Potential Defects and Improvements of Equivalent Uniform Dose Prediction Model Based on the Analysis of Radiation-Induced Brain Injury

PurposeTo study the impact of dose distribution on volume-effect parameter and predictive ability of equivalent uniform dose (EUD) model, and to explore the improvements.Methods and MaterialsThe brains of 103 nasopharyngeal carcinoma patients treated with IMRT were segmented according to dose distribution (brain and left/right half-brain for similar distributions but different sizes; VD with different D for different distributions). Predictive ability of EUDVD (EUD of VD) for radiation-induced brain injury was assessed by receiver operating characteristics curve (ROC) and area under the curve (AUC). The optimal volume-effect parameter a of EUD was selected when AUC was maximal (mAUC). Correlations between mAUC, a and D were analyzed by Pearson correlation analysis. Both mAUC and a in brain and half-brain were compared by using paired samples t-tests. The optimal DV and VD points were selected for a simple comparison.ResultsThe mAUC of brain/half-brain EUD was 0.819/0.821 and the optimal a value was 21.5/22. When D increased, mAUC of EUDVD increased, while a decreased. The mAUC reached the maximum value when D was 50–55 Gy, and a was always 1 when D ≥55 Gy. The difference of mAUC/a between brain and half-brain was not significant. If a was in range of 1 to 22, AUC of brain/half-brain EUDV55 Gy (0.857–0.830/0.845–0.830) was always larger than that of brain/half-brain EUD (0.681–0.819/0.691–0.821). The AUCs of optimal dose/volume points were 0.801 (brain D2.5 cc), 0.823 (brain V70 Gy), 0.818 (half-brain D1 cc), and 0.827 (half-brain V69 Gy), respectively. Mean dose (equal to EUDVD with a = 1) of high-dose volume (V50 Gy–V60 Gy) was superior to traditional EUD and dose/volume points.ConclusionVolume-effect parameter of EUD is variable and related to dose distribution. EUD with large low-dose volume may not be better than simple dose/volume points. Critical-dose-volume EUD could improve the predictive ability and has an invariant volume-effect parameter. Mean dose may be the case in which critical-dose-volume EUD has the best predictive ability.

Mathematical Modeling of Uniform and Nonuniform Malignian and Normal Tissues Irradiation. Mathematical Analysis of the Tumour Grid Irradiation

Purpose: On base created mathematical model (MM) modified Veybull distribution, intended for NTCP calculation, depending on irradiated volume V and uniform irradiation dose D, to develop the MM, which allows to realize transition from nonuniform dose in tissue to the equivalent, uniform identical dose. To research the hypothesis, under what condition lumpy sharing dose in system tumors+normal tissues will be more efficient, than uniform dose. Material and Methods: Lumpy sharing dose are described as a differential histogram dose-volume (DDVH). The MM for calculation transition lumpy distribution of the absence of the beam complication probability (ACPr) in tissue is designed. It was used for MM conclusion, which allows to calculate transition values of the Adequate Dose (AD) of the uniform irradiation tissues, which use brings about ACPr in tissues. Results: On base of the suggestions and proved affirmation MMs are received, which allow for lumpy distribution of local NTCP values, presented as a DHDV, to calculate transition values ACPr, as well as select from it MM for reduction of the lumpy sharing dose. On base created MM question was explored, in what case tumors and normal tissue through a grid irradiation will be more effective than uniform irradiation. Conclusion: The transition from lumpy sharing doses in tissues to equivalent uniform dose present the significant interest for the RT planning efficiency. Their study is necessary, where the radiation of biosubjects is influenced.

Yttrium-90 TOF-PET-Based EUD Predicts Response Post Liver Radioembolizations Using Recommended Manufacturer FDG Reconstruction Parameters

