Equivalent Uniform Dose Values Research Articles

Impact of Number and Placement of High-dose Vertices on Equivalent Uniform Dose and Peak-to-valley Ratio for Lattice Radiotherapy

Aims: This study evaluated the influence of high dose (HD) vertex numbers and its placement on equivalent uniform dose (EUD) and peak-to-valley dose ratio (PVDR) in lattice radiotherapy (LRT). Settings and Design: One hundred and eighty-eight RapidArc (RA) plans were created for a cohort of 15 patients. Materials and Methods: RA plans were created with zero to eight HD vertices to analyze their relationship with EUD. Eight lattices were systematically and optimally placed (by avoiding proximity to organs at risks [OARs]) to study the impact of vertex placement. Variations in PVDR were assessed using PVDR1 (mean dose to HD vertices by the difference of mean doses to planning target volume [PTV] and HD vertices) and PVDR2 (D10/D90 of PTV in composite plans) across 38 RA plans with HD vertex doses of 9 Gy, 12 Gy, 15 Gy, and 18 Gy. PVDR3 (product of PVDR1 and PVDR2) was evaluated for its variation with peak dose. Statistical Analysis Used: Hypothesis testing between vertex placements was performed using a two-tailed Student’s t-test. Results: EUD values ranged from 32.88 Gy to 40.63 Gy. In addition, statistical analysis revealed significant associations (P = 0.0074) between the placement patterns of HD vertices, both in systematic and optimized arrangements. The PVDR and D10/D90 product values were 1.6, 1.8, 2.1, and 2.3 for peak doses of 9 Gy, 12 Gy, 15 Gy, and 18 Gy, respectively. Conclusions: The addition of one HD vertex increased EUD, emphasizing the impact of individual vertex increments on outcomes. Systematic and optimized vertex placements enhance EUD, with optimized placement yielding better doses to PTV and OARs. PVDR3 offers superior dose reporting for LRT compared to PVDR1 and PVDR2.

Radiobiological analysis of VMAT treatment plan with flattened and flattening filter free photon beam: an EUD and TCP based comparative study.

This study aimed to evaluate the dosimetric and radiobiological differences between 6MV flattened filter (FF) and flattening filter free (FFF) using volumetric modulated arc (VMAT) technique for head and neck (H&N) cancer patients. Fifteen patients with H&N carcinoma were selected and treated with VMAT with FF (VMATFF) treatment plan. Retrospectively, additional VMAT treatment plans were developed using FFF beams (VMATFFF). Radiobiological parameters, such as equivalent uniform dose (EUD), tumor cure probability (TCP), and normal tissue complication probability (NTCP), were calculated using Niemierko's model for both VMATFF and VMATFFF. Correlation between dosimetric and radiobiological data were analyzed and compared. The conformity index (CI) was 0.975 ± 0.014 (VMATFF) and 0.964 ± 0. 019 (VMATFFF) with p ≥ 0.05. Statistically, there was an insignificant difference in the planning target volume (PTV) results for TCP (%) values, with values of 81.20 ± 0.88% (VMATFF) and 81.01 ± 0.92 (%) (VMATFF). Similarly, there was an insignificant difference in the EUD (Gy) values, which were 71.53 ± 0.33 Gy (VMATFF) and 71.46 ± 0.34 Gy (VMATFFF). The NTCP values for the spinal cord, left parotid, and right parotid were 6.54 × 10-07%, 8.04%, and 7.69%, respectively, in the case of VMATFF. For VMATFFF, the corresponding NTCP values for the spinal cord, parotids left, and parotid right were 3.09 × 10-07%, 6.57%, and 6.73%, respectively. The EUD and Mean Dose to PTV were strongly correlated for VMATFFF. An increased mean dose to the PTV and greater TCP were reported for the VMATFF, which can enhance the delivery of the therapeutic dose to the target.

Influence of Dose Distribution in the Target on the Values of Integral Radiobiological Criteria Based on Synthetic Dose-Volume Histograms

