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Melanoma is one of the most life-threatening skin cancers; immune checkpoint blockade is widely used in the treatment of melanoma because of its remarkable efficacy.
This study aimed to conduct a comprehensive bibliometric analysis of research conducted in recent decades on immune checkpoint blockade for melanoma, while exploring research trends and public interest in this topic.
We summarized the articles in the Web of Science Core Collection on immune checkpoint blockade for melanoma in each year from 1999 to 2020. The R package bibliometrix was used for data extraction and visualization of the distribution of publication year and the top 10 core authors. Keyword citation burst analysis and cocitation networks were calculated with CiteSpace. A Gunn online world map was used to evaluate distribution by country and region. Ranking was performed using the Standard Competition Ranking method. Coauthorship analysis and co-occurrence were analyzed and visualized with VOSviewer.
After removing duplicates, a total of 9169 publications were included. The distribution of publications by year showed that the number of publications rose sharply from 2015 onwards and either reached a peak in 2020 or has yet to reach a peak. The geographical distribution indicated that there was a large gap between the number of publications in the United States and other countries. The coauthorship analysis showed that the 149 top institutions were grouped into 8 clusters, each covering approximately a single country, suggesting that international cooperation among institutions should be strengthened. The core author extraction revealed changes in the most prolific authors. The keyword analysis revealed clustering and top citation bursts. The cocitation analysis of references from 2010 to 2020 revealed the number of citations and the centrality of the top articles.
This study revealed trends in research and public interest in immune checkpoint blockade for melanoma. Our findings suggest that the field is growing rapidly, has several core authors, and that the United States is taking the lead position. Moreover, cooperation between countries should be strengthened, and future research hot spots might focus on deeper exploration of drug mechanisms, prediction of treatment efficacy, prediction of adverse events, and new modes of administration, such as combination therapy, which may pave the way for further research.
In the past 10 years, although the frequency of melanoma has continued to increase, the lethality of advanced melanoma has decreased. Nevertheless, melanoma is still one of the most life-threatening skin cancers [
Bibliometric analysis is a quantitative science approach using methods such as co-occurrence analysis and citation analysis to evaluate research performance [
Bibliographic data for the analysis were all acquired from the Web of Science Core Collection, which includes the Science Citation Index Expanded, Social Science Citation Index, and Emerging Source Citation Index [
A total of 24,093 documents were retrieved from the Web of Science Core Collection. After excluding documents that were published as preprints in 2021 and then published as final versions in 2022 and documents with an unknown publication date, 24,086 documents remained in the bibliometric analysis and visualization. The search details are presented as a flowchart (
Detailed search flowchart, showing steps in the identification and screening of papers. Publication years spanned 1999 to 2021. Only documents published in English were included. Endnote was used to remove duplicates. The R package Bibliometrix was used to remove documents that were published as preprints in 2021 by extracting the publication date.
The retrieval characteristics used for publications on ICB for melanoma included the distribution of publication year, country and region, organization, journal, core authors, keywords, and key references. The detailed search strategy is shown in
Distribution of publications by year. (A) The cumulative number of publications and (B) the annual number of publications on immune checkpoint blockade for melanoma. The peak of cumulative publications occurred in 2020. The annual number of publications increased relatively slowly from 1999 to 2021 and sharply from 2014 to 2017 and onwards. The peak of annual publication either occurred in 2020 or has yet to occur. The publication data for 2021 does not include data for December.
As for geographical distribution, 24,086 documents were published from 117 different countries and regions. Studies involving multiple countries were included in the analysis, with each country being counted individually. We classified documents by country and visualized the spatial distribution as a heatmap (
Geographical distribution of global publications. The green-to-red gradient represents a decreasing number of publications. Gray represents countries with no publications.
Top 12 most productive countries and regions.
