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Ogawa, Kazuhiko

Publications and source records attributed to Ogawa, Kazuhiko.

Nationwide, Multicenter, Retrospective Study on High-Dose-Rate Brachytherapy as Monotherapy for Prostate Cancer

Purpose: To present, analyze, and discuss results of a nationwide, multicenter, retrospective study on high-dose-rate brachytherapy (HDR-BT) as monotherapy for low-, intermediate-, and high-risk prostate cancer. Methods and Materials: From 1995 through 2013, 524 patients, 73 (14%) with low-risk, 207 (40%) with intermediate-risk, and 244 (47%) with high-risk prostate cancer, were treated with HDR-BT as monotherapy at 5 institutions in Japan. Dose fractionations were 27 Gy/2 fractions for 69 patients (13%), 45.5 Gy/7 fractions for 168 (32%), 49 Gy/7 fractions for 149 (28%), 54 Gy/9 fractions for 130 (25%), and others for 8 (2%). Of these patients, 156 (30%) did not receive androgen deprivation therapy, and 202 patients (39%) did receive androgen deprivation therapy <1 year, 112 (21%) for 1-3 years, and 54 (10%) for >3 years. Median follow-up time was 5.9 years (range, 0.4-18.1 years), with a minimum of 2 years for surviving patients. Results: After 5 years, respective actuarial rates of no biochemical evidence of disease, overall survival, cause-specific survival, and metastasis-free survival for all patients were 92%, 97%, 99%, and 94%. For low/intermediate/high-risk patients, the 5-year no biochemical evidence of disease rates were 95%/94%/89%, the 5-year overall survival rates were 98%/98%/94%, the 5-year cause-specific survival rates were 98%/100%/98%, and the 5-year metastasis-free survival rates were 98%/95%/90%, respectively. The cumulative incidence of late grade 2 to 3 genitourinary toxicity at 5 years was 19%, and that of late grade 3 was 1%. The corresponding incidences of gastrointestinal toxicity were 3% and 0% (0.2%). No grade 4 or 5 of either type of toxicity was detected. Conclusions: The findings of this nationwide, multicenter, retrospective study demonstrate that HDR-BT as monotherapy was safe and effective for all patients with low-, intermediate-, and high-risk prostate cancer.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

High-Dose-Rate Brachytherapy as Monotherapy for Intermediate- and High-Risk Prostate Cancer: Clinical Results for a Median 8-Year Follow-Up

Purpose: To present mature results of high-dose-rate brachytherapy (HDR-BT) as monotherapy for intermediate- and high-risk prostate cancer. Methods and Materials: From 1995 through 2012, 190 patients, 79 with intermediate-risk and 111 with high-risk prostate cancer, were treated with HDR-BT alone using 48 Gy/8 fractions, 54 Gy/9 fractions, or 45.5 Gy/7 fractions over 4 to 5 days. Neoadjuvant with or without adjuvant androgen deprivation therapy was administered to 139 patients, 35 intermediate- and 104 high-risk. Results: Median follow-up time was 92 months (range, 10-227 months), with a minimum of 2 years for surviving patients. Respective rates of cause-specific survival, overall survival, metastasis-free survival, and biochemical no evidence of disease for the intermediate-risk patients were 100%, 100%, 96%, and 93% at 5 years, and 100%, 96%, 91%, and 91% at 8 years. Corresponding rates for the high-risk patients were 97%, 93%, 84%, and 81% at 5 years, and 93%, 81%, 74%, and 77% at 8 years. The cumulative incidence of late grade 2 to 3 genitourinary toxicity was 5% at 5 years and 10% at 8 years, and that of late grade 3 was 0 at 5 years and 1% at 8 years. The cumulative incidence of late grade 2-3 gastrointestinal toxicity was 4% at 5 years and 6% at 8 years, and that of late grade 3 was 0 at 5 years and 2% at 8 years. No grade 4 or 5 toxicity was detected. Conclusions: Our single-institution study with a median 8-year follow-up showed that HDR-BT as monotherapy was safe and effective for patients with intermediate- and high-risk prostate cancer.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Reference respiratory waveforms by minimum jerk model analysis

