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High and ultra-high dose-rate delivery in a clinical proton therapy setting

Applicant Psoroulas Serena
Number 200882
Funding scheme Project funding
Research institution Paul Scherrer Institut
Institution of higher education Paul Scherrer Institute - PSI
Main discipline Other disciplines of Physics
Start/End 01.03.2022 - 28.02.2026
Approved amount 236'964.00
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All Disciplines (2)

Discipline
Other disciplines of Physics
Technical Physics

Keywords (7)

Pencil beam scanning; Beam delivery systems; Proton Therapy; FLASH irradiations; Hypofractionation; Breath-hold; Ultra-high dose-rate (UHDR)

Lay Summary (German)

Lead
Bei Strahlentherapie mittels Protonen wird das gesunde Gewebe besser geschont und damit Nebenwirkungen für Patienten reduziert. Bei der Behandlung von Tumoren, die sich mit der Atmung bewegen (bspw. Lunge) wird sie jedoch kaum eingesetzt. Eine Steigerung der Dosisrate würde es erlauben, auch bewegte Tumore in kürzerer Zeit unter quasi-statischen Bedingungen zu bestrahlen, in dem der Patient die Atmung anhält. Zudem zeigen neuere biologische Studien, dass eine Vervielfachung der Dosisrate die Schonung des gesunden Gewebes bei gleicher Tumorkontrolle verbessern kann (sog. "FLASH"-Effekt).
Lay summary

Inhalt und Ziel des Forschungsprojekts

Unser Ziel ist eine Reduktion der Bestrahlungszeit für zwei Szenarien: a) Bestrahlungen in 5-10 Sekunden für bewegte Tumore; und b) Bestrahlung kleiner Zielvolumen in weniger als 1 Sekunde um den FLASH-Effekt zu maximieren. Dazu werden Bestrahlung mit hohem Protonenstrahlstrom sowie Optimierungen bei der Bestrahlungstechnik untersucht. Mit Simulationen von Patientenbestrahlungen werden die vielversprechendsten Lösungen eruiert, die im Behandlungsraum Gantry 2 am Paul Scherrer Institut experimentell verifiziert werden.

Wissenschaftlicher und gesellschaftlicher Kontext des Forschungsprojekts

Unser Projekt wird die Machbarkeit von Behandlungen mit sehr hohen Dosisraten in einer klinischen Umgebung demonstrieren. Neben einer generellen Effizienzsteigerung durch die Verkürzung der Bestrahlungszeit, kann damit die Effektivität der Behandlung von bewegten Tumoren oder Tumoren in der Nähe von strahlenempfindlichen Organen erhöht werden.

Direct link to Lay Summary Last update: 26.01.2022

Lay Summary (Italian)

Lead
La protonterapia è una forma di radioterapia che limita il danno ai tessuti sani, riducendo gli effetti collaterali per il paziente. Al momento, tuttavia, viene poco utilizzata nel trattamento di tumori che si muovono con la respirazione, ad esempio nel tumore al polmone. Aumentare l'intensità della radiazione permetterebbe di trattare i tumori in movimento in condizioni quasi-statiche, mentre il paziente trattiene il respiro. Inoltre, recenti studi biologici su cellule e animali hanno mostrato che aumentare l'intensità della radiazione puo' aumentare la resistenza dei tessuti sani a parità di danno per il tessuto tumorale (detto 'effetto FLASH').
Lay summary

Soggetto e obiettivo

Il nostro obiettivo sarà ridurre il tempo di trattamento, in due scenari: a) l'irraggiamento di un tumore in 5-10 secondi, per il trattamento di tumori in movimento; e b) l'irraggiamento di un tumore in meno di 1 secondo, per sfruttare l'effetto FLASH. Per raggiungere questi obiettivi, ci concentreremo sia sull'aumento dell'intensità dei fasci di protoni, sia sull'aumento dell'efficienza della tecnica di irraggiamento. Sulla base di simulazioni di irraggiamento ai pazienti, in entrambi gli scenari considerati, sceglieremo le soluzioni tecnologiche più promettenti, e le verificheremo sperimentalmente nella sala di trattamento Gantry 2 al Paul Scherrer Institut - Centro di Protonterapia.

