Equivalent Uniform Dose Research Articles

A comparative study of volumetric modulated arc therapy plans based on the equivalent uniform dose optimization for left-sided breast cancer

PurposeTo investigate the effect of equivalent uniform dose (EUD)-based optimization on radiotherapy planning for left-sided breast cancer after mastectomy. MethodsTwelve patients treated with left-sided breast cancer using volumetric modulated arc therapy (VMAT) were retrospectively enrolled in this study. Four plans were generated for each patient. Plan A was optimized based on only physical parameters. EUD with α > 0 to organ at risk (OARs) was added in Plan B on the basis of Plan A; EUD with α < 0 to planning tumor volume (PTV) was added in Plan C on the basis of Plan A; EUD constraints were added for both OARs and PTV in Plan D. The quality of plans was evaluated in terms of Vx (volume percent of PTV or OARs received xGy dose), Dx (dose received by volume above x% of PTV or OARs), conformity index (CI), mean dose (Dmean), maximum dose (Dmax) and minimum dose (Dmin). ResultsFor PTV: Plan A vs. Plan B, the difference of D2 and CI was statistically significant (P < 0.05); Plan A vs. Plan C, the differences in D98, Dmean and HI were statistically significant (P < 0.05); Plan A vs. Plan D, differences in D2, Dmean and HI were statistically significant (P < 0.05). For OARs: Plan A vs. Plan B, and Plan A vs. Plan D, the differences in V5, V10, V20, V30, Dmean of the left lung and V10, V20, V30, Dmean of the heart were statistically significant (P < 0.05), the differences in Dmean of the thyroid and contralateral breast and the D2 and Dmax of spinal cord and spinal cord planning risk volume (PRV) were statistically significant (P < 0.05); Plan A vs. Plan C, only the difference in Dmax of spinal cord was statistically significant (P < 0.05). ConclusionCompared with DV condition, the dosimetric data with EUD-based optimization for OARs and PTV confer advantages in terms of the mean dose region of the left lung, heart, thyroid and contralateral (right) breast and the maximum dose of the spinal cord, and the improvement of the conformity and homogeneity of the target.

Do Dosiomic Features Extracted From Planned 3-Dimensional Dose Distribution Improve Biochemical Failure-Free Survival Prediction: an Analysis Based on a Large Multi-Institutional Data Set

The objective of this work was to investigate whether including additional dosiomic features can improve biochemical failure-free survival prediction compared with models with clinical features only or with clinical features as well as equivalent uniform dose and tumor control probability. This retrospective study included 1852 patients who received diagnoses of localized prostate cancer between 2010 and 2016 and were treated with curative external beam radiation therapy in Albert, Canada. A total of 1562 patients from 2 centers were used for developing 3 random survival forest models: Model A included only 5 clinical features; Model B included 5 clinical features, equivalent uniform dose, and tumor control probability; and Model C considered 5 clinical features and 2074 dosiomic features derived from the planned dose distribution of the clinical target volume and planning target volume with further feature selection to determine prognostic features. No feature selection was performed for models A and B. Two hundred ninety patients from another 2 centers were used for independent validation. Individual model-based risk stratification was examined, and the log-rank tests were performed to test statistically significant differences between the risk groups. The 3 models' performances were evaluated using Harrell's concordance index (C-index) and compared using one-way repeated-measures analysis of variance with post hoc paired t test. Model C selected 6 dosiomic features and 4 clinical features to be prognostic. There were statistically significant differences between the 4 risk groups for both training and validation data sets. The C-index for the out-of-bag samples of the training data set was 0.650, 0.648, and 0.669 for models A, B, and C, respectively. The C-index for the validation data set for models A, B, and C was 0.653, 0.648, and 0.662, respectively. Although gains were modest, Model C was statistically significantly better than models A and B. Dosiomics contain information beyond common dose-volume histogram metrics from planned dose distributions. Incorporation of prognostic dosiomic features in biochemical failure-free survival outcome models can lead to statistically significant although modest improvement in performance.

Comparison of Online-Onboard Adaptive Intensity-Modulated Radiation Therapy or Volumetric-Modulated Arc Radiotherapy With Image-Guided Radiotherapy for Patients With Gynecologic Tumors in Dependence on Fractionation and the Planning Target Volume Margin

