Ryo Toya

Grading Astrocytic Tumors by Using Apparent Diffusion Coefficient Parameters: Superiority of a One- versus Two-Parameter Pilot Method

PURPOSE To assess the utility of both minimum apparent diffusion coefficients (ADCs) and ADC difference values for grading astrocytic tumors at magnetic resonance imaging. MATERIALS AND METHODS The hospitals institutional review board approved this retrospective study and waived informed consent. Fifty patients (23 male patients, 27 female patients; median age, 53 years) with newly diagnosed astrocytic tumors were evaluated. Two observers blinded to clinical information independently measured the ADCs by manually placing three to five regions of interest (40-60 mm(2)) within the solid tumor either with or without contrast material-enhanced components and calculated the average ADC. Minimum and maximum ADCs were selected, and the difference between them was recorded as the ADC difference value. These ADC values were used as the parameters for tumor grading and were compared by using the Kruskal-Wallis test and receiver operating characteristic (ROC) curve analysis. RESULTS According to ROC analyses for distinguishing tumor grade, minimum ADCs showed the largest areas under the ROC curve. Minimum ADCs optimally helped distinguish grade 1 from higher-grade tumors at a cutoff value of 1.47 x 10(-3) mm(2)/sec and grade 4 from lower-grade tumors at a cutoff value of 1.01 x 10(-3) mm(2)/sec (P < .001 for both). ADC difference values helped distinguish grade 2 from grade 3 tumors at a cutoff value of 0.31 x 10(-3) mm(2)/sec (P < .001). When tumors were graded by using the combined minimum ADC and ADC difference cutoff values mentioned above (the two-parameter method), the following positive predictive values were obtained: grade 1 tumors, 73% (eight of 11); grade 2 tumors, 100% (five of five); grade 3 tumors, 67% (eight of 12); and grade 4 tumors, 91% (20 of 22). CONCLUSION Using a combination of minimum ADCs and ADC difference values (the two-parameter method) facilitates the accurate grading of astrocytic tumors.

Magnetic resonance imaging of pilocytic astrocytomas: Usefulness of the minimum Apparent Diffusion Coefficient (ADC) value for differentiation from high-grade gliomas

Background: On contrast-enhanced magnetic resonance (MR) images, pilocytic astrocytomas (PAs) are usually well-enhanced tumors that may mimic high-grade gliomas (HGGs). On the other hand, it has been suggested that areas exhibiting minimum apparent diffusion coefficient (ADC) values reflect the sites of highest cellularity within heterogeneous tumors. Purpose: To test the hypothesis that the cellularity of PAs is significantly different to the cellularity of HGGs, which should result in significant differences in minimum ADC values. Material and Methods: Between 1999 and 2005, 15 patients (nine males, six females) with histopathologically confirmed PAs underwent pretreatment MR examination including diffusion-weighted (DW) imaging. We reviewed their MR findings with respect to the size, location, morphology, contrast enhancement, and minimum ADC value of the tumors. The minimum ADC values of the 15 PAs were compared with those of 104 HGGs diagnosed during the same period. Results: The diameter of the 15 PAs ranged from 11 to 60 mm (mean 36 mm); all were located around the ventricles, and all contained enhancing components. All except two small (11 and 14 mm) PAs contained cystic components. The minimum ADC values were significantly higher in PAs (median 1.688, range 1.375–1.897×10−3 mm2/s) than HGGs (0.997, 0.543–2.024×10−3 mm2/s) (P<0.0001), although there was substantial overlap. Among the tumors with enhancing components, all but one PA were differentiated from the 76 HGGs with enhancing components (0.922, 0.543–1.462×10−3 mm2/s) when the minimum ADC cutoff value was set at 1.5×10−3 mm2/s. Conclusion: The minimum ADC value may be helpful for the differentiation between PAs and HGGs. A tumor with enhancing components should be PA instead of HGG when the minimum ADC value is higher than 1.5×10−3 mm2/s.

