A Critical Analysis of the Overall Uncertainties in the Radiotherapy Treatment Process
DOI:
https://doi.org/10.29384/rbfm.2025.v19.19849001822Keywords:
Quality assurance, disease staging, dose delivered, dose pre-scribed, translational studies, dosimetry, overall uncertaintiesAbstract
The integration of all the steps involved in the treatment process is quite complex, as it involves the correct knowledge of the dose-response curves developed in laboratory experiments, the translation of these results to the clinic, the adequate delineation of the tumor, the appropriate dose prescribed for each type of tumor and delivered daily to the patient. For example, the correct assessment of the dose administered to a patient strongly depends on an interconnected chain of steps executed harmoniously, as the demand for accuracy of a given dosimetry procedure is very high. In this case, the measurement results must be represented the best possible reported values with their typical uncertainties to allow clinical results to be achieved and comparable with those of other institutions. The robustness of the chain of events is often fragile, with uncertainties at each stage sometimes not considered or sometimes difficult to estimate, requiring different conceptual and statistical approaches at various times in the decision-making process. As a result, as the additive sequence of uncertainties is generally not fully considered, and the clinical outcome may not be as anticipated. The objective of this review is to critically and constructively highlight the weak points observed in the interrelationship of all steps that lead to better tumor control and ultimately, to provoke a reflection on the theme.
Downloads
References
Van Dyck J and de Almeida C E. Highlights of Technology Trends in Radiation Oncology. Tópicos Especiais em Física Médica e Radioproteção 2023; Ed. Atena ISBN978652580442-2.
Symonds P and Jones GDD. FLASH Radiotherapy: the next technological advances in radiation therapy. 2019; Clin. Oncol 31405-406.
Bourhis J, Montay-Gruel P, Goncalves JP, et al. Clinical translation of FLASH radiotherapy: why and how. Radiother Oncol. 2019;139 v 11-17. 2019.
DeLaney T F Charged Particles Issues: Particle Radiation Therapy. Semin. Radiat Oncol 2018; 28 (2) pp 75-78
Haddad C. Os desafios físicos e dosimétricos para o uso de fontes seladas de 125I. Tópicos Especiais em Física Médica e Radioproteção 2023 Ed. Atena ISBN978652580442-2.
Nath R et al. Guidelines by the AAPM and GEC-ESTRO on the innovative brachytherapy devices and application. Medical Physics 2016; V43 3178-3205.
The ISO Guide on the Expression of Uncertainty in Measurement INTERNATIONAL COMMITTEE FOR WEIGHTS AND MEASURES, Evaluation of Measurement Data - Guide to the Expression of Uncertainty in Measurement, JCGM 100: 2008; BIPM, Paris
de Almeida C E. Incertezas na determinação da dose absorvida no alvo terapêutico. Tópicos Especiais em Física Médica e Radioproteção 2023; Ed. Atena ISBN978652580442-2.
Okunieff PD, Morgan A, Niemierko H and Suit H. Radiation dose response of human tumors Int. J. Radiat. Oncol.Biol. Phys. 1995; 32: 1227-1237.
Bentzen SM, Constine LS, Deasy JO et al. Quantitative analysis of normal tissue effects in the clinic (QUANTEC): an introduction to the scientific issues. Int. J. Radiat. Oncol.Biol. Phys 2010;76: S3-S9.
Merwe Van der, Van Dyck J, Healy B. et al. Accuracy requirements and uncertainties in radiotherapy: a report of the International Atomic Energy Agency. 2017; Acta Radiologica. Vol 56. Issue 1.
Boyer, A.L and Schulteiss T. Effect of dosimetric and clinical uncertainty on complication-free local tumor control. Radiother. Oncol. 1998; 11:65-71.
Mijnheer, B.J, Battermann JJ. And Wambersie A. What degree of accuracy is required and can be achieved in photon and neutron therapy. Radiother. Oncol.1987; 8:237-252.
ICRU # 24 Determination of the absorbed dose in a patient irradiated by beams of X or gamma rays in radiotherapy procedures. Washington.1976.
Wambersie A., Dutreix J. and Dutreix A. Dosimetric precision required in radiotherapy Consequences of the choices and performance required of detectors. J. Belge. Radiol 1969; 52: 94-104.
Wambersie A., what accuracy is required and can be achieved in radiation therapy (Review of radiobiological and clinical data Radiochim Acta 2001; 89: 255-263.
