Tumor Control Probability Values Research Articles

Tumor Control and Normal Tissue Complications in High-dose-rate Brachytherapy for Cervical Cancer Patients Using Ir-192 Radioactive Source.

The purpose of the study was to calculate, tumor control probability (TCP) and normal tissue complication probability (NTCP) in cervical cancer patients and to clinically correlate the outcomes with a follow-up period of 24 months. One hundred and fifty patients were included in the present study who received 46 Gy/23 fractions/4½ weeks of external beam radiotherapy with concurrent cisplatin chemotherapy, followed by intracavitary brachytherapy of 3 different fractionations regimens, i.e., 9.5 Gy per fraction of two fractions (50 patients in Arm1), 7.5 Gy per fraction of three fractions (50 patients in Arm2), and 6.0 Gy per fraction of four fractions (50 patients in Arm3). The median TCP value for Arm1, Arm2, and Arm3 was 99.6%, 94%, and 98.1%, respectively, (P < 0.01). The median NTCP value for bladder in Arm1, Arm2, and Arm3 was 0.17%, 0.04%, and 0.07%, respectively, (P = 0.05). The median NTCP value for rectum in Arm1, Arm2, and Arm3 was 4.73%, 4.35%, and 3.17%, respectively, (P = 0.052). The overall survival (OS) of 90%, 86%, and 84% was found for Arm1, Arm2, and Arm3, respectively, at 24 months of follow-up. TCP, NTCP, and OS rates were found higher in Arm1 as compared to the other two arms. The complications found in all arms were less, low grade, and manageable. Hence, Arm1, i.e., 9.5 Gy per fraction of two fractions can be concluded as the optimum fractionation regime in terms of radiobiological parameters as well as overall patient comfort.

Dose-response modeling and treatment plan assessment with a python software toolkit

This software assistant aims at calculating the dose-response relations of tumors and normal tissues, or clinically assessing already determined values by other researchers. It can also indicate the optimal dose prescription by optimizing the expected treatment outcome. The software is developed solely in python programming language, and it employs PSFL license for its Graphical User Interface (GUI), NUMPY, MATPLOTLIB, and SCIPY libraries. It comprises of two components. The first is the Dose-response relations derivation component, which takes as input the dose volume histograms (DVHs) of patients and their recorded responses regarding a given clinical endpoint to determine the parameters of different tumor control probability (TCP) or normal tissue complication probability (NTCP) models. The second is the Treatment Plan Assessment component, which uses the DVHs of a plan and the dose-response parameters values of the involved tumors and organs at risk (OARs) to calculate their expected responses. Additionally, the overall probabilities of benefit (PB), injury (PI) and complication-free tumor control (P+) are calculated. The software calculates rapidly the corresponding generalized equivalent uniform doses (gEUD) and biologically effective uniform doses (D‾‾) for the Lyman-Kutcher-Burman (LKB), parallel volume (PV) and relative seriality (RS) models respectively, determining the model parameters. In the Dose-Response Relations Derivation component, the software plots the dose-response curves of the irradiated organ with the relevant confidence internals along with the data of the patients with and without toxicity. It also calculates the odds ratio (OR) and the area under the curve (AUC) of different dose metrics or model parameter values against the individual patient outcomes to determine their discrimination capacity. It also performs a goodness-of-fit evaluation of any model parameter set. The user has the option of viewing plots like Scatter, 3D surfaces, and Bootstrap plots. In the Treatment Plan Assessment part, the software calculates the TCP and NTCP values of the involved tumors and OARs, respectively. Furthermore, it plots the dose-response curves of the TCPs, NTCPs, PB, PI, and P+ for a range of prescription doses for different treatment plans. The presented software is ideal for efficiently conducting studies of radiobiological modeling. Furthermore, it is ideal for performing treatment plan assessment, comparison, and optimization studies.

Radiobiological evaluation of hypo-fractionated breast cancer radiotherapy regimens in comparison with conventional approaches