Radiation-induced Parotid Gland Changes in Oral Cancer Patients: Correlation Between Parotid Volume and Saliva Production

OBJECTIVE To evaluate whether saliva production reflects the parotid volume during the course of radiation therapy (RT) in patients with head-and-neck cancer. METHODS Twenty patients with advanced oral squamous cell carcinomas, who were treated with preoperative chemo-RT, underwent morphological assessment with CT or MRI and functional assessment with the Saxon test. For the Saxon test, saliva production was measured by weighing a gauze pad before and 2 min after chewing without swallowing; the low-normal value is 2 g. Saliva production and parotid volumes before and 2 weeks after RT were compared with the paired t-test, the Spearman rank correlation test and the Fisher exact test. RESULTS After 30 Gy irradiation, mean saliva production was decreased from 4.2 to 1.0 g (P < 0.01); the reduction in saliva production ranged from 1.7 to 5.4 g (mean 3.2 g). The mean parotid volume was decreased from 68.2 to 47.9 cm(3) (P < 0.01); the post-RT:pre-RT parotid volume ratio ranged from 54% to 85% (mean 71%). Although the initial parotid ;volume was correlated with initial saliva production (r = 0.47, P = 0.04), no significant correlation was noted after RT (r = 0.08, P = 0.71), and there were considerable individual variations. The parotid volume ratio was inversely correlated with the saliva-reduction amount (r = - 0.79, P < 0.01). CONCLUSIONS There was a correlation between decreased parotid gland volume and decreased saliva production in patients with head-and-neck cancer undergoing RT. Parotid volume reduction may predict parotid gland function.

Phase II Study of Preoperative Concurrent Chemoradiation Therapy With S-1 in Patients With T4 Oral Squamous Cell Carcinoma

PURPOSE To determine the feasibility and efficacy of preoperative concurrent chemoradiation therapy (CCRT) with S-1, an oral fluoropyrimidine derivative, in patients with T4 oral squamous cell carcinoma (SCC). METHODS AND MATERIALS Only patients with histologically proven T4 oral SCC were included. Radiotherapy (total dose, 30 Gy) was delivered in 2-Gy daily fractions over a period of 3 weeks. Concurrently, S-1 (80 mg/m(2)/day) was administered orally twice daily for 14 consecutive days. RESULTS We enrolled 46 patients. All underwent radiotherapy as planned; however, oral S-1 was discontinued in 3 patients who manifested acute toxicity. Grade 3 toxicities were mucositis (20%), anorexia (9%), and neutropenia (4%). We encountered no Grade 4 adverse events or serious postoperative morbidity requiring surgical intervention. After CCRT, 32 of the 46 patients underwent radical resection; in 17 (53%) of the operated patients, the pathologic response was complete. During follow-up ranging from 7 to 58 months (median, 22 months), tumor control failed in 5 (16%) of the 32 operated patients; there were 3 local and 2 regional failures. Of the 14 non-operated patients, 8 (57%) manifested local (n = 7) or regional failure (n = 1). The 3-year overall survival rate for all 46 patients was 69%; it was significantly higher for operated than for non-operated patients (82% vs. 48%; p = 0.0288). CONCLUSION Preoperative CCRT with S-1 is feasible and effective in patients with T4 oral SCC. Even in inoperable cases, CCRT with S-1 provides adequate tumor control.

IL-6 controls resistance to radiation by suppressing oxidative stress via the Nrf2-antioxidant pathway in oral squamous cell carcinoma

Background:In promoting tumour malignancy IL-6 signalling is considered to have an important role. However, the biological roles of IL-6 on radiosensitivity in oral squamous cell carcinoma (OSCC) remain largely unclear. The objective of this study is to determine the effects and molecular mechanisms of IL-6 on radiosensitivity in OSCC.Methods:Two OSCC cell lines, and OSCC tissue samples with radioresistant cells were used. We examined the effects of IL-6, or tocilizumab, a humanised anti-human IL-6 receptor antibody, or both on radiosensitivity and DNA damage after X-ray irradiation in vitro. In addition, we investigated the involvement of the Nrf2-antioxidant pathway in IL-6-mediated radioresistant mechanisms using OSCC cell lines and tissues.Results:Increased levels of IL-6 suppressed radiation-induced cell death, and the blockade of IL-6 signalling by tocilizumab sensitised tumour cells to radiation. The radioresistant effect of IL-6 was associated with decreased DNA damage after radiation. We also found that IL-6 promotes the activation of not only the downstream molecule STAT3 but also the Nrf2-antioxidant pathway, leading to a significant decrease in oxidative stress by upregulating Mn-SOD.Conclusions:These results indicate that the blockade of IL-6 signalling combined with conventional radiotherapy could augment the treatment response and survival rate in patients with radioresistant OSCC.

