2023 The Authors. Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)

Objectives: To report stage-specific patterns of treatment and the influence of management and treatment type on survival rates for people newly diagnosed with small cell lung cancer (SCLC)., Design: Cross-sectional patterns of care study; analysis of data prospectively collected for the Victorian Lung Cancer Registry (VLCR)., Setting, Participants: All people diagnosed with SCLC in Victoria during 1 April 2011 - 18 December 2019., Main Outcome Measures: Stage-specific management and treatment of people with SCLC; median survival time., Results: During 2011-19, 1006 people were diagnosed with SCLC (10.5% of all lung cancer diagnoses in Victoria); their median age was 69 years (interquartile range [IQR], 62-77 years), 429 were women (43%), and 921 were current or former smokers (92%). Clinical stage was defined for 896 people (89%; TNM stages I-III, 268 [30%]; TNM stage IV, 628 [70%]) and ECOG performance status at diagnosis for 663 (66%; 0 or 1, 489 [49%]; 2-4, 174 [17%]). The cases of 552 patients had been discussed at multidisciplinary meetings (55%), 377 people had received supportive care screening (37%), and 388 had been referred for palliative care (39%). Active treatment was received by 891 people (89%): chemotherapy, 843 (84%); radiotherapy, 460 (46%); chemotherapy and radiotherapy, 419 (42%); surgery, 23 (2%). Treatment had commenced within fourteen days of diagnosis for 632 of 875 patients (72%). Overall median survival time from diagnosis was 8.9 months (IQR, 4.2-16 months; stage I-III: 16.3 [IQR, 9.3-30] months; stage IV: 7.2 [IQR, 3.3-12] months). Multidisciplinary meeting presentation (hazard ratio [HR], 0.66; 95% CI, 0.58-0.77), multimodality treatment (HR, 0.42; 95% CI, 0.36-0.49), and chemotherapy within fourteen days of diagnosis (HR, 0.68; 95% CI, 0.48-0.94) were each associated with lower mortality during follow-up., Conclusion: Rates of supportive care screening, multidisciplinary meeting evaluation, and palliative care referral for people with SCLC could be improved. A national registry of SCLC-specific management and outcomes data could improve the quality and safety of care., (© 2023 The Authors. Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)

