MRI texture analysis of T2-weighted images is preferred over magnetization transfer imaging for readily longitudinal quantification of gut fibrosis.

OBJECTIVES: To investigate the value of magnetization transfer (MT) MRI and texture analysis (TA) of T2-weighted MR images (T2WI) in the assessment of intestinal fibrosis in a mouse model. METHODS: Chronic colitis was induced in mice by cyclic administration of dextran sodium sulphate (DSS) resulting in chronic inflammation and progressive bowel fibrosis. Mice underwent 7-T MR imaging at various time points. Bowel wall MT ratio (MTR) and textural features (skewness, kurtosis, entropy), extracted by a filtration histogram technique, were correlated with histopathology. Performance of both techniques were validated using antifibrotic therapy. Finally, a retrospective study was conducted in five patients with Crohn's disease (CD) who underwent bowel surgery. RESULTS: MTR and texture entropy correlated with histopathological fibrosis (r = .85 and .81, respectively). Entropy was superior to MTR for monitoring bowel fibrosis in the presence of coexisting inflammation (linear regression R2 = .93 versus R2 = .01). Furthermore, texture entropy was able to assess antifibrotic therapy response (placebo mice versus treated mice at endpoint scan; Δmean = 0.128, p < .0001). An increase in entropy was indicative of fibrosis accumulation in human CD strictures (inflammation: 1.29; mixed strictures: 1.4 and 1.48; fibrosis: 1.73 and 1.9). CONCLUSION: MT imaging and TA of T2WI can both noninvasively detect established intestinal fibrosis in a mouse model. However, TA is especially useful for the longitudinal quantification of fibrosis in mixed inflammatory-fibrotic tissue, as well as for antifibrotic treatment response evaluation. This accessible post-processing technique merits further validation as the benefits for clinical practice as well as antifibrotic trial design would be numerous. KEY POINTS: • Magnetization transfer MRI and texture analysis of T2-weighted MR images can detect established bowel fibrosis in an animal model of gut fibrosis. • Texture entropy is able to identify and monitor bowel fibrosis progression in an inflammatory context and can assess the response to antifibrotic treatment. • A proof-of-concept study in five patients with Crohn's disease suggests that texture entropy can detect and grade fibrosis in human intestinal strictures.

Feasibility study using iodine quantification on dual-energy CT enterography to distinguish normal small bowel from active inflammatory Crohn's disease.

BACKGROUND: Assessment of Crohn's disease (CD) activity is important to identify patients with active inflammation for therapy management. Quantitative analysis can provide objective measurement of disease presence. PURPOSE: To evaluate the feasibility of quantitative analysis of contrast-enhanced dual-energy computed tomography (DECT) data in detection of small bowel inflammation in patients with CD with an emphasis on iodine quantification. MATERIAL AND METHODS: DECT enterography was prospectively performed in 20 patients with active CD and in 20 healthy individuals, as the control group. Iodine overlay images were created. Wall thickness, attenuation, absolute iodine density, relative iodine density, and fat fraction were measured in the terminal ileum of all patients by two radiologists. Intraclass correlation coefficients were calculated to assess inter-rater agreement. Parameters were compared between patient groups using mixed model analysis. Receiver operating characteristic (ROC) analysis was performed. RESULTS: Both absolute and relative iodine density were significantly higher in active disease than in normal small bowel (all P < 0.001). In contrast, measurement of fat fraction was not significantly different in affected terminal ileal loops compared to normal terminal ileum ( P = 0.075). ROC analysis demonstrated a similar excellent diagnostic accuracy of wall thickness, attenuation, and absolute and relative iodine density with area under the ROC curve (AUC) values in the range of 0.96 for attenuation to 1 for relative iodine density. CONCLUSION: DECT with iodine quantification can be used in distinguishing normal small bowel from active inflammatory CD. Further research should investigate the value of iodine quantification in grading CD activity and in monitoring therapeutic response.

Prevalence and prognosis of low-volume, oligorecurrent, hormone-sensitive prostate cancer amenable to lesion ablative therapy.

