Cars 2015 classification and staging of lung cancer 1.6
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CARS 2015 – 29th International Congress and Exhibition - Barcelona Wednesday, June 24, 2015 9:00–16:00
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Cars 2015 classification and staging of lung cancer 1.6
- 1. CLASSIFICATION AND STAGING OF LUNG CANCER
- 2. INDEX • Relevance • WHO classification of tumours of the lung • TNM • Lung carcinoma stages • Positron Emission Tomography (PET) • EBUS-TBNA / EUS-FNA • Novel approaches in lung cancer diagnostic, staging and treatment • Conclusions
- 3. Relevance • Most common cause of cancer death • Second most common cancer in men and women • 1,59 million deaths in 2012 • 158,040 deaths estimated in 2015 in USA • More individuals die from lung cancer than from colorectal, breast and prostate cancer combined
- 4. Relevance
- 5. WHO classification of tumours of the lung International Agency for Research on Cancer 4th Edition
- 6. Epithelial tumours • Adenocarcinoma • Squamous cell carcinoma • Small cell carcinoma • Large cell carcinoma • Adenosquamous carcinoma • Sarcomatoid carcinoma • Carcinoid tumour • Salivary gland tumours • Papillomas • Adenomas • Adenocarcinoma • Squamous cell carcinoma • Neuroendocrine tumours • Large cell carcinoma • Adenosquamous carcinoma • Pleomprphic carcinoma • Spindle cell carcinoma • Giant cell carcinoma • Carcinosarcoma • Pulmonary blastoma • Other and unclassified carcinoma • Salivary gland-type tumours • Papillomas • Adenomas 2004 2015 International Agency for Research on Cancer 4th Edition
- 7. Adenocarcinoma • Mixed subtype • Acinar • Papillary • Bronchioloalveolar • Solid • Lepidic • Acinar • Papillary • Micropapillary • Solid • Invasive • Colloid • Fetal • Enteric • Minimally invasive - MIA • Non-mucinous • Mucinous • Preinvasive lesions • Atypical adenomatous hyperplasia • Adenocarcinoma in situ • Non mucinous • Mucinous 2004 2015 International Agency for Research on Cancer 4th Edition
- 8. TNM Detterbeck et al. CHEST 2013; 143(5)(Suppl):e191S–e210S
- 9. Stage groups and subgroups according to TNM Detterbeck et al. CHEST 2013; 143(5)(Suppl):e191S–e210S
- 10. Lung carcinoma stages (I and II) Detterbeck et al. CHEST 2013; 143(5)(Suppl):e191S–e210S
- 11. Lung carcinoma stages (III) Detterbeck et al. CHEST 2013; 143(5)(Suppl):e191S–e210S
- 12. Lung carcinoma stages (IV) Detterbeck et al. CHEST 2013; 143(5)(Suppl):e191S–e210S
- 13. IASLC lymph node map Detterbeck et al. CHEST 2013; 143(5)(Suppl):e191S–e210S
- 14. J Thorac Oncol. 2014;9: 1618–1624
- 15. J Pathol 2014; 232: 121–133 PD-1-pathway blockers Immuno-regulatory antibodies for the treatment of cancer. Honeychurch et al. Expert Opin Biol Ther. 2015 Jun;15(6):787-801.
- 16. Diagnosing and Staging Lung Cancer Involving the Mediastinum Murgu et al. CHEST 2015; 147(5): 1401 - 1412
- 17. Positron Emission Tomography (PET) - Staging: T N M - Restaging - Treatment efficacy assessment - Radiotherapy planning
- 18. Positron Emission Tomography (PET) Andrea Gallamini et Al. Cancers 2014, 6, 1821-1889 - Changes the management in 20-30% of patients with NSCLC - T staging: accurate in up to 86% of patients - N staging: metabolic info, but sensitivity 45% - M staging: unsuspected distant M in 28% of patients. Impact on treatment in 53% - Limitations: low sensitivity for cerebral imaging and high rate of false positive results (infections, sarcoidosis etc.)
- 19. Positron Emission Tomography (PET) Andrea Gallamini et Al. Cancers 2014, 6, 1821-1889
- 20. EBUS-TBNA / EUS-FNA Murgu et al. CHEST 2015; 147(5): 1401 - 1412
- 21. EBUS-TBNA / EUS-FNA Murgu et al. CHEST 2015; 147(5): 1401 - 1412
- 22. NOVEL APPROACHES IN LUNG CANCER DIAGNOSTIC AND STAGING
- 23. Andreo et al. Arch Bronconeumol. 2015;51:e8–e11.