Background: Asthma epidemics associated with thunderstorms have had catastrophic effects on individuals and emergency services. Seasonal allergic rhinitis (SAR) is present in the vast majority of people who develop thunderstorm asthma (TA), but there is little evidence regarding risk factors for TA among the SAR population., Objective: We sought to identify risk factors for a history of TA and hospital presentation in a cohort of individuals with SAR., Methods: This multicenter study recruited adults from Melbourne, Australia, with a past diagnosis of TA and/or self-reported SAR. Clinical information, spirometry results, white blood cell count, ryegrass pollen-specific (RGP-sp) IgE concentration, and fractional exhaled nitric oxide were measured to identify risk factors for a history of TA in individuals with SAR., Results: From a total of 228 individuals with SAR, 35% (80 of 228) reported SAR only (the I-SAR group), 37% (84 of 228) reported TA symptoms but had not attended hospital for treatment (the O-TA group), and 28% (64 of 228) had presented to the hospital for TA (the H-TA group). All patients in the H-TA group reported a previous asthma diagnosis. Logistic regression analysis of factors associated with O-TA and H-TA indicated that lower FEV 1 value and an Asthma Control Questionnaire score higher than 1.5 were associated with H-TA. Higher blood RGP-sp IgE concentration, eosinophil counts, and fractional exhaled nitric oxide level were significantly associated with both O-TA and H-TA. Receiver operating curve analysis showed an RGP-sp IgE concentration higher than 10.1 kU/L and a prebronchodilator FEV 1 value of 90% or lower to be biomarkers of increased H-TA risk., Conclusion: Clinical tests can identify risk of a history of TA in individuals with SAR and thereby inform patient-specific treatment recommendations., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate short-term change in oxygenation and feasibility of physiotherapy-assisted prone or modified prone positioning in awake, ward-based patients with COVID-19., Design: Retrospective observational cohort study., Setting: General wards, single-centre tertiary hospital in Australia., Participants: Patients were included if ≥18 years, had COVID-19, required FiO 2  ≥ 0.28 or oxygen flow rate ≥4 l/minute and consented to positioning., Main Outcome Measures: Feasibility measures included barriers to therapy, assistance required, and comfort. Short-term change in oxygenation (SpO 2 ) and oxygen requirements before and 15 minutes after positioning., Results: Thirteen patients, mean age 75 (SD 14) years; median Clinical Frailty Scale score 6 (IQR 4 to 7) participated in 32 sessions of prone or modified prone positioning from a total of 125 ward-based patients admitted with COVID-19 who received physiotherapy intervention. Nine of thirteen patients (69%) required physiotherapy assistance and modified positions were utilised in 8/13 (62%). SpO2 increased in 27/32 sessions, with a mean increase from 90% (SD 5) pre-positioning to 94% (SD 4) (mean difference 4%; 95%CI 3 to 5%) after 15 minutes. Oxygen requirement decreased in 14/32 sessions, with a mean pre-positioning requirement of 8 l/minute (SD 4) to 7 l/minute (SD 4) (mean difference 2 l/minute; 95%CI 1 to 3 l/minute) after 15 minutes. In three sessions oxygen desaturation and discomfort occurred but resolved immediately by returning supine., Conclusion: Physiotherapy-assisted prone or modified prone positioning may be a feasible option leading to short-term improvements in oxygenation in awake, ward-based patients with hypoxemia due to COVID-19. Further research exploring longerterm health outcomes and safety is required., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)

Introduction: Multidisciplinary Meetings (MDM) are recommended in routine lung cancer care, however its broader impacts demand further evaluation. We assessed the drivers and impacts of MDM presentation in the Victorian Lung Cancer Registry (VLCR)., Methods: We examined the effect of MDM presentation on receipt of treatment and survival in VLCR patients diagnosed between 2011 and 2020. We compared patient characteristics, drivers of MDM discussion and survival between the two groups., Results: Of 9,628 patients, 5,900 (61.3%) were discussed at MDM, 3,728 (38.7%) were not. In the non-MDM group, a lower proportion received surgery (22.1% vs. 31.2%), radiotherapy (34.2% vs. 44.4%) and chemotherapy (44.7% vs. 49.0%). Patients were less likely to be discussed if ≥80 years (OR 0.73, p < 0.001), of ECOG performance status (PS) 4 (OR 0.23, p < 0.001), clinical stage IV (OR 0.34, p < 0.001) or referred from regional (OR 0.52, p < 0.001) or private hospital (OR 0.18, p < 0.001). MDM-presented patients had better median survival (1.70 vs 0.75 years, p < 0.001) and lower adjusted mortality risk (HR 0.75; 0.71-0.80, p < 0.001), a protective effect consistent across all hospital types. Undocumented PS, histopathology and clinical stage were associated with lower likelihood of MDM discussion and worse mortality., Conclusions: In the VLCR, being male, ≥80 years, of poorer PS, advanced clinical stage and poor clinical characterisation significantly disadvantaged patients in relation to MDM discussion. MDM-discussed patients were more likely to undergo treatment and had a 25% lower risk of mortality. This study supports the use of MDMs in lung cancer and identifies areas of inequity to be addressed., (Copyright © 2021. Published by Elsevier B.V.)

