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Objective: This study aimed to evaluate the efficacy and toxicity of proton beam therapy combined with cisplatin intra-arterial infusion via a superficial temporal artery as treatment for maxillary sinus carcinoma., Methods: Twenty-six patients with confirmed maxillary sinus carcinoma were enrolled in this study from May 2009 to April 2011. Patients underwent proton beam therapy and intra-arterial infusion chemotherapy with cisplatin., Results: The median total dose was 70.4 GyE per 32 fractions, and the median dose of cisplatin was 300 mg/body for six cycles of intra-arterial infusion. The 3-year overall survival rate was 58% for all patients (n = 26), 58% for patients with stage T4 disease (n = 12), 57% for patients with

In patients undergoing radiotherapy for localized prostate cancer, dose-volume histograms and clinical variables were examined to search for correlations between radiation treatment planning parameters and late rectal bleeding. We analyzed 129 patients with localized prostate cancer who were managed from 2002 to 2010 at our institution. They were treated with 3D conformal radiation therapy (3D-CRT, 70 Gy/35 fractions, 55 patients) or intensity-modulated radiation therapy (IMRT, 76 Gy/38 fractions, 74 patients). All radiation treatment plans were retrospectively reconstructed, dose-volume histograms of the rectum were generated, and the doses delivered to the rectum were calculated. Time to rectal bleeding ranged from 9-53 months, with a median of 18.7 months. Of the 129 patients, 33 patients had Grade 1 bleeding and were treated with steroid suppositories, while 25 patients with Grade 2 bleeding received argon plasma laser coagulation therapy (APC). Three patients with Grade 3 bleeding required both APC and blood transfusion. The 5-year incidence rate of Grade 2 or 3 rectal bleeding was 21.8% for the 3D-CRT group and 21.6% for the IMRT group. Univariate analysis showed significant differences in the average values from V65 to V10 between Grades 0-1 and Grades 2-3. Multivariate analysis demonstrated that patients with V65 ≥ 17% had a significantly increased risk (P = 0.032) of Grade 2 or 3 rectal bleeding. Of the 28 patients of Grade 2 or 3 rectal bleeding, 17 patients (60.7%) were cured by a single session of APC, while the other 11 patients required two sessions. Thus, none of the patients had any further rectal bleeding after the second APC session., (© The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

This study sought to demonstrate the feasibility of estimating the source strength during implantation in brachytherapy. The requirement for measuring the strengths of the linked sources was investigated. The utilized sources were (125)I with air kerma strengths of 8.38-8.63 U (μGy m(2) h(-1)). Measurements were performed with a plastic scintillator (80 mm × 50 mm × 20 mm in thickness). For a source-to-source distance of 10.5 mm and at source speeds of up to 200 mm s(-1), a counting time of 10 ms and a detector-to-needle distance of 5 mm were found to be the appropriate measurement conditions. The combined standard uncertainty (CSU) with the coverage factor of 1 (k = 1) was ∼15% when using a grid to decrease the interference by the neighboring sources. Without the grid, the CSU (k = 1) was ∼5%, and an 8% overestimation due to the neighboring sources was found to potentially cause additional uncertainty. In order to improve the accuracy in estimating source strength, it is recommended that the measurment conditions should be optimized by considering the tradeoff between the overestimation due to the neighboring sources and the intensity of the measured value, which influences the random error., (© The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

The post-implantation dosimetry for brachytherapy using Monte Carlo calculation by EGS5 code combined with the source strength regression was investigated with respect to its validity. In this method, the source strength for the EGS5 calculation was adjusted with the regression, so that the calculation would reproduce the dose monitored with the glass rod dosimeters (GRDs) on a water phantom. The experiments were performed, simulating the case where one of two (125)I sources of Oncoseed 6711 was lacking strength by 4-48%. As a result, the calculation without regression was in agreement with the GRD measurement within 26-62%. In this case, the shortage in strength of a source was neglected. By the regression, in order to reflect the strength shortage, the agreement was improved up to 17-24%. This agreement was also comparable with accuracy of the dose calculation for single source geometry reported previously. These results suggest the validity of the dosimetry method proposed in this study.

