Interinstitutional beam model portability study in a mixed vendor environment.

A 6 MV flattened beam model for a Varian TrueBeamSTx c-arm treatment delivery system in RayStation, developed and validated at one institution, was implemented and validated at another institution. The only parameter value adjustments were to accommodate machine output at the second institution. Validation followed MPPG 5.a. recommendations, with particular attention paid to IMRT and VMAT deliveries. With this minimal adjustment, the model passed validation across a broad spectrum of treatment plans, measurement devices, and staff who created the test plans and executed the measurements. This work demonstrates the possibility of using a single template model in the same treatment planning system with matched machines in a mixed vendor environment.

Initial clinical experience with ArcCHECK for IMRT/VMAT QA.

Many devices designed for the purpose of performing patient-specific IMRT/VMAT QA are commercially available. In this work we report our experience and initial clinical results with the ArcCHECK. The ArcCHECK consists of a cylindrical array of diode detectors measuring entry and exit doses. The measured result is a cumulative dose displayed as a 2D matrix. The detector array requires both an absolute dose calibration, and a calibration of the detector response, relative to each other. In addition to the calibrations suggested by the manufacturer, various tests were performed in order to assess its stability and performance prior to clinical introduction. Tests of uniformity, linearity, and repetition rate dependence of the detector response were conducted and described in this work. Following initial test-ing, the ArcCHECK device was introduced in the clinic for routine patient-specific IMRT QA. The clinical results from one year of use were collected and analyzed. The gamma pass rates at the 3%/3 mm criterion were reported for 3,116 cases that included both IMRT and VMAT treatment plans delivered on 18 linear accelera-tors. The gamma pass rates were categorized based on the treatment site, treatment technique, type of MLCs, operator, ArcCHECK device, and LINAC model. We recorded the percent of failures at the clinically acceptable threshold of 90%. In addition, we calculated the threshold that encompasses two standard deviations (2 SD) (95%) of QAs (T95) for each category investigated. The commissioning measurements demonstrated that the device performed as expected. The uniformity of the detector response to a constant field arc delivery showed a 1% standard deviation from the mean. The variation in dose with changing repetition rate was within 1 cGy of the mean, while the measured dose showed a linear relation with delivered MUs. Our initial patient QA results showed that, at the clinically selected passing criterion, 4.5% of cases failed. On average T95 was 91%, rang-ing from 73% for gynecological sites to 96.5% for central nervous system sites. There are statistically significant differences in passing rates between IMRT and VMAT, high-definition (HD) and non-HD MLCs, and different LINAC models (p-values << 0.001). An additional investigation into the failing QAs and a com-parison with ion-chamber measurements reveals that the differences observed in the passing rates between the different studied factors can be largely explained by the field size dependence of the device. Based on our initial experience with the ArcCHECK, our passing rates are, on average, consistent with values reported in the AAPM TG-119. However, the significant variations between QAs that were observed based on the size of the treatment fields may need to be corrected to improve the specificity and sensitivity of the device.

Experimental investigation of a moving averaging algorithm for motion perpendicular to the leaf travel direction in dynamic MLC target tracking.

PURPOSE: In dynamic multileaf collimator (MLC) motion tracking with complex intensity-modulated radiation therapy (IMRT) fields, target motion perpendicular to the MLC leaf travel direction can cause beam holds, which increase beam delivery time by up to a factor of 4. As a means to balance delivery efficiency and accuracy, a moving average algorithm was incorporated into a dynamic MLC motion tracking system (i.e., moving average tracking) to account for target motion perpendicular to the MLC leaf travel direction. The experimental investigation of the moving average algorithm compared with real-time tracking and no compensation beam delivery is described. METHODS: The properties of the moving average algorithm were measured and compared with those of real-time tracking (dynamic MLC motion tracking accounting for both target motion parallel and perpendicular to the leaf travel direction) and no compensation beam delivery. The algorithm was investigated using a synthetic motion trace with a baseline drift and four patient-measured 3D tumor motion traces representing regular and irregular motions with varying baseline drifts. Each motion trace was reproduced by a moving platform. The delivery efficiency, geometric accuracy, and dosimetric accuracy were evaluated for conformal, step-and-shoot IMRT, and dynamic sliding window IMRT treatment plans using the synthetic and patient motion traces. The dosimetric accuracy was quantified via a tgamma-test with a 3%/3 mm criterion. RESULTS: The delivery efficiency ranged from 89 to 100% for moving average tracking, 26%-100% for real-time tracking, and 100% (by definition) for no compensation. The root-mean-square geometric error ranged from 3.2 to 4.0 mm for moving average tracking, 0.7-1.1 mm for real-time tracking, and 3.7-7.2 mm for no compensation. The percentage of dosimetric points failing the gamma-test ranged from 4 to 30% for moving average tracking, 0%-23% for real-time tracking, and 10%-47% for no compensation. CONCLUSIONS: The delivery efficiency of moving average tracking was up to four times higher than that of real-time tracking and approached the efficiency of no compensation for all cases. The geometric accuracy and dosimetric accuracy of the moving average algorithm was between real-time tracking and no compensation, approximately half the percentage of dosimetric points failing the gamma-test compared with no compensation.

