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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., Competing Interests: Competing interests: CMR has consulted regarding oncology drug development with AbbVie, Amgen, AstraZeneca, Epizyme, Genentech/Roche, Ipsen, Jazz, Lilly, and Syros. He serves on the scientific advisory boards of Bridge Medicines, Earli, and Harpoon Therapeutics. HSP has received speaker and advisory board honoraria from Ipsen, Eisai, Pfizer, and Bristol Myers Squibb. MZ has received research support (to institution) from Bristol Myers Squibb and Exelixis. He has received advisory board honoraria from Aveo, Exelixis, Janssen, Pfizer, and EMD Serono. WLA is a data safety monitoring board member for Lilly. KJH has received research funding from AstraZeneca, Boehringer-Ingelheim, MSD, and Replimune. He serves on the scientific advisory boards of Arch Oncology, AstraZeneca, Bristol Myers Squibb, Boehringer-Ingelheim, Codiak BioSciences, Inzen Therapeutics, ISA Pharma, Merck-Serono, MSD, Pfizer, and Replimune. He serves on the speaker’s bureau for Bristol Myers Squibb, MSD, and Replimune. DD has received research support (to institution) from Ambrx Biopharma, Beigene, Bristol Myers Squibb, EpimAb, Harbour BioMed, Maxinovel, MSD, Olema Pharmaceuticals, Pfizer, PhamAbcine, Roche, and Haihe Biopharma. She serves on the scientific advisory board of MSD and has received travel support from Novartis. AGH has nothing to disclose. SJO has served on the scientific advisory boards of Biontech, Ultimovacs, Merck, ImaginAB, and Array. He was a consultant for Rad Immune, Bristol Myers Squibb, and Biontech; has served on the speaker’s board for Bristol Myers Squibb; and has received honoraria from Array, Ultimovacs, Merck, Rad Immune, ImaginAB, Biontech, and Bristol Myers Squibb. TDC has received honoraria from AstraZeneca, Merck USA, Novartis, Roche, and Specialized Therapeutics Australia; travel/accommodation support from Astellas; conference support from Novartis; and research support (to institution) from Daiichi Sankyo, Beigene, Janssen, Amgen, Exelixis, Merck, Immutep, and Clovis. He serves on the scientific advisory boards of AstraZeneca, Novartis, and Cipla. GMW has received speaker honoraria from AstraZeneca, Medtronic, Johnson & Johnson, and Device Technologies Australia and consulting fees (Expert Input Forum) from MSD. RRJ has nothing to disclose. DEG has received research funding from AstraZeneca, BerGenBio, and Karyopharm. He serves on the scientific advisory boards of Regeneron, Sanofi, Jansen, Mirati, and Catalyst and on the steering committee of Bristol Myers Squibb. He is a shareholder in Gilead. JER has received research funding (institutional) from Bayer, SeaGen, AstraZeneca, Roche/Genentech, Astellas, and QED Therapeutics. He has received consulting fees from IMVax, Century Tx, Aadi, Alligator, Hengrui, Bayer, SeaGen, AstraZeneca, Roche/Genentech, Astellas, QED Therapeutics, Bristol Myers Squibb, Merck, Pfizer, Pharmacyclics, Boehringer Ingelheim, GlaxoSmithKline, Infinity, Janssen, Mirati, EMD-Serono, Gilead, Lilly, Tyra Biosciences, and Pharmacyclics. He has received honoraria from EMD-Serono, Research to Practice, MJH LifeSciences, Medscape, Uptodate, Clinical Care Options, and OncLive. CR has received research funding (institutional) from Viralytics, Roche, Viralytics/Merck, and Eisai and has participated in a consulting/advisory role with Bristol Myers Squibb. She has received honoraria from Bristol Myers Squibb, Pfizer, Novartis, and Eisai and travel, accommodations, and expenses from Astellas Pharma, Roche, Janssen, GlaxoSmithKline, Bristol Myers Squibb, and Ipsen. DCC has nothing to disclose. BDC has received research funding from Viralytics, Galectin Therapeutics, Clinigen, AstraZeneca (research institution), and Bristol Myers Squibb (research institution). He has participated on the scientific advisory boards of Clinigen, Cullinan Oncology, and Nektar. He is a data safety monitoring board member for Merck USA. JRM has received research funding (institutional) from Sillagen, Vyriad, Replimune, Corvus Pharmaceuticals, Tizona, Trishula Therapeutics, Merck, Eisai, Genentech, Peloton Therapeutics, Seagen, Rubius Therapeutics, and BioNtech. He has participated on the scientific advisory board of Merck. YR is an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey, USA, and stockholder in Merck & Co., Inc., Rahway, New Jersey, USA. EVS is an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey, USA, and stockholder in Merck & Co. Inc., Rahway, New Jersey, USA. LG is a former contractor to Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey, USA, and stockholder in Merck & Co., Inc., Rahway, New Jersey, USA. SG has received honoraria from SITC advances in Cancer Immunotherapy as the Salt Lake City Program Organizer and presenter, travel support from QED Biopharmaceutical, as well as funding for other clinical trials from Bristol Myers Squibb, Rexahn, Incyte, Novartis, LSK, Five Prime, Mirati, QED, Debiopharm, Merck, Pfizer, AstraZeneca, MedImmune, Clovis, Immunocore, Elevar Therapeutics, and Seattle Genetics., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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: 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.)