- 24. Izumo et al. Jpn J Clin Oncol 2014;44(10)
- 25. Fiz et al. BMC Medical Imaging 2014, 14:22
- 27. AJRCCM Articles in Press. June-2015 as 10.1164/rccm.201502-0205OC
- 28. Herth FJF, et al. Thorax 2015;70:326–332.
- 29. Eur Respir J 2013; 41: 1401–1408
- 30. NEJM, DOI: 10.1056/NEJMoa1504601 - AEGIS-1 and AEGIS-2 - Independent, prospective, multicenter, observational studies - Classifier + Bronchoscopy - sensitivity of 96% in AEGIS1 and 98% in AEGIS2
- 31. J Thorac Oncol. 2015;10: 237–249 Dual-energy CT - Diffusion-weighted MRI - Sodium (23Na) MRI - 3′-deoxy-3′-[18F]-fluorothymidine PET - Others… Dynamic contrast-enhanced CT
- 32. Mehta et al. CHEST 2014; 145(3):464–472 Artificial Intelligence in Medicine 60 (2014) 165–177
- 33. Omlor et al. Respiratory Research (2015) 16:64 Eur Respir J 2012; 40: 448–454 Nanotechnology in respiratory medicine A breath test for malignant mesothelioma using an electronic nose
- 34. Conclusions • Tobacco prevention remains the cornerstone in the battle against lung cancer • Lung Cancer is a complex disease and multidisciplinary approach is needed in order to obtain best results • Continuous modification and upgrading of the lung cancer classification American Journal of Respiratory and Critical Care Medicine, Vol. 191, No. 12 (2015), pp. 1471.
- 35. Conclusions • Importance of international meetings and consensuses in order to achieve maximum level of standardization • Implementation of new technologies for enhancing diagnostic, staging and treatment of lung cancer • A field of great advances, and more exciting results to come in future years
- 36. Thanks a lot!
Hinweis der Redaktion
- Lung cancer is one of the world´s leading health problems. It is Most common cause of cancer death in the whole world and second most common cancer in men and women. Only in 2012 it is estimated that there were 1,59 million deaths due to lung cancer, and this year almost 160,000 deaths are estimated in the USA. It is interesting that more individuals die from lung cancer than from colorectal, breast and prostate cancer combined. * Hao Zang. New PET/CT volumetric, http://www.lung.org/lung-disease/lung-cancer/resources/facts-figures/lung-cancer-fact-sheet.html American Lung Association. Lung cancer fact sheet
- These are some of the mayor international and national associations which have active role in the fight against this lethal disease.
- One of these organizations – The WHO has recently published the new classification of lung tumours. In comparison with the previous 2004 edition there are some changes. Due to molecular biology advances we are beginning to understand better the genetics of lung cancer. This new knowledge also gave us chance for new treatment approaches. Emerging treatments and its specific targets makes us to go further every time. Therefore the number of tumours is always growing. Four main groups are Epithelial tumours, Mesenchymal, Lymphohistiocytic and Tumours of ectopic origin.
- Probably the most important group – the epithelial tumours, has more detailed pathologic classification. You can see the difference between the WHO classification of 2004 and the recent one.
- As we can see classification of adenocarcinomas, one of the most diagnosed type of carcinomas, has also lived thru important change in the last decade. And various subtypes emerged.
- TNM classification of lung tumours.
- Tumor staging is essential for modern treatment strategy. It also is a very important prognostic tool, and also a tool for a tumor response assessment. Here we can see lung cancer stage groups and respective subgroups.
- Normal or pathologic mediastinum has great implication on lung cancer staging. It is one of the crucial steps as it in most of the cases makes the difference when the type of the treatment is decided. This is a lymph node map and we can see the great number of lymph nodules lies in the mediastinum.
- - The new IASLC database, the 8th edition, will be published in 2016. It has information on more than 90,000 new patients diagnosed of lung cancer between 1999 and 2010. - After exclusions almost 80,000 patients will be included in analyses.
- The figure on the left shows us an evolution of a genomic classification of lung cancer. A great number of mutations related to lung cancer is discovered. On the right we can see that many of them are being targeted for the therapeutic purposes. This is a field that is evolving daily with various clinical trials ongoing.
- On the previous slides we have seen the revised IASLC system, but in order to help clinicians in their routine practice the ACCP proposed 4 categories with respect to the radiographic characteristics of the primary tumor and the lymph nodes based on CT scan findings. Depending on the group, proceeding to invasive staging is recommended or not.
