Purpose/Objective(s) Stereotactic body radiation therapy (SBRT) with boosting of dominant intraprostatic lesions (DILs) has been shown to be effective in managing unfavorable-intermediate and high-risk prostate cancer. The ARGOS-CLIMBER trial is a phase I/II study utilizing a combined PSMA PET/MRI approach to identify DILs and affected lymph nodes in this patient population. This interim analysis looked at the acute toxicity resulting from five fraction SBRT treatments with simultaneous boosting of focal disease. Materials/Methods Patients were included if they had unfavorable-intermediate or high-risk disease, were ECOG 0-1, age >18 with histologically confirmed carcinoma of the prostate. Patients with clinical T4, prior prostate treatment, or those who could not receive PET/MRI were excluded. SBRT treatments were planned to 35Gy/5 fractions to the prostate with a maximum boost up to 50Gy/5 fractions. Seminal vesicles (SV) and pelvic lymph nodes could receive 25Gy/5 with a maximum boost up to 35Gy/5 fractions for positive nodes (up to 50Gy/5 for involved SV). Toxicity was assessed according to CTCAE V5.0 during and at 6 weeks post-treatment. Results In total 50 patients were treated. A minority were rural (9%) or low-income (11%) from a socioeconomic perspective. Patients were found to have the following T staging by MRI: T0 n = 1 (2%), T1c n = 8 (16%), T2a n = 9 (18%), T2b n = 4 (8%), T2c n = 2 (4%), T3a n = 18 (36%), T3b n = 6 (12%), T4 n = 2 (4%). Nodal staging by MRI found N0: n = 45 (90%) and N1: n = 5 (10%) whereas PET imaging identified N0: n = 40 (80%) and N1: n = 10 (20%). Overall, n = 36 (72%) had lymph nodes electively covered to 25 Gy with a median D99 of 24.1 Gy (range = 23.79 – 25.3). A total of n = 10 (20%) of patients had PET-identified lymph node disease boosted to 35Gy with a median D99 of 34.8 Gy (range = 33.97-35.7). The median D99% DIL coverage was 42.5 Gy (range = 40.0 – 50.5). SBRT-related acute toxicity was collected. The highest acute GI toxicity per patient was no toxicity n = 20 (40%), grade 1 n = 20 (40%), grade 2 n = 9 (18%), and grade 3 n = 1 (2%). The highest acute GU toxicity per patient was no toxicity n = 13 (26%), grade 1 n = 21 (42%), grade 2 n = 15 (30%), and grade 3 n = 1(2%). The highest acute sexual toxicity per patient was no toxicity n = 40 (80%), grade 1 n = 4 (8%), grade 2 n = 2 (4%), grade 3 n = 4 (8%). The grade three toxicities were categorized as follows: GI - diarrhea n = 1, GU - pain from fiducials and catheterization n = 1, Sexual - Erectile dysfunction n = 4. The highest other acute toxicities per patient were no toxicity n = 35 (70%), Grade 1 n = 14 (28%), and Grade 2 n = 1 (2%). Other toxicities included pain, fatigue, insomnia, and anxiety. There were no acute grade 4 or 5 toxicities identified. Conclusion PSMA PET and MRI-guided SBRT boosting of DILs was found to be both feasible and safe with a limited acute toxicity profile. Ongoing follow-up is underway to identify late toxicities, quality of life, and disease-free survival associated with focused SBRT treatments.

Rectal MR is the key diagnostic exam at initial presentation for rectal cancer patients. It is the primary determinant in establishing clinical stage for the patient and greatly impacts the clinical decision-making process. Consequently, structured reporting for MR is critically important to ensure that all required information is provided to the clinical care team. The SAR initial staging reporting template has been constructed to address these important items, including locoregional extent and factors impacting the surgical approach and management of the patient. Potential outputs to each item are defined, requiring the radiologist to commit to a result. This provides essential information to the surgeon or oncologist to make specific treatment deisions for the patient. The SAR Initial Staging MR reporting template has now been officially adopted by the NAPRC (National Accreditation Program for Rectal Cancer) under the American College of Surgery. With the recent revisions to the reporting template, this user guide has been revamped to improve its practicality and support to the radiologist to complete the structured report. Each line item of the report is supplemented with clinical perspectives, images, and illustrations to help the radiologist understand the potential implications for a given finding. Common errors and pitfalls to avoid are highlighted. Ideally, rectal MR interpretation should not occur in a vacuum but in the context of a multi-disciplinary tumor board to ensure that healthcare providers use common terminology and share a solid understanding of the strengths and weaknesses of MR.

