Y Chen

Adaptive Radiotherapy for Head-and-Neck Cancer: Initial Clinical Outcomes From a Prospective Trial

PURPOSEnTo present pilot toxicity and survival outcomes for a prospective trial investigating adaptive radiotherapy (ART) for oropharyngeal squamous cell carcinoma.nnnMETHODS AND MATERIALSnA total of 24 patients were enrolled in an institutional review board-approved clinical trial; data for 22 of these patients were analyzed. Daily CT-guided setup and deformable image registration permitted serial mapping of clinical target volumes and avoidance structures for ART planning. Primary site was base of tongue in 15 patients, tonsil in 6 patient, and glossopharyngeal sulcus in 1 patient. Twenty patients (91%) had American Joint Committee on Cancer (AJCC) Stage IV disease. T stage distribution was 2 T1, 12 T2, 3 T3, 5 T4. N stage distribution was 1 N0, 2 N1, 5 N2a, 12 N2b, and 2 N2c. Of the patients, 21 (95%) received systemic therapy.nnnRESULTSnWith a 31-month median follow-up (range, 13-45 months), there has been no primary site failure and 1 nodal relapse, yielding 100% local and 95% regional disease control at 2 years. Baseline tumor size correlated with absolute volumetric treatment response (p = 0.018). Parotid volumetric change correlated with duration of feeding tube placement (p = 0.025). Acute toxicity was comparable to that observed with conventional intensity-modulated radiotherapy (IMRT). Chronic toxicity and functional outcomes beyond 1 year were tabulated.nnnCONCLUSIONnThis is the first prospective evaluation of morbidity and survival outcomes in patients with locally advanced head-and-neck cancer treated with automated adaptive replanning. ART can provide dosimetric benefit with only one or two mid-treatment replanning events. Our preliminary clinical outcomes document functional recovery and preservation of disease control at 1-year follow-up and beyond.

Adaptive radiotherapy for head and neck cancer - Dosimetric results from a prospective clinical trial

PURPOSEnTo conduct a clinical trial evaluating adaptive head and neck radiotherapy (ART).nnnMETHODSnPatients with locally advanced oropharyngeal cancer were prospectively enrolled. Daily CT-guided setup and deformable image registration permitted mapping of dose to avoidance structures and CTVs. We compared four planning scenarios: (1) original IMRT plan aligned daily to marked isocenter (BB); (2) original plan aligned daily to bone (IGRT); (3) IGRT with one adaptive replan (ART1); and (4) actual treatment received by each study patient (IGRT with one or two adaptive replans, ART2).nnnRESULTSnAll 22 study patients underwent one replan (ART1); eight patients had two replans (ART2). ART1 reduced mean dose to contralateral parotid by 0.6 Gy or 2.8% (paired t-test; p=0.003) and ipsilateral parotid by 1.3 Gy (3.9%) (p=0.002) over the IGRT alone. ART2 further reduced the mean contralateral parotid dose by 0.8 Gy or 3.8% (p=0.026) and ipsilateral parotid by 4.1 Gy or 9% (p=0.001). ART significantly reduced integral body dose.nnnCONCLUSIONSnThis pilot trial suggests that head and neck ART dosimetrically outperforms IMRT. IGRT that leverages conventional PTV margins does not improve dosimetry. One properly timed replan delivers the majority of achievable dosimetric improvement. The clinical impact of ART must be confirmed by future trials.

SU‐GG‐J‐146: Evaluation of Parotid Density Changes during IMRT of Head‐And‐Neck Cancer

Purpose: To evaluate the change in parotid gland density over the course of treatment for patients who have undergone adaptive radiation therapy to the head‐and‐neck. Method and Materials:Computed tomography(CT)images from sixteen patients were analyzed to assess the change in mean parotid density and parotid volume over the course of treatment. Daily CTimages were acquired for a group of patients treated with adaptive radiation therapy using a CT‐on‐rails unit. A total of 529 CT scans (∼33 fractions per patient) were analyzed. Parotid contours were deformed from the planning CT to each treatment day CTimage using an in‐house deformable image registration tool. The parotid volume, and average and standard deviation in CT number (HU) were obtained for each treatment fraction. Linear regression analysis was performed with a 95% confidence interval to determine the rate and trend of parotid density change. The Pearson correlation coefficient was used to evaluate possible correlations with parotid volume and function measurements. Results: Eleven of the sixteen patients showed a steady decrease in density for both parotids over the course of treatment. Two patients showed a steady decrease only in their ipsilateral parotid. The linear regression analysis for this subset of patients (p‐value <0.01) revealed an average rate of decrease of 0.30 HU/fraction (range 0.13–0.70 HU/fraction). The density reduction correlated well with parotid volume change (in 24/32 instances), and was moderately correlated with patient follow‐up saliva‐flow measurements (9 patients, correlation coefficient range 0.27–0.63) for the first two follow‐up appointments. Conclusion: The mean parotid density decreased steadily and correlated well with the volume shrinkage in most patients observed in this study. In the limited available data, the density change also correlated with saliva‐flow, which warrants future studies with a larger patient population and additional treatment parameters.

