Cervical cancer is the fourth most common cancer among women worldwide, while in low- and medium-income countries it ranks second in both incidence and mortality. Radiotherapy for cervical cancer, especially brachytherapy, has been used for more than 100 years. The positive clinical outcomes of radical radiotherapy for cervical cancer benefit from the combination of external beam radiotherapy (EBRT) and brachytherapy, which provides a medium preventive dose in low-risk areas and a high radical dose in high-risk areas, especially in areas adjacent to sources in brachytherapy. Intensity-modulated radiation therapy (IMRT) reduces the dose to adjacent organs around the target volume, which is conducive to reducing radiation-related side effects. Compared with conventional brachytherapy, image-guided brachytherapy not only increases the dose-volume histogram parameters of target volumes, but also brings benefits to local control, and survival of patients with cervical cancer.[4,5]
When a published article quotes another article, a citation is generated. Despite some limitations, such as self-citing from authors or journals, the quality of highly cited articles seems to be better than that of less cited articles, thus rendering citations an objective indicator.[6,7] In this report, we use bibliometric analysis to identify the 100 most cited articles on cervical cancer radiotherapy.
2 Materials and methods
Our research did not require ethics approval because all the data in this study were based on public publications. All databases and journals included in the Web of Science and Scopus databases were used to search for eligible studies. The search strategy to identify studies on cervical cancer radiotherapy is shown in Table 1. The search time ranged from 1900 to September 29, 2019. Articles were ranked based on the total citations received from the 2 databases. One hundred articles about radiotherapy for cervical cancer were identified.
Older studies tend to accumulate a larger number of citations; thus, to account for the year and month of publication, an index of citations per year (CPY) was calculated as the total citations from 2 databases divided by the years of publication up to September 2019 for each article. The author, journal, year, and month of publication, country or region, and radiotherapy technologies were recorded. Article types were categorized into an original study, recommendation, guideline, and review. Original studies were further categorized into clinic, physics, and radiobiology. Two independent authors (Zhao HF and Zhao ZP) performed the search and extracted information from the articles. Discrepancies were resolved by consultation with a third author (Tang XD). VOSviewer (Leiden University, Leiden, Netherlands) was used to analyze the relations among coauthors who have more than 4 articles among the 100 most cited articles.
The 100 most cited articles on cervical cancer radiotherapy were published from 1964 and 2016, and the number of citations ranged from 3478 to 211, including a total of 49,262 citations as of September 29, 2019 (Table 2 ). The CPY index ranged from 70.4 to 13.1. Nine articles had over 1000 citations at the time of our search; of these 9 articles, 2 are recommendations from Groupe Européen de Curiethérapie and the European Society for Radiotherapy & Oncology.[8,9] The most cited articles were divided into 5-year periods. The 5-year period with the largest number of articles was 1999 to 2004 with 29 articles, followed by 2004 to 2009 with 22 articles (Fig. 1). The journal International Journal of Radiation Oncology, Biology, Physics had the highest number of articles (42 articles), followed by Radiotherapy and Oncology with 13 articles, Cancer with 8 articles and Journal of Clinical Oncology with 7 articles. The remaining journals (Gynecologic Oncology, British Journal of Cancer, American Journal of Obstetrics, and Gynecology, and Brachytherapy) each published 5 or fewer of the 100 most cited articles (see Table 3).
According to the signature unit of the first author, the 100 most cited articles on cervical cancer radiotherapy were from 17 countries or regions, with most publications being from the United States (38 articles), followed by Austria (15 articles), Canada (8 articles), France (8 articles), and the United Kingdom (7 articles). The remaining countries or regions (Japan, Denmark, Italy, The Netherlands, Norway, Taiwan Republic of China) each published 6 or fewer of the most 100 cited articles (see Table 4).
Seventy-eight first authors contributed to articles on the 100 most cited articles. Five authors (first author) were credited with having at least 3 of the most 100 cited articles. Among these authors, Perez, CA had 6 articles, Dimopoulos, JCA had 4 articles, and Eifel, PJ, Pötter, R, and Viswanathan, AN had 3 articles. The first authors, corresponding authors and coauthors with the largest number of the 100 most cited articles are listed in Table 5. The relations among coauthorship with more than 4 of the most 100 cited articles are shown in Figure 2.
The 100 most cited articles were categorized as original studies (86 articles), recommendations (5 articles), guidelines (5 articles), and reviews (4 articles) (see Table 6). Among the 100 most cited articles, intracavitary (IC) brachytherapy and 3-dimensional conformal radiotherapy (3D-CRT) were the most commonly used treatment techniques (see Table 6). Among the 100 most cited articles, articles involving EBRT were categorized by technology, and the relationship between article number and year range of publication is shown in Figure 3. Articles involving brachytherapy were also categorized by technology, and the same relationship is shown in Figure 4. The relations among cooccurrences of no less than 2 of the most cited articles are shown in Figure 5.