Transplantation of fecal microbiota (FMT) is now standard of care in treatment of recurrent Clostridioides difficile infections (rCDI). Research addresses whether FMT is also effective for other disorders associated with dysbiosis of the gut. To facilitate safe and cost-effective FMT, stool banks have been founded to provide ready-to-use FMT suspensions and to ensure quality assurance. Stool banks can operate at an institutional or regional/national level. Stool banks prepare feces suspensions of stool(s) from extensively screened healthy donors. Suspensions are quarantined at -80°C and only used for FMT after retesting of the donor. Standardization of stool banking is required because it enables stool banks to cooperate and compare their products and performance, which will provide important information for quality improvement. Ongoing and future studies with FMT should finally result in the development of standardized bacterial mixtures as microbiota modulating therapies for (r)CDI and other potential indications. Stool banks may help to facilitate these developments.

Subunits of interleukin-23 (IL-23) and its receptor have been identified as susceptibility genes in genome-wide association studies (GWAs) in ulcerative colitis (UC). Moreover, functional pre-clinical studies have shown that IL-23 is a key cytokine in the pathogenesis of UC. Here, we define an IL-23-induced transcriptomic signature in lamina propria mononuclear cells (LPMCs). We hypothesised that this signature would be enriched in active UC (aUC) compared with inactive UC (iUC) and healthy controls (HC), and enriched in anti-TNFα non-responders compared with anti-TNFα responders. LPMCs were isolated from colonic biopsies obtained endoscopically from 5 aUC and cultured in the presence or absence of IL-23 for 4 h. Cells were lysed, RNA was extracted and RNA sequencing performed using the Illumina platform. Analysis of differentially expressed genes (DEGs) was performed between the untreated and IL-23 treated LPMCs using DESeq2, filtered with p < 0.01 and examined for enrichment in biological pathways using Ingenuity Pathway Analysis (IPA). To assess association of the transcriptomic signature to clinical phenotypes, Gene Set Variation Analysis (GSVA) enrichment scores were calculated in open access data sets of microarray data of colonic biopsies from HC and UC including the ACT1 trial (GSE16879 HC = 6, UC = 24; GSE57091 HC = 11, iUC = 23, aUC = 74; GSE23597 anti-TNFα responders = 2, non-responders = 7). In total, 112 DEGs were identified, including IL22, IFNγ and IL17F which are downstream targets IL-23. Canonical pathway analysis of the DEGs demonstrated ‘Th17 activation’ pathway as the most significantly enhanced. GSVA enrichment scores using the ‘LPMC untreated v IL23’ signature showed a significantly higher score in UC compared with HC in data set GSE16879 (p = 0.006). Furthermore, there was significantly greater enrichment in aUC compared with iUC in data set GSE59071 (p < 0.00001). However, GSVA enrichment scores calculated on colonic biopsies of patients with UC before commencing anti-TNFα therapy did not show a significant difference between anti-TNFα responders and non-responders (dataset GSE16879 p = 0.07; dataset GSE23597 p = 0.1). The herein described IL-23 signature induces an appropriate and expected downstream transcriptional profile. GSVA enrichment scores in open access datasets shows enrichment in aUC compared with both HC and iUC. However, enrichment scores were not significantly different when comparing anti-TNFα responders and non-responders though this may be due to lack of power due to a low sample numbers. Transcriptomic signatures have the potential to act as biomarkers to aid clinical decision making.

