Medical Policy



Subject: MRI of the Bone Marrow
Document #: RAD.00054 Current Effective Date:    06/28/2017
Status: Reviewed Last Review Date:    05/04/2017

Description/Scope

This document addresses magnetic resonance imaging (MRI) of the bone marrow, a non-invasive imaging procedure used to survey multiple anatomic areas in the axial and appendicular skeleton.

Note: This document does not address the use of MRI for visualization of bone marrow edema or localized structures adjacent to an injured joint.

Note: Please see the following documents for additional information related to other specialized MRI tests:

Position Statement

Investigational and Not Medically Necessary:

The use of magnetic resonance imaging (MRI) of the bone marrow is considered investigational and not medically necessary for all indications.

Rationale

MRI of the bone marrow has been proposed as a diagnostic tool to evaluate the initial tumor burden within the bone marrow from neoplastic infiltration and marrow replacement, or to assess treatment response to chemotherapy, radiation therapy or neoadjuvant therapy for hematological malignancies, including, but not limited to leukemias and multiple myeloma (Angtuaco, 2004). Despite consensus in the peer-reviewed published literature that MRI is a highly sensitive test for visualizing the extent of bone marrow changes, the primary limitation of this imaging modality is its lack of specificity to differentiate between tumor borders and any surrounding edema for most bone marrow disorders. Additionally, at this time there are no well-designed clinical trials demonstrating how this imaging procedure is used in directing treatment or that it improves outcomes.

According to Nöbauer and Uffmann (2005), MRI "has become the preferred imaging modality for the evaluation of bone marrow," as it is the "only modality that allows direct visualization of the bone marrow in vivo." They suggest that the utility of MRI, in combination with "projection radiography or CT, should enable the clinician to choose an adequate diagnostic strategy." However, the authors acknowledge the lack of specificity provided by MR images, without the initial use of conventional radiography or computed tomography (CT) modalities, may limit the value of this imaging modality. Specifically, as part of the diagnostic process, MRI of the bone marrow provides only nonspecific information in the evaluation of individuals with suspected bone marrow tumors.

A limited number of studies have been published focusing on MR imaging for the assessment of bone marrow response to treatment in chronic leukemia (Lecouvet, 1997). Vande Berg and colleagues (1995) have reported on the lack of value of sequential quantitative MR imaging of the bone marrow in predicting response to treatment in individuals with acute myelogenous leukemia.

In the initial evaluation of individuals with multiple myeloma, the National Cancer Institute (NCI, 2017) recommends evaluation of a number of parameters, including:

Detection of lytic bone lesions or generalized osteoporosis in skeletal x-rays, or whole-body or spinal and pelvic magnetic resonance imaging scans, or focal bone lesions on positron emission tomography-computed tomography scan (Dimopoulos, 2015).

MRI of the bone marrow has been suggested as a measure to evaluate therapy response and monitoring of individuals with multiple myeloma. The results of a single, large, phase III clinical trial conducted by the Arkansas Cancer Research Center (Walker, 2007) suggest that MRI of the bone marrow may contain specific prognostic information. The investigators recommend use of MRI of the bone marrow every 6 months in the individual with progressive or symptomatic multiple myeloma. This study, however, did not demonstrate that individual treatment plans were altered by the information obtained from the sequential imaging or that health outcomes were affected by the use of this imaging modality.

A subsequent cohort study (Ailawadhi, 2010) evaluated the extent of bone marrow infiltration with multiple myeloma in 170 individuals, including 144 individuals with active multiple myeloma (nontransplantation, irrespective of treatment status), using MRI of the bone marrow (BM-MRI) to quantify disease burden and validate a staging system by correlating BM-MRI with common clinical and laboratory parameters. Advanced stage disease (> stage I) based on Durie-Salmon (DS) staging or International Staging System (ISS) criteria was observed in 122 subjects (84%) and 77 subjects (53%), respectively. Lytic bone disease was noted in 120 individuals (83%). The investigators reported a significant association between BM-MRI involvement and DS stage (p=0.0006), ISS stage (p=0.0001), the presence of lytic bone disease (p<0.0001) and mean beta-2 microglobulin levels (p<0.0001). Among subjects with previously untreated multiple myeloma, there was a significant association between BM-MRI stage and overall survival (OS) (univariate, p=0.013; multivariate, p=0.045). Plasmacytosis on bone marrow biopsy at diagnosis was not predictive of OS (p=0.91). The investigators concluded that this:

