Andrew Ju

Hypofractionated stereotactic body radiation therapy as monotherapy for intermediate-risk prostate cancer

BackgroundHypofractionated stereotactic body radiation therapy (SBRT) has been advanced as monotherapy for low-risk prostate cancer. We examined the dose distributions and early clinical outcomes using this modality for the treatment of intermediate-risk prostate cancer.MethodsForty-one sequential hormone-naïve intermediate-risk prostate cancer patients received 35–36.25 Gy of CyberKnife-delivered SBRT in 5 fractions. Radiation dose distributions were analyzed for coverage of potential microscopic ECE by measuring the distance from the prostatic capsule to the 33 Gy isodose line. PSA levels, toxicities, and quality of life (QOL) measures were assessed at baseline and follow-up.ResultsAll patients completed treatment with a mean coverage by the 33 Gy isodose line extending >5 mm beyond the prostatic capsule in all directions except posteriorly. Clinical responses were documented by a mean PSA decrease from 7.67 ng/mL pretreatment to 0.64 ng/mL at the median follow-up of 21 months. Forty patients remain free from biochemical progression. No Grade 3 or 4 toxicities were observed. Mean EPIC urinary irritation/obstruction and bowel QOL scores exhibited a transient decline post-treatment with a subsequent return to baseline. No significant change in sexual QOL was observed.ConclusionsIn this intermediate-risk patient population, an adequate radiation dose was delivered to areas of expected microscopic ECE in the majority of patients. Although prospective studies are needed to confirm long-term tumor control and toxicity, the short-term PSA response, biochemical relapse-free survival rate, and QOL in this interim analysis are comparable to results reported for prostate brachytherapy or external beam radiotherapy.Trial registrationThe Georgetown Institutional Review Board has approved this retrospective study (IRB 2009–510).

Yttrium-90 Radioembolization in Patients with Hepatocellular Carcinoma Who have Previously Received Sorafenib

Purpose: Yttrium-90 radioembolization (RE) is a locoregional therapy option for hepatocellular carcinoma (HCC). Sorafenib is a multikinase inhibitor used in HCC that can potentially affect the efficacy of RE by altering tumor vascularity or suppressing post-irradiation angiogenesis. The safety and efficacy of sorafenib followed by RE has not been previously reported. Materials and Methods: Patients with HCC who received RE after sorafenib were included in this retrospective review. Overall survival, toxicity, and maximal radiographic response and necrosis criteria were examined. Results: Ten patients (15 RE administrations) fit the inclusion criteria. All were Barcelona Clinic Liver Cancer (BCLC) stage C. Median follow-up was 16.5 weeks. Median overall survival and radiographic progression-free survival were 30 and 28 weeks, respectively. Significant differences in overall survival were seen based on Child-Pugh class (p = 0.002) and radiographic response (p = 0.009). Three patients had partial response, six had stable disease, and one had progressive disease. Grade 1 or 2 acute fatigue, anorexia, and abdominal pain were common. Three patients had Grade 3 ascites in the setting of disease progression. Two patients had Grade 3 biochemical toxicity. One patient was sufficiently downstaged following RE and sorafenib to receive a partial hepatectomy. Conclusion: Yttrium-90 RE in patients with HCC who have received sorafenib demonstrate acceptable toxicity and rates of radiographic response. However, the overall survival is lower than that reported in the literature on RE alone or sorafenib alone. This may be due in part to more patients in this study having advanced disease compared to these other study populations. Larger prospective studies are needed to determine whether the combination of RE and sorafenib is superior to either therapy alone.

Conditionally reprogrammed normal and primary tumor prostate epithelial cells: a novel patient-derived cell model for studies of human prostate cancer

Our previous study demonstrated that conditional reprogramming (CR) allows the establishment of patient-derived normal and tumor epithelial cell cultures from a variety of tissue types including breast, lung, colon and prostate. Using CR, we have established matched normal and tumor cultures, GUMC-29 and GUMC-30 respectively, from a patients prostatectomy specimen. These CR cells proliferate indefinitely in vitro and retain stable karyotypes. Most importantly, only tumor-derived CR cells (GUMC-30) produced tumors in xenografted SCID mice, demonstrating maintenance of the critical tumor phenotype. Characterization of cells with DNA fingerprinting demonstrated identical patterns in normal and tumor CR cells as well as in xenografted tumors. By flow cytometry, both normal and tumor CR cells expressed basal, luminal, and stem cell markers, with the majority of the normal and tumor CR cells expressing prostate basal cell markers, CD44 and Trop2, as well as luminal marker, CD13, suggesting a transit-amplifying phenotype. Consistent with this phenotype, real time RT-PCR analyses demonstrated that CR cells predominantly expressed high levels of basal cell markers (KRT5, KRT14 and p63), and low levels of luminal markers. When the CR tumor cells were injected into SCID mice, the expression of luminal markers (AR, NKX3.1) increased significantly, while basal cell markers dramatically decreased. These data suggest that CR cells maintain high levels of proliferation and low levels of differentiation in the presence of feeder cells and ROCK inhibitor, but undergo differentiation once injected into SCID mice. Genomic analyses, including SNP and INDEL, identified genes mutated in tumor cells, including components of apoptosis, cell attachment, and hypoxia pathways. The use of matched patient-derived cells provides a unique in vitro model for studies of early prostate cancer.

