Multiparametric Magnetic Resonance Imaging (MRI) as an Outcome Predictor for Anal Canal Cancer Managed with Chemoradiotherapy
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ABSTRACT:
DISEASE(S): Cancer-bowel-anal,Anal Cancer
PROVIDER: 2461578 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Interventions: Single arm prospective observationaI imaging biomarker study.
Patients will have standard treatment, consisting of neoadjuvant chemoradiotherapy followed by surgery. There will be no change to the patient’s treatment by participating in this study. Patients participating in this study will have multi-parametric MRI and PET/CT at the following 3 time-points:
1. Prior to chemoradiotherapy
2. During the third week of chemoradiotherapy
3. Post chemoradiotherapy, within 1 week prior to surgery.
A multi-parametric MRI incorporates standard morphological as well as diffusion weighted imaging and dynamic contrast enhanced sequences.
The total follow-up duration will be 2 years from date of surgery.
Primary outcome(s): Correlation of multi-parametric MRI (diffusion weighted imaging (DWI) and dynamic contrast enhanced (DCE)) at 3 Tesla with surgical histopathology tumour regression grade (TRG).
Histopathological assessment will be performed on surgical specimens. TRG assessment will be performed as per the modified classification of Ryan et al set out in the AJCC Cancer Staging Manual, 7th Edition as follows:
TRG 0 (complete response) - no viable cancer cells
TRG 1 (moderate response) - single cells or small groups of cancer cells
TRG 2 (minimal response) - residual cancer outgrown by fibrosis
TRG 3 (poor response) - minimal or no tumour kill; extensive residual cancer.
[At baseline pre-chemoradiotherapy, week 3 of chemoradiotherapy, and post-chemoradiotherapy (within 1 week prior to surgery) ]
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Project description:Treatment of peripheral T-cell lymphoma is inadequate but investigation of their genetics demonstrated that some are derived from normal follicular helper (Tfh) T-cells. The sanroque mouse strain bears a mutation that increases Tfh cell number and heterozygous animals (Roquinsan/+) develop lymphomas similar to human Tfh lymphoma. We have begun to characterise the lymphomas by whole exome sequencing and gene expression profiling. Interleukin-2-inducible kinase (ITK) is expressed in Tfh lymphoma and ibrutinib is a small molecule inhibitor of mouse and human ITK and a potential therapeutic agent. A preclinical study of ibrutinib in established lymphoma was then carried out and showed lymphoma regression in 8/12 (67%) of mice. Using T2-weighted MRI to assess lymph node volume and diffusion weighted MRI scanning as a measure of function, we showed that treatment increased mean apparent diffusion coefficient (ADC) suggesting cell death, and that change in ADC following treatment correlated with change in lymphoma volume. We suggest that heterozygous sanroque mice produce genetically diverse Tfh cell derived lymphomas in an immunocompetent animal and are a useful model system for preclinical testing.
2018-09-26 | GSE120402 | GEO
Project description:The study is designed to evaluate the value of DWI-MRI (Diffusion weighted magnetic resonance imaging) in predicting the efficacy of liver metastases after chemotherapy in colorectal cancer.
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Project description:Background:To evaluate the association of multiparametric and multiregional MRI-features with key molecular characteristics in patients with newly-diagnosed glioblastoma. Methods:Retrospective data evaluation was approved by the local ethics committee of the University of Heidelberg (ethics approval number: S-320/2012) and informed consent was waived. Preoperative MRI-features were correlated with key molecular characteristics within a single-institutional cohort of 152 patients with newly-diagnosed glioblastoma. Preoperative MRI-features (n=31) included multiparametric (anatomical, diffusion-, perfusion-, and susceptibility-weighted images) and multiregional (contrast enhancing and non-enhancing FLAIR-hyperintense) information with (histogram) quantification of tumor volumes, volume ratios, apparent diffusion coefficients, cerebral blood flow / volume (CBF / CBV) and intratumoral susceptibility signals. Molecular characteristics determined with the Illumina Infinium HumanMethylation450 array included global DNA-methylation subgroups (e.g. mesenchymal (MES), RTK I “PGFRA”, RTK II “classic”), MGMT-promoter methylation status and hallmark copy-number-variations (EGFR-, PDGFRA-, MDM4- and CDK4-amplification; PTEN-, CDKN2A-, NF1- and RB1-loss). Univariate analyses (voxel-lesion-symptom-mapping for tumor location, Wilcoxon-test for all other MRI-features) as well as machine-learning models were applied to study the strength of association and discriminative value of MRI-features for predicting underlying molecular characteristics. Results: There was no tumor location predilection for any of the assessed molecular parameters (permutation-adjusted p>0.05 each). Univariate imaging parameter associations were noted for EGFR amplification and CDKN2A loss, both demonstrating increased nrCBV and nrCBF values (performance of these parameters, as assessed by the area under the ROC curve ranged from 63 to 69%, FDR-adjusted p<0.05, respectively). Subjecting all MRI-features to machine-learning-based classification allowed to predict EGFR amplification status and the RTK II “classic” GB subgroup with a moderate, yet significantly greater accuracy (63% for EGFR [p<0.01] and 61% for RTK II [p=0.01]) than the prediction by chance, whereas prediction accuracy for all other molecular parameters was non-significant (p>0.05, all models). Conclusions: In summary, we found univariate associations between established MRI-features and molecular characteristics, however not of sufficient strength to allow the generation of machine-learning classification models for reliable and clinically meaningful prediction of the assessed molecular characteristics in patients with newly-diagnosed glioblastoma.