Abstract Purpose: This study compares tumor control probability (TCP) and normal tissue complication probability (NTCP) across different hypo-fractionated (HypoRT) and conventional breast radiotherapy regimens using radiobiological models. Materials and methods: Computed tomography data from 30 patients with left breast-conserving surgery were used to evaluate three HypoRT regimens (39 Gy and 41·6 Gy in 13 fractions, and 40 Gy in 15 fractions) and a conventional regimen (50 Gy in 25 fractions). Dose-volume histograms (DVHs) were extracted for radiobiological calculations using Equivalent Uniform Dose (EUD) and Poisson models for TCP, and EUD and LKB (Lyman-Kutcher-Burman) models for NTCP. Results: Conventional treatment achieved significantly higher TCP (95%) than all HypoRT regimens (p &lt; 0·001), with no significant differences between HypoRT regimens (p &gt; 0·05. The 39 Gy/13 fraction regimen showed the lowest lung NTCP (p &lt; 0·05). HypoRT regimens had significantly lower NTCP for the lungs and heart compared to the conventional regimen (p &lt; 0·01). TCP and NTCP values from Poisson and LKB models were higher than those from the EUD model (p &lt; 0·01). Conclusion: HypoRT regimens reduced NTCP, with the lowest values in the regime of 39 Gy/13 fractions regimen, though the conventional regimen had higher TCP.

Hypoxia dose painting in SBRT – the virtual clinical trial approach

Background Treating hypoxic tumours remains a challenge in radiotherapy as hypoxia leads to enhanced tumour aggressiveness and resistance to radiation. As escalating the doses is rarely feasible within the healthy tissue constraints, dose-painting strategies have been explored. Consensus about the best of care for hypoxic tumours has however not been reached because, among other reasons, the limits of current functional in-vivo imaging systems in resolving the details and dynamics of oxygen transport in tissue. Computational modelling of the tumour microenvironment enables the design and conduction of virtual clinical trials by providing relationships between biological features and treatment outcomes. This study presents a framework for assessing the therapeutic influence of the individual characteristics of the vasculature and the resulting oxygenation of hypoxic tumours in a virtual clinical trial on dose painting in stereotactic body radiotherapy (SBRT) circumventing the limitations of the imaging systems. Material and methods The homogeneous doses required to overcome hypoxia in simulated SBRT treatments of 1, 3 or 5 fractions were calculated for tumours with heterogeneous oxygenation derived from virtual vascular networks. The tumour control probability (TCP) was calculated for different scenarios for oxygenation dynamics resulting on cellular reoxygenation. Results A three-fractions SBRT treatment delivering 41.9 Gy (SD 2.8) and 26.5 Gy (SD 0.1) achieved only 21% (SD 12) and 48% (SD 17) control in the hypoxic and normoxic subvolumes, respectively whereas fast reoxygenation improved the control by 30% to 50%. TCP values for the individual tumours with similar characteristics, however, might differ substantially, highlighting the crucial role of the magnitude and time evolution of hypoxia at the microscale. Conclusion The results show that local microvascular heterogeneities may affect the predicted outcome in the hypoxic core despite escalated doses, emphasizing the role of theoretical modelling in understanding of and accounting for the dominant factors of the tumour microenvironment.

Comparing biological and physical cost functions in VMAT planning for pediatric nasopharyngeal cancer

BackgroundVolumetric Modulated Arc Therapy (VMAT) is an option for the delivery of Radiotherapy treatment technique for pediatric nasopharyngeal cancer, VMAT is the most common treatment technique for pediatric nasopharyngeal cancer. The use of a combination of both biological and physical parameters in VMAT planning optimization may produce better target coverage and sparing of critical organs. This work was to compare Biological Cost Functions (BCFs) and Physical Cost Functions (PCFs) in the VMAT of pediatric nasopharyngeal cancer patients. MethodVMAT plans for 20 nasopharyngeal pediatric cancer patients were created using Monaco 5.11® treatment planning system (TPS). Three VMAT plans were retrospectively generated for each patient using BCFs, PCFs and mixed plan with a total dose of 61.2 Gy in 34 fractions to planning target volume (PTV). All plans were adjusted to deliver 95% of the prescribed dose to 95% of the PTV. The calculated plans were qualitatively and quantitatively evaluated using the dose-volume histogram (DVH). ResultsThe coverage of the target and the maximum dose for the three plans were nearly the same, and better sparing was achieved in the serial organs (spinal cord and brain stem) with PCFs. On the contrary, more dose spring was observed using the BCFs in the organs at risk (OARs) that were not involved in the dose optimization, such as the optic nerve maximum dose, with a significant p-value (0.035 and 0.0001) respectively. Using the PCFs, both parotids received a lower mean dose, but not for the oral cavity, which had a lower mean dose using BCFs (p=<0.0001). The same values of tumor control probability (TCP) were found for both cost functions in PTVs and normal tissue complications probability (NTCP) (99%). The values reported were as follows: spinal cord = 0.5%, brain stem = 19.1%, and brain = 90.7% for BCFs, compared to spinal cord = 0.3%, brain stem = 14.9%, and brain = 90.7% for PCFs. The delivery time was found to be less in BCFs (p=0.005). ConclusionThe BCFs are superior to the PCFs in conformity index and time of radiation delivery. However, PCFs were better at dose sparing for the serial organs and achieving a sharper falloff dose around the involved volumes. A patient-specific clinical compromise is recommended to gain the best plan that meets the clinical goals.

