Hiroshi Taguchi

Real-time tumor-tracking radiotherapy for adrenal tumors

PURPOSE To investigate the three-dimensional movement of internal fiducial markers near the adrenal tumors using a real-time tumor-tracking radiotherapy (RTRT) system and to examine the feasibility of high-dose hypofractionated radiotherapy for the adrenal tumors. MATERIALS AND METHODS The subjects considered in this study were 10 markers of the 9 patients treated with RTRT. A total of 72 days in the prone position and 61 treatment days in the supine position for nine of the 10 markers were analyzed. All but one patient were prescribed 48 Gy in eight fractions at the isocenter. RESULTS The average absolute amplitude of the marker movement in the prone position was 6.1+/-4.4 mm (range 2.3-14.4), 11.1+/-7.1 mm (3.5-25.2), and 7.0+/-3.5 mm (3.9-12.5) in the left-right (LR), craniocaudal (CC), and anterior-posterior (AP) directions, respectively. The average absolute amplitude in the supine position was 3.4+/-2.9 mm (0.6-9.1), 9.9+/-9.8 mm (1.1-27.1), and 5.4+/-5.2 mm (1.7-26.6) in the LR, CC, and AP directions, respectively. Of the eight markers, which were examined in both the prone and supine positions, there was no significant difference in the average absolute amplitude between the two positions. No symptomatic adverse effects were observed within the median follow-up period of 16 months (range 5-21 months). The actuarial freedom-from-local-progression rate was 100% at 12 months. CONCLUSIONS Three-dimensional motion of a fiducial marker near the adrenal tumors was detected. Hypofractionated RTRT for adrenal tumors was feasible for patients with metastatic tumors.

Clinical outcomes of stereotactic brain and/or body radiotherapy for patients with oligometastatic lesions.

OBJECTIVE Several recent studies have shown that oligometastatic disease has curative potential, although it was previously considered to signal a patients last stage of life. Stereotactic body radiotherapy has been available for extra-cranial metastases in addition to stereotactic cranial radiotherapy for brain metastases. The aim of the present study was to retrospectively evaluate the clinical outcomes of stereotactic radiotherapy for patients with oligometastatic lesions. METHODS Between 1999 and 2008, 41 patients with five or fewer detectable metastases were treated with stereotactic radiotherapy at our institution. The treated oligometastatic lesions were in the brain, lung and adrenal glands. RESULTS With a median follow-up period of 20 months, the 3-year overall survival, progression-free survival, local control and distant control rates were 39%, 20%, 80% and 35%, respectively, and the respective 5-year rates were 28%, 20%, 80% and 35%. The median survival time was 24 months. According to interval to recurrence, the 3- and 5-year overall survival rates were 19% and 10%, respectively, for patients with <12 months (n = 18), compared with 53% and 40% for those with > or =12 months (n = 23) (P = 0.006). CONCLUSIONS Precise stereotactic radiotherapy was effective in controlling oligometastatic lesions for patients with a median survival time of 24 months. Interval to recurrence may impact the overall survival rate and should be included in the stratification criteria in a prospective randomized trial to investigate the benefits of stereotactic radiotherapy for patients with oligometastases.

Three-Dimensional Intrafractional Motion of Breast During Tangential Breast Irradiation Monitored With High-Sampling Frequency Using a Real-Time Tumor-Tracking Radiotherapy System