Patients with newly diagnosed locally advanced cervical carcinomas or recurrences after surgery undergoing radiochemotherapy whose tumor is unsuited for a brachytherapy boost need high-dose percutaneous radiotherapy with small margins to compensate for clinical target volume deformations and set-up errors. Cone-beam computed tomography-based online adaptive radiotherapy (ART) has the potential to reduce planning target volume (PTV) margins below 5 mm for these tumors. To compare online ART technologies with image-guided radiotherapy (IGRT) for gynecologic tumors. This comparative effectiveness study comprised all 7 consecutive patients with gynecologic tumors who were treated with ART with artificial intelligence segmentation from January to May 2022 at the West German Cancer Center. All adapted treatment plans were reviewed for the new scenario of organs at risk and target volume. Dose distributions of adapted and scheduled plans optimized on the initial planning computed tomography scan were compared. Online ART for gynecologic tumors. Target dose coverage with ART compared with IGRT for PTV margins of 5 mm or less in terms of the generalized equivalent uniform dose (gEUD) without increasing the gEUD for the organs at risk (bladder and rectum). The first 10 treatment series among 7 patients (mean [SD] age, 65.7 [16.5] years) with gynecologic tumors from a prospective observational trial performed with ART were compared with IGRT. For a clinical PTV margin of 5 mm, IGRT was associated with a median gEUD decrease in the interfractional clinical target volume of -1.5% (90% CI, -31.8% to 2.9%) for all fractions in comparison with the planned dose distribution. Online ART was associated with a decrease of -0.02% (90% CI, -3.2% to 1.5%), which was less than the decrease with IGRT (P < .001). This was not associated with an increase in the gEUD for the bladder or rectum. For a PTV margin of 0 mm, the median gEUD deviation with IGRT was -13.1% (90% CI, -47.9% to 1.6%) compared with 0.1% (90% CI, -2.3% to 6.6%) with ART (P < .001). The benefit associated with ART was larger for a PTV margin of 0 mm than of 5 mm (P = .004) due to spreading of the cold spot at the clinical target volume margin from fraction to fraction with a median SD of 2.4 cm (90% CI, 1.9-3.4 cm) for all patients. This study suggests that ART is associated with an improvement in the percentage deviation of gEUD for the interfractional clinical target volume compared with IGRT. As the gain of ART depends on fractionation and PTV margin, a strategy is proposed here to switch from IGRT to ART, if the delivered gEUD distribution becomes unfavorable in comparison with the expected distribution during the course of treatment.

Validation of prediction models for radiation-induced late rectal bleeding: Evidence from a large pooled population of prostate cancer patients

PurposeTo validate published models for the risk estimate of grade ≥ 1 (G1+), grade ≥ 2 (G2+) and grade = 3 (G3) late rectal bleeding (LRB) after radical radiotherapy for prostate cancer in a large pooled population from three prospective trials. Materials and methodsThe external validation population included patients from Europe, and Oceanian centres enrolled between 2003 and 2014. Patients received 3DCRT or IMRT at doses between 66–80 Gy. IMRT was administered with conventional or hypofractionated schemes (2.35–2.65 Gy/fr). LRB was prospectively scored using patient-reported questionnaires (LENT/SOMA scale) with a 3-year follow-up.All Normal Tissue Complication Probability (NTCP) models published until 2021 based on the Equivalent Uniform Dose (EUD) from the rectal Dose Volume Histogram (DVH) were considered for validation.Model performance in validation was evaluated through calibration and discrimination. ResultsSixteen NTCP models were tested on data from 1633 patients. G1+ LRB was scored in 465 patients (28.5%), G2+ in 255 patients (15.6%) and G3 in 112 patients (6.8%). The best performances for G2+ and G3 LRB highlighted the importance of the medium–high doses to the rectum (volume parameters n = 0.24 and n = 0.18, respectively). Good performance was seen for models of severe LRB. Moreover, a multivariate model with two clinical factors found the best calibration slope. ConclusionFive published NTCP models developed on non-contemporary cohorts were able to predict a relative increase in the toxicity response in a more recent validation population. Compared to QUANTEC findings, dosimetric results pointed toward mid-high doses of rectal DVH. The external validation cohort confirmed abdominal surgery and cardiovascular diseases as risk factors.

Abstract P1-10-14: Higher radiation dose to the heart in left sided breast cancer; anatomy versus dosimetry

Abstract Abstract: Background: There is assumption that omitting the internal mammary chain radiotherapy (IMC RT) in patients with breast cancer (BC) will significantly reduce the cardiac exposure for all patients regardless the cardiac anatomy of each patient. Aim: to evaluate the impact of IMC RT on the dose received by the heart and its chambers in patients with favorable versus unfavorable cardiac anatomy. Patients and methods: CT scans were obtained of 20 patients with left-sided BC, 10 with favorable and 10 with unfavorable cardiac anatomy. Three plans were generated for each patient, one treating only the breast with tangents, and one treating the breast and IMC with wide photon tangents, and one treating the breast and IMC to 50Gy with photon tangent fields and a matching medial electron field. Dose volume histograms (DVHs) were generated for the heart and chambers. The equivalent uniform doses (EUDs) were calculated for each DVH, and the mean EUDs for plans with unfavorable and favorable cardiac anatomy were compared using a two-sided two-sample T-test Results: The mean dose received by the heart from plans with tangents plus IMC fields in patients with favorable cardiac anatomy was significantly lower than that received from plans with tangents only or wide tangents in patients with unfavorable anatomy (P &amp;lt; .0001). The average EUD for plans with tangents and IMC fields in the favorable group was 16 Gy (SD = 4.5) as compared to 36 Gy (SD = 3.6) and 37 Gy (SD = 5.1) for plans with tangents only and wide tangents in the unfavorable group, respectively ((P &amp;lt; .0001). The doses to the right ventricle were not significantly different. Conclusions: Ttreatment plans should be individualized based on the cardiac anatomy of each patient. Citation Format: Mohamed Alm El-Din, Andrzej Niemierko, Alphonse Taghian. Higher radiation dose to the heart in left sided breast cancer; anatomy versus dosimetry [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-10-14.

