Robert Reznik

Phenotypic Manifestations of Inflammatory Bowel Disease Differ Between Hispanics and Non-Hispanic Whites: Results of a Large Cohort Study

OBJECTIVES:Hispanics are the fastest growing minority in the United States, yet few studies have examined the phenotypes of inflammatory bowel disease (IBD) in this population. No studies compare IBD presentation between foreign and US-born Hispanics. Our aim was to compare phenotypic characteristics of IBD between Hispanics and non-Hispanic Whites (NHWs), as well as between US-born and foreign-born Hispanics.METHODS:We retrospectively identified cohorts of adult IBD patients from 1998 to 2009 and compared ethnic variation in phenotype, including disease type (Crohns disease or ulcerative colitis (UC)), extra-intestinal manifestations (EIMs), Montreal classification, surgeries, hospitalizations, and medication prescription.RESULTS:A total of 325 patients were included; 208 were Hispanics. Foreign-born Hispanics, accounting for 68% of the total, were diagnosed at an older age than US-born Hispanics and NHWs (45 vs. 25 and 27, respectively, P<0.05). Foreign-born Hispanics manifested more UC than US-born Hispanics or NHWs (59.9% vs. 41% and 28.2%, respectively, P<0.05). No difference was noted in the prevalence of EIMs between Hispanics and NHWs. More upper gastrointestinal tract Crohns was observed in NHWs (12.5% vs. 3.9%, P<0.05). The incidence density rate of IBD-related surgeries in NHWs was higher than in Hispanics (22.9 vs. 7.3 surgeries/100 person-years, P<0.01, hazard ratio: 0.3, 95% confidence interval: 0.14–0.5). Hispanic patients had fewer prescriptions for biologics and immunomodulators than NHWs (22.2% vs. 55.6%, P<0.01 and 35.7% vs. 53.8%, P<0.01, respectively).CONCLUSIONS:This study demonstrates differences in IBD presentation among NHW, US-born Hispanic, and foreign-born Hispanic groups. Further investigation to identify environmental and genetic differences between ethnic groups affected by IBD is warranted.

Four-Dimensional Magnetic Resonance Imaging With 3-Dimensional Radial Sampling and Self-Gating-Based K-Space Sorting: Early Clinical Experience on Pancreatic Cancer Patients.

PURPOSE To apply a novel self-gating k-space sorted 4-dimensional MRI (SG-KS-4D-MRI) method to overcome limitations due to anisotropic resolution and rebinning artifacts and to monitor pancreatic tumor motion. METHODS AND MATERIALS Ten patients were imaged using 4D-CT, cine 2-dimensional MRI (2D-MRI), and the SG-KS-4D-MRI, which is a spoiled gradient recalled echo sequence with 3-dimensional radial-sampling k-space projections and 1-dimensional projection-based self-gating. Tumor volumes were defined on all phases in both 4D-MRI and 4D-CT and then compared. RESULTS An isotropic resolution of 1.56 mm was achieved in the SG-KS-4D-MRI images, which showed superior soft-tissue contrast to 4D-CT and appeared to be free of stitching artifacts. The tumor motion trajectory cross-correlations (mean ± SD) between SG-KS-4D-MRI and cine 2D-MRI in superior-inferior, anterior-posterior, and medial-lateral directions were 0.93 ± 0.03, 0.83 ± 0.10, and 0.74 ± 0.18, respectively. The tumor motion trajectories cross-correlations between SG-KS-4D-MRI and 4D-CT in superior-inferior, anterior-posterior, and medial-lateral directions were 0.91 ± 0.06, 0.72 ± 0.16, and 0.44 ± 0.24, respectively. The average standard deviation of gross tumor volume calculated from the 10 breathing phases was 0.81 cm(3) and 1.02 cm(3) for SG-KS-4D-MRI and 4D-CT, respectively (P=.012). CONCLUSIONS A novel SG-KS-4D-MRI acquisition method capable of reconstructing rebinning artifact-free, high-resolution 4D-MRI images was used to quantify pancreas tumor motion. The resultant pancreatic tumor motion trajectories agreed well with 2D-cine-MRI and 4D-CT. The pancreatic tumor volumes shown in the different phases for the SG-KS-4D-MRI were statistically significantly more consistent than those in the 4D-CT.

