Masataka Oita

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.

Development of MRI phantom equivalent to human tissues for 3.0‐T MRI

PURPOSE A 3.0-T MRI phantom (called the CAGN-3.0T phantom) having human-equivalent relaxation times and human-equivalent conductivity was developed. METHODS The ingredients of the phantom are carrageenan (as a gelatinizer), agarose (as a T2-relaxation modifier), GdCl3 (as a T1-relaxation modifier), NaCl (as a conductivity modifier), and NaN3 (as an antiseptic). Numerous samples with varying concentrations of agarose, GdCl3, and NaCl were prepared, and T1 and T2 values were measured using 3.0-T MRI. RESULTS The T1 values of the CAGN-3.0T phantom were unaffected by NaCl, while the T2 values were only slightly affected. Based on the measured data, empirical formulae were devised to express the relationships between the concentrations of agarose, GdCl3, and NaCl and the relaxation times. The formula for expressing the conductivity of the CAGN-3.0T phantom was obtained. CONCLUSIONS By adjustments to the concentrations of agarose, GdCl3, and NaCl, the relaxation times and conductivity of almost all types of human tissues can be simulated by CAGN-3.0T phantoms. The phantoms have T1 values of 395-2601 ms, T2 values of 29-334 ms, and conductivity of 0.27-1.26 S/m when concentrations of agarose, GdCl3, and NaCl are varied from 0 to 2.0 w/w%, 0 to 180 μmol/kg, and 0 to 0.7 w/w%, respectively. The CAGN-3.0T phantom has sufficient strength to replicate the torso without using reinforcing agents, and can be cut with a knife into any shape.

Characterization of stochastic noise and post-irradiation density growth for reflective-type radiochromic film in therapeutic photon beam dosimetry.

The aim of this study is to investigate the dosimetric uncertainty of stochastic noise and the post-irradiation density growth for reflective-type radiochromic film to obtain the appropriate dose from the exactly controlled film density. Film pieces were irradiated with 6-MV photon beams ranging from 0 to 400cGy. The pixel values (PVs) of these films were obtained using a flatbed scanner at elapsed times of 1min to 120h between the end of irradiation and the film scan. The means and standard deviations (SDs) of the PVs were calculated. The SDs of the converted dose scale, usd, and the dose increases resulting from the PV increases per ±29min at each elapsed time, utime, were computed. The combined dose uncertainties from these two factors, uc, were then calculated. A sharp increase in the PV occurred within the first 3h after irradiation, and a slight increase continued from 3h to 120h. usd was independent of post-irradiation elapsed time. Sharp decreases in utime were obtained within 1h after irradiation, and slight decreases in utime were observed from 1 to 24h after irradiation. uc first decreased 1h after irradiation and remained constant afterward. Assuming that the post-irradiation elapsed times of all of the related measurements are synchronized within ±29min, the elapsed time should be at least 1h in our system. It is important to optimize the scanning protocol for each institution with consideration of the required measurement uncertainty and acceptable latency time.

Influence of multi-leaf collimator leaf transmission on head and neck intensity-modulated radiation therapy and volumetric-modulated arc therapy planning

The aim of this study was to quantify the effect of multi-leaf collimators (MLCs) with different leaf widths on the planning of intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT). Toward this objective, dose transmission through a high-definition 120-leaf MLC (HD120MLC) and 120-leaf Millennium MLC (M120MLC) was investigated, using it with a test case and clinical case studies. In test case, studies with IMRT and VMAT plans, the difference in MLC leaf width had a limited effect on planning target volumes (PTVs). Organs at risk (OARs) were more affected by a reduction in dose transmission through the MLC than by a reduction in MLC leaf width. The results of the test case studies and clinical case studies were mostly similar. In the latter, the different MLCs had no effect on the PTV regardless of the treatment method; however, the HD120MLC plans achieved dose reductions to OARs similar to or larger than the dose reduction of the M120MLC plans. The similar results of the test case and clinical case studies showed that despite a limitation of the irradiation field size, the HD120MLC plans were superior.

SU-F-T-332: Dose Impact of Rectal Gas On Prostate VMAT

PURPOSE The aim of this study to evaluate influence of rectal gas on dose distribution during prostate VMAT. METHODS Our subjects were 10 patients who have received VMAT for prostate cancer at our hospital. In this study, we made four types of VMAT plan. The angles of rotation were as follows: clockwise from 181-179° and 179-181° (Full arc), clockwise from 200-160° and counter-clockwise from 160-200° (Partial arc1), clockwise from 220- 140° and counter-clockwise from 140-220° (Partial arc2), clockwise from 240-120° and counter-clockwise from 120-240° (Partial arc3). The rectal contour used for the reference treatment plan each had 5% or less rectal gas. In order to evaluate the effects of the rectal gas on the dose distribution, we created a rectal contour for assessment separate from the contour used for the reference treatment plans. In the contour for evaluation, the Hounsfield unit (HU) value of the gas was assigned for the total volume of the rectal contour. A HU value of -950 was adopted for simulating the rectal gas. The 3DVH version 2.2 was used for evaluation, and evaluation was performed based on the concordance rate between the contour being evaluated and that of the reference treatment plans. The dose difference (DD), distance to agreement (DTA), and gamma analysis (GA) were used to obtain the concordance rate. The contours being evaluated were CTV, PTV, rectum and bladder. RESULTS The results of DD, DTA, and GA showed that the rectum, the CTV and rectum had the lowest concordance rates. Irrespective of DD, DTA, or GA, the treatment plan based on full arc had a higher concordance rate. CONCLUSION With respect to the effect of rectal gas on the dose distribution in prostate VMAT, it was shown that full arc might be the least susceptible.

