Vivek N. Patel

Suspension Matrices for Improved Schwann-Cell Survival after Implantation into the Injured Rat Spinal Cord

Trauma to the spinal cord produces endogenously irreversible tissue and functional loss, requiring the application of therapeutic approaches to achieve meaningful restoration. Cellular strategies, in particular Schwann-cell implantation, have shown promise in overcoming many of the obstacles facing successful repair of the injured spinal cord. Here, we show that the implantation of Schwann cells as cell suspensions with in-situ gelling laminin:collagen matrices after spinal-cord contusion significantly enhances long-term cell survival but not proliferation, as well as improves graft vascularization and the degree of axonal in-growth over the standard implantation vehicle, minimal media. The use of a matrix to suspend cells prior to implantation should be an important consideration for achieving improved survival and effectiveness of cellular therapies for future clinical application.

A Realistic Utilization of Nanotechnology in Molecular Imaging and Targeted Radiotherapy of Solid Tumors

Precise dose delivery to malignant tissue in radiotherapy is of paramount importance for treatment efficacy while minimizing morbidity of surrounding normal tissues. Current conventional imaging techniques, such as magnetic resonance imaging (MRI) and computerized tomography (CT), are used to define the three-dimensional shape and volume of the tumor for radiation therapy. In many cases, these radiographic imaging (RI) techniques are ambiguous or provide limited information with regard to tumor margins and histopathology. Molecular imaging (MI) modalities, such as positron emission tomography (PET) and single photon-emission computed-tomography (SPECT) that can characterize tumor tissue, are rapidly becoming routine in radiation therapy. However, their inherent low spatial resolution impedes tumor delineation for the purposes of radiation treatment planning. This review will focus on applications of nanotechnology to synergize imaging modalities in order to accurately highlight, as well as subsequently target, tumor cells. Furthermore, using such nano-agents for imaging, simultaneous coupling of novel therapeutics including radiosensitizers can be delivered specifically to the tumor to maximize tumor cell killing while sparing normal tissue.

Ethnic heterogeneity and prostate cancer mortality in Hispanic/Latino men: a population-based study

Background Few studies focus on prostate cancer (PCa) outcomes in Hispanic/Latino men. Our study explores whether Hispanic/Latino subgroups demonstrate significantly different prostate cancer-specific mortality (PCSM) relative to Non-Hispanic White (NHW) and Non-Hispanic Black (NHB) men. Methods We extracted a population-based cohort of men diagnosed with local-regional PCa from 2000-2013 (n= 486,865). PCSM was measured in racial/ethnic groups: NHW (n=352,886), NHB (n= 70,983), Hispanic/Latino (n= 40,462), and Asian American/Pacific Islander (n= 22,534). PCSM was also measured in Hispanic/Latino subgroups: Mexican (n= 8,077), Puerto Rican (n= 1,284), South or Central American (n= 3,021), Cuban (n= 788), and Dominican (n= 300). We conducted univariable and multivariable analyses (MVA) to compare risk for PCSM. Results Compared to NHW men, results showed worse outcomes for NHB men with similar outcomes for Hispanic/Latino men. In MVA with NHW men as a reference, NHB (HR= 1.15, p <0.001) men had significantly worse PCSM and Hispanic/Latino (HR= 1.02, p= 0.534) men did not show a significant difference. In a second MVA, Puerto Rican (HR= 1.71, p <0.001) and Mexican (HR= 1.21, p= 0.008) men had significantly higher PCSM. With NHB men as a reference, the MVA showed Puerto Rican (HR= 1.50, p= 0.006) men with higher PCSM and Mexican (HR= 1.08, p= 0.307) men with no significant difference. Conclusions Our findings indicate previously unknown disparities in PCSM for Puerto Rican and Mexican American men.BACKGROUND Few studies focus on prostate cancer (PCa) outcomes in Hispanic/Latino men. Our study explores whether Hispanic/Latino subgroups demonstrate significantly different prostate cancer-specific mortality (PCSM) relative to Non-Hispanic White (NHW) and Non-Hispanic Black (NHB) men. METHODS We extracted a population-based cohort of men diagnosed with local-regional PCa from 2000-2013 (n= 486,865). PCSM was measured in racial/ethnic groups: NHW (n=352,886), NHB (n= 70,983), Hispanic/Latino (n= 40,462), and Asian American/Pacific Islander (n= 22,534). PCSM was also measured in Hispanic/Latino subgroups: Mexican (n= 8,077), Puerto Rican (n= 1,284), South or Central American (n= 3,021), Cuban (n= 788), and Dominican (n= 300). We conducted univariable and multivariable analyses (MVA) to compare risk for PCSM. RESULTS Compared to NHW men, results showed worse outcomes for NHB men with similar outcomes for Hispanic/Latino men. In MVA with NHW men as a reference, NHB (HR= 1.15, p <0.001) men had significantly worse PCSM and Hispanic/Latino (HR= 1.02, p= 0.534) men did not show a significant difference. In a second MVA, Puerto Rican (HR= 1.71, p <0.001) and Mexican (HR= 1.21, p= 0.008) men had significantly higher PCSM. With NHB men as a reference, the MVA showed Puerto Rican (HR= 1.50, p= 0.006) men with higher PCSM and Mexican (HR= 1.08, p= 0.307) men with no significant difference. CONCLUSIONS Our findings indicate previously unknown disparities in PCSM for Puerto Rican and Mexican American men.

