M.L. Belli

Early changes of parotid density and volume predict modifications at the end of therapy and intensity of acute xerostomia

PurposeTo quantitatively assess the predictive power of early variations of parotid gland volume and density on final changes at the end of therapy and, possibly, on acute xerostomia during IMRT for head-neck cancer.Materials and methodsData of 92 parotids (46 patients) were available. Kinetics of the changes during treatment were described by the daily rate of density (rΔρ) and volume (rΔvol) variation based on weekly diagnostic kVCT images. Correlation between early and final changes was investigated as well as the correlation with prospective toxicity data (CTCAEv3.0) collected weekly during treatment for 24/46 patients.ResultsA higher rΔρ was observed during the first compared to last week of treatment (−0,50 vs −0,05HU, p-value = 0.0001). Based on early variations, a good estimation of the final changes may be obtained (Δρ: AUC = 0.82, p = 0.0001; Δvol: AUC = 0.77, p = 0.0001).Both early rΔρ and rΔvol predict a higher “mean” acute xerostomia score (≥ median value, 1.57; p-value = 0.01). Median early density rate changes for patients with mean xerostomia score ≥ / < 1.57 were −0.98 vs −0.22 HU/day respectively (p = 0.05).ConclusionsEarly density and volume variations accurately predict final changes of parotid glands. A higher longitudinally assessed score of acute xerostomia is well predicted by higher rΔρ and rΔvol in the first two weeks of treatment: best cut-off values were −0.50 HU/day and −380 mm3/day for rΔρ and rΔvol respectively. Further studies are necessary to definitively assess the potential of early density/volume changes in identifying more sensitive patients at higher risk of experiencing xerostomia.ZusammenfassungZielZiel der Studie ist die Untersuchung der prädiktiven Aussagekraft von frühen Veränderungen in Volumen und Dichte der Ohrspeicheldrüse in Bezug auf die finale Verformung zum Ende der Therapie sowie das Risiko von Xerostomie während der intesitätsmodulierten Strahlentherapie (IMRT) bei Kopf und Hals Tumoren.Materialien und MethodenDie Studie umfasst 46 Patienten (92 Speicheldrüsen). Für 24 Patienten wurden prospektiv gesammelte Toxizitätsdaten (CTCAEv3.0) während der Therapie ausgewertet. Die Reaktion auf die Behandlung wurde beobachtet anhand der tägliche Veränderung der Dichte (rΔρ) sowie des Volumens (rΔvol) der Ohrspeicheldrüsen. Die Beziehung zwischen frühen und späten Veränderungen, sowie der Zusammenhang mit den wöchentlich dokumentieren Toxitätsdaten wurde für 24 der 46 Fälle untersucht.ErgebnisseAm Anfang der Therapie wurde ein höheres rΔρ beobachtet (−0,50 vs −0,05HU, p-Wert = 0,0001) als gegen Therapieende. Basierend auf frühen Veränderungen kann die finale Verformung der Speicheldrüsen gut abgeschätzt werden (Δρ: AUC = 0.82, p = 0.0001; Δvol: AUC = 0.77, p = 0.0001). Sowohl der frühe rΔρ- als auch der rΔvol-Wert sagen eine höheres „mittlere“ Auftreten von Xerostomie für den Durchschnitt der untersuchten Population vorher (1.57; p-Wert = 0.01, log. Regression). Die mittlere frühe Veränderung der Dichte für Patienten mit mittlerem Xerostomie-Wert ≥ / < 1.57 waren −0.98 bzw. −0.22 HU (p = 0.05, Mann–Whitney-Test).SchlussfolgerungFrühe Dichte- und Volumenvariationen können präzise letztendliche Änderungen der Ohrspeicheldrüse vorhersagen. Eine akuten Xerostomie kann gut durch größere rΔρ- und rΔvol-Werte in den ersten zwei Behandlungswochen vorhergesagt werden: die beste Cut-off-Werte für rΔρ und rΔvol waren jeweils −0.50 HU/ Tag und −380 mm3/day. Weitere Studien sind notwendig, um das ganze Potenzial der frühen Dichte/ Volumen Änderungen für die Identifizierung sensibler Patienten mit einemerhöhten Mundtrockenheitsrisiko zu beurteilen.

