Hiroaki Akasaka

Patterns of failure after multimodal treatments for high-grade glioma: effectiveness of MIB-1 labeling index.

BackgroundThe purpose of the present study was to analyze the recurrence pattern of high-grade glioma treated with a multimodal treatment approach and to evaluate whether the MIB-1 labeling index (LI) could be a useful marker for predicting the pattern of failure in glioblastoma (GB).Methods and materialsWe evaluated histologically confirmed 131 patients with either anaplastic astrocytoma (AA) or GB. A median dose was 60 Gy. Concomitant and adjuvant chemotherapy were administered to 111 patients. MIB-1 LI was assessed by immunohistochemistry. Recurrence patterns were categorized according to the areas of recurrence as follows: central failure (recurrence in the 95% of 60 Gy); in-field (recurrence in the high-dose volume of 50 Gy; marginal (recurrence outside the high-dose volume) and distant (recurrence outside the RT field).ResultsThe median follow-up durations were 13 months for all patients and 19 months for those remaining alive. Among AA patients, the 2-year progression-free and overall survival rates were 23.1% and 39.2%, respectively, while in GB patients, the rates were 13.3% and 27.6%, respectively. The median survival time was 20 months for AA patients and 15 months for GB patients. Among AA patients, recurrences were central in 68.7% of patients; in-field, 18.8%; and distant, 12.5%, while among GB patients, 69.0% of recurrences were central, 15.5% were in-field, 12.1% were marginal, and 3.4% were distant. The MIB-1 LI medians were 18.2% in AA and 29.8% in GB. Interestingly, in patients with GB, the MIB-1 LI had a strong effect on the pattern of failure (P = 0.014), while the extent of surgical removal (P = 0.47) and regimens of chemotherapy (P = 0.57) did not.ConclusionsMIB-1 LI predominantly affected the pattern of failure in GB patients treated with a multimodal approach, and it might be a useful tool for the management of the disease.

Sparing of tissue by using micro-slit-beam radiation therapy reduces neurotoxicity compared with broad-beam radiation therapy

Micro-slit-beam radiation therapy (MRT) using synchrotron-generated X-ray beams allows for extremely high-dose irradiation. However, the toxicity of MRT in central nervous system (CNS) use is still unknown. To gather baseline toxicological data, we evaluated mortality in normal mice following CNS-targeted MRT. Male C57BL/6 J mice were head-fixed in a stereotaxic frame. Synchrotron X-ray-beam radiation was provided by the SPring-8 BL28B2 beam-line. For MRT, radiation was delivered to groups of mice in a 10 × 12 mm unidirectional array consisting of 25-μm-wide beams spaced 100, 200 or 300 μm apart; another group of mice received the equivalent broad-beam radiation therapy (BRT) for comparison. Peak and valley dose rates of the MRT were 120 and 0.7 Gy/s, respectively. Delivered doses were 96–960 Gy for MRT, and 24–120 Gy for BRT. Mortality was monitored for 90 days post-irradiation. Brain tissue was stained using hematoxylin and eosin to evaluate neural structure. Demyelination was evaluated by Klüver–Barrera staining. The LD50 and LD100 when using MRT were 600 Gy and 720 Gy, respectively, and when using BRT they were 80 Gy and 96 Gy, respectively. In MRT, mortality decreased as the center-to-center beam spacing increased from 100 μm to 300 μm. Cortical architecture was well preserved in MRT, whereas BRT induced various degrees of cerebral hemorrhage and demyelination. MRT was able to deliver extremely high doses of radiation, while still minimizing neuronal death. The valley doses, influenced by beam spacing and irradiated dose, could represent important survival factors for MRT.

Comparison of dosimetric parameters in the treatment planning of magnetic resonance imaging–based intracavitary image-guided adaptive brachytherapy with and without optimization using the central shielding technique

Abstract This study aimed to compare dosimetric parameters between non-optimized and optimized treatment planning (NOP and OP, respectively) of magnetic resonance imaging (MRI) –based intracavitary (IC) image-guided adaptive brachytherapy (IGABT) using the central shielding (CS) technique for cervical cancer. Fifty-three patients treated with external beam radiotherapy using CS and MRI-based IGABT with the IC approach alone were evaluated. The total high-risk clinical target volume (HR-CTV) D90 was aimed at >70 Gy equivalent dose in 2 Gy fractions (EQD2). In the small HR-CTV group (≤30 cm3), the mean D90s for NOP/OP were 98.6/80.7 Gy. In the large (30.1–40 cm3) and extensive (>40 cm3) HR-CTV groups, the mean D90s were 81.9/77.5 and 71.1/73.6 Gy, respectively. The mean D2cc values for organs at risks (OARs) in OP were acceptable in all groups, despite the high bladder D2cc in the NOP. The correlation between HR-CTV at first brachytherapy (BT) and NOP D90 was stronger than that between HR-CTV at first BT and OP D90. The targeted HR-CTV D90 and dose constraints of D2cc for OARs were both achieved in 16 NOP/47 OP patients for the bladder, 39/50 for the rectum, and 47/50 for the sigmoid colon (P < 0.001, P = 0.007, and P = 0.34, respectively). For small tumors, the role of optimization was to reduce the D2cc for OARs while maintaining the targeted D90. However, optimization was of limited value for extensive tumors. Methods of optimization in IGABT with CS for cervical cancer should be standardized while considering its effectiveness and limitations.

