[Trial manufacture of a plunger shield for a disposable plastic syringe].

A syringe-type radiopharmaceutical being supplied by a manufacturer has a syringe shield and a plunger shield, whereas an in-hospital labeling radiopharmaceutical is administered by a disposable plastic syringe without the plunger shield. In cooperation with Nihon Medi-Physics Co. Ltd., we have produced a new experimental plunger shield for the disposable plastic syringe. In order to evaluate this shielding effect, we compared the leaked radiation doses of our plunger shield with those of the syringe-type radiopharmaceutical (Medi shield type). Our plunger shield has a lead plate of 21 mm in diameter and 3 mm thick. This shield is equipped with the plunger-end of a disposal plastic syringe. We sealed 99mTc solution into a plastic syringe (Terumo Co.) of 5 ml with our plunger shield and Medi shield type of 2 ml. We measured leaked radiation doses around syringes using fluorescent glass dosimeters (Dose Ace). The number of measure points was 18. The measured doses were converted to 70 microm dose equivalent at 740 MBq of radioactivity. The results of our plunger shield and the Medi shield type were as follows: 4-13 microSv/h and 3-14 microSv/h at shielding areas, 3-545 microSv/h and 6-97 microSv/h at non-shielding areas, 42-116 microSv/h and 88-165 microSv/h in the vicinity of the syringe shield, and 1071 microSv/h and 1243 microSv/h at the front of the needle. For dose rates of shielding areas around the syringe, the shielding effects were approximately the same as those of the Medi shield type. In conclusion, our plunger shield may be useful for reducing finger exposure during the injection of an in-hospital labeled radiopharmaceutical.

Uncertainty in treatment of head-and-neck tumors by use of intraoral mouthpiece and embedded fiducials.

PURPOSE: To reduce setup error and intrafractional movement in head-and-neck treatment, a real-time tumor tracking radiotherapy (RTRT) system was used with the aid of gold markers implanted in a mouthpiece. METHODS AND MATERIALS: Three 2-mm gold markers were implanted into a mouthpiece that had been custom made for each patient before the treatment planning process. Setup errors in the conventional immobilization system using the shell (manual setup) and in the RTRT system (RTRT setup) were compared. Eight patients with pharyngeal tumors were enrolled. RESULTS: The systematic setup errors were 1.8, 1.6, and 1.1 mm in the manual setup and 0.2, 0.3, and 0.3 mm in the RTRT setup in right-left, craniocaudal, and AP directions, respectively. Statistically significant differences were observed with respect to the variances in setup error (p <0.001). The systematic and random intrafractional errors were maintained within the ranges of 0.2-0.6 mm and 1.0-2.0 mm, respectively. The rotational systematic and random intrafractional errors were estimated to be 2.2-3.2 degrees and 1.5-1.6 degrees , respectively. CONCLUSIONS: The setup error and planning target volume margin can be significantly reduced using an RTRT system with a mouthpiece and three gold markers.

Speed and amplitude of lung tumor motion precisely detected in four-dimensional setup and in real-time tumor-tracking radiotherapy.

BACKGROUND: To reduce the uncertainty of registration for lung tumors, we have developed a four-dimensional (4D) setup system using a real-time tumor-tracking radiotherapy system. METHODS AND MATERIALS: During treatment planning and daily setup in the treatment room, the trajectory of the internal fiducial marker was recorded for 1 to 2 min at the rate of 30 times per second by the real-time tumor-tracking radiotherapy system. To maximize gating efficiency, the patient's position on the treatment couch was adjusted using the 4D setup system with fine on-line remote control of the treatment couch. RESULTS: The trajectory of the marker detected in the 4D setup system was well visualized and used for daily setup. Various degrees of interfractional and intrafractional changes in the absolute amplitude and speed of the internal marker were detected. Readjustments were necessary during each treatment session, prompted by baseline shifting of the tumor position. CONCLUSION: The 4D setup system was shown to be useful for reducing the uncertainty of tumor motion and for increasing the efficiency of gated irradiation. Considering the interfractional and intrafractional changes in speed and amplitude detected in this study, intercepting radiotherapy is the safe and cost-effective method for 4D radiotherapy using real-time tracking technology.

Development of a wavelength-separated type scintillator with optical fiber (SOF) dosimeter to compensate for the Cerenkov radiation effect.

