Image-Guided FLASH Proton Therapy. A dream? Naivety? Arrogance? Or a Necessity?

• Autorzy: Lang, Karol
• Języki publikacji: EN

Abstrakty

EN

Objective: The in-vivo therapy guidance by imaging and dosimetry of proton irradiations, generically known as proton range verification, are some of the most underinvested aspects of radiation oncology. They trail behind other advances in radiation therapy due to the scarcity of sensitive instruments compounded by the lack of treatment protocols for precision monitoring of effects of beam radiation. This is despite that such measurements may dramatically enhance the treatment accuracy and lower the postradiation toxicity, thus improving the entire outcome of cancer therapy. Methods: In this contribution, we focus on the motivation of designing and building of an in-beam time-of-flight (ToF) positron-emission-tomography (PET) scanner with the depth- -of-interaction (DoI) capability for high sensitivity and improved fidelity of imaging. A scanner could be augmented with a tungsten collimator that would enable prompt-gamma imaging (PGI) via single-photon emission computed tomography (SPECT) technique. Results: We present selected results of our pre-clinical experiments with a FLASH proton beam and discuss other related ideas towards improving and expanding the use of PET/PGI/SPECT detectors for proton therapy. A scanner provides an access to data during the spill and past the spill permitting to capture the beam interaction and kinetic monitoring of its effect thus allowing a thorough assessment of each irradiation. Conclusions: A novel scanner for multiple modalities can substantially improve the treatment precision of proton therapy leading to less toxic outcome of irradiations. Using it in the FLASH modality would additionally expand the patient reach of proton therapy.

Słowa kluczowe

EN

proton therapy; FLASH effect; image-guidance; proton range verification; brain cancer; PET scanner; nuclear medical imaging; radiopharmaceuticals; theranostics; multimodal treatment; AI/ML PET; CASTOR; TPPT Consortium

• Czasopismo: Bio-Algorithms and Med-Systems
• Rocznik: 2024
• Tom: Vol. 20, Special issue
• Strony: 17--26
• Opis fizyczny: Bibliogr. 52 poz., rys., tab.

