Re-irradiation Using Stereotactic Radiotherapy: A Bibliometric Analysis of Research Trends

The objective of this research is to conduct a comprehensive bibliometric analysis using the Web of Science Core Collection (WoSCC) to examine the current research topics and trends pertaining to stereotactic-based re-irradiation. A bibliometric search was conducted for re-irradiation-related literature published in English from the WoSCC database from 1991 to 2022, using VOSviewer to visualize the results. The extracted information comprises the publication year, overall citation count, average citation rate, keywords, and research domains. We conducted a literature review to identify trends in research on re-irradiation. A total of 19,891 citations were found in 924 qualifying papers that came from 48 different nations. The number of publications and citations has grown steadily since 2008 with the highest number of publications in the year 2018. Similarly, a substantial increase in the number of citations has increased since 2004 and the citation growth rate has been positive between 2004 and 2019 with a peak in 2013. The top authorship patterns were six authors (111 publications and 2498 citations), whereas the highest number of citations per publication was attained with an authorship pattern of 17 authors (C/P = 41.1). The collaboration patterns analysis showed that the largest proportion of publications emanated from the United States with 363 publications (30.9%), followed by Germany with 102 publications (8.7%), and France with 92 publications (7.8%). The majority of the analyzed studies were focused on the brain (30%), head and neck (13%), lung (12%), and spine (10%) and there have been emerging studies on the use of re-irradiation for lung, prostate, pelvic and liver utilizing stereotactic radiotherapy. The main areas of interest have changed over time and are now based on a multidisciplinary approach that integrates advanced imaging techniques, stereotactic treatment delivery, the toxicity of organs at risk, quality of life, and treatment outcomes.


Introduction And Background
Re-irradiation is used to treat recurrent or residual tumors following prior radiotherapy. In recent decades, advancements in cancer detection, staging, and management have resulted in improved disease outcomes and higher survival rates [1]. In comparison to three or four decades ago, patients receiving current appropriate care are expected to have an improved quality of life [1,2]. The issue of a localized disease recurrence in an otherwise healthy patient necessitating extra modes of treatment measures for local control and palliation has come into focus as a result of the increased control rate and survival. To maximize response and survival, current therapeutic approaches place a greater emphasis on organs at risk and their function. The increased use of innovative methods and technology, particularly in radiotherapy, has led to better normal tissue sparing, which has improved the quality of life. Stereotactic-based re-irradiation has emerged as a viable treatment option for patients with loco-regional recurrence, with few other treatment options. This treatment approach delivers high doses of radiation to the tumor with pinpoint accuracy while sparing the healthy tissue. It has been used to treat patients who have failed prior radiation therapy, as well as those who are not surgical candidates. More retrospective clinical data have been reported and published in the last two decades with generally good efficacy and acceptable toxicity [3][4][5][6][7][8]. As a result, re-irradiation using stereotactic radiotherapy is considered a more accurate treatment, delivering a highly biologically effective dose (BED) to tumors while minimizing the dose absorbed by normal tissues, potentially reducing radiotherapy's toxicity and side effects.
The bibliometric analysis emphasizes the key studies and topics that have influenced the management and understanding of a disease of interest and uses citation data to evaluate an article's academic effect in its chosen subject [9,10]. The bibliometric analysis enables researchers to examine the most recent findings and familiarize themselves with the areas of research that are most important. It is a very helpful tool for evaluating academic ability within a certain academic topic that employs citation patterns and frequency as objective indicators [11,12]. Additionally, a specific academic community's most significant journals, authors, contributing institutions, and nations can be identified using article citation counts [13].
Studies on re-irradiation using stereotactic radiotherapy have increasingly been published for malignancies in different regions [3][4][5][6][7][8]. The bibliometric analysis of the literature, however, is limited. In this bibliometric analysis, we aim to examine the publication patterns, research trends, keywords, countries, journals, collaboration network, and citation impact of research on re-irradiation using stereotactic radiotherapy from 1990 to 2022 using the Web of Science. Further, we wish to present an overview of the literature published in the last two decades for different tumor sites that have used re-irradiation.

