Clinical benefits of new immobilization system for hypofractionated radiotherapy of intrahepatic hepatocellular carcinoma by helical tomotherapy

Medical Dosimetry ] (2016) ]]]–]]]

Medical Dosimetry journal homepage: www.meddos.org

Clinical benefits of new immobilization system for hypofractionated radiotherapy of intrahepatic hepatocellular carcinoma by helical tomotherapy Yong Hu, B.S., Yong-Kang Zhou, M.S., Yi-Xing Chen, M.D., Shi-Ming Shi, M.S., and Zhao-Chong Zeng, M.D., Ph.D. Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China

A R T I C L E I N F O

A B S T R A C T

Article history: Received 19 February 2016 Accepted 30 October 2016

Objective: A comprehensive clinical evaluation was conducted, assessing the Body Pro-Lok immobilization and positioning system to facilitate hypofractionated radiotherapy of intrahepatic hepatocellular carcinoma (HCC), using helical tomotherapy to improve treatment precision. Methods: Clinical applications of the Body Pro-Lok system were investigated (as above) in terms of interfractional and intrafractional setup errors and compressive abdominal breath control. To assess interfractional setup errors, a total of 42 patients who were given 5 to 20 fractions of helical tomotherapy for intrahepatic HCC were analyzed. Overall, 15 patients were immobilized using simple vacuum cushion (group A), and the Body Pro-Lok system was used in 27 patients (group B), performing megavoltage computed tomography (MVCT) scans 196 times and 435 times, respectively. Pretreatment MVCT scans were registered to the planning kilovoltage computed tomography (KVCT) for error determination, and group comparisons were made. To establish intrafractional setup errors, 17 patients with intrahepatic HCC were selected at random for immobilization by Body Pro-Lok system, undergoing MVCT scans after helical tomotherapy every week. A total of 46 MVCT re-scans were analyzed for this purpose. In researching breath control, 12 patients, randomly selected, were immobilized by Body Pro-Lok system and subjected to 2-phase 4-dimensional CT (4DCT) scans, with compressive abdominal control or in freely breathing states, respectively. Respiratory-induced liver motion was then compared. Results: Mean interfractional setup errors were as follows: (1) group A: X, 2.97 ⫾ 2.47 mm; Y, 4.85 ⫾ 4.04 mm; and Z, 3.77 ⫾ 3.21 mm; pitch, 0.66 ⫾ 0.621; roll, 1.09 ⫾ 1.061; and yaw, 0.85 ⫾ 0.821; and (2) group B: X, 2.23 ⫾ 1.79 mm; Y, 4.10 ⫾ 3.36 mm; and Z, 1.67 ⫾ 1.91 mm; pitch, 0.45 ⫾ 0.381; roll, 0.77 ⫾ 0.631; and yaw, 0.52 ⫾ 0.491. Between-group differences were statistically significant in 6 directions (p o 0.05). Mean intrafractional setup errors with use of the Body Pro-Lok system were as follows: X, 0.41 ⫾ 0.46 mm; Y, 0.86 ⫾ 0.80 mm; Z, 0.33 ⫾ 0.44 mm; and roll, 0.12 ⫾ 0.191. Mean liverinduced respiratory motion determinations were as follows: (1) abdominal compression: X, 2.33 ⫾ 1.22 mm; Y, 5.11 ⫾ 2.05 mm; Z, 2.13 ⫾ 1.05 mm; and 3D vector, 6.22 ⫾ 1.94 mm; and (2) free breathing: X, 3.48 ⫾ 1.14 mm; Y, 9.83 ⫾ 3.00 mm; Z, 3.38 ⫾ 1.59 mm; and 3D vector, 11.07 ⫾ 3.16 mm. Between-group differences were statistically different in 4 directions (p o 0.05). Conclusions: The Body Pro-Lok system is capable of improving interfractional and intrafractional setup accuracy and minimizing tumor movement owing to respirations in patients with intrahepatic HCC during hypofractionated helical tomotherapy. & 2016 American Association of Medical Dosimetrists.

