Rafael R. Mañon

Assessment of parotid gland dose changes during head and neck cancer radiotherapy using daily megavoltage computed tomography and deformable image registration.

PURPOSE To analyze changes in parotid gland dose resulting from anatomic changes throughout a course of radiotherapy in a cohort of head-and-neck cancer patients. METHODS AND MATERIALS The study population consisted of 10 head-and-neck cancer patients treated definitively with intensity-modulated radiotherapy on a helical tomotherapy unit. A total of 330 daily megavoltage computed tomography images were retrospectively processed through a deformable image registration algorithm to be registered to the planning kilovoltage computed tomography images. The process resulted in deformed parotid contours and voxel mappings for both daily and accumulated dose-volume histogram calculations. The daily and cumulative dose deviations from the original treatment plan were analyzed. Correlations between dosimetric variations and anatomic changes were investigated. RESULTS The daily parotid mean dose of the 10 patients differed from the plan dose by an average of 15%. At the end of the treatment, 3 of the 10 patients were estimated to have received a greater than 10% higher mean parotid dose than in the original plan (range, 13-42%), whereas the remaining 7 patients received doses that differed by less than 10% (range, -6-8%). The dose difference was correlated with a migration of the parotids toward the high-dose region. CONCLUSIONS The use of deformable image registration techniques and daily megavoltage computed tomography imaging makes it possible to calculate daily and accumulated dose-volume histograms. Significant dose variations were observed as result of interfractional anatomic changes. These techniques enable the implementation of dose-adaptive radiotherapy.

Evaluation of geometric changes of parotid glands during head and neck cancer radiotherapy using daily MVCT and automatic deformable registration

BACKGROUND AND PURPOSE To assess and evaluate geometrical changes in parotid glands using deformable image registration and megavoltage CT (MVCT) images. METHODS A deformable registration algorithm was applied to 330 daily MVCT images (10 patients) to create deformed parotid contours. The accuracy and robustness of the algorithm was evaluated through visual review, comparison with manual contours, and precision analysis. Temporal changes in the parotid gland geometry were observed. RESULTS The deformed parotid contours were qualitatively judged to be acceptable. Compared with manual contours, the uncertainties of automatically deformed contours were similar with regard to geometry and dosimetric endpoint. The day-to-day variations (1 standard deviation of errors) in the center-of-mass distance and volume were 1.61mm and 4.36%, respectively. The volumes tended to decrease with a median total loss of 21.3% (6.7-31.5%) and a median change rate of 0.7%/day (0.4-1.3%/day). Parotids migrated toward the patient center with a median total distance change of -5.26mm (0.00 to -16.35mm) and a median change rate of -0.22mm/day (0.02 to -0.56mm/day). CONCLUSION The deformable image registration and daily MVCT images provide an efficient and reliable assessment of parotid changes over the course of a radiation therapy.

Real-Time Tumor Tracking in the Lung Using an Electromagnetic Tracking System

PURPOSE To describe the first use of the commercially available Calypso 4D Localization System in the lung. METHODS AND MATERIALS Under an institutional review board-approved protocol and an investigational device exemption from the US Food and Drug Administration, the Calypso system was used with nonclinical methods to acquire real-time 4-dimensional lung tumor tracks for 7 lung cancer patients. The aims of the study were to investigate (1) the potential for bronchoscopic implantation; (2) the stability of smooth-surface beacon transponders (transponders) after implantation; and (3) the ability to acquire tracking information within the lung. Electromagnetic tracking was not used for any clinical decision making and could only be performed before any radiation delivery in a research setting. All motion tracks for each patient were reviewed, and values of the average displacement, amplitude of motion, period, and associated correlation to a sinusoidal model (R(2)) were tabulated for all 42 tracks. RESULTS For all 7 patients at least 1 transponder was successfully implanted. To assist in securing the transponder at the tumor site, it was necessary to implant a secondary fiducial for most transponders owing to the transponders smooth surface. For 3 patients, insertion into the lung proved difficult, with only 1 transponder remaining fixed during implantation. One patient developed a pneumothorax after implantation of the secondary fiducial. Once implanted, 13 of 14 transponders remained stable within the lung and were successfully tracked with the tracking system. CONCLUSIONS Our initial experience with electromagnetic guidance within the lung demonstrates that transponder implantation and tracking is achievable though not clinically available. This research investigation proved that lung tumor motion exhibits large variations from fraction to fraction within a single patient and that improvements to both transponder and tracking system are still necessary to create a clinical daily-use system to assist with actual lung radiation therapy.