Relationship between the Patients’ Setup Errors with Dosimetric and Radiobiologic Parameters in Whole Breast Radiotherapy

Purpose: This study aimed to investigate the effect of the patients’ setup errors on dosimetric and radiobiologic parameters for left-sided Whole-Breast Irradiation (WBI) in three different radiotherapy techniques, including Intensity-Modulated Radiation Therapy (IMRT), Field-In-Field (FIF), and Conventional Wedge (CW). Materials and Methods: Computed Tomography (CT) images of 10 female patients with early-stage left-sided breast cancer were used to simulate different radiotherapy techniques (IMRT, FIF, and CW). The dosimetric parameters; Conformity Index (CI), Homogeneity Index (HI), the dose received by at least 95% (D95%) of Planning Tumor Volume (PTV), the volume of lung and heart that respectively received at least 20% (V20%) and 40% (V40%) of the prescribed dose, as well as, the radiobiologic parameters, including Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP) were assessed for setup errors in patients. The setup errors were assessed by shifting the isocenters and gantry angles of the treatment plans. Results: The D95% of the PTV for an isocenter misplacement plan in the posterior direction decreased by 66.99 (IMRT), 71.86 (CW), and 68.25% (FIF). The TCP of the PTV was reduced by 26.66, 39.16, and 36.97% for IMRT, CW, and FIF techniques, respectively. Increasing gantry angle by a ±10 degree caused a 43%, 41%, and 41% decrease in the D95% of IMRT, FIF, and CW techniques, respectively. The TCP values decreased about 18% in all three techniques with a ±10 degree gantry angle shift; however, the NTCP values of the heart and lungs increased for all three methods. The CI and HI values had significantly more changes with increasing setup errors in the IMRT than in the two techniques. Conclusion: The radiobiologic parameters in IMRT were less sensitive to setup errors compared to FIF and CW techniques. The radiobiological parameters can help estimate the setup errors along with physical parameters during breast radiotherapy.

Introducing new plan evaluation indices for prostate dose painting IMRT plans based on apparent diffusion coefficient images

BackgroundDose painting planning would be more complicated due to different levels of prescribed doses and more complex evaluation with conventional plan quality indices considering uniform dose prescription. Therefore, we tried to introduce new indices for evaluating the dose distribution conformity and homogeneity of treatment volumes based on the tumoral cell density and relative volumes of each lesion in prostate IMRT.MethodsCT and MRI scans of 20 male patients having local prostate cancer were used for IMRT DP planning. Apparent diffusion coefficient (ADC) images were imported to a MATLAB program to identify lesion regions based on ADC values automatically. Regions with ADC values lower than 750 mm2/s and regions with ADC values higher than 750 and less than 1500 mm2/s were considered CTV70Gy (clinical tumor volume with 70 Gy prescribed dose), and CTV60Gy, respectively. Other regions of the prostate were considered as CTV53Gy. New plan evaluation indices based on evaluating the homogeneity (IOE(H)), and conformity (IOE(C)) were introduced, considering the relative volume of each lesion and cellular density obtained from ADC images. These indices were compared with conventional homogeneity and conformity indices and IOEs without considering cellular density. Furthermore, tumor control probability (TCP) was calculated for each patient, and the relationship of the assessed indices were evaluated with TCP values.ResultsIOE (H) and IOE (C) with considering cellular density had significantly lower values compared to conventional indices and IOEs without considering cellular density. (P < 0.05). TCP values had a stronger relationship with IOE(H) considering cell density (R2 = -0.415), and IOE(C) without considering cell density (R2 = 0.624).ConclusionIOE plan evaluation indices proposed in this study can be used for evaluating prostate IMRT dose painting plans. We suggested to consider cell densities in the IOE(H) calculation formula and it’s appropriate to calculate IOE(C) without considering cell density values.