Purpose: To investigate the influence of absorbed dose distribution in the tumor volume on the values of
 integral radiobiological criteria, such as the probability of local tumor control (Tumor Control Probability, TCP) and normal tissue complication probability (NTCP), based on synthetic dose-volume histograms (DVH), which enables to assess the treatment effectiveness and probability of complications
 from healthy organs and tissues.
 Material and methods: Synthetic dose-volume histograms were considered theoretically possible to analyze the dependence of equivalent uniform dose (EUD) on values of Nimirko model parameters and absorbed dose distribution for both tumor and critical organs. The calculation was carried out in Wolfram
 Mathematica program based on the algorithm, where an array of absorbed dose values per fraction of
 irradiation volume with step by absorbed dose was calculated for the given values of absorbed dose and
 the parameter determining the width of distribution. The resulting array was differentiated to obtain
 the differential DVH. The EUD values were obtained from the normalized differential DVHs.
 Results: During analysis of EUD value dependence on parameter a values determining degree of nonlinearity of absorbed dose summation in sub-volumes of irradiation and on absorbed dose distribution
 the following was revealed: for critical organs at high values of parameter a the essential role belongs to
 high and average values of absorbed dose, and for tumors at low values of parameter a the main role belongs to the minimum value of absorbed dose. Thus, the value of parameter a should be negative for a
 tumor, and positive for critical organs, and should be specifically defined for specific structures.
 Conclusion: To improve the predictive value (prediction) of the effect of radiotherapy using the
 TCP/NTCP Nimirko model, an adequate definition of the parameter a, the value of which can only be determined from absorbed dose distributions over the volume of anatomical structures within clinical trials, is necessary.

A novel knowledge-based prediction model for estimating an initial equivalent uniform dose in semi-auto-planning for cervical cancer

BackgroundWe developed a novel concept, equivalent uniform length (EUL), to describe the relationship between the generalized equivalent uniform dose (EUD) and the geometric anatomy around a tumor target. By correlating EUL with EUD, we established two EUD–EUL knowledge-based (EEKB) prediction models for the bladder and rectum that predict initial EUD values for generating quality treatment plans.MethodsEUL metrics for the rectum and bladder were extracted and collected from the intensity-modulated radiotherapy therapy (IMRT) plans of 60 patients with cervical cancer. The two EEKB prediction models were built using linear regression to establish the relationships between EULr and EUDr (EUL and EUD of rectum) and EULb, and EUDb (EUL and EUD of bladder), respectively. The EE plans were optimized by incorporating the predicted initial EUD parameters for the rectum and bladder with the conventional pinnacle auto-planning (PAP) initial dose parameters for other organs. The efficiency of the predicted initial EUD values were then evaluated by comparing the consistency and quality of the EE plans, PAP plans (based on default PAP initial parameters), and manual plans (designed manually by different dosimetrists) for a sample of 20 patients.ResultsLinear regression analyses showed a significant correlation between EUL and EUD (R2 = 0.79 and 0.69 for EUDb and EUDr, respectively). In a sample of 20 patients, the average bladder V40 and V50 derived from the EE plans were significantly lower (V40: 30.00 ± 5.76, V50: 14.36 ± 4.00) than the V40 and V50 values derived from manual plans (V40: 36.03 ± 8.02, V50: 19.02 ± 5.42). Compared with the PAP plans, the EE plans produced significantly lower average V30 and Dmean values for the bladder (V30: 50.55 ± 6.33, Dmean: 31.48 ± 1.97 Gy).ConclusionsOur EEKB prediction models predicted reasonable initial EUD values for the rectum and bladder based on patient-specific geometric EUL values, thereby improving optimization and planning efficiency.

I-124 PET/CT image-based dosimetry in patients with differentiated thyroid cancer treated with I-131: correlation of patient-specific lesional dosimetry to treatment response.

The objective of this study is to evaluate the lesion absorbed dose (AD), biological effective dose (BED), and equivalent uniform dose (EUD) to clinical-response relationship in lesional dosimetry for 131I therapy. Nineteen lesions in four patients with metastatic differentiated thyroid cancer (DTC) were evaluated. The patients underwent PET/CT imaging at 2h, 24h, 48h, 72h, and 96h post administration of ~ 33-65MBq (0.89-1.76mCi) of 124I before undergoing 131I therapy. The 124I PET/CT images were used to perform dosimetry calculations for 131I therapy. Lesion dose-rate values were calculated using the time-activity data and integrated over the measured time points to obtain AD and BED. The Geant4 toolkit was used to run Monte Carlo on spheres the same size as the lesions to estimate EUD. The lesion AD, BED, and EUD values were correlated with response data (i.e. change in lesion size pre- and post-therapy): complete response (CR, i.e. disappearance of the lesion), partial response (PR, i.e. any decrease in lesion length), stable disease (SD, i.e., no change in length), and progressive disease (PD, i.e., any increase in length). The lesion responses were CR and PR (58%, 11/19 lesions), SD (21%, 4/19), and PD (21%, 4/19). For CR and PR lesions, the ADs, BEDs and EUDs were > 75Gy for 82% (9/11) and < 75Gy for 18% (2/11). The ADs and BEDs were < 75Gy for SD and PD lesions. By performing retrospective dosimetry calculations for 131I therapy based on 124I PET/CT imaging, we evaluated the correlation of three dosimetric quantities to lesional response. When lesion AD, BED, and EUD values were > 75Gy, 47% (9/19) of the lesions had a CR or PR. The AD, BED, and EUD values for SD and PD lesions were < 75Gy. The data presented herein suggest that the greater the lesion AD, BED, and/or EUD, the higher the probability of a therapeutic response to 131I therapy.

