Dosimetry of eye plaques for ocular tumors presents unique challenges in brachytherapy. The challenges in accurate dosimetry are in part related to the steep dose gradient in the tumor and critical structures that are within millimeters of radioactive sources. In most clinical applications, calculations of dose distributions around eye plaques assume a homogenous water medium and full scatter conditions. Recent Monte Carlo (MC)-based eye-plaque dosimetry simulations have demonstrated that the perturbation effects of heterogeneous materials in eye plaques, including the gold-alloy backing and Silastic insert, can be calculated with reasonable accuracy. Even additional levels of complexity introduced through the use of gold foil "seed-guides" and custom-designed plaques can be calculated accurately using modern MC techniques. Simulations accounting for the aforementioned complexities indicate dose discrepancies exceeding a factor of ten to selected critical structures compared to conventional dose calculations. Task Group 129 was formed to review the literature; re-examine the current dosimetry calculation formalism; and make recommendations for eye-plaque dosimetry, including evaluation of brachytherapy source dosimetry parameters and heterogeneity correction factors. A literature review identified modern assessments of dose calculations for Collaborative Ocular Melanoma Study (COMS) design plaques, including MC analyses and an intercomparison of treatment planning systems (TPS) detailing differences between homogeneous and heterogeneous plaque calculations using the American Association of Physicists in Medicine (AAPM) TG-43U1 brachytherapy dosimetry formalism and MC techniques. This review identified that a commonly used prescription dose of 85 Gy at 5 mm depth in homogeneous medium delivers about 75 Gy and 69 Gy at the same 5 mm depth for specific (125)I and (103)Pd sources, respectively, when accounting for COMS plaque heterogeneities. Thus, the adoption of heterogeneous dose calculation methods in clinical practice would result in dose differences >10% and warrant a careful evaluation of the corresponding changes in prescription doses. Doses to normal ocular structures vary with choice of radionuclide, plaque location, and prescription depth, such that further dosimetric evaluations of the adoption of MC-based dosimetry methods are needed. The AAPM and American Brachytherapy Society (ABS) recommend that clinical medical physicists should make concurrent estimates of heterogeneity-corrected delivered dose using the information in this report's tables to prepare for brachytherapy TPS that can account for material heterogeneities and for a transition to heterogeneity-corrected prescriptive goals. It is recommended that brachytherapy TPS vendors include material heterogeneity corrections in their systems and take steps to integrate planned plaque localization and image guidance. In the interim, before the availability of commercial MC-based brachytherapy TPS, it is recommended that clinical medical physicists use...

Recent technological advances enable radiation therapy to be delivered in a highly conformal manner to targets located almost anywhere in the body. This capability has renewed the clinical interest in hypofractionation wherein the tumor is delivered a few fractions of very large dose per fraction. Extrapolating clinical experience from conventional regimens to fractions of high dose is important to designing hypofractionated treatments. The concept of biologically effective dose (BED) based on the linear-quadratic (LQ) formulation e(-(alphaD+betaD2) is a useful tool for intercomparing conventional fractionations but may be hampered if the value of alpha/beta is dose range dependent and/or when extrapolating to fractions of high dose because the LQ curve bends continuously on the log-linear plot. This does not coincide with what is observed experimentally in many clonogenic cell survival studies at high dose wherein radiation dose-response relationships more closely approximate a straight line. Intercomparison of conventional fractionations with hypofractionated regimens may benefit from BED calculations which instead use a dose range independent linear-quadratic-linear (LQ-L) formulation which better fits the experimental data across a wider range of dose. The dosimetric implications of LQ-L are explored using a simple model which requires only the specification of a dose D(T) at which the LQ curve transitions to final linearity and the log(e) cell kill per Gy in the final linear portion of the survival curve at high dose. It is shown that the line tangent to the LQ curve at transition dose D(T) can often be used to approximate the final slope of the dose response curve. When D(T) = 2alpha/ beta Gy, the line tangent to the LQ curve at D(T) intersects the e(-alphaD) and e(-betaD2) curves at dose alpha/ beta Gy and also closely fits the linear response in the high dose region of some classic in vitro cell survival curves for which the value of alpha/beta is low. It is hypothesized that D(T) will increase as the magnitude of alpha/beta increases. Examples are presented illustrating how to recognize LQ-L behavior in multifraction isoeffect studies of late responses such as spinal cord and lung. When planning hypofractionated regimens involving reactions with low alpha/beta, recognizing LQ-L behavior could be important because the dose-response is likely to transition to final linearity within the contemplated range of hypofractional doses.

During a 21-year period, 66 patients with uterine sarcomas were treated at California Medical Center. Histological diagnoses were mixed mesodermal sarcoma in 32 patients (48%), leiomyosarcoma in 24 (36%), and endometrial stromal sarcoma in 10 (15%) patients. The majority of patients (73%) had Stage I tumors. The treatment consisted of surgery alone in 27 (41%), surgery in combination with radiation therapy in 36 (55%), and radiation therapy alone in three (4%) patients. The overall 1-, 2-, and 5-year actuarial survival was 74%, 57%, and 38%, respectively. The 1-, 2-, and 5-year actuarial survival for the 27 surgery alone patients was 73%, 50%, and 25%, which compared with 75%, 61%, and 44% for the 36 surgery plus radiation therapy patients (P = 0.12). The disease-free survival was better for the surgery plus radiation therapy patients, as compared with the surgery alone group (38% vs. 18% at 5 years, P = 0.081). The 5-year survival by histology was 70% for the 10 endometrial stromal sarcoma patients, 40% for the 24 leiomyosarcoma patients, and 23% for the 32 mesodermal sarcoma patients (P = 0.064). As expected, survival depended on the stage of disease (P less than 0.0001). Treatment failure was observed in 35 (53%) patients, which included 9 (14%) with failure in the pelvis. There was no difference in the incidence of failure among patients in the three treatment groups and also in the three histologic groups. There was, however, a significant difference in the incidence of pelvic failure between surgery alone and surgery plus radiation therapy patients. In the 27 surgery alone patients, nine (33%) relapsed in the pelvis, whereas none of the 36 surgery plus radiation therapy patients had locoregional failure, P less than 0.0001. Adjuvant radiation therapy is an important treatment in the management of patients with sarcoma of the uterus.

Background: Although several environmental factors predict mammographic density, estimates of its heritability have been quite high. We investigated whether part of the presumed heritability might be attributed to differential sharing of modifiable risk factors in monozygotic (MZ) and dizygotic (DZ) twins. Methods: We measured percent and absolute mammographic density using mammograms from 257 MZ and 296 DZ twin pairs. The correlation of intrapair mammographic density was compared according to zygosity across strata of modifiable risk factors. Portions of variance attributable to additive genetic factors, shared environment, and individual environment were calculated using a variance component methodology in the entire set, and within twin pairs stratified by environmental trait similarity. Results: Both percent density and absolute mammographic density were more highly correlated between