Rank | Country/region | Publications | Citations | Citations per publication |
1 | United States | 11,113 | 642,788 | 57.84 |
2 | China (mainland) | 2345 | 45,215 | 19.28 |
3 | Germany | 2223 | 129,248 | 58.14 |
4 | Italy | 1847 | 87,903 | 47.59 |
5 | France | 1601 | 128,827 | 80.47 |
6 | Japan | 1598 | 53,323 | 33.37 |
7 | England | 1464 | 97,981 | 66.93 |
8 | Australia | 1381 | 81,059 | 58.70 |
9 | Netherland | 1087 | 75,699 | 69.64 |
10 | Switzerland | 945 | 50,695 | 53.64 |
11 | Canada | 862 | 77,164 | 89.52 |
12 | Spain | 658 | 58,543 | 88.97 |
The information on leading organizations was analyzed with VOSviewer. Generally, 24,086 documents were published by 13,359 different organizations. After merging duplicates and excluding disjointed organizations, a final total of 243 organizations met the inclusion threshold and are shown in the visualization. The top 10 most productive organizations are listed in
Top 10 most productive organizations.
Rank | Organization | Country | Articles | Citations | Total link strengtha |
1 | Memorial Sloan Kettering Cancer Center | United States | 903 | 120,565 | 3183 |
2 | University of Texas MD Anderson Cancer Center | United States | 859 | 54,089 | 2381 |
3 | National Cancer Institute | United States | 645 | 71,055 | 759 |
4 | Dana-Farber Cancer Institute | United States | 617 | 82,093 | 3079 |
5 | University of Sydney | Australia | 537 | 33,668 | 2749 |
6 | University of Pittsburgh | United States | 505 | 25,886 | 1310 |
7 | Harvard Medical School | United States | 480 | 21,477 | 1317 |
8 | University of California Los Angeles | United States | 476 | 50,391 | 1926 |
9 | Massachusetts General Hospital | United States | 440 | 32,663 | 1634 |
10 | Mayo Clinic | United States | 367 | 27,207 | 823 |
aTotal link strength in VOSviewer represents all links between a given node and other nodes, which indicates how the entry interacts with other entries. The strength of a link is given by a nonnegative number. If one node has no links with other nodes, the total strength of the link equals zero.
Coauthorship analysis of organizations. Plot showing a coauthorship analysis of organizations. The normalization method was fractionalization. The weight was the number of publications. The thickness of the lines indicates the strength of coauthorship relationships. Different colors indicate clusters.
Core journals were identified by analysis of publication sources. After analyzing bibliographies, we extracted the top 10 most prolific journals along with their impact factor (IF) in 2020 and 2021 in the field of ICB for melanoma (
Top 10 most prolific journals.
Rank | Journal | Publications | Impact factor (2020) | Impact factor (2021) |
1 |
|
1051 | 32.956 | 44.544 |
2 |
|
677 | 5.442 | 6.958 |
3 |
|
627 | 9.727 | 12.701 |
4 |
|
602 | 10.107 | 12.531 |
5 |
|
589 | 9.913 | 13.751 |
6 |
|
508 | 5.869 | 8.11 |
7 |
|
498 | 18.274 | 32.976 |
8 |
|
465 | 4.11 | 4.456 |
9 |
|
359 | 4.886 | 5.422 |
10 |
|
336 | 5.085 | 7.561 |
Information on authors and co-authors was also analyzed with VOSviewer. A total of 24,086 publications were produced by a total of 93,587 authors. The 3 most important evaluation criteria for core authors included the number of published documents, total citations, and the H index. Therefore, we extracted and visualized the top 10 most prolific authors according to these criteria (
Top 10 core authors by number of publications.
Rank | Authors | Organizations | Publications | Citations | H index |
1 | Paolo A Ascierto | National Tumour Institute, Fondazione G. Pascale (Italy) | 312 | 10,756 | 64 |
2 | F Stephen Hodi | Dana-Farber/Brigham and Women’s Cancer Center (US) | 301 | 35,302 | 93 |
3 | Caroline Robert | Institut de Cancérologie Gustave Roussy (France) | 265 | 27,523 | 78 |
4 | Jedd D Wolchok | Memorial Sloan Kettering Cancer Center (US) | 252 | 47,787 | 99 |
5 | Antoni Ribas | University of California Los Angeles (US) | 233 | 30,109 | 88 |
6 | Georgina V Long | University of Sydney (Australia) | 190 | 13,657 | 67 |
7 | Dirk Schadendorf | University Hospital Essen (German) | 184 | 11,733 | 68 |
8 | John M Kirkwood | University of Pittsburgh Medical Center (US) | 159 | 8493 | 56 |
9 | Reinhard Dummer | University of Zurich (Switzerland) | 152 | 7641 | 46 |
10 | Steven A Rosenberg | National Cancer Institute (US) | 139 | 27,236 | 99 |
Overlay visualization of coauthorship relationships between authors. The analysis method was Linlog/modularity. The weight was citations. Scores are the average year of publication. The thickness of the lines indicates the strength of the relationships. The colors of the circles represent the average year of publication.
