The Association Between Liver and Tumor [18F]FDG Uptake in Patients with Diffuse Large B Cell Lymphoma During Chemotherapy.

PURPOSE: The aim of this study was to explore the association between liver, mediastinum and tumor 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) uptake during chemotherapy in diffuse large B cell lymphoma (DLBCL). PROCEDURES: Nineteen patients with proven DLBCL underwent positron emission tomography (PET)/X-ray computed tomography scan at baseline, 1 week and 2 cycles after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy, and again after chemotherapy completion. The mean and maximal standardized uptake value (SUVmean and SUVmax) of the liver and mediastinum were measured and correlated with the tumor SUVmax, SUVsum, whole-body metabolic tumor volume (MTVwb), and total lesion glycolysis (TLG). RESULTS: At baseline, both the liver and mediastinum SUVmean and SUVmax correlated inversely with the tumor MTVwb or TLG (p < 0.01 or 0.001). The liver SUVmean and SUVmax increased significantly after 1 week of R-CHOP therapy and remained at the high level until chemotherapy completion. The mediastinum SUVmean and SUVmax remained stable during chemotherapy. The tumor SUVmax, SUVsum, MTVwb, and TLG decreased significantly after 1 week of R-CHOP therapy. The change of the liver SUVmean correlated inversely with the change of tumor MTVwb and TLG after 1 week of chemotherapy (p < 0.05, respectively). The intersubject variability of liver and mediastinum [18F]FDG uptake ranged from 11 to 26 %. CONCLUSIONS: The liver [18F]FDG uptake increased significantly after R-CHOP therapy. One of the possible reasons is the distribution of a greater fraction of the tracer to healthy tissues rather than tumor after effective chemotherapy. The variability of the liver [18F]FDG uptake during chemotherapy might affect the visual analysis of the interim PET scan and this needs to be confirmed in future studies with a large patient cohort. In addition, the intersubject variability of the liver and mediastinum [18F]FDG uptake should be considered.

Differentiation of Diffuse Large B-cell Lymphoma From Follicular Lymphoma Using Texture Analysis on Conventional MR Images at 3.0 Tesla.

RATIONAL AND OBJECTIVES: Diffuse large B-cell lymphoma (DLBCL) represents the most common type of aggressive non-Hodgkin lymphoma (NHL); follicular lymphoma (FL) is the most frequent indolent NHL. The aim of this study was to investigate whether texture-based analysis of conventional magnetic resonance imaging (MRI) allows discrimination of DLBCL from FL, and further, to correlate the MRI texture features with diffusion-weighted imaging apparent diffusion coefficient (ADC) value and tumor tissue cellularity. MATERIALS AND METHODS: Forty-one patients with histologically proven NHL (30 DLBCL and 11 FL) underwent conventional MRI and diffusion-weighted imaging examination before treatment. Based on regions of interest, texture analysis was performed on T1-weighted images pre- and postcontrast enhancement and on T2-weighted images with and without fat suppression, and features derived from the run-length matrix- and co-occurrence matrix-based methods were analyzed. Receiver operating characteristic curves were performed for the three most discriminative texture features for the differentiation of the two most common types of lymphoma. The analyzed MRI texture features were correlated with the ADC value and the tumor tissue cellularity. RESULTS: We found that on T1-weighted images postcontrast enhancement, run-length matrix-based texture analysis for lesion classification differentiated DLBCL from FL, with specificity and sensitivity of 76.6% and 76.5%, respectively. There was no correlation between the texture features and the ADC value or tumor tissue cellularity. CONCLUSIONS: DLBCL and FL can be differentiated by means of texture analysis on T1-weighted MRI postcontrast enhancement. These results could serve as a basis for the use of the texture features on conventional MRI as adjunct to clinical examination to distinguish DLBCL from FL.

Early interim PET/CT predicts post-treatment response in diffuse large B-cell lymphoma.

