Masao Tanooka

Neoadjuvant short-course hyperfractionated accelerated radiotherapy (SC-HART) combined with S-1 for locally advanced rectal cancer

The purpose of this study was to examine the safety and feasibility of a novel protocol of neoadjuvant short-course hyperfractionated accelerated radiotherapy (SC-HART) combined with S-1 for locally advanced rectal cancer. A total of 56 patients with lower rectal cancer of cT3N1M0 (Stage III b) was treated with SC-HART followed by radical surgery, and were analyzed in the present study. SC-HART was performed with a dose of 2.5 Gy twice daily, with an interval of at least 6 hours between fractions, up to a total dose of 25 Gy (25 Gy in 10 fractions for 5 days) combined with S-1 for 10 days. Radical surgery was performed within three weeks following the end of the SC-HART. The median age was 64.6 (range, 39–85) years. The median follow-up term was 16.3 (range, 2–53) months. Of the 56 patients, 53 (94.4%) had no apparent adverse events before surgery; 55 (98.2%) completed the full course of neoadjuvant therapy, while one patient stopped chemotherapy because of Grade 3 gastrointestinal toxicity (CTCAE v.3). The sphincter preservation rate was 94.6%. Downstaging was observed in 45 patients (80.4%). Adjuvant chemotherapy was administered to 43 patients (76.8%). The local control rate, disease-free survival rate and disease-specific survival rate were 100%, 91.1% and 100%, respectively. To conclude, SC-HART combined with S-1 for locally advanced rectal cancer was well tolerated and produced good short-term outcomes. SC-HART therefore appeared to have a good feasibility for use in further clinical trials.

Dosimetric and delivery characterizations of full-arc and half-arc volumetric-modulated arc therapy for maxillary cancer.

We compared the efficiency and accuracy of full-arc and half-arc volumetric-modulated arc therapy (VMAT) delivery for maxillary cancer. Plans for gantry rotation angles of 360° and 180° (full-arc and half-arc VMAT) were created for six maxillary cancer cases with the Monaco treatment planning system, and delivered using an Elekta Synergy linear accelerator. Full-arc and half-arc VMAT were compared with regard to homogeneity index (HI), conformity index (CI), mean dose to normal brain, total monitor units (MU), delivery times, root mean square (r.m.s.) gantry accelerations (°/s2), and r.m.s. gantry angle errors (°). The half-arc VMAT plans achieved comparable HI and CI to the full-arc plans. Mean doses to the normal brain and brainstem with the half-arc VMAT plans were on average 16% and 17% lower than those with the full-arc VMAT plans. For other organs at risk (OARs), no significant DVH differences were observed between plans. Half-arc VMAT resulted in 11% less total MU and 20% shorter delivery time than the full-arc VMAT, while r.m.s. gantry acceleration and r.m.s. gantry angle error during half-arc VMAT delivery were 30% and 23% less than those during full-arc VMAT delivery, respectively. Furthermore, the half-arc VMAT plans were comparable with the full-arc plans regarding dose homogeneity and conformity in maxillary cancer, and provided a statistical decrease in mean dose to OAR, total MU, delivery time and gantry angle error. Half-arc VMAT plans may be a suitable treatment option in radiotherapy for maxillary cancer.

Efficacy of Polaprezinc for Acute Radiation Proctitis in a Rat Model

PURPOSE The purpose of the present study was to standardize the experimental rat model of radiation proctitis and to examine the efficacy of polaprezinc on radiation proctitis. METHODS AND MATERIALS A total of 54 female Wistar rats (5 weeks old) were used. The rats were divided into three groups: those treated with polaprezinc (PZ+), those treated with base alone, exclusive of polaprezinc (PZ-), and those treated without any medication (control). All the rats were irradiated to the rectum. Polaprezinc was prepared as an ointment. The ointment was administered rectally each day after irradiation. All rats were killed on the 10th day after irradiation. The mucosal changes were evaluated endoscopically and pathologically. The results were graded from 0 to 4 and compared according to milder or more severe status, as applicable. RESULTS According to the endoscopic findings, the proportion of mild changes in the PZ+, PZ-, and control group was 71.4%, 25.0%, and 14.3% respectively. On pathologic examination, the proportion of low-grade findings in the PZ+, PZ-, and control group was 80.0%, 58.3%, and 42.9% for mucosal damage, 85.0%, 41.7%, and 42.9% for a mild degree of inflammation, and 50.0%, 33.3%, and 4.8% for a shallow depth of inflammation, respectively. The PZ+ group tended to have milder mucosal damage than the other groups, according to all criteria used. In addition, significant differences were observed between the PZ+ and control groups regarding the endoscopic findings, degree of inflammation, and depth of inflammation. CONCLUSIONS This model was confirmed to be a useful experimental rat model for radiation proctitis. The results of the present study have demonstrated the efficacy of polaprezinc against acute radiation-induced rectal disorders using the rat model.