Optimized stereotactic volumetric modulated arc therapy as an alternative to brachytherapy for vaginal cuff boost. A dosimetric study

We evaluate the role of stereotactic body radiotherapy using volumetric modulated arc therapy (VMAT) technique as an alternative to high-dose rate brachytherapy (HDR-BT) in the treatment of vaginal cuff in postoperative endometrial cancer. CT scans of 8 patients were used in this study. The clinical target volume (CTV) was defined as the 0.5 cm tissue around the applicator (then subtracting the applicator). Total dose was 30Gy delivered in 5 fractions. In HDR-BT, dose was prescribed at a distance of 0.5 cm from the surface applicator. For VMAT irradiation, a planning target volume (PTV) was obtained from CTV by an expansion of 3 mm. Two VMAT plans were generated using a full arc rotation. The first plan was optimized with an anatomy-based optimization module (PO-VMAT) using a 1mm multileaf collimator beam margin to enhance dose heterogeneity and dose fallout outside the target. The second plan was generated with a full-inverse planning module (FI-VMAT). Conformity (CI100, CI50, CI25), gradient (GI) indexes, and integral doses were calculated. To account for various dose heterogeneity distributions we calculated the equivalent uniform dose (EUD) using the Niemerko model. A Kruskal-Wallis analysis of variance followed by Dunn’s-type multiple comparisons was performed. Dose distributions were more heterogeneous with HDR-BT: Dmean was 144.2% of prescription dose for CTV in HDR-BT and 118.5 and 108.6% for PTV in PO-VMAT and FI-VMAT, respectively. The mean values of EUD for CTV were 136.9%, 130.0 %, and 111.0% of prescription dose in HDR-BT, PO-VMAT, and FI-VMAT plans, respectively. GI indexes were 2.81, 3.41, and 4.14 for HDR-BT, PO-VMAT, and FI-VMAT, respectively. Near-maximal doses (D0.1cc) for rectum and bladder were significantly higher in HDR-BT plans compared to PO-VMAT and FI-VMAT plans (rectum: 131.2% vs112.8% vs 112.0%, respectively; bladder: 129.2% vs 108.7%, and 109.8%, respectively). PO-VMAT plans were able to mimic the HDR-BT dose distribution, showing a successful capability of highly conformal dose distribution, EUD values similar to HDR-BT, and steep dose-gradient outside PTV, then providing a reasonable alternative to brachytherapy.

Comparison of nodal irradiation dose using radiotherapy for patients with thoracic esophageal cancer.

The present study aimed to compare incidental nodal irradiation (INI) doses using volume-modulated arc therapy (VMAT), 5-field intensity-modulated radiotherapy (5F-IMRT) and 3D-conformal radiotherapy (3D-CRT) treatment plans for patients with thoracic esophageal cancer (EC). A total of 15 patients with thoracic EC were selected for participation between October 2016 and July 2017 at the Hangzhou Cancer Hospital. Regional lymph nodal stations were contoured according to 3D CT-based images of the Japan Esophageal Society Guidelines. All patients were treated with 60 Gy using VMAT, 5F-IMRT and 3D-CRT plans. Dose-volume histograms of planning target volume (PTV), lung, heart, spinal cord and incidental nodal irradiation were compared between the three plans. 5F-IMRT was superior in PTV_V95% (the volume of the PTV receiving 95% of the prescription dose, P=0.003) and the VMAT plan was best in terms of conformal index (P=0.005). V20 and V30 were reduced by 10.7-22.6% (P=0.002) and 12.8-21% (P=0.026), respectively, in normal lung tissue using the VMAT plan. 5F-IMRT demonstrated the lowest maximum dose (Dmax) for the spinal cord (P=0.037). For the INI, 3D-CRT exhibited the highest equivalent uniform dose (EUD) values for 106pre (P=0.014) and 106tb-L (P=0.03) in upper-thoracic EC. The mean EUD of all lymph nodal regions in middle-thoracic EC were >40 Gy in VMAT and 5F-IMRT plans; the VMAT plan had higher EUD values in lower-thoracic EC compared with 5F-IMRT, 3D-CRT plans for INI. VMAT were comparable to the 5F-IMRT plan with respect to dosimetric characteristics for planning and INI doses to thoracic nodal levels NO 105-112 are considerable for thoracic EC.

