ERS/ESTS/ESTRO/ESR/ESTI/EFOMP statement on management of incidental findings from low dose CT screening for lung cancer.

BACKGROUND: Screening for lung cancer with low radiation dose computed tomography has a strong evidence base, is being introduced in several European countries and is recommended as a new targeted cancer screening programme. The imperative now is to ensure that implementation follows an evidence-based process that will ensure clinical and cost effectiveness. This European Respiratory Society (ERS) task force was formed to provide an expert consensus for the management of incidental findings which can be adapted and followed during implementation. METHODS: A multi-European society collaborative group was convened. 23 topics were identified, primarily from an ERS statement on lung cancer screening, and a systematic review of the literature was conducted according to ERS standards. Initial review of abstracts was completed and full text was provided to members of the group for each topic. Sections were edited and the final document approved by all members and the ERS Science Council. RESULTS: Nine topics considered most important and frequent were reviewed as standalone topics (interstitial lung abnormalities, emphysema, bronchiectasis, consolidation, coronary calcification, aortic valve disease, mediastinal mass, mediastinal lymph nodes and thyroid abnormalities). Other topics considered of lower importance or infrequent were grouped into generic categories, suitable for general statements. CONCLUSIONS: This European collaborative group has produced an incidental findings statement that can be followed during lung cancer screening. It will ensure that an evidence-based approach is used for reporting and managing incidental findings, which will mean that harms are minimised and any programme is as cost-effective as possible.

European Respiratory Society guideline on various aspects of quality in lung cancer care.

This European Respiratory Society guideline is dedicated to the provision of good quality recommendations in lung cancer care. All the clinical recommendations contained were based on a comprehensive systematic review and evidence syntheses based on eight PICO (Patients, Intervention, Comparison, Outcomes) questions. The evidence was appraised in compliance with the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Evidence profiles and the GRADE Evidence to Decision frameworks were used to summarise results and to make the decision-making process transparent. A multidisciplinary Task Force panel of lung cancer experts formulated and consented the clinical recommendations following thorough discussions of the systematic review results. In particular, we have made recommendations relating to the following quality improvement measures deemed applicable to routine lung cancer care: 1) avoidance of delay in the diagnostic and therapeutic period, 2) integration of multidisciplinary teams and multidisciplinary consultations, 3) implementation of and adherence to lung cancer guidelines, 4) benefit of higher institutional/individual volume and advanced specialisation in lung cancer surgery and other procedures, 5) need for pathological confirmation of lesions in patients with pulmonary lesions and suspected lung cancer, and histological subtyping and molecular characterisation for actionable targets or response to treatment of confirmed lung cancers, 6) added value of early integration of palliative care teams or specialists, 7) advantage of integrating specific quality improvement measures, and 8) benefit of using patient decision tools. These recommendations should be reconsidered and updated, as appropriate, as new evidence becomes available.

Variable radiological lung nodule evaluation leads to divergent management recommendations.

Radiological evaluation of incidentally detected lung nodules on computed tomography (CT) influences management. We assessed international radiological variation in 1) pulmonary nodule characterisation; 2) hypothetical guideline-derived management; and 3) radiologists' management recommendations.107 radiologists from 25 countries evaluated 69 CT-detected nodules, recording: 1) first-choice composition (solid, part-solid or ground-glass, with percentage confidence); 2) morphological features; 3) dimensions; 4) recommended management; and 5) decision-influencing factors. We modelled hypothetical management decisions on the 2005 and updated 2017 Fleischner Society, and both liberal and parsimonious interpretations of the British Thoracic Society 2015 guidelines.Overall agreement for first-choice nodule composition was good (Fleiss' κ=0.65), but poorest for part-solid nodules (weighted κ 0.62, interquartile range 0.50-0.71). Morphological variables, including spiculation (κ=0.35), showed poor-to-moderate agreement (κ=0.23-0.53). Variation in diameter was greatest at key thresholds (5 mm and 6 mm). Agreement for radiologists' recommendations was poor (κ=0.30); 21% disagreed with the majority. Although agreement within the four guideline-modelled management strategies was good (κ=0.63-0.73), 5-10% of radiologists would disagree with majority decisions if they applied guidelines strictly.Agreement was lowest for part-solid nodules, while significant measurement variation exists at important size thresholds. These variations resulted in generally good agreement for guideline-modelled management, but poor agreement for radiologists' actual recommendations.