Keywords: Helical tomotherapy Abdominal compression Setup errors Intrahepatic carcinoma

Background Reprint requests to: Zhao-Chong Zeng, Department of Radiation Oncology, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China. E-mail: [email protected] http://dx.doi.org/10.1016/j.meddos.2016.10.005 0958-3947/Copyright Ó 2016 American Association of Medical Dosimetrists

Liver cancer is much more common in men than in women. In men, it is the second leading cause of cancer death in less developed countries and worldwide. In more developed countries,

Y. Hu et al. / Medical Dosimetry ] (2016) ]]]–]]]

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it is the sixth leading cause of cancer death among men. An estimated 782,500 cases of newly diagnosed liver cancer and 745,500 related deaths occurred internationally during 2012, with China alone accounting for approximately 50% of case totals and deaths.1 Most (70% to 90%) primary liver cancers globally are hepatocellular carcinoma (HCC).1 Radiotherapy has been a mainstay of treatment for locally advanced and medically unresectable HCC.2,3 Stereotactic body radiotherapy (SBRT) is a safe and effective alternative treatment in patients who are ineligible for ablation/resection of intrahepatic HCC.4-7 Current advancements in radiotherapeutic precision have underscored the importance of patient immobilization, target positioning , and organ motion control for treatment success, particularly in complex cases of intrahepatic HCC requiring higher doses. During normal breathing, liver movement ranges from 5 to 50 mm.8,9 It is, thus, imperative to limit such movement and enhance target positioning through improved and reproducible patient immobilization.10 Patient comfort, safety, and benefit are also concerns of radiotherapy oncologists and therapists in prior computed tomography (CT) simulations. The Body Pro-Lok system (CIVCO Medical Solutions, Coralville, IA) provides an easy-to-use modular framework suitable for SBRT setup intricacies, offering respiratory belt and plate options to help control patient breathing through abdominal compression (AC). AC has been widely used in radiotherapy to reduce liver respiratory motion, and for most patients, motion of liver tumors is significantly reduced in 3 dimensions by this means.10,11

Gutiérrez et al.12 have proven the clinical use of the Body ProLok system in liver SBRT, but only in terms of interfractional setup error. This report details our comprehensive evaluation of the Body Pro-Lok system in conjunction with megavoltage CT (MVCT) for hypofractionated helical tomotherapy of intrahepatic HCC.

Methods and Materials Patients All patients studied underwent treatment in our department between January 2012 and December 2015. Each had Child-Pugh A liver function and Karnofsky performance status 4 80. On average, 15 fractions (range: 5 to 20) of helical tomotherapy were delivered, with a single-dose range of 2.5 to 10 Gy. Demographics and clinical characteristics of patients studied for interfractional setup errors are shown in Table 1. Overall, 42 patients (men, 37; women, 5; age range: 32 to 80 years) with intrahepatic HCC were selected at random for immobilization by either simple vacuum cushion (group A, n ¼ 15) or Body ProLok system (group B, n ¼ 27), performing pretreatment MVCT scans 196 and 435 times, respectively. Regarding intrafractional setup errors, 17 patients with intrahepatic HCC immobilized using Body Pro-Lok system were selected at random for weekly MVCT scanning after helical tomotherapy, assessing a total of 46 MVCT re-scans for intrafractional setup accuracy. To evaluate breath control, 12 patients (free of cardiopulmonary disease) immobilized using Body Pro-Lok system were selected at random for 2-phase 4-dimensional CT (4D-CT) scans in abdominal compressive and free-breathing states. Patients with colostomies and ascites were excluded. Patient breathing was kept regular after a training session under AC. This study was approved by the ethics committee of Zhongshan hospital, Fudan university (Ethics approved no: 2011-235), and informed consent was obtained.

