Alpha dose modeling in diffusing alpha-emitters radiation therapy-Part I: single-seed calculations in one and two dimensions.
DaRT
Targeted Alpha Therapy
alpha dose calculations
brachytherapy
Journal
Medical physics
ISSN: 2473-4209
Titre abrégé: Med Phys
Pays: United States
ID NLM: 0425746
Informations de publication
Date de publication:
Mar 2023
Mar 2023
Historique:
revised:
01
09
2022
received:
06
06
2021
accepted:
29
09
2022
pubmed:
6
12
2022
medline:
22
3
2023
entrez:
5
12
2022
Statut:
ppublish
Résumé
Diffusing alpha-emitters Radiation Therapy ("DaRT") is a new method, presently in clinical trials, which allows treating solid tumors by alpha particles. DaRT relies on interstitial seeds carrying μCi-level A previous study introduced a simplified framework, the "Diffusion-Leakage (DL) model", for DaRT alpha dose calculations, and employed it to a point source, as a basic building block of arbitrary configurations of line sources. The aim of this work, which is divided into two parts, is to extend the model to realistic seed geometries (in Part I), and to employ single-seed calculations to study the properties of DaRT seed lattices (Part II). Such calculations can serve as a pragmatic guide for treatment planning in future clinical trials. We derive a closed-form asymptotic solution for an infinitely long cylindrical source, and extend it to an approximate time-dependent expression that assumes a uniform temporal profile at all radial distances from the source. We then develop a finite-element one-dimensional numerical scheme for a complete time-dependent solution of this geometry and validate it against the closed-form expressions. Finally, we discuss a two-dimensional axisymmetric scheme for a complete time-dependent solution for a seed of finite diameter and length. Different solutions are compared over the relevant parameter space, providing guidelines on their usability and limitations. We show that approximating the seed as a finite line source comprised of point-like segments significantly underestimates the correct alpha dose, as predicted by the full two-dimensional calculation. The time-dependent one-dimensional solution is shown to coincide to sub-percent-level with the two-dimensional calculation in the seed midplane, and maintains an accuracy of a few percent up to ∼2 mm from the seed edge. For actual treatment plans, the full two-dimensional solution should be used to generate dose lookup tables, similarly to the TG-43 format employed in conventional brachytherapy. Given the accuracy of the one-dimensional solution up to ∼2 mm from the seed edge it can be used for efficient parametric studies of DaRT seed lattices.
Sections du résumé
BACKGROUND
BACKGROUND
Diffusing alpha-emitters Radiation Therapy ("DaRT") is a new method, presently in clinical trials, which allows treating solid tumors by alpha particles. DaRT relies on interstitial seeds carrying μCi-level
PURPOSE
OBJECTIVE
A previous study introduced a simplified framework, the "Diffusion-Leakage (DL) model", for DaRT alpha dose calculations, and employed it to a point source, as a basic building block of arbitrary configurations of line sources. The aim of this work, which is divided into two parts, is to extend the model to realistic seed geometries (in Part I), and to employ single-seed calculations to study the properties of DaRT seed lattices (Part II). Such calculations can serve as a pragmatic guide for treatment planning in future clinical trials.
METHODS
METHODS
We derive a closed-form asymptotic solution for an infinitely long cylindrical source, and extend it to an approximate time-dependent expression that assumes a uniform temporal profile at all radial distances from the source. We then develop a finite-element one-dimensional numerical scheme for a complete time-dependent solution of this geometry and validate it against the closed-form expressions. Finally, we discuss a two-dimensional axisymmetric scheme for a complete time-dependent solution for a seed of finite diameter and length. Different solutions are compared over the relevant parameter space, providing guidelines on their usability and limitations.
RESULTS
RESULTS
We show that approximating the seed as a finite line source comprised of point-like segments significantly underestimates the correct alpha dose, as predicted by the full two-dimensional calculation. The time-dependent one-dimensional solution is shown to coincide to sub-percent-level with the two-dimensional calculation in the seed midplane, and maintains an accuracy of a few percent up to ∼2 mm from the seed edge.