Data Source and Search Strategy
The dataset used in this work was retrieved from Web of Science Core Collection (WoSCC). The WoSCC is the largest database of cited scientific publications in the world, and it can be used to assess the academic significance of works on a given topic. A comprehensive search of WoSCC was performed using the strategy as follows: (TS=(reirradiation OR re-irradiation) AND TS=(stereotactic* OR SBRT OR SABR)) AND TS= (radiosurgery OR radiotherapy OR "radiation therapy"), where TS refers to "topic". The search fields comprised the article title, abstract, and keywords. As a quantity indicator, the results were refined to include manuscripts written in English and published between 1st January 1991 and 31st December 2022. Further, we assessed the influence of the research on the scientific community using the Science Citation Index Impact Factor as a quality indicator.
Original studies, abstracts, and reviews were the only article categories considered; editorial content, letters, corrections, and retractions were not included. Cases relating to each of the chosen documents were constructed in a bibliographic data frame. Every record included bibliographic information on the author, their affiliation, the title, an abstract, keywords, the name of the journal, the year of publication, the volume, issue, page, publisher, country, and the total number of citations. "Article proceedings papers" pertain to individual articles that have undergone a peer-review process and are presented at conferences or symposiums. These papers encompass original research findings, methodologies, and results. They are typically published within conference proceedings. On the other hand, "proceedings papers" encompass the collective compilation of papers presented at a conference or symposium. These papers may encompass various types of content, including research articles, review articles, case studies, and technical reports.
The strength of bibliometric analysis revolves around its ability to provide powerful quantitative and qualitative indicators of the title under study. The total number of publications (TP) is an important quantitative index to measure publication growth over the years. Other indices such as total citation (TC), non-cited publications (NCP), cited publications (CP) and citation per publication (C/P) contribute to the qualitative assessment in bibliometric analysis [14][15][16].
The key data about data collection (annual scientific production, average number of citations per year), sources (most significant most referenced, as well as dynamics), researchers (most relevant authors and associations, corresponding author's nation, nation-specific production), and reports (most worldwide cited documents, the most frequently used keywords, words dynamics) were presented in the summary function in order to highlight the key findings. The annual growth rate was used to describe the ratio of scientific production across time.
The most relevant countries were ranked by the country of corresponding authors. Country links were used to indicate author occurrences in national scholarly articles (the number of documents indicates author occurrences by country). The degree of international cooperation for a certain nation was measured by the proportion of papers with at least one co-author who was employed abroad as opposed to the corresponding authors [17]. Based on authorship associations, the most productive countries were determined. Correspondence analysis and clustering techniques were used to find common terms and author/institution relationships in research topics. A thematic map was generated from the keyword network using a clustering algorithm.

Data Analysis
Bibliographic analysis tools were used to obtain meaningful data [18]. MS Excel (V16.0) was used to perform basic functions and plot publication and citation trends. VOS Viewer (version 1.6.15) was used for data visualization, including journals, researchers, individual publications, citations, bibliographic linkage, cocitation, or co-authorship relationships. The whole process was verified by two authors to ensure data accuracy.

Publications and Document Types
A total of 924 publications were identified, with an average of 30 publications per year. Table 1 displays the distribution of publications, indicating that the majority consisted of research articles (76.6%), followed by review articles (19.6%), article proceedings papers (3.0%), and proceedings papers (0.5%). The total number of citations for the publications was 19,891, with an average citation rate of 22.6 citations per publication. In total, 10.4% were NCP and 89.6% were CP. The highest citation per publication was achieved for a proceeding paper (C/P = 50.3). Furthermore, of the studies, 299 (32.3%) were retrospective and 96 (21.2%) were prospective.    Figure 1A. Publication trends indicate that research on reirradiation using stereotactic radiotherapy has increased over time.

TP -total publications; TC -total citations
Keywords and Co-occurrence Figure 2A illustrates the top keywords (n=50) identified in this study used by most authors in the field of reirradiation. Based on the findings depicted in Figure 2A, it is evident that the keywords "re-irradiation," "toxicity," "recurrence," "radiation therapy," and "local control" are the most commonly utilized terms in this field of study. Keyword combinations are used in the systematic review protocol to give a comprehensive overview of research trends. The visualization of the frequently used keywords and their correlation using the VOS viewer is shown in Figure 2B. The network includes five clusters and 48 nodes, respectively. The representation in Figure 2B presents a visual analysis of the keywords provided by the authors, where the size of each node corresponds to its frequency of repetition. Links between nodes indicate cooccurrences in the same article and the color of a node signifies the cluster it belongs to, and different clusters are characterized by different colors. The shorter the spacing between keywords, the more often the keywords will appear together. This demonstrates that the domains of "re-irradiation" and "toxicity" span the biggest and most evident area using rigorous bibliometric metrics.

FIGURE 2: Illustration of top keywords (A) and and overly visualization of co-occurrence analysis visualization of keywords in WoSCC (B).
WoSCC -Web of Science Core Collection

SBRT -stereotactic body radiotherapy; SABR -stereotactic ablative radiotherapy
The Geographical Contribution of Publications Table 3 shows the overall publication distributions from the top 20 countries. Forty-eight different countries produced 924 publications in the field of re-irradiations. The collaboration patterns analysis showed that the United States was the most productive country, with 363 publications (30.9%), followed by Germany with 102 publications (8.7%), and France with 92 publications (7.8%). Further, the United States contributed the most number of citations (33.9%), followed by Germany (13.8%) and France (4.8%), respectively. The citation per publication was highest in the Netherlands (C/P=42.9) followed by Germany (C/P=36.4) and Canada (C/P=26.1).   Collaboration Pattern Figure 4 illustrates the collaboration network between countries in the field of re-irradiation using stereotactic radiotherapy. USA and Canada had the highest collaboration in terms of publications (n=42) followed by USA and China (n=17) and USA and Netherlands (n=15). The United States collaborated with 14 countries for publications, followed by Canada with four countries and Germany with three countries.