2016-11-23 | GSE85539 | GEO
Project description:Objective: to focus on the molecular mechanisms involved in the dystrophic process that leads to selective wasting of single muscles or muscle groups in Facioscapulohumeral muscular dystrophy (FSHD). By muscle MRI we observed that T2-short tau inversion recovery (T2-STIR) sequences identify two different patterns in which each muscle can be found before the irreversible dystrophic alteration, marked as T1-weighted sequence hyperintensity. We studied these conditions in order to obtain further information on the disease pathogenesis. Design: histopathology, gene expression profiling and real time PCR were performed on muscle biopsies. Subjects: muscles (n=8) with different MRI pattern (T1-weighted normal/T2-STIR normal and T1-weighted normal/T2-STIR hyperintense) from FSHD patients. Data were also compared with inflammatory myopathies (n=7), dysferlinopathies (n=4) and normal controls (n=7). Results: myopathic and inflammatory changes characterize T2-STIR hyperintense FSHD muscles, at variance with T2-STIR normal muscles. These two states can be easily distinguished from each other by their transcriptional profile. Comparison of T2-STIR hyperintense FSHD muscles with muscles of inflammatory myopathies shows peculiar changes, although many alterations are shared among these conditions. Conclusions: at the single muscle level, different stages of the disease correspond to the two MRI patterns. T2-STIR hyperintense FSHD muscles are more similar to inflammatory myopathies than to T2-STIR normal FSHD muscles or other muscular dystrophies, and share with them upregulation of genes involved in innate and adaptive immunity. Our data suggest that selective inflammation, together with perturbation in biological processes such as neoangiogenesis, lipid metabolism and adipokine production, may play a role in FSHD progression. 26 samples of human muscle muscle tissue were analysed using the Illumina beadchip technology.
2012-09-14 | E-GEOD-26852 | biostudies-arrayexpress
Project description:MRI is a potentially powerful tool to reliably determine the intra-abdominal tumor load and relations with intra-abdominal organs. In recent years diffusion weighted MRI has proven its value as a highly sensitive technique to detect small malignant disease in a wide variety of cancers [1-3]. However, literature concerning the clinical impact of detecting peritoneal metastases with MRI is very limited. Therefore, there is a need for a large randomized multicenter trial to determine whether dedicated MRI can be used as a selection tool for CRS-HIPEC candidates in daily practice.
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Project description:Interventions: Cohort: 10 patients with histologically proven squamous cell carcinoma (SCC) of the anus, presenting to Austin Health for chemo-radiotherapy from June 2015.
Observation: for up to 3 years post-radiotherapy.
Interventions additional to standard procedures for purpose of study are administered by qualified health professionals and include:
Pre-radiotherapy imaging:
During standard MRI imaging session – non-standard diffusion weighted MRI (dwMRI) and dynamic contrast enhanced (DCE) MRI scans within Radiology facility.
During standard CT simulation session – additional CT scan in prone position within Austin Radiation Oncology.
Post-Radiotherapy - 3-4 weeks post completion of radiotherapy - non-standard timepoint for these scans
MRI session – including dwMRI and DCE MRI scans within Radiology facility.
PET session - PET imaging within Austin Nuclear & Molecular Imaging department.