A GPU based high‐resolution multilevel biomechanical head and neck model for validating deformable image registration

PURPOSE Validating the usage of deformable image registration (dir) for daily patient positioning is critical for adaptive radiotherapy (RT) applications pertaining to head and neck (HN) radiotherapy. The authors present a methodology for generating biomechanically realistic ground-truth data for validating dir algorithms for HN anatomy by (a) developing a high-resolution deformable biomechanical HN model from a planning CT, (b) simulating deformations for a range of interfraction posture changes and physiological regression, and (c) generating subsequent CT images representing the deformed anatomy. METHODS The biomechanical model was developed using HN kVCT datasets and the corresponding structure contours. The voxels inside a given 3D contour boundary were clustered using a graphics processing unit (GPU) based algorithm that accounted for inconsistencies and gaps in the boundary to form a volumetric structure. While the bony anatomy was modeled as rigid body, the muscle and soft tissue structures were modeled as mass-spring-damper models with elastic material properties that corresponded to the underlying contoured anatomies. Within a given muscle structure, the voxels were classified using a uniform grid and a normalized mass was assigned to each voxel based on its Hounsfield number. The soft tissue deformation for a given skeletal actuation was performed using an implicit Euler integration with each iteration split into two substeps: one for the muscle structures and the other for the remaining soft tissues. Posture changes were simulated by articulating the skeletal structure and enabling the soft structures to deform accordingly. Physiological changes representing tumor regression were simulated by reducing the target volume and enabling the surrounding soft structures to deform accordingly. Finally, the authors also discuss a new approach to generate kVCT images representing the deformed anatomy that accounts for gaps and antialiasing artifacts that may be caused by the biomechanical deformation process. Accuracy and stability of the model response were validated using ground-truth simulations representing soft tissue behavior under local and global deformations. Numerical accuracy of the HN deformations was analyzed by applying nonrigid skeletal transformations acquired from interfraction kVCT images to the models skeletal structures and comparing the subsequent soft tissue deformations of the model with the clinical anatomy. RESULTS The GPU based framework enabled the model deformation to be performed at 60 frames/s, facilitating simulations of posture changes and physiological regressions at interactive speeds. The soft tissue response was accurate with a R(2) value of >0.98 when compared to ground-truth global and local force deformation analysis. The deformation of the HN anatomy by the model agreed with the clinically observed deformations with an average correlation coefficient of 0.956. For a clinically relevant range of posture and physiological changes, the model deformations stabilized with an uncertainty of less than 0.01 mm. CONCLUSIONS Documenting dose delivery for HN radiotherapy is essential accounting for posture and physiological changes. The biomechanical model discussed in this paper was able to deform in real-time, allowing interactive simulations and visualization of such changes. The model would allow patient specific validations of the dir method and has the potential to be a significant aid in adaptive radiotherapy techniques.

Image-guided bolus electron conformal therapy – a case study

We report on our initial experience with daily image guidance for the treatment of a patient with a basal cell carcinoma of the nasal dorsum using bolus electron conformal therapy. We describe our approach to daily alignment using treatment machine‐integrated megavoltage (MV) planar imaging in conjunction with cone beam CT (CBCT) volumetric imaging to ensure the best possible setup reproducibility. Based on MV imaging, beam aperture misalignment with the intended treatment region was as large as 0.5 cm in the coronal plane. Four of the five fractions analyzed show induced shifts when compared to digitally reconstructed radiographs (DRR), in the range of 0.2−0.5 cm. Daily inspection of CBCT images show that the bolus device can have significant tilt in any given direction by as much as 13° with respect to beam axis. In addition, we show that CBCT images reveal air gaps between bolus and skin that vary from day to day, and can potentially degrade surface dose coverage. Retrospective dose calculation on CBCT image sets shows that when daily shifts based on MV imaging are not corrected, geometrical miss of the planning target volume (PTV) can cause an underdosing as large as 14% based on DVH analysis of the dose to the 90% of the PTV volume. PACS number: 87.55.kh

A Comparison of Soft-Tissue Implanted Markers and Bony Anatomy Alignments for Image-Guided Treatments of Head-and-Neck Cancers

