[Show abstract][Hide abstract] ABSTRACT: Purpose:
To evaluate the dose-response relationship for development of acute radiation mucositis (ARM) using an oral mucosal dose surface model (OMDS-model) in carbon ion radiotherapy (C-ion RT) for head and neck tumors.
Thirty-nine patients receiving C-ion RT for head and neck cancer were evaluated for ARM (once per week for 6 weeks) according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, and the Radiation Therapy Oncology Group (RTOG) scoring systems. The irradiation schedule typically used was 64 Gy [relative biological effectiveness (RBE)] in 16 fractions for 4 weeks. Maximum point doses in the palate and tongue were compared with ARM in each patient.
The location of the ARM coincided with the high-dose area in the OMDS-model. There was a clear dose-response relationship between maximum point dose and ARM grade assessed using the RTOG criteria but not the CTCAE. The threshold doses for grade 2-3 ARM in the palate and tongue were 43.0 Gy(RBE) and 54.3 Gy(RBE), respectively.
The OMDS-model was useful for predicting the location and severity of ARM. Maximum point doses in the model correlated well with grade 2-3 ARM.
PLoS ONE 10/2015; 10(10):e0141734. DOI:10.1371/journal.pone.0141734 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
The purpose of this study was to assess the incidence, risk factors, and dose-volume relationship of radiation-induced rib fracture (RIRF) after carbon ion radiotherapy for lung cancer.
Material and methods:
Fifty-seven ribs of 18 patients with peripheral stage I non-small cell lung cancer treated with carbon ion radiotherapy were analyzed on rib fracture. The patients were treated at a total dose of 52.8 Gy [relative biologic effectiveness (RBE)] or 60.0 Gy (RBE) in 4 fractions and were followed at least six months. Patient characteristics and dosimetric parameters were analyzed for associations with RIRF.
Eighteen patients and 57 ribs were included in this study. The median length of follow-up was 36.5 months. RIRF was observed in seven (39%) of the 18 patients, and in 11 (19%) of 57 ribs. Only one patient developed symptomatic fracture. The distance from the ribs to the tumor site was significantly shorter in fractured ribs than in non-fractured ribs (1.4 ± 0.3 cm vs. 2.5 ± 0.3 cm). Receiver operating characteristic curve analysis showed that [Formula: see text] as a cut-off value for discriminating RIRF had the largest area under the curve (AUC =0.78). Comparison of the two-year cumulative incidence of RIRF among two groups as determined by cut-off values, yielded the following result: 53% vs. 4% [[Formula: see text], ≥ 38.2 Gy (RBE) or less]. Results from the two groups were significantly different (p < 0.05).
The crude incidence of RIRF after carbon ion radiotherapy was 39% but incidence of symptomatic fracture was low. The [Formula: see text] as cut-off values may be helpful for discriminating the risk of RIRF.
[Show abstract][Hide abstract] ABSTRACT: Background:
The purpose of this study was to compare carbon ion radiotherapy (C-ion RT) and stereotactic radiotherapy (SBRT) with photon beams for the treatment of hepatocellular carcinoma (HCC), specifically with regard to the dose volume parameters for target coverage and normal tissue sparing.
Data of 10 patients who were treated using C-ion RT with a total dose of 60 Gy(RBE) in four fractions were used. The virtual plan of SBRT was simulated on the treatment planning computed tomography images of C-ion RT. Dose volume parameters such as minimum dose covering 90 % of the planning target volume (PTV D90), homogeneity index (HI), conformity index (CI), mean liver dose (MLD), volume of the liver receiving 5 to 60 Gy (V5-60), and max point dose (Dmax) of gastrointestinal (GI) tract were calculated from both treatment plans.