A Comparative Evaluation of 3 Different Free-Form Deformable Image Registration and Contour Propagation Methods for Head and Neck MRI: The Case of Parotid Changes During Radiotherapy:

Purpose: To validate and compare the deformable image registration and parotid contour propagation process for head and neck magnetic resonance imaging in patients treated with radiotherapy using 3 different approaches—the commercial MIM, the open-source Elastix software, and an optimized version of it. Materials and Methods: Twelve patients with head and neck cancer previously treated with radiotherapy were considered. Deformable image registration and parotid contour propagation were evaluated by considering the magnetic resonance images acquired before and after the end of the treatment. Deformable image registration, based on free-form deformation method, and contour propagation available on MIM were compared to Elastix. Two different contour propagation approaches were implemented for Elastix software, a conventional one (DIR_Trx) and an optimized homemade version, based on mesh deformation (DIR_Mesh). The accuracy of these 3 approaches was estimated by comparing propagated to manual contours in terms of average symmetric distance, maximum symmetric distance, Dice similarity coefficient, sensitivity, and inclusiveness. Results: A good agreement was generally found between the manual contours and the propagated ones, without differences among the 3 methods; in few critical cases with complex deformations, DIR_Mesh proved to be more accurate, having the lowest values of average symmetric distance and maximum symmetric distance and the highest value of Dice similarity coefficient, although nonsignificant. The average propagation errors with respect to the reference contours are lower than the voxel diagonal (2 mm), and Dice similarity coefficient is around 0.8 for all 3 methods. Conclusion: The 3 free-form deformation approaches were not significantly different in terms of deformable image registration accuracy and can be safely adopted for the registration and parotid contour propagation during radiotherapy on magnetic resonance imaging. More optimized approaches (as DIR_Mesh) could be preferable for critical deformations.

The Shape of Parotid DVH Predicts the Entity of Gland Deformation During IMRT for Head and Neck Cancers

The Jacobian of the deformation field of the registration between images taken during Radiotherapy is a measure of compression/expansion of the voxels within an organ. The Jacobian mean value was applied to investigate possible correlations between parotid deformation and anatomical, clinical and dosimetric parameters. Data of 84 patients were analyzed. Parotid deformation was evaluated through Jacobian maps of images taken at the start and at the end of the treatment. Several clinical, geometrical and dosimetric factors were considered. Correlation between Jacobian mean value and these parameters was assessed through Spearman’s test. Univariate and multivariate logistic analyses were performed by considering as the end point the first quartile value of the Jacobian mean value. Parotid dose volume histograms were stratified according to gland deformation, assessing the most predictive dose-volume combination. At multivariate analysis, age (p = 0.02), overlap between tumor volume and parotid gland (p = 0.0006) and the parotid volume receiving more than 10 Gy (p = 0.02) were found as the best independent predictors, by considering Jacobian mean value fist quartile, the parotid volume receiving more than 10 Gy and 40 Gy were found as the most predictive dosimetric parameters. Parotid glands were divided in three different sub-groups (bad-, medium- and good dose volume histogram). The risk to have Jacobian means value lower than first quartile was 39.6% versus 19.6% versus 11.3% in these three groups. By including in the multivariate analysis this “dose volume grouping” parameter, age and bad dose volume histogram were found as the most predictive parameters for large shrinkage. The pattern of parotid deformation may be well predicted by some pre-treatment variables; a bad dose volume histogram seems the most important predictor.

Early volume variation of positive lymph nodes assessed by in-room mega voltage CT images predicts risk of loco-regional relapses in head and neck cancer patients treated with intensity-modulated radiotherapy

