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- MATERIALS AND METHODS
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.
MR imaging was superior to radiographs for lesion detection in the spine (76% v 42% of patients) and pelvis (75% v 46% of patients). The RSS was superior to the limited MR imaging survey for the detection of bone involvement in the patient population (87.5% v 79% of patients). If the RSS had been replaced by the MR imaging survey for patient staging, 7/80 patients would have been categorized as stage I and one as stage II MM on the basis of normal MR findings and biological findings consistent with these stages.
Substitution of the RSS by a limited spinal and pelvic marrow MR survey would lead to ‘understaging’ of 10% of patients with otherwise stage III MM on the basis of blood tests and the conventional RSS.
Multiple myeloma (MM) is a malignant disorder of plasma cells that seed throughout the bone marrow, usually produce a monoclonal immunoglobulin in the blood, urine, or both, and cause lytic bone lesions (Malpas & Caroll, 1995; Salmon & Cassady, 1995). The variability in individual symptoms and rate of disease progression, as well as the necessity to optimize therapy regimens, have raised the need for staging of the disease (Boccadoro & Pileri, 1997). Durie & Salmon (1975) showed that lytic bone lesions, haemoglobin, serum calcium and monoclonal component blood levels were significantly correlated with tumour mass and patient eventual survival. Their clinical staging system (Table I) based on these four parameters is still used for therapeutic management because of its easy application. Radiologists are routinely involved in patient staging, and discovery of at least two unequivocal rounded, punched-out lytic bone lesions indicates stage III MM for which immediate treatment is indicated (Durie & Salmon, 1975; Healy & Armstrong, 1994; Boccadoro & Pileri, 1995; Salmon & Cassady, 1995).
The superiority of MR imaging over plain radiographs for the detection of spinal bone lesions has been repeatedly demonstrated (Daffner et al, 1986; Ludwig et al, 1987; Fruehwald et al, 1988; Moulopoulos et al, 1994; Carlson et al, 1995; Tertti et al, 1995). The prognostic significance of bone marrow MR imaging has been demonstrated in early and advanced MM (Moulopoulos et al, 1995; Vande Berg et al, 1996; Weber et al, 1997; Zagdanski et al, 1997; Lecouvet et al, 1998). Several authors have suggested that MR imaging could play a role in the staging of the disease (Carlson et al, 1995; Stabler et al, 1996), but this issue has not been properly addressed.
The present study aimed to determine whether the conventional RSS could be replaced by an MR imaging survey limited to the spinal and pelvic marrow in the staging of advanced MM. We also determined the real importance of the conventional RSS in the staging of stage III MM, and compared the respective sensitivity of radiographs and MR imaging to detect bone lesions in well-defined anatomic areas.
- Top of page
- MATERIALS AND METHODS
A relatively simple staging system based on blood tests and conventional radiographs of the skeleton was proposed by Salmon and Durie more than two decades ago, and is still currently used to guide therapeutic decision in patients with MM (Durie & Salmon, 1975). Stage I patients with limited alterations in blood parameters and fewer than two bone lesions on conventional radiographs are not treated and are followed-up clinically (Hjorth et al, 1993; Alexanian & Dimopoulos, 1995). Stage II or III patients with more severe blood changes and/or multiple bone lesions on conventional radiographs require immediate initiation of chemotherapy (Boccadoro & Pileri, 1995).
Development of MR imaging as a tool to investigate bone marrow has raised the hope that it could also be used in MM staging (Carlson et al, 1995; Stabler et al, 1996). The results of the current study, based on the combined investigation of a series of 80 stage III MM patients by using conventional radiographs and MR imaging, confirm the important role of medical imaging in MM staging and the superiority of MR imaging over radiographs for lesion detection in given skeletal areas. However, this study reveals that substitution of the RSS by an MR imaging survey limited to the spine and pelvis would have caused understaging of eight patients, with a possible negative impact on patient management.
