Personalized Lung Cancer Therapy Research Articles

Spatially Preserved Multi-Region Transcriptomic Subtyping and Biomarkers of Chemoimmunotherapy Outcome in Extensive-Stage Small Cell Lung Cancer.

Transcriptomic subtyping holds promise for personalized therapy in extensive-stage small cell lung cancer (ES-SCLC). In this study, we aimed to assess intratumoral transcriptomic subtype diversity and to identify biomarkers of long-term chemoimmunotherapy benefit in human ES-SCLC. We analyzed tumor samples from 58 patients with ES-SCLC enrolled in two multicenter single-arm phase IIIb studies evaluating frontline chemoimmunotherapy in Spain: n = 32 from the IMfirst trial and n = 26 from the CANTABRICO trial. We used the GeoMx Digital Spatial Profiler system to perform multi-region transcriptomic analysis. For subtype classification, we performed hierarchical clustering using the relative expression of ASCL1 (SCLC-A), NEUROD1 (SCLC-N), POU2F3 (SCLC-P), and YAP1 (SCLC-Y). Subtype distribution was found to be similar between bothcohorts, except for SCLC-P, which was not identified in the CANTABRICO_DSP cohort. A total of 44% of the patients in both cohorts had tumors with multiple coexisting transcriptional subtypes. Transcriptional subtypes or subtype heterogeneity was not associated with outcomes. Most potential targets did not show subtype-specific expression. Consistently in both cohorts, tumors from patients with long-term benefit (time to progression ≥12 months) contained an IFNγ-dominated mRNA profile, including enhanced capacity for antigen presentation. Hypoxia and glycolytic pathways were associated with resistance to chemoimmunotherapy. This work suggests that intratumoral heterogeneity, inconsistent association with outcome, and unclear subtype-specific target expression might be significant challenges for subtype-based precision oncology in SCLC. Preexisting IFNγ-driven immunity and mitochondrial metabolism seem to be correlates of long-term efficacy in this study, although the absence of a chemotherapy control arm precludes concluding that these are predictive features specific for immunotherapy.

Imaging Biomarkers of Tumour Proliferation and Invasion for Personalised Lung Cancer Therapy.

Personalised treatment in oncology has seen great developments over the last decade, due to both technological advances and more in-depth knowledge of radiobiological processes occurring in tumours. Lung cancer therapy is no exception, as new molecular targets have been identified to further increase treatment specificity and sensitivity. Yet, tumour resistance to treatment is still one of the main reasons for treatment failure. This is due to a number of factors, among which tumour proliferation, the presence of cancer stem cells and the metastatic potential of the primary tumour are key features that require better controlling to further improve cancer management in general, and lung cancer treatment in particular. Imaging biomarkers play a key role in the identification of biological particularities within tumours and therefore are an important component of treatment personalisation in radiotherapy. Imaging techniques such as PET, SPECT, MRI that employ tumour-specific biomarkers already play a critical role in patient stratification towards individualized treatment. The aim of the current paper is to describe the radiobiological challenges of lung cancer treatment in relation to the latest imaging biomarkers that can aid in the identification of hostile cellular features for further treatment adaptation and tailoring to the individual patient’s needs.

Abstract 4256: Multiplex fast FISH assay for detecting ROS1, RET and MET aberrations in FFPE specimens using BioView image analysis

