Masayoshi Miyazaki

Craniocaudal Safety Margin Calculation Based on Interfractional Changes in Tumor Motion in Lung SBRT Assessed With an EPID in Cine Mode

PURPOSE To evaluate setup error and interfractional changes in tumor motion magnitude using an electric portal imaging device in cine mode (EPID cine) during the course of stereotactic body radiation therapy (SBRT) for non-small-cell lung cancer (NSCLC) and to calculate margins to compensate for these variations. MATERIALS AND METHODS Subjects were 28 patients with Stage I NSCLC who underwent SBRT. Respiratory-correlated four-dimensional computed tomography (4D-CT) at simulation was binned into 10 respiratory phases, which provided average intensity projection CT data sets (AIP). On 4D-CT, peak-to-peak motion of the tumor (M-4DCT) in the craniocaudal direction was assessed and the tumor center (mean tumor position [MTP]) of the AIP (MTP-4DCT) was determined. At treatment, the tumor on cone beam CT was registered to that on AIP for patient setup. During three sessions of irradiation, peak-to-peak motion of the tumor (M-cine) and the mean tumor position (MTP-cine) were obtained using EPID cine and in-house software. Based on changes in tumor motion magnitude (∆M) and patient setup error (∆MTP), defined as differences between M-4DCT and M-cine and between MTP-4DCT and MTP-cine, a margin to compensate for these variations was calculated with Strooms formula. RESULTS The means (±standard deviation: SD) of M-4DCT and M-cine were 3.1 (±3.4) and 4.0 (±3.6) mm, respectively. The means (±SD) of ∆M and ∆MTP were 0.9 (±1.3) and 0.2 (±2.4) mm, respectively. Internal target volume-planning target volume (ITV-PTV) margins to compensate for ∆M, ∆MTP, and both combined were 3.7, 5.2, and 6.4 mm, respectively. CONCLUSION EPID cine is a useful modality for assessing interfractional variations of tumor motion. The ITV-PTV margins to compensate for these variations can be calculated.

Influence of Rotational Setup Error on Tumor Shift in Bony Anatomy Matching Measured with Pulmonary Point Registration in Stereotactic Body Radiotherapy for Early Lung Cancer

OBJECTIVE To examine the correlation between the patient rotational error measured with pulmonary point registration and tumor shift after bony anatomy matching in stereotactic body radiotherapy for lung cancer. METHODS Twenty-six patients with lung cancer who underwent stereotactic body radiotherapy were the subjects. On 104 cone-beam computed tomography measurements performed prior to radiation delivery, rotational setup errors were measured with point registration using pulmonary structures. Translational registration using bony anatomy matching was done and the three-dimensional vector of tumor displacement was measured retrospectively. Correlation among the three-dimensional vector and rotational error and vertebra-tumor distance was investigated quantitatively. RESULTS The median and maximum rotational errors of the roll, pitch and yaw were 0.8, 0.9 and 0.5, and 6.0, 4.5 and 2.5, respectively. Bony anatomy matching resulted in a 0.2-1.6 cm three-dimensional vector of tumor shift. The shift became larger as the vertebra-tumor distance increased. Multiple regression analysis for the three-dimensional vector indicated that in the case of bony anatomy matching, tumor shifts of 5 and 10 mm were expected for vertebra-tumor distances of 4.46 and 14.1 cm, respectively. CONCLUSIONS Using pulmonary point registration, it was found that the rotational setup error influences the tumor shift. Bony anatomy matching is not appropriate for hypofractionated stereotactic body radiotherapy with a tight margin.

Dose-volume-response analysis in stereotactic radiotherapy for early lung cancer

BACKGROUND AND PURPOSE Japanese and Western approaches to stereotactic ablative radiotherapy (SABR) are considerably different, particularly with respect to dose prescription and reporting, which makes comparisons of Japanese versus European or American results challenging. Using individual patient data, the aim of this study was to analyze the dose-local-control relationship and its impact on survival. MATERIAL AND METHODS Patients receiving SABR for single-lesion early stage NSCLC in Osaka (OM) or Groningen (GN) were analyzed. Doses were recalculated using state-of-the-art dose calculation algorithms and expressed as biologically effective dose (BED) at PTV margin. Survival, local control (LC), and effect of treatment failure in operable and inoperable patients on survival were analyzed. RESULTS Between 2006 and 2010, 383 patients were included. The BED at PTV periphery was 102 Gy₁₀ (±21) in GN and 83 Gy₁₀ (±5) in OM. Unadjusted overall survival (OS) was better in OM (72% vs 52%; p<0.001), but GTVs and performance status (PS) were also significantly more favorable in OM. Adjusted for GTV and PS, OS was not different between institutions (HR 0.88; p=0.47). LC was better in GN (93% vs 84%; p<0.05). Local control predicted survival in operable patients: Adjusted for GTV and PS, the HR of local failure for OS was 7.5 (2-27; p=0.003) for operable, and 1.1 (0.7-1.9; p=0.6) for inoperable patients. CONCLUSIONS Sufficient dose is crucial for local control, which was a significant factor for survival for operable patients.