PURPOSE To evaluate the three-dimensional intrafraction motion of the breast during tangential breast irradiation using a real-time tracking radiotherapy (RT) system with a high-sampling frequency. METHODS AND MATERIALS A total of 17 patients with breast cancer who had received breast conservation RT were included in this study. A 2.0-mm gold marker was placed on the skin near the nipple of the breast for RT. A fluoroscopic real-time tumor-tracking RT system was used to monitor the marker. The range of motion of each patient was calculated in three directions. RESULTS The mean +/- standard deviation of the range of respiratory motion was 1.0 +/- 0.6 mm (median, 0.9; 95% confidence interval [CI] of the marker position, 0.4-2.6), 1.3 +/- 0.5 mm (median, 1.1; 95% CI, 0.5-2.5), and 2.6 +/- 1.4 (median, 2.3; 95% CI, 1.0-6.9) for the right-left, craniocaudal, and anteroposterior direction, respectively. No correlation was found between the range of motion and the body mass index or respiratory function. The mean +/- standard deviation of the absolute value of the baseline shift in the right-left, craniocaudal, and anteroposterior direction was 0.2 +/- 0.2 mm (range, 0.0-0.8 mm), 0.3 +/- 0.2 mm (range, 0.0-0.7 mm), and 0.8 +/- 0.7 mm (range, 0.1-1.8 mm), respectively. CONCLUSION Both the range of motion and the baseline shift were within a few millimeters in each direction. As long as the conventional wedge-pair technique and the proper immobilization are used, the intrafraction three-dimensional change in the breast surface did not much influence the dose distribution.

Efficacy of preoperative radiotherapy to portal vein tumor thrombus in the main trunk or first branch in patients with hepatocellular carcinoma

BackgroundThe prognosis of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) in the main trunk or the first branch is very poor.MethodsRadiotherapy (RT) to PVTT was followed by hepatectomy within 2 weeks. The dose used was 30–36 Gy, in 10–12 fractions, for 15–20 days. The efficacy of preoperative RT to PVTT in the main trunk or first branch was evaluated by comparing results in patients who underwent hepatectomy (group R; n = 15) with preoperative RT and those without preoperative RT (group N; n = 28).ResultsThe 1-, 3-, and 5-year survival rates in group R were 86.2%, 43.5%, and 34.8%, respectively, while these values in group N were 39.0%, 13.1%, and 13.1%, respectively. The survival curve of group R was significantly better than that of group N (P = 0.0359). In group R, five (83.3%) of six patients whose tumor thrombus was completely necrosed (based on pathological examination) and whose follow-up period was over 2 years survived for more than 2 years. Female sex (P = 0.0066), multiple tumors (P = 0.0369), and absence of preoperative RT (P = 0.0359) were ranked as significant factors for a poor prognosis by univariate analysis. Multivariate analysis revealed absence of preoperative RT and female sex to be significant factors for a poor prognosis.ConclusionPreoperative RT to PVTT in the main trunk or first branch improved the prognosis of patients with HCC with PVTT, and could be a promising new modality in the treatment of these patients.

Efficacy of therapy for advanced hepatocellular carcinoma: intra-arterial 5-fluorouracil and subcutaneous interferon with image-guided radiation.

Background and Aim:  To evaluate the efficacy of intra‐arterial 5‐fluorouracil (5‐FU) and subcutaneous interferon (IFN) combined with image‐guided radiation therapy (IGRT) in advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT).

Long-term Outcomes of Fractionated Stereotactic Radiotherapy for Intracranial Skull Base Benign Meningiomas in Single Institution

