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W. Tan
Moderator of
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E07 - Staging in the Molecular Era (ID 7)
- Event: WCLC 2013
- Type: Educational Session
- Track: Imaging, Staging & Screening
- Presentations: 4
- Moderators:R. Bowman, W. Tan
- Coordinates: 10/29/2013, 14:00 - 15:30, Bayside 204 A+B, Level 2
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E07.1 - TNM Classification with Image Guided Interventions Such as EBUS / EUS (ID 403)
14:05 - 14:25 | Author(s): F.J. Herth
- Abstract
Abstract
ENDOBRONCHIAL ULTRASOUND The integration of ultrasound technology and flexible fiberbronchoscopy enables imaging of lymph nodes, lesions and vessels located beyond the tracheobronchial mucosa. Developed in 2002, the EBUS-bronchoscope looks similar to a normal bronchovideoscope, but is 6.9mm wide and has a 2mm instrument channel and a 30 degree side viewing optic. Furthermore, a curved linear array ultrasonic transducer sits on the distal end and can be used either with direct contact to the mucosal surface or via an inflatable balloon which can be attached at the tip. This allows a conventional endoscopic picture side-by-side with the ultrasonic view. US scanning is performed at a frequency of 7.5-12 MHz with tissue penetration of 20 – 50mm. An ultrasound processor processes the US image. Procedure: The actual TBNA is performed by direct transducer contact with the wall of the trachea or bronchus. When a lesion is outlined, a needle of 21 gauge (NA-201SX-4022; Olympus Corporation, Tokyo, Japan) can be advanced through the working channel and lymph nodes can be punctured under real-time ultrasound visualisation. At the same time colour Doppler can be used to identify surrounding vascular structures. Once the target lymph node or mass has been clearly identified with EBUS, the needle is inserted under real-time US guidance. Suction is applied with a syringe, and the needle is moved back and forth inside the lesion. Lymph node stations that can be reached via EBUS are the highest mediastinal (station 1), the upper paratracheal (2L and 2R), lower paratracheal (4R and 4L), the subcarinal (station 7), the hilar (station 10) as well as the interlobar (station 11) and the lobar nodes (station 12). The highest staging N should be biopsied first otherwise the needle needs to be changed each time. Results: In recently published meta-analysis EBUS-TBNA has been shown to have a high-pooled sensitivity of 93% and specificity of 100% . Multiple publications have shown that even in patients with lymph nodes under 1cm (which had been termed N0 by CT criteria), with the use of EBUS-TBNA a large percentage could still be shown to have N2/N3 disease (some despite also being negative on PET-CT). Complications such as bleeding or infection are very rare and have only been reported as case reports. Endoesophageal ultrasound Gastroenterologists have been using this technique for many years in the investigation of oesophageal and pancreatic malignancies. Mediastinal EUS-FNAs were first used in the early 1990s and have subsequently become a popular method to diagnose a variety of intra-abdominal and intrathoracic masses, including mediastinal lesion. Procedure The linear EUS-Scope (has the same basic architecture as the EBUS and uses a scanner of between 5 and 10 MHz. The penetrating ultrasound depth can be up to 8cm. Needles used for biopsy are 19 or 21gauge, again equipped with a stylet. The procedure is usually performed on an outpatient basis and takes approx 30min. However, EUS-FNA has limited access as only lymph node stations 2L, 4L, 7, 8 and 9 are accessible through a transesophageal approach. Lymph node station 5 is not routinely accessible via EUS, and may require transvascular FNA.. Results. EUS is especially useful in staging of the posterior mediastinum. Multiple publications and a meta-analysis on EUS-FNA have shown a high sensitivity and specificity. Even in patients without mediastinal lymph node enlargement on CT, EUS-FNA has been able to demonstrate metastases in 25% of lung cancer patients. Also, the left adrenal can be reached and identified in 97% of cases. It has a so-called ‘seagull’ shape on ultrasound and is particularly well visualised in cases of metastatic enlargement. Furthermore, the left lobe of liver can also be reached. The hilar and pre-carinal lymph nodes cannot be reached. EUS is also more accurate and has a higher predictive value than either PET scan or CT for posterior mediastinal lymph nodes. The procedure carries only a very small risk of mediastinitis or bleeding. . For both techniques it´s important to remember, however, that with EBUS and EUS the negative predictive value is limited and therefore samples which do not contain tumour cells require follow up with a more definitive procedure such as mediastinoscopy