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We quantified dose variation effects due to respiratory-induced intrafractional motion in conventional carbon-ion prostate treatment by using four-dimensional computed tomography (4DCT). 4DCT scans of 20 patients were acquired under free-breathing conditions using a 256 multi-slice CT scanner. The clinical target volume (CTV) was defined as the prostate and the seminal vesicle. Two types of planning target volumes (PTVs) were defined to minimize excessive dose to the rectum. The first PTV (= PTV1) was cal- culated by adding a 3D uniform margin to the CTV. The second PTV (= PTV2) was cut in a straight line from the top surface of the rectum from PTV1. Compensating boli were designed for the respective PTVs at the peak-exhalation phase, and carbon-ion dose distributions for a single respiratory cycle were calculated using these boli. Dose conformation to prostate, CTV, PTV1 and PTV2 were unchanged for all respiratory phases. The dose for >95% volume irradiation (D95) was 97.7% for prostate, 92.5% for CTV, 74.1% for PTV1 and 96.1% for PTV2 averaged over all patients. The rectum volume at inhalation phase receiving ≤50% of the prescribed dose was smaller than the planning dose due to the abdominal thickness variation. The target dose is not affected by intrafractional respiration in carbon-ion prostate treatment. Small dose variations, however, were observed due to respiratory-induced abdominal thickness variation; therefore the geometrical changes should be considered for prostate particle therapy.

Purpose: When CT data with a thick slice thickness are used in treatment planning, geometrical uncertainty may induce dosimetric errors. We evaluated carbon ion dose variations due to different CT slice thicknesses using a four-dimensional (4D) carbon ion beam dose calculation, and compared results between ungated and gated respiratory strategies. Material and Methods: Seven lung patients were scanned in 4D mode with a 0.5-mm slice thickness using a 256-multi-slice CT scanner. CT images were averaged with various numbers of images to simulate reconstructed images with various slice thicknesses (0.5 mm-5.0 mm). Two scenarios were studied (respiratory-ungated and -gated strategies). Range compensators were designed for each of the CT volumes with coarse inter-slice spacing to cover the internal target volume (ITV), as defined from 4DCT. Carbon ion dose distribution was computed for each resulting ITV on the 0.5-mm slice 4DCT data. The accumulated dose distribution was then calculated using deformable registration for 4D dose assessment. Results: The magnitude of over- and under-dosage was found to be larger with the use of range compensators designed with a coarser inter-slice spacing than those obtained with a 0.5-mm slice thickness. Although no under dosage was observed within the clinical target volume (CTV) region, D95 remained at over 97% of the prescribed dose for the ungated strategy and 95% for the gated strategy for all slice thickness. Inter-slice spacing of less than 3 mm may be able minimize dose variation between the ungated and gated strategies. Conclusions: Although volumes with increased inter-slice spacing may reduce geometrical accuracy at a certain respiratory phase, this does not significantly affect delivery of the accumulated dose to the target during the treatment course.

The concept of internal target volume is of marked importance for radiotherapy to lung tumors as respiration-induced motion is important. Individualized assessment of motion is required as tumour site may not predict the extent or pattern of tumour motion. We performed volumetric cine scanning using the 256-multi-slice CT (256MSCT) to study tumor motion during free breathing in 14 inpatients who were treated with carbon-ion radiotherapy. Motion assessment in 16 respiratory phases of the cine CT revealed most tumors to show hysteresis-like behavior. Isocenter displacement between peak exhalation and inhalation for the average of the right and left lungs were 7 mm, 7 mm and 15 mm for the upper, middle and lower lobes, respectively. Cine CT with the 256MSCT improved the evaluation of tumor displacement and overcomes some of the limitations associated with current CT methods. Volumetric cine CT data provides useful data on motion for planning in all radiation approaches for lung tumors.

Purpose To enhance the precision of treatment planning for tumors which move under respiration, we developed a respiratory-correlated segment reconstruction method (RS) based on the Feldkamp–Davis–Kress algorithm (FDK) which provides high temporal resolution and a high signal-to-noise ratio. We compared full-scan (FS-FDK) and RS-FDK with regard to dose distribution in heavy ion treatment planning. Materials and methods Data acquisition for RS-FDK is done using a respiratory sensing system in cine scan mode with a 256-multi-detector row CT (256-MDCT). To evaluate the accuracy of irradiation of moving tumors, dose distributions with each algorithm were compared in heavy ion treatment planning using beam parameters obtained with FS-FDK. Results Images obtained using RS-FDK did not show motion artifacts and visualized the edges of the liver and pulmonary vessels more clearly than those with FS-FDK. The iso-dose distributions for FS-FDK covered the target volume; in contrast, RS-FDK with the beam parameter of FS-FDK image provided an insufficient dose to the target and a considerable dose to normal tissues around it. Conclusions The information provided by RS-FDK improves accuracy in the prescription of dose-to-target volume. Further, RS-FDK allows greater precision in the delivery of radiotherapy, including 4D radiation therapy.