Table 1 Patient demographics and clinical characteristics Group A (n ¼ 15)

Group B (n ¼ 27)

14 (93.3%) 1 (6.7%)

23 (85.2%) 4 (14.8%)

7 (46.7%) 8 (53.3%)

14 (51.9%) 13 (48.1%)

10 (66.7%) 2 (13.3%) 3 (20.0%)

17 (63.0%) 6 (22.2%) 4 (14.8%)

Intrahepatic lesions, n (%) Solitary Multiple nodules

9 (60.0%) 6 (40.0%)

16 (59.3%) 11 (40.7%)

Diameter, n (%) r 5 cm 4 5 cm

8 (53.3%) 7 (46.7%)

16 (59.3%) 11 (40.7%)

Tumor location n (%) Left lobe of liver Right lobe of liver Left and right lobes

5 (33.3%) 9 (60.0%) 1 (6.7%)

7 (25.9%) 15 (55.6%) 5 (18.5%)

5 (33.3%) 10 (66.7%)

9 (33.3%) 18 (66.7%)

9 (60.0%) 4 (26.7%) 2 (13.3%)

18 (66.7%) 5 (18.5%) 4 (14.8%)

6 (40.0%) 9 (60.0%)

10 (37.0%) 17 (63.0%)

Sex, n (%) Men Women Age, n (%) r 60 years old 4 60 years old BMI, n (%) r 24 24 to 27 4 27

Postoperative recurrence, n (%) Yes No PTV volume, n (%) r 300 cc 300 to 1000 cc 4 1000 cc Normal liver volume, n (%) r 1000 cc 4 1000 cc Image registration distance, mean ⫾ SD cm SD ¼ standard deviation.

p Value 0.435

0.747

0.750

0.963

0.710

0.558

1.000

0.827

0.850

12.42 ⫾ 5.88

10.84 ⫾ 4.34

0.328

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Data definition and statistical analysis Setup errors were assessed through X (left-right [LR]), Y (cranial-caudal [CC]), and Z (anterior-posterior [AP]) axial measurements, as well as pitch (CC inclination), roll (rotation in gantry circling motion), and yaw (CC rotation in horizontal plane) determinations. Likewise, respiratory motions of liver were gauged by X, Y, and Z axial values (as above). The 3D motion vector for center of tumor was calculated as follows: V ¼ (△X2 þ △Y2 þ △Z2)1/2. All measurements were expressed as mean ⫾ standard deviation. Analysis of variance (ANOVA) was applied to intrafraction setup errors and respiratory-induced liver motions, using Student's t-test to compare interfractional setup errors by group (A vs B). Patient demographics and clinical characteristics were subjected to chi-square (χ2) test. All calculations relied on standard software (SPSS v15.0 for Windows; SPSS Inc, Chicago, IL), setting statistical significance at p o 0.05.

Results

Fig. Body Pro-Lok system (CIVCO), used in conjunction with helical tomotherapy, includes carbon fiber platform, customizable vacuum cushion, abdominal compression bridge, respiratory plate, and knee and foot sponges. (Color version of figure is available online.)

Interfractional setup errors As shown in Table 1, patient demographics and clinical characteristics did not differ significantly by group (p 4 0.05). Regions of interest for MVCT scanning areas (which may significantly affect pitch and yaw values) were 12.42 ⫾ 5.88 cm in group A and 10.84 ⫾ 4.34 cm in group B, (p ¼ 0.328). Interfractional setup errors were anisotropic, and as shown in Table 2, differences were manifested in 6 directions. Respective values of pitch and yaw before manual adjustment (i.e., presetting to zero) were 0.66 ⫾ 0.621and 0.85 ⫾0.821 for group A and were 0.45 ⫾ 0.381 and 0.52 ⫾ 0.491 for group B. Pitch and yaw values of group A were significantly greater when compared with group B (p o 0.001). Better interfractional immobilization effect was observed in group B (BodyPro-Lok system: X, 2.23 ⫾ 1.79 mm; Y, 4.10 ⫾ 3.36 mm; Z, 1.67 ⫾ 1.91 mm; and roll, 0.77 ⫾ 0.631), compared with group A (simple vacuum cushion: X, 2.97 ⫾ 2.47 mm; Y, 4.85 ⫾ 4.04 mm; Z, 3.77 ⫾ 3.21 mm; and roll, 1.09 ⫾ 1.061). Statistically significant differences were confirmed for X (p o 0.001), Y (p o 0.05), Z (p o 0.001), and roll (p o 0.001) determinants.