The aim of this study is to demonstrate the feasibility of estimating the strength of the moving radiation source during patient implantation. The requirement for the counting time was investigated by comparing the results of the measurements for the static source with those for the source moving at 2, 5, 10 and 20 cm s(-1). The utilized source was (125)I with an air-kerma strength of 0.432 U (μGym(2)h(-1)). The detector utilized was a plastic scintillation detector (8 cm × 5 cm × 2 cm in thickness) set at 8 cm away from the needle to guide the source. Experiments were conducted in order to determine the most desirable counting time. Analysis using the maximum of the measured values while the source passed through the needle indicated that the results for the moving source increased more than those for the static source as the counting time decreased. The combined standard uncertainty, with the coverage factor of 1, was within 4% at the counting time of 100 ms. This investigation supported the feasibility of the method proposed for estimating the source strength during the implantation procedure, regardless of the source speed. The method proposed is a potential option for reducing the risk of accidental replacements of sources with those of incorrect strengths.

This study investigated the maximum tolerated dose (MTD) of S-1 with concurrent radiotherapy in patients with head and neck cancer, based on the frequency of dose-limiting toxicities (DLT). S-1 was administered orally at escalating doses from 40 mg/m(2) b.i.d. on the days of delivering radiotherapy, which was given at a total dose of 64-70 Gy in 32-35 fractions over 6-7 weeks. A total of 12 patients (3 patients at 40 mg/m(2), 6 patients at 60 mg/m(2), and 3 patients at 80 mg/m(2)) were enrolled in this trial. At the dose of 80 mg/m(2), two of the three patients developed DLT (Grade 3 anorexia and rhabdomyolysis) due to S-1, so the MTD was determined to be 80 mg/m(2). Among the 12 enrolled patients, 9 (75%) showed a complete response and 3 (25%) showed a partial response. The overall response rate was 100%. The recommended dose of S-1 with concurrent radiotherapy is 60 mg/m(2).

We investigated the uncertainty in patient set-up margin analysis with a small dataset consisting of a limited number of clinical cases over a short time period, and propose a method for determining the optimum set-up margin. Patient set-up errors from 555 registration images of 15 patients with prostate cancer were tested for normality using a quantile-quantile (Q-Q) plot and a Kolmogorov-Smirnov test with the hypothesis that the data were not normally distributed. The ranges of set-up errors include the set-up errors within the 95% interval of the entire patient data histogram, and their equivalent normal distributions were compared. The patient set-up error was not normally distributed. When the patient set-up error distribution was assumed to have a normal distribution, an underestimate of the actual set-up error occurred in some patients but an overestimate occurred in others. When using a limited dataset for patient set-up errors, which consists of only a small number of the cases over a short period of time in a clinical practice, the 2.5% and 97.5% intervals of the actual patient data histogram from the percentile method should be used for estimating the set-up margin. Since set-up error data is usually not normally distributed, these intervals should provide a more accurate estimate of set-up margin. In this way, the uncertainty in patient set-up margin analysis in radiation therapy can be reduced.

The post-exposure density growth (PEDG) is one of the characteristics of radiochromic film (RCF). In film dosimetry using RCF and a flatbed scanner, pixel values read out from the RCF are converted to dose (hereafter, film dose) by using a calibration curve. The aim of this study is to analyze the relationship between the pixel value read out from the RCF and the PEDG, and that between the film dose converted from the RCF and the PEDG. The film (GAFCHROMIC EBT) was irradiated with 10-MV X-rays in an ascending 11-dose-step arrangement. The pixel values of the irradiated EBT film were measured at arbitrary hours using an Epson flatbed scanner. In this study, the reference time was 24 h after irradiation, and all dose conversions from the pixel values read out from the EBT film were made using a calibration curve for 24 h after irradiation. For delivered doses of 33 and 348 cGy, the measured pixel values at 0.1 and 16 h after irradiation represented ranges of -9.6% to -0.7% and -3.9% to -0.3%, respectively, of the reference value. The relative changes between the pixel values read out from the EBT film at each elapsed time and that at the reference time decreased with increasing delivered dose. However, the difference range for all the film doses had a width of approximately -10% of the reference value at elapsed times from 0.1 to 16 h, and it showed no dependence on the delivered dose.