In cone-beam geometry, image quality may be degraded or artifacts may occur if the cone angle is substantially wide. This is because a cone-beam scan along a circular orbit does not collect the complete set of data required to make an exact reconstruction of all volumetric data. To increase temporal resolution and thus image quality in cone-beam geometry, Silver proposed the new half-scan algorithm (NHS-FDK), which extends Parker's weighting function (HS-FDK) by utilizing a larger range up to 2pi. Here, we evaluated these algorithms for hepatic contrast-enhanced CT in cine scan mode using a 256-detector row CT. The full-scan (FS-FDK) images show uniform distribution of the image noise and CT-number uniformity. Image noise and CT-number uniformity with HS-FDK and NHS-FDK images follow the initial projection angle. HS-FDK images therefore have more changeable higher intensity (brighter) and a lower intensity (darker) areas than respective FS-FDK and NHS-FDK images. We concluded that, considering the trade-off between image quality and temporal resolution, the NHS-FDK algorithm is useful in volumetric cine imaging for the abdomen.

The combination-weighted Feldkamp algorithm (CW-FDK) was developed and tested in a phantom in order to reduce cone-beam artefacts and enhance cranio-caudal reconstruction coverage in an attempt to improve image quality when utilizing cone-beam computed tomography (CBCT). Using a 256-slice cone-beam CT (256CBCT), image quality (CT-number uniformity and geometrical accuracy) was quantitatively evaluated in phantom and clinical studies, and the results were compared to those obtained with the original Feldkamp algorithm. A clinical study was done in lung cancer patients under breath holding and free breathing. Image quality for the original Feldkamp algorithm is degraded at the edge of the scan region due to the missing volume, commensurate with the cranio-caudal distance between the reconstruction and central planes. The CW-FDK extended the reconstruction coverage to equal the scan coverage and improved reconstruction accuracy, unaffected by the cranio-caudal distance. The extended reconstruction coverage with good image quality provided by the CW-FDK will be clinically investigated for improving diagnostic and radiotherapy applications. In addition, this algorithm can also be adapted for use in relatively wide cone-angle CBCT such as with a flat-panel detector CBCT.

Purpose: To evaluate the toxicity and efficacy of carbon ion radiotherapy (CIRT) for locally advanced cervical cancer by two phase I/II clinical trials. Methods and Materials: Between June 1995 and January 2000, 44 patients were treated with CIRT. Thirty patients had stage IIIB disease and 14 patients had stage IVA disease. Median tumor size was 6.5 cm (4.2-11.0 cm). The treatment consisted of 16 fractions of whole pelvic irradiation and 8 fractions of local boost. In the first study, the total dose ranged from 52.8 to 72.0 gray equivalent (GyE) (2.2 to 3.0 GyE/fraction). In the second study, the whole pelvic dose was fixed at 44.8 GyE, and an additional 24.0 or 28.0 GyE was given to the cervical tumor (total dose: 68.8 or 72.8 GyE). Results: No patient developed severe acute toxicity. In contrast, 8 patients developed major late gastrointestinal complications. The doses resulting in major complications were over 60 GyE. All patients with major complications were surgically salvaged. The 5-year local control rates for patients in the first and second studies were 45% and 79%, respectively. When treated with 62.4 GyE or more, the local control was favorable even for the patients with stage IVA disease (69%) or for those with tumors > 6.0 cm (64%). Conclusions: In CIRT for advanced cervical cancer, the dose to the intestines should be limited to less than 60 GyE to avoid major complications. Although the number of patients was small, the results supported the continued investigation to confirm therapeutic efficacy.