CONCLUSIONS
CONCLUSIONS
For actual treatment plans, the full two-dimensional solution should be used to generate dose lookup tables, similarly to the TG-43 format employed in conventional brachytherapy. Given the accuracy of the one-dimensional solution up to ∼2 mm from the seed edge it can be used for efficient parametric studies of DaRT seed lattices.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1793-1811Subventions
Organisme : Alpha TAU Medical Ltd.
ID : 87873311
Informations de copyright
© 2022 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.
Références
Sgouros G, Roeske JC, McDevitt MR, et al. Committee SNMMIRD, Bolch WE, Meredith RF, Wessels BW, Zanzonico PB. MIRD Pamphlet No. 22 (abridged): radiobiology and dosimetry of alpha-particle emitters for targeted radionuclide therapy. J Nucl Med. 2010;51:311-328. 20080889[pmid].
Targeted Alpha Therapy Working Group, Parker C, Lewington V, Shore N, et al. Targeted alpha therapy, an emerging class of cancer agents: a review. JAMA Oncol. 2018;4:1765-1772.
McDevitt MR, Sgouros G, Sofou S. Targeted and nontargeted α-particle therapies. Annu Rev Biomed Eng. 2018;20:73-93.
Guerra Liberal FD, O'Sullivan JM, McMahon SJ, Prise KM. Targeted alpha therapy: current clinical applications. Cancer Biother Radiopharm. 2020;35:404-417.
Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369:213-223.
Arazi L, Cooks T, Schmidt M, Keisari Y, Kelson I. Treatment of solid tumors by interstitial release of recoiling short-lived alpha emitters. Phys Med Biol. 2007;52:5025-5042.
Cooks T, Arazi L, Schmidt M, Marshak G, Kelson I, Keisari Y. Growth retardation and destruction of experimental squamous cell carcinoma by interstitial radioactive wires releasing diffusing alpha-emitting atoms. Int J Cancer. 2008;122:1657-1664.
Cooks T, Schmidt M, Bittan H, Lazarov E, Arazi L, Kelson I, Keisari Y. Local control of lung derived tumors by diffusing alpha-emitting atoms released from intratumoral wires loaded with radium-224. Int J Radiat Oncol Biol Physics. 2009a;74:966-973.
Lazarov E, Arazi L, Efrati M, et al. Comparative in vitro microdosimetric study of murine- and human-derived cancer cells exposed to alpha particles. Radiat Res. 2011;177:280-287.
Cooks T, Tal M, Raab S, et al. Intratumoral 224Ra-loaded wires spread alpha-emitters inside solid human tumors in athymic mice achieving tumor control. Anticancer Res. 2012;32:5315-5321.
Cooks T, Arazi L, Efrati M, et al. Interstitial wires releasing diffusing alpha emitters combined with chemotherapy improved local tumor control and survival in squamous cell carcinoma-bearing mice. Cancer. 2009;115:1791-1801.
Horev-Drori G, Cooks T, Bittan H, et al. Local control of experimental malignant pancreatic tumors by treatment with a combination of chemotherapy and intratumoral 224Radium-loaded wires releasing alpha-emitting atoms. Transl Res. 2012;159:32-41.
Milrot E, Jackman A, Flescher E, et al. Enhanced killing of cervical cancer cells by combinations of methyl jasmonate with cisplatin, X or alpha radiation. Invest New Drugs. 2013;31:333-344.
Reitkopf-Brodutch S, Confino H, Schmidt M, et al. Ablation of experimental colon cancer by intratumoral 224Radium-loaded wires is mediated by alpha particles released from atoms which spread in the tumor and can be augmented by chemotherapy. Int J Radiat Biol. 2015;91:179-186.
Keisari Y, Hochman I, Confino H, Korenstein R, Kelson I. Activation of local and systemic anti-tumor immune responses by ablation of solid tumors with intratumoral electrochemical or alpha radiation treatments. Cancer Immunol Immunother. 2014;63:1-9.
Confino H, Hochman I, Efrati M, et al. Tumor ablation by intratumoral Ra-224-loaded wires induces anti-tumor immunity against experimental metastatic tumors. Cancer Immunol Immunother. 2015;64:191-199.
Confino H, Schmidt M, Efrati M, et al. Inhibition of mouse breast adenocarcinoma growth by ablation with intratumoral alpha-irradiation combined with inhibitors of immunosuppression and CpG. Cancer Immunol Immunother. 2016;65:1149-1158.