Pineal Region Glioblastoma, a Case Report and Literature Review

Introduction Pineal region glioblastoma multiforme (GBM) is a rare disease entity with a generally poor prognosis. We present a case of a patient with an unresectable pineal region GBM treated with chemoradiation with favorable outcome. Case background A 65-year-old patient who was presented with visual symptoms was found to have a pineal region tumor on imaging. A stereotactic biopsy showed a World Health Organization Grade IV GBM, O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylated, isocitrate dehydrogenase 1 and 2 wild type. The patient was treated with radiotherapy with concurrent temozolomide, followed by adjuvant temozolomide. Disease progression occurred at 58 weeks post-biopsy, which prompted the initiation of bevacizumab. The patient was alive and functioning well as of his last follow up, 166 weeks from the initial biopsy. Discussion On our review of the literature, 24 cases of pineal region GBM have been reported. The median reported survival for these previously reported cases was 6 months (range, 2–24 months). This patient has the longest overall survival reported to date for a patient with this diagnosis. This is the first patient in the literature with pineal region GBM who has been reported to have MGMT promoter methylation. Concluding remarks Although pineal region GBM is a rare disease entity with a generally poor prognosis, long-term survival is achievable for select patients. MGMT promoter methylation may potentially have prognostic value. Favorable control of recurrent disease with the use of bevacizumab is possible.

SU‐E‐T‐67: A Simple Tool for Evaluation of Fiducial Placement for CyberKnife SRS/SBRT Treatment

Purpose: To develop a simple software tool to help determine whether a fiducial placement meets the Spacing and Collinearity criteria for CyberKnife 6D target tracking. Methods: An Excel spreadsheet has been developed for this purpose. The spreadsheet calculates distances and angles for all possible combinations of fiducial triplets based on the fiducial coordinates entered. In general, a group of 4 fiducials forms 4 triplets; a group of 6 fiducials forms 20 triplets. Distance between any two points in 3D space can be calculated easily. Angles formed by lines joining a fiducial triplet are calculated by using the law of cosines. Calculations using scalar product of vectors method are also implemented and used as a redundancy check. Fiducial placement and CyberKnife treatment data from 78 prostate patients were analyzed. Results: The spreadsheet checks each fiducial triplet against the Spacing & Collinearity Thresholds. Distances or angles failed to meet the thresholds are flagged. If none of the fiducial triplets meet the criteria, extra fiducials need to be implanted. Of the 78 patients studied, most patients were implanted with 4 fiducials; seven patients had 3, and twenty patients had 6 fiducials. A total of the 345 fiducials and 600+ triplets were analyzed. The study showed that 72% of the fiducial distances exceeded the 20‐mm Spacing Threshold, and 99% of the fiducial angles exceeded the 15‐degree Collinearity Threshold. Conclusions: We have developed an Excel spreadsheet to verify that a fiducial placement meets the Cyberknife 6D tracking criteria before patient treatment.Analyzing past patient data helps provide guidance on how fiducial placement may be improved. It is important that least one of the fiducial triplets exceed both Spacing and Collinearity Thresholds, as the study has found that there were cases where a fiducial triplet met the Spacing criteria but failed Collinearity criteria, and vice versa.

A Single-Institution Analysis of 126 Patients Treated with Stereotactic Radiosurgery for Brain Metastases

