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N. Alam
Moderator of
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MS06 - Surgeons as Drivers of NSCLC Research (ID 23)
- Event: WCLC 2013
- Type: Mini Symposia
- Track: Surgery
- Presentations: 4
- Moderators:N. Alam, Y.T. Kim
- Coordinates: 10/28/2013, 14:00 - 15:30, Bayside 105, Level 1
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MS06.1 - How Do I Contribute to the IASLC Staging Projects? (ID 481)
14:05 - 14:25 | Author(s): R. Rami-Porta
- Abstract
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Abstract
The IASLC Staging Projects The International Association for the Study of Lung Cancer (IASLC) now has four staging projects. The first one, for lung cancer, originated during an international workshop on intrathoracic staging organized at the Royal Brompton Hospital, London, UK, in 1996. (1) It is an ongoing project with two phases: a retrospective phase, during which 81,495 analyzable lung cancer patients diagnosed between 1990 and 2000 were registered: 68,463 non-small cell lung cancers (NSCLC) and 13,032 small cell lung cancers (SCLC) (2); and a prospective phase, that includes 78,640 analyzable cases of NSCLC and 5,912 cases of SCLC diagnosed between 1999 and 2010. The retrospective database was used to revise the 6[th] edition of the tumour, node and metastases (TNM) classification and prepare for the 7[th] edition; (3, 4, 5) the data of the prospective phase will be used to inform the 8[th] edition of the TNM classification due to be published in 2016. This writer chairs the Lung Cancer Domain. In 2008, mesothelioma was incorporated into the activities of the IASLC Staging Project lead by Dr. Valerie Rusch as chair of the Mesothelioma Domain. As with lung cancer, a call was made to collect retrospective series from around the world and, at the same time, an online registration system was created for prospective collection of data. The retrospective mesothelioma database contains 3,101 surgically treated patients. This population was first analysed to assess the existing TNM classification and staging system for mesothelioma. (6) These analyses showed that more data are needed to refine the classification beyond what the retrospective database can do. In essence, more detailed data on the T, N and M descritpors is needed. The prospective collection of data is an ongoing project that collects surgically and non-surgically treated patients and is intended to inform the 8[th] edition of the TNM classification. In 2009, thymic malignancies were incorporated into the IASLC Staging and Prognostic Factors Committee (SPFC). So far, more than 10,000 retrospective cases have been collected and are now being analysed by the statistitians at Cancer Research And Biostatistics (CRAB), in Seattle, WA, USA. The main objective of these analyses is to establish a TNM classification for thymomas and thymic carcinomas. The Thymic Domain of the Committee is chaired by Dr. Frank Detterbeck. (7) Finally, also in 2009, oesophageal cancer was incorporated into the activities of the IASLC SPFC under the leadership of Dr. Tom Rice, who is the chair of the Oesophageal Cancer Domain of the SPFC. More than 10,000 cases are registered in a database stored and analysed at the Cleveland Clinic, Cleveland, OH, USA. The surgical cases were used to inform the 7[th] edition. Plans are made to analyse the non-surgical series and validate data to inform the 8[th] edition of the TNM classification. How to contribute Individuals, institutions, cooperative groups and proprietors of registries can contribute by submitting their databases directly to CRAB, provided their databases include the information that is essential for the IASLC Staging Projects, i.e. clinical and pathological data on the different T, N and M descriptors, treatment modality and survival. CRAB statisticians have to be informed about the characteristics of the databases to assess if they are useful for the project prior to submission. This is, indeed, the easiest way to contribute: to submit your database. CRAB accepts databases on lung cancer and mesothelioma. Databases of thymic malignancies can be submitted either to CRAB or to the International Thymic Malignancies Interest Group (ITMIG). ITMIG will assess the data and will forward the specific staging data to CRAB for analysis. Those wishing to contribute oesophageal cancer cases should get in touch with the chair of the Oesophageal Cancer Domain of the SPFC, Dr. Tom Rice, at the Cleveland Clinic, Cleveland, OH, USA. Contribution is best through the Worldwide Esophageal Cancer Collaboration (WECC). Those who want to contribute prospective cases can use the on-line registration system that CRAB has established for lung cancer