IMRT Reduces Acute Toxicity in Patients Treated With Preoperative Chemoradiation for Gastric Cancer.

PURPOSE: Preoperative chemoradiation is being currently evaluated in 2 randomized international trials. However, chemoradiation for gastric cancer can be associated with relatively high rates of acute toxicity. We compared rates of toxicity, toxicity-related events, and oncologic outcomes in patients treated with intensity modulated radiation therapy (IMRT) and those treated with 3-dimensional conformal radiation therapy (3DCRT). METHODS AND MATERIALS: We retrospectively reviewed records of 202 patients with consecutive gastric cancer treated with preoperative intent radiation therapy at our institution from 1998 to 2018. Patients with gastroesophageal junction involvement and those with metastatic disease were excluded. Eighty-two patients received 3DCRT, and 120 patients received IMRT. The median radiation dose was 45 Gy, and 99% received concurrent chemotherapy. RESULTS: There were no significant differences between the 3DCRT and IMRT groups regarding sex, race, histology, tumor location, histology, or nodal stage. The rate of grade 3 to 4 acute toxicity was significantly lower in patients treated with IMRT compared with 3DCRT (49% vs 70%, P = .004). The composite rate of toxicity-related events (hospitalization, feeding tube use, intravenous rehydration, or radiation therapy breaks) was also significantly lower in patients treated with IMRT compared with 3DCRT (56% vs 85%, P <.001). In addition, 68% of patients who received IMRT and 73% of patients who received 3DCRT underwent subsequent surgical resection (P = .245). Among patients who underwent surgery, the 3-year overall survival rates were not significantly different between those treated with IMRT and 3DCRT (71% vs 69%, P = .786). Patients receiving IMRT had a significantly higher absolute nadir lymphocyte count compared with patients receiving 3DCRT (median, 0.21 vs 0.16 K/UL; P = .047). CONCLUSIONS: Our study suggests that IMRT might significantly reduce rates of grade 3 to 4 acute toxicity and toxicity-related events compared with 3DCRT, with no significant difference in oncologic outcomes. IMRT is an appropriate and possibly preferable radiation modality in patients treated with preoperative chemoradiation for gastric cancer.

Four-dimensional IMRT treatment planning using a DMLC motion-tracking algorithm.

The purpose of this study is to develop a four-dimensional (4D) intensity-modulated radiation therapy (IMRT) treatment-planning method by modifying and applying a dynamic multileaf collimator (DMLC) motion-tracking algorithm. The 4D radiotherapy treatment scenario investigated is to obtain a 4D treatment plan based on a 4D computed tomography (CT) planning scan and to have the delivery flexible enough to account for changes in tumor position during treatment delivery. For each of 4D CT planning scans from 12 lung cancer patients, a reference phase plan was created; with its MLC leaf positions and three-dimensional (3D) tumor motion, the DMLC motion-tracking algorithm generated MLC leaf sequences for the plans of other respiratory phases. Then, a deformable dose-summed 4D plan was created by merging the leaf sequences of individual phase plans. Individual phase plans, as well as the deformable dose-summed 4D plan, are similar for each patient, indicating that this method is dosimetrically robust to the variations of fractional time spent in respiratory phases on a given 4D CT planning scan. The 4D IMRT treatment-planning method utilizing the DMLC motion-tracking algorithm explicitly accounts for 3D tumor motion and thus hysteresis and nonlinear motion, and is deliverable on a linear accelerator.

Use of MV and kV imager correlation for maintaining continuous real-time 3D internal marker tracking during beam interruptions.