Individualized estimates of intensity-modulated radiotherapy plans after breast conservation surgery for left-sided breast cancer

ObjectivesThe purpose of this study was to explore the influence of individual patient factors, such as volume of the planning target volume (PTV) (VPTV), cardiothoracic ratio (CTR), central lung distance (CLD), and maximal heart distance (MHD), on the design of treatment plans in terms of target dose coverage, integral dose, and dose to organs at risk (OAR) in early breast cancer.MethodsNinety-six patients were selected for this study. Radiation doses of 50 Gy and a simultaneous dose of 60 Gy in 25 fractions were administered to the whole breast and tumor bed, respectively. The intensity modulation plan (IMRT) of each patient uses both physical parameters and an equivalent uniform dose (EUD) to optimize the target function. Univariate and multivariate linear regression were used to analyze the relationship between predictive impact factors and OAR percent dose volume, conformity index (CI), and homogeneity index (HI).ResultsThe average CI and HI values of the left breast cancer plan were 0.595 ± 0.071 (0.3–0.72) and 1.095 ± 0.023 (1.06–1.18), respectively. The CTR (B = 0.21, P = 0.045), VPTV (B = 0.63, P = 0.000), volume of the lung (Vlung) (B = − 0.29, P = 0.005), and MHD (B = 0.22, P = 0.041) were identified as factors influencing the CI index of the left breast cancer intensity modulation plan. VPTV (B = 1.087, P = 0.022) was identified as the influencing factor of the HI index of the left breast cancer intensity modulation plan. volume of the heart (Vheart) (B = − 0.43, P = 0.001) and CLD (B = 0.28, P = 0.008) were influencing factors of the volume of lung (Vlung20) of the lung. The prediction formulas for left-sided breast cancer are noted as follows: CI = 0.459 + 0.19CTR-0.16CLD, Vlung10 = 35.5–0.02Vheart; and Vlung20 = 21.48 + 2.8CLD-0.018Vheart.ConclusionsCTR, CLD, and MHD can predict the rationality of the parameters of the left breast cancer IMRT. The calculation formula generated based on this information can help the physicist choose the optimal radiation field setting method and improve the quality of the treatment plan.

Effective optimization strategy for large optimization volume object, remaining volume at risk (RVR): α-value selection and usage from generalized equivalent uniform dose (gEUD) curve deviation perspective

Objective. A large optimization volume for intensity-modulated radiation therapy (IMRT), such as the remaining volume at risk (RVR), is traditionally unsuitable for dose-volume constraint control and requires planner-specific empirical considerations owing to the patient-specific shape. To enable less empirical optimization, the generalized equivalent uniform dose (gEUD) optimization is effective; however, the utilization of parameter a-values remains elusive. Our study clarifies the a-value characteristics for optimization and to enable effective a-value use. Approach. The gEUD can be obtained as a function of its a-value, which is the weighted generalized mean; its curve has a continuous, differentiable, and sigmoid shape, deforming in its optimization state with retained curve characteristics. Using differential geometry, the gEUD curve changes in optimization is considered a geodesic deviation intervened by the forces between deforming and retaining the curve. The curvature and gradient of the curve are radically related to optimization. The vertex point (a = a k ) was set and the a-value roles were classified into the following three parts of the curve with respect to the a-value: (i) high gradient and middle curvature, (ii) middle gradient and high curvature, and (iii) low gradient and low curvature. Then, a strategy for multiple a-values was then identified using RVR optimization. Main results. Eleven head and neck patients who underwent static seven-field IMRT were used to verify the a-value characteristics and curvature effect for optimization. The lower a-value (i) (a = 1–3) optimization was effective for the whole dose-volume range; in contrast, the effect of higher a-value (iii) (a = 12–20) optimization addressed strongly the high-dose range of the dose volume. The middle a-value (ii) (around a = a k ) showed intermediate but effective high-to-low dose reduction. These a-value characteristics were observed as superimpositions in the optimization. Thus, multiple gEUD-based optimization was significantly superior to the exponential constraints normally applied to the RVR that surrounds the PTV, normal tissue objective (NTO), resulting in up to 25.9% and 8.1% improvement in dose-volume indices D2% and V10Gy, respectively. Significance. This study revealed an appropriate a-value for gEUD optimization, leading to favorable dose-volume optimization for the RVR region using fixed multiple a-value conditions, despite the very large and patient-specific shape of the region.

