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To visualize intratumoral hypoxic areas and their reoxygenation before and during fractionated radiation therapy (RT), (18)F-fluoromisonidazole positron emission tomography and computed tomography (F-MISO PET/CT) were performed. A total of 10 patients, consisting of four with head and neck cancers, four with gastrointestinal cancers, one with lung cancer, and one with uterine cancer, were included. F-MISO PET/CT was performed twice, before RT and during fractionated RT of approximately 20 Gy/10 fractions, for eight of the 10 patients. F-MISO maximum standardized uptake values (SUVmax) of normal muscles and tumors were measured. The tumor-to-muscle (T/M) ratios of F-MISO SUVmax were also calculated. Mean SUVmax ± standard deviation (SD) of normal muscles was 1.25 ± 0.17, and SUVmax above the mean + 2 SD (≥1.60 SUV) was regarded as a hypoxic area. Nine of the 10 tumors had an F-MISO SUVmax of ≥1.60. All eight tumors examined twice showed a decrease in the SUVmax, T/M ratio, or percentage of hypoxic volume (F-MISO ≥1.60) at approximately 20 Gy, indicating reoxygenation. In conclusion, accumulation of F-MISO of ≥1.60 SUV was regarded as an intratumoral hypoxic area in our F-MISO PET/CT system. Most human tumors (90%) in this small series had hypoxic areas before RT, although hypoxic volume was minimal (0.0-0.3%) for four of the 10 tumors. In addition, reoxygenation was observed in most tumors at two weeks of fractionated RT.

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OBJECTIVE: Long-term survival and late toxicities of a randomized Phase II study of chemoradiotherapy for esophageal cancer were analyzed. METHODS: Eligible patients were <75 years old and performance status 0-2, and had Stages II-IVA esophageal cancer. For arm A (short-term infusion), cisplatin 70 mg/m(2) Days 1 and 29 and 5-fluorouracil 700 mg/m(2) Days 1-5 and 29-33 were given concurrently with radiotherapy of 60 Gy/30 fr/7 weeks (1 week split). For arm B (protracted infusion), cisplatin 7 mg/m(2) Days 1-5, 8-12, 29-33 and 36-40, and 5-fluorouracil 250 mg/m(2) Days 1-14 and 29-42 were given with the same radiotherapy. Two cycles of consolidation cisplatin/5-fluorouracil chemotherapy were given to both arms. RESULTS: Between 2001 and 2006, 91 patients were enrolled; 46 were randomized to arm A, and 45 to arm B. The 2- and 5-year overall survival rates for arm A were 46 and 35% (95% confidence interval: 22-48%), while those for arm B were 44 and 22% (11-35%), respectively. Excluding four patients with early death, seven (17%) patients in arm A and eight (18%) in arm B showed late toxicities of Grade 3 or more. Most of the toxicities were cardiac or pleural toxicities. Patients with severe late toxicities often had coexistent hypothyroidism. There were three patients with a secondary malignancy possibly related to treatment. CONCLUSIONS: Low-dose protracted infusion chemotherapy with radiotherapy is not superior to full-dose short-term infusion chemotherapy with radiotherapy for esophageal cancer. Late toxicities, including cardiac and pleural toxicities, hypothyroidism and secondary malignancy, should be carefully monitored.

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BACKGROUND: To determine the clinical results of radiotherapy (RT) for esophageal cancer in Japan. MATERIALS AND METHODS: A questionnaire-based survey was conducted for esophageal cancer treated by definitive RT between 1999 and 2003. Clinical results of definitive RT for patients were collected from 9 major institutions. Only patients with good performance status (PS 0-2) who received a total dose of 50 Gy or more were included. Patients were classified into three groups: (A) stage I, (B) resectable stages II-III, (C) unresectable stages III-IVA. For group A, all patients treated by RT alone or chemo-radiotherapy (CRT) were included. For groups B and C, only those treated by CRT were included. RESULTS: In total, 167 patients were included in group A, 239 in group B, and 244 in group C. Approximately half of the patients in group A were treated by CRT. The median total RT dose ranged from 60 to 66 Gy. The median and range of the 5-year overall survival rates were 56% (48-83%) for group A, 29% (12-52%) for group B, and 19% (0-31%) for group C, respectively. A wide disparity in overall survival rates was noted among the institutions. A significant correlation between the number of patients treated per year and the 5-year overall survival rate was noted for groups B and C (both p < 0.05). CONCLUSION: Although the overall survival rates for stage I esophageal cancer were excellent, a significant disparity in survival rates was noted among the institutions for stage II-IVA tumors treated by CRT.