The integration of onboard kV imaging together with a MV electronic portal imaging device (EPID) on linear accelerators (LINAC) can provide an easy to implement real-time 3D organ position monitoring solution for treatment delivery. Currently, real-time MV-kV tracking has only been demonstrated by simultaneous imagining by both MV and kV imaging devices. However, modalities such as step-and-shoot IMRT (SS-IMRT), which inherently contain MV beam interruptions, can lead to loss of target information necessary for 3D localization. Additionally, continuous kV imaging throughout the treatment delivery can lead to high levels of imaging dose to the patient. This work demonstrates for the first time how full 3D target tracking can be maintained even in the presence of such beam interruption, or MV/kV beam interleave, by use of a relatively simple correlation model together with MV-kV tracking. A moving correlation model was constructed using both present and prior positions of the marker in the available MV or kV image to compute the position of the marker on the interrupted imager. A commercially available radiotherapy system, equipped with both MV and kV imaging devices, was used to deliver typical SS-IMRT lung treatment plans to a 4D phantom containing internally embedded metallic markers. To simulate actual lung tumor motion, previous recorded 4D lung patient motion data were used. Lung tumor motion data of five separate patients were inputted into the 4D phantom, and typical SS-IMRT lung plans were delivered to simulate actual clinical deliveries. Application of the correlation model to SS-IMRT lung treatment deliveries was found to be an effective solution for maintaining continuous 3D tracking during 'step' beam interruptions. For deliveries involving five or more gantry angles with 50 or more fields per plan, the positional errors were found to have < or =1 mm root mean squared error (RMSE) in all three spatial directions. In addition to increasing the robustness of MV-kV tracking against beam interruption, it was also found that use of correlation can be an effective way of lowering kV dose to the patient and for increasing kV image quality by reduction of MV scatter interference.

Assessment of setup uncertainty in hypofractionated liver radiation therapy with a breath-hold technique using automatic image registration-based image guidance.

BACKGROUND: Target localization in radiation therapy is affected by numerous sources of uncertainty. Despite measures to minimize the breathing motion, the treatment of hypofractionated liver radiation therapy is further challenged by residual uncertainty coming from involuntary organ motion and daily changes in the shape and location of abdominal organs. To address the residual uncertainty, clinics implement image-guided radiation therapy at varying levels of soft-tissue contrast. This study utilized the treatment records from the patients that have received hypofractionated liver radiation therapy using in-room computed tomography (CT) imaging to assess the setup uncertainty and to estimate the appropriate planning treatment volume (PTV) margins in the absence of in-room CT imaging. METHODS: We collected 917 pre-treatment daily in-room CT images from 69 patients who received hypofractionated radiation therapy to the liver with the inspiration breath-hold technique. For each treatment, the daily CT was initially aligned to the planning CT based on the shape of the liver automatically using a CT-CT alignment software. After the initial alignment, manual shift corrections were determined by visual inspection of the two images, and the corrections were applied to shift the patient to the physician-approved treatment position. Considering the final alignment as the gold-standard setup, systematic and random uncertainties in the automatic alignment were quantified, and the uncertainties were used to calculate the PTV margins. RESULTS: The median discrepancy between the final and automatic alignment was 1.1 mm (0-24.3 mm), and 38% of treated fractions required manual corrections of ≥3 mm. The systematic uncertainty was 1.5 mm in the anterior-posterior (AP) direction, 1.1 mm in the left-right (LR) direction, and 2.4 mm in the superior-inferior (SI) direction. The random uncertainty was 2.2 mm in the AP, 1.9 mm in the LR, and 2.2 mm in the SI direction. The PTV margins recommended to be used in the absence of in-room CT imaging were 5.3 mm in the AP, 3.5 mm in the LR, and 5.1 mm in the SI direction. CONCLUSIONS: Manual shift correction based on soft-tissue alignment is substantial in the treatment of the abdominal region. In-room CT can reduce PTV margin by up to 5 mm, which may be especially beneficial for dose escalation and normal tissue sparing in hypofractionated liver radiation therapy.

Proton beam therapy outcomes for localized unresectable hepatocellular carcinoma.

BACKGROUND AND PURPOSE: This study documents the utilization and efficacy of proton beam therapy (PBT) in western patients with localized unresectable hepatocellular carcinoma (HCC). METHODS AND METHODS: Forty-six patients with HCC, Child-Pugh class of A or B, no prior radiotherapy history, and ECOG performance status 0-2 received PBT at our institution from 2007 to 2016. Radiographic control within the PBT field (local control, LC) and overall survival (OS) were calculated from the start of PBT. RESULTS: Most (83%) patients had Child-Pugh class A. Median tumor size was 6 cm (range, 1.5-21.0 cm); 22% of patients had multiple tumors and 28% had tumor vascular thrombosis. Twenty-five (54%) patients received prior treatment. Median biologically effective dose (BED) was 97.7 GyE (range, 33.6-144 GyE) administered in 15 fractions. Actuarial 2-year LC and OS rates were 81% and 62% respectively; median OS was 30.7 months. Out-of-field intrahepatic failure was the most common site of disease progression. Patients receiving BED ≥90 GyE had a significantly better OS than those receiving BED <90 GyE (49.9 vs. 15.8 months, p = 0.037). A trend toward 2-year LC improvement was observed in patients receiving BED ≥90 GyE compared with those receiving BED <90 GyE (92% vs. 63%, p = 0.096). On multivariate analysis, higher BED (p = 0.023; hazard ratio = 0.308) significantly predicted improved OS. Six (13%) patients experienced acute grade 3 toxicity. CONCLUSIONS: High-dose PBT is associated with high rates of LC and OS for unresectable HCC. Dose escalation may further improve outcomes.

