ITMIG July 2014 Update

ITMIG Activities and Projects

One of the ITMIG Mission is to get Members involved in works and scientific projects. ITMIG is a very active Scientific Society: several ad hoc Committees and Working Groups have been created to enhance its working as well as to improve scientific knowledge on particular issues of thymic diseases. Regular conference calls to update projects within the members are the characteristic of the existing working groups and committees. Some of these groups are: Database, Research, Membership, Education, Communication and Steering Committees, and workgroups on Thymic carcinoma, Biology, Prospective database, Global Asset project and the Annual Meeting. Any ITMIG member is welcome to participate in any committee or conference calls if they wish. In addition there are many projects under development and many that are waiting for someone to provide the energy to move them along. If you are interested in joining any of these groups, have a new idea to bring forward or just want to explore how to get more involved, please contact Pam Bruce (pbruce@thymic.org).

Below some brief reports about Committees/Working Groups’ activity.

 

ITMIG Database Update (by: J.Huang, New York)

A central priority of ITMIG was the collection of worldwide data and the development of a centralized retrospective database. This served as a major driver for the development of a formal staging classification. This database was also intended as a resource for the investigation of clinical issues, including histology, treatment, prognosis, autoimmune disease, and second malignancies, as existing institutional and other population-based registries have been limited in their ability to address many specific questions. 

  From September 2012 to February 2013, a total of 6097 cases were submitted from 47 institutions across 15 countries spanning North and South America, Europe, and Asia. That this effort was completed in less than 6 months is a testament to the engagement of the ITMIG membership. We then invested a great deal of time to clean the data and fill in missing values as much as possible. Our initial groundbreaking projects on Thymic carcinoma, neuroendocrine tumors and the WHO classification led to further refinements in the data-elements and structure of the database.  In addition, we developed a statistical core, led by Xiaopan Yao, to assist in appropriately structuring studies to address the questions of interest as well as statistical analysis.

This database now offers members a large and rich data set for research. Contributors to the database were invited to submit research proposals to ITMIG through a Request for Applications in September of 2013.  Although the process of refining the database for use took a lot of effort and time, we are in the process of conducting the analyses needed for each of these. The first series of analyses is nearing completion, and in keeping with the collaborative culture of ITMIG, we have encouraged investigators posing similar questions to join together.  A manuscript providing an overview of the database is in press in the Journal of Thoracic Oncology. The initial groundbreaking studies have been presented and accepted for publication, and additional projects are moving through the analysis process. 

Accrual to a more detailed prospective database is now under way, starting with patients diagnosed after 1-1-21012. We thank those centers contributing and encourage others to join in. Innovative approaches are being developed to make this a leap above a simple prospective registry, for the center participating in this upgraded approach (the GLOBAL ASSET project)L Thais approach involved management of local variability in care, comprehensive data collection and Bayesian analysis.  The ITMIG International retrospective and prospective Databases provide a foundation for collaborative research and are well poised to be a major step toward in advancing our understanding of these orphan diseases.

 

Education committee and JTO supplement (by: E. Marom, Houston)

An exciting supplement is slated to be published in the Journal of Thoracic Oncology (JTO), September 2014. This is the 2nd ITMIG supplement of JTO that sets global standards as a foundation for collaboration. The supplement includes several consensus papers addressing areas in which there was a particular need for clinical guidance. In addition, the Education Committee selected topics related to mediastinal disease where the existing knowledge needs to be more widely appreciated – these had been the subject of several fascinating presentations at the 4th ITMIG Annual Conference in Bethesda, September 2013. Most notably, the supplement contains the proposals for the first formal, validated stage classification for thymic malignancy. This is the product of the International Association for the Study of Lung Cancer (IASLC) and ITMIG thymic staging committee, and is based on the ITMIG retrospective data as well as additional data contributed by other organizations (the JART, ESTS), representing a database of over 10,000 thymic malignancy cases.

Among the topics in this supplement are a Modern Definition of Mediastinal Compartments, an ITMIG Node Map for Thymic Malignancies, and a Guide to Measuring Radiographic Response to Treatment. We hope these detailed standard clarifications will promote a scientifically-based data collection and assessment approach and enhance robust data collection and correct universal staging. Other manuscripts include: Approaching the Patient with an Anterior Mediastinal Mass: a Guide for Radiologists; Approaching the Patient with an Anterior Mediastinal Mass: a Guide for Clinicians; and Histologic Classification of Thymoma: a Practical Guide for Routine Cases as well as Genetic Alterations in Thymic Malignancies, Infectious Syndromes associated with Thymic Malignancies; Alterations of the Immune System in Thymic Malignancies and Neurologic Paraneoplastic Syndromes. Finally, the supplement includes three manuscripts outlining the proposed stage classification: one dedicated to the T-staging descriptors, another dedicated to the N and M descriptors and the third to the proposals for Stage Group Classifications.

Thank you to all members of the Education Committee, of the Database Committee, all those who served as authors and co-authors of these superb manuscripts, on the extended work groups reviewing these manuscripts and the entire ITMIG community who contributed cases to our database and who commented on the manuscripts distributed and approved them. This entire work has proved to be what ITMIG has always stood for: an international collaboration to promote a scientifically-based approach, and facilitate dissemination of knowledge about thymic malignanices and other mediastinal diseases, in order to improve patient outcomes.

 

Thymic carcinoma Working-Group (by: A. Rimner, New York)

Dr. Usman Ahmad at the AATSThe ITMIG thymic carcinoma working group consists of 32 members and holds monthly teleconferences. Thus far our work has resulted in two manuscripts submitted for publication: one study on the outcomes of thymic carcinomas based on the retrospective international ITMIG database which is the largest study on thymic carcinomas with over 1000 patients included. The other study focused on the even rarer neuroendocrine tumors of the thymus and presents the largest study of its kind with over 200 patients. These will be landmark papers against which the outcomes of future studies will have to be measured.

