A seed specific dose kernel method for low-energy brachytherapy dosimetry.

We describe a method for independently verifying the dose distributions from pre- and post-implant brachytherapy source distributions. Monte Carlo calculations have been performed to characterize the three-dimensional dose distribution in water phantom from a low-energy brachytherapy source. The calculations are performed in a voxelized, Cartesian coordinate geometry and normalized based upon a separate Monte Carlo calculation for the seed specific air-kerma strength to produce an absolute dose grid with units of cGy hr(-1) x U(-1). The seed-specific, three-dimensional dose grid is stored as a text file for processing using a separate visual basic program. This program requires the coordinate positions of each seed in the pre- or post-plan and sums the kernel file for a three-dimensional composite dose distribution. A kernel matrix size of 81x81x81 with a voxel size of 1.0x1.0x1.0 mm3 was chosen as a compromise between calculation time, kernel size, and truncation of the stored dose distribution as a function of radial distance from the midpoint of the seed. Good agreement is achieved for a representative pre- and post-plan comparison versus a commercial implementation of the TG-43 brachytherapy dosimetry protocol

Time-course of effects of external beam radiation on [18F]FDG uptake in healthy tissue and bone marrow.

The utility of PET for monitoring responses to radiation therapy have been complicated by metabolically active processes in surrounding normal tissues. We examined the time-course of [18F]FDG uptake in normal tissues using small animal-dedicated PET during the 2 month period following external beam radiation. Four mice received 12 Gy of external beam radiation, in a single fraction to the left half of the body. Small animal [18F]FDG-PET scans were acquired for each mouse at 0 (pre-radiation), 1, 2, 3, 4, 5, 8, 12, 19, 24, and 38 days following irradiation. [18F]FDG activity in various tissues was compared between irradiated and non-irradiated body halves before, and at each time point after irradiation. Radiation had a significant impact on [18F]FDG uptake in previously healthy tissues, and time-course of effects differed in different types of tissues. For example, liver tissue demonstrated increased uptake, particularly over days 3-12, with the mean left to right uptake ratio increasing 52% over mean baseline values (p < 0.0001). In contrast, femoral bone marrow uptake demonstrated decreased uptake, particularly over days 2-8, with the mean left to right uptake ratio decreasing 26% below mean baseline values (p = 0.0005). Significant effects were also seen in lung and brain tissue. Radiation had diverse effects on [18F]FDG uptake in previously healthy tissues. These kinds of data may help lay groundwork for a systematically acquired database of the time-course of effects of radiation on healthy tissues, useful for animal models of cancer therapy imminently, as well as interspecies extrapolations pertinent to clinical application eventually

Safety and efficacy of stereotactic body radiation therapy in the treatment of pulmonary metastases from high grade sarcoma.

Introduction. Patients with high-grade sarcoma (HGS) frequently develop metastatic disease thus limiting their long-term survival. Lung metastases (LM) have historically been treated with surgical resection (metastasectomy). A potential alternative for controlling LM could be stereotactic body radiation therapy (SBRT). We evaluated the outcomes from our institutional experience utilizing SBRT. Methods. Sixteen consecutive patients with LM from HGS were treated with SBRT between 2009 and 2011. Routine radiographic and clinical follow-up was performed. Local failure was defined as CT progression on 2 consecutive scans or growth after initial shrinkage. Radiation pneumonitis and radiation esophagitis were scored using Common Toxicity Criteria (CTC) version 3.0. Results. All 16 patients received chemotherapy, and a subset (38%) also underwent prior pulmonary metastasectomy. Median patient age was 56 (12-85), and median follow-up time was 20 months (range 3-43). A total of 25 lesions were treated and evaluable for this analysis. Most common histologies were leiomyosarcoma (28%), synovial sarcoma (20%), and osteosarcoma (16%). Median SBRT prescription dose was 54 Gy (36-54) in 3-4 fractions. At 43 months, local control was 94%. No patient experienced G2-4 radiation pneumonitis, and no patient experienced radiation esophagitis. Conclusions. Our retrospective experience suggests that SBRT for LM from HGS provides excellent local control and minimal toxicity

Online Adaptive Radiation Therapy: Implementation of a New Process of Care.

Onboard magnetic resonance imaging (MRI) guided radiotherapy is now clinically available in nine centers in the world. This technology has facilitated the clinical implementation of online adaptive radiotherapy (OART), or the ability to alter the daily treatment plan based on tumor and anatomical changes in real-time while the patient is on the treatment table. However, due to the time sensitive nature of OART, implementation in a large and busy clinic has many potential obstacles as well as patient-related safety considerations. In this work, we have described the implementation of this new process of care in the Department of Radiation Oncology at the University of California, Los Angeles (UCLA). We describe the rationale, the initial challenges such as treatment time considerations, technical issues during the process of re-contouring, re-optimization, quality assurance, as well as our current solutions to overcome these challenges. In addition, we describe the implementation of a coverage system with a physician of the day as well as online planners (physicists or dosimetrists) to oversee each OART treatment with patient-specific 'hand-off' directives from the patient's treating physician. The purpose of this effort is to streamline the process without compromising treatment quality and patient safety. As more MRI-guided radiotherapy programs come online, we hope that our experience can facilitate successful adoption of OART in a way that maximally benefits the patient

