Frédéric Lecouvet

Magnetic Resonance Imaging of the Axial Skeleton for Detecting Bone Metastases in Patients With High-Risk Prostate Cancer: Diagnostic and Cost-Effectiveness and Comparison With Current Detection Strategies

PURPOSE To evaluate the diagnostic performance, costs, and impact on therapy of one-step magnetic resonance imaging (MRI) of the axial skeleton (MRIas) for detecting bone metastases in patients with high-risk prostate cancer (PCa). PATIENTS AND METHODS Sixty-six consecutive patients with high-risk PCa prospectively underwent MRIas in addition to the standard sequential work-up (SW) of bone metastases (technetium-99m bone scintigraphy [BS] completed with targeted x-rays [TXR] in patients with equivocal BS findings and with MRI obtained on request [MRIor] in patients with inconclusive BS/TXR findings). Panel review of initial and 6-month follow-up MRI findings, BS/TXR, and all available baseline and follow-up clinical and biologic data were used as the best valuable comparator to define metastatic status. Diagnostic effectiveness of MRIas alone was compared with each step of the SW. Impact of MRIas screening on patient management and costs was evaluated. RESULTS On the basis of the best valuable comparator, 41 patients (62%) had bone metastases. Sensitivities were 46% for BS alone, 63% for BS/TXR, 83% for BS/TXR/MRIor, and 100% for MRIas; the corresponding specificities were 32%, 64%, 100%, and 88%, respectively. MRIas was significantly more sensitive than any other approach (P < .05, McNemar). MRIas identified metastases in seven (30%) of 23 patients considered negative and eight (47%) of 17 patients considered equivocal by other strategies, which altered the initially planned therapy. Economic impact was variable among countries, depending on reimbursement rates. CONCLUSION MRIas is more sensitive than the current SW of radiographically identified bone metastases in high-risk PCa patients, which impacts the clinical management of a significant proportion of patients.

Can Whole-body Magnetic Resonance Imaging with Diffusion-weighted Imaging Replace Tc 99m Bone Scanning and Computed Tomography for Single-step Detection of Metastases in Patients with High-risk Prostate Cancer?

BACKGROUND Technetium Tc 99m bone scintigraphy (BS) and contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) of the pelvis and abdomen are universally recommended for detecting prostate cancer (PCa) metastases in cancer of all stages. However, this two-step approach has limited sensitivity and specificity. OBJECTIVE Evaluate the diagnostic accuracy of whole-body MRI (WBMRI) as a one-step screening test for PCa metastases. DESIGN, SETTING, AND PARTICIPANTS One hundred consecutive PCa patients at high risk for metastases prospectively underwent WBMRI, CT, and BS completed with targeted x-rays (BS/TXR) in case of equivocal BS. Four independent reviewers reviewed the images. MEASUREMENTS This study compares the diagnostic performance of WBMRI, CT, BS, and BS/TXR in detecting PCa metastases using area under the curve (AUC) receiver operator characteristics. A best valuable comparator (BVC) approach was used to adjudicate final metastatic status in the absence of pathologic evaluation. RESULTS AND LIMITATIONS Based on the BVC, 68 patients had metastases. The sensitivity of BS/TXR and WBMRI for detecting bone metastases was 86% and 98-100%, respectively (p<0.04), and specificity was 98% and 98-100%, respectively. The first and second WBMRI readers respectively identified bone metastases in 7 and 8 of 55 patients with negative BS/TXR. The sensitivity of CT and WBMRI for detecting enlarged lymph nodes was similar, at 77-82% for both; specificity was 95-96% and 96-98%, respectively. The sensitivity of the combination of BS/TXR plus CT and WBMRI for detecting bone metastases and/or enlarged lymph nodes was 84% and 91-94%, respectively (p=0.03-0.10); specificities were 94-97% and 91-96%, respectively. The 95% confidence interval of the difference between the AUC of the worst WBMRI reading and the AUC of any of the BS/TXR plus CT lay within the noninferiority margin of ±10% AUC. CONCLUSIONS WBMRI outperforms BS/TXR in detecting bone metastases and performs as well as CT for enlarged lymph node evaluation. WBMRI can replace the current multimodality metastatic work-up for the concurrent evaluation of bones and lymph nodes in high-risk PCa patients.

Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015

The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed available evidence for the ten most important areas of controversy in advanced prostate cancer management. Recommendations based on expert opinion are presented. Detailed decisions on treatment will involve clinical consideration of disease extent and location, prior treatments, host factors, patient preferences and logistical and economic constraints.

Skeletal survey in advanced multiple myeloma: radiographic versus MR imaging survey

In an attempt to compare the sensitivity of bone radiographs and bone marrow magnetic resonance (MR) imaging for bone lesion detection in patients with stage III multiple myeloma (MM) and to evaluate the possible consequences of the replacement of the conventional radiographic skeletal survey (RSS) by an MR survey of the spinal and pelvic bone marrow in these patients, we obtained MR studies of the thoracic and lumbar spine, pelvis and proximal femurs in addition to the conventional RSS (including radiographs of the skull, entire spine, pelvis, ribs, humerus and femurs) in 80 consecutive patients with newly diagnosed stage III MM according to the Durie and Salmon staging system (based on blood tests and on the RSS). The performance of MR and radiographic studies to detect bone lesions in given anatomic areas and in given patients were compared. The consequences on MM staging following the substitution of the RSS by the MR survey were assessed.

Magnetic resonance imaging of the normal bone marrow

Abstract The bone marrow is a complex organ that contains fat and nonfat cells, the proportions of which vary greatly with age and in the different bones of the skeleton. Magnetic resonance (MR) imaging provides information on the composition of the medullary cavity of any given bone and on the distribution of red and yellow marrow in the skeleton. This article deals with the wide spectrum of appearances of the normal bone marrow at MR imaging.

Magnetic resonance imaging of normal bone marrow.

Abstract. The appearance in magnetic resonance imaging (MRI) of the bones depends, to a large extent, on the unmineralized content of the bone cavities. Because yellow marrow contains a large number of fat protons and red marrow a significant number of water protons, MRI offers the opportunity to map the distribution of red and yellow marrow. In addition, red marrow MR appearance varies according to the relative proportion of fat and nonfat cells. Variations in the composition of red marrow and its distribution among normal subjects, mainly in relation to age and sex, contribute to creating a wide spectrum in bone MR appearance, which must be known in order to avoid confusion with bone marrow abnormalities.

Optimal management of metastatic castration-resistant prostate cancer: highlights from a European Expert Consensus Panel.

The exponential growth of novel therapies for the treatment of metastatic castration-resistant prostate cancer (mCRPC) over the last decade has created an acute need for education and guidance of clinicians regarding optimal strategies for patient management. A multidisciplinary panel of 21 European experts in mCRPC assembled for comprehensive discussion and consensus development, seeking to move the field forward and provide guidance and perspectives on optimal selection and sequencing of therapeutic agents and monitoring of response to treatment and disease progression. A total of 110 clinically-relevant questions were addressed and a modified Delphi method was utilised to obtain a consensus. The panel reached a consensus on several important issues, providing recommendations on appropriate phase III clinical trial end-points and optimal strategies for imaging and monitoring of bone metastases. Guidance regarding selection and sequencing of therapy in patients with newly diagnosed or progressive mCRPC is emphasised, including the use of novel bone-targeted agents, chemotherapy, androgen receptor pathway-targeted agents and immunotherapy. The impact of drug resistance and prostate-specific antigen flare on treatment decisions was also addressed. Ultimately, individualised therapy for patients with mCRPC is dependent on continued refinement of clinical decision-making based on patient and disease characteristics. This consensus statement offers clinicians expert guidance on the implementation of recent advances to improve patient outcome, focusing on the future of prostate cancer care.