or VATS. Combining EBUS and EUS For tissue sampling of mediastinal lymph nodes after conventional TBNA, the present authors prefer minimally invasive methods such as EBUS-TBNA and EUS-FNA to more invasive procedures such as mediastinoscopy and VATS. EUS-FNA and EBUS-TBNA have been shown to prevent mediastinoscopies to a large extent. EBUS-TBNA and EUS-FNA have a complementary reach in analysing mediastinal nodes whereby EBUS has access to the paratracheal, subcarinal and hilar regions and EUS to the lower mediastinum and aortopulmonary window. As shown above, EUS and EBUS provide access to different areas of the mediastinum. In combining techniques, most lymph node stations as well as the left adrenal gland can be reached (apart from stations 5 and 6). In six recent series the accuracy of EUS-FNA and EBUS-TBNA used in combination for the diagnosis of mediastinal cancer was 95% . Using the EBUS-Scope for both endobronchial as well as endoesophagel sampling, the sensitivity for cancer detection could be shown to be as high as 96% (EUS 89%, EBUS 91%), specificity 100% and negative predictive value of 96% (EUS 82%, EBUS 92%). CONCLUSION Overall, EBUS and EUS are safe and effective techniques for the staging of the mediastinum. They are minimally invasive and reduce the number of invasive staging procedures. Currently, the main limitation for EBUS and EUS are that they are predominantly performed at centres of excellence and hence only on selected patients. Training of physicians and surgeons remains the issue and performance of an adequate amount of procedures per year is required in order to maintain competency. Reimbursement remains an issue in some countries as well as the actual implementation into cancer guidelines within the hospitals. Increasingly both techniques are being used in hospitals across the world improving the diagnostic yield. Combined EBUS and EUS ought to be regarded as the “first techniques into the mediastinum”, called “complete endo-echo staging”. -
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E07.2 - Image Interpretation and New Adenocarcinoma-Classification (ID 404)
14:25 - 14:45 | Author(s): K. Garg
- Abstract
Abstract
There is a widely divergent clinical, radiologic, molecular and pathologic spectrum within lung adenocarcinoma. Remarkable advances in understanding of the genetic mechanisms that underlie lung adenocarcinoma have altered the diagnostic criteria that determine subsequent treatment. The use of the term bronchioloalveolar carcinoma (BAC) encompassed a broad spectrum of tumors ranging from solitary small peripheral lung tumors with a 100% 5-year survival to widespread advanced disease with a 10% 3-5 year survivals, with widely varying use of terminology even after publication of the 2004 WHO Classification. There are also clinical, radiologic, immunohistochemical, and molecular differences that are distinguishable among the subsets of mucinous and non-mucinous types of adenocarcinoma. In 2011, a new Classification of Lung Adenocarcinoma was therefore proposed by the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society. The 2011 classification addressed three important weaknesses in the previous classification. First, it eliminated the term BAC. Second, it added new terminologies of carcinoma-in-situ, and minimally invasive adenocarcinoma to recognize that minimal invasion (< 5mm). Third, it replaced the terminology of mixed adenocarcinoma. The widespread availability of MDCT and abundance of new information obtained especially from low-dose CT lung cancer screening programs, have increased our understanding of the types and management of small peripheral lung nodules encountered in daily clinical practice, in particular, the importance and prevalence of subsolid pulmonary nodules (atypical adenomatous hyperplasia (AAH), ground glass nodules (GGN) and part-solid nodules). Thin section CT has emerged as a new biomarker for lung adenocarcinoma subtypes. The staging system is based solely on the anatomic extent of the disease. Other factors, such as clinical symptoms or molecular biological characterization of the tumor or attenuation of nodules on CT are not factored in the new TNM classification. Increasing T status reflects tumors that are larger or invasive. In lung cancer nodal staging depends on the location of involved nodes (as opposed to the number of nodes). The M descriptor defines the presence or absence of distant metastatic disease. In 2007, The International Association for the Study of Lung Cancer (IASLC) revised the lung cancer stage groupings based on newer survival data. In the 7[th] edition of TNM classification of lung cancer, following modifications were made: (a) Size cut points, in addition to the 3 cm cut point that traditionally separated T1 and T2 tumors, was introduced at 2, 5, and 7 cm. T1 tumors were now