Thymoma is a vital part of thymic epithelial tumors, and with continuous study, it has gradually been found to have different characteristics from other thymic epithelial tumors. Therefore, to explore the most concerned and cutting-edge hotspots in the field of thymoma research, we have constructed this bibliometric analysis specifically for thymoma, trying to sort out the current status of existing thymoma research by summarizing the most 100 cited articles on thymoma and providing a practical reference for future thymoma research.
Original articles accounted for 3/4 (75/100) of the literature included in this study. However, it is important to note that most of these (52/75) were retrospective studies, which we believe is associated with a lower incidence of thymoma. The lower incidence makes conducting prospective studies on thymoma challenging, but 12 works are still prospective studies. The most cited article in this study was the 1981 publication by Masaoka et al., which followed 96 patients with thymoma for up to 10 years and explored the effects of staging and different treatment modalities [9]. Of the top 100 most cited works, the top 10 were original retrospective studies. Prospective studies are mainly aimed at chemoradiotherapy for thymoma. However, they were all single-arm studies, and there are studies of postoperative radiotherapy for thymoma patients who had a complete resection [10]. The study is still ongoing, and the results are worth expecting.
The United States has the highest number of published and cited in the top 100 most cited articles, reaching 41 and 6786, respectively. However, the top three most cited articles are from Japan. All of these articles were retrospective studies with large sample sizes, and all patients were followed up for a long time (up to 44 years) [9, 11, 12]. Therefore, their research results are significant for diagnosing and treating thymoma. We believe this is related to differences in the pooled incidence of thymoma in different races. For example, based on the Surveillance, Epidemiology, and End Results (SEER) database, the incidence of thymic tumors in North America is 2.14 per 1 million, and the incidence of thymic tumors in Asians (3.74 per 1 million) is higher than that of the Caucasian ethnic group (1.89 per 1 million), so thymoma in Asian populations are relatively more common. Hence, large sample size studies on thymoma are also easier to conduct.
Through VOSviewer analysis, thymic carcinoma and invasive thymoma are the two keywords with higher density. Since both are attributed to thymic epithelial tumors, thymoma and thymic carcinoma are often studied together in the existing literature. For example, the International Agency for Research on Cancer (IARC) published the WHO classification of thymic epithelial tumors in March 2005, based on a multidisciplinary symposium organized by the International Thymic Malignancy Interest Group (ITMIG) in December 2011 [13]. Thymoma is an inert tumor that occurs, develops, metastasizes, and recurs more slowly. However, some thymomas have the characteristic of aggressive growth. Therefore, the treatment and prognosis of invasive thymoma have become a hot topic in thymoma research. Recent studies of invasive thymoma have focused on more minimally invasive surgical modalities [14] and treatment for neoplasm with intravascular growth [15–17].
Surgery is currently the first choice for thymoma treatment, and its position in treating thymoma and even thymic epithelial tumors has been recognized [9, 11]. However, in recent years, research on the treatment of thymoma has gradually focused on radiotherapy and chemotherapy, with more prospective studies and randomized controlled trials [10, 18–20], which will provide a higher level of evidence for the development of thymoma treatment regimens. Currently, immunotherapy studies on thymoma have also been published, and higher PD-L1 expression was linked with a better response to treatment with immune checkpoint inhibitors but with a relatively high incidence of immune-related adverse events. Therefore, immunotherapy is not yet the standard adjuvant therapy for thymoma, and large sample size studies are required to confirm its safety.
Many studies have found that thymoma is associated with autoimmune diseases, especially myasthenia gravis. Therefore, myasthenia gravis has become one of the hot keywords in this study. In addition, immune disease-related words such as systemic-lupus-erythematosus, lichen-planus, t-cells, and red-cell aplasia also appeared in the top 100 keywords, and according to VOSviewer cluster analysis, the frequency of such words has gradually increased in recent years. Our team has also found that surgery has a certain effect on treating non-myasthenia Gravis autoimmune diseases [21]. Similarly, laboratory research on thymoma has gradually increased in recent years, and since 2000, the number of highly cited laboratory studies on thymoma has gradually increased. In total, 11 laboratory studies were included in this study, and KIT, interleukin-1alpha, PD-1/PD-L1, and titin antibodies were the hot spots. It can be seen that the research on thymoma is no longer limited to the characteristics of clinical pathology and the prognosis of treatment. The horizontal study of the association of thymoma with other diseases and the longitudinal study of the molecular gene mechanism of thymoma is receiving increasing attention.
There are several limitations to our study. First, although we used an authoritative database to identify articles, articles have different numbers of citations in different databases due to coverage differences. Therefore, there is a certain bias in the selection of literature. Second, citation analysis may not be a perfect measure of an article's impact on its field. Since the number of citations usually increases with time, the earlier articles potentially have an artificially higher impact than the more recent articles. In any case, citation analysis is still the best measurement for studies, and it can reflect the value of old articles in this field to some extent. Third, we cannot exclude self-citation from journals and authors.