A free user friendly program for evaluation of radiotherapy plans based on different dose response models

Introduction: Radiotherapy (RT) plan evaluation using dose response models has become a feasible approach in routine clinical practice. Although there are several tools for this task, they suffer from limitations including number of different dose response models and parameters. In the present study, we aimed to develop a free program for RT plan evaluation based on a variety dose response models and parameters. Materials and Methods: The program was developed in MATLAB. It includes four dose response models for normal tissue complication probability (NTCP) including Lyman-Kutcher-Burman (LKB), Relative Seriality, Logit and Parallel. The program required dose-volume histogram (DVH) data, number of fractions and the total RT dose. Other user inputs include a number of model parameters which are available in separate sheets. The program also calculates biological effective dose (BED), equivalent uniform dose (EUD) and biological equivalent uniform dose (BEUD). To evaluate the program, its results from sixteen patients were compared against previously validated software codes. Each model’s results were compared for various parameters. The computed NTCP, BED, EUD and BEUD values were compared with the expected values using a spreadsheet. Results: There was a good agreement between the results of our program and the standard software. Different model parameters resulted in different predicted values depending on the model and the parameters used. All calculated dose response outputs were calculated exactly the same as the standard codes. Conclusion: The results presented here indicate that the developed program is validated. This free and user friendly software can help physicists and clinicians to evaluate treatment plans on a radiobiological basis using different models directly and easily.

Unilateral cochlea sparing in locoregionally advanced head and neck cancer: aplanning study.

Cochlea sparing can reduce late ototoxicity in head and neck cancer patients treated with cisplatin-based radiochemotherapy. In this situation, amean cochlear dose (MCD) constraint of 10 Gy has been suggested by others based on the dose-effect relationship of clinical data. We aimed to investigate whether this is feasible for primary and postoperative radiochemotherapy in locoregionally advanced tumors without compromising target coverage. Ten patients treated with definitive and ten patients treated with adjuvant intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy were investigated. The cochleae and aplanning risk volume (PRV) with a3 mm margin were newly delineated, whereas target volumes and other organs at risk were not changed. The initial plan was recalculated with aconstraint of 10 Gy (MCD) on the low-risk side. The quality of the resulting plan was evaluated using the difference in the equivalent uniform dose (EUD). Aunilateral MCD of below 10 Gy could be achieved in every patient. The mean MCD was 6.8 Gy in the adjuvant cohort and 7.6 Gy in the definitive cohort, while the non-spared side showed amean MCD of 18.7 and 30.3 Gy, respectively. The mean PRV doses were 7.8 and 8.4 Gy for the spared side and 18.5 and 29.8 Gy for the non-spared side, respectively. The mean EUD values of the initial and recalculated plans were identical. Target volume was not compromised. Unilateral cochlea sparing with anMCD of less than 10 Gy is feasible without compromising the target volume or dose coverage in locoregionally advanced head and neck cancer patients treated with IMRT. Aprospective evaluation of the clinical benefit of this approach as well as further investigation of the dose-response relationship for future treatment modification appears promising.

Impact of the NTCP modeling on medical decision to select eligible patient for proton therapy: the usefulness of EUD as an indicator to rank modern photon vs proton treatment plans

Purpose: The aim of this study is to evaluate the impact of normal tissue complication probability (NTCP)-based radiobiological models on the estimated risk for late radiation lung damages. The second goal is to propose a medical decision-making approach to select the eligible patient for particle therapy.Materials and methods: Fourteen pediatric patients undergoing cranio-spinal irradiation were evaluated. For each patient, two treatment plans were generated using photon and proton therapy with the same dose prescriptions. Late radiation damage to lung was estimated using three NTCP concepts: the Lyman-Kutcher-Burman, the equivalent uniform dose (EUD) and the mean lung dose according to the quantitative analysis of normal tissue effects in the clinic QUANTEC review. Wilcoxon paired test was used to calculate p-value.Results: Proton therapy achieved lower lung EUD (Gy). The average NTCP values were significantly lower with proton plans, p < .05, using the three NTCP concepts. However, applying the same TD50/5 using radiobiological models to compare NTCP from proton and photon therapy, the ΔNTCP was not a convincing method to measure the potential benefit of proton therapy. Late radiation pneumonitis estimated from the mean lung dose model correlated with QUANTEC data better.Conclusions: Treatment effectiveness assessed on NTCP reduction depends on radiobiological predictions and parameters used as inputs for in silico evaluation. Because estimates of absolute NTCP values from LKB and GN models are imprecise due to EUD ≪ TD50/5, a reduction of the EUD value with proton plans would better predict a reduction of dose/toxicity. The EUD concept appears as a robust radiobiological surrogate of the dose distribution to select the optimal patient’s plan.

A Feasibility Study of Personalized Prescription Schemes for Glioblastoma Patients Using a Proliferation and Invasion Glioma Model.