subdivided into T1a and T1b around the 2 cm cut point. T2 tumors were subdivided into T2a and T2b around the 5 cm cut point, and tumors larger than 7 cm. were classified as T3. (b) Cases in which additional tumor nodules are found were reclassified. Those in the same lobe as the primary tumor are now classified as T3, those in the other ipsilateral lobes are T4 and those in the opposite lung are now M1a. (c) Cases associated with pleural or pericardial nodules or effusions were reclassified from T4 to M1a. M1 disease due to distant metastasis was reclassified as M1b. A new IASLC nodal chart, with precise definitions was also agreed, reconciling the previous differences between the Japanese and Mountain-Dresler charts. The concept of nodal zones was introduced to make such classification relevant to those dealing with bulky nodal deposits that transgress the boundaries of individual nodal stations. Further improvements in stage discrimination and management of lung cancer could be expected in the future, as more robust data related to genetic make-up and biological behavior affecting survival of tumors becomes available. -
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E07.3 - IASLC Staging Projects Update (ID 405)
14:45 - 15:05 | Author(s): R. Rami-Porta
- Abstract
Abstract
Background The origin of the International Association for the Study of Lung Cancer (IASLC) Lung Cancer Staging Project took place during an international workshop on intrathoracic staging organized at the Royal Brompton Hospital, London, UK, in 1996. (1) At that time, the 6[th] edition of the tumour, node and metastasis (TNM) classification was in press, but its limitations and weaknesses were discussed in an international and multidisciplinary forum. The main conclusion was the need for a large international database that could be used to refine and update the TNM classification of lung cancer. Two years later, the IASLC Board approved the creation of an International Staging Committee (ISC), whose first co-chairs were Mr. Peter Goldstraw and the late Dr. Robert Ginsberg. An international call was made to promote participation and data sharing, and potential participants were summoned to subsequent meetings and workshops. Data on lung cancer patients diagnosed from 1990 to 2000 were collected from 46 different sources in 20 countries around the world. Data were stored, managed and analysed at Cancer Research And Biostatistics (CRAB), a biostatistics agency based in Seattle, WA, USA. By the end of 2005, 100,869 cases had been registered and 81,495 were analyzable: 68,463 non-small cell lung cancers (NSCLC) and 13,032 small cell lung cancers (SCLC). (2) The analyses of these cases allowed the IASLC to issue recommendations for changes to the 6[th] edition of the TNM classification. The recommendations were accepted by the Union for International Cancer Control (UICC) and by the American Joint Committee on Cancer (AJCC), and were introduced in the 7[th] edition of the TNM classification. (3, 4, 5) With the revision undertaken for the 7[th] edition, a new period of data-based revisions started, with the IASLC leading the revision process and informing the UICC and the AJCC of the potential changes in the classification based on the analyses of its growing international databases. The analyses of the retrospective IASLC database showed that a more detailed database, containing specific information on T, N and M descriptors, would be necessary to continue the revision process. Therefore, in 2009, a call was made for international participation in the prospective collection of data to inform the 8[th] edition of the TNM classification of lung cancer, due to be published in 2016. (6) The IASLC Prospective Phase of the Lung Cancer Staging Project This prospective phase of the project included a new retrospective collection of data from 1999 to 2010. 94,684 patients were collected: 78,640 analyzable cases of NSCLC and 5,912 analyzable cases of SCLC. These cases will be used to inform the 8[th] edition of the TNM classification and are now being analysed at CRAB. Expansion to Other Thoracic Malignancies The ISC incorporated mesothelioma in 2008 and thymic malignancies and oesophageal cancer in 2009. The structure of the ISC was modified to accommodate more tumours and members. Four domains were created: lung cancer domain (chaired by this writer), mesothelioma domain (chaired by Dr. Valerie Rusch), thymic malignancies domain (chaired by Dr. Frank Detterbeck) and oesophageal cancer domain (chaired by Dr. Tom Rice). To increase the participation of more specialists without increasing the number of ISC members and the budget, advisory boards for mesothelioma, thymic malignancies and oesophageal cancer were created. The retrospective database of mesothelioma contains 3,101 surgically treated patients, and its first