BACKGROUND: (18)F-FDG-PET/CT has been widely used in the staging of malignant lymphomas, and accepted as a tool for response assessment. Among PET parameters, the most frequently studied is maximal standardized uptake value (SUVmax). Metabolic tumor burden (MTB) is a parameter in which both metabolic tumor volume (MTV) and tumor activity are integrated. Here, we analyzed the prognostic value of SUVmax, SUVsum (sum of the SUVmax), whole-body MTV (MTVwb) and MTBwb from baseline and interim PET/CT in patients with diffuse large B-cell lymphoma (DLBCL). MATERIAL AND METHODS: Twenty-nine patients with histologically proven DLBCL were imaged by PET/CT before treatment (Exam I), and one week after the first dose of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy (Exam II). Biopsy specimens were examined by an expert hematopathologist, the Ki-67 proliferation index (PI) was estimated for each biopsy site from the MIB-1 stained sections. The response evaluation was performed after chemotherapy completion (6-8 cycles). RESULTS: All patients had one or more visualized lymphomatous lesions on (18)F-FDG-PET/CT. The SUVmax of the whole-body (BmSUVmax) was higher than the SUVmax at biopsy site (BxSUVmax) (mean: 20.1 vs. 17.3, p < 0.01). The PI correlated with the BxSUVmax (p < 0.05). One week after chemotherapy, SUVmax, SUVsum, MTVwb, and MTBwb decreased significantly (p < 0.01, respectively), SUVsum, MTVwb and MTBwb at Exam II correlated with chemotherapy response at treatment completion (p < 0.05, respectively). CONCLUSION: SUVmax is more accurate to detect tumor aggressiveness than biopsy in DLBCL, since BmSUVmax represents the most aggressive tumor of the patient. Interim PET/CT as early as one week after R-CHOP therapy predicts response. Thus, it could be used as a tool for guidance of risk stratification in DLBCL.

Correlations between functional imaging markers derived from PET/CT and diffusion-weighted MRI in diffuse large B-cell lymphoma and follicular lymphoma.

OBJECTIVES: To investigate the correlations between functional imaging markers derived from positron emission tomography/computed tomography (PET/CT) and diffusion-weighted magnetic resonance imaging (DWI) in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Further to compare the usefulness of these tumor markers in differentiating diagnosis of the two common types of Non-Hodgkin's lymphoma (NHL). MATERIALS AND METHODS: Thirty-four consecutive pre-therapy adult patients with proven NHL (23 DLBCL and 11 FL) underwent PET/CT and MRI examinations and laboratory tests. The maximum standardized uptake value (SUV(max)), metabolic tumor volume (MTV), and metabolic tumor burden (MTB) were determined from the PET/CT images. DWI was performed in addition to conventional MRI sequences using two b values (0 and 800 s/mm(2)). The minimum and mean apparent diffusion coefficient (ADC(min) and ADC(mean)) were measured on the parametric ADC maps. RESULTS: The SUV(max) correlated inversely with the ADC(min) (r =  -0.35, p<0.05). The ADC(min), ADC(mean), serum thymidine kinase (TK), Beta 2-microglobulin (B2m), lactate dehydrogenase (LD), and C-reactive protein (CRP) correlated with both whole-body MTV and whole-body MTB (p<0.05 or 0.01). The SUV(max), TK, LD, and CRP were significantly higher in the DLBCL group than in the FL group. Receiver operating characteristic curve analysis showed that they were reasonable predictors in differentiating DLBCL from FL. CONCLUSIONS: The functional imaging markers determined from PET/CT and DWI are associated, and the SUV(max) is superior to the ADC(min) in differentiating DLBCL from FL. All the measured serum markers are associated with functional imaging markers. Serum LD, TK, and CRP are useful in differentiating DLBCL from FL.

Comparison of different MRI sequences in lesion detection and early response evaluation of diffuse large B-cell lymphoma--a whole-body MRI and diffusion-weighted imaging study.

