Shinsuke Yano

Clinical outcomes of 3D conformal hypofractionated single high-dose radiotherapy for one or two lung tumors using a stereotactic body frame

PURPOSE This study was performed to evaluate the clinical outcomes of three-dimensional (3D) conformal hypofractionated single high-dose radiotherapy for one or two lung tumors using a stereotactic body frame. MATERIALS AND METHODS Forty patients who were treated between July 1998 and November 2000 and were followed for >10 months were included in this study. Of the 40 patients, 31 had primary lung cancer and 9 had metastatic lung cancer. The primary lung cancer was staged as T1N0M0, T2N0M0, and T3N0M0 in 19, 8, and 4 patients, respectively. The primary sites of metastatic lung cancer were the colon in 4, tongue in 2, and osteosarcoma, lung cancer, and hepatocellular carcinoma in 1 each. 3D treatment planning was performed to maintain the target dose homogeneity within 15% and to decrease the irradiated lung volume from >20 Gy to <25%. All patients were irradiated using a stereotactic body frame and received 4 times 10-12 Gy single high-dose radiation at the isocenter during a period of 5-13 days (median 12). RESULTS The initial 3 patients received 40, and the remaining 37 patients received 48 Gy after dose escalation. Of the 33 tumors followed >6 months, 6 tumors (18%) disappeared completely after treatment. Twenty-five tumors (76%) decreased in size by 30% or more after treatment. Therefore, 31 tumors (94%) showed a local response. During the follow-up of 4-37 months (median 19), no pulmonary complications greater than National Cancer Institute-Common Toxicity Criteria Grade 2 were noted. Of the 16 patients with histologically confirmed T1N0M0 primary lung cancer who received 48 Gy, all tumors were locally controlled during the follow-up of 6-36 months (median = 19). In 9 tumors with lung metastases that were irradiated with 48 Gy in total, 2 tumors did not show a local response. Finally, 3 tumors (33%) with lung metastases relapsed locally at 6-12 months (median 7) after treatment during the follow-up of 3-29 months (median 18). CONCLUSION 3D conformal hypofractionated single high-dose radiotherapy of 48 Gy in 4 fractions using a stereotactic body frame was useful for the treatment of lung tumors.

The effectiveness of an immobilization device in conformal radiotherapy for lung tumor: reduction of respiratory tumor movement and evaluation of the daily setup accuracy.

PURPOSE To evaluate the daily setup accuracy and the reduction of respiratory tumor movement using a body frame in conformal therapy for solitary lung tumor. METHODS AND MATERIALS Eighteen patients with a solitary lung tumor underwent conformal therapy using a body frame. The body shell of the frame was shaped to the patients body contour. The respiratory tumor movement was estimated using fluoroscopy, and if it was greater than 5 mm, pressure was applied to the patients abdomen with the goal of minimizing tumor movement. CT images were then obtained, and a treatment planning was made. A total dose of 40 or 48 Gy was delivered in 4 fractions. Portal films were obtained at each treatment, and the field displacements between them and the simulation films were measured for daily setup errors. The patients were repositioned if the setup error was greater than 3 mm. Correlations were analyzed between patient characteristics and the tumor movement, or the tumor movement reduction and the daily setup errors. RESULTS Respiratory tumor movement ranged from 0 to 20 mm (mean 7.7 mm). The abdominal press reduced the tumor movement significantly from a range of 8 to 20 mm to a range of 2 to 11 mm (p = 0.0002). Daily setup errors were within 5 mm in 90%, 100%, and 93% of all verifications in left-right, anterior-posterior, and cranio-caudal directions, respectively. Patient repositioning was performed in 25% of all treatments. No significant correlation was detected between patient characteristics and tumor movement, tumor movement reduction, and the daily setup errors. CONCLUSIONS The abdominal press was successful in reducing the respiratory tumor movement. Daily setup accuracy using the body frame was acceptable. Verification should be performed at each treatment in hypofractionated conformal therapy.

