Photon- and Proton-Mediated Biological Effects: What Has Been Learned?

Abstract

The current understanding of the effects of radiation is gradually becoming broader. However, it still remains unclear why some patients respond to radiation with a pronounced positive response, while in some cases the disease progresses. This is the motivation for studying the effects of radiation therapy not only on tumor cells, but also on the tumor microenvironment, as well as studying the systemic effects of radiation. In this framework, we review the biological effects of two types of radiotherapy: photon and proton irradiations. Photon therapy is a commonly used type of radiation therapy due to its wide availability and long-term history, with understandable and predictable outcomes. Proton therapy is an emerging technology, already regarded as the method of choice for many cancers in adults and children, both dosimetrically and biologically. This review, written after the analysis of more than 100 relevant literary sources, describes the local effects of photon and proton therapy and shows the mechanisms of tumor cell damage, interaction with tumor microenvironment cells and effects on angiogenesis. After systematic analysis of the literature, we can conclude that proton therapy has potentially favorable toxicological profiles compared to photon irradiation, explained mainly by physical but also biological properties of protons. Despite the fact that radiobiological effects of protons and photons are generally similar, protons inflict reduced damage to healthy tissues surrounding the tumor and hence promote fewer adverse events, not only local, but also systemic.

Upright proton therapy for esthesioneuroblastoma: a single-institution experience

“…As demonstrated in some studies, PT not only has dosimetric advantages, but also favorable profiles of treatment-related toxicity ( 24 ). In our study, acute radiation toxicity was typically represented by grade 1-2 local mucositis and grade 1-2 dermatitis.…”

An Overview of Head and Neck Tumor Reirradiation: What Has Been Achieved So Far?

“…Lupu-Plesu et al (2017) presented a comparative analysis of proton and photon therapies on lymphangiogenesis, inflammation and proliferative responses in head and neck squamous cell carcinoma models [88]. The convincing evidence on the biological benefits of PT may have profound clinical implications [89,90]. The clinical use of PT is steadily gaining momentum with the building of new proton centers around the globe, which ensures more facile recruitment of patients into study groups [91].…”

Proton Treatment Suppresses Exosome Production in Head and Neck Squamous Cell Carcinoma

“…Proton therapy (PT) offers advantages over XRT because it can deliver an optimal radiation dose with precision to tumors while sparing the surrounding normal tissues, thus resulting in less treatment-related toxicity with comparable treatment response and disease-free survival [ 3 , 6 , 7 ]. However, a knowledge gap exists not only in the presumed biological advantage of PT over XRT, but also in the molecular and cellular effects of PT on anti-tumor immune responses [ 8 , 9 ]. Anti-tumor immune responses are of particular interest because of the recent success of immunotherapy in patients with advanced and/or unresectable HNSCC, resulting in full resolution of the disease in some instances, albeit in a small percentage of patients [ 10 ].…”

“…Several studies have shown that PT induces a markedly variable and favorable biological response in terms of gene and protein expression in target tissues compared to XRT. PT inhibits factors that contribute to angiogenesis, inflammation, and DNA damage and favors tumor development and growth, while XRT increases these factors [ 3 , 6 , 8 , 12 , 13 ]. Furthermore, transcriptomic studies in murine models of colon cancer have shown that PT activates anti-tumor immune response pathways [ 9 ].…”