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BACKGROUND AND PURPOSE: Postoperative adjuvant treatment with strontium-90 radiation therapy (RT) is a proven technique for reducing the recurrence of pterygium. This randomized trial was conducted to evaluate whether a total dose of 40 Gy provides a better local control rate than a total dose of 30 Gy for surgically resected pterygia. PATIENTS AND METHODS: A single institutional randomized trial was conducted. Between 1999 and 2003, 74 pterygia in 71 patients were randomly allocated to 30 Gy/3 fractions/15 days (arm A) or to 40 Gy/4 fractions/22 days (arm B). Only primary pterygia for which RT could be started within 3 days of surgical resection were included. Postoperative RT was given by a strontium-90 eye applicator, and a dose of 10 Gy per fraction was delivered in weekly fractions (day 1, 8, 15, 22). RESULTS: Of the 74 pterygia treated, 73 in 70 patients were analyzed. Of the 73 pterygia, 41 were allocated to arm A, and the remaining 32 to arm B. The 2-year local control rates for arm A and arm B were 85% and 75%, respectively, without significant difference. No serious acute and late complications were noted in either arm. CONCLUSION: Our new standard fractionation for postoperative RT for pterygia is 30 Gy/3 fractions.

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OBJECTIVE: The purpose of this retrospective study was to analyze the results of accelerated hyperfractionation for patients with moderately advanced (T2 and T3) laryngeal cancer. METHODS: Between 1998 and 2007, 9 supraglottic carcinomas (6 T2N0M0, 2 T2N2M0, 1 T3N0M0), 30 glottic carcinomas (25 T2N0M0, 5 T3N0M0), and 1 T2N0M0 subglottic carcinoma were treated with definitive radiotherapy using accelerated hyperfractionation without concurrent chemotherapy. The dose-fractionation for 35 patients was 72.8 Gy/56 fractions/5.6 weeks, and that for four patients treated between 1998 and 2001 was 72 Gy/60 fractions/6 weeks. One patient who had been treated with steroid therapy for systemic lupus erythematosus was treated by 67.8 Gy/44 fractions/4.4 weeks. RESULTS: The local control and overall survival probabilities at 5 years for supraglottic carcinomas were 75% and 86%, respectively. Those for glottic carcinomas were 80% and 92%, respectively. The 5-year local control probabilities for T2 and T3 tumors were 85% and 56%, respectively. This excellent local control rate especially for T2 laryngeal carcinomas may be attributable to the effect of accelerated hyperfractionation. No late toxicities of grade 2 or more was noted among the 39 patients treated with 72.8 Gy/56 fractions or 72 Gy/60 fractions. CONCLUSION: Accelerated hyperfractionation of 72.8 Gy/56 fractions/5.6 weeks using 1.3 Gy/fraction seems a safe and effective dose-fractionation for patients with moderately advanced laryngeal carcinomas.

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OBJECTIVE: The aim of this study was to analyze the clinical results of our adaptive radiation therapy scheme of a two-step intensity-modulated radiotherapy (IMRT) method for nasopharyngeal cancer (NPC) at Kinki University Hospital. METHODS: Between 2000 and 2007, 35 patients with Stage I-IVB NPC treated by IMRT were included. For all patients, treatment-planning computed tomography was done twice before and during IMRT to a total dose of 60-70 Gy/28-35 fractions (median 68 Gy). Chemotherapy (cisplatin 80 mg/m(2)/3 weeks x 1-3 courses) was given concurrently with IMRT for 31 patients. RESULTS: The 3- and 5-year overall survival rates for the 31 patients treated with concurrent chemotherapy were 88% and 83%, respectively. The 3- and 5-year loco-regional control rates for the 31 patients were 93% and 87%, respectively. Planning target volume delineation for the primary site or involved nodes was insufficient for three early cases, resulting in marginal recurrence in the three patients (9%). Except for one patient with early death, xerostomia scores at 1-2 years were: Grade 0, 11; Grade 1, 17; Grade 2, 5; Grade 3, 1. CONCLUSIONS: Excellent overall survival and loco-regional control rates were obtained by a two-step IMRT method with concurrent chemotherapy for NPC, although marginal recurrence was noted in some early cases.