The scintillator with optical fiber (SOF) dosimeter consists of a miniature scintillator mounted on the tip of an optical fiber. The scintillator of the current SOF dosimeter is a 1-mm diameter hemisphere. For a scintillation dosimeter coupled with an optical fiber, measurement accuracy is influenced by signals due to Cerenkov radiation in the optical fiber. We have implemented a spectral filtering technique for compensating for the Cerenkov radiation effect specifically for our plastic scintillator-based dosimeter, using a wavelength-separated counting method. A dichroic mirror was used for separating input light signals. Individual signal counting was performed for high- and low-wavelength light signals. To confirm the accuracy, measurements with various amounts of Cerenkov radiation were performed by changing the incident direction while keeping the Ir-192 source-to-dosimeter distance constant, resulting in a fluctuation of <5%. Optical fiber bending was also addressed; no bending effect was observed for our wavelength-separated SOF dosimeter.

Feasibility of synchronization of real-time tumor-tracking radiotherapy and intensity-modulated radiotherapy from viewpoint of excessive dose from fluoroscopy.

PURPOSE: Synchronization of the techniques in real-time tumor-tracking radiotherapy (RTRT) and intensity-modulated RT (IMRT) is expected to be useful for the treatment of tumors in motion. Our goal was to estimate the feasibility of the synchronization from the viewpoint of excessive dose resulting from the use of fluoroscopy. METHODS AND MATERIALS: Using an ionization chamber for diagnostic X-rays, we measured the air kerma rate, surface dose with backscatter, and dose distribution in depth in a solid phantom from a fluoroscopic RTRT system. A nominal 50-120 kilovoltage peak (kVp) of X-ray energy and a nominal 1-4 ms of pulse width were used in the measurements. RESULTS: The mean +/- SD air kerma rate from one fluoroscope was 238.8 +/- 0.54 mGy/h for a nominal pulse width of 2.0 ms and nominal 100 kVp of X-ray energy at the isocenter of the linear accelerator. The air kerma rate increased steeply with the increase in the X-ray beam energy. The surface dose was 28-980 mGy/h. The absorbed dose at a 5.0-cm depth in the phantom was 37-58% of the peak dose. The estimated skin surface dose from one fluoroscope in RTRT was 29-1182 mGy/h and was strongly dependent on the kilovoltage peak and pulse width of the fluoroscope and slightly dependent on the distance between the skin and isocenter. CONCLUSION: The skin surface dose and absorbed depth dose resulting from fluoroscopy during RTRT can be significant if RTRT is synchronized with IMRT using a multileaf collimator. Precise estimation of the absorbed dose from fluoroscopy during RT and approaches to reduce the amount of exposure are mandatory.

Three-dimensional conformal setup (3D-CSU) of patients using the coordinate system provided by three internal fiducial markers and two orthogonal diagnostic X-ray systems in the treatment room.

PURPOSE: To test the accuracy of a system for correcting for the rotational error of the clinical target volume (CTV) without having to reposition the patient using three fiducial markers and two orthogonal fluoroscopic images. We call this system "three-dimensional conformal setup" (3D-CSU). METHODS AND MATERIALS: Three 2.0-mm gold markers are inserted into or adjacent to the CTV. On the treatment couch, the actual positions of the three markers are calculated based on two orthogonal fluoroscopies crossing at the isocenter of the linear accelerator. Discrepancy of the actual coordinates of gravity center of three markers from its planned coordinates is calculated. Translational setup error is corrected by adjustment of the treatment couch. The rotation angles (alpha, beta, gamma) of the coordinates of the actual CTV relative to the planned CTV are calculated around the lateral (x), craniocaudal (y), and anteroposterior (z) axes of the planned CTV. The angles of the gantry head, collimator, and treatment couch of the linear accelerator are adjusted according to the rotation of the actual coordinates of the tumor in relation to the planned coordinates. We have measured the accuracy of 3D-CSU using a static cubic phantom. RESULTS: The gravity center of the phantom was corrected within 0.9 +/- 0.3 mm (mean +/- SD), 0.4 +/- 0.2 mm, and 0.6 +/- 0.2 mm for the rotation of the phantom from 0-30 degrees around the x, y, and z axes, respectively, every 5 degrees. Dose distribution was shown to be consistent with the planned dose distribution every 10 degrees of the rotation from 0-30 degrees. The mean rotational error after 3D-CSU was -0.4 +/- 0.4 (mean +/- SD), -0.2 +/- 0.4, and 0.0 +/- 0.5 degrees around the x, y, and z axis, respectively, for the rotation from 0-90 degrees. CONCLUSIONS: Phantom studies showed that 3D-CSU is useful for performing rotational correction of the target volume without correcting the position of the patient on the treatment couch. The 3D-CSU will be clinically useful for tumors in structures such as paraspinal diseases and prostate cancers not subject to large internal organ motion.