OBJECTIVES: To describe the anatomical patterns of prostate cancer (PCa) recurrence after primary therapy and to investigate if patients with low-volume disease have a better prognosis as compared with their counterparts. MATERIALS AND METHODS: Patients eligible for an 18-F choline positron-emission tomography (PET)-computed tomography (CT) were enrolled in a prospective cohort study. Eligible patients had asymptomatic biochemical recurrence after primary PCa treatment and testosterone levels >50 ng/mL. The number of lesions was counted per scan. Patients with isolated local recurrence (LR) or with ≤3 metastases (with or without LR) were considered to have low-volume disease and patients with >3 metastases to have high-volume disease. Descriptive statistics were used to report recurrences. Cox regression analysis was used to investigate the influence of prognostic variables on the time to developing castration-resistant PCa (CRPC). RESULTS: In 208 patients, 625 sites of recurrence were detected in the lymph nodes (N1/M1a: 30%), the bone (18%), the prostate (bed; 11%), viscera (4%), or a combination of any of the previous (37%). In total, 153 patients (74%) had low-volume recurrence and 55 patients (26%) had high-volume recurrence. The 3-year CRPC-free survival rate for the whole cohort was 79% (95% confidence interval 43-55), 88% for low-volume recurrences and 50% for high-volume recurrences (P < 0.001). Longer PSA doubling time at time of recurrence and low-volume disease were associated with a longer time to CRPC. CONCLUSIONS: Three out of four patients with PCa with a 18-F choline PET-CT-detected recurrence have low-volume disease, potentially amenable to local therapy. Patients with low-volume disease have a better prognosis as compared with their counterparts. Lymph node recurrence was the most dominant failure pattern.

Prevalence of CT features of axial spondyloarthritis in patients with Crohn's disease.

Background The sacroiliac joint and spine are seen on abdominal computed tomography (CT) and may show structural lesions as part of spondyloarthritis. Purpose To determine the prevalence of CT features of spondyloarthritis in patients with Crohn's disease (CD). Material and Methods A retrospective study of structural lesions of spondyloarthritis on abdominal CT was performed. The sacroiliac joints and spine of 120 patients were studied: study group I consisted of 40 patients with known CD and inflammatory back pain, group II involved 40 patients with CD without inflammatory back pain, and group III consisted of 40 patients without known joint or inflammatory bowel disease. Recorded CT features included sclerosis, erosions or ankylosis of the sacroiliac joint, enthesopathy, spinal syndesmophytes, and costovertebral joint lesions. Results CT showed structural lesions of the sacroiliac joints in 19/40 (48%) patients with CD and inflammatory back pain (sclerosis [n = 14; 35%], erosions [n = 14; 35%], ankylosis [n = 3; 8%]), in 8/40 (8%) patients with CD without inflammatory back pain (sclerosis [n = 3; 8%], erosions [n = 4; 10%], ankylosis [n = 3; 8%]), and in 3/40 (8%) patients without known joint or bowel disease (sclerosis [n = 2; 5%], ankylosis [n = 1; 3%]). Syndesmophytes were exclusively seen in group I (n = 6; 15%). Conclusion CT of the abdomen in patients with CD and inflammatory back pain shows structural lesions of the sacroiliac joint, entheses, or spine in almost half of the patients. Awareness and knowledge of these findings may guide the referring clinician to further clinical evaluation, imaging, and biomarker evaluation of the disease.

Prognostic factors influencing prostate cancer-specific survival in non-castrate patients with metastatic prostate cancer.

BACKGROUND: In non-castrate prostate cancer (PCa), the prognostic value of the number of metastases on prostate cancer-specific survival (PCSS) is not well studied. METHODS: We retrospectively analyzed the medical records of 1,206 patients, referred for radiotherapy of the prostate (bed) following diagnosis of PCa. Distant metastases (nodal, skeletal, and/or visceral) developed in 121 patients following curative treatment, of which 80 with complete records were not castrated at time of metastasis. The treatment at time of metastases was androgen deprivation therapy (ADT; n = 22), active surveillance (n = 10) or metastasis-directed therapy (MDT; n = 48). Cox-regression analyses were used to examine the influence of different variables on PCSS. RESULTS: The median follow-up from primary PCa treatment was 6.9 years with a median interval from diagnosis to first metastatic event of 4.1 year (range: 0.2-15 years). The primary site of metastases was limited to lymph nodes (48%), bone (39%), and viscera (1%) or a combination (12%). Median PCSS from diagnosis of noncastrate metastases was 6.6 years (95% confidence interval [CI], 5.6-7.7 years). A longer premetastatic PSA doubling time (DT) (hazard ratio [HR] 0.73; 95% CI: 0.57-0.92), a lower number of metastases at first presentation (HR 1.07; 95% CI: 1.02-1.12) and pattern of metastatic spread (HR 3.6; 95% CI: 1.13-11.8 for extensive vs. minimal) were associated with improved PCSS. CONCLUSION: A longer PSA DT, involvement of nodes or axial skeleton and a lower number of metastases are associated with an improved PCSS in non-castrated patients developing metastases.

