Haruo Matsushita

Intraoperative radiation therapy (IORT) for previously untreated malignant gliomas

BackgroundIntraoperative radiation therapy (IORT) is one of the methods used to deliver a large single dose to the tumor tissue while reducing the exposure of normal surrounding tissue. However, the usefulness of intraoperative electron therapy for malignant gliomas has not been established.MethodsDuring the period from 1987 to 1997, 32 patients with malignant gliomas were treated with IORT. The histological diagnoses were anaplastic astrocytoma in 11 patients and glioblastoma in 21 patients. Therapy consisted of surgical resection and intraoperative electron therapy using a dose of 12–15 Gy (median, 15 Gy). The patients later underwent postoperative external radiation therapy (EXRT) with a median total dose of 60 Gy. Each of the 32 patients treated with IORT was randomly matched with patients who had been treated with postoperative EXRT alone (control). Patients were matched according to histological grade, age, extent of tumor removal, and tumor location.ResultsIn the anaplastic astrocytoma group, the one-, two- and five-year survival rates were 81%, 51% and 15%, respectively in the IORT patients and 54%, 43% and 21%, respectively in the control patients. In the glioblastoma group, one-, two- and five-year survival rates were 63%, 26% and 0%, respectively in the IORT patients and 70%, 18% and 6%, respectively in the control patients. There was no significant difference between survival rates in the IORT patients and control patients in either the anaplastic astrocytoma group or glioblastoma group.ConclusionsIORT dose not improve survival of patients with malignant gliomas compared to that of patients who have received EXRT alone.

Evaluation of various deformable image registration algorithms for thoracic images

We evaluated the accuracy of one commercially available and three publicly available deformable image registration (DIR) algorithms for thoracic four-dimensional (4D) computed tomography (CT) images. Five patients with esophagus cancer were studied. Datasets of the five patients were provided by DIR-lab (dir-lab.com) and consisted of thoracic 4D CT images and a coordinate list of anatomical landmarks that had been manually identified. Expert landmark correspondence was used for evaluating DIR spatial accuracy. First, the manually measured displacement vector field (mDVF) was obtained from the coordinate list of anatomical landmarks. Then the automatically calculated displacement vector field (aDVF) was calculated by using the following four DIR algorithms: B-spine implemented in Velocity AI (Velocity Medical, Atlanta, GA, USA), free-form deformation (FFD), Horn–Schunk optical flow (OF) and Demons in DIRART of MATLAB software. Registration error is defined as the difference between mDVF and aDVF. The mean 3D registration errors were 2.7 ± 0.8 mm for B-spline, 3.6 ± 1.0 mm for FFD, 2.4 ± 0.9 mm for OF and 2.4 ± 1.2 mm for Demons. The results showed that reasonable accuracy was achieved in B-spline, OF and Demons, and that these algorithms have the potential to be used for 4D dose calculation, automatic image segmentation and 4D CT ventilation imaging in patients with thoracic cancer. However, for all algorithms, the accuracy might be improved by using the optimized parameter setting. Furthermore, for B-spline in Velocity AI, the 3D registration error was small with displacements of less than ∼10 mm, indicating that this software may be useful in this range of displacements.

