scholarly journals Theoretical derivation and clinical dose-response quantification of a unified multi-activation (UMA) model of cell survival from a logistic equation

BJR|Open ◽  
2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Shidong Li
Keyword(s):  
Cell Survival ◽  
Normal Tissue ◽  
Dose Range ◽  
Normal Tissue Complication Probability ◽  
Order Reaction ◽  
Second Order Reaction ◽  
X Ray ◽  
Tumour Control ◽  
Tumour Control Probability ◽  
X Ray Imaging

Objective: To theoretically derive a unified multiactivation (UMA) model of cell survival after ionising radiation that can accurately assess doses and responses in radiotherapy and X-ray imaging. Methods: A unified formula with only two parameters in fitting of a cell survival curve (CSC) is first derived from an assumption that radiation-activated cell death pathways compose the first- and second-order reaction kinetics. A logit linear regression of CSC data is used for precise determination of the two model parameters. Intrinsic radiosensitivity, biologically effective dose (BED), equivalent dose to the traditional 2 Gy fractions (EQD2), tumour control probability, normal-tissue complication probability, BED50 and steepness (Γ50) at 50% of tumour control probability (or normal-tissue complication probability) are analytical functions of the model and treatment (or imaging) parameters. Results: The UMA model has almost perfectly fit typical CSCs over the entire dose range with R2≥0.99. Estimated quantities for stereotactic body radiotherapy of early stage lung cancer and the skin reactions from X-ray imaging agree with clinical results. Conclusion: The proposed UMA model has theoretically resolved the catastrophes of the zero slope at zero dose for multiple target model and the bending curve at high dose for the linear quadratic model. More importantly, it analytically predicts dose–responses to various dose–fraction schemes in radiotherapy and to low dose X-ray imaging based on these preclinical CSCs. Advances in knowledge: The discovery of a unified formula of CSC over the entire dose range may reveal a common mechanism of the first- and second-order reaction kinetics among multiple CD pathways activated by ionising radiation at various dose levels.

scholarly journals Monte Carlo Calculation of Radioimmunotherapy with90Y-,177Lu-,131I-,124I-, and188Re-Nanoobjects: Choice of the Best Radionuclide for Solid Tumour Treatment by Using TCP and NTCP Concepts

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
S. Lucas ◽  
O. Feron ◽  
B. Gallez ◽  
B. Masereel ◽  
C. Michiels ◽  
...  
Keyword(s):  
Treatment Efficacy ◽  
Solid Tumour ◽  
Normal Tissue ◽  
Monte Carlo Calculation ◽  
Normal Tissue Complication Probability ◽  
Small Cell ◽  
Small Cell Lung ◽  
Tumour Control ◽  
Improve Treatment ◽  
Tumour Control Probability

Radioimmunotherapy has shown that the use of monoclonal antibodies combined with a radioisotope like131I or90Y still remains ineffective for solid and radioresistant tumour treatment. Previous simulations have revealed that an increase in the number of90Y labelled to each antibody or nanoobject could be a solution to improve treatment output. It now seems important to assess the treatment output and toxicity when radionuclides such as90Y,177Lu,131I,124I, and188Re are used. Tumour control probability (TCP) and normal tissue complication probability (NTCP) curves versus the number of radionuclides per nanoobject were computed with MCNPX to evaluate treatment efficacy for solid tumours and to predict the incidence of surrounding side effects. Analyses were carried out for two solid tumour sizes of 0.5 and 1.0 cm radius and for nanoobject (i.e., a radiolabelled antibody) distributed uniformly or nonuniformly throughout a solid tumour (e.g., Non-small-cell-lung cancer (NSCLC)).90Y and188Re are the best candidates for solid tumour treatment when only one radionuclide is coupled to one carrier. Furthermore, regardless of the radionuclide properties, high values of TCP can be reached without toxicity if the number of radionuclides per nanoobject increases.

scholarly journals Influence of Urethra Sparing on Tumor Control Probability and Normal Tissue Complication Probability in Focal Dose Escalated Hypofractionated Radiotherapy: A Planning Study Based on Histopathology Reference

2021 ◽  
Vol 11 ◽  
Author(s):  
Simon K. B. Spohn ◽  
Ilias Sachpazidis ◽  
Rolf Wiehle ◽  
Benedikt Thomann ◽  
August Sigle ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Normal Tissue ◽  
Normal Tissue Complication Probability ◽  
Tumor Control ◽  
Planning Study ◽  
Tumour Control ◽  
Tumour Control Probability ◽  
Psma Pet ◽  
Pet Ct ◽  
Dose Constraints

