Hajime Monzen

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.

Arsenic trioxide induces selective tumour vascular damage via oxidative stress and increases thermosensitivity of tumours

It has previously been found that the anti-leukaemia agent Arsenic Trioxide (ATO) causes vascular shutdown in solid tumours and markedly sensitizes tumours to hyperthermia. The present study was designed to evaluate the mechanism of action and dose-dependence of ATO-induced thermosensitization in FSaII and SCK murine tumours. The role of oxidative stress was studied by observing ATO-induced vascular shutdown in vivo and ATO-induced endothelial cell adhesion molecule expression in vitro in the presence or absence of an antioxidant. It was found that a dose as low as 2 mg/kg ATO impaired vascular function, as estimated by 86Rb uptake, in the tumour. The degree of tumour growth delay induced by 1 h of hyperthermia at 42.5°C, applied 2 h after ATO injection, was proportional to the dose of ATO administered. In addition, it was found that ATO can directly thermosensitize tumour cells in vitro. The development of massive tissue necrosis in the tumour was observed in the days after treatment, especially with the combination of ATO and heating. ATO-induced adhesion molecule expression in vitro was abolished when the anti-oxidant n-acetyl-cysteine (NAC) was introduced prior to exposure, while the addition of NAC in vivo partially blocked ATO-induced vascular shutdown. These results suggest that the expression of adhesion molecules by the vasculature due to oxidative stress contribute to the ATO-induced selective tumour vascular effects observed and that the clinical use of ATO to increase tumour thermosensitivity via direct cellular and vascular effects appears feasible.

Predictive uncertainty in infrared marker-based dynamic tumor tracking with Vero4DRT

PURPOSE To quantify the predictive uncertainty in infrared (IR)-marker-based dynamic tumor tracking irradiation (IR Tracking) with Vero4DRT (MHI-TM2000) for lung cancer using logfiles. METHODS A total of 110 logfiles for 10 patients with lung cancer who underwent IR Tracking were analyzed. Before beam delivery, external IR markers and implanted gold markers were monitored for 40 s with the IR camera every 16.7 ms and with an orthogonal kV x-ray imaging subsystem every 80 or 160 ms. A predictive model [four-dimensional (4D) model] was then created to correlate the positions of the IR markers (PIR) with the three-dimensional (3D) positions of the tumor indicated by the implanted gold markers (Pdetect). The sequence of these processes was defined as 4D modeling. During beam delivery, the 4D model predicted the future 3D target positions (Ppredict) from the PIR in real-time, and the gimbaled x-ray head then tracked the target continuously. In clinical practice, the authors updated the 4D model at least once during each treatment session to improve its predictive accuracy. This study evaluated the predictive errors in 4D modeling (E4DM) and those resulting from the baseline drift of PIR and Pdetect during a treatment session (EBD). E4DM was defined as the difference between Ppredict and Pdetect in 4D modeling, and EBD was defined as the mean difference between Ppredict calculated from PIR in updated 4D modeling using (a) a 4D model created from training data before the model update and (b) an updated 4D model created from new training data. RESULTS The mean E4DM was 0.0 mm with the exception of one logfile. Standard deviations of E4DM ranged from 0.1 to 1.0, 0.1 to 1.6, and 0.2 to 1.3 mm in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions, respectively. The median elapsed time before updating the 4D model was 13 (range, 2-33) min, and the median frequency of 4D modeling was twice (range, 2-3 times) per treatment session. EBD ranged from -1.0 to 1.0, -2.1 to 3.3, and -2.0 to 3.5 mm in the LR, AP, and SI directions, respectively. EBD was highly correlated with BDdetect in the LR (R = -0.83) and AP directions (R = -0.88), but not in the SI direction (R = -0.40). Meanwhile, EBD was highly correlated with BDIR in the SI direction (R = -0.67), but not in the LR (R = 0.15) or AP (R = -0.11) direction. If the 4D model was not updated in the presence of intrafractional baseline drift, the predicted target position deviated from the detected target position systematically. CONCLUSIONS Application of IR Tracking substantially reduced the geometric error caused by respiratory motion; however, an intrafractional error due to baseline drift of >3 mm was occasionally observed. To compensate for EBD, the authors recommend checking the target and IR marker positions constantly and updating the 4D model several times during a treatment session.