Body Pro-Lok system The Body Pro-Lok system (provided by CIVCO) used in this study consists of a lightweight carbon fiber platform, a patient customizable vacuum cushion, an AC bridge, a respiratory plate, and knee and foot sponges (Fig.). Additional accessories, such as a respiratory belt, forehead-bracing bridge, patient handgrips, and a shoulder-restraint bridge are also available. Using the Body Pro-Lok system, patients were immobilized and localized in supine position, with arms raised to foreheads during CT simulation, MVCT scanning, and each treatment fraction. Patients would switch to forced shallow breathing for satisfactory AC.13 Assessing interfractional and intrafractional setup errors Pretreatment and posttreatment region-of-interest MVCT scans were performed in fine (2-mm slice), normal (4-mm slice), or coarse (6-mm slice) mode, largely depending on tumor size and treatment fractions stipulated in our department. MVCT images were registered to planning kilovoltage CT images. Owing to current incapability to correct pitch and yaw directions of helical tomotherapy, these 2 parameters were preset to zero before manual adjustment. Roll corrections were achieved by automatic gantry rotation.12 Automatic lateral, vertical, longitudinal, and roll movements were initiated by the radiation therapist (resetting panel button), once corrections were verified by the radiation oncologist before radiation delivery. Interfraction and intrafraction setup errors in 3D translational, pitch, yaw, and roll directions were obtained and analyzed.

Intrafractional setup errors

4D-CT imaging of liver displacement

Intrafractional setup errors calculated for each translational dimension and for roll are summarized in Table 3. Based on bony structure correlation, overall mean setup deviations were as follows: X, 0.39 ⫾ 0.41 mm (range: 0 to 2.10 mm); Y, 0.68 ⫾ 0.66 mm (range: 0 to 2.60 mm); Z, 0.22 ⫾ 0.32 mm (range: 0 to 1.50 mm); and roll, 0.08 ⫾ 0.121 (range: 01 to 0.401). Based on target structure correlation, overall mean setup deviations were as follows: X, 0.41 ⫾ 0.46 mm (range: 0 to 2.10 mm); Y, 0.86 ⫾ 0.80 mm (range: 0 to 2.60 mm); Z, 0.33 ⫾ 0.44 mm (range: 0 to 2.00 mm); and roll 0.12 ⫾ 0.191 (range, 01 to 1.001). Intrafractional setup errors (Z 1 mm) in X, Y, and Z axial directions were 3-, 12-, and 2-fold in bony correlation and 5-, 17-, and 5-fold in target correlation, respectively. Roll error (4 0.31) was 2- and 4-fold in bony and target correlations. CC displacements of bone and liver were in same direction, which was cranial. Intrafractional setup errors based on target structure correlation were slightly greater

A big-bore scanner (Somatom Sensation Open CT; Siemens, Erlangen, Germany) was engaged for 4D-CT imaging. Patients were immobilized by Body Pro-Lok system, with or without AC. With satisfactory AC (respiratory cycle 4 5 seconds), the Res Low Breath Rate (X-ray tube setting: 120 kV, 400 mAs; pitch, 0.1; 3-mm reconstructed thickness) scanning mode was applied. The phase of respiratory wave was manually adjusted and confirmed by CT-simulation technician before 4DCT image reconstruction. 4D-CT images generated from respiratory raw data were sorted into 10 series of CT images (CT0-CT90) according to respiratory cycle, with CT0 as end-inspiration phase and CT50 as end-expiration phases.14 Datasets of 4DCT scans were then transferred to treatment planning software (TPS) (Oncentra v4.3; Nucletron Corp, Veenendaal, The Netherlands), with all liver contours being drawn by an experienced observer (H.Y.) and confirmed by a single physician (Y.K.Z.). Liver contours were delineated at all phases of 4D-CT images and finally copied manually to a single plan. Relative hepatic coordinates were automatically generated to calculate respiratory motions of the liver in various axial directions, obtaining a range of liver respiratory motion from center of tumor in each coordinate. Maximum range of liver motion in any axis represented the difference between corresponding maximum and minimum values. Table 2 Comparison of interfractional setup errors in 6 directions by group Group