Contesto socio-scientifico

Il nostro progetto permetterà di dimostrare la fattibilità di trattamenti ultra-rapidi in ambito clinico. Diminuendo il tempo di irraggiamento, sarà possibile non solo aumentare l'efficacia dei trattamenti di tumori mobili o di tumori vicini ad organi sensibili alla radiazione; trattamenti più rapidi contribuiranno in generale ad aumentare l'efficienza dei trattamenti di protonterapia.

Direct link to Lay Summary Last update: 26.01.2022

Responsible applicant and co-applicants

Employees

Name Institute

Project partner

Associated projects

Number Title Start Funding scheme
185082 New concept for adaptive real time tumour tracking 01.10.2019 Project funding
190663 Feasibility of conformal FLASH on a clinical proton gantry 01.12.2019 Spark

Abstract

Increase of the dose delivered to tumours, sparing of the healthy organs, and treatment efficiency are three drivers of innovation in radiation therapy. Proton therapy allows sparing healthy organs better than standard radiation therapy, therefore allowing higher doses to the tumours, and/or limiting radiation-induced side effects. The most advanced form of proton therapy, pencil beam scanning, is highly successful for many tumour indications, but because it is very sensitive to tumour motion has been only partly applied in cases like liver and lung cancer. Increasing the dose rate at which patients are treated makes an interesting scenario for the future of proton therapy: it would not only generally improve the efficiency of the treatments (with lower irradiation times), but would also allow treating moving tumours for example while patients hold their breath. It would also allow delivering more dose in a single treatment session, making the whole course of treatment shorter. Last but not least, ongoing biological experiments have shown that ultra-high dose rates may increase radiation resistance in healthy tissues, thanks to a biological mechanism not yet fully understood (the so-called ‘FLASH effect’). On the other hand, it is unclear how to realise such short irradiation times, particularly for large, deep-seated tumours: for treatments in a single breath-hold, the whole treatment should take only 5-10 s, and less than a second for FLASH treatments. In our project, we want to investigate possible, realistic clinical scenarios for realizing high and ultra-high dose-rate irradiation. We will investigate first which beam optics solutions could achieve 50, resp. >100 nA, at isocentre (breath-hold resp. FLASH irradiation scenario), for conventional gantries used in proton therapy. We will also look into the energy switching strategy since the most common strategy to change the energy within a field (performing the change at the accelerator or right after the accelerator) is too slow for the low irradiation times we consider in this study. As a further way to increase efficiency in the delivery, we also want to investigate the possibility of using different beam sizes within the same patient field, with larger beam sizes delivered in the inner part of the dose distribution (to remove as much as possible dead times necessary to steer the beam from one to another position inside the tumour volume) and smaller sizes in the outer parts of the dose distribution (to enhance sparing of surrounding organs). We will use the clinical treatment room Gantry 2 at PSI as a test bench for this project. We will consider the three research topics (beam optics, energy switching strategy, and beam size optimization) from a point of view of treatment efficiency, and based on simulation as well as experimental results we will propose an innovative treatment modality, treating patients at (ultra-)high dose-rates. Finally, we will test this modality on different patient fields: moving tumours treated at our centre (proposing to treat them in breath-hold instead of with other motion-mitigation modalities), hypofractionated treatments (treatments with more dose per treatment session, not usually performed at our centre), and FLASH treatments of a deep-seated tumour (a first proof-of-principle for our field). We will deliver these treatments to phantoms and perform the same quality assurance testing as in our clinical practice, to show the clinical potential of our solution. Upon completion of the project, PSI Gantry 2 will be the first clinical unit ready to implement single-breath-hold irradiations and FLASH irradiations. Reaching these goals would also open the field to additional sparing and treatment opportunity, such as, for example, the further sparing of the immune system in radiation therapy treatments or the treatments of heart arrhythmia, both possible thanks to the very short treatment times.
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