scholarly journals A Mathematical Model of Thyroid Disease Response to Radiotherapy

Mathematics ◽  
2021 ◽  
Vol 9 (19) ◽  
pp. 2365
Author(s):  
Araceli Gago-Arias ◽  
Sara Neira ◽  
Filippo Terragni ◽  
Juan Pardo-Montero
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Disease ◽  
Experimental Studies ◽  
Absorbed Dose ◽  
Continuous Model ◽  
Tumor Control ◽  
Tumor Control Probability ◽  
Response Dynamics ◽  
Thyroid Cells ◽  
Treatment Individualization

We present a mechanistic biomathematical model of molecular radiotherapy of thyroid disease. The general model consists of a set of differential equations describing the dynamics of different populations of thyroid cells with varying degrees of damage caused by radiotherapy (undamaged cells, sub-lethally damaged cells, doomed cells, and dead cells), as well as the dynamics of thyroglobulin and antithyroglobulin autoantibodies, which are important surrogates of treatment response. The model is presented in two flavours: on the one hand, as a deterministic continuous model, which is useful to fit populational data, and on the other hand, as a stochastic Markov model, which is particularly useful to investigate tumor control probabilities and treatment individualization. The model was used to fit the response dynamics (tumor/thyroid volumes, thyroglobulin and antithyroglobulin autoantibodies) observed in experimental studies of thyroid cancer and Graves’ disease treated with 131I-radiotherapy. A qualitative adequate fitting of the model to the experimental data was achieved. We also used the model to investigate treatment individualization strategies for differentiated thyroid cancer, aiming to improve the tumor control probability. We found that simple individualization strategies based on the absorbed dose in the tumor and tumor radiosensitivity (which are both magnitudes that can potentially be individually determined for every patient) can lead to an important raise of tumor control probabilities.

scholarly journals Thyroid Dose and Hypothyroidism as a Result of Radiation Therapy for Head and Neck Malignancies and Brain Tumors in Iran

2020 ◽  
Author(s):  
Samira Yazdani ◽  
Fathollah Bouzarjomehri ◽  
Eric Slessinger
Keyword(s):  
Radiation Therapy ◽  
Head And Neck ◽  
Absorbed Dose ◽  
In Vivo Dosimetry ◽  
Tumor Control ◽  
Average Dose ◽  
Thyroid Function Tests ◽  
X Rays ◽  
Tumor Control Probability ◽  
Prescription Dose

Purpose: Radiation Therapy has a fundamental role in the treatment of cancer. Achieving Tumor Control Probability (TCP), while avoiding normal tissue complication is the goal of this treatment modality. The sensitivity of the thyroid gland to radiation increases the risk of developing secondary thyroid cancer and hypothyroidism. Materials and Methods: The average dose to the thyroid from head and neck irradiation was measured using in vivo dosimetry (Thermolumincsence Dosimetry). The Radiotherapy technique was given using 6 MV x-rays from an Elekta compact linear accelerator and conformal technique delivered 1.8 to 2.0 Gy over 5 sequential days per week. Results: The average absorbed dose to the thyroid from head and neck radiotherapy was 4.4% of the prescription dose and from whole brain radiotherapy was 0.7% of the prescription dose. Thyroid Stimulating Hormone (TSH) levels were determined in 30 patients before and after completion of radiation therapy. The average concentration of TSH increased from 0.88 +/- 0.55 (pre-radiotherapy) to 1.7 +/- 0.66 (post-radiotherapy), (p < 0.05). Conclusion: Thyroid absorbed dose was less than the threshold dose for patients who received radiotherapy to the head and neck based on thyroid function tests

scholarly journals RADT-30. COPLANAR AND NON-COPLANAR VMAT ARC SETTING FOR GLIOBLASTOMA MULTIFORME – DOSIMETRIC AND RADIOBIOLOGICAL COMPARISONS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii188-ii188
Author(s):  
Vanessa Moldoveanu ◽  
Mihai Dumitrache ◽  
Xenia Bacinschi ◽  
Luiza Serbanescu ◽  
Rodica Anghel
Keyword(s):  
Glioblastoma Multiforme ◽  
Organs At Risk ◽  
Absorbed Dose ◽  
Target Volume ◽  
Tumor Control ◽  
Normal Brain ◽  
Tumor Control Probability ◽  
Equivalent Uniform Dose ◽  
Dose Volume Histograms ◽  
Arc Setting