A deliverable four-dimensional intensity-modulated radiation therapy-planning method for dynamic multileaf collimator tumor tracking delivery.

PURPOSE: To develop a deliverable four-dimensional (4D) intensity-modulated radiation therapy (IMRT) planning method for dynamic multileaf collimator (MLC) tumor tracking delivery. METHODS AND MATERIALS: The deliverable 4D IMRT planning method involves aligning MLC leaf motion parallel to the major axis of target motion and translating MLC leaf positions by the difference in the target centroid position between respiratory phases of the 4D CT scan. This method ignores nonlinear respiratory motion and deformation. A three-dimensional (3D) optimal method whereby an IMRT plan on each respiratory phase of the 4D CT scan was independently optimized was used for comparison. For 12 lung cancer patient 4D CT scans, individual phase plans and deformable dose-summed 4D plans using the two methods were created and compared. RESULTS: For each of the individual phase plans, the deliverable method yielded similar isodose distributions and dose-volume histograms. The deliverable and 3D optimal methods yielded statistically equivalent dose-volume metrics for both individual phase plans and 4D plans (p > 0.05 for all metrics compared). The deliverable method was affected by 4D CT artifacts in one case. Both methods were affected by high vector field variations from deformable registration. CONCLUSIONS: The deliverable method yielded similar dose distributions for each of the individual phase plans and statistically equivalent dosimetric values compared with the 3D optimal method, indicating that the deliverable method is dosimetrically robust to the variations of fractional time spent in respiratory phases on a given 4D CT scan. Nonlinear target motion and deformation did not cause significant dose discrepancies.

On the accuracy of a moving average algorithm for target tracking during radiation therapy treatment delivery.

Real-time tumor targeting involves the continuous realignment of the radiation beam with the tumor. Real-time tumor targeting offers several advantages such as improved accuracy of tumor treatment and reduced dose to surrounding tissue. Current limitations to this technique include mechanical motion constraints. The purpose of this study was to investigate an alternative treatment scenario using a moving average algorithm. The algorithm, using a suitable averaging period, accounts for variations in the average tumor position, but respiratory induced target position variations about this average are ignored during delivery and can be treated as a random error during planning. In order to test the method a comparison between five different treatment techniques was performed: (1) moving average algorithm, (2) real-time motion tracking, (3) respiration motion gating (at both inhale and exhale), (4) moving average gating (at both inhale and exhale) and (5) static beam delivery. Two data sets were used for the purpose of this analysis: (a) external respiratory-motion traces using different coaching techniques included 331 respiration motion traces from 24 lung-cancer patients acquired using three different breathing types [free breathing (FB), audio coaching (A) and audio-visual biofeedback (AV)]; (b) 3D tumor motion included implanted fiducial motion data for over 160 treatment fractions for 46 thoracic and abdominal cancer patients obtained from the Cyberknife Synchrony. The metrics used for comparison were the group systematic error (M), the standard deviation (SD) of the systematic error (sigma) and the root mean square of the random error (sigma). Margins were calculated using the formula by Stroom et al. [Int. J. Radiat. Oncol., Biol., Phys. 43(4), 905-919 (1999)]: 2sigma + 0.7sigma. The resultant calculations for implanted fiducial motion traces (all values in cm) show that M and sigma are negligible for moving average algorithm, moving average gating, and real-time tracking (i.e., M and sigma = 0 cm) compared to static beam (M = 0.02 cm and sigma = 0.16 cm) or gated beam delivery (M = -0.05 and 0.16 cm at both exhale and inhale, respectively, and sigma = 0.17 and 0.26 cm at both exhale and inhale, respectively). Moving average algorithm sigma = 0.22 cm has a slightly lower random error than static beam delivery sigma = 0.24 cm, though gating, moving average gating, and real-time tracking have much lower random error values for implanted fiducial motion. Similar trends were also observed for the results using the external respiratory motion data. Moving average algorithm delivery significantly reduces M and sigma compared with static beam delivery. The moving average algorithm removes the nonstationary part of the respiration motion which is also achieved by AV, and thus the addition of the moving average algorithm shows little improvement with AV. Overall, a moving average algorithm shows margin reduction compared with gating and static beam delivery, and may have some mechanical advantages over real-time tracking when the beam is aligned with the target and patient compliance advantages over real-time tracking when the target is aligned to the beam.

