Bone Involvement In Myeloma Research Articles

Novel CT-Based Bone Strength Assessment By Finite Element Analysis for Monitoring Bone Involvement in Myeloma: a Proof of Concept Study

IntroductionMyeloma (MM) is characterized by osteolytic bone disease, detected in up to 80% of patients, increasing the risk for skeletal related events (SREs), causing morbidity, undermining quality of life and impairing survival. Current imaging modalities provide qualitative measures of bone involvement, often after irreversible damage has occurred.Bone strains are a biomechanical measure of bone strength which quantifies bone relative deformation in response to applied force. As a result of load on bone strains develop which may lead to fracture, once strain magnitude reaches the yield strain. Lytic bone lesions cause local weakening expressed by an increase in local strains.We developed CT-based finite element analysis (CTFEA), a novel measure designed to accurately estimate bone strains based on conventional CT scans. We hypothesize this tool may enable quantifying changes in bone strength over time, by monitoring strain. In this concept study we explore the sensitivity and responsiveness of CTFEA in myeloma patients to detect bone-disease progression and treatment response, and explore clinical correlates.MethodsPatients: A pilot retrospective study. After approval by the institutional ethics committee, 16 MM patients, with at least 2 consecutive CT scans including the spine and at least the proximal 1/3 of the femur since 2010 were identified. Demographic, clinical and radiographic data were abstracted from medical records.CTFEA: Femurs of interest were segmented from the CT scan, and a computational model was created with “stiffness” changing from point to point according to CT's gray values. The computational model was loaded virtually with a physiological stance position contact hip force (2.5 X body weight) applied on the femur's head. An elastic finite element analysis was performed that predicts the displacements and strains at any point within the bone (Figure 1). The locations of interest where the larger change in material properties may occur between consecutive CT scans were determined by computing the relative difference in Hounsfield unit (HU) radio-density along bone's axis. At these locations the principal strains were extracted and monitored. A monotonic increase in strains implies deterioration of bone strength, and vice versa. For patients with lytic lesions, bone strength is quantified by monitoring the principal strains in lesions vicinity. Healing is quantified by a decrease in strains. The CTFEA results were compared to conventional radiographic and laboratory measures.ResultsTable 1 summarizes individual patient clinical data at the time points of each of the CT-scans as well as the calculated CTFEA strain values at the location of maximum HU change of the initial 7 patients. Complete analysis of femur and vertebral strain for 16 patients will be presented at the meeting. Indeed no visible change in strain is demonstrated for smoldering MM (SMM) patients (Pts 15 and 16), whereas a monotonic increase is seen for patient 3, RRMM, with successive relapses without visible tumor identified in the femur in CT scans.Patient 17 (RRMM) with a lytic tumor at the distal femur, shows an initial deterioration of bone strength followed by a monotonic improvement until almost full regain of strength after 19 months.Patient 10 (NDMM) with a lytic tumor in the vicinity of the lesser trochanter, achieved a partial response of MM following anti-myeloma induction within 6 weeks, and as well as a significant increase in bone strength. Patient 13 had a rapid MM response but parallel worsening strain in the right femur, patient 18 had a MM partial response over 5 months with slight worsening of strain.ConclusionsPromising trends were found between CTFEA strain prediction and MM clinical course. SMM patients had minimal changes whereas a patient with progressive disease had a monotonic increase in strains. A decrease in strain was seen in some but not all who responded to therapy. The preliminary study is to be enhanced by considering vertebrae, analyzing further patients as well as prospective validation against SREs, to refine calibrate and tailor this measurement. By providing a quantitative metric of bone strain, this tool may allow monitoring bone strength throughout myeloma evolvement, prior to development of SREs. This may support physicians making personalized medical and surgical treatment decisions and provide a useful surrogate endpoint for clinical drug development. [Display omitted] DisclosuresYosibash:PerSimiO: Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Trabelsi:PerSimiO: Equity Ownership, Membership on an entity's Board of Directors or advisory committees.

Bone mineral density utilization in patients with newly diagnosed multiple myeloma.

