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. 2024 Sep 26;10(19):e38475. doi: 10.1016/j.heliyon.2024.e38475

Research landscape of radiotherapy for nasopharyngeal carcinoma from 1959 to 2022: A bibliometric analysis

Kaichun Huang a,b, Xinqing Yang g, Cuidai Zhang a,b, Xuejia Liu f, Yingji Hong a,b, Qingxin Cai a,b, Mei Li a,b, Zhixiong Lin a,b, Yizhou Yang a,b,c,d,e,⁎
PMCID: PMC11470525  PMID: 39397984

Abstract

Background

Radiotherapy, as the main treatment method for nasopharyngeal carcinoma (NPC), has evolved over time, but there has been no bibliometric study on NPC radiotherapy to date. In our study, the scientific achievements of NPC radiotherapy around the world were evaluated by bibliometric analyses, and the previous research hotspots and future trends are described.

Methods

Original articles related to NPC radiotherapy were obtained from the Web of Science Core Collection. To identify research hotspots and future trends, countries/regions, institutions, journals, references, authors, and keywords were evaluated and visualized by Excel, VOSviewer, and CiteSpace.

Results

From 1959 to 2022, 7139 original articles were collected. The annual publications showed an increasing trend, especially after 2011. China had the most publications (n = 3719, 52.09 %). Sun Yat-sen University has the most publications and citations among institutions. Jun Ma is most productive and SR Baker has the highest co-cited centrality. International Journal of Radiation Oncology-Biology-Physics is the core journal, with most publications, citations and co-citations. Analysis of keywords showed intensity-modulated radiotherapy and chemoradiotherapy were the main keywords, and multicenter showed the strongest burst.

Conclusion

NPC radiotherapy has attracted increasing attention, and precision and artificial intelligence may be the future trends in this field.

Keywords: Nasopharyngeal carcinoma, Radiotherapy, WoSCC, Bibliometric

1. Background

Nasopharyngeal carcinoma (NPC), characterized by distinct geographical distribution and particularly prevalent in east and southeast Asia, is an epithelial carcinoma that originates from the inner lining of the nasopharyngeal mucosa and is commonly found in the pharyngeal recess (fossa of Rosenmüller), which is distinct from other epithelial head and neck tumors, but originates from similar cell or tissue lineages with them [1]. The clinical behavior of NPC depends on its histological subtype. Epstein-Barr virus (EBV) infection is associated with it in approximately 70–80 percent of cases, and treatment does not vary by histological subtype. Mortality associated with NPC has improved over the last decade due to early detection and advances in treatment [2].

Radiotherapy is the primary treatment for NPC, especially in non-metastatic disease [1,3]. With the development of science and technology, photon-based radiotherapy has experienced traditional two-dimensional (2D) radiotherapy and three-dimensional (3D) conformal radiotherapy, and developed into intensity modulated radiation therapy (IMRT), which is the most commonly used for NPC at present [4,5]. The exploration of advanced radiotherapy techniques such as volumetric modulated arc radiation therapy (VMAT), proton therapy, carbon-ion radiotherapy and boron capture neutron therapy in the treatment of NPC is also progressing [[6], [7], [8], [9], [10]]. While great progress has been made in the study of radiotherapy for NPC over the past decades, and most studies of radiotherapy for NPC have focused on improving survival and reducing toxicity, it remains difficult to balance the efficacy of radiotherapy with the quality of life for patients [11,12].

Against the background of emphasizing the individualized comprehensive treatment for cancer patients, the exploration of radiotherapy combined with other treatments (chemotherapy, immunotherapy, etc.) seems to have become the current mainstream development direction for research on NPC [1]. On the basis of treatment strategies that combine multiple treatment modalities, balancing efficacy and adverse effects seems to become more difficult [13].

In this study, we applied bibliometric analysis to analyze the countries, institutions, journals, authors, references and keywords of documents related to NPC radiotherap, which no scholars explored before, for the purpose of systematically assessing the current status and research trends in NPC. The bibliometric analysis of NPC radiotherapy was carried out using quantitative research methods and visualization tools including VOSviewer [[14], [15], [16]] and CiteSpace [[17], [18], [19]], taking literature systems and biometric characteristics as the study objects.

2. Methods

2.1. Data retrieval strategy

The literature of original research on NPC and radiotherapy from 1900 to Oct. 2022 was searched from the Science Citation Index-Expanded (SCIE) of the Web of Science Core Collection (WoSCC). As one of the most professional and authoritative citation databases, WoSCC has a powerful index function, which contains basic information such as author, institution, country/region, funding institution, author keywords, as well as reference information. The search was conducted until Oct. 30, 2022, and only English original articles were collected. The following keywords were used in the database retrieval by Boolean search operators: ((TS=(carcinoma) OR TS=(cancer) OR TS=(tumor) OR TS=(neoplasm) OR TS=(sarcoma)) AND LA=(English) AND DT=(Article)) AND ((TS= (radiation therapy) OR TS= (radiation treatment) OR TS=(radiotherapy) OR TS=(RT)) AND LA=(English) AND DT=(Article)) AND ((TS=(nasopharyngeal) OR TS=(nasopharynx) OR TS=(rhinopharyngeal)) AND LA=(English) AND DT=(Article)). The search history is presented in Table S1. In this study, the impact factor (IF) of journals from the Journal Citation Reports (https://jcr.clarivate.com), and the H-index for journals was obtained from Scimago Journal & Country Rank (https://www.scimagojr.com).

