Locoregional control after intensity-modulated radiotherapy for nasopharyngeal carcinoma with an anatomy-based target definition.

OBJECTIVE: The objective of the study was to evaluate locoregional control after intensity-modulated radiotherapy for nasopharyngeal cancer using a target definition along with anatomical boundaries. METHODS: Forty patients with biopsy-proven squamous cell or non-keratinizing carcinoma of the nasopharynx who underwent intensity-modulated radiotherapy between April 2006 and November 2009 were reviewed. There were 10 females and 30 males with a median age of 48 years (range, 17-74 years). More than half of the patients had T3/4 (n = 21) and/or N2/3 (n = 24) disease. Intensity-modulated radiotherapy was administered as 70 Gy/33 fractions with or without concomitant chemotherapy. The clinical target volume was contoured along with muscular fascia or periosteum, and the prescribed radiotherapy dose was determined for each anatomical compartment and lymph node level in the head and neck. RESULTS: One local recurrence was observed at Meckel's cave on the periphery of the high-risk clinical target volume receiving a total dose of <63 Gy. Otherwise, six locoregional failures were observed within irradiated volume receiving 70 Gy. Local and nodal control rates at 3 years were 91 and 89%, respectively. Adverse events were acceptable, and 25 (81%) of 31 patients who were alive without recurrence at 2 years had xerostomia of ≤Grade 1. The overall survival rate at 3 years was 87%. CONCLUSIONS: Target definition along with anatomically defined boundaries was feasible without compromise of the therapeutic ratio. It is worth testing this method further to minimize the unnecessary irradiated volume and to standardize the target definition in intensity-modulated radiotherapy for nasopharyngeal cancer.

Experimental evaluation of a spatial resampling technique to improve the accuracy of pencil-beam dose calculation in proton therapy.

PURPOSE: In proton therapy, pencil-beam algorithms (PBAs) are the most widely used dose calculation methods. However, the PB calculations that employ one-dimensional density scaling neglect the effects of lateral density heterogeneity on the dose distributions, whereas some particles included in such pencil beams could overextend beyond the interface of the density heterogeneity. We have simplified a pencil-beam redefinition algorithm (PBRA), which was proposed for electron therapy, by a spatial resampling technique toward an application for proton therapy. The purpose of this study is to evaluate the calculation results of the spatial resampling technique in terms of lateral density heterogeneity by comparison with the dose distributions that were measured in heterogeneous slab phantoms. METHODS: The pencil beams are characterized for multiple residual-range (i.e., proton energy) bins. To simplify the PBRA, the given pencil beams are resampled on one or two transport planes, in which smaller sub-beams that are parallel to each other are generated. We addressed the problem of lateral density heterogeneity comparing the calculation results to the dose distributions measured at different depths in heterogeneous slab phantoms using a two-dimensional detector. Two heterogeneity slab phantoms, namely, phantoms A and B, were designed for the measurements and calculations. In phantom A, the heterogeneity slab was placed close to the surface. On the other hand, in phantom B, it was placed close to the Bragg peak in the mono-energetic proton beam. RESULTS: In measurements, lateral dose profiles showed a dose reduction and increment in the vicinity of x = 0 mm in both phantoms at depths z = 142 and 161 mm due to lateral particle disequilibrium. In phantom B, these dose reduction∕increment effects were higher∕lower, respectively, than those in phantom A. This is because a longer distance from the surface to the heterogeneous slab increases the strength of proton scattering. Sub-beams, which were generated from the resampling plane, formed a detouring∕overextending path that was different from that of elemental pencil beams. Therefore, when the spatial resampling was implemented at the surface and immediately upstream of the lateral heterogeneity, the calculation could predict these dose reduction∕increment effects. Without the resampling procedure, these dose reduction∕increment effects could not be predicted in both phantoms owing to the blurring of the pencil beam. We found that the PBA with the spatial resampling technique predicted the dose reduction∕increment at the dose profiles in both phantoms when the sampling plane was defined immediately upstream of the heterogeneous slab. CONCLUSIONS: We have demonstrated the implementation of a spatial resampling technique for pencil-beam calculation to address the problem of lateral density heterogeneity. While further validation is required for clinical use, this study suggests that the spatial resampling technique can make a significant contribution to proton therapy.

Apparent absence of a proton beam dose rate effect and possible differences in RBE between Bragg peak and plateau.

PURPOSE: Respiration-gated irradiation for a moving target requires a longer time to deliver single fraction in proton radiotherapy (PRT). Ultrahigh dose rate (UDR) proton beam, which is 10-100 times higher than that is used in current clinical practice, has been investigated to deliver daily dose in single breath hold duration. The purpose of this study is to investigate the survival curve and relative biological effectiveness (RBE) of such an ultrahigh dose rate proton beam and their linear energy transfer (LET) dependence. METHODS: HSG cells were irradiated by a spatially and temporally uniform proton beam at two different dose rates: 8 Gy/min (CDR, clinical dose rate) and 325 Gy/min (UDR, ultrahigh dose rate) at the Bragg peak and 1.75 (CDR) and 114 Gy/min (UDR) at the plateau. To study LET dependence, the cells were positioned at the Bragg peak, where the absorbed dose-averaged LET was 3.19 keV/microm, and at the plateau, where it was 0.56 keV/microm. After the cell exposure and colony assay, the measured data were fitted by the linear quadratic (LQ) model and the survival curves and RBE at 10% survival were compared. RESULTS: No significant difference was observed in the survival curves between the two proton dose rates. The ratio of the RBE for CDR/UDR was 0.98 +/- 0.04 at the Bragg peak and 0.96 +/- 0.06 at the plateau. On the other hand, Bragg peak/plateau RBE ratio was 1.15 +/- 0.05 for UDR and 1.18 +/- 0.07 for CDR. CONCLUSIONS: Present RBE can be consistently used in treatment planning of PRT using ultrahigh dose rate radiation. Because a significant increase in RBE toward the Bragg peak was observed for both UDR and CDR, further evaluation of RBE enhancement toward the Bragg peak and beyond is required.

[Use experience and problems in the optimization of intensity modulated radiation therapy (IMRT)--Focus on head & neck].

We present the main points of the optimization in IMRT. The skin surface of the planned target volume was reduced by a few millimeters, in view of the limitations of a calculation grid in accurately estimating the influence of build-up or contamination of electrons. Air cavities such as nasal or oral cavities were, in general, filled with water equivalent density in the dose calculation. Planned target volume was contracted by 5 mm when PTV of a higher prescribed dose was delineated adjacent to it. The 5 mm width of ring-shaped ROI was set at 5 mm outside of the entire PTV to eliminate hot spots. Physical quality assurance is extremely important to eradicate unexpected dose inhomogeneity, and meticulous efforts are required.

Evaluation of the usefulness of a MOSFET detector in an anthropomorphic phantom for 6-MV photon beam.

In order to evaluate the usefulness of a metal oxide-silicon field-effect transistor (MOSFET) detector as a in vivo dosimeter, we performed in vivo dosimetry using the MOSFET detector with an anthropomorphic phantom. We used the RANDO phantom as an anthropomorphic phantom, and dose measurements were carried out in the abdominal, thoracic, and head and neck regions for simple square field sizes of 10 x 10, 5 x 5, and 3 x 3 cm(2) with a 6-MV photon beam. The dose measured by the MOSFET detector was verified by the dose calculations of the superposition (SP) algorithm in the XiO radiotherapy treatment-planning system. In most cases, the measured doses agreed with the results of the SP algorithm within +/-3%. Our results demonstrated the utility of the MOSFET detector for in vivo dosimetry even in the presence of clinical tissue inhomogeneities.

Improved dose-calculation accuracy in proton treatment planning using a simplified Monte Carlo method verified with three-dimensional measurements in an anthropomorphic phantom.

Treatment planning for proton tumor therapy requires a fast and accurate dose-calculation method. We have implemented a simplified Monte Carlo (SMC) method in the treatment planning system of the National Cancer Center Hospital East for the double-scattering beam delivery scheme. The SMC method takes into account the scattering effect in materials more accurately than the pencil beam algorithm by tracking individual proton paths. We confirmed that the SMC method reproduced measured dose distributions in a heterogeneous slab phantom better than the pencil beam method. When applied to a complex anthropomorphic phantom, the SMC method reproduced the measured dose distribution well, satisfying an accuracy tolerance of 3 mm and 3% in the gamma index analysis. The SMC method required approximately 30 min to complete the calculation over a target volume of 500 cc, much less than the time required for the full Monte Carlo calculation. The SMC method is a candidate for a practical calculation technique with sufficient accuracy for clinical application.

Dosimetric verification in inhomogeneous phantom geometries for the XiO radiotherapy treatment planning system with 6-MV photon beams.

We have developed a practical dose verification method for radiotherapy treatment planning systems by using only a Farmer ionization chamber in inhomogeneous phantoms. In particular, we compared experimental dose verifications of multi-layer phantom geometries and laterally inhomogeneous phantom geometries for homogeneous and inhomogenous dose calculations by using the fast-Fourier-transform convolution, fast-superposition, and superposition in the XiO radiotherapy treatment-planning system. We applied the dose verification method to three kernel-based algorithms in various phantom geometries with water-, lung- and bone-equivalent media of different field sizes. These calculations were then compared with experimental measurements by use of the Farmer ionization chamber. The fast-Fourier-transform convolution algorithm overestimated the dose by about 8% in the lung phantom geometry. The superposition algorithm and the fast-superposition algorithm were both accurate to better than 2% when compared to the measurements even for complex geometries. Our dose verification method was able to clarify the differences and equivalences of the three kernel-based algorithms and measurements with use only of commonly available apparatus. This will be generally useful in commissioning of inhomogeneity-correction algorithms in the clinical practice of treatment planning.

[Improvement of dose monitor system in rotational gantry for proton therapy at national cancer center hospital East].

Quality assurance and quality control of delivered dose are important in proton therapy. The delivered proton dose is controlled using a dose monitor system which consists of two ionization chambers filled with free air. Response of the monitor for the delivered dose changes under the influence of temperature and pressure of surrounding air. In the dose monitor system at the National Cancer Center Hospital East, the monitor is near an X-tray tube which operates at a high temperature and is frequently used in every patient setup. Therefore the response of the dose monitor changes a lot with the temperature of the X-ray tube. In this report, temperature and pressure influence on the dose monitor was investigated in detail. Furthermore, a new method was presented to correct the monitor response using the real-time data of temperature and pressure at any time for each patient. This method improved the accuracy of delivered dose from 1% to 0.5%.

Experimental verification of proton beam monitoring in a human body by use of activity image of positron-emitting nuclei generated by nuclear fragmentation reaction.

Proton therapy is a form of radiotherapy that enables concentration of dose on a tumor by use of a scanned or modulated Bragg peak. Therefore, it is very important to evaluate the proton-irradiated volume accurately. The proton-irradiated volume can be confirmed by detection of pair-annihilation gamma rays from positron-emitting nuclei generated by the nuclear fragmentation reaction of the incident protons on target nuclei using a PET apparatus. The activity of the positron-emitting nuclei generated in a patient was measured with a PET-CT apparatus after proton beam irradiation of the patient. Activity measurement was performed in patients with tumors of the brain, head and neck, liver, lungs, and sacrum. The 3-D PET image obtained on the CT image showed the visual correspondence with the irradiation area of the proton beam. Moreover, it was confirmed that there were differences in the strength of activity from the PET-CT images obtained at each irradiation site. The values of activity obtained from both measurement and calculation based on the reaction cross section were compared, and it was confirmed that the intensity and the distribution of the activity changed with the start time of the PET imaging after proton beam irradiation. The clinical use of this information about the positron-emitting nuclei will be important for promoting proton treatment with higher accuracy in the future.

[Evaluation of therapeutic carbon-beam attenuation in inhomogeneous layered phantoms: Comparison with the present method using a water phantom.].

Carbon-beam therapy has been successfully carried out at HIMAC, Japan. This treatment offers two advantages over conventional radiation therapy: better dose concentration due to the Bragg peak and higher RBE. In treatment planning at HIMAC, the dose distribution is calculated based on dose measurements in water. We previously made three types of phantoms by using CT images: a liver-cancer phantom and two lung-cancer phantoms (one with bone and one without it). This study evaluates carbon-beam attenuation in inhomogeneous layered phantoms and compares their results with beam attenuation in a water phantom. The phantoms consist of plates of tissue-equivalent materials for the x-rays; these plates are stacked along the beam direction. The beam attenuation in the lung-cancer phantom (with bone) is about 23%, similar to the result in the water phantom, attenuation in the lung-cancer phantom (without bone) is about 25%, which is higher than the result in the water phantom by 2%. Finally, the beam attenuation in the liver-cancer phantom is about 33%, which is lower than the result in the water phantom by 3%. Our evaluation of the carbon-beam attenuation using inhomogeneous layered phantoms is successful and comparison with the results in a water phantom is possible.