Stephanie T. Chang

Gemcitabine Chemotherapy and Single-Fraction Stereotactic Body Radiotherapy for Locally Advanced Pancreatic Cancer

PURPOSE Fractionated radiotherapy and chemotherapy for locally advanced pancreatic cancer achieves only modest local control. This prospective trial evaluated the efficacy of a single fraction of 25 Gy stereotactic body radiotherapy (SBRT) delivered between Cycle 1 and 2 of gemcitabine chemotherapy. METHODS AND MATERIALS A total of 16 patients with locally advanced, nonmetastatic, pancreatic adenocarcinoma received gemcitabine with SBRT delivered 2 weeks after completion of the first cycle. Gemcitabine was resumed 2 weeks after SBRT and was continued until progression or dose-limiting toxicity. The gross tumor volume, with a 2-3-mm margin, was treated in a single 25-Gy fraction by Cyberknife. Patients were evaluated at 4-6 weeks, 10-12 weeks, and every 3 months after SBRT. RESULTS All 16 patients completed SBRT. A median of four cycles (range one to nine) of chemotherapy was delivered. Three patients (19%) developed local disease progression at 14, 16, and 21 months after SBRT. The median survival was 11.4 months, with 50% of patients alive at 1 year. Patients with normal carbohydrate antigen (CA)19-9 levels either at diagnosis or after Cyberknife SBRT had longer survival (p <0.01). Acute gastrointestinal toxicity was mild, with 2 cases of Grade 2 (13%) and 1 of Grade 3 (6%) toxicity. Late gastrointestinal toxicity was more common, with five ulcers (Grade 2), one duodenal stenosis (Grade 3), and one duodenal perforation (Grade 4). A trend toward increased duodenal volumes radiated was observed in those experiencing late effects (p = 0.13). CONCLUSION SBRT with gemcitabine resulted in comparable survival to conventional chemoradiotherapy and good local control. However, the rate of duodenal ulcer development was significant.

Impact of Integrated PET/CT on Variability of Target Volume Delineation in Rectal Cancer

Several studies have demonstrated substantial variability among individual radiation oncologists in defining target volumes using computed tomography (CT). The objective of this study was to determine the impact of combined positron emission tomography and computed tomography (PET/CT) on inter-observer variability of target volume delineation in rectal cancer. We also compared the relative concordance of two PET imaging tracers, 18F-fluorodeoxyglucose (FDG) and 18F-fluorodeoxythymidine (FLT), against conventional computed tomography (CT). Six consecutive patients with locally advanced rectal cancer were enrolled onto an institutional protocol involving preoperative chemoradiotherapy and correlative studies including FDG- and FLT-PET scans acquired in the treatment position. Using these image data sets, four radiation oncologists independently delineated primary and nodal gross tumor volumes (GTVp and GTVn) for a hypothetical boost treatment. Contours were first defined based on CT alone with observers blinded to the PET images, then based on combined PET/CT. An inter-observer similarity index (SI), ranging from a value of 0 for complete disagreement to 1 for complete agreement of contoured voxels, was calculated for each set of volumes. For primary gross tumor volume (GTVp), the difference in estimated SI between CT and FDG was modest (CT SI = 0.77 vs. FDG SI = 0.81), but statistically significant (p = 0.013). The SI difference between CT and FLT for GTVp was also slight (FLT SI = 0.80) and marginally non-significant (p < 0.082). For nodal gross tumor volume, (GTVn), SI was significantly lower for CT based volumes with an estimated SI of 0.22 compared to an estimated SI of 0.70 for FDG-PET/CT (p < 0.0001) and an estimated SI of 0.70 for FLT-PET/CT (p < 0.0001). Boost target volumes in rectal cancer based on combined PET/CT results in lower inter-observer variability compared with CT alone, particularly for nodal disease. The use of FDG and FLT did not appear to be different from this perspective.

Identification of a biomarker panel using a multiplex proximity ligation assay improves accuracy of pancreatic cancer diagnosis

BackgroundPancreatic cancer continues to prove difficult to clinically diagnose. Multiple simultaneous measurements of plasma biomarkers can increase sensitivity and selectivity of diagnosis. Proximity ligation assay (PLA) is a highly sensitive technique for multiplex detection of biomarkers in plasma with little or no interfering background signal.MethodsWe examined the plasma levels of 21 biomarkers in a clinically defined cohort of 52 locally advanced (Stage II/III) pancreatic ductal adenocarcinoma cases and 43 age-matched controls using a multiplex proximity ligation assay. The optimal biomarker panel for diagnosis was computed using a combination of the PAM algorithm and logistic regression modeling. Biomarkers that were significantly prognostic for survival in combination were determined using univariate and multivariate Cox survival models.ResultsThree markers, CA19-9, OPN and CHI3L1, measured in multiplex were found to have superior sensitivity for pancreatic cancer vs. CA19-9 alone (93% vs. 80%). In addition, we identified two markers, CEA and CA125, that when measured simultaneously have prognostic significance for survival for this clinical stage of pancreatic cancer (p < 0.003).ConclusionsA multiplex panel assaying CA19-9, OPN and CHI3L1 in plasma improves accuracy of pancreatic cancer diagnosis. A panel assaying CEA and CA125 in plasma can predict survival for this clinical cohort of pancreatic cancer patients.

RevaTen platelet-rich plasma improves cardiac function after myocardial injury.