The 4 recommendations from Groupe Européen de Curiethérapie and the European Society for Radiotherapy & Oncology all received a high number of citations (1819, 1659, 394, and 318; ranked 5, 6, 33, and 46) and had high CPY index values (133.1, 115.7, 53.1, and 35.0; ranked 3, 4, 14, and 25).[8–11] Recommendations for a high dose rate from the American Brachytherapy Society published in 2000 also received a high number of citations (630, ranked 15) and a high CYP index value (33.0, ranked 28).
There are several literature databases, such as the Web of Science, Google Scholar, and Scopus databases, that provide data on citation counts. Generally, Google Scholar can help to retrieve the most obscure information, but it is rarely used in systematic literature searches (such as meta-analyses, systematic review, and bibliometric analyses) due to inconsistent accuracy in the results, inadequate citation information and a lack of updates. In meta-analyses, the use of multiple databases can improve the query yield, which may reduce the chances of omitting articles of interest. Similarly, the Web of Science and the Scopus databases were used to retrieve articles in this study.
For locally advanced cervical cancer, concomitant chemotherapy, and radiation therapy is the modern treatment modality. EBRT and brachytherapy are 2 indispensable treatment modalities in radiotherapy.[14–17] Delineation the of clinical target volume has always been an important topic in radiotherapy. Two articles about delineation of clinical target volume for IMRT postoperative and definitive treatment were both listed in the 100 most cited articles.[14,18] For brachytherapy, recommendations for delineation of target volumes, such as high-risk clinical target volume, and intermediate-risk clinical target volume, were also included in the 100 most cited articles. The high citations of these articles adequately illustrated the importance of target delineation.
In the earlier period, EBRT used large anterior and posterior opposed fields. With the advancement of radiotherapy equipment technology, such as multileaf collimator and computer-aided treatment planning systems, 3D-CRT has gradually been applied. IMRT has emerged with further advances in treatment technologies, such as inverse treatment planning systems and control systems of linear accelerators. Small bowel, rectum, bladder and bone marrow sparing with IMRT is superior to a conventional beam arrangement with a similar target coverage.[3,20] As shown in Figure 3, among the 100 most cited articles, article involving conventional radiotherapy were first published in 1965 to 1969, 3D-CRT technology was first mentioned in 1980 to 1984, and IMRT technology was first mentioned in 2000 to 2004. In a European study on magnetic resonance imaging (MRI)-guided brachytherapy in locally advanced cervical cancer, IMRT was not mandatory, and clinical outcome benchmarks were established. In image-guided intensity-modulated external beam radiochemotherapy and MRI-based adaptive brachytherapy in locally advanced cervical cancer (EMBRACE II), IMRT and daily image guided radiotherapy were mandatory. With daily image guided radiotherapy and couch correction, a margin reduction from 10 to 5 mm can be performed without compromising target coverage.
As shown in Figure 4, among the 100 most cited articles, an article involving intracavitary brachytherapy (IC-BT) was first published in 1960 to 1964, while intracavitary and interstitial brachytherapy (IC/IS-BT) was first mentioned in 2000 to 2004. In the early period, IC-BT had a pear-shaped absorbed dose distribution using standard source loading, and the prescribed dose was delivered to point A of the Manchester system. With the application of 3D imaging, IC-BT can be optimized to the sculpted pear dose, increasing the dose to target volumes and reducing the dose to organs at risk.[4,23] However, the optimization of IC-BT has some limitations due to the high dose gradient of brachytherapy. In practice, the planning-aim isodose cannot be placed more than 25 mm from the tandem at the level of Point A.[24,25] Combined intracavitary-interstitial (IC/IS) applicators have been developed for targeting tumors that are not well covered by IC applicators.[26–29] IC/IS applicators allow for improved dose conformality, and target dose escalation and/or dose de-escalation in organs at risk can be carried out.[27,30] The use of IC/IS-BT in large tumors significantly increased local control without increasing morbidity. Based on these advantages, in the EMBRACE II study, the proportion of IC/IS-BT was increased (from 21% to more than 30%) to meet the planning aims and dose-volume histogram constraints of EMBRACE II.
Eleven authors (total coauthor) were credited with having no fewer than 6 articles on the 100 most cited articles. As shown in Figure 2, among these authors, at the time of publication, Potter R, Kirisits C, Dimopoulos JCA, Lang S, Berger D, and Georg P are all from the Medical University of Vienna, Austria. These authors have 17, 16, 13, 10, 9, and 8 articles among the 100 most cited articles, respectively. Their articles are mostly about brachytherapy. From the concentration of authors’ distribution, we can see that the Medical University of Vienna contributes most to radiotherapy, especially brachytherapy, for cervical cancer and leads to the development of new technologies.
