Artificial intelligence (AI) has made a tremendous impact in the space of healthcare, and proton therapy is not an exception. Proton therapy has witnessed growing popularity in oncology over recent decades, and researchers are increasingly looking to develop AI and machine learning tools to aid in various steps of the treatment planning and delivery processes. This review delves into the emergent role of AI in proton therapy, evaluating its development, advantages, intended clinical contexts, and areas of application. Through the analysis of 76 studies, we aim to underscore the importance of AI applications in advancing proton therapy and to highlight their prospective influence on clinical practices.
- MeSH
- lidé MeSH
- nádory * radioterapie terapie MeSH
- plánování radioterapie pomocí počítače metody MeSH
- protonová terapie * metody MeSH
- strojové učení MeSH
- umělá inteligence * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
PURPOSE: Patients with p16 positive tonsillar cancer (p16 + TC) have an excellent prognosis and long-life expectancy. Deintensification of therapy is a prevalent topic of discussion. Proton radiotherapy is one way to reduce radiation exposure and thus reduce acute and late toxicity. The aim is to evaluate treatment outcomes and toxicity of postoperative treatment with intensity-modulated proton therapy (IMPT). METHODS: Between September 2013 and November 2021, 47 patients with p16 + TC were treated postoperatively with IMPT. Median age was 54.9 (38.2-74.9) years, 31 were males and 16 were females. All patients had squamous cell carcinoma and underwent surgery as a primary treatment. Median dose of radiotherapy was 66 GyE in 33 fractions. Bilateral neck irradiation was used in 39 patients and unilateral in 8. Concomitant chemotherapy was applied in 24 patients. RESULTS: Median follow-up time was 4.2 (0.15-9.64) years. Five-year overall survival, relapse free survival and local control were 95.7%, 97.8% and 100%. The most common acute toxicities were dermatitis and mucositis, with grade 2 + in 61.7% and 70.2% of patients. No acute percutaneous gastrostomy insertion was necessary and intravenous rehydration was used in 12.8% of patients. The most common late toxicity was grade 1 xerostomia in 70.2% of patients and grade 2 in 10.6% of patients. Subcutaneous fibrosis of grades 2 and 3 occurred in 17.0% and 2.1% of patients, respectively. One patient developed late severe dysphagia and became PEG-dependent. CONCLUSION: IMPT for the postoperative treatment of p16 + TC is feasible with excellent efficiency and acceptable acute and late toxicity.
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- protonová terapie * metody škodlivé účinky MeSH
- radioterapie s modulovanou intenzitou * metody škodlivé účinky MeSH
- retrospektivní studie MeSH
- senioři MeSH
- spinocelulární karcinom * radioterapie patologie terapie chirurgie MeSH
- tonzilární nádory * radioterapie patologie chirurgie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Boron has been suggested to enhance the biological effectiveness of proton beams in the Bragg peak region via the p + 11B → 3α nuclear capture reaction. However, a number of groups have observed no such enhancement in vitro or questioned its proposed mechanism recently. To help elucidate this phenomenon, we irradiated DU145 prostate cancer or U-87 MG glioblastoma cells by clinical 190 MeV proton beams in plateau or Bragg peak regions with or without 10B or 11B isotopes added as sodium mercaptododecaborate (BSH). The results demonstrate that 11B but not 10B or other components of the BSH molecule enhance cell killing by proton beams. The enhancement occurs selectively in the Bragg peak region, is present for boron concentrations as low as 40 ppm, and is not due to secondary neutrons. The enhancement is likely initiated by proton-boron capture reactions producing three alpha particles, which are rare events occurring in a few cells only, and their effects are amplified by intercellular communication to a population-level response. The observed up to 2-3-fold reductions in survival levels upon the presence of boron for the studied prostate cancer or glioblastoma cells suggest promising clinical applications for these tumour types.