ABSTRACT Background. We investigated the possibility to early identify non-responding patients based on FDG-PET positive lymph nodes (PNs) volume variation assessed with in-room images. Material and methods. Twenty-seven head and neck cancer patients with at least one pre-treatment PNs were retrospectively analyzed; they received 54 Gy, 66 Gy, 69 Gy in 30 fractions on precautionary lymph nodal (N), primary (T) and PET positive (BTV) planning target volumes (PTVs), respectively with Helical TomoTherapy (SIB approach). PNs volume changes during treatment were assessed based on megavoltage computed tomography (MVCT) used for image guidance as ratio between volumes at fractions 10/20/30 and at first fraction. Data on T, N and M relapses (rT, rN, rM) were collected for all patients. The difference of PNs volume changes, during treatment, between patients with versus without relapses was tested (Mann-Whitney test). The impact of shrinkage on the corresponding survival curves (Cox proportional-hazard regression), dividing between no/moderate versus large shrinkage (based on ROC curve best cut-off value) was also investigated. Results. Median follow-up was 27.4 m (3.7–108.9). The numbers for rT, rN, rM were 5, 4, 6, respectively. Differences in PNs shrinkage were found between patients with and without rT/rN at all considered timing [fr 20, rT: 0.56 vs. 1.07 (median), p = 0.06; rN: 0.57 vs. 1.25, p = 0.07]. Differences were lower for rM. Survival curves provide high hazard ratios (HR) between PNs changes and rT/rN at all considered timing [fr 20, rT: best cut-off = 0.58, HR 5.1 (95% CI 0.5–49.4), p = 0.12; rN: best cut-off = 0.98, HR 14.9 (1.6–142.9), p = 0.01]. Conclusion. A limited shrinkage of PNs during treatment is associated with poorer outcome in terms of T/N relapses. The early variation of PNs observed on in-room images may provide useful information about the individual response with potential application in guiding an early adaptation of the treatment.

Likelihood-fuzzy analysis of parotid gland shrinkage in radiotherapy patients.

In head-and-neck radiotherapy, an early detection of patients who will undergo parotid glands shrinkage during the treatment is of primary importance, since this condition has been found to be associated with acute toxicity. In this work, a recently proposed approach, here named Likelihood-Fuzzy Analysis, based on both statistical learning and Fuzzy Logic, is proposed to support the identification of early predictors of parotid shrinkage from Computed Tomography images acquired during radiotherapy. For this purpose, a set of textural image parameters was extracted and considered as candidate of parotid shrinkage prediction; for all these parameters and combinations of maximum three of them, a fuzzy rule base was extracted, gaining very good results in terms of accuracy, sensitivity and specificity. The performance of classification was also compared to a classical Fishers Linear Discriminant Analysis and found to provide better results. Moreover, the use of Fuzzy Logic allowed obtaining an interpretable description of the relations between textural features and the shrinkage process.

Quantifying the robustness of [ 18 F]FDG-PET/CT radiomic features with respect to tumor delineation in head and neck and pancreatic cancer patients

PURPOSE To investigate the robustness of PET radiomic features (RF) against tumour delineation uncertainty in two clinically relevant situations. METHODS Twenty-five head-and-neck (HN) and 25 pancreatic cancer patients previously treated with 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT)-based planning optimization were considered. Seven FDG-based contours were delineated for tumour (T) and positive lymph nodes (N, for HN patients only) following manual (2 observers), semi-automatic (based on SUV maximum gradient: PET_Edge) and automatic (40%, 50%, 60%, 70% SUV_max thresholds) methods. Seventy-three RF (14 of first order and 59 of higher order) were extracted using the CGITA software (v.1.4). The impact of delineation on volume agreement and RF was assessed by DICE and Intra-class Correlation Coefficients (ICC). RESULTS A large disagreement between manual and SUV_max method was found for thresholds  ≥50%. Inter-observer variability showed median DICE values between 0.81 (HN-T) and 0.73 (pancreas). Volumes defined by PET_Edge were better consistent with the manual ones compared to SUV40%. Regarding RF, 19%/19%/47% of the features showed ICC < 0.80 between observers for HN-N/HN-T/pancreas, mostly in the Voxel-alignment matrix and in the intensity-size zone matrix families. RFs with ICC < 0.80 against manual delineation (taking the worst value) increased to 44%/36%/61% for PET_Edge and to 69%/53%/75% for SUV40%. CONCLUSIONS About 80%/50% of 72 RF were consistent between observers for HN/pancreas patients. PET_edge was sufficiently robust against manual delineation while SUV40% showed a worse performance. This result suggests the possibility to replace manual with semi-automatic delineation of HN and pancreas tumours in studies including PET radiomic analyses.