X

Y

Z

Roll

Pitch

Yaw

Group A (n ¼ 196) Group B (n ¼ 435) F value T value p Value

2.97 ⫾ 2.47 2.23 ⫾ 1.79 16.602 4.254 o 0.001

4.85 ⫾ 4.04 4.10 ⫾ 3.36 8.124 2.410 0.016

3.77 ⫾ 3.21 1.67 ⫾ 1.91 152.645 10.189 o 0.001

1.09 ⫾ 1.06 0.77 ⫾ 0.63 48.653 4.783 o 0.001

0.66 ⫾ 0.62 0.45 ⫾ 0.38 61.587 5.117 o 0.001

0.85 ⫾ 0.82 0.52 ⫾ 0.49 55.580 6.358 o 0.001

All axial (X,Y,Z) measurements expressed in mm; roll, pitch, and yaw expressed as degree.

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4 Table 3 Intrafractional setup errors by registration method Registration method

X

Y

Z

Roll

Bony (n ¼ 46) Target (n ¼ 46) Maximum (bony) Maximum (target) F value p Value

0.39 ⫾ 0.41 0.41 ⫾ 0.46 2.10 2.10 0.082 0.775

0.68 ⫾ 0.66 0.86 ⫾ 0.80 2.60 2.60 1.377 0.244

0.22 ⫾ 0.32 0.33 ⫾ 0.44 1.50 2.00 1.686 0.197

0.08 ⫾ 0.12 0.12 ⫾ 0.19 0.40 1.00 0.980 0.325

All axial (X,Y,Z) measurements expressed in mm; roll expressed as degree.

than those based on bony structure correlation, but the 2 methods did not differ significantly (p 4 0.05). Breath control Table 4 provides a detailed listing of respiratory amplitude data for the 12 patients studied in free-breathing states and under AC. Positioning of AC was dictated by intrahepatic tumor location (subxyphoid, 6; caudal region [between xyphoid and umbilicus], 6). Breath amplitude was effectively reduced in all patients by AC, especially in CC motion. Median, minimal, and maximal values of excursions under AC were 5.11, 2.00, and 8.80 mm for CC motion; 2.33, 0.90, and 5.30 mm for LR motion; 2.13, 0.50, and 4.10 mm for AP motion; and 6.22, 2.34, and 9.43 mm in 3D vector, respectively. In CC direction, 50.00% of excursions with free breathing were 4 10 mm, whereas 41.67% of excursions with AC were o 5 mm; and a 43.81% reduction in 3D vector respiratory motion was achievable using AC. Respiratory-induced CC liver motion in the freebreathing state was significantly more than that seen with AC (p o 0.001, combined F test). Significant differences (p o 0.05) in LR and AP control were also documented for the 2 breathing states.

