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At least 37 records · Page 2

Gravity in mammalian organ development: differentiation of cultured lung and pancreas rudiments during spaceflight

Organ culture of embryonic mouse lung and pancreas rudiments has been used to investigate development and differentiation, and to assess the effects of microgravity on culture differentiation, during orbital spaceflight of the shuttle Endeavour (mission STS-54). Lung rudiments continue to grow and branch during spaceflight, an initial result that should allow future detailed study of lung morphogenesis in microgravity. Cultured embryonic pancreas undergoes characteristic exocrine acinar tissue and endocrine islet tissue differentiation during spaceflight, and in ground controls. The rudiments developing in the microgravity environment of spaceflight appear to grow larger than their ground counterparts, and they may have differentiated more rapidly than controls, as judged by exocrine zymogen granule presence.

STS-54 Shuttle Project↗

Differentiation of pancreatic neuroendocrine tumors from pancreas renal cell carcinoma metastases on CT using qualitative and quantitative features

Purpose: To assess qualitative and quantitative imaging features on enhanced CT that may differentiate pancreatic neuroendocrine tumors (PNETs) from pancreatic renal cell carcinoma (RCC) metastases. Methods: This IRB-approved multi-center retrospective case–control study compared 43 resected PNETs and 28 resected RCC metastases with pre-operative enhanced CT identified consecutively between 2003 and 2017. Two blinded radiologists (R1/R2) independently assessed tumor location, attenuation (relative to pancreas), composition (solid/cystic/mixed), homogeneity (homogeneous/heterogeneous), calcification, multiplicity, and for main pancreatic duct (MPD) dilation. Tumors were segmented for quantitative texture analysis. Data were analyzed with Chi square, logistic regression, and receiver operating characteristic (ROC). Inter-observer agreement was assessed (Cohen’s kappa). Results: There was no difference in age, gender, location, attenuation, or composition (P > 0.05) between groups. PNETs were larger than RCC metastases (37 ± 23 mm vs. 26 ± 21 mm, P = 0.038), more frequently solitary (P < 0.001), subjectively more heterogeneous (P = 0.033/0.144, R1/R2), and associated with calcification (P = 0.002/0.004) and MPD dilation (P = 0.025/0.006). Agreement for subjective features was moderate-to-almost perfect (K = 0.4879–0.9481). Quantitative texture analysis showed higher entropy in PNETs (6.32 ± 0.49 versus 5.96 ± 0.53; P = 0.004) with no difference in other features studied (P > 0.05). Entropy had ROC area under the curve for diagnosis of PNET of 0.77 ± 0.06, with optimal sensitivity/specificity of 71.4/79.1%. Conclusions: Compared to pancreatic RCC metastases, PNETs are larger, more frequently solitary, contain calcification, show MPD dilation, and are subjectively and quantitatively more heterogeneous tumors.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

110 Patients with adenosquamous carcinomas of the pancreas (PASC): imaging differentiation of small (≤ 3 cm) versus large (> 3 cm) tumors

Objective: This study examined radiological imaging features of small (≤ 3 cm) and large (> 3 cm) adenosquamous carcinomas of the pancreas (PASC) lesions to better understand the morphology of these lesions. Methods: Images from 110 patients with pathologically proven PASC (80 males and 30 females, mean age: 62.6 years) were retrospectively reviewed. Two radiologists analyzed images and reached a consensus regarding the following features: location, shape, margins, presence of solid and necrotic components, rim enhancement, density/intensity during the portal venous phase, invasion of surrounding organs, vascular invasion, venous tumor thrombus formation, and enlarged lymph nodes. Differences in the imaging features between the two groups were evaluated with the Chi-square test or Fisher’s exact test. Results: There were 41 small PASC lesions (mean age: 60.59 years) and 69 large PASC lesions (63.74 years). Statistical analysis demonstrated significant differences in the location, shape, adjacent organ and vessel invasion, and venous tumor thrombus formation (P < 0.05). Small PASC lesions were more frequently detected in the pancreatic head and had an ovoid shape. There was no significant difference in the presence of solid and necrotic components (P = 0.090), including approximately 3/4 of the lesions with necrosis and 1/4 purely solid lesions, enlarged lymph nodes (P = 0.068) and other features. Conclusion: Regardless of the tumor size, 75% of PASC lesions present with central necrosis while 25% are purely solid. Small PASC lesions can be associated with lymph node metastasis at a relatively early stage. Large PASC lesions are likely to invade adjacent tissues and be associated with venous tumor thrombus formation.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Demonstration of Safety and Feasibility of Hydrogel Marking of the Pancreas–Duodenum Interface for Image Guided Radiation Therapy (IGRT) in a Porcine Model: Implications in IGRT for Pancreatic Cancer Patients