TCP post-radioembolization and TCP post-EBRT in HCC are similar and can be predicted using the in vitro radiosensitivity

BackgroundTumor equivalent uniform dose (EUD) is proposed as a predictor of patient outcome after liver radioembolization (RE) of hepatocellular carcinoma (HCC) and can be evaluated with 90Y-TOF-PET. The aim is to evaluate the correlation between PET-based tumors EUD and the clinical response evaluated with dual molecular tracer (11C-acetate and 18F-FDG) PET/CT post-RE.Methods34 HCC tumors in 22 patients were prospectively evaluated. The metabolic response was characterized by the total lesion metabolism variation (ΔTLM) between baseline and follow-up. This response allowed to compute a tumor control probability (TCP) as a function of the tumor EUD.ResultsThe absorbed dose response correlation was highly significant (R = 0.72, P < 0.001). With an absorbed dose threshold of 40 Gy, the metabolic response was strongly different in both groups (median response 35% versus 100%, P < 0.001). Post-RE TCP as a function of the EUD was very similar to that observed in external beam radiation therapy (EBRT), with TCP values equal to 0.5 and 0.95 for a EUD of 51 Gy and 100 Gy, respectively. The TCP was perfectly predicted by the Poisson model assuming an inter tumor radiosensitivity variation of 30% around the HCC cell in vitro value.ConclusionsEUD-based 90Y TOF-PET/CT predicts the metabolic response post-RE in HCC assessed using dual molecular PET tracers and provides a similar TCP curve to that observed in EBRT. In vivo and in vitro HCC radiosensitivities are similar. Both TCPs show that a EUD of 100 Gy is needed to control HCC for the three devices (resin spheres, glass spheres, EBRT). Observed absorbed doses achieving this 100 Gy-EUD ranged from 190 to 1800 Gy!

Dosimetric Comparison and TCP-NTCP Modeling for Lung, Heart, Left Anterior Descending, and Right Coronary Artery in Left-sided Breast Cancer Conventional and Hypofractionated Radiotherapy

Background: The aim of this study was to evaluate the dose distribution, as well as tumor control probability (TCP) and normal tissue complications probability (NTCP) models for females with left-sided breast cancer for 3D-CRT, 6, and 9 fields intensity modulated radiotherapy (IMRT) and hypofractionated tangential plans. Methods: Eighty females with left-sided breast cancer (N1T1 – N3T3) were included in this study. The patients were divided into breast conserving surgery (BCS) (n= 50) and mastectomy (n=30) patients. 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, using TPS. Dose assessments were performed, employing the TPS, and TCP-NTCP models of stated modalities were done, using Poisson linear-quadatric (PLQ) and Lyman-Kutcher-Burman (LKB) models on MATLAB and R software. Results: For the BCS and post-mastectomy patients, 6FIMRT imposed lower doses to ipsilateral lung, heart, LAD, RCA, and contralateral breast compared to 9FIMRT, hypofractionated RT, and 3D-CRT (P &lt; 0.005). Also, the NTCPs of the mentioned normal tissues for 6FIMRT were lower than other methods for both BCS and post-mastectomy groups. Moreover, it was found that the V20Gy for Ipsilateral lung and the V25Gy for heart, LAD, and RCA of 6FIMRT, 9FIMRT, and hypofractionated RT was significantly lower compared to 3D-CRT (P &lt; 0.005) for both BCS and mastectomy groups, while there were no significant differences among them for the 6FIMRT and 9FIMRT with hypofractionated RT (P &gt; 0.005). The TCP values of 9FIMRT, 6FIMRT, and hypofractionated RT were not considerably different; however, the TCP values of 3D-CRT were lower compared to other stated methods. Conclusions: 6FIMRT is a suitable choice for RT of patients with left-sided breast cancer compared to other mentioned modalities, as a result of providing adequate PTV dose coverage and TCPs. Also, it may impose lower doses and NTCPs for OARs. Hypofractionated RT is a good alternative to reduce treatment time for patients with breast cancer.

Voxel-Level BED Corrected Dosimetric and Radiobiological Assessment of 2 Kinds of Hybrid Radiotherapy Planning Methods for Stage III NSCLC.