2.2. Statistical and bibliometric analysis

The descriptive statistical analysis and generating graphs were performed on Microsoft Office Excel 2016 (Microsoft, Redmond, WA, USA), and an exponential regression model was used to evaluate the trends of annual publications by it. VOSviewer (1.6.18) and CiteSpace V (5.8.R3) were used for bibliometric visualization.

VOSviewer is a software developed by van Eck and Waltman for constructing and visualizing bibliometric networks, which was used to perform the co-citation analysis of authors/references/journals, co-occurrence analysis of author keywords, and co-authorship analysis of countries/institutions/authors.

CiteSpace, as another widely used bibliometric tool, was applied to perform co-authorship analysis among institutions, citation burst analysis of keywords, and timeline view analysis of co-cited references (label clusters with tiles, keywords and abstracts). The parameter settings of CiteSpace were as follows: time span = Jan. 1959–Dec. 2022, slice length = 1, selection criteria = top 50 per slice, node types = (reference/institution/keyword), pruning = (pathfinder and pruning the merged network), and visualization = (cluster view-static and show merged network).

3. Results

3.1. Analysis of the annual trend in publications on NPC radiotherapy

On the basis of the WoSCC database, 7139 publications related to NPC radiotherapy between 1900 and October 31, 2022 are included in this study, with the earliest published in 1959. With the exponential linear regression model, the annual publication volume of NPC radiotherapy showed an upward trend over time (Fig. 1, R2figR2 = 0.8849). It had a relatively stable growth before 2011, and a relatively rapid growth after that. Annual publications related to NPC radiotherapy exceeded 100 in 1996, 200 in 2002, and 500 in 2012, doubling in nine years. While the number of publications declined in 2018, the overall trend remained on the increase. This reveals that interest of scholars in NPC radiotherapy is gradually increasing, and it has become a research hotspot.

Fig. 1.

Fig. 1

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The annual publications curve showing the annual publication trend and exponential fitting curve of original articles on NPC radiotherapy from 1999 to 2022 in WoSCC database.

3.2. Analysis of publications by countries/regions, institutions and authors

In order to identify leaders in NPC radiotherapy research, we analyzed the countries/regions, institutions, and authors to which publications in this field belong from 1959 to 2022. Fig. 2A shows the top 10 countries/regions in terms of total number of NPC radiotherapy publications and their citations. China ranked first with 3719 publications (52.09 %) and 76,875 citations, the United States ranked second with 1190 publications (16.67 %) and 50,789 citations, and Taiwan ranked third with 597 publications (8.36 %) and 16,729 citations (Table 1). Although China has the largest number of publications, the analysis of collaborative relationships between countries reveals that the country/region with the highest total link strength (TLS) is the United States, followed by China, and Canada in third place (Fig. 2B).

Fig. 2.

Fig. 2

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Visualization of the analyses of countries/regions. (A) The top 10 productive countries/regions and citations of them. (B) Visualization network of the cooperative partnerships between countries/regions conducted by VOSviewer. The nodes with the same color represent the same cluster, implying a close partnership. The larger the node's size or the width of the connecting line, the closer the relative degree of co-occurrence.

Table 1.

Top 10 productive countries/regions and institutions related to radiotherapy of NPC.

Rank Countries/Regions Documents Percentage Citations TLS Institutions Documents Citations TLS
1 China 3719 52.09 % 76875 689 Sun Yat-sen University 1045 25720 1141
2 USA 1190 16.67 % 50789 757 The University of Hong Kong 252 10026 347
3 Taiwan 597 8.36 % 16729 180 The Chinese University of Hong Kong 230 13397 321
4 Japan 239 3.35 % 4589 98 Fudan University 230 5412 286
5 Singapore 196 2.75 % 7496 204 Guangxi Medical University 202 3224 215
6 Canada 190 2.66 % 9910 241 Chang Gung University 157 3968 311
7 Italy 186 2.61 % 4189 135 Southern Medical University 154 2247 224
8 Turkey 164 2.30 % 2703 86 Central South University 140 3406 108
9 England 156 2.19 % 6802 157 Fujian Medical University 127 2578 218
10 Netherlands 143 2.00 % 7022 176 Guangzhou Medical University 125 2196 208
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The details of the top 10 active institutions are listed in Table 1, with Sun Yat-sen University in China having the largest of 1045 publications (Fig. 3A, S = 0.9337, (Q, S) = 0.7002) and 25720 citations, obviously higher than any other institutions. The second one was the University of Hong Kong (252 publications and 10026 citations). The Chinese University of Hong Kong and Fudan University were tied for third with 230 publications, but the number of citations of the Chinese University of Hong Kong (13,397 citations) was significantly higher than that of Fudan University (5412 citations). In addition, the partnership among institutions shows that Sun Yat-sen University has closest cooperation with institutions in the field, with the highest TLS = 1141 (Fig. 3B).