Discussion Given that total doses are delivered in only a few fractions, tumor positioning is critical in hypofractionated helical tomotherapy of intrahepatic HCC. Specialized immobilization systems, such as SBRT body frames, are thus commonly used to improve setup accuracy and reproducibility.15 Cao et al.16 have previously examined rotational errors in setup of SBRT for liver cancer, comparing errors of stereotactic body frame use (pitch, 0.06 ⫾ 0.681; roll, 0.29 ⫾ 0.621; and yaw 0.24 ⫾ 0.611) with random errors (pitch, 0.801; roll, 1.051; and yaw, 0.611). Gutiérrez et al.12 have also studied interfractional setup errors of the Body Pro-Lok system for liver SBRT using helical tomotherapy. Mean interfractional setup errors (⫾ standard deviation) were 0.9 ⫾ 3.1 mm, 1.2 ⫾ 5.5 mm, and 6.5 ⫾ 2.6 mm for lateral (IEC-X), longitudinal (IEC-Y), and vertical (IEC-Z) variations in their study, respectively. Maximum CC motion was 17.1 mm. When compared with the

stereotactic body frame, combined use of the Body Pro-Lok system and the MVCT of tomotherapy helped to minimize interfractional setup error in image-guided SBRT and to improve treatment accuracy. In our study, mean interfractional setup errors were as follows: X, 2.23 ⫾ 1.79 mm; Y, 4.10 ⫾ 3.36 mm; Z, 1.67 ⫾ 1.91 mm; pitch, 0.45 ⫾ 0.381; roll, 0.77 ⫾ 0.631; and yaw, 0.52 ⫾ 0.491. Mean intrafractional setup errors with use of the Body Pro-Lok system were as follows: X, 0.41 ⫾ 0.46 mm; Y, 0.86 ⫾ 0.80 mm; Z, 0.33 ⫾ 0.44 mm; and roll, 0.12 ⫾ 0.191. Intrafractional setup error o 1 mm was achieved for most patients in 3D translational directions. The CC displacements of bone and liver were both cranial, which we attribute to body relaxation under AC. Intrafractional setup error has assumed increasing importance in the setting of intensity-modulated radiation therapy with image-guided radiation therapy, because interfractional setup error can be adjusted. Use of the Body Pro-Lok system for radiotherapy of intrahepatic HCC proved far superior to a simple vacuum cushion for immobilization and positioning, in addition to outperforming the SBRT body frame as noted earlier. Setup times for the Body Pro-Lok system and the simple vacuum cushion are comparable (3 to 5 minutes). The therapist had sufficient chance to prepare the Body Pro-Lok board and accessories as patients entered treatment rooms and were readied for therapy. Hawkins et al.17 have examined residual error in liver positioning using kV cone-beam CT for high-precision liver cancer radiation therapy. Liver position in radiation therapy guided by MV orthogonal imaging was within 5 mm of planned position in most patients. Patients were positioned supine, with arms above the head in either a chest board (MedTec Inc, Orange City, IA) or in an evacuated immobilization bag (Vac-Lok; Bionix Medical Technologies, Toledo, OH), and with a leg immobilizer beneath the knees; active breathing control was used to immobilize the liver during planning CT scans and treatment. Because the Body Pro-Lok board could not be moved in pitch and yaw during our delivery of helical tomotherapy, the opportunity for treatment error remained. However, satisfactory target correction was confirmed by radiation clinician and therapist. The lower the 2 values are at baseline, before manually resetting to zero, the better the registration effect would be. In using the Body Pro-Lok system, pitch and yaw values were reduced from 0.66 ⫾ 0.621 to 0.45 ⫾ 0.381 and from 0.85 ⫾ 0.821 to 0.52 ⫾ 0.491, respectively. These values were lower than those reported by Cao et al.,16 indicating that the Body Pro-Lok system does improve correctional precision and reduce residual treatment error in interfractional delivery of image-guided radiotherapy. The benefit of AC for reducing respiratory motion of liver is well-known. In doing so, internal target volume18-21 is reduced (to avoid unnecessary parenchymal irradiation) without risking inadequate tumor coverage. By using AC with a stereotactic body frame, Wunderink et al.22 were able to reduce respiratory motion of hepatic tumors (median residual excursion: CC, 4.1 mm; AP, 2.4 mm; and LR, 1.8 mm), limiting excursions in 3 dimensions to small, reproducible levels. Eccles et al.10 also found that

Table 4 Breath amplitude of patients in different states of breathing (N ¼ 12) Breathing state