and mesothelioma. There also is an on-line registration system for thymic tumours provided by the ITMIG. Submitting retrospective databases and on-line registration of prospective cases take time and may cost money. In order to facilitate grant application to those who need the assistance of a data manager, CRAB has prepared a document describing the project that can be used to complete the grant application forms. This document can be accessed through the IASLC website at www.iaslc.org. Go to ‘Staging’ and there you will find all the necessary information about the IASLC Staging Projects. Those who cannot participate submitting cases can participate analysing data not directly related to the main staging projects. An outline of the research project has to be sent to the Chair of the IASLC SPFC stating the objectives and the variables needed for the study. Approval will be granted based on the availability of data, the relevance of the project and the willingness of the applicant to pay for the CRAB statisticians’ work required for the extraction and analysis of data. (9) 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. 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. 7. Detterbeck FC, Huang J. Overview. J Thorac Oncol 2011;6(Suppl 3):s1689-1690. 8. Rice TW et al. 7[th] edition of the AJCC Cancer Staging Manual: esophageal and esophagogastric junction. Ann Surg Oncol 2010;17:1721-1724. 9. Goldstraw P et al. We probably have the answer: now what is the question? J Thorac Oncol 2009:4:939-940.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MS06.2 - Clinical Trial and Research Cooperation (ID 482)
14:25 - 14:45 | Author(s): W.Z. Zhong, Y. Wu
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Abstract
Clinical research in non-small-cell lung cancer is a rapidly evolving field. We conducted a survey of lung cancer surgical clinical trials listed on clinicaltrials.gov. 658 records were found, which were mainly consisted of trials studying the surgical procedure and (neo) adjuvant therapy. Phase III trials account for 15.5%. Only 34.9 %( 230 records) trials were completed, and 43 studies present results in clinicaltrials.gov. The median time to completion (MTC) of Ph III surgical procedure trials was 9.4 years. The MTC of Ph III neo-adjuvant and adjuvant trials had not been reached but are longer than 10 years. In comparison, the MTC of Ph III trials in first line setting were only 4.5 years. We summarized the characteristics of these trials with real-world case examples. Our analyses reveal that it is critically needed for regulatory authorities, clinical trial sponsors, collaborative research groups, and academic institutions to work together to build the infrastructure and research cooperation for clinical trials with surgical components. In 2007, a national collaborative clinical research group, Chinese Thoracic Oncology Group (CTONG), was established. CTONG is a network of researchers, physicians and healthcare professionals in public institutions across China. Currently, there are 22 member hospitals in the group. A CTONG-sponsored trial (CTONG1104) is discussed to illustrate our experience with surgical clinical trials. In summary, to expedite clinical research in early stage lung cancer, it is necessary for investigators to collaborate in cooperative clinical trials. As cancer treatment is multidisciplinary, while retaining a surgical focus, surgical trials require multidisciplinary collaboration.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MS06.3 - Randomized Trial of VATS vs Axillary Thoracotomy for Lobectomy (ID 483)
14:45 - 15:05 | Author(s): L. Hao
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- Presentation
Abstract
Background: Since video-assisted thoracoscopic surgery (VATS) was first reported in the 1990s, this approach has been rapidly gaining popularity worldwide because of its less morbidity and expedited patient recovery. As a milestone, VATS lobectomy was first introduced into NCCN Guidelines in 2006, and then has been recommended as a reasonable and acceptable alternative in the treatment of non-small cell lung cancer (NSCLC) since 2007. However, whether VATS’s superiority really exists in the domain of NSCLC has raised unprecedented dispute in the past two decades, especially when compared to other minimally invasive approaches like axillary thoracotomy. Major debates have involved surgical trauma, post-operative neuralgia, shoulder dysfunction, influence on respiratory function/quality of life (QOL), and finally oncologic outcomes. So far, strong evidence demonstrating decreased morbidity and equivalent long-term survival of the new technique is lacking. In an attempt to obtain a better answer, we designed and initiated this multicenter