OBJECTIVE To investigate the outcome of linac-based fractionated stereotactic radiotherapy over the last 10 years for intracranial skull base benign meningiomas in patients who were inoperable, who had residual tumors with some components of high mitotic index after surgery and who experienced relapse of the tumor. METHODS Twenty-seven patients with intracranial skull base benign meningiomas treated with fractionated stereotactic radiotherapy were retrospectively reviewed. Twenty-seven cases were diagnosed as benign meningiomas on pathological (17 cases) or radiological (10 cases) examination. The median follow-up time was 90 months after initial treatment and 63 months after fractionated stereotactic radiotherapy. The median biological equivalent dose calculated using an α/β ratio of 2.0 Gy was 82.0 Gy (range, 60-106 Gy). RESULTS The 5-year overall survival was 95.7 (95% confidence interval: 87.3-100)% after initial treatment and 96.2 (88.8-100)% after fractionated stereotactic radiotherapy. The 5-year overall survival and local control rate of patients who received fractionated stereotactic radiotherapy alone were both 100%. The 5-year progression-free survival and local control rate after fractionated stereotactic radiotherapy were all 100% with a tumor volume of <9.1 cc and 68.2 (37.2-99.2) and 75.8 (45.2-100)% for the tumors 9.1 cc, respectively. The difference was significant in progression-free survival (P = 0.022) and local control rate (P = 0.044). The local control rate was significantly worse in patients who received fractionated stereotactic radiotherapy for relapsed tumors (P = 0.01). No late radiation damage was observed in the follow-up period. CONCLUSIONS The long-term outcome suggests that fractionated stereotactic radiotherapy is a safe and effective treatment for intracranial skull base benign meningioma, especially for those who have tumors <9.1 cc or would receive fractionated stereotactic radiotherapy with or without surgery as the initial treatment.

Low-dose Craniospinal Irradiation and Ifosfamide, Cisplatin and Etoposide for Non-metastatic Embryonal Tumors in the Central Nervous System

OBJECTIVE The current study was conducted to evaluate the effects of low-dose craniospinal irradiation (CSI) combined with chemotherapy on non-metastatic embryonal tumors in the central nervous system (CNS), including medulloblastoma and supra-tentorial primitive neuroectodermal tumors (ST-PNET). METHODS All patients were treated according to the following protocol. After surgery, the patients < or =5 years old received 18 Gy and the patients >5 years old received 24 Gy CSI. The dose to the primary tumor bed was 39.6-54 Gy. Chemotherapy consisted of ifosfamide, cisplatin and etoposide (ICE chemotherapy). RESULTS Sixteen patients aged 0.5-20.4 (median 6.1) years were enrolled and followed for 11-165 (median 112) months. Both 5-year actuarial overall survival (OAS) and progression-free survival (PFS) were 81% (95% confidence interval (CI): 62-100%) for the 16 patients. Both 5-year OAS and PFS were 82% (CI: 59-100%) for the patients with medulloblastoma and 80% (CI: 45-100%) for the patients with ST-PNET. Both 5-year OAS and PFS were 75% for the eight patients < or =5 years old and 88% for the eight patients >5 years old. Both 5-year OAS and PFS were 100% for six average-risk patients (3 years or older, total resection and posterior fossa) and 70% for 10 poor-risk patients (others). The median total intellectual quotient at the last follow-up was 85 (ranging from 48 to 103) in 12 patients who were followed for 3-145 (median 49) months. Eight patients received hormone replacement therapy. CONCLUSION Low-dose CSI and ICE chemotherapy may have a role as a treatment option for a subset of patients with non-metastatic embryonal tumors in the CNS.

Accurate Analysis of the Change in Volume, Location, and Shape of Metastatic Cervical Lymph Nodes During Radiotherapy

PURPOSE To establish a method for the accurate acquisition and analysis of the variations in tumor volume, location, and three-dimensional (3D) shape of tumors during radiotherapy in the era of image-guided radiotherapy. METHODS AND MATERIALS Finite element models of lymph nodes were developed based on computed tomography (CT) images taken before the start of treatment and every week during the treatment period. A surface geometry map with a volumetric scale was adopted and used for the analysis. Six metastatic cervical lymph nodes, 3.5 to 55.1 cm(3) before treatment, in 6 patients with head and neck carcinomas were analyzed in this study. Three fiducial markers implanted in mouthpieces were used for the fusion of CT images. Changes in the location of the lymph nodes were measured on the basis of these fiducial markers. RESULTS The surface geometry maps showed convex regions in red and concave regions in blue to ensure that the characteristics of the 3D tumor geometries are simply understood visually. After the irradiation of 66 to 70 Gy in 2 Gy daily doses, the patterns of the colors had not changed significantly, and the maps before and during treatment were strongly correlated (average correlation coefficient was 0.808), suggesting that the tumors shrank uniformly, maintaining the original characteristics of the shapes in all 6 patients. The movement of the gravitational center of the lymph nodes during the treatment period was everywhere less than ±5 mm except in 1 patient, in whom the change reached nearly 10 mm. CONCLUSIONS The surface geometry map was useful for an accurate evaluation of the changes in volume and 3D shapes of metastatic lymph nodes. The fusion of the initial and follow-up CT images based on fiducial markers enabled an analysis of changes in the location of the targets. Metastatic cervical lymph nodes in patients were suggested to decrease in size without significant changes in the 3D shape during radiotherapy. The movements of the gravitational center of the lymph nodes were almost all less than ±5 mm.