Domankevich V, Cohen A, Efrati M, et al. Combining alpha radiation-based brachytherapy with immunomodulators promotes complete tumor regression in mice via tumor-specific long-term immune response. Cancer Immunol Immunother. 2019;68:1949-1958.
Domankevich V, Efrati M, Schmidt M, et al. RIG-1-like receptor activation synergizes with intratumoral alpha radiation to induce pancreatic tumor rejection, triple-negative breast metastases clearance, and antitumor immune memory in mice. Front Oncol. 2020;10:990.
Keisari Y, Popovtzer A, Kelson I. Effective treatment of metastatic cancer by an innovative intratumoral alpha particle-mediated radiotherapy in combination with immunotherapy: a short review. J Phys Conf Ser. 2020;1662:012016.
Keisari Y, Kelson I. The potentiation of anti-tumor immunity by tumor abolition with alpha particles, protons, or carbon ion radiation and its enforcement by combination with immunoadjuvants or inhibitors of immune suppressor cells and checkpoint molecules. Cells. 2021;10(2):228.
Del Mare S, Nishri Y, Shai A, et al. Diffusing alpha-emitters radiation therapy promotes a proimmunogenic tumor microenvironment and synergizes with programmed cell death protein 1 blockade. Int J Radiat Oncol Biol Phys. Article in press. doi: 10.1016/j.ijrobp.2022.08.043
Popovtzer A, Rosenfeld E, Mizrachi A, et al. Initial safety and tumor control results from a “first-in-human” multicenter prospective trial evaluating a novel alpha-emitting radionuclide for the treatment of locally advanced recurrent squamous cell carcinomas of the skin and head and neck. Int J Radiat Oncol Biol Phys. 2019;106:571-578.
Arazi L, Cooks T, Schmidt M, Keisari Y, Kelson I. The treatment of solid tumors by alpha emitters released from 224 Ra-loaded sources-internal dosimetry analysis. Phys Med Biol. 2010;55:1203.
Bellia S, Feliciani G, Duca M, et al. Clinical evidence of abscopal effect in cutaneous squamous cell carcinoma treated with diffusing alpha emitters radiation therapy: a case report. J Contemp Brachytherapy. 2019;11:449-457.
Arazi L. Diffusing alpha-emitters radiation therapy: approximate modeling of the macroscopic alpha particle dose of a point source. Phys Med Biol. 2020;65:015015.
Jähne B, Heinz G, Dietrich W. Measurement of the diffusion coefficients of sparingly soluble gases in water. J Geophys Res. 1987;92:10767-10776.
NRC. Risk Assessment of Radon in Drinking Water. National Academy Press; 1999.
Gonick HC. Lead-binding proteins: a review. J Toxicol. 2011;2011:686050.
Jain RK. Transport of molecules in the tumor interstitium: a review. Cancer Res. 1987;47:3039-3051.
Pluen A, Boucher Y, Ramanujan S, et al. Role of tumor-host interactions in interstitial diffusion of macromolecules: Cranial vs. subcutaneous tumors. Proc Natl Acad Sci. 2001;98:4628-4633.
Brown EB, Boucher Y, Nasser S, Jain RK. Measurement of macromolecular diffusion coefficients in human tumors. Microvasc Res. 2004;67:231-236.
Press WH, Teukolsky SA, Vetterling WT, Flannery BP. Numerical Recipes 3rd Edition: The Art of Scientific Computing. Cambridge University Press; 2007.
Kis T. Tridiagonal Matrix Algorithm (Thomas Alg.) (tridiagonal), 2021. Accessed: September 28, 2021.
Rivard MJ, Coursey BM, DeWerd LA, et al. Update of AAPM Task Group No. 43 Report: a revised AAPM protocol for brachytherapy dose calculations. Med Phys. 2004;31:633-674.
Abramowitz M, Stegun IA, eds., Handbook of Mathematical Functions with Formulas, Graphs, and Mathematical Tables, 9th printing, chapter ”Modified Bessel Functions I and K” section 9.6, pp. 374-377. Dover; 1972.
Nudat3 database, National Nuclear Data Center.