Introduction
Plasma cell tumors are plasma cell malignancies characterized by the abnormal proliferation of primary malignant plasma cells in the bone marrow and the production of monoclonal immunoglobulins [
1]. According to the difference of serum abnormal immunoglobulin (M protein), it can be divided into 8 types: IgG type, IgA type, light chain type, IgD type, IgM type, IgE type, biclonal or polyclonal type, and non-secretory type. The main clinical manifestations are CRAB symptoms, namely hypercalcemia, renal insufficiency, anemia, and bone disease [
2]. 80–90% of patients with multiple myeloma will develop into bone disease. Although the treatment of MM has been greatly developed, MM is still an incurable disease with very different survival outcomes. Therefore, a simple and accurate systematic scoring method is urgently needed to evaluate the prognosis of patients and to improve the clinical management process of patients. At present, a number of studies have evaluated the factors affecting the prognosis of MM. These studies have shown the following: fluroine-18 fluorodexyglucose positron emission tomography/computed tomography (
18F-FDG PET/CT) characteristics (such as EMD, focal lesions (FLs), maximum standardized uptake value (SUVmax), and so on) and a lot of laboratory indicators (such as hemoglobin (Hb), albumin (Alb), creatinine (Cr), blood calcium (Ca
2+), lactate dehydrogenase (LDH), β
2 microglobulin (β
2-M), C-reactive protein(CRP), percentage of circulating plasma cells (CPC%), and so on) can more accurately evaluate the prognosis of patients [
3‐
11].
SUVmax is the most widely used in PET/CT parameters. Metabolic tumor volume (MTV) is a lesion metabolic volume parameter calculated on the basis of SUVmax, which is obtained by volume segmentation of lesions with high FDG uptake by setting a threshold. Total lesion glycolysis (TLG) is the product of MTV and mean standardized uptake value (SUVmean), metabolic tumor volume of all lesions (aMTV), and total lesion glycolysis of all lesions (aTLG) integrate the internal information of all lesions, quantify the total metabolic tumor burden, and can more comprehensively reflect the proliferation capacity, metabolic volume, and metabolic activity of systemic tumors. SUVmax of the lesion with the largest MTV (mSUVmax) can more accurately reflect the SUVmax value at the maximum tumor burden than SUVmax.
At present, there are few related studies using aMTV, aTLG, and mSUVmax to predict the prognosis of MM patients. In this study, 38 patients with newly diagnosed multiple myeloma (NDMM) from the Central People's Hospital of Yichang were retrospectively analyzed to study the relationship between 18F-FDG PET/CT imaging parameters, clinical laboratory parameters, and prognosis.
Discussion
At present, the commonly used inspection methods mainly include X-ray, CT, MRI, PET/CT and so on. The European Myeloma Network and European Society for Oncology guidelines recommend whole-body low-dose CT as the imaging method of choice for the initial evaluation of MM-related osteolytic lesions. MRI is the gold standard imaging method for detecting bone marrow involvement. PET/CT can provide valuable prognostic data and is the preferred technique for predicting and evaluating treatment response so far [
12]. X-ray, CT, and MRI all have certain limitations. They can only judge the extent or size of the lesion but cannot judge the metabolism of the lesion.
18F-FDG PET/CT, as a safe and non-invasive imaging examination method, can reflect changes in glucose metabolism before bone destruction occurs and can directly show the activity of the lesion. In addition, PET/CT is a whole-body inspection method and it can also greatly improve the detection rate of extramedullary lesions. For MM bone lesions, PET/CT can identify more than 90% of osteolytic lesions and 6% of osteogenic lesions [
13], with high sensitivity and specificity. PET/CT semi-quantitative parameters (aMTV and aTLG) have the advantages of reflecting biological information (such as the degree of metabolism and proliferation of tumor cells) and the volume of systemic tumors. They can comprehensively reflect the location and activity of systemic tumor lesions by evaluating the level of glucose metabolism. mSUVmax is the SUVmax value of the largest tumor burden lesions. They can better evaluate the tumor burden of NDMM patients than conventional PET parameters. There have been many studies applying PET/CT to the prognostic evaluation of MM. Their research has shown that patients with FLs ≥ 3, EMD, and high FDG intake have lower PFS and OS [
4,
5,
7,
9‐
11,
14‐
16]. A total of 192 patients were included in the study by Ntambi et al. The results showed that the prognosis of MM patients with TLG > 620 g and MTV > 210 cm
3 was worse, all
p < 0.05 [35]. The study of Fonti et al. showed that patients with MTV ≥ 42.2 mL had shorter PFS than MTV < 42.2 mL (
x2 = 3.9,
p = 0.04), and patients with MTV ≥ 77.6 mL had shorter OS than MTV < 77.6 mL (
x2 = 56.3,
p < 0.0001) [36]. Fonti et al. obtained more accurate results after a longer follow-up of MM patients: MM patients with MTV ≤ 39.4 mL had better PFS and OS than patients with MTV > 39.4 mL (
p = 0.0004,
p = 0.0001). The results of our study showed that PFS of NDMM patients with aMTV ≥ 90.97 cm
3 was 18.124 times that of patients with aMTV < 90.97cm
3,
p = 0.038; OS of NDMM patients with aMTV ≥ 90.97 cm
3 was 82.554 times that of patients with aMTV < 90.97 cm
3,
p = 0.038; The OS of NDMM patients with mSUVmax ≥ 5.8 was 23.095 times that of patients with mSUVmax < 5.8,
p = 0.008; the OS of NDMM patients with EMD was 7.918 times that of patients without EMD,
p = 0.012. In fact, aMTV shows tumor metabolic burden of whole body, and probably because of this intrinsic feature, it surpasses the prognostic value of some visual parameters of 18F-FDG PET/CT, such as SUVmax and mSUVmax. In this study, “patients with aTLG ≥ 283.31 g have a worse prognosis” is only statistically significant in univariate analysis, while in multivariate analysis, there is no significant correlation between aTLG and prognosis, which may be due to the small sample size. Further verification will be carried out by increasing the sample size in future.