Abstract Background: Biomarker testing in lung cancer is often limited by a lack of sufficient formalin fixed, paraffin embedded (FFPE) tissue for comprehensive genomic profiling. To promote personalized therapy for lung cancer, a multiplex FISH assay was developed to simultaneously assess aberrations in ROS1, RET, and MET on a single FFPE specimen slide. Methods: Specimens included primary tumor (N = 39) as well as biopsies from a variety of metastatic sites (N = 16). These included 12 samples with ROS1 rearrangements, 3 samples with RET rearrangements, and 11 samples with MET amplification reported by a previously validated laboratory test method. A probe mix contained 6 differentially labeled fluorescent probes: 3' ROS1, 5' ROS1, 3' RET, 5' RET, MET and CEP7. The probes were formulated in Vysis IntelliFISH Hybridization Buffer to allow for a 2 h hybridization time. BioView imaging platform and Duet software algorithm were used to perform automated slide scanning and digital analysis. Specimens were considered positive for ROS1 or RET rearrangement if >15% evaluated cells contained a break apart (rearranged) signal. Specimens were considered positive for MET amplification if >15% of cells had MET/CEP7 ratio >2 and positive for polysomy if >15% of cells had 5 or more MET signals copies. Results: The 6 color FISH assay was 97% concordant for ROS1 rearrangement and 100% concordant for RET rearrangement. The average background percentage of positive tumor cells in cases without known gene rearrangements was approximately 5%, yielding a negative cutoff threshold of approximately 15%, in accordance with cutoff thresholds reported in literature. The 6 color FISH assay was 91% concordant for MET amplification or polysomy. Results were interpretable for 98% of targets analyzed by the 6 color FISH method. Four samples failed on analysis for one of the targets due to lack of sufficient cells or lack of adequate hybridization signal. Conclusion: A newly developed 6-color FISH assay allows simultaneous detection of three genomic abnormalities using only 1 specimen slide. This feature combined with rapid hybridization in IntelliFISH buffer and automated BioView slide imaging and analysis can significantly increase the yield of molecular testing on limited lung cancer tissue samples. Careful pathologic correlation for tumor cell identification and careful assessment of hybridization quality are necessary to optimize the accuracy of this test method. Citation Format: Irina A. Sokolova, Patrick Bedroske, Tatyana A. Grushko, Amber R. Schneider, Kristine Jacobson, Jesse S. Voss, Yishay Tauber, Yossi Avisror, Vitaliy Shkolnik, Katerina Pestova, Katherine B. Geiersbach. Multiplex fast FISH assay for detecting ROS1, RET and MET aberrations in FFPE specimens using BioView image analysis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4256.

Umbrella study of anticancer agents in Chinese patients with NSCLC.

e20044 Background: As the rapidly increasing of potential anti-cancer agents, it has significantly improved clinical outcomes of non-small cell lung cancer (NSCLC). However, it has been challenged by the accurately characterize the genome changes which link to the response to specific targeted therapeutics. This umbrella study aimed to provide real-world data on the efficacy of targeted therapies by multiple gene sequencing in NSCLC of Chinese population and explore for the implementation of personalized lung cancer therapy in clinical practice. Methods: This study consists of five biomarker matched arms and one non-biomarker matched arm. Within biomarker matched arms, the different cohorts will test, 1) EGFR mutation for response to gefitinib, apatinib or osimertinib; 2) ALK fusion for response to crizotinib; 3) BRAF V600E mutation for response to trametinib; 4) MET amplification for response to CT053PTSA; 5) VEGFR mutation for response to apatinib or famitinib. Within the non-biomarker matched arm, cohort will test docetaxel or carboplatin. We will perform multiple gene testing on tumor tissue, pleural fluid, plasma and peripheral blood leucocyte of all patients. Results: A total of 336 patients were enrolled in this study, including 307 lung adenocarcinomas, 27 squamous cell carcinomas, and two adenosquamous carcinomas. Approximately 40% of patients carried at least one actionable mutation. The most frequently mutated genes were TP53 and EGFR, and the percentage of EGFR mutation subtypes 19Del, L858R and T790M were 25%, 19% and 16% respectively. In addition, the mutually exclusive mutations were significantly observed between EGFR and STK11 in TP53-mut patients. All patients will be allocated a corresponding arm according to their mutated genome profile and the clinical follow-up was still in progress. Conclusions: Multiple gene sequencing could be a useful selector for personalized lung cancer targeted therapy. Furthermore, mutation coexistence and mutual exclusion might be further predictors for the risk of drug resistant, recurrence at multivariate analyzes.