Genetic determinants and potential therapeutic targets for pancreatic adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer deaths in both men and women in the United States, carrying a 5-year survival rate of approximately 5%, which is the poorest prognosis of any solid tumor type. Given the dismal prognosis associated with PDAC, a more thorough understanding of risk factors and genetic predisposition has important implications not only for cancer prevention, but also for screening techniques and the development of personalized therapies. While screening of the general population is not recommended or practicable with current diagnostic methods, studies are ongoing to evaluate its usefulness in people with at least 5- to 10-fold increased risk of PDAC. In order to help identify high-risk populations who would be most likely to benefit from early detection screening tests for pancreatic cancer, discovery of additional pancreatic cancer susceptibility genes is crucial. Thus, specific gene-based, gene-product, and marker-based testing for the early detection of pancreatic cancer are currently being developed, with the potential for these to be useful as potential therapeutic targets as well. The goal of this review is to provide an overview of the genetic basis for PDAC with a focus on germline and familial determinants. A discussion of potential therapeutic targets and future directions in screening and treatment is also provided.

Dosimetric evaluation of simultaneous integrated boost during stereotactic body radiation therapy for pancreatic cancer

Stereotactic body radiation therapy (SBRT) provides a promising way to treat locally advanced pancreatic cancer and borderline resectable pancreatic cancer. A simultaneous integrated boost (SIB) to the region of vessel abutment or encasement during SBRT has the potential to downstage otherwise likely positive surgical margins. Despite the potential benefit of using SIB-SBRT, the ability to boost is limited by the local geometry of the organs at risk (OARs), such as stomach, duodenum, and bowel (SDB), relative to tumor. In this study, we have retrospectively replanned 20 patients with 25Gy prescribed to the planning target volume (PTV) and 33~80Gy to the boost target volume (BTV) using an SIB technique for all patients. The number of plans and patients able to satisfy a set of clinically established constraints is analyzed. The ability to boost vessels (within the gross target volume [GTV]) is shown to correlate with the overlap volume (OLV), defined to be the overlap between the GTV + a 1(OLV1)- or 2(OLV2)-cm margin with the union of SDB. Integral dose, boost dose contrast (BDC), biologically effective BDC, tumor control probability for BTV, and normal tissue complication probabilities are used to analyze the dosimetric results. More than 65% of the cases can deliver a boost to 40Gy while satisfying all OAR constraints. An OLV2 of 100cm(3) is identified as the cutoff volume: for cases with OLV2 larger than 100cm(3), it is very unlikely the case could achieve 25Gy to the PTV while successfully meeting all the OAR constraints.

Surgical Excision and Adjuvant Brachytherapy vs External Beam Radiation for the Effective Treatment of Keloids: 10-Year Institutional Retrospective Analysis

Background Surgically excised keloids reportedly recur at a rate of >45%. Post-excision radiation (RT) has been delivered via external beam radiotherapy (EBRT) or interstitial high dose rate (HDR) brachytherapy. Despite historical data showing 10% to 20% keloid recurrences with post-excision RT, there is a paucity of high-quality evidence comparing keloid recurrences between the two RT modalities. Objectives We performed the largest single-institution case-control retrospective study (2004-2014) of keloid recurrence rates and complications between post-excision EBRT and HDR brachytherapy. Methods One-hundred and twenty-eight patients, with 264 keloid lesions, were treated by excision alone (n = 28), post-excision EBRT (n = 197), or post-excision HDR brachytherapy (n = 39). Patient and keloid recurrence data were analyzed using mixed effect Cox regression modeling with a statistical threshold of P < .05. Results Fifty-four percent of keloids recurred after surgical excision alone (9-month median follow up); 19% of keloids recurred with post-excision EBRT (42-month median follow up); 23% of keloids recurred with post-excision brachytherapy (12-month median follow up). Adjuvant EBRT and brachytherapy each showed significant control of keloid recurrence compared to excision alone (P < .01). EBRT significantly delayed the time of keloid recurrence over brachytherapy by a mean difference of 2.5 years (P < .01). Conclusions Post-excision RT shows significant reduction in keloid recurrence compared to excision alone. While the recurrence control rates are not statistically different between EBRT and brachytherapy, keloids treated with EBRT recurred significantly later than those treated by HDR brachytherapy by a mean of 2.5 years. Further workup with a randomized control study will help to refine optimal adjuvant RT treatment. Level of Evidence: 3

