Evaluation of plan robustness on the dosimetry of volumetric arc radiotherapy (VMAT) with set-up uncertainty in Nasopharyngeal carcinoma (NPC) radiotherapy

Purpose To evaluate the sensitivity to set up the uncertainty of VMAT plans in Nasopharyngeal carcinoma (NPC) treatment by proposing a plan robustness evaluation method. Methods 10 patients were selected for this study. A 2-arc volumetric-modulated arc therapy (VMAT) plan was generated for each patient using Varian Eclipse (13.6 Version) treatment planning system (TPS). 5 uncertainty plans (U-plans) were recalculated based on the first 5 times set-up errors acquired from cone-beam computer tomography (CBCT). The dose differences of the original plan and perturbed plan corresponded to the plan robustness for the structure. Tumor control probability (TCP) and normal tissues complication probability (NTCP) were calculated for biological evaluation. Results The mean dose differences of D98% and D95% (ΔD98% and ΔD95%) of PTVp were respectively 3.30 Gy and 2.02 Gy. The ΔD98% and ΔD95% of CTVp were 1.12 Gy and 0.58 Gy. The ΔD98% and ΔD95% of CTVn were 1.39 Gy and 1.03 Gy, distinctively lower than those in PTVn (2.8 Gy and 2.0 Gy). The CTV-to-PTV margin increased the robustness of CTVs. The ΔD98% and ΔD95% of GTVp were 0.56 Gy and 0.33 Gy. GTVn exhibited strong robustness with little variation of D98% (0.64 Gy) and D95% (0.39 Gy). No marked mean dose variations of Dmean were seen. The mean reduction of TCP (ΔTCP) in GTVp and CTVp were respectively 0.4% and 0.3%. The mean ΔTCPs of GTVn and CTVn were 0.92% and 1.3% respectively. The CTV exhibited the largest ΔTCP (2.2%). In OARs, the brain stem exhibited weak robustness due to their locations in the vicinity of PTV. Bilateral parotid glands were sensitive to set-up uncertainty with a mean reduction of NTCP (ΔNTCP) of 6.17% (left) and 7.70% (right). The Dmax of optical nerves and lens varied slightly. Conclusion VMAT plans had a strong sensitivity to set-up uncertainty in NPC radiotherapy, with increasing risk of underdose of tumor and overdose of vicinal OARs. We proposed an effective method to evaluate the plan robustness of VMAT plans. Plan robustness and complexity should be taken into account in photon radiotherapy.

Theoretical Evaluation of the Impact of Hyperthermia in Combination with Radiation Therapy in an Artificial Immune—Tumor-Ecosystem

There is some evidence that radiotherapy (RT) can trigger anti-tumor immune responses. In addition, hyperthermia (HT) is known to be a tumor cell radio-sensitizer. How HT could enhance the anti-tumor immune response produced by RT is still an open question. The aim of this study is the evaluation of potential dynamic effects regarding the adaptive immune response induced by different combinations of RT fractions with HT. The adaptive immune system is considered as a trainable unit (perceptron) which compares danger signals released by necrotic or apoptotic cell death with the presence of tumor- and host tissue cell population-specific molecular patterns (antigens). To mimic the changes produced by HT such as cell radio-sensitization or increase of the blood perfusion after hyperthermia, simplistic biophysical models were included. To study the effectiveness of the different RT+HT treatments, the Tumor Control Probability (TCP) was calculated. In the considered scenarios, the major effect of HT is related to the enhancement of the cell radio-sensitivity while perfusion or heat-based effects on the immune system seem to contribute less. Moreover, no tumor vaccination effect has been observed. In the presented scenarios, HT boosts the RT cell killing but it does not fundamentally change the anti-tumor immune response.