The PTV D90 was 59.6 ± 0.2 Gy(RBE) in C-ion RT, as compared to 56.6 ± 0.3 Gy in SBRT (p < 0.05). HI and CI were 1.19 ± 0.03 and 0.79 ± 0.06, respectively in C-ion RT, as compared to 1.21 ± 0.01 and 0.37 ± 0.02, respectively in SBRT. Only CI showed a significant difference between two modalities. Mean liver dose was 8.1 ± 1.4 Gy(RBE) in C-ion RT, as compared to 16.1 ± 2.5 Gy in SBRT (p < 0.05). V5 to V50 of liver were higher in SBRT than C-ion RT and significant differences were observed for V5, V10 and V20. Dmax of the GI tract was higher in SBRT than C-ion RT, but did not show a significantly difference.
C-ion RT provides an advantage in both target conformity and normal liver sparing compared with SBRT.
[Show abstract][Hide abstract] ABSTRACT: Key Clinical MessageInterstitial pneumonia (IP) sometimes precedes collagen vascular disease (CVD) onset. A patient with bladder cancer and mild IP received pelvic irradiation and experienced unexpectedly severe urinary toxicity followed by polymyositis onset and fatal IP exacerbation. Careful observation for “alarm adverse effects” of radiotherapy in IP patients may help predicting CVD onset.
[Show abstract][Hide abstract] ABSTRACT: Particle therapy, such as proton and carbon-ion radiotherapy, has better dose distribution than X-irradiation. Therefore, high dose of particle therapy is expected to control the primary tumor without high sever adverse effects. Several studies have reported that efficacy and safety of particle therapy for lung cancer, and we will review the overview these clinical results.
[Show abstract][Hide abstract] ABSTRACT: Aim:
To evaluate dosimetric differences between carbon ion radiotherapy (C-ion RT) and stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC).
Patients and methods:
Thirteen stage I NSCLC cases were planned with C-ion RT and SBRT. Prescription of the dose and fractionation (fr) for stage IA and IB in C-ion RT were 52.8 Gy (RBE)/4fr and 60.0 Gy (RBE)/4fr, respectively and those in SBRT were 52.8 Gy/4fr and 60.0 Gy/4fr, respectively.
The conformity index (CI) for planning target volume of C-ion RT was significantly lower than that of SBRT. The normal lung doses in C-ion RT were significantly lower those that in SBRT. In particularly, for a larger tumor, C-ion RT was lower CI and normal lung dose than SBRT.
C-ion RT has an advantage in both target conformity and sparing of normal lung in stage I NSCLC.
Anticancer research 09/2014; 34(9):5099-104. · 1.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Non-proliferating cells, such as mature neurons, are generally believed to be more resistant to X-rays than proliferating cells, such as glial and vascular endothelial cells. Therefore, the late adverse effects of radiotherapy on the brain have been attributed to the radiation-induced damage of glial and vascular endothelial cells. However, little is known about the radiosensitivities of neurons and glial cells due to difficulties in culturing these cells, particularly neurons, independently. In the present study, primary dissociated neurons and glial cultures were prepared separately from the hippocampi and cerebrum, respectively, which had been obtained from the same fetal rat on embryonic day 18. X-irradiations of 50 Gy were performed on the cultured neurons and glial cells at 7 and 21 days in vitro (DIV). The cells were fixed at 24 h after irradiation. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling was then performed to measure the apoptotic indices (AIs). The AIs of non-irradiated and irradiated neurons at 7 DIV were 23.7±6.7 and 64.9±4.8%, and those at 21 DIV were 52.1±17.4 and 44.6±12.5%, respectively. The AIs of non-irradiated and irradiated glial cells at 7 DIV were 5.8±1.5 and 78.4±3.3% and those at 21 DIV were 9.6±2.6 and 86.3±4.9%, respectively. Glial cells and neurons were radiosensitive at 7 DIV. However, while glial cells were radiosensitive at 21 DIV, neurons were not.
Experimental and therapeutic medicine 09/2014; 8(3):754-758. DOI:10.3892/etm.2014.1802 · 1.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose
To determine the efficacy and safety of oral S-1 in combination with cisplatin and thoracic radiotherapy in patients with unresectable stage III non-small-cell lung cancer (NSCLC).