PurposeExplaining why 90Y TOF-PET based equivalent uniform dose (EUD) using recommended manufacturer FDG reconstruction parameters has been shown to predict response.MethodsThe hot rods insert of a Jaszczak deluxe phantom was partially filled with a 2.65 GBq 90Y - 300ml DTPA water solution resulting in a 100 Gy mean absorbed dose in the 6 sectors. A two bed 20min/position acquisition was performed on a 550ps- and on a 320ps- TOF-PET/CT and reconstructed with recommended manufacturer FDG reconstruction parameters, without and with additional filtering. The whole procedure was repeated on both PET after adding 300ml of water (50Gy setup). The phantom was acquired again after decay by a factor of 10 (5Gy setup), but with 200min per bed position. For comparison, the phantom was also acquired with 18F activity corresponding to a clinical FDG whole body acquisition.ResultsThe 100Gy-setup provided a hot rod sectors image almost as good as the 18F phantom. However, despite acquisition time compensation, the 5Gy-setup provides much lower quality imaging. TOF-PET based sectors EUDs for the three large rod sectors agreed with the actual EUDs computed with a radiosensitivity of 0.021Gy-1 well in the range observed in external beam radiotherapy (EBRT), i.e. 0.01-0.04Gy-1. This agreement explains the reunification of the dose-response relationships of the glass and resin spheres in HCC using the TOF-PET based EUD. Additional filtering reduced the EUDs agreement quality.ConclusionsRecommended manufacturer FDG reconstruction parameters are suitable in TOF-PET post 90Y liver radioembolization for accurate tumour EUD computation. The present results rule out the use of low specific activity phantom studies to optimize reconstruction parameters.

Individualised dosimetry and safety of SIRT for intrahepatic cholangiocarcinoma

Background The aim of this study was to investigate the safety and efficacy of selective internal radiation therapy (SIRT) with 90Y resin microspheres for the treatment of Intrahepatic Cholangiocarcinoma (ICC). A total of 23 SIRT procedures from 18 ICC subjects were analysed to determine a lesion-based dose/response relationship with absorbed dose measures from 90Y PET and metabolic response as measured on [18F]FDG PET. Average absorbed dose (Davg), minimum dose to 70% of the volume (D70), volume receiving at least 50 Gy (V50), biological effective dose (BED) and equivalent uniform dose (EUD), were compared to changes in metabolic volume, maximum standardised uptake value (SUVmax) and total lesion glycolysis (TLG). Dose to normal liver was assessed with changes in liver uptake rate as measured with [99mTc]mebrofenin scintigraphy for a cohort of 20 subjects with primary liver malignancy (12 ICC, 8 hepatocellular carcinoma (HCC)). Results Thirty-four lesions were included in the analysis. A relationship was found between metabolic response and both Davg and EUD similar to that seen previously in metastatic colorectal cancer (mCRC), albeit trending towards a lower response plateau. Both dose and SUV coefficient of variation within the lesion (CoVdose and CoVSUV), baseline TLG and EUD were found to be mildly significant predictors of response. No strong correlation was seen between normal liver dose and change in [99mTc]mebrofenin liver uptake rate; low baseline uptake rate was not indicative of declining function following SIRT, and no subjects dropped into the ‘poor liver function’ category. Conclusions ICC lesions follow a similar dose–response trend as mCRC, however, despite high lesion doses a full metabolic response was rarely seen. The CoV of lesion dose may have a significant bearing on response, and EUD correlated more tightly with metabolic response compared to Davg. SIRT in primary liver malignancy appears safe in terms of not inducing a clinically significant decline in liver function, and poor baseline uptake rate is not predictive of a reduction in function post SIRT.

A Novel Fuzzy Logic Guided Method for Automatic gEUD-based Inverse Treatment Planning

Generalized equivalent uniform dose (gEUD) -based hybrid objective functions are widely used in intensity modulated radiotherapy (IMRT). To improve its efficiency, a novel fuzzy logic guided inverse planning method was developed for the automatic parameters optimization of the gEUD-based radiotherapy optimization. Simple inference rules were formulated according to the knowledge of the treatment planner. Then they automatically and iteratively guide the parameters modification according to the percentage of deviation between the current dose and the prescribed dose. weighting factors and prescribed dose were automatically adjusted by developed fuzzy inference system (FIS). The performance of the FIS was tested on ten prostate cancer cases. Experimental results indicate that proposed automatic method can yield comparable or better plans than manual method. The fuzzy logic guided automatic inverse planning method of parameters optimization can significantly improve the efficiency of the method of manually adjusting parameters, and contributes to the development of fully automated planning.