Respiratory Gating during Stereotactic Body Radiotherapy for Lung Cancer Reduces Tumor Position Variability

Purpose We evaluated the effects of respiratory gating on treatment accuracy in lung cancer patients undergoing lung stereotactic body radiotherapy by using electronic portal imaging device (EPID) images. Materials and Methods Our study population consisted of 30 lung cancer patients treated with stereotactic body radiotherapy (48 Gy/4 fractions/4 to 9 days). Of these, 14 were treated with- (group A) and 16 without gating (group B); typically the patients whose tumors showed three-dimensional respiratory motion ≧5 mm were selected for gating. Tumor respiratory motion was estimated using four-dimensional computed tomography images acquired during treatment simulation. Tumor position variability during all treatment sessions was assessed by measuring the standard deviation (SD) and range of tumor displacement on EPID images. The two groups were compared for tumor respiratory motion and position variability using the Mann-Whitney U test. Results The median three-dimensional tumor motion during simulation was greater in group A than group B (9 mm, range 3–30 mm vs. 2 mm, range 0–4 mm; p<0.001). In groups A and B the median SD of the tumor position was 1.1 mm and 0.9 mm in the craniocaudal- (p = 0.24) and 0.7 mm and 0.6 mm in the mediolateral direction (p = 0.89), respectively. The median range of the tumor position was 4.0 mm and 3.0 mm in the craniocaudal- (p = 0.21) and 2.0 mm and 1.5 mm in the mediolateral direction (p = 0.20), respectively. Conclusions Although patients treated with respiratory gating exhibited greater respiratory tumor motion during treatment simulation, tumor position variability in the EPID images was low and comparable to patients treated without gating. This demonstrates the benefit of respiratory gating.

Concurrent chemoradiotherapy with S‑1 in patients with stage III‑IV oral squamous cell carcinoma: A retrospective analysis of nodal classification based on the neck node level

The aim of the present study was to retrospectively evaluate the treatment outcomes of concurrent chemoradiotherapy (CCRT) with S-1, an oral fluoropyrimidine anticancer agent, for advanced oral squamous cell carcinoma (SCC). The study population consisted of 47 patients with clinical stage III or IV oral SCC, who underwent CCRT with S-1. Pretreatment variables, including patient age, clinical stage, T classification, midline involvement of the primary tumor and nodal status, were analyzed as predictors of survival. In addition to the N classification (node-positive, multiple and contralateral), the prognostic impact of the level of nodal involvement was assessed. Nodal involvement was mainly observed at levels Ib and II; involvement at levels Ia and III-V was considered to be anterior and inferior extension, respectively, and was recorded as extensive nodal involvement (ENI). The 3-year overall survival (OS) and progression-free survival (PFS) rates were 37 and 27%, respectively. A finding of ENI was a significant factor for OS [hazard ratio (HR)=2.16; 95% confidence interval (CI): 1.03-4.55; P=0.038] and PFS (HR=2.65; 95% CI: 1.32-5.33; P=0.005); the 3-year OS and PFS rates in patients with vs. those without ENI were 23 vs. 50% and 9 vs. 43%, respectively. The other variables were not significant. Therefore, CCRT with S-1 may be an alternative treatment for advanced oral SCC; favorable outcomes are expected in patients without ENI.