Non-alcoholic fatty liver disease (NAFLD) has become a pandemic, affecting up to 25% of the global population, with high incidence and prevalence in North America.1 The spectrum of disease ranges from simple steatosis to steatohepatitis, with or without fibrosis (NASH). It is important to be able to diagnose patients with simple steatosis, but even more so to identify those with NASH given their increased risk of progression to cirrhosis. The gold standard for NASH diagnosis remains liver biopsy. However, given its invasive nature and recognized sampling error from heterogeneity of disease distribution, there has been an increase in the use of non-invasive techniques.2 MRI-fat fraction (MR-FF) is validated for the assessment of hepatic steatosis3 and MR elastography (MRE) for fibrosis.4 MRE requires special hardware and software not readily available. As such, a more readily available imaging modality known as gadoxetic-acid enhanced MRI (GE-MRI), has shown to potentially differentiate simple steatosis from NASH.5 To determine if GE-MRI can differentiate NAFLD from healthy controls compared to MR-FF, and/or simple steatosis from NASH compared to MRE. Healthy controls and NAFLD patients provided informed written consent to participate in this cross-sectional cohort study. The study was approved by the Research Ethics Board at Western University. The diagnosis of NAFLD was based on the AASLD definition.6 These NAFLD patients were divided into those with simple steatosis or NASH based on liver biopsy or transient elastography. All patients underwent MRI-FF, MRE, and GE-MRI. A total of 17 patients were studied. Five healthy control and 12 NAFLD patients, of whom 3 had biopsy proven NASH and 4 had fibrosis based on transient elastography, the remaining 5 had simple steatosis. GE-MRI was able to differentiate healthy patients from NAFLD patients [mean enhancement difference -35.07 ± 11.66 (p=0.0088)]. MR-FF had a statistically significant difference [0.2823 ± 0.03726 (p<0.0001)] and differentiated all patients with NAFLD. GE-MRI was not able to differentiate between hepatic steatosis and NASH, but there was a mean difference in enhancement of 18.67. MRE was able to differentiate between all patients with simple steatosis and NASH with statistical significance [mean difference -1.799 (95% CI = -3.584 to -0.01313, p=0.0482)]. This study shows the difference in enhancement on GE-MRI is much lower in patients with fatty liver and particularly those with liver fibrosis, potentially due to altered hepatocyte uptake of gadoxetic acid. Given the small patient size, specific cut-off values cannot reliably be established. The study also confirms that MR-FF is a reliable modality for the diagnosis of NAFLD, but not liver fibrosis, and that MRE is reliable for the diagnosis of NASH. None

The balance between regulatory T cells (Treg) and Th17 cells is thought to play a key role in the development and outcomes of human autoimmune and inflammatory diseases. Therapeutic targeting of gut trafficking lymphocytes using vedolizumab, an anti-integrin monoclonal antibody, is an effective treatment for IBD. However, little is known about the effect of vedolizumab on different effector T-cell subsets or Tregs. We analysed the profile of circulating gut homing effector memory T-cell subsets and Tregs as well as the Treg/Th17 immune balance in ulcerative colitis (UC) patients. We also evaluated the longitudinal impact of vedolizumab on a small cohort of prospectively recruited patients. Using multi-parametric flow cytometry, we analysed the gut homing (β7+) effector T cells (CD4+CD45RA-CD45RO+CCR7-) and their functional lineages (Th1, Th2, and Th17) based on chemokine receptor expression (CXCR3, CCR4, and CCR6, respectively) as well as memory Treg (CD4+CD25+CD127-CD45RA-CCR4+) from peripheral blood of healthy controls (HC) and UC patients. Peripheral blood was taken from patients before their first dose of vedolizumab and at each subsequent infusion. The ratio of gut homing Treg to Th17 cells was significantly lower in UC (n = 21) compared with HC (1.4 in HC vs. 0.5 in UC, p = 0.01). Although there was minimal impact on gut homing Th1 and Th2 cells in vedolizumab treated (n = 15) patients (comparison between baseline [BL] and Week 14), both gut homing Th17 and Treg compartments increased over the same time period (from 17.3% at BL to 45.3% at Week 14 for Th17 and from 9.7% to 57.2% for Treg). Intriguingly, while comparing clinical response to vedolizumab (30% fall in SCCAI at Week 14 compared with BL), preliminary data indicated that the magnitude of increase in gut homing Tregs at Week 2 is much higher in responders compared with non-responders (3-fold increase in responders vs. −0.4-fold increase in non-responders). This increase was more prominent in the gut homing Treg/Th17 ratio in responders at Week 2 (6-fold increase in responders vs. −0.7-fold increase in non-responders, p = 0.02) and could distinguish between the two groups, thereby increasing the positive probability of response to 80%. UC is characterised by a shift in the proportional abundance of Treg and TH17 cells, implicating a disruption of Treg/Th17 immune balance. The magnitude of increase in the gut homing Treg/Th17 ratio following vedolizumab therapy could differentiate between responders and non-responders to treatment as early as at Week 2 (following the first dose of vedolizumab infusion), raising the possibility that this test could be used as an early biomarker to aid decision-making in clinical practice.