Fig. 3.

Fig. 3

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Visualization for the analyses of institutions. (A) The top 10 productive institutions on NPC radiotherapy original articles. (B) Visualization network of the cooperative partnerships between institutions conducted by VOSviewer.

The top 10 productive authors and the top 10 co-cited authors with centrality related to NPC radiotherapy from 1959 to 2022 are shown in Table 2. The visualization of cooperative partnerships between authors based on the number of publications is shown in Fig. 4A. The top ten authors were all from China, among which Jun Ma had the most publications (n = 238), the most citations (n = 8488), and the highest TLS value of 2297. Ying Sun ranked second with 212 publications, 6992 citations and a TLS value of 2088. Among the top 10 co-cited authors, six were from the United State. In terms of centrality for co-cited authors, SR Baker from the United States was ranked first (C = 0.46), KK FU from the United States was ranked second (C = 0.44), and JH Yan from China was ranked third (C = 0.37). The TLS based visualization of the co-cited authors is shown in Fig. 4B, with AWM Lee at the center of the field followed by ATC Chan and DTT Chua.

Table 2.

The 10 most productive authors and the top 10 co-cited authors with the highest centrality.

Rank Author Documents Countries/Regions Citations TLS Co-Cited Author Countries/Regions Citations TLS Centrality
1 Ma, Jun 238 China 8488 2297 BAKER, SR USA 41 1026 0.46
2 Sun, Ying 212 China 6992 2088 FU, KK USA 224 5806 0.44
3 Mai, Hai-qiang 135 China 3095 1487 YAN, JH China 147 3350 0.37
4 Mao, Yan-ping 117 China 4232 1130 NEEL, HB USA 97 2179 0.31
5 Tang, Ling-long 112 China 3909 1067 LEVENDAG, PC Netherlands 205 5382 0.29
6 Chen, Lei 108 China 4006 1056 SYED, AMN USA 47 1079 0.28
7 Liu, Li-zhi 91 China 3616 790 NOWAK, PJCM Austria 36 852 0.24
8 Chen, Qiu-yan 90 China 1317 1079 HUNT, MA USA 136 2703 0.24
9 Lin, Ai-hua 88 China 3670 857 EISBRUCH, A USA 699 16799 0.23
10 Hu, Chaosu 87 China 1462 372 HO, JHC Hongkong 257 5381 0.22
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Fig. 4.

Fig. 4

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Authors partnership Network. Visualization network of authors (A) and co-cited authors (B) related to NPC radiotherapy.

3.3. Analysis of journals and co-cited journals

To identify the authoritative journals in the field of NPC radiotherapy, the journals and co-cited journals in this field were analyzed and their top 10 are listed in detail in Table 3, and half of the top 10 journals with publications and 7 of the top 10 co-cited journals with citations belong to the United States. The top 10 cited and co-cited journals were all classified as Journal Citation Reports (JCR) Q1/Q2 in 2021, except Oncotarget, which has not been included in WoSCC database since 2017. According to the network visualization map (Fig. 5A), density map (Fig. 5B) and co-citation network visualization map of journals in this field (Fig. 5C), it is not difficult to find that International Journal of Radiation Oncology - Biology - Physics, whose H-index is 257, is the core journal in this field. In the field of NPC radiotherapy, the journal had the most publications (n = 449), the highest total citations of 32,202, and the highest co-citations of 27585 among journals. The second and third most productive journals were Head and Neck-Journal for the Sciences and Specialties of the Head and Neck (n = 284) and Radiotherapy and Oncology (n = 237). The second and third most co-cited journals were Journal of Clinical Oncology (10030 citations) and Radiotherapy and Oncology (8817 citations), and New England Journal of Medicine had the highest H-index of 1079 and the highest IF of 176.082 among the top 10 journals, which shown its far-reaching impact in the field. However, the IF of the top 10 journals is not more than 10, while top 10 co-cited journals have excellent IFs. Among the top 10 co-cited journals, New England Journal of Medicine had the highest IF, followed by Lancet Oncology (IF = 54.433) and Journal of Clinical Oncology (IF = 50.793).

Table 3.

The top 10 productive journals and the top 10 co-cited journals with TLS about radiotherapy of NPC.