Purpose: CyberKnife{sup ®} robotic surgery system has the ability to deliver radiation to a tumor subject to respiratory movements using Synchrony{sup ®} mode with less than 2 mm tracking accuracy. However, rapid and rough motion tracking causes mechanical tracking errors and puts mechanical stress on the robotic joint, leading to unexpected radiation delivery errors. During clinical treatment, patient respiratory motions are much more complicated, suggesting the need for patient-specific modeling of respiratory motion. The purpose of this study was to propose a novel method that provides a reference respiratory wave to enable smooth tracking for each patient. Methods: The minimum jerk model, which mathematically derives smoothness by means of jerk, or the third derivative of position and the derivative of acceleration with respect to time that is proportional to the time rate of force changed was introduced to model a patient-specific respiratory motion wave to provide smooth motion tracking using CyberKnife{sup ®}. To verify that patient-specific minimum jerk respiratory waves were being tracked smoothly by Synchrony{sup ®} mode, a tracking laser projection from CyberKnife{sup ®} was optically analyzed every 0.1 s using a webcam and a calibrated grid on a motion phantom whose motion was in accordance with three pattern waves (cosine, typical free-breathing, and minimum jerk theoretical wave models) for the clinically relevant superior–inferior directions from six volunteers assessed on the same node of the same isocentric plan. Results: Tracking discrepancy from the center of the grid to the beam projection was evaluated. The minimum jerk theoretical wave reduced the maximum-peak amplitude of radial tracking discrepancy compared with that of the waveforms modeled by cosine and typical free-breathing model by 22% and 35%, respectively, and provided smooth tracking for radial direction. Motion tracking constancy as indicated by radial tracking discrepancy affected by respiratory phase was improved in the minimum jerk theoretical model by 7.0% and 13% compared with that of the waveforms modeled by cosine and free-breathing model, respectively. Conclusions: The minimum jerk theoretical respiratory wave can achieve smooth tracking by CyberKnife{sup ®} and may provide patient-specific respiratory modeling, which may be useful for respiratory training and coaching, as well as quality assurance of the mechanical CyberKnife{sup ®} robotic trajectory.

60 APPLIED LIFE SCIENCES↗

Novel Radiobiological Gamma Index for Evaluation of 3-Dimensional Predicted Dose Distribution

Purpose: To propose a gamma index-based dose evaluation index that integrates the radiobiological parameters of tumor control (TCP) and normal tissue complication probabilities (NTCP). Methods and Materials: Fifteen prostate and head and neck (H&N) cancer patients received intensity modulated radiation therapy. Before treatment, patient-specific quality assurance was conducted via beam-by-beam analysis, and beam-specific dose error distributions were generated. The predicted 3-dimensional (3D) dose distribution was calculated by back-projection of relative dose error distribution per beam. A 3D gamma analysis of different organs (prostate: clinical [CTV] and planned target volumes [PTV], rectum, bladder, femoral heads; H&N: gross tumor volume [GTV], CTV, spinal cord, brain stem, both parotids) was performed using predicted and planned dose distributions under 2%/2 mm tolerance and physical gamma passing rate was calculated. TCP and NTCP values were calculated for voxels with physical gamma indices (PGI) >1. We propose a new radiobiological gamma index (RGI) to quantify the radiobiological effects of TCP and NTCP and calculate radiobiological gamma passing rates. Results: The mean RGI gamma passing rates for prostate cases were significantly different compared with those of PGI (P<.03–.001). The mean RGI gamma passing rates for H&N cases (except for GTV) were significantly different compared with those of PGI (P<.001). Differences in gamma passing rates between PGI and RGI were due to dose differences between the planned and predicted dose distributions. Radiobiological gamma distribution was visualized to identify areas where the dose was radiobiologically important. Conclusions: RGI was proposed to integrate radiobiological effects into PGI. This index would assist physicians and medical physicists not only in physical evaluations of treatment delivery accuracy, but also in clinical evaluations of predicted dose distribution.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Optimization of leaf margins for lung stereotactic body radiotherapy using a flattening filter-free beam

Purpose: The authors sought to determine the optimal collimator leaf margins which minimize normal tissue dose while achieving high conformity and to evaluate differences between the use of a flattening filter-free (FFF) beam and a flattening-filtered (FF) beam. Methods: Sixteen lung cancer patients scheduled for stereotactic body radiotherapy underwent treatment planning for a 7 MV FFF and a 6 MV FF beams to the planning target volume (PTV) with a range of leaf margins (−3 to 3 mm). Forty grays per four fractions were prescribed as a PTV D95. For PTV, the heterogeneity index (HI), conformity index, modified gradient index (GI), defined as the 50% isodose volume divided by target volume, maximum dose (Dmax), and mean dose (Dmean) were calculated. Mean lung dose (MLD), V20 Gy, and V5 Gy for the lung (defined as the volumes of lung receiving at least 20 and 5 Gy), mean heart dose, and Dmax to the spinal cord were measured as doses to organs at risk (OARs). Paired t-tests were used for statistical analysis. Results: HI was inversely related to changes in leaf margin. Conformity index and modified GI initially decreased as leaf margin width increased. After reaching a minimum, the two values then increased as leaf margin increased (“V” shape). The optimal leaf margins for conformity index and modified GI were −1.1 ± 0.3 mm (mean ± 1 SD) and −0.2 ± 0.9 mm, respectively, for 7 MV FFF compared to −1.0 ± 0.4 and −0.3 ± 0.9 mm, respectively, for 6 MV FF. Dmax and Dmean for 7 MV FFF were higher than those for 6 MV FF by 3.6% and 1.7%, respectively. There was a positive correlation between the ratios of HI, Dmax, and Dmean for 7 MV FFF to those for 6 MV FF and PTV size (R = 0.767, 0.809, and 0.643, respectively). The differences in MLD, V20 Gy, and V5 Gy for lung between FFF and FF beams were negligible. The optimal leaf margins for MLD, V20 Gy, and V5 Gy for lung were −0.9 ± 0.6, −1.1 ± 0.8, and −2.1 ± 1.2 mm, respectively, for 7 MV FFF compared to −0.9 ± 0.6, −1.1 ± 0.8, and −2.2 ± 1.3 mm, respectively, for 6 MV FF. With the heart inside the radiation field, the mean heart dose showed a V-shaped relationship with leaf margins. The optimal leaf margins were −1.0 ± 0.6 mm for both beams. Dmax to the spinal cord showed no clear trend for changes in leaf margin. Conclusions: The differences in doses to OARs between FFF and FF beams were negligible. Conformity index, modified GI, MLD, lung V20 Gy, lung V5 Gy, and mean heart dose showed a V-shaped relationship with leaf margins. There were no significant differences in optimal leaf margins to minimize these parameters between both FFF and FF beams. The authors’ results suggest that a leaf margin of −1 mm achieves high conformity and minimizes doses to OARs for both FFF and FF beams.