Can clinically relevant dose errors in patient anatomy be detected by gamma passing rate or modulation complexity score in volumetric-modulated arc therapy for intracranial tumors?

Abstract We investigated whether methods conventionally used to evaluate patient-specific QA in volumetric-modulated arc therapy (VMAT) for intracranial tumors detect clinically relevant dosimetric errors. VMAT plans with coplanar arcs were designed for 37 intracranial tumors. Dosimetric accuracy was validated by using a 3D array detector. Dose deviations between the measured and planned doses were evaluated by gamma analysis. In addition, modulation complexity score for VMAT (MCSv) for each plan was calculated. Three-dimensional dose distributions in patient anatomy were reconstructed using 3DVH software, and clinical deviations in dosimetric parameters between the 3DVH doses and planned doses were calculated. The gamma passing rate (GPR)/MCSv and the clinical dose deviation were evaluated using Pearsons correlation coefficient. Significant correlation (P < 0.05) between the clinical dose deviation and GPR was observed with both the 3%/3 mm and 2%/2 mm criteria in clinical target volume (D99), brain (D2), brainstem (D2) and chiasm (D2), albeit that the correlations were not ‘strong’ (0.38 < |r| < 0.54). The maximum dose deviations of brainstem were up to 4.9 Gy and 2.9 Gy for Dmax and D%, respectively in the case of high GPR (98.2% with 3%/3 mm criteria). Regarding MCSv, none of the evaluated organs showed a significant correlation with clinical dose deviation, and correlations were ‘weak’ or absent (0.01 < |r| < 0.21). The use of high GPR and MCSv values does not always detect dosimetric errors in a patient. Therefore, in-depth analysis with the DVH for patient-specific QA is considered to be preferable for guaranteeing safe dose delivery.

Couch height–based patient setup for abdominal radiation therapy

There are 2 methods commonly used for patient positioning in the anterior-posterior (A-P) direction: one is the skin mark patient setup method (SMPS) and the other is the couch height-based patient setup method (CHPS). This study compared the setup accuracy of these 2 methods for abdominal radiation therapy. The enrollment for this study comprised 23 patients with pancreatic cancer. For treatments (539 sessions), patients were set up by using isocenter skin marks and thereafter treatment couch was shifted so that the distance between the isocenter and the upper side of the treatment couch was equal to that indicated on the computed tomographic (CT) image. Setup deviation in the A-P direction for CHPS was measured by matching the spine of the digitally reconstructed radiograph (DRR) of a lateral beam at simulation with that of the corresponding time-integrated electronic portal image. For SMPS with no correction (SMPS/NC), setup deviation was calculated based on the couch-level difference between SMPS and CHPS. SMPS/NC was corrected using 2 off-line correction protocols: no action level (SMPS/NAL) and extended NAL (SMPS/eNAL) protocols. Margins to compensate for deviations were calculated using the Stroom formula. A-P deviation > 5mm was observed in 17% of SMPS/NC, 4% of SMPS/NAL, and 4% of SMPS/eNAL sessions but only in one CHPS session. For SMPS/NC, 7 patients (30%) showed deviations at an increasing rate of > 0.1mm/fraction, but for CHPS, no such trend was observed. The standard deviations (SDs) of systematic error (Σ) were 2.6, 1.4, 0.6, and 0.8mm and the root mean squares of random error (σ) were 2.1, 2.6, 2.7, and 0.9mm for SMPS/NC, SMPS/NAL, SMPS/eNAL, and CHPS, respectively. Margins to compensate for the deviations were wide for SMPS/NC (6.7mm), smaller for SMPS/NAL (4.6mm) and SMPS/eNAL (3.1mm), and smallest for CHPS (2.2mm). Achieving better setup with smaller margins, CHPS appears to be a reproducible method for abdominal patient setup.