An analysis of thoracic and abdominal tumour motion for stereotactic body radiotherapy patients.

An analysis of thoracic and abdominal tumour motion for stereotactic body radiotherapy patients was performed using more than 70 h of tumour motion estimated from the correlation between the external and internal motion for 143 treatment fractions in 42 patients. The tumour sites included lungs (30 patients) and retroperitoneum (12 patients). The overall mean respiratory-induced peak-to-trough distance was 0.48 cm, with individual treatment fraction means ranging from 0.02 to 1.44 cm. The overall mean respiratory period was 3.8 s, with individual treatment fraction means ranging from 2.2 to 6.4 s. In 57 treatment fractions (40%), the mean respiratory-induced peak-to-trough distance was greater than 0.5 cm. In general, tumour motion was predominantly superior-inferior (60% of all the treatment fractions), while anterior-posterior and left-right motion were 22% and 18%, respectively. The motion was predominantly linear, and the overall mean of the first principal component was 94%. However, for motion magnitude, direction and linearity, large variations were observed from patient to patient, fraction to fraction and cycle to cycle.

A monoscopic method for real-time tumour tracking using combined occasional x-ray imaging and continuous respiratory monitoring.

Three major linear accelerator vendors offer gantry-mounted single (monoscopic) x-ray imagers. The use of monoscopic imaging to estimate three-dimensional (3D) target positions has not been fully explored. The purpose of this work is to develop and investigate a robust monoscopic method for real-time tumour tracking, combining occasional x-ray imaging and continuous external respiratory monitoring, and compare this with an established stereoscopic method. Monoscopic estimation of 3D target positions is a two-step procedure. Step (1) is similar to the stereoscopic approach using combined occasional x-ray imaging and real-time external respiratory monitoring, i.e. to establish the correlation between the target coordinates T(x, y, z) and the external respiratory signal (R) (sECM: stereoscopic external correlation model). However, in monoscopic estimation, the correlation between the two coordinates (xp, yp) projected on the imager plane and the external respiratory signal (mECM: monoscopic external correlation model) is established. With only a single projection, the component of the 3D target position, which is along the x-ray imaging direction, is unresolved. Therefore, step (2) is used to estimate the unresolved component (z( parallel)) by building a correlation model between the unresolved component and the two other components projected on the imager (ICM: internal correlation model) with a prior 3D target trajectory that may be obtained by 4DCT, MV/kV imaging or 4DCBCT. At the time of prediction, (xp, yp) are estimated from (R) using the correlation model in step (1), and then z( parallel) is estimated from the estimated (xp, yp) using the correlation model in step (2). The performance of the proposed method was evaluated under various model update intervals and compared with the stereoscopic estimation method using 160 tumour trajectory and external respiratory motion data recorded at 25 Hz from 46 thoracic and abdominal cancer patients who underwent hypofractionated stereotactic radiotherapy by a CyberKnife system. The precision of the input data used in this study to represent tumour motion was assessed using x-ray imaging to be 1.5 +/- 0.8 mm. Monoscopic imaging every 30/60 s with updating ICM every 120/180 s can estimate target positions with a 1 mm root-mean-square error (RMSE) for 63/53% or a 2 mm RMSE for 93/91%, respectively. In contrast, stereoscopic x-ray imaging every 30/60 s can estimate target motion within a 1 mm RMSE for 72/58% or a 2 mm RMSE for 95/92%, respectively. The overall 3D error of the monoscopic estimation is approximately 10% higher than comparable stereoscopic imaging methods when the period between imaging is 1 s or more, and 40% higher for continuous imaging. The promising result may be explained by the fact that superior/inferior motion-the major axis of tumour motion-is fully resolved even in the monoscopic view for coplanar treatments, and tumour motion in each dimension is relatively well correlated.

Development and preliminary evaluation of a prototype audiovisual biofeedback device incorporating a patient-specific guiding waveform.