SU‐E‐J‐225: Quantitative Evaluation of Rigid and Non‐Rigid Motion of Liver Tumors Using Stereo Imaging During SBRT

PURPOSEnTo quantitatively evaluate rigid and nonrigid motion of liver tumors based on fiducial tracking in 3D by stereo imaging during CyberKnife SBRT.nnnMETHODSnTwenty-five liver patients previously treated with three-fractions of SBRT were retrospectively recruited in this study. During treatment, the 3D locations of fiducials were reported by the CyberKnife system after two orthogonal kV X-ray images were taken and further validated by geometry derivations. A total of 5004 pairs of X-ray images acquired during the course of treatment for all the patients, were analyzed. For rigid motion, the rotational angles and translational shifts by aligning 3D fiducial groups in different image pairs after least-square fitting were reported. For nonrigid motion, the relative interfractional tumor shape variations were reported and correlated to the sum of inter-fiducial distances. The individual fiducial displacements were also reported after rigid corrections and without angle corrections.nnnRESULTSnThe relative tumor volume variation indicated by the inter-fiducial distances demonstrated an increasing trend in the second (101.6±3.4%) and third fraction (101.2±5.6%) among most patients. The cause could be possibly due to radiation-induced edema. For all the patients, the translational shift was 8.1±5.7 mm, with shifts in LR, AP and SI were 2.1±2.4 mm, 2.8±2.9 mm and 6.7±5.1 mm, respectively. The greatest translation shift occurred in SI, mainly due the breathing motion of diaphragm The rotational angles were 1.1±1.7°, 1.9±2.6° and 1.6±2.2°, in roll, pitch, and yaw, respectively. The 3D fiducial displacement with rigid corrections were 0.2±0.2 mm and increased to 0.6±0.3 mm without rotational corrections.nnnCONCLUSIONnThe fiducial locations in 3D can be precisely reconstructed from CyberKnife stereo imaging system during treatment. The fiducials provide close estimation of both rigid and nonrigid motion of .liver tumors. The reported data could be further utilized for tumor margin design and motion management in in conventional linac-based treatments.

SU-E-T-119: Dosimetric and Mechanical Characteristics of Elekta Infinity LINAC with Agility MLC

PURPOSEnElekta Infinity is the one of the latest generation LINAC with unique features. Two Infinity LINACs are recently commissioned at our institution. The dosimetric and mechanical characteristics of the machines are presented.nnnMETHODSnBoth Infinity LINACs with Agility MLC (160 leaves with 0.5 cm leaf width) are configured with five electron energies (6, 9, 12, 15, and 18 MeV) and two photon energies (6 and 15 MV). One machine has additional photon energy (10 MV). The commissioning was performed by following the manufacturers specifications and AAPM TG recommendations. Beam data of both electron and photon beams are measured with scanning ion chambers and linear diode array. Machines are adjusted to have the dosimetrically equivalent characteristics.nnnRESULTSnThe commissioning of mechanical and imaging system meets the tolerances by TG recommendations. The PDD1 0 of various field sizes for 6 and 15 MV shows < 0.5% difference between two machines. For each electron beams, R8 0 matches with < 0.4 mm difference. The symmetry and flatness agree within 0.8% and 0.9% differences for photon beams, respectively. For electron beams, the differences of the symmetry and flatness are within 1.2% and 0.8%, respectively. The mean inline penumbras for 6, 10, and 15 MV are respectively 5.1±0.24, 5.6±0.07, and 5.9±0.10 mm for 10×10 cm at 10 cm depth. The crossline penumbras are larger than inline penumbras by 2.2, 1.4, and 1.0 mm, respectively. The MLC transmission factor with interleaf leakage is 0.5 % for all photon energies.nnnCONCLUSIONnThe dosimetric and mechanical characteristics of two Infinity LINACs show good agreements between them. Although the Elekta Infinity has been used in many institutions, the detailed characteristics of the machine have not been reported. This study provides invaluable information to understand the Infinity LINAC and to compare the quality of commissioning data for other LINACs.

