Nobuhiko Yoshikawa

Preliminary results of MRI-assisted high-dose-rate interstitial brachytherapy for uterine cervical cancer

PURPOSE To investigate the effectiveness of our novel MRI-assisted high-dose-rate interstitial brachytherapy for uterine cervical cancer. METHODS AND MATERIALS Between June 2005 and June 2009, 29 previously untreated patients with cervical cancer were enrolled (2 T2b, 2 T3a, 19 T3b, and 6 T4 tumors). We implanted MRI-compatible plastic catheters using our unique ambulatory technique. The total treatment doses were 30-36 Gy (6 Gy per fraction) combined with external beam radiotherapy. RESULTS The median D90 (high-risk clinical target volume), D(2 cc) (bladder), and D(2 cc) (rectum) per fraction were 6.9, 5, and 4.6 Gy, respectively. The 3-year local control rates were 100%, 95%, and 83% for T2, T3, and T4 tumors, respectively. Grade 3 or 4 late complications occurred in 4 patients. CONCLUSIONS Our preliminary evaluation of image-based high-dose-rate interstitial brachytherapy showed favorable local treatment results with an acceptable complication rate.

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.

Sivelestat sodium hydrate reduces radiation-induced lung injury in mice by inhibiting neutrophil elastase

The aim of this study was to investigate whether sivelestat, a neutrophil elastase (NE) inhibitor, mitigates radiation-induced lung injury in mice. C57BL/6J mice were administered a dose of 20 Gy to the bilateral whole lungs. Sivelestat was administered immediately before and 1 h after irradiation in group RE2, and immediately before and 1, 3 and 6 h after irradiation in group RE4. Group R received irradiation without sivelestat injection. Mice that did not receive sivelestat injection or irradiation were used as controls. NE activity was measured 24 and 48 h after irradiation, and the mice were sacrificed 24 h, 48 h and 15 weeks after irradiation for histopathological examination. In groups RE2 and RE4, NE activity was significantly suppressed until 48 h after irradiation compared to group R. The degree of lung damage in each group was scored during histopathological examination. Results showed that the scores of groups RE2 and RE4 were significantly lower compared to those of group R 15 weeks after irradiation. In conclusion, sivelestat reduced radiation‑induced lung injury in the mice by suppressing NE activity and excessive inflammatory reactions.

Treatment results of image-guided high-dose-rate interstitial brachytherapy for pelvic recurrence of uterine cancer

PURPOSE We analyzed clinical data to evaluate the effectiveness of image-guided high-dose-rate interstitial brachytherapy (HDR-ISBT) for pelvic recurrence of uterine cancer. METHODS AND MATERIALS Between 2003 and 2011, 56 patients were treated with HDR-ISBT with or without external beam radiotherapy (EBRT). The median followup time was 33 months (range, 1-109 months). Pre-ISBT treatments included radical hysterectomy for 35 patients (Group A), radical hysterectomy with postoperative radiotherapy for 8 patients (Group B), and radical radiotherapy for 13 patients (Group C). We initiated MRI-assisted CT-based planning for the last 49 patients. The median ISBT single fraction dose was 6 Gy. The median total doses were 30 and 54 Gy with and without EBRT (range, 30-50 Gy) for Group A, respectively and 48 Gy without EBRT for Groups B and C. RESULTS The 3-year local control (LC) rates were 85%, 75%, and 46% for Groups A, B, and C, respectively (p = 0.017). The 3-year LC rates were 84%, 73%, and 33% for clinical target volume at the time of HDR-ISBT of <10, 10-29, and ≥30 cc, respectively (p = 0.005). The 3-year LC results tended to be higher for patients whose D100 (clinical target volume) was equal or higher than 67.1 Gy (p = 0.098). A total of 13 late complications of Grades 3-5 occurred in 11 patients (20%). CONCLUSIONS Our image-guided HDR-ISBT for pelvic recurrence of uterine cancer provided good treatment outcomes. The treatment results for patients who underwent radical surgery with or without postoperative radiotherapy are better than those for patients who underwent radical radiotherapy.