Abstract OBJECTIVES To evaluate three different arc arrangements in glioblastoma multiforme (GBM) treatment planning. METHODS Eighteen GBM patients were replanned by using one full arc (1FA), two full coplanar arcs (2FA), and three full non- coplanar arcs (3FA). Dose-volume histograms (DVHs) were used to calculate conformity (CI), homogeneity (HI) and gradient indices (GI), the dose received by 5% (D5%) and 95% (D95%) of the planning target volume (PTV) and maximum (Dmax) and minimum (Dmin) absorbed dose for organs at risk (OARs), including normal brain (brain excluding PTV). General equivalent uniform dose (gEUD) for both PTV and OARs and EUD based tumor control probability (TCP) and normal tissue control probability (NTCP) were calculated as radiobiological parameters. Monitor units (MUs) were also computed and compared. RESULTS All three plans resulted in similar conformity, while 2FA resulted in a better homogeneity than 1FA (0.06vs. 0.07, p=0.007). 2FA vs. 1FA dose analysis for PTV revealed a lower D5% (61.28 vs. 61.37 Gy, p=0.014), a higher D95% (58.7 vs. 58.47 Gy, p=0.008) and a higher TCP (37.73 vs.37.38%, p=0.008). The utilization of 3FA did not significantly change the outcome of PTV but managed to decrease GI in comparison to both 1FA and 2FA (4.11 vs. 5.19 and 5.49, p&lt; 0.05). Regarding NB, 1FA scored a higher Dmax than 2FA (62.32 vs. 61.98 Gy, p=0.005), while 3FA scored a higher Dmin than 1FA and 2FA (2.52 vs. 1.08 and 1.10 Gy, p&lt; 0.05). No difference in NB NTCP was noted between techniques. Furthermore, 3FA yielded more MUs when compared to coplanar patters (566.74 vs. 486.78, p= 0.015 for 1FA and 495.98, p=0.019 for 2FA). CONCLUSION Although all three approaches resulted in clinical admissible outcome, the utilization of complex non-coplanar arrangement resulted in a stepper dose fall off but did not improve PTV results and increased machine MUs.

scholarly journals FOXE1-Dependent Regulation of Macrophage Chemotaxis by Thyroid Cells In Vitro and In Vivo

2021 ◽  
Vol 22 (14) ◽  
pp. 7666
Author(s):  
Sara C. Credendino ◽  
Marta De Menna ◽  
Irene Cantone ◽  
Carmen Moccia ◽  
Matteo Esposito ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Immune Cells ◽  
Cancer Susceptibility ◽  
Macrophage Infiltration ◽  
M2 Macrophage ◽  
Thyroid Cells ◽  
Transcriptional Alterations ◽  
Cancer Phenotypes

Forkhead box E1 (FOXE1) is a lineage-restricted transcription factor involved in thyroid cancer susceptibility. Cancer-associated polymorphisms map in regulatory regions, thus affecting the extent of gene expression. We have recently shown that genetic reduction of FOXE1 dosage modifies multiple thyroid cancer phenotypes. To identify relevant effectors playing roles in thyroid cancer development, here we analyse FOXE1-induced transcriptional alterations in thyroid cells that do not express endogenous FOXE1. Expression of FOXE1 elicits cell migration, while transcriptome analysis reveals that several immune cells-related categories are highly enriched in differentially expressed genes, including several upregulated chemokines involved in macrophage recruitment. Accordingly, FOXE1-expressing cells induce chemotaxis of co-cultured monocytes. We then asked if FOXE1 was able to regulate macrophage infiltration in thyroid cancers in vivo by using a mouse model of cancer, either wild type or with only one functional FOXE1 allele. Expression of the same set of chemokines directly correlates with FOXE1 dosage, and pro-tumourigenic M2 macrophage infiltration is decreased in tumours with reduced FOXE1. These data establish a novel link between FOXE1 and macrophages recruitment in the thyroid cancer microenvironment, highlighting an unsuspected function of this gene in the crosstalk between neoplastic and immune cells that shape tumour development and progression.

scholarly journals Automated Non-Coplanar VMAT for Dose Escalation in Recurrent Head and Neck Cancer Patients

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1910
Author(s):  
Kaley Woods ◽  
Robert K. Chin ◽  
Kiri A. Cook ◽  
Ke Sheng ◽  
Amar U. Kishan ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Dose Escalation ◽  
Volumetric Modulated Arc Therapy ◽  
Normal Tissue Complication Probability ◽  
Tumor Control ◽  
Tumor Control Probability ◽  
Increased Risk ◽  
Recurrent Head

This study evaluates the potential for tumor dose escalation in recurrent head and neck cancer (rHNC) patients with automated non-coplanar volumetric modulated arc therapy (VMAT) stereotactic body radiation therapy (SBRT) planning (HyperArc). Twenty rHNC patients are planned with conventional VMAT SBRT to 40 Gy while minimizing organ-at-risk (OAR) doses. They are then re-planned with the HyperArc technique to match these minimal OAR doses while escalating the target dose as high as possible. Then, we compare the dosimetry, tumor control probability (TCP), and normal tissue complication probability (NTCP) for the two plan types. Our results show that the HyperArc technique significantly increases the mean planning target volume (PTV) and gross tumor volume (GTV) doses by 10.8 ± 4.4 Gy (25%) and 11.5 ± 5.1 Gy (26%) on average, respectively. There are no clinically significant differences in OAR doses, with maximum dose differences of <2 Gy on average. The average TCP is 23% (± 21%) higher for HyperArc than conventional plans, with no significant differences in NTCP for the brainstem, cord, mandible, or larynx. HyperArc can achieve significant tumor dose escalation while maintaining minimal OAR doses in the head and neck—potentially enabling improved local control for rHNC SBRT patients without increased risk of treatment-related toxicities.