Gimeracil, an inhibitor of dihydropyrimidine dehydrogenase (DPYD), partially inhibits homologous recombination (HR) repair and has a radiosensitizing effect as well as enhanced sensitivity to Camptothecin (CPT). DPYD is the target protein for radiosensitization by Gimeracil. We investigated the mechanisms of sensitization of radiation and CPT by DPYD inhibition using DLD-1 cells treated with siRNA for DPYD. We investigated the focus formation of various kinds of proteins involved in HR and examined the phosphorylation of RPA by irradiation using Western blot analysis. DPYD depletion by siRNA significantly restrained the formation of radiation-induced foci of Rad51 and RPA, whereas it increased the number of foci of NBS1. The numbers of colocalization of NBS1 and RPA foci in DPYD-depleted cells after radiation were significantly smaller than in the control cells. These results suggest that DPYD depletion is attributable to decreased single-stranded DNA generated by the Mre11/Rad50/NBS1 complex-dependent resection of DNA double-strand break ends. The phosphorylation of RPA by irradiation was partially suppressed in DPYD-depleted cells, suggesting that DPYD depletion may partially inhibit DNA repair with HR by suppressing phosphorylation of RPA. DPYD depletion showed a radiosensitizing effect as well as enhanced sensitivity to CPT. The radiosensitizing effect of DPYD depletion plus CPT was the additive effect of DPYD depletion and CPT. DPYD depletion did not have a cell-killing effect, suggesting that DPYD depletion may not be so toxic. Considering these results, the combination of CPT and drugs that inhibit DPYD may prove useful for radiotherapy as a method of radiosensitization.

Objective: Low-dose-rate (LDR) brachytherapy is an effective treatment for tongue cancer. However, little is known about the biological mechanism underlying this therapy, characterized by delivery of continuous exposures of LDR irradiation. It is reported that lower microvessel density (MVD), lower Ki-67 index or higher expression of endogenous hypoxic markers such as carbonic CA IX and Glut-1 are related to the poor control of tumors treated with external irradiation. To elucidate the biological characteristics of LDR brachytherapy, we analyzed our results in cases of tongue cancer treated with LDR brachytherapy by using immunohistochemical stainings with antibodies against Ki-67 and MVD, Glut-1 and CA IX., Methods: The prognostic value of Ki-67 index, MVD and the expression of CA IX and Glut-1 was assessed in 68 tongue cancers treated with LDR brachytherapy. The specimens were taken from tongue cancers before radiation therapy and immunohistochemical staining was performed., Results: The local recurrence-free survival rates were significantly different between T1+T2 and T3 (P = 0.00067), but not between low and high Ki-67 indexes (P = 0.54), between low and high MVD (P = 0.071), low and high CA IX indexes (P = 0.062) or low and high Glut-1 indexes (P = 0.107). T stage, the size of the tumor was the only significant factor for local control in multivariate analyses (P = 0.0377)., Conclusion: LDR could overcome the radioresistence of non-cycling and hypoxic cells; however, we cannot draw firm conclusions due to the limited number of patients.