Case-Control Study on Lung Cancer and Residential Radon in South Korea

Background/Purpose: Radon exposure is a major risk factor of lung cancer. The World Health Organization (WHO) defines radon as the major cause of lung cancer following smoking, with 3-14% of lung cancer occurring worldwide. The WHO recommends radon concentration lower than 100 Bq/m3. In recent years, most of the advances in personalized therapy in Non Small Cell Lung Cancer (NSCLC) patients also occurred in non-smokers. The purpose of this study was to assess the effect of residential radon exposure on the risk of lung cancer in non-smokers and female in Korea.Method: This study was designed a multicenter hospital-based case and community-based control study in Korea. The seasonal correction was applied to the measured values of the radon concentration in both the case and control groups. Total 1053 (481 cases and 572 controls) were included in the data. 1:1 propensity score matching was performed considering age, sex, smoking status, involuntary smoking status, number of ventilation, impervious ratio, and type of house. Odds ratio for the risk of lung cancer according to the status of smoking and sex were performed using logistic regression and nonlinear regression analysis.Result: After seasonal correction, mean and standard deviation of radon concentration was 69.67±49.99 Bq/m3 in cases and 60.45±44.57 Bq/m3 in controls. 200 cases and 200 controls were matched and 51% were females. When we analyzed radon concentration as continuous, we observed an adjusted odds ratio of 1.92(95% CI : 1.13-3.25) in never-smokers and 1.19(95% CI : 0.68-2.09) in smokers. The adjusted odds ratio was 1.93(95% CI : 1.09-3.43) in females and 1.19(95% CI : 0.72-7.98) in males.Conclusion: Residential radon increases lung cancer risk among non-smoker and female. Therefore, intensive investigation of the relationship between lung cancer risk and smoking status or sex should be conducted to elucidate this results.

Prevalence of Epidermal Growth Factor Receptor Mutations in Patients with Non-Small Cell Lung Cancer in Turkish Population.

Aims:Epidermal growth factor receptor mutation analysis in non-small cell lung cancer is important for selecting patients who will receive treatment with tyrosine kinase inhibitors. In this study, we aimed to investigate the prevalence of epidermal growth factor receptor mutations and mutation patterns in the Turkish population.Methods:We retrospectively reviewed molecular pathology reports of 959 cases with lung cancer analysed for epidermal growth factor receptor mutations. We analysed all four epidermal growth factor receptor exon mutations using a real-time polymerase chain reaction platform.Results:In this study, the epidermal growth factor receptor mutation rate in the Turkish population was 16.7% (160 of 959). The epidermal growth factor receptor mutation frequency was significantly higher in women (37.1%, n=96) than in men (9.1%, n=64) (p<0.001). In addition, the epidermal growth factor receptor mutation rate was higher in the adenocarcinoma histologic type (p<0.001). Patients with mutations were older than those without mutations (p=0.003). The most frequent mutations were exon 19 deletions (48.8%, 78/160) and exon 21 L858R point mutations (38.1.1%, 61/160). We also detected compound mutation patterns in three cases (1.9%).Conclusion:The prevalence of epidermal growth factor receptor mutations in the Turkish population was slightly higher than that in the Caucasian population and lower than that in the East Asian population. The results of this study may provide guidance in personalized therapy of non-small cell lung cancer in the Turkish population.

