Proton Therapy in Head and Neck Cancer Treatment: State of the Problem and Development Prospects (Review)

Гордон, Константин; Смык, Даниил; Гулидов, И. А.

doi:10.17691/stm2021.13.4.08

Cited by 12 publications

(10 citation statements)

References 74 publications

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“…PT is a generally accepted irradiation method that allows significant reduction of the dose to surrounding tissues, especially relevant for head-and-neck tumors ( 20 ). However, its use is limited by complexity, big size and high costs of the equipment.…”

Section: Discussionmentioning

confidence: 99%

Upright proton therapy for esthesioneuroblastoma: a single-institution experience

Gordon,

Gulidov,

Smyk

et al. 2024

Front. Oncol.

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AimThis study presents an analysis (efficacy and toxicity) of outcomes in patients with esthesioneuroblastoma after pencil beam proton therapy with a fixed beamline in the upright position.BackgroundEsthesioneuroblastoma (ENB) is an extremely rare tumor of sinonasal area located in critical proximity to vital structures. Proton therapy (PT) is often considered the optimal radiation treatment for head-and-neck tumors, although of limited availability. Upright PT delivered using fixed pencil beamline and rotating chair is a fairly promising option.MethodsThis is a single-center experience describing the outcomes of PT in 14 patients with ENB treated between January 2016 and October 2022; half of the cases had a history of previous irradiation. The therapy was applied using a fixed pencil beamline with 6D-chair for positioning. The median dose was 63 GyRBE (total range 48–70 GyRBE; based on 1.1 RBE multiplier for protons) with 2.0 GyRBE per fraction. The mean gross tumor volume was 109.5 cm3 (17.1–257.7 cm3). Patient demography, pathology, treatment parameters and toxicity data were analyzed. Radiation-induced reactions were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v 4.0.ResultsThe median follow-up time was 28 months. The 1- and 2-year locoregional control rates constituted 100% and 88.9%, respectively; the median duration of local control was 52 months. The 1- and 2-year progression-free survival (PFS) rates constituted 92.9% and 75.0%, respectively; the median PFS duration was 52 months. The 1- and 2-year overall survival (OS) rates constituted 92.9% and 84.4%, respectively. Two patients died of non-cancer-related causes (coronavirus-induced pneumonia) and 1 patient died of tumor progression. All patients tolerated PT well without any treatment gaps. Serious late toxicity reactions included glaucoma in 1 patient and cataract in 2 patients, in over half a year since irradiation.ConclusionPT with upright design of the unit affords promising outcomes in terms of disease control and toxicity rates in ENB, a sinonasal tumor of complicated localization.

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Section: Discussionmentioning

confidence: 99%

Upright proton therapy for esthesioneuroblastoma: a single-institution experience

Gordon,

Gulidov,

Smyk

et al. 2024

Front. Oncol.

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“…IL-6 expression has been associated with poor response to chemoradiotherapy and poor prognosis in patients with HNSCC [ 96 ], as well as radiation resistance and chronic post-irradiation toxicity development [ 99 ]. These findings identify PT as a highly promising approach in HNSCC treatment, as the conventional photonic options have already reached their technical limits [ 38 , 100 , 101 ].…”

Section: Local and Systemic Effects Of Proton Irradiationmentioning

confidence: 99%

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

Jumaniyazova

Смык

Vishnyakova

et al. 2022

Life

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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.

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“…Intensity-modulated proton therapy (IMPT) is a promising alternative to conventional photon-based IMRT. 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 ].…”

Section: Introductionmentioning

confidence: 99%

“…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 ].…”

Section: Introductionmentioning

confidence: 99%

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

Chimote,

Lehn,

Bhati

et al. 2024

Cancers

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Proton therapy (PT) is emerging as an effective and less toxic alternative to conventional X-ray-based photon therapy (XRT) for patients with advanced head and neck squamous cell carcinomas (HNSCCs) owing to its clustered dose deposition dosimetric characteristics. For optimal efficacy, cancer therapies, including PT, must elicit a robust anti-tumor response by effector and cytotoxic immune cells in the tumor microenvironment (TME). While tumor-derived exosomes contribute to immune cell suppression in the TME, information on the effects of PT on exosomes and anti-tumor immune responses in HNSCC is not known. In this study, we generated primary HNSCC cells from tumors resected from HNSCC patients, irradiated them with 5 Gy PT or XRT, and isolated exosomes from cell culture supernatants. HNSCC cells exposed to PT produced 75% fewer exosomes than XRT- and non-irradiated HNSCC cells. This effect persisted in proton-irradiated cells for up to five days. Furthermore, we observed that exosomes from proton-irradiated cells were identical in morphology and immunosuppressive effects (suppression of IFN-γ release by peripheral blood mononuclear cells) to those of photon-irradiated cells. Our results suggest that PT limits the suppressive effect of exosomes on cancer immune surveillance by reducing the production of exosomes that can inhibit immune cell function.

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Proton Therapy in Head and Neck Cancer Treatment: State of the Problem and Development Prospects (Review)

Cited by 12 publications

References 74 publications

Upright proton therapy for esthesioneuroblastoma: a single-institution experience

Upright proton therapy for esthesioneuroblastoma: a single-institution experience

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

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

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