AGH University of Science and Technology Faculty of Physics and Applied Computer Science Engineering thesis Semiconductor pixel detectors for characterisation of therapeutic proton beams Paulina Stasica Medical Physics Supervisor: dr inż. Jan Gajewski Proton Radiotherapy Group The Henryk Niewodniczanski Institute of Nuclear Physics Polish Academy of Sciences Kraków, January 2020 dr inż. Jan Gajewski Instytut Fizyki Jądrowej PAN Merytoryczna ocena pracy przez opiekuna: Pani Paulina Stasica przygotowała pracę inżynierską, która jest elementem projektu ba- dawczego Fundacji na Rzecz Nauki Polskiej zatytułowanego „Ocena niepewności zasięgu efektu biologicznego w celu poprawy skuteczności radioterapii protonowej w Centrum Cyklotronowym Bronowic”, realizowanego w Instytucie Fizyki Jądrowej PAN w Krakowie. Praca inżynierska podzielona jest na trzy części: wstęp teoretyczny, część opisującą zasto- sowane metody eksperymentalne oraz wyniki i dyskusję pomiarów i symulacji Monte Carlo. Pracę kończy rozdział z wnioskami. We wstępie teoretycznym zostały opisane formy oddziaływań wysokoenergetycznych pro- tonów z materią oraz podstawy radioterapii protonowej, w tym rola względnej wydajności biologicznej i jej zależność od liniowego przekazu energii. W kolejnym rozdziale opisano zastosowanie półprzewodnikowych detektorów pikselowych typu Timepix MiniPIX do pomiaru depozycji energii w mieszanych polach promieniowania indukowanych przez wiązkę protonową. Opisano dwa typy eksperymentów przeprowadzonych przez Autorkę pracy, mających na celu zbadanie zdolności pomiaru depozycji energii przez detektor Timepix w referencyjnych polach kwazi-monoenergetycznych wiązek protonowych oraz w mieszanych polach indukowanych przez wiązki protonowe w wodzie. Dodatkowo Autorka opisała sposób przeprowadzania symulacji Monte Carlo oraz metody analizy danych. W trzeciej części Autorka przedstawia wyniki zmierzonych depozycji energii pomiarów ka- libracyjnych oraz pomiarów na różnych głębokościach w wodzie, wzdłuż rdzenia ołówkowej wiązki protonowej. Wyniki pomiarów porównane są z wynikami symulacji Monte Carlo oraz z danymi tablicowymi. Praca zbudowana jest w sposób uporządkowany i spójny. Zawiera wprowadzenie, metody, wyniki oraz dyskusję. Praca zawiera bibliografię składającą się z 31 pozycji. Oprawa typogra- ficzna jest wykonana w sposób staranny, a rysunki i wykresy są czytelne i prawidłowo opisane. Wyniki pracy zostały zawarte w streszczeniu przygotowanych przez Autorkę pracy na konferen- cję The European Society for Radiotherapy and Oncology Congresses (kwiecień 2020, Wiedeń), na której będą prezentowane w ustnym wystąpieniu. Końcowa ocena pracy przez opiekuna: 5.0 Data: 7.1.2020r. Podpis: .................................. Skala ocen: 5.0 – bardzo dobra, 4.5 – plus dobra, 4.0 – dobra, 3.5 – plus dostateczna, 3.0 – dostateczna, 2.0 – niedostateczna amended), is allowed to use (without renumeration and without attaining the author's consent) the work created by the student resulting from fulfilling the duties connected with his studies, as well as to make the work available to the minister in charge of higher education and science, and to make use of works located in databases kept by the minister in order to verify the thesis with the usage of Jednolity System Antyplagiatowy [the Uniform Anti-plagiarism System]. The minister in charge of higher education and science is allowed to make use of final diploma theses located in databases kept by him to the extent necessary to ensure the correct maintenance and development of these databases and IT systems working with them; 2. pursuant to Article 342 section 3 item 5 and Article 347 section 1 of the act - Law on higher education and science the minister in charge of higher education and science maintains a database called the repository of written final diploma theses, which includes: the title and content of the final diploma thesis; full name of the author of the final diploma thesis; PESEL number of the author of the final diploma thesis and if they do not have PESEL – the number of the document confirming their identity and the name of the country that issued the document; full name of the thesis supervisor, PESEL number and if they do not have PESEL – the number of the document confirming their identity and the name of the country that issued the document; full name of the thesis reviewer, PESEL number and if they do not have PESEL – the number of the document confirming their identity and the name of the country that issued the document; the name of the university; the date of the final diploma examination; the field of study, level and educational profile. 