Radiation therapy for loco-regionally recurrent esophageal cancer after surgery

PURPOSE To evaluate the treatment outcome of radiation therapy for 33 loco-regionally recurrent esophageal cancer patients. METHODS Between 1988 and 1997, 33 patients with loco-regional recurrence of esophageal cancer after curative surgery received radiation therapy at an average total dose of 61 Gy. The site of recurrence was the supraclavicular region in 14 patients, the mediastinal region in 13 patients, and both the supraclavicular and mediastinal regions in six patients. If patients had ether distant metastasis or malignant pleural effusion, they were excluded from analysis. Patients who received prophylactic postoperative irradiation were also excluded from analysis. RESULTS The median survival period was 7 months. The survival rates at 1, 2, and 3 years were 33, 15, and 12%, respectively. In univariate analysis, patients with a short time interval between surgery and recurrence (P=0.0098) and patients with recurrence in both the supraclavicular and mediastinal regions (P=0.036) had a worse prognosis. In multivariate analysis, the time interval between surgery and recurrence (P<0.001) and age (worse prognosis in younger patients, P=0.019) were the significant prognostic factors. Complete or partial responses were observed in nine (27%) and 21 (64%) of the patients, respectively. Changes in clinical symptoms, such as dysphagia, chest pain and back pain, could be evaluated in 11 patients, and improvement in symptoms was obtained in eight (73%) patients. CONCLUSIONS The prognosis of patients who received radiation therapy for postoperative loco-regional recurrence of esophageal cancer is poor. However, there is symptomatic relief in a significant proportion of such patients, and long-term survival is possible in some patients.

Radiation therapy for limited-stage small-cell esophageal cancer

Between 1985 and 1999, 20 patients with limited-stage small-cell carcinoma of the esophagus (SCEC) received radiation therapy at Tohoku University Hospital and Miyagi Cancer Center Hospital. Twelve patients received definitive radiation therapy and eight patients received postoperative prophylactic irradiation after surgery. The 1-, 2-, and 5-year survival rates of all cases were 44%, 37%, and 19%, respectively. Distant metastasis was the most frequent pattern of recurrence. Survival rates differed significantly between the 6 patients who were not treated with chemotherapy (median survival time, 5 months) and the 14 patients who were (24 months) (p = 0.0061). Good local control rates can be obtained by definite or postoperative radiation therapy for SCEC. However, SCEC should be regarded as a systemic disease, and chemotherapy should be given. Multiinstitutional studies are needed to obtain sufficiently large populations for investigation and optimization of local therapy for this disease.

Results of radiation therapy combined with nedaplatin (cis-diammine-glycoplatinum) and 5-Fluorouracil for postoperative locoregional recurrent esophageal cancer

BackgroundAlthough the effectiveness of radiotherapy with concurrent administration of several anti-tumor drugs for postoperative recurrent esophageal cancer has been demonstrated, the results are not satisfactory. The purpose of the present study was to evaluate the effectiveness and safety of radiotherapy combined with nedaplatin and 5-FU for postoperative locoregional (excluding hematogenous metastasis) recurrent esophageal cancer.MethodsIn June 2000, we started a phase II study on treatment of postoperative locoregional recurrent esophageal cancer with radiotherapy (60 Gy/30 fr/6 weeks) combined with chemotherapy consisting of two cycles of nedaplatin (70 mg/m2/2 h) and 5-FU (500 mg/m2/24 h for 5 days).The primary endpoint of the present study was overall survival rate, and the second endpoints were irradiated-field control rate, tumor response and toxicity.ResultsA total of 30 patients were included in this study. The 1-year and 3-year overall survival rates were 60.6% and 56.3%, respectively, with a median survival period of 39.0 months, and the 1-year and 3-year irradiated-field control rates were 86.4% and 72%, respectively. Complete response and partial response were observed in 13.3% and 60.0% of the patients, respectively. Grade 3 or higher leukocytopenia and thrombocytopenia were observed in 30% and 3.3% of the patients, respectively, but renal toxicity of grade 3 or higher was not observed. The regimen was completed in 76.7% of the patients.In univariate analysis, the difference between survival rate in preradiotherapy performance status, recurrent pattern (worse for patients with anastomotic recurrence) and age (worse for younger patients) were statistically significant.ConclusionRadiotherapy combined with nedaplatin and 5-FU is a safe and effective salvage treatment for postoperative locoregional recurrent esophageal cancer.