Purpose: This study investigates the feasibility of personalizing radiotherapy prescription schemes (treatment margins and fractional doses) for glioblastoma (GBM) patients and their potential benefits using a proliferation and invasion (PI) glioma model on phantoms. Methods and Materials: We propose a strategy to personalize radiotherapy prescription schemes by simulating the proliferation and invasion of the tumor in 2D according to the PI glioma model. We demonstrate the strategy and its potential benefits by presenting virtual cases, where the standard and personalized prescriptions were applied to the tumor. Standard prescription was assumed to deliver 46 Gy in 23 fractions to the initial, gross tumor volume (GTV1) plus a 2 cm margin and an additional 14 Gy in 7 fractions to the boost GTV2 plus a 2 cm margin. The virtual cases include the tumors with a moving velocity of 0.029 (slow-move), 0.079 (average-move), and 0.13 (fast-move) mm/day for the gross tumor volume (GTV) with a radius of 1 (small) and 2 (large) cm. For each tumor size and velocity, the margin around GTV1 and GTV2 was varied between 0–6 cm and 1–3 cm, respectively. Equivalent uniform dose (EUD) to normal brain was constrained to the EUD value obtained by using the standard prescription. Various linear dose policies, where the fractional dose is linearly decreasing, constant, or increasing, were investigated to estimate the temporal effect of the radiation dose on tumor cell-kills. The goal was to find the combination of margins for GTV1 and GTV2 and a linear dose policy, which minimize the tumor cell-surviving fraction (SF) under a normal tissue constraint. The efficacy of a personalized prescription was evaluated by tumor EUD and the estimated survival time. Results: The personalized prescription for the slow-move tumors was to use 3.0–3.5 cm margins for GTV1, and a 1.5 cm margin for GTV2. For the average- and fast-move tumors, it was optimal to use a 6.0 cm margin for GTV1 and then 1.5–3.0 cm margins for GTV2, suggesting a course of whole brain therapy followed by a boost to a smaller volume. It was more effective to deliver the boost sequentially using a linearly decreasing fractional dose for all tumors. Personalized prescriptions led to surviving fractions of 0.001–0.465% compared to the standard prescription, and increased the tumor EUDs by 25.3–49.3% and estimated survival times by 7.6–22.2 months. Conclusions: Personalizing treatment margins based on the measured proliferative capacity of GBM tumor cells can potentially lead to significant improvements in tumor cell kill and related clinical outcomes.

Prescription dose evaluation for APBI with noninvasive image-guided breast brachytherapy using equivalent uniform dose.

Noninvasive image-guided breast brachytherapy (NIBB) is an attractive novel approach to deliver accelerated partial breast irradiation (APBI). Calculations of equivalent uniform dose (EUD) were performed to identify the appropriate APBI dose for this technique. APBI plans were developed for 15 patients: five with three-dimensional conformal APBI (3D-CRT), five with multi-lumen intracavitary balloons (m-IBB), and five simulating NIBB treatment. Prescription doses of 34.0 and 38.5 Gy were delivered in 10 fractions for m-IBB and 3D-CRT, respectively. Prescription doses ranging from 34.0 to 38.5 Gy were considered for NIBB. Dose-volume histogram data from all 3D-CRT, m-IBB, and NIBB plans were used to calculate the biologically effective EUD and corresponding EUD to the PTV_eval using the following equation: EUD = EUBED/(n [1 + EUD/α/β]). An α/β value of 4.6 Gy was assumed for breast tumor. EUD for varying NIBB prescription doses were compared with EUD values for the other APBI techniques. Mean PTV_eval volume was largest for 3D-CRT (372.9 cm(3)) and was similar for NIBB and m-IBB (88.7 and 87.2 cm(3), respectively). The EUD value obtained by prescribing 38.5 Gy with 3D-CRT APBI was 38.6 Gy. The EUD value of 34.0 Gy prescribed with m-IBB was 34.4 Gy. EUD values for NIBB ranged from 33.9 to 38.2 Gy for prescription doses ranging from 34.0 to 38.5 Gy. Using EUD calculations to compare APBI techniques and treatment doses, a prescription dose of 36.0 Gy in 10 fractions using NIBB has a comparable biologic equivalent dose to other established brachytherapy techniques.