Surveillance or metastasis-directed Therapy for OligoMetastatic Prostate cancer recurrence (STOMP): study protocol for a randomized phase II trial.

BACKGROUND: Metastases-directed therapy (MDT) with surgery or stereotactic body radiotherapy (SBRT) is emerging as a new treatment option for prostate cancer (PCa) patients with a limited number of metastases (≤3) at recurrence - so called "oligometastases". One of the goals of this approach is to delay the start of palliative androgen deprivation therapy (ADT), with its negative impact on quality of life. However, the lack of a control group, selection bias and the use of adjuvant androgen deprivation therapy prevent strong conclusions from published studies.The aim of this multicenter randomized phase II trial is to assess the impact of MTD on the start of palliative ADT compared to patients undergoing active surveillance. METHODS/DESIGN: Patients with an oligometastatic recurrence, diagnosed on choline PET/CT after local treatment with curative intent, will be randomised in a 1:1 ratio between arm A: active surveillance only and arm B: MTD followed by active surveillance. Patients will be stratified according to the location of metastasis (node vs. bone metastases) and PSA doubling time (≤3 vs. > 3 months). Both surgery and SBRT are allowed as MDT. Active surveillance means 3-monthly PSA testing and re-imaging at PSA progression. The primary endpoint is ADT-free survival. ADT will be started in both arms at time of polymetastatic disease (>3 metastatic lesions), local progression or symptoms. The secondary endpoints include progression-free survival, quality of life, toxicity and prostate-cancer specific survival. DISCUSSION: This is the first randomized phase 2 trial assessing the possibility of deferring palliative ADT with MDT in oligometastatic PCa recurrence. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01558427.

Completion surgery after intensity-modulated arc therapy in the treatment of locally advanced cervical cancer: feasibility, surgical outcome, and oncologic results.

INTRODUCTION: Since the addition of chemotherapy to radiotherapy, the survival rates of locally advanced cervical cancer (LACC) have improved but are still disappointing. Therefore, the idea of surgery after chemoradiation in case of LACC or bulky disease was adopted. One of the concerns regarding surgery following chemoradiotherapy is surgery-related morbidity. AIM: The objectives of this study were to investigate the feasibility of surgery after advanced radiotherapy techniques such as intensity-modulated arc therapy (IMAT) and to describe the morbidity. METHODS: This was a prospective study of primary inoperable LACC patients primary treated with IMAT, in most cases combined with weekly cisplatin. Then the resectability was reevaluated. If resectable patients were treated with Wertheim type 2 surgery ± pelvic lymphadenectomy (on positron emission tomography-computed tomography indication). If tumor is not resectable, patients were treated with brachytherapy. RESULTS: Since 2006, 41 consecutive patients were included. After neoadjuvant IMAT, 34 were considered resectable and underwent surgery, whereas 7 proceeded with brachytherapy. The operative mortality rate was nil. There were no major perioperative complications. No ureter, bladder, or bowel injuries occurred. No postoperative urinary/digestive fistulae or stenoses were noted. Eleven patients had postoperatively urinary retention problems. At the time of discharge, 5 patients still needed self-catheterization. All problems resolved within 3 months. In 4 cases, we saw significant lymphoceles. In all patients intended to treat, overall survival and disease-free survival at 3 years were 63% and 74%. In the Wertheim group, overall survival and disease-free survival at 3 years were 81% and 91%. CONCLUSIONS: Completing surgery after chemoradiation therapy (with IMAT) for LACC or bulky disease is feasible, and complication rates are comparable with those of primary surgery for cervical cancer.

Clinical and Genomic Differences Between Advanced Molecular Imaging-detected and Conventional Imaging-detected Metachronous Oligometastatic Castration-sensitive Prostate Cancer.