analysis has been already published. (7) The International Mesothelioma Interest Group (IMIG) and the Mesothelioma Applied Research Foundation (MARF) collaborate with the IASLC Mesothelioma Staging Project. The prospective collection of cases is now ongoing, includes surgically and non-surgically treated patients, and is intended to inform the 8[th] edition of the TNM classification. A side-project on volumetric computerized tomography for clinical staging is also underway. The retrospective database of thymic malignancies has data on more than 10,000 cases, and the prospective collection of data is ongoing. The ISC works closely with the International Thymic Malignancies Interest Group (ITMIG) (8) and with thymic working groups of scientific societies, such as the European Society of Thoracic Surgeons, the European Association for Cardiothoracic Surgery, etc. The main objective is to device a data-driven, internationally acceptable TNM classification for thymic malignancies, both thymomas and thymic carinomas. The retrospective database of the oesophageal cancer is kept at the Cleveland Clinic, Cleveland, OH, USA, and contains data on more than 10,000 patients. Cases are provided by members of the Worldwide Esophageal Cancer Collaboration (WECC). (9) The revised 7[th] edition of the TNM classification of oesophageal cancer was based on the analyses of the surgically treated patients of this database. (10) Expansion to Prognostic Factors Given the importance of more precise prognostication, besides that provided by the TNM classification and staging system, the IASLC Board decided to expand the activities of the Committee to prognostic factors. To make this activity more patent, the name of the Committee was changed to Staging and Prognostic Factors Committee in February 2013. References 1. Goldstraw P. Report on the international workshop on intrathoracic staging, London, October 1996. Lung Cancer 1997;18:107-111. 2. Goldstraw P, Crowley JJ . The International Association for the Study of Lung Cancer international staging project on lung cancer. J Thorac Oncol 2006;1:281-286 3. Goldstraw P, ed. Staging manual in thoracic oncology. Orange Park, FL: Editorial Rx Press; 2009. 4. Sobin L, et al., eds. TNM classification of malignant tumours. 7[th] edition. Oxford: Wiley-Blackwell; 2009;138-146. 5. Edge SB et al., eds. Cancer staging manual. 7[th] edition. New York: Springer; 2010;253-270. 6. Giroux DJ et al. The IASLC lung cancer staging project. Data elements for the prospective project. J Thorac Oncol 2009;4:679-683. 7. Rusch VW et al. Initial analysis of the International Association for the Study of Lung Cancer mesothelioma database. J Thorac Oncol 2012;7:1631-1639. 8. Detterbeck FC, Huang J. Overview. J Thorac Oncol 2011;6(Suppl 3):s1689-1690. 9. Rice TW et al. Worldwide esophageal cancer collaboration. Dis Esophagus 2009;22:1-8. 10. Rice TW et al. 7[th] edition of the AJCC Cancer Staging Manual: esophageal and esophagogastric junction. Ann Surg Oncol 2010;17:1721-1724. -
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E07.4 - PET/CT/MRI for diagnosis and staging of non-small cell lung cancer (ID 406)
15:05 - 15:25 | Author(s): Y. Ichikawa
- Abstract
Abstract
Tumor diagnosis, tumor staging, and patient treatment in clinical oncology depend on morphological and molecular imaging procedures, such as magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET). Radiological and functional imaging studies, however, have well-known, inherent limitations that limit their diagnostic accuracy in assessing tumor stage and therapeutic response. Both CT and MRI provide mainly morphological information on the tumor and potential metastasis. However, the lack of functional information frequently limits the value of these studies when assessing lymph nodes metastasis. Accurate staging of patients with non-small cell lung cancer (NSCLC) is of paramount importance because stage significantly affects both treatment options and prognosis. The management of NSCLC often requires a multimodality approach for accurate diagnosis and staging and for patient treatment. Some of the most important advances in the treatment of lung cancer have been the development and implementation of accurate and functional imaging. In numerous studies the diagnostic capability of whole-body MRI, PET and PET/CT for cancer staging has been evaluated and compared. In the primary evaluation of pulmonary lesions, fluorodeoxyglucose (FDG)-PET scans are useful for distinguishing benign from malignant etiologies. Several studies investigating the accuracy of FDG-PET in diagnosing malignant pulmonary lesions have estimated its sensitivity and specificity to be 96.8% and 77.8%, respectively. In the same analysis, FDG-PET was found to be superior to CT for evaluating nodal and distant metastases and changed therapeutic management