The GIST of it all: management of gastrointestinal stromal tumors (GIST) from the first steps to tailored therapy. A bibliometric analysis

In total, 5040 publications (only considering articles and reviews) in English related to GIST were identified in the time period 1984–2022. In 1984, the first GIST-specific study was published. General information about included studies are given in Supplementary Table 1. The number of GIST-related publications per year constantly increased over time with a prominent increase from year 2000 on (Fig. 1, Supplementary Table 1). The annual growth rate is 6.61% with in average 29.62 citations per publication.

In terms of scientific productivity per country regarding GIST research, as measured by number of author appearances per country affiliation, USA, China, Japan, Italy, and Germany show the highest scientific productivity (Fig. 2a, Supplementary Table 2). Most frequent collaborations were formed between USA-Germany, USA-China, USA-Italy, USA-Belgium, and USA-Finland (Fig. 2a, Supplementary Table 2). Regarding the number of total publications in the GIST research field, highest total article numbers show USA, China, Japan, Italy, and Korea, whereby country assignment was determined according to the affiliation of the corresponding author (Fig. 2b, Supplementary Table 2). Concerning citation numbers of published articles, USA, Japan, China, Germany, and Italy are the top countries in terms of total citations, whereby Finland, Iceland, Sweden, USA, and Belgium are the top countries in respect of average article citations (Fig. 2c, Supplementary Table 2).

Most productive authors in respect of total number of published articles (without considering author position) in the GIST field are Heinrich M. C., Blay J. Y., Hirota S., Fletcher J. A., and Nishida T. (Table 1, Supplementary Table 3). Most cited publications (total citations and average citations per year) are given in Table 2 and Supplementary Table 3. The journals publishing most of the studies in the GIST research field are shown in Table 3 and Supplementary Table 3.

Among the most frequently occurring author keywords and keywords-plus are terms such as “Imatinib,” “(C-)KIT,” “PDGFRA,” “Sunitinib,” “Mutations,” “Diagnosis,” and “Prognosis” (Table 4, Supplementary Table 4). Most prominent keywords (including author keywords and keywords-plus) were illustrated by a co-occurrence network analysis using the VOSviewer software (Fig. 3a). Additionally, a co-occurrence network analysis was conducted using terms occurring in titles and abstracts of all included studies using the VOSviewer software (Fig. 3b). In synopsis, both co-occurrence network analyses show four major topic clusters which are associated with surgical management and TKI treatment including development/characterization of novel inhibitors, diagnostic workup, and molecular pathophysiology of GIST (Fig. 3a, b). When analyzing the most frequently occurring keywords over time separately for the time spans 1984–2000 (105 publications), 2001–2010 (1418 publications), 2011–2016 (1631 publications), and 2017–2022 (1886 publications), trends regarding all four major topic clusters as described above are evident: in the topic cluster of surgical management over time, increasingly minimally invasive approaches are represented in the literature, starting from open surgery over laparoscopic surgery to endoscopic resection techniques such as endoscopic submucosal dissection or endoscopic full-thickness resection (Fig. 3a, b, Supplementary Figure 1, Supplementary Table 4). However, although thoroughly and increasingly dealing with minimally invasive approaches, the explicit role of surgery for multiple recurrences, extended multivisceral resections in locally advanced disease, and resection of metastases, especially depending on TKI-sensitivity of the tumor, is not extensively represented in the literature (Fig. 3a, b, Supplementary Figure 1, Supplementary Table 4). In the TKI cluster, an increasing number of novel TKIs with respective clinical trials are represented in the literature (Fig. 3a, b, Supplementary Figure 1, Supplementary Table 4). In the topic clusters of molecular pathophysiology and diagnostic workup, increasing identification of specific mutations in certain genes with varying pathophysiological roles were analyzed. With that, more specific molecular diagnostic approaches to stratify patients into more specific treatment groups of TKIs were developed (Fig. 3a, b, Supplementary Figure 1, Supplementary Table 4). However, although the topic clusters 2–4 thoroughly deal with personalization of TKI therapy according to the mutational profile of the tumor especially under conditions of primary TKI therapy resistance, addressing the low percentage of remaining TKI-resistant GIST remains a main future issue to be addressed in clinical studies yet being infrequently addressed in the literature (Fig. 3a, b, Supplementary Figure 1, Supplementary Table 4). Also, potential individualization of treatment regimens of specific TKIs, as well as the potential influence of genetic germline variants on TKI resistance is not yet extensively represented in the literature and might be addressed in future studies (Fig. 3a, b, Supplementary Figure 1, Supplementary Table 4). Since relatively favorable 5- and 10-year overall survival rates are reached at least in a local disease setting [14], and since progression-free survival rates are lower than overall survival rates [14, 15] in the context of increasing minimally invasive and tailored therapy approaches, quality of life during and post GIST treatment comes into focus and is not yet majorly reflected in the literature, especially regarding surgery-related quality of life, being a further issue to be addressed in future studies (Fig. 3a, b, Supplementary Figure 1, Supplementary Table 4).