The aim of this research was to investigate the effectiveness of a novel audio-visual biofeedback respiratory training tool to reduce respiratory irregularity. The audiovisual biofeedback system acquires sample respiratory waveforms of a particular patient and computes a patient-specific waveform to guide the patient's subsequent breathing. Two visual feedback models with different displays and cognitive loads were investigated: a bar model and a wave model. The audio instructions were ascending/descending musical tones played at inhale and exhale respectively to assist in maintaining the breathing period. Free-breathing, bar model and wave model training was performed on ten volunteers for 5 min for three repeat sessions. A total of 90 respiratory waveforms were acquired. It was found that the bar model was superior to free breathing with overall rms displacement variations of 0.10 and 0.16 cm, respectively, and rms period variations of 0.77 and 0.33 s, respectively. The wave model was superior to the bar model and free breathing for all volunteers, with an overall rms displacement of 0.08 cm and rms periods of 0.2 s. The reduction in the displacement and period variations for the bar model compared with free breathing was statistically significant (p = 0.005 and 0.002, respectively); the wave model was significantly better than the bar model (p = 0.006 and 0.005, respectively). Audiovisual biofeedback with a patient-specific guiding waveform significantly reduces variations in breathing. The wave model approach reduces cycle-to-cycle variations in displacement by greater than 50% and variations in period by over 70% compared with free breathing. The planned application of this device is anatomic and functional imaging procedures and radiation therapy delivery.

Guiding curve based on the normal breathing as monitored by thermocouple for regular breathing.

Adapting radiation fields to a moving target requires information continuously on the location of internal target by detecting it directly or indirectly. The aim of this study is to make the breathing regular effectively with minimizing stress to the patient. A system for regulating patient's breath consists of a respiratory monitoring mask (ReMM), a thermocouple module, a screen, inner earphones, and a personal computer. A ReMM with thermocouple was developed previously to measure the patient's respiration. A software was written in LabView 7.0 (National Instruments, TX), which acquires respiration signal and displays its pattern. Two curves are displayed on the screen: One is a curve indicating the patient's current breathing pattern; the other is a guiding curve, which is iterated with one period of the patient's normal breathing curve. The guiding curves were acquired for each volunteer before they breathed with guidance. Ten volunteers participated in this study to evaluate this system. A cycle of the representative guiding curve was acquired by monitoring each volunteer's free breathing with ReMM and was then generated iteratively. The regularity was compared between a free breath curve and a guided breath curve by measuring standard deviations of amplitudes and periods of two groups of breathing. When the breathing was guided, the standard deviation of amplitudes and periods on average were reduced from 0.0029 to 0.00139 (arbitrary units) and from 0.359 s to 0.202 s, respectively. And the correlation coefficients between breathing curves and guiding curves were greater than 0.99 for all volunteers. The regularity was improved statistically when the guiding curve was used.

Geometric uncertainty of 2D projection imaging in monitoring 3D tumor motion.

The purpose of this study was to investigate the accuracy of two-dimensional (2D) projection imaging methods in three-dimensional (3D) tumor motion monitoring. Many commercial linear accelerator types have projection imaging capabilities, and tumor motion monitoring is useful for motion inclusive, respiratory gated or tumor tracking strategies. Since 2D projection imaging is limited in its ability to resolve the motion along the imaging beam axis, there is unresolved motion when monitoring 3D tumor motion. From the 3D tumor motion data of 160 treatment fractions for 46 thoracic and abdominal cancer patients, the unresolved motion due to the geometric limitation of 2D projection imaging was calculated as displacement in the imaging beam axis for different beam angles and time intervals. The geometric uncertainty to monitor 3D motion caused by the unresolved motion of 2D imaging was quantified using the root-mean-square (rms) metric. Geometric uncertainty showed interfractional and intrafractional variation. Patient-to-patient variation was much more significant than variation for different time intervals. For the patient cohort studied, as the time intervals increase, the rms, minimum and maximum values of the rms uncertainty show decreasing tendencies for the lung patients but increasing for the liver and retroperitoneal patients, which could be attributed to patient relaxation. Geometric uncertainty was smaller for coplanar treatments than non-coplanar treatments, as superior-inferior (SI) tumor motion, the predominant motion from patient respiration, could be always resolved for coplanar treatments. Overall rms of the rms uncertainty was 0.13 cm for all treatment fractions and 0.18 cm for the treatment fractions whose average breathing peak-trough ranges were more than 0.5 cm. The geometric uncertainty for 2D imaging varies depending on the tumor site, tumor motion range, time interval and beam angle as well as between patients, between fractions and within a fraction.

Does Unintentional Splenic Radiation Predict Outcomes After Pancreatic Cancer Radiation Therapy?