Background/purpose: To access the comparative dosimetric and radiobiological advantages of two methods of intensity-modulated radiation therapy (IMRT)-based hybrid radiotherapy planning for stage III nonsmall cell lung cancer (NSCLC). Methods: Two hybrid planning methods were respectively characterized by conventional fraction radiotherapy (CFRT) and stereotactic body radiotherapy (SBRT) and CFRT and simultaneous integrated boost (SIB) planning. All plans were retrospectively completed using the 2 methods for 20 patients with stage III NSCLC. CFRT and SBRT dose regimes 2 Gy × 30 f and 12.5 Gy × 4 f were, respectively, used for planning target volume of lymph node (PTVLN) and planning target volume of the primary tumor (PTVPT), while dose regimes 2 Gy × 26 f for PTVLN and sequential 2 Gy × 4 f for PTVLN combined with 12.5 Gy × 4 f for PTVPT were adopted for CFRT and SIB plans. SBRT and SIB EQD2 dose were calculated voxel by voxel, and then, respectively, superimposed with 30-fraction and 26-fraction CFRT plan dose to achieve biological equivalent dose (BED) dosimetric parameters of CFRT and SBRT and CFRT and SIB plans. Tumor control probability (TCP)/normal tissue complication probability (NTCP) was, respectively, calculated by equivalent uniform dose/Lyman–Kutcher–Burman models. BED plan parameters and TCP/NTCP were analyzed between 2 methods of hybrid planning. Primary tumor/lymph node (LN)/total TCP values were, respectively, evaluated as a function of the radiation dose needed to control 50% of tumor (TCD50) for 20 patients. Dosimetric errors were analyzed by nontransit electronic portal imaging device dosimetry measurement during hybrid plan delivery. Results: Statistically lower BED plan parameters of PTVLN D2 and homogeneity index resulted in slightly lower averaged LN/total TCP curves by CFRT and SIB planning. The gaps between Max and Min LN/total TCP curves were significantly closer for CFRT and SIB planning, which indicated better robustness of LN/total TCPs. A lower esophagus dose resulted in a lower esophagus NTCP by CFRT and SIB planning, which may be compromised by 1 week shorter overall treatment time by CFRT and SIB irradiation. Spinal cord Dmax was significantly reduced by CFRT and SIB plans. The dose verification results of the subplans involved in hybrid plans were acceptable, which showed that the 2 methods of hybrid planning could be delivered accurately in our center. Conclusion: CFRT and SIB plannings have more advantages on BED plan parameters and TCP/NTCP than CFRT and SBRT planning, and both methods of IMRT-based hybrid planning could be executed accurately for stage III NSCLC. The effectiveness of the results needs to be validated in the hybrid trial.

A treatment planning study of urethra-sparing intensity-modulated proton therapy for localized prostate cancer.

Urethra-sparing radiation therapy for localized prostate cancer can reduce the risk of radiation-induced genitourinary toxicity by intentionally underdosing the periurethral transitional zone. We aimed to compare the clinical impact of a urethra-sparing intensity-modulated proton therapy (US-IMPT) plan with that of conventional clinical plans without urethral dose reduction. This study included 13 patients who had undergone proton beam therapy. The prescribed dose was 63 GyE in 21 fractions for 99% of the clinical target volume. To compare the clinical impact of the US-IMPT plan with that of the conventional clinical plan, tumor control probability (TCP) and normal tissue complication probability (NTCP) were calculated with a generalized equivalent uniform dose-based Lyman-Kutcher model using dose volume histograms. The endpoints of these model parameters for the rectum, bladder, and urethra were fistula, contraction, and urethral stricture, respectively. The mean NTCP value for the urethra in US-IMPT was significantly lower than that in the conventional clinical plan (0.6% vs. 1.2%, p<0.05). There were no statistically significant differences between the conventional and US-IMPT plans regarding the mean minimum dose for the urethra with a 3-mm margin, TCP value, and NTCP value for the rectum and bladder. Additionally, the target dose coverage of all plans in the robustness analysis was within the clinically acceptable range. Compared with the conventional clinically applied plans, US-IMPT plans have potential clinical advantages and may reduce the risk of genitourinary toxicities, while maintaining the same TCP and NTCP in the rectum and bladder.

A radiobiological comparison of hypo-fractionation versus conventional fractionation for breast cancer 3D-conformal radiation therapy.

The present research was aimed to compare the toxicity and effectiveness of conventional fractionated radiotherapy versus hypo-fractionated radiotherapy in breast cancer utilizing a radiobiological model. Thirty-five left-sided breast cancer patients without involvement of the supraclavicular and axillary lymph nodes (with the nodal stage of N0) that had been treated with conventional or hypo-fractionated were incorporated in this study. A radiobiological model was performed to foretell normal tissue complication probability (NTCP) and tumor control probability (TCP). The data represented that TCP values for conventional and hypo-fractionated regimens were 99.16 ± 0.09 and 95.96 ± 0.48, respectively (p = 0.00). Moreover, the NTCP values of the lung for conventional and hypo-fractionated treatment were 0.024 versus 0.13 (p = 0.035), respectively. Also, NTCP values of the heart were equal to zero for both regimens. In summary, hypo-fractionated regimens had comparable efficacy to conventional fraction radiation therapy in the case of dosimetry parameters for patients who had left breast cancer. But, utilizing the radiobiological model, conventional fractionated regimens presented better results compared to hypo-fractionated regimens.