In metastatic castration-sensitive prostate cancer (mCSPC), disease volume plays an integral role in guiding treatment recommendations, including selection of docetaxel therapy, metastasis-directed therapy, and radiation to the prostate. Although there are multiple definitions of disease volume, they have commonly been studied in the context of metastases detected via conventional imaging (CIM). One such numeric definition of disease volume, termed oligometastasis, is heavily dependent on the sensitivity of the imaging modality. We performed an international multi-institutional retrospective review of men with metachronous oligometastatic CSPC (omCSPC), detected via either advanced molecular imaging alone (AMIM) or CIM. Patients were compared with respect to clinical and genomic features using the Mann-Whitney U test, Pearson's χ2 test, and Kaplan-Meier overall survival (OS) analyses with a log-rank test. A total of 295 patients were included for analysis. Patients with CIM-omCSPC had significantly higher Gleason grade group (p = 0.032), higher prostate-specific antigen at omCSPC diagnosis (8.0 vs 1.7 ng/ml; p < 0.001), more frequent pathogenic TP53 mutations (28% vs 17%; p = 0.030), and worse 10-yr OS (85% vs 100%; p < 0.001). This is the first report of clinical and biological differences between AMIM-detected and CIM-detected omCSPC. Our findings are particularly important for ongoing and planned clinical trials in omCSPC. PATIENT SUMMARY: Metastatic prostate cancer with just a few metastases only detected via newer scanning methods (called molecular imaging) is associated with fewer high-risk DNA mutations and better survival in comparison to metastatic cancer detected via conventional scan methods.

Value of magnetic resonance and ¹8FDG PET-CT in predicting tumor response and resectability of primary locally advanced cervical cancer after treatment with intensity-modulated arc therapy: a prospective pathology-matched study.

OBJECTIVE: To report on the value of magnetic resonance imaging (MRI) and 2-deoxy-2-[18] fluoro-D-glucose positron emission tomography computed tomography (¹8FDG PET-CT) in predicting resectability and pathological response of primary locally advanced cervical cancer after neoadjuvant intensity-modulated arc therapy (IMAT) with or without cisplatin (C). METHODS AND MATERIALS: Twenty-seven patients with International Federation of Gynecology and Obstetrics stages IB2 to IVA cervical cancer were treated with IMAT-C followed by extrafascial hysterectomy (EH). All patients received MRI and ¹8FDG PET-CT after IMAT-C. The end points of this study were to: 1. Assess the ability of MRI to predict negative surgical margins (R0). 2. Assess the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of MRI in predicting the following situation at the EH specimen: "no residual disease or minimal microscopically visible residual tumor." 3. Assess the sensitivity, specificity, PPV, and NPV value of ¹8FDG PET-CT in predicting "no residual viable tumor cells" at the EH specimen. RESULTS: An R0 resection was obtained in all patients. None of the EH specimens contained macroscopically visible tumor. In 13 patients, no viable tumor cells were found and only 14 had residual microscopic disease. Twenty-four of 27 MRIs were able to correctly predict R0 resection. A negative MRI was 100% predictive for the end point "R0 resection." The specificity and NPV of MRI (end point 2) were 74% and 100%, respectively. No sensitivity or PPV could be calculated. The sensitivity, specificity, PPV, and NPV of ¹8FDG PET-CT were 29%, 62%, 44%, and 44%, respectively (end point 3). CONCLUSIONS: A negative MRI after IMAT-C predicts 100% correctly for R0 resection. The role of FDG PET-CT in predicting viable tumor cells at EH specimen is at least debatable.

18F-PSMA-11 Versus 68Ga-PSMA-11 Positron Emission Tomography/Computed Tomography for Staging and Biochemical Recurrence of Prostate Cancer: A Prospective Double-blind Randomised Cross-over Trial.