In total, 30,486 keywords were extracted from 24,086 documents after removing duplicates. We used a network and overlay visualization of author-given keywords to analyze the co-occurrence of keywords. A total of 30,486 keywords were analyzed, of which the 180 most frequently occurring that met the inclusion threshold were grouped into 2 clusters (
Co-occurrence analysis of keywords. These two plots show the co-occurrence of keywords. The normalization method we chose was Linlog/modularity. The weight was occurrence for each plot. (A) shows the 180 top-occurring items among 30,486 keywords, grouped into 2 clusters, with the colors of the circles representing each cluster. (B) shows the keywords grouped by year of publication, with the colors of the circles representing the average year.
Top 25 keywords with the strongest frequency bursts. A strong frequency burst indicates that a variable has undergone a great change in a short period of time. The red bars indicate the durations of the bursts.
The number of citations of the publications was mainly extracted with bibliometrix. The top 10 most highly cited documents were extracted and are listed in
Top 10 most highly cited publications.
Rank | Title | DOIa | Source | Publication date | Total citationsb |
1 | Improved Survival with Ipilimumab in Patients with Metastatic Melanoma [ |
10.1056/NEJMoa1003466 |
|
Aug 2010 | 9549 |
2 | Safety, Activity, and Immune Correlates of Anti-Pd-1 Antibody in Cancer [ |
10.1056/NEJMoa1200690 |
|
Jun 2012 | 7926 |
3 | The Blockade of Immune Checkpoints in Cancer Immunotherapy [ |
10.1038/nrc3239 |
|
Apr 2012 | 7160 |
4 | Safety and Activity of Anti-Pd-L1 Antibody in Patients with Advanced Cancer [ |
10.1056/NEJMoa1200694 |
|
Jun 2012 | 5026 |
5 | Pembrolizumab Versus Chemotherapy for Pd-L1-Positive Non-Small-Cell Lung Cancer [ |
10.1056/NEJMoa1606774 |
|
Nov 2016 | 4794 |
6 | Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma [ |
10.1056/NEJMoa1504030 |
|
Sep 2015 | 4751 |
7 | PD-1 Blockade Induces Responses by Inhibiting Adaptive Immune Resistance [ |
10.1038/nature13954 |
|
Nov 2014 | 3514 |
8 | Nivolumab in Previously Untreated Melanoma Without Braf Mutation [ |
10.1056/NEJMoa1412082 |
|
Jan 2015 | 3421 |
9 | Pembrolizumab Versus Ipilimumab in Advanced Melanoma [ |
10.1056/NEJMoa1503093 |
|
Jun 2015 | 3376 |
10 | Predictive Correlates of Response to the Anti-Pd-L1 Antibody Mpdl3280a in Cancer Patients | 10.1038/nature14011 |
|
Nov 2014 | 3087 |
aDOI: Digital Object Identifier.
bTotal citations were until the end of December 2021.
For a comprehensive analysis of citations, we used CiteSpace (version 5.8R3) to evaluate cocitation references (
Cocitation analysis of references. Using CiteSpace, we performed a cocitation analysis of references from 2010 to 2020. In CiteSpace, the size of a circle indicates the number of documents cited. The purple area of the circle indicates the centrality of a document.
This study updates current knowledge on research interests related to ICB for melanoma, providing researchers and physicians an overview of the landscape of the field and potential future research hot spots. We conducted a comprehensive search of literature published on this topic before December 2021 in the Web of Science Core Collection. We retrieved 24,086 bibliographies and performed a bibliometric analysis.