High Dose Three-Dimensional Conformal Boost Using the Real-Time Tumor Tracking Radiotherapy System in Cervical Cancer Patients Unable to Receive Intracavitary Brachytherapy

Purpose The purpose of this study is to evaluate the clinical results of treatment with a high dose of 3-dimensional conformal boost (3DCB) using a real-time tracking radiation therapy (RTRT) system in cervical cancer patients. Materials and Methods Between January 2001 and December 2004, 10 patients with cervical cancer were treated with a high dose 3DCB using RTRT system. Nine patients received whole pelvis radiation therapy (RT) with a median dose of 50 Gy (range, 40-50 Gy) before the 3DCB. The median dose of the 3DCB was 30 Gy (range, 25-30 Gy). Eight patients received the 3DCB twice a week with a daily fraction of 5 Gy. The determined endpoints were tumor response, overall survival, local failure free survival, and distant metastasis free survival. The duration of survival was calculated from the time of the start of radiotherapy. Results All patients were alive at the time of analysis and the median follow-up was 17.6 months (range, 4.9-27.3 months). Complete response was achieved in nine patients and one patient had a partial response. The 1- and 2-year local failure free survival was 78.8% and 54%, respectively. The 1- and 2-year distant metastasis free survival was 90% and 72%, respectively. Late toxicity of a grade 2 rectal hemorrhage was seen in one patient. A subcutaneous abscess was encountered in one patient. Conclusion The use of the high dose 3DCB in the treatment of cervical cancer is safe and feasible where intracavitary brachytherapy (ICBT) is unable to be performed. The escalation of the 3DCB dose is currently under evaluation.

Prognostic significance of clusterin expression in advanced-stage cervical cancer treated with curative intended radiotherapy.

Objective Overexpression of clusterin (CLU), an antiapoptotic molecule, has been reported to induce resistance to radiotherapy (RT) in a variety of cancer cell types. The aim of this study was to evaluate the significance of CLU expression to predict survival of patients with advanced-stage cervical cancer who received curative intended RT. Methods Biopsy tissue specimens of advanced-stage cervical cancer before curative intended RT were obtained from 34 patients who were treated at Hokkaido University Hospital between 1998 and 2008 and whose complete medical records were available. The expression of CLU protein was analyzed by immunohistochemistry. Findings were evaluated in relation to several clinicopathological factors. Survival analyses were performed using the Kaplan-Meier curves and the log-rank test. Independent prognostic factors were determined by multivariate Cox regression analysis. Results Clusterin protein was mainly present in the cytoplasm of cervical cancer cells. The expression of CLU protein in cervical cancer tissues before curative intended RT was not significantly related to any clinicopathological factors analyzed, including age, clinical stage, histologic type, and response to RT. Univariate analysis on prognostic factors showed that histologic type (P = 0.001), and CLU expression (P = 0.02) were related to survival. Multivariate analysis revealed that both histologic type (P = 0.002), and CLU expression (P = 0.02) were independent prognostic factors for overall survival. Conclusion We conclude that CLU could be a new molecular marker to predict overall survival of patients with advanced-stage cervical cancer treated with curative intended RT.