MR Imaging of Rectal Cancer: Radiomics Analysis to Assess Treatment Response after Neoadjuvant Therapy.

Purpose To investigate the value of T2-weighted-based radiomics compared with qualitative assessment at T2-weighted imaging and diffusion-weighted (DW) imaging for diagnosis of clinical complete response in patients with rectal cancer after neoadjuvant chemotherapy-radiation therapy (CRT). Materials and Methods This retrospective study included 114 patients with rectal cancer who underwent magnetic resonance (MR) imaging after CRT between March 2012 and February 2016. Median age among women (47 of 114, 41%) was 55.9 years (interquartile range, 45.4-66.7 years) and median age among men (67 of 114, 59%) was 55 years (interquartile range, 48-67 years). Surgical histopathologic analysis was the reference standard for pathologic complete response (pCR). For qualitative assessment, two radiologists reached a consensus. For radiomics, one radiologist segmented the volume of interest on high-spatial-resolution T2-weighted images. A random forest classifier was trained to separate the patients by their outcomes after balancing the number of patients in each response category by using the synthetic minority oversampling technique. Statistical analysis was performed by using the Wilcoxon rank-sum test, McNemar test, and Benjamini-Hochberg method. Results Twenty-one of 114 patients (18%) achieved pCR. The radiomic classifier demonstrated an area under the curve of 0.93 (95% confidence interval [CI]: 0.87, 0.96), sensitivity of 100% (95% CI: 0.84, 1), specificity of 91% (95% CI: 0.84, 0.96), positive predictive value of 72% (95% CI: 0.53, 0.87), and negative predictive value of 100% (95% CI: 0.96, 1). The diagnostic performance of radiomics was significantly higher than was qualitative assessment at T2-weighted imaging or DW imaging alone (P < .02). The specificity and positive predictive values were significantly higher in radiomics than were at combined T2-weighted and DW imaging (P < .0001). Conclusion T2-weighted-based radiomics showed better classification performance compared with qualitative assessment at T2-weighted and DW imaging for diagnosing pCR in patients with locally advanced rectal cancer after CRT. © RSNA, 2018 Online supplemental material is available for this article.

Gadolinium-Based Contrast Agent During Pelvic MRI: Contribution to Patient Management in Rectal Cancer.

BACKGROUND: Few publications exist regarding gadolinium-enhanced sequences in rectal MRI. None have evaluated its potential impact on patient management. OBJECTIVE: This study aimed to assess whether gadolinium-enhanced sequences, including dynamic contrast enhancement, change radiologic interpretation and clinical management of rectal cancer. DESIGN: This is a retrospective analysis of 100 rectal MRIs (50 baseline and 50 postneoadjuvant treatment), both without and with gadolinium-enhanced sequences. Treatment plans were rendered based on each radiologic interpretation for each case by a single experienced surgeon. Differences in radiologic interpretation and management were statistically analyzed. SETTINGS: The study was conducted at the Memorial Sloan Kettering Cancer Center. PATIENTS: Patients undergoing rectal MRI between 2011 and 2015 for baseline tumor staging and/or postneoadjuvant restaging were included. MAIN OUTCOME MEASURES: Primary outcome measures were changes in radiologic tumor stage, tumor margins, and surgical planning with the use of gadolinium at baseline and postneoadjuvant time points. RESULTS: At baseline, tumor downstaging occurred in 8 (16%) of 50 and upstaging in 4 (8%) of 50 with gadolinium. Postneoadjuvant treatment, upstaging occurred in 1 (2%) of 50 from T2 to T3a. At baseline, mean distances from tumor to anorectal ring, anal verge, and mesorectal fascia were not statistically different with gadolinium. However, in 7 patients, differences could have resulted in treatment changes, accounted for by changes in relationships to anterior peritoneal reflection (n = 4), anorectal ring (n = 2), or anal verge (n = 1). Postneoadjuvant treatment, distances to anorectal ring and anal verge (in centimeters) were statistically smaller with gadolinium (p = 0.0017 and p = 0.0151) but could not have resulted in clinically significant treatment changes. LIMITATIONS: This study was limited by its retrospective design. CONCLUSIONS: The use of gadolinium at baseline MRI could have altered treatment in 24% of patients because of differences in tumor stage or position. Postneoadjuvant treatment, gadolinium resulted in statistically smaller distances to sphincters, which could influence surgical decision for sphincter-preserving rectal resection. See Video Abstract at http://links.lww.com/DCR/A444.

The enone motif of (+)-grandifloracin is not essential for 'anti-austerity' antiproliferative activity.

We report the synthesis and biological evaluation of three analogues of the natural product (+)-grandifloracin (+)-1. All three analogues exhibit enhanced antiproliferative activity against PANC-1 and HT-29 cells compared to the natural product. The retention of activity in an analogue lacking the enone functional group, 9, implies this structural element is not an essential part of the (+)-grandifloracin pharmacophore.

Valuable new cyclohexadiene building blocks from cationic η5-iron-carbonyl complexes derived from a microbial arene oxidation product.