A number of imaging scans are required to map disease for targeting of radiotherapy (RT), including CT, PET and MRI. Each provides slightly different information about the position, shape and composition of the disease that is used by a Radiation Oncologist to define where to target the radiation and how much radiation to deliver. We aim to add an extra, non-standard MRI imaging sequence called a diffusion weighted (dwMRI) scan, to understand the characteristics of the disease and how its use may change the size or shape of the target area so as to ensure complete treatment coverage and improved outcomes from treatment. Additionally, the use of contrast with MRI, dynamic contrast enhanced MRI (DCEMRI) has been shown in other cancer sites to help better identify and show the disease and to show response to treatment, and we wish to verify this in anal
Primary outcome(s): Identify the differences in radiotherapy target volume definition on standard (CT, T1/T2 MRI and PET) versus non-standard imaging modalities (dwMRI & DCE-MRI).[2 years post-radiotherapy]
Study Design: Purpose: Treatment; Allocation: Non-randomised trial; Masking: Open (masking not used);Assignment: Single group
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Project description:Objective: to focus on the molecular mechanisms involved in the dystrophic process that leads to selective wasting of single muscles or muscle groups in Facioscapulohumeral muscular dystrophy (FSHD). By muscle MRI we observed that T2-short tau inversion recovery (T2-STIR) sequences identify two different patterns in which each muscle can be found before the irreversible dystrophic alteration, marked as T1-weighted sequence hyperintensity. We studied these conditions in order to obtain further information on the disease pathogenesis. Design: histopathology, gene expression profiling and real time PCR were performed on muscle biopsies. Subjects: muscles (n=8) with different MRI pattern (T1-weighted normal/T2-STIR normal and T1-weighted normal/T2-STIR hyperintense) from FSHD patients. Data were also compared with inflammatory myopathies (n=7), dysferlinopathies (n=4) and normal controls (n=7). Results: myopathic and inflammatory changes characterize T2-STIR hyperintense FSHD muscles, at variance with T2-STIR normal muscles. These two states can be easily distinguished from each other by their transcriptional profile. Comparison of T2-STIR hyperintense FSHD muscles with muscles of inflammatory myopathies shows peculiar changes, although many alterations are shared among these conditions. Conclusions: at the single muscle level, different stages of the disease correspond to the two MRI patterns. T2-STIR hyperintense FSHD muscles are more similar to inflammatory myopathies than to T2-STIR normal FSHD muscles or other muscular dystrophies, and share with them upregulation of genes involved in innate and adaptive immunity. Our data suggest that selective inflammation, together with perturbation in biological processes such as neoangiogenesis, lipid metabolism and adipokine production, may play a role in FSHD progression.
2012-09-14 | GSE26852 | GEO
Project description:We report the results of a molecular study in thirty-seven cases of gliomatosis cerebri, correlating these results with prognosis. The well-known prognostic factors of gliomas, i.e., age, KPS, histology (Grade 2 vs. 3), or contrast enhancement, was predictive of response or outcome only in a percentage of patients but not in all patients. We identified an 8 miRNA signature able to predict patient prognosis with microarray gene expression profiling. The 8 gene features were used to built a prediction method able to distinguish patients with good prognosis (more likely to be responsive to therapy) from patients with a poor prognosis (less likely to be responsive to therapy). Keywords: miRNA expression profile Fifty-nine patients, between 12- and 73-years-old, with clinical signs of increased intracranial pressure were admitted to our institutions between January 2000 to September 2005. Pre-operative neuroradiological studies (CT scan and MRI) showed diffuse infiltrative processes involving more than two different lobes, no identifiable focal mass, and contrast enhancement absent or less than 1 cm in diameter. Written informed consent and tumour DNA were obtained for molecular analysis. Other eligibility criteria included a Karnofsky Performance Scale index (KPS) >50, normal bone marrow function (white blood cell count >3.0X109/l, neutrophil count >1.5X109/l, platelet count >100X109/l, and haemoglobin >10g/dL), normal liver function (aspartate aminotransferase or alanine aminotransferase <2 times the upper limit of laboratory normal, normal bilirubin, and alkaline phosphatase < 2 times the upper limit of normal), and normal renal function (serum creatinine <1.5 mg/dL). The patients received chemotherapy with temozolamide and radiotherapy. The TMZ schedule consisted of 150 to 200 mg/m2 was orally administered once daily on days 1 to 5. Treatment cycles were repeated every 28 days, with a maximum of 24 months. All patients had a monthly neurological and performance status evaluation and a radiological (MRI) evaluation every 2 to 3 months. Responses were evaluated according to previously described criteria (8): a clinical response was defined as an improvement of a neurological deficit or cognitive function evaluated by Mini-Mental Status Examination, an improvement of at least 75% in seizure frequency, or the disappearance of intracranial hypertension. When radiological MRI scans showed a reduction of more than 50% in the hyper intense area it was considered a partial response (PR), and a <50% regression or an objective regression of mass effect, was considered a minor response (MR). Disease was considered as stable when no clinical or radiological changes were seen for at least 6 months, whereas neurological deterioration, a need to increase corticosteroids, or evidence of tumour progression on MRI (an increase in the T2 or the appearance of contrast enhancement) indicated tumour progression.
2011-01-07 | E-GEOD-19870 | biostudies-arrayexpress