Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

MR mammography

Ilse Vejborg, MD

Carsten Conrad, MD

Stig M Nielsen, MD

Leslie Christensen, MD

The purpose of the study is to determine whether MR of the breast is a better screening tool than mammography combined with ultrasound of the breast in women with BRCA1 or BRCA2 gene mutations.

Study type : Interventional Study design: Diagnostic,Prospective,Non Randomised,Blinded,Efficacy study

Further study details as provided by DBCG ( Danish Breast Cancer Cooperative Group):

Primary outcome measures:

Diagnostic outcome of a yearly screening with MR versus combined mammography and ultrasound of the breast measured by accuracy, sensitivity, specificity, positive and negative predictive values.

Secondary outcome measures:

Comparison of diagnostic outcome of MR versus combined mammography and ultrasound, in women with dense breast tissue compared with women with fatty breast tissue.

Comparison of the cancers found in women with BRCA gene mutations compared with the cancers found in the background population in respect of morphology, size, histological type, axillary lymph node status and grade.

Study start : January 2007. Expected completion 2010.

Women with BRCA gene mutations are more likely than others to develop the disease at a young age when breast density is higher than at older age.The tumours often are more rapidly developing with a short presymptomatic phase. These factors are known to reduce the effectiveness of screening with mammography and mammography seems to have a low sensitivity in women with BRCA gene mutations. Other studies have shown that more than 50% of the cancers appears as interval cancers between two mammography screening examinations and many have positive axillary nodes at the time of diagnosis.

Around 610 women are tested BRCA gene positive in Denmark in year 2006. These women are offered a yearly screening with mammography combined with ultrasound and a clinical examination. The trial will test whether this screening offer should be combined with or replaced by MR mammography.

National Screening in Denmark With MR Versus Mammography and Ultrasound of Women With BRCA1 or BRCA2 Mutations

National Screening i Danmark Med MR-scanning af Brystet Kontra Klinisk Mammografi Hos Kvinder Der er bærere af Risikogivende BRCA1 Eller BRCA2 Mutationer

Danish Breast Cancer Cooperative Group

Symptoms and General Pathology

Digestive System Diseases

Neoplasm Metastasis

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Rectal Diseases

Hematinics

All Drugs and Chemicals

Liver Extracts

Total diagnostic evaluation with MRI of the liver, abdomen, colonography and rectum in one session combined with CT thorax

Standard preoperative diagnostic evaluation for patients with rectal cancer, incl. CT thorax, abdomen and MRI of the rectum and colonoscopy

Altered planned surgical procedure if MR colonoscopy reveals synchronous cancer or larger polyps

MR colonography and MR of the liver

Standard diagnostic evaluation

Michael P Achiam, MD, Ph.D.

Patients with rectal cancer undergo MRI of the rectum, CT of the thorax and abdomen (or thorax x-ray and ultrasonic liver evaluation) and colonoscopy as a total diagnostic evaluation before surgery. MR colonography have been shown to have high sensitivity and specificity for larger polyps and cancer and MRI of the liver have been shown to have similar or higher sensitivity than CT of the liver for metastasis. Since patients already undergo MR of the rectum, the investigators have proposed a total diagnostic evaluation with MRI of the liver, abdomen, colonography and rectum in one session (minus thorax evaluation) instead of two or three different methods of evaluation. The investigators hypothesis is that the total MR evaluation is equal or superior to the existing preoperative evaluation regarding the diagnosis of synchronous cancers and liver metastasis and regarding cost-benefit for the total diagnostic evaluation.