Dutreix A When and how can we improve precision in radiotherapy Radiother. Oncol 1984; 1:275-292.
Roberts AS., Hendry JH Swindell JM et al Compensation for changes inn dose rate in radical low-dose rate brachytherapy: a radiobiological analysis of a randomized clinical trial. Radiother. Oncol 2004; 70: 63-74.
a) Muñoz A. E., Peixoto J. G., de Almeida C. E. A critical review of translational processes in pre-clinical radiotherapy associated with limitations in the dosimetry of conformational biological irradiators. 2017; Braz. Journal of Radiation Sciences.
b) Muñoz A.E. Pickler A., Mantuano A., Salata A. and de Almeida C.E. Feasibility study of the Fricke Chemical dosimeter as an independent dosimetric system for the small animal radiation research platform (SARRP). Physica Médica, 2020; (71) 168-175.2020. doi.org/10.1016/j.emp.
c) Muñoz A. E., Gomez C B., Alaminos-Bouza A and de Almeida CE. Integrating X-ray millimetric field dosimetry with a synthetic diamond detector into the treatment system commissioning of a preclinical irradiator. Med. Phys. 2021; 48(7) 4038-4052.
Pedersen H, Keith K. Kunugi A., Hammer C. G., et al Radiation Biology Irradiator Dose Verification Survey Radiation Research,185(2):2016;163-16 https://doi.org/10.1667/RR14155.1
Hackam, D. G.; Redelmeir, D. A. Translation of Research Evidence from Animals to Humans.2006; JAMA, vol. 296, no. 14, pp. 1727–1732.
Butterworth, K. T.; Prise, K. M.; Verhaegen, F. Small animal image-guided radiotherapy: status, considerations and potential for translational impact. Br. J. Radiol., 2015; vol. 88, no. 1045, p. 20140634.
Ghita, M.; Mcmahon, S. J.; Thompson, H. F.; et al K. M. Small field dosimetry for the small animal radiotherapy research platform (SARRP), Radiat. Oncol., 2017; vol. 12, no. 1, pp. 1–10.
Desrosiers, M.; Dewerd, L.; Deye, J.; Lindsay I, P.; Murphy, M. K.; et al, H. The Importance of Dosimetry Standardization in Radiobiology. J. Res. Natl. Inst. Stand. Technol., 2013; vol. 118, pp. 403–418.
Sparano, J.A., et al. "Tailoring adjuvant chemotherapy for breast cancer." (2018); New England Journal of Medicine. [Link](https://doi.org/10.1056/NEJMoa1804710)
Spratt, D.E., et al. "Deciphering the molecular profile of prostate cancer." 2018; JAMA Oncology. (doi.org/10.1001/jamaoncol.2018.0001)
Loibl, S., et al. PIK3CA mutations and response to PI3K inhibitors in breast cancer." Clinical Cancer Research. 2019; (doi.org/10.1158/1078-0432.CCR-18-2763)
Mateo, J., et al. DNA damage response gene defects in prostate cancer. 2020; Journal of Clinical Oncology. (doi.org/10.1200/JCO.20.00124)
Formenti, S.C., et al. RADVAX trials: Radiation and immunotherapy. 2018; Nature Medicine. (doi.org/10.1038/s41591-018-0136-9)
Cardoso, F., et al.; MammaPrint and risk assessment in breast cancer. 2016; New England Journal of Medicine. (https://doi.org/10.1056/NEJMoa1602253)
Antonarakis, E.S., et al. AR-V7 and treatment response in prostate cancer. The Lancet Oncology. 2019; doi.org/10.1016/S1470-2045(18)30566-9)
Jiang, F., et al. Liquid biopsies in real-time cancer treatment monitoring. 2020; Artificial Intelligence in Cancer. (doi.org/10.1016/j.aic.2020.1027)
Jiang, F., et al. AI algorithms in radiation therapy. Artificial Intelligence. in Cancer. 2020; (hdoi.org/10.1016/j.aic.2020.1027)
Freedman, R.A., et al. Challenges in molecular testing accessibility for cancer patients. 2021; Journal of Clinical Oncology. doi.org/10.1200/JCO.21.00001)
Smith, B.D., et al. Impact of treatment delays on cancer care outcomes. Cancer. 2019; (doi.org/10.1002/cncr.31994)
Lee, C.I., et al. (2020). "Errors in biopsy procedures and guidance in cancer diagnosis." *Radiology*. (doi.org/10.1148/radiol.2020201300)
Wong, K.H., et al. Challenges in adaptive radiation therapy implementation." Radiotherapy and Oncology. 2018; (doi.org/10.1016/j.radonc.2018.03.001
Andreo, P. Uncertainties in dosimetric data and beam calibration. Int. J. Radiat. Oncol. Biol. Phys., 1990; v. 19, n. 5, p. 1233-1247.