SU-E-J-214: Assessment of Rotational Lung Tumor Motion and Its Influence On Treatment Margins for Stereotactic Body Radiosurgery (SBRT)

Purpose: To quantify rotational motion of lung tumors under radiotherapy based on fiducial imaging. Tumor rotational motion in lung has not been well understood due to difficulties of imaging and target delineation. In this study the rotational motion of fiducial clusters were measured for assessing the treatment margins necessary for adequate dose coverage to CTV. Methods: 25 patients who underwent CyberKnife based SBRT were recruited. Three to five fiducials were implanted in or near the tumor. The reference fiducial locations were determined using a breath‐hold CT. Orthogonal X‐ray image pairs were acquired for modeling and tumor tracking during treatment. These images were used to reconstruct the fiducial locations in 3D. A rigid‐body registration was derived between the measured and reference fiducial locations. The mean distance between the corresponding fiducial pairs was used to evaluate the registration. 2796 pairs of images in 106 fractions of treatment were analyzed. The rotational motion of fiducial clusters was used to simulate the tumor rotational motion for assessing the adequacy of the PTV margins. A margin of 3mm was used to expand the upper lobe (UL) target and 5 mm for lower lobe (LL) target. Additional tracking errors were included in the analysis for tumor coverage under alignment of the rotated CTV with the PTV. Results: The tumor rotational angles in LL and UL were 0.25°±5.7° vs 0.40°±2.1° in roll, — 0.21°±7.3° vs 0.05°±1.8° in pitch, and 0.23°±5.3° vs. 0.1°±2.1° in yaw, respectively. In 94.4% (LL) and 97.1% (UL) of the total imaged tumor locations, the CTV was 100% covered by the corresponding PTV. The mean missing coverage of the CTV for the rest locations were of 4.4% and 1%, respectively. Conclusion: The reported angles were highly correlated to the distance to the diaphragm. Appropriate margins need to be applied for different lobes to ensure CTV coverage.

SU‐E‐J‐147: Internal Brain Motion Between CT and MR Scanning

Purpose: To evaluate the internal brain motion between two imaging studies of CT and MRI. A study with 30 healthy volunteers with MRI scans in 4 different positions showed significant brain to skull motion up to 1 cm. Such motion among patients for radiotherapy to the brain is evaluated in this study. Methods: Twenty‐five patients underwent MRI and CT scans in the same day for radiotherapy planning were recruited. A whole brain fusion was first performed. Three to five pairs of control points were selected on both CT and MRI for starting an automated intensity based registration. The fusion was reviewed and fine‐tuned for the best skull‐to‐skull matching. To study potential internal brain motion, a subsequent fine‐tuning of the fusion was performed by matching the visible features, such as gyri, sulci and fissures, near the tumor site. The second fusion was reviewed and fine‐tuned by two physicists until the best visible feature matching could be agreed upon. The resulting rotation and translation between the whole brain and feature‐based fusions indicated potential internal brain motion between the two scans. Results: Between two fusions the mean internal shifts in x (LR), y (AP) and z (SI) were 0.34±0.95 mm, 0.21±1.18 mm and −0.34±0.8 mm, respectively. The mean overall shift was 1.4±1.1 mm, and the largest shift was 3.5 mm. The mean rotation angles were 0.22±1.32° (pitch), 0.14±0.4° (yaw) and 0.08±0.53° (roll), respectively. The pitch motion was predominant (head up and down) due to difference of couch tops of CT and MRI scanners. Conclusion: Our study showed small but measurable internal brain motion among radiotherapy patients with typical clinical setting for CT and MRI imaging. Therefore the CT‐MRI fusion should be carefully checked for internal structure matching. An additional treatment margin may be needed if an internal motion is observed.