Rank Journals Countries Publications Citations TLS H-index IF JCR Co-Cited Journals Countries Co-Citations TLS H-index IF JCR
1 International Journal of Radiation Oncology - Biology - Physics USA 449 32202 12847 257 8.013 Q1 International Journal of Radiation Oncology - Biology - Physics USA 27585 722047 257 8.013 Q1
2 Head and Neck-Journal for the Sciences and Specialties of the Head and Neck USA 284 6703 4316 127 3.821 Q1 Journal of Clinical Oncology USA 10030 322812 574 50.739 Q1
3 Radiotherapy and Oncology Netherlands 237 9616 5224 163 6.901 Q1 Radiotherapy and Oncology Netherlands 8817 283208 163 6.901 Q1
4 Oral Oncology England 194 3661 3778 121 5.972 Q1 Cancer USA 8799 320943 315 6.921 Q1
5 Radiation Oncology England 155 2611 2432 78 4.309 Q2 Head and Neck-Journal for the Sciences and Specialties of the Head and Neck USA 5466 219900 127 3.821 Q1
6 Cancer USA 150 9441 4282 315 6.921 Q1 Cancer Research USA 3199 112111 466 13.312 Q1
7 Frontiers in Oncology Switzerland 131 526 1754 102 5.738 Q2 Laryngoscope USA 3117 218156 157 2.970 Q2
8 Oncotarget USA 123 2239 1930 148 5.168 (2016) Q2(2016) Oral Oncology England 3087 109849 121 5.972 Q1
9 Plos One USA 120 2734 1571 367 3.752 Q2 New England Journal of Medicine USA 2482 92989 1079 176.082 Q1
10 BMC Cancer England 111 2012 2006 139 4.638 Q2 Lancet Oncology England 2317 84610 355 54.433 Q1
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Fig. 5.

Fig. 5

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Visualization of the analyses of journals and co-cited journals. Visualization network and density map of journals (A and B) and network of co-cited journals (C) related to NPC radiotherapy. In the density map, brighter nodes indicate greater journal influence.

3.4. Analysis of references and co-cited references

The top 10 references with most citations of NPC radiotherapy research are shown in Table 4. The article “Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized intergroup study 0099” published by Al-sarraf M et al. in Journal of Clinical Oncology in 1998 was the most cited (n = 1622). It was far more cited than the second most cited article “Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial” published by Nutting C et al. (n = 1082) from Lancet Oncology in 2011. In addition to the above references, no other references have been cited more than 1000 times. The results reveal that only 12 articles have been cited more than 500 times and 84 articles have been cited more than 200 times in this field. We found that 9 of the 10 most cited articles were clinical studies, and all of them were published before 2007 except for the second, fifth and ninth articles.

Table 4.

Top 10 most cited original articles concerning NPC radiotherapy.

Rank Title Journal First Author Year Citations
1 Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized intergroup study 0099 Journal of Clinical Oncology Al-Sarraf, M 1998 1622
2 Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial Lancet Oncology Nutting, C 2011 1082
3 Intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: an update of the UCSF experience International Journal of Radiation Oncology - Biology - Physics Lee, N 2002 772
4 Quantification of plasma Epstein-Barr virus DNA in patients with advanced nasopharyngeal carcinoma New England Journal of Medicine Lin, JC 2004 605
5 Head and neck squamous cell carcinoma: update on epidemiology, diagnosis, and treatment Mayo Clinic Proceedings Marur, S 2016 600
6 Phase III study of concurrent chemoradiotherapy versus radiotherapy alone for advanced nasopharyngeal carcinoma: positive effect on overall and progression-free survival Journal of Clinical Oncology Lin, JC 2003 586
7 Quantitative analysis of cell-free Epstein-Barr virus DNA in plasma of patients with nasopharyngeal carcinoma Cancer Research Lo, YMD 1999 585
8 Retrospective analysis of 5037 patients with nasopharyngeal carcinoma treated during 1976–1985 - overall survival and patterns of failure International Journal of Radiation Oncology - Biology - Physics Lee, AWM 1992 521
9 Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial Lancet Oncology Sun, Y 2016 516
10 Xerostomia and quality of life after intensity-modulated radiotherapy vs. conventional radiotherapy for early-stage nasopharyngeal carcinoma: initial report on a randomized controlled clinical trial International Journal of Radiation Oncology - Biology - Physics Pow, E 2006 509
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The visualized network of co-cited references is shown in Fig. 6A, and the top 10 of them in co-citations are listed in Table 5. The article "Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized intergroup study 0099″ published in Journal of Clinical Oncology by Al-Sarraf M et al. ranks first with 949 co-citations and has the largest TLS (n = 15,655). In addition, we clustered co-cited references, and the results are presented as a timeline view (Fig. 6B). It reveals that "mean dose" (cluster 0, log-likelihood ratio = 16,717.43, P < 0.0001) and "NPC radioresistance" (cluster 57, log-likelihood ratio = 930.32, P < 0.0001) were the research hotspots in the past decade, and the former was much more popular than the latter. The mean dose in cluster 0 includes the mean dose of NPC radiotherapy and chemotherapy, while cluster 57 includes the radioresistance of NPC tissues and cells in clinical and laboratory studies. Looking at the past two decades, in addition to the previously mentioned clusters 0 and 57, "treatment result" (cluster 2, log-likelihood ratio = 5318.94, P < 0.0001) and "parotid gland" (cluster 3, log-likelihood ratio = 22,567.15, P < 0.0001) are also research hotspots in the field of NPC radiotherapy.