Background: External beam radiotherapy (XRT) has been a standard treatment for clinically localized prostate cancer. However, preservation of erectile function following XRT is controversial. In this study, the influence of XRT on erectile function of patients with clinically organ-confined or locally advanced prostate cancer was retrospectively evaluated., Methods: The study included 34 of 84 patients with organ-confined or locally advanced prostate cancer who underwent XRT between 1995 and 2002. Erectile function following radiotherapy was assessed by a simple mailed questionnaire that was constructed for the study. To determine the predictive factors for erectile dysfunction following radiotherapy, data were analyzed by multivariate analysis with the Cox proportional hazards model., Results: The modality of XRT was the only factor to independently predict erectile dysfunction following XRT. The maintenance rates of erectile function were 47.6% at 1 year and 19% at 3 years in patients who received the 3-dimensional conformal radiotherapy, which were significantly higher than in those who received conventional radiotherapy (P = 0.026)., Conclusions: XRT significantly reduced the maintenance rate of erectile function during the follow-up period, with the rate being 19% at 3 years in patients who received 3-dimensional conformal radiation. The XRT modality was involved in the reduction of erectile function. These results suggest that erectile dysfunction is a possible adverse event following XRT.

Background: To investigate and analyze changes in irradiated salivary gland function of patients with head and neck tumors treated with radiotherapy., Methods: Thirty-seven patients with head and neck tumors, who received 40-70 Gy of irradiation to all major salivary glands, were analyzed. The weights of saliva secreted for 10 minutes at rest, and for 5 minutes with vitamin C stimulation, were measured. The salivary gland function was defined by the weight of saliva., Results: With vitamin C stimulation, the weight of saliva in patients whose doses were < or =50 Gy, was significantly higher than that of patients whose doses were > or = 58 Gy (2.48 +/- 0.33 g vs. 0.73 +/- 0.18 g, P = 0.0003). When doses administered to salivary glands were < or =50 Gy, the stimulated saliva secretion recovered over time, after irradiation. However, when the doses of irradiation were > or = 58 Gy, there was no recovery in saliva secretion even after a few years. Multiple regression analysis showed that age and chemotherapy may not affect salivary gland function even years after radiotherapy., Conclusion: When salivary glands were irradiated with doses < or =50 Gy, gradual recovery of salivary gland function was observed over time, whereas there was no significant recovery when the irradiation dose was >58 Gy.

Purpose: We report the treatment results and complications of external beam radiation monotherapy for localized or locally advanced prostate cancer patients., Methods: Fifty-four patients with T(1b-3a)N(0)(pN(0))M(0) prostate cancer were treated with external beam radiation monotherapy between 1989 and 2001 at four institutes., Results: During the 4-122 month follow-up period (median: 25 months), 11 (20%) patients experienced biochemical failure, including one with simultaneous local recurrence. The 2-year actuarial biochemical control rate was 85%. Univariate analysis showed that the clinical T classification (P = 0.01), Gleason score (P = 0.006), pretreatment PSA (P = 0.02) and PSA nadir value (P = 0.01) were associated with a higher probability of biochemical failure. Multivariate analysis using the Cox proportional hazards model demonstrated that only the PSA nadir value was a strong predictor of PSA recurrence (P < 0.01). Adverse events were mild and tolerable. No severe urinary or bowel complications were observed., Conclusions: External beam radiation monotherapy is effective for clinically organ-confined prostate cancer with a low incidence of severe complications in a mean follow-up period of 2 years.

We report our experiences of four cases with meningeal hemangiopericytoma treated with surgery and postoperative radiotherapy and survey the literature to elucidate the efficacy of radiotherapy. Patients were treated with surgical resection and 46-52 Gy postoperative radiotherapy. Three patients had local control for 30, 54 and 138 months, respectively and one patient had local recurrence after 49 months. Distant metastases were observed in two patients; one had multiple bone, liver and lung metastases and the other multiple bone and brain metastases. For bone and brain metastases, better tumor control was obtained with palliative radiotherapy and stereotactic radiotherapy. Literature analyses demonstrated that surgery and postoperative radiotherapy of 50 Gy or more resulted in significantly better local control than surgery alone (p = 0.02). Stereotactic radiosurgery was effective for intracranial recurrence or metastasis, especially when the tumor volume was <8 cm(3) and >15 Gy at the 50% isodose line was used. Radiotherapy for bone metastases was also effective for palliation.