Assessment with cone-beam computed tomography of intrafractional motion and interfractional position changes of resectable and borderline resectable pancreatic tumours with implanted fiducial marker

OBJECTIVE The volume of targets to which a high radiation dose can be delivered is limited for pancreatic radiotherapy. We assessed changes in movements of pancreatic tumours between simulation and treatment and determined compensatory margins. METHODS For 23 patients, differences in implanted fiducial marker motion magnitude (MMM) and mean marker position (MMP) between four-dimensional CT and cone-beam CT were measured. Subsequently, residual uncertainty was simulated after no action level (NAL) and extended no action level (eNAL) protocols were adopted. RESULTS With no correction, respective 95th percentile of MMM were 4.5 mm, 6.2 mm and 16.0 mm and systematic (random) errors of MMP were 2.8 mm (3.3 mm), 3.2 mm (2.0 mm) and 5.9 mm (4.0 mm) in the left-right (L-R), anteroposterior (A-P) and superoinferior (S-I) directions, so that large margins were required (L-R, 10.5 mm; A-P, 11.7 mm; and S-I, 24.8 mm). NAL reduced systematic errors of MMP, but resultant margins remained large (L-R, 8.0 mm; A-P, 9.6 mm; and S-I, 18.1 mm). eNAL compensated for time trends and obtained minimal margins (L-R, 6.7 mm; A-P, 6.7 mm; and S-I, 15.2 mm). CONCLUSION Motion magnitude and position of pancreatic tumours during simulation are frequently not representative of that during treatment. eNAL compensated for systematic interfractional position change and would be a practical approach for improving targeting accuracy. Advances in knowledge: Considerably large margins, especially in the S-I direction, were required to compensate for intrafractional motion and interfractional position changes of the pancreatic tumour. An application of eNAL was an effective strategy to diminish these margins.

Effect of various methods for rectum delineation on relative and absolute dose-volume histograms for prostate IMRT treatment planning

Several reports have dealt with correlations of late rectal toxicity with rectal dose-volume histograms (DVHs) for high dose levels. There are 2 techniques to assess rectal volume for reception of a specific dose: relative-DVH (R-DVH, %) that indicates relative volume for a vertical axis, and absolute-DVH (A-DVH, cc) with its vertical axis showing absolute volume of the rectum. The parameters of DVH vary depending on the rectum delineation method, but the literature does not present any standardization of such methods. The aim of the present study was to evaluate the effects of different delineation methods on rectal DVHs. The enrollment for this study comprised 28 patients with high-risk localized prostate cancer, who had undergone intensity-modulated radiation therapy (IMRT) with the prescription dose of 78Gy. The rectum was contoured with 4 different methods using 2 lengths, short (Sh) and long (Lg), and 2 cross sections, rectum (Rec) and rectal wall (Rw). Sh means the length from 1cm above the seminal vesicles to 1cm below the prostate and Lg the length from the rectosigmoid junction to the anus. Rec represents the entire rectal volume including the rectal contents and Rw the rectal volume of the area with a wall thickness of 4mm. We compared dose-volume parameters by using 4 rectal contour methods for the same plan with the R-DVHs as well as the A-DVHs. For the high dose levels, the R-DVH parameters varied widely. The mean of V70 for Sh-Rw was the highest (19.4%) and nearly twice as high as that for Lg-Rec (10.4%). On the contrary, only small variations were observed in the A-DVH parameters (4.3, 4.3, 5.5, and 5.5cc for Sh-Rw, Lg-Rw, Sh-Rec, and Lg-Rec, respectively). As for R-DVHs, the parameters of V70 varied depending on the rectal lengths (Sh-Rec vs Lg-Rec: R = 0.76; Sh-Rw vs Lg-Rw: R = 0.85) and cross sections (Sh-Rec vs Sh-Rw: R = 0.49; Lg-Rec vs Lg-Rw: R = 0.65). For A-DVHs, however, the parameters of Sh rectal A-DVHs hardly changed regardless of differences in rectal length at all dose levels. Moreover, at high dose levels (V70), the parameters of A-DVHs showed less dependence on rectal cross sections (Sh-Rec vs Sh-Rw: R = 0.66; Lg-Rec vs Lg-Rw: R = 0.59). This study showed that A-DVHs were less dependent on the delineation methods than R-DVHs, especially for evaluating the rectal dose at higher dose levels. It can therefore be assumed that, in addition to R-DVHs, A-DVHs can be used for evaluating rectal toxicity.