novel BM-MRI staging system presented herein is accurate for predicting the extent of disease burden, is more reproducible than the currently used terminology for BM-MRI reporting, correlates well with currently used clinical and laboratory parameters for the assessment of disease, and correlates with survival outcome in patients with myeloma. However, larger prospective studies are warranted for the further validation of BM-MRI staging in patients with multiple myeloma, including its correlation with cytogenetic and molecular markers of disease.

The National Comprehensive Cancer Network® (NCCN® , 2016) Clinical Practice Guideline (CPG) for multiple myeloma includes recommendations for the initial diagnostic work-up and surveillance/follow-up of individuals with suspected or confirmed multiple myeloma. For the initial diagnostic work-up of suspected multiple myeloma, a radiographic skeletal survey, including the spine, pelvis, skull, humeri, and femurs, remains the standard method for imaging screening. "Imaging with whole body MRI or whole body PET/CT scan" is useful under some circumstances for the assessment of the extent and nature of soft tissue disease arising from bone lesions, and can detect unsuspected, asymptomatic lesions. "Additional testing (whole body MRI or whole body PET/CT scan) is recommended to discern active (symptomatic) from smoldering (asymptomatic) myeloma, if skeletal survey is negative..." To assess response (follow-up/surveillance) after primary therapy for active (symptomatic) myeloma, the NCCN guideline recommends whole body MRI, whole body low-dose CT, or PET/CT scan "as clinically indicated." The NCCN CPG does not include a recommendation for use of an MRI of the bone marrow over a standard skeletal survey for the diagnosis and surveillance/follow-up of multiple myeloma (NCCN, 2016).

An updated International Myeloma Working Group consensus statement (Dimopoulos, 2015) recommends use of standard whole body MRI testing for multiple myeloma as follows:

MRI is the imaging gold-standard method for the detection of bone marrow involvement in MM (grade A). We stress that MRI detects bone marrow involvement and not bone destruction. MRI of the spine and pelvis can detect approximately 90% of focal lesions in MM, and thus, it can be used in cases where WB-MRI [whole body-MRI] is not available (grade B). MRI is the procedure of choice to evaluate a painful lesion in patients with myeloma, mainly in the axial skeleton, and detect spinal cord compression (grade A)... MRI should be part of the staging procedures in patients with SBP [solitary bone plasmacytoma] to better assess the extent of the local tumor and reveal occult lesions elsewhere (grade A) (Dimopoulos, 2015).

For follow-up of individuals before or after different therapies, the systematic performance of standard MRI in the absence of clinical indications is not recommended. "Novel clinical studies have to include MRI for the response evaluation in an effort to clarify the role of MRI in this important field of myeloma therapy" (Dimopoulos, 2015).  

In summary, the available evidence in the medical literature is insufficient to demonstrate that MRI of the bone marrow offers improved outcomes over other diagnostic imaging procedures in the evaluation of initial tumor burden within the bone marrow from neoplastic infiltration and marrow replacement, or, to assess treatment response.

Background/Overview

Bone marrow is a soft, sponge-like tissue present in the center of most bones. Its main function is hematopoiesis, that is, it produces erythrocytes, leukocytes, and platelets to maintain oxygenation, immune function, and auto-restoration of the body. Hematological malignancies arising in the bone marrow include, but are not limited to, leukemias and multiple myeloma (NCI, 2017). Treatment effects due to irradiation, chemotherapy or neoadjuvant therapy treatment regimens may change one or several of the components of the bone marrow at the cellular level, thereby causing local or generalized changes in bone marrow signal intensity evident on magnetic resonance images.