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 < 0.05)., 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., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

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 (<60 years: 2.0 years; 60-69 years: 1.5 years; 70-79 years: 1.6 years; ≥80 years: 1.0 years; p<0.001). Amongst those diagnosed with stage 1 or 2 lung cancer, there was no significant difference in adjusted-mortality between age groups. However, in those diagnosed with stage 3 or 4 disease, the eldest patients had an increased adjusted-mortality risk of 28% compared with patients younger than 60 years old (p=0.005), associated with markedly reduced probability of cancer treatment, after controlling for sex, performance status, comorbidities and histology type (OR 0.24, compared with <60 years old strata; p<0.001). Compared to younger patients, older patients with advanced-stage lung cancer have a disproportionately higher risk of mortality and lower likelihood of receiving cancer treatments, even when performance status and comorbidity are equivalent. These healthcare inequities could be indicative of widespread treatment nihilism towards elderly patients., Competing Interests: Conflict of interest: J. Pham has nothing to disclose. Conflict of interest: M. Conron has nothing to disclose. Conflict of interest: G. Wright has nothing to disclose. Conflict of interest: P. Mitchell has nothing to disclose. Conflict of interest: D. Ball reports lectures fees from AstraZeneca outside the submitted work. Conflict of interest: J. Philip has nothing to disclose. Conflict of interest: M. Brand has nothing to disclose. Conflict of interest: J. Zalcberg reports support for data collection from AstraZeneca, BMS, MSD and Abbvie outside the submitted work. Conflict of interest: R.G. Stirling has nothing to disclose., (Copyright ©The authors 2021.)

Background: Epidemic thunderstorm asthma (ETSA) severely affected Melbourne, Australia in November 2016. There is scant literature on the natural history of individuals affected by ETSA., Objective: A multicentre 12-month prospective observational study was conducted assessing symptomatology and behaviors of ETSA-affected individuals., Methods: We used a structured phone questionnaire to assess asthma symptom frequency, inhaled preventer use, asthma action plan ownership and healthcare utilization over 12 months since the ETSA. Analysis of results included subgroup analyses of the "current," "past," "probable," and "no asthma" subgroups defined according to their original 2016 survey responses., Results: Four hundred forty-two questionnaires were analyzed. Eighty percent of individuals reported ongoing asthma symptoms at follow-up, of which 28% were affected by asthma symptoms at least once a week. Risk of persistent asthma symptoms was significantly higher in those with prior asthma diagnosis, current asthma, and probable undiagnosed asthma (all p < 0.01). Of 442 respondents, 53% were prescribed inhaled preventers, of which 51% were adherent at least 5 days a week. Forty-two percent had a written asthma action plan and 16% had sought urgent medical attention for asthma in the preceding year., Conclusions: Following an episode of ETSA, patients experience a pivotal change in asthma trajectory with both loss of asthma control and persistence of de novo asthma. Suboptimal rates of inhaled preventer adherence and asthma action plan ownership may contribute to asthma exacerbation risk and susceptibility to future ETSA episodes. Longer-term follow-up is needed to determine the extent and severity of this apparent change., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (Copyright © 2019. Asia Pacific Association of Allergy, Asthma and Clinical Immunology.)

Background: Clinical audit may improve practice in cancer service provision. The UK National Lung Cancer Audit (NLCA) collects data for all new cases of thoracic cancers., Aim: To collect similar data for our Victorian patients from six hospitals within the Victorian Comprehensive Cancer Centre and associated Western and Central Melbourne Integrated Cancer Service., Methods: We conducted a retrospective audit of all newly diagnosed patients with lung cancer and mesothelioma in 2013 across the six Victorian Comprehensive Cancer Centre/Western and Central Melbourne Integrated Cancer Service hospitals. The objectives were to adapt the NLCA data set for use in the Australian context, to analyse the findings using descriptive statistics and to determine feasibility of implementing a routine, ongoing audit similar to that in the UK. Individual data items were adapted from the NLCA by an expert steering committee. Data were collated from the Victorian Cancer Registry, Victorian Admitted Episodes Dataset and individual hospital databases. Individual medical records were audited for missing data., Results: Eight hundred and forty-five patients were diagnosed across the sites in 2013. Most were aged 65-80 (55%) and were male (62%). Most had non-small-cell lung cancer (81%) with 9% diagnosed with small cell lung cancer and 2% with mesothelioma. Data completeness varied significantly between fields. For those with higher levels of completeness, headline indicators of clinical care were comparable with NLCA data. The Victorian population seem to lack access to specialist lung cancer nurse services., Conclusion: Lung cancer care at participating hospitals appeared to be comparable with the UK in 2013. In future, prospective data collection should be harmonised across sites and correlated with survival outcomes. One area of concern was a lack of documented access to specialist nursing services., (© 2018 Royal Australasian College of Physicians.)