VMAT–SBRT planning based on an average intensity projection for lung tumors located in close proximity to the diaphragm: a phantom and clinical validity study

The aim of the this study was to validate the use of an average intensity projection (AIP) for volumetric-modulated arc therapy for stereotactic body radiation therapy (VMAT–SBRT) planning for a moving lung tumor located near the diaphragm. VMAT–SBRT plans were created using AIPs reconstructed from 10 phases of 4DCT images that were acquired with a target phantom moving with amplitudes of 5, 10, 20 and 30 mm. To generate a 4D dose distribution, the static dose for each phase was recalculated and the doses were accumulated by using the phantom position known for each phase. For 10 patients with lung tumors, a deformable registration was used to generate 4D dose distributions. Doses to the target volume obtained from the AIP plan and the 4D plan were compared, as were the doses obtained from each plan to the organs at risk (OARs). In both phantom and clinical study, dose discrepancies for all parameters of the dose volume (Dmin, D99, Dmax, D1 and Dmean) to the target were <3%. The discrepancies of Dmax for spinal cord, esophagus and heart were <1 Gy, and the discrepancy of V20 for lung tissue was <1%. However, for OARs with large respiratory motion, the discrepancy of the Dmax was as much as 9.6 Gy for liver and 5.7 Gy for stomach. Thus, AIP is clinically acceptable as a planning CT image for predicting 4D dose, but doses to the OARs with large respiratory motion were underestimated with the AIP approach.

Preliminary analysis of the sequential simultaneous integrated boost technique for intensity-modulated radiotherapy for head and neck cancers

The aim of this study was to compare three strategies for intensity-modulated radiotherapy (IMRT) for 20 head-and-neck cancer patients. For simultaneous integrated boost (SIB), doses were 66 and 54 Gy in 30 fractions for PTVboost and PTVelective, respectively. Two-phase IMRT delivered 50 Gy in 25 fractions to PTVelective in the First Plan, and 20 Gy in 10 fractions to PTVboost in the Second Plan. Sequential SIB (SEQ-SIB) delivered 55 Gy and 50 Gy in 25 fractions, respectively, to PTVboost and PTVelective using SIB in the First Plan and 11 Gy in 5 fractions to PTVboost in the Second Plan. Conformity indexes (CIs) (mean ± SD) for PTVboost and PTVelective were 1.09 ± 0.05 and 1.34 ± 0.12 for SIB, 1.39 ± 0.14 and 1.80 ± 0.28 for two-phase IMRT, and 1.14 ± 0.07 and 1.60 ± 0.18 for SEQ-SIB, respectively. CI was significantly highest for two-phase IMRT. Maximum doses (Dmax) to the spinal cord were 42.1 ± 1.5 Gy for SIB, 43.9 ± 1.0 Gy for two-phase IMRT and 40.3 ± 1.8 Gy for SEQ-SIB. Brainstem Dmax were 50.1 ± 2.2 Gy for SIB, 50.5 ± 4.6 Gy for two-phase IMRT and 47.4 ± 3.6 Gy for SEQ-SIB. Spinal cord Dmax for the three techniques was significantly different, and brainstem Dmax was significantly lower for SEQ-SIB. The compromised conformity of two-phase IMRT can result in higher doses to organs at risk (OARs). Lower OAR doses in SEQ-SIB made SEQ-SIB an alternative to SIB, which applies unconventional doses per fraction.

Accumulated Dose of Intensity-Modulated Radiotherapy for Head and Neck Cancer Using Deformable Registration of Two Sets of Computed Tomography Images

Purpose: The aim of this study was, using deformable image registration (DIR), to evaluate alteration of dose distribution caused by patient’s anatomical structure changes during a two-phase intensity-modulated radiotherapy (IMRT). Methods: IMRT consisted of an initial plan delivering 53 Gy to gross tumor volume (GTV) and 45 Gy to elective volumes and a boost plan delivering 16.96 Gy to GTV. The subjects were 10 patients with head and neck cancer who underwent computed tomography (CT) scans twice (first CT before treatment and second CT before boost). A sum of the initial and the boost plans for the first CT was Original total plan. Using DIR, the original boost and a modified new boost plan were recalculated on the second CT and summed with the initial plan to create total plans: DIR plan and modified DIR plan. Results: Mean dose (Dmean) of the ipsilateral and contralateral parotids were increased by 8.0% (P<0.01) and 6.8% (P<0.05) in DIR plan compared with Original total plan. Compared with DIR plan, modified DIR plan reduced Dmean of the ipsilateral parotid (P<0.01). Dose to 95% of the volume (D95) to clinical target volume for GTV (CTV1) of DIR plan was significantly higher than that of Original total plan (P<0.01) and modified DIR plan (P<0.01). Conclusions: Dose summation using DIR demonstrated that the body shrinking during IMRT significantly increased the doses of both parotids and CTV1. Modified DIR plan compensated the increases in doses of the ipsilateral parotid and CTV1.