Dosimetric comparison of Acuros XB, AAA, and XVMC in stereotactic body radiotherapy for lung cancer

PURPOSE To compare the dosimetric performance of Acuros XB (AXB), anisotropic analytical algorithm (AAA), and x-ray voxel Monte Carlo (XVMC) in heterogeneous phantoms and lung stereotactic body radiotherapy (SBRT) plans. METHODS Water- and lung-equivalent phantoms were combined to evaluate the percentage depth dose and dose profile. The radiation treatment machine Novalis (BrainLab AG, Feldkirchen, Germany) with an x-ray beam energy of 6 MV was used to calculate the doses in the composite phantom at a source-to-surface distance of 100 cm with a gantry angle of 0°. Subsequently, the clinical lung SBRT plans for the 26 consecutive patients were transferred from the iPlan (ver. 4.1; BrainLab AG) to the Eclipse treatment planning systems (ver. 11.0.3; Varian Medical Systems, Palo Alto, CA). The doses were then recalculated with AXB and AAA while maintaining the XVMC-calculated monitor units and beam arrangement. Then the dose-volumetric data obtained using the three different radiation dose calculation algorithms were compared. RESULTS The results from AXB and XVMC agreed with measurements within ± 3.0% for the lung-equivalent phantom with a 6 × 6 cm(2) field size, whereas AAA values were higher than measurements in the heterogeneous zone and near the boundary, with the greatest difference being 4.1%. AXB and XVMC agreed well with measurements in terms of the profile shape at the boundary of the heterogeneous zone. For the lung SBRT plans, AXB yielded lower values than XVMC in terms of the maximum doses of ITV and PTV; however, the differences were within ± 3.0%. In addition to the dose-volumetric data, the dose distribution analysis showed that AXB yielded dose distribution calculations that were closer to those with XVMC than did AAA. Means ± standard deviation of the computation time was 221.6 ± 53.1 s (range, 124-358 s), 66.1 ± 16.0 s (range, 42-94 s), and 6.7 ± 1.1 s (range, 5-9 s) for XVMC, AXB, and AAA, respectively. CONCLUSIONS In the phantom evaluations, AXB and XVMC agreed better with measurements than did AAA. Calculations differed in the density-changing zones (substance boundaries) between AXB/XVMC and AAA. In the lung SBRT cases, a comparative analysis of dose-volumetric data and dose distributions with XVMC demonstrated that the AXB provided better agreement with XVMC than AAA. The computation time of AXB was faster than that of XVMC; therefore, AXB has better balance in terms of the dosimetric performance and computation speed for clinical use than XVMC.

Reduction of infracardiac intestinal activity by a small amount of soda water in technetium-99m tetrofosmin myocardial perfusion scintigraphy with adenosine stress

BackgroundIn technetium (Tc)-99m myocardial perfusion imaging (MPI), intestinal activity often interferes with the assessment of myocardial perfusion of the inferior wall. We examined whether a small amount of soda water prevents intestinal activity and improves image quality of the inferior wall in Tc-99m tetrofosmin MPI.Methods and ResultsNinety-five patients referred for 1-day rest/stress Tc-99m tetrofosmin MPI were assigned to one of two groups automatically, according to the data when they underwent MPI: the soda water group (n=63) ingested 100 mL soda water just before image acquisition after adenosine stress, and the control group (n=32) underwent no intervention. The frequency of intestinal activity was assessed visually on planar images. The inferior myocardial wall and the abdominal activity adjacent to the myocardium were assessed quantitatively on three different planar images during stress, and the mean inferior wall-to-abdomen (1/A) count ratio was calculated. The frequency of intestinal activity was 69.8% in the soda water group, and 90.6% in the control group (P=.038). The I/A count ratio was significantly higher in the soda water group than in the control group (1.98±0.51 vs 1.50±0.35, respectively, P<.0001, ±SD).ConclusionsThe intake of 100 mL of soda water improves intestinal activity and improves the image quality of the inferior wall.