Clinical log data analysis for assessing the accuracy of the CyberKnife fiducial-free lung tumor tracking system

PURPOSE The CyberKnife Xsight Lung Tracking (XLT) and 1-View tracking systems can synchronize beam targeting to a visible lung tumor with respiratory motion during irradiation without requiring internal fiducial markers. The systems use a correlation model that relates external marker positions to tumor positions as well as a prediction model that predicts the targets future position. In this study, the correlation and prediction model uncertainties related to the CyberKnife fiducial-free tumor tracking system were evaluated using clinical log data. METHODS AND MATERIALS Data from 211 fractions in 42 patients with lung tumors were analyzed. Log files produced by the CyberKnife Synchrony system were acquired after each treatment; the mean correlation and prediction errors for each patient were calculated. Additionally, we examined the tracking tumor-related parameters and analyzed the relationships between the model errors and tracking tumor-related parameters. RESULTS The overall means ± standard deviations (SDs) of the correlation errors were 0.70 ± 0.43 mm, 0.36 ± 0.16 mm, 0.44 ± 0.22 mm, and 0.95 ± 0.43 mm for the superoinferior (SI), left-right (LR), anteroposterior (AP), and radial directions, respectively. The overall means ± SDs of the prediction errors were 0.13 ± 0.11 mm, 0.03 ± 0.02 mm, 0.03 ± 0.02 mm, and 0.14 ± 0.11 mm for the SI, LR, AP, and radial directions, respectively. There were no significant differences in these errors between the XLT and 1-View tracking methods. The tumor motion amplitude was moderately associated with the correlation error and strongly related to the prediction error in the SI and radial directions. CONCLUSIONS Clinical log data analysis can be used to determine the necessary margin sizes in treatment plans to compensate for correlation and prediction errors in the CyberKnife fiducial-free lung tumor tracking system. The tumor motion amplitude may facilitate margin determination.

Application of dual-energy CT to suppression of metal artefact caused by pedicle screw fixation in radiotherapy: a feasibility study using original phantom

The objective of the present study was the determination of the potential dosimetric benefits of using metal-artefact-suppressed dual-energy computed tomography (DECT) images for cases involving pedicle screw implants in spinal sites. A heterogeneous spinal phantom was designed for the investigation of the dosimetric effect of the pedicle-screw-related artefacts. The dosimetric comparisons were first performed using a conventional two-directional opposed (AP-PA) plan, and then a volumetric modulated arc therapy (VMAT) plan, which are both used for the treatment of spinal metastases in our institution. The results of Acuros® XB dose-to-medium (Dm) and dose-to-water (Dw) calculations using different imaging options were compared with experimental measurements including the chamber and film dosimetries in the spinal phantom. A dual-energy composition image with a weight factor of  -0.2 and a dual-energy monochromatic image (DEMI) with an energy level of 180 keV were found to have superior abilities for artefact suppression. The Dm calculations revealed greater dosimetric effects of the pedicle screw-related artefacts compared to the Dw calculations. The results of conventional single-energy computed tomography showed that, although the pedicle screws were made from low-Z titanium alloy, the metal artefacts still have dosimetric effects, namely, an average (maximum) Dm error of 4.4% (5.6%) inside the spinal cord for a complex VMAT treatment plan. Our findings indicate that metal-artefact suppression using the proposed DECT (DEMI) approach is promising for improving the dosimetric accuracy near the implants and inside the spinal cord (average (maximum) Dm error of 1.1% (2.0%)).

A Comparison of Physical vs. Nonphysical Wedge Modalities in Radiotherapy

This chapter discusses the clinical application and implementation of wedge techniques in radiation therapy. Coverage of the target region with a curative dose is critical for treating several cancer types; to that end, wedge filters are commonly used to improve dose uniformity to the target volume. Initially, wedges designed for this purpose were physical and were made of high-density materials such as lead or steel. Subsequently, nonphysical wedges were introduced; these improved the dose uniformity using computer systems in lieu of physical materials. As wedge systems evolve, however, they each continue to have their advantages and disadvantages. When using physical wedges, it is difficult to control the generation of secondary radiation resulting from the collision of the radiation beam with the wedge body; conversely, nonphysical wedges do not create any secondary radiation because there is no physical interference with the beam. On the other hand, nonphysical wedges are less suitable for treating moving tumors, such as those in the lung, and physical wedges have better dose coverage to the target volume than nonphysical wedges. This chapter aims to guide decision-making regarding the choice of wedge types in various clinical situations.

Medical Application of Nonwoven Fabrics - Intra-abdominal Spacers for Particle Therapy

The authors aimed to introduce a medical application for nonwoven fabric as spacers in particle therapy. Particle therapy, exhibiting more focused effects on target tissues, has emerged as a promising treatment modality. However, close proximity of tumor tissue and adjacent organs makes delivery of curative doses to the tumor difficult because severe radiation morbidities might occur. A method using surgically placed GORE-TEX sheets as a spacer has been reported. Although this method provides for separation of adjacent organs, the material is not resorbed. To overcome these anatomical and therapeutic difficulties, and to deliver effective radiation doses to treat upper abdominal tumors, we have developed a nonwoven fabric spacer composed of bioabsorbable suture material. The absorbable polyglycolic acid (PGA) spacer had water-equivalent, biocompatible, and thickness-retaining properties. Although further evaluation is warranted in a clinical setting, the PGA spacer may be effective to block particle beams and to separate normal tissues from the radiation field. These findings suggest that the nonwoven-fabric PGA spacer might become a useful device in particle therapy.