We have successfully completed a survey of the ITMIG membership on the management of complex clinical scenarios of thymic carcinoma patients. This is currently prepared for presentation at the 2014 Annual ITMIG Meeting and subsequent publication.

Currently, several other projects are ongoing or planned, including studies of rare thymic carcinoma subtypes, such as thymic adenocarcinomas, central pathology review of thymic carcinomas for classification and grading, failure patterns in thymic carcinomas, outcomes of thymic carcinomas treated with non-surgical treatments, outcomes of various chemotherapy regimen as well as exploration of immunotherapy for thymic carcinomas. The prospective ITMIG database is open for data collection and will permit even more detailed analyses of prognostic and predictive factors as well as optimal treatment paradigms.

 

Two ITMIG Guys at the AATS

Dr. Usman Ahmad and Dr. Pier Luigi Filosso presented ITMIG papers at the 94th American Association for Thoracic Surgery (AATS) Meeting (Toronto, April 26-30, 2014). Both are the results of a scientific collaboration between ITMIG and ESTS. The first, an oral presentation entitled “Outcomes of Thymic Carcinoma: A Joint Analysis of International Thymic Tumor Databases” was a comprehensive review by Dr. Ahmad, concerning the outcome of 1042 thymic carcinomas retrospectively collected by joining the ITMIG and ESTS datasets. It represents the largest series of Thymic Carcinoma ever collected, and showed that even though the majority of tumor presented at an advanced stage, the observed survival was more favorable than previously reported (5-year OS was 80% for Masaoka Stage I/II, 60% for stage III, 40% for IVa and 30% for IVb tumors); tumor stage and completeness of resection demonstrated to be the strongest prognostic factors, while tumor histologic subtype was not associated with outcomes.

The second paper, “Outcome of Primary Neuroendocrine Tumors of the Thymus: A Joint Analysis of the International Thymic Malignancy Interest Group and the European Society of Thoracic Surgeons Databases” was a poster presentation by Dr. Pier Luigi Filosso. The collaboration between ITMIG and ESTS made possible to collect the largest number of patients (205) with such rare neoplasm. Overall Survival (OS) and Cumulative Incidence of Recurrence (CIR) were the evaluated outcome measures. Thymic Neuroendocrine Tumors were characterized by a very aggressive biological behavior, with 5-year OS and CIR of 63% and 34%, respectively. Early stage and a complete resection significantly improved patients’ survival, while histology did not influence OS and CIR.

 

The 2014 ITMIG Meeting

The next ITMIG Meeting will take place in Antwerp (Belgium) on September 5-6, 2014. Antwerp is the capital of the Flanders province and it is one of the largest seaport in Europe. Historically, it hosted the 1920 Summer Olympic Games, but it is well-recognized as the city of Rubens, the famous Flemish Baroque painter. During World War II the city was severely damaged by German missiles, and rebuilt after the war in a modern style. The Meeting and setting in Antwerp therefore will be a combination of history, culture and science.

The Scientific Program Committee (Chairs Paul van Schil and Dirk van Raemdonck) have developed a program organized in several sessions: Immunotherapy for Thymic Cancers, Surgical approach to the Thymus (from minimally to maximally invasive, in collaboration with the 2 European Societies of Thoracic Surgery- ESTS & EACTS), Thymic-related Neurological problems, Tumor growth kinetics and population modeling and Multimodality approach to the Thymic neoplasms. Finally, an interesting lecture on the history of thymic surgery in Japan and around the world will be given by Prof. Meinoshin Okumura. We hope to see you in Antwerp!

More details are available at www.itmig2014.org.

 

The 2015 ITMIG Meeting

Planning is already underway for the 2015 ITMIG Meeting. This will take place in Shanghai, China in October 2015. The meeting will be planned so there is an opportunity to spend a few extra days getting to know this part of the world for those coming from further away. More details will be available by the time of the Antwerp meeting.

 

Thymic Cancer Genome Atlas (TCGA) Project

The National Cancer Institute in the US (NCI) agreed to perform whole genome sequencing of thymic malignancies, thanks to the strength of the thymic community. Led by Philipp Ströbel, multiple ITMIG institutions from around the world were able to donate thymic tissue that met strict quality criteria. In the end we assembled 124 evaluable cases – a real tribute to the collaborative spirit and willingness to get engaged. The analysis is underway. This represents a huge springboard for basic science research, and has set the stage for the formation of a Biology workgroup, led by Nicolas Girard.

 

The WHO Histologic Classification

The World Health Organization (WHO) is issuing a new edition of the Classification of Tumors of the Lung, Pleura, Thymus and Heart (4th Edition). The thymic chapters are based heavily on the work done by the pathology workgroup during 2 international workshops organized by ITMIG, led by Alex Marx. It also builds on the analysis of outcomes gleaned from the ITMIG retrospective database. It is no surprise that the authors of these chapters include most of the pathology experts that participated in the ITMIG led efforts in 2011-13.

 

The ITMIG Website Overhaul

Behind the scenes, the ITMIG website has been undergoing a complete overhaul, led by Marlies Keijzers and Pam Bruce, with the technical support organized by Jose Arenas. This involves a completely new platform, a new look, and a great expansion in what the website is capable of handling. The new site is currently undergoing some final review and testing, and will be ready to go live in August of 2014. We encourage everyone to get involved in keeping it current by providing or suggesting new content or features that should be added. The new platform makes it much easier to make this be an active hub to foster collaboration for those interested in thymic and other mediastinal diseases.