Pravastatin reduces radiation-induced damage in normal tissues

Pravastatin is an inhibitor of 3-hydroxy-3-methyl- glutaryl-coenzyme A reductase that has been reported to have therapeutic applications in a range of inflammatory conditions. The aim of the present study was to assess the radioprotective effects of pravastatin in an experimental animal model. Mice were divided into two groups: The control group received ionizing radiation with no prior medication, while the pravastatin group received pravastatin prior to ionizing radiation. Pravastatin was administered orally at 30 mg/kg body weight in drinking water at 24 and 4 h before irradiation. Intestinal crypt epithelial cell survival and the incidence of apoptosis in the intestine and lung were measured post-irradiation. The effect of pravastatin on intestinal DNA damage was determined by immunohistochemistry. Finally, the effect of pravastatin on tumor response to radiotherapy was examined in a mouse mesothelioma xenograft model. Pravastatin increased the number of viable intestinal crypts and this effect was statistically significant in the ileum (P<0.0001). The pravastatin group showed significantly lower apoptotic indices in all examined parts of the intestine (P<0.0001) and tended to show reduced apoptosis in the lung. Pravastatin reduced the intestinal expression of ataxia-telangiectasia mutated and gamma-H2AX after irradiation. No apparent pravastatin-related differences were observed in the response of xenograft tumors to irradiation. In conclusion, pravastatin had radioprotective effects on the intestine and lung and reduced radiation-induced DNA double-strand breaks. Pravastatin may increase the therapeutic index of radiotherapy.

Body mass index can affect gastrointestinal and genitourinary toxicity in patients with prostate cancer treated with external beam radiation therapy

The aim of the present study was to determine the impact of obesity on radiation-induced gastrointestinal (GI) and genitourinary (GU) toxicity. The cases of 54 patients with prostate cancer, treated with three-dimensional conformal radiation therapy (RT), were reviewed. For each patient, the body mass index (BMI), distance between the prostate and rectum (D) on a computerised tomography scan and the dosimetric parameters of the rectum and bladder in the planning data of RT, were analyzed. GI and GU toxicity was assessed during and following RT. The results of the patients with a BMI of <25 (lower BMI) were compared with those of the patients with a BMI of ≥25 (higher BMI). The higher BMI group exhibited significantly lower doses of V60 and V65 in the rectum than the lower BMI group. No significant differences were found in D and bladder doses between the two groups. The incidence of acute GI and GU toxicity and late GI and GU toxicity were 41.7, 19.4, 35.3 and 5.7% in the lower BMI group, respectively, and 27.8, 27.8, 5.9 and 35.3% in the higher BMI group, respectively. In addition, a significant difference was found in the incidence of late GU toxicity between the two groups. Among patients who underwent RT for prostate cancer, those with higher BMIs had a tendency to show lower incidences of GI toxicity and higher incidences of GU toxicity than patients with lower BMIs. To conclude, an increased effort must be made to reduce rectal doses in patients with lower BMIs. Conversely, increased care for GU toxicity must be provided for overweight patients.

Prognostic value of pretreatment volume-based quantitative 18F-FDG PET/CT parameters in patients with malignant pleural mesothelioma

PURPOSE To investigate the relationships between pretreatment volume-based quantitative 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) parameters and overall survival (OS) in patients with malignant pleural mesothelioma (MPM). MATERIALS AND METHODS We retrospectively reviewed data from 201 MPM patients, of whom 38 underwent surgical resection, and calculated the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), including primary tumors and nodal or distant metastatic lesions, on pretreatment 18F-FDG PET/CT. Relationships between clinicopathological factors (age, sex, performance status, European Organization for Research and Treatment of Cancer [EORTC] score, histological subtype, TNM stage, and treatment strategy), volume-based quantitative PET/CT parameters, and OS were evaluated using a Cox proportional hazards model and log-rank test. RESULTS The median follow-up was 15 months (range, 1-96 months; median, 17 months). In a univariate analysis of all patients, older age (p<0.05), high EORTC score (p<0.001), non-epithelioid histological subtype (p<0.001), high T stage (p<0.001), positive N/M status (p<0.05, p<0.001), advanced TNM stage (p<0.001), non-surgical treatment (p<0.001), and high SUVmax (p<0.001), MTV (p<0.001), or TLG (p<0.001) were associated with significantly shorter OS. A multivariate analysis confirmed non-epithelioid subtype (hazard ratio [HR]: 1.69, 95% confidence interval [CI]: 1.14-2.48; p<0.05), non-surgical treatment (HR: 0.58, 95% CI: 0.34-0.95; p<0.05), and high TLG (HR: 1.97, 95% CI: 1.14-3.44; p<0.05) as independent negative predictors. CONCLUSIONS Pretreatment volume-based quantitative 18F-FDG PET/CT parameters, especially TLG, could serve as potential surrogate markers for MPM prognosis.

