Z Saleh

Treatment planning constraints to avoid xerostomia in head-and-neck radiotherapy: an independent test of QUANTEC criteria using a prospectively collected dataset.

PURPOSE The severe reduction of salivary function (xerostomia) is a common complication after radiation therapy for head-and-neck cancer. Consequently, guidelines to ensure adequate function based on parotid gland tolerance dose-volume parameters have been suggested by the QUANTEC group and by Ortholan et al. We perform a validation test of these guidelines against a prospectively collected dataset and compared with a previously published dataset. METHODS AND MATERIALS Whole-mouth stimulated salivary flow data from 66 head-and-neck cancer patients treated with radiotherapy at the British Columbia Cancer Agency (BCCA) were measured, and treatment planning data were abstracted. Flow measurements were collected from 50 patients at 3 months, and 60 patients at 12-month follow-up. Previously published data from a second institution, Washington University in St. Louis (WUSTL), were used for comparison. A logistic model was used to describe the incidence of Grade 4 xerostomia as a function of the mean dose of the spared parotid gland. The rate of correctly predicting the lack of xerostomia (negative predictive value [NPV]) was computed for both the QUANTEC constraints and Ortholan et al. recommendation to constrain the total volume of both glands receiving more than 40 Gy to less than 33%. RESULTS Both datasets showed a rate of xerostomia of less than 20% when the mean dose to the least-irradiated parotid gland is kept to less than 20 Gy. Logistic model parameters for the incidence of xerostomia at 12 months after therapy, based on the least-irradiated gland, were D(50) = 32.4 Gy and and γ = 0.97. NPVs for QUANTEC guideline were 94% (BCCA data), and 90% (WUSTL data). For Ortholan et al. guideline NPVs were 85% (BCCA) and 86% (WUSTL). CONCLUSION These data confirm that the QUANTEC guideline effectively avoids xerostomia, and this is somewhat more effective than constraints on the volume receiving more than 40 Gy.

Dose-volume factors correlating with trismus following chemoradiation for head and neck cancer

Background. To investigate the dose-volume factors in mastication muscles that are implicated as possible causes of trismus in patients following treatment with intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy for head and neck cancers. Material and methods. All evaluable patients treated at our institution between January 2004 and April 2009 with chemotherapy and IMRT for squamous cell cancers of the oropharynx, nasopharynx, hypopharynx or larynx were included in this analysis (N = 421). Trismus was assessed using CTCAE 4.0. Bi-lateral masseter, temporalis, lateral pterygoid and medial pterygoid muscles were delineated on axial computed tomography (CT) treatment planning images, and dose-volume parameters were extracted to investigate univariate and multimetric correlations. Results. Forty-six patients (10.9%) were observed to have chronic trismus of grade 1 or greater. From analysis of baseline patient characteristics, toxicity correlated with primary site and patient age. From dose-volume analysis, the steepest dose thresholds and highest correlations were seen for mean dose to ipsilateral masseter (Spearmans rank correlation coefficient Rs = 0.25) and medial pterygoid (Rs = 0.23) muscles. Lyman-Kutcher-Burman modeling showed highest correlations for the same muscles. The best correlation for multimetric logistic regression modeling was withV68Gy to the ipsilateral medial pterygoid (Rs = 0.29). Conclusion. Chemoradiation-induced trismus remains a problem particularly for patients with oropharyngeal carcinoma. Strong dose-volume correlations support the hypothesis that limiting dose to the ipsilateral masseter muscle and, in particular, the medial pterygoid muscle may reduce the likelihood of trismus.

A magnetic resonance imaging-based approach to quantify radiation-induced normal tissue injuries applied to trismus in head and neck cancer

