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

      review-article
      , MD, PhD, , , MD, DSc
      Modern Technologies in Medicine
      Privolzhsky Research Medical University
      proton therapy, head and neck cancer, reirradiation therapy

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          Abstract

          Proton therapy (PT) due to dosimetric characteristics (Bragg peak formation, sharp dose slowdown) is currently one of the most high-tech 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.

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          Most cited references77

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          Cancer statistics, 2020

          Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2016) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2017) were collected by the National Center for Health Statistics. In 2020, 1,806,590 new cancer cases and 606,520 cancer deaths are projected to occur in the United States. The cancer death rate rose until 1991, then fell continuously through 2017, resulting in an overall decline of 29% that translates into an estimated 2.9 million fewer cancer deaths than would have occurred if peak rates had persisted. This progress is driven by long-term declines in death rates for the 4 leading cancers (lung, colorectal, breast, prostate); however, over the past decade (2008-2017), reductions slowed for female breast and colorectal cancers, and halted for prostate cancer. In contrast, declines accelerated for lung cancer, from 3% annually during 2008 through 2013 to 5% during 2013 through 2017 in men and from 2% to almost 4% in women, spurring the largest ever single-year drop in overall cancer mortality of 2.2% from 2016 to 2017. Yet lung cancer still caused more deaths in 2017 than breast, prostate, colorectal, and brain cancers combined. Recent mortality declines were also dramatic for melanoma of the skin in the wake of US Food and Drug Administration approval of new therapies for metastatic disease, escalating to 7% annually during 2013 through 2017 from 1% during 2006 through 2010 in men and women aged 50 to 64 years and from 2% to 3% in those aged 20 to 49 years; annual declines of 5% to 6% in individuals aged 65 years and older are particularly striking because rates in this age group were increasing prior to 2013. It is also notable that long-term rapid increases in liver cancer mortality have attenuated in women and stabilized in men. In summary, slowing momentum for some cancers amenable to early detection is juxtaposed with notable gains for other common cancers.
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            Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial

            Summary Background Xerostomia is the most common late side-effect of radiotherapy to the head and neck. Compared with conventional radiotherapy, intensity-modulated radiotherapy (IMRT) can reduce irradiation of the parotid glands. We assessed the hypothesis that parotid-sparing IMRT reduces the incidence of severe xerostomia. Methods We undertook a randomised controlled trial between Jan 21, 2003, and Dec 7, 2007, that compared conventional radiotherapy (control) with parotid-sparing IMRT. We randomly assigned patients with histologically confirmed pharyngeal squamous-cell carcinoma (T1–4, N0–3, M0) at six UK radiotherapy centres between the two radiotherapy techniques (1:1 ratio). A dose of 60 or 65 Gy was prescribed in 30 daily fractions given Monday to Friday. Treatment was not masked. Randomisation was by computer-generated permuted blocks and was stratified by centre and tumour site. Our primary endpoint was the proportion of patients with grade 2 or worse xerostomia at 12 months, as assessed by the Late Effects of Normal Tissue (LENT SOMA) scale. Analyses were done on an intention-to-treat basis, with all patients who had assessments included. Long-term follow-up of patients is ongoing. This study is registered with the International Standard Randomised Controlled Trial register, number ISRCTN48243537. Findings 47 patients were assigned to each treatment arm. Median follow-up was 44·0 months (IQR 30·0–59·7). Six patients from each group died before 12 months and seven patients from the conventional radiotherapy and two from the IMRT group were not assessed at 12 months. At 12 months xerostomia side-effects were reported in 73 of 82 alive patients; grade 2 or worse xerostomia at 12 months was significantly lower in the IMRT group than in the conventional radiotherapy group (25 [74%; 95% CI 56–87] of 34 patients given conventional radiotherapy vs 15 [38%; 23–55] of 39 given IMRT, p=0·0027). The only recorded acute adverse event of grade 2 or worse that differed significantly between the treatment groups was fatigue, which was more prevalent in the IMRT group (18 [41%; 99% CI 23–61] of 44 patients given conventional radiotherapy vs 35 [74%; 55–89] of 47 given IMRT, p=0·0015). At 24 months, grade 2 or worse xerostomia was significantly less common with IMRT than with conventional radiotherapy (20 [83%; 95% CI 63–95] of 24 patients given conventional radiotherapy vs nine [29%; 14–48] of 31 given IMRT; p<0·0001). At 12 and 24 months, significant benefits were seen in recovery of saliva secretion with IMRT compared with conventional radiotherapy, as were clinically significant improvements in dry-mouth-specific and global quality of life scores. At 24 months, no significant differences were seen between randomised groups in non-xerostomia late toxicities, locoregional control, or overall survival. Interpretation Sparing the parotid glands with IMRT significantly reduces the incidence of xerostomia and leads to recovery of saliva secretion and improvements in associated quality of life, and thus strongly supports a role for IMRT in squamous-cell carcinoma of the head and neck. Funding Cancer Research UK (CRUK/03/005).
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              Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC): an introduction to the scientific issues.