ERS statement on harmonised standards for lung cancer registration and lung cancer services in Europe.

The European Respiratory Society (ERS) task force for harmonised standards for lung cancer registration and lung cancer services in Europe recognised the need to create a single dataset for use in pan-European data collection and a manual of standards for European lung cancer services.The multidisciplinary task force considered evidence from two different sources, reviewing existing national and international datasets alongside the results of a survey of clinical data collection on lung cancer in 35 European countries. A similar process was followed for the manual of lung cancer services, with the task force using existing guidelines and national or international recommendations for lung cancer services to develop a manual of standards for services in Europe.The task force developed essential and minimum datasets for lung cancer registration to enable all countries to collect the same essential data and some to collect data with greater detail. The task force also developed a manual specifying standards for lung cancer services in Europe.Despite the wide variation in the sociopolitical landscape across Europe, the ERS is determined to encourage the delivery of high-quality lung cancer care. Both the manual of lung cancer services and the minimum dataset for lung cancer registration will support this aspiration.

Adjuvant immunotherapy and targeted therapy in early and locally advanced resectable lung cancer: expanding treatment tentacles?

Adjuvant platinum-based chemotherapy has been the main treatment following surgical resection with curative intent in early and locally advanced nonsmall cell lung cancer (NSCLC) albeit with a 5% improvement in 5-year survival rates. Recent advances in biomarkers pave the way for targeted treatments and immunotherapy in a broader spectrum of patients with subsequently improved clinical outcomes. Targeted treatments and immunotherapy have established their place in the adjuvant setting of resected NSCLC.

Lung cancer: an update on the multidisciplinary approach from screening to palliative care.

This issue of Breathe aims to provide a succinct overview of the current state of play in various aspects in thoracic oncology https://bit.ly/3XQexmp.

The Role of Biomarkers in Lung Cancer Screening.

BACKGROUND: Lung Cancer Screening (LCS) is an evolving field with variations in its implementation in various countries. There are only scarce data from National LCS programs. AIM: We aim to provide an up-to-date overview of the current evidence regarding the use of biomarkers in LCS. MATERIALS AND METHODS: A multidisciplinary Task Force experts' panel collaborated and conducted a systematic literature search, followed by screening, review and synthesis of available evidence. RESULTS: Biomarkers in LCS could be used to improve risk stratification in high-risk participants, improve clarification regarding indeterminate lung nodules and avoid overdiagnosis in suspicious lung findings. Currently, there seem to be promising biomarkers (blood/serum/breath) that have been studied in various trials; however, there is still a lack of solid evidence in clinical validation that would pave the way for their integration into LCS programs. CONCLUSIONS: Biomarkers are the next logical step in improving the LCS pathway and its efficiency by playing an adjuvant role in a minimally invasive way. National LCS programs and pilot studies should integrate biomarkers to validate their accuracy in real-life LCS participants.

18F-FDG PET/CT anatomic and metabolic guidance in CT-guided lung biopsies.

PURPOSE: To evaluate the role of Fluorine-18 fluorodeoxyglucose (18F-FDG) PET/CT as a metabolic guide in increasing the accuracy, diagnostic yield and safety of CT-guided percutaneous needle lung biopsy (PNB). METHODS AND MATERIALS: Retrospective analysis of 340 consecutive patients with suspicious lung nodules, masses or extensive disease that underwent lung biopsy over a 3-year period. Patients were divided into three groups; those that had PET/CT prior to the biopsy, those that had PET-CT following the biopsy and those who did not undergo PET-CT. Correlation was made with the histopathological result. RESULTS: 353 PNBs were performed (median lesion size 30 mm, 7-120 mm) with overall diagnostic rate of 83.9 % (95.8 % malignant). Biopsy success rate was 88.8 % with PET-CT pre-PNB, versus 78.9 % of 175 PNB without PET-CT upfront (p < 0.01 Fisher exact test). Correct targeting to PET-CT-maximum activity area (MAA) was present in 87.1 %. Biopsy success rate was 88.8 % for PNBs targeting the PET-CT-MAA region and only 52.8 % for PNBs not targeting the PET-CT-MAA (p < 0.0001). PET-CT pre-PNB had higher rates of PET-CT-MAA targeting compared to PET-CT post PNB (91.0 % v 80.0 %, p = 0.01). The availability of PET-CT before the PNB lead to significantly increased biopsy success rates in patients with a mass (OR:7.01p = 0.004), compared to a nodule (p = 0.498) or multiple nodules (p = 0.163). Patients with a PET-CT pre-PNB underwent fewer PNB passes (mean 2.6 v 3.1, p < 0.0001 Mann Whitney U). Serious complications were less common in PET-CT pre-PNB group (4.5 % v 10.9 %, p < 0.05). Pre-PNB PET-CT performance improvement applied to all 3 radiologists and was greatest for masses and infiltrative abnormalities. CONCLUSION: Metabolic information provided by 18F-FDG PET/CT and PNB localisation to the PET-CT maximum activity region is associated with higher diagnostic biopsy rates especially in masses and appears to account for improved performance, less needle passes and complications when available pre-biopsy.