in 18% of the cases studied. However, PET has been shown to be less sensitive for characterizing smaller lung lesions. The positive predictive value (PPV) of FDG-PET is significantly lower for lesions smaller than 1 cm than for larger lesions (0.36 vs 0.90, p=0.015). The lower PPV for smaller lesions reflects a higher rate of false-positive FDG-PET scans. A comparison of the characteristics of PET-negative and PET-positive tumors has shown significant differences in lesion size (p < 0.001), histopathological type (p < 0.001), and pathological stage (p = 0.028). Both lesion size (p < 0.001) and histopathological tumor type (p < 0.001) were significant factors for determining whether PET results were negative or positive. This study established that negative PET findings were likely for lesions 2 cm or smaller and for adenocarcinomas (i.e., adenocarcinoma in situ and well-differentiated adenocarcinomas). A meta-analysis of 59 studies has shown that PET/CT is useful for detecting lymph node metastasis and extrathoracic metastasis. PET/CT is significantly more sensitive and specific than conventional CT alone and more sensitive than PET alone for staging NSCLC. Furthermore, PET/CT demonstrates excellent sensitivity (0.91) and specificity (0.98) for bone metastasis. However, PET/CT has high specificity but low sensitivity for detecting brain metastasis. The question of bone metastasis was most thoroughly answered by a recent meta-analysis of 17 studies comparing FDG-PET/CT, FDG-PET, MRI, and bone scintigraphy. The pooled sensitivity of each of the modalities in the detection of metastasis was 92%, 87%, 77%, and 86%, respectively, and the specificity was 98%, 94%, 92%, and 88%, respectively. When compared with other imaging modalities, FDG-PET appears to offer no additional information regarding the presence of metastatic disease in the brain. The current standard of care is to evaluate the brain metastasis with MRI in all patients, except those with clinical stage IA disease. A recent study of 1122 patients with PET-CT–determined stage I (T1-2N0) NSCLC suggests that invasive staging is not indicated for such patients, especially if a PET scan of the mediastinum is negative. Several studies have assessed the prognostic implications of mediastinal PET findings in patients undergoing curative resection of NSCLC. The rates of locoregional and distant recurrence are higher in patients with positive mediastinal PET findings than in patients with negative findings for the N0/N1 subset. The higher rate of locoregional failure in patients with positive preoperative PET findings in the mediastinum might lead to postoperative radiation therapy. Although chemotherapy is recommended for most patients with N1 disease, chemotherapy is generally not recommended for patients with N0 disease. The higher rate of distant failure in patients with positive preoperative mediastinal PET findings might lead to chemotherapy being recommended. On the other hand, pathologic confirmation with invasive mediastinal staging, either by mediastinoscopy alone or by mediastinoscopy combined with thoracotomy, is recommended if mediastinal lymph node abnormalities are detected with PET-CT. Several recent studies have shown that diffusion-weighted magnetic resonance imaging (DWI) has a higher specificity for N staging of NSCLC than does FDG PET/CT and has the potential to be a reliable alternative noninvasive imaging method for the preoperative staging of mediastinal and hilar lymph nodes in patients with NSCLC. Short inversion time inversion-recovery (STIR) turbo spin-echo (SE) MRI may be useful for distinguishing metastatic lymph nodes from nonmetastatic lymph nodes in patients with NSCLC. This imaging method might be more sensitive and accurate than CT, conventional T1-weighted MRI, FDG PET, or FDG PET/CT. We can prospectively compare the diagnostic capabilities of STIR turbo SE imaging, DWI, and FDG PET/CT for N staging in patients with NSCLC. In patients with NSCLC, quantitative and qualitative assessments of N staging obtained with STIR turbo SE MR imaging are more sensitive and more accurate than those obtained with DWI or FDG PET/CT. A new technology, PET-MRI, is now being established. To guarantee the clinically valuable, time- and cost-efficient use of PET/MRI, it is essential that appropriate indications be chosen, that cross-modality training be performed, that the acquisition protocols be optimized, and that the images be carefully reviewed, taking into account potential artifacts. Additional studies are needed to determine how PET/MRI might best be used clinically and to prospectively verify its clinical abilities. The increased use of FDG-PET will help clinicians to select the most appropriate treatments for each patient and thereby improve outcomes and avoid toxic therapies that are unlikely to be beneficial.