BACKGROUND AND PURPOSE In this study we investigated the ability of textures from T1-weighted MRI scans post-contrast (T1wpost) to identify the critical muscle(s) for radiation-induced trismus. MATERIALS AND METHODS The study included ten cases (Trismus: ≥Grade 1), and ten age-sex-tumor-location-and-stage-matched controls treated with intensity-modulated radiotherapy to 70Gy@2.12Gy in 2005-2009. Trismus status and T1wPost were conducted within one year post-radiotherapy. For the masseter, lateral and medial pterygoids, and temporalis (M/LP/MP/T), 24 textures were extracted (Grey Level Co-Occurrence (GLCM), Histogram, and Shape). Univariate logistic regression with Bootstrapping (1000 populations) was applied to compare the muscle mean dose (Dmean) and textures between cases and controls (ipsilateral muscles); candidate predictors were suggested by an average p≤0.20 across all Bootstrap populations. RESULTS Dmean to M/LP/MP (p=0.03/0.14/0.09), one MP/T (p=0.12/0.17), and three M (p=0.14-0.19) textures were candidate predictors. Three of these textures were GLCM- and two Histogram textures with the former being generally higher and the latter lower for cases compared to controls. The Dmean to M and MP, and Haralick Correlation (GLCM) of MP presented with the best discriminative ability (area under the receiver-operating characteristic curve: 0.85, 0.77, and 0.78), and the correlation between Dmean and this texture was weak (Spearmans rank correlation coefficient: 0.26-0.27). CONCLUSIONS Our exploratory study points towards an interplay between the dose to the masseter, and the medial pterygoid together with the local relationship between the mean MRI intensity relative to its variance of the medial pterygoid for radiation-induced trismus. This opens up for exploration of this interplay within the radiation-induced trismus etiology in the larger multi-institutional setting.

A multiple-image-based method to evaluate the performance of deformable image registration in the pelvis

Deformable image registration (DIR) is essential for adaptive radiotherapy (RT) for tumor sites subject to motion, changes in tumor volume, as well as changes in patient normal anatomy due to weight loss. Several methods have been published to evaluate DIR-related uncertainties but they are not widely adopted. The aim of this study was, therefore, to evaluate intra-patient DIR for two highly deformable organs-the bladder and the rectum-in prostate cancer RT using a quantitative metric based on multiple image registration, the distance discordance metric (DDM). Voxel-by-voxel DIR uncertainties of the bladder and rectum were evaluated using DDM on weekly CT scans of 38 subjects previously treated with RT for prostate cancer (six scans/subject). The DDM was obtained from group-wise B-spline registration of each patients collection of repeat CT scans. For each structure, registration uncertainties were derived from DDM-related metrics. In addition, five other quantitative measures, including inverse consistency error (ICE), transitivity error (TE), Dice similarity (DSC) and volume ratios between corresponding structures from pre- and post- registered images were computed and compared with the DDM. The DDM varied across subjects and structures; DDMmean of the bladder ranged from 2 to 13 mm and from 1 to 11 mm for the rectum. There was a high correlation between DDMmean of the bladder and the rectum (Pearsons correlation coefficient, R p  =  0.62). The correlation between DDMmean and the volume ratios post-DIR was stronger (R p  =  0.51; 0.68) than the correlation with the TE (bladder: R p  =  0.46; rectum: R p  =  0.47), or the ICE (bladder: R p  =  0.34; rectum: R p  =  0.37). There was a negative correlation between DSC and DDMmean of both the bladder (R p  =  -0.23) and the rectum (R p  =  -0.63). The DDM uncertainty metric indicated considerable DIR variability across subjects and structures. Our results show a stronger correlation with volume ratios and with the DSC using DDM compared to using ICE and TE. The DDM has the potential to quantitatively identify regions of large DIR uncertainties and consequently identify anatomical/scan outliers. The DDM can, thus, be applied to improve the adaptive RT process for tumor sites subject to motion.

Proton Treatment Planning

The differences between planning proton-beam therapy and photon-beam therapy derive from the differences in the physics of protons and photons, namely [1]: That protons have a finite and controllable (through choice of energy) penetration in depth with virtually no exit dose (Fig. 3.1). That the penetration of protons is strongly affected by the nature (e.g., density) of the tissues through which they pass, while photons are much less affected (density changes generally give rise to only small intensity changes, except for the lung). Therefore, heterogeneities are much more important in proton-beam therapy than in photon-beam therapy (Fig. 3.2). The apparatus for proton-beam delivery is different, and its details affect the dose distributions (Chap. 2).

Results of a 10-year survey of workload for 10 treatment vaults at a high-throughput comprehensive cancer center