To clarify the characteristics of magnetic resonance (MR) imaging of radiation-induced brain injury following carbon ion radiotherapy and to observe the changes in lesions over time, we evaluated 40 patients with radiation-induced brain injury from carbon ion radiotherapy for head and neck tumors. Their primary lesions received a radiation dose of 48 to 70.4 Gray equivalent (GyE) in 16 to 18 fractions. MR imaging of radiation-induced brain injury was graded as follows: Grade 1: change in focal white matter; focal contrast enhancement and surrounding edema; Grade 2: nonenhanced area or cystic lesion in enhanced lesion; Grade 3: focal necrosis with mass effect; and Grade 4: mass effect requiring surgical intervention. Radiation-induced brain injury appeared as early as 2 months and as late as 57 months after carbon ion therapy (mean interval, 22.2 months). MR findings of initial lesion were Grade 1 in 26 cases (65.0%), Grade 2 in 13 (32.5%), and Grade 3 in 1 (2.5%). Brain injury was always found in the radiation field initially, but cystic lesion and edema later extended outside the field in 10 cases (25.0%). In follow-up MR studies, size of edema or enhanced lesion was reduced in 17 patients (42.5%) without treatment. Two cases with large cystic lesions required surgery. Improvement of radiation-induced brain injury was observed more often than had been previously described. Because edema and cystic lesion can occasionally extend outside the radiation field, such findings do not exclude the possibility of radiation-induced brain injury. Careful observation is recommended because cystic lesions can enlarge enough to require surgical treatment in some cases.

Objective Chordoma is a rare malignant bone tumor that arises from notochord remnants. This is the first trial to investigate the utility of 11C-methionine(MET) positron emission tomography(PET) in the imaging of chordoma before and after carbon-ion radiotherapy(CIRT). Design and patients Fifteen patients with chordoma were investigated with MET-PET before and after CIRT and the findings analyzed visually and quantitatively. Tumor MET uptake was evaluated by tumor-to-nontumor ratio(T/N ratio). Results In 12(80%) patients chordoma was clearly visible in the baseline MET-PET study with a mean T/N ratio of 3.3±1.7. The MET uptake decreased significantly to 2.3±1.4 after CIRT(P＜0.05). A significant reduction in tumor MET uptake of 24% was observed after CIRT. Fourteen (93%) patients showed no local recurrence after CIRT with a median follow-up time of 20 months. Conclusion This study has demonstrated that MET-PET is feasible for imaging of chordoma. MET-PET could provide important tumor metabolic information for the therapeutic monitoring of chordoma after CIRT.

Background and purpose : Heavy ion radiotherapy is a promising modality because of its excellent dose localization and high biological effect on tumors. Using carbon beams, a dose escalation study was conducted for the treatment of stage I non-small cell lung cancer (NSCLC) to determine the optimal dose. Materials and methods : The first stage phase I/II trial using 18 fractions over 6 weeks for 47 patients and the second one using nine fractions over 3 weeks for 34 patients were conducted by the dose escalation method from 59.4 to 95.4 Gray equivalents (GyE) in incremental steps of 10% and from 68.4 to 79.2 GyE in 5% increments, respectively. The local control and survival rates were obtained using the Kaplan–Meier method. Results : Radiation pneumonitis at grade III occurred in three of 81 patients, but they fully recovered. This was not a dose-limiting factor. The local control rates in the first and second trials were 64% and 84%, respectively. The total recurrence rate in both trials was 23.2%. The infield local recurrence in the first trial was significantly dependent on carbon dose. The doses greater than 86.4 GyE at 18 fractions and 72 GyE at nine fractions achieved a local control of 90% and 95%, respectively. The 5 year overall and cause-specific survivals in 81 patients were 42% and 60%, respectively. Conclusions : With our dose escalation study, the optimum safety and efficacy dose of carbon beams was determined. Carbon beam therapy attained almost the same results as surgery for stage I NSCLC although this was a I/II study.

Four-dimensional computed tomography (4D CT) is a dynamic volume imaging system of moving organs with an image quality comparable to conventional CT. With 4D CT, one could carry out not only new diagnoses but also provide new interventional therapy by real-time observation of its procedure. In order to realize 4D CT, we have developed a novel 2D detector on the basis of the present CT technology, and mounted it on the gantry frame of the state of the art CT-scanner. We have evaluated its performances with standard stationary phantoms and scanned normal volunteers. In the present report, we describe the results of such performance evaluations.

The National Institute of Radiological Sciences in Chiba, Japan (NIRS) has the highest number of patients with lung cancer treated with carbon ion beams in the world. This report describes the techniques and clinical trials that have been undertaken at NIRS and preliminary results of a current study on single-fraction irradiation. The data are compared to recent results for the treatment of peripheral stage I lung cancer from the literature.