Biooxidation of benzoic acid by Ralstonia eutropha B9 provides an unusual cyclohexadiene carboxy diol that contains a quaternary stereocentre. Tricarbonyliron derivatives of this chiron, on treatment with acid, give two isomeric η(5)-cyclohexadienyl complexes as observed by NMR spectroscopy. Both of these can be subjected to the addition of nucleophiles to provide isomeric cyclohexadiene complexes with new substituent patterns, several of which have been characterised crystallographically. De-metallation of these provides a versatile library of cyclohexadiene building blocks, the utility of which is demonstrated by formal syntheses of oseltamivir. The mechanism of product formation and its stereochemical implications are discussed, as are the procedures undertaken to establish the enantiopurity of a representative cyclohexadiene product.

Expanding the chiral pool: oxidation of meta-bromobenzoic acid by R. eutrophus B9 allows access to new reaction manifolds.

Metabolism of meta-bromobenzoic acid by the blocked mutant Ralstonia eutrophus B9 affords an enantiopure dearomatised halodiene-diol which we demonstrate is a versatile chiron for organic synthesis. The presence of the halogen leads to reactivity that is distinct to that observed for the non-halogenated analogue and also serves as a synthetic handle for further functionalisation.

Radiogenomics of rectal adenocarcinoma in the era of precision medicine: A pilot study of associations between qualitative and quantitative MRI imaging features and genetic mutations.

OBJECTIVE: To investigate associations between genetic mutations and qualitative as well as quantitative features on MRI in rectal adenocarcinoma at primary staging. METHODS: In this retrospective study, patients with rectal adenocarcinoma, genome sequencing, and pretreatment rectal MRI were included. Statistical analysis was performed to evaluate associations between qualitative features obtained from subjective evaluation of rectal MRI and gene mutations as well as between quantitative textural features and gene mutations. For the qualitative evaluation, Fisher's Exact test was used to analyze categorical associations and Wilcoxon Rank Sum test was used for continuous clinical variables. For the quantitative evaluation, we performed manual segmentation of T2-weighted images for radiomics-based quantitative image analysis. Thirty-four texture features consisting of first order intensity histogram-based features (n = 4), second order Haralick textures (n = 5), and Gabor-edge based Haralick textures were computed at two different orientations. Consensus clustering was performed with 34 computed texture features using the K-means algorithm with Euclidean distance between the texture features. The clusters resulting from the algorithm were then used to enumerate the prevalence of gene mutations in those clusters. RESULTS: In 65 patients, 45 genes were mutated in more than 3/65 patients (5%) and were included in the statistical analysis. Regarding qualitative imaging features, on univariate analysis, tumor location was significantly associated with APC (p = 0.032) and RASA1 mutation (p = 0.032); CRM status was significantly associated with ATM mutation (p = 0.021); and lymph node metastasis was significantly associated with BRCA2 (p = 0.046) mutation. However, these associations were not significant after adjusting for multiple comparisons. Regarding quantitative imaging features, Cluster C1 had tumors with higher mean Gabor edge intensity compared with cluster C2 (θ = 0°, p = 0.018; θ = 45°, p = 0.047; θ = 90°, p = 0.037; cluster C3 (θ = 0°, p = 0.18; θ = 45°, p = 0.1; θ = 90°, p = 0.052), and cluster C4 (θ = 0°, p = 0.016; θ = 45°, p = 0.033; θ = 90°, p = 0.014) suggesting that the cluster C1 had tumors with more distinct edges or heterogeneous appearance compared with other clusters. CONCLUSIONS: Although this preliminary study showed promising associations between quantitative features and genetic mutations, it did not show any correlation between qualitative features and genetic mutations. Further studies with larger sample size are warranted to validate our preliminary data.

Evaluation of the physicochemical and functional stability of diluted REMSIMA® upon extended storage--A study compliant with NHS (UK) guidance.

A newly licensed biosimilar product containing infliximab as the active pharmaceutical ingredient has recently been marketed under the brand name Remsima®. We have evaluated the stability of Remsima® diluted in sodium chloride solution and stored in polyolefin bags at 2-8°C using a range of techniques to assess the physico-chemical and functional integrity of the drug over time. The methods and techniques employed are fully compliant with NHS (UK) guidance for evaluating the stability of biologicals, enabling the data to be used for the application of an extended shelf-life to Remsima products in the UK, when prepared under a Section 10 exemption or a Specials Licence. The results clearly demonstrate physico-chemical and functional stability of the drug over the 7 day period of the study, when prepared as described here under aseptic conditions in accordance with the Summary of manufacturers Product Characteristics.

Accessing the antipodal series in microbial arene oxidation: a novel diene rearrangement induced by tricarbonyliron(0) complexation.

A cyclohexadiene ligand prepared by microbial arene 1,2-dihydroxylation undergoes spontaneous rearrangement upon complexation to tricarbonyliron(0). Subsequent iron removal affords a novel route to formal arene 2,3-dihydroxylation products enantiomeric to those obtainable by direct microbial arene oxidation.

A cobalt complex of a microbial arene oxidation product.

We report the first synthesis of a cobalt Cp diene complex wherein the diene is derived by microbial dearomatising dihydroxylation of an aromatic ring. The complex has been characterised crystallographically and its structure is compared to that of an uncomplexed diene precursor.