Design of a compensating bolus by use of exhalation CT data for covering residual motion in respiratory-gated charged-particle lung therapy: four-dimensional carbon beam dose calculation.

We developed an algorithm which we used to design a compensating bolus by using respiratory-gated CT data for respiratory-gated carbon beam lung therapy and evaluated it by calculating dose distributions as a function of time. Four-dimensional CT (4DCT) images were obtained for seven lung cancer patients under free breathing conditions. The internal target volume (ITV) was calculated by maximum intensity projection processing which use of three types of gross tumor volumes (GTVs): at peak exhalation and with a 5 mm shift of the GTV to both superior and inferior sides. Then a compensating bolus was designed which use of the ITV and applied to 4DCT data at the gating window (around exhalation phase). The carbon beam distribution was calculated by a pencil-beam algorithm as a function of time. The compensating bolus provides a sufficient prescribed dose to the target in the gating window and minimizes any excessive dose to the normal tissues. The metric of dosimetric assessment metrics of D95 in all patients is greater than 96% of the prescribed dose in the gating window. Our results will be beneficial for improving the accuracy of charged-particle radiotherapy for hospitals where 4DCT cannot be used.

Carbon ion radiotherapy for stage I non-small cell lung cancer using a regimen of four fractions during 1 week.

BACKGROUND: A phase I/II study was first conducted for the treatment of stage I non-small cell lung cancer (NSCLC) from 1994 to 1999 to determine the optimal dose. On the basis on the results, a phase II study using a regimen of four fractions during 1 week was performed. The purpose of the present study was to determine the local control and 5-year survival rates. METHODS: From December 2000 to November 2003, 79 patients with 80 primary lesions were treated. Using a fixed dose of 52.8 GyE for stage IA NSCLC and 60.0 GyE for stage IB NSCLC in four fractions during 1 week, the primary tumors were irradiated with carbon beams alone. The average age of the patients was 74.8 years. Sixty-two (78.5%) of these patients were medically inoperable. Local control and survival were determined using the Kaplan-Meier method. The data were statistically processed using the log-rank test. RESULTS: All patients were observed for a minimum of 3 years or until death, with a median follow-up time of 38.6 months, ranging from 2.5 to 72.2 months. The local control rate for all patients was 90% (T1: 98%, T2: 80%). The patients' 5-year lung cancer-specific survival rate was 68% (IA: 87%, IB: 42%). The overall survival was 45% (IA: 62%, IB: 25%). Half of the deaths were attributable to intercurrent diseases. No toxic reactions in the lung greater than grade 3 were detected. CONCLUSION: Carbon ion beam radiotherapy with a regimen of four fractions during 1 week has been proven as a valid alternative to surgery for stage I NSCLC and to offer particular benefits, especially for elderly and inoperable patients.

Inhibition of potential lethal damage repair and related gene expression after carbon-ion beam irradiation to human lung cancer grown in nude mice.

Using cultured and nude mouse tumor cells (IA) derived from a human lung cancer, we previously demonstrated their radiosensitivity by focusing attention on the dynamics of tumor clonogens and the early and rapid survival recovery (potential lethal damage repair: PLD repair) occurring after X-ray irradiation. To the authors' knowledge, this is the first study demonstrating gene expression in association with PLD repair after carbon-ion beam or X-ray irradiation to cancer cells. In this study we tried to detect the mechanism of DNA damage and repair of the clonogens after X-ray or carbon-ion beam irradiation. At first, colony assay method was performed after irradiation of 12 Gy of X-ray or 5 Gy of carbon-ion beam to compare the time dependent cell survival of the IA cells after each irradiation pass. Second, to search the genes causing PLD repair after irradiation of X-ray or carbon-ion beam, we evaluated gene expressions by using semi-quantitative RT-PCR with the selected 34 genes reportedly related to DNA repair. The intervals from the irradiation were 0, 6, 12 and 24 hr for colony assay method, and 0, 3, 18 hr for RT-PCR method. From the result of survival assays, significant PLD repair was not observed in carbon-ion beam as compared to X-ray irradiation. The results of RT-PCR were as follows. The gene showing significantly higher expressions after X-ray irradiation than after carbon-ion beam irradiation was PCNA. The genes showing significantly lower expressions after X-ray irradiation rather than after carbon-ion beam irradiation were RAD50, BRCA1, MRE11A, XRCC3, CHEK1, MLH1, CCNB1, CCNB2 and LIG4. We conclude that PCNA could be a likely candidate gene for PLD repair.