Methods and materials
S-1 (50 mg/m2) was administered orally twice daily for 14 days, with cisplatin (40 mg/m2) on days 1 and 8 of each cycle every 3 weeks, for 2–4 cycles. Thoracic radiation therapy was administered in 2 Gy fractions five times weekly for a total dose of 60 Gy. The primary endpoint was the response rate, and secondary endpoints included progression-free survival, overall survival and safety.
Forty-one patients were enrolled in this study. The objective response rate was 87.8% (98% CI: 77.8–97.8%). The median progression-free survival was 467 days (15.4 months), and the median survival time was 904 days (29.7 months). The overall survival rates at 1- and 2-years were 85.7% and 52.9%, respectively. Hematological toxicities included grade 3/4 neutropenia (17%) and grade 3/4 leukopenia (27%). No grade 3 febrile neutropenia was detected, and grade 3/4 non-hematological toxicities were also mild. A grade 3 gastrointestinal hemorrhage was observed in one patient.
The combination of oral S-1 plus cisplatin with concurrent radiotherapy is a promising treatment with a high efficacy and lower toxicity in patients with locally advanced NSCLC.
Lung Cancer 12/2013; 82(3):449–454. DOI:10.1016/j.lungcan.2013.09.004 · 3.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study was conducted to investigate the feasibility and survival benefits of combined treatment with radiotherapy and temozolomide (TMZ), which has been covered by the national health insurance in Japanese patients with glioblastoma since September 2006. Between September 2006 and December 2011, 47 patients with newly diagnosed and histologically confirmed glioblastoma received radiotherapy for 60 Gy in 30 fractions. Among them, 45 patients (TMZ group) received concomitant TMZ (75 mg/m(2)/day, every day) and adjuvant TMZ (200 mg/m(2)/day, 5 days during each 28-days). All 36 of the glioblastoma patients receiving radiotherapy between January 1988 and August 2006 were analyzed as historical controls (control group). All patients were followed for at least 1 year or until they died. The median survival was 15.8 months in the TMZ group and 12.0 months in the control group after a median follow-up of 14.0 months. The hazard ratio for death in the TMZ group relative to the control group was 0.52 (P<0.01); the 2-year survival rate was 27.7% in the TMZ group and 14.6% in the control group. Hematologic toxicity of grade 3 and higher was observed in 20.4% in the TMZ group. Multivariate analysis showed that extent of surgery had the strongest impact on survival (P<0.01), while the use of TMZ had the second largest impact on survival (P = 0.035). The results indicate that combined treatment with radiotherapy and TMZ has a significant survival benefit for Japanese patients with newly diagnosed glioblastoma with slightly higher toxicities than previously reported.
PLoS ONE 11/2013; 8(11):e78943. DOI:10.1371/journal.pone.0078943 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Neurons are essential components of neural circuits and provide brain function organization. We previously reported that X irradiation induces apoptosis in immature neurons. To the best of our knowledge, there have been few reports investigating the effects of X irradiation on mature neurons. We analyzed the effects of X irradiation on the morphology, density and cytoskeletal proteins in dendritic spines on mature neurons. We prepared developing hippocampal neurons from 18 days embryo by using Banker's method. Neurons at 21 days in vitro were X irradiated at several doses and were immediately fixed. To evaluate the dendritic spine morphology and density, the neurons were transfected with a reporter plasmid for enhanced green fluorescent protein (GFP). Changes in the dendritic spines as a result of X irradiation were evaluated using electron microscopy. To analyze the cytoskeletal proteins within the dendritic spines, we performed immunocytochemistry to detect filamentous actin (F-actin), drebrin and PSD-95. X irradiation immediately changed the dendritic spine morphology, and the irradiated spines were significantly thinner and longer than the nonirradiated spines. X irradiation decreased the dendritic spine density in a dose-dependent manner. Electron microscopy confirmed these changes of dendritic spines by X irradiation. Immunohistochemical studies showed that X irradiation decreased the accumulation of drebrin and F-actin, but not PSD-95, within the dendritic spines. These results suggest that X irradiation immediately decreases the dendritic spine density and changes the morphology of mature neurons by reducing the abundance of cytoskeletal proteins. The abnormal dendritic spines may be associated with acute adverse effects after X irradiation in a clinical setting, although further investigations are warranted to validate these findings.