Do we apply a personalised lung cancer therapy? Use of molecular tests in scheduling a multilineage treatment in a patient with lung adenocarcinoma

Molecularly targeted therapies, which can be used in genetically selected patients, play an increasing role in the multidisciplinary approach to the treatment of lung cancer. Treatment personalisation extends the scope of therapy, prolongs survival of patients and decreases the risk of life-threatening side effects. In this report, we present the diagnostic and therapeutic history of a 57-year-old male with lung adenocarcinoma and activating EGFR gene mutation. The whole therapeutic approach involved a diagnostic segmentectomy, cytoreductive surgery of the primary tumour, and a palliative hemipelvectomy of metastases in the right hip joint followed by adjuvant radiotherapy as well as six lines of systemic treatment based on standard cytostatics and novel personalised agents. Regardless of a patient’s good performance status and relatively good tolerance of the treatment, futile continuation of the therapy despite the lack of a longer stabilisation of the disease remains questionable.

Genomic profiling of non-small cell lung cancer: A pilot study from South India

&lt;p&gt;Introduction: Lung cancer accounts for the highest mortality globally, and there is a need to find new strategies and novel treatment options. Lung cancer is genetically heterogeneous across various ethnic populations, and therefore identifying the mutational landscape in Indian patients is important. Methods: The aim of the pilot study is to identify the prevalence and temporal sequence of molecular lesions in lung cancer patients from a regional cancer institute in South India using the circulating tumor DNA technique. Genotyping was performed on 26 newly diagnosed metastatic lung cancer patients using Illumina Omni Express Exome. Chip data were inspected using Genome Studio and subsequently exported for use with PLINK and further annotation was performed. Results: Seven genes including TP53 (61.5%), MUC16 (57.6%), KRAS (38.4%), STK11 (19.2%), Epidermal growth factor receptor (15.3%), ataxia telangiectasia mutated (15.3%), and nuclear factor-κβ (7.6%) demonstrated high incidence of mutations in patients. The other genes identified were observed in &amp;lt;5% of patients. Several types of mutations including missense, silent, nonsense, and frameshift mutations were observed in these genes. Conclusion: Integration of mutational profiling to identify gene mutations is required to facilitate personalized lung cancer therapy.&lt;/p&gt;

Detection of ALK fusion transcripts in FFPE lung cancer samples by NanoString technology

BackgroundALK-rearranged lung cancers exhibit specific pathologic and clinical features and are responsive to anti-ALK therapies. Therefore, the detection of ALK-rearrangement is fundamental for personalized lung cancer therapy. Recently, new molecular techniques, such as NanoString nCounter, have been developed to detect ALK fusions with more accuracy and sensitivity.MethodsIn the present study, we intended to validate a NanoString nCounter ALK-fusion panel in routine biopsies of FFPE lung cancer patients. A total of 43 samples were analyzed, 13 ALK-positive and 30 ALK-negative, as previously detected by FISH and/or immunohistochemistry.ResultsThe NanoString panel detected the presence of the EML4-ALK, KIF5B-ALK and TFG-ALK fusion variants. We observed that all the 13 ALK-positive cases exhibited genetic aberrations by the NanoString methodology. Namely, six cases (46.15%) presented EML-ALK variant 1, two (15.38%) presented EML-ALK variant 2, two (15.38%) presented EML-ALK variant 3a, and three (23.07%) exhibited no variant but presented unbalanced expression between 5’/3’ exons, similar to other positive samples. Importantly, for all these analyses, the initial input of RNA was 100 ng, and some cases displayed poor RNA quality measurements.ConclusionsIn this study, we reported the great utility of NanoString technology in the assessment of ALK fusions in routine lung biopsies of FFPE specimens.

Biomarker Testing for Personalized Therapy in Lung Cancer in Low- and Middle-Income Countries.

There have been many important advances in personalized therapy for patients with lung cancer, particularly for those with advanced disease. Molecular testing is crucial for implementation of personalized therapy. Although the United States and many Western countries have come far in the implementation of personalized therapy for lung cancer, there are substantial challenges for low- and middle-income countries (LMICs). Globally, the LMICs display great heterogeneity in the pattern of implementation of molecular testing and targeted therapy. The current review presents an attempt to identify the challenges and obstacles for the implementation of molecular testing and the use of targeted therapies in these areas. Lack of infrastructure, lack of technical expertise, economic factors, and lack of access to new drugs are among the substantial barriers.