The term oligometastatic (OM) was introduced to describe patients with a limited number of clinically detectable metastases for which local ablative therapy could potentially provide improved disease-free survival or even cure. The incidence of an oligometastatic disease distribution is difficult to estimate. The purpose of this analysis was to describe the reasons precluding trial participation in our trial of SBRT for oligometastatic cancer. We retrospectively audited all patients who were screened for participation in a single-arm phase II trial designed for patients with OM cancer (up to 5 sites of extra-cranial metastases). Study participants received local ablative therapy to all known sites of disease and at least one index lesion was treated with 5 fraction SBRT (study intervention). Eligibility criteria required baseline computed tomography (CT) ≤1 month prior to enrolment, and all cases were discussed at peer-review rounds to confirm eligibility. Between Mar 7 2013 and Nov 17 2017, 236 patients were screened and 145 (61%) enrolled to the study. The reasons for screen failure included patients declining study participation in 4% (9/236) [n = 9; 4 with <5 mets, and 5 with uncertain number] and 12% (29/236) having >5 metastases upon restaging baseline scans. Of the remaining 53 patients who had ≤5 metastases but were not enrolled, reasons for screen failure included uncertainty that the primary tumor was controlled (n=9), lesions where alternative ablative therapy was recommended (n=10), not suitable for SBRT (n=18; size n=3, non-SBRT strategy preferred n=8, toxicity risk n=4, previous RT field overlap n=3), high subjective risk of systemic relapse (n=9; progressive disease during restaging scans n=4, not suitable for comprehensive ablative therapy n=1, plan for systemic therapy n=4) or other reasons (n=7; e.g. index lesion resolution, index lesion was a primary tumor, presence of cranial metastases). In our review of a cohort of patients flagged to be potential candidates for enrollment in a clinical trial of SBRT for OM cancer, 87% of patients were confirmed to have <5 metastases. The screen failure rate was high. The most common reason for exclusion was detection of >5 metastases (12%) while a small group of patients (5%) were deemed to be at high risk of systemic relapse based on clinical factors and peer review rounds. Reporting of the characteristics of screen failed patients are important in the interpretation of trial results.

Objectives: We aimed to assess the asymptomatic Clostridium difficile carriage rates following fecal microbiota transplantation (FMT). Methods: All patients who underwent FMT for recurrent Clostridium difficile infection (CDI) via colonoscopy or sigmoidoscopy between June 2013 and April 2015 and had a minimum of 8-week follow-up post FMT at two tertiary care referral centres were included in the study. Patients were prospectively followed both clinically and with stool assessments for 8 weeks post FMT. Assessments occurred at 1 week and 4 weeks post FMT to assess for failure. Failure was defined as presence of diarrhoeal symptoms and a positive CDI stool test by polymerase chain reaction for toxin gene (PCR) at any time point during the 8-week follow-up period. CDI stool testing using PCR was performed at weeks 1 and 4 post FMT in asymptomatic patients as well. Results: 167 patients were included. Twenty-eight patients (16.7% (28/167)) were FMT failures throughout the 8-week period. At week 1, seven patients had already failed the FMT. Of the remaining 160 patients, 144 were asymptomatic, and among these, 141 were negative for C. difficile toxin gene by PCR. This resulted in an asymptomatic carriage rate of 2.1% (3/144). At week 4, 143 patients had not yet failed FMT. Of these patients 129 patients were asymptomatic and among those, 125 were negative by PCR, resulting in an asymptomatic carriage rate of 3% (3/129). Conclusions: Asymptomatic carriage after FMT is rare. This suggests that testing for cure after FMT in asymptomatic patients is not necessary. (C) 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Background Personal health information, including diagnoses and hospital admissions, is routinely