Clinical experience using a video‐guided spirometry system for deep inhalation breath‐hold radiotherapy of left‐sided breast cancer

The purpose was to report clinical experience of a video‐guided spirometry system in applying deep inhalation breath‐hold (DIBH) radiotherapy for left‐sided breast cancer, and to study the systematic and random uncertainties, intra‐ and interfraction motion and impact on cardiac dose associated with DIBH. The data from 28 left‐sided breast cancer patients treated with spirometer‐guided DIBH radiation were studied. Dosimetric comparisons between free‐breathing (FB) and DIBH plans were performed. The distance between the heart and chest wall measured on the digitally reconstructed radiographs (DRR) and MV portal images, dDRR(DIBH) and dport(DIBH), respectively, was compared as a measure of DIBH setup uncertainty. The difference (Δd) between dDRR(DIBH) and dport(DIBH) was defined as the systematic uncertainty. The standard deviation of Δd for each patient was defined as the random uncertainty. MV cine images during radiation were acquired. Affine registrations of the cine images acquired during one fraction and multiple fractions were performed to study the intra‐ and interfraction motion of the chest wall. The median chest wall motion was used as the metric for intra‐ and interfraction analysis. Breast motions in superior–inferior (SI) direction and “AP” (defined on the DRR or MV portal image as the direction perpendicular to the SI direction) are reported. Systematic and random uncertainties of 3.8 mm and 2 mm, respectively, were found for this spirometer‐guided DIBH treatment. MV cine analysis showed that intrafraction chest wall motions during DIBH were 0.3 mm in “AP” and 0.6 mm in SI. The interfraction chest wall motions were 3.6 mm in “AP” and 3.4 mm in SI. Utilization of DIBH with this spirometry system led to a statistically significant reduction of cardiac dose relative to FB treatment. The DIBH using video‐guided spirometry provided reproducible cardiac sparing with minimal intra‐ and interfraction chest wall motion, and thus is a valuable adjunct to modern breast treatment techniques. PACS number: 87.55.kh, 87.55.ne, 87.55.tg

Palliative radiation therapy for superior vena cava syndrome in metastatic Wilms tumor using 10XFFF and 3D surface imaging to avoid anesthesia in a pediatric patient—a teaching case

a Department of Radiation Oncology, University of California Los Angeles, Los Angeles, California b Children’s Hospital Los Angeles, Los Angeles, California c University of Cincinnati College of Medicine, Cincinnati, Ohio d Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California e Department of Radiation Oncology, Keck School of Medicine of the University of Southern California, Los Angeles, California

TH-EF-BRA-07: Evaluation of Internal Target Volume Derived From a Prototype 4D-MRI Sequence with 3D Radial Stack-Of-Stars Trajectory and K-Space Self-Gating