To test the feasibility and safety of injecting a high-contrast hydrogel marker at the head of the pancreas (HOP) and duodenum interface and assesses the marker visibility on cone beam computed tomography (CBCT) to localize this important boundary during image guided radiation therapy in a porcine model.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

An Interpretable Planning Bot for Pancreas Stereotactic Body Radiation Therapy

Pancreas stereotactic body radiation therapy (SBRT) treatment planning requires planners to make sequential, time-consuming interactions with the treatment planning system to reach the optimal dose distribution. We sought to develop a reinforcement learning (RL)–based planning bot to systematically address complex tradeoffs and achieve high plan quality consistently and efficiently.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

SU-E-J-226: Propagation of Pancreas Target Contours On Respiratory Correlated CT Images Using Deformable Image Registration

Purpose: Respiratory Correlated CT (RCCT) scans to assess intra-fraction motion among pancreatic cancer patients undergoing radiotherapy allow for dose sparing of normal tissues, in particular for the duodenum. Contour propagation of the gross tumor volume (GTV) from one reference respiratory phase to 9 other phases is time consuming. Deformable image registration (DIR) has been successfully used for high contrast disease sites but lower contrast for pancreatic tumors may compromise accuracy. This study evaluates the accuracy of Fast Free Form (FFF) registration-based contour propagation of the GTV on RCCT scans of pancreas cancer patients. Methods: Twenty-four pancreatic cancer patients were retrospectively studied; 20 had tumors in the pancreatic head/neck, 4 in the body/tail. Patients were simulated with RCCT and images were sorted into 10 respiratory phases. A radiation oncologist manually delineated the GTV for 5 phases (0%, 30%, 50%, 70% and 90%). The FFF algorithm was used to map deformations between the EE (50%) phase and each of the other 4 phases. The resultant deformation fields served to propagate GTV contours from EE to the other phases. The Dice Similarity Coefficient (DSC), which measures agreement between the DIR-propagated and manually-delineated GTVs, was used to quantitatively examine DIR accuracy. Results: Average DSC over all scans and patients is 0.82 and standard deviation is 0.09 (DSC range 0.97–0.57). For GTV volumes above and below the median volume of 20.2 cc, a Wilcoxon rank-sum test shows significantly different DSC (p=0.0000002). For the GTVs above the median volume, average +/− SD is 0.85 +/− 0.07; and for the GTVs below, the average +/− SD is 0.75 +/−0.08. Conclusion: For pancreatic tumors, the FFF DIR algorithm accurately propagated the GTV between the images in different phases of RCCT, with improved performance for larger tumors.

60 APPLIED LIFE SCIENCES↗

TU-AB-BRA-11: Indications for Online Adaptive Radiotherapy Based On Dosimetric Consequences of Interfractional Pancreas-To-Duodenum Motion in MRI-Guided Pancreatic Radiotherapy

Purpose: Dose limiting structures, such as the duodenum, render the treatment of pancreatic cancer challenging. In this multi-institutional study, we assess dosimetric differences caused by interfraction pancreas-to-duodenum motion using MR-IGRT to determine the potential impact of adaptive replanning. Methods: Ten patients from two institutions undergoing MRI-guided radiotherapy with conventional fractionation (n=5) or SBRT (n=5) for pancreatic cancer were included. Initial plans were limited by duodenal dose constraints of 50 Gy (0.5 cc)/31 Gy (0.1 cc) for conventional/SBRT with prescriptions of 30 Gy/5 fractions (SBRT) and 40–50 Gy/25 fractions (conventional). Daily volumetric MR images were acquired under treatment conditions on a clinical MR-IGRT system. The correlation was assessed between interfractional GTV-to-duodenum positional variation and daily recalculations of duodenal dose metrics. Positional variation was quantified as the interfraction difference in Hausdorff distance from simulation baseline (ΔHD) between the GTV and proximal duodenal surface, or volume overlap between GTV and duodenum for cases with HD{sub 0}=0 (GTV abutting duodenum). Adaptation was considered indicated when daily positional variations enabled dose escalation to the target while maintaining duodenal constraints. Results: For fractions with ΔHD>0 (n=14, SBRT only), the mean interfraction duodenum dose decrease from simulation to treatment was 44±53 cGy (maximum 136 cGy). A correlation was found between ΔHD and dosimetric difference (R{sup 2}=0.82). No correlation was found between volume of overlap and dosimetric difference (R{sup 2}=0.31). For 89% of fractions, the duodenum remained overlapped with the target and the duodenal dose difference was negligible. The maximum observed indication for adaptation was for interfraction ΔHD=11.6 mm with potential for adaptive dose escalation of 136 cGy. Conclusion: This assessment showed that Hausdorff distance was a reasonable metric to use to determine the indication for adaptation. Adaptation was potentially indicated in 11% of the treatments (fractions where GTV-to-duodenum distance increased from simulation), with a feasible average dose escalation of 7.0%. MB, LH, JO, RK, PP: research and/or travel funding from ViewRay Inc. PP: research grant from Varian Medical Systems and Philips Healthcare.