FIGURE 4: Study collaboration between different countries in the field of re-irradiation.
Three-Factor Analysis (Countries, Keywords, and Journals) Figure 5 shows a three-factor analysis of the relationships between countries, keywords, and journals. We show that the top five countries (USA, Germany, France, Italy, and Japan) publish their reirradiation literature primarily using four main keywords: reirradiation, toxicity, recurrence, and radiotherapy. These countries and keywords have strong relationships with three journals (International Journal of Radio Oncology Biology Physics, Journal of Neuro-Oncology, and Radiotherapy and Oncology). The leading positions of developed countries in medicine and medical journals with great influence in this field make these countries the most important sources of publications and publishing institutions.  Notably, keywords such as "overall survival," "brain metastases," "stereotactic radiotherapy," and "stereotactic radiosurgery" emerged as a prevalent theme during the initial phase from 1990 to 2008. Subsequently, in the period from 2008 to 2022, these keywords merged with the themes of "re-irradiation" and "radiotherapy," demonstrating an evolving trend in the research landscape. Highly Cited Articles Table 4 lists the top 10 publications based on the overall number of citations and the number of citations rate each year [19][20][21][22][23][24][25][26][27][28]. Among them, three articles referred to spinal metastasis [19,21,28], and three articles referred to gliomas [22][23][24]. Out of the top 10 articles with the highest number of citations, six were published in the International Journal of Radiation Oncology Biology Physics, which has an impact factor of 7.04.

Discussion
Re-irradiation for loco-regional recurrences is becoming more common as cancer patients live longer [29]. This bibliometric analysis demonstrates that research on re-irradiation using stereotactic radiotherapy has steadily increased over the past three decades, with a marked increase in the last decade. This may enable a paradigm shift in the critical clinical setting where alternative treatment options are limited. Recent advances in treatment techniques, such as the ability to account for dose accumulation, deformable registration, intensity modulation, and image guidance make it a more compelling option [30]. Furthermore, the availability of new techniques such as stereotactic radiotherapy, image-guided radiosurgery, and brachytherapy have led many clinicians to consider re-irradiation for more sites. This is because these techniques can preserve critical and slow-reacting tissues. The most important factor in planning is that these techniques can be used to determine the dose of various tissues within the irradiated volume.
One of the most prevalent side effects for cancer patients is brain metastases and using stereotactic radiosurgery has long been regarded as the gold standard of care with sufficient literature support [31][32][33].
Over the course of the last decade, the utilization of stereotactic ablation radiotherapy (SABR or SBRT) has experienced a notable expansion. Initially, SABR was restricted to early-stage primary lung cancer, but as part of the results of several clinical studies, its use is now extended to non-pulmonary primary disease sites as well as oligometastatic settings. There is evidence that SABR is well tolerated and achieves high local control rates in some settings [34]. Many studies have examined SBRT for spinal metastases in pre-irradiated areas over the past decade [35][36][37]. In all studies, image-guided radiosurgery, intensity modulated radiotherapy (IMRT), or robotic stereotactic radiosurgery systems were used for highly conformal dose distributions.
The term bibliometrics simply refers to a set of methods (statistical and mathematical) for measuring and analyzing the quantity and quality of publications [18]. This analysis uses the simplest method available to assess a researcher's productivity (the number of articles published in WoSCC). While it is a very straightforward indicator that is easy to calculate, one should be extremely cautious when comparing different groups based on it. Although the number of publications reflects productivity, it does not address the quality of the articles [18]. In addition to productivity, performance indicators can be used to identify the quality of the publication. An impact factor derived from the Journal Citation Index was used to measure quality in this study. As is well known, a journal's impact factor and an article's citation rate are the key metrics for assessing their respective impact [38]. To our knowledge, no literature analysis on reirradiation has been performed. As a result, this study is the first to examine the bibliometric characteristics and evaluate the citation patterns of radiation studies at various sites in order to present an impact indicator in this sector.

Limitations
Identifying publications was limited to the Web of Science search engine, so publications from other databases or in languages other than English may have been missed, leading to bias in citation statistics. Several variables affect citation counts, including the author, the field of study, and time since publication. For instance, early publications typically had more citations. Since the key articles analyzed with the highest number of citations were published before 2013, some new publications may have been overlooked. The study used annual citation counts to compensate for the effect of publication time on the most cited articles.

Conclusions
To our knowledge, this is the latest bibliometric analysis of the most cited studies on re-irradiation. Our results provide insight into the historical development of reirradiation and important advances in its application to cancer therapy. Re-irradiation management presently relies on a multidisciplinary integration of sophisticated imaging, stereotactic therapy delivery, toxicity, and biological dose buildup. The main areas of interest have changed over time and are now based on a multidisciplinary approach that integrates advanced imaging techniques like deformable registration, stereotactic treatment delivery, the toxicity of organs at risk from re-irradiation, quality of life, sustainability of treatments, overall efficacy and effectiveness of treatments and treatment outcomes. This study helps researchers identify the most influential research on reirradiation and current research priorities.

Conflicts of interest:
In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.