60 APPLIED LIFE SCIENCES↗

Phase 2 Study of Docetaxel, Cisplatin, and Concurrent Radiation for Technically Resectable Stage III-IV Squamous Cell Carcinoma of the Head and Neck

Purpose: We investigated the efficacy and safety of weekly low-dose docetaxel and cisplatin therapy concurrent with conventionally fractionated radiation in patients with technically resectable stage III-IV squamous cell carcinoma of the head and neck. Methods and Materials: Between March 2004 and October 2011, we enrolled 117 patients, of whom 116 were analyzable (43 had oropharyngeal cancer, 54 had hypopharyngeal cancer, and 19 had laryngeal cancer), and 85 (73%) had stage IV disease. Radiation consisted of 66 Gy in 33 fractions. Docetaxel, 10 mg/m{sup 2}, followed by cisplatin, 20 mg/m{sup 2}, administered on the same day were given once a week for 6 cycles. The primary endpoint was overall complete response (CR) rate after chemoradiation therapy. Human papillomavirus (HPV) DNA in oropharyngeal cancer was examined by PCR. Results: Of 116 patients, 82 (71%) completed treatment per protocol; 102 (88%) received the full radiation therapy dose; and 90 (78%) and 12 (10%) patients received 6 and 5 chemotherapy cycles, respectively. Overall CR rate was 71%. After median follow-up of 50.9 months (range: 15.6-113.9 months for surviving patients), 2-year and 4-year overall survival rates were 82% and 68%, respectively. Cumulative 2-year and 4-year local failure rates were 27% and 28%, respectively, whereas distant metastasis rates were 15% and 22%, respectively. HPV status in oropharyngeal cancer was not associated with treatment efficacy. Acute toxicity included grade 3 and 4 in-field mucositis in 73% and 5% of patients, respectively, whereas myelosuppression and renal injury were minimal. No patients died of toxicity. Feeding tube dependence in 8% and tracheostomy in 1% of patients were evident at 2 years postchemoradiation therapy in patients who survived without local treatment failure. Conclusions: Local control and survival with this regimen were satisfactory. Although acute toxicity, such as mucositis, was common, late toxicity, such as laryngoesophageal dysfunction, was minimal. Therapy using weekly low-dose docetaxel and cisplatin concurrent with radiation warrants further evaluation.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Impact of Intraluminal Brachytherapy on Survival Outcome for Radiation Therapy for Unresectable Biliary Tract Cancer: A Propensity-Score Matched-Pair Analysis

Purpose: To determine whether adding intraluminal brachytherapy (ILBT) to definitive radiation therapy (RT) for unresectable biliary tract cancer has a positive impact on survival outcome. Methods and Materials: The original cohort comprised 209 patients, including 153 who underwent external beam RT (EBRT) alone and 56 who received both ILBT and EBRT. By matching propensity scores, 56 pairs (112 patients) consisting of 1 patient with and 1 patient without ILBT were selected. They were well balanced in terms of sex, age, performance status, clinical stage, jaundice, and addition of chemotherapy. The impact of ILBT on overall survival (OS), disease-specific survival (DSS), and local control (LC) was investigated. Results: The 2-year OS rates were 31% for the ILBT+ group and 40% for theILBT– group (P=.862). The 2-year DSS rates were 42% for the ILBT+ group and 41% for the ILBT– group (P=.288). The 2-year LC rates were 65% for the ILBT+ group and 35% for the ILBT– group (P=.094). Three of the 4 sensitivity analyses showed a significantly better LC for the ILBT+ group (P=.010, .025, .049), and another showed a marginally better LC (P=.068), and none of the sensitivity analyses showed any statistically significant differences in OS or DSS. Conclusions: In the treatment for unresectable biliary tract cancer, the addition of ILBT to RT has no impact on OS or DSS but is associated with better LC. Therefore, the role of ILBT should be addressed by other measures than survival benefit, for example, by less toxicity, prolonged biliary tract patency decreasing the need for further palliative interventions, or patient quality of life.

62 RADIOLOGY AND NUCLEAR MEDICINE↗