Introduction/background: An individual patient data metaanalysis was performed to determine clinical outcomes, and to propose a risk stratification system, related to the comprehensive treatment of patients with oligometastatic NSCLC., Materials and Methods: After a systematic review of the literature, data were obtained on 757 NSCLC patients with 1 to 5 synchronous or metachronous metastases treated with surgical metastectomy, stereotactic radiotherapy/radiosurgery, or radical external-beam radiotherapy, and curative treatment of the primary lung cancer, from hospitals worldwide. Factors predictive of overall survival (OS) and progression-free survival were evaluated using Cox regression. Risk groups were defined using recursive partitioning analysis (RPA). Analyses were conducted on training and validating sets (two-thirds and one-third of patients, respectively)., Results: Median OS was 26 months, 1-year OS 70.2%, and 5-year OS 29.4%. Surgery was the most commonly used treatment for the primary tumor (635 patients [83.9%]) and metastases (339 patients [62.3%]). Factors predictive of OS were: synchronous versus metachronous metastases (P < .001), N-stage (P = .002), and adenocarcinoma histology (P = .036); the model remained predictive in the validation set (c-statistic = 0.682). In RPA, 3 risk groups were identified: low-risk, metachronous metastases (5-year OS, 47.8%); intermediate risk, synchronous metastases and N0 disease (5-year OS, 36.2%); and high risk, synchronous metastases and N1/N2 disease (5-year OS, 13.8%)., Conclusion: Significant OS differences were observed in oligometastatic patients stratified according to type of metastatic presentation, and N status. Long-term survival is common in selected patients with metachronous oligometastases. We propose this risk classification scheme be used in guiding selection of patients for clinical trials of ablative treatment., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Aim: A survey of management of lung cancer diagnosed in Victoria in 2003 was commissioned by the Victorian Cooperative Oncology Group to identify gaps in the management of this disease. Results from a similar survey in 1993 were available to identify differences in the disease, management and outcomes. This paper details results of the surgically managed subset within the larger study., Methods: All patients diagnosed with lung cancer in the first 6 months of 2003 were identified from the Victorian Cancer Registry. Registry research staff completed a detailed questionnaire using primary source documents from hospitals and consulting rooms. The survey data were then de-identified with respect to patient and treating clinician prior to statistical analysis by the investigators., Results: From eligible cases identified, non-small cell lung cancer was confirmed in 655 cases with a minimum of 6 years of follow-up. Thoracotomy was performed in 145 cases (22%), but only 130 received the intended resection. Compared with 1993, significant differences were increased use of preoperative positron emission tomography (PET) scanning (79% vs 0%), relatively fewer resections (20% vs 25%), lower pneumonectomy rate (14% vs 25%) and higher sub-lobar resection rate (22% vs 11%). The 30-day mortality remained below 2%. Positive resection margin (21%) and abandoned resection rates (10%) were much higher than expected. Overall 5-year survival was 42%, unchanged from 1993., Conclusion: Irrespective of widespread introduction of PET scanning, thoracotomy without resection was common. While operative mortality and overall survival were well within benchmark standards, futile thoracotomy and positive resection margin rates were unacceptably high., (© 2013 Wiley Publishing Asia Pty Ltd.)