IMPT of head and neck cancer: unsupervised machine learning treatment planning strategy for reducing radiation dermatitis

Radiation dermatitis is a major concern in intensity modulated proton therapy (IMPT) for head and neck cancer (HNC) despite its demonstrated superiority over contemporary photon radiotherapy. In this study, dose surface histogram data extracted from forty-four patients of HNC treated with IMPT was used to predict the normal tissue complication probability (NTCP) of skin. Grades of NTCP-skin were clustered using the K-means clustering unsupervised machine learning (ML) algorithm. A new skin-sparing IMPT (IMPT-SS) planning strategy was developed with three major changes and prospectively implemented in twenty HNC patients. Across skin surfaces exposed from 10 (S10) to 70 (S70) GyRBE, the skin's NTCP demonstrated the strongest associations with S50 and S40 GyRBE (0.95 and 0.94). The increase in the NTCP of skin per unit GyRBE is 0.568 for skin exposed to 50 GyRBE as compared to 0.418 for 40 GyRBE. Three distinct clusters were formed, with 41% of patients in G1, 32% in G2, and 27% in G3. The average (± SD) generalised equivalent uniform dose for G1, G2, and G3 clusters was 26.54 ± 6.75, 38.73 ± 1.80, and 45.67 ± 2.20 GyRBE. The corresponding NTCP (%) were 4.97 ± 5.12, 48.12 ± 12.72 and 87.28 ± 7.73 respectively. In comparison to IMPT, new IMPT-SS plans significantly (P < 0.01) reduced SX GyRBE, gEUD, and associated NTCP-skin while maintaining identical dose volume indices for target and other organs at risk. The mean NTCP-skin value for IMPT-SS was 34% lower than that of IMPT. The dose to skin in patients treated prospectively for HNC was reduced by including gEUD for an acceptable radiation dermatitis determined from the local patient population using an unsupervised MLA in the spot map optimization of a new IMPT planning technique. However, the clinical finding of acute skin toxicity must also be related to the observed reduction in skin dose.

Machine-learning-based prediction of the effectiveness of the delivered dose by exhale-gated radiotherapy for locally advanced lung cancer: The additional value of geometric over dosimetric parameters alone.

This study aimed to assess interfraction stability of the delivered dose distribution by exhale-gated volumetric modulated arc therapy (VMAT) or intensity-modulated arc therapy (IMAT) for lung cancer and to determine dominant prognostic dosimetric and geometric factors. Clinical target volume (CTVPlan) from the planning CT was deformed to the exhale-gated daily CBCT scans to determine CTVi, treated by the respective dose fraction. The equivalent uniform dose of the CTVi was determined by the power law (gEUDi) and cell survival model (EUDiSF) as effectiveness measure for the delivered dose distribution. The following prognostic factors were analyzed: (I) minimum dose within the CTVi (Dmin_i), (II) Hausdorff distance (HDDi) between CTVi and CTVPlan, (III) doses and deformations at the point in CTVPlan at which the global minimum dose over all fractions per patient occurs (PDmin_global_i), and (IV) deformations at the point over all CTVi margins per patient with the largest Hausdorff distance (HDPworst). Prognostic value and generalizability of the prognostic factors were examined using cross-validated random forest or multilayer perceptron neural network (MLP) classifiers. Dose accumulation was performed using back deformation of the dose distribution from CTVi to CTVPlan. Altogether, 218 dose fractions (10 patients) were evaluated. There was a significant interpatient heterogeneity between the distributions of the normalized gEUDi values (p<0.0001, Kruskal-Wallis tests). Accumulated gEUD over all fractions per patient was 1.004-1.023 times of the prescribed dose. Accumulation led to tolerance of ~20% of fractions with gEUDi <93% of the prescribed dose. Normalized Dmin >60% was associated with predicted gEUD values above 95%. Dmin had the highest importance for predicting the gEUD over all analyzed prognostic parameters by out-of-bag loss reduction using the random forest procedure. Cross-validated random forest classifier based on Dmin as the sole input had the largest Pearson correlation coefficient (R=0.897) in comparison to classifiers using additional input variables. The neural network performed better than the random forest classifier, and the gEUD values predicted by the MLP classifier with Dmin as the sole input were correlated with the gEUD values characterized by R=0.933 (95% CI, 0.913-0.948). The performance of the full MLP model with all geometric input parameters was slightly better (R=0.952) than that based on Dmin (p=0.0034, Z-test). Accumulated dose distributions over the treatment series were robust against interfraction CTV deformations using exhale gating and online image guidance. Dmin was the most important parameter for gEUD prediction for a single fraction. All other parameters did not lead to a markedly improved generalizable prediction. Dosimetric information, especially location and value of Dmin within the CTV i , are vital information for image-guided radiation treatment.