Tumor location, cirrhosis, and surgical history contribute to tumor movement in the liver, as measured during stereotactic irradiation using a real-time tumor-tracking radiotherapy system.

PURPOSE: To investigate the three-dimensional (3D) intrafractional motion of liver tumors during real-time tumor-tracking radiotherapy (RTRT). MATERIALS AND METHODS: The data of 20 patients with liver tumors were analyzed. Before treatment, a 2-mm gold marker was implanted near the tumor. The RTRT system used fluoroscopy image processor units to determine the 3D position of the implanted marker. A linear accelerator was triggered to irradiate the tumor only when the marker was located within a permitted region. The automatically recorded tumor-motion data were analyzed to determine the amplitude of the tumor motion, curve shape of the tumor motion, treatment efficiency, frequency of movement, and hysteresis. Each of the following clinical factors was evaluated to determine its contribution to the amplitude of movement: tumor position, existence of cirrhosis, surgical history, tumor volume, and distance between the isocenter and the marker. RESULTS: The average amplitude of tumor motion in the 20 patients was 4 +/- 4 mm (range 1-12), 9 +/- 5 mm (range 2-19), and 5 +/- 3 mm (range 2-12) in the left-right, craniocaudal, and anterior-posterior (AP) direction, respectively. The tumor motion of the right lobe was significantly larger than that of the left lobe in the left-right and AP directions (p = 0.01). The tumor motion of the patients with liver cirrhosis was significantly larger than that of the patients without liver cirrhosis in the left-right and AP directions (p < 0.004). The tumor motion of the patients who had received partial hepatectomy was significantly smaller than that of the patients who had no history of any operation on the liver in the left-right and AP directions (p < 0.03). Thus, three of the five clinical factors examined (i.e., tumor position in the liver, cirrhosis, and history of surgery on the liver) significantly affected the tumor motion of the liver in the transaxial direction during stereotactic irradiation. Frequency analysis revealed that for 9 (45%) of the 20 tumors, the cardiac beat caused measurable motion. The 3D trajectory of the tumor showed hysteresis for 4 (20%) of the 20 tumors. The average treatment efficiency of RTRT was 40%. CONCLUSIONS: Tumor location, cirrhosis, and history of surgery on the liver all had an impact on the intrafractional tumor motion of the liver in the transaxial direction. This finding should be helpful in determining the smallest possible margin in individual cases of radiotherapy for liver malignancy.

Calculation of rotational setup error using the real-time tracking radiation therapy (RTRT) system and its application to the treatment of spinal schwannoma.