Comparison of a Hybrid IMRT/VMAT technique with non-coplanar VMAT and non-coplanar IMRT for unresectable olfactory neuroblastoma using the RayStation treatment planning system—EUD, NTCP and planning study

The purpose of this study was to compare hybrid intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (Hybrid IMRT/VMAT), with non-coplanar (nc) IMRT and nc-VMAT treatment plans for unresectable olfactory neuroblastoma (ONB). Hybrid IMRT/VMAT, nc-IMRT and nc-VMAT plans were optimized for 12 patients with modified Kadish C stage ONB. Dose prescription was 65 Gy in 26 fractions. Dose–volume histogram parameters, conformation number (CN), homogeneity index (HI), integral dose and monitor units (MUs) delivered per fraction were assessed. Equivalent uniform dose (EUD) and normal tissue complication probability (NTCP) based on the EUD model (NTCPLogit) and the Lyman–Kutcher–Burman model (NTCPLKB) were also evaluated. We found that the Hybrid IMRT/VMAT plan significantly improved the CN for clinical target volume (CTV) and planning treatment volume (PTV) compared with the nc-VMAT plan. In general, sparing of organs at risk (OARs) is similar with the three techniques, although the Hybrid IMRT/VMAT plan resulted in a significantly reduced Dmax to contralateral (C/L) optic nerve compared with the nc-IMRT plan. The Hybrid IMRT/VMAT plan significantly reduce EUD to the ipsilateral (I/L) and C/L optic nerve in comparison with the nc-IMRT plan and nc-VMAT plan, but the difference in NTCP between the three technique was <1%. We concluded that the Hybrid IMRT/VMAT technique can offer improvement in terms of target conformity and EUD for optic nerves, while achieving equal or better OAR sparing compared with nc-IMRT and nc-VMAT, and can be a viable radiation technique for treating unresectable ONB. However, the clinical benefit of these small differences in dosimetric data, EUD and NTCP of optic nerves may be minimal.

Normal tissue complication probabilities (NTCP) of urethral stricture following salvage SBRT or HDR for periurethral recurrences following prior definitive radiation therapy.

246 Background: SBRT and HDR brachytherapy have emerged as definitive salvage re-irradiation options for men with locally recurrent prostate cancer after prior radiation therapy (RT). Toxicity with re-irradiation remains a concern in this setting, particularly for salvage of periurethral recurrences. We calculated the normal tissue complication probability (NTCP) of urethral stricture following salvage re-irradiation (HDR and SBRT) after previous definitive RT (external beam or HDR) for periurethral recurrences. Methods: Two upfront definitive treatment plans were generated for 5 men with localized prostate cancer: External Beam RT (EBRT1) to a dose of 79.2 Gy in 1.8 Gy fractions and HDR monotherapy (HDR1), 13.5 Gy x 2 implants. Periurethral recurrences were virtually created on diagnostic MRI scans for each of the five men and defined as a recurrent dominant intraprostatic lesion (DIL). Three salvage RT plans were generated for each patient (constraints in Table): HDR salvage (10 Gy whole gland; 13.5 Gy to DIL; 2 implants), SBRTr with maximal rectal sparing (constraints designed for salvage following prior EBRT; 30 Gy in 5 fractions whole gland; 40 Gy in 5 fractions to DIL), and SBRTu with maximal urethral sparing (constraints designed for patients with prior HDR monotherapy; same Rx). DVH data was collected for each plan (previous RT and each salvage approach) and the equivalent uniform dose (EUD) was calculated. NTCP for the urethral stricture in the summed plans (prior definitive treatment + each salvage plan) was calculated by the Lyman-Kutcher-Burman model using the following parameters: (α/β = 5Gy; TD50= 116.7; m = 0.23; n = 0.3). Results: Prescription coverage of 90% of the DIL volume was achieved for each plan. The mean NTCP of urethral stricture for EBRT1 + HDR salvage was 55.2% (range, 52.2-59.1%) and for HDR1 + HDR salvage was 49.2% (42.9-57.5%). For EBRT1 + SBRTr and EBRT1 + SBRTu the NTCP for urethral stricture was 54.0% (50.4-61.0%) and 43.2% (39.4-48.4%), respectively. The NTCP of urethral stricture for HDR1 + SBRTr was 48.1% (41.0-57.2%) and for HDR1 + SBRTu was 37.6% (30.9-44.6%). Conclusions: In this modeling analysis of salvage RT for periurethral recurrences following previous RT (EBRT or HDR monotherapy), the NTCP for urethral stricture was numerically lowest for salvage SBRT using maximum urethral sparing dose constraints in comparison to salvage SBRT with maximum rectal sparing constraints or salvage HDR brachytherapy. This type of analysis lends insight into personalized treatment planning based on previous RT modality and previous dose to organs at risk. Expanded analysis is underway. [Table: see text]

Revisiting the formalism of equivalent uniform dose based on the linear-quadratic and universal survival curve models in high-dose stereotactic body radiotherapy