Background: There is at present no consensus on the policy for the treatment of patients with low-grade gliomas (LGGs)., Methods: This report is a retrospective multi-institutional study of 100 patients (ages 16-65 years) with astrocytoma (grade II), oligodendroglioma, anaplastic oligodendroglioma and anaplastic oligoastrocytoma of the supratentorial areas which were treated with surgery and postoperative radiotherapy at five university hospitals in northern Japan between 1990 and 1997 when MRI was routinely used to determine the target volume. Most patients were irradiated with 50-60 Gy. The target volume usually covered the areas with T2 prolongation of MRI with a margin of 2 cm., Results: The disease-specific 5-year survival rate was 87.4% for patients with oligodendroglioma and 75.3% for patients with astrocytoma. Survival for patients with astrocytoma in the MRI era appears to be improved compared with historical controls in the literature. Patients with astrocytoma aged 40 years and under had a significantly better disease-specific survival rate than those over 40 years (P < 0.05) and patients with oligodendroglioma and oligoastrocytoma showed a similar tendency. Patients with astrocytoma who had over 50% of their tumor removed had a significantly better survival rate than those who had less than 50% removed (P < 0.05). Chemotherapy appeared to improve the disease-specific survival rate of patients with oligodendroglioma but not that of patients with astrocytoma., Conclusion: Oligodendroglioma has a more protracted course of disease progression than astrocytoma. This particular feature and the sensitivity of LGGs to chemotherapy as well as their relevant prognostic factors, such as age, histopathology and amount of tumor removal, should be taken into account before any decision on treatment methods for LGGs is made.

We report a case of extravasation of an antitumor agent by preoperative magnetic resonance (MR) imaging. MR studies demonstrated a decreased signal intensity on T1- and T2-weighted images and a strong enhancement of contrast media in injured tissue, including subcutaneous adipose tissue and deep fascia, which was cicatrical macroscopically. The MR findings were in good agreement with the macroscopic findings. We believe that MR imaging is useful for estimating deep tissue damage due to extravasation of an antitumor agent.

A small percentage of children with acute lymphocytic leukemia experience relapse in the central nervous system in spite of prophylaxis. Diffuse leptomeningeal infiltration is common but an intracranial leukemic mass or spinal cord involvement is a rare manifestation. We report a child with acute lymphocytic leukemia who simultaneously developed a pineal tumor and an intradural spinal cord mass as her first relapse. She was successfully managed by comprehensive combined treatment including peripheral blood stem cell transplantation. She remains in continuous complete remission for more than 5 years without further evidence of neurological sequelae.

Background: To report the results of radiotherapy for patients with failure, adverse reactions or relative contraindications to the use of steroids or immunosuppressants, by using newly developed quantitative indexes., Methods: Fourteen female and six male patients with Graves' ophthalmopathy were treated with radiotherapy between 1989 and 1996. Prior to radiotherapy, eight patients received treatment with prednisone, four received immunosuppressants and four received a combination of both. Four patients with contraindications to steroids were initially managed with radiotherapy. Most of the patients received a dose of 24-28 Gy in 2 Gy fractions. We used the newly developed motility limitation index to assess extraocular motility., Results: Treatment was well tolerated. There have been no late complications. All 12 patients with soft tissue signs such as edema, irritation, tearing and pain were improved. Proptosis did not improve or improved only slightly, 3 mm at best. However, proptosis in all but two has been stabilized and has not deteriorated in the follow-up period. Most of the patients have experienced an improvement of eye-muscle motility. Extraocular muscles that work for elevation were impaired more severely than the other muscles and this tended to remain. Of the 16 patients using steroids before or when radiotherapy was initiated, 15 were tapered off and only one patient required additional steroids, thus sparing the majority from steroid adverse reactions., Conclusion: Radiotherapy was effective in preventing exacerbations of active inflammatory ophthalmopathy in patients with Graves' disease with minimal morbidity and thus eliminated the adverse reactions associated with protracted corticosteroid use. The newly developed motility limitation index was useful in detecting delicate changes in motility of individual extraocular muscles.