Objectives: To identify areas to improve patient management in lung cancer, which remains the greatest cause of death from cancer in Australia., Design and Setting: Retrospective survey of all cases of lung cancer reported to the Victorian Cancer Registry from 1 January to 30 June 2003 and followed up for 5 years., Main Outcome Measures: Patient and disease characteristics, investigations, staging, treatment, cause of death, survival., Results: 841 patients were included. Smoking data were available for 799, of whom 63 (7.9%) had never smoked. Of 655 non-small cell lung cancer (NSCLC) cases, 198 (30.2%) were treated with curative intent, 125 (19.1%) by surgery and 73 (11.1%) by radiotherapy with or without chemotherapy. Only 7 (6.9%) of surgical patients with complete R0 resection had adjuvant chemotherapy. Of 101 small cell lung cancer (SCLC) cases, a third had limited stage disease which was mostly treated with curative intent by chemotherapy with or without radiotherapy. Patients whose cases were discussed at a multidisciplinary meeting (MDM) were significantly more likely to receive anticancer treatment and had longer survival; on multivariate analysis, MDM discussion was an independent prognostic factor. Compared with a similar survey 10 years earlier, the median age of patients diagnosed with lung cancer had increased by almost 3 years, the proportion of affected men decreased and adenocarcinoma was more frequent, while 10% of patients continued to have no pathologically confirmed diagnosis and 26% continued to receive no anticancer treatment. The number of patients with NSCLC who went on to a definitive surgical procedure fell with no detriment to survival, which likely reflected better staging with the introduction of positron emission tomography scanning., Conclusions: Opportunities to improve patient management included increasing the proportion with a pathologically confirmed diagnosis and greater use of postsurgical adjuvant chemotherapy. A high proportion of patients received no treatment, with underuse of chemotherapy and radiotherapy. Critically, the low rate of case discussions at MDMs needs to increase. However, effective strategies are required to identify cases early, as over two-thirds currently present with incurable disease.

Unlabelled: The identification of robust prognostic factors for patients with early-stage non-small cell lung cancer (NSCLC) is clinically important. The International Association for the Study of Lung Cancer has identified both sex and the maximum standardized uptake value (SUVmax) of (18)F-FDG in the primary tumor as measured by PET as potential prognostic variables. We examined the prognostic value of SUVmax in a surgical cohort of patients with NSCLC and disaggregated the findings by sex., Methods: Patients who had undergone a preoperative PET/CT scan and surgical resection with curative intent from 2001 to 2009 were identified from a prospective database. An SUVmax cutoff was calculated using receiver-operating-characteristic curves. Overall survival was correlated with SUVmax for the whole cohort and disaggregated by sex., Results: Inclusion criteria were met by 189 patients: 127 (67%) men and 62 (33%) women. Five-year survival was 54.6% for the whole cohort, 47.7% for men, and 68.2% for women. SUVmax correlated negatively with survival in a univariate analysis for the whole cohort (hazard ratio [HR], 2.51; 95% confidence interval [CI], 1.54-4.09; P < 0.001) and men (HR, 3.42; 95% CI, 1.94-6.05; P < 0.001) but not for women (HR, 1.61; 95% CI, 0.43-3.12; P = 0.77), using 8 as a cutoff. In multivariate analysis, SUVmax correlated with overall survival for the whole cohort (HR, 1.70; 95% CI, 1.05-2.99; P = 0.05) and men (HR, 2.40; 95% CI, 1.32-4.37; P = 0.004) but not for women (HR, 0.80; 95% CI, 0.15-4.47; P = 0.80)., Conclusion: SUVmax independently predicted overall survival for men but not for women in this surgical cohort. Our results suggest that SUVmax is an independent prognostic variable in men with surgically treated early NSCLC.

