Shirin Sioshansi

The impact of prescription depth, dose rate, plaque size, and source loading on the central axis using 103Pd, 125I, and 131Cs.

PURPOSE Modern dosimetry data are not available for Collaborative Ocular Melanoma Study-based eye plaques. This report aims to provide these data for eye plaques ranging from 10 to 22 mm, and for three different low-energy, photon-emitting radionuclides. METHODS AND MATERIALS Recent publications on brachytherapy dosimetry parameters for 103Pd, 125I, and 131Cs were evaluated for use as eye plaque reference data. These data were entered into the Pinnacle treatment planning system for 3D calculations of brachytherapy dose distributions along the central axis for depths ranging from -1 to 10 mm based on the origin positioned at the inner sclera. In accordance with the original Collaborative Ocular Melanoma Study protocol and in the absence of radionuclide-specific heterogeneity factors, inhomogeneity corrections were not applied. RESULTS As expected due to the mean photon energies, 103Pd, 125I, and 131Cs provided increasingly penetrating dose distributions. Dose distribution tables were prepared for fully loaded plaques and for plaques with the central source(s) removed. Over the entire range of central axis depths, and for all plaque sizes and loadings, 131Cs produced minimal outer scleral doses. Similarly, 103Pd generally produced more favorable dose distributions than 125I for depths less than 4mm. CONCLUSIONS A modern analysis of eye plaque dosimetry evaluated dose as a function of lesion height and applicator size, and showed dependence on radionuclide selection and implant duration. For a fixed dose at the prescription point, we observed higher scleral dose corresponded with lower photon energy for a variety of plaque sizes and lesion heights.

Survival among patients with 10 or more brain metastases treated with stereotactic radiosurgery

OBJECT The goal of this study was to evaluate outcomes in patients with ≥ 10 CNS metastases treated with Gamma Knife stereotactic radiosurgery (GK-SRS). METHODS Patients with ≥ 10 brain metastases treated using GK-SRS during the period between 2004 and 2010 were identified. Overall survival and local and regional control as well as necrosis rates were determined. The influence of age, sex, histological type, extracranial metastases, whole-brain radiation therapy, and number of brain metastases was analyzed using the Kaplan-Meier method. Univariate (log-rank) analyses were performed, with a p value of < 0.05 considered significant. RESULTS Fifty-three patients with ≥ 10 brain metastases were treated between 2004 and 2010. All had a Karnofsky Performance Status score of ≥ 70. Seventy-two percent had either non-small cell lung cancer (38%) or breast cancer (34%); melanoma, small cell lung cancer, renal cell carcinoma, and testicular, colon, and ovarian cancer contributed the remaining 28%. On average, 10.9 lesions were treated in a single session. Sixty-four percent of patients received prior whole-brain radiation therapy. The median survival was 6.5 months. One-year overall survival was 42% versus 14% when comparing breast cancer and other histological types, respectively (p = 0.074). Age, extracranial metastases, number of brain metastases, and previous CNS radiation therapy were not significant prognostic factors. Although the median time to local failure was not reached, the median time to regional failure was 3 months. Female sex was associated with longer time to regional failure (p = 0.004), as was breast cancer histological type (p = 0.089). No patient experienced symptomatic necrosis. CONCLUSIONS Patients with ≥ 10 brain metastases who received prior CNS radiation can safely undergo repeat treatment with GK-SRS. With median survival exceeding 6 months, aggressive local treatment remains an option; however, rapid CNS failure is to be expected. Although numbers are limited, patients with breast cancer represent one group of individuals who would benefit most, with prolonged survival and extended time to CNS recurrence.

Triple negative breast cancer is associated with an increased risk of residual invasive carcinoma after lumpectomy

To assess the potential mechanisms that may underlie increased local failure in triple negative (TN) breast cancers, an analysis was performed of the risk of residual carcinoma after lumpectomy with correlation to pathologic factors, including molecular phenotype.

Treatment planning of a skin-sparing conical breast brachytherapy applicator using conventional brachytherapy software

PURPOSE AccuBoost is a noninvasive image-guided technique for the delivery of partial breast irradiation to the tumor bed and currently serves as an alternate to conventional electron beam boost. To irradiate the target volume while providing dose sparing to the skin, the round applicator design was augmented through the addition of an internally truncated conical shield and the reduction of the source to skin distance. METHODS Brachytherapy dose distributions for two types of conical applicators were simulated and estimated using Monte Carlo (MC) methods for radiation transport and a conventional treatment planning system (TPS). MC-derived and TPS-generated dose volume histograms (DVHs) and dose distribution data were compared for both the conical and round applicators for benchmarking purposes. RESULTS Agreement using the gamma-index test was > or = 99.95% for distance to agreement and dose accuracy criteria of 2 mm and 2%, respectively. After observing good agreement, TPS DVHs and dose distributions for the conical and round applicators were obtained and compared. Brachytherapy dose distributions generated using Pinnacle for ten CT data sets showed that the parallel-opposed beams of the conical applicators provided similar PTV coverage to the round applicators and reduced the maximum dose to skin, chest wall, and lung by up to 27%, 42%, and 43%, respectively. CONCLUSIONS Brachytherapy dose distributions for the conical applicators have been generated using MC methods and entered into the Pinnacle TPS via the Tufts technique. Treatment planning metrics for the conical AccuBoost applicators were significantly improved in comparison to those for conventional electron beam breast boost.