Radiation Research 04/2013; 179(6). DOI:10.1667/RR3098.1 · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Esophageal cancer patients are often associated with multiple primary cancers (MPC). The aim of this study is to evaluate the effect of MPC on prognosis in esophageal cancer patients treated by radiotherapy. Between 2001 and 2008, esophageal cancer patients treated by definitive radiotherapy at Gunma Cancer Center were retrospectively reviewed. Exclusion criteria were preoperative or postoperative radiotherapy, palliative radiotherapy, follow-up of <6 months, radiation dose of <50 Gy and no information on MPC. We analyzed 167 esophageal cancer patients and 56 (33.5%) were associated with MPC. Gastric cancer was the most frequent tumor (38.2%), followed by head and neck cancer (26.5%). Median follow-up time was 31.5 months (range 6.1-87.3 months). Patients with MPC included more stage I/II esophageal cancer than those without MPC (66.1% vs. 36.9%, P < 0.01). The 5-year overall survival rate for esophageal cancer with MPC was relatively better than those without MPC (46.1% vs. 26.7%), although the difference did not reach statistical significance in univariate analysis (P = 0.09). Stage I/II esophageal cancer patients had a significantly better overall survival than stage III/IV patients (P < 0.01). Among esophageal cancer patients with MPC, there was no difference in overall survival between antecedent and synchronous cancer (P = 0.59). Our study indicated that the prognosis of esophageal cancer patients treated by radiotherapy was primarily determined by the clinical stage itself, but not the presence of MPC.
Journal of Radiation Research 02/2013; 54(4). DOI:10.1093/jrr/rrt002 · 1.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recently, it has become clear that acute hypoxia affecting radioresistance exists widely in tumor tissues. Concurrently, hypoxia-inducible factor-1α (HIF-1α) is recognized as an essential transcriptional factor, enabling cells to survive through hypoxia. However, it is unclear as to whether HIF-1α plays a direct role in the radioresistance caused by acute hypoxia. Therefore, in this study, we investigated the in vitro response of the human lung adenocarcinoma cell line, A549, to ionizing radiation in an experimental model that imitates acute hypoxia in the presence and absence of HIF-1α expression, using the HIF-1α inhibitor 5-[1-(phenylmethyl)-1H-indazol-3-yl]-2-furanmethanol (YC-1). Cells were treated with or without 10 μM YC-1 for 2 h. Cells were exposed to either 95% N(2) and 5% CO(2) (hypoxic condition of <0.1 mmHg) or atmospheric air (normoxic condition) for 1 h, and irradiated with 2, 5 and 10 Gy. Western blot analysis revealed that, without YC-1, cells exposed to hypoxic conditions expressed increased levels of HIF-1α compared with those exposed to normoxic conditions. Under hypoxic conditions, HIF-1α expression was suppressed by YC-1 to the same extent as that observed in cells exposed to normoxic conditions without YC-1. Clonogenic survival assay revealed that under hypoxic conditions there was no significant difference between the surviving fraction of cells treated with YC-1 and without YC-1 at any dose point examined. The oxygen enhancement ratio at 10% surviving fraction was calculated as 2.7 and 2.6 in the presence and the absence of YC-1, respectively. These results indicate that HIF-1α itself is not an immediate cause of acute hypoxia-induced radioresistance in A549 cells.
Experimental and therapeutic medicine 09/2012; 3(1):141-145. DOI:10.3892/etm.2011.373 · 1.27 Impact Factor