Spleen Dose–Volume Parameters as a Predictor of Treatment-related Lymphopenia During Definitive Chemoradiotherapy for Esophageal Cancer

Aim: Our study sought to identify dosimetric predictors of treatment-related lymphopenia during chemoradiotherapy for esophageal cancer. Materials and Methods: Patients with esophageal cancer who had received definitive chemoradiotherapy at our Institution were retrospectively assessed. The absolute volume of the spleen, body, and bone marrow that had received 5, 10, 20, and 30 Gy and the mean splenic dose were recorded. Results: Multivariate linear regression analysis revealed that docetaxel use and spleen dose–volume parameters (V5, V10, V20, V30, and mean splenic dose) were significant independent factors negatively influencing the absolute lymphocyte count at nadir. An increase of 1 Gy in mean splenic dose predicted a 2.9% decrease in nadir absolute lymphocyte count. Univariable logistic regression analysis showed that the mean splenic dose was a significant predictor of grade 4 lymphopenia. None of the body or bone marrow dose–volume parameters significantly predicted lymphopenia. Conclusion: Higher spleen dose–volume parameters were associated with severe lymphopenia during chemoradiotherapy.

Image quality of four-dimensional cone-beam computed tomography obtained at various gantry rotation speeds for liver stereotactic body radiation therapy with fiducial markers

In this study, qualities of 4D cone-beam CT (CBCT) images obtained using various gantry rotation speeds (GRSs) for liver stereotactic body radiation therapy (SBRT) with fiducial markers were quantitatively evaluated. Abdominal phantom containing a fiducial marker was moved along a sinusoidal waveform, and 4D-CBCT images were acquired with GRSs of 50-200° min-1. We obtained the 4D-CBCT projection data from six patients who underwent liver SBRT and generated 4D-CBCT images at GRSs of 67-200° min-1, by varying the number of projection data points. The image quality was evaluated based on the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and structural similarity index (SSIM). The fiducial marker positions with different GRSs were compared with the setup values and a reference position in the phantom and clinical studies, respectively. The root mean square errors (RMSEs) were calculated relative to the reference positions. In the phantom study, the mean SNR, CNR, and SSIM decreased from 37.6 to 10.1, from 39.8 to 10.1, and from 0.9 to 0.7, respectively, as the GRS increased from 50 to 200° min-1. The fiducial marker positions were within 2.0 mm at all GRSs. Similarly, in the clinical study, the mean SNR, CNR, and SSIM decreased from 50.4 to 13.7, from 24.2 to 6.0, and from 0.92 to 0.73, respectively. The mean RMSEs were 2.0, 2.1, and 3.6 mm for the GRSs of 67, 100, and 200° min-1, respectively. We conclude that GRSs of 67 and 85° min-1 yield images of acceptable quality for 4D-CBCT in liver SBRT with fiducial markers.

Effect of metal-containing topical agents on surface doses received during external irradiation

Abstract The ability of topical metal-containing agents (MCAs) to enhance radiation dermatitis remains controversial. In the present study, we evaluated increases in surface doses associated with topical agents at different application thicknesses and with MCAs versus non-metal containing agents (NMCAs). We assessed two clinically available MCAs, zinc oxide ointment (ZOO) and silver sulfadiazine cream (SSDC), and eight NMCAs. Surface doses were measured using a Markus chamber placed on a polystyrene phantom. To evaluate the role of application thickness, each agent was applied to the chamber in oil-slick (<0.1-mm), 1-mm and 5-mm layers prior to irradiation of a 10 × 10 cm field with 4-, 6- and 10-MV X-ray beams. The surface dose enhancement ratio (SDER) was calculated as the ratio of the surface dose with an agent to the dose without an agent. The SDER values for the eight NMCAs, ZOO and SSDC at an oil-slick thickness were 101.6–104.6% (mean: 103.3%), 104.5% and 105.0%, respectively, using a 6-MV X-ray beam. The corresponding values at a 1-mm thickness were 196.8–237.8% (mean: 215.7%), 229.3% and 201.4%, respectively, and those at a 5-mm thickness were 342.2–382.4% (mean: 357.9%), 357.1% and 352.6%, respectively. A similar tendency was found using 4- and 10-MV X-ray beams. The lack of a significant difference in surface dose enhancement between MCAs and NMCAs, particularly when applied in oil-slick layers, suggests that MCAs do not need to be avoided or applied in a restricted manner during radiotherapy for dosimetric reasons.