Colorectal cancer (CRC) is among the most common cancer forms in Denmark with an approximate of 4300 new cases in Denmark annually, of which rectal cancer represents approximately 1400 new cases each year. It is also well known that synchronous cancer and polyps are present in up to 11% and 58% respectively in patients with CRC. It is assumed that adenomas constitute a precursor for cancer and it is thus speculated that the detection and removal of the adenoma could reduce the incidence and mortality of colorectal cancer. Danish Colorectal Cancer Group (DCCG) and the Danish Surgical Society (DKS) currently recommend full colonic investigation as part of the preoperative assessment, which also includes MRI of the rectum, ultrasound of the liver and chest X-ray (or abdominal /chest CT) to locate possible metastasis or synchronous tumors. However, it is often difficult to implement the preoperative colonic investigation due to lack of capacity or tumor stenosis. A recent Danish study showed that up to 78% of all patients with colorectal cancer had not received the full colonic investigation preoperatively. In this instance the recommendation from DCCG \& DKS is that patients in the absence of complete colonic investigation preoperatively, should undergo colonoscopy within 3 months postoperatively.

Within the last 15 years new non-invasive imaging techniques have been developed, this includes MR colonography (MRC). Like conventional colonoscopy, MRC requires bowel cleansing, since feces can create artifacts that can hide or mimic polyps and abnormalities. After cleansing the colon is distended by water using a rectal catheter. Since it is only water that needs to pass through a possibly stenotic colon segment, there is a better chance to successfully examine the entire colon compared to a colonoscopy. A recent study showed a 98% success rate using MRC to examine the entire colon in patients with CRC having colon stenosis. The MRC is preformed after the colon is fully distended with water and depending on the resolution needed the scan times are between 10 and 15 minutes. Data processing, reconstruction and analysis are made at an independent workstation.

The advantages of MRC are its non-invasive nature, short examination time, and the fact that sedation is unnecessary. This makes it possible for patients to be discharged directly after the imaging procedure as opposed to the necessity for admission after a colonoscopy until the effects of the sedative drugs have worn off. Furthermore, it is assumed that patient compliance is much higher in MRC, since almost every patient finds it less unpleasant than colonoscopy.

MRI of the liver is a well-known procedure that has shown good results in the diagnosis of hepatic metastases and primary cancers. Several studies have shown that it is equal or better than CT and ultrasound of the liver.

Currently there are no studies, which make the overall preoperative assessment by means of one investigating technique, namely MRI. The investigators have previously studied the sensitivity/specificity and patient satisfaction by MRI colonography with fecal tagging. In this study the investigators want to investigate the quality of MR-colonography with bowel cleansing, also assessing the economical aspects of an overall examination of the rectum, colon and liver in patients with rectal cancer.

Total Preoperative MR Diagnostic Evaluation Versus Standard Diagnostic Evaluation in Patients With Rectal Cancer

Prospective Randomized Study of Total Preoperative MR Diagnostic Evaluation Versus Standard Diagnostic Evaluation in Patients With Rectal Cancer

Herlev Hospital

Senior Resident, M.D., ph.d.

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Liver Neoplasms

Kidney Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Liver Diseases

Adenocarcinoma

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

30 patients with liver tumour and 15 patients with kidney tumour will be enrolled.

Patients will have a regular hepatic or kidney MRI investigation; we will add our sequences on their initial protocol. At first, one thermometry sequence is performed before angular correction is achieved with the following parameters: FOV=300 mm, matrix=96\*96, TE/TR=18/72 ms, 67 lines/TR, Sense factor=1.4, 5 slices (4 coronal et 1 sagittal), 30° Flip angle.

In order to determine the main direction of motion, a set of 200 images are acquired during motion with two interleaved orthogonal slices (one coronal and one sagittal) centered on the region of interest, with the read out direction aligned with the head-feet direction. True-fisp images are acquired during 40 seconds with the following parameters: FOV=400 mm, matrix=128\*109, TE/TR=1.2/2.43 ms, 60° flip angle, and 6 mm slice thickness.

Then the tested software proposes an angular correction to minimize out of plane motion. For each set of orientations, MR thermometry is performed

Hervé TRILLAUD, Pr

Several technological challenges exist to apply Magnetic Resonance guided High Intensity Focused Ultrasound (MRgHIFU) for treatment of liver or kidney in particular challenges related to the motion of these organs. This study tests a new software to improve thermometry accuracy in mobile organs in patients with liver or kidney tumors. In the same time, the trajectory of the target in 3D is analyzed.