The geometric accuracy of frameless stereotactic radiosurgery using a 6D robotic couch system

The aim of this paper is to assess the overall geometric accuracy of the Novalis system using the Robotic Tilt Module in terms of the uncertainty in frameless stereotactic radiotherapy. We analyzed the following three metrics: (1) the correction accuracy of the robotic couch, (2) the uncertainty of the isocenter position with gantry and couch rotation, and (3) the shift in position between the isocenter and central point detected with the ExacTrac x-ray system. Based on the concept of uncertainty, the overall accuracy was calculated from these values. The accuracy in positional correction with the robotic couch was 0.07 +/- 0.22 mm, the positional shift of the isocenter associated with gantry rotation was 0.35 mm, the positional shift of the isocenter associated with couch rotation was 0.38 mm and the difference in position between the isocenter and the ExacTrac x-ray system was 0.30 mm. The accuracy of intracranial stereotactic radiosurgery with the Novalis system in our clinic was 0.31 +/- 0.77 mm. The overall geometric accuracy based on the concept of uncertainty was 0.31 +/- 0.77 mm, which is within the tolerance given in the American Association of Physicists in Medicine report no. 54.

Geometrical differences in target volumes between slow CT and 4D CT imaging in stereotactic body radiotherapy for lung tumors in the upper and middle lobe

Since stereotactic body radiotherapy (SBRT) was started for patients with lung tumor in 1998 in our institution, x-ray fluoroscopic examination and slow computed tomography (CT) scan with a rotation time of 4 s have been routinely applied to determine target volumes. When lung tumor motion observed with x-ray fluoroscopy is larger than 8 mm, diaphragm control (DC) is used to reduce tumor motion during respiration. After the installation of a four-dimensional (4D) CT scanner in 2006, 4D CT images have been supplementarily acquired to determine target volumes. It was found that target volumes based on slow CT images were substantially different from those on 4D CT images, even for patients with lung tumor motion no larger than 8 mm. Although slow CT scan might be expected to fare well for lung tumors with motion range of 8 mm or less, the potential limitations of slow CT scan are unknown. The purpose of this study was to evaluate the geometrical differences in target volumes between slow CT and 4D CT imaging for lung tumors with motion range no larger than 8 mm in the upper and middle lobe. Of the patients who underwent SBR between October 2006 and April 2008, 32 patients who had lung tumor with motion range no larger than 8 mm and did not need to use DC were enrolled in this study. Slow CT and 4D CT images were acquired under free breathing for each patient. Target volumes were manually delineated on slow CT images (TV(slow CT)). Gross tumor volumes were also delineated on each of the 4D CT volumes and their union (TV(4D CT)) was constructed. Volumetric and statistical analyses were performed for each patient. The mean +/- standard deviation (S.D.) of TV(slow CT)/TV(4D CT) was 0.75 +/- 0.17 (range, 0.38-1.10). The difference between sizes of TV(slow CT) and TV(4D CT) was not statistically significant (P = 0.096). A mean of 8% volume of TV(slow CT) was not encompassed in TV(4D CT) (mean +/- S.D. = 0.92 +/- 0.07). The patients were separated into two groups to test whether the quality of target delineation on slow CT scans depends on respiratory periods below or above the CT rotation time of 4 s. No significant difference was observed between these groups (P = 0.229). Even lung tumors with motion range no larger than 8 mm might not be accurately depicted on slow CT images. When only a single slow CT scan was used for lung tumors with motion range of 8 mm or less, 95% confidence values for additional margins for TV(slow CT) to encompass TV(4D CT) were 4.0, 5.4, 4.9, 5.1, 1.8, and 1.7 mm for lateral, medial, ventral, dorsal, cranial, and caudal directions, respectively.