A scoping review of lung cancer surgery with curative intent: workup, fitness assessment, clinical outcomes.

Lung cancer surgery with curative intent has significantly developed over recent years, mainly focusing on minimally invasive approaches that do not compromise medical efficiency and ensure a decreased burden on the patient. It is directly linked with an efficient multidisciplinary team that will perform appropriate pre-operative assessment. Caution is required in complex patients with several comorbidities to ensure a meaningful and informed thoracic surgery referral leading to optimal patient outcomes.

Interventional bronchoscopy in lung cancer treatment.

Interventional bronchoscopy has seen significant advancements in recent decades, particularly in the context of lung cancer. This method has expanded not only diagnostic capabilities but also therapeutic options. In this article, we will outline various therapeutic approaches employed through either a rigid or flexible bronchoscope in multimodal lung cancer treatment. A pivotal focus lies in addressing central airway obstruction resulting from cancer. We will delve into the treatment of initial malignant changes in central airways and explore the rapidly evolving domain of early peripheral malignant lesions, increasingly discovered incidentally or through lung cancer screening programmes. A successful interventional bronchoscopic procedure not only alleviates severe symptoms but also enhances the patient's functional status, paving the way for subsequent multimodal treatments and thereby extending the possibilities for survival. Interventional bronchoscopy proves effective in treating initial cancerous changes in patients unsuitable for surgical or other aggressive treatments due to accompanying diseases. The key advantage of interventional bronchoscopy lies in its minimal invasiveness, effectiveness and favourable safety profile.

Stage I and II nonsmall cell lung cancer treatment options.

Chest radiography, computed tomography (CT) and positron emission tomography (PET)-CT are required for staging nonsmall cell lung cancers. Stage I cancers may be up to 4 cm in maximal diameter, with stage IA tumours being up to 3 cm and stage IB up to 4 cm. A lung cancer becomes stage II if the tumour is between 4 and ≤5 cm (stage IIA), or it spreads to ipsilateral peribronchial or hilar lymph nodes (stage IIB). Stage IA tumours should be surgically resected, ideally using minimally invasive methods. Lobectomy is usually performed, although some studies have shown good outcomes for sublobar resections. If surgery is not possible, stereotactic body radiotherapy is a good alternative. This involves delivering a few high-dose radiation treatments at very high precision. For stage IB to IIB disease, combinations of surgery, chemotherapy or immunotherapy and radiotherapy are used. There is evidence that neoadjuvant treatment (immunotherapy with nivolumab and chemotherapy for stage IB and II) optimises outcomes. Adjuvant chemotherapy with a platinum-based doublet (typically cisplatin+vinorelbine) should be offered for resected stage IIB tumours and considered for resected IIA tumours. Adjuvant pembrolizumab is used for stage IB-IIIA following resection and adjuvant platinum-based chemotherapy. Osimertinib may be used for resected stage IB to IIIA cancers which have relevant mutations (epidermal growth factor receptor exon 19 deletions or exon 21 (L858R) substitution). There are no fixed guidelines for follow-up, but most centres recommend 6-monthly CT scanning for the first 2-3 years after definitive treatment, followed by annual scans.

Lung cancer screening: where do we stand?