Sci-Fri PM: Topics - 04: What if bystander effects influence cell kill within a target volume? Potential consequences of dose heterogeneity on TCP and EUD on intermediate risk prostate patients

In vitro evidence has suggested that radiation induced bystander effects may enhance non-local cell killing which may influence radiotherapy treatment planning paradigms. This work applies a bystander effect model, which has been derived from published in vitro data, to calculate equivalent uniform dose (EUD) and tumour control probability (TCP) and compare them with predictions from standard linear quadratic (LQ) models that assume a response due only to local absorbed dose. Comparisons between the models were made under increasing dose heterogeneity scenarios. Dose throughout the CTV was modeled with normal distributions, where the degree of heterogeneity was then dictated by changing the standard deviation (SD). The broad assumptions applied in the bystander effect model are intended to place an upper limit on the extent of the results in a clinical context. The bystander model suggests a moderate degree of dose heterogeneity yields as good or better outcome compared to a uniform dose in terms of EUD and TCP. Intermediate risk prostate prescriptions of 78 Gy over 39 fractions had maximum EUD and TCP values at SD of around 5Gy. The plots only dropped below the uniform dose values for SD ∼ 10 Gy, almost 13% of the prescribed dose. The bystander model demonstrates the potential to deviate from the common local LQ model predictions as dose heterogeneity through a prostate CTV is varies. The results suggest the potential for allowing some degree of dose heterogeneity within a CTV, although further investigations of the assumptions of the bystander model are warranted.

Volume of high-dose regions and likelihood of locoregional control after perioperative high-dose-rate brachytherapy: do hotter implants work better?

To determine whether perioperative high-dose-rate brachytherapy (PHDRB) implants with larger high-dose regions produce increased locoregional control. Patients (n=166) enrolled in several PHDRB prospective studies conducted at the University of Navarre were analyzed. The PHDRB was given to total doses of 16Gy/4 b.i.d. or 24Gy/6 b.i.d. treatments for negative or close/positive margins along with 45Gy/25 Rx of external beam radiation therapy. The histogram-based generalized equivalent uniform dose (EUD) formulism was used to quantify and standardize the dose-volume histogram into 2-Gy equivalents. The region of interest analyzed included: tissue volume encompassed by the prescription isodose of 4Gy (TV100). Routine dose reporting parameters such as physical dose and single-point 2-Gy equivalent dose were used for reference. After a median followup of 7.4 years (range, 3-12+), 50 patients have failed, and 116 remain controlled at last followup. Overall, EUD was not different in the patients who failed compared with controls (89.1Gy vs. 86.5Gy; p=not significant). When patients were stratified by risk using the University of Navarre Predictive Model, very high-risk patients (i.e., tumors ≥3cm resected with close <1mm/positive margins) had an improved locoregional control with higher EUD values (p=0.028). This effect was not observed in low-, intermediate-, and high-risk University of Navarre Predictive Model categories. In very high-risk patients, enlarged high-dose regions can produce a dose-response effect. Routine dose reporting methods such as physical dose and single-point 2-Gy equivalent dose may not show this effect, but it can be revealed by histogram-based EUD assessment.

Analysis of equivalent uniform dose (EUD) and conventional radiation treatment parameters after primary and re-irradiation of malignant glioma

BackgroundRe-irradiation is a reasonable second treatment option for patients with recurrent malignant glioma (MG) after previous radio(chemo)therapy. However, only limited data is available allowing for a precise selection of patients suitable for re-treatment in regard to safety and efficacy.MethodsUsing the department database, 58 patients with two courses of percutaneous radiation were identified. Besides classical dose-volume histogram (DVH) parameters equivalent uniform dose (EUD) values were calculated for the tumor and organs at risk (OARs), retrospectively analyzed and correlated to survival outcome parameters. Cumulative EUD values were also calculated in all cases where previous OAR DVHs were available.ResultsMedian follow-up was 265 days and no relevant toxicity was observed after re-irradiation in our patient cohort during follow-up. Time interval between first and second irradiation was regularly above 6 months. As a conservative estimation of the cumulative EUD to the OARs, the EUDs of first and second irradiation were added. Median cumulative EUD to the optic chiasm was 48.8 Gy (range, 2.5–76.5 Gy), 57.4 Gy (range, 2.7–75.3 Gy) to the brainstem, 20.9/22.1 Gy (range, 0.0–68.3 Gy) to the right/left optic nerve and 73.8 Gy (range, 64.9–77.3 Gy) to the brain. No correlation between treated volume and survival was seen.ConclusionsThis study provides retrospective estimates on cumulative doses at the OARs. EUD values are derived and may serve as reference for further studies, including planning studies where specific constraints are needed.