PURPOSE To compare the geometric alignments of soft-tissue implanted markers to the traditional bony-based alignments in head-and-neck cancers, on the basis of daily image guidance. Dosimetric impact of the two alignment techniques on target coverage is presented. METHODS AND MATERIALS A total of 330 retrospective alignments (5 patients) were performed on daily megavoltage computed tomography (MVCT) image sets using both alignment techniques. Intermarker distances were tracked for all fractions to assess marker interfractional stability. Using a deformable image registration algorithm, target cumulative doses were calculated according to generated shifts on daily MVCT image sets. Target D95 was used as a dosimetric endpoint to evaluate each alignment technique. RESULTS Intermarker distances overall were stable, with a standard deviation of <1.5 mm for all fractions and no observed temporal trends. Differences in shift magnitudes between both alignment techniques were found to be statistically significant, with a maximum observed difference of 8 mm in a given direction. Evaluation of technique-specific dose coverage based on D95 of target clinical target volume and planning target volume shows small differences (within +/-5%) compared with the kilovoltage CT plan. CONCLUSION The use of daily MVCT imaging demonstrates that implanted markers in oral tongue and soft-palate cancers are stable localization surrogates. Alignments based on implanted markers generate shifts comparable overall to the traditional bony-based alignment, with no observed systematic difference in magnitude or direction. The cumulative dosimetric impact on target clinical target volume and planning target volume coverage was found to be similar, despite large observed differences in daily alignment shifts between the two techniques.

Megavoltage Computed Tomography Image-based Low-dose Rate Intracavitary Brachytherapy Planning for Cervical Carcinoma

Initial results of megavoltage computed tomography (MVCT) brachytherapy treatment planning are presented, using a commercially available helical tomotherapy treatment unit and standard low dose rate (LDR) brachytherapy applicators used for treatment of cervical carcinoma. The accuracy of MVCT imaging techniques, and dosimetric accuracy of the CT based plans were tested with in-house and commercially-available phantoms. Three dimensional (3D) dose distributions were computed and compared to the two dimensional (2D) dosimetry results. Minimal doses received by the 2 cm3 of bladder and rectum receiving the highest doses (DB2cc and DR2cc, respectively) were computed from dose-volume histograms and compared to the doses computed for the standard ICRU bladder and rectal reference dose points. Phantom test objects in MVCT image sets were localized with sub-millimetric accuracy, and the accuracy of the MVCT-based dose calculation was verified. Fifteen brachytherapy insertions were also analyzed. The ICRU rectal point dose did not differ significantly from DR2cc (p=0.749, mean difference was 24 cGy ± 283 cGy). The ICRU bladder point dose was significantly lower than the DB2cc (p=0.024, mean difference was 291 cGy ± 444 cGy). The median volumes of bladder and rectum receiving at least the corresponding ICRU reference point dose were 6.1 cm3 and 2.0 cm3, respectively. Our initial experience in using MVCT imaging for clinical LDR gynecological brachytherapy indicates that the MVCT images are of sufficient quality for use in 3D, MVCT-based dose planning.

Abstract 1403: Harnessing nanoparticles to improve toxicity after head and neck radiation

PURPOSE: To evaluate the ability of cerium oxide nanoparticles (CeO 2 ) to decrease xerostomia and skin reactions in athymic mice. METHODS: The head and neck (HN A) received no radiation exposure; B) received a single dose of 17.5 Gy; and C) received 30 Gy/6 fractions. In each cohort, animals were randomized into three groups (N=10 per group): 1) intraperitoneal (i.p.) injection of saline; 2) i.p. injection of 15 nM CeO 2; and 3) i.p. injection of 15 µM CeO 2 . Two independent double-blinded researchers graded radiation-induced dermatitis and hyperpigmentation at 1, 4, and 12 weeks after radiation therapy according to CTC v. 3.0 criteria. Ninety days after radiation, all mice were anesthetized and stimulated salivary flow was measured after subcutaneous pilocarpine injection (2mg/kg of B.W.) RESULTS: Stimulated sialometry strongly demonstrated improved salivary production in all CeO 2 groups compared to controls not receiving CeO 2 (mean salivary flow 204 vs. 115 µL/10min p=.0002). Grade 3 dermatitis was more prevalent in the fractionated vs. the single fraction cohort. In the fractionated cohort, the incidence of grade 3 dermatitis 1 week after radiation was decreased in the 15 µM CeO 2 group compared to the non-CeO 2 controls (10% vs. 100% incidence of Grade 3 dermatitis, respectively). A similar effect in reduction of grade 3 dermatitis was seen in the 15 µM CeO 2 group when compared to non-CeO 2 controls in both radiation cohorts for all time points evaluated. This effect was not appreciated in the 15 nM CeO 2 group. There was decrease in skin hyperpigmentation at 12 weeks in the 15 µM CeO 2 group compared to the 15 nM CeO 2 and non-CeO 2 groups (50, 70, and 90% grade 2, respectively). There were four Grade V toxicities in the fractionated cohort; three in the 15 nM CeO 2 group and one in the non-CeO 2 group. No Grade V toxicities were noted in the 15 µM CeO 2 group of mice. Additionally, there were no adverse effects noted in the groups of mice receiving CeO 2 without radiation. CONCLUSIONS: This study suggests that cerium oxide nanoparticles may have a radiation protective effect on salivary production. Parallel observations indicate a reduction in Grade 3 radiation-induced dermatitis and skin hyperpigmentation. The use of cerium oxide nanoparticles as a radioprotectant may be a feasible concept, but should be tested in a larger cohort of mice using a 15 µM concentration of CeO 2 . Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1403.

