{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T03:31:46Z","timestamp":1784604706014,"version":"3.55.0"},"reference-count":23,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,31]],"date-time":"2021-12-31T00:00:00Z","timestamp":1640908800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Regional Development Fund-Project: &quot;Engineering Applications of Microworld Physics&quot;","award":["No.  CZ.02.1.01\/0.0\/0.0\/16_019\/0000766"],"award-info":[{"award-number":["No.  CZ.02.1.01\/0.0\/0.0\/16_019\/0000766"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: A favourable dose distribution has been described for proton beam therapy (PBT) of anal cancer in dosimetric studies. The relationship between dosimetric parameters in bone marrow and haematologic toxicity, treatment interruptions, and treatment efficacy has also been documented. There are only few references on clinical results of PBT for anal cancer. The primary objective of the retrospective study was to assess the efficacy of pencil beam scanning intensity-modulated proton therapy (PBS IMPT) in the definitive chemoradiotherapy of anal cancer. Secondary objectives were established to identify the risks of acute chronic toxicity risks and to assess colostomy rates. Materials and methods: Patients were treated for biopsy-proven squamous cell cancer (SCC) of the anus at initial or advanced stages. Eligible patients received PBS IMPT at a single institution. Treatment was administered in two volumes: 1\u2014tumour with margins plus involved lymph nodes; 2\u2014regional lymph node groups: perirectal (mesorectal), obturatory, inguinal, internal, external, and common iliac. The total doses of 57.5 GyE and 45 GyE, respectively, were administered in volumes 1 and 2 in 25 fractions, 5 fractions per week, respectively (a simultaneous integrated boost). Concomitant chemotherapy cisplatinum (CDDP) plus 5-FU or CDDP plus capecitabine was administered as per protocol. The treatment effect was assessed using DRE (digital rectal examination) and MRI (magnetic resonance imaging) within the follow-up period. Toxicity was scaled using CTCAE version 4.0 criteria. Results: 39 of 41 patients treated during the period of February 2014\u2013August 2021 were eligible for analysis. All patients completed treatment, 76.9% without interruption. The median treatment time was 35 days (32\u201335). The median follow-up period was 30 months, 34 patients are alive to-date, 5 patients died prior to the date of analysis, and 2 deaths were unrelated to the primary disease. The 2-year overall survival, relapse-free survival, and colostomy-free survival were 94.2%, 93.8%, and 91.0%, respectively. Complete regression was achieved in 36 patients (92.3%), partial regression was achieved in 2 (5.1%), and immediate progression at end of treatment occurred in 1 patient (2.6%). Salvage resection was indicated for two patients in partial regression and due to severe chronic dermatologic toxicity. The grade 3 and 4 haematological toxicity rates were 7.7% and 5.1%, respectively. The most frequent non-haematological acute toxicities of grade 3\u20134 observed were dermatitis (23.1%), diarrhoea (7.7%), and dehydration (7.7%). Chronic toxicity emerged predominantly as skin atrophy\/ulceration grade 2 (26.5%) and grade 3\u20134 (5.8%), and radiation proctitis grade 2 (38.2%) and grade 3 (2.9%). Discussion, conclusions: This single-institution study showed the high efficacy of PBS IMPT, achieving a high rate of complete regression. The haematological acute toxicity of grade 3\u20134 remained low; however, the impact of altered chemotherapy (CDDP instead of mitomycin C) remains unclear. The incidence of other acute toxicities shares similarity with photon therapy investigated in large studies. The acute toxicity completely resolved in all patients, had no lethal outcomes, and never resulted in the necessity for colostomy. By contrast, it was chronic toxicity, skin ulceration, perirectal fistulation, and fibrosis that resulted in salvage surgery and\/or the need for a colostomy. A challenging question remains: to what extent can PBT prevent chronic toxicity? Longer follow-up remains necessary.