Four-dimensional Monte Carlo simulations demonstrating how the extent of intensity-modulation impacts motion effects in proton therapy lung treatments

To compare motion effects in intensity modulated proton therapy (IMPT) lung treatments with different levels of intensity modulation. Spot scanning IMPT treatment plans were generated for ten lung cancer patients for 2.5Gy(RBE) and 12Gy(RBE) fractions and two distinct energy-dependent spot sizes (σ ∼8-17 mm and ∼2-4 mm). IMPT plans were generated with the target homogeneity of each individual field restricted to <20% (IMPT20%). These plans were compared to full IMPT (IMPTfull), which had no restriction on the single field homogeneity. 4D Monte Carlo simulations were performed upon the patient 4DCT geometry, including deformable image registration and incorporating the detailed timing structure of the proton delivery system. Motion effects were quantified via comparison of the results of the 4D simulations (4D-IMPT20%, 4D-IMPTfull) with those of a 3D Monte Carlo simulation (3D-IMPT20%, 3D-IMPTfull) upon the planning CT using the equivalent uniform dose (EUD), V95 and D1-D99. The effects in normal lung were quantified using mean lung dose (MLD) and V90%. For 2.5Gy(RBE), the mean EUD for the large spot size is 99.9% ± 2.8% for 4D-IMPT20% compared to 100.1% ± 2.9% for 4D-IMPTfull. The corresponding values are 88.6% ± 8.7% (4D-IMPT20%) and 91.0% ± 9.3% (4D-IMPTfull) for the smaller spot size. The EUD value is higher in 69.7% of the considered deliveries for 4D-IMPTfull. The V95 is also higher in 74.7% of the plans for 4D-IMPTfull, implying that IMPTfull plans experience less underdose compared to IMPT20%. However, the target dose homogeneity is improved in the majority (67.8%) of plans for 4D-IMPT20%. The higher EUD and V95 suggests that the degraded homogeneity in IMPTfull is actually due to the introduction of hot spots in the target volume, perhaps resulting from the sharper in-target dose gradients. The greatest variations between the IMPT20% and IMPTfull deliveries are observed for patients with the largest motion amplitudes. These patients would likely be treated using gating or another motion mitigation technique, which was not the focus of this study. For the treatment parameters considered in this study, the differences between IMPTfull and IMPT20% are only likely to be clinically significant for patients with large (>20 mm) motion amplitudes.

TU-A-108-02: A 4D Monte Carlo Study Quantifying Changes in the Interplay Effect as a Function of Treatment Delivery Parameters in Proton Beam Scanning for Lung

Purpose: To assess the impact of delivery parameters of a pencil beam scanning proton therapy system on the dosimetric interplay effect during lung treatments. Methods: 4D Monte Carlo simulations were performed using TOPAS for 5 lung cancer patients with varying tumor sizes (50.4–167.1cc) and superior‐inferior (SI) motion amplitudes (2.9–30.1mm). Each patient was planned based on a 4DCT scan. The complete time structure of the proton fields was incorporated into the simulation framework by including the time required to deposit dose, scan the beam laterally, change the beam energy and the time required for magnet settling. Changes in the 4D dose distribution resulting from altering the spot size, energy switch time, magnet settling time, initial breathing phase, spot spacing, scanning direction, scanning speed, beam current and breathing period were determined using deformable image registration. The metrics used for analysis were mean dose, minimum dose, maximum dose, dose homogeneity, equivalent uniform dose (EUD), lung V 5, V 20 and mean lung dose. Results: In general, longer delivery times led to less interplay and the interplay effect could not be predicted using motion amplitude alone. Larger spot sizes (σ ∼9–16mm) gave a EUD of 99.0% + 4.4% (1 standard deviation) of the prescription dose in 1 fraction compared to 86.1% + 13.1% for smaller spots (σ ∼2–4mm). Smaller spot sizes gave EUD values as low as 65.3% in 1 fraction. Target dose homogeneity improved with reduced spot spacing. The interplay effect can vary significantly with initial breathing phase. No definitive benefit was observed when scanning predominantly parallel or perpendicular to the SI axis. Conventional fractionation reduced interplay, giving EUD values of at least 84.7% and 100.0% for the small and larger spot sizes respectively. Conclusion: The interplay effect is highly patient specific and varies based on the motion amplitude, tumor location and various delivery parameters. This project was supported by the National Cancer Institute Grant No. R01 CA111590

Radiobiological evaluation of dose calculation algorithms in RapidArc planning of esophageal cancer treatment plans

