To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The Second ESMO Consensus Conference on ...Lung Cancer was held on 11–12 May 2013 in Lugano. A total of 35 experts met to address several questions on management of patients with non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, early stage disease, locally advanced disease and advanced (metastatic) disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on recommendations for pathology and molecular biomarkers in relation to the diagnosis of lung cancer, primarily non-small-cell carcinomas.
Lung cancer screening using low-dose CT (LDCT) was shown to reduce lung cancer mortality by 20% in the National Lung Screening Trial.
The pilot UK Lung Cancer Screening (UKLS) is a randomised ...controlled trial of LDCT screening for lung cancer versus usual care. A population-based questionnaire was used to identify high-risk individuals. CT screen-detected nodules were managed by a pre-specified protocol. Cost effectiveness was modelled with reference to the National Lung Cancer Screening Trial mortality reduction.
247 354 individuals aged 50-75 years were approached; 30.7% expressed an interest, 8729 (11.5%) were eligible and 4055 were randomised, 2028 into the CT arm (1994 underwent a CT). Forty-two participants (2.1%) had confirmed lung cancer, 34 (1.7%) at baseline and 8 (0.4%) at the 12-month scan. 28/42 (66.7%) had stage I disease, 36/42 (85.7%) had stage I or II disease. 35/42 (83.3%) had surgical resection. 536 subjects had nodules greater than 50 mm(3) or 5 mm diameter and 41/536 were found to have lung cancer. One further cancer was detected by follow-up of nodules between 15 and 50 mm(3) at 12 months. The baseline estimate for the incremental cost-effectiveness ratio of once-only CT screening, under the UKLS protocol, was £8466 per quality adjusted life year gained (CI £5542 to £12 569).
The UKLS pilot trial demonstrated that it is possible to detect lung cancer at an early stage and deliver potentially curative treatment in over 80% of cases. Health economic analysis suggests that the intervention would be cost effective-this needs to be confirmed using data on observed lung cancer mortality reduction.
ISRCTN 78513845.
•This ESMO Clinical Practice Guideline provides key recommendations and algorithms for managing oncogene-addicted mNSCLC.•ESMO-MCBS scores are given to describe the levels of evidence for treatment ...choices.•ESCAT scores are given to describe the evidence level for genomic alterations as biomarkers for using targeted therapies.•Recommendations are based on available scientific data and the authors’ collective expert opinion.•In clinical practice, all recommendations provided need to be discussed with patients in a shared decision-making approach.
•This ESMO Clinical Practice Guideline provides key recommendations and algorithms for managing non-oncogene-addicted mNSCLC.•ESMO-MCBS scores are given to describe the levels of evidence for ...treatment choices.•ESCAT scores are given to describe the evidence level for genomic alterations as biomarkers for using targeted therapies.•Recommendations are based on available scientific data and the authors’ collective expert opinion.•In clinical practice, all recommendations provided need to be discussed with patients in a shared decision-making approach.
The evolution of personalised medicine in lung cancer has dramatically impacted diagnostic pathology. Current challenges centre on the growing demands placed on small tissue samples by molecular ...diagnostic techniques. In this review, expert recommendations are provided regarding successful identification of anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC). Steps to correctly process and conserve tumour tissue during diagnostic testing are essential to ensure tissue availability. For example, storing extra tissue sections ready for molecular diagnostic steps allows faster testing and preserves tissue. Fluorescence in situ hybridisation (FISH) is commonly used to detect ALK rearrangements, with most laboratories favouring screening by immunohistochemistry followed by a confirmatory FISH assay. Reverse transcription-polymerase chain reaction can also identify ALK fusion gene mRNA transcripts but can be limited by the quality of RNA and the risk that rare fusion variants may not be captured. Next-generation sequencing (NGS) technology has recently provided an alternative method for detecting ALK rearrangements. While current experience is limited, NGS is set to become the most efficient approach as an increasing number of genetic abnormalities is required to be tested. Upfront, reflex testing for ALK gene rearrangement should become routine as ALK tyrosine kinase inhibitor therapy moves into the first-line setting. Guidelines recommend that EGFR and ALK tests are carried out in parallel on all confirmed and potential adenocarcinomas, and this is more efficient in terms of tissue usage and testing turnaround time for both of these actionable gene alterations. The practice of sequential testing is not recommended. Identification of ALK rearrangements is now essential for the diagnosis of NSCLC, underpinned by the benefits of ALK inhibitors. As scientific understanding and diagnostic technology develops, ALK testing will continue to be an evolving and challenging paradigm.
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