Background The objective of this study was to report our institutional experience with Gamma Knife® Radiosurgery (GKRS) in the treatment of patients with brain metastases. Methods Retrospectively collected demographic and clinical data on 126 patients with intracranial metastases were reviewed. The patients in our study underwent GKRS at Vidant Medical Center between 2009 and 2014. Kaplan–Meier curves were used to compare survival based on clinical characteristics for univariate analysis, and a Cox proportional hazards model was used for multivariate analysis. Results The median age of the patient population was 62 years. Medicare patients constituted 51% of our patient cohort and Medicaid patients 15%. The most common tumor histologies were non-small cell lung cancer (50%), breast cancer (12.7%), and melanoma (11.9%). The median overall survival time for all patients was 5.8 months. Patients with breast cancer had the longest median survival time of 9.15 months, while patients with melanoma had the shortest median survival time of 2.86 months. On univariate analysis, the following factors were predictors for improved overall survival, ECOG score 0 or 1 vs. 2 or greater (17.0 vs. 1.8 months, p < 0.001), controlled extracranial disease vs. progressive extracranial disease (17.4 vs. 4.6 months, p = 0.0001), recursive partitioning analysis Stage I vs. II–III (18.2 vs. 6.2 months, p < 0.007), multiple GKRS treatments (p = 0.002), prior brain metastasectomy (p = 0.012), and prior chemotherapy (p = 0.021). Age, ethnicity, gender, previous external beam radiation therapy, number of brain metastases, and hemorrhagic vs. non-hemorrhagic tumors were not predictors of longer median survival time. Number of metastatic brain lesions of 1–3 vs. ≥4 (p = 0.051) and insurance status of Medicare/Medicaid vs. commercial insurance approached significance (13.7 vs. 6.8 months, p = 0.08). On multivariate analysis, ECOG performance status 0–1 (p < 0.001), multiple GKRS treatments (p = 0.003), and control of extracranial disease (p = 0.001) remained significant predictors of survival. Conclusion ECOG score, control of extracranial disease, and multiple GKRS treatments are predictors of longer median survival following GKRS in our patient population. GKRS is an effective treatment for brain metastases, but these factors may be considered in patient selection for GKRS.

SU-G-201-07: Dosimetric Verification of a 3D Printed HDR Skin Brachytherapy Applicator

PURPOSE The use of radiation as a treatment modality for skin cancer has increased significantly over the last decade with standardized applicators. Utilizing 3D printing, the ability to make applicators specifically designed for each patients anatomy has become economically feasible. With this in mind it was the aim of this study to determine the dosimetric accuracy of a 3-D printed HDR brachytherapy applicator for the skin. METHODS A CT reference image was used to generate a custom applicator based on an anthropomorphic head and neck phantom. To create the applicator a 1cm expansion anteriorly with 0.5cmX0.5cm trenches on the outer surface that were spaced 1cm sup-inf to accommodate standard 6F flexible catheters. The applicator was printed using PLA material using a printrbot simple printer. A treatment plan optimized to deliver a clinically representative volume was created in Oncentra and delivered with a nucletron afterloader. Measurements were made using TLDs and EBT3 gafchromic film that were placed between the applicator and the phantoms forehead. An additional piece of film was also used to qualitatively asses the dose distribution in the transverse plane. Using a standard vaginal cylinder and bolus, a standardized curve correlating TLD and film exposure-to-radiation dose was established by irradiating film to known doses (200,500,700 cGy) at a 3.5 cm radius distance. RESULTS Evaluated TLDs showed the absolute dose delivered to the skin surface using the 3-D printed bolus was 615cGy±6%, with a mean predicted TPS value in the measured area of 617.5±7%. Additionally, planar dose distributions had good qualitative agreement with calculated TPS isodoses. CONCLUSION This work demonstrates patient specific 3-D printed HDR brachytherapy applicators for skin cancer treatments are practical and accurate in TPS calculations but additional measurements are needed to verify additional sites and dose at depth.

SU-E-T-216: Intercomparison of CyberKnife and GammaKnife Stereotactic Radiosurgery Treatment Plans for Metastatic Brain Tumors

PURPOSE Over 40,000 patients are treated annually for metastatic brain tumors. A common method of treatment for these patients is stereotactic radiosurgery (SRS). Two commercially available options for treatment of SRS are the CyberKnife and GammaKnife. The purpose of this work was to perform a detailed comparison of the quality of the two techniques for the treatment of metastatic brain tumors using quantitative parameters. METHODS Six patients with small metastatic brain tumors (Range: 2.2cc- 14.6cc) that had previously received SRS treatment via the GammaKnife system were planned for equivalent treatment using the CyberKnife treatment planning system. To quantify the quality of the individual plans, the conformity number (CN), homogeneity index (HI) and gradient score index (GSI) were measured and compared. Both plans were created to delivery equivalent tumor coverage (Range: 10-14Gy) to the equivalent prescription volume. This was typically 99% prescription dose coverage to the GTV for both plans. RESULTS The calculated average HI was 0.497±0.155 versus 0.600±0.049, CI was 0.596±0.159 versus 0.865±0.022, and GSI was 41.4±17.8 versus 65.1±20.09 for CyberKnife vs GammaKnife respectively. Lower HI values imply a higher uniformity of dose throughout the target. CI ideally would be 1.000, and the closest to this value is to one, the better is the conformality to the treated site. High values for GSI implies a steeper dose falloff from the tumor to normal tissue and therefore is preferable. For this study statistical significance was achieved for CI, however due to the small sample size differences in HI and GSI were not statistically significant. CONCLUSION This data suggests that SRS treatments on CyberKnife and GammaKnife are of similar quality, with Gamma Knife able to deliver a slightly more conformal plan for the treatment of brain metastases.