Liver and kidney tumors represent a major health problem because most patients are unsuitable for curative treatment with surgery. Thus, percutaneous ablation, using radio frequency (RF), is preferred : an interstitial electrode that delivers alternative current is placed into the tissue. Consequently, the development of an accurate and completely non-invasive method based on MR guided HIFU treatment is of particular interest since the energy source is located outside the body. There is no incision. For the patient, it provides a treatment option with reduced trauma and improved quality of life, and for the society, it provides reduced hospitalization time and reduced costs.

MRgHIFU has already been tested clinically in tumors of immobilized tissues as uterine leiomyoma. However, several technological challenges exist to apply it for treatment of the liver or the kidney especially challenges related to the motions of these organs. In order to improve the therapeutic efficiency and the safety of the intervention, real time mapping of temperature and thermal dose appear to offer the best strategy to optimize such interventions and provide clinical therapy endpoints. Among imaging modalities, MRI Proton Resonance Frequency based method appears to be the ideal tool for temperature mapping.

One major drawback of PRF thermometry is its high sensitivity to motion. Therefore motion correction is necessary to use PRF thermometry in mobile organs such as the liver or kidneys. To correct artefacts generated in temperature maps by periodical organ motion, a new technique was developed in the IMF lab of Bordeaux University Hospital.

The primary outcome of this study is to evaluate the precision of multiplanar MR imaging with real time motion compensation in hepatic or renal tumour patient.

Secondary outcomes are :

* Characterization of 3d movements of the tumour and test if imaging is improved when the imaging plan contains the main axis of movement.
* Ballistic: we need to identify all anatomical structures which are in the way of the HIFU beam in order to define the types of tumour suitable for future treatments
* Another outcome is to define what modifications are needed in order to treat patients such as depth of treatment, power level. We also need to see the target, ribs, and the transducer in order to evaluate the number of transducer elements to be turned off during treatment.

Hepatic and Renal Thermography Using Magnetic Resonance Imaging

To test the ability of this method to improve thermometry accuracy, temperature standard deviations will be studied. Indeed, temperature standard deviations reflect thermometry inaccuracy in absence of temperature variations. Temperature standard deviation in each pixel will be measured over a temporal window. Two regions of interest (ROI) determined by the operator will be considered: the first one in the tumor, the second one for the whole organ.

To characterize tumor motion in the 3 dimensions during respiratory cycles :

To study the ability of this approach to determinate the 3D trajectory of a target, motion projections on three orthogonal axes will be analyzed from the MRI two orthogonal slices. If the motion can be assimilated to a rectilinear displacement, there will be amplitude minimization after angular correction.

we need to see all anatomical structures in the path of the HIFU cone. Depth of the tumour, number of ribs in the pathway, presence of sensitive organ in the pathway or in PTV vicinity will be recorded

To define what improvements are needed on the HIFU platform in order to enhance its therapeutical abilities (depth of treatment, power level...) Amount of transducer's elements masked by rib's shadow, calculation of power level required for treatment, required number of HIFU transducer elements to be turn-off will be calculated.

University Hospital, Bordeaux

Carcinoma, Hepatocellular

Body Weight

Neoplastic Processes

The patients responding to the chemotherapy, i.e. who show at least a non progressive disease

The patients non responding to the chemotherapy, i.e. who show a progressive disease

