Jessica R. Hiatt

Toxicity of Three-Dimensional Conformal Radiotherapy for Accelerated Partial Breast Irradiation

PURPOSE To assess the incidence and severity of late normal tissue toxicity using three-dimensional conformal radiotherapy to deliver accelerated partial breast irradiation. METHODS AND MATERIALS A total of 60 patients were treated with three-dimensional conformal radiotherapy for accelerated partial breast irradiation. Treatment planning and delivery were in strict accordance with the technique and specified dose-volume constraints of the National Surgical Adjuvant Breast and Bowel Project B-39/Radiation Therapy Oncology Group 0413 protocol. Late toxicity was evaluated according to the Radiation Therapy Oncology Group grading schema. The cosmetic outcome was scored using the Harvard criteria. Univariate logistic regression analysis was performed to evaluate the correlation of dosimetric variables with outcome. RESULTS At a median follow-up of 15 months, moderate-to-severe late toxicity developed in 10% of patients. The most pronounced late toxicity was subcutaneous fibrosis: 25% Grade 2-4 and 8.3% Grade 3-4. The modified planning tumor volume/whole breast volume ratio, ratio of the volume of breast tissue receiving 5%, 20%, 50%, and 80% of the prescription dose to the whole breast volume, and maximal dose within the breast correlated with the development of fibrosis (p = .10, p = .03, p = .04, p = .06, p = .09, and p = .046, respectively). The overall cosmetic outcome was good to excellent in 81.7%, fair in 11.7%, and poor in 6.7%. The presence of subcutaneous fibrosis, modified planning tumor volume/whole breast volume ratio, ratio of the volume of breast tissue receiving 5% and 20% of the prescription dose to the whole breast volume, and pathologic specimen volume correlated with the risk of a fair/poor cosmetic outcome (p < .001, p = .02, p = .05, p = .04, p = .01, respectively). CONCLUSION The three-dimensional conformal radiotherapy technique for accelerated partial breast irradiation as specified in the National Surgical Adjuvant Breast and Bowel Project B-39/Radiation Therapy Oncology Group 0413 protocol resulted in a remarkably high rate of moderate-to-severe late normal tissue effects, despite the relatively brief follow-up period. The toxic events correlated clearly with several dose-volume parameters.

The Effect of Dose-Volume Parameters and Interfraction Interval on Cosmetic Outcome and Toxicity After 3-Dimensional Conformal Accelerated Partial Breast Irradiation

PURPOSE To evaluate dose-volume parameters and the interfraction interval (IFI) as they relate to cosmetic outcome and normal tissue effects of 3-dimensional conformal radiation therapy (3D-CRT) for accelerated partial breast irradiation (APBI). METHODS AND MATERIALS Eighty patients were treated by the use of 3D-CRT to deliver APBI at our institutions from 2003-2010 in strict accordance with the specified dose-volume constraints outlined in the National Surgical Adjuvant Breast and Bowel Project B39/Radiation Therapy Oncology Group 0413 (NSABP-B39/RTOG 0413) protocol. The prescribed dose was 38.5 Gy in 10 fractions delivered twice daily. Patients underwent follow-up with assessment for recurrence, late toxicity, and overall cosmetic outcome. Tests for association between toxicity endpoints and dosimetric parameters were performed with the chi-square test. Univariate logistic regression was used to evaluate the association of interfraction interval (IFI) with these outcomes. RESULTS At a median follow-up time of 32 months, grade 2-4 and grade 3-4 subcutaneous fibrosis occurred in 31% and 7.5% of patients, respectively. Subcutaneous fibrosis improved in 5 patients (6%) with extended follow-up. Fat necrosis developed in 11% of women, and cosmetic outcome was fair/poor in 19%. The relative volume of breast tissue receiving 5%, 20%, 50%, 80%, and 100% (V5-V100) of the prescribed dose was associated with risk of subcutaneous fibrosis, and the volume receiving 50%, 80%, and 100% (V50-V100) was associated with fair/poor cosmesis. The mean IFI was 6.9 hours, and the minimum IFI was 6.2 hours. The mean and minimum IFI values were not significantly associated with late toxicity. CONCLUSIONS The incidence of moderate to severe late toxicity, particularly subcutaneous fibrosis and fat necrosis and resulting fair/poor cosmesis, remains high with continued follow-up. These toxicity endpoints are associated with several dose-volume parameters. Minimum and mean IFI values were not associated with late toxicity.