Dosimetric quantities and cell survival for spatially fractionated radiation therapy

Purpose: Spatially Fractionated Radiation Therapy (SFRT) is characterized by large differences in peak and valley doses. Preclinical and clinical studies suggest that differences in biological mechanisms lead to differential normal tissue and tumor response compared to uniform irradiation. We hypothesize that to evaluate clinical effectiveness and understand fundamental biological mechanisms, radiobiological rather than physical dose quantities should be utilized for comparisons. The aim of this work is to determine whether Equivalent Uniform Dose (EUD) is a superior predictor of cell survival than absorbed dose.Methods: Absorbed dose parameters were compared to the Equivalent Uniform Dose to assess their predictive value for the relative effectiveness of uniform and SFRT with X-rays. A Bayesian bootstrap technique was utilized to model uncertainties in the biological fit parameters for a human fibroblast (MRC5) and two human tumor cell lines (LN18 and A549). Dose uncertainties were evaluated through measurements and error modeling of SFRT profiles. A dimensionless Relative Effectiveness Factor (REF) is proposed to quantify differences between uniform and SFRT irradiation.Results: For all cell lines, cell survival after SFRT matched uniform irradiation within the estimated uncertainties at equal values of the EUD. Average and peak dose showed poor correlation with in vitro cell survival. The proposed REF factor is dose dependent and suggests enhanced cell killing for both tumor cell lines (1.14 ± .08 for LN18, 1.32 ± .13 for A549 at 8 Gy EUD) for SFRT. Normal human fibroblasts showed reduced cell killing relative to uniform irradiation (.58 ± .06 for MRC5). Synthetically generated SFRT dose profiles revealed that EUD uncertainties are dominated by valley dose uncertainties, especially at high doses.Discussion: EUD is more predictive of cell survival than average or valley dose. Valley dose is close to equal to the EUD for values &gt;10 Gy and has the advantage of being independent of uncertainties in biological parameters. The REF is a novel and useful metric to compare quantitative differences in SFRT and uniform irradiation.Conclusion: EUD is recommended for comparisons of SFRT and uniform irradiation. The results suggest an increase in survival of normal-human fibroblast cells and reduced survival for both tumor cell lines after SFRT relative to uniform irradiation.

Comparison of intensity-modulated radiation therapy (IMRT), 3D conformal proton therapy and intensity-modulated proton therapy (IMPT) for the treatment of metastatic brain cancer.

The purpose of this study has been to compare photon intensity modulated radiation therapy (IMRT) against both conformal and intensity modulated proton therapy (IMPT) plans for metastatic brain cancer. Ten IMRT patients with brain cancer were chosen retrospectively, with prescription doses in the range of 20 to 40 Gy, delivered in 3 to 5 fractions using Varian TrueBeam STx machine. Three proton plans with proton double scattering, single collimation static-IMPT, and energy layer by layer collimation dynamic-IMPT were then generated for the same patients using the Mevion S250 system for conformal plans and the S250i system for IMPT plans. Each plan had respective treatment planning systems that include Brainlab iPlan for IMRT, Varian Eclipse for proton double scattering, and RaySearch Raystation for IMPT. Dosimetric and radiobiologic comparisons were made through dose-volume histogram (DVH) analysis of the target and the organs at risk (OAR); and with parameters of equivalent uniform dose (EUD), tumor control probability (TCP), and normal tissue complication probability (NTCP), respectively. A set of variables α/β ratio, survival fraction, and clonogenic cell density were selected and varied to observe their effect on the abovementioned parameters. Doses were observed to be more homogeneous for patients with brain malignancies with photon IMRT treatments, while dose conformity is improved with proton PBS treatments. Normal tissue is, on average, spared more through both proton treatment options. The minimum doses, closely approximated by dose to 98% of the target volume, are similar across treatment modalities with slight variations.

Comparison of intensity-modulated proton therapy (IMPT) versus intensity-modulated radiation therapy (IMRT) for the treatment of head and neck cancer based on radiobiological modelling

Abstract Aim: The aim of our study is to retrospectively report the radiobiological aspects for intensity-modulated proton therapy (IMPT) against intensity-modulated radiation therapy (IMRT) for patients with head and neck cancer treated at our institution. A secondary goal is to reinforce current model-based approaches to head and neck cancer patient selection for IMPT. Materials and Methods: Eighteen patients were evaluated with prescription doses ranging from 50 to 70 Gy delivered in 2 Gy per fraction. The dose volume histograms (DVH) were used to calculate equivalent uniform dose (EUD), tumour control probability (TCP) and normal tissue complication probability (NTCP) for biophysical comparison using mechanistic mathematical dose response models. Absolute values of TCP and NTCP were then compared between IMPT and IMRT. Results: The dose models demonstrate a minimal radiobiological advantage for IMPT compared to IMRT in treating head and neck cancers. Absolute values of TCP were slightly higher, while absolute values of NTCP were slightly lower for IMPT versus IMRT. Conclusions: Further studies are needed to determine if the radiobiological advantage indeed translates to a therapeutic advantage for patients.