Twórcy

autor

Lang, Karol

• The University of Texas at Austin, Austin, Texas, USA,

Bibliografia

• 1. www.who.int [Internet]. World Health Organization [cited 2024 July 27]. Available from: https://www.who.int/news/item/0102-2024-global-cancer-burden-growing-amidst-mounting-need-for-services.
• 2. Wilson RR. Radiological use of fast protons. Radiology 1946 Nov;47: 487-91. doi: https://doi.org/10.1148/47.5.487.
• 3. ptcog.ch [Internet]. Particle Therapy Co-Operative (PTCOG) Group [cited 2024 July 27]. Available from: https://www.ptcog.ch/index.php/.
• 4. Parodi K, Enghardt W, Haberer T. In-beam PET measurements of β+ radioactivity induced by proton beams. Phys. Med. Biol. 2002;47:21-36.
• 5. Enghardt W, Crespo P, Fiedler F, Hinz R, Parodi K, Pawelke J, et al. Charged hadron tumour therapy monitoring by means of PET. NIMA 2004;525:284-8.
• 6. Crespo P, Shakirin G, Fiedler F, Enghardt W, Wagner A. Direct time-offlight for quantitative, real-time in-beam PET: A concept and feasibility study. Phys Med Biol. 2007;52:6795-811.
• 7. Knopf A, Parodi K, Bortfeld T, Shih HA, Paganetti H. Systematic analysis of biological and physical limitations of proton beam range verification with offline PET/CT scans. Phys. Med. Biol. 2009;54:4477-95. doi: https://doi.org/10.1088/0031-9155/54/14/008.
• 8. Zhu X, El Fakhri G. Proton therapy verification with PET imaging. Theranostics. 2013 Sep 19;3(10):731-40. doi: https://doi.org/10.7150/thno.5162.
• 9. Min CH, Zhu X, Winey BA, Grogg K, Testa M, El Fakhri G, et al. Clinical Application of In-Room Positron Emission Tomography for In Vivo Treatment Monitoring in Proton Radiation Therapy. Int J Radiat Oncol Biol Phys. 2013 May 1; 86(1):183-9. doi: https://doi.org/10.1016/j.ijrobp.2012.12.010.
• 10. Paganetti H, El Fakhri G. Monitoring proton therapy with PET. Br J Radiol 2015;88:20150173. https://doi.org/10.1259/bjr.20150173.
• 11. Seco J, Clasie B, Partridge M. Review on the characteristics of radiation detectors for dosimetry and imaging. Phys. Med. Biol. 2014;59(20):R303-47. https://doi.org/10.1088/0031-9155/59/20/R303.
• 12. Seco J, Spadea MF. Imaging in particle therapy: State of the art and future perspective. Acta Oncol. 2015;54(9):1254-8.
• 13. Shusharina N, Fullerton B, Adams JA, Sharp GC, Chan AW. Impact of aeration change and beam arrangement on the robustness of proton plans. J Appl Clin Med Phys 2019;20(3):14-21. doi: https://doi.org/10.1002/ acm2.12503.
• 14. Grogg K, Zhu X, Shih H, Alpert N, El Fakhri G. Proton Range Verification with PET Imaging in Brain and Head and Neck Cancers. J. Nucl. Med. 2018 May; 59(Supplement 1):658.
• 15. Durante M, Parodi K. Radioactive Beams in Particle Therapy: Past, Present, and Future. Front Phys. 2020 Aug 28; 8:1-13. doi: https://doi.org/10.3389/fphy.2020.00326.
• 16. Krishnamoorthy S, Teo B-KK, Zou W, McDonough J, Karp JS, Surti S. A Proof-of-Concept Study of an In-Situ Partial-Ring Time-of-Flight PET Scanner for Proton Beam Verification. IEEE 2021;5:5.
• 17. Silva F, Campello MPC, Paulo A. Radiolabeled Gold Nanoparticles for Imaging and Therapy of Cancer Materials. Materials. 2021;14(1):4. doi: https://doi.org/10.3390/ma14010004.
• 18. Favaudon V, Caplier L, Monceau V, Pouzoulet F, Sayarath M, Fouillade C, et al. Ultrahigh Dose-Rate Flash Irradiation Increases the Differential Response Between Normal and Tumor Tissue in Mice. Sci. Trans. Med. 2014;6(245):245ra93. doi: https://doi.org/10.1126/scitranslmed.3008973.
• 19. Fouillade C, Favaudon V, Vozenin MC, Romeo P-H, Bourhis J, Verrelle P, et al. Hopes of high dose-rate radiotherapy. Bull Cancer 2017;104:380-84.