MRI is a diagnostic technique that uses a cylindrical magnet and radio waves to produce high quality multiplanar images of organs and structures within the body without x-rays or radiation. These images can show the difference between normal and diseased tissue. MRI is used for imaging the brain, the spine, the soft tissue of joints, and the inside of bones. To undertake extensive coverage of the skeleton with MRI of the bone marrow, phased assay MR coils are often used. Compared with other imaging modalities, MRI is the only technique able to directly visualize bone marrow with its different components of red and yellow marrow. MRI as an imaging technique is most often used when preliminary diagnostics or symptoms suggest an abnormal condition requires further analysis. A posting in the American College of Radiology Bulletin (ACR, 2008) states that MRI of the bone marrow (that is, CPT 77084) is a stand-alone code used for bone marrow survey and should not be used as an "add-on" code to describe extra imaging sequences (for example, fat-saturated [FAT SAT] proton density-weighted MR imaging sequences), for visualizing irregularities in the articular cartilage of the knee and with other ankle and spine imaging.

For the initial diagnostic workup of multiple myeloma, many institutions utilize conventional radiographs of the axial skeleton and proximal extremities. This approach is still accepted as an important component of the clinical tumor staging system of Durie and Salmon, which defines the selection of the adequate therapy regimen (Durie and Salmon, 1975; Schmidt, 2007). In addition to MRI, other diagnostic imaging procedures are available to assess the bone marrow and allow for recognition of the effects of treatment on myeloma cells within the skeletal system, including skeletal radiographic surveys, CT, and nuclear scintigraphy (Schmidt, 2007). The combination of the staging system of Durie and Salmon and MRI has been proposed as a tool for clinical staging and prediction of survival in individuals with multiple myeloma (Baur, 2002; Lecouvet, 1998).  

Definitions

Durie-Salmon Staging System (DSSS): A staging system for multiple myeloma used as a predictor of health care outcomes; currently used as a standard for ongoing clinical trials.

Magnetic resonance imaging (MRI): A diagnostic technique that uses a cylindrical magnet and radio waves to produce high quality multiplanar images of organs and structures within the body without x-rays or radiation.

Multiple myeloma: A highly treatable, but rarely curable systemic malignancy of plasma cells.

Coding

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services are Investigational and Not Medically Necessary:

CPT  
77084 Magnetic resonance (eg, proton) imaging, bone marrow blood supply
   
ICD-10 Diagnosis  
  All diagnoses
   
References

Peer Reviewed Publications:

  1. Ailawadhi S, Abdelhalim AN, Derby L, et al. Extent of disease burden determined with magnetic resonance imaging of the bone marrow is predictive of survival outcome in patients with multiple myeloma. Cancer. 2010; 116(1):84-92.
  2. Angtuaco EJ, Fassas AB, Walker R, et al. Multiple myeloma: clinical review and diagnostic imaging. Radiology 2004; 231(1):11-13.
  3. Baur A, Stäbler A, Nagel D, et al. Magnetic resonance imaging as a supplement for the clinical staging system of Durie and Salmon? Cancer. 2002; 95(6):1334-1345.
  4. Durie BGM, Salmon SE. A clinical staging system for multiple myeloma: correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer. 1975; 36:842-854.
  5. Lecouvet FE, Vande Berg BC, Michaux L, et al. Early chronic lymphocytic leukemia: prognostic value of quantitative bone marrow MR imaging findings and correlation with hematologic variables. Radiology. 1997; 204:813-818.
  6. Lecouvet FE, Vande Berg BC, Michaux L, et al. Stage III multiple myeloma: clinical and prognostic value of spinal bone marrow MR imaging. Radiology. 1998; 209(3):653-660.
  7. Moulopoulos LA, Dimopoulos MA, Smith TL, et al. Prognostic significance of magnetic resonance imaging in patients with asymptomatic multiple myeloma. J Clin Oncol. 1995; 13(1):251-256.
  8. Moulopoulos LA, Dimopoulos MA, Weber D, et al. Magnetic resonance imaging in the staging of solitary plasmacytoma of bone. J Clin Oncol. 1993; 11(7):1311-1315.
  9. Nöbauer I, Uffmann M. Differential diagnosis of focal and diffuse neoplastic diseases of bone marrow in MRI. Eur J Radiol. 2005; 55(1):2-32.
  10. Schmidt GP, Kramer H, Reiser MF, Glaser C. Whole-body magnetic resonance imaging and positron emission tomography-computed tomography in oncology. Top Magn Reson Imaging. 2007; 18(3):193-202.
  11. Vande Berg BC, Lecouvet FE, Michaux L, et al. Stage I multiple myeloma: value of MR imaging of the bone marrow in the determination of prognosis. Radiology. 1996; 201(1):243-246.
  12. Vande Berg SC, Schmitz PJ, Scheiff JM, et al. Acute myeloid leukemia: lack of predictive value of sequential quantitative MR imaging during treatment. Radiology. 1995; 197(1):301-305.
  13. Walker R, Barlogie B, Haessler J, et al. Magnetic resonance imaging in multiple myeloma: diagnostic and clinical implications. J Clin Oncol. 2007; 25(9):1121-1128.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. American College of Radiology (ACR) Bulletin. ACR Radiology Coding Source™. January 2008; 63(1):28. Available at: http://www.acr.org/Advocacy/Economics-Health-Policy/Billing-Coding/Coding-Source-List. Accessed on February 23, 2017.
  2. Dimopoulos MA, Hillengass J, Usmani S, et al. Role of magnetic resonance imaging in the management of patients with multiple myeloma: a consensus statement. J Clin Oncol. 2015; 33(6):657-664.
  3. Dimopoulos MA, Kyle R, Fermand JP, et al. Consensus recommendations for standard investigative workup: report of the International Myeloma Workshop Consensus Panel 3. Blood. 2011; 117(18):4701-4705.
  4. NCCN Clinical Practice Guidelines in Oncology® . © 2016 National Comprehensive Cancer Network, Inc. Multiple myeloma. V.3.2017. Revised November 28, 2016. For additional information visit the NCCN website: http://www.nccn.org/index.asp. Accessed on February 23, 2017.
Websites for Additional Information
  1. National Cancer Institute (NCI). Cancer imaging program. Available at: http://imaging.cancer.gov/. Accessed on February 23, 2017.
  2. National Cancer Institute (NCI). Plasma cell neoplasms (including multiple myeloma) treatment (PDQ® ). Last modified February 3, 2017. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/myeloma/healthprofessional. Accessed on February 23, 2017.
Index

Multiple Myeloma

The use of specific product names is illustrative only.  It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available. 

Document History
Status Date Action
Reviewed 05/04/2017 Medical Policy & Technology Assessment Committee (MPTAC) review.
Reviewed 05/03/2017 Hematology/Oncology Subcommittee review. Updated Rationale, Background, References, and Websites for Additional Information sections.
Reviewed 05/05/2016 MPTAC review.
Reviewed 05/04/2016 Hematology/Oncology Subcommittee review. Updated References and Websites for Additional Information sections. Removed ICD-9 codes from Coding section.
Reviewed 05/07/2015 MPTAC review.
Reviewed 05/06/2015 Hematology/Oncology Subcommittee review. Updated References and Websites for Additional Information sections. Format changes throughout document.
Reviewed 05/15/2014 MPTAC review.
Reviewed 05/14/2014 Hematology/Oncology Subcommittee review. Updated Rationale, Background, References, Websites for Additional Information, and Index sections.
Reviewed 05/09/2013 MPTAC review.
Reviewed 05/08/2013 Hematology/Oncology Subcommittee review. Updated Rationale, Background, References, and Websites for Additional Information.
Reviewed 05/10/2012 MPTAC review.
Reviewed 05/09/2012 Hematology/Oncology Subcommittee review. Updated References.
Reviewed 02/16/2012 MPTAC review. Updated Description (added a Note), Rationale, Discussion, References, and Websites for Additional Information.
Reviewed 02/17/2011 MPTAC review. Updated Description, Rationale, Background, Coding, References, Web Sites for Additional Information, and the Index.
Reviewed 02/25/2010 MPTAC review. Updated Description and References.
Reviewed 02/26/2009 MPTAC review. Updated Description, Rationale and References.
New 02/21/2008 MPTAC review. Initial document development.