Estimating the Dose-Response Relationship for Ocular Pain after Radiotherapy of Head and Neck Cancers and Skull Base Tumors based on the LKB Radiobiological Model.

Radiotherapy is considered a compromise between the amount of killed tumor cells and the damage caused to the healthy tissue. Regarding this, radiobiological modeling is performed to individualize and optimize treatment strategies. This study aimed to determine the normal tissue complication probability (NTCP) of acute ocular pain following radiotherapy. In this prospective observational study, the clinical data were collected from 45 patients with head and neck cancers and skull-base tumors, and dosimetric data were recorded after contouring the eye globe. Acute ocular pain was prospectively assessed with a three-month follow-up. The Lyman-Kutcher-Berman (LKB) parameters were estimated using the Area Under Curve (AUC) of Receiver Operating Characteristic (ROC) maximization and Maximum Likelihood (MLH) methods, and the NTCP of acute ocular pain was then determined using generalized LKB radiobiological model. The model performance was evaluated with AUC, Brier score, and Hosmer-Lemeshow tests. Six out of 45 (13.33%) patients developed acute ocular pain (grade 1 or more). LKB model showed a weak dose-volume effect (n=0.09), tolerance dose for a 50% complication (TD50) of 27.54 Gy, and slope parameter (m) of 0.38. The LKB model showed high prediction performance. The LKB model predicted that NTCP would be less than 25% if the generalized equivalent uniform dose (gEUD) was kept below 20 Gy. The LKB model showed a high performance in determining the NTCP of ocular pain so that the probability of ocular pain will be less than 25% if the eye globe mean dose is kept below 12 Gy.

Potential advantages of gEUD optimisation as compared with conventional physical optimisation for stereotactic treatment planning

Abstract Introduction: A small number of studies have confirmed the advantage of generalised equivalent uniform dose (gEUD) optimisation for some standard clinical scenarios; however, its performance with complicated stereotactic treatments is yet to be explored. Therefore, this study compared two planning optimisation methods, gEUD and Physical dose, in stereotactic treatments for several complex anatomical locations. Methods: Thirty patients were selected, ten each for sites of brain, lung and spine. Two stereotactic plans were generated for each case using the gEUD objective and Physical objective cost functions. Within each of the three sites, dosimetric indices for conformity, gradient and homogeneity, along with parameters of monitor units and dose–volume histograms (DVHs), were compared for statistical significance. Additionally, patient-specific quality assurance was conducted using portal dosimetry, and the gamma passing rate between the two plans was evaluated. Results: Optimisation was better with a gEUD objective as compared with Physical objective, notably sparing critical organs. Overall, the differences in mean values for six critical organs at risk favoured gEUD-based over Physical-based plans (all six 2-tailed p-values were &lt; 0·0002). Furthermore, all differences in mean values for DVH parameters favoured gEUD-based plans: GTVmean, GTVmax, PTVD100V, homogeneity index, gradient index and monitor unit (treatment time) (each 2-tailed p &lt; 0·05). Conclusions: gEUD optimisation in stereotactic treatment plans has a clear and general statistical advantage over Physical dose optimisation.

Contralateral esophageal sparing technique in definitive radiotherapy for non-small cell lung cancer: dosimetric parameters and normal tissue complication probability modeling.

The purpose of this study was to assess the benefit of the contralateral esophageal sparing technique (CEST) in definitive radiotherapy of non-small cell lung cancer (NSCLC). We retrospectively reviewed radiation plans for 13 patients who underwent definitive chemoradiation for locally advanced NSCLC. Alternative plans were prepared with the use of CEST, with an additional margin of 5 mm from planning treatment volume (PTV). Normal tissue complication probability (NTCP) analyses for the esophagus and tumor control probability (TCP) for the PTV were performed for original and CEST plans using the equivalent uniform dose (EUD)-based mathematical model. In all cases, the CEST plan allowed for the reduction of esophageal dose, with a mean of 3.8 Gy (range, 0.7 to 8.7 Gy). The mean reductions of V40 and V60 to the esophagus were 6.4 Gy (range, 2.1 to 17.2 Gy) and 1.9 Gy (range, 3.4 to 10.0 Gy), respectively. There was no substantial decrease in the maximal dose to the esophagus. Reduction of NTCP was achieved for all patients (range, 5-73%), and TCP was not affected (-1.8 to +6.7%). The application of CEST in definitive radiotherapy of locally advanced NSCLC allows for reducing selected dosimetric parameters to the esophagus without compromising TCP.