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PURPOSE: A randomized phase II study was conducted to compare the toxicity and efficacy of combining short-term chemotherapy (CT) or protracted CT with radiotherapy (RT) for esophageal cancer. MATERIALS AND METHODS: Eligible patients were <75 years and with performance status (PS) of 0-2, and had stages II-IVA esophageal cancer. Two cycles of cisplatin 70 mg/m(2) for 1 day and 5FU 700 mg/m(2) for 5 days (arm A) or cisplatin 7 mg/m(2) for 10 days and 5FU 250 mg/m(2) for 14 days (arm B) were given with RT of 60Gy/30 fractions/7 weeks (1-week split). RESULTS: Of 91 patients enrolled, 46 were randomized to arm A and 45 to arm B. Two cycles of CT were given concurrently with RT for 89% in arm A and for 71% in arm B with significant difference (P=.031). The 2- and 5-year overall survival rates for arm A were 46% and 35%, while those for arm B were 44% and 24%, respectively, without significant difference. The 2- and 5-year progression-free survival rates for arm A were 30% and 30%, while those for arm B were 29% and 12%, respectively. CONCLUSIONS: Protracted infusion CT with RT provides no advantage over standard short-term infusion CT with RT for esophageal cancer.

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BACKGROUND: The aim of this article is to report the treatment outcomes, toxicities, and dosimetric feasibility of our simultaneous-boost intensity-modulated radiotherapy (SIB-IMRT) protocol. METHODS: Thirteen patients with malignant gliomas treated between December 2000 and September 2004 were enrolled in this study. Two planning target volumes (PTVs) were defined in the present study. Our IMRT regimen delivered 70 Gy/28 fractions (fr)/daily; 2.5 Gy to the gross tumor volume (GTV) with a 0.5-cm margin, defined as the PTV-G, and 56 Gy/28 fr/daily, with 2.0 Gy to the surrounding edema, defined as the planning target volume annulus (PTV-a). Eleven of the 13 patients received one or two courses of nimustine hydrochloride (ACNU) (100 mg/m(2)) and vincristine (1.2 mg/body) and interferon-beta (3 x 10(6) units) three times weekly during the period of radiotherapy. Adjuvant chemotherapy, ACNU (100 mg/m(2)) and vincristine (1.2 mg/body), was repeated every 6 weeks and interferon-beta was repeated every 2 weeks. The treatment outcomes, toxicity, and dosimetric feasibility were assessed. RESULTS: All the patients experienced tumor recurrence. The median progression-free survival times for patients with grade III tumors and glioblastome were 7.5 and 8.0 months, respectively. The 1-year and 2-year overall survival rates for all the patients were 77% and 31%, respectively. Four patients experienced acute grade 1/2 toxicities during the treatment. No late toxicity related to radiotherapy has been seen. Analyses with dose-volume histograms confirmed excellent conformity of dose distributions in the two target volumes, PTV-G and PTV-a, with the sparing of organs at risk. CONCLUSION: Our IMRT regimen did not prevent tumor progression. However, the ability of IMRT to deliver highly conformative doses to two contiguous targets, GTV and the surrounding edema, justifies its application to malignant gliomas.

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BACKGROUND: We reviewed clinical results of chemoradiotherapy (CRT) in the treatment of patients with advanced esophageal cancer with fistulae that developed before or during CRT. METHODS AND MATERIALS: The study group included 16 patients with fistulous esophageal cancer treated by means of CRT between 1999 and 2006. Nine patients had fistulae before CRT, whereas 7 developed fistulae during CRT. The group included 12 men and four women with a median age of 55 years (range, 37-77 years). There were 9 patients with Stage III disease and 7 with Stage IV disease. All tumors were squamous cell carcinomas. Two courses of concurrent chemotherapy were combined with radiation therapy; 60 Gy/30 fractions/7 weeks (1-week split). For 15 patients, low-dose protracted chemotherapy with 5-fluorouracil (250-300 mg/m(2) x 14 days) and cisplatin (7 mg/m(2) x 10 days) was administered, whereas full-dose cisplatin and 5-fluorouracil were administered to the remaining patient. RESULTS: The planned dose of 60 Gy was delivered to 11 patients (69%), whereas radiation therapy was terminated early in 5 patients (40-58 Gy) because of acute toxicities, including two treatment-related deaths. Disappearance of fistulae was noted during or after CRT in 7 patients (44%). All three esophagomediastinal fistulae were closed, but only four of 13 esophagorespiratory fistulae were closed by CRT. For patients with Stage III, 1- and 2-year survival rates were 33% and 22%, respectively. Median survival time was 8.5 months. CONCLUSION: Despite significant toxicity, concurrent CRT appears effective at closing esophageal malignant fistulae.