OBJECTIVE Cell therapy is an exciting area of investigation for repair of injured myocardial tissue. Platelet-rich plasma (PRP) is an autologous fractionation of whole blood containing high concentrations of growth factors including vascular endothelial growth factor and insulin-like growth factor, among many others. PRP has been shown to safely and effectively enhance healing of musculoskeletal tissue primarily by reparative cell signaling. Despite a growing body of evidence on PRPs safety and efficacy, limited studies have been performed using PRP in cardiovascular tissues. Utilizing a murine myocardial permanent ligation and ischemia/reperfusion model, this study sought to determine whether RevaTen PRP (Menlo Park, CA, USA), a proprietary formulation of PRP, improves cardiac function as measured by left ventricular ejection fraction (LVEF). METHODS Via thoracotomy, the left anterior descending arteries (LAD) of 28 mice were occluded by suture either permanently or for 45 min to induce ischemic injury and then reperfused. Mice undergoing permanent ligation had intramyocardial injections of either RevaTen PRP (n=5) or phosphate-buffered saline (PBS; n=4). Magnetic resonance (MR) imaging was performed to calculate LVEF at 7 days. Mice undergoing ischemia and reperfusion had intramyocardial injections of either PRP (n=10) or PBS (n=9) and underwent MR imaging to calculate LVEF at 21 days. Hearts were harvested for histologic examination following imaging. RESULTS Compared with PBS controls, RevaTen PRP-treated animals that underwent LAD ligation had a 38% higher LVEF 7 days after injury (PRP=36.1±6.1%; PBS=26.4±3.6%, P=.027). Compared with PBS controls, PRP-treated animals who underwent ischemia-reperfusion of the LAD had a 28% higher LVEF 21 days after injury (PRP=37.6±4.8%, control=29.3±9.7%, P=.038). Histologic analysis suggested the presence of more scar tissue in the control group compared to the PRP-treated animals. CONCLUSION MR imaging demonstrated a positive effect of RevaTen PRP on left ventricular function in both a ligation and ischemia-reperfusion murine model. Our results suggest RevaTen PRP should be investigated further as a potential point-of-care biologic treatment following myocardial injury.

Stereotactic Body Radiotherapy for Unresectable Pancreatic Cancer

Pancreatic cancer is a devastating disease with few effective treatment modalities. Recent technological advances have made possible the delivery of single-fraction stereotactic body radiotherapy (SBRT) to patients with locally advanced pancreatic tumors. This paper presents experience at Stanford University with SBRT for patients with unresectable pancreatic cancer. Pancreatic tumors of up to 100 cm3 could be treated. Patients achieved greater than 90% local control for the remainder of their lives. Currently, the standard dose for pancreatic tumors treated at this institution is 25 Gy given in a single fraction. Four-dimensional CT and PET scans have been essential for optimal treatment planning. PET-CT scanning may be a more effective method for evaluating tumor response than conventional CT scanning. Adjuvant systemic therapies could be administered in coordination with SBRT. SBRT is an effective method of treating patients resulting in excellent local control. Current research is aimed at defining the optimal method of combining this treatment with other cancer therapies.

Sonography of the normal appendix: its varied appearance and techniques to improve its visualization.

Abstract The sonographic identification of the normal appendix is crucial to the success of ultrasound as an effective screening method for diagnosing acute appendicitis. The normal appendix can be challenging to identify on sonography, however, because it is a narrow tubular structure and has variable sonographic appearances. Moreover, the tip of the appendix can be quite variable in location. In this article, we review the various sonographic appearances of the normal appendix and highlight strategies to improve its visualization.

Metastatic Melanoma in the Chest and Abdomen: The Great Radiologic Imitator

Metastatic melanoma causes an unpredictable variety of manifestations in the chest and abdomen that may be indistinguishable from other diseases by imaging alone. Melanoma metastases commonly involve the lymph nodes, lungs, liver, and small bowel, but virtually any organ can be affected. Newer modalities, such as contrast-enhanced ultrasound and whole-body magnetic resonance imaging, may provide more sensitive detection of metastatic melanoma for diagnosis, staging, and surveillance. An understanding of the predominantly hematogenous nature of metastatic spread by melanoma as well as a high index of suspicion in any patient with a history of melanoma may allow for more precise and confident diagnosis.

Imaging of Primary Gastrointestinal Lymphoma

Primary gastrointestinal (GI) lymphoma most often arises from stomach, small bowel, or colon. The 2 most common subtypes of primary GI lymphoma include low-grade mucosa-associated lymphoid tissue lymphoma, strongly associated with Helicobacter pylori infection, and high-grade diffuse, large B-cell lymphoma. Primary GI lymphoma demonstrates a myriad of imaging manifestations that can commonly mimic other pathologies. Timely and accurate diagnosis remains important because treatment and prognosis of primary GI lymphoma differ significantly from other GI malignancies and even lymphoma of other primary sites.

The imaging findings of typical and atypical genital and gynecologic infections

Genital and gynecologic infections are common medical problems, affecting millions of women worldwide. The spectrum of these infections extends from the labia, including processes such as necrotizing fasciitis and anogenital warts, to the upper reproductive tracts in conditions including endometritis and pelvic inflammatory disease. Although often a clinical diagnosis, the radiologist plays an important role in determining the etiology of acute abdominal and pelvic pain as well as facilitating the diagnosis for cases which are not clinically straightforward. Imaging also plays an important role in assessing the complications and sequelae of these conditions, including infertility, chronic abdominal and pelvic pain, and pelvic adhesions. Familiarity with the appearances of these infections, their complications, and their potential mimics on sonography, computed tomography, magnetic resonance imaging, and hysterosalpingography is important for timely diagnosis and optimal clinical outcomes.

Sonographic Differentiation of Complicated From Uncomplicated Appendicitis: Implications for Antibiotics-First Therapy

To evaluate sonographic findings as indicators of complicated versus uncomplicated appendicitis in the setting of known appendicitis, a necessary distinction in deciding whether to proceed with antibiotic therapy or with appendectomy.