&NA; The workload for shielding purposes of modern linear accelerators (linacs) consists of primary and scatter radiation which depends on the dose delivered to isocenter (cGy) and leakage radiation which depends on the monitor units (MUs). In this study, we report on the workload for 10 treatment vaults in terms of dose to isocenter (cGy), monitor units delivered (MUs), number of treatment sessions (Txs), as well as, use factors (U) and modulation factors (CI) for different treatment techniques. The survey was performed for the years between 2006 and 2015 and included 16 treatment machines which represent different generations of Varian linear accelerators (6EX, 600C, 2100C, 2100EX, and TrueBeam) operating at different electron and x‐ray energies (6, 9, 12, 16 and 20 MeV electrons and, 6 and 15 MV x‐rays). An institutional review board (IRB) approval was acquired to perform this study. Data regarding patient workload, dose to isocenter, number of monitor units delivered, beam energies, gantry angles, and treatment techniques were exported from an ARIA treatment management system (Varian Medical Systems, Palo Alto, Ca.) into Excel spreadsheets and data analysis was performed in Matlab. The average (± std‐dev) number of treatment sessions, dose to isocenter, and number of monitor units delivered per week per machine in 2006 was 119 ± 39 Txs, (300 ± 116) × 102 cGys, and (78 ± 28) × 103 MUs respectively. In contrast, the workload in 2015 was 112 ± 40 Txs, (337 ± 124) × 102 cGys, and (111 ± 46) × 103 MUs. 60% of the workload (cGy) was delivered using 6 MV and 30% using 15 MV while the remaining 10% was delivered using electron beams. The modulation factors (MU/cGy) for IMRT and VMAT were 5.0 (± 3.4) and 4.6 (± 1.6) respectively. Use factors using 90° gantry angle intervals were equally distributed (˜0.25) but varied considerably among different treatment techniques. The workload, in terms of dose to isocenter (cGy) and subsequently monitor units (MUs), has been steadily increasing over the past decade. This increase can be attributed to increased use of high dose hypo‐fractionated regimens (SBRT, SRS) and the increase in use of IMRT and VMAT, which require higher MUs per cGy as compared to more conventional treatment (3DCRT). Meanwhile, the patient workload in terms of treatment sessions per week remained relatively constant. The findings of this report show that variables used for shielding purposes still fall within the recommendation of NCRP Report 151.