Background: The world's most catastrophic and deadly thunderstorm asthma epidemic struck Melbourne, Australia, on November 21, 2016., Objective: Among thunderstorm-affected patients presenting to emergency rooms (ERs), we investigated risk factors predicting severe attacks requiring admission to hospital., Methods: Thunderstorm-affected patients were identified from ER records at the eight major Melbourne health services and interviewed by telephone. Risk factors for hospital admission were analyzed., Results: We interviewed 1435/2248 (64%) of thunderstorm-affected patients, of whom 164 (11.4%) required hospital admission. Overall, rhinitis was present in 87%, and current asthma was present in 28%. Odds for hospital admission were higher with increasing age (odds ratio 1.010, 95% CI 1.002, 1.019) and among individuals with current asthma (adjusted odds ratio [aOR] 1.87, 95% CI 1.26, 2.78). Prior hospitalization for asthma in the previous 12 months further increased the odds for hospital admission (aOR 3.16, 95% CI 1.63, 6.12). Among patients of Asian ethnicity, the odds for hospital admission were lower than for non-Asian patients (aOR 0.59, 95% CI 0.38, 0.94), but higher if born in Australia (OR = 5.42, 95% CI 1.56, 18.83)., Conclusions: In epidemic thunderstorm asthma patients who presented to the ER, higher odds for hospital admission among patients with known asthma were further amplified by recent asthma admission, highlighting the vulnerability conferred by suboptimal disease control. Odds for hospital admission were lower in Asian patients born overseas, but higher in Asian patients born locally, than in non-Asian patients; these observations suggest susceptibility to severe thunderstorm asthma may be enhanced by gene-environment interactions., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: The treatment of choice for early stage non-small cell lung cancer (NSCLC) is surgical resection. Little is known about the short- and long-term outcomes among very elderly patients. We sought to determine predictors of short- and long-term survival among octogenarians undergoing curative-intent resection for NSCLC in Victoria, Australia., Methods: We retrospectively reviewed data from all patients aged ≥80 years who underwent curative-intent resection for NSCLC over 12 years (January 2005-December 2016) across five tertiary centres. We examined effect of age, stage of disease, extent of surgery and lung function on short- and long-term survival., Results: Two hundred patients aged ≥80 years underwent curative-intent resections. Mortality at 30 and 120 days was 2.9% and 5.9%, respectively. Increased early mortality was observed among those ≥83 years, at 30 days (6.8% versus 0.8%, P = 0.044) and 120 days (12.2% versus 2.3%, P = 0.0096). Early mortality was highest among patients ≥83 years requiring lobectomy, compared to sub-lobar resection at 120 days (17% versus 3.8%, P = 0.019). Long-term survival was predicted by age and stage of disease. Among patients with Stage I disease aged <83 years, lobectomy was associated with superior 5-year survival, compared to sub-lobar resection (83% versus 61%, P = 0.02)., Conclusion: In carefully selected elderly patients undergoing curative-intent resection of early stage NSCLC, both short- and long-term outcomes appear consistent with younger historical cohorts. Early mortality was associated with lobectomy in those with advanced age. Older patients undergoing lobectomy appeared to be at highest risk for early mortality, while younger patients with Stage I disease undergoing at least lobectomy appear to have the best long-term survival., (© 2018 Royal Australasian College of Surgeons.)