Treatment outcome of high-dose image-guided intensity-modulated radiotherapy using intra-prostate fiducial markers for localized prostate cancer at a single institute in Japan

BackgroundSeveral studies have confirmed the advantages of delivering high doses of external beam radiotherapy to achieve optimal tumor-control outcomes in patients with localized prostate cancer. We evaluated the medium-term treatment outcome after high-dose, image-guided intensity-modulated radiotherapy (IMRT) using intra-prostate fiducial markers for clinically localized prostate cancer.MethodsIn total, 141 patients with localized prostate cancer treated with image-guided IMRT (76 Gy in 13 patients and 80 Gy in 128 patients) between 2003 and 2008 were enrolled in this study. The patients were classified according to the National Comprehensive Cancer Network-defined risk groups. Thirty-six intermediate-risk patients and 105 high-risk patients were included. Androgen-deprivation therapy was performed in 124 patients (88%) for a median of 11 months (range: 2–88 months). Prostate-specific antigen (PSA) relapse was defined according to the Phoenix-definition (i.e., an absolute nadir plus 2 ng/ml dated at the call). The 5-year actuarial PSA relapse-free survival, the 5-year distant metastasis-free survival, the 5-year cause-specific survival (CSS), the 5-year overall survival (OS) outcomes and the acute and late toxicities were analyzed. The toxicity data were scored according to the Common Terminology Criteria for Adverse Events, version 4.0. The median follow-up was 60 months.ResultsThe 5-year PSA relapse-free survival rates were 100% for the intermediate-risk patients and 82.2% for the high-risk patients; the 5-year actuarial distant metastasis-free survival rates were 100% and 95% for the intermediate- and high-risk patients, respectively; the 5-year CSS rates were 100% for both patient subsets; and the 5-year OS rates were 100% and 91.7% for the intermediate- and high-risk patients, respectively. The Gleason score (<8 vs. ≥8) was significant for the 5-year PSA relapse-free survival on multivariate analysis (p = 0.044). There was no grade 3 or 4 acute toxicity. The incidence of grade 2 acute gastrointestinal (GI) and genitourinary (GU) toxicities were 1.4% and 8.5%, respectively. The 5-year actuarial likelihood of late grade 2–3 GI and GU toxicities were 6% and 6.3%, respectively. No grade 4 GI or GU late toxicity was observed.ConclusionsThese medium-term results demonstrate a good tolerance of high-dose image-guided IMRT. However, further follow-up is needed to confirm the long-term treatment outcomes.

Radiation therapy combined with cis-diammine-glycolatoplatinum (Nedaplatin) and 5-fluorouracil for untreated and recurrent esophageal cancer.

From January 1999 to November 2000, a total of 24 esophageal cancer patients (17 untreated and 7 recurrent cases) were treated with radiation therapy (60–70 Gy) combined with cis-diammine-glycolatoplatinum (Nedaplatin) (80–120 mg/body) and 5-fluorouracil (5-FU) (500–1,000 mg/body/24 h, continuous infusion for 5 days). Grade III leukocytopenia was observed in 6 (25%) of the patients. Grade III and IV thrombocytopenia was observed in one patient each. The 1-year and 2-year survival rates for definitively irradiated patients were 59% and 39%, respectively, and for patients with postoperative recurrence 69% and 69%, respectively. High-dose radiation combined with Nedaplatin and 5-FU is a safe and effective method for treating esophageal cancer.

Prognostic factors for local control of stage I non-small cell lung cancer in stereotactic radiotherapy: a retrospective analysis