Fig. 6.

Fig. 6

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The co-cited references related to NPC radiotherapy. (A) Visualization network of co-cited references. (B) The timeline view of co-cited references related to NPC radiotherapy with relevant clusters.

Table 5.

Top 10 co-cited references involved in NPC radiotherapy.

Rank Title Year First Author Journal IF Co-citations TLS
1 Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized intergroup study 0099 1998 Al-Sarraf, M Journal of Clinical Oncology 50.739 949 15655
2 Intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: an update of the UCSF experience 2002 Lee, N International Journal of Radiation Oncology - Biology - Physics 8.013 529 8719
3 Phase III study of concurrent chemoradiotherapy versus radiotherapy alone for advanced nasopharyngeal carcinoma: Positive effect on overall and progression-free survival 2003 Lin, JC Journal of Clinical Oncology 50.739 439 7671
4 Nasopharyngeal carcinoma 2005 Wei, WI Lancet 202.731 417 4654
5 How does intensity-modulated radiotherapy versus conventional two-dimensional radiotherapy influence the treatment results in nasopharyngeal carcinoma patients? 2011 Lai, SZ International Journal of Radiation Oncology - Biology - Physics 8.013 389 5854
6 Intensity-modulated radiation therapy with or without chemotherapy for nasopharyngeal carcinoma: Radiation therapy oncology group phase II trial 0225 2009 Lee, N Journal of Clinical Oncology 50.739 370 6146
7 Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial 2016 Sun, Y Lancet Oncology 54.433 359 5907
8 Nasopharyngeal carcinoma 2016 Chua, MLK Lancet 202.731 353 3255
9 Nasopharyngeal carcinoma 2019 Chen, YP Lancet 202.731 352 3399
10 Nonparametric-estimation from incomplete observations 1958 Kaplan, EL Journal of the American Statistical Association 4.369 345 5123
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3.5. Keyword analysis of citation burst and co-occurrence

The keyword co-occurrence analysis with VOSviewer can clarify the co-occurrence relation between keywords and identify hot topics in the NPC radiotherapy field. As shown in Table 6, the top 20 keywords of co-occurrence frequency mainly involved radiotherapy, chemotherapy and prognosis of NPC. A visualization of the network for the top 50 co-occurrence keywords is shown in Fig. 7A. Obviously the core nodes of the five clusters represented by different colors in the figure are "nasopharyngeal carcinoma", "survival", "intensity-modulated radiotherapy" and "head and neck" cancer "and" chemoradiotherapy ".

Table 6.

Top 20 co-occurrence keywords involved in the research of NPC radiotherapy.

Rank Keywords Occurrences TLS Rank Keywords Occurrences TLS
1 Nasopharyngeal Carcinoma 3601 4503 11 EBV 171 242
2 Radiotherapy 1300 2028 12 Cisplatin 160 344
3 Intensity-Modulated Radiotherapy 873 1409 13 Metastasis 130 238
4 Head and Neck Cancer 690 1004 14 Cancer 122 186
5 Prognosis 450 879 15 Nasopharynx 119 159
6 Chemoradiotherapy 442 921 16 Apoptosis 117 162
7 Chemotherapy 322 691 17 Quality of Life 114 229
8 Survival 215 457 18 Radiation 110 150
9 Induction Chemotherapy 194 462 19 Xerostomia 105 187
10 Magnetic Resonance Imaging 183 293 29 Prognostic Factor 102 202
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Fig. 7.

Fig. 7

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Visualization of core author keywords related to NPC radiotherapy. (A) Network visualization of top 50 author keywords. (B) Top 25 keywords with the strongest citation bursts in publications.Red indicates the time when the keyword was mainly present.

The top 25 keywords with the strongest citation bursts resulting from the analysis of keyword citation burst in NPC radiotherapy from 1959 to 2022 are listed in Fig. 7B from top to bottom in terms of burst strength. The analysis, carried out by CiteSpace, includes the burst intensity and duration, which can reflect the research hotspots of NPC radiotherapy in a certain period. We found that nine of these keywords bursts ended in 2022, and they lasted less than six years. This reveals that they may be emerging research hotspots in recent years. The keyword with strongest burst was the “multicenter” (Strength = 71.46), followed by “outcome” (Strength = 53.21), and “irradiation” (Strength = 44.57), “local control” (Strength = 31.02) and “proliferation” (Strength = 26.63) rank from third to fifth. In addition, the keyword "failure" has been burst for the longest time (23 years), which may mean that it has been a hot topic related to NPC radiotherapy for years.