PURPOSE: The efficacy of a prototypic fluoroscopic real-time tracking radiation therapy (RTRT) system using three gold markers (2 mm in diameter) for estimating translational error, rotational setup error, and the dose to normal structures was tested in 5 patients with spinal schwannoma and a phantom. METHODS AND MATERIALS: Translational error was calculated by comparing the actual position of the marker closest to the tumor to its planned position, and the rotational setup error was calculated using the three markers around the target. Theoretically, the actual coordinates can be adjusted to the planning coordinates by sequential rotation of gamma degrees around the z axis, beta degrees around the y axis, and alpha degrees around the x axis, in this order. We measured the accuracy of the rotational calculation using a phantom. Five patients with spinal schwannoma located at a minimum of 1-5 mm from the spinal cord were treated with RTRT. Three markers were inserted percutaneously into the paravertebral deep muscle in 3 patients and surgically into two consecutive vertebral bones in two other patients. RESULTS: In the phantom study, the discrepancies between the actual and calculated rotational error were -0.1 +/- 0.5 degrees. The random error of rotation was 5.9, 4.6, and 3.1 degrees for alpha, beta, and gamma, respectively. The systematic error was 7.1, 6.6, and 3.0 degrees for alpha, beta, and gamma, respectively. The mean rotational setup error (0.2 +/- 2.2, -1.3 +/- 2.9, and -1.3 +/- 1.7 degrees for alpha, beta, and gamma, respectively) in 2 patients for whom surgical marker implantation was used was significantly smaller than that in 3 patients for whom percutaneous insertion was used (6.0 +/- 8.2, 2.7 +/- 5.9, and -2.1 +/- 4.6 degrees for alpha, beta, and gamma). Random translational setup error was significantly reduced by the RTRT setup (p < 0.0001). Systematic setup error was significantly reduced by the RTRT setup only in patients who received surgical implantation of the marker (p < 0.0001). The maximum dose to the spinal cord was estimated to be 40.6-50.3 Gy after consideration of the rotational setup error, vs. a planned maximum dose of 22.4-51.6 Gy. CONCLUSION: The RTRT system employing three internal fiducial markers is useful to reduce translational setup error and to estimate the dose to the normal structures in consideration of the rotational setup error. Surgical implantation of the marker to the vertebral bone was shown to be sufficiently rigid for the calculation of the rotational setup error. Fractionated radiotherapy for spinal schwannoma using the RTRT system may well be an alternative or supplement to surgical treatment.

Three-dimensional intrafractional movement of prostate measured during real-time tumor-tracking radiotherapy in supine and prone treatment positions.

PURPOSE: To quantify three-dimensional (3D) movement of the prostate gland with the patient in the supine and prone positions and to analyze the movement frequency for each treatment position. METHODS AND MATERIALS: The real-time tumor-tracking radiotherapy (RTRT) system was developed to identify the 3D position of a 2-mm gold marker implanted in the prostate 30 times/s using two sets of fluoroscopic images. The linear accelerator was triggered to irradiate the tumor only when the gold marker was located within the region of the planned coordinates relative to the isocenter. Ten patients with prostate cancer treated with RTRT were the subjects of this study. The coordinates of the gold marker were recorded every 0.033 s during RTRT in the supine treatment position for 2 min. The patient was then moved to the prone position, and the marker was tracked for 2 min to acquire data regarding movement in this position. Measurements were taken 5 times for each patient (once a week); a total of 50 sets for the 10 patients was analyzed. The raw data from the RTRT system were filtered to reduce system noise, and the amplitude of movement was then calculated. The discrete Fourier transform of the unfiltered data was performed for the frequency analysis of prostate movement. RESULTS: No apparent difference in movement was found among individuals. The amplitude of 3D movement was 0.1-2.7 mm in the supine and 0.4-24 mm in the prone positions. The amplitude in the supine position was statistically smaller in all directions than that in the prone position (p < 0.0001). The amplitude in the craniocaudal and AP directions was larger than in the left-right direction in the prone position (p < 0.0001). No characteristic movement frequency was detected in the supine position. The respiratory frequency was detected for all patients regarding movement in the craniocaudal and AP directions in the prone position. The results of the frequency analysis suggest that prostate movement is affected by the respiratory cycle and is influenced by bowel movement in the prone position. CONCLUSION: The results of this study have confirmed that internal organ motion is less frequent in the supine position than in the prone position in the treatment of prostate cancer. RTRT would be useful in reducing uncertainty due to the effects of the respiratory cycle, especially in the prone position.

Tolerance of organs at risk in small-volume, hypofractionated, image-guided radiotherapy for primary and metastatic lung cancers.