SU-EE-A3-05: Accuracy Testing of Deformable Registration Using Dosimetric End-Points

Purpose: To develop a dose‐based evaluation method to assess deformable image registration accuracy Method and Materials: An algorithm developed for deformable registration of MVCT to kVCT images was evaluated. The algorithm allows the generation of automatic contours on MVCT images by transferring the kVCT contours using the deformation map. The automatically generated MVCT contours can thus be used to test the deformation algorithm by comparing these contours with manual contours. Instead of a geographic contour comparison, dosimetric endpoints were evaluated after the dose distribution was calculated in the MVCT images. Three dosimetric endpoints (Dmax, Dmean, and Dose to the hottest 2 cc (Dmax (2cc)) were compared for spinal cord contours. The evaluation of geometric end‐points is directly related to the clinical information that needs to be evaluated if daily images are used for adaptive radiation therapy. A total of 93 daily megavoltage CT (MVCT) images from three patients treated for cancers in the head and neck region were evaluated. Results: Averaged over all images the calculated Dmax differed between the automatic and manual contours by 1.1 % with a standard deviation of 3.5 %. The respective values for Dmean and Dmax(2cc) are 0.1 ± 2.5 % and 1.8 ± 2.4 %. Maximum deviations between the dosimetric endpoints were 12 % for Dmax, 8% for Dmean, and 13 % for Dmax(2cc). Conclusions: Using deformable image registration,dosimetric end‐points can be generated from automatic contours in the spinal cord region that differ from manual contours by 1–2 % on average with a standard deviation of 2.5 to 3.5 %. In the spinal cord region the developed deformable image registration appears to provide sufficient accuracy to support clinical decisions. Conflict of interest: Research supported by the vendor that is commercializing the algorithm. Several co‐authors are vendor employees.

SU‐FF‐J‐19: Adaptive Radiation Therapy Using Helical Tomotherapy

Purpose: To describe and illustrate the processes required for adaptive radiotherapy(ART) with a helical tomotherapy system. Method and Materials:ART is a radiation treatment process where the subsequent delivery can be modified using a systematic feedback of the geometric and dosimetric information in the previous fractions. The first step in the process is CT guidance to achieve soft tissue localization. Dose recalculation is used to determine the dose delivered on a daily basis. Deformable image registration is required to place the daily image set, and hence regions of interest, in a common coordinate system. The total doses delivered are accumulated, and the treatment is evaluated relative to the original treatment plan. If significant deficiencies are noted in the dose delivery, plan re‐optimization can be performed to compensate for these deficiencies and make the treatment delivery more closely match the intent of the original treatment plan. Results: Prostate and head and neck cases have been used as clinical examples to test this adaptive strategy. Plan re‐optimization can maintain plan quality with no major degradation in most cases if two or three re‐optimizations are performed during the course of the treatment. Conclusions:ART provides a powerful tool to improve the delivery of radiotherapy, especially in situations where there is significant deformation of anatomy during a course of radiotherapy. In addition, it provides a powerful tool to retrospectively or prospectively examine the doses received by regions of interest, and hence, more accurately define tolerance doses for normal anatomy and curative doses for tumors.Conflict of Interest: Several of the authors are employees of TomoTherapy, Inc., and portions of this research have been funded by TomoTherapy, Inc.