4. Discussion

In recent years, bibliometric analysis has been widely used by scholars to shed light on the current and evolving trends in cancer research [[20], [21], [22]]. Although currently excellent local-regional control rates have been achieved with the use of IMRT, the management of failure remains one of the greatest challenges for NPC, so it is necessary to identify current and future hotspots of NPC radiotherapy research [23,24]. As we understood, this study is the first systematic literature search and bibliometric analysis for NPC radiotherapy research, and illustrates past research hotspots and future research trends.

Due to the unique epidemiology of NPC, which includes race, striking geographical distribution, dietary habits of susceptible populations, Epstein-Barr virus (EBV) infection, genetic and environmental risk factors, it is not surprising that China ranks first in the number of publications (52.09 %) on NPC radiotherapy [1,2,25]. The top 10 most productive institutions are all from China and are concentrated in the southeastern coastal region, which also indicates the dominance of China in the field. It is obvious that China is engaged in extensive cooperation with other countries/regions in this field, and the Sun Yat-sen University ranks first in the publications and citations and is the leader of NPC radiotherapy research in the world with far more publications and citations than other institutions.

We identified influential experts related to NPC radiotherapy by publications and citations of authors and centrality of co-cited authors. The top 10 authors are all from China and most of them belong to Sun Yat-sen University, which provides evidence for the dominant position of China, especially Sun Yat-sen University, in NPC radiotherapy research. Despite such great publications and citations by scholars from mainland China, five of the top 10 co-cited authors with centrality are from the United States, while one is from mainland China and he does not rank within the top 10 of publications and citations. Thus, the influence of the United States in the research of NPC radiotherapy remains strong.

4.1. Limitations and future research directions

According to the results of the journals and co-cited journals analysis, the International Journal of Radiation Oncology - Biology - Physics is the most core journal for NPC radiotherapy research. Intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: an update of the UCSF experience, published by N Lee et al., in 2002, is by far the most cited article on NPC radiotherapy in the journal, and the article lays the foundation for IMRT to become a common treatment for NPC by revealing its excellent local area control and better protection of neighboring organs [26]. Apart from it, three other papers published in the journal ranked in the top 10 most cited and co-cited references, which also had a significant impact on NPC radiotherapy research. AMN Lee et al. performed a retrospective analysis of 5037 NPC patients from Queen Elizabeth Hospital in Hong Kong between 1976 and 1985. Based on a large number of patients and long-term observation, they made a detailed analysis of the characteristics of patients, their failure pattern and survival rate, and they concluded that the improvement of technical precision and dose control of radiotherapy, prophylactic irradiation of patients with negative lymph nodes, improved computed tomography and flexible endoscopy for local evaluation, adjuvant chemotherapy, etc., are beneficial to improve the survival rate of patients, and provide a more solid foundation for future clinical trials to improve treatment [27]. The study of E Pow et al. revealed in 2006 that IMRT was significantly superior to conventional radiotherapy in terms of parotid gland preservation and improvement of life quality in early-stage disease [28]. Based on this, more and more scholars began to focus on side effects and the life quality of NPC patients after radiotherapy. Compared with 2D radiotherapy, IMRT has a greater improvement in the treatment effect of nasopharyngeal cancer patients, mainly manifested as a higher local tumor control rate in nasopharyngeal cancer patients, especially in early T stage patients, as revealed by SZ Lai et al. from the team of Ma Jun [29]. It is obvious that the research published in International Journal of Radiation Oncology - Biology - Physics has greatly promoted the popularization of advanced techniques of NPC radiotherapy and the change of treatment strategies.

4.2. Challenges in clinical application and further recommendations

Another well-known journal in the field of radiotherapy, Radiotherapy and Oncology, also has a significant influence on NPC radiotherapy research. Although there are fewer publications related to NPC radiotherapy in this journal than in Head and Neck-Journal for the Sciences and Specialties of the Head and Neck (237 vs. 284), publications in this field published in Radiotherapy and Oncology are cited far above in another (9616 vs. 6703). However, none of the publications from Radiotherapy and Oncology ranks in the top 10 most cited and co-cited references. The same situation applies to Cancer, and only 150 publications on NPC Radiotherapy were published in it (ranking eighth) with the total citations of 9441 (ranking fourth) after Radiotherapy and Oncology. Nevertheless, the high citation frequency of their publications in NPC radiotherapy research indicates that they have had a profound impact in the field.