Current status of stereotactic body radiotherapy for lung cancer

Stereotactic radiotherapy (SRT) for extracranial tumors has been recently performed to treat lung and liver cancers, and has subsequently been named stereotactic body radiotherapy (SBRT). The advantages of hypofractionated radiotherapy for treating lung tumors are a shortened treatment course that requires fewer trips to the clinic than a conventional program, and the adoption of a smaller irradiated volume allowed by greater setup precision. This treatment is possible because the lung and liver are considered parallel organs at risk. The preliminary clinical results, mostly reported on lung cancer, have been very promising, including a local control rate of more than 90%, and a relatively low complication rate. The final results of a few clinical trials are awaited. SBRT may be useful for the treatment of stage I lung tumors.

Evaluation of dynamic tumour tracking radiotherapy with real-time monitoring for lung tumours using a gimbal mounted linac

PURPOSE To evaluate feasibility and acute toxicities after dynamic tumour tracking (DTT) irradiation with real-time monitoring for lung tumours using a gimbal mounted linac. MATERIALS AND METHODS Spherical gold markers were placed around the tumour using a bronchoscope prior to treatment planning. Prescription dose at the isocentre was 56 Gy in 4 fractions for T2a lung cancer and metastatic tumour, and 48 Gy in 4 fractions for the others. Dose-volume metrics were compared between DTT and conventional static irradiation using in-house developed software. RESULTS Of twenty-two patients enrolled, DTT radiotherapy was successfully performed for 16 patients, except 4 patients who coughed out the gold markers, one who showed spontaneous tumour regression, and one where the abdominal wall motion did not correlate with the tumour motion. Dose covering 95% volume of GTV was not different between the two techniques, while normal lung volume receiving 20 Gy or more was reduced by 20%. A mean treatment time per fraction was 36 min using DTT. With a median follow-up period of 13.2 months, no severe toxicity grade 3 or worse was observed. CONCLUSIONS DTT radiotherapy using a gimbal mounted linac was clinically feasible for lung treatment without any severe acute toxicity.

Comparison of three radiotherapy treatment planning protocols of definitive external-beam radiation for localized prostate cancer

BackgroundThree radiotherapy treatment planning (RTTP) protocols for definitive external-beam radiation for localized prostate cancer, designed and clinically applied at Kyoto University, were compared.MethodsTreatment plans were created according to three different RTTP protocols (old three-dimensional conformal radiotherapy [3D-CRT], new 3D-CRT, and intensity-modulated radiotherapy [IMRT]) on computed tomography (CT) data sets of five patients with localized prostate cancer. The dynamic-arc conformal technique was used in the 3D-CRT protocols. Differences in dose distribution were evaluated and compared based on dose-volume histogram (DVH) analyses.ResultsThe coverage of the clinical target volume (= prostate alone) was comparable among the three RTTP protocols. However, the average values for the percent volume that received at least 95% of the prescription dose (V95), the percent of the prescription dose covering 95% of the volume (D95), and the conformity index of the planning target volume (PTV) were 99%, 97%, and 0.88 for the IMRT; 93.9%, 94.5%, and 0.76 for the new 3D-CRT; and 59.6%, 82.9%, and 0.6 for the old 3D-CRT protocol, respectively. Inhomogeneity of doses to the PTV was larger with the IMRT protocol than with the new 3D-CRT protocol. Doses to both the rectal wall and bladder wall were almost comparable with the new 3D-CRT and IMRT protocols, but were lower with the old 3D-CRT protocol, due to the lowest prescription dose and incomplete dose coverage of the PTV.ConclusionThe old 3D-CRT protocol could not achieve the goals for the PTV set in the IMRT protocol. The new 3D-CRT and IMRT protocols were generally comparable in terms of both the PTV coverage and normal tissue-sparing, although the IMRT protocol achieved the most conformal dose distribution to the PTV, in return for a larger, but acceptable, dose inhomogeneity.