Validation of the Calypso Surface Beacon Transponder

Calypso L-shaped Surface Beacon transponder has recently become available for clinical applications. We herein conduct studies to validate the Surface Beacon transponder in terms of stability, reproducibility, orientation sensitivity, cycle rate dependence, and respiratory waveform tracking accuracy. The Surface Beacon was placed on a Quasar respiratory phantom and positioned at the isocenter with its two arms aligned with the lasers. Breathing waveforms were simulated, and the motion of the transponder was tracked. Stability and drift analysis: sinusoidal waveforms (200 cycles) were produced, and the amplitudes of phases 0% (inhale) and 50% (exhale) were recorded at each breathing cycle. The mean and standard deviation (SD) of the amplitudes were calculated. Linear least-squares fitting was performed to access the possible amplitude drift over the breathing cycles. Reproducibility: similar setting to stability and drift analysis, and the phantom generated 100 cycles of the sinusoidal waveform per run. The Calypso systems was re-setup for each run. Recorded amplitude and SD of 0% and 50% phase were compared between runs to assess contribution of Calypso electromagnetic array setup variation. Beacon orientation sensitivity: the Calypso tracks sinusoidal phantom motion with a defined angular offset of the beacon to assess its effect on SD and peak-to-peak amplitude. Rate dependence: sinusoidal motion was generated at cycle rates of 1 Hz, .33 Hz, and .2 Hz. Peak-to-peak displacement and SDs were assessed. Respiratory waveform tracking accuracy: the phantom reproduced recorded breathing cycles (by volunteers and patients) were tracked by the Calypso system. Deviation in tracking position from produced waveform was used to calculate SD throughout entire breathing cycle. Stability and drift analysis: Mean amplitude ± SD of phase 0% or 50% were 20.01±0.04 mm and -19.65±0.08 mm, respectively. No clinically significant drift was detected with drift measured as 5.1×10-5 mm/s at phase 0% and -6.0×10-5 mm/s at phase 50%. Reproducibility: The SD of the setup was 0.06 mm and 0.02 mm for phases 0% and 50%, respectively. The combined SDs, including both setup and intrarun error of all runs at phases 0% and 50%, were 0.07 mm and 0.11 mm, respectively. Beacon orientation: SD ranged from 0.032 mm to 0.039 mm at phase 0% and from 0.084 mm to 0.096 mm at phase 50%. The SD was found not to vary linearly with Beacon angle in the range of 0° and 15°. A positive systematic error was observed with amplitude 0.07 mm/degree at phase 0% and 0.05 mm/degree at phase 50%. Rate dependence: SD and displacement amplitudes did not vary significantly between 0.2 Hz and 0.33 Hz. At 1 Hz, both 0% and 50% amplitude measurements shifted up appreciably, by 0.72 mm and 0.78 mm, respectively. As compared with the 0.33 Hz data, SD at phase 0% was 1.6 times higher and 5.4 times higher at phase 50%. Respiratory waveform tracking accuracy: SD of 0.233 mm with approximately normal distribution in over 134 min of tracking (201468 data points). The Surface Beacon transponder appears to be stable, accurate, and reproducible. Submillimeter resolution is achieved throughout breathing and sinusoidal waveforms. PACS number(s): 87.50.ct, 87.50.st, 87.50.ux, 87.50.wp, 87.50.yt.Calypso L‐shaped Surface Beacon transponder has recently become available for clinical applications. We herein conduct studies to validate the Surface Beacon transponder in terms of stability, reproducibility, orientation sensitivity, cycle rate dependence, and respiratory waveform tracking accuracy. The Surface Beacon was placed on a Quasar respiratory phantom and positioned at the isocenter with its two arms aligned with the lasers. Breathing waveforms were simulated, and the motion of the transponder was tracked. Stability and drift analysis: sinusoidal waveforms (200 cycles) were produced, and the amplitudes of phases 0% (inhale) and 50% (exhale) were recorded at each breathing cycle. The mean and standard deviation (SD) of the amplitudes were calculated. Linear least‐squares fitting was performed to access the possible amplitude drift over the breathing cycles. Reproducibility: similar setting to stability and drift analysis, and the phantom generated 100 cycles of the sinusoidal waveform per run. The Calypso systems was re‐setup for each run. Recorded amplitude and SD of 0% and 50% phase were compared between runs to assess contribution of Calypso electromagnetic array setup variation. Beacon orientation sensitivity: the Calypso tracks sinusoidal phantom motion with a defined angular offset of the beacon to assess its effect on SD and peak‐to‐peak amplitude. Rate dependence: sinusoidal motion was generated at cycle rates of 1 Hz, .33 Hz, and .2 Hz. Peak‐to‐peak displacement and SDs were assessed. Respiratory waveform tracking accuracy: the phantom reproduced recorded breathing cycles (by volunteers and patients) were tracked by the Calypso system. Deviation in tracking position from produced waveform was used to calculate SD throughout entire breathing cycle. Stability and drift analysis: Mean amplitude ± SD of phase 0% or 50% were 20.01±0.04 mm and ‐19.65±0.08 mm, respectively. No clinically significant drift was detected with drift measured as 5.1×10‐5 mm/s at phase 0% and ‐6.0×10‐5 mm/s at phase 50%. Reproducibility: The SD of the setup was 0.06 mm and 0.02 mm for phases 0% and 50%, respectively. The combined SDs, including both setup and intrarun error of all runs at phases 0% and 50%, were 0.07 mm and 0.11 mm, respectively. Beacon orientation: SD ranged from 0.032 mm to 0.039 mm at phase 0% and from 0.084 mm to 0.096 mm at phase 50%. The SD was found not to vary linearly with Beacon angle in the range of 0° and 15°. A positive systematic error was observed with amplitude 0.07 mm/degree at phase 0% and 0.05 mm/degree at phase 50%. Rate dependence: SD and displacement amplitudes did not vary significantly between 0.2 Hz and 0.33 Hz. At 1 Hz, both 0% and 50% amplitude measurements shifted up appreciably, by 0.72 mm and 0.78 mm, respectively. As compared with the 0.33 Hz data, SD at phase 0% was 1.6 times higher and 5.4 times higher at phase 50%. Respiratory waveform tracking accuracy: SD of 0.233 mm with approximately normal distribution in over 134 min of tracking (201468 data points). The Surface Beacon transponder appears to be stable, accurate, and reproducible. Submillimeter resolution is achieved throughout breathing and sinusoidal waveforms. PACS number(s): 87.50.ct, 87.50.st, 87.50.ux, 87.50.wp, 87.50.yt