PURPOSE: To determine the organ at risk and the maximum tolerated dose (MTD) of radiation that could be delivered to lung cancer using small-volume, image-guided radiotherapy (IGRT) using hypofractionated, coplanar, and noncoplanar multiple fields. MATERIALS AND METHODS: Patients with measurable lung cancer (except small-cell lung cancer) 6 cm or less in diameter for whom surgery was not indicated were eligible for this study. Internal target volume was determined using averaged CT under normal breathing, and for patients with large respiratory motion, using two additional CT scans with breath-holding at the expiratory and inspiratory phases in the same table position. Patients were localized at the isocenter after three-dimensional treatment planning. Their setup was corrected by comparing two linacographies that were orthogonal at the isocenter with corresponding digitally reconstructed images. Megavoltage X-rays using noncoplanar multiple static ports or arcs were used to cover the parenchymal tumor mass. Prophylactic nodal irradiation was not performed. The radiation dose was started at 60 Gy in 8 fractions over 2 weeks (60 Gy/8 Fr/2 weeks) for peripheral lesions 3.0 cm or less, and at 48 Gy/8 Fr/2 weeks at the isocenter for central lesions or tumors more than 3.0 cm at their greatest dimension. RESULTS: Fifty-seven lesions in 45 patients were treated. Tumor size ranged from 0.6 to 6.0 cm, with a median of 2.6 cm. Using the starting dose, 1 patient with a central lesion died of a radiation-induced ulcer in the esophagus after receiving 48 Gy/8 Fr at isocenter. Although the contour of esophagus received 80% or less of the prescribed dose in the planning, recontouring of esophagus in retrospective review revealed that 1 cc of esophagus might have received 42.5 Gy, with the maximum dose of 50.5 Gy. One patient with a peripheral lesion experienced Grade 2 pain at the internal chest wall or visceral pleura after receiving 54 Gy/8 Fr. No adverse respiratory reaction was noted in the symptoms or respiratory function tests. The 3-year local control rate was 80.4% +/- 7.1% (a standard error) with a median follow-up period of 17 months for survivors. Because of the Grade 5 toxicity, we have halted this Phase I/II study and are planning to rearrange the protocol setting accordingly. The 3-year local control rate was 69.6 +/- 10.6% for patients who received 48 Gy and 100% for patients who received 60 Gy (p = 0.0442). CONCLUSIONS: Small-volume IGRT using 60 Gy in eight fractions is highly effective for the local control of lung tumors, but MTD has not been determined in this study. The organs at risk are extrapleural organs such as the esophagus and internal chest wall/visceral pleura rather than the pulmonary parenchyma in the present protocol setting. Consideration of the uncertainty in the contouring of normal structures is critically important, as is uncertainty in setup of patients and internal organ in the high-dose hypofractionated IGRT.

[Accuracy of absorbed dose calculation and measurement of scatter factors with different depth of mini-phantoms using a pinpoint ionization chamber].

The output factor of high-energy X-ray machines varies with collimation. According to Khan's theory, collimator and phantom scatter factors contribute to total scatter factor. For precise X-ray irradiation, the two factors need to be taken into consideration. To obtain proper factors, we made two original polystyrene cylindrical mini-phantoms. These phantoms are both 4 cm in diameter and have a pinpoint ion chamber placed at a depth of 5 cm and 10 cm, respectively. Using a 6 MV X-ray machine, collimator scatter factors were calculated for various field arrangements (i.e., field sizes ranging from 4 cm x 4 cm to 40 cm x 40 cm at isocenter). To determine if calculated values were appropriate, we measured point doses of 20 X-ray irradiation patterns using a Farmer-type ion chamber with a water equivalent phantom at depths of 5 cm and 10 cm, respectively. Two hundred MUs were irradiated to the above-mentioned depths for each field. Based on the measured doses, variations were obtained for four calculation methods. Accounting for 1) secondary collimator (jaw) setting, 2) blocked field (multi-leaf collimator) setting, 3) Khan's theory using a 5 cm mini-phantom, and 4) Khan's theory using a 10 cm mini-phantom. Dose variations in each method of calculation were as follows: 1) +0.3 to +10.2% (mean, +2.0 to +3.2%) , 2) -2.3 to 0.0% (mean, -0.8 to -0.6%), 3) 0.0 to +1.5% (mean, +0.1 to +0.3%), 4) 0.0 to +1.4% (mean, -0.1 to +0.1%).

Evaluation of the effectiveness of the stereotactic body frame in reducing respiratory intrafractional organ motion using the real-time tumor-tracking radiotherapy system.