- MeSH
- bor chemie MeSH
- glioblastom radioterapie farmakoterapie MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádory prostaty radioterapie farmakoterapie MeSH
- protonová terapie * metody MeSH
- protony MeSH
- terapie metodou neutronového záchytu (bor-10) * metody MeSH
- viabilita buněk účinky léků účinky záření MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND PURPOSE: As no guidelines for pencil beam scanning (PBS) proton therapy (PT) of paediatric posterior fossa (PF) tumours exist to date, this study investigated planning techniques across European PT centres, with special considerations for brainstem and spinal cord sparing. MATERIALS AND METHODS: A survey and a treatment planning comparison were initiated across nineteen European PBS-PT centres treating paediatric patients. The survey assessed all aspects of the treatment chain, including but not limited to delineations, dose constraints and treatment planning. Each centre planned two PF tumour cases for focal irradiation, according to their own clinical practice but based on common delineations. The prescription dose was 54 Gy(RBE) for Case 1 and 59.4 Gy(RBE) for Case 2. For both cases, planning strategies and relevant dose metrics were compared. RESULTS: Seventeen (89 %) centres answered the survey, and sixteen (80 %) participated in the treatment planning comparison. In the survey, thirteen (68 %) centres reported using the European Particle Therapy Network definition for brainstem delineation. In the treatment planning study, while most centres used three beam directions, their configurations varied widely across centres. Large variations were also seen in brainstem doses, with a brainstem near maximum dose (D2%) ranging from 52.7 Gy(RBE) to 55.7 Gy(RBE) (Case 1), and from 56.8 Gy(RBE) to 60.9 Gy(RBE) (Case 2). CONCLUSION: This study assessed the European PBS-PT planning of paediatric PF tumours. Agreement was achieved in e.g. delineation-practice, while wider variations were observed in planning approach and consequently dose to organs at risk. Collaboration between centres is still ongoing, striving towards common guidelines.
- MeSH
- celková dávka radioterapie * MeSH
- dítě MeSH
- infratentoriální nádory * radioterapie MeSH
- kritické orgány účinky záření MeSH
- lidé MeSH
- mozkový kmen účinky záření MeSH
- plánování radioterapie pomocí počítače * metody MeSH
- předškolní dítě MeSH
- protonová terapie * metody MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Geografické názvy
- Evropa MeSH
Nádory krčního úseku jícnu jsou vzácným onemocněním, které se standardně léčí samostatnou (definitivní) chemoradioterapií bez chirurgického výkonu. Chemoradioterapie je provázena několika kontroverzemi, z nichž hlavní je nejistota v účinné dávce a přínosu dávkové eskalace. Běžná aplikovaná normofrakcionovaná dávka je přes 60 Gy. Příznivá dávková distribuce predikuje benefit protonové radioterapie (PRT). V PTC Praha lze výsledky PRT hodnotit u 29 nemocných, kteří byli ozařováni do c. d. 70 GyE technikou „pencil beam scanning“ IMPT s konkomitantní chemoterapií carboplatina + paclitaxel. U 18, resp. 7 nemocných byla dosažena kompletní, resp. parciální regrese, response rate je 86,3 %. Medián sledování je 14 měsíců (2,6–66,0). Medián přežívání je 13,7 měs., 2leté přežívání 45 %. Medián doby do relapsu/progrese je 28,7 měs., 2leté přežívání bez relapsu je 52 %. V době analýzy přežívá 13 nemocných, 12 z nich v kompletní regresi onemocnění. Akutní toxicita nepřesahuje stupeň 2 kromě kožní (st. 3 u 22,6 %). Chronická toxicita nepřesahuje st. 2 kromě 2 případů tracheoezofageální píštěle v místě primárního postižení u onemocnění stadia T4. PRT v mírně eskalované dávce s konkomitantní chemoterapií dosáhla vysokou protinádorovou účinnost, naproti tomu parametry přežívání jsou zřejmě vlivem velkého podílu primárně lokoregionálně pokročilých onemocnění méně příznivé. Přesto určitý podíl nemocných dlouhodobě přežívá s kompletní regresí onemocnění. Obligátní výskyt lymfopenie a řada recentních poznatků v protinádorové imunologii vyžaduje rozvahu nad dosavadním konceptem určování objemu a frakcionace.
Cancer of cervical esophagus belongs to rare diseases. Its standard treatment includes definitive chemoradiotherapy without subsequent surgery. There are several controversies concerning chemoradiotherapy, the most substantial of them being uncertain effective dose and uncertain benefit of dose escalation. The doses exceeding 60 Gy in 30 fractions are frequently administered. A benefit of proton radiotherapy (PRT) is predicted by favorable dose distribution. The results of PRT administered in PTC Prague have been assessed in 29 patients who have been irradiated up to 70 Gy (equivalent) in 35 fractions using pencil beam scanning technique with concomitant weekly chemotherapy carboplatinum plus paclitaxel. A complete and partial regression has been achieved in 18 and 7 patients respectively, response rate 86,3%. The median follow up time is 14 months (2,6-66,0). Median survival time is 13,7 months, 2-year survival 45%, median time to relapse/progression 28,7 months and 2-year relapse free survival 52%. 13 patients survive at the time of analysis, 12 in complete regression. The acute toxicity does not exceed the grade 2, except radiation dermatitis (22,6% grade 3). The late toxicity does not exceed grade 2, except tracheoesophageal fistulation in 2 patients with primary T4 lesion. The PRT in moderately escalated dose with concomitant chemotherapy achieved a high antitumor efficacy opposed to less favorable survival results, presumably originating of substantial number of locoregionally advanced diseases. Still a durable complete regression long time survival is being observed in a certain share of patients. A lymphopenia is obligatory and in a scope of recent observations in antitumor immunology it desires a deeper contemplation on target volume and fractionation concept.