SU-F-T-681: Does the Biophysical Modeling for Immunological Aspects in Radiotherapy Precisely Predict Tumor and Normal Tissue Responses?

PURPOSE Recent advances in immunotherapy make possible to combine with radiotherapy. The aim of this study was to assess the TCP/NTCP model with immunological aspects including stochastic distribution as intercellular uncertainties. METHODS In the clinical treatment planning system (Eclipse ver.11.0, Varian medical systems, US), biological parameters such as α/β, D50, γ, n, m, TD50 including repair parameters (bi-exponential repair) can be set as any given values to calculate the TCP/NTCP. Using a prostate cancer patient data with VMAT commissioned as a 6-MV photon beam of Novalis-Tx (BrainLab, US) in clinical use, the fraction schedule were hypothesized as 70-78Gy/35-39fr, 72-81Gy/40-45fr, 52.5-66Gy/16-22fr, 35-40Gy/5fr of 5-7 fractions in a week. By use of stochastic biological model applying for Gaussian distribution, the effects of the TCP/NTCP variation of repair parameters of the immune system as well as the intercellular uncertainty of tumor and normal tissues have been evaluated. RESULTS As respect to the difference of the α/β, the changes of the TCP/NTCP were increased in hypo-fraction regimens. The difference between the values of n and m affect the variation of the NTCP with the fraction schedules, independently. The elongation of repair half-time (long) increased the TCP/NTCP twice or much higher in the case of hypo-fraction scheme. For tumor, the repopulation parameters such as Tpot and Tstart, which is immunologically working to the tumor, improved TCP. CONCLUSION Compared to default fixed value, which has affected by the probability of cell death and cure, hypo-fractionation schemes seemed to have advantages for the variations of the values of m. The possibility of an increase of the α/β or TD50 and repair parameters in tumor and normal tissue by immunological aspects were highly expected. For more precise prediction, treatment planning systems should be incorporated the complicated biological optimization in clinical practice combined with basic experiments data.

SU‐F‐T‐33: Air‐Kerma Strength and Dose Rate Constant by the Full Monte Carlo Simulations

PURPOSE In general, the air-kerma strength (Sk) has been determined by the energy weighting the photon energy fluence and the corresponding mass-energy absorption coefficient or mass-energy transfer coefficient. Kerma is an acronym for kinetic energy released per unit mass, defined as the sum of the initial kinetic energies of all the charged particles. Monte Carlo (MC) simulations can investigate the kinetic energy of the charged particles after photo interactions and sum the energy. The Sk of 192 Ir source is obtained in the full MC simulation and finally the dose rate constant Λ is determine. METHODS MC simulations were performed using EGS5 with the microSelectron HDR v2 type of 192 Ir source. The air-kerma rate obtained to sum the electron kinetic energy after photoelectric absorption or Compton scattering for transverse-axis distance from 1 to 120 cm with a 10 m diameter air phantom. Absorbed dose in water is simulated with a 30 cm diameter water phantom. The transport cut-off energy is 10 keV and primary photons from the source need two hundred and forty billion in the air-kerma rate and thirty billion in absorbed dose in water. RESULTS Sk is multiplied by the square of the distance in air-kerma rate and determined by fitting a linear function. The result of Sk is (2.7039±0.0085)*10--11 µGy m2 Bq-1 s-1 . Absorbed dose rate in water at 1 cm transverse-axis distance D(r0 , θ0 ) is (3.0114±0.0015)*10-11 cGy Bq-1 s-1 . CONCLUSION From the results, dose rate constant Λ of the microSelectron HDR v2 type of 192 Ir source is (1.1137±0.0035) cGy h-1 U-1 by the full MC simulations. The consensus value conΛ is (1.109±0.012) cGy h-1 U-1 . The result value is consistent with the consensus data conΛ.

SU-E-T-146: Effects of Uncertainties of Radiation Sensitivity of Biological Modelling for Treatment Planning

PURPOSE The aim of this study was to evaluate the distribution of uncertainty of cell survival by radiation, and assesses the usefulness of stochastic biological model applying for gaussian distribution. METHODS For single cell experiments, exponentially growing cells were harvested from the standard cell culture dishes by trypsinization, and suspended in test tubes containing 1 ml of MEM(2×106 cells/ml). The hypoxic cultures were treated with 95% N2 -5% CO2 gas for 30 minutes. In vitro radiosensitization was also measured in EMT6/KU single cells to add radiosensitizer under hypoxic conditions. X-ray irradiation was carried out by using an Xray unit (Hitachi X-ray unit, model MBR-1505R3) with 0.5 mm Al/1.0 mm Cu filter, 150 kV, 4 Gy/min). In vitro assay, cells on the dish were irradiated with 1 Gy to 24 Gy, respectively. After irradiation, colony formation assays were performed. Variations of biological parameters were investigated at standard cell culture(n=16), hypoxic cell culture(n=45) and hypoxic cell culture(n=21) with radiosensitizers, respectively. The data were obtained by separate schedule to take account for the variation of radiation sensitivity of cell cycle. RESULTS At standard cell culture, hypoxic cell culture and hypoxic cell culture with radiosensitizers, median and standard deviation of alpha/beta ratio were 37.1±73.4 Gy, 9.8±23.7 Gy, 20.7±21.9 Gy, respectively. Average and standard deviation of D5 0 were 2.5±2.5 Gy, 6.1±2.2 Gy, 3.6±1.3 Gy, respectively. CONCLUSION In this study, we have challenged to apply these uncertainties of parameters for the biological model. The variation of alpha values, beta values, D5 0 as well as cell culture might have highly affected by probability of cell death. Further research is in progress for precise prediction of the cell death as well as tumor control probability for treatment planning.

SU‐E‐T‐484: Impact of Multileaf Collimator Leaf Positioning Accuracy on Intensity Modulated Radiation Therapy

Purpose: It is reported to have an impact on dose due to uncertainty of MLC drive control in IMRT using MLC. It is reported to have displacement of about 0.5mm in a month as changes over time of MLC drive control accuracy installed in LINAC made by SIEMENS. There is fear that these changes over time contribute to dose distribution when SMLC‐IMRT is practiced. Methods: For LINAC, We used PRIMUS High‐Energy KD2 7467 (Siemens Medical Systems) that generates 10MV‐X rays. MLC installed in this therapy machine is MLC‐20A (Toshiba Medical Systems) with lower collimator replaced by MLC of 29 pairs and adopts double focus that does focusing with two aspects in a structure of MLCs leaf tip and side contacting always parallel to dose angle. We used Kodak Extended Dose Range2 (Carestream health Inc.) for film, D.D.system (R‐TECH Inc.) for film analyzer, flat bed scanner ES‐10000G (EPSON Corp.) for film reader and Xio‐version4.50.00 (ELEKTA) for RTP. We studied the impact of MLC drive control accuracy on dose evaluation (gamma analysis) measuring IMRTdose distribution as well as evaluating MLC drive control accuracy (resting positional accuracy and position reproducibility) once a week for 60 days. Results: MLC positional accuracy tended to expand by 0.1–0.15mm in one week accompanied by changes over time and tended to expand by about 1mm in 60 days. The reproducibility was within 0.2mm for roughly over 95%. For prostate gland IMRT, I did not see a significant difference in pass rate of y analysis if the resting positional accuracy of MLC is about 1 mm. Conclusions: It was suggested that it would be an effective index to continue IMRT safely in the future by practicing regular management upon setting an acceptable value by MLC positional accuracy test. This study was supported, in part, by a grant of the Japanese Society of Radiologocal Technology(JSRT)

SU‐GG‐T‐545: Analysis of Biological Effective Doses for 4D‐SBRT Using a Model Based Simulation

Purpose: Four‐dimensional radiotherapy(4DRT) using respiratory gating system and other techniques to control patient breathing are useful for stereotactic body radiotherapy. However, treatment time in 4DRT also will be elongated by the degree of synchronization. In such a situation, the synchronization, internal margin and the target localization might have effects on the target as to tumorcontrol probability. The purpose of this study was to investigate the relationship of biological effective dose(BED) between respiratory motion patterns, gate parameters and target positioning accuracies using a model based simulation. Method and Materials: A virtual square of dimension 512×512 matrices of interest FOVs were used in this simulation. The pseudo tumor was set on the virtual matrices. The motion of the sphere was modeled by a simple cosine curve, and a sinusoidal breathing curve simulated by mathematical equation. A minimal time interval and various motion parameters such as amplitudes, target volumes, and gate parameters were set in this simulation. Then the probability densities of the target in each parameters ware calculated. Using calculated data sets, BEDs for the target were determined by changing two modeled curves of motion, margins, and gate parameters, respectively. Results: Various patterns such as tumor size, motion function, amplitude, gate parameters and size of margins of BEDs for the target were calculated. The result showed that it depended upon target volume and gate parameter. The approximate equation of optimal internal margins for target volume of 99% BED coverage was also determined. Conclusion: In this study, we have calculated BED based optimal internal margins of the moving target. This study also showed a method of 4DRT taking into account BED. Further research is in progress to evaluate the effect of elongation of patient irradiation and shape of the target by gate parameter settings.