randomized controlled trial (RCT) in China, which compared VATS and axillary approaches in terms of various surgical and oncologic outcomes for early stage NSCLC. Methods: 400 patients were planned to be recruited in this study since 2008, and then randomized into VATS group (Experimental group) and axillary thoracotomy group (Control group). The Inclusion Criteria include: ①Clinical early stage NSCLC, no hilar and mediastinal lymphadenopathy (short diameter ≤ 1 cm assessed on computed tomography scan); ②No medical contraindications to lung resection; ③Age ≤ 75 years old and ≥18 years old; ④Ability to give informed consent. And the Exclusion Criteria are: ①Evidence of invasion into neighboring organs; ②Extensive pleura symphysis; ③Central tumors; ④Inability to tolerate single-lung ventilation; ⑤Previous thoracotomy or high-dose radiation on the chest ; ⑥Pregnant or lactating female patients; ⑦Inability to sign the informed consent form because of psychological, family and society factors; ⑧History of other malignancies in the past 5 years except for non-melanoma skin cancer, cervix cancer in situ or early-stage prostate cancer; ⑨Other uncontrolled factors (like intra-operative conversion to thoracotomy). Surgery criteria would be a radical lobectomy plus hilar and mediastinal lymph node dissection. Also, the VATS lobectomy was defined by the avoidance of rib-spreading and use of the thoracoscope for visualization. The total number of ports is not relevant in this definition, but is typically 3 and 4. Five-year overall survival (OS) and disease-free survival (DFS), as the primary endpoints will be evaluated. Peri-operative parameters, including post-operative chest pain, cytokines response, post-operative respiratory reserve, Karnofsky performance status and QOL would be explored. In addition, operation time, intra-operative blood loss, chest tube drainage, indwelling period of chest tube, etc. would be documented and compared between two groups. Lung Cancer Symptom Scale (LCSS) was adopted to estimate the QOL before operation and at post-operative standpoints of 1, 3, 6, 9 and 12 months. Post-operative respiratory function would be measured in first three months, while Karnofsky performance status and chest pain at the standpoint of 1 year after surgery. Cytokines response, to be exact, serum levels of IL-2, IL-4, IL-6, IL-10, TNF and IFN-r, would be analyzed in first 48 hours after surgery. Randomization was done via an interactive web response system with computer-generated randomization codes. This study has been registered in Clinicaltrials.gov (NCT01102517) and sponsored by Sun Yat-sen University Clinical Research 5010 plan as well as Guangdong provincial high-tech projects. Result: Five leading hospitals throughout China contributed to this RCT. 425 patients was recruited up to May 2013; nonetheless, 336 patients were finally analyzed in the study. The latest DMC review happened on May 2013 and our RCT was regarded to be strictly adhering to the protocol with good quality control. No surgery-related mortality was documented in both VATS and axillary thoracotomy groups. Unfortunately, four patients in the study group were excluded because of intra-operative conversion to axillary thoracotomy. The conversion rate was 0.94% (4/425) in our study. Another fact needs to be clarified that the remaining 85 patients were excluded due to a variety of reasons, which included extensive pleura symphysis (9 patients), benign pulmonary lesions (35 patients), small cell lung cancer (3 patients), accidental pleural metastasis (2 patients), Age > 75 years old (2 patients), invalid case report forms (13 patients), and inability to adhere to the randomized surgical approaches (21 patients). As a result, 175 patients in VATS group and 161 patients in axillary thoracotomy group were finalized and analyzed by the database. No significant difference between the two groups in terms of the anatomical location of the tumors, histological subtypes and clinical stages. Impressively, the operation time for the VATS lobectomy group was significantly shorter than that of the control group (150 min vs. 170 min, P<0.05). There was also remarkably less intra-operative blood loss in the study group (100 ml vs. 150 ml, P<0.001). Another important finding was that no significant differences were identified regarding the number of cleared lymph nodes and number of lymph node regions (10 vs 12; 5 vs 5, respectively). The peri-operative complication rates, once again, showed no significant difference between the two groups. Patients who undertook VATS lobectomy experienced significantly better post-operative QOL, and the superiority was showed in all the aspects of LCSS. When looking at cytokines response which may