Safety and Efficacy of Stereotactic Body Radiation Therapy in the Treatment of Pulmonary Metastases from High Grade Sarcoma

Introduction. Patients with high-grade sarcoma (HGS) frequently develop metastatic disease thus limiting their long-term survival. Lung metastases (LM) have historically been treated with surgical resection (metastasectomy). A potential alternative for controlling LM could be stereotactic body radiation therapy (SBRT). We evaluated the outcomes from our institutional experience utilizing SBRT. Methods. Sixteen consecutive patients with LM from HGS were treated with SBRT between 2009 and 2011. Routine radiographic and clinical follow-up was performed. Local failure was defined as CT progression on 2 consecutive scans or growth after initial shrinkage. Radiation pneumonitis and radiation esophagitis were scored using Common Toxicity Criteria (CTC) version 3.0. Results. All 16 patients received chemotherapy, and a subset (38%) also underwent prior pulmonary metastasectomy. Median patient age was 56 (12–85), and median follow-up time was 20 months (range 3–43). A total of 25 lesions were treated and evaluable for this analysis. Most common histologies were leiomyosarcoma (28%), synovial sarcoma (20%), and osteosarcoma (16%). Median SBRT prescription dose was 54 Gy (36–54) in 3-4 fractions. At 43 months, local control was 94%. No patient experienced G2-4 radiation pneumonitis, and no patient experienced radiation esophagitis. Conclusions. Our retrospective experience suggests that SBRT for LM from HGS provides excellent local control and minimal toxicity

Irradiation of the potential cancer stem cell niches in the adult brain improves progression-free survival of patients with malignant glioma

<p>Abstract</p> <p>Background</p> <p>Glioblastoma is the most common brain tumor in adults. The mechanisms leading to glioblastoma are not well understood but animal studies support that inactivation of tumor suppressor genes in neural stem cells (NSC) is required and sufficient to induce glial cancers. This suggests that the NSC niches in the brain may harbor cancer stem cells (CSCs), Thus providing novel therapy targets. We hypothesize that higher radiation doses to these NSC niches improve patient survival by eradicating CSCs.</p> <p>Methods</p> <p>55 adult patients with Grade 3 or Grade 4 glial cancer treated with radiotherapy at UCLA between February of 2003 and May of 2009 were included in this retrospective study. Using radiation planning software and patient radiological records, the SVZ and SGL were reconstructed for each of these patients and dosimetry data for these structures was calculated.</p> <p>Results</p> <p>Using Kaplan-Meier analysis we show that patients whose bilateral subventricular zone (SVZ) received greater than the median SVZ dose (= 43 Gy) had a significant improvement in progression-free survival if compared to patients who received less than the median dose (15.0 vs 7.2 months PFS; P = 0.028). Furthermore, a mean dose >43 Gy to the bilateral SVZ yielded a hazard ratio of 0.73 (P = 0.019). Importantly, similarly analyzing total prescription dose failed to illustrate a statistically significant impact.</p> <p>Conclusions</p> <p>Our study leads us to hypothesize that in glioma targeted radiotherapy of the stem cell niches in the adult brain could yield significant benefits over radiotherapy of the primary tumor mass alone and that damage caused by smaller fractions of radiation maybe less efficiently detected by the DNA repair mechanisms in CSCs.</p

Patient specific quality assurance for the delivery of intensity modulated radiotherapy.

A patient specific quality assurance program has been developed to facilitate the clinical implementation of intensity modulated radiotherapy (IMRT) delivered using a micro-multileaf collimator. The methodology includes several dosimetric tasks that are performed prior to the treatment of each patient. Film dosimetry is performed for each individual field and for the multifield composite plan. Individual field measurements are performed at a depth of 5 cm in a water equivalent slab phantom; export of dose calculations from the treatment planning system is similarly specified. For the composite distribution, parameters from the patient plan are applied to an IMRT phantom, and film is exposed in an axial orientation. Distributions are compared with the aid of software developed for the specific tasks. The measured and calculated dose distributions can be superimposed and positioned graphically using move, rotate, and mirror tools, as well as by specifying isocenter coordinates and using fiducial marks. Horizontal and vertical profiles are available for analysis. Dose difference, distance-to-agreement, and gamma index, the minimum scaled multidimensional distance between a measurement and a calculation point determined in combined dose and physical distance space, are calculated along a specified isodose line and displayed. gamma provides an excellent measure of disagreement between measurement and calculation for complex intensity distributions. We specify 3% dose difference and 3 mm distance as our scaling acceptability criteria. Absolute dosimetry for each composite plan is performed using an ionization chamber. To date, excellent agreement between measurements and calculations has been observed