PURPOSE 4D-MRI based on resorting of 2D-cine-MRI images shows great potential to assess tumor motion more accurately compared to 4D-CT, however, it suffers from low through-plane resolution and stitching artifacts. 4D-MRI based on 3D acquisition results in stitching-artifact-free images with high in-plane and through-plane resolutions. In this study, we report our early clinical experience of a prototype 4D-MRI sequence with 3D stack-of-stars (SOS) trajectory for internal target volume (ITV) definition. METHODS Ten patients with 13 total lesions (7 pancreatic, 1 lung with 2 lesions, 1 liver with 3 lesions and 1 esophagus) were recruited. 4D-MRI used in-plane radial and through-plane Cartesian sampling. Two imaging orientations, i.e. axial slab (A) and coronal slab (B), were compared. ITVs were derived from 3-bin (ITV3), 5-bin (ITV5) and 10-bin (ITV10) reconstruction protocols. ITV5 was set as standard and minimum expansion of ITV3 needed to encompass ITV5 was derived. Similarity index was calculated from ITV3 and ITV5 (SI3/5), and ITV10 and ITV5 (SI10/5). Imaging noise was calculated for both method A and B. Wilcoxon-rank-sum test was performed with a p value <0.05 deemed as significant. RESULTS No significant difference (p=0.34) was observed from method A and B, indicating a uniform imaging noise distribution from 3D acquisition. Imaging noise and artifacts were visually different from different binning protocols, with more bins resulting in more noise, more artifacts and larger ITV. On average, ITV differs by 7% (1%-19%) comparing ITV3 with ITV5 for the patient cohort. For the pancreas sub-group, ITV differs by 4% (1%-6%). An average of 2.3mm (2mm-3mm) expansion was needed for ITV3 to encompass ITV5. SI10/5 was 0.93±0.03 (mean±σ) and SI3/5 was 0.95±0.03. CONCLUSION 4D-MRI with 3D SOS trajectory was evaluated on 10 patients. Significant difference in ITV was observed with different binning protocols. Imaging noise was similar irrespective of the imaging orientations. This work is partially supported by NIH R03CA173273 and CTSI core voucher award.

TH‐CD‐204‐01: FEATURED PRESENTATION and BEST IN PHYSICS (JOINT IMAGING‐THERAPY): Novel SG‐KS‐4D‐MRI Sequence Reduces 4D Rebinning Artifacts and Improves GTV Contouring Consistency for Pancreatic Cancer Patients

Purpose: Dynamic magnetic resonance imaging (MRI) has been used to characterize tumor motion but real time acquisition has been limited to 2-dimensions. Methods have been developed to reconstruct four-dimensional MRI (4D-MRI) based on time-stamped 2D images or 2D K-space data. These methods suffer from anisotropic resolution and rebinning artifacts. We have developed a self-gating based K-space sorted 4D-MRI (SG-KS-4D-MRI) method to overcome these limitations and in this study apply it to monitoring organ motion of pancreatic cancer patients. Methods: Ten patients were imaged using 4D-CT, cine 2D-MRI and the SG-KS-4D-MRI method, which is a spoiled gradient recalled echo (GRE) sequence with 3D radial-sampling K-space projections and 1D projection-based self-gating. Tumor volumes were drawn at the end of exhalation phases in the 4D-MRI and 4D-CT, and mapped to the other phases using deformable registration. The tumor volumes and motion trajectories were compared. Results: An isotropic resolution of 1.6 mm was achieved in the SG-KS-4D-MRI images, which showed superior soft tissue contrast to 4D-CT and appeared to be free of rebinning artifacts. SG-KS-4D-MRI was able to detect out-of-plane tumor motion and showed good correlation with 4D-CT and cine 2D-MRI in superior-inferior direction with a correlation coefficient of 0.91±0.06 and 0.93±0.03, respectively. The average standard deviation of GTV (GTV_σ) calculated from ten breathing phases were 0.81 cc and 1.02 cc for SG-KS-4D-MRI and 4D-CT (p=0.004) respectively. Conclusion: A novel SG-KS-4D-MRI acquisition method capable of reconstructing rebinning-artifact-free high resolution 4D-MRI images was used to quantify pancreas tumor motion. The resultant pancreatic tumor motion trajectories better agreed with 2D-cine-MRI and 4D-CT in the SI direction than the other 2 directions due to smaller motions in those directions. The pancreatic tumor volumes derived using SG-KS-4D-MRI were significantly more consistent than those from the 4D-CT.This work is supported in part by NIH grant 1R03CA173273-01. This study is supported in part by NIH 1R03CA173273