• 20. Montay-Gruel P, Petersson K, Jaccard M, Boivin G, Germond J-F, Petit B, et al. Irradiation in a flash: unique sparing of memory in mice after whole brain irradiation with dose rates above 100Gy/s. Radiother Oncol. 2017;124(3):365-69. https://doi.org/10.1016/j.radonc.2017.05.003.
• 21. Patriarca A, Fouillade C, Auger M, Martin F, Pouzoulet F, Nauraye C, et al. Experimental Set-up for FLASH Proton Irradiation of Small Animals Using a Clinical System. Int J Radiation Oncol Biol Phys 2018;102(3):619-26. doi: https://doi.org/10.1016/j.ijrobp.2018.06.403.
• 22. Vozenin MC, De Fornel P, Petersson K, Favaudon V, Jaccard M, Germond J-F, et al. The advantage of FLASH radiotherapy confirmed in mini-pig and cat-cancer patients. Clin Cancer Res. 2019 Jan 1;25(1):35-42.
• 23. Vozenin MC, Hendry JH, Limoli CL. Biological benefits of ultrahigh dose rate FLASH radiotherapy: Sleeping beauty awoken. Clin Oncol (R Coll Radiol). 2019;31(7):407-15.
• 24. Bourhis J, Montay-Gruel P, Goncalves JP, Bailat C, Petit B, Ollivier J, et al. Clinical translation of FLASH radiotherapy: Why and how? Radiother Oncol. 2019 Oct 8; 139:11-7. doi: https://doi.org/10.1016/j.radonc.2019.04.
• 25. Montay-Gruel P, Acharya MM, Petersson K, Alikhani L, Yakkala C, Allen BD, et al. Longterm neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species. Proc Natl Acad Sci USA. 2019 May 28;116(22):10943-51. doi: https://doi.org/10.1073/pnas.
• 26. Hughes JR, Parsons JL. FLASH Radiotherapy: Current Knowledge and Future Insights Using Proton-Beam Therapy. Int. J. Mol. Sci. 2020;21: 6492. doi: https://doi.org/10.3390/ijms21186492.
• 27. Fouillade C, Curras-Alonso S, Giuranno L, Quelennec E, Heinrich S, Bonnet-Boissinot S, et al. FLASH irradiation spares lung progenitor cells and limits the incidence of radio-induced senescence. Clin Cancer Res. 2020;26(6):1497-1506. https://doi.org/10.1158/1078-0432. CCR-19-1440.
• 28. Schuler E, Acharya M, Montay-Gruel P, Loo Jr. BW, Vozenin M-C, Maxim PG. Ultra-high dose rate electron beams and the FLASH effect: From preclinical evidence to a new radiotherapy paradigm, Med Phys. 2022;49:2082-95. doi: https://doi.org/10.1002/mp.15442.
• 29. Lin B, Gao F, Yang Y, Wu D, Zhang Y, Feng G, et al. FLASH Radiotherapy: History and Future. Front. Oncol. 2021;11:644400. doi: https://doi. org/10.3389/fonc.644400.
• 30. Montay-Gruel P, Acharya MM, Gon P, Jorge C, Petit B, Petridis IG, et al. Hypofractionated FLASH-RT as an Effective Treatment against Glioblastoma that Reduces Neurocognitive Side Effects in Mice. Clin Cancer Res. 2021;27:775-84. doi: https://doi.org/10.1158/1078-0432.CCR-20-0894.
• 31. Vozenin MC, Bourhis J, Durante M. Towards clinical translation of FLASH radiotherapy. Nat Rev Clin Oncol. 2022;19:791-803. https://doi.org/10.1038/s41571-022-00697-z.
• 32. Spitz DR, Buettner GR, Petronek MS, St-Aubin JJ, Flynn RT, Waldron TJ, et al. An integrated physico-chemical approach for explaining the differential impact of FLASH versus conventional dose rate irradiation on cancer and normal tissue responses. Radiother Oncol. 2019;139:23-7. doi: https://doi.org/10.1016/j.radonc.2019.03.028.
• 33. Maxim PG, Keall P, Cai J. FLASH radiotherapy: Newsflash or flash in the pan? Med. Phys. 2019;46:4287-90. doi: https://doi.org/10.1002/ mp.13685.
• 34. Lin B, Gao F, Yang Y, Wu D, Zhang Y, Feng G, et al. FLASH Radiotherapy: History and Future. Front. Oncol. 2021;11:644400. doi: https://doi. org/10.3389/fonc.2021.644400.
• 35. Favaudon V, Labarbe R, Limoli CL. Model studies of the role of oxygen in the FLASH effect. Med. Phys. 2022;439:2068-81. doi: https://doi.org/10.1002/mp.15129.
• 36. Leavitt RJ, Almeida A, Grilj V, Montay-Gruel P, Godfroid C, Petit B, et al. Hypoxic tumors are sensitive to FLASH radiotherapy. bioRxiv. 2022;11(27):1-18. doi: https://doi.org/10.1101/2022.11.27.518083.