Normal 0 false false false EN-US X-NONE X-NONE Purpose: The purpose of current study is to investigate the impact of tissue heterogeneity corrections in Acuros XB algorithm (AXB) and Anisotropic Analytical Algorithm (AAA) on RapidArc esophageal cancer treatment plans using equivalent uniform dose (EUD) calculations and tumor control probability (TCP). Methods: Ten esophageal cancer cases were selected for the current study. All cases were planned using RapidArc technique in Eclipse treatment planning system (10.0.28). The treatment plans were inversely optimized using progressive resolution optimizer and each optimized plan was calculated using AAA with tissue heterogeneity correction. The AAA plans were then normalized such that prescription dose covered 95% of the planning target volume (PTV). The AXB plans were generated by recalculating the normalized AAA plans using AXB with tissue heterogeneity correction for identical monitor units and beam parameters as in the corresponding AAA plans. The EUD and TCP calculations were then performed on the AAA and AXB plans. Results: For PTV, the EUD values in AXB plans were always lower than in AAA plans with an average difference of 1.3%. Similarly, AXB calculations produced smaller magnitude of EUD for the organs at risk (OARs) compared to AAA calculations. On average, in AXB plans, the lung EUD was lower by 3.5%, the liver EUD was lower by 2.3%, the heart EUD was lower by 2.8%, and the spinal cord EUD was lower by 1.8%. The TCP of AXB plans was lower by average difference of 7.1% compared to that of AAA plans. Conclusion: In comparison to AAA calculations, the preliminary results presented in the current study showed that AXB calculations produced lower EUD and TCP for the PTV as well as lower EUD for OARs in the esophageal cancer treatment plans created by RapidArc planning technique.

Interplay effects in proton scanning for lung: a 4D Monte Carlo study assessing the impact of tumor and beam delivery parameters

Relative motion between a tumor and a scanning proton beam results in a degradation of the dose distribution (interplay effect). This study investigates the relationship between beam scanning parameters and the interplay effect, with the goal of finding parameters that minimize interplay. 4D Monte Carlo simulations of pencil beam scanning proton therapy treatments were performed using the 4DCT geometry of five lung cancer patients of varying tumor size (50.4–167.1 cc) and motion amplitude (2.9–30.1 mm). Treatments were planned assuming delivery in 35 × 2.5 Gy(RBE) fractions. The spot size, time to change the beam energy (τes), time required for magnet settling (τss), initial breathing phase, spot spacing, scanning direction, scanning speed, beam current and patient breathing period were varied for each of the five patients. Simulations were performed for a single fraction and an approximation of conventional fractionation. For the patients considered, the interplay effect could not be predicted using the superior–inferior motion amplitude alone. Larger spot sizes (σ ∼ 9–16 mm) were less susceptible to interplay, giving an equivalent uniform dose (EUD) of 99.0 ± 4.4% (1 standard deviation) in a single fraction compared to 86.1 ± 13.1% for smaller spots (σ ∼ 2–4 mm). The smaller spot sizes gave EUD values as low as 65.3% of the prescription dose in a single fraction. Reducing the spot spacing improved the target dose homogeneity. The initial breathing phase can have a significant effect on the interplay, particularly for shorter delivery times. No clear benefit was evident when scanning either parallel or perpendicular to the predominant axis of motion. Longer breathing periods decreased the EUD. In general, longer delivery times led to lower interplay effects. Conventional fractionation showed significant improvement in terms of interplay, giving a EUD of at least 84.7% and 100.0% of the prescription dose for the small and larger spot sizes respectively. The interplay effect is highly patient specific, depending on the motion amplitude, tumor location and the delivery parameters. Large degradations of the dose distribution in a single fraction were observed, but improved significantly using conventional fractionation.

Radiation treatment parameters for re-irradiation of malignant glioma

Most patients with malignant glioma ultimately fail locally or loco-regionally after the first treatment, with re-irradiation being a reasonable treatment option. However, only limited data are presently available allowing for a precise selection of patients suitable for re-treatment with regard to safety and efficacy. Using the department database, 39patients with a second course of radiation were identified. Doses to gross tumor volume (GTV), planning target volume (PTV), and relevant organs at risk (OARs; brainstem, optic chiasm, optic nerves, brain) were retrospectively analyzed and correlated to outcome parameters. Relevant treatment parameters including D(max), D(min), D(mean), and volume (ml) were obtained. Equivalent uniform dose (EUD) values were calculated for the tumor and OARs. To address the issue of radiation necrosis/leukoencephalopathy posttherapeutic MRI images were routinely examined every 3months. Median follow-up was 147days. The time interval between first and second irradiation was regularly greater than 6months. Median EUDs to the OARs were 11.9Gy (range 0.7-27.4Gy) to the optic chiasm, 17.6Gy (range 0.7-43.0Gy) to the brainstem, 4.9/2.1Gy (range 0.3-24.5Gy) to the right/left optic nerve, and 29.4Gy (range 25.2-32.5Gy) to the brain. No correlation between treated volume and survival was observed. Cold spots and dose did not correlate with survival. Re-irradiated volumes were treated with on average lower doses if they were larger and vice versa. In general, re-irradiation is a safe and feasible re-treatment option. No relevant toxicity was observed after re-irradiation in our patient cohort during follow-up. In this regard, this analysis provides baseline data for the selection of putative patients. EUD values are derived and may serve as reference for further studies, including intensity-modulated radiotherapy (IMRT) protocols.