Bone disease is a major cause for morbidity in multiple myeloma (MM), with the main focus concerning the manifestation as osteolytic lesions. Bone mineral loss is another reflection of myeloma bone involvement. Recently, osteoporosis has been omitted as a defining criterion for symptomatic disease in MM. We conducted a retrospective study to evaluate the use of bone mineral density (BMD) exams by dual-energy X-ray absorptiometry (DXA) among MM patients in a tertiary medical care centre. One-hundred seventy three patients were included. The T-scores of lumbar spine (LS), left femur neck (FN) and left total hip (TH) were obtained and analysed. The extent of osteolytic disease was categorized based on six bony areas. There was a strong correlation between spine and femur's T-scores (r = 0.56-0.61, p < 0.0001), although different sets of variables were correlated with LS and femur's T-scores. There was no correlation between BMD measurements and osteolytic disease extent. Patients with vertebral fracture(s) had significant lower T-scores of the spine in comparison to patients without vertebral fractures. Sixty-three patients (36.4% of the cohort) had follow-up DXA exam. In general, there was an increase in the LS T-scores, while femoral values decreased. However, in patients who achieved complete response (CR) and in those who retained CR during follow-up, femoral BMD increased as well. Because correlation between BMD and the extent of osteolytic lesions was not seen, our data support the recent exclusion of BMD assessment from the definition of symptomatic myeloma. Still, its use should be considered for evaluation of age- or therapy-related osteoporosis. Copyright © 2016 John Wiley & Sons, Ltd.

Solitary Extramedullary Plasmacytoma of the Parotid Gland Imaged With 18F-FDG PET/CT

A 75-year-old woman presented with a 1-year history of an enlarging mass in the left parotid gland. Biopsy revealed a parotid plasmacytoma, and the patient was referred for a staging F-FDG PET/CT to evaluate the presence of multiple myeloma bone involvement. The PET/CT scan showed intense FDG uptake in the neck mass but no FDG-avid lymphadenopathy or distant metastases. Plasmacytoma involving the parotid gland is extremely rare. We present the F-FDG PET/CT imaging of solitary parotid plasmacytoma.

The Role of Digital Tomosynthesis In the Staging of Newly Diagnosed Multiple Myeloma: Preliminary Data

AbstractAbstract 4057 Introduction:Multiple myeloma (MM) is a malignant plasma cell disorder which involves the skeleton in more than 80% of patients at diagnosis. Bone lesions in MM are screened with radiological skeletal bone survey (SBS) due to its low cost and widespread availability. Even though bone lesions can be missed by SBS, more sensitive newer imaging techniques are not currently recommended for routine use due to low availability, complicated methodology, and cost. X-ray digital tomosynthesis (DT) is a technique for producing thin slice images using conventional x-ray systems to maximize in-plane spatial resolution. DT has already been described for several mammographic, dental and thoracic applications to reduce overlap of tissue, but has not been studied in MM. The aim of our study was to determine the usefulness of DT in the staging of myeloma and to assess its strengths and limitations. Patients and Methods:We are conducting a prospective IRB approved study that has currently enrolled 19 newly diagnosed MM or Monoclonal Gammopathy of Undetermined Significance (MGUS) patients. Our target study population is 50 patients. Diagnosis and staging were made according to standard Durie-Salmon (DS) criteria. All the patients that were consented for our study underwent DT and SBS on the same day or within 60 days of each other (average 6.2 days) before treatment. Imaging findings from DT were compared to those seen in SBS with regard to the number and site of lesions detected. DT added coronal views of the thoracolumbar spine and pelvis to the routine SBS. These sites were chosen because they include a large percentage of the hematopoetically active marrow, are a significant source of morbidity, and are frequently obscured on SBS. A senior radiology resident and a Musculoskeletal fellowship trained (MSK) radiologist initially reviewed DT images independently and subsequently those images were reviewed together to achieve inter-observer agreement. Both of these imagers were blinded to the results of the skeletal survey. A different MSK radiologist, who was blinded to the DT results, interpreted the SBS. Results:Comparing DT to SBS, it was found that in 9 out of 19 patients (47.3%), DT detected more lesions (Table 1). Three out of 19 patients (15.7%) had a change in their staging due to findings seen in the DT study (upstaged from IA to IIIA, IB to IIIB and MGUS to IIIA). Nine out of 19 patients (47.3%) had negative myeloma bone involvement on both DT and SBS. One out of 19 patients (5.2%) had a suspicious lesion seen on the SBS that was cleared as negative with DT. Twelve patients were male, seven patients were female. The average age was 65.Sample lytic lesions on DT: [Display omitted] [Display omitted] [Display omitted] Discussion:In MM, imaging is needed to determine the stage of disease and to anticipate impending pathologic fractures. The prognostic value of bone involvement is exemplified by the fact that the traditionally used DS staging system includes radiographically evident lytic bone lesions as a criterion. The use of magnetic resonance imaging (MRI) and fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) with computed tomography (CT) have been studied in MM with varied results. Previous studies suggest that both FDG-PET in combination with low-dose CT and whole-body MRI might be more sensitive than SBS for screening multiple myeloma lesions. However the identification of marrow invasion in these methods is not specific for myelomatous bony destruction, and may need to be differentiated from other infiltrative processes such as hemangiomas and marrow reconversion in anemia. Marrow imaging might result in an over-staging without clear benefits for the patients. Our preliminary data in a small number of cases suggest that there is a group of patients in whom DT might detect other unsuspected sites of bone involvement. Digital Tomosynthesis resulted in more accurate staging in a small group of patients that would have been otherwise under-staged. Furthermore unrecognized areas of bone destruction were identified which rendered some patients eligible for bisphosphonates and palliative radiation therapy due to the newly discovered lesions seen on DT. Conclusions:Digital Tomosynthesis demonstrated increased sensitivity in the detection of osseous MM in the thoracolumbar spine and pelvis. Therefore, the preliminary data from our small prospective study shows encouraging results for the use of digital DT in the initial diagnosis and staging of MM. Disclosures:No relevant conflicts of interest to declare.