Antiangiogenesis therapy using a novel angiogenesis inhibitor, anginex, following radiation causes tumor growth delay

BackgroundThe present study investigated whether treatment with anginex, a novel antiangiogenic peptide, could block re-vascularization after radiation treatment.MethodsA squamous cell (SCCVII) xenograft tumor mouse model was employed to assess the effects of anginex given post-radiation on tumor growth, microvessel density (MVD), and oxygen levels. The oxygen status was determined by the partial pressure of O2.ResultsTumors in untreated mice increased threefold in 7.0 days, anginex-treated tumors (10 mg/kg intraperitoneal, twice) required 7.3 ± 0.9 days, and tumors exposed to 8-Gy radiation increased threefold over 11 days. Combination treatment of anginex and radiation caused the tumors to grow threefold in 16.1 ± 1.6 days, a delay which was significant and deemed supra-additive. Oxygen levels in tumors treated by stand-alone or combination therapies were significantly reduced; for example from 19.5 ± 4.9 mmHg in controls to 9.7 ± 1.9 mmHg in combination-treated, size-matched tumors. In addition, immunohistochemistry showed a decrease in MVD in the tumors treated with anginex, radiation, or the combination. These results suggest that a combination of anginex and radiation can greatly affect the amount of functional vasculature in tumors and prolong radiation-induced tumor regression.ConclusionAntiangiogenesis therapy with anginex, in addition to radiotherapy, will be useful by blocking angiogenesis-dependent regrowth of vessels.

Exploring a technique for reducing the influence of scattered rays from surrounding organs to the heart during myocardial perfusion scintigraphy with technetium-99m sestamibi and technetium-99m tetrofosmin

We have devised a new position (Monzen position) which can suppress the influence of scattered rays from surrounding organs (liver, etc.) when conducting myocardial imaging. Unlike the conventional techniques, which require a waiting period of 30-60 minutes before imaging can be started after the infusion of technetium-99m sestamibi or technetium-99m tetrofosmin, this position allows single-photon emission tomography to be started about 5-10 minutes after the infusion of the tracer. Therefore, with this technique the total time required for imaging is reduced and consequently the physical and mental burden of the patient is also reduced. Furthermore, the number of patients who can receive this test at any facility can be increased. This position may also be applicable in myocardial scintigraphy using some other tracers.

Commissioning and quality assurance of Dynamic WaveArc irradiation.

A novel three‐dimensional unicursal irradiation technique “Dynamic WaveArc” (DWA), which employs simultaneous and continuous gantry and O‐ring rotation during dose delivery, has been implemented in Vero4DRT. The purposes of this study were to develop a commissioning and quality assurance procedure for DWA irradiation, and to assess the accuracy of the mechanical motion and dosimetric control of Vero4DRT. To determine the mechanical accuracy and the dose accuracy with DWA irradiation, 21 verification test patterns with various gantry and ring rotational directions and speeds were generated. These patterns were irradiated while recording the irradiation log data. The differences in gantry position, ring position, and accumulated MU (EG,ER, and EMU, respectively) between the planned and actual values in the log at each time point were evaluated. Furthermore, the doses delivered were measured using an ionization chamber and spherical phantom. The constancy of radiation output during DWA irradiation was examined by comparison with static beam irradiation. The mean absolute error (MAE) of EG and ER were within 0.1° and the maximum error was within 0.2°. The MAE of EMU was within 0.7 MU, and maximum error was 2.7 MU. Errors of accumulated MU were observed only around control points, changing gantry, and ring velocity. The gantry rotational range, in which EMU was greater than or equal to 2.0 MU, was not greater than 3.2%. It was confirmed that the extent of the large differences in accumulated MU was negligibly small during the entire irradiation range. The variation of relative output value for DWA irradiation was within 0.2%, and this was equivalent to conventional arc irradiation with a rotating gantry. In conclusion, a verification procedure for DWA irradiation was designed and implemented. The results demonstrated that Vero4DRT has adequate mechanical accuracy and beam output constancy during gantry and ring rotation. PACS number: 87