A Composite Model for Classifying Parotid Shrinkage in Radiotherapy Patients Using Heterogeneous Data

The identification of head-and-neck radiotherapy patients who will probably undergo the parotid gland shrinkage would help to plan adaptive therapy for them. The goal of this paper is to build predictive models to be included in a Decision Support System, able to operate with a wide set of heterogeneous data and classify parotid shrinkage. The main idea is to combine a set of models, each of them working distinctly with a group of features regarding clinical data, dosimetric data, or information extracted from Computed Tomography images, into one or more composite models using the most informative variables, in order to obtain more accurate and reliable decisions. Each of these models is built by using Likelihood-Fuzzy Analysis, which is based on both statistics and fuzzy logic, in order to grant semantic interpretability. This solution presents good accuracy, sensitivity and specificity, and compared with the wellknown Fisher’s Linear Discriminant Analysis results more effective in parotids classification, even in case of missing values. The best models operating with available features are achieved, and the advantages of acquiring data from different sources are outlined. Other interesting findings regard the confirmation of already known predictors, and the individuation of others still undisclosed.

Validation of a method for “dose of the day” calculation in head-neck tomotherapy by using planning ct-to-MVCT deformable image registration

PURPOSE The aim of this study was to test the feasibility and dosimetric accuracy of a method that employs planning CT-to-MVCT deformable image registration (DIR) for calculation of the daily dose for head and neck (HN) patients treated with Helical Tomotherapy (HT). METHODS For each patient, the planning kVCT (CTplan) was deformably registered to the MVCT acquired at the 15th therapy session (MV15) with a B-Spline Free Form algorithm using Mattes mutual information (open-source software 3D Slicer), resulting in a deformed CT (CTdef). On the same day as MVCT15, a kVCT was acquired with the patient in the same treatment position (CT15). The original HT plans were recalculated both on CTdef and CT15, and the corresponding dose distributions were compared; local dose differences <2% of the prescribed dose (DD2%) and 2D/3D gamma-index values (2%-2mm) were assessed respectively with Mapcheck SNC Patient software (Sun Nuclear) and with 3D-Slicer. RESULTS On average, 87.9%±1.2% of voxels were found for DD2% (on average 27 slices available for each patient) and 94.6%±0.8% of points passed the 2D gamma analysis test while the 3D gamma test was satisfied in 94.8%±0.8% of bodys voxels. CONCLUSIONS This study represents the first demonstration of the dosimetric accuracy of kVCT-to-MVCT DIR for dose of the day computations. The suggested method is sufficiently fast and reliable to be used for daily delivered dose evaluations in clinical strategies for adaptive Tomotherapy of HN cancer.

EP-1852: Predictive role of FDG-PET/CT image-derived parameters in locally advanced oropharyngeal cancer

S871 ________________________________________________________________________________ patients with high-risk extremity soft tissue sarcoma. A twotier registration was used to align the tumor VOI within each dynamic frame at TP1 and align the volumes at TP2 to the volumes at TP1. After registration, the voxel-wise transfer constant K within a VOI covering the whole tumor normalized to a reference region of normal tissue area closed to the tumor was calculated. The responder threshold was determined by linear regression via evaluating the 95% confidence interval [-T, T] in the residuals from the reference region. The difference of the voxel-wise ΔK within the tumor between TP1 and TP2 was calculated. Three classes of voxels within the tumor VOI were determined: voxels having ΔK value exceed threshold T were designated in red, below -T were designated in blue, and otherwise designated in green indicating no significant change. The volume fractions with respect to three subvolumes of the tumor VOI were computed as F+ (red voxels), F-(blue voxels) and F0 (green voxels).

EP-1815: Towards adaptive Tomotherapy: planning CT to MVCT deformable image registration for dose calculation

S851 ________________________________________________________________________________ Conclusion: A method has been developed to assist the adaptive planning process for lung patients receiving FFF VMAT radiotherapy. This provides a means of assessing the dosimetric effect of tumour changes to determine whether a new treatment plan is necessary. It showed that for 25% of patients who received full treatment replans no replan was necessary, as the dosimetric effect of tumour shrinkage was insignificant in terms of both target coverage and OAR doses. Therefore it allows significant time savings in the treatment replanning process. Use of the technique is limited to patients who display tumour volume changes with no other significant changes to internal/external anatomy.