Mitchell, Elyse

14597 Background: Permanent seed implant (PSI) brachytherapy is a common treatment modality for low-risk prostate cancer. Post implant dosimetry (PID) is utilized to asses the quality of the implant. Significant prostate swelling occurs as a result of the implant procedure, and this swelling subsides over time. PID completed on Day 0 after the implant procedure captures the prostate swelling from the procedure. Conversely, PID completed one month later does not have this swelling. PID can therefore show great variation, depending on the timing of the analysis. It is hypothesized that PID completed on Day 0 demonstrates lower dosimetric parameters than PID completed one month later. Methods: Thirteen low risk prostate cancer patients, (Stage ≤ T2, PSA < 13.9, Gleason Score ≤7) were implanted with 125Iodine seeds, with a prescription dose of 145Gy to the prostate plus a 5mm margin. Computed Tomography (CT) PID was completed for each patient on day 0 and on average 33 days following the implant. The prostate was contoured on each axial CT image and the data was analyzed using commercially available PSI planning software. The dose which encompassed 90% of the prostate volume (D90) was calculated for day 0 and day 33 PID. Results: On average, the prostate volume contoured was larger on day 0 PID (Avg. 44.9 cc; range 19–97 cc) compared to day 33 PID (Avg. 38.9 cc; range 18–59 cc) (P = 0.068). The D90 values however, were significantly higher on day 33 PID (Avg.163.7 Gy; range 125–212 Gy) than on day 0 PID (Avg.149 Gy; range 112–166 Gy) (P = 0.003). This D90 relationship was even demonstrated paradoxically in two patients whose contoured prostate volume was larger on the day 33 PID as compared to the day 0 PID. Conclusions: Timing does matter in the analysis of post implant dosimetry for PSI brachytherapy. The D90 values were significantly greater on day 33 PID compared to Day 0 PID while the contoured prostate volumes were not. Future studies which use PID planning to evaluate implant quality should specify the timing of the PID, as this would facilitate cross study comparison. No significant financial relationships to disclose.

15639 Background: Permanent prostate brachytherapy (PPB) assesses implant quality but may suffer significant variability due to: 1) Prostate edema may occur during the procedure which usually subsides within several months, and 2) interobserver variability of CT- derived prostate volumes. An analysis is described, which uses the seeds as prostate fiducials to produce an implant reference volume (IRV). The ratio of the IRV volumes at day 0 and day 33 provides a unique way to quantify prostate edema; thus reducing this factor as a source of variability. Methods: Thirteen low risk prostate cancer patients, (Stage ≤ T2, PSA<13.9, Gleason Score ≤7) were implanted with 125Iodine seeds (77% stranded; prescription dose of 145 Gy). PPB was completed for each patient on day 0 and 33 ±3 days following the implant. The IRV was defined as the volume obtained by contouring the outer most peripheral seeds, circumferentially, on each axial image, resulting in a 3D volume. Contouring was performed by three separate investigators (KJM, DCG, EKM), who were blinded with respect to patient identification. The IRV's were compared both by investigator and by time of PPB (day 0 vs. day 33). The radiation dose encompassing 90% (D90) of the IRV and Prostate (PST) was calculated and compared . Results: The IRVs contoured were reproducible between the investigators with a maximum mean difference of .56 (SD .33) cc. There was no statistical difference between any of the investigators contoured volume (minimum Spearman correlation was 0.978). The average IRV was significantly larger on day 0 (Avg. 52.7;SD 19.7 cc) compared to day 33 (Avg. 44.6; SD 19.1 cc) (p<0.001). The day 0 IRV was an average of 1.18 times larger than the Day 33 PRV. There was no difference between either the day 0 D90PST (Avg.149.1; SD18.7 cGy) vs the day 0 D90IRV (Avg.149.8, SD 27.5 cGy) (p=.442) nor between the day 33 D90PST (Avg.163.7; SD22.7 cGy) vs the day 33 D90IRV (Avg.166.6, SD 30.3 cGy) (p=.257). Both the D90IRV and D90PST were significantly different at day 0 vs 33 (p=.0003, p=<.0001 respectively). Conclusions: The IRV analysis demonstrates no significant interobserver variability, provides accurate quantification of prostate swelling after PPB, and is an accurate objective surrogate analysis for PSI quality. No significant financial relationships to disclose.