BACKGROUND: Fluorine-18 (18F)-labelled prostate-specific membrane antigen (PSMA) offers several advantages over gallium-68 (68Ga) in terms of costs, yield, transport/distribution, and image resolution. OBJECTIVE: This trial investigates the new radiotracer 18F-PSMA-11 via a prospective, intraindividual crossover design. The trial was powered for noninferiority of 18F-PSMA-11 over 68Ga-PSMA-11 positron emission tomography (PET)/computed tomography (CT) in terms of the number of positive PET scans. Secondary endpoints were as follows: (1) superiority of 18F-PSMA-11 over 68Ga-PSMA-11 with respect to the number of positive PET scans, the total number of suspicious prostate cancer lesions, and the miPSMA expression score of corresponding lesions; (2) correlation of the PET/CT images with available follow-up data for 18F-PSMA-11 and 68Ga-PSMA-11; and (3) assessment of the interobserver variability. DESIGN, SETTING, AND PARTICIPANTS: Prostate cancer patients (primary or biochemical recurrence) were randomised in a double-blind crossover design whereby each patient received both 18F-PSMA-11 and 68Ga-PSMA-11 PET/CT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: All scans were reviewed and scored by three independent experienced nuclear physicians following the proposed guideline for the interpretation of PSMA-ligand PET/CT, as described by Eiber et al. RESULTS AND LIMITATIONS: In total, 82 patients were included for scan analyses. The primary endpoint was met: per patient, the proportions of positive scans rated by the three readers were 67%/67%, 65%/65%, and 73%/70% for 18F-PSMA-11/68Ga-PSMA-11 PET/CT. The miPSMA expression score was higher for 18F-PSMA-11 than for 68Ga-PSMA-11 for the reference reader. Follow-up data showed identical estimated sensitivity for both the 18F-PSMA-11 and the 68Ga-PSMA-11 scan (0.92, 0.83, and 0.92 for the three readers). A fair to good agreement among readers (at patient level) was obtained, which was demonstrated by a Light's kappa value of 0.59 for both tracers. CONCLUSIONS: The tracer 18F-PSMA-11 is noninferior to68Ga-PSMA-11. Superiority of 18F-PSMA-11 was limited to the miPSMA expression score, given by the reference reader. Inter-rater agreement was fair to good, and equal for both radiotracers. PATIENT SUMMARY: In this study, we compared two radiotracers: 18F-PSMA-11 and 68Ga-PSMA-11. We proved that 18F-PSMA-11 is not inferior to 68Ga-PSMA-11 for detecting prostate cancer and thus can be used as an alternative. Possible superiority of this tracer should be further investigated in specific subpopulations.

Impact of 18F-PSMA-11 PET/CT on Management of Biochemical Recurrence and High-Risk Prostate Cancer Staging : 18F-PSMA-11 PET/CT and Impact on Prostate Cancer Management.

PURPOSE: In this study, we evaluated the impact of 18F-PSMA-11 PET/CT on the patient management plan in patients with primary or recurrent disease. Furthermore, a correlation between PET findings and other modalities was performed. PROCEDURES: In this prospective observational study, 60 prostate cancer patients (9 primary staging, 51 biochemical recurrence) were imaged with 18F-PSMA-11 PET/CT. Pre- and post-scan questionnaires were completed by the treating physician to observe changes in therapy intent. Follow-up data (histological confirmation, MRI imaging, and PSA values after radiotherapy without implementation of systemic therapy) was correlated with the 18F-PSMA-11 findings. RESULTS: The patient-based detection rate was 82% and a management change was seen in 52% of the cases. The heterogeneous characteristics of the included patients resulted in a widely varying treatment change, mostly originating from an increase of disease extent on 18F-PSMA-11 PET/CT. CONCLUSION: 18F-PSMA-11 PET/CT showed to be a highly promising method for the detection of prostate cancer lesions.

Long-Term Outcomes and Genetic Predictors of Response to Metastasis-Directed Therapy Versus Observation in Oligometastatic Prostate Cancer: Analysis of STOMP and ORIOLE Trials.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The initial STOMP and ORIOLE trial reports suggested that metastasis-directed therapy (MDT) in oligometastatic castration-sensitive prostate cancer (omCSPC) was associated with improved treatment outcomes. Here, we present long-term outcomes of MDT in omCSPC by pooling STOMP and ORIOLE and assess the ability of a high-risk mutational signature to risk stratify outcomes after MDT. The primary end point was progression-free survival (PFS) calculated using the Kaplan-Meier method. High-risk mutations were defined as pathogenic somatic mutations within ATM, BRCA1/2, Rb1, or TP53. The median follow-up for the whole group was 52.5 months. Median PFS was prolonged with MDT compared with observation (pooled hazard ratio [HR], 0.44; 95% CI, 0.29 to 0.66; P value < .001), with the largest benefit of MDT in patients with a high-risk mutation (HR high-risk, 0.05; HR no high-risk, 0.42; P value for interaction: .12). Within the MDT cohort, the PFS was 13.4 months in those without a high-risk mutation, compared with 7.5 months in those with a high-risk mutation (HR, 0.53; 95% CI, 0.25 to 1.11; P = .09). Long-term outcomes from the only two randomized trials in omCSPC suggest a sustained clinical benefit to MDT over observation. A high-risk mutational signature may help risk stratify treatment outcomes after MDT.