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The repository does not contain theses including information protected pursuant to regulations governing the protection of classified information. * - delete as necessary; ** - enter TAK/YES if you agree to provide access to final diploma thesis, NIE/NO – if you do not agree; if you do not fill this in you are not consenting to share your work. Acknowledgements This engineering thesis was performed in the frame of the Foundation of Polish Science project titled: Quantification of biological range uncertainties towards an improved patient treatment in CCB Cracow proton beam therapy centre leaded by dr Antoni Rucinski at The Henryk Niewodniczanski Institute of Nuclear Physics Polish Academy of Sciences. Foremost, I would like to thank my supervisor dr inż. Jan Gajewski for providing me with a continuous support and guidance through this work. I wish to express my sincere thanks also to dr Antoni Ruciński, for valuable comments on this thesis. I would like to acknowledge all the great people involved in the project: hab. prof. Carlos Granja, PhD Cristina Oancea, prof. Angelo Schavi, dr inż. Marzena Rydygier and doctoral students mgr inż. Jakub Baran and mgr Monika Pawlik- Niedźwiecka. 6 Acronym List BP Bragg peak CCB Cyclotron Centre Bronowice CERN European Organization for Nuclear Research dLET Dose - averaged LET IDD Integral depth dose LET Linear energy transfer MC Monte Carlo MPV Most probably value RBE Relative biological effectiveness SOBP Spread-out Bragg peak UJF Nuclear Physiscs Institute of The Czech Academy of Sciences 7 Abstract The application of protons in radiotherapy allows to maximize dose deposition in the tumor, while protecting normal tissue, due to depth-dose characteristics in water or tissue of this particle type. In the case of photons, the physical dose is correlated to the biological effect, whereas for charged particles a modifying factor, radiobiological effectiveness (RBE), has to be applied. In proton therapy clinical practice RBE is assumed to be a constant value of 1.1, however this assumption does not reflect the reality. RBE value depends on different factors, as for instance particle ionization density that can be described by linear energy transfer (LET). Development of variable RBE-based treatment planning requires experimental validation of proton LET in water. In the frame of this work measurements and data analysis were performed, as well as comparison of experimental results to Monte Carlo (MC) simulations aiming at more precise characterisation of proton pencil beams in water. Measurements were performed by means of compact Timepix MiniPIX semiconductor pixel detector placed in an in-house developed PMMA waterproof detector holder used for detector positioning in water phantom. MiniPIX chip provides information about energy deposited by single particle, its position and direction, while penetrating the sensor. Detector calibration in air was performed for seven proton beam nominal en- ergies. Next, the energy depositions were measured at different positions in depth along the beam in water. The experimental LET spectra were compared to MC GATE simulations. A good agreement between calibration measurements and MC simulations was observed for measurements performed at energies ranging from 70 to 200 MeV, however there is discrepancy in the case of measurements performed be- low 70 MeV. The results of the measurements and MC simulations performed along the proton pencil beam longitudinal profile are presented and discussed. The software tools developed in the frame of this work will allow further analysis of data from other measurements performed at different positions in water phantom. Experimental validation of LET is necessary in order to implement variable RBE- based treatment planning systems to clinical practice of proton radiotherapy. 8 Contents Spis treści 9 1 Purpose 10 2 Introduction and research background 11 2.1 Protons interactions with matter . 14 2.2 Stopping power . 15 2.3 Linear energy transfer . 16 2.4 Relative biological effectiveness . 16 3 Methods 19 3.1 Timepix detectors and PIXet Pro software . 19 3.2 Data collection . 21 3.2.1 Calibration . 21 3.2.2 Longitudinal