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 < .001) cohorts. Detailed analysis of TNM stage sex differences revealed a consistent pattern of men having worse survival than women across stages in both cohorts., Conclusion: The poorer survival in men with NSCLC presents research and clinical communities with an important challenge. This study's findings suggest that for men and women diagnosed with NSCLC, and managed surgically, stage-specific outcomes should be quoted separately and consideration to a rapid prognostic score with sex combined with staging as a key element., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: A multidisciplinary collaboration investigated the world's largest, most catastrophic epidemic thunderstorm asthma event that took place in Melbourne, Australia, on Nov 21, 2016, to inform mechanisms and preventive strategies., Methods: Meteorological and airborne pollen data, satellite-derived vegetation index, ambulance callouts, emergency department presentations, and data on hospital admissions for Nov 21, 2016, as well as leading up to and following the event were collected between Nov 21, 2016, and March 31, 2017, and analysed. We contacted patients who presented during the epidemic thunderstorm asthma event at eight metropolitan health services (each including up to three hospitals) via telephone questionnaire to determine patient characteristics, and investigated outcomes of intensive care unit (ICU) admissions., Findings: Grass pollen concentrations on Nov 21, 2016, were extremely high (>100 grains/m 3 ). At 1800 AEDT, a gust front crossed Melbourne, plunging temperatures 10°C, raising humidity above 70%, and concentrating particulate matter. Within 30 h, there were 3365 (672%) excess respiratory-related presentations to emergency departments, and 476 (992%) excess asthma-related admissions to hospital, especially individuals of Indian or Sri Lankan birth (10% vs 1%, p<0·0001) and south-east Asian birth (8% vs 1%, p<0·0001) compared with previous 3 years. Questionnaire data from 1435 (64%) of 2248 emergency department presentations showed a mean age of 32·0 years (SD 18·6), 56% of whom were male. Only 28% had current doctor-diagnosed asthma. 39% of the presentations were of Asian or Indian ethnicity (25% of the Melbourne population were of this ethnicity according to the 2016 census, relative risk [RR] 1·93, 95% CI 1·74-2·15, p <0·0001). Of ten individuals who died, six were Asian or Indian (RR 4·54, 95% CI 1·28-16·09; p=0·01). 35 individuals were admitted to an intensive care unit, all had asthma, 12 took inhaled preventers, and five died., Interpretation: Convergent environmental factors triggered a thunderstorm asthma epidemic of unprecedented magnitude, tempo, and geographical range and severity on Nov 21, 2016, creating a new benchmark for emergency and health service escalation. Asian or Indian ethnicity and current doctor-diagnosed asthma portended life-threatening exacerbations such as those requiring admission to an ICU. Overall, the findings provide important public health lessons applicable to future event forecasting, health care response coordination, protection of at-risk populations, and medical management of epidemic thunderstorm asthma., Funding: None., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY NC ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Lung cancer has markedly poorer survival in men. Recognized important prognostic factors are divided into host, tumour and environmental factors. Traditional staging systems that use only tumour factors to predict prognosis are of limited accuracy. By examining sex-based patterns of disease-specific survival in non-small cell lung cancer patients, we determined the effect of sex on the prognostic value of additional host factors., Methods: Two cohorts of patients treated surgically with curative intent between 2000 and 2009 were utilized. The primary cohort was from Melbourne, Australia, with an independent validation set from the American Surveillance, Epidemiology and End Results (SEER) database. Univariate and multivariate analyses of validated host-related prognostic factors were performed in both cohorts to investigate the differences in survival between men and women., Results: The Melbourne cohort had 605 patients (61% men) and SEER cohort comprised 55 681 patients (51% men). Disease-specific 5-year survival showed men had statistically significant poorer survival in both cohorts (P < 0.001); Melbourne men at 53.2% compared with women at 68.3%, and SEER 53.3% men and 62.0% women were alive at 5 years. Being male was independently prognostic for disease-specific mortality in the Melbourne cohort after adjustment for ethnicity, smoking history, performance status, age, pathological stage and histology (hazard ratio = 1.54, 95% confidence interval: 1.10-2.16, P = 0.012)., Conclusions: Sex differences in non-small cell lung cancer are important irrespective of age, ethnicity, smoking, performance status and tumour, node and metastasis stage. Epidemiological findings such as these should be translated into research and clinical paradigms to determine the factors that influence the survival disadvantage experienced by men., (© 2016 Royal Australasian College of Surgeons.)