Purpose To examine the equivalent uniform dose (EUD) formalism using the universal survival curve (USC) applicable to high-dose stereotactic body radiotherapy (SBRT). Materials and methods For nine non-small-cell carcinoma cell (NSCLC) lines, the linear-quadratic (LQ) and USC models were used to calculate the EUD of a set of hypothetical two-compartment tumor dose–volume histogram (DVH) models. The dose was varied by ±5%, ±10%, and ±20% about the prescription dose (60 Gy/3 fractions) to the first compartment, with fraction volume varying from 1% and 5% to 30%. Clinical DVHs of 21 SBRT treatments of NSCLC prescribed to the 70–83% isodose lines were also considered. The EUD of non-standard SBRT dose fractionation (EUDSBRT) was further converted to standard fractionation of 2 Gy (EUDCFRT) using the LQ and USC models to facilitate comparisons between different SBRT dose fractionations. Tumor control probability (TCP) was then estimated from the LQ- and USC-EUDCFRT. Results For non-standard SBRT fractionation, the deviation of the USC- from the LQ-EUDSBRT is largely limited to 5% in the presence of dose variation up to ±20% to fractional tumor volume up to 30% in all NSCLC cell lines. Linear regression with zero constant yielded USC-EUDSBRT = 0.96 × LQ-EUDSBRT (r2 = 0.99) for the clinical DVHs. Converting EUDSBRT into standard 2‑Gy fractions by the LQ formalism produced significantly larger EUDCFRT than the USC formalism, particularly for low $$\alpha /\beta$$ α / β ratios and large fraction dose. Simplified two-compartment DVH models illustrated that both the LQ- and USC-EUDCFRT values were sensitive to cold spot below the prescription dose with little volume dependence. Their deviations were almost constant for up to 30% dose increase above the prescription. Linear regression with zero constant yielded USC-EUDCFRT = 1.56 × LQ-EUDCFRT (r2 = 0.99) for the clinical DVHs. The clinical LQ-EUDCFRT resulted in median TCP of almost 100% vs. 93.8% with USC-EUDCFRT. Conclusion A uniform formalism of EUD should be defined among the SBRT community in order to apply it as a single metric for dose reporting and dose–response modeling in high-dose-gradient SBRT because its value depends on the underlying cell survival model and the model parameters. Further investigations of the optimal formalism to derive the EUD through clinical correlations are warranted.

RADT-30. COPLANAR AND NON-COPLANAR VMAT ARC SETTING FOR GLIOBLASTOMA MULTIFORME – DOSIMETRIC AND RADIOBIOLOGICAL COMPARISONS

OBJECTIVES To evaluate three different arc arrangements in glioblastoma multiforme (GBM) treatment planning. METHODS Eighteen GBM patients were replanned by using one full arc (1FA), two full coplanar arcs (2FA), and three full non- coplanar arcs (3FA). Dose-volume histograms (DVHs) were used to calculate conformity (CI), homogeneity (HI) and gradient indices (GI), the dose received by 5% (D5%) and 95% (D95%) of the planning target volume (PTV) and maximum (Dmax) and minimum (Dmin) absorbed dose for organs at risk (OARs), including normal brain (brain excluding PTV). General equivalent uniform dose (gEUD) for both PTV and OARs and EUD based tumor control probability (TCP) and normal tissue control probability (NTCP) were calculated as radiobiological parameters. Monitor units (MUs) were also computed and compared. RESULTS All three plans resulted in similar conformity, while 2FA resulted in a better homogeneity than 1FA (0.06vs. 0.07, p=0.007). 2FA vs. 1FA dose analysis for PTV revealed a lower D5% (61.28 vs. 61.37 Gy, p=0.014), a higher D95% (58.7 vs. 58.47 Gy, p=0.008) and a higher TCP (37.73 vs.37.38%, p=0.008). The utilization of 3FA did not significantly change the outcome of PTV but managed to decrease GI in comparison to both 1FA and 2FA (4.11 vs. 5.19 and 5.49, p< 0.05). Regarding NB, 1FA scored a higher Dmax than 2FA (62.32 vs. 61.98 Gy, p=0.005), while 3FA scored a higher Dmin than 1FA and 2FA (2.52 vs. 1.08 and 1.10 Gy, p< 0.05). No difference in NB NTCP was noted between techniques. Furthermore, 3FA yielded more MUs when compared to coplanar patters (566.74 vs. 486.78, p= 0.015 for 1FA and 495.98, p=0.019 for 2FA). CONCLUSION Although all three approaches resulted in clinical admissible outcome, the utilization of complex non-coplanar arrangement resulted in a stepper dose fall off but did not improve PTV results and increased machine MUs.