Geometric and dosimetric accuracy of dynamic tumor-tracking conformal arc irradiation with a gimbaled x-ray head.

PURPOSE The Vero4DRT system has the capability for dynamic tumor-tracking (DTT) stereotactic irradiation using a unique gimbaled x-ray head. The purposes of this study were to develop DTT conformal arc irradiation and to estimate its geometric and dosimetric accuracy. METHODS The gimbaled x-ray head, supported on an O-ring gantry, was moved in the pan and tilt directions during O-ring gantry rotation. To evaluate the mechanical accuracy, the gimbaled x-ray head was moved during the gantry rotating according to input command signals without a target tracking, and a machine log analysis was performed. The difference between a command and a measured position was calculated as mechanical error. To evaluate beam-positioning accuracy, a moving phantom, which had a steel ball fixed at the center, was driven based on a sinusoidal wave (amplitude [A]: 20 mm, time period [T]: 4 s), a patient breathing motion with a regular pattern (A: 16 mm, average T: 4.5 s), and an irregular pattern (A: 7.2-23.0 mm, T: 2.3-10.0 s), and irradiated with DTT during gantry rotation. The beam-positioning error was evaluated as the difference between the centroid position of the irradiated field and the steel ball on images from an electronic portal imaging device. For dosimetric accuracy, dose distributions in static and moving targets were evaluated with DTT conformal arc irradiation. RESULTS The root mean squares (RMSs) of the mechanical error were up to 0.11 mm for pan motion and up to 0.14 mm for tilt motion. The RMSs of the beam-positioning error were within 0.23 mm for each pattern. The dose distribution in a moving phantom with tracking arc irradiation was in good agreement with that in static conditions. CONCLUSIONS The gimbal positional accuracy was not degraded by gantry motion. As in the case of a fixed port, the Vero4DRT system showed adequate accuracy of DTT conformal arc irradiation.

Dosimetric comparison of RapidPlan and manually optimized plans in volumetric modulated arc therapy for prostate cancer

PURPOSE This study evaluated whether RapidPlan based plans (RP plans) created by a single optimization, are usable in volumetric modulated arc therapy (VMAT) for patients with prostate cancer. METHODS We used 51 previously administered VMAT plans to train a RP model. Thirty RP plans were created by a single optimization without planner intervention during optimization. Differences between RP plans and clinical manual optimization (CMO) plans created by an experienced planner for the same patients were analyzed (Wilcoxon tests) in terms of homogeneity index (HI), conformation number (CN), D95%, and D2% to planning target volume (PTV), mean dose, V50Gy, V70Gy, V75Gy, and V78Gy to rectum and bladder, monitor unit (MU), and multi-leaf collimator (MLC) sequence complexity. RESULTS RP and CMO values for PTV D95%, PTV D2%, HI, and CN were significantly similar (p<0.05 for all). RP mean dose, V50Gy, and V70Gy to rectum were superior or comparable to CMO values; RP V75Gy and V78Gy were higher than in CMO plans (p<0.05). RP bladder dose-volume parameter values (except V78Gy) were lower than in CMO plans (p<0.05). MU values were RP: 730±55MU and CMO: 580±37MU (p<0.05); and MLC sequence complexity scores were RP: 0.25±0.02 and CMO: 0.35±0.03 (p<0.05). CONCLUSIONS RP plans created by a single optimization were clinically acceptable in VMAT for patient with prostate cancer. Our simple model could reduce optimization time, independently of planners skill and knowledge.