- Klíčová slova
- protonová chemoradioterapie,
- MeSH
- chemoradioterapie metody MeSH
- lidé MeSH
- lymfopenie MeSH
- nádory jícnu * farmakoterapie radioterapie MeSH
- protonová terapie * metody MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH
BACKGROUND: We retrospectively analyzed the 5-year biochemical disease-free survival (bDFS) and occurrence of late toxicity in prostate cancer patients treated with pencil beam scanning (PBS) proton radiotherapy. METHODOLOGY: In the period from January 2013 to June 2018, 853 patients with prostate cancer were treated with an ultra-hypofractionated schedule (36.25 GyE/five fractions). The mean PSA value was 6.7 (0.7-19.7) μg/L. There were 318 (37.3%), 314 (36.8%), and 221 (25.9%) patients at low (LR), favorable intermediate (F-IR), and unfavorable intermediate risk (U-IR), respectively. Neoadjuvant hormonal therapy was administered to 197 (23.1%) patients, and 7 (0.8%) patients had adjuvant hormonal therapy. The whole group of patients reached median follow-up time at 62.7 months, and their mean age was 64.8 (40.0-85.7) years. The bDFS rates and late toxicity profile were evaluated. RESULTS: Median treatment time was 10 (7-38) days. Estimated 5-year bDFS rates were 96.5%, 93.7%, and 91.2% for low-, favorable intermediate-, and unfavorable intermediate-risk groups, respectively. Cumulative late toxicity (CTCAE v4.0) of G2+ was as follows: gastrointestinal (GI)-G2: 9.1%; G3: 0.5%; genitourinary (GU)-G2: 4.3%, and no G3 toxicity was observed. PSA relapse was observed in 58 (6.8%) patients: 16 local, 22 lymph node, 4 bone recurrences, and 10 combined sites of relapse were detected. Throughout the follow-up period, 40 patients (4.7%) died, though none due to prostate cancer. CONCLUSION: Ultra-hypofractionated proton beam radiotherapy is an effective treatment for low- and favorable intermediate-risk prostate cancer, with long-term bDFS rates comparable to other techniques. It is promising for unfavorable intermediate-risk prostate cancer and has acceptable long-term GI and favorable GU toxicity.
- Publikační typ
- časopisecké články MeSH
Východiska: Vliv ionizujícího záření indikovaného k léčbě zhoubných nádorů na imunitní systém zůstával dlouho stranou hlavního zájmu. Problematika v současnosti nabývá na významu, zejména v souvislosti s rozvojem a dostupností imunoterapeutické léčby. Radioterapie je v léčbě nádorových onemocnění schopna ovlivnit imunogenicitu nádoru zvýšením exprese některých antigenů specifických pro nádor. Tyto antigeny mohou být zpracovány imunitním systémem a stimulovat naivní lymfocyty k přeměně na tumor specifické lymfocyty. Lymfocytární populace je zároveň mimořádně citlivá na nízké dávky ionizujícího záření a radioterapie často indukuje těžkou lymfopenii. Závažná lymfopenie je negativním prognostickým faktorem řady nádorových onemocnění a negativně ovlivňuje i účinnost následné imunoterapeutické léčby. Cíl: V článku shrnujeme možné ovlivnění imunitního systému radioterapií s důrazem na ovlivnění cirkulujících imunitních buněk zářením a důsledky tohoto ovlivnění pro vývoj nádorového onemocnění. Závěr: Lymfopenie je významným faktorem ovlivňujícím výsledky onkologické léčby a její výskyt je při radioterapii častý. Strategie redukující riziko lymfopenie spočívají v akceleraci léčebných režimů, redukci cílových objemů, zkracování beam-on time ozařovačů, v optimalizaci radioterapie na nové kritické orgány, použití částicové radioterapie a v dalších postupech redukujících integrální dávku záření.