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BACKGROUND AND PURPOSE: To analyze the interfractional set-up errors and intrafractional organ motions and to define appropriate planning target volume (PTV)- and planning organs at risk volume (PRV)-margins in intensity-modulated radiotherapy (IMRT) for head and neck tumors. PATIENTS AND METHODS: Twenty-two patients with head and neck or brain tumors who were treated with IMRT were enrolled. The set-up errors were defined as the displacements of the coordinates of bony landmarks on the beam films from those on the simulation films. The organ motions were determined as the displacements of the coordinates of the landmarks on the images recorded every 3 min for 15 min on the X-ray simulator from those on the initial image. RESULTS: The standard deviations (SDs) of the systematic set-up errors (Sigma-INTER) and organ motions (Sigma-intra) distributed with a range of 0.7-1.3 and 0.2-0.8 mm, respectively. The average of the SDs of the random set-up errors (sigma-INTER) and organ motions (sigma-intra) ranged from 0.7 to 1.6 mm and from 0.3 to 0.6 mm, respectively. Appropriate PTV-margins and PRV-margins for all the landmarks ranged from 2.0 to 3.6 mm and from 1.8 to 2.4 mm, respectively. CONCLUSIONS: We have adopted a PTV-margin of 5mm and a PRV-margin of 3mm for head and neck IMRT at our department.

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OBJECTIVE: Our aim was to evaluate predictors of xerostomia in patients with head and neck cancers treated with intensity-modulated radiation therapy (IMRT). METHODS: Thirty-three patients with pharyngeal cancer were evaluated for xerostomia after having been treated with IMRT. All patients were treated with whole-neck irradiation of 46-50 Gy by IMRT, followed by boost IMRT to the high-risk clinical target volume to a total dose of 56-70 Gy in 28-35 fractions (median, 68 Gy). For boost IMRT, a second computed tomography (CT-2) scan was done in the third to fourth week of IMRT. Xerostomia was scored 3-4 months after the start of IMRT. RESULTS: The mean doses to the contralateral and ipsilateral parotid glands were 24.0 +/- 6.2 and 30.3 +/- 6.6 Gy, respectively. Among the 33 patients, xerostomia of grades 0, 1, 2 and 3 was noted in one, 18, 12 and two patients, respectively. Although the mean dose to the parotid glands was not correlated with the grade of xerostomia, the initial volume of the parotid glands was correlated with the grade of xerostomia (P = 0.04). Of 17 patients with small parotid glands (< or =38.8 ml) on initial CT (CT-1), 11 (65%) showed grade 2 or grade 3 xerostomia, whereas only three (19%) of 16 patients with larger parotid glands showed grade 2 xerostomia (P < 0.05). The mean volume of the parotid glands on CT-1 was 43.1 +/- 15.2 ml, but decreased significantly to 32.0 +/- 11.4 ml (74%) on CT-2 (P < 0.0001). CONCLUSIONS: Initial volumes of the parotid glands are significantly correlated with the grade of xerostomia in patients treated with IMRT. The volume of the parotid glands decreased significantly during the course of IMRT.