collected in administrative databases. Patients enrolling on clinical trials consent to separate collection and storage of their personal health information. We evaluated patient preferences for linking long-term data from administrative databases with clinical trials.Methods Adults with cancer attending outpatient clinics at 3 Ontario hospitals were surveyed about their willingness, when faced with the hypothetical scenario of participating in a clinical trial, to provide potentially identifying information such as initials and date of birth to facilitate long-term research access to normally de-identified publicly collected databases.ResultsOf 569 patients surveyed, 335 (59%) were women, 452 (79%) were white, 385 (68%) had a post-secondary education, and 386 (68%) had never participated in a clinical trial. Median age in the group was 59 years. Most participants (93%, cohort 1) would allow long-term access to their information and allow personal information to be used to match clinical trial with administrative data. At the time of clinical trial closure, two thirds of participants (68%, cohort 2) preferred to make additional clinical information available through linkage with administrative databases, and 8 (9%) preferred to have no further information made available to researchers. No significant differences were found in the subset of patients who were part of a clinical trial and those who had never participated (p = 0.65).Interpretation Almost all patients would allow a clinical trial research team to access their confidential information, providing a more comprehensive assessment of an intervention's long-term risks and benefits.

The use of positron emission tomography (PET) with radiolabeled choline analogues has shown promise in detection of prostate cancer (CaP) recurrence after definitive local therapy. Magnetic Resonance Imaging (MRI) is increasingly used for CaP staging and has superior soft-tissue resolution and options for multiparametric and functional imaging. The simultaneous use of PET and MRI has been enabled by a new generation of hybrid PET/MRI scanners. We designed a pilot study examining the feasibility of hybrid PET/MRI using 18F-FCH for evaluating men with suspected CaP recurrence who were being considered for local salvage therapies after initial radical prostatectomy (RP) or radical radiation therapy (RT). Seventeen men (out of a planned 20) with suspected CaP recurrence and negative conventional restaging (bone scan and computed tomography) have been accrued: 10 post-RP and 7 post-RT. PET/MRI were acquired as follows: T2W MRI and PET of the pelvis with body-array coil followed by whole-body PET/MRI using 3 to 5 bed positions (from skull vertex to proximal femora) with simultaneous PET and MRI followed by MR only imaging of the pelvis. A consensus report of the PET/MRI was generated by joint read by a radiologist and nuclear medicine physician. Questionnaires were completed by the referring physicians prior to and after imaging reports to investigate the clinical impact of PET/MRI. Median prostate-specific antigen (PSA) of the 10 post-RP men at the time of PET/MRI imaging was 0.575 (range 0.19-7.77). Seven of 10 (70%) had an initial Gleason Score (GS) of 7, and 2 of 10 (20%) had GS of 8-9. One did not have a GS available due to previous hormonal effects. Four of 10 post-RP men had lesions detected on PET/MRI. Lesions were primarily in regional or distant nodal regions and most had concordant PET and MRI findings. In 50% (2 of 4) with positive PET/MRI findings and 33% (2 of 6) with negative findings there was a change in the degree of certainty as to suspected site of recurrence. Change in management occurred in 100% (4 of 4) with positive PET/MRI and 0 of 6 with negative PET/MRI. Preliminary analysis for 4 of 7 post-RT men has been performed. Two men had lesions detected on PET/MRI; 1 isolated to the prostate and 1 in regional nodes. Two had negative PET/MRI. Results for the completed radiation therapy cohort (planned n=10) will also be presented. 18F-FCH PET/MRI shows promise for men with suspected CaP recurrence following RP or RT. PET/MRI findings had impact on clinical certainty of sites of recurrence and management.