First, using the bibliometric method, we analyzed chronological trends in the publications. The results show that from 1999 to 2013, the annual number of publications was rather small, with a small, linear slope of growth. The number of newly published papers from 1999 to 2013 remained under 200, with rather small growth every year. The next period was from 2014 to 2016, when publications related to ICB grew rapidly. The annual number of publications grew to over 1000, but did not reach 2000, which is consistent with previous research [
The chronological trend was reflected in several critical articles and specific time points, which enables us to reveal the roadmap for this field. The very first research on ICB was on CTLA-4 blockade, which was conduced beginning in 1987 and was first proved in 2011 [
As for geographical distribution, among the 80 different countries and regions involved in this bibliometric analysis, the most prolific are listed in
For the most productive journals, considering the evidence for the total number of publications and IF, the
In the aspect of cooperation between authors, the network analysis showed that most cooperation took place within countries, and that there was little cooperation between countries. The same phenomenon was also revealed by a coauthorship analysis of organizations, in which clusters showed intricate connections within countries and lesser connections between clusters. These findings suggest that cooperation between states represents an area that should be strengthened.
We also performed analysis of keywords and burst terms to investigate research trends, finding that the change in focus was remarkable. Generally, research trends and the public interest changed in two major aspects: from the laboratory to translational medicine and clinical research, as well as from early ICB developments, such as CTLA-4, to later ones, such as PD-1 and PD-L1 blockades. The focus of research gradually changed from mechanisms to efficacy and adverse events. This indicates that the theory was becoming mature and that the application of ICB therapy was being explored, including enhancing its efficacy, reducing its adverse effects, and expanding its use to other, more specific cancer types [
From the initial research on the mechanisms of immunotherapy, including the alteration of immune cells and immune molecules under ICB treatment to subsequent translational, clinical research into the interactions of immune checkpoints with costimulatory molecules, cancer drive genes, and cancer hallmarks, studies investigating the mechanism of ICB have been maturing. In the next several years, screening of biomarkers to predict treatment efficacy and adverse events, improve the efficacy of ICB and reduce adverse events, explore drug combinations, and extend the indications for ICB might become hot spots in this clearly evolving field of research.
As far as we know, this is the first study to use a bibliometric analysis to investigate research trends and public interest in ICB for melanoma. Our bibliometric analysis was much more comprehensive and intuitive than a literature review would have been, because of our use of systematic searching and quantitative statistical analysis. Moreover, we used not only CiteSpace, but also VOSviewer and the R package bibliometrix for better data extraction, bibliometric analysis, and visualization. However, this study still has some limitations. We only extracted literature from the Web of Science Core Collection database, and although this approach left little possibility for ignoring some of the documents, this type of literature might have had fewer citations. Furthermore, the bibliometric analysis methods we used can only be applied to general information, rather than full texts. Thus, we might have lost important information that only existed in the full text of the articles, such as the authors’ points of view and their prospective opinions of the field.
Our bibliometric analysis should help researchers to understand the trends and public interest in ICB for melanoma. The annual number of publications was rather small, without obvious research trends at the beginning of this century, but has gradually matured in the past 6 years. In the past 2 decades, the United States has contributed the most to this field, followed by China and Germany. The top 3 most productive journals were the
Comprehensive searching strategy.
T-lymphocyte associated protein-4
US Food and Drug Administration
immune checkpoint blockades
impact factor
programmed death receptor 1
ligands of programmed death receptor 1
This study was supported by grants from the National Natural Science Foundation of China (31800979 and 82102891), the Natural Science Foundation of China for Outstanding Young Scholars (82022060), the National Key Research and Development Program of China (2019YFA0111600 and 2019YFE0120800), the Major International (Regional) Joint Research Program of China (81620108024), the Natural Science Foundation of Hunan Province for outstanding Young Scholars (2019JJ30040), the Natural Science Foundation of Hunan Province of China (2018SK2082 and 2020JJ4884), the Scientific Research Project of Hunan Health and Family Planning Commission (B20180855), and the Youth Science Foundation of Xiangya Hospital (2020Q02).
None declared.