Browsing by Author "Pombar, Miguel"

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    Evaluation of indirect damage and damage saturation effects in dose- response curves of hypofractionated radiotherapy of early-stage NSCLC and brain metastases
    (2021) Gago-Arias, Araceli; Neira, Sara; Pombar, Miguel; Gomez-Caamano, Antonio; Pardo-Montero, Juan
    Background and purpose: To investigate the possible contribution of indirect damage and damage saturation to tumour control obtained with SBRT/SRS treatments for early-stage NSCLC and brain metastases. Methods and materials: We have constructed a dataset of early-stage NSCLC and brain metastases dose- response. These data were fitted to models based on the linear-quadratic (LQ), the linear-quadratic-linear (LQL), and phenomenological modifications of the LQ-model to account for indirect cell damage. We use the Akaike-Information-Criterion formalism to compare performance, and studied the stability of the results with changes in fitting parameters and perturbations on dose/TCP values. Results: In NSCLC, a modified LQ-model with a beta-term increasing with dose yields the best-fits for oc/ fi = 10 Gy. Only the inclusion of very fast accelerated proliferation or low oc/fi values can eliminate such superiority. In brain, the LQL model yields the best-fits, and the ranking is not affected by variations of fitting parameters or dose/TCP perturbations. Conclusions: For oc/fi = 10 Gy, a modified LQ-model with a beta-term increasing with dose provides better fits to NSCLC dose-response curves. For brain metastases, the LQL provides the best fit. This might be interpreted as a hint of indirect damage in NSCLC, and damage saturation in brain metastases. The results for NSCLC are strongly dependent on the value of oc/fi and may require further investigation, while those for brain seem to be clearly significant. Our results can assist in the design of improved radiotherapy for NSCLC and brain metastases, aiming at avoiding over/under-treatment. (c) 2021 The Author(s). Published by Elsevier B.V. Radiotherapy and Oncology 101 (2021) 1-8 This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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    Quantification of internal dosimetry in PET patients II: Individualized Monte Carlo-based dosimetry for [18F]fluorocholine PET
    (2021) Neira, Sara; Guiu-Souto, Jacobo; Pais, Paulino; Martinez de Llano, Sofia Rodriguez; Fernandez, Carlos; Pubul, Virginia; Ruibal, Alvaro; Pombar, Miguel; Gago-Arias, Araceli; Pardo-Montero, Juan
    Purpose To obtain individualized internal doses with a Monte Carlo (MC) method in patients undergoing diagnostic [18F]FCH-PET studies and to compare such doses with the MIRD method calculations. Methods A patient cohort of 17 males were imaged after intravenous administration of a mean [18F]FCH activity of 244.3 MBq. The resulting PET/CT images were processed in order to generate individualized input source and geometry files for dose computation with the MC tool GATE. The resulting dose estimates were studied and compared to the MIRD method with two different computational phantoms. Mass correction of the S-factors was applied when possible. Potential sources of uncertainty were closely examined: the effect of partial body images, urinary bladder emptying, and biokinetic modeling. Results Large differences in doses between our methodology and the MIRD method were found, generally in the range +/- 25%, and up to +/- 120% for some cases. The mass scaling showed improvements, especially for non-walled and high-uptake tissues. Simulations of the urinary bladder emptying showed negligible effects on doses to other organs, with the exception of the prostate. Dosimetry based on partial PET/CT images (excluding the legs) resulted in an overestimation of mean doses to bone, skin, and remaining tissues, and minor differences in other organs/tissues. Estimated uncertainties associated with the biokinetics of FCH introduce variations of cumulated activities in the range of +/- 10% in the high-uptake organs. Conclusions The MC methodology allows for a higher degree of dosimetry individualization than the MIRD methodology, which in some cases leads to important differences in dose values. Dosimetry of FCH-PET based on a single partial PET study seems viable due to the particular biokinetics of FCH, even though some correction factors may need to be applied to estimate mean skin/bone doses.
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    Quantification of internal dosimetry in PET patients: individualized Monte Carlo vs generic phantom-based calculations
    (2020) Neira, Sara; Guiu-Souto, Jacobo; Diaz-Botana, Pablo; Pais, Paulino; Fernandez, Carlos; Pubul, Virginia; Ruibal, Alvaro; Candela-Juan, Cristian; Gago-Arias, Araceli; Pombar, Miguel; Pardo-Montero, Juan
    Purpose The purpose of this work is to calculate individualized dose distributions in patients undergoing(18)F-FDG PET/CT studies through a methodology based on full Monte Carlo (MC) simulations and PET/CT patient images, and to compare such values with those obtained by employing nonindividualized phantom-based methods. Methods We developed a MC-based methodology for individualized internal dose calculations, which relies on CT images (for organ segmentation and dose deposition), PET images (for organ segmentation and distributions of activities), and a biokinetic model (which works with information provided by PET and CT images) to obtain cumulated activities. The software vGATE version 8.1. was employed to carry out the Monte Carlo calculations. We also calculated deposited doses with nonindividualized phantom-based methods (Cristy-Eckerman, Stabin, and ICRP-133). Results Median MC-calculated dose/activity values are within 0.01-0.03 mGy/MBq for most organs, with higher doses delivered especially to the bladder wall, major vessels, and brain (medians of 0.058, 0.060, 0.066 mGy/MBq, respectively). Comparison with values obtained with nonindividualized phantom-based methods has shown important differences in many cases (ranging from -80% to + 260%). These differences are significant (p < 0.05) for several organs/tissues, namely, remaining tissues, adrenals, bladder wall, bones, upper large intestine, heart, pancreas, skin, and stomach wall. Conclusions The methodology presented in this work is a viable and useful method to calculate internal dose distributions in patients undergoing medical procedures involving radiopharmaceuticals, individually, with higher accuracy than phantom-based methods, fulfilling the guidelines provided by the European Council directive 2013/59/Euratom.