SU‐E‐J‐63: Initial Validation of the Surface Beacon Transponder

Purpose: Varian’s L shaped surface beacon transponder for the Calypso system has recently been cleared for real time tracking anywhere on body. We herein conduct initial validation of the surface beacon transponder in preparation for clinical implementations. Methods: The surface beacon transponder was placed on a respiratory phantom to conduct the following three tests. 1) Stability: the phantom was turned on to produce the same breathing cycle repeatedly, and the associated transponder motion was then recorded. The mean and standard deviations of the amplitude were calculated for phase 0% and 50% over all the cycles. We also looked for any possible baseline drift. 2) Reproducibility: the phantom/transponder was setup to the same position multiple times, and motion from each session was recorded. The mean and standard deviation of the amplitude of phase 0% were calculated over all sessions. 3) Transponder placement sensitivity: it is recommended to align two arms of the transponder to the lateral and sagittal lasers. With patient breathing, transponder position might vary during the treatment. We manually introduced 14° yaw to the transponder placement and calculated the amplitude difference compared to when transponder was perfectly aligned (0°). Results: 1) Stability: the means and standard deviations for 0% and 50% were 1.39±0.01 cm and −0.03±0.005 cm. The baseline seemed to drift up: i.e. the amplitude was shifted slightly higher each breathing cycle. 2) Reproducibility: 1.36±0.02 cm. 3) Transponder placement sensitivity: the amplitudes were 1.55 cm at 14° vs. 1.35 cm at 0°. Conclusion: The surface beacon transponder appears to be relatively stable and reproducible. More study is needed to confirm the baseline drift. It is important to align the transponder to the lasers, and users should be cautious about the possible amplitude change due to transponder yaws.

SU-E-J-64: Landmark and ROI-Enhancement-Assisted Inter-Patient Deformable Registration of 3D Bladder CT Images

PURPOSE Deformable image registration (DIR) of the pelvis, and in particular, the bladder, is known to be a difficult problem. We tested several pre-processing strategies to improve the effectiveness of registration. METHODS We studied the use of automatically-derived landmarks (LMs) and enhanced regions of interest (ROIs) to improve existing DIR algorithms, such as B-Spline. The three outstanding LMs in the bladder are the two ureteral orifices and the internal urethral orifice.We used 10 pelvic CT image sets with bladders of different shapes (either full or empty). Interpatient registration was performed using four Methods: 1. B-Spline, standard intensity-based B-Spline registration;2. LM B-Spline, B-Spline registration with forced matching of corresponding landmarks;3. ROI enhancement (ROI Enh) B-Spline, signal intensity of the bladder ROI enhanced during pre-processing to weigh the bladder more when registering; 4. LM + ROI Enh B-Spline. RESULTS 1. B-Spline DIR resulted in poor registration due to the variance of shapes and sizes among the bladders.2. LM B-Spline achieved the least distance between landmarks, albeit with poor Dice coefficient values and high registration uncertainty. This method is reliant on the number of landmarks. 3. ROI Enh B-Spline achieved a higher Dice coefficient and lower registration uncertainty but larger LM distance, when compared to LM B-Spline. This method is most applicable where ROI volume boundary alignment is sufficient. 4. LM + ROI Enh B-Spline achieved the best Result, when taking into account of all the quantitative and qualitative measurements. In general, we observed a tradeoff between achieving a reliable bladder registration and reliable registration of other parts, such as bones. CONCLUSION We developed three methods to improve DIR by combining existing approaches. For DIR of bladders, the application of LMs plus ROI Enh B-Spline achieved the best overall results, based on quantitative results and physician opinion.

Feasibility study of individualized optimal positioning selection for left‐sided whole breast radiotherapy: DIBH or prone

Abstract The deep inspiration breath hold (DIBH) and prone (P) position are two common heart‐sparing techniques for external‐beam radiation treatment of left‐sided breast cancer patients. Clinicians select the position that is deemed to be better for tissue sparing based on their experience. This approach, however, is not always optimum and consistent. In response to this, we develop a quantitative tool that predicts the optimal positioning for the sake of organs at risk (OAR) sparing. Sixteen left‐sided breast cancer patients were considered in the study, each received CT scans in the supine free breathing, supine DIBH, and prone positions. Treatment plans were generated for all positions. A patient was classified as DIBH or P using two different criteria: if that position yielded (1) lower heart dose, or (2) lower weighted OAR dose. Ten anatomical features were extracted from each patients data, followed by the principal component analysis. Sequential forward feature selection was implemented to identify features that give the best classification performance. Nine statistical models were then applied to predict the optimal positioning and were evaluated using stratified k‐fold cross‐validation, predictive accuracy and receiver operating characteristic (AUROC). For heart toxicity‐based classification, the support vector machine with radial basis function kernel yielded the highest accuracy (0.88) and AUROC (0.80). For OAR overall toxicities‐based classification, the quadratic discriminant analysis achieved the highest accuracy (0.90) and AUROC (0.84). For heart toxicity‐based classification, Breast volume and the distance between Heart and Breast were the most frequently selected features. For OAR overall toxicities‐based classification, Heart volume, Breast volume and the distance between ipsilateral lung and breast were frequently selected. Given the patient data considered in this study, the proposed statistical model is feasible to provide predictions for DIBH and prone position selection as well as indicate important clinical features that affect the position selection.