Purpose: Defining prostate cancer (PCa) lesion clinical target volumes (CTVs) for multiparametric magnetic resonance imaging (mpMRI) could support focal boosting or treatment to improve outcomes or lower morbidity, necessitating appropriate CTV margins for mpMRI-defined gross tumor volumes (GTVs). This study aimed to identify CTV margins yielding 95% coverage of PCa tumors for prospective cases with high likelihood.Methods and Materials: Twenty-five men with biopsy-confirmed clinical stage T1 or T2 PCa underwent pre-prostatectomy mpMRI, yielding T2-weighted, dynamic contrast-enhanced, and apparent diffusion coefficient images. Digitized whole-mount histology was contoured and registered to mpMRI scans (error <= 2 mm). Four observers contoured lesion GTVs on each mpMRI scan. CTVs were defined by isotropic and anisotropic expansion from these GTVs and from multiparametric (unioned) GTVs from 2 to 3 scans. Histologic coverage (proportions of tumor area on coregistered histology inside the CTV, measured for Gleason scores [GSs] >= 6 and >= 7) and prostate sparing (proportions of prostate volume outside the CTV) were measured. Nonparametric histologic-coverage prediction intervals defined minimal margins yielding 95% coverage for prospective cases with 78% to 92% likelihood.Results: On analysis of 72 true-positive tumor detections, 95% coverage margins were 9 to 11 mm (GS >= 6) and 8 to 10 mm (GS >= 7) for single-sequence GTVs and were 8 mm (GS >= 6) and 6 mm (GS >= 7) for 3-sequence GTVs, yielding CTVs that spared 47% to 81% of prostate tissue for the majority of tumors. Inclusion of T2-weighted contours increased sparing for multiparametric CTVs with 95% coverage margins for GS >= 6, and inclusion of dynamic contrast-enhanced contours increased sparing for GS >= 7. Anisotropic 95% coverage margins increased the sparing proportions to 71% to 86%.Conclusions: Multiparametric magnetic resonance imaging-defined GTVs expanded by appropriate margins may support focal boosting or treatment of PCa; however, these margins, accounting for interobserver and intertumoral variability, may preclude highly conformal CTVs. Multiparametric GTVs and anisotropic margins may reduce the required margins and improve prostate sparing. (C) 2016 Elsevier Inc. All rights reserved.

Background Laparoscopic gastrectomy has gained acceptance as treatment for early gastric cancer. However, its role for advanced gastric cancer remains unclear. This study aimed to compare the oncologic outcomes between laparoscopic and open gastrectomy in the management of advanced gastric cancer for patients receiving adjuvant chemoradiotherapy.Methods This study reviewed consecutive patients treated with gastric cancer resection and adjuvant chemoradiation (45 Gy/25 with 5-fluorouracil [FU]-based chemotherapy), at a quaternary care comprehensive cancer center between 1 Jan 2000 and 30 Nov 2009. Of 203 patients, 21 were treated with laparoscopic gastrectomy. These patients were compared with patients who had open surgery and evaluated for overall survival, relapse-free survival, and site of first disease recurrence.Results The 21 patients in the laparoscopic group had a median age of 61.3 years (range, 28.2-76.6 years) and a median follow-up period of 21.3 months (range, 6.7-50.4 months). The majority of the patients (71%) were men. Most of these patients had tumor node metastasis (TNM) v6 stage 2 (33%) or 3 (52%) disease as classified by the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC). The demographic characteristics of the laparoscopic and open groups were similar. The incidence of recurrence was 38.1% (8/21) in the laparoscopic group and 36.8% (67/182) in the open group. In the laparoscopic group, the site of first recurrence was distant in three patients, peritoneal in four patients, and mixed in one patient (locoregional and distant). The recurrence patterns did not differ significantly between the laparoscopic and open surgery groups. In the open group, recurrence was distant in 26 patients, peritoneal in 12 patients, and locoregional in 15 patients. At presentation, 14 patients showed a mixed pattern. The 3-year relapse-free survival rate was 58% (range, 50-66%), and the difference between the two groups by Gray's test was not significant (P = 0.32). The 3-year overall survival rate was 65.9% (range, 58-73%) and did not differ significantly between the two groups in the univariate (P = 0.92) or multivariate (P = 0.54) analysis.Conclusion The study findings suggest that laparoscopic gastrectomy is an oncologically safe procedure for advanced gastric cancer with outcomes similar to those for open resection.