To compare different MRI sequences for the detection of lesions and the evaluation of response to chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL), 18 patients with histology-confirmed DLBCL underwent 3-T MRI scanning prior to and 1 week after chemotherapy. The MRI sequences included T1-weighted pre- and post-contrast, T2 -weighted with and without fat suppression, and a single-shot echo-planar diffusion-weighted imaging (DWI) with two b values (0 and 800 s/mm(2)). Conventional MRI sequence comparisons were performed using the contrast ratio between tumor and normal vertebral body instead of signal intensity. The apparent diffusion coefficient (ADC) of the tumor was measured directly on the parametric ADC map. The tumor volume was used as a reference for the evaluation of chemotherapy response. The mean tumor volume was 374 mL at baseline, and decreased by 65% 1 week after chemotherapy (p < 0.01). The T2 -weighted image with fat suppression showed a significantly higher contrast ratio compared with images from all other conventional MRI sequences, both before and after treatment (p < 0.01, respectively). The contrast ratio of the T2 -weighted image with fat suppression decreased significantly (p < 0.01), and that of the T1 -weighted pre-contrast image increased significantly (p < 0.01), after treatment. However, there was no correlation between the change in contrast ratio and tumor volume. The mean ADC value was 0.68 × 10(-3) mm(2)/s at baseline; it increased by 89% after chemotherapy (p < 0.001), and the change in ADC value correlated with the change in tumor volume (r = 0.66, p < 0.01). The baseline ADC value also correlated inversely with the percentage change in ADC after treatment (r = -0.62, p < 0.01). In conclusion, this study indicates that T2-weighted imaging with fat suppression is the best conventional sequence for the detection of lesions and evaluation of the efficacy of chemotherapy in DLBCL. DWI with ADC mapping is an imaging modality with both diagnostic and prognostic value that could complement conventional MRI.

ADC measurements in diffuse large B-cell lymphoma and follicular lymphoma: a DWI and cellularity study.

PURPOSE: Diffusion-weighted magnetic resonance imaging (DW-MRI) allows quantifying the random motion of water molecules in tissue by means of apparent diffusion coefficient (ADC) measurements. The aim of the study was to determine whether ADC measurements allow discrimination of diffuse large B-cell lymphoma (DLBCL) from follicular lymphoma (FL), and to examine the relationship between cellularity and ADC value of the tumor using DWI. MATERIALS AND METHODS: Thirty-two patients with histologically proven non-Hodgkin lymphoma (21 with DLBCL and 11 with FL, 17 males and 15 females, mean age 62±13 years) underwent conventional MRI and DWI examination before treatment. The ADC values of DLBCL were compared to those of FL. The ADC value of the tumor was also correlated with the tumor tissue cellularity. RESULTS: The mean ADC value of DLBCL was not significantly different from that of FL (0.70±0.16×10(-3)mm(2)/s vs. 0.76±0.12×10(-3)mm(2)/s, P=0.21). The cellularity of DLBCL was significantly lower than that of FL (2991±351 cells/view vs. 4412±767 cells/view, P<0.001). There was no correlation between the ADC value and the tissue cellularity of the tumor in patients with DLBCL and FL. CONCLUSION: ADC measurements could not differentiate between DLBCL and FL, and there was no correlation between the ADC value and cellularity of the tumor in patients with DLBCL and FL.

Glucose metabolism correlated with cellular proliferation in diffuse large B-cell lymphoma.