Whole Body MRI Versus Skeletal Survey in Multple Myeloma.

BACKGROUND: Bone involvement in myeloma is conventionally assessed by radiographic skeletal survey (plain x-rays of spine, skull, chest, pelvis and long bones). However this may not pick up bony involvement in all patients who may then present with serious complications of myeloma bone disease such as spinal cord compression. Whole body MRI may be better than skeletal survey at evaluating myeloma bone involvement.AIMS: To compare the evaluation of myeloma bone involvement by conventional radiographic skeletal survey (RSS) with whole body magnetic resonance imaging (MRI).METHODS: 35 patients with multiple myeloma (median age 68 yrs, range 46–81) underwent conventional RSS and whole body MRI. 19 of the patients had newly diagnosed multiple myeloma and 16 had relapsed multiple myeloma. The extent of myeloma bone involvement was evaluated in both RSS and MRI as follows: the body was divided up into ten areas: skull, cervical spine, ribs, thoracic spine, lumbar spine, pelvis, right arm, left arm, right leg, left leg. In each area the extent of myeloma bone involvement was scored in both RSS and MRI as follows: 0 = normal; 1 = one focus of abnormality; 2 = more than one focus of abnormality; 3 = diffuse disease. The scores for each of the ten areas were combined to give an overall score out of thirty for both RSS and MRI.RESULTS: 30 of the 35 patients (85.7%) had evidence of bone involvement on MRI. This compares with 22 out of the 35 (62.9%) on RSS. The mean score for the extent of myeloma bone involvement on MRI was significantly higher than that for RSS (MRI mean score: 15.5 out of 30 (median 17, range 0–30); RSS mean score: 5.5 out of 30 (median 3, range 0 to 24); p<0.001). MRI was superior to RSS in all ten areas evaluated both in terms of lesion detection and extent of disease. The greatest difference between MRI and RSS was seen in the cervical, thoracic and lumbar spine, while the smallest difference was seen in the ribs and skull. Eight of the patients had no bone involvement detectable on RSS but did have bone involvement on MRI and this resulted in upstaging on Durie-Salmon staging in four patients.SUMMARY/CONCLUSIONS: RSS has limited sensitivity and a significant ionising patient dose. It is a cumbersome procedure taking up to 30 minutes. Whole body MRI gives improved sensitivity and appreciation of anatomic location of disease. It is non-ionising and can be rapidly acquired at low cost. We conclude that whole body MRI is superior to conventional RSS in both the identification and evaluation of extent of bone involvement in multiple myeloma.

The critical role of interleukin-6, interleukin-1B and macrophage colony-stimulating factor in the pathogenesis of bone lesions in multiple myeloma.

Lytic bone lesions and hypercalcemia are common features of multiple myeloma. In contrast, they are exceptional in other B-cell malignancies. Myeloma bone involvement is related to an uncoupling process associating increased osteoclastic resorption with decreased bone formation. Several osteoclast-activating factors, such as interleukin-1, macrophage colony-stimulating factor, and interleukin-6, are involved in this process. However, interleukin-6, the major myeloma cell growth factor, plays a critical role in myeloma-induced bone resorption.

Mechanisms of Bone Lesions in Multiple Myeloma

Lytic bone lesions and hypercalcemia are common features of multiple myeloma; however, they are exceptional in other B-cell malignancies. Myeloma bone involvement is related to an uncoupling process associating an increased osteoclastic resorption with decreased bone formation. Several osteoclast-activating factors such as interleukin-1 (IL-1), tumor necrosis factor, and interleukin-6 (IL-6) are involved in this process. IL-6, the major myeloma cell growth factor, could play a critical role in myeloma-induced bone resorption in association with other known or unknown hematopoietic growth factors, however.