Biomarker Testing for Personalized Therapy in Lung Cancer in Low- and Middle-Income Countries

There have been many important advances in personalized therapy for patients with lung cancer, particularly for those with advanced disease. Molecular testing is crucial for implementation of personalized therapy. Although the United States and many Western countries have come far in the implementation of personalized therapy for lung cancer, there are substantial challenges for low- and middle-income countries (LMICs). Globally, the LMICs display great heterogeneity in the pattern of implementation of molecular testing and targeted therapy. The current review presents an attempt to identify the challenges and obstacles for the implementation of molecular testing and the use of targeted therapies in these areas. Lack of infrastructure, lack of technical expertise, economic factors, and lack of access to new drugs are among the substantial barriers.

Epidermal growth factor receptor T790M testing in progressed lung cancer: A review of sensitive methods for analysis of tissue and liquid biopsy samples.

Lung cancer is one of the major causes of mortality worldwide and is on the rise in India. The identification of epidermal growth factor receptor (EGFR) mutations in nonsmall cell lung cancer (NSCLC) has paved the way for personalized therapy in lung cancer with EGFR-tyrosine kinase inhibitors (TKIs). Despite the proven efficacy of EGFR-TKIs in patients harboring EGFR mutations, their clinical utility is limited by the development of acquired resistance mechanisms by the tumor cells. T790M mutation accounts for 60% of all resistance mechanisms to EGFR TKIs and is responsible for treatment failure with first- and second-generation TKIs. With the development of novel therapeutic agents such as osimertinib to overcome this resistance mechanism, it is essential to detect patients harboring T790M mutation. There are several limitations with the use of tissue biopsy specimens for molecular testing such as poor quality and quantity of sample, tumor heterogeneity, occurrence of complications, and issues with repeat biopsy. Liquid biopsy offers a noninvasive approach that can be used for diagnostic purposes as well as for monitoring treatment response and evaluation of resistance mechanisms. This review focuses on the methods for molecular testing of tissue and liquid biopsy specimens for EGFR mutations, particularly EGFR T790M mutation.

Twenty Years of the Pulmonary Pathology Society.

The year 2015 marked the 20-year anniversary of the Pulmonary Pathology Society (PPS). It was founded in 1995, under the leadership of William Travis, MD (USA), with Thomas Colby, MD (USA); Samuel Hammar, MD (USA); Bruce Mackay, MD (USA); Helmut Popper, MD (Austria); and Osamu Matsubara, MD, PhD (Japan), among others. The PPS elected Dr Thomas Colby as its first president. Today, the PPS is an international society with 300 members from more than 25 countries. The PPS is a partner society with the College of American Pathologists (CAP) and the 2 organizations have cosponsored a number of educational activities and courses together at the CAP annual meeting and elsewhere for the past decade. The PPS has held an annual companion meeting at the United States and Canadian Academy of Pathology meeting each year since 1996 and a stand-alone meeting every 2 years. The 2015 PPS Biennial Meeting was cosponsored by the CAP and was held in San Francisco in June. Hosted by now past-president Kevin O. Leslie, MD, the 3-day meeting was likened by one colleague as ‘‘science fiction coming true.’’ The lecture lineup, carefully selected by an all-star Program Committee chaired by Philip T. Cagle, MD, a former president of the PPS, provided hot-off-the-press insight into one pulmonary pathology topic after another. It is from those presentations that most of the articles included in Part I of this ARCHIVES Special Section arise. As president of the PPS, it is a privilege and a pleasure to present this Special Section. Erik Thunnissen, MD, PhD, and colleagues provide a sophisticated discussion of how we can reduce medical error by identifying ex vivo artifacts in lung specimens; Maxwell Smith, MD, updates our understanding of interstitial lung disease; and Anja Roden, MD, and Eunhee Yi, MD, expand our understanding of pulmonary Langerhans cell histiocytosis. Further, Aliya Husain, MD, and Edward Garrity, MD, discuss airway changes in patients with lung transplants; Eric Bernicker, MD, describes how a team of clinicians, basic scientists, and pathologists can work together to make true personalized lung cancer therapy a reality; and Keith Kerr, BSc, MB, ChB, FRCPath, FRCPE, and Marianne Nicolson, MD, FRCP, provide a fascinating examination of PD-L1 as the ‘‘third dimension’’ of lung cancer therapy. We had a number of abstracts presented at the meeting that are included in this Special Section as well. Part II will continue the discussion of lung pathology from other PPS members. Many thanks to these pulmonary pathologists for sharpening the cutting edge of pulmonary pathology diagnosis and therapy.