Introduction: Lung adenocarcinoma is a heterogeneous group of tumors with a highly variable prognosis, not well predicted by the current pathologic classification system. The 2004 World Health Organization classification results in virtually all tumors encountered in clinical practice being allocated to the adenocarcinoma of mixed subtype category. A new classification developed by an international multidisciplinary expert panel sponsored by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society, is based on histomorphologic subtype and has recently been validated in a North American series of 514 stage I lung adenocarcinomas. We investigated the relationship between the new classification and patient survival in a series of Australian patients with stages I, II, and III lung adenocarcinoma., Methods: We identified 210 patients from a surgical database who underwent resection of lung adenocarcinoma from 1996 to 2009. Two pathologists, blinded to patient outcome, independently performed histopathologic subtyping according to the new classification. Kaplan-Meier curves were used to calculate 5-year survival for each separate histopathologic subtype/variant. Univariate and multivariate analyses were undertaken to control for validated prognostic factors., Results: We confirmed that the new subtypes of adenocarcinoma in situ, minimally invasive adenocarcinoma and lepidic-predominant adenocarcinoma had a 5-year survival approaching 100%, whereas micropapillary-predominant and solid with mucin-predominant adenocarcinomas were associated with particularly poor survival. Papillary-predominant and acinar-predominant adenocarcinomas had an intermediate prognosis. This effect persisted after controlling for stage., Conclusions: Classification of lung adenocarcinoma according to the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification correlated with 5-year survival. These relationships persisted after controlling for known prognostic patient and tumor characteristics. The new classification has advantages not only for individual patient care but also for better selection and stratification for clinical trials and molecular studies.

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.

Background: Non-small-cell lung cancer is a leading cause of cancer morbidity and mortality in Australia. Brain metastases are common, and rapidly fatal if untreated. Optimal management consists of resection and whole brain irradiation. However, there is a paucity of local data documenting survival after such treatment., Methods: Medical records for all patients who underwent complete resection of non-small-cell lung cancer at one institution between January 1999 and December 2003 were reviewed in order to determine survival after initial surgery. The survival of all patients was compared with patients who underwent resection of synchronous or metachronous brain metastases and whole brain irradiation as part of their lung cancer management., Results: Between 1 January 1999 and 31 December 2003, 170 patients underwent complete resection of non-small-cell lung cancer by a thoracic surgeon. Resection of synchronous or metachronous brain metastases followed by whole brain irradiation was also carried out on 15 of these patients. Complete cerebral resection was achieved in 12 cases. The overall 5-year survival after attempted curative resection of brain metastases and successful complete resection was 60% and 70%, respectively. The survival of patients with both cerebral metastasectomy and lung cancer resection approximated that of the cohort of patients that only required complete resection of their lung cancer., Conclusions: Control of local disease at each site and long-term survival after lung resection and resection of either synchronous or metachronous brain METASTASIS and whole brain irradiation is readily achievable. We believe this should continue as the standard of care for this presentation.

F-18 fluorodeoxyglucose-positron emission tomography (PET) was investigated in patients with suspected residual disease or intrathoracic recurrence after pneumonectomy. Patients were identified from a prospective database. Impact of PET on staging and patient management was assessed. Clinical outcome was used to assess appropriateness of management. PET was performed in 17 cases, either post-operatively (n = 8), or later for suspected recurrence (n = 9) in patients with good performance status and without extensive disease on conventional imaging. PET changed treatment in 10 cases (59%). In five patients (29%), PET changed treatment intent (curative versus non-curative) from radical radiotherapy (RT) to palliative RT (n = 1), or observation or supportive care (n = 3), or from palliative to radical RT (n = 1). In a further patient with unexplained pain, PET appropriately showed no evidence of disease. In additional five cases (29%), PET influenced choice of RT dose and the use of concurrent chemotherapy (n = 3) or target volume (n = 2). Patients without tumour or with limited disease on PET had favourable outcomes whereas those with extensive disease suffered early tumour progression. PET was discordant with conventional assessment in >50% of cases. PET may be valuable after pneumonectomy if the patient is being considered for adjuvant or salvage radiotherapy although specificity may be reduced due to post-operative inflammatory changes.