Quantitative imaging: Correlating image features with the segmentation accuracy of PET based tumor contours in the lung

The purpose of this study was to investigate the correlation between image features extracted from PET images and the accuracy of manually drawn lesion contours in the lung. Such correlations are interesting in that they could potentially be used in predictive models to help guide physician contouring. In this work, 26 synthetic PET datasets were created using an anthropomorphic phantom and Monte Carlo simulation. Manual contours of simulated lesions were provided by 10 physicians. Contour accuracy was quantified using five commonly used similarity metrics which were then correlated with several features extracted from the images. Features were sub-divided into three groups using intensity, geometry, and texture as categorical descriptors. When averaged among the participants, the results showed relatively strong correlations with complexity and contrastI (r≥0.65, p<0.001), and moderate correlations with several other image features (r≥0.5, p<0.01). The predictive nature of these correlations was improved through stepwise regression and the creation of multi-feature models. Imaging features were also correlated with the standard deviation of contouring error in order to investigate inter-observer variability. Several features were consistently identified as influential including integral of mean curvature and complexity. These relationships further the understanding as to what causes variation in the contouring of PET positive lesions.

Disparities in Hispanic/Latino and non-Hispanic Black men with low-risk prostate cancer and eligible for active surveillance: a population-based study

BackgroundNon-Hispanic Black (NHB) men are at an increased risk for aggressive prostate cancer (PCa), making active surveillance (AS) potentially less optimal in this population. This concern has not been explored in other minority populations—specifically, Hispanic/Latino men. We recently found that Mexican-American men demonstrate an increased risk of PCa-specific mortality, and we hypothesized that they may also be at risk for an adverse outcome on AS.MethodsUsing the Surveillance, Epidemiology, and End Results (SEER) program, we extracted a population-based cohort of men diagnosed from 2004 to 2013 with localized or regional PCa, who had ≤2 cores of only Grade Group (GG) 1 cancer, and underwent radical prostatectomy (RP) with available biopsy and surgical pathology results. We measured discovery of high-risk PCa at RP and collected socioeconomic status (SES) data across different racial/ethnic groups. We defined aggressive tumors as either an upgrade to GG 3 or higher (GG3+) cancer or non-organ-confined disease (≥pT3a or N1). Univariate and multivariate logistic regression models were developed to assess the association between racial/ethnic categories and the previously mentioned adverse oncologic outcomes both with and without adjusting for SES factors.ResultsNHB and Mexican-American men were significantly more likely to have aggressive PCa, following RP. In multivariable logistic regression adjusting for SES factors and relative to non-Hispanic White (NHW) men, Mexican-American men had at increased odds of upgrading to GG3+ (OR 1.67; 95% CI [1.00–2.90]). NHB men were more likely to have non-organ-confined disease (OR 1.34; 95% CI [1.06–1.69]), while Mexican-American men had a similar risk to NHW men.ConclusionAmong individuals with low-risk PCa and eligible for AS, Mexican-American and NHB men are at an increased risk of harboring more aggressive disease at RP. This novel finding among Mexican-Americans deserves further evaluation.

Abstract PR04: Ethnic heterogeneity and prostate cancer mortality in Hispanic/Latino men