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., (Copyright © 2017 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) against EGFR mutant lung adenocarcinoma develops after a median of nine to thirteen months. Upregulation of the interleukin-6 (IL-6)/Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway may be a potential source of resistance to EGFR TKIs. We undertook a detailed assessment of the IL-6/JAK1/phosphorylated STAT3 (pSTAT3) pathway in resected lung adenocarcinoma specimens, with special interest in whether the presence of an EGFR mutation enriched for pSTAT3 positivity. Tumours from 143 patients with resected lung adenocarcinoma were assessed. EGFR and KRAS mutation status were scanned for with high-resolution melting and confirmed by polymerase chain reaction. Immunohistochemisty (IHC) was performed for IL-6, gp130, JAK1 and pSTAT3. Two methods for assigning IHC positivity were assessed (the presence of any positivity, and the presence of positivity at an H score >40). We found statistically significant associations between IL-6, JAK1 and pSTAT3 measured by IHC, consistent with the activation of the pathway in clinical specimens. No relationship was demonstrated between members of this pathway and oncogenic mutations in EGFR or KRAS. However, a proportion of tumours with EGFR mutations showed staining for IL-6, JAK1 and pSTAT3. No correlations with clinicopathologic features or survival outcomes were found for IL-6, JAK1 or pSTAT3 staining. The presence of EGFR or KRAS mutations did not enrich for the activation of IL-6, JAK1 or pSTAT3. pSTAT3 may still play a role in resistance to EGFR TKIs in clinical practice.

Introduction: Non-small-cell lung cancer outcomes are poor but heterogeneous, even within stage groups. To improve prognostic precision we aimed to develop and validate a simple prognostic model using patient and disease variables., Methods: Prospective registry and study data were analysed using Cox proportional hazards regression to derive a prognostic model (hospital 1, n=695), which was subsequently tested (Harrell's c-statistic for discrimination and Cox-Snell residuals for calibration) in two independent validation cohorts (hospital 2, n=479 and hospital 3, n=284)., Results: The derived Lung Cancer Prognostic Index (LCPI) included stage, histology, mutation status, performance status, weight loss, smoking history, respiratory comorbidity, sex, and age. Two-year overall survival rates according to LCPI in the derivation and two validation cohorts, respectively, were 84, 77, and 68% (LCPI 1: score⩽9); 61, 61, and 42% (LCPI 2: score 10-13); 33, 32, and 14% (LCPI 3: score 14-16); 7, 16, and 5% (LCPI 4: score ⩾15). Discrimination (c-statistic) was 0.74 for the derivation cohort, 0.72 and 0.71 for the two validation cohorts., Conclusions: The LCPI contributes additional prognostic information, which may be used to counsel patients, guide trial eligibility or design, or standardise mortality risk for epidemiological analyses.

Background: The association between socio-economic 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: A total of 2369 consecutive lung cancer patients managed by St Vincent's Hospital lung multidisciplinary meeting between 2001 and 2014 were included. Postcode data stratified participants by Socio-economic indexes for areas, a validated measure of SES, and by geographical location, an important socio-economic factor in Australia., Results: There was no difference between socio-economic groups in age (68 years), sex (63% males) or presentation (75% symptomatic). Low socio-economic 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 SES, 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 socio-economic 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 are reassuring, but suggest that there is a population of these patients with advanced lung cancer who are not referred for multidisciplinary care. Further studies are required to define this group better and determine the barriers to referral to improve overall lung cancer outcomes., (© 2017 Royal Australasian College of Physicians.)