reflect the acute surgical injuries or trauma, IL-2, IL-4, IL-6, IL-10, TNF and IFN-r consistently demonstrated lower expression levels throughout the time in the VATS group. However, only the patients who recruited in Sun Yat-sen University Cancer Center underwent the evaluation of cytokines response (180 patients). Regarding the primary endpoints, although longer follow-up is still needed before drawing a clear conclusion, initial analyze did show no significant difference was seen between the two groups regarding OS and DFS. We considered these results were premature, but we also believed current data tended to demonstrate a statistical non-inferiority result. Conclusions: Our multicenter RCT has illustrated that VATS approach is a safe approach for the treatment of early stage NSCLC, and may be superior to axillary thoracotomy approach in terms of intra-operative blood loss, acute surgical injuries and post-operative QOL. However, we also realized that longer follow-up is necessary to determine its oncologic equivalency.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MS06.4 - Into the Lab: The Surgeon as Translational Researcher (ID 484)
15:05 - 15:25 | Author(s): G.M. Wright
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Abstract
Introduction Building translational research capacity is a daunting task if a thoracic surgeon has not inherited a fully set up laboratory. It is possible, however, for a thoracic surgeon to be involved in and even drive translational research. Given that surgeons are the major procurers of tissue and data in lung cancer, it should actually be more commonplace. It requires passion, organization, the understanding and assistance of colleagues, and the ability to seize what opportunities exist and create new ones with strategic collaboration. Creating this capacity also involves modifying surgical practice to facilitate research then building the relationships, funding and infrastructure. In this article, these building blocks are explored. A translational research project is presented as a successful application of this formula. Building Blocks As a principle, the pillars research capacity-building are: ~ Research-Based Surgical Practice ~ Relationships ~ Infrastructure ~ Funding Sources For individual surgeons and circumstances, these may differ. Some components may already exist and some may seem unattainable. It is often overlooked that simple changes to standard practice can make research a natural activity. For example, focusing audits on the procedures that are the subject of potential research, aligning timing of routine follow-up so that outcome assessment becomes automatic, or a policy that all tissue excess to diagnostic needs is routinely stored in a tissue bank. A research coordinator, at least part-time, is essential for any sustainable research activity. Beyond that, key relationships may differ. For me, the most important initial relationship is an anatomical pathologist with a keen interest in lung. Without such a person to review and precisely classify tumors, the power and applicability of any study is seriously diminished. However, a relationship with a laboratory-based clinician or scientist is necessary in order to have access, training and conduct of the benchtop component of research. The surgeon should be active in these endeavours (at least initially) to promote goodwill and a free-flowing exchange of ideas. Other clinicians or specialist scientists may then need to be involved depending on the scope of the potential research projects. Whatever infrastructure is available for research will often need to be augmented. Many useful research tests are already available in a diagnostic pathology laboratory (e.g. advanced immunohistochemistry, mutation screening, PCR). Some facilities may be shared with researchers in other specialties, resulting in synergies for both groups. This may be the way to acquire part time bench space, for example. After determining what capabilities are required to conduct the projected range of research, funding will be the next concern. It is not usually possible to get large project and infrastructure support without a track record and without the funds it is difficult to get a good track record. Therefore preliminary work needs to be funded from a range of more modest resources to pay for direct research costs and services outside any collaborative effort. Local organizations such as Rotary, Apex etc. are often keen to donate to research with a potential impact on their community. This could, for example, fund the construction of tissue microarrays or purchase of essential equipment. Anything that a name can be attached to is usually fair game for such donors. Hospital research foundations are the