              Advances in dose-volume/outcome (or normal tissue complication probability, NTCP) modeling since the seminal Emami paper from 1991 are reviewed. There has been some progress with an increasing number of studies on large patient samples with three-dimensional dosimetry. Nevertheless, NTCP models are not ideal. Issues related to the grading of side effects, selection of appropriate statistical methods, testing of internal and external model validity, and quantification of predictive power and statistical uncertainty, all limit the usefulness of much of the published literature. Synthesis (meta-analysis) of data from multiple studies is often impossible because of suboptimal primary analysis, insufficient reporting and variations in the models and predictors analyzed. Clinical limitations to the current knowledge base include the need for more data on the effect of patient-related cofactors, interactions between dose distribution and cytotoxic or molecular targeted agents, and the effect of dose fractions and overall treatment time in relation to nonuniform dose distributions. Research priorities for the next 5-10 years are proposed. Copyright 2010 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Sovrem Tekhnologii Med
                Sovrem Tekhnologii Med
                stm
                Modern Technologies in Medicine
                Privolzhsky Research Medical University (Russia )
                2076-4243
                2309-995X
                2021
                28 August 2021
                : 13
                : 4
                : 70-80
                Affiliations
                [1]Senior Researcher, Proton Therapy Department; A. Tsyb Medical Radiological Research Centre — Branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, 4 Koroleva St., Kaluga Region, Obninsk, 249036, Russia
                [2]Junior Researcher, Proton Therapy Department; A. Tsyb Medical Radiological Research Centre — Branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, 4 Koroleva St., Kaluga Region, Obninsk, 249036, Russia
                [3]Professor, Head of the Proton Therapy Department; A. Tsyb Medical Radiological Research Centre — Branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, 4 Koroleva St., Kaluga Region, Obninsk, 249036, Russia
                Author notes
                Corresponding author: Konstantin B. Gordon, e-mail: gordon@ 123456mrrc.obninsk.ru

                Authors’ contribution: all authors have equal participation in the article writing.

                Conflicts of interest. The authors declare no conflicts of interest related to the present study.

                How to cite: Gordon K.B., Smyk D.I., Gulidov I.А. Proton therapy in head and neck cancer treatment: state of the problem and development prospects (review). Sovremennye tehnologii v medicine 2021; 13(4): 70, https://doi.org/10.17691/stm2021.13.4.08

                Article
                10.17691/stm2021.13.4.08
                8482826
                9ccf95b9-59bb-4fdf-8dd3-481ab6f4c096

                This is an open access article under the CC BY 4.0 license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 11 February 2021
                Funding
                The study had no special financing.
                Categories
                Reviews

                proton therapy,head and neck cancer,reirradiation therapy

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