Most laryngeal cancers are squamous cell carcinomas, and adenocarcinomas account for < 1% of cancers of the larynx. Among them, mucoepidermoid carcinoma is extremely rare and there is little agreement about the treatment of this carcinoma. We encountered one patient with mucoepidermoid carcinoma of the bilateral vocal cords (T1bN0M0, Stage 1). For this, most investigators recommended a surgical procedure. However, because of his old age, the early stage and low grade of histopathology, we treated this patient with radiotherapy alone, delivered by accelerated hyperfractionation, which is a more effective strategy for treating radioresistant tumors than conventional irradiation. Following radiotherapy, the tumor disappeared and the patient has been alive and well for more than six years. An old patient with mucoepidermoid carcinoma of the larynx was successfully treated with radiotherapy alone.

Background: To correlate the imaging and pathological features and to discuss therapeutic modalities and the prognosis of malignant lymphoma originating in the parotid gland, which is relatively rare., Methods: The subjects were five patients with malignant lymphoma originating in the parotid gland. Three and two patients were stage I and stage II, respectively. CT examination was applied to all, whereas only one case was examined by MRI. All were treated with radiotherapy following surgery or chemotherapy. Three patients underwent combination chemotherapy, such as with MACOP-P or VEPA, following surgery., Results: Although malignant lymphoma originating in the parotid gland is histologically described as low-grade non-Hodgkin's lymphoma, two and one of the cases were classified as intermediate and high grade in the present series, respectively. These three exhibited a tendency for infiltration into the adjacent tissue and tumor inhomogeneity in the imaging findings, suggesting a correlation with histologically intermediate or high-grade non-Hodgkin's lymphoma. It was successfully controlled by radiotherapy, with dosages ranging from 40 to 44 Gy. The patients were followed for 2-8 years. No relapse was found in the three patients with stage I. However, both stage II patients had relapses and were subjected to additional radiotherapy combined with chemotherapy. Since then, no tumor relapse has been noted at either this or other sites., Conclusions: Malignant lymphoma including intermediate or high grade originating in the parotid gland indicated satisfactory prognosis following radiotherapy and chemotherapy.

We report our experience with radiotherapy for three patients with cervical carcinoma in whom surgery had been downgraded to the performance of exploratory laparotomy only, because of extensive primary tumor or nodal invasion to the surrounding organs and vessels. Tumor invasion to the bladder, side wall invasion or unresectable nodal disease at the time of exploration prevented definitive surgery in our case series. After laparotomy, we carried out radiation therapy consisting of external irradiation to the pelvis and intracavitary irradiation with high dose rate 60Co or low dose rate 137Cs sources. Local and regional control was obtained in all three patients, and there was no locoregional recurrence during > 5 years of follow-up. One patient died of paraaortic lymph node metastases, but she had no pelvic recurrence. Several authors have reported an increased risk of small bowel obstruction in patients who undergo laparotomy before radiotherapy. None of our patients developed small bowel obstruction, although one had anal bleeding which was cured by conservative therapy. Radiotherapy was effective for locoregional control in all three patients with unresectable cervical carcinoma.

Collagen disease are frequently associated with malignant tumors. Recently, radiotherapy combined with chemotherapy has been recommended for improving the efficacy of treatment for nasopharyngeal carcinoma. Two patients with nasopharyngeal carcinoma complicated by collagen diseases (dermatomyositis in one, and Sjögren's syndrome with mixed connective tissue disease in the other) were given radiotherapy combined with chemotherapy consisting of cis-platinum and 5-fluorouracil. Following this combination therapy, both patients developed retropharyngeal abscess and ulceration of the mucosal membrane on the posterior wall of the oropharynx; there was no tumor cell involvement. Because these injuries were more severe than would have been expected from radiotherapy alone, it is recommended that special attention be paid to combination therapy in patients with nasopharyngeal carcinoma complicated by collagen disease.