<\/jats:p>","DOI":"10.3390\/cancers14010185","type":"journal-article","created":{"date-parts":[[2022,1,3]],"date-time":"2022-01-03T20:49:38Z","timestamp":1641242978000},"page":"185","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pencil Beam Scanning (PBS) Intensity-Modulated Proton Therapy (IMPT) Chemoradiotherapy for Anal Canal Cancer\u2014Single Institution Experience"],"prefix":"10.3390","volume":"14","author":[{"given":"Pavel","family":"V\u00edtek","sequence":"first","affiliation":[{"name":"Proton Therapy Center Czech, 180 00 Prague, Czech Republic"},{"name":"Department of Oncology, 2nd Faculty of Medicine, Charles University Prague and Motol University Hospital, V \u00davalu 84, 150 06 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji\u0159\u00ed","family":"Kube\u0161","sequence":"additional","affiliation":[{"name":"Proton Therapy Center Czech, 180 00 Prague, Czech Republic"},{"name":"Department of Oncology, 2nd Faculty of Medicine, Charles University Prague and Motol University Hospital, V \u00davalu 84, 150 06 Prague, Czech Republic"},{"name":"Department of Health Care Disciplines and Population Protection, Faculty of Biomedical Engineering, Czech Technical University Prague, S\u00edtn\u00e1 Square 3105, 272 01 Kladno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5301-0101","authenticated-orcid":false,"given":"Vladim\u00edr","family":"Vondr\u00e1\u010dek","sequence":"additional","affiliation":[{"name":"Proton Therapy Center Czech, 180 00 Prague, Czech Republic"},{"name":"Department of Health Care Disciplines and Population Protection, Faculty of Biomedical Engineering, Czech Technical University Prague, S\u00edtn\u00e1 Square 3105, 272 01 Kladno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6581-5583","authenticated-orcid":false,"given":"Michal","family":"Andrlik","sequence":"additional","affiliation":[{"name":"Proton Therapy Center Czech, 180 00 Prague, Czech Republic"},{"name":"Department of Health Care Disciplines and Population Protection, Faculty of Biomedical Engineering, Czech Technical University Prague, S\u00edtn\u00e1 Square 3105, 272 01 Kladno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mat\u011bj","family":"Navr\u00e1t\u00edl","sequence":"additional","affiliation":[{"name":"Proton Therapy Center Czech, 180 00 Prague, Czech Republic"},{"name":"Department of Health Care Disciplines and Population Protection, Faculty of Biomedical Engineering, Czech Technical University Prague, S\u00edtn\u00e1 Square 3105, 272 01 Kladno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radek","family":"Zapletal","sequence":"additional","affiliation":[{"name":"Proton Therapy Center Czech, 180 00 Prague, Czech Republic"},{"name":"Department of Oncology, 2nd Faculty of Medicine, Charles University Prague and Motol University Hospital, V \u00davalu 84, 150 06 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Haas","sequence":"additional","affiliation":[{"name":"Proton Therapy Center Czech, 180 00 Prague, Czech Republic"},{"name":"Department of Oncology, 2nd Faculty of Medicine, Charles University Prague and Motol University Hospital, V \u00davalu 84, 150 06 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate\u0159ina","family":"D\u011bde\u010dkov\u00e1","sequence":"additional","affiliation":[{"name":"Proton Therapy Center Czech, 180 00 Prague, Czech Republic"},{"name":"Department of Oncology, 2nd Faculty of Medicine, Charles University Prague and Motol University Hospital, V \u00davalu 84, 150 06 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbora","family":"Ondrov\u00e1","sequence":"additional","affiliation":[{"name":"Proton Therapy Center Czech, 180 00 Prague, Czech Republic"},{"name":"Department of Oncology, 2nd Faculty of Medicine, Charles University Prague and Motol University Hospital, V \u00davalu 84, 150 06 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Grebenyuk","sequence":"additional","affiliation":[{"name":"Department of Health Protection and Disaster Medicine, Pavlov First Saint Petersburg State Medical University, Lva Tolstogo 6-8, 197020 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jozef","family":"Rosina","sequence":"additional","affiliation":[{"name":"Department of Health Care Disciplines and Population Protection, Faculty of Biomedical Engineering, Czech Technical University Prague, S\u00edtn\u00e1 Square 3105, 272 01 Kladno, Czech Republic"},{"name":"Department of Medical Biophysics and Informatics, 3rd Faculty of Medicine, Charles University, Rusk\u00e1 87, 116 36 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1007\/BF02586980","article-title":"Combined therapy for cancer of the anal canal: A preliminary report","volume":"17","author":"Nigro","year":"1974","journal-title":"Dis. 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