Although there are few publications on NPC radiotherapy in the Journal of Clinical Oncology (n = 63), some key studies have been published in it. Based on its second rank in both cited and co-cited journals and an article from it ranked first in both cited and co-cited references, Journal of Clinical Oncology highlights its key position in NPC radiotherapy research. A randomized phase III trial published in the Journal of Clinical Oncology in 1998 compared chemoradiotherapy with radiotherapy alone for patients with NPC and found that chemoradiotherapy was superior to radiotherapy alone in terms of progression-free survival (PFS) and overall survival (OS) for patients with advanced NPC [30]. This study is the one mentioned above that ranks first in both cited (n = 1622) and co-cited (n = 949) references. Another phase III study published in the same journal in 2003 by JC Lin et al. confirmed the conclusion of the previous study [31]. They have laid a solid foundation for the clinical application and research of concurrent chemoradiotherapy for NPC, and promoted the change of treatment strategy for NPC. It is interesting to note that only three of the top 10 cited and co-cited references were published in the last decade, and two of them were reviews. The only one original article of the three papers, a multicenter Phase III clinical trial published in 2016 in Lancet Oncology by Y Sun et al., revealed that the addition of induction chemotherapy to concurrent chemoradiotherapy may benefit patients with locally advanced NPC [32].

Clustering based on co-cited references helps scholars understand research hotspots in a particular field over a certain period of time. In order to clarify the research hotspots, we analyzed the references related to NPC radiotherapy from 1959 to 2022 and their significance according to the timeline. We found that the cluster 0 ″mean dose" was the most popular research direction in recent years, which contained most publications among clusters (n = 2653). Studies in cluster 0 mainly focused on adjuvant chemotherapy, detectable plasma EBV DNA, curative radiotherapy, tumor response, T4 NPC, and 5-year disease-free survival (DFS). With the innovation of radiotherapy technology, especially the popularization of IMRT, scholars who have broken the limitations in recent years have focused on the actual average total dose and fractionated dose delivered to the gross tumor volume (GTV), the clinical target volume (CTV) and the average dose delivered to organs at risk (OARs) in NPC radiotherapy research, they were designed to avoid unnecessary irradiation of low-risk areas for reducing a range of toxic side effects such as dysphagia, xerostomia and radiation-induced facial lymphedema, while improving patients' survival [[33], [34], [35], [36]]. This means that in recent years, research on NPC radiotherapy has focused on dosimetry. Whether it is the improvement of the GTV/CTV dose and boundaries or the dose limitation of OARs, the ultimate goal is to achieve the best dose distribution to maintain a balance between quality of life and survival, and scholars are still searching for that balance, and may continue to do so for a long time [[37], [38], [39]]. In the contemporary era with various tumor treatment methods, radiotherapy alone has long been unable to meet the needs of NPC treatment, and radiotherapy in combination with chemotherapy/immunotherapy has become the current mainstream. It seems that the current research on the dose/pattern of radiotherapy has reached a bottleneck. Academics have shown great enthusiasm for studying the dose/pattern of chemotherapy/immunotherapy in combination with radiotherapy for NPC, and future research in this field may focus on a combination treatment strategy of multiple drugs and radiotherapy in the absence of radiotherapy technological innovations [[40], [41], [42], [43], [44]]. Due to the association of EBV infection with the pathogenesis of NPC and the concentration of plasma EBV DNA has impact on the treatment and tumor progression of NPC, it has been studied as a biomarker for years [45,46]. To guide more effective treatment strategies, the exploration of various biomarkers, including EBV, clinical/imaging features, etc., may be a research trend in the future [[47], [48], [49]].

Looking at clusters 2 and 3 with larger sample sizes in recent years, scholars seem never to reduce their concern about the toxic side effects and various outcomes of treatment. This also has been confirmed by citation burst and co-occurrence analysis of keywords. Over time, scholars no longer only pay attention to the OS of NPC patients after radiotherapy, but also a variety of outcomes, including DFS, PFS, disease-specific survival (DSS), distant metastasis-free survival (DMFS), loco-regional relapse free survival (LRRFS), etc., have gradually been paid attention, which means a more comprehensive and objective evaluation of treatment efficacy [50,51]. Since NPC patients have a longer survival time after treatment, demand of patients for better life quality is increasing. As an unavoidable problem in radiotherapy, toxicity has always been a very vexing problem and is also a hot topic in recent years according to the citation burst analysis of keywords (Strength = 17.8). In the background, radiotherapy preserving efficacy and attenuating toxicity gradually becomes the research trend of scholars. The team of ZX Lin and the team of JJ Pan and SJ Lin from China have made prominent contributions to preserve efficacy and attenuate toxicity radiotherapy of NPC. The team of SJ Lin and JJ Pan proposed the concept of reduced target volume by reducing the scope of subclinical lesions for the first time in the world in 2009, and subsequently updated their research results in 2014 and 2022, which was regarded as an improved volume reduction pattern for NPC radiotherapy without affecting the efficacy [[52], [53], [54]]. The team of ZX Lin tends to conduct a series of studies on a specific OAR, and their research on the thyroid in NPC radiotherapy has had a great international impact. They carefully evaluated the correlation between the size of thyroid glands and the changes of related hormones in NPC patients after radiotherapy, and concluded that the radiation-induced changes depend on the average thyroid dose and the correlation between thyroid antibodies and thyroid hormones in radiation-induced hypothyroidism, and proposed to reduce thyroid dose in NPC radiotherapy [55,56]. The comparison of radiation dose risk for thyroid and pituitary gland, and follow-up of thyroid volume and hormone up to 48 months after radiotherapy further supported the previous conclusions [57,58]. The radiation-induced hypothyroidism prediction model/nomogram to guide more effective thyrotoxic reduction radiotherapy strategies was also developed by them [59,60]. Although the two teams have given us two directions to explore preserve efficacy and attenuate toxicity of NPC radiotherapy, advance patterns remain to be further studied.