Estimation of Radiotherapy Efficiency of Head-and-Neck Cancer Based

Purpose: Evaluation of the expected effectiveness of radiation therapy based on models of the local tumor control probability (Tumor Control Probability – TCP) for the head-neck cancer. Material and methods: The study used data from 11 patients with locally advanced head-neck cancer (larynx, oropharynx, and oral cavity). For each patient two dosimetric treatment plans have been prepared: SIB-VMAT (70 Gy per tumor, 50 Gy per lymph nodes, 25 fractions) and SEQ-VMAT (70 Gy per tumor, 50 Gy per lymph nodes, 35 fractions). The developed plans were analyzed using A. Niemierko's TCP model with parameters obtained by B. Maciejewski (TCD50 = 70.26 Gy with a 49-day total treatment time), taking into account the dose–volume histograms and the total treatment time. Results: The developed plans ensured a high level of coverage (98–98 %) of the Clinical treatment volume (CTV) in all but one patient. The average TCP SIB-VMAT is 99.9 % due to the very short total treatment time. The average TCP for SEQ-VMAT is 61.0%. For one patient, both SIB-VMAT and SEQ-VMAT showed zero expected efficacy due to 95–95 % CTV coverage. Conclusion: The use of TCP model allows analyzing personalized treatment plans for patients and developing adaptive treatment regimens with an increase in the total dose, dose per fraction, and a decrease in the total treatment time.

The Impact of Different Timing Schedules on Prostate HDR-Mono-Brachytherapy. A TCP Modeling Investigation

Background: Mechanistic TCP (tumor control probability) models exist that account for possible re-sensitization of an initially hypoxic tumor during treatment. This phenomenon potentially explains the better outcome of a 28-day vs 14-day treatment schedule of HDR (high dose rate) brachytherapy of low- to intermediate-risk prostate cancer as recently reported. Methods: A TCP model accounting for tumor re-sensitization developed earlier is used to analyze the reported clinical data. In order to analyze clinical data using individual TCP model, TCP distributions are constructed assuming inter-individual spread in radio-sensitivity. Results: Population radio-sensitivity parameter values are found that result in TCP population values which are close to the reported ones. Using the estimated population parameters, two hypothetical regimens are investigated that are shorter than the ones used clinically. The impact of the re-sensitization rate on the calculated treatment outcome is also investigated as is the anti-hypothesis that there is no re-sensitization during treatment. Conclusions: The carried out investigation shows that the observed clinical data cannot be described without assuming an initially hypoxic state of the tumor followed by re-oxygenation and, hence, re-sensitization. This phenomenon explains the better outcome of the prolonged treatment schedule compared to shorter regimens based on the fact that prostate cancer is a slowly repopulating tumor.

A Mathematical Model of Thyroid Disease Response to Radiotherapy

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.

Computational simulator that calculates tumor control probability in a tumor heterogeneously irradiated for fractionated radiation oncology treatments

Although in the ionizing radiation field many concepts and processes are currently recognized as radiobiological, there are also probabilistic ones, and a probabilistic treatment makes a better understanding about them. The purpose of this study is to develop a new radiobiological simulator that calculates the tumor control probability (TCP) for a tumor heterogeneously irradiated from a fractioned treatment. The three possible types of cells and the results of interactions of ionizing radiation with each cell of a determined volume are analyzed. For an irradiated region with a dose per fraction d, the simulator determines the radiation biological effects using the cell kill ( K) and cell sub-lethal damage, volume, cell density, cell repair of damaged cells during the interfractions, and number of fractions. K is determined from its probabilistic complement, the cell survival ( S), described with the linear-quadratic (LQ) S(d) model as K = 1 − LQ S( d). TCP is calculated from computational simulations as in the ratio of simulations with K = 100% and their total. This application opens new avenues for theoretical and experimental investigations concerning simulations of radiation treatments, and methodologies for therapy optimizations. Our simulator represents a novel methodology as TCP is calculated without analytical formulas, but based on its own probabilistic definition.

Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP) in Mono and Dual-isocentric Techniques of Breast Cancer Radiation Therapy

Background: Nowadays, radiation therapy plays an important role in the treatment of breast cancer. The important point is the optimal control of the tumor along with the protection of organs at risk. This study aims to investigate and compare the radiobiological factors of the tumor and organs at risk in two different radiation therapy techniques of breast cancer.Methods: Ten left-sided breast cancer patients with breast-conservative surgery were selected for this study. Three-dimensional treatment planning was performed using CT scan images of the patients using PCRT 3D software. Two different tangential external beam techniques were compared: first, dual-isocentric technique (DIT) with two isocentre, one on the breast tissue, and the other one on the supraclavicular lymph nodes and second, a mono-isocentric technique (MIT) with one isocentre at the intersection of the tangential and the supraclavicular field. The total prescribed dose was 5000 cGy per 25 fractions. Dose-volume histograms (DVHs), Tumor control probability (TCP), and normal tissue complication probability (NTCP) curves were used to compare the dosimetric and radiobiological parameters of the tissues in the prementioned techniques. Results: The results showed that the maximum doses in planning target volume (PTV) with mean values of 109% and 110% in the SI and DIT were not significantly different in both techniques and that they were indeed at the optimum level based on the RTOG 1005 protocol. The dose homogeneity index in MMIT was more than that in DIT, while the conformity index and the mean TCP did not show a significant difference in the two techniques. Furthermore, minimum, mean, and maximum dose in the lung and the probability of pneumonitis decreased in MIT. On the other hand, the maximum dose, the dose of 33%, 66%, and 100% of the heart, and the probability of pericarditis in MIT were lower than the figure in DIT. Conclusion: Due to the absence of hot spots at the intersection of tangential and supraclavicular fields and the reduction of mechanical movements of the coach and collimator in MIT, the superiority of this method was confirmed.