Development of generalized time-dependent TCP model and the investigation of the effect of repopulation and weekend breaks in fractionated external beam therapy

We developed a tumor control probability (TCP) model that incorporates variable time intervals between fractions and a kick-off time (Tk) for radiation-induced accelerated tumor proliferation. The resulting Lee-Rosen model, TCPLR, was used to compute TCPs for treatment courses with and without weekend treatment for tumors with different proliferation rates – slow (prostate), moderate (breast), and rapid (head and neck). TCPs were computed using ideal uniform dose distributions and actual patient plans. The doses for the uniform plans were the mean doses for the prostate and breast cases and the minimum tumor dose for the head and neck case. The TCPLR model predictions agreed with expectations that TCP increases with increasing Tk in all cases. For standard fractionation, as Tk increased from 0 to 4 weeks, TCP increased for the patient distributions by 74.7% for the head and neck cancer, by 6.2% for the breast cancer, and by 2.4% for the prostate cancers. For the uniform dose distributions, the increases were 79.2%, 5.7%, and 2.3%, respectively. TCP increased as the number of weekend breaks decreased. The effect of weekend breaks decreased as the tumor proliferation rate decreased. For the head and neck tumor, notable decreases in TCP of 6.0% (uniform dose distribution) and 6.8% (actual plan dose distribution) were observed with Friday starts compared to Monday starts for the standard 5 fx/wk schedule (Tk = 4 wk). The 7 fx/wk schedule produced increases in TCP of 17.0% and 20.5% for the uniform and patient dose distributions, respectively, compared to the standard schedule. For the breast cancer, starting the 5 fx/wk schedule on Friday decreased the TCP by 0.2% (Tk = 4 wk) compared to a Monday start. The 7 fx/wk schedule produced increases of 0.3% and 0.4% in TCP compared to the standard schedule for the uniform and patient dose distributions, respectively (Tk = 4 wk). For the prostate cancer, the change in TCP for 5 fx/wk schedules starting on different days was 0.1%. The 7 fx/wk schedule increased TCP by 0.8% compared to the standard schedule (Tk = 4 wk). TCP values for the uniform dose distributions for the standard schedule (Tk = 4 wk) agreed with the TCP values for the actual dose distributions within 4.5% for the head and neck tumor and within 0.2% for the breast and prostate tumors. This good agreement suggests that the doses chosen for the uniform dose distributions were good approximations to the clinical doses. The results for head and neck tumors support, in part, the current practice of hyperfractionated/accelerated radiotherapy. They also suggest that shortening the overall treatment time for conventional fractions by eliminating weekend breaks might be beneficial. The predicted effect on TCP of the various schedules studied was insignificant for prostate and breast tumors, suggesting that a weekend treatment might not be necessary for patients starting radiotherapy on a Friday. There is significant uncertainty in the values of the model parameters chosen for these calculations, and no consideration was given to the potential effects of these various schedules on normal tissues.

Tumour control probability of a UK cohort of lung SABR patients

AbstractAims:The aim of this work is to report on the tumour control probability (TCP) of a UK cohort of lung stereotactic ablative radiotherapy patients (n = 198) for a range of dose and fractionations common in the UK.Materials and methods:TCP values for 3 (54 Gy), 5 (55 and 60 Gy) and 8 (50 Gy) fraction (#) schemes were calculated with the linear-quadratic Marsden TCP model using the Biosuite software.Results:TCP values of 100% were computed for the 3 # and for 5 # (α/β = 10 Gy) cohorts; reduced to 99% (range 97–100) for the 5 # cohort only when an α/β of 20 Gy was used. The average TCP value for the 50 Gy in 8 # regime was 97% (range 92–99, α/β = 10 Gy) and 64% (range 48–79, α/β = 20 Gy). Statistical significant differences were observed between the α/β of 10 Gy versus 20 Gy groups and between all data grouped by fraction.Conclusion:TCPs achievable with current planning techniques in the UK have been presented. The ultra-conservative 50 Gy in 8 # scheme returns a significantly lower TCP than the other regimes.