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.

The Implications of Breast Cancer Molecular Phenotype for Radiation Oncology

The identification of distinct molecular subtypes of breast cancer has advanced the understanding and treatment of breast cancer by providing insight into prognosis, patterns of recurrence, and effectiveness of therapy. The prognostic significance of molecular phenotype with regard to distant recurrences and overall survival are well established in the literature and has been readily incorporated into systemic therapy management decisions. However, despite the accumulating data suggesting similar prognostic significance for locoregional recurrence, integration of molecular phenotype into local management decision making has lagged. Although there are some conflicting reports, collectively the literature supports a low risk of local recurrence (LR) in the hormone receptor (HR) positive luminal subtypes compared to HR negative subtypes [triple negative (TN) and HER2-enriched]. The development of targeted therapies, such as trastuzumab for the treatment of HER2-enriched subtype, has been shown to mitigate the increased risk of LR. Unfortunately, no such remedy exists to address the increased risk of LR for patients with TN tumors, making it a clinical challenge for radiation oncologists. In this review we discuss the correlation between molecular subtype and LR following either breast conservation therapy or mastectomy. We also explore the possible mechanisms for increased LR in TN breast cancer and radiotherapeutic implications for this population, such as the safety of breast conservation, consideration of dose escalation, and the appropriateness of accelerated partial breast irradiation.

Diaphragm injury after liver stereotactic body radiation therapy

Stereotactic body radiation therapy (SBRT) is an increasingly common treatment for lung and liver malignancies. Chest wall toxicity following SBRT for peripheral tumors has been reported and there are published dose constraint guidelines to minimize the risk for rib fracture, chest wall necrosis, and cutaneous ulceration.1-4 There are no documented reports of diaphragm injury after SBRT and no defined tolerance dose. We describe in this report the clinical course of a patient who developed severe back pain following liver SBRT and was found to have focal necrosis, fibrosis, and atrophy of the diaphragm in the high-dose region on autopsy.

Local recurrence and survival following stereotactic radiosurgery for brain metastases from small cell lung cancer

PURPOSE Stereotactic radiosurgery (SRS) represents a treatment option for patients with brain metastases from small cell lung cancer (SCLC) following prior cranial radiation. Inferior local control has been described. We reviewed our failure patterns following SRS treatment to evaluate this concern. METHODS AND MATERIALS Individuals with SCLC who received SRS for brain metastases from 2004 to 2011 were identified. Central nervous system (CNS) disease was detected and followed by gadolinium-enhanced, high-resolution magnetic resonance (MR) imaging. SRS dose was prescribed to the tumor periphery. Local recurrence was defined by increasing lesion size or enhancement, MR-spectroscopy, and perfusion changes consistent with recurrent disease or pathologic confirmation. Any new enhancing lesion not identified on the SRS planning scan was considered a regional failure. Overall survival (OS) and CNS control were evaluated using the Kaplan-Meier method. Factors predicted to influence outcome were tested by univariate log-rank analysis and Cox regression. RESULTS Fifteen males and 25 females (median age of 61 years [range, 36-79]) of which 39 received prior brain irradiation were identified. In all, 132 lesions (3.3 per patient) between 0.4 and 4.7 cm received a median dose of 16 Gy (12-22 Gy). Thirteen metastases (10%) ultimately recurred locally with 6- and 12-month control rates of 81% and 69%, respectively. Only 1 of 110 metastases <2 cm recurred. Local failure was more likely for size >2 cm (P < .001) and dose <16 Gy (P < .001). The median OS was 6.5 months, and the time to regional CNS recurrence was 5.2 months. For patients with single brain metastases, both OS (P = .037) and regional CNS recurrence (P = .003) were improved. CNS control (P = .001), and survival (P = .057), were also longer for patients with controlled systemic disease. CONCLUSIONS Local control following SRS for SCLC metastases is achievable for lesions <2 cm. For metastases >2 cm, local failure is more common than expected. Patients with controlled systemic disease and limited CNS involvement would benefit most from aggressive treatment.

Hepatocellular carcinoma recurrence pattern following liver transplantation and a suggested surveillance algorithm

PURPOSE This study aims to evaluate the recurrence pattern of hepatocellular carcinoma (HCC) following liver transplantation. MATERIALS AND METHODS A total of 54 patients underwent liver transplantation for HCC; 9 patients developed biopsy-proven recurrent HCC (16.6%). The site of HCC recurrence along with other factors was analyzed. RESULTS Seven patients were diagnosed with HCC prior to liver transplantation and 2 patients had incidental HCC in the explanted liver. Two patients had locoregional recurrence, 4 patients had distant metastasis, and 3 patients had synchronous locoregional recurrence and distant metastasis. CONCLUSION A significant proportion of HCC recurrence following liver transplantation is extrahepatic.