PurposeMultiparametric magnetic resonance tomography (mpMRI) and prostate specific membrane antigen positron emission tomography (PSMA-PET/CT) are used to guide focal radiotherapy (RT) dose escalation concepts. Besides improvements of treatment effectiveness, maintenance of a good quality of life is essential. Therefore, this planning study investigates whether urethral sparing in moderately hypofractionated RT with focal RT dose escalation influences tumour control probability (TCP) and normal tissue complication probability (NTCP).Patients and Methods10 patients with primary prostate cancer (PCa), who underwent 68Ga PSMA-PET/CT and mpMRI followed by radical prostatectomy were enrolled. Intraprostatic tumour volumes (gross tumor volume, GTV) based on both imaging techniques (GTV-MRI and -PET) were contoured manually using validated contouring techniques and GTV-Union was created by summing both. For each patient three IMRT plans were generated with 60 Gy to the whole prostate and a simultaneous integrated boost up to 70 Gy to GTV-Union in 20 fractions by (Plan 1) not respecting and (Plan 2) respecting dose constraints for urethra as well as (Plan 3) respecting dose constraints for planning organ at risk volume for urethra (PRV = urethra + 2mm expansion). NTCP for urethra was calculated applying a Lyman-Kutcher-Burman model. TCP-Histo was calculated based on PCa distribution in co-registered histology (GTV-Histo). Complication free tumour control probability (P+) was calculated. Furthermore, the intrafractional movement was considered.ResultsMedian overlap of GTV-Union and PRV-Urethra was 1.6% (IQR 0-7%). Median minimum distance of GTV-Histo to urethra was 3.6 mm (IQR 2 – 7 mm) and of GTV-Union to urethra was 1.8 mm (IQR 0.0 – 5.0 mm). The respective prescription doses and dose constraints were reached in all plans. Urethra-sparing in Plans 2 and 3 reached significantly lower NTCP-Urethra (p = 0.002) without significantly affecting TCP-GTV-Histo (p = p > 0.28), NTCP-Bladder (p > 0.85) or NTCP-Rectum (p = 0.85), resulting in better P+ (p = 0.006). Simulation of intrafractional movement yielded even higher P+ values for Plans 2 and 3 compared to Plan 1.ConclusionUrethral sparing may increase the therapeutic ratio and should be implemented in focal RT dose escalation concepts.

scholarly journals 4-Methylumbelliferone administration enhances radiosensitivity of human fibrosarcoma by intercellular communication

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ryo Saga ◽  
Yusuke Matsuya ◽  
Rei Takahashi ◽  
Kazuki Hasegawa ◽  
Hiroyuki Date ◽  
...  
Keyword(s):  
Intercellular Communication ◽  
Dose Range ◽  
Synthesis Inhibitor ◽  
X Ray ◽  
Tumour Control ◽  
Synergetic Effects ◽  
Fibrosarcoma Cells ◽  
Oxidative Stress Level ◽  
Human Fibrosarcoma Cells

AbstractHyaluronan synthesis inhibitor 4-methylumbelliferone (4-MU) is a candidate of radiosensitizers which enables both anti-tumour and anti-metastasis effects in X-ray therapy. The curative effects under such 4-MU administration have been investigated in vitro; however, the radiosensitizing mechanisms remain unclear. Here, we investigated the radiosensitizing effects under 4-MU treatment from cell experiments and model estimations. We generated experimental surviving fractions of human fibrosarcoma cells (HT1080) after 4-MU treatment combined with X-ray irradiation. Meanwhilst, we also modelled the pharmacological effects of 4-MU treatment and theoretically analyzed the synergetic effects between 4-MU treatment and X-ray irradiation. The results show that the enhancement of cell killing by 4-MU treatment is the greatest in the intermediate dose range of around 4 Gy, which can be reproduced by considering intercellular communication (so called non-targeted effects) through the model analysis. As supposed to be the involvement of intercellular communication in radiosensitization, the oxidative stress level associated with reactive oxygen species (ROS), which leads to DNA damage induction, is significantly higher by the combination of 4-MU treatment and irradiation than only by X-ray irradiation, and the radiosensitization by 4-MU can be suppressed by the ROS inhibitors. These findings suggest that the synergetic effects between 4-MU treatment and irradiation are predominantly attributed to intercellular communication and provide more efficient tumour control than conventional X-ray therapy.

Dosimetric and radiobiological evaluation of four radiation techniques in preoperative rectal cancer radiotherapy

2020 ◽  
pp. 1-8
Author(s):  
Vasiliki Softa ◽  
Yiannis Kiouvrekis ◽  
Anna Makridou ◽  
Constantin Kappas ◽  
George Kyrgias ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Radiation Therapy ◽  
Normal Tissue ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Normal Tissue Complication Probability ◽  
Locally Advanced Rectal Cancer ◽  
The Other ◽  
Tumour Control ◽  
Femoral Heads

Abstract Purpose: To compare tumour dose distribution, conformality, homogeneity, normal tissue avoidance, tumour control probability (TCP) and normal tissue complication probability (NTCP) using 3D conformal radiation therapy (3DCRT), 3- and 4-field intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) in patients with locally advanced rectal cancer. Materials and methods: Twenty-four patients staged T1–3N+M0 with locally advanced rectal cancer underwent neoadjuvant chemoradiation therapy. Four different radiotherapy plans were prepared for each patient: 3DCRT, 3- and 4-field IMRT and VMAT are evaluated for target distribution using CI and homogeneity index (HI), normal tissue avoidance using Dmax, V45, V40, V50 and TCP and NTCP using the Lyman–Kutcher–Burman model. Results: VMAT has better HI (HI = 1·32) and 3DCRT exhibited better conformality (CI = 1·05) than the other radiotherapy techniques. With regard to normal tissue avoidance, all radiotherapy plans met the constraints. Dmax in the 3DCRT plans was statistically significant (p = 0·04) for bladder and no significant differences in V40 and V50. In the bowel bag, no significant differences in Dmax for any radiotherapy plan and V40 was lower in 3DCRT than VMAT (p = 0·024). In the case of femoral heads, 3DCRT has a statistically significant lower dose on Dmax than 4-field IMRT (p = 0·00 « 0·05). VMAT has the biggest TCP (80·76%) than the other three radiotherapy plans. With regard to normal tissue complications, probabilities were shown to be very low, of the order of 10-14 and 10-41 for bowel bag and femoral heads respectively. Conclusions: It can be concluded that 3DCRT plan improves conformity and decreases radiation sparing in the organ at risks, but the VMAT plan exhibits better homogeneity and greater TCP.

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