X

Y

Z

3D vector

Abdominal compression (AC) Free breathing (FB) AC maximum FB maximum AC minimum FB minimum F value p Value

2.33 ⫾ 1.22 3.48 ⫾ 1.14 5.30 5.60 0.90 2.00 5.807 0.025

5.11 ⫾ 2.05 9.83 ⫾ 3.00 8.80 15.10 2.00 3.90 20.178 o 0.001

2.13 ⫾ 1.05 3.38 ⫾ 1.59 4.10 5.30 0.50 0.80 5.148 0.033

6.22 ⫾ 1.94 11.07 ⫾ 3.16 9.43 16.26 2.34 4.70 20.505 o 0.001

All measurements expressed in mm.

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interfractional liver deformations in patients undergoing SBRT with AC, after rigid liver-to-liver registrations on respiratory sorted CBCT scans, were small in most patients (o 5 mm). Furthermore, Case et al.9 have reported that interfractional and intrafractional changes in amplitude of liver motion are small (o 2 mm) in the Y axis with use of AC. In our study, respiratory motions under AC were as follows: X, 2.33 ⫾ 1.22 mm; Y, 5.11 ⫾ 2.05 mm; Z, 2.13 ⫾ 1.05 mm; and 3D vector, 6.22 ⫾ 1.94 mm. Nevertheless, these values of respiratory motion were higher than those cited by other investigators earlier. It may be that holding time and site of compression are factors. AC was subxyphoid in 6 of our patients and more caudal in location (between xyphoid and umbilicus) for 6 others. Perhaps, the benefit of AC may diminish as the breath plate is moved away from xyphoid process. In our study of breath control, patients would also undergo AC for  25 minutes, including setup, MVCT, image-guided scan, and treatment.23 This period was much longer than that used in efforts reported earlier, so lengthy AC is clearly a topic for future research.

Conclusion In patients undergoing low-fractionated helical tomotherapy for intrahepatic HCC, the Body Pro-Lok system is capable of reducing interfractional and intrafractional setup errors and minimizing tumor movement caused by respiratory fluctuations. References 1. Torre, L.A.; Bray, F.; Siegel, R.L.; et al. Global cancer statistics, 2012. CA Cancer J. Clin. 65(2):87–108; 2015. 2. Zeng, Z.C.; Tang, Z.Y.; Yang, B.H.; et al. Comparison between radioimmunotherapy and external beam radiation therapy for patients with hepatocellular carcinoma. Eur. J. Nucl. Med. Mol. Imaging 29(12):1657–68; 2002. 3. Yamada, K.; Izaki, K.; Sugimoto, K.; et al. Prospective trial of combined transcatheter arterial chemoembolization and three-dimensional conformal radiotherapy for portal vein tumor thrombus in patients with unresectable hepatocellular carcinoma. Int. J. Radiat. Oncol. Biol. Phys. 57(1):113–9; 2003. 4. Huertas, A.; Baumann, A.S.; Saunier-Kubs, F.; et al. Stereotactic body radiation therapy as an ablative treatment for inoperable hepatocellular carcinoma. Radiother. Oncol. 115(2):211–6; 2015. 5. Jung, J.; Yoon, S.M.; Han, S.; et al. Alpha-fetoprotein normalization as a prognostic surrogate in small hepatocellular carcinoma after stereotactic body radiotherapy: A propensity score matching analysis. BMC Cancer 15(1):987; 2015.