Standardized uptake value (SUV) is a marker of tumor glucose metabolism detected by [18F]-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG-PET/CT). The maximum SUV of the whole-body (BmSUV(max)) reflects the tumor aggressiveness in non-Hodgkin lymphoma. To evaluate the correlation between SUV(max) at biopsy site (BxSUV(max)) and proliferation potential of tumor cells in untreated diffuse large B-cell lymphoma (DLBCL), fifteen pre-therapy PET/CT scans in patients with histologically proven DLBCL were retrospectively analyzed together with Ki-67 proliferation index. The BmSUV(max) and BxSUV(max) were evaluated from the fused PET/CT images. Ki-67 proliferation index was measured in the biopsy specimens using an immunohistochemical technique in archival paraffin-embedded sections. The BmSUV(max) was significantly higher than the BxSUV(max) (mean 19.6 vs.16.6, p < 0.01). The BxSUV(max) correlated with the Ki-67 proliferation index (r = 0.7, p < 0.01), but no correlation was detected between the BmSUV(max) and the Ki-67 proliferation index. The results indicate that tumor proliferation potential might be predicted in vivo by FDG-PET/CT images. Thus, PET/CT is useful to guide biopsy by selecting sites with the BmSUV(max) when clinically appropriate.

PET imaging in a longitudinal non-Hodgkin's lymphoma study: association with tumor volume.

BACKGROUND: Computed tomography (CT) is generally used in the evaluation of the treatment response of non-Hodgkin's lymphoma (NHL) patients. Instead of morphological images, positron emission tomography (PET) shows metabolic information that is connected to tumor activity, cell proliferation rate, and, thus, prognosis. PURPOSE: To determine the prognostic value of PET for tumor volume reduction measured by CT and magnetic resonance imaging (MRI) along with clinical characteristics in NHL patients. MATERIAL AND METHODS: We imaged 21 B-cell type NHL patients using whole-body 18F-FDG-PET at the onset and the completion of treatment and at six-month follow-up. The maximum standardized uptake value (SUV(max)) was calculated. Morphological tumor volume calculations were assessed using both MRI and CT. Additionally, patients underwent thorough clinical examination including several laboratory tests. RESULTS: A high SUV(max) was able to predict significant tumor volume reduction at the beginning of treatment, but the relation to pure tumor volume was poor. CONCLUSION: The SUV(max) values derived from FDG-PET seemed to correlate with volume changes but not with their absolute values or laboratory tests. Unlike MRI and CT, FDG-PET showed the disappearance of active tumors after treatment.

No correlation between glucose metabolism and apparent diffusion coefficient in diffuse large B-cell lymphoma: a PET/CT and DW-MRI study.

PURPOSE: Both positron emission tomography/computed tomography (PET/CT) and diffusion-weighted magnetic resonance imaging (DW-MRI) are oncologic feasible techniques for evaluating the malignancy of tumors. Standardized uptake value (SUV) is a marker of tumor glucose metabolism detected by PET/CT. Apparent diffusion coefficient (ADC) measured by DWI can provide information about tissue cellularity. The aim of the study was to evaluate the correlation between SUV and ADC in untreated diffuse large B-cell lymphoma (DLBCL). MATERIALS AND METHODS: Fifteen pre-therapy patients with histologically proven DLBCL underwent PET/CT and DWI examinations within two days. Tumor glucose metabolism was evaluated by the maximum and mean SUV (SUV(max) and SUV(mean)) on the PET/CT images. The mean ADC value was measured directly on the parametric ADC maps. RESULTS: In total, 28 lymphoma lesions with best match PET/CT and DWI were identified and evaluated. The mean SUV(max) and SUV(mean) were 16.8 and 11.1, respectively; the mean ADC was 0.74 × 10(-3)mm(2)/s. There was no correlation between the mean ADC and the SUV(max) or SUV(mean). CONCLUSION: SUV determined from PET/CT and ADC value measured from DWI are different indices for the diagnosis of tumor malignancy, they may provide complimentary functional information of tumor tissue.

Diffusion-weighted MRI in early chemotherapy response evaluation of patients with diffuse large B-cell lymphoma--a pilot study: comparison with 2-deoxy-2-fluoro- D-glucose-positron emission tomography/computed tomography.

