## 4 Discussion
Although most of the patients have a good prognosis with a standard treatment, and experience remission of the disease, some of them may experience relapse of the disease after the first line of treatment. FL is characterized by a high probability of BMI, and at least 70% of the patients have BMI, whereas the involvement of other organs is infrequent. Factors such as BMI can help identify disease extension and identify patients who may experience clinical failure and adjust therapeutic strategy accordingly. The results of this study demonstrate that the most reliable method to determine BMI in these patients remains the BMB. However, [18]FFDG PET/CT can be used as a complementary method. In contrast, when aggressive types of NHL were investigated, our results demonstrated that the [18]FFDG PET/CT achieves moderate sensitivity and high specificity. [18]FFDG PET/CT is a more sensitive method for detecting BMI compared to the BMB. Both the sensitivity and specificity of [18]F-PET/CT is higher for patients with aggressive NHL compared with patients with indolent NHL. The [18]FFDG PET/CT showed higher diagnostic accuracy for the assessment of aggressive NHL patients than indolent histologic subtypes of NHL, probably due to the high metabolic activity of the aggressive tumors. In highly aggressive subtypes, it is even more important to identify the extent of the disease as early as possible. When separating the population and investigating the most common aggressive subtype of NHL, DLBCL, from all eligible studies the sensitivity and specificity of FDG PET/CT in determining BMI was 77% and 92%, respectively. A previous meta-analysis conducted by [PERSON] et al. [11] in a study with a much smaller sample size, the authors found a higher sensitivity (88.7%) and specificity (99.8%) for [18]FFDG PET/CT in detecting BMI in DLBCL patients compared to our results. As a result of the presented findings, a combination of [18]FFDG PET/CT and BMB are be useful for improving the accuracy of BMI assessment and reducing the sampling error issue of BMB. This systematic review involved some limitations. In some studies PET/CT images were interpreted using qualitative criteria [15; 16; 17; 19; 20; 22; 26; 29; 31; 34; 35; 36; 37; 38; 39; 42; 43; 47; 48; 50; 52; 53; 54], whereas in other studies both qualitative and quantitative criteria were used [18; 23; 24; 25; 27; 28; 30; 32; 33; 40; 41; 44; 45; 46; 49; 51; 55]. As the qualitative evaluation is based on a subject's experience, this might underestimate the PET/CT diagnostic performance. Quantification using PET/CT images has shown improvement in the prediction of BMI compared to a qualitative analysis [51]. In addition, an even more improved prediction of BMI might be feasible with the use of radiomics that extract quantitative markers. The role of radiomic features in extracting useful information for diagnosis via BMI [18]FFDG PET/CT images has been shown in recent studies for the MCL [60] and DLBCL [61]. PET/MRI can also be used as a better predictor of BMI compared to BMB for NHL [62]. Compared with PET/CT, it is expected that PET/MRI can provide comparable detectability for lymphoma imaging [63; 64]. Other factors that might affect the results include region-specific and genetics-related differences; however, it was not possible to investigate these factors with the given data. The pattern and degree of bone marrow metabolic activity changes with age and FDG distribution is consequently affected. Previous studies have already concluded that SUV\({}_{\text{max}}\) in bone marrow is decreases with aging [65; 66]; therefore, differences among some studies evaluating PET/CT for BMI may be explained by possible variations in population ages in the samples used. However, the studies included in this review do not provide sufficient evidence to derive conclusions on how age-relatedchanges might affect PET/CT performance. Lastly, this systematic review included patients who were newly diagnosed with NHL.