Magnetic resonance imaging of the bone marrow in hematological malignancies

Abstract. Despite its lack of specificity, magnetic resonance imaging (MRI) of the bone marrow has the potential to play a role in the management of patients with primary neoplastic disorders of the hematopoietic system, including lymphomas, leukemias and multiple myeloma. In addition to its use in the assessment of suspected spinal cord compression, bone marrow MRI could be used as a prognostic method or as a technique to assess the response to treatment. The current review addresses the common patterns of bone marrow involvement observed in primary neoplasms of the bone marrow, basic technical principles of bone marrow MRI, and several applications of MRI in selected clinical situations.

Multidetector spiral CT arthrography of the shoulder. Clinical applications and limits, with MR arthrography and arthroscopic correlations

Although MR imaging and MR arthrography are the first choice modalities for shoulder imaging, CT arthrography (CTA) may be used successfully to address many clinical questions. The advent of submillimeter multiple detector CT technology and subsequent excellent three-plane resolution has considerably increased the quality of CTA examinations and has propelled this technique to the forefront in a growing number of indications. The combined use of iodinated contrast material for fluoroscopic confirmation of the articular position of the needle before injection of gadolinium chelates for MR arthrography offers the unique opportunity to compare CTA and MRA findings in carefully selected cases. This paper illustrates capabilities and limits of CTA for the study of rotator cuff tears, shoulder instability, cartilage lesions, anatomical variants and abnormalities of the glenoid labrum, with correlations to MR arthrography and surgical findings.

Prevention of Bone Metastases in Patients with High-risk Nonmetastatic Prostate Cancer Treated with Zoledronic Acid: Efficacy and Safety Results of the Zometa European Study (ZEUS)

BACKGROUND Patients with high-risk localised prostate cancer (PCa) are at risk of developing bone metastases (BMs). Zoledronic acid (ZA) significantly reduces the incidence of skeletal complications in castration-resistant metastatic PCa versus placebo. OBJECTIVE To investigate ZA for the prevention of BMs in high-risk localised PCa. DESIGN, SETTING, AND PARTICIPANTS Randomised open-label multinational study with patients having at least one of the following: prostate-specific antigen ≥20 ng/ml, node-positive disease, or Gleason score 8-10. INTERVENTION Standard PCa therapy alone or combined with 4mg ZA intravenously every 3 mo for ≤4 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS BMs were assessed using locally evaluated bone-imaging procedures (BIPs), with subsequent blinded central review. Patients with BMs, time to BMs, overall survival, and adverse events were compared between treatment groups. RESULTS AND LIMITATIONS A total of 1393 of 1433 randomised patients were used for intention-to-treat (ITT) efficacy analyses, with 1040 patients with BIP-BM outcome status at 4±0.5 yr. The local urologist/radiologist diagnosed BIP-BMs in 88 of 515 patients (17.1%) in the ZA group and 89 of 525 patients (17.0%) in the control group (chi-square test: p=0.95), with a difference between proportions of 0.1% (95% confidence interval [CI], -4.4 to 4.7) in favour of the control group. In the ITT population (n=1393), the Kaplan-Meier estimated proportion of BMs after a median follow-up of 4.8 yr was 14.7% in the ZA group versus 13.2% in the control group (log-rank: p=0.65). Low hot spot numbers on bone scans were confirmed as metastases with additional imaging. Central reviews of BIPs were possible only on a subset of patients. CONCLUSIONS ZA administered every 3 mo was demonstrated to be ineffective for the prevention of BMs in high-risk localised PCa patients at 4 yr. PATIENT SUMMARY Zoledronic acid administered every 3 mo was demonstrated to be ineffective for the prevention of bone metastases in high-risk nonmetastatic PCa patients at 4 yr. TRIAL REGISTRATION The ZEUS trial is registered in the Dutch trial register www.trialregister.nl and the ISRCTN register at http://www.controlled-trials.com/ISRCTN66626762.