PURPOSE: To evaluate the effectiveness of the stereotactic body frame (SBF), with or without a diaphragm press or a breathing cycle monitoring device (Abches), in controlling the range of lung tumor motion, by tracking the real-time position of fiducial markers. METHODS AND MATERIALS: The trajectories of gold markers in the lung were tracked with the real-time tumor-tracking radiotherapy system. The SBF was used for patient immobilization and the diaphragm press and Abches were used to actively control breathing and for self-controlled respiration, respectively. Tracking was performed in five setups, with and without immobilization and respiration control. The results were evaluated using the effective range, which was defined as the range that includes 95% of all the recorded marker positions in each setup. RESULTS: The SBF, with or without a diaphragm press or Abches, did not yield effective ranges of marker motion which were significantly different from setups that did not use these materials. The differences in the effective marker ranges in the upper lobes for all the patient setups were less than 1mm. Larger effective ranges were obtained for the markers in the middle or lower lobes. CONCLUSION: The effectiveness of controlling respiratory-induced organ motion by using the SBF+diaphragm press or SBF + Abches patient setups were highly dependent on the individual patient reaction to the use of these materials and the location of the markers. They may be considered for lung tumors in the lower lobes, but are not necessary for tumors in the upper lobes.

[Gated Radiotherapy]

Recent external radiotherapy requires precise localization of the target because advance in diagnostic imaging has made it possible to visualize a tiny tumor which would be curable with focused high dose irradiation. However, tumors in respiratory and bowel organs have been difficult to be given the high dose because of 1 to 3 cm movement during delivery of irradiation. Respiratory-gating techniques have been used with medical linear accelerators and particle therapy machines. Real-time tumor-tracking radiotherapy has been realized using fluoroscopic x-rays, internal gold-markers, and pattern recognition technology. Advantage and disadvantage of each gating technique have been realized. Active breath control method would be a cost-effective way of precise treatment without gating. More work is required to find the relationship between abdominal wall and internal movement of the tumor in many respiratory-gating radiotherapy and between the internal markers and target volume in real-time tracking radiotherapy.

Reduction in acute morbidity using hypofractionated intensity-modulated radiation therapy assisted with a fluoroscopic real-time tumor-tracking system for prostate cancer: preliminary results of a phase I/II study.

PURPOSE: The positioning of the prostate is improved with the use of the fluoroscopic real-time tumor-tracking radiation therapy system for prostate cancer. The acute radiation reaction and preliminary tumor response of prostate cancer to hypofractionated intensity-modulated radiation therapy assisted with real-time tumor-tracking radiation therapy were investigated in this study. METHODS: Patients were classified into prognostic risk groups on the basis of the presence of the pretreatment prostate-specific antigen, clinical stage, and histologic differentiation. Neoadjuvant hormonal therapy was administered to patients in the high-risk group for 6 months before radiation therapy commenced. The intensity-modulated radiation therapy employed a segmental multileaf collimator, which generated a field made up of two or more shaped subfields using forward planning. Real-time tumor-tracking radiation therapy was used for the precise positioning of the prostate to minimize geometric uncertainties, while the dose was escalated in increments of 5 Gy from 65 Gy using a daily dose of 2.5 Gy (65 Gy/2.5 Gy), following the dose-escalation rules. Acute and late gastrointestinal and genitourinary morbidities due to radiation therapy were scored according to the toxicity criteria of Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer. RESULTS: Thirty-one patients were enrolled in this study between 1998 and 2001. Eighteen patients were classified as being members of the high-risk group. Total dose was escalated, with 65 Gy/2.5 Gy being administered to 12 patients and 70 Gy/2.5 Gy to 19 patients. The median follow-up period was 37 months (range, 30-43 months), and 19 months (range, 10-27 months), for the 65-Gy and 70-Gy arms, respectively. Patients experienced no acute toxicity and grade 1 late gastrointestinal toxicity (8.3%) in the 65-Gy/2.5-Gy arm. Patients in the 70-Gy/2.5-Gy arm experienced grade 1 acute gastrointestinal toxicity (5.3%) and grade 1 and 2 acute genitourinarytoxicities (15.8%). No patients experienced dose-limiting toxicity (defined as a grade 3 or higher acute toxicity) or a grade 2 or higher late complication in this study period. One and two prostate-specific antigen relapses were observed in the 65-Gy and 70-Gy arms, respectively. CONCLUSION: Up to 70 Gy/2.5 Gy, equivalent to 80 Gy with a daily dose of 2.0 Gy, assuming alpha/beta ratio of 1.5, intensity-modulated radiation therapy assisted with real-time tumor-tracking radiation therapy was administered safely with a reasonable biochemical control rate. A further dose-escalation study using this system is justifiable.