- The images we have seen on the previous slide are made with PET/CT. In recent years it has become a cornerstone for staging, restaging, treatment efficacy assessment and radiotherapy planning. In addition to conventional staging it changes the management in 20-30% of patients with NSCLC. It is used for T-staging although with some limitations. It is probably most useful in the evaluation of tumor spread to the pleura. Even so it gives an accurate T stage in up to 86% of patients.
- In addition to conventional staging it changes the management in 20-30% of patients with NSCLC. It is used for: T-staging although with some limitations. It is probably most useful in the evaluation of tumor spread to the pleura. Even so it gives an accurate T stage in up to 86% of patients. N staging. It adds metabolic information to otherwise morphologically undetectable nodal dissemination. But with sensitivity of only 45%, FN and FP reported, further EBUS-TBNA and EUS-FNA have been recommended after PET. M staging: detects unsuspected distant M in up to 28% of patients, changing the treatment plan in up to 53% of cases.
- PET-CT has shown promising results in Interim response during the treatment (for example between two Qt sessions) and also at Final Tumor Response after the treatment is done.
- Once the PET CT or CT mediastinal staging is realized, and high or intermediate suspicion of N2,3 involvement was detected, guidelines recommend use of invasive needle techniques such as EBUS and EUS. Preferably before the surgical approach. The utility of radial or lineal ultra sound probe for guiding the needle biopsy has already been proven, and it forms a part of a daily routine. It could be used for Staging, Diagnostics and recently treatment of lung cancer (ablation).
- Combining the existing techniques elevates the level of sensitivity.
- Endobronchial ultrasound elastography is a new technique for describing the stiffness of tissue during endobronchial ultrasound-guided transbronchial needle aspiration. It could help predict malignancy in lymph nodes and improve specimen recovery. This is a video from the first case report published in Spain.
- Another study that included larger number of samples, also showed high correlation between elastoraphy and pathological findings.
- Another approach to determinate malignancy of lymph nodes could be fractal dimension analysis. In this study the authors applied a previous processing method to improve the quality of the images and to enhance the details. This way they could distinguish malignant nodes from non-malignant.
- Virtual bronchoscopic navigation (VBN) is a method in which virtual bronchoscopic images of the bronchial path to a peripheral lesion are generated and used as a guide to navigate the bronchoscope. In this study which included 200 patients, the diagnostic yield for small peripheral pulmonary lesions was increased when VBN combined with EBUS.
- The diagnostic yield of the combined bronchoscopic approach with endobronchial ultrasound and navigation for peripheral pulmonary lesions is higher than each technique alone. This was a randomized trial: a 3mm ultrathin bronchoscope (UTB group) vs. 4mm thin bronchoscope with a guide sheath (TB GS group).
- Another novel technique for sampling solitary pulmonary nodules using a transparenchymal approach.
- Confocal laser endomicroscopy is a novel endoscopic technique that may allow imaging of living cells in lung tissue in vivo. Endomicroscopy allowed subsurface imaging with detailed analysis of cellular and subcellular structures. Neoplastic changes could be predicted with high accuracy (sensitivity 96.0%, specificity 87.1%, accuracy 91.0%).
- The combination of genomic classifier improves the diagnostic performance of bronchoscopy and it has a sensitivity of 96% in AEGIS-1 and 98% in AEGIS-2, independent of lesion size and location.
- In this review the authors talk about new imaging technologies. Both dual energy CT and Dynamic contrast-enhanced CT are systems based on contrast enhancement resulting with better image characteristic. Dual CT consists in applying 2 x-ray tubes in one CT system. Dynamic contrast-enhanced CT realizes consecutive CT scans that are acquired after the injection of contrast material. Other techniques are also mentioned such as: diffusion wighted MRI, Sodium 23 MRI and new PET technique.
- Various tools for management of pulmonary nodules have emerged. One of them is volumetric method. The addition of nodule volume to existing malignancy prediction models increases the proportion of nodules correctly classified. Also various automatic detection methods for lung nodules have emerged, which harness the possibilities of the latest software aplications.
- And finally some futuristic approaches, but very soon it could become mainstream in lung cancer diagnostic and treatment. The use of nanotechnology is in expansion and a variety of treatment possibilities is on its way. Also development of new biomarkers, or new sensors which are able to detect lung cancer molecular traces in exhaled air. Finally, the recent Googles patent, the wristband that could detect cancer and other diseases. A theme that also appeared in one of the Holiwood blockbusters.