Patterns of care for people with small cell lung cancer in Victoria, 2011-19: a retrospective, population-based registry data study.

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.

Multidisciplinary team discussion: the emerging gold standard for management of cardiopulmonary complications of connective tissue disease.

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.

Thunderstorm asthma in seasonal allergic rhinitis: The TAISAR study.

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 FEV1 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 FEV1 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.

The 2016 Melbourne thunderstorm asthma epidemic: Risk factors for severe attacks requiring hospital admission.

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.

The Victorian Comprehensive Cancer Centre lung cancer clinical audit: collecting the UK National Lung Cancer Audit data from hospitals in Australia.

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.

Lung cancer prognostic index: a risk score to predict overall survival after the diagnosis of non-small-cell lung cancer.

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.

Lung cancer and socio-economic status: inextricably linked to place of residence.

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.

Prevalence, morphology, and natural history of FGFR1-amplified lung cancer, including squamous cell carcinoma, detected by FISH and SISH.

The aim of this study was to investigate the prevalence of fibroblast growth factor receptor 1 (FGFR1) amplification by fluorescence in situ hybridization (FISH) in a lung cancer patient cohort and to correlate results with morphology, silver in situ hybridization (SISH), and patient outcome. FGFR1 FISH and SISH were performed in 406 and 385 lung cancer cases, respectively, and the results were compared. High-level FGFR1 amplification was defined as the ratio of FGFR1/centromere 8 ≥2, or tumor cell percentage with ≥15 signals ≥10%, or average number of signals/tumor cell nucleus ≥6. Low-level amplification was defined as tumor cell percentage with ≥5 signals ≥50%. Of 406 tumors tested, there were 191 squamous cell carcinomas, 28 carcinomas with focal squamous morphology, 24 large cell carcinomas with squamous immunoprofile, 115 adenocarcinomas, 17 neuroendocrine tumors, and 31 carcinomas without squamous morphology or immunoprofile. FGFR1 FISH was assessable in 368 tumors, with FGFR1 amplification identified in 50, including 48 tumors with either squamous morphology or immunoprofile (48 of 225, 21.3%), and two 'marker-null' tumors without squamous or glandular morphology or immunoprofile (2 of 143, 1.4%; P<0.0001). FGFR1 SISH was assessable in 347 tumors. All 46 FGFR1 FISH-amplified tumors with tumor available for testing showed amplification with SISH, while all other tumors were negative. There was no relationship between FGFR1 amplification status and disease-free (P=0.88, HR=1.04, 95% confidence interval (CI)=0.67-1.60) or overall survival (P=0.97, HR=1.01, 95% CI=0.65-1.58) in surgically radically treated patients with tumors with any squamous morphology or immunoprofile. FGFR1 amplification is a common abnormality in tumors with any squamous morphology or immunoprofile, but it is also present in 'marker-null' tumors. The results of FGFR1 SISH showed 1:1 correlation with the results of FGFR1 FISH, indicating that SISH may be an alternative method to detect FGFR1 amplification. No relationship was detected between patient outcome and FGFR1 amplification.

The prognostic significance of aldehyde dehydrogenase 1A1 (ALDH1A1) and CD133 expression in early stage non-small cell lung cancer.

BACKGROUND: Expression of aldehyde dehydrogenase 1A1 (ALDH1A1) and CD133 has been functionally associated with a stem cell phenotype in normal and malignant cells. The prevalence of such cells in solid tumours should therefore correlate with recurrence and/or metastasis following definitive surgical resection. The aim of this study was to evaluate the prognostic significance of ALDH1A1 and CD133 in surgically resected, early stage non-small cell lung cancer (NSCLC). METHODS: A retrospective analysis of ALDH1A1 and CD133 expression in 205 patients with pathologic stage I NSCLC was performed using immunohistochemistry. The association between the expression of both markers and survival was determined. RESULTS: We identified 62 relapses and 58 cancer-related deaths in 144 stage 1A and 61 stage 1B patients, analysed at a median of 5-years follow-up. Overexpression of ALDH1A1 and CD133, detected in 68.7% and 50.7% of primary tumours, respectively, was an independent prognostic indicator for overall survival by multivariable Cox proportional hazard model (p=0.017 and 0.039, respectively). Overexpression of ALDH1A1, but not of CD133, predicted poor recurrence-free survival (p=0.025). When categorised into three groups according to expression of ALDH1A1/CD133, patients with overexpression of both ALDH1A1 and CD133 belonged to the group with the shortest recurrence-free and overall survival (p=0.015 and 0.017, respectively). CONCLUSIONS: Expression of ALDH1A1 and CD133, and coexpression of ALDH1A1 and CD133, is strongly associated with poor survival in early-stage NSCLC following surgical resection. These data are consistent with the hypothesis that expression of stem cell markers correlates with recurrence as an indirect measure of self-renewal capacity.

Impacts of lung cancer multidisciplinary meeting presentation: Drivers and outcomes from a population registry retrospective cohort study.

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.

Physiotherapy-assisted prone or modified prone positioning in ward-based patients with COVID-19: a retrospective cohort study.

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 FiO2 ≥ 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 (SpO2) 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.

Integrated mutation, copy number and expression profiling in resectable non-small cell lung cancer.

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.

Genomic and Clinical Significance of Multiple Primary Lung Cancers as Determined by Next-Generation Sequencing.

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.

Excess mortality and undertreatment in elderly lung cancer patients: treatment nihilism in the modern era?

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.

Recurrent lung nodules as a presentation of ventricular septal defect-related endocarditis.

Infective endocarditis is an uncommon microbial infection of the endocardial surface of the heart. Patients with structural heart disease, such as a ventricular septal defect, are at higher risk for infective endocarditis and clinicians must have a high index of suspicion in such patients presenting with recurrent fevers. We present a patient with a known ventricular septal defect presenting with recurrent fevers associated with migratory lung nodules following a "low-risk" dental procedure without antibiotic prophylaxis. The unusual presentation delayed the diagnosis of the migratory lung lesions as septic pulmonary emboli and consequentially the diagnosis of ventricular septal defect related infective endocarditis. The patient made an uneventful recovery following antibiotic therapy and surgical intervention.

Continued loss of asthma control following epidemic thunderstorm asthma.

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.

Molecular profiling of non-small cell lung cancer: of what value in clinical practice?

Future improvements in lung cancer survival are likely to come from delineating its putative oncogenic pathways. The development of microarray technology to perform thousands of simultaneous genetic experiments and the linking of this to clinical information is an imperative for refining our current treatments and developing new ones. This paper reviews the state of this research, describes a typical microarray experiment and the implications for diagnosis and treatment of non-small cell lung cancer.

Outcomes following resection of non-small cell lung cancer in octogenarians.

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.

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.

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.