Lung cancer screening (LCS) programmes have emerged over recent years around the world. LCS programmes present differences in delivery, inclusion criteria and resource allocation. On a national scale, only a few LCS programmes have been fully established, but more are anticipated to follow. Evidence has shown that, in combination with a low-dose chest computed tomography scan, smoking cessation should be offered as part of a LCS programme for improved patient outcomes. Promising tools in LCS include further refined risk prediction models, the use of biomarkers, artificial intelligence and radiomics. However, these tools require further study and clinical validation is required prior to routine implementation.

New diagnostic and nonsurgical local treatment modalities for early stage lung cancer.

This paper highlights developments in diagnostic and nonsurgical local treatment modalities that have changed the management of early-stage lung cancer. These innovations aim to enhance diagnostic accuracy, minimize invasiveness, and improve patient outcomes. Liquid biopsies are emerging as promising tools for non-invasive diagnosis and monitoring, enabling earlier intervention without being standardized yet as well as not yet anchored in the guidelines. Endobronchial navigation has emerged as an innovative tool. By combining electromagnetic or GPS-like technology with 3D imaging and a steerable catheter, it enables accurate biopsy of small, peripheral lesions that were once challenging to sample, with a very low pneumothorax rate. Regarding nonsurgical treatments, stereotactic body radiotherapy (SBRT) continues to shine as a non-invasive local treatment modality for early-stage lung cancer and is the guideline-recommended standard-of-care for inoperable patients and patients refusing the risk of surgical resection. The low toxicity and excellent local control has made it an attractive alternative to surgery even in fitter patients. Percutaneous ablative techniques utilising energies such as microwave or pulse-field electroporation are options for patients who are not candidates for surgery or SBRT. Bronchoscopic ablation delivers the same energies but with a very lower pneumothorax rate and it is therefore also open to patients with multiple and bilateral lesions.

Unravelling the diagnostic pathology and molecular biomarkers in lung cancer.

The progress in lung cancer treatment is closely interlinked with the progress in diagnostic methods. There are four steps before commencing lung cancer treatment: estimation of the patient's performance status, assessment of disease stage (tumour, node, metastasis), recognition of histological subtype, and detection of biomarkers. The resection rate in lung cancer is <30% and >70% of patients need systemic therapy, which is individually adjusted. Accurate histological diagnosis is very important and it is the basis of further molecular diagnosis. In many cases only small biopsy samples are available and the rules for their assessment are defined in this review. The use of immunochemistry with at least thyroid transcription factor 1 (TTF1) and p40 is decisive in distinction between lung adenocarcinoma and squamous cell carcinoma. Molecular diagnosis and detection of known driver mutations is necessary for introducing targeted therapy and use of multiplex gene panel assays using next-generation sequencing is recommended. Immunotherapy with checkpoint inhibitors is the second promising method of systemic therapy with best results in tumours with high programmed death-ligand 1 (PD-L1) expression on cancer cells. Finally, the determination of a full tumour pattern will be possible using artificial intelligence in the near future.

How will lung cancer screening and lung nodule management change the diagnostic and surgical lung cancer landscape?

INTRODUCTION: Implementation of lung cancer screening, with its subsequent findings, is anticipated to change the current diagnostic and surgical lung cancer landscape. This review aimed to identify and present the most updated expert opinion and discuss relevant evidence regarding the impact of lung cancer screening and lung nodule management on the diagnostic and surgical landscape of lung cancer, as well as summarise points for clinical practice. METHODS: This article is based on relevant lectures and talks delivered during the European Society of Thoracic Surgeons-European Respiratory Society Collaborative Course on Thoracic Oncology (February 2023). Original lectures and talks and their relevant references were included. An additional literature search was conducted and peer-reviewed studies in English (December 2022 to June 2023) from the PubMed/Medline databases were evaluated with regards to immediate affinity of the published papers to the original talks presented at the course. An updated literature search was conducted (June 2023 to December 2023) to ensure that updated literature is included within this article. RESULTS: Lung cancer screening suspicious findings are expected to increase the number of diagnostic investigations required therefore impacting on current capacity and resources. Healthcare systems already face a shortage of imaging and diagnostic slots and they are also challenged by the shortage of interventional radiologists. Thoracic surgery will be impacted by the wider lung cancer screening implementation with increased volume and earlier stages of lung cancer. Nonsuspicious findings reported at lung cancer screening will need attention and subsequent referrals where required to ensure participants are appropriately diagnosed and managed and that they are not lost within healthcare systems. CONCLUSIONS: Implementation of lung cancer screening requires appropriate mapping of existing resources and infrastructure to ensure a tailored restructuring strategy to ensure that healthcare systems can meet the new needs.