Here, we report strong evidence for a role of the FNDC3B gene in craniofacial development. Chromosomal microarray identified deletions at 3q26.31 in two patients with dysmorphic facial features. Parental FISH studies demonstrated that they are de novo; therefore, these two 3q26.31 microdeletions likely contribute to the patients' dysmorphic features. Interestingly, the minimal region of overlap contains only the FNDC3B gene. Ffibronectin domain III‐containing protein 3B (FNDC3B), also known as factor for adipocyte differentiation‐104 (FAD104), was first identified as a positive regulator of adipogenesis in a mouse model. Excitingly, further studies in a mouse model have recently demonstrated that FNDC3B is required for normal calvarial bone formation and negatively regulated calvarial cell differentiation through inhibition of BMP/Smad signaling. fndc3b‐deficient mice have multiple cranial and skeletal malformations, such as craniosynostosis‐like premature calvarial ossification, and skeletal deformities in the anterior fontanel and femurs. In summary, we report the first two patients with de novo 3q26.31 microdeletions. Both have dysmorphic features, consistent with the phenotypes seen in fndc3b‐deficient mice in animal studies, which imply a critical role of FNDC3B in human craniofacial development. © 2016 Wiley Periodicals, Inc.

The ability to identify the clinical nature of the recurrent duplication of chromosome 17q12 has been limited by its rarity and the diverse range of phenotypes associated with this genomic change. In order to further define the clinical features of affected patients, detailed clinical information was collected in the largest series to date (30 patients and 2 of their siblings) through a multi‐institutional collaborative effort. The majority of patients presented with developmental delays varying from mild to severe. Though dysmorphic features were commonly reported, patients do not have consistent and recognizable features. Cardiac, ophthalmologic, growth, behavioral, and other abnormalities were each present in a subset of patients. The newly associated features potentially resulting from 17q12 duplication include height and weight above the 95th percentile, cataracts, microphthalmia, coloboma, astigmatism, tracheomalacia, cutaneous mosaicism, pectus excavatum, scoliosis, hypermobility, hypospadias, diverticulum of Kommerell, pyloric stenosis, and pseudohypoparathryoidism. The majority of duplications were inherited with some carrier parents reporting learning disabilities or microcephaly. We identified additional, potentially contributory copy number changes in a subset of patients, including one patient each with 16p11.2 deletion and 15q13.3 deletion. Our data further define and expand the clinical spectrum associated with duplications of 17q12 and provide support for the role of genomic modifiers contributing to phenotypic variability. © 2015 Wiley Periodicals, Inc.

AbstractThe International Standards for Cytogenomic Arrays (ISCA) Consortium is a worldwide collaborative effort dedicated to optimizing patient care by improving the quality of chromosomal microarray testing. The primary effort of the ISCA Consortium has been the development of a database of copy number variants (CNVs) identified during the course of clinical microarray testing. This database is a powerful resource for clinicians, laboratories, and researchers, and can be utilized for a variety of applications, such as facilitating standardized interpretations of certain CNVs across laboratories or providing phenotypic information for counseling purposes when published data is sparse. A recognized limitation to the clinical utility of this database, however, is the quality of clinical information available for each patient. Clinical genetic counselors are uniquely suited to facilitate the communication of this information to the laboratory by virtue of their existing clinical responsibilities, case management skills, and appreciation of the evolving nature of scientific knowledge. We intend to highlight the critical role that genetic counselors play in ensuring optimal patient care through contributing to the clinical utility of the ISCA Consortium's database, as well as the quality of individual patient microarray reports provided by contributing laboratories. Current tools, paper and electronic forms, created to maximize this collaboration are shared. In addition to making a professional commitment to providing complete clinical information, genetic counselors are invited to become ISCA members and to become involved in the discussions and initiatives within the Consortium.