de Almeida C. E., E. Sibata C.H. et al. Análise da frequência de erros de cálculo nas fichas de tratamento detectadas no double check. Boletim ABFM. 1979;
Holdsworth C., Hummel-Kramer SM and Phillips M. Scripting in radiation therapy: an automatic 3D beam-naming system. 2011; Med Dosim 36 (3) 272-275.
Kirova, Y. De Almeida C.E. Canary P and Kuroki I. Heart coronary and breast cancer. Journ. Breast. 2012; 20(2) 196-7 2011. doi: 10.1016/j.Breast .
Y, Massabeau, C. Fournier-Bidoz N. Heart, coronaries and breast cancer radiotherapy Br J Radiol;86(1025): 2013; doi: 10.1259/bjr.20120643.
Venarini S. Fournier-Bidoz C N. de Almeida C E. Ser-vois V. Campana F. Mosseri V. Fourquet A and Kirova Y. Visualization of the Left Anterior Descending Coronary Artery on Computed Tomographic Images Used for the Planning of Breast Radiation Treatments Br J Radiol 2013; 86(1025):20120643.doi: 10.1259/bjr.20120643. Epub 2013
Van Dyk J. The Modern Technology of Radiation Oncology Vol 4. Medical Physics Publishing.2020
Unkelback J. and Paganetti Robust proton treatment planning: physical and biological optimization. Se. Tad. Oncol. 2017; 28(2)88-96 doi: 101016/j.serradonc.2017.11.005
de Almeida C.E and Salata C. Absolute Reference and Relative Dosimetry in Radiotherapy, 2022; Book Dosimetry Intech Open. http://dx.doi/10.5772/intechOpen.98044
Andreo P. Burns D. Nahum A. Seuntjens J and Attix F. Fundamentals of Ionizing Radiation Dosimetry. 2017; New York: John Wiley & Sons Inc.,
IAEA. Technological Reports Series no 398: Absorbed dose determination in external beam radiotherapy. Vienna: IAEA, 2024.
McEwen. M. Primary standards of air kerma for 60C and x-rays and absorbed dose in photon and electron beams. AAPM Summer School, 2009.
de Almeida C.E Considerações gerais sobre um sistema de medição. 2023; Tópicos Especiais em Física Médica e Radioproteção 2023 Ed. Atena ISBN978652580442-2
de Almeida C.E and Erika Fatores de correção usados para a realização das grandezas Tópicos Especiais em Física Médica e Radioproteção 2023; Ed. Atena ISBN978652580442-
de Almeida C.E; Malamut C. and Rodrigues L.; Experimental arrangement and data acquisition for Exposure air kerma standards for cobalt-60 gamma rays. . Journal of Medical Physics 1996; v 21 pp.1-5.
de Almeida C. E. E. Bases físicas de um programa de garantia da qualidade em IMRT. Rio de
Thwaites. D.I. Uncertainties at the end point of the basic dosimetry chain. 2012; IAEA. Measurement Assurance in Dosimetry 239-255.
Gilbert, E. S. The impact of dosimetry uncertainties on dose-response analyses. Health Phys., 2009; v. 97, n. 5, p. 487-492.
Ibrahim, M.; Aqueel, M. Uncertainty assessment: relative versus absolute point dose measurement for patient specific Quality Assurance in EBRT. Progress in Medical Physics, 2017; v. 28, n. 3, p. 111-121.
Castro P., Garcia-Vicente F., Minguez C. et al Study of the uncertainty in the determination of the absorbed dose to water during external beam radiotherapy calibration. J. Appl. Clin Med Phys 9(1) 70-76. 2008; Doi: 10.1120/jacmp.v9i1.26776
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Carlos Eduardo de Almeida

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
The submission of original articles to the Brazilian Journal of Medical Physics implies the transfer, by the authors, of the rights of print and digital publication. Copyright for published articles remains with the author, with journal rights on first publication. Authors may only use the same results in other publications by clearly indicating this journal as the original publisher. As we are an open access journal, free use of articles in educational, scientific, non-commercial applications is allowed, as long as the source is cited.
The Brazilian Journal of Medical Physics is under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0).