60 APPLIED LIFE SCIENCES↗

Surgical Resection for Metastatic Tumors in the Pancreas: A Single-Center Experience and Systematic Review

Background: Metastatic lesion to the pancreas accounts for approximately 2% of pancreatic neoplasms. There is no prospective, randomized or case-controlled study evaluating the role of pancreatic metastasectomy. Methods: The PubMed, EMBASE, and Cochrane Library electronic databases were searched for studies published between January 1, 2001 and December 31, 2017. Studies with five or more patients who received pancreatic metastasectomy and data from our institution (29 patients) were included. The Kaplan–Meier method was used for survival analysis. Results: A total of 414 patients from 20 institutions who underwent pancreatic resections were included. Of the reported 31 kinds of primary neoplasms, renal-cell carcinoma (RCC) comprised the most (54.3%). At the time of diagnosis, although 40.3% patients were asymptomatic, abdominal pain (34.8%) and jaundice (20.6%) were relatively common. As for surgical type, pancreatoduodenectomy, total pancreatectomy, distal pancreatectomy, and enucleation took up 37.9%, 11.4%, 43.5%, and 7.2% respectively. The mortality and morbidity rates were 1.4% and 48.3% respectively. Patients with symptoms at the time of diagnosis had significantly shorter survival compared with asymptomatic patients (p = 0.017). Those with RCC as primary tumor had significantly longer survival compared with non-RCC patients (p < 0.001). Positive margin also predicts worse prognosis (p = 0.035). Conclusions: Pancreatic metastasectomy is safe and associated with acceptable short- and intermediate-term results. In the conditions of RCC as the primary tumor, being asymptomatic, or negative resection margin, a better prognosis after resection can be achieved.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

BefA, a microbiota-secreted membrane disrupter, disseminates to the pancreas and increases β cell mass

Microbiome dysbiosis is a feature of diabetes, but how microbial products influence insulin production is poorly understood. Here, we report the mechanism of BefA, a microbiome-derived protein that increases proliferation of insulin-producing β cells during development in gnotobiotic zebrafish and mice. BefA disseminates systemically by multiple anatomic routes to act directly on pancreatic islets. We detail BefA’s atomic structure, containing a lipid-binding SYLF domain, and demonstrate that it permeabilizes synthetic liposomes and bacterial membranes. A BefA mutant impaired in membrane disruption fails to expand β cells, whereas the pore-forming host defense protein, Reg3, stimulates β cell proliferation. Our work demonstrates that membrane permeabilization by microbiome-derived and host defense proteins is necessary and sufficient for β cell expansion during pancreas development, potentially connecting microbiome composition with diabetes risk.

59 BASIC BIOLOGICAL SCIENCES↗

Preliminary results of fast neutron treatments in carcinoma of the pancreas

A group of 30 patients with adenocarcinoma of the pancreas including some patients with very advanced disease, were treated with the so-called mixed beam modality employing photon treatments three times per week and neutron treatments twice a week. Two hundred Rads or equivalent Rads (RBE 3.3) were given in daily fractions aiming at a total dose of 6000 Rads in 6 to 8 weeks. The treatments were well tolerated and significant palliation was achieved in 26 to 30 cases. Twelve months survival was 33 percent with a median survival of 7 months or 210 days. Treatment techniques and localization procedures are discussed.

Gahbauer, R.↗

Invasive intraductal papillary mucinous neoplasms of the pancreas: relationships between mural nodules detected on thin-section contrast-enhanced MDCT and invasive components