ERS International Congress 2023: highlights from the Thoracic Oncology Assembly.

Lung cancer is the leading cause of cancer mortality in the world. It greatly affects the patients' quality of life, and is thus a challenge for the daily practice in respiratory medicine. Advances in the genetic knowledge of thoracic tumours' mutational landscape, and the development of targeted therapies and immune checkpoint inhibitors, have led to a paradigm shift in the treatment of lung cancer and pleural mesothelioma. During the 2023 European Respiratory Society Congress in Milan, Italy, experts from all over the world presented their high-quality research and reviewed best clinical practices. Lung cancer screening, management of early stages of lung cancer, application of artificial intelligence and biomarkers were discussed and they will be summarised here.

Stage III NSCLC treatment options: too many choices.

Stage III nonsmall cell lung cancer (NSCLC) represents a wide range of tumour (T1 to T4) and nodal (N0 to N3) components, requiring variable management and a multidisciplinary approach. Recent advancements in minimally invasive techniques, molecular biology and novel drug discoveries have accelerated the refinement of stage III NSCLC management. The latest developments in staging include the forthcoming update of the nodal component in the 9th TNM (tumour-node-metastasis) edition, which emphasises the critical role for endobronchial ultrasonography in mediastinal staging. Recent treatment developments include the use of immunotherapy and targeted molecular therapy in both the neoadjuvant and adjuvant setting, either in combination with other modalities or used alone as consolidation. Surgical and radiotherapy advancements have further enhanced patient outcomes. These developments have significantly improved the prognosis for patients with stage III NSCLC. Fast-changing recommendations have also brought about a challenge, with clinicians facing a number of options to choose from. Therefore, a multimodal approach by a multidisciplinary team has become even more crucial in managing stage III NSCLC.

The Naples Prognostic Score Is a Useful Tool to Assess Surgical Treatment in Non-Small Cell Lung Cancer.

Different prognostic scores have been applied to identify patients with non-small cell lung cancer who have a higher probability of poor outcomes. In this study, we evaluated whether the Naples Prognostic Score, a novel index that considers both inflammatory and nutritional values, was associated with long-term survival. This study presents a retrospective propensity score matching analysis of patients who underwent curative surgery for non-small cell lung cancer from January 2016 to December 2021. The score considered the following four pre-operative parameters: the neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, serum albumin, and total cholesterol. The Kaplan-Meier method and Cox regression analysis were performed to evaluate the relationship between the score and disease-free survival, overall survival, and cancer-related survival. A total of 260 patients were selected for the study, though this was reduced to 154 after propensity score matching. Post-propensity Kaplan-Meier analysis showed a significant correlation between the Naples Prognostic Score, overall survival (p = 0.018), and cancer-related survival (p = 0.007). Multivariate Cox regression analysis further validated the score as an independent prognostic indicator for both types of survival (p = 0.007 and p = 0.010, respectively). The Naples Prognostic Score proved to be an easily achievable prognostic factor of long-term survival in patients with non-small cell lung cancer after surgical treatment.

ERS International Congress 2022: highlights from the Thoracic Oncology Assembly.

Thoracic malignancies are associated with a substantial public health burden. Lung cancer is the leading cause of cancer-related mortality worldwide, with significant impact on patients' quality of life. Following 2 years of virtual European Respiratory Society (ERS) Congresses due to the COVID-19 pandemic, the 2022 hybrid ERS Congress in Barcelona, Spain allowed peers from all over the world to meet again and present their work. Thoracic oncology experts presented best practices and latest developments in lung cancer screening, lung cancer diagnosis and management. Early lung cancer diagnosis, subsequent pros and cons of aggressive management, identification and management of systemic treatments' side-effects, and the application of artificial intelligence and biomarkers across all aspects of the thoracic oncology pathway were among the areas that triggered specific interest and will be summarised here.