We find that positron emission tomography (PET, Strength = 21.92) is also a core keyword in NPC radiotherapy research. The currently advocated individual radiotherapy is in essence precision radiotherapy which means preserving effect and reducing toxicity,and the use of PET can make the treatment more accurate no matter before, during and after NPC radiotherapy [[61], [62], [63]]. There are two main directions in NPC radiotherapy research of PET in recent years. One is PET, used for NPC, combined with artificial intelligence (AI) such as deep learning for early cancer detection, diagnosis, classification and grading, molecular characterization of tumors, prediction of patient prognosis and treatment response, personalized therapy, automated radiotherapy workflow, etc [[64], [65], [66]]. Another direction is to treat imaging guidance of PET as a biomarker for biology-guided radiotherapy (BGRT) [67]. BGRT has been shown to benefit patients with NPC, and PET without the use of the unconventional tracer 18F-fluorodeoxyglucose has been shown to have the potential to direct clinical BGRT [68,69]. Rapid advances in functional and biological imaging, predictive biomarker/assays, the development of BGRT induced by different biomarkers, and the advantages of BGRT in individualized precision therapy indicate that BGRT may be one of long-term goals for the development of NPC radiotherapy [70].

5. Conclusions

In conclusion, precision is the vital goal for cancer treatment, especially in radiotherapy. The pursuit of precision strike treatment strategies that preserve efficacy and attenuate toxicity is a continuing hot topic in NPC radiotherapy. Based on this, the exploration of the application of AI in radiotherapy, radiotherapy in combination with other therapies and the BGRT depending on various biomarkers are likely to be long-term research trends in the near future for NPC radiotherapy.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Data availability statement

Data included in article/supplementary material is referenced in the article.

Funding

This research was funded by Science and Technology Special Fund of Guangdong Province of China, grant number 190829105556145.

CRediT authorship contribution statement

Kaichun Huang: Writing – original draft, Data curation. Xinqing Yang: Writing – review & editing, Validation, Project administration. Cuidai Zhang: Visualization, Formal analysis. Xuejia Liu: Visualization. Yingji Hong: Data curation. Qingxin Cai: Visualization, Data curation. Mei Li: Data curation. Zhixiong Lin: Writing – review & editing, Validation, Supervision, Project administration, Funding acquisition, Conceptualization. Yizhou Yang: Writing – original draft, Validation, Project administration, Methodology, Conceptualization.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

Thanks to Prof. Dr. Gabriele and Dr. Beatrice Menz, who are affiliated to the Department of Radiation Oncology, Faculty of Medicine, University of Freiburg, Freiburg, Germany, German Cancer Consortium (DKTK), Partner Site Freiburg, Freiburg, Germany and German Cancer Research Center (DKFZ), Heidelberg, Germany, for the polishing of the manuscript language and grammar and for the assistance of the manuscript revision.

Footnotes

Appendix A

Supplementary data to this article can be found online at https://doi.org/10.1016/j.heliyon.2024.e38475.

Contributor Information

Kaichun Huang, Email: 958164603@qq.com.

Xinqing Yang, Email: greensnow2182@vip.163.com.

Cuidai Zhang, Email: zcd159179@163.com.

Xuejia Liu, Email: 625879949@qq.com.

Yingji Hong, Email: 598380936@qq.com.

Qingxin Cai, Email: 1003834128@qq.com.

Mei Li, Email: limei00182@139.com.

Zhixiong Lin, Email: zxlin5@qq.com.

Yizhou Yang, Email: yangyizhou0510@163.com.

List of abbreviations

2D

two-dimensional

3D

three-dimensional

AI

artificial intelligence

BGRT

biology-guided radiotherapy

CTV

clinical target volume

DFS

disease-free survival

DMFS

distant metastasis-free survival

DSS

disease-specific survival

EBV

Epstein-Barr virus

GTV

gross tumor volume

IF

impact factor

IMRT

intensity modulated radiation therapy

JCR

Journal Citation Reports

LRRFS

loco-regional relapse free survival

NPC

nasopharyngeal carcinoma

OARs

organs at risk

OS

overall survival

PFS

progression-free survival

SCIE

Science Citation Index-Expanded

TLS

total link strength

VMAT

volumetric modulated arc radiation therapy

WoSCC

Web of Science Core Collection

Appendix A. Supplementary data

The following is the Supplementary data to this article.

Multimedia component 1
mmc1.xlsx (9.4KB, xlsx)

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