Proton therapy (PT) due to dosimetric characteristics (Bragg peak formation, sharp dose slowdown) is currently one of the most hightech techniques of radiation therapy exceeding the standards of photon methods.In recent decades, PT has traditionally been used, primarily, for head and neck cancers (HNC) including skull base tumors. Regardless of the fact that recently PT application area has significantly expanded, HNC still remain a leading indication for proton radiation since PT's physic-dosimetric and radiobiological advantages enable to achieve the best treatment results in these tumors.The present review is devoted to PT usage in HNC treatment in the world and Russian medicine, the prospects for further technique development, the assessment of PT's radiobiological features, a physical and dosimetric comparison of protons photons distribution. The paper shows PT's capabilities in the treatment of skull base tumors, HNC (nasal cavity, paranasal sinuses, nasopharynx, oropharynx, and laryngopharynx, etc.), eye tumors, sialomas. The authors analyze the studies on repeated radiation and provide recent experimental data on favorable profile of proton radiation compared to the conventional radiation therapy.The review enables to conclude that currently PT is a dynamic radiation technique opening up new opportunities for improving therapy of oncology patients, especially those with HNC.

Aim This study presents an analysis (efficacy and toxicity) of outcomes in patients with skull-base chordomas or chondrosarcomas treated with a fixed horizontal pencil proton beam. Background Chordomas (CAs) and chondrosarcomas (CSAs) are rare tumours that are usually located near the base of the skull and very close to the brain's most critical structures. Proton therapy (PT) is often considered the best radiation treatment for these diseases, but it is still a limited resource. Active scanning PT delivered via a fixed pencil beamline might be a promising option. Methods This is a single-centre experience describing the results of proton therapy for 31 patients with CA (n = 23) or CSA (n = 8) located near the base of the skull. Proton therapy was utilized by a fixed pencil beamline with a chair to position the patient between May 2016 and November 2020. Ten patients underwent resection (32.2%), 15 patients (48.4%) underwent R2 resection, and 6 patients had unresectable tumours (19.4%). In 4 cases, the tumours had been previously irradiated. The median PT dose was 70 GyRBE (relative biological efficacy, 1.1) [range, 60 to 74] with 2.0 GyRBE per fraction. The mean GTV volume was 25.6 cm3 [range, 4.2–115.6]. Patient demographics, pathology, treatment parameters, and toxicity were collected and analysed. Radiation-induced reactions were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v 4.0. Results The median follow-up time was 21 months [range, 4 to 52]. The median overall survival (OS) was 40 months. The 1- and 2-year OS was 100%, and the 3-year OS was 66.3%. Four patients died due to non-cancer-related reasons, 1 patient died due to tumour progression, and 1 patient died due to treatment-related injuries. The 1-year local control (LC) rate was 100%, the 2-year LC rate was 93.7%, and the 3-year LC rate was 85.3%. Two patients with CSA exhibited progression in the neck lymph nodes and lungs. All patients tolerated PT well without any treatment interruptions. We observed 2 cases of ≥ grade 3 toxicity, with 1 case of grade 3 myelitis and 1 case of grade 5 brainstem injury. Conclusion Treatment with a fixed proton beam shows promising disease control and an acceptable toxicity rate, even the difficult-to-treat subpopulation of patients with skull-base chordomas or chondrosarcomas requiring dose escalation.

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.

Локальный рецидив после первичной лучевой терапии опухолей полости носа возникает у 18-40% пациентов в первые 5 лет от момента окончания лечения. Основной метод лечения рецидивов – хирургический, но в ситуации, когда хирургическое лечение по каким-то причинам провести невозможно, методами выбора остаются химио- и/или лучевая терапия. Радикальные дозы первичного лечения практически не оставляют резерва толерантности окружающих здоровых тканей, что выражается в повышении вероятности развития поздних лучевых осложнений. Протонная терапия за счет особенностей распределения дозы, позволяет уменьшить нагрузку на окружающие здоровые ткани, что потенциально должно привести к снижению количества поздних лучевых осложнений и улучшить переносимость лечения. В работе приведен собственный опыт применения протонной терапии в качестве методики повторного облучения у пациентки с рецидивом опухоли полости носа. Данным примером мы показали, что курс протонной терапии может быть успешно реализован в качестве метода повторного лечения у пациентов с рецидивами опухолей полости носа, одной из наиболее сложных локализаций с точки зрения дозиметрического планирования в лучевой терапии.