Planning the breast boost: comparison of three techniques and evolution of tumor bed during treatment.

PURPOSE To evaluate the accuracy of two clinical techniques for electron boost planning compared with computed tomography (CT)-based planning. Additionally, we evaluated the tumor bed characteristics at whole breast planning and boost planning. METHODS AND MATERIALS A total of 30 women underwent tumor bed boost planning within 2 weeks of completing whole breast radiotherapy using three planning techniques: scar-based planning, palpation/clinical-based planning, and CT-based planning. The plans were analyzed for dosimetric coverage of the CT-delineated tumor bed. The cavity visualization score was used to define the CT-delineated tumor bed as well or poorly defined. RESULTS Scar-based planning resulted in inferior tumor bed coverage compared with CT-based planning, with the minimal dose received by 90% of the target volume >90% in 53% and a geographic miss in 53%. The results of palpation/clinical-based planning were significantly better: 87% and 10% for the minimal dose received by 90% of the target volume >90% and geographic miss, respectively. Of the 30 tumor beds, 16 were poorly defined by the cavity visualization score. Of these 16, 8 were well demarcated by the surgical clips. The evaluation of the 22 well-defined tumor beds revealed similar results. A comparison of the tumor bed volume from the initial planning CT scan to the boost planning CT scan revealed a decrease in size in 77% of cases. The mean decrease in volume was 52%. CONCLUSION The results of our study have shown that CT-based planning allows for optimal tumor bed coverage compared with clinical and scar-based approaches. However, in the setting of a poorly visualized cavity on CT without surgical clips, palpation/clinical-based planning can help delineate the appropriate target volumes and is superior to scar-based planning. CT simulation at boost planning could allow for a reduction in the boost volumes.

Dose Modeling of Noninvasive Image-Guided Breast Brachytherapy in Comparison to Electron Beam Boost and Three-Dimensional Conformal Accelerated Partial Breast Irradiation

PURPOSE To perform dose modeling of a noninvasive image-guided breast brachytherapy (NIIGBB) for comparison to electrons and 3DCRT. METHODS AND MATERIALS The novel technology used in this study is a mammography-based, noninvasive breast brachytherapy system whereby the treatment applicators are centered on the planning target volume (PTV) to direct (192)Ir emissions along orthogonal axes. To date, three-dimensional dose modeling of NIIGBB has not been possible because of the limitations of conventional treatment planning systems (TPS) to model variable tissue deformation associated with breast compression. In this study, the TPS was adapted such that the NIIGBB dose distributions were modeled as a virtual point source. This dose calculation technique was applied to CT data from 8 patients imaged with the breast compressed between parallel plates in the cranial-caudal and medial-lateral axes. A dose-volume comparison was performed to simulated electron boost and 3DCRT APBI. RESULTS The NIIGBB PTV was significantly reduced as compared with both electrons and 3DCRT. Electron boost plans had a lower D(min) than the NIIGBB technique but higher V(100), D(90), and D(50). With regard to PTV coverage for APBI, the only significant differences were minimally higher D(90), D(100), V(80), and V(90), with 3DCRT and D(max) with NIIGBB. The NIIGBB technique, as compared with electrons and 3D-CRT, achieved a lower maximum dose to skin (60% and 10%, respectively) and chest wall/lung (70-90%). CONCLUSIONS NIIGBB achieves a PTV that is smaller than electron beam and 3DCRT techniques. This results in significant normal tissue sparing while maintaining dosimetric benchmarks to the target tissue.