SU‐E‐J‐197: Tracking Tumor Response Over Treatment Course in IMRT and Proton Patients

Purpose: To assess the changes in tumor mass and volume for NSCLC patients treated with either protons or IMRT. Methods: Analyses were done on the T50 phase from weekly 4DCTs of patients with stage 3 NSCCLC treated on an IRB approved trial comparing IMRT with passively scattered protons. Patients received either 74 GY or 66 Gy in 2 Gy fractions with concurrent chemotherapy. We performed deformable registration to segment the GTV on each CT. The deformable registration process was 1) rigid registration to determine the region of the GTV 2) deformation of the contours from the planning CT 3) thresholding to account for cavities formed inside the GTV. The resultant contours were used to determine volume and mass, as determined from the TPSs CT‐to‐density curve, change over course of treatment. Results: We analyzed 48 patients 30 were treated with IMRT and 18 with protons. The ratio of GTV volume and mass between the final week CT and planning CT were 0.80 ± .21 % and 0.77 ± 0.25% for IMRT and 0.71 ± 0.21% and 0.66 ± 0.24% for protons. Conclusion: We found that tumors shrank 20‐30% when treated with concurrent chemo‐radiotherapy at 2 Gy/fraction. In addition we noted that the remaining tumor, on average, had a lower density at the end of treatment. A difference was noted between protons and IMRT but was not statistically significant. This work was, in part, funded by the National Cancer Institute.

TU‐A‐WAB‐11: Tumor Shrinkage Prediction Using CT Image Features

PURPOSEnTo develop a quantitative image feature model to predict non-small cell lung cancer (NSCLC) volume shrinkage from standard of care pre-treatment CT images.nnnMETHODSn64 stage II-IIIB NSCLC patients with similar treatments were all imaged using the same CT scanner and protocol. For each patient, the planning gross tumour volume (GTV) was deformed onto the week six treatment image, and tumour shrinkage was quantified as the deformed GTV volume divided by the planning GTV volume. Geometric, intensity histogram, absolute gradient image, co-occurrence matrix, and run-length matrix 3D quantitative image features were extracted multiple times from each planning GTV using a variety of feature extraction parameters. Prediction models were generated using principal component regression with simulated annealing subset selection; performance was quantified using the mean squared error (MSE) between the predicted and observed tumour shrinkages. Cross validation and permutation tests were used to validate the results.nnnRESULTSnThe optimal model gave a strong correlation between the observed and predicted shrinkages with r=0.81 and MSE =0.0086. Compared to predictions based on the mean population shrinkage (i.e. predicted shrinkage = mean shrinkage; MSE =0.0251) this resulted a 2.92 fold reduction in MSE. That is, the tumor shrinkage uncertainty was reduced by a factor of approximately three.nnnCONCLUSIONnA quantitative image feature model can use existing CT images to successfully predict tumour shrinkage and provide additional information for clinical decisions regarding patient risk stratification, treatment, and prognosis.

TH‐A‐116‐03: Photon and Proton Radiotherapy of the Lung Would Benefit From 4D Dose Calculation Techniques

PURPOSEnTo compare the effects of respiratory motion by calculating four-dimensional (4D) dose accumulation on proton and photon radiotherapy plans for a stage III lung cancer cohort.nnnMETHODS AND MATERIALSnThis study used passively scattered proton therapy (PSPT) and photon intensity modulated radiotherapy (IMRT) plans designed to meet the same criteria for an ongoing clinical trial. For 20 patients, 4D dose evaluation was calculated on both the PSPT and IMRT plans by accumulating individual phase dose using an intensity-based in-house deformable image registration algorithm. The resulting 4D dose accumulation method was compared against current standard of three dimensional (3D) dose as calculated on the average CT.nnnRESULTSnBoth proton and photon plans demonstrated dosimetric differences when accounting for respiratory motion using 4D dose calculation methods. Reported 4D-3D values are mean plus one standard deviation. 4D-3D difference in PTV 95% dose coverage was >2% for 5 IMRT (0.5±1.1Gy) and 4 PSPT plans (0.5±0.8Gy). The structural doses most affected by respiratory motion were normal structures distal to the tumor, such as esophagus V65 (IMRT: -0.5±1.2Gy, PSPT: -0.4±1.4), mean heart (IMRT: - 0.4±0.6 Gy, PSPT: -0.3±0.9 Gy) and spinal cord maximum (IMRT: 0.0±0.2Gy, PSPT: 1.5±2.9Gy). No correlations were found between tumor motion and the change in 4D dose difference for any lung, heart, or spine dose-volume index.nnnCONCLUSIONSnThe use of 4D dose evaluation techniques at time of treatment planning revealed small but significant respiratory motion induced deviations from the 3D planned dose for both photon and proton therapy. In both modalities, differences between 3D and 4D dose distributions are patient dependent; no population trends were found correlating dose differences to the extent of tumor motion. The implementation of 4D dose calculation methods for proton and photon lung cancer radiotherapy plans may help identify patients for whom respiratory motion alters the planned dose distribution. This project is supported by grant P01CA021239 from the National Cancer Institute.