Purpose: To elucidate the relationships between mural nodules (MNs) and invasive components in patients with invasive intraductal papillary mucinous neoplasm (IPMN) on the basis of thin-section contrast-enhanced multidetector CT (CE-MDCT) and pathologic findings. Methods: This retrospective study included 28 patients with surgically confirmed invasive IPMN. Two radiologists independently evaluated the thin-section (1-mm section thickness, no overlap) triple-phase CE-MDCT images for MNs, invasive components, and the continuity between them using a five-point scale (confidence scores of 1–3 as negative, 4 and 5 as positive). Kappa statistic was used to evaluate interobserver agreement. The CE-MDCT findings were correlated with pathologic findings. Results: Interobserver agreement was good or excellent. MNs consisting of tumor cells were recognized in 12 (42.9%) of 28 patients with no discrepancy between the two radiologists. Invasive components were detected in 85.7% and 82.1% in the pancreatic parenchymal phase for radiologist 1 and 2, respectively, and recognized as hypoattenuating areas. Pathologic continuities between MNs and invasive components were confirmed in five (41.7%) of 12 patients with MNs and these were detected on CE-MDCT. When combined seven patients without continuities between MNs and invasive components and 16 patients without MNs, the invasive components pathologically derived from non-nodular low-height papillary epithelium in 23 (82.1%) of 28 patients. Conclusions: The invasive components derived more often from low-height papillary epithelium without MN appearance on CE-MDCT than from MN. Careful attention should be paid to the existence of an invasive component even in the absence of an enhancing MN.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

A dosimetric comparison of proton and photon therapy in unresectable cancers of the head of pancreas

Purpose: Uncontrolled local growth is the cause of death in ∼30% of patients with unresectable pancreatic cancers. The addition of standard-dose radiotherapy to gemcitabine has been shown to confer a modest survival benefit in this population. Radiation dose escalation with three-dimensional planning is not feasible, but high-dose intensity-modulated radiation therapy (IMRT) has been shown to improve local control. Still, dose-escalation remains limited by gastrointestinal toxicity. In this study, the authors investigate the potential use of double scattering (DS) and pencil beam scanning (PBS) proton therapy in limiting dose to critical organs at risk. Methods: The authors compared DS, PBS, and IMRT plans in 13 patients with unresectable cancer of the pancreatic head, paying particular attention to duodenum, small intestine, stomach, liver, kidney, and cord constraints in addition to target volume coverage. All plans were calculated to 5500 cGy in 25 fractions with equivalent constraints and normalized to prescription dose. All statistics were by two-tailed paired t-test. Results: Both DS and PBS decreased stomach, duodenum, and small bowel dose in low-dose regions compared to IMRT (p < 0.01). However, protons yielded increased doses in the mid to high dose regions (e.g., 23.6–53.8 and 34.9–52.4 Gy for duodenum using DS and PBS, respectively; p < 0.05). Protons also increased generalized equivalent uniform dose to duodenum and stomach, however these differences were small (<5% and 10%, respectively; p < 0.01). Doses to other organs-at-risk were within institutional constraints and placed no obvious limitations on treatment planning. Conclusions: Proton therapy does not appear to reduce OAR volumes receiving high dose. Protons are able to reduce the treated volume receiving low-intermediate doses, however the clinical significance of this remains to be determined in future investigations.

60 APPLIED LIFE SCIENCES↗

SU-E-T-539: Maximum Energy of Helium and Carbon Ions Clinically Needed for Spine, Lung, Prostate and Pancreas Cancer

Purpose: Maximum available kinetic energy of accelerated heavy ions is a critical parameter to consider during the establishment of a heavy ion therapy center. It dictates the maximum range in tissue and determines the size and cost of ion gantry. We have started planning our heavy ion therapy center and we report on the needed ion range. Methods: We analyzed 50 of random SBRT-spine, SBRT- lung, prostate and pancreatic cancer patients from our photon clinic. In the isocentric axial CT cut we recorded the maximum water equivalent depth (WED4Field) of PTV’s most distal edge in four cardinal directions and also in a beam direction that required the largest penetration, WEDGantry. These depths were then used to calculate the percentage of our patients we would be able to treat as a function of available maximum carbon and helium beam energy. Based on the Anterior-Posterior WED for lung patients and the maximum available ion energy we estimated the largest possible non-coplanar beam entry angle φ (deviation from vertical) in the isocentric vertical sagittal plane. Results: We found that if 430MeV/u C-12, equivalently 220MeV/u He-4, beams are available, more than 96% (98%) of all patients can be treated without any gantry restrictions (in cardinals angles only) respectively. If the energy is reduced to 400MeV/u C-12, equivalently 205MeV/u He-4, the above fractions reduce to 80% (87%) for prostate and 88% (97%) for other sites. This 7% energy decrease translates to almost 5% gantry size and cost decrease for both ions. These energy limits in combination with the WED in the AP direction for lung patients resulted in average non-coplanar angles of φ430MeV/u = 68°±8° and φ400MeV/u = 65°±10° if nozzle clearance permits them. Conclusion: We found that the two worldwide most common maximum carbon beam energies will treat above 80% of all our patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