BackgroundThe purpose of this study is to investigate the prognostic factors of stereotactic radiotherapy for stage I NSCLC to improve outcomes.MethodsStage I non-small cell lung cancer patients who were treated with stereotactic radiotherapy between 2005 and 2009 at our hospital were enrolled in this study. The primary endpoint was local control rate. Survival estimates were calculated from the completion date of radiotherapy using the Kaplan-Meier method. The prognostic factors including patients’ characteristics and dose-volume histogram parameters were evaluated using Cox’s proportional hazard regression model.ResultsEighty patients (81 lesions) treated with 3 dose levels, 48 Gy/4 fractions, 60 Gy/8 fractions and 60 Gy/15 fractions, were enrolled in this study. Median follow-up was 30.4 months (range, 0.3 – 78.5 months). A Cox regression model showed T factor (p = 0.013), biological effective dose calculated from prescribed dose (BED10) (p = 0.048), and minimum dose for PTV (p = 0.013) to be prognostic factors for local control. Three-year overall survival rate and local control rate were 89.9% (T1: 86.8%, T2: 100%) and 89.0% (T1: 97.9%; T2: 64.8%), respectively. When the 3-year local control rates were examined by prescribed doses, they were 100% for the dose per fraction of 48 Gy /4 fractions (105.6 Gy BED10), 82.1% for 60 Gy/8 fractions (105 Gy BED10), and 57.1% for 60 Gy/15 fractions (84 Gy BED10). The median value of the minimum dose for PTV (%) was 89.88 (%), and the 3-year local control rates were 100% in those with the minimum dose for PTV (%) ≥ 89.88% and 79.2% in those with the minimum dose for PTV (%) < 89.88%.ConclusionsOur results suggest that T factor, BED10, and minimum dose for PTV influence the local control rate. Local control rate can be improved by securing the minimum dose for PTV.

Long-term bresults of radiotherapy combined with nedaplatin and 5-fluorouracil for postoperative loco-regional recurrent esophageal cancer: update on a phase II study

BackgroundIn 2006, we reported the effectiveness of chemoradiotherapy for postoperative recurrent esophageal cancer with a median observation period of 18 months. The purpose of the present study was to update the results of radiotherapy combined with nedaplatin and 5-fluorouracil (5-FU) for postoperative loco-regional recurrent esophageal cancer.MethodsBetween 2000 and 2004, we performed a phase II study on treatment of postoperative loco-regional recurrent esophageal cancer with radiotherapy (60 Gy/30 fractions/6 weeks) combined with chemotherapy consisting of two cycles of nedaplatin (70 mg/m2/2 h) and 5-FU (500 mg/m2/24 h for 5 days).The primary endpoint was overall survival rate, and the secondary endpoints were progression-free survival rate, irradiated-field control rate and chronic toxicity.ResultsA total of 30 patients were enrolled in this study. The regimen was completed in 76.7% of the patients. The median observation period for survivors was 72.0 months. The 5-year overall survival rate was 27.0% with a median survival period of 21.0 months. The 5-year progression-free survival rate and irradiated-field control rate were 25.1% and 71.5%, respectively. Grade 3 or higher late toxicity was observed in only one patient. Two long-term survivors had gastric tube cancer more than 5 years after chemoradiotherapy.Pretreatment performance status, pattern of recurrence (worse for patients with anastomotic recurrence) and number of recurrent lesions (worse for patients with multiple recurrent lesions) were statistically significant prognostic factors for overall survival.ConclusionsRadiotherapy combined with nedaplatin and 5-FU is a safe and effective salvage treatment for postoperative loco-regional recurrent esophageal cancer. However, the prognosis of patients with multiple regional recurrence or anastomotic recurrence is very poor.

Fatal hemorrhage in irradiated esophageal cancer patients

Between 1980 and 1994, 423 patients with esophageal cancer were given curative radiation therapy. Of these patients, 31 died of massive hemorrhage and were used as the subjects of analysis in this study. The incidence of massive hemorrhage in all patients was 7% (31/423). In the 31 patients who died of massive hemorrhage, 27 had local tumors and two had no tumors at hemorrhage (two unknown cases). The mean time interval from the start of radiation to hemorrhage was 9.2 months. In 9 autopsy cases the origin of hemorrhage was a tear of the aorta in 5 cases, necrotic local tumor in 3 cases and esophageal ulcer in 1 case. The positive risk factors for this complication seemed to be excess total dose, infection, metallic stent, and tracheoesophageal fistula. Chest pain or sentinel hemorrhage proceeding to massive hemorrhage was observed in about half of the patients.