An integrated Monte Carlo dosimetric verification system for radiotherapy treatment planning

An integrated Monte Carlo (MC) dose calculation system, MCRTV (Monte Carlo for radiotherapy treatment plan verification), has been developed for clinical treatment plan verification, especially for routine quality assurance (QA) of intensity-modulated radiotherapy (IMRT) plans. The MCRTV system consists of the EGS4/PRESTA MC codes originally written for particle transport through the accelerator, the multileaf collimator (MLC), and the patient/phantom, which run on a 28-CPU Linux cluster, and the associated software developed for the clinical implementation. MCRTV has an interface with a commercial treatment planning system (TPS) (Eclipse, Varian Medical Systems, Palo Alto, CA, USA) and reads the information needed for MC computation transferred in DICOM-RT format. The key features of MCRTV have been presented in detail in this paper. The phase-space data of our 15 MV photon beam from a Varian Clinac 2300C/D have been developed and several benchmarks have been performed under homogeneous and several inhomogeneous conditions (including water, aluminium, lung and bone media). The MC results agreed with the ionization chamber measurements to within 1% and 2% for homogeneous and inhomogeneous conditions, respectively. The MC calculation for a clinical prostate IMRT treatment plan validated the implementation of the beams and the patient/phantom configuration in MCRTV.

Influence of Radiation Dose Rate and Lung Dose on Interstitial Pneumonitis after Fractionated Total Body Irradiation: Acute Parotitis May Predict Interstitial Pneumonitis

This study evaluated patients for the influence of the dose rate and lung dose of fractionated total body irradiation (TBI) in preparation for allogeneic bone marrow transplantation (BMT) on the subsequent development of interstitial pneumonitis (IP). Sixty-six patients at our institute were treated with TBI followed by BMT. All of the patients received a total TBI dose of 12 Gy given in 6 fractions over 3 days and were divided into 3 groups according to the radiation dose rate and lung dose: group A, lung dose of 8 Gy (n = 18); group B, lung dose of 12 Gy at 8 cGy/min (n = 25); and group C, lung dose of 12 Gy at 19 cGy/min (n = 23). The overall survival rate, the cumulative incidence of relapse, and the cumulative incidence of IP were evaluated in relation to various potential indicators of future IP. There were no significant differences in survival and relapse rates between patient group A and combined groups B and C. Clinically significant IP occurred in 13 patients. The cumulative incidence of IP was significantly higher in patients who developed acute parotitis as indicated by either an elevation in the serum amylase level or parotid pain of grade 1 to 2. There was no difference in IP incidence among groups A, B, and C. There was no significant difference in IP incidence between lung dose values of 8 Gy (with lung shielding) and 12 Gy (without lung shielding) and between dose rate values of 8 cGy/min and 19 cGy/ min, at least when TBI was given in 6 fractions. The presence of acute parotitis during or just after TBI may be a predictor of IP.

Effect of circulating antigen on immunoscintigraphy of ovarian cancer patients using Anti-CA125 monoclonal antibody

The murine monoclonal antibody (mAb) 145–9 recognizes an epitope present on CA125 but different from the epitope defined by the mAb OC125. To evaluate the clinical usefulness of the 145–9 antibody, immunoscintigraphy was performed in ovarian cancer patients and the effect of circulating CA125 on tumor imaging was investigated. Two milligrams (74 MBq) of 111In‐labeled 145–9 was injected intravenously into 11 patients with ovarian cancer. Pre‐injection serum CA125 concentrations were between 166 U/ml and 7414 U/ml. Tumors were visualized in 10 of 11 patients. In two patients, lymph nodes that were not detected by other imaging modalities but were clinically suspected as metastases were visualized. There was no correlation between serum CA125 level and antibody uptake in the tumors. Immune complexes between the antibody and circulating antigen were observed in sera of all the patients, but the fraction of radioactivity in complex form did not correlate well with serum CA125 levels. The immune complexes survived in the circulation and the circulating radiolabel, including immune complexes, was still bound to solid‐phase CA125. The plasma clearance rate and hepatic uptake of the antibody were not significantly affected by circulating CA125. In conclusion, the antibody 145–9 formed complexes with CA125 in vivo but this did not compromise the outcome of antibody imaging. The antibody 145–9 can be used in immunoscintigraphy of ovarian cancer irrespective of serum CA125 level.