Purpose: Few studies have focused on the rapidly growing and extremely diverse Hispanic/Latino population in regards to prostate cancer outcomes. Our study explores whether heterogeneity between Hispanic/Latino men of diverse ancestry potentially contributes to unexplored disparities in five-year prostate cancer-specific mortality and all-cause mortality. Patients and Methods: From the Surveillance, Epidemiology, and End Results program (SEER), we designed a population-based cohort of men diagnosed with local-regional prostate cancer (n= 432,356) from 2000-2012. Five-year cumulative incidence of prostate cancer-specific mortality was obtained using competing risks analysis and all-cause mortality was determined by using one minus the Kaplan-Meier survival estimate of overall survival. This was examined for different racial and/or ethnic groups: Non-Hispanic White (n= 313,514), Non-Hispanic Black (n= 62,346), Hispanic/Latino (n= 36,407), and Asian American/Pacific Islander (n= 20,089). We also measured prostate cancer-specific and all-cause mortalities in Hispanic/Latino subgroups: Mexican (n= 7,273), Puerto Rican (n= 1,174), South or Central American (n= 2,666), Cuban (n= 747), and Dominican (n= 292). Results: In all racial/ethnic groups, five-year cumulative incidence rates were highest for Non-Hispanic Black men at 15.96% (95% CI: 15.6 - 16.3) and were lowest in Hispanic/Latino men at 13.08% (95% CI: 12.6 - 13.5) and Asian American/Pacific Islander men at 13.33% (95% CI: 12.7 - 13.9). Within ethnic subgroups, Puerto Rican men at 22.06% (95% CI: 19.4 - 25.1) and Cuban men 20.91% (95% CI: 17.8 - 24.5) showed significantly higher five-year all-cause mortality than all other groups. Mexican men showed the third highest rate of all groups with 16.47% (95% CI: 15.4 - 17.6). For five-year prostate cancer-specific mortality, both Non-Hispanic Black and Hispanic/Latino men showed similar rates that were higher than other racial/ethnic groups with 3.39% (95% CI: 3.22 - 3.57) and 3.29% (95% CI: 3.07 - 3.52), respectively. For ethnic subgroups, Puerto Rican men at 5.26% (95% CI: 3.88 - 6.92) and Mexican men at 4.77% (95% CI: 4.19 - 5.40) showed significantly higher five-year prostate cancer-specific mortality than all other groups. Cuban and Dominican men showed high rates of both five-year all-cause and prostate cancer-specific mortality, but without significance. Conclusions: Our findings indicate previously unknown disparities in five-year prostate cancer-specific mortality in Mexican and Puerto Rican men. We also note the increased all-cause mortality within Puerto Rican men diagnosed with prostate cancer, of which may be influenced by comorbid disease. These findings should be further explored and considered in screening and management guidelines. Citation Format: Felix M. Chinea, Vivek N. Patel, Deukwoo Kwon, Chris J. Lopez, Narottam Lamichhane, Sanoj Punnen, Erin Kobetz, Matthew C. Abramowitz, Alan Pollack. Ethnic heterogeneity and prostate cancer mortality in Hispanic/Latino men. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr PR04.

SU-D-202-02: Quantitative Imaging: Correlation Between Image Feature Analysis and the Accuracy of Manually Drawn Contours On PET Images

PURPOSE To evaluate the correlation between image features and the accuracy of manually drawn target contours on synthetic PET images METHODS: A digital PET phantom was used in combination with Monte Carlo simulation to create a set of 26 simulated PET images featuring a variety of tumor shapes and activity heterogeneity. These tumor volumes were used as a gold standard in comparisons with manual contours delineated by 10 radiation oncologist on the simulated PET images. Metrics used to evaluate segmentation accuracy included the dice coefficient, false positive dice, false negative dice, symmetric mean absolute surface distance, and absolute volumetric difference. Image features extracted from the simulated tumors consisted of volume, shape complexity, mean curvature, and intensity contrast along with five texture features derived from the gray-level neighborhood difference matrices including contrast, coarseness, busyness, strength, and complexity. Correlation between these features and contouring accuracy were examined. RESULTS Contour accuracy was reasonably well correlated with a variety of image features. Dice coefficient ranged from 0.7 to 0.90 and was correlated closely with contrast (r=0.43, p=0.02) and complexity (r=0.5, p<0.001). False negative dice ranged from 0.10 to 0.50 and was correlated closely with contrast (r=0.68, p<0.001) and complexity (r=0.66, p<0.001). Absolute volumetric difference ranged from 0.0002 to 0.67 and was correlated closely with coarseness (r=0.46, p=0.02) and complexity (r=0.49, p=0.008). Symmetric mean absolute difference ranged from 0.02 to 1 and was correlated closely with mean curvature (r=0.57, p=0.02) and contrast (r=0.6, p=0.001). CONCLUSION The long term goal of this study is to assess whether contouring variability can be reduced by providing feedback to the practitioner based on image feature analysis. The results are encouraging and will be used to develop a statistical model which will enable a prediction of contour accuracy based purely on image feature analysis.

SU-F-J-69: The Dosimetric Impact of Interfraction Anorectum and Bladder Variability in Prostate Radiation Therapy