Escalation of radiotherapy dose in large locally advanced drug-resistant gastrointestinal stromal tumors by multi-shell simultaneous integrated boost intensity-modulated technique: a feasibility study

BackgroundResistance to conventional dose schemes and radiotoxicity of healthy tissue is a clinical challenge in the radiation therapy of large locally advanced drug-resistant gastrointestinal stromal tumor (LADR-GIST). This study aimed to assess the feasibility of using multi-shell Simultaneous Integrated Boost Intensity-Modulated modality (SIB-IMRT) strategy to provide a safe and effective escalation dose regimen for LADR-GIST.Methods7 patients with LADR-GIST were selected in this study. The modified SIB-IMRT plans for all patients were generated by delivering different escalation-dose gradients to four ring shaped regions (shells) within the gross tumor volume (GTV). The doses of the central volume of the tumor (GTVcenter) were escalated up to 70–92.5 Gy (25 fractions), while the doses of planning target volume (PTV) and shell-1 were kept at 50.0 Gy. Based on different escalation-dose gradients, the modified SIB-IMRT plans were divided into four groups (SIB-IMRT groups). For comparison purposes, plans obtained by conventional IMRT technique (Con-IMRT) with 50 Gy (25 fractions) were also generated for all patients (Con-IMRT group). All plans were normalized to cover 95% of the PTV with the prescribed dose of 50.0 Gy. The equivalent uniform dose (EUD), relative equivalent uniform dose (rEUD), dose volume histogram (DVH), dose profile, conformity index (CI) and monitor unit (MU) were evaluated in five groups. The Friedman Test was performed to determine whether there were significant differences (P < 0.05).ResultsCompared with the Con-IMRT group, the EUD of GTV (EUDGTV) and rEUD of SIB-IMRT groups were improved when escalation-dose gradient was increased, and the improvement became significant when the escalation-dose gradient reached 20% of the prescription dose. The rEUD tended to be stable as the escalation-dose gradient went up to 25% of the prescription dose. There were no significant differences in CIs and DVH metrics for OARs between the Con-IMRT group and any SIB-IMRT group, but the significant differences were observed between the SIB10-IMRT group and the SIB25-IMRT group. For the SIB-IMRT groups, as the dose gradient became steeper in the dose profiles, the higher dose was mainly accumulated in the inner part of GTV accompanied with a higher MU.ConclusionsThe proposed multi-shell SIB-IMRT strategy is feasible in dosimetry for LADR-GIST and can acquire higher therapeutic gain without sacrifice of healthy tissues. It appears that the scheme of delivering 20% of the prescribed escalation-dose gradient to the target volume can provide satisfactory dose irradiation for LADR-GIST, and it should be evaluated in future clinical study.

Incidental nodal irradiation in patients with esophageal cancer undergoing (chemo)radiation with 3D-CRT or VMAT

The extent of elective nodal irradiation (ENI) in patients undergoing definitive chemoradiotherapy (dCRT) for esophageal squamous cell carcinoma (ESCC) remains unclear. The aim of this dosimetric study was to evaluate the extent of incidental nodal irradiation using modern radiation techniques. A planning target volume (PTV) was generated for 30 patients with node-negative esophageal carcinoma (13 cervical/upper third, 7 middle third, 10 lower third/abdomen). Thereby, no elective nodal irradiation (ENI) was intended. Both three-dimensional conformal radiotherapy (3D-CRT) and volumetric-modulated arc therapy (VMAT) treatment plans (50 Gy in 25 fractions) were calculated for all patients. Fifteen nodal stations were contoured according to the definitions of the AJCC and investigated in regard to dosimetric parameters. Compared to 3D-CRT, VMAT was associated with lower dose distribution to the organs at risk (lower Dmean, V20 and V30 for the lungs and lower Dmean and V30 for the heart). For both techniques, the median Dmean surpassed 40 Gy in 12 of 15 (80%) nodal stations. However, VMAT resulted in significantly lower Dmeans and equivalent uniform doses (EUD) compared to 3D-CRT for eight nodal stations (1L, 2L, 2R, 4L, 7, 8L, 10L, 15), while differences did not reach significance for seven nodal station (1R, 4R, 8U, 8M, 10R, 16). For dCRT of ESCC, the use of VMAT was associated with significantly lower median (incidental) doses to eight of 15 regional lymph node areas compared to 3D-CRT. However, given the small absolute differences, these differences probably do not impair (regional) tumor control rates.

Automatic Radiobiological Comparison of Radiation Therapy Plans: An Application to Gastric Cancer.