easiest target for competitive grants. Specialist societies commonly have foundations for distributing grants-in-aid. Participation in capitation-funded clinical trials may provide the salary for a research coordinator, allowing their spare time to be dedicated to translational projects. An Example of Surgeon Driven Translational Research After several years of building relationships, collaborations, infrastructure and funding, our group was able to assess our core research advantages. Figure 1 plots the gradual ascent to critical mass for research funding in our thoracic unit.Figure 1 Our example project investigated the genomic/transcriptomic landscape of the recently classified subtypes of lung adenocarcinoma.[1] Other than one gene expression study[2] using outdated array-based platforms and subtype classifications, no molecular signature has been reported to correlate to the morphology seen by the pathologist under the microscope. It is debated whether these subtypes are genetically different or just a spectrum of the same tumour. Inter-observer differences in classifying these subtypes are particularly problematic for the new micropapillary subtype; therefore a molecular marker is an important goal. To investigate these new subtypes (table 1), we carefully selected tumors with classical morphological regions of the differing subtypes. From this group, 29 tumours were selected with known mutations in one or more of EGFR, KRAS, BRAF and TP53. These would be the most likely cases to prove our hypothesis that there are differential genomic aberrations within subtypes of the same tumor.Table 1. Subtypes of lung adenocarcinoma investigated, as classified in the 2011 IASLC/ATS/ERS pathological classification of lung adenocarcinoma.
After marking the subtypes in areas of tumor purity > 50%, punches of formalin-fixed paraffin embedded tumor were deparaffinized and DNA was extracted. High resolution melting was then used to screen for mutations in all selected subtypes of each tumor. In 3 out of 11 KRAS mutant tumors and 2 out of 4 BRAF mutant tumors, heterogeneity was found in mutation status between subtypes of lesser and higher metastatic potential. No differences were seen between subtypes for EGFR mutant tumors, however we did find a single case of very high copy number of the EGFR mutant allele mapping only to the micropapillary subtype in the tumor. The significance of this finding is far-reaching. It provides a genetic basis to support the new pathological classification and may inform its next revision. It also brings into question the accuracy of small biopsies in detecting mutations other than EGFR. It has the potential to unravel the biological evolution of lung adenocarcinoma, with EGFR apparently an early event, whereas KRAS and BRAF may be acquired later and result in a transition to a more malignant subtype phenotype within a given tumor. Conclusion This example demonstrates that surgeons can drive important translational research as well as advancing other researchers’ goals. Although it takes years to develop such programs, once critical mass is achieved the results create further opportunities to sustain future research and incorporate advances in sequencing platforms and knowledge in lung cancer biology.Subtype Description Lepidic Minimal metastatic potential. Malignant cells growing along but not invading airway walls Acinar Moderate metastatic potential. Glandular structures in invasive stroma Papillary Moderate metastatic potential. Branching structures with fibrovascular stromal cores covered by malignant cells. Solid with/without mucin High metastatic potential. Sheets or nests of malignant cells with or without intracellular mucin. Micropapillary High metastatic potential. Papillary tufts of tumor cells without fibrovascular cores either lying apparently free in alveolar spaces or surrounded by thin fibrous septa, often at a tumor’s edge. References
1 Travis, W. D. et al. International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 6, 244–285 (2011). 2 Bryant, C. M. et al. Clinically relevant characterization of lung adenocarcinoma subtypes based on cellular pathways: an international validation study. PLoS One 5, e11712 (2010). Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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O13 - Limited Resections (ID 101)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Surgery
- Presentations: 1
- Moderators:G.M. Wright, K. Kernstine
- Coordinates: 10/29/2013, 10:30 - 12:00, Bayside 204 A+B, Level 2
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O13.08 - DISCUSSANT (ID 3924)
11:45 - 12:00 | Author(s): N. Alam
- Abstract
- Presentation
Abstract not provided
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