To the best of our knowledge, since Durie & Salmon (1975) emphasized the prognostic significance of bone radiographs in MM and incorporated the RSS in their staging system, the exact contribution of this radiological survey to patient categorization and therapeutic decision has never been quantitatively determined. Herein, we demonstrated that this survey played a decisive role for clinical management in 34% of patients with stage III disease.
Most of all, the current study demonstrated limitations in the value of MR imaging of the spine and pelvis for the detection of marrow involvement in a population of stage III MM patients despite its superiority over plain radiographs in defined skeletal areas. Actually, in this series of 80 patients with biopsy-proven marrow infiltration by neoplastic plasma cells, MR imaging failed to detect marrow involvement in 17 (21%) patients, whereas the RSS was normal in only 10 (12.5%) patients. Furthermore, replacement of the RSS by an MR imaging study of spinal and pelvic bones would have caused ‘understaging’ in eight patients. In addition, seven out of these eight patients would have been considered as stage I patients on the basis of minor blood tests alterations and normal MR studies. Treatment could have been unnecessarily delayed in these seven patients.
The limited sensitivity of MR imaging for the detection of marrow involvement has already been observed in previous studies of haematological malignancies and could be tentatively explained by either the limited sensitivity of the performed sequences or the limited proportion of bone marrow spaces that were investigated. First, the limited sensitivity of T1- and T2*-weighted MR images to diffuse marrow infiltration has been previously demonstrated in MM and several other haematological malignancies (Baur et al, 1997; Lecouvet et al, 1997b, 1998). Libshitz et al (1992) reported normal MR findings in 7/23 patients with stage III MM. An insufficient alteration in the fat/non-fat marrow balance could explain the relatively low sensitivity (Baur et al, 1997). Second, an insufficient volume of bone marrow could have been explored in the limited MR surveys, because the thoraco-lumbar spine and the pelvis only contain approximately 70% of the haemopoietic marrow of the whole skeleton, 30% was not therefore investigated (Cristy, 1981).
Several options can be proposed to overcome these limitations. On the one hand, to improve the sensitivity of conventional MR images to marrow infiltration, the performance of other sequences such as opposed phase gradient echo technique should be further evaluated (Stabler et al, 1996) and the role of quantitative MR imaging methods, dynamic studies of contrast enhancement, diffusion MR imaging, and MR spectroscopic studies of the bone marrow should be assessed. On the other hand, to increase the proportion of investigated marrow spaces, whole body MR imaging for marrow lesion detection should be evaluated. The feasibility of this technique has been suggested in recent studies of secondary bone lesions in non-haematological malignancies (Eustace et al, 1997; Steinborn et al, 1997). An alternative approach for myeloma staging could be a combination of an MR study of the spine and pelvis with a radiographic assessment limited to the peripheral skeleton. Review of the most commonly involved sites on plain radiographs in the total patient population and in those with normal MRI findings and biological findings consistent with stage I or II MM shows that the skull and ribs were by far the areas in which lytic lesions were the most frequently detected. Radiographs of the skull and ribs could be the more fruitful adjunct to MR images of the spine and pelvis that provide a limited view of marrow spaces.
Two points must be stressed. First, the study population consisted of patients with stage III MM. The observation that MR imaging is inferior to plain radiographs for lesion detection in a patient population only applies to stage III patients. It has been demonstrated that in patients with low tumour burden, MR imaging — even if limited to the spine and pelvis — was superior to RSS for detection of marrow involvement in a patient population (Moulopoulos et al, 1995; Vande Berg et al, 1996; Zagdanski et al, 1997). Second, according to our results, determination of stage III MM relied on blood tests in two-thirds of patients and the RSS was the determinant in one third of cases. It should not be concluded that conventional radiographs were unnecessary in two-thirds of patients. Initial radiographic findings are essential for the assessment of fracture risk and as a baseline evaluation for subsequent follow-up during treatment.
In conclusion, MR imaging of the spinal and pelvic bone marrow, despite its superiority over radiographs for lesion detection in well-defined skeletal areas, appears insufficient for the staging of MM patients with advanced disease. Further work is warranted to improve the sensitivity of MR imaging before its hypothetical use in the staging of MM.