Stefano Colagrande, MD

One of the most recent and interesting field of diagnostic imaging is diffusion-weighted MR imaging (DW-MRI). Various studies evaluated the application of DW-MRI to diffuse liver disease and focal liver lesions providing controversial results, probably due to the difficult reproducibility of the apparent diffusion coefficient (ADC) measurements. It is conceivable that a wide inter/intra-individual variability actually exists in the apparent diffusion coefficient (ADC)-values, and that each apparent diffusion coefficient (ADC)-value presents an higher reliability in measuring the temporal changes of water diffusion within the same individual (longitudinal-evaluation), than in characterizing tissues between different patients (transverse-evaluation). For these reasons, some previous studies assessed the application of DW-MRI in predicting the chemotherapy (CHT) outcome in liver metastases. The rationale of these studies was the overt biochemical changes shown by the neoplastic cells after CHT and the sensitivity of DW-MRI in the identification of such changes. The same authors noticed that the metastatic lesions with the lowest ADC-values present also the best outcome after CHT. Moreover, these studies suggest that it could be possible to assess if each single patient will respond (R) or not (NR) to the CHT through liver DW-MRI performed from 3 days to 3 weeks after the beginning of CHT.

In R patients an increase of the mean diameter of the neoplastic cells should be present from the first week of CHT with a consequent reduction of the ADC-value. Then, the ADC-value should increase after 2-3 weeks due to the reduction of the cellular volume and to the increase of the membrane permeability. In NR patients, these biochemical changes should not be present with a consequent constant ADC-value before/after CHT. Our multicentre study will allow the recruitment of a higher number of patients vs. previous studies. Moreover, presently the outcome of CHT in liver metastases is evaluated only after 2-3 cycles of CHT according to the RECIST (Response-Evaluation-Criteria-In-Solid-Tumors) and then merely on a dimensional basis. Anyway, frequently liver metastases in R patients, can not show any significant dimensional change, while they present several biochemical/metabolic changes, not included in the RECIST, but probably detectable by DW-MRI.

The principal objective of the study is the early assessment of CHT outcome in liver metastases and advanced hepatocellular carcinoma (HCC). Patients with liver metastasis will be stratified as R and NR on the basis of the contrast-enhanced CT examination performed 20 days after the beginning of the second cycle of CHT; patients with HCC undergoing therapy with Sorafenib will be stratified as R and NR on the basis of the contrast-enhanced CT examination performed 90 days after the beginning of the therapy. The ADC-values obtained before and after the first CHT cycle will be compared between each patient category to assess the grade of agreement between the dimensional and functional parameters. Moreover, the investigators' aim is to assess whether those liver metastases or HCCs presenting a lower ADC-value before CHT are actually more responsive to CHT in comparison to liver metastases and HCCs presenting a higher ADC-value.

Secondary objectives: to propose some additional functional criteria to the RECIST 1.1 and mRECIST (for HCC) criteria based on water diffusion and biochemical changes of the neoplastic cells. As a further objective it is possible to hypothesize a different response to CHT of the different tumor histotypes detectable from the different ADC changes induced by CHT.

Patient population

Inclusion criteria:

* of age, compliant, patients enrolled for CHT, without major contraindications to the MR examination;
* non-confluent liver metastases, from every primary carcinoma histotype biopsy/surgical-proven, without intralesional necrosis/calcification involving \>30% of their volume;
* multiple confluent hepatocellular carcinomas, histotype biopsy/surgical-proven in prevision of treatment with Sorafenib;
* at least one marker lesion allowing reproducible ADC measurements, i.e. placed at the level of the lower right liver segments;
* detection/enrolment by contrast-enhanced CT before CHT that allow to define the lesion size or the gross parenchymal involvement (if HCC).

Each patient will sign an informed consent, after the procedure will be completely explained.

For the metastasis: three diameter of each marker lesion will be measured, and the mean/minimal/maximal ADC±standard deviation will be quantified by region-of-interests (ROIs) placed within the lesion avoiding lesion margins and the necrotic/intratumoral calcification areas. All measurements will be repeated for three times even at the level of the adjacent liver parenchyma (within 3 cm from the lesion margins, keeping a ROI diameter \>2 cm). Consequently, the absolute values (s/mm2) of ADC, and the ADC percentages vs. the adjacent liver parenchyma measured at the different times will be compared.