Curative treatment of Stage I non-small-cell lung cancer with carbon ion beams using a hypofractionated regimen.

PURPOSE: A phase I/II study on carbon ion radiotherapy for Stage I non-small-cell lung cancer (NSCLC) was first conducted between 1994 and 1999 and determined the optimal dose. Second, a Phase II study using the optimal dose was performed. The purpose of the present study was to clarify the local control and 5-year survival rates. METHODS AND MATERIALS: Between April 1999 and December 2000, 50 patients with 51 primary lesions were treated. Using a fixed dose of 72 GyE in nine fractions over 3 weeks, the primary tumors were irradiated with carbon ion beams alone. The average age of the patients was 74.5 years. Thirty-three (66%) of these were medically inoperable. Local control and survival were determined by using the Kaplan-Meier method and the data were statistically processed by using the log-rank test. RESULTS: All patients were observed for a minimum of 5 years or until death with a median follow-up time of 59.2 months (range, 6.0-83.0 months). The local control rate for all patients was 94.7%. The patients' 5-year cause-specific survival rate was 75.7% (IA: 89.4; IB: 55.1), and overall survival 50.0% (IA: 55.2; IB: 42.9). No toxic reactions in the lung greater than Grade 3 were detected. CONCLUSIONS: Carbon ion radiotherapy, a new treatment modality with superior benefits in terms of quality of life and activity of daily living, has been proven as a valid alternative to surgery for Stage I NSCLC and to offer particular benefits, especially for elderly and inoperable patients.

Four-dimensional measurement of lung tumor displacement using 256-multi-slice CT-scanner.

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 tumor site may not predict the extent or pattern of tumor 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.

Respiratory correlated segment reconstruction algorithm towards four-dimensional radiation therapy using carbon ion beams.

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.

A combination-weighted Feldkamp-based reconstruction algorithm for cone-beam CT.

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.

Successful surgical treatment for life threatening metastatic thoracic and cervical pheochromocytoma.

A 53 year-old woman had been followed up since 1996 after receiving bilateral adrenalectomy for the treatment of bilateral adrenal pheochromocytoma in von Hippel-Lindau (VHL) disease. In March 2003, she suffered from cough, dizziness and faint, and was referred to our hospital. The radiographic findings exhibited the presence of hypervascular tumors in the left hilum, left apex of the lung and the left neck. Tumor progression was suspected to occlude the left main pulmonary artery and hormonal assays showed elevated levels of the plasma norepinephrine, which may cause fatal complications. Percutaneous needle biopsy of the left cervical tumor revealed metastatic pheochromocytoma. After embolization of the main feeding artery, surgical resection of the tumor resulted in control of excess catecholamine release and symptoms.

Huge localized fibrous tumor of the pleura resembling a mediastinal tumor: report of a case.

A 67-year-old man was admitted to our hospital because of an abnormal chest echoic lesion detected incidentally by echocardiography. A chest roentgenogram showed the presence of a giant mass, and computed tomography of the chest confirmed the presence of a mass with a nonhomogeneous density in the left mediastinum, just adjacent to the left ventricle of the heart. Percutaneous aspiration cytology of the mass showed benign fibrous cells and a small amount of lymphocytes. The preoperative diagnosis of the tumor suggested a thymoma, and the patient underwent a thoracotomy. A pedunculated tumor arose from the visceral pleura of the left upper lobe of the lung, and it was capsulated within the pleura. The tumor measured 15 x 12 x 8 cm in size and it was successfully resected. The pathological diagnosis of the tumor was benign localized fibrous tumor of the pleura.