Epigenetics in Personalized Management of Lung Cancer.

In last several years, the focus on the origin and progression of human cancers has shifted from genetic to epigenetic regulation, with particular attention to methylation and acetylation events that have profound effect on the eventual expression of oncogenes and the suppression of tumor suppressors. A few drugs targeting these epigenetic changes have already been approved for treatment, albeit not for lung cancer. With the recent advances in the push towards personalized therapy, questions have been asked about the possible targeting of epigenetic events for personalized lung cancer therapy. Some progress has been made but a lot needs to be done. In this chapter, a succinct review of these topics is provided.

Frequency of EGFR mutations in non-small cell lung cancer patients: screening data from West Siberia.

Incorporation of molecular analysis of the epidermal growth factor receptor (EGFR) gene into routine clinical practice has shown great promise to provide personalized therapy of the non-small cell lung cancer (NSCLC) in the developed world. However, the genetic testing of EGFR mutations has not yet become routine clinical practice in territories remote from the central regions of Russia. Therefore, we aimed to study the frequency of major types of activating mutations of the EGFR gene in NSCLC patients residing in West Siberia. We examined EGFR mutations in exons 19 and 21 in 147 NSCLC patients (excluding squamous cell lung carcinomas) by real time polymerase chain reaction. EGFR mutations were detected in 28 of the 147 (19%) patients. There were 19 (13%) cases with mutations in exon 19 and 9 cases (6%) in exon 21. Mutations were more frequently observed in women (42%, p=0.000) than in men (1%). A significantly higher incidence of EGFR mutations was observed in bronchioloalveolar carcinomas (28%, p=0.019) and in adenocarcinomas (21%, p=0.024) than in large cell carcinomas, mixed adenocarcinomas, and NOS (4%). The EGFR mutation rate was much higher in never-smokers than in smokers: 38% vs. 3% (p=0.000). The frequency of EGFR mutations in the Kemerovo and Tomsk regions was 19%. The incorporation of molecular analysis of the EGFR gene into routine clinical practice will allow clinicians to provide personalised therapy, resulting in a significant increase in survival rates and improvement in life quality of advanced NSCLC patients.

Beyond ALK-RET, ROS1 and other oncogene fusions in lung cancer.

Fusions of the RET and ROS1 protein tyrosine kinase oncogenes with several partner genes were recently identified as new targetable genetic aberrations in cases of non-small cell lung cancer (NSCLC) lacking activating EGFR, KRAS, ALK, BRAF, or HER2 oncogene aberrations. RET and ROS1 fusion-positive tumors are mainly observed in young, female, and/or never smoking patients. Studies based on in vitro and in vivo (i.e., mouse) models and studies of several fusion-positive patients indicate that inhibiting the kinase activity of the RET and ROS1 fusion proteins is a promising therapeutic strategy. Accordingly, there are several ongoing clinical trials aimed at examining the efficacy of tyrosine kinase inhibitors (TKIs) against RET and ROS1 proteins in patients with fusion-positive lung cancer. Other gene fusions (NTRK1, NRG1, and FGFR1/2/3) that are targetable by existing TKIs have also been identified in NSCLCs. Options for personalized lung cancer therapy will be increased with the help of multiplex diagnosis systems able to detect multiple druggable gene fusions.

