MS 06.01 Proposal of Change for Future Staging System for Thymic Tumor

Abstract

Although Masaoka clinic-pathological staging system has been accepted as the global standard staging system for thymic epithelial tumors, several problems of this staging system have been pointed out because clinical practices in diagnosis, medical treatment and surgical procedure has enormously advanced during more than 30 years. Furthermore, there has not been a TNM classification system approved by UICC to describe a tumor’s clinical status adequately. To overcome these situations, International Thymic Malignancy Interest Group (ITMIG) established global database and proposed a novel staging system based on TNM definition in collaboration with IASLC staging committee in 2016. This is a great progress in clinical medicine in the field of thymic epithelial tumor, but as a matter of fact, stage grouping according to this novel TNM classification is mostly defined by tumor invasion to adjacent organs similarly to Masaoka staging system. Japanese Association for Research of the Thymus (JART) established by Akira Masaoka and colleagues contributed to the ITMIG project of global database, and several studies using JART database were performed and reported from Japanese researchers. Novel findings in the JART database study are reviewed and new insights in further modification in TNM staging system are addressed in the present article. The significance of involved organs as a prognostic factor has been a great interest, because some structures are easily resected while others are difficult to be completely resected. Actually, some previous studies showed prognostic significance of involvement of the great vessels. Based on the ITMIG database, involvement of the pericardium alone is defined as T2 in the UICC TNM classification while involvement of SVC and brachiocephalic vein is defined as T3 and involvement of the aorta, aortic branches and intrapericardial vessels is defined as T4. One of the JART database study focusing on the involved organs in Masaoka stage III tumors showed that invasion to the chest wall is an independent prognostic factor by multivariate analysis while involvement of the great vessels is not. The hazard ratio of involvement of the chest wall is 4.07. Invasion to the chest wall is defined as T3, but when invasion to the sternum is extended, resection of the chest wall including sternum is sometimes a difficult procedure, and complete resection is hard to be achieved. Lymphatic channels are distributed in the chest wall, of which involvement by the tumor can result in nodal metastasis. Thus, invasion to the chest wall might be considered as an important factor to determine the tumor spread, and therefore, as one factor in T definition. Involvement of SVC and brachiocephalic vein is defined as T3, but is heterogenous variable because some tumors invade to the outer surface of the vessel but others enter the lumen of the vessel, which can result in pulmonary metastasis. The extent in involvement of the great vessels could be a significant factor in T definition. Tumor size could reflect the time from initiation of the tumor and the larger tumor is more likely to be in an advanced status. Actually, tumor size is a critical factor in T definition in lung cancers. In thymic epithelial tumors, however, T definition does not reflect the tumor size. Using JART database, oncological significance of the tumor size was examined in thymoma and thymic carcinoma, separately. In thymoma, the rate of R0 resection in the tumors less than 5.0 cm, 5.1 to 10 cm, and more than 10.1 cm was 94.4%, 91.3%, and 84.0%, respectively. Recurrence rate after R0 resection in the tumors less than 5.0 cm, 5.1 to 10 cm, and more than 10.1 cm was 3.0%, 8.9% and 27.2%, respectively. In thymic carcinoma, the rate of R0 resection in the tumors less than 5.0 cm, 5.1 to 10 cm, and more than 10.1 cm was 80.2%, 63.2%, and 62.5%, respectively. Recurrence rate after R0 resection in the tumors less than 5.0 cm, 5.1 to 10 cm, and more than 10.1 cm was 28.2%, 53.7% and 62.5%, respectively. Thus, there was apparent difference in oncological behavior between tumors less than 5.0 cm and those more than 5.1 cm both in thymoma and thymic carcinoma. These observations suggest that tumors size also should be included in T definition in thymic epithelial tumors. Finally, the category of Masaoka stage IVA disease includes pleural dissemination, but the situation of pleural dissemination varies greatly from a single lesion to numerous lesions. Furthermore, some disseminations are resectable while others are not. JART study revealed that the number of disseminated lesions on the pleura In conclusion, T definition remains to be further evaluated in reference to tumor size, chest wall invasion and extent of involvement of the great vessels. M definition also remains to be further discussed in terms of extent of the pleural dissemination. Thymic carcinoma, TNM classification, Thymoma