scholarly journals Y-90 SIRT: evaluation of TCP variation across dosimetric models

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Benjamin J. Van ◽  
Yuni K. Dewaraja ◽  
Mamadou L. Sangogo ◽  
Justin K. Mikell
Keyword(s):  
Standard Model ◽  
Volume Fraction ◽  
Liver Tumors ◽  
Package Insert ◽  
Absorbed Dose ◽  
Tumor Control ◽  
Partition Model ◽  
Pet Ct ◽  
The Standard Model ◽  
Biological Outcomes

Abstract Introduction Much progress has been made in implementing selective internal radiation therapy (SIRT) as a viable treatment option for hepatic malignancies. However, there is still much need for improved options for calculating the amount of activity to be administered. To make advances towards this goal, this study examines the relationship between predicted biological outcomes of liver tumors via tumor control probabilities (TCP) and parenchyma via normal tissue complication probabilities (NTCP) given variations in absorbed dose prescription methodologies. Methods Thirty-nine glass microsphere treatments in 35 patients with hepatocellular carcinoma or metastatic liver disease were analyzed using 99mTc-MAA SPECT/CT and 90Y PET/CT scans. Predicted biological outcomes corresponding to the single compartment (standard) model and multi-compartment (partition) dosimetry model were compared using our previously derived TCP dose-response curves over a range of 80–150 Gy prescribed absorbed dose to the perfused volume, recommended in the package insert for glass microspheres. Retrospective planning dosimetry was performed on the MAA SPECT/CT; changes from the planned infused activity due to selection of absorbed dose level and dosimetry model (standard or partition) were used to scale absorbed doses reported from 90Y PET/CT including liver parenchyma and lesions (N = 120) > 2 ml. A parameterized charting system was developed across all potential prescription options to enable a clear relationship between standard prescription vs. the partition model-based prescription. Using a previously proposed NTCP model, the change in prescribed dose from a standard model prescription of 120 Gy to the perfused volume to a 15% NTCP prescription to the normal liver was explored. Results Average TCP predictions for the partition model compared with the standard model varied from a 13% decrease to a 32% increase when the prescribed dose was varied across the range of 80–150 Gy. In the parametrized chart comparing absorbed dose prescription ranges across the standard model and partition models, a line of equivalent absorbed dose to a tumor was identified. TCP predictions on a per lesion basis varied between a 26% decrease and a 81% increase for the most commonly chosen prescription options when comparing the partition model with the standard model. NTCP model was only applicable to a subset of patients because of the small volume fraction of the liver that was targeted in most cases. Conclusion Our retrospective analysis of patient imaging data shows that the choice of prescribed dose and which model to prescribe potentially contribute to a wide variation in average tumor efficacy. Biological response data should be included as one factor when looking to improve patient care in the clinic. The use of parameterized charting, such as presented here, will help direct physicians when transitioning to newer prescription methods.

scholarly journals Investigation of whether in-room CT-based adaptive intracavitary brachytherapy for uterine cervical cancer is robust against interfractional location variations of organs and/or applicators

2016 ◽  
Vol 57 (6) ◽  
pp. 677-683 ◽  
Author(s):  
Yoshifumi Oku ◽  
Hidetaka Arimura ◽  
Tran Thi Thao Nguyen ◽  
Yoshiyuki Hiraki ◽  
Masahiko Toyota ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Radiation Treatment ◽  
Organs At Risk ◽  
Normal Tissue Complication Probability ◽  
Uterine Cervical Cancer ◽  
Intracavitary Brachytherapy ◽  
Conformity Index ◽  
Tumor Control ◽  
Tumor Control Probability ◽  
Target Volumes

Abstract This study investigates whether in-room computed tomography (CT)-based adaptive treatment planning (ATP) is robust against interfractional location variations, namely, interfractional organ motions and/or applicator displacements, in 3D intracavitary brachytherapy (ICBT) for uterine cervical cancer. In ATP, the radiation treatment plans, which have been designed based on planning CT images (and/or MR images) acquired just before the treatments, are adaptively applied for each fraction, taking into account the interfractional location variations. 2D and 3D plans with ATP for 14 patients were simulated for 56 fractions at a prescribed dose of 600 cGy per fraction. The standard deviations (SDs) of location displacements (interfractional location variations) of the target and organs at risk (OARs) with 3D ATP were significantly smaller than those with 2D ATP (P &lt; 0.05). The homogeneity index (HI), conformity index (CI) and tumor control probability (TCP) in 3D ATP were significantly higher for high-risk clinical target volumes than those in 2D ATP. The SDs of the HI, CI, TCP, bladder and rectum D2cc, and the bladder and rectum normal tissue complication probability (NTCP) in 3D ATP were significantly smaller than those in 2D ATP. The results of this study suggest that the interfractional location variations give smaller impacts on the planning evaluation indices in 3D ATP than in 2D ATP. Therefore, the 3D plans with ATP are expected to be robust against interfractional location variations in each treatment fraction.

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