PURPOSE: To determine whether severity of lymphopenia is dependent on radiation dose and fractional volume of spleen irradiated unintentionally during definitive chemoradiation (CRT) in patients with locally advanced pancreatic cancer (LAPC). METHODS: 177 patients with LAPC received induction chemotherapy (mainly gemcitabine-based regimens) followed by CRT (median 50.4 Gy with concurrent capecitabine) from January 2006 to December 2012. Absolute lymphocyte count (ALC) was recorded at baseline, before CRT, and 2 to 10 weeks after CRT. Splenic dose-volume histogram (DVH) parameters were reported as mean splenic dose (MSD) and percentage of splenic volume receiving at least 5- (V5), 10- (V10), 15- (V15), and 20-Gy (V20) dose. Overall survival (OS) was analyzed with use of the Cox model, and development of post-CRT severe lymphopenia (ALC <0.5 K/UL) was assessed by multivariate logistic regression with use of baseline and treatment factors. RESULTS: The median post-CRT ALC (0.68 K/UL; range, 0.13-2.72) was significantly lower than both baseline ALC (1.42 K/UL; range, 0.34-3.97; P<.0001) and pre-CRT ALC (1.32 K/UL, range 0.36-4.82; P<.0001). Post-CRT ALC <0.5 K/UL was associated with inferior OS on univariate analysis (median, 11.1 vs 15.3 months; P=.01) and multivariate analysis (hazard ratio = 1.66, P=.01). MSD (9.8 vs 6 Gy, P=.03), median V10 (32.6 vs 16%, P=.04), V15 (23.2 vs 9.5%, P=.03), and V20 (15.4 vs 4.6%, P=.02) were significantly higher in patients with severe lymphopenia than in those without. On multivariate analysis, postinduction lymphopenia (P<.001; odds ratio [OR] = 5.25) and MSD (P=.002; OR= 3.42) were independent predictors for the development of severe post-CRT lymphopenia. CONCLUSION: Severe post-CRT lymphopenia is an independent predictor of poor OS in LAPC patients receiving CRT. Higher splenic doses increase the risk for the development of severe post-CRT lymphopenia. When clinically indicated, assessment of splenic DVHs before the acceptance of treatment plans may minimize the risk of severe post-CRT lymphopenia.

Focal Radiation Therapy Dose Escalation Improves Overall Survival in Locally Advanced Pancreatic Cancer Patients Receiving Induction Chemotherapy and Consolidative Chemoradiation.

PURPOSE: To review outcomes of locally advanced pancreatic cancer (LAPC) patients treated with dose-escalated intensity modulated radiation therapy (IMRT) with curative intent. METHODS AND MATERIALS: A total of 200 patients with LAPC were treated with induction chemotherapy followed by chemoradiation between 2006 and 2014. Of these, 47 (24%) having tumors >1 cm from the luminal organs were selected for dose-escalated IMRT (biologically effective dose [BED] >70 Gy) using a simultaneous integrated boost technique, inspiration breath hold, and computed tomographic image guidance. Fractionation was optimized for coverage of gross tumor and luminal organ sparing. A 2- to 5-mm margin around the gross tumor volume was treated using a simultaneous integrated boost with a microscopic dose. Overall survival (OS), recurrence-free survival (RFS), local-regional and distant RFS, and time to local-regional and distant recurrence, calculated from start of chemoradiation, were the outcomes of interest. RESULTS: Median radiation dose was 50.4 Gy (BED = 59.47 Gy) with a concurrent capecitabine-based (86%) regimen. Patients who received BED >70 Gy had a superior OS (17.8 vs 15.0 months, P=.03), which was preserved throughout the follow-up period, with estimated OS rates at 2 years of 36% versus 19% and at 3 years of 31% versus 9% along with improved local-regional RFS (10.2 vs 6.2 months, P=.05) as compared with those receiving BED ≤70 Gy. Degree of gross tumor volume coverage did not seem to affect outcomes. No additional toxicity was observed in the high-dose group. Higher dose (BED) was the only predictor of improved OS on multivariate analysis. CONCLUSION: Radiation dose escalation during consolidative chemoradiation therapy after induction chemotherapy for LAPC patients improves OS and local-regional RFS.

Immobilization effect of air-injected blanket (AIB) for abdomen fixation.