To determine the feasibility of diffusion-weighted MRI (DWI) in the evaluation of the early chemotherapeutic response in patients with aggressive non-Hodgkin's lymphoma (NHL), eight patients with histologically proven diffuse large B-cell lymphoma were imaged by MRI, including DWI, and positron emission tomography/computed tomography (PET/CT) before treatment (E1), and after 1 week (E2) and two cycles (E3) of chemotherapy. In all patients, whole-body screening using T(1) - and T(2) -weighted images in the coronal plane was performed. To quantitatively evaluate the chemotherapeutic response, axial images including DWI were acquired. Apparent diffusion coefficient (ADC) maps were reconstructed, and the ADC value of the tumor was measured. In addition, the tumor volume was estimated on axial T(2) -weighted images. The maximum standardized uptake value (SUV(max) ) and active tumor volume were measured on fused PET/CT images. Lymphomas showed high signal intensity on DW images and low signal intensity on ADC maps, except for necrotic foci. The mean pre-therapy ADC was 0.71 × 10(-3) mm(2) /s; it increased by 77% at E2 (p < 0.05) and 24% more at E3 (insignificant); the total increase was 106% (p < 0.05). The mean tumor volume by MRI was 276 mL at baseline; it decreased by 58% at E2 (p < 0.05) and 65% more at E3 (p < 0.05), giving a total decrease of 84% (p < 0.05). All the imaged pre-therapy tumors were strongly positive on PET/CT, with a mean SUV(max) of 20. The SUV(max) decreased by 60% at E2 (p < 0.05) and 59% more at E3 (p < 0.05), giving a total decrease of 83% (p < 0.05). The active tumor burden decreased by 66% at E2 (p < 0.05). At baseline, both central and peripheral tumor ADC values correlated inversely with SUV(max) (p < 0.05), and also correlated inversely with active tumor burden on PET/CT and with tumor volume on MRI at E2 (p < 0.05). In conclusion, the results of DWI in combination with whole-body MRI were comparable with those of integrated PET/CT.

Early treatment response evaluation in patients with diffuse large B-cell lymphoma--a pilot study comparing volumetric MRI and PET/CT.

PURPOSE: The purpose of this study is to evaluate the time course of early chemotherapy response in patients with aggressive non-Hodgkin's lymphoma (NHL) by magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT). PROCEDURES: Eight patients with histologically proven aggressive NHL were imaged by MRI and PET/CT before treatment (E1), 1 week (E2), and two cycles (E3) after chemotherapy. RESULTS: The mean tumor volume on MRI was 276 mL at baseline; it decreased 58% at E2 (p < 0.05) and 65% further at E3 (p < 0.05), giving a total decrease of 84% (p < 0.05). All the imaged pre-therapy tumors were strongly positive on PET/CT, with a mean maximum standardized uptake value (SUV(max)) of 20. The SUV(max) decreased 60% at E2 (p < 0.05) and 59% further at E3 (p < 0.05), giving a total decrease of 83% (p < 0.05). The active tumor burden (mean 229 mL) decreased 66% at E2 (p < 0.05). The tumor volume on MRI correlated with the active tumor volume on fused PET/CT images in the same region of interest at both E1 and E2 (r = 0.88, p < 0.01, respectively). CONCLUSIONS: Standard chemotherapy causes rapid decrease of both tumor metabolic activity and volume as early as 1 week, which continues to decline during therapy. Both volumetric MRI and PET/CT are valuable tools for early treatment response evaluation of aggressive NHL.

Computed tomography-based tumor volume in non-Hodgkin lymphoma: clinical correlation and comparison with magnetic resonance imaging.

OBJECTIVES: To evaluate the prognostic significance of tumor volume in computed tomographic (CT) images of non-Hodgkin lymphoma patients. To compare CT volumes with those measured by magnetic resonance imaging (MRI). METHODS: Twenty-five patients with B cell-type non-Hodgkin lymphoma (16 men, 9 women, age range, 48-77 years) were imaged with CT at 5 time points. The volumes and volume reductions were associated with clinical characteristics and treatment outcome. The CT-derived tumor volumes were correlated with MRI volumes derived earlier for the same patients. RESULTS: Good agreement was found between 1-dimensional (1D), 2D, