Dosimetric evaluation of incorporating the revised V4.0 calibration protocol for breast intraoperative radiotherapy with the INTRABEAM system.

In breast-targeted intraoperative radiotherapy (TARGIT) clinical trials (TARGIT-B, TARGIT-E, TARGIT-US), a single fraction of radiation is delivered to the tumor bed during surgery with 1.5- to 5.0-cm diameter spherical applicators and an INTRABEAM x-ray source (XRS). This factory-calibrated XRS is characterized by two depth-dose curves (DDCs) named "TARGIT" and "V4.0." Presently, the TARGIT DDC is used to treat patients enrolled in clinical trials; however, the V4.0 DDC is shown to better represent the delivered dose. Therefore, we reevaluate the delivered prescriptions under the TARGIT protocols using the V4.0 DDC. A 20-Gy dose was prescribed to the surface of the spherical applicator, and the TARGIT DDC was used to calculate the treatment time. For a constant treatment time, the V4.0 DDC was used to recalculate the dosimetry to evaluate differences in dose rate, dose, and equivalent dose in 2-Gy fractions (EQD2) for an α/ß = 3.5 Gy (endpoint of locoregional relapse). At the surface of the tumor bed (i.e., spherical applicator surface), the calculations using the V4.0 DDC predicted increased values for dose rate (43-16%), dose (28.6-23.2 Gy), and EQD2 (95-31%) for the 1.5- to 5.0-cm diameter spherical applicator sizes, respectively. In general, dosimetric differences are greatest for the 1.5-cm diameter spherical applicator. The results from this study can be interpreted as a reevaluation of dosimetry or the dangers of underdosage, which can occur if the V4.0 DDC is inadvertently used for TARGIT clinical trial patients. Because the INTRABEAM system is used in TARGIT clinical trials, accurate knowledge about absorbed dose is essential for making meaningful comparisons between radiation treatment modalities, and reproducible treatment delivery is imperative. The results of this study shed light on these concerns.

Evaluation of the dosimetric impact of manufacturing variations for the INTRABEAM x-ray source.

INTRODUCTION: INTRABEAM x-ray sources (XRSs) have distinct output characteristics due to subtle variations between the ideal and manufactured products. The objective of this study is to intercompare 15 XRSs and to dosimetrically quantify the impact of manufacturing variations on the delivered dose. METHODS AND MATERIALS: The normality of the XRS datasets was evaluated with the Shapiro-Wilk test, the accuracy of the calibrated depth-dose curves (DDCs) was validated with ionization chamber measurements, and the shape of each DDC was evaluated using depth-dose ratios (DDRs). For 20 Gy prescribed to the spherical applicator surface, the dose was computed at 5-mm and 10-mm depths from the spherical applicator surface for all XRSs. RESULTS: At 5-, 10-, 20-, and 30-mm depths from the source, the coefficient of variation (CV) of the XRS output for 40 kVp was 4.4%, 2.8%, 2.0%, and 3.1% and for 50 kVp was 4.2%, 3.8%, 3.8%, and 3.4%, respectively. At a 20-mm depth from the source, the 40-kVp energy had a mean output in Gy/Minute = 0.36, standard deviation (SD) = 0.0072, minimum output = 0.34, and maximum output = 0.37 and a 50-kVp energy had a mean output = 0.56, SD = 0.021, minimum output = 0.52, and maximum output = 0.60. We noted the maximum DRR values of 2.8% and 2.5% for 40 kVp and 50 kVp, respectively. For all XRSs, the maximum dosimetric effect of these variations within a 10-mm depth of the applicator surface is ≤ 2.5%. The CV increased as depth increased and as applicator size decreased. CONCLUSION: The American Association of Physicist in Medicine Task Group-167 requires that the impurities in radionuclides used for brachytherapy produce ≤ 5.0% dosimetric variations. Because of differences in an XRS output and DDC, we have demonstrated the dosimetric variations within a 10-mm depth of the applicator surface to be ≤ 2.5%.

AAPM Task Group Report 267: A joint AAPM GEC-ESTRO report on biophysical models and tools for the planning and evaluation of brachytherapy.

Brachytherapy utilizes a multitude of radioactive sources and treatment techniques that often exhibit widely different spatial and temporal dose delivery patterns. Biophysical models, capable of modeling the key interacting effects of dose delivery patterns with the underlying cellular processes of the irradiated tissues, can be a potentially useful tool for elucidating the radiobiological effects of complex brachytherapy dose delivery patterns and for comparing their relative clinical effectiveness. While the biophysical models have been used largely in research settings by experts, it has also been used increasingly by clinical medical physicists over the last two decades. A good understanding of the potentials and limitations of the biophysical models and their intended use is critically important in the widespread use of these models. To facilitate meaningful and consistent use of biophysical models in brachytherapy, Task Group 267 (TG-267) was formed jointly with the American Association of Physics in Medicine (AAPM) and The Groupe Européen de Curiethérapie and the European Society for Radiotherapy & Oncology (GEC-ESTRO) to review the existing biophysical models, model parameters, and their use in selected brachytherapy modalities and to develop practice guidelines for clinical medical physicists regarding the selection, use, and interpretation of biophysical models. The report provides an overview of the clinical background and the rationale for the development of biophysical models in radiation oncology and, particularly, in brachytherapy; a summary of the results of literature review of the existing biophysical models that have been used in brachytherapy; a focused discussion of the applications of relevant biophysical models for five selected brachytherapy modalities; and the task group recommendations on the use, reporting, and implementation of biophysical models for brachytherapy treatment planning and evaluation. The report concludes with discussions on the challenges and opportunities in using biophysical models for brachytherapy and with an outlook for future developments.

Relationships among micronuclei, nucleoplasmic bridges and nuclear buds within individual cells in the cytokinesis-block micronucleus assay.

Micronuclei have been used extensively in studies as an easily evaluated indicator of DNA damage but little is known about their association with other types of damage such as nucleoplasmic bridges and nuclear buds. Here, radiation-induced clastogenic events were evaluated via the cytokinesis-block micronucleus assay in two normal human lymphoblastoid cell lines exposed to neutrons or γ-radiation. DNA damage induced by the chemical agents mitomycin C and phleomycin was also evaluated in two normal and two mitochondrial mutant human lymphoblastoid cell lines. In addition to micronuclei, nucleoplasmic bridges and nuclear buds were enumerated by recording the coincident presence of these end points within individual cells, and the associations among these three end points were evaluated for all treatment conditions. The common odds ratios for micronuclei and nucleoplasmic bridges were found to be significantly larger than unity, indicating that the presence of one or more micronuclei in a cell imposes a significant risk of having one or more nucleoplasmic bridges in that same cell, and vice versa. The strength of this association did not change significantly with radiation dose or concentration of the chemical clastogens. Common odds ratios for association between micronuclei and buds, and between bridges and buds were also found to be significantly higher than unity. However, associations between micronuclei and buds could not be calculated for some treatments due to heterogeneity in the odds ratios and hence may depend on chemical clastogen concentration or radiation dose. This study provides evidence of how paired analyses among genetic end points in the cytokinesis-block micronucleus assay can provide information concerning abnormalities of cell division and possibly about structural chromosomal rearrangements induced by clastogens.

Proton versus photon radiation therapy: A clinical review.

While proton radiation therapy offers substantially better dose distribution characteristics than photon radiation therapy in certain clinical applications, data demonstrating a quantifiable clinical advantage is still needed for many treatment sites. Unfortunately, the number of patients treated with proton radiation therapy is still comparatively small, in some part due to the lack of evidence of clear benefits over lower-cost photon-based treatments. This review is designed to present the comparative clinical outcomes between proton and photon therapies, and to provide an overview of the current state of knowledge regarding the effectiveness of proton radiation therapy.

Characterization of the Response of 9L and U-251N Orthotopic Brain Tumors to 3D Conformal Radiation Therapy.

In a study employing MRI-guided stereotactic radiotherapy (SRS) in two orthotopic rodent brain tumor models, the radiation dose yielding 50% survival (the TCD50) was sought. Syngeneic 9L cells, or human U-251N cells, were implanted stereotactically in 136 Fischer 344 rats or 98 RNU athymic rats, respectively. At approximately 7 days after implantation for 9L, and 18 days for U-251N, rats were imaged with contrast-enhanced MRI (CE-MRI) and then irradiated using a Small Animal Radiation Research Platform (SARRP) operating at 220 kV and 13 mA with an effective energy of ∼70 keV and dose rate of ∼2.5 Gy per min. Radiation doses were delivered as single fractions. Cone-beam CT images were acquired before irradiation, and tumor volumes were defined using co-registered CE-MRI images. Treatment planning using MuriPlan software defined four non-coplanar arcs with an identical isocenter, subsequently accomplished by the SARRP. Thus, the treatment workflow emulated that of current clinical practice. The study endpoint was animal survival to 200 days. The TCD50 inferred from Kaplan-Meier survival estimation was approximately 25 Gy for 9L tumors and below 20 Gy, but within the 95% confidence interval in U-251N tumors. Cox proportional-hazards modeling did not suggest an effect of sex, with the caveat of wide confidence intervals. Having identified the radiation dose at which approximately half of a group of animals was cured, the biological parameters that accompany radiation response can be examined.