A new device for reducing the amplitude of breathing motion by pressing a patient's abdomen using an air-injected blanket (AIB) for external beam radiation treatments has been designed and tested. The blanket has two layers sealed in all four sides similar to an empty pillow made of urethane. The blanket is spread over the patient's abdomen with both ends of the blanket fixed to the sides of the treatment couch or a baseboard. The inner side, or patient side, of the blanket is thinner and expands more than the outer side. When inflated, the blanket balloons and effectively puts an even pressure on the patient's abdomen. Fluoroscopic observation was performed to verify the usefulness of AIB for patients with lung, breast cancer, or abdominal cancers. Internal organ movement due to breathing was monitored and measured with and without AIB. With the help of AIB, the average range of diaphragm motion was reduced from 2.6 to 0.7 cm in the anterior-to-posterior direction and from 2.7 to 1.3 cm in the superior-to-inferior direction. The motion range in the right-to-left direction was negligible, for it was less than 0.5 cm. These initial testing demonstrated that AIB is useful for reducing patients' breathing motion in the thoracic and abdominal regions comfortably and consistently.

Internal respiratory surrogate in multislice 4D CT using a combination of Fourier transform and anatomical features.

PURPOSE: The purpose of this study was to develop a novel algorithm to create a robust internal respiratory signal (IRS) for retrospective sorting of four-dimensional (4D) computed tomography (CT) images. METHODS: The proposed algorithm combines information from the Fourier transform of the CT images and from internal anatomical features to form the IRS. The algorithm first extracts potential respiratory signals from low-frequency components in the Fourier space and selected anatomical features in the image space. A clustering algorithm then constructs groups of potential respiratory signals with similar temporal oscillation patterns. The clustered group with the largest number of similar signals is chosen to form the final IRS. To evaluate the performance of the proposed algorithm, the IRS was computed and compared with the external respiratory signal from the real-time position management (RPM) system on 80 patients. RESULTS: In 72 (90%) of the 4D CT data sets tested, the IRS computed by the authors' proposed algorithm matched with the RPM signal based on their normalized cross correlation. For these data sets with matching respiratory signals, the average difference between the end inspiration times (Δtins) in the IRS and RPM signal was 0.11 s, and only 2.1% of Δtins were more than 0.5 s apart. In the eight (10%) 4D CT data sets in which the IRS and the RPM signal did not match, the average Δtins was 0.73 s in the nonmatching couch positions, and 35.4% of them had a Δtins greater than 0.5 s. At couch positions in which IRS did not match the RPM signal, a correlation-based metric indicated poorer matching of neighboring couch positions in the RPM-sorted images. This implied that, when IRS did not match the RPM signal, the images sorted using the IRS showed fewer artifacts than the clinical images sorted using the RPM signal. CONCLUSIONS: The authors' proposed algorithm can generate robust IRSs that can be used for retrospective sorting of 4D CT data. The algorithm is completely automatic and requires very little processing time. The algorithm is cost efficient and can be easily adopted for everyday clinical use.

IMRT treatment planning on 4D geometries for the era of dynamic MLC tracking.

The problem addressed here was to obtain optimal and deliverable dynamic multileaf collimator (MLC) leaf sequences from four-dimensional (4D) geometries for dynamic MLC tracking delivery. The envisaged scenario was where respiratory phase and position information of the target was available during treatment, from which the optimal treatment plan could be further adapted in real time. A tool for 4D treatment plan optimization was developed that integrates a commercially available treatment planning system and a general-purpose optimization system. The 4D planning method was applied to the 4D computed tomography planning scans of three lung cancer patients. The optimization variables were MLC leaf positions as a function of monitor units and respiratory phase. The objective function was the deformable dose-summed 4D treatment plan score. MLC leaf motion was constrained by the maximum leaf velocity between control points in terms of monitor units for tumor motion parallel to the leaf travel direction and between phases for tumor motion parallel to the leaf travel direction. For comparison and a starting point for the 4D optimization, three-dimensional (3D) optimization was performed on each of the phases. The output of the 4D IMRT planning process is a leaf sequence which is a function of both monitor unit and phase, which can be delivered to a patient whose breathing may vary between the imaging and treatment sessions. The 4D treatment plan score improved during 4D optimization by 34%, 4%, and 50% for Patients A, B, and C, respectively, indicating 4D optimization generated a better 4D treatment plan than the deformable sum of individually optimized phase plans. The dose-volume histograms for each phase remained similar, indicating robustness of the 4D treatment plan to respiratory variations expected during treatment delivery. In summary, 4D optimization for respiratory phase-dependent treatment planning with dynamic MLC motion tracking improved the 4D treatment plan score by 4-50% compared with 3D optimization. The 4D treatment plans had leaf sequences that varied from phase to phase to account for anatomic motion, but showed similar target dose distributions in each phase. The current method could in principle be generalized for use in offline replanning between fractions or for online 4D treatment planning based on 4D cone-beam CT images. Computation time remains a challenge.