Background: The effect of ionizing radiation on the immune system during the treatment of malignant tumors has long remained a point of great interest. This issue is currently gaining importance, especially in connection with the advancing development and availability of immunotherapeutic treatment. During cancer treatment, radiotherapy has the ability to influence the immunogenicity of the tumor by increasing the expression of certain tumor-specific antigens. These antigens can be processed by the immune system, stimulating the transformation of na?ve lymphocytes into tumor-specific lymphocytes. However, at the same time, the lymphocyte population is extremely sensitive to even low doses of ionizing radiation, and radiotherapy often induces severe lymphopenia. Severe lymphopenia is a negative prognostic factor for numerous cancer diagnoses and negatively impacts the effectiveness of immunotherapeutic treatment. Aim: In this article, we summarize the possible influence of radiotherapy on the immune system, with a particular emphasis on the impact of radiation on circulating immune cells and the subsequent consequences of this influence on the development of cancer. Conclusion: Lymphopenia is an important factor influencing the results of oncological treatment, with a common occurrence during radiotherapy. Strategies to reduce the risk of lymphopenia consist of accelerating treatment regimens, reducing target volumes, shortening the beam-on time of irradiators, optimizing radiotherapy for new critical organs, using particle radiotherapy, and other procedures that reduce the integral dose of radiation.
- Klíčová slova
- protinádorová imunitní reakce,
- MeSH
- lidé MeSH
- lymfopenie * etiologie MeSH
- radioterapie škodlivé účinky MeSH
- tolerance záření MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Cíl práce: Cílem práce je analýza 6letého přežití bez biochemického relapsu (bDFS) a profilu pozdní toxicity u nemocných s karcinomem prostaty léčených ultrahypofrakcionovanou protonovou radioterapií.
Objective: The aim of the paper is an analysis of the six-year biochemical disease-free survival (bDFS) rate and of the late toxicity profile in patients with prostate cancer treated with ultra-hypofractionated proton radiotherapy. Material and methods: Between March 2013 and February 2016, a total of 275 patients were treated with ultra-hypofractionated proton radiotherapy (36.25 GyE/5 fractions). The median follow-up time is 69 months. There were 118 (42.9%) patients with low and 157 (57.1%) patients with intermediate-risk prostate cancer. Fifty (18.2%) patients received neoadjuvant hormone therapy, while none had adjuvant hormone therapy. Results: The estimated six-year bDFS rate was 97.1% (SD 1.7%) and 89.9% (SD 3.0%) for low- and intermediate-risk prostate cancer, respectively. Cumulative late toxicity (CTCAE-v.4) grade ≥ 2 was found for gastrointestinal toxicity (GI) in 17 (6.2%) patients and for genitourinary toxicity (GU) in 11 (4.0%) patients. The estimated cumulative GI toxicity grade ≥ 2 at six years was 6.3% GI and 4.1% for GU toxicity. PSA relapse was observed in 16 (5.8%) patients. During the course of follow-up, 14 (5.1%) patients died. Conclusion: Ultra-hypofractionated proton radiotherapy with the PBS technique is highly effective in treating low- and intermediate-risk prostate cancer with a favourable profile of late gastrointestinal and genitourinary toxicity.
INTRODUCTION: Glomus jugulare tumours (GJT) are benign tumours that arise locally and destructively in the base of the skull and can be successfully treated with radiotherapy. Patients have a long-life expectancy and the late effects of radiotherapy can be serious. Proton radiotherapy reduces doses to critical organs and can reduce late side effects of radiotherapy. The aim of this study was to report feasibility and early clinical results of 12 patients treated using proton therapy. METHODS: Between December 2013 and June 2019, 12 patients (pts) with GJT (median volume 20.4 cm3 ; range 8.5-41 cm3 ) were treated with intensity modulated proton therapy (IMPT). Median dose was 54 GyE (Gray Equivalents) (50-60 GyE) with daily fractions of 2 GyE. Twelve patients were analysed with a median follow-up time of 42.2 months (11.3-86.7). Feasibility, dosimetric parameters, acute and late toxicity and local effect on tumour were evaluated in this retrospective study. RESULTS: All patients finished treatment without interruption, with excellent dosimetric parameters and mild acute toxicity. Stabilisation of tumour size was detected on MRI in all patients. No changes in symptoms were observed in comparison with pre-treatment conditions. No late effects of radiotherapy were observed. CONCLUSION: Pencil-beam scanning proton radiotherapy is highly feasible in the treatment of large GJT with mild acute toxicity and promising short-term results. Longer follow-up and larger patient cohorts are required to further identify the role of pencil-beam scanning (PBS) for this indication.
- MeSH
- celková dávka radioterapie MeSH
- lidé MeSH
- plánování radioterapie pomocí počítače metody MeSH
- protonová terapie * škodlivé účinky metody MeSH
- protony MeSH
- radioterapie s modulovanou intenzitou * škodlivé účinky metody MeSH
- retrospektivní studie MeSH
- tumor glomus jugulare * etiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
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-tumour with margins plus involved lymph nodes; 2-regional 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-August 2021 were eligible for analysis. All patients completed treatment, 76.9% without interruption. The median treatment time was 35 days (32-35). 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 3-4 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 3-4 (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 3-4 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.
- Publikační typ
- časopisecké články MeSH