Three-dimensional radiochromic film dosimetry for volumetric modulated arc therapy using a spiral water phantom

We validated 3D radiochromic film dosimetry for volumetric modulated arc therapy (VMAT) using a newly developed spiral water phantom. The phantom consists of a main body and an insert box, each of which has an acrylic wall thickness of 3 mm and is filled with water. The insert box includes a spiral film box used for dose-distribution measurement, and a film holder for positioning a radiochromic film. The film holder has two parallel walls whose facing inner surfaces are equipped with spiral grooves in a mirrored configuration. The film is inserted into the spiral grooves by its side edges and runs along them to be positioned on a spiral plane. Dose calculation was performed by applying clinical VMAT plans to the spiral water phantom using a commercial Monte Carlo-based treatment-planning system, Monaco, whereas dose was measured by delivering the VMAT beams to the phantom. The calculated dose distributions were resampled on the spiral plane, and the dose distributions recorded on the film were scanned. Comparisons between the calculated and measured dose distributions yielded an average gamma-index pass rate of 87.0% (range, 91.2–84.6%) in nine prostate VMAT plans under 3 mm/3% criteria with a dose-calculation grid size of 2 mm. The pass rates were increased beyond 90% (average, 91.1%; range, 90.1–92.0%) when the dose-calculation grid size was decreased to 1 mm. We have confirmed that 3D radiochromic film dosimetry using the spiral water phantom is a simple and cost-effective approach to VMAT dose verification.

Development of a Three-dimensional Surgical Navigation System with Magnetic Resonance Angiography and a Three-dimensional Printer for Robot-assisted Radical Prostatectomy

We sought to develop a surgical navigation system using magnetic resonance angiography (MRA) and a three-dimensional (3D) printer for robot-assisted radical prostatectomy (RARP). Six patients with pathologically proven localized prostate cancer were prospectively enrolled in this study. Prostate magnetic resonance imaging (MRI), consisting of T2-weighted sampling perfection with application-optimized contrasts using different flip-angle evolutions (SPACE) and true fast imaging with steady-state precession (true FISP), reconstructed by volume rendering, was followed by dynamic contrast-enhanced MRA performed with a volumetric interpolated breath-hold examination (VIBE) during intravenous bolus injection of gadobutrol. Images of arterial and venous phases were acquired over approximately 210 seconds. Selected images were sent to a workstation for generation of 3D volume-rendered images and standard triangulated language (STL) files for 3D print construction. The neurovascular bundles (NVBs) were found in sequence on non-contrast images. Accessory pudendal arteries (APAs) were found in all cases in the arterial phase of contrast enhancement but were ill-defined on non-contrast enhanced MRA. Dynamic contrast-enhanced MRA helped to detect APAs, suggesting that this 3D system using MRI will be useful in RARP.

Evaluation of local look diffusion tensor imaging for magnetic resonance tractography of the periprostatic neurovascular bundle

The purpose of this study was to compare diffusion tensor imaging using the local look technique and sensitivity encoding for tractography of the periprostatic neurovascular bundle. We compared the surrounding tissues of the prostate in eight healthy volunteers. The results of tractography in terms of the numbers of fibers and the fractional anisotropy map were evaluated. Distortion was evaluated using the dice similarity coefficient between isotropic diffusion images created from diffusion tensor images and T2-weighted images. The number of lines in tractography was significantly greater in diffusion tensor imaging using the local look technique (p < 0.001). Although there was no difference in image distortion of the prostate between methods, an artifact appeared in the center of the diffusion tensor image using sensitivity encoding. In conclusion, diffusion tensor imaging using the local look technique was superior to that using sensitivity encoding for tractography of the periprostatic neurovascular bundle.