• 37. Bogaerts E, Macaeva E, Isebaert S, Haustermans K. Potential Molecular Mechanisms behind the Ultra-High DoseRate “FLASH” Effect, Int. J. Mol. Sci. 2022;23:1-20. doi: https://doi.org/10.3390/ijms232012109.
• 38. Lin B, Huang D, Gao F, Yang Y, Wu D, Zhang Y, et al. Mechanisms of FLASH effect. Front Oncol. 2022;12:995612. doi: https://doi.org/10.3389/fonc.2022.995612.
• 39. Wardman P. Radiotherapy Using High-Intensity Pulsed Radiation Beams (FLASH): A Radiation-Chemical Perspective. Radiat. Res. 2020;194:607-17. doi: https://doi.org/10.1667/RADE-19-00016.
• 40. utaustinportugal.org [Internet]. TOF-PET for Proton Therapy (TPPT) - In-beam Time-of-Flight (TOF) Positron Emission Tomography (PET) for proton radiation therapy, consortium of the University of Texas at Austin (K. Lang, PI), UT Cancer Center (N. Sahoo, PI) and Portugal (V. Varela, PI) [cited 2024 July 27]. Available from: https://utaustinportugal.org/projects/tppt/.
• 41. mdanderson.org [Internet]. MD Anderson Cancer Center operates in Houston two Proton Therapy Centers. A second center started treating its first patients at the end of 2023 [cited 2024 July 27]. Available from: https://www.mdanderson.org/cmp/proton-therapy.html.
• 42. Cesar JP, Bugalho R, Caramelo F, Coutinho T, Crespo P, Da Silva JC et al. Time-of-Flight PET for Range Verification in Proton Therapy Treatment. Poster presentation at the 2022 IEEE Nuclear Science Symposium, Medical Imaging Conference and Room Temperature Semiconductor Detector Conference; 2022 Nov 5-12; Milan, Italy.
• 43. Lang K. Towards high sensitivity and high-resolution PET scanners: Imaging-guided proton therapy and total body imaging, Bio-Algorithms and Med-Systems 2022;18(1):96-106. https://doi.org/10.2478/ bioal-2022-0079.
• 44. petsyselectronics.com [Internet]. PETsys Electronics S.A., Edificio Tecnologia I, 24 e 26 2740-257, Porto Salvo, Oeiras, Portugal [cited 2024 July 27]. Available from: https://www.petsyselectronics.com/web/.
• 45. hamamatsu.com [Internet ]. We used the SiPM model S14161- 3050HS-08, manufactured by Hamamatsu Photonics K. K., Hamamatsu City, Japan, and Bridgewater, NJ 08807-0910, USA [cited 2024 July 27]. Available from: https://www.hamamatsu.com.
• 46. Abouzahr F, Cesar JP, Crespo P, Gajda MJ, Hu Z, Kaye W, et al. The first PET glimpse of a proton FLASH beam, Phys. Med. Biol. 2023;68:125001. doi: https://doi.org/10.1088/1361-6560/acd29e.
• 47. Abouzahr F, Cesar JP, Crespo P, Gajda MJ, Hu Z, Kaye W, et al. The first probe of a FLASH proton beam by PET. Phys. Med. Biol. 2023;68:235004. doi: https://doi.org/10.1088/1361-6560/ad0901.
• 48. Titt U, Yang M, Wang X, Iga K, Fredette N, Schueler E, et al. Design and validation of a synchrotron proton beam line for FLASH radiotherapy preclinical research experiments. Med Phys. 2021;49(1):1-13 doi: https://doi.org/10.1002/mp.15370.
• 49. Bass SD, Mariazzi S, Moskal P, Stepien E. Colloquium: Positronium physics and biomedical applications. Rev. Mod. Phys. 2023;95;021002.
• 50. Merlin T, Stute S, Benoit D, Bert J, Carlier T, Comtat C, et al. CASToR: A generic data organization and processing code framework for multimodal and multi-dimensional tomographic reconstruction. Phys. Med. Biol. 2018;63:185005. doi: https://doi.org/10.1088/1361-6560/aadac1.
• 51. Agostinelli S, Allison J, Amako K, Apostolakis J, Araujo H, Arce P, et al. Geant4 - A Simulation Toolkit. Nucl. Instrum. Meth. A 2003;506:250-303.
• 52. Layden C, Klein K, Matava W, Sadam A, Abouzahr F, Proga M, et al. Design and modeling of a high-resolution and high-sensitivity PET brain scanner with double-ended readout, Biomed. Phys. Eng. Express 2022;8:025011.

Identyfikatory

DOI

10.5604/01.3001.0054.8930