Dosimetric comparison and TCP-NTCP modelling for lung, heart, left anterior descending and right coronary artery in left sided breast cancer conventional and hypofractionated radiotherapy

BackgroundThe aim of this study was to evaluate the dose distribution, and also tumor control probability (TCP) and normal tissue complications probability (NTCP) models of left sided breast cancer females for 3D-CRT, 6 and 9 fields IMRT and hypofractionated tangential plans.MethodsSixty left sided breast cancer females were included in this study. CT simulation images of the patients were imported on the treatment planning software (TiGRT, LinaTech, China), and the tangential treatment plans of the mentioned methods were done for each patient. The dosimetric evaluation, and TCP-NTCP models of stated modalities were done using Poisson Linear-Quadatric (PLQ) and Lyman-Kutcher-Burman (LKB) models on the MATLAB and R softwares.ResultsThe mean (± SD) dose to ipsilateral lung, heart, LAD and RCA with/without internal mammary fields for 6FIMRT was lower compared to other modalities. Furthermore, V20Gy for Ipsilateral lung and V25Gy for heart, LAD and RCA of 6FIMRT was lower than other methods. In addition, the PTV dose coverage was higher for 9FIMRT and hypofractionated RT, while it may be lower for 3D-CRT among the studied methods. Although TCP values of 9 and 6fieds and hypofractionated was not significantly different, the TCPs of them were higher compared to 3D-CRT. However, the NTCP for ipsilateral lung, heart, LAD and RCA of 6FIMRT was lower than others.Conclusion6FIMRT is suitable choice for RT of breast cancer patients compared to other mentioned modalities, as a result of providing adequate PTV dose coverage and TCP, and also lower imposed dose and NTCP for OARs. Hypofractionated RT is a good alternative to reduce treatment time for the breast cancer patients.Trial registrationThis study was approved by the ethical board of Isfahan University of Medical Sciences, Isfahan, Iran (IR.MUI.MED.REC.1399.677).

Evaluation of Target Autocrop Function in Nasopharyngeal Carcinoma SIB IMRT Plan

Purpose A new target autocrop function was introduced in the Varian Eclipse™ treatment planning software (version 15.5 above). The study aimed to evaluate this new target autocrop impact on nasopharyngeal carcinoma (NPC) plan quality and delivery efficiency. Methods Randomly 66 approved NPC simultaneous integrated boost (SIB) intensity modulated radiation therapy (IMRT) treatment plans were retrospectively studied. The manual cropping-based plans served as reference and were designed using sliding-window IMRT. Reference plans were re-optimized with identical planning parameters following the institutional clinical protocol except for the optimization objective of the manual cropping targets deleted. Additionally, each target within 5mm of another had one lower objective at 100% volume and one upper objective at 0% volume for the autocrop plans. Plan quality was assessed based on selected parameters, including TCP (tumor control probability), NTCP (normal tissue complication probability), conformality index (CI), homogeneity index (HI), and dose-volume characteristics. Additionally, the delivery efficiency, the total plan treatment time defined as a sum of monitor units (MUs) for each treated field, and delivery accuracy, γ passing rate of treatment plan quality assurance (QA) also were compared. Results Both the manual cropping plans and the autocrop plans could be approved by an experienced oncologist. Overall, the autocrop plans could provide approximately a 13% reduction in linac MU while maintaining comparable plan quality, radiobiological ranking, and accuracy to that of the manual cropping plans. Conclusions The new target autocrop tip facilitated the SIB IMRT plans for nasopharyngeal cancer patients. The autocrop could guarantee the quality and delivery accuracy of the radiotherapy plan, improved the planning efficiency, treatment efficiency, and reduced machine wear and tear. It was a promising tool for optimal plan selection for NPC SIB IMRT.