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PURPOSE: To prospectively evaluate aortic and hepatic enhancement and depiction of hypervascular hepatocellular carcinoma (HCC) between two contrast materials with moderate and high iodine concentrations when administered at same iodine dose and injection duration at multi-detector row helical computed tomography (CT). MATERIALS AND METHODS: Institutional review board approval and informed patient consent were obtained. One hundred eighty-six patients were studied, and 67 patients with hypervascular HCC were identified. Ninety-four patients were assigned to receive iohexol 350 (mg iodine per milliliter) with protocol A; 92, iohexol 300 with protocol B. In both protocols, iohexol with same iodine load per weight (518 mg/kg) was administered with same injection duration (25 seconds). Multiphase CT scanning was started 10, 20, 50, and 180 seconds after the trigger (threshold level set at increase of 100 HU over baseline CT number of aorta). Enhancement of aorta and liver was measured in 186 patients. Tumor-to-liver contrast was measured in 67 patients with hypervascular HCC. Statistical analysis was performed with Mann-Whitney U test. RESULTS: Medians of aortic enhancement during four phases were 325, 185, 112, and 69 HU with protocol A. Corresponding values were 344, 266, 121, and 73 HU with protocol B. During all phases, aortic enhancement was significantly higher with protocol B (P = .046, P < .001, P < .001, and P = .002). Hepatic enhancement during four phases was 6, 21, 48, and 34 HU with protocol A. Corresponding values were 3, 17, 47, and 35 HU with protocol B. Hepatic enhancement was significantly higher with protocol A during first and second phases (P < .001 for both), although there was no significant difference between protocols during third and fourth phases (P = .778 and P = .178, respectively). Medians of tumor-to-liver contrast during four phases were 22, 34, 0.5, and -1.1 HU with protocol A. Corresponding values were 23, 45, 0, and -8.6 HU with protocol B. Tumor-to-liver contrast was significantly higher with protocol B during second phase (P = .049), although there was no difference between protocols during other phases. CONCLUSION: When total iodine dose was adjusted to body weight and injection duration was fixed, rapid administration of moderate concentration of contrast material was more effective for depiction of hypervascular HCC than was high concentration of contrast material.

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BACKGROUND: We carried out the present study to investigate the feasibility and effectiveness of concurrent chemoradiotherapy (CT-RT) for postoperative recurrent esophageal cancer, which are, at present, unclear. METHODS: Between 1998 and 2002, 16 patients with postoperative loco-regional recurrence of esophageal cancer, and two patients with incompletely resected esophageal cancer were treated with concurrent CT-RT. Patients received protracted infusion of 5-FU 250-300 mg/m(2) on days 1 to 14, 1 hour infusion of cisplatin 10 mg/body on days 1 to 5 and 8 to 12, and a concurrent radiotherapy (RT) dose of 30 Gy in 15 fractions over 3 weeks. This treatment schedule was repeated twice with a gap of 1 week, for a total RT dose of 60 Gy administered over 7 weeks. RESULTS: Of the 18 patients, 13 (72%) completed the CT-RT protocol. A total RT dose of 60 Gy was administered for all except two patients, and doses of chemotherapy were reduced for five patients. Although grade 3 hematological toxicities were frequently noted, non-hematological toxicities of grades 3 and 4 were few. Of the 18 tumors, five (28%) showed complete response (CR). For patients without prior chemotherapy, the CR rate was 40% (4/10). The 2-year survival rate of 13 patients without distant metastases was 19%, with a median survival time of 9.5 months. CONCLUSION: The concurrent CT-RT protocol appears feasible and effective for patients with postoperative recurrent or residual esophageal cancer.

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OBJECTIVE: This study was designed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of weekly docetaxel in combination with concurrent radiotherapy for treating head and neck cancer. METHODS: Twelve patients with unresectable or postoperative head and neck cancers were enrolled in a dose-escalating phase I study. Eleven of the 12 patients were postoperative patients with intermediate or high pathological risk features. Radiotherapy was delivered as a standard fractionation regimen (2 Gy/day, 5 fractions/week) to a total dose of 60-70 Gy. The starting dose of docetaxel was 10 mg/m(2) (once per week) with a subsequent dose escalation of 5 mg/m(2) in cohorts of three patients. In 2001 and 2002, 12 patients completing three dose levels were included in the study. RESULTS: The MTD of docetaxel was 20 mg/m(2). With the third dose level (20 mg/m(2)), DLT was observed in two of three patients. One experienced grade IV mucositis and another suffered from prolonged grade III mucositis-enforced treatment delay for 13 days. Hematological toxicity was minimal. Mucositis was the DLT of concurrent chemoradiotherapy using weekly docetaxel administration for head and neck cancer. CONCLUSIONS: We identified the recommended phase II dose of docetaxel as 15 mg/m(2) administered weekly with concurrent radiotherapy for head and neck cancers.

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