PURPOSE In the era of dose escalation and numerous protocols evaluating radiation delivery to the prostate, it is imperative to achieve accurate and standardized daily set up. At the Sylvester Comprehensive Cancer Center, patients are instructed to drink 8 ounces of water 30 minutes prior to RT and follow a low residue diet to ensure that the anorectum is not distended and the bladder is adequately filled. If daily CBCT imaging shows any variation, the patient is removed from the table and drinks water or evacuates their rectum prior to a repeat CBCT. Here we attempt to quantify the efficacy of this procedure. METHODS CBCTs were collected for 5 patients receiving 40 fractions of definitive treatment for prostate cancer. CBCTs were imported into MIM (v6.5.7, Cleveland OH) and the bladder, anorectum, and prostate were contoured. Using the daily registration reviewed by the attending physician, the planning dose was rigidly transferred to the daily CBCT. On days that multiple CBCTs were performed due to inadequate anorectum or bladder preparation, the repeated and final CBCTs were evaluated for variations in V40Gy and V65Gy to both the anorectum and bladder. RESULTS A high level of variability in doses to the anorectum and bladder was found in the scans that were not utilized for treatment. The aggregate lower quartile for the unused versus used CBCTs was 27.2% vs. 16.83% for V40Gy and 8.53% vs. 5.66% for V65Gy bladder. The upper quartiles showed to be 48.88% vs. 41.92% and 21.05% vs. 20.55%. The combined lower quartile for the unused vs. used CBCTs was 8.24% vs. 5.49% for V40Gy and 0.57% vs. 0.0% for V65Gy anorectum. The upper quartiles were 34.35% vs. 33.25% and 18.37% vs. 16.11%. CONCLUSION This study shows that daily imaging is insufficient and that proper bladder and anorectum preparation are essential to deliver proper treatment.

Going the distance: validation of Acuros and AAA at an extended SSD of 400 cm

Accurate dose calculation and treatment delivery is essential for total body irradiation (TBI). In an effort to verify the accuracy of TBI dose calculation at our institution, we evaluated both the Varian Eclipse AAA and Acuros algorithms to predict dose distributions at an extended source-to-surface distance (SSD) of 400 cm. Measurements were compared to calculated values for a 6 MV beam in physical and virtual phantoms at 400 cm SSD using open beams for both 5×5 and 40×40 cm2 field sizes. Inline and crossline profiles were acquired at equivalent depths of 5 cm, 10 cm, and 20 cm. Depth-dose curves were acquired using EBT2 film and an ion chamber for both field sizes. Finally, a RANDO phantom was used to simulate an actual TBI treatment. At this extended SSD, care must be taken using the planning system as there is good relative agreement between measured and calculated profiles for both algorithms, but there are deviations in terms of the absolute dose. Acuros has better agreement than AAA in the penumbra region. PACS number(s): 87.55.kd.Accurate dose calculation and treatment delivery is essential for total body irradiation (TBI). In an effort to verify the accuracy of TBI dose calculation at our institution, we evaluated both the Varian Eclipse AAA and Acuros algorithms to predict dose distributions at an extended source‐to‐surface distance (SSD) of 400 cm. Measurements were compared to calculated values for a 6 MV beam in physical and virtual phantoms at 400 cm SSD using open beams for both 5×5 and 40×40 cm2 field sizes. Inline and crossline profiles were acquired at equivalent depths of 5 cm, 10 cm, and 20 cm. Depth‐dose curves were acquired using EBT2 film and an ion chamber for both field sizes. Finally, a RANDO phantom was used to simulate an actual TBI treatment. At this extended SSD, care must be taken using the planning system as there is good relative agreement between measured and calculated profiles for both algorithms, but there are deviations in terms of the absolute dose. Acuros has better agreement than AAA in the penumbra region. PACS number(s): 87.55.kd

Lack of Association between COX-2 Staining Level and Biochemical Recurrence Following Salvage Radiation Therapy for Recurrent Prostate Cancer.

ObjectiveThe ability to predict which men will experience biochemical recurrence (BCR) after salvage radiation therapy (SRT) for recurrent prostate cancer following radical prostatectomy has potential for improvement. Cyclooxygenase-2 (COX-2) overexpression has previously correlated with poor clinical outcomes following primary treatment for prostate cancer; however, its predictive ability in the specific setting of SRT has not been examined to date. This study evaluated the association between COX-2 staining intensity and BCR following SRT for recurrent prostate cancer.MethodsWe utilized a cohort of 151 patients who underwent SRT between July 1987 and July 2003. COX-2 staining intensity in primary tumor samples was detected using monoclonal antibodies and quantified using a computer-assisted method. The association between COX-2 staining intensity and BCR was evaluated using multivariable Cox regression models.ResultsWhen examining COX-2 staining level as three-level categorical variable (low, moderate, high) based on approximate sample tertiles, there was no evidence of an association with BCR (P = 0.18). More specifically, in comparison to patients with low staining intensity, there was no significant difference in risk of BCR for moderate (relative risk [RR], 1.17; P = 0.56) or high (RR, 0.72; P = 0.22) COX-2 staining intensity patients. This lack of association was also observed when considering COX-2 staining intensity as a continuous variable (RR, 0.83; P = 0.15).ConclusionOur results indicate that COX-2 staining intensity is likely of little use in discriminating prognosis of SRT. It appears that the search for prognostic factors associated with BCR should continue elsewhere in order to further enhance patient selection for SRT.