Role of vaginal pallor reaction in predicting late vaginal stenosis after high-dose-rate brachytherapy in treatment-naive patients with cervical cancer

Objective To assess actual rates of late vaginal stenosis and identify predisposing factors for complications among patients with previously untreated cervical cancer following high-dose-rate brachytherapy. Methods We performed longitudinal analyses of 57 patients using the modified Dische score at 6, 12, 18, 24, 36, and 60 months after treatment, which consisted of 15 interstitial brachytherapys and 42 conventional intracavitary brachytherapys, with a median follow-up time of 36 months (range, 6 to 144 months). Results More than half of the patients developed grade 1 (mild) vaginal stenosis within the first year of follow-up, and grade 2 (97.5%, moderate) to grade 3 (severe) stenosis gradually increased with time. Actual stenosis rates for grade 1, 2, and 3 were 97.5% (95% confidence interval [CI], 92.7 to 97.5), 60.7% (95% CI, 42.2 to 79.3), and 7.4% (95% CI, 0 to 18.4) at 3 years after treatment. Pallor reaction grade 2-3 at 6 months was only a statistically significant predisposing factor for grade 2-3 late vaginal stenosis 3 years or later with a hazard ratio of 3.48 (95% CI, 1.32 to 9.19; p=0.018) by a multivariate Cox proportional hazard model. Patients with grade 0-1 pallor reaction at 6 months showed a grade ≥2 vaginal stenosis rate of 53%, whereas the grade 2-3 pallor reaction group achieved a grade ≥2 vaginal stenosis rate at 3 years at 100% (p=0.001). Conclusion High-dose-rate brachytherapy was associated with high incidence of late vaginal stenosis. Pallor reaction grade 2-3 at 6 months was predictive of late grade 2-3 vaginal stenosis at 3 years after treatment. These findings should prove helpful for patient counseling and preventive intervention.

Three-dimensional image-based high-dose-rate interstitial brachytherapy for mobile tongue cancer

To investigate the influence of a 3D image-based treatment-planning method for high-dose-rate interstitial brachytherapy (HDR-ISBT) for mobile tongue cancer, we analyzed dose–volume histogram results for the clinical target volume (CTV) and the mandible. Between October 2010 and November 2011, one and four patients having T2 and T3 tumors, respectively, were treated with HDR-ISBT. Multiplane implantation using 9–15 treatment applicators was performed. Lugols iodine staining, metal markers, ultrasonography, and magnetic resonance imaging were used to identify the contours of the gross tumor volume (defined as the CTV). The results of the image-based treatment plan were compared with those of the conventional simulated plan on the basis of a reference point 5 mm from the applicator position. The mean D90(CTV) and V100(CTV) were 112% of the prescribed dose (PD) and 98.1%PD, respectively, for the image-based plan, and 113%PD and 97.2%PD, respectively, for the conventional plan. The median CTVref/Vref was 0.23 for the image-based plan and 0.16 for the conventional plan (P = 0.01). The mean D0.1 cm3 (mandible), D1 cm3 (mandible), and D2 cm3 (mandible) were 80.1%PD, 62.5%PD, and 55.7%PD, respectively, for the image-based plan, and 109.1%PD (P = 0.02), 82.4%PD (P = 0.005), and 74%PD (P = 0.004), respectively, for the conventional plan). Image-based treatment planning may achieve high-conformity radiotherapy for the CTV and decrease irradiated doses to the mandible.

Edema worsens target coverage in high-dose-rate interstitial brachytherapy of mobile tongue cancer: a report of two cases.

Purpose We report our study on two patients to highlight the risk of underdosage of the clinical target volume (CTV) due to edema during high-dose-rate interstitial brachytherapy (HDR-ISBT) of mobile tongue cancer. Material and methods To treat the lateral side of the CTV, flexible applicator tubes were implanted on the mouth floor. Two-dimensional planning was performed using X-ray images for Case 1, and three-dimensional (3D) planning was performed using computed tomography (CT) for Case 2. Prescribed doses for both cases were 54 Gy in nine fractions. Case reports Case 1 was treated for cancer of the right lateral border of the tongue in 2005. Tongue edema occurred after implantation, and part of the lateral border of the tongue protruded between the applicator tubes. Acute mucosal reaction abated in the protruded area earlier than in the other parts of the CTV. In this case, the tumor recurred in this area 5 months after the treatment. Case 2 was treated for cancer of the left lateral border of the tongue. Because tongue edema occurred in this case also, plastic splints were inserted between the applicator tubes to push the edematous region into the irradiated area. The mucosal surface of the CTV was covered by the 70% isodose, and 100% isodose line for before and after splint insertion. Local control of the tumor was achieved 4 years after treatment. Discussion and conclusions To ensure sufficient target coverage, 3D image-based planning using CT should be performed, followed by re-planning using repeated CT as needed. Also, the development of devices to prevent protrusion of the edematous tissue outside the target area will help to ensure the full dosing of CTV.