For HCC: three diameter of gross parenchymal involvement will be measured, and the mean/minimal/maximal ADC±standard deviation will be quantified by large region-of-interests (ROIs) placed within the liver lobe containing the involvement. All measurements will be repeated for three times even at the level of the adjacent normal liver parenchyma (within 3 cm from the lesion margins, keeping a ROI diameter \>2 cm). Consequently, the absolute values (s/mm2) of ADC, and the ADC percentages vs. the adjacent liver parenchyma measured at the different times will be compared.

Imaging

For metastasis: patients will be scanned by DW-MRI and contrast-enhanced CT before the beginning of CHT (Time 0). The time between the initial MRI and contrast-enhanced CT should not be superior to one week. MRI examination will be repeated within one week (Time 1) and 20 days from the beginning of the first cycle of CHT (Time 2), and 20 days from the beginning of the second cycle of CHT (Time 3).

For HCC: patients will be scanned by DW-MRI and contrast-enhanced CT before the beginning of CHT (Time 0). The time between the initial MRI and contrast-enhanced CT should not be superior to one week. MRI examination will be repeated after 30 days (Time 1), 60 days and 90 days (Time 3) from the beginning of the CHT.

Contrast-enhanced CT will be performed contemporarily or within one week after the last MRI examination.

Contrast-enhanced CT examination will be performed according to an established protocol by using a 16/64-row equipment according to the centre involved, contrast bolus-track technology, slice- thickness reconstruction of 3 mm, before/after ev. injection of iodinated contrast agent (3 mL/s), during arterial/portal phase.

All MR examinations will be carried out using the following 1.5-T units:

* Gyroscan ACS NT Intera Release 12 (Philips, Eindhoven, The Netherlands) (Trieste and Florence), gradient strength, 30 mT/m; slew rate, 120 T/m/s; six-channel phased array multicoil;
* Magnetom Avanto (Siemens, Erlangen, Germany) (Treviso and Napoli), gradient strength, 45 mT/m; slew rate, 200 T/m/s; 2 phased-array coils with 18 elements. The different MR equipments employed by the different centers will be calibrated by a dedicated phantom.

The phased array multicoil will be adequately positioned to cover the upper abdomen of the subject lying in a supine position, the arms extended over the head to avoid artifacts. Patients, fasting from 4 hours, will be instructed to maintain a constant respiration depth, even with the possibility to use exogenous oxygen delivery to avoid deep respiration. All acquisitions will be obtained by single-shot sequence to obtain immediately/automatically the ADC-values.

The protocol included the following acquisitions:

1. T2-weighted half-Fourier single-shot turbo spin-echo (HASTE) free-breath sequence; transverse/coronal plane; TR/TE, 810/80 ms; echo-train length, 69; slice number, 40; slice thickness, 5 mm; intersection gap, 10%; field of view, 300-420 mm; effective matrix size, 256 x 165; number signal averages (NSA), 1; total acquisition time, 2-3 min;
2. T1-weighted 2D gradient echo in/out phase breath-hold sequence; transverse plane; TR/TE, 231-121/ 14.6-2.3 ms; slice thickness, 5 mm; slice number, 24; intersection gap,10%; flip angle, 80°; sense factor, 1.5; field of view, 300-420 mm; effective matrix size, 256 x 165; NSA, 1; total acquisition time, 18 s;
3. D-weighted echo-planar imaging (EPI) single-shot free-breath sequences will be acquired on transverse plane with variable EPI factor and the following parameters. Fat suppression will be obtained by spectral pre-saturation inversion recovery. Isotropic motion probing gradients will be applied for each DwI acquisition and for each b-value will be obtained images and corresponding ADC map.

The investigators presently define as R those patients who show a reduction of the liver metastasis or HCC diameter ≥30% on contrast-enhanced CT at three weeks after the beginning of the second CHT cycle; if not, it was considered NR. Changes in tumor size after treatment were calculated by using the formula % Vend =(VB -Vend)/VBx100, where VB was lesion size before treatment (maximum transverse diameter) and Vend was lesion size 20 days after the second administration.