There are currently 4 staging systems commonly used to assess the prognosis of MM, including ISS, DS, Revised International Staging System, and Durie-Salmon Plus. ISS divides patients into three different groups based on β
2M and serum albumin levels. DS combines the number of X-ray osteolytic lesions with a variety of clinical factors (such as serum calcium, hemoglobin levels, the number of M proteins, and renal function) for staging [
17]. Revised International Staging System is based on the ISS combined with LDH and cytogenetics (t(14;16), t(4;14), del17p) for abnormal staging, which improves the prognostic value of the ISS staging system [
18]. Durie-Salmon Plus is based on the number of lesions in
18F-FDG PET/CT for staging and is divided into subtypes A and B based on whether EMD and Cr > 2.0 mg/dL [
17]. The study by Deng et al. showed that compared with DS, DS Plus and Revised International Staging System have better potential in the characteristics and stratification of MM patients [
19]. In the study of Hu et al., they found that β
2M, LDH, FLs, and SUVmax are independent factors that predict OS in MM patients, and DS staging cannot predict OS in MM patients. They proposed a new staging system based on β
2M, FLs, SUVmax, and LDH. ISS and new staging system have shown great ability to distinguish between patients with poor prognosis and patients with good prognosis. However, ISS cannot distinguish the prognosis of stage II and stage III patients (
p = 0.226). The results show that compared with ISS, NSS is a better prognostic model for OS in MM patients [
11]. The study by Abe et al. combined
18F-FDG PET/CT with the proportion of CPC as a risk model for predicting the risk of newly diagnosed MM patients and divided the patients into three groups: PET-CPC stage I is no high-risk PET/CT Patients with low expression of CPC, stage III are patients with high-risk PET/CT performance and high CPC levels, and the remaining patients are classified as stage II. The conclusion of their study is that the three stages patients have significant differences in PFS and OS (
p = 0.001). The PET-CPC staging system can predict the survival outcome of newly diagnosed MM patients [
20]. Although the new staging system of Abe et al. and Hu et al. can predict the prognosis of patients well, they did not include aMTV and mSUVmax in the new staging system. This study included aMTV, mSUVmax, and EMD to develop a new staging system. The prognosis system can better evaluate the prognosis of patients than the ISS staging system: the 3-year OS rate in the NS staging system is 100.0, 53.5, and 32.1%,
p = 0.000; the 3-year OS rate in the ISS staging system is 66.7, 63.3, and 48.8%, respectively,
p = 0.145.
In recent years, cytogenetics and other indicators are also of great significance to the prognosis of MM. FISH has become a routine test for the prognostic stratification of MM patients. The characteristic genetic indicators are commonly superdiploid, 17p deletion, 1q21 amplification, and translocation Wait. For example, t(4;14), t(14;16), and 17p deletions are often considered to be related to the poor prognosis of MM patients. Yuan Jian et al. retrospectively analyzed the genetic data of 229 newly treated MM patients, and the results showed that 17p deletion, t(4;14), and 1q21 amplification are poor prognostic factors for MM patients [
21]. Since this study is a retrospective study and the economic conditions of patients are limited, only a small number of patients underwent FISH test. This study still needs to further expand the sample, incorporate genetic indicators into the prognostic analysis, and further combine PET/CT imaging indicators and laboratory parameters to achieve the fusion of genetics, imaging, and laboratory parameters, which will help guide NDMM patients’ diagnosis, treatment, and prognosis.
Conclusion
aMTV was better than other parameters, even SUVmax, in predicting PFS and OS in patients with NDMM. Compared with ISS, NS established in this study based on the results of Cox analysis can better evaluate the OS of MM patients. Although the new staging can more accurately predict the OS of MM patients to a certain extent, the limitation of this study lies in its retrospective nature and small sample, the selection of samples is biased, and the cytogenetic indicators have not been included, which is very important for verification. As a result, a large-sample prospective study still needs to be further confirmed.
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