We have published 2 articles on bibliometric analysis in Brachytherapy and Journal of Contemporary Brachytherapy, respectively, on cervical cancer brachytherapy and prostate cancer brachytherapy. Through such a bibliometric analysis of the most cited articles,[34,35] we can observe technical progress over a long period of time, the current situation and future directions of this field. These articles can broaden the horizon and the overall thinking in this field among young doctors. The current article can be used as a first step into this area and to keep track of top organizations, authors, and publications in the field, as well as hot issues in the field.
In the cooccurrence diagram of Figure 5, out of140 occurrences, the item “brachytherapy” has appeared 10 times. This indicates that brachytherapy plays an important role in the radiotherapy of cervical cancer and is indispensable. Han et al reported that in the matched cohort between 2000 and 2009 (median follow-up 3.4 years), brachytherapy treatment was associated with a higher 4-year cause-specific survival rate (64.3% vs 51.5%, P < .001) and overall survival rates (58.2% vs 46.2%, P < .001). An analysis of the National Cancer Data showed that from 2004 to 2010, new technologies, such as IMRT or stereotactic body radiation therapy (SBRT), have been increasingly used for boost after pelvic EBRT. However, the median survival of patients who received brachytherapy was significantly higher than that of patients who underwent IMRT or SBRT boost (70.9 vs 47.1 months, P = .01). With the development of EBRT technology, especially the application of SBRT boost technology in the treatment of cervical cancer, the curative effect of patients with SBRT or IMRT boost is also improved. An updated propensity score matching study based on National Cancer Data showed no significant difference in overall survival for patients who received SBRT boost versus BT boost (hazard ratio = 1.477, 95% confidence interval = 0.746–2.926, P = .263) but a significant overall survival detriment in patients who received IMRT boost versus brachytherapy boost (hazard ratio = 1.455, 95% confidence interval = 1.300–1.628, P < .001). Compared with the research data of Gill et al, this study increased the data from 2011 to 2013. In addition, the patients who received SBRT boost and IMRT boost were separated in propensity-matched Kaplan–Meier analysis. This indicates that SBRT technology has made great progress in recent years. At the same time, SBRT technology is much more effective than IMRT in boost after EBRT. Therefore, SBRT has the potential of alternative therapy in patients who are not suitable for brachytherapy. This hypothesis was also preliminarily confirmed by Hsieh et al. They retrospectively analyzed 9 brachytherapy-unsuitable cervical cancers treated with definitive whole pelvic radiotherapy followed by SBRT boost via helical tomotherapy. The locoregional control rate at 3 year was 78%. Only 2 patients had residual tumors after treatment, and the others were tumor-free. Two patients experienced grade 3 acute toxicity, and no grade 3 or 4 chronic toxicity was found. Compared with IMRT, SBRT can give a higher equivalent biological dose under the same dose constraints to normal tissues due to the application of a multiple field setup and/or flattening filter-free mode. A higher dose gradient in brachytherapy is one of the factors for good tumor control by external irradiation combined with brachytherapy. A study from Dyk, P et al indicated that the total dose delivered to the gross tumor volume from combined MRI-guided high dose rate and positron emission tomography/computed tomography-guided IMRT is highly correlated with local tumor control. When the dose to the peripheral area of high-risk tumor volume (HR-CTV) reaches the prescribed dose, the dose to gross tumor volume will reach a very high level, due to the high dose gradient in brachytherapy. This is why the dwell times in needles are normally limited to 10%–20% of that used for dwell positions in the intracavitary part in the IC/IS-BT, to provide a higher dose at the center of the implant from the intracavitary components while homogeneously covering the lateral parametrial disease.[23,27]
This study has some limitations. First, although we used 2 databases to identify articles, articles have different numbers of citations in different databases due to coverage differences. Although the retrieval based on 2 databases can increase the comprehensiveness of the literature query, there is a large overlap in the number of citations in the 2 databases. Second, since the number of citations usually increases with time, the earlier articles potentially have an artificially higher impact than the more recent articles. To counter this effect, we also used the CPY index to rerank the identified articles. Third, we cannot exclude self-citation from journals and authors.
To the best of our knowledge, this report describes the first bibliometric analysis of the 100 most cited articles on cervical cancer radiotherapy. Our study presents a detailed list and an analysis of the 100 most cited articles on cervical cancer radiotherapy to provide, insight into historical developments and enable important advances in this field to be recognized. Brachytherapy is an indispensable part of radiotherapy for cervical cancer. The International Journal of Radiation Oncology Biology Physics is the journal with the most publications related to cervical cancer radiotherapy. The Medical University of Vienna had the most achievements on cervical cancer radiotherapy, especially brachytherapy, and may be a good candidate for collaborative research in this field.
Data analysis: Zhipeng Zhao, Hongfu Zhao.
Data curation: Zhipeng Zhao, Xiaodi Tang, Hongfu Zhao.
Methodology: Xiaodi Tang, Xin Mu.
Project administration: Hongfu Zhao.
Software: Xin Mu.
Supervision: Hongfu Zhao.
Writing – original draft: Zhipeng Zhao, Xiaodi Tang.
Writing – review & editing: Hongfu Zhao.
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