Application of biological optimization of hypofractionated radiotherapy post conservative surgery for breast cancer*

Abstract Objective The aim of the study was to discuss the application of biological optimization and its difference from physical optimization in hypofractionated radiotherapy for breast cancer after conservative surgery. Methods This retrospective study enrolled 15 randomly chosen patients with left-sided breast cancer who received radiotherapy. The volumetric arc therapy (VMAT) technique was used to redesign treatment plans with physical functions (PF) group, biological-physical functions combined (BF + PF and PF + BF) groups, and biological functions (BF) group. The dosimetric differences based on the above four optimization methods were assessed by calculating and analyzing the corresponding dose-volume parameters. Results The target parameters of the four groups differed significantly (P &lt; 0.05) except for the conformity index (CI). The tumor control probability (TCP) values in the BF and BF + PF groups were higher than those in the PF and PF + BF groups. Moreover, the dose-volume parameters of the ipsilateral lung in the BF group were less than those of three other groups, while the monitor unit (MU) in the BF group was approximately 16% lower than those of the PF and PF + BF groups. Conclusion Biological functions were useful to increase the equivalent uniform dose (EUD) and TCP values of the target, decrease the dose-volume parameters of the organs-at-risk (OARs), and improve treatment efficiency.

Radiobiological Evaluation of Dosimetric Plans for Stereotactic Radiotherapy for Prostate Cancer According to Fractionation Regimen

Objective. To determine the most effective irradiation regimen (total dose and dose per fraction) for hypofractionated treatment for prostate carcinomas according the TCP/NTCP radiobiological criteria.Material and methods. Using the tomographic information of five patients with low-risk prostate adenocarcinoma as an example, the authors devised dosimetric radiation therapy plans using the volumetric modulated arc therapy (VMAT) procedure. They considered the range of total doses of 33.5 to 38 Gy administered in 4 and 5 fractions. Based on the equivalent uniform dose concept proposed by A. Niemierko and on the computed differential dose volume histograms, the investigators modeled local tumor control probability (TCP) values, by taking into account the uncertainties of main radiobiological parameters, and estimated normal tissue complication probabilities (NTCP) for the anterior rectal wall as the organ most at risk of irradiation. An effective dosimetric plan was selected according to the UTCP criterion and the probability of complication-free tumor control, i.e. TCP (1 – NTCP).Results. The results of modeling the UTCP criterion show that with a higher total dose, the TCP value increases and so does the NTCP value, therefore the optimal radiation therapy plans are to irradiate with a total dose of 34 Gy over 4 fractions or with a dose of 36–37 Gy over 5 fractions. The difference between the fractionation regimens is that the UTCP value is achieved with a higher TCP value over 4 fractions and with a lower load on the rectal wall over 5 fractions.Conclusion. The choice of a specific fractionation regimen should be determined from the calculated values of differential dose volume histograms for each patient, as well as from radiobiological criteria, such as TCP, NTCP and UTCP.

Calculating the Individualized Fraction Regime in Stereotactic Body Radiotherapy for Non-Small Cell Lung Cancer Based on Uncomplicated Tumor Control Probability Function

To calculate the individualized fraction regime (IFR) in stereotactic body radiotherapy (SBRT) for non-small cell lung cancer (NSCLC) patients using the uncomplicated tumor control probability (UTCP, P+) function. 33 patients with peripheral lung cancer or lung metastases who had undergone SBRT were analyzed. Treatment planning was performed using the dose regime of 48 Gy in 4 fractions. Dose volume histogram (DVH) data for the gross tumor volume (GTV), lung, chest wall (CW) and rib were exported and the dose was multiplied from 1% to 200% at a resolution of 1%. For each dose fraction, P+ values were calculated by considering the tumor control probability (TCP), radiation-induced pneumonitis (RIP), chest wall pain (CWP) and radiation-induced rib fracture (RIRF). UTCP values as a function of physical dose were plotted and the maximum P+ values corresponded to the optimal therapeutic gain. IFR in 3 fractions was also calculated with the same method by converted the dose using the linear quadratic (LQ) model. 33 patients attained an IFR using the introduced methods. All the patients achieved TCP value higher than 92.0%. The IFR ranged from 3×10.8 Gy to 3×12.5 Gy for 3 fraction regimes and from 4×9.2 Gy to 4×10.7 Gy for 4 fraction regimes, respectively. Four patients with typical tumor characteristics demonstrated the IFR was patient-specific and could maximize the therapeutic gain. Patients with large tumor were associated with lower TCP, UTCP and smaller fractional dose than patients with small tumor. Patients with tumor adjacent to the organ at risk (OAR) or at high risk of RIP showed lower UTCP and smaller fractional dose compared with patients with tumor away from the OAR. The proposed method is capable of predicting the IFR for NSCLC patients undergoing SBRT. Further validation is required in clinical samples.

Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP) with Consideration of Cell Biological Effect

In radiotherapy, Tumor Control Probability (TCP) is a parameter used to calculate the percentage of tumor killing, while its effect on normal tissue damage describe by Normal Tissue Complication Probability (NTCP). Both TCP and NTCP depend on fractionation and cell biological effects such as repopulation, repair, redistribution and re-oxygenation. It also depends on the statistical distribution model used. One model that can review the biological effects of cells is the Poisson model. In this research, we modified the Poisson model by considering the four biological effects mentioned above on TCP and only the effect of repair on NTCP. The objective of this research is to investigate the most dominant effect that influences TCP value and the effect of repair on NTCP. The results show that the effect of repair and repopulation cause tumor cells cannot be erased completely while the effects of resenitization (re-oxygenation and redistribution) can facilitate tumor cells to die. It can be seen that the most dominant biological effect is the repair effect on the tumor. This effect can be minimized by reducing the length of dose delivery time. Furthermore, the repair effect on normal tissue can reduce the value of NTCP about 9% compared with other models. By using the ISO-NTCP curve we also get the spinal cord repair time after 15 hours.

Calculating the individualized fraction regime in stereotactic body radiotherapy for non-small cell lung cancer based on uncomplicated tumor control probability function

BackgroundTo calculate the individualized fraction regime (IFR) in stereotactic body radiotherapy (SBRT) for non-small cell lung cancer (NSCLC) patients using the uncomplicated tumor control probability (UTCP, P+) function.MethodsThirty-three patients with peripheral lung cancer or lung metastases who had undergone SBRT were analyzed. Treatment planning was performed using the dose regime of 48 Gy in 4 fractions. Dose volume histogram (DVH) data for the gross tumor volume (GTV), lung, chest wall (CW) and rib were exported and the dose bin was multiplied by a certain percentage of the dose in that bin which ranged from 1 to 200% in steps of 1%. For each dose fraction, P+ values were calculated by considering the tumor control probability (TCP), radiation-induced pneumonitis (RIP), chest wall pain (CWP) and radiation-induced rib fracture (RIRF). UTCP values as a function of physical dose were plotted and the maximum P+ values corresponded to the optimal therapeutic gain. The IFR in 3 fractions was also calculated with the same method by converting the dose using the linear quadratic (LQ) model.ResultsThirty-three patients attained an IFR using the introduced methods. All the patients achieved a TCP value higher than 92.0%. The IFR ranged from 3 × 10.8 Gy to 3 × 12.5 Gy for 3 fraction regimes and from 4 × 9.2 Gy to 4 × 10.7 Gy for 4 fraction regimes. Four patients with typical tumor characteristics demonstrated that the IFR was patient-specific and could maximize the therapeutic gain. Patients with a large tumor had a lower TCP and UTCP and a smaller fractional dose than patients with a small tumor. Patients with a tumor adjacent to the organ at risk (OAR) or at a high risk of RIP had a lower UTCP and a smaller fractional dose compared with patients with a tumor located distant from the OAR.ConclusionsThe proposed method is capable of predicting the IFR for NSCLC patients undergoing SBRT. Further validation in clinical samples is required.

Modelling the effect of spread in radiosensitivity parameters and repopulation rate on the probability of tumour control

PurposeTo investigate the impact of a variable inter-individual spread in the tumour cell radiosensitivity and repopulation rate on the tumour control probability (TCP). MethodsThe radiosensitivity parameters and the repopulation rate are presumed to be log-normally distributed among the population. Corresponding distributions of TCP across the population are built using a Monte-Carlo simulation algorithm. An analytical formula for the TCP distribution is derived for the case of variability in radiosensitivity only and found to be in excellent agreement with the corresponding Monte-Carlo simulations. Results and ConclusionsIt is found that a large variation in individual-patient radiosensitivity results in a dichotomous TCP distribution over the population. In general, the form and width of the TCP distribution depend on the variation in the radiosensitivity. Accounting for tumour repopulation and its variability leads to lower TCP values as expected. It is shown that for a standard fractionation regimen resulting in a population TCP of almost zero, a simple change of the regimen to a hypofractionated one (i.e. typical of SBRT), a decrease in the physical dose is possible such that a beneficial tumour treatment outcome can be still achieved. The reduction in dose will in turn reduce eventual adverse effects caused in the surrounding healthy tissues. This theoretical finding is supported by the increasing amount of clinical evidence for the efficacy of SBRT. The desirability of a pre-clinical independent estimation of the individual radiosensitivity is emphasised.