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6. Wang, P.M.; Chung, N.N.; Hsu, W.C.; et al. Stereotactic body radiation therapy in hepatocellular carcinoma: Optimal treatment strategies based on liver segmentation and functional hepatic reserve. Rep. Pract. Oncol. Radiother. 20 (6):417–24; 2015. 7. Meng, M.; Wang, H.; Zeng, X.; et al. Stereotactic body radiation therapy: A novel treatment modality for inoperable hepatocellular carcinoma. Drug. Discov. Ther. 9(5):372–9; 2015. 8. Balter, J.M.; Dawson, L.A.; Kazanjian, S.; et al. Determination of ventilatory liver movement via radiographic evaluation of diaphragm position. Int. J. Radiat. Oncol. Biol. Phys. 51(1):267–70; 2001. 9. Case, R.B.; Moseley, D.J.; Sonke, J.J.; et al. Interfraction and intrafraction changes in amplitude of breathing motion in stereotactic liver radiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 77(3):918–25; 2010. 10. Eccles, C.L.; Dawson, L.A.; Moseley, J.L.; et al. Interfraction liver shape variability and impact on GTV position during liver stereotactic radiotherapy using abdominal compression. Int. J. Radiat. Oncol. Biol. Phys. 80(3):938–46; 2011. 11. Heinzerling, J.H.; Anderson, J.F.; Papiez, L.; et al. Four-dimensional computed tomography scan analysis of tumor and organ motion at varying levels of abdominal compression during stereotactic treatment of lung and liver. Int. J. Radiat. Oncol. Biol. Phys. 70(5):1571–8; 2008. 12. Gutiérrez, A.N.; Stathakis, S.; Crownover, R.; et al. Clinical evaluation of an immbolization system for stereotactic body radiotherapy using helical tomotherapy. Med. Dosim. 36(2):126–9; 2011. 13. Keall, P.J.; Mageras, G.S.; Balter, J.M.; et al. The management of respiratory motion in radiation oncology report of AAPM Task Group 76. Med. Phys. 33 (10):3874–900; 2006. 14. Xi, M.; Liu, M.Z.; Zhang, L.; et al. How many sets of 4DCT images are sufficient to determine internal target volume for liver radiotherapy? Radiother. Oncol. 92 (2):255–9; 2009. 15. Benedict, S.H.; Yenice, K.M.; Followill, D.; et al. Stereotactic body radiation therapy: The report of AAPM Task Group 101. Med. Phys. 37(8):4078–101; 2010. 16. Cao, M.; Lasley, F.D.; Das, I.J.; et al. Evaluation of rotational errors in treatment setup of stereotactic body radiation therapy of liver cancer. Int. J. Radiat. Oncol. Biol. Phys. 84(3):e435–40; 2012. 17. Hawkins, M.A.; Brock, K.K.; Eccles, C.; et al. Assessment of residual error in liver position using kV cone-beam computed tomography for liver cancer highprecision radiation therapy. Int. J. Radiat. Oncol. Biol. Phys. 66(2):610–9; 2006. 18. Liu, J.; Wang, J.Z.; Zhao, J.D.; et al. Use of combined maximum and minimum intensity projections to determine internal target volume in 4-dimensional CT scans for hepatic malignancies. Radiat. Oncol. 7:11; 2012. 19. Gong, G.; Yin, Y.; Xing, L.; et al. Comparison of internal target volumes for hepatocellular carcinoma defined using 3DCT with active breathing coordinator and 4DCT. Technol. Cancer Res. Treat. 10(6):601–6; 2011. 20. Xi, M.; Liu, M.Z.; Deng, X.W.; et al. Defining internal target volume (ITV) for hepatocellular carcinoma using four-dimensional CT. Radiother. Oncol. 84 (3):272–8; 2007. 21. Akino, Y.; Oh, R.J.; Masai, N.; et al. Evaluation of potential internal target volume of liver tumors using cine-MRI. Med. Phys. 41(11):111704; 2014. 22. Wunderink, W.; Méndez Romero, A.; de Kruijf, W.; et al. Reduction of respiratory liver tumor motion by abdominal compression in stereotactic body frame, analyzed by tracking fiducial markers implanted in liver. Int. J. Radiat. Oncol. Biol. Phys. 71(3):907–15; 2008. 23. Sheng, K.; Gou, S.; Wu, J.; et al. Denoised and texture enhanced MVCT to improve soft tissue conspicuity. Med. Phys. 41(10):101916; 2014.