Prevalence of poor cardiac anatomy in carcinoma of the breast treated with whole-breast radiotherapy: reconciling modern cardiac dosimetry with cardiac mortality data

Purpose:The purpose of the study was to identify patient characteristics that predict for increased cardiac exposure through dosimetric analysis of the anatomy of a cohort of women treated with left-sided tangential breast radiation. Statistical analyses estimations for the appropriate sample sizes required for detection of significant differences in cardiac mortality at 15 years were conducted, assuming a threshold V25 for radiation-induced coronary artery disease (CAD) beyond which women are at risk for radiation-induced coronary artery disease. Methods and Materials:Detailed heart dosimetry was recorded. Clinical factors (age, history of CAD, diabetes, receipt of cardiotoxic agents, weight/body mass index) and anatomic factors (heart volume, breast volume, cardiac contact distance) were recorded for each patient. Results:The average heart V25 was 3.57%. The median percentage of the heart included in the tangential beam was 4.02%. There were no clinical or anatomic factors that predict suboptimal heart anatomy (ie, V25 of ≥6%) on multivariate analysis. The sample size calculations using thresholds for induction of CAD of V25 ≥1%, 6%, and 10% yielded sample sizes of 1314, 9504, and 61,342, respectively; considering node-positive breast cancer mortality and 15% loss to follow-up, these change to 2237, 16,166, and 104,334, respectively. Conclusions:Current studies with modern radiotherapy techniques would be underpowered to detect a difference in cardiac mortality where only some women are at risk. The heart, chest wall, and breast have a complex relationship to tangential breast radiation, and their interplay prevented this anatomic metric’s success.

Modeling study for optimization of skin dose for partial breast irradiation using Xoft Axxent electronic brachytherapy applicator

PURPOSE Balloon brachytherapy with the MammoSite system (Hologic Inc., Bedford, MA) is a widely used approach for accelerated partial breast irradiation. Inherent to this approach, high skin doses can occur if the balloon to skin distance is small. This has been associated with late skin toxicity, particularly telangiectasia. The Xoft Axxent electronic brachytherapy balloon applicator (Xoft, Fremont, CA) is a novel device for accelerated partial breast irradiation. It is unique in that it uses an electronic 50-kV source. This source has a pronounced anisotropy with constriction of isodose distribution at the proximal end of the catheter. This anisotropy can be considered as an advantage to optimize skin dose when the cavity to skin distance is small. In this study, we simulated various balloon-insertion orientations to optimized skin surface dose. METHODS Breast phantoms were constructed of tissue-equivalent material. Xoft Axxent balloon catheters were inserted at a distance of 6mm from the surface. The catheter was placed at three different catheter to surface orientations: (1) perpendicular to the surface, (2) oblique to the surface (45 degrees), and (3) parallel to the surface. Three-dimensional treatment planning was then performed using Nucletrons Plato planning system (Nucletron, Columbia, MD). Multiple dwell positions were used, and the dose was optimized to the target volume. The target volume was defined as volume from the balloon surface to 1-cm distance from the balloon surface or to the phantom surface (if less then 1cm from the balloon surface). Target volume coverage was compared between plans using dose-volume histograms. Surface doses were compared using isodose line distribution and surface point doses. Plato planned surface doses were then verified by direct measurement using Landauer Dot InLight dosimeters (Landauer, Glenwood, IL). RESULTS Excellent target coverage was obtained for all three catheter orientations with a D(95) of > or =95%. Surface dose was lowest for the perpendicular orientation with a calculated dose of 99%. The parallel orientation had the highest surface dose of 164%. The oblique orientation showed intermediate results with a surface dose of 117%. Measured surface doses were reproducible and correlated well with calculated values. CONCLUSION Optimized Xoft Axxent balloon catheter orientation using source anisotropy and multiple dwell positions can be used to minimize excessive skin dose and yet maintain optimal tumor cavity coverage when the cavity to skin distance is small. This has the potential to decrease skin late effects and improve cosmetic outcome. Further clinical study is warranted.

