Current and future of immunotherapy for thyroid cancer based on bibliometrics and clinical trials

Abstract

Background: Thyroid cancer is a leading endocrine malignancy, with anaplastic and medullary subtypes posing treatment challenges. Existing therapies have limited efficacy, highlighting a need for innovative approaches.

Methods: We analyzed 658 articles and 87 eligible clinical trials using bibliometric tools and database searches, including annual publication and citation trends, were executed using Web of Science, CiteSpace, and VOS Viewer.

Results: Post-2018, there is a surge in thyroid cancer immunotherapy research, primarily from China and the University of Pisa. Of the 87 trials, 32 were Phase I and 55 were Phase II, mostly exploring combination therapies involving immune checkpoint inhibitors.

Conclusion: The study's dual approach verifies the swift advancement of thyroid cancer immunotherapy from diverse perspectives. Immune checkpoint inhibitors have become the preferred regimen for advanced MTC and ATC in late therapeutic lines. However, since ICB plays a pivotal role in ATC, current clinical trial data show that ATC patients account for more and the curative effect is more accurate. Anticipated future developments are inclined toward combination regimens integrating immunotherapy with chemotherapy or targeted therapies. Emerging approaches, such as bispecific antibodies, cytokine-based therapies, and adoptive cell therapies like CAR-T and TCR-T, are exhibiting considerable potential. Upcoming research is expected to concentrate on refining the tumor immune milieu and discovering novel biomarkers germane to immunotherapeutic interventions.

Keywords: Anaplastic thyroid carcinoma (ATC); Clinical Trials; Immune checkpoint inhibitor; Immunotherapy; Medullary thyroid carcinoma (MTC); PD-1/PD-L1; Scientometric analysis; Thyroid cancer.

Fig. 1

a The number of publications and the number of citations by year. The regression model is y = 3.8229e^0.102x (R² = 0.3968). b The geographical visualization of publications for immunotherapy in thyroid cancer

Fig. 2

a The top 11 countries with the largest number of publications. b The map of international cooperation relationship. The size of a node represents the publication number of a country. c The top 10 institutions with the largest number of publications. d The co-occurrence map of institutions which had related publications in the field of immunotherapy in thyroid cancer

Fig. 3

a Highly published authors. b The network map of researching authors who were co-cited over 30 times

Fig. 4

a The co-citation analysis of the journals. b The co-citation analysis of references

Fig. 5

a The time axis view of references. b The high reference outbreak analysis

Fig. 6

a The co-occurrence map of the keywords with high frequency. b The overlay visualization of keywords. The average year of keyword by assigning different colors to the nodes. c The timeline view of keywords from Citespace. The top 11 clusters were selected in our analysis. d The top 20 keywords with the strongest citation bursts from Citespace

Fig. 7

a The annual distribution of clinical trials from 1997 to 2022. The start date was regarded as the time of clinical trials. b The distribution of phases for all clinical trials. c The distribution of the main types of immunotherapies in all clinical trials

Fig. 8

a The annual distribution of the main types of immunotherapies including ICB, CK, ACT, and Vaccines from 1997 to 2022. b The distribution of some common combined therapies. ICB plus TI referred to ICB combined with targeted therapy. ICBs in combination referred to several ICBs that were used simultaneously in a clinical trial. CK (single/combined) referred to CK that was used as a single agent or combined with other therapies. ACT (single/combined) referred to ACT that was used as a single agent or combined with other therapies. V (single/combined) referred to vaccines that were used as a single agent or combined with other therapies. ICB plus Ch referred to ICB combined with chemotherapy. ICB plus Ra referred to ICB combined with radiotherapy

Fig. 9

The mechanism of PD-1 immune checkpoint inhibitor combined with lenvatinib (TKI) in the treatment of thyroid cancer