On the basis of the dimensional reduction of liver metastases and parenchymal involvement (for HCC) on contrast-enhanced CT on Time 3 vs. Time 0 scan, each patient will be classified as R or NR according to the RECIST and mRECIST criteria. Afterwards, on the basis of the ADC-values measured during the different MR examinations, the inter/intra-individual ADC-values will be compared to the results of contrast-enhanced CT to assess the relation between reduction of the liver metastasis diameter and:

* increase of the ADC-value on Time 3 (after the end of CHT);
* reduction of the ADC-value on Time 1 (very early assessment);
* increase of the ADC-value on Time 2 (early assessment); and to assess whether the lesions with the highest pre-treatment ADC-value present also the highest dimensional reduction and the highest ADC-value at the end of CHT; In each center each evaluation will be performed three times by two blinded observers (all trained how to place the ROI by an inter-centre conference) to assess the reproducibility of all measurements. The observers who will assess the MR images will be different from the observers assessing the CT images and will not be aware about the size changes after CHT. The investigators will perform data mathematical fitting on multi-b DW-MRI data sets to calculate the true diffusion and the perfusion fraction.

Statistical analysis will employ linear regression analysis to assess the association between the ADC-value changes and the CHT outcome.

The transferability of the results of the present study to the clinical practice will be possible after the achievement of the primary objective, corresponding to the possibility of stratifying patients as R and NR to CHT through DW-MRI just after one week of treatment and/or with the pre-treatment ADC assessment. Nowadays, it is necessary to wait 20-30 days after the end of the second or third CHT cycle to know the individual outcome of CHT. This determines 2-3 months of ineffective therapy with consequent avoidable pain for the patients related to drug administration, and unusable costs. The possibility to know the response of each patient to CHT well in advance will allow avoiding vain drug administration to patients who could attempt a different treatment or drug combinations reducing treatment costs.

The clinical transferability of the present study will be performed after the achievement of one or both the secondary objectives, corresponding to the identification of functional criteria based on water diffusion and biochemical features of the neoplastic cells which can be proposed as additional or alternative criteria to the RECIST 1.1 and mRECIST, and to the identification of a different response to CHT of different tumor histotypes. If only one of these objectives will be reached this study will achieve an important result, allowing a more correct assessment of individual response to CHT.

Use of DwI-MR to Predict Chemotherapy Response of Liver Metastases and Hepatocarcinoma

Assessment of Diffusion-weighted Magnetic Resonance (MR) Imaging to Predict Chemotherapy Outcome in Liver Metastases and Hepatocellular Carcinoma (HCC)

Linear regression analysis to assess the association between the ADC-value changes and the CHT outcome.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
National Screening in Denmark With MR Versus Mammography and Ultrasound of Women With BRCA1 or BRCA2 Mutations	NCT00413491	Breast Cancer	MR mammography MR	25 Years - 70 Years	Danish Breast Cancer Cooperative Group
Total Preoperative MR Diagnostic Evaluation Versus Standard Diagnostic Evaluation in Patients With Rectal Cancer	NCT01544452	Rectal Cancer Liver Metastasi...	MR colonography... Standard diagno...	18 Years -	Herlev Hospital
Hepatic and Renal Thermography Using Magnetic Resonance Imaging	NCT01197820	Liver Tumors Kidney Carcinom...	MRI	18 Years -	University Hospital, Bordeaux
Use of DwI-MR to Predict Chemotherapy Response of Liver Metastases and Hepatocarcinoma	NCT01411579	Liver Metastase... Hepatocarcinoma		18 Years - 80 Years	University of Florence

Spots Global Cancer Trial Database for mr

Every month we try and update this database with for mr cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for mr

Every month we try and update this database with for mr cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for mr cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.