Dosimetric Feasibility of Dose Escalation Using SBRT Boost for Stage III Non-Small Cell Lung Cancer

Purpose: Standard chemoradiation therapy for stage III non-small cell lung cancer (NSCLCa) results in suboptimal outcomes with a high rate of local failure and poor overall survival. We hypothesize that dose escalation using stereotactic body radiotherapy (SBRT) boost could improve upon these results. We present here a study evaluating the dosimetric feasibility of such an approach. Methods: Anonymized CT data sets from five randomly selected patients with stage III NSCLCa undergoing definitive chemoradiation therapy in our department with disease volumes appropriate for SBRT boost were selected. Three-dimensional conformal radiation therapy (3D-CRT) plans to 50.4 Gy in 28 fractions were generated follow by SBRT plans to two dose levels, 16 Gy in two fractions and 28 Gy in two fractions. SBRT plans and total composite (3D-CRT and SBRT) were optimized and evaluated for target coverage and dose to critical structures; lung, esophagus, cord, and heart. Results: All five plans met predetermined target coverage and normal tissue dose constraints. PTV V95 was equal to or greater than 95% in all cases. The cumulative lung V20 and V5 of the combined 3D-CRT and SBRT plans were less than or equal to 30 and 55%, respectively. The 5 cc esophageal dose was less than 12 Gy for all low and high dose SBRT plans. The cumulative dose to the esophagus was also acceptable with less than 10% of the esophagus receiving doses in excess of 50 Gy. The cumulative spinal cord dose was less than 33 Gy and heart V25 was less than 5%. Conclusion: The combination of chemoradiation to 50.4 Gy followed by SBRT boost to gross disease at the primary tumor and involved regional lymph nodes is feasible with respect to normal tissue dose constraints in this dosimetric pilot study. A phase I/II trial to evaluate the clinical safety and efficacy of this approach is being undertaken.

Axillary lymph node dose with tangential whole breast radiation in the prone versus supine position: a dosimetric study

BackgroundProne breast positioning reduces skin reaction and heart and lung dose, but may also reduce radiation dose to axillary lymph nodes (ALNs).MethodsWomen with early stage breast cancer treated with whole breast irradiation (WBI) in the prone position were identified. Patients treated in the supine position were matched for treating physician, laterality, and fractionation. Ipsilateral breast, tumor bed, and Level I, II, and III ALNs were contoured according to the RTOG breast atlas. Clips marking surgically removed sentinel lymph nodes (SLN)s were contoured. Treatment plans developed for each patient were retrospectively analyzed. V90% and V95% was calculated for each axillary level. When present, dose to axillary surgical clips was calculated.ResultsTreatment plans for 46 women (23 prone and 23 supine) were reviewed. The mean V90% and V95% of ALN Level I was significantly lower for patients treated in the prone position (21% and 14%, respectively) than in the supine position (50% and 37%, respectively) (p < 0.0001 and p < 0.0001, respectively). Generally, Level II & III ALNs received little dose in either position. Sentinel node biopsy clips were all contained within axillary Level I. The mean V95% of SLN clips was 47% for patients treated in the supine position and 0% for patients treated in the prone position (p < 0.0001). Mean V90% to SLN clips was 96% for women treated in the supine position but only 13% for women treated in the prone position.ConclusionsStandard tangential breast irradiation in the prone position results in substantially reduced dose to the Level I axilla as compared with treatment in the supine position. For women in whom axillary coverage is indicated such as those with positive sentinel lymph node biopsy who do not undergo completion axillary dissection, treatment in the prone position may be inappropriate.