(1) Aim: This study was conducted to radiobiologically compare radiotherapy plans for gastric cancer with a newly developed software tool. (2) Methods: Treatment planning was performed on two computational phantoms simulating adult male and female patients. Three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) plans for gastric cancer were generated with three-photon beam energies. The equivalent uniform dose (EUD), tumor control probability (TCP) of the target and normal tissue control probability (NTCP) of eight different critical organs were calculated. A new software was employed for these calculations using the EUD-based model and dose-volume-histogram data. (3) Results: The IMRT and VMAT plan led to TCPs of 51.3-51.5%, whereas 3D-CRT gave values up to 50.2%. The intensity-modulated techniques resulted in NTCPs of (5.3 × 10-6-3.3 × 10-1)%. The corresponding NTCPs from 3D-CRT were (3.4 × 10-7-7.4 × 10-1)%. The above biological indices were automatically calculated in less than 40 s with the software. (4) Conclusions: The direct and quick radiobiological evaluation of radiotherapy plans is feasible using the new software tool. The IMRT and VMAT reduced the probability of the appearance of late effects in most of the surrounding critical organs and slightly increased the TCP compared to 3D-CRT.

Machine learning-based normal tissue complication probability model for predicting albumin-bilirubin (ALBI) grade increase in hepatocellular carcinoma patients

Purpose:The aim of this study was to develop a normal tissue complication probability model using a machine learning approach (ML-based NTCP) to predict the risk of radiation-induced liver disease in hepatocellular carcinoma (HCC) patients.Materials and methods:The study population included 201 HCC patients treated with radiotherapy. The patients’ medical records were retrospectively reviewed to obtain the clinical and radiotherapy data. Toxicity was defined by albumin-bilirubin (ALBI) grade increase. The normal liver dose-volume histogram was reduced to mean liver dose (MLD) based on the fraction size-adjusted equivalent uniform dose (2 Gy/fraction and α/β = 2). Three types of ML-based classification models were used, a penalized logistic regression (PLR), random forest (RF), and gradient-boosted tree (GBT) model. Model performance was compared using the area under the receiver operating characteristic curve (AUROC). Internal validation was performed by 5-fold cross validation and external validation was done in 44 new patients.Results:Liver toxicity occurred in 87 patients (43.1%). The best individual model was the GBT model using baseline liver function, liver volume, and MLD as inputs and the best overall model was an ensemble of the PLR and GBT models. An AUROC of 0.82 with a standard deviation of 0.06 was achieved for the internal validation. An AUROC of 0.78 with a standard deviation of 0.03 was achieved for the external validation. The behaviors of the best GBT model were also in good agreement with the domain knowledge on NTCP.Conclusion:We propose the methodology to develop an ML-based NTCP model to estimate the risk of ALBI grade increase.

Increased relative biological effectiveness and periventricular radiosensitivity in proton therapy of glioma patients

PurposeCurrently, there is an intense debate on variations in intra-cerebral radiosensitivity and relative biological effectiveness (RBE) in proton therapy of primary brain tumours. Here, both effects were retrospectively investigated using late radiation-induced brain injuries (RIBI) observed in follow-up after proton therapy of patients with diagnosed glioma. MethodsIn total, 42 WHO grade 2–3 glioma patients out of a consecutive patient cohort having received (adjuvant) proton radio(chemo)therapy between 2014 and 2017 were eligible for analysis. RIBI lesions (symptomatic or clinically asymptomatic) were diagnosed and delineated on contrast-enhanced T1-weighted magnetic resonance imaging scans obtained in the first two years of follow-up. Correlation of RIBI location and occurrence with dose (D), proton dose-averaged linear energy transfer (LET) and variable RBE dose parameters were tested in voxel- and in patient-wise logistic regression analyses. Additionally, anatomical and clinical parameters were considered. Model performance was estimated through cross-validated area-under-the-curve (AUC) values. ResultsIn total, 64 RIBI lesions were diagnosed in 21 patients. The median time between start of proton radio(chemo)therapy and RIBI appearance was 10.2 months. Median distances of the RIBI volume centres to the cerebral ventricles and to the clinical target volume border were 2.1 mm and 1.3 mm, respectively. In voxel-wise regression, the multivariable model with D, D × LET and periventricular region (PVR) revealed the highest AUC of 0.90 (95 % confidence interval: 0.89–0.91) while the corresponding model without D × LET revealed a value of 0.84 (0.83–0.86). In patient-level analysis, the equivalent uniform dose (EUD11, a = 11) in the PVR using a variable RBE was the most prominent predictor for RIBI with an AUC of 0.63 (0.32–0.90). ConclusionsIn this glioma cohort, an increased radiosensitivity within the PVR was observed as well as a spatial correlation of RIBI with an increased RBE. Both need to be considered when delivering radio(chemo)therapy using proton beams.