Special issue on personalized therapy in lung cancer.

Targeted therapy and immunotherapy are so inspiring when updates in personalized medicine in lung cancer come into mind. We hope the hot topics listed in this issue of Translational Lung Cancer Research ( TLCR ) journal will be quite encouraging and appealing to you.

Barriers to implementation

2,3 Biomarker-directed therapy may significantly improve treatment outcomes, including response, quality of life and progression-free survival, 1 and in some cases may even improve overall survival. Canadian consensus guidelines on biomarker testing in lung cancer have been published, 4 and multiple personalized treatment options in advanced lung cancer, based on biomarker testing, are now funded in provinces across Canada. But most patients are still not getting the molecular pathology testing that would permit them to receive personalized lung cancer therapy. Several barriers continue to hinder the application of this knowledge, including lack of integration of biomarker testing into routine pathology practice, lack of knowledge dissemination to involved specialties (beyond medical oncology and academic pathology), absence of specific or sufficient funding for biomarker testing, and insufficient tumour samples for testing. All of these culminate in Canada’s current failure to routinely offer the “right drug to the right person at the right time” in lung cancer. Recent studies in patients with metastatic non-small cell lung cancer (NSCLC) have demonstrated that response to systemic treatment depends on pathologic subtype and the presence of specific alterations within the NSCLC genome. 5 It is of pressing clinical importance to determine the histopathologic and molecular features of NSCLC tumours in order to guide appropriate treatment options for patients. 6

Combining COPD with clinical, pathological and demographic information refines prognosis and treatment response prediction of non-small cell lung cancer.

BackgroundAccurate assessment of a patient’s risk of recurrence and treatment response is an important prerequisite of personalized therapy in lung cancer. This study extends a previously described non-small cell lung cancer prognostic model by the addition of chemotherapy and co-morbidities through the use of linked SEER-Medicare data.Methodology/Principal FindingsData on 34,203 lung adenocarcinoma and 26,967 squamous cell lung carcinoma patients were used to determine the contribution of Chronic Obstructive Pulmonary Disease (COPD) to prognostication in 30 treatment combinations. A Cox model including COPD was estimated on 1,000 bootstrap samples, with the resulting model assessed on ROC, Brier Score, Harrell’s C, and Nagelkerke’s R2 metrics in order to evaluate improvements in prognostication over a model without COPD. The addition of COPD to the model incorporating cancer stage, age, gender, race, and tumor grade was shown to improve prognostication in multiple patient groups. For lung adenocarcinoma patients, there was an improvement on the prognostication in the overall patient population and in patients without receiving chemotherapy, including those receiving surgery only. For squamous cell carcinoma, an improvement on prognostication was seen in both the overall patient population and in patients receiving multiple types of chemotherapy. COPD condition was able to stratify patients receiving the same treatments into significantly (log-rank p<0.05) different prognostic groups, independent of cancer stage.Conclusion/SignificanceCombining patient information on COPD, cancer stage, age, gender, race, and tumor grade could improve prognostication and prediction of treatment response in individual non-small cell lung cancer patients. This model enables refined prognosis and estimation of clinical outcome of comprehensive treatment regimens, providing a useful tool for personalized clinical decision-making.

Year in review 2013: Lung cancer, respiratory infections, tuberculosis, cystic fibrosis, pleural diseases, bronchoscopic intervention and imaging

This Year in Review examines the most relevant articles published on lung cancer, respiratory infections, tuberculosis (TB), cystic fibrosis (CF), pleural diseases, and interventional pulmonology and imaging in Respirology and other respiratory medicine journals during 2013. Important findings are highlighted with comments in the following sections, each of which was contributed by an author as named in the beginning of each section.