Interface dosimetry for electronic brachytherapy intracavitary breast balloon applicators

In this study, we evaluate the attenuation of the dose due to barium‐impregnation in the region between the surface of an electronic brachytherapy (EBT) balloon applicator for accelerated partial breast irradiation (APBI) and the prescription point at 1 cm depth in tissue. To perform the study, depth dose curves were calculated using a general purpose multi‐particle transport code (FLUKA) for a range of balloon wall thicknesses with and without barium impregnation. Numerical data were verified with experimental readings using a parallel plate extrapolation ionization chamber for different wall thicknesses. Depth dose curves computed using both numerical and experimental methods show a 6.0% attenuation of the dose at the 1.0 cm prescription line due to the impregnation of barium in the balloon material, which agrees well with the manufacturers specification. By applying this single attenuation factor, dose calculations throughout the entire planned volume are uniformly affected. However, at the balloon surface, attenuation on the order of 18.0% is observed. The AAPM TG‐43 source data currently incorporated in commercially‐available treatment planning systems do not account for the variable dose distributions attributable to balloon wall attenuation. Our results show that variable attenuation factors that may have clinical significance should be applied in order to determine near‐surface dose distributions when using barium impregnated balloons for intracavitary breast brachytherapy. Dose distributions at distances greater than 1 cm from the surface of the balloon appear to be accurately represented without further modification. PACS numbers: 87.53.Jw, 87.55.D‐, 87.55.d, 87.55.Qr, 87.55.K‐

A revised dosimetric characterization of the model S700 electronic brachytherapy source containing an anode-centering plastic insert and other components not included in the 2006 model

PURPOSE The model S700 Axxent electronic brachytherapy source by Xoft, Inc., was characterized by Rivard et al. in 2006. Since then, the source design was modified to include a new insert at the source tip. Current study objectives were to establish an accurate source model for simulation purposes, dosimetrically characterize the new source and obtain its TG-43 brachytherapy dosimetry parameters, and determine dose differences between the original simulation model and the current model S700 source design. METHODS Design information from measurements of dissected model S700 sources and from vendor-supplied CAD drawings was used to aid establishment of an updated Monte Carlo source model, which included the complex-shaped plastic source-centering insert intended to promote water flow for cooling the source anode. These data were used to create a model for subsequent radiation transport simulations in a water phantom. Compared to the 2006 simulation geometry, the influence of volume averaging close to the source was substantially reduced. A track-length estimator was used to evaluate collision kerma as a function of radial distance and polar angle for determination of TG-43 dosimetry parameters. Results for the 50 kV source were determined every 0.1 cm from 0.3 to 15 cm and every 1° from 0° to 180°. Photon spectra in water with 0.1 keV resolution were also obtained from 0.5 to 15 cm and polar angles from 0° to 165°. Simulations were run for 10(10) histories, resulting in statistical uncertainties on the transverse plane of 0.04% at r = 1 cm and 0.06% at r = 5 cm. RESULTS The dose-rate distribution ratio for the model S700 source as compared to the 2006 model exceeded unity by more than 5% for roughly one quarter of the solid angle surrounding the source, i.e., θ ≥ 120°. The radial dose function diminished in a similar manner as for an (125)I seed, with values of 1.434, 0.636, 0.283, and 0.0975 at 0.5, 2, 5, and 10 cm, respectively. The radial dose function ratio between the current and the 2006 model had a minimum of 0.980 at 0.4 cm, close to the source sheath and for large distances approached 1.014. 2D anisotropy function ratios were close to unity for 50° ≤ θ ≤ 110°, but exceeded 5% for θ < 40° at close distances to the sheath and exceeded 15% for θ > 140°, even at large distances. Photon energy fluence of the updated model as compared to the 2006 model showed a decrease in output with increasing distance; this effect was pronounced at the lowest energies. A decrease in photon fluence with increase in polar angle was also observed and was attributed to the silver epoxy component. CONCLUSIONS Changes in source design influenced the overall dose rate and distribution by more than 2% in several regions. This discrepancy is greater than the dose calculation acceptance criteria as recommended in the AAPM TG-56 report. The effect of the design change on the TG-43 parameters would likely not result in dose differences outside of patient applicators. Adoption of this new dataset is suggested for accurate depiction of model S700 source dose distributions.