Radiotherapy and surgery-an indispensable duo in the treatment of retroperitoneal sarcoma.

The authors undertook a systematic review to designate the role that radiotherapy (RT) might play in the treatment of retroperitoneal sarcomas. Correlating with recent literature, the objective of this review was to evaluate whether there was enough evidence for the authors to develop an institutional treatment protocol concerning the use of RT in the treatment of retroperitoneal sarcoma. Furthermore, this was a call for surgeons to talk to radiation oncologists before performing surgery. The 2 objectives of this review were: 1) to determine the benefit of RT in terms of local control and/or survival in the treatment of retroperitoneal sarcomas and 2) to discover the optimal timing of RT in the treatment sequence. A computerized literature search was performed in the PubMed database, the Cochrane Library database, and reference lists; and journals also were searched by hand to identify all retrospective and prospective reports published since 1998 relating to RT treatment of adult retroperitoneal sarcoma. Mainly, analyses were sought that were based on a 5-year local control rate (LCR), 5-year disease-free survival, and 5-year overall survival (OS). If only 2 years follow-up were available, then the authors also noted this outcome. Toxicity data were collected and analyzed separately. The synthesis of the literature was based on 9 prospectively nonrandomized studies and 10 retrospective studies that, together, reviewed a total of 1426 patients. The 5-year LCR varied from 27% to 62%, and the results from other reports fell in between those values. The 5-year OS rate ranged from 12% to 90%, and complete resection and tumor grade were the most important prognostic factors in most studies. This review resulted in 7 recommendations concerning the use of RT in the treatment of retroperitoneal sarcoma. The authors concluded that there is good evidence from multiple single-institutions studies that RT improves the LCR in patients with retroperitoneal sarcoma. Until now, there has not been a translation of this approach into survival benefit. The current results indicated that preoperative external-beam RT followed by radical surgery seems to be the preferred sequence, and adding intraoperative RT is a safe procedure for dose escalation in the upper abdomen.

Variability of CT contrast enhancement in the pancreas: a cause for concern?

BACKGROUND: Multidetector CT is a valuable technique for diagnosis/staging in several pancreatic pathologies. Diagnosis is usually based on tissue density measurements. Recently, newer functional CT techniques have been introduced. The aim of this study was to assess variability in perfusion and dual-energy CT data, and to compare these data with density measurements in the pancreas of a healthy population. METHODS: Two groups were included: 20 patients underwent perfusion CT imaging, and 10 patients were scanned using a dual-energy protocol. In both groups, tissue density [Hounsfield units (HU)] was measured in the pancreatic head, body and tail. Functional data were calculated (blood flow/blood volume in the perfusion CT group, iodine concentration in the dual-energy group), and variability was assessed. RESULTS: Density measurements were comparable for the perfusion and dual-energy CT groups, and ranged from 14 to 60 HU. Maximal enhancement differences between the head/body/tail of the pancreas ranged between 2 and 21 HU. Considerable variability was observed, both in density measurements (ranging from 3 to 34%) and in functional parameters (mean variability in perfusion CT parameters blood flow and blood volume was 21.3 and 10% respectively; mean variability in dual-energy iodine-mapping results was 24.4%). CONCLUSION: This study demonstrated the presence of important intraindividual variability in pancreatic tissue contrast enhancement, regardless of the CT technique used. Considering the variability observed in this study, the use of cut-off values to characterize pancreatic pathologies seems troublesome, and morphologic primary and secondary changes will remain important, even when using novel functional imaging techniques. and IAP.

Assessment of tumor vascularization in pancreatic adenocarcinoma using 128-slice perfusion computed tomography imaging.

OBJECTIVE: Computed tomography (CT) perfusion studies can provide valuable information regarding tumor vascularization. We report on a study assessing CT perfusion characteristics in the normal pancreas and in patients with pancreatic adenocarcinoma. METHODS: Twenty healthy subjects and 20 patients with histologically confirmed pancreatic adenocarcinoma were included in the study after written informed consent and approval by our institutional review board. All subjects underwent perfusion CT imaging of the pancreas using 128-slice dual-source CT. The scanning sequence included 18 scans. Parametric maps of blood volume (BV), blood flow (BF), and permeability surface area product (PS) were generated and compared with density measurements. RESULTS: In normal pancreas, no significant difference in perfusion values was observed between head, body, and tail of the pancreas. Mean organ values were 76.76 (SD, 15.6) mL/100 g/min, 15.80 (SD, 2.40) mL/100 g, and 27.74 (SD, 16.8) mL/100 g/min for BF, BV, and PS, respectively. Compared with the normal pancreas, a 60% reduction in BF and BV was observed in the tumor tissue. Perfusion values gradually increased toward the tumor rim. Necrotic tumor areas were identified in 25% of patients. No significant differences were observed when comparing normal pancreas and healthy pancreatic tissue in adenocarcinoma patients. CONCLUSIONS: The feasibility of whole-tumor perfusion imaging using 128-slice CT was demonstrated in patients with pancreatic adenocarcinoma. Perfusion CT provides additional information compared with image assessment based on density measurements (Hounsfield units) and allows noninvasive assessment of vascularization in the tumor tissue.

Assessment of neovascular permeability in a pancreatic tumor model using dynamic contrast-enhanced (DCE) MRI with contrast agents of different molecular weights.

OBJECT: We evaluated the relationship of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)-derived pharmacokinetic parameters and contrast agents with different molecular weights (MW) in a pancreatic tumor mouse model. MATERIALS AND METHODS: Panc02 tumors were induced in mice at the hind leg. DCE-MRI was performed using Gadolinium (Gd)-based contrast agents with different MW: Gd-DOTA (0.5 kDa), P846 (3.5 kDa), and P792 (6.47 kDa). Quantitative vascular parameters (AUC, K(trans), V(e), and V(p)) were calculated according to a modified Tofts two-compartment model. Values for all contrast groups were compared for tumor and control (muscle) tissues. RESULTS: Values for K(trans) and V(e) were significantly higher in tumor tissue than in muscle tissue. When comparing contrast agents, lowest absolute K(trans) values were observed using P792. The relative increase in K(trans) in tumor tissue compared with normal tissue was highest after the use of P792. In both tumor and normal tissues, K(trans) decreased with increasing molecular weight of the contrast agent used. CONCLUSION: It was demonstrated that values for the different DCE-MRI vascular (permeability) parameters are highly dependent on the contrast agent used. Due to their potential to better differentiate tumor from muscle tissue, higher molecular weight contrast agents show promise when evaluating tumors using DCE-MRI.

Acute pancreatitis: radiologic scores in predicting severity and outcome.

Acute pancreatitis (AP) is a common inflammatory disease which can be mild and self-limiting without complications or severe with prolonged hospitalization, high morbidity, and high mortality. Different radiological scoring systems to predict severity and outcome in AP have been developed since the early 1990s. In the meantime, new insights in the pathophysiology of AP and consequently, therapeutic management of these patients have been introduced. The purpose of this review is therefore (1) to describe the current terminology and new concepts in the pathophysiology, (2) to outline the long existing and newly developed radiological scoring systems in prediction of severity and outcome with their respective advantages and limitations, and (3) to define the role of radiological prognostic scoring systems in the new environment of perception of the last decade. Risk stratification in AP requires scoring systems that can be calculated early in the course of disease which allows time for intervention. For that reason, scoring systems based on necrosis are not useful in severity prediction. The recent developed radiological scoring systems based on signs of systemic inflammatory response syndrome and organ dysfunction are promising in prediction of severity early after onset of AP.

Intensity-modulated arc therapy with simultaneous integrated boost in the treatment of primary irresectable cervical cancer. Treatment planning, quality control, and clinical implementation.

PURPOSE: To report on the planning procedure, quality control, and clinical implementation of intensity-modulated arc therapy (IMAT) delivering a simultaneous integrated boost (SIB) in patients with primary irresectable cervix carcinoma. PATIENTS AND METHODS: Six patients underwent PET-CT (positron emission tomography-computed tomography) and MRI (magnetic resonance imaging) before treatment planning. Prescription (25 fractions) was (1) a median dose (D(50)) of 62, 58 and 56 Gy to the primary tumor (GTV_cervix), primary clinical target volume (CTV_cervix) and its planning target volume (PTV_cervix), respectively; (2) a D(50) of 60 Gy to the PET-positive lymph nodes (GTV_nodes); (3) a minimal dose (D(98)) of 45 Gy to the planning target volume of the elective lymph nodes (PTV_nodes). IMAT plans were generated using an anatomy-based exclusion tool with the aid of weight and leaf position optimization. The dosimetric delivery of IMAT was validated preclinically using radiochromic film dosimetry. RESULTS: Five to nine arcs were needed to create valid IMAT plans. Dose constraints on D(50) were not met in two patients (both GTV_cervix: 1 Gy and 3 Gy less). D(98) for PTV_nodes was not met in three patients (1 Gy each). Film dosimetry showed excellent gamma evaluation. There were no treatment interruptions. CONCLUSION: IMAT allows delivering an SIB to the macroscopic tumor without compromising the dose to the elective lymph nodes or the organs at risk. The clinical implementation is feasible.

Antiangiogenic versus cytotoxic therapeutic approaches in a mouse model of pancreatic cancer: an experimental study with a multitarget tyrosine kinase inhibitor (sunitinib), gemcitabine and radiotherapy.

This work evaluated SU11248 (sunitinib) as a potential therapeutic agent, alone or in combination with the cytotoxic agent gemcitabine or radiotherapy in a murine model of pancreatic cancer. Panc02 cells were injected subcutaneously into HsdOla/MF1 mice (n=222). Treatment was administered during 1 week: sunitinib (SUN), gemcitabine (GEM), radiotherapy (RT), RT+SUN and GEM+SUN. Mice were sacrificed 14 days after treatment. The effect on microvessel density (MVD) was measured by CD31 staining. Apoptosis (sFAS, cleaved caspase-3) and proangiogenic proteins (VEGF, PlGF, EGF) were measured with ELISA and immunohistochemistry. At day 14, tumors in all groups increased significantly despite treatment. Only after RT/SUN treatment tumor growth slowed down, although the accretion was still significant (P=0.033). Highest levels of apoptosis were seen in GEM/SUN, RT/SUN and RT treated mice (respectively P<0.001, P<0.01 and P<0.05 compared to placebo). MVD was lowest in RT/SUN treated mice [compared to placebo (P<0.05), GEM (P<0.05) and GEM/SUN (P<0.01)]. Highest VEGF levels were seen after RT and RT/SUN treatment [vs. placebo (P<0.001) and vs. other treatments (P<0.01 for all comparisons)]. GEM and SUN in monotherapy lead to an up-regulation of PlGF and EGF, respectively. In conclusion, the combination treatments RT/SUN and GEM/SUN result in a more potent anti-angiogenic and antitumor effect when compared to either treatment alone. Multitargeted angiogenesis inhibitor therapy with sunitinib combined with either radiotherapy or gemcitabine may be a novel approach for human pancreatic cancer.

Joint coordinate system for biomechanical analysis of the sacroiliac joint.

Sacroiliac joint (SIJ) biomechanics have been described in both in vitro and in vivo studies. A standard for joint coordinate systems has been created by the International Society of Biomechanics for most of the joints in the human body. However, a standardized joint coordinate system for sacroiliac joint motion analysis is currently still lacking. This impedes the comparison across studies and hinders communication among scientists and clinicians. As SIJ motion is reported to be quite limited, a proper standardization and reproducibility of this procedure is essential for the interpretation of future biomechanical SIJ studies. This paper proposes a joint coordinate system for the analysis of sacroiliac joint motion, based on the procedure developed by Grood and Suntay, using semi-automated anatomical landmarks on 3D joint surfaces. This coordinate system offers high inter-rater reliability and aspires to a more intuitive representation of biomechanical data, as it is aligned with SIJ articular surfaces. This study aims to encourage further reflection and debate on biomechanical data representation, in order to facilitate interpretation of SIJ biomechanics and improve communication between researchers and clinicians. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.