Radiation oncology has undergone transformative advances in delivery technology and treatment precision over the past several decades. Photon-based radiotherapy, encompassing conventional X-ray techniques and later intensity-modulated approaches, has served as the backbone of radiotherapy [1]. Proton therapy, although only introduced clinically in the 1950s and approved as a radiation treatment option by the United States Food and Drug Administration in 1988, has achieved increasing clinical uptake in recent decades [2], driven by technological advancements in delivery and declining infrastructure costs [3].

Despite the rapid rise in clinical interest in proton therapy, the bibliometric trajectory of proton- versus photon-based research has not been systematically compared. Evaluating how research output has evolved according to the modality of radiation treatment and by study design can provide insights into the scientific maturity, thematic focus, and evidence hierarchy underpinning each field.

The aim of this analysis is to map the global evolution of the photon and proton radiotherapy literature from 1940 to 2025 and to delineate differences in study-design composition between the two modalities.

We searched PubMed (Medline), EMBASE, and Cochrane Library up until November 13, 2025. An evidence synthesis librarian (GB) selected and applied keywords and subject headings from the controlled vocabulary thesaurus in EMBASE (Emtree) and PubMed (MeSH) (see Supplementary Methods for search strategy). No restrictions for language or article type were used.

Search results were screened to identify which articles reported on photon and proton radiotherapy. Articles that overlapped were classified as photon. Articles were further classified based on study design—commentary/editorial, dosimetry study, technical/physics study, case report/series, cohort study, phase I/II trial, phase III trial, review/meta-analyses or protocols. All screening and classification were conducted in duplicate by one human reviewer (RC) and within a heuristic-based software environment employing ChatGPT-5 (DZ). Any discrepancies were resolved by discussion with the other coauthors, with ChatGPT-5 probed to provide logic behind its screening decision.

Trends in the number of articles over time by photon and proton radiotherapy, and further by study type, were depicted graphically. All analyses were conducted using StataBE 18.0 (StataCorp LLC, College Station, TX, USA).

A total of 19,961 articles were published from 1940 to 2025. Of these, 53% studied photon radiotherapy, and 47% studied proton radiotherapy. The overall literature has expanded exponentially since the 1990s (Fig. 1), with over 1,000 articles published in 2025. Photon publications historically predominated, but proton-related research accelerated rapidly after 2015. Subgroup analyses revealed consistent growth of proton studies across study types (Fig. 2)—commentaries, dosimetry/technical studies, clinical trials and reviews. There are now nearly double the number of protocol publications on protons than photons.

From our bibliometric analysis, we found that there has been an exponential increase in radiotherapy research since the 1990s. Furthermore, there has been a specific acceleration in proton radiotherapy research over the past decade, both in absolute volume and relative to photon literature. Whereas photon publications historically dominated, the trend has reversed, marking a paradigm shift in the research landscape. Subgroup analyses by study type reveal this trend prevails across all studies. Our finding of an increased volume of commentary, dosimetry/technical studies, and clinical trials suggests there is an overall growing interest in protons across the entire spectrum of research.

The rapid expansion of proton therapy centers worldwide has created an urgent need for high-quality research to better define the biological, clinical, and technical benefits of this modality so that patients can receive the most appropriate and evidence-based treatment. In this context, the marked rise in proton-related publications over the past decade is encouraging. It reflects growing scientific engagement with this treatment modality and aligns with technological advances such as on-board volumetric imaging [4], pencil-beam scanning [5], adaptive proton therapy [6], and emerging ultra-high-dose-rate approaches [7,8]. It is also particularly noteworthy that more phase III trials are now being published with proton therapy than photon therapy (Fig. 2G), as the proton community seems to be committed to both producing voluminous research as well as high-quality phase III research despite fewer than 2% of external beam radiotherapy courses in the United States—the country with the most proton therapy centers—being delivered with proton therapy [2].

While our analysis shows that the growth in proton research has coincided with a decline in photon therapy publications, this should not be interpreted as reducing the clinical relevance of photon therapy. Photon-based radiotherapy remains the cornerstone of cancer treatment worldwide, and the observed decline may underscore a gap in ongoing scientific investment. Sustained momentum in photon research is essential to drive technological innovation and, importantly, to strengthen the evidence base needed for personalized radiotherapy. Photon therapy continues to evolve rapidly, with innovations such as magnetic resonance imaging linear accelerator systems [9], online adaptive radiotherapy [10], integration of functional and biological imaging [11], and artificial intelligence-enhanced planning [12]. These advances may narrow the clinical or dosimetric differences between photons and protons in selected scenarios.

As proton therapy becomes increasingly available and draws greater research and patient attention, we hope to see the costs of proton therapy decrease as treatment becomes more efficient and effective, which may help to reduce geospatial disparities currently seen with proton therapy treatment [13]. As the benefits of proton therapy are not fully defined for many disease sites, while the high levels of research are encouraging, the field must work to maintain an objective evidence base by strengthening comparative-effectiveness studies and ensuring that both positive and negative findings are consistently reported. Several such comparative trials are expected to read out in the coming years [14,15], and only through transparent, comprehensive, and methodologically rigorous evaluation can clinicians and researchers clearly define where each modality provides meaningful clinical benefit and make treatment decisions aligned with high-quality evidence.

Limitations of our study are that all comparative photon-versus-proton studies were classified as photon studies and we excluded pediatric publications, decisions that both may have underestimated the volume of proton therapy research. A more fundamental limitation is the structural asymmetry inherent to keyword-based bibliometric methodology. Proton therapy studies routinely include "proton" as a keyword or title term, whereas photon-based radiotherapy, as the default treatment modality, is rarely indexed with "photon" as an explicit descriptor in the title or abstract. Consequently, a search for "radiotherapy" alone retrieves hundreds of thousands of records, while studies explicitly specifying "photon" number approximately 5,000. Our dataset therefore captures a systematically smaller proportion of the photon literature than the proton literature, and the apparent crossover in publication volume around 2020 should be interpreted in this context rather than as a true reflection of the relative quantity of clinical research conducted in each modality. Notwithstanding these methodological constraints, the trajectory of growth in proton therapy research over the past decade is consistent across all study design subgroups, suggesting the overall directional findings remain robust.

In summary, the profound growth in research on proton therapy highlights the scientific momentum behind this expanding radiotherapy treatment modality. Through ongoing research and technological advances, the delivery and benefits of this advanced modality are expected to improve further. At the same time, photon therapy has similarly evolved and improved. Continued research in photon-based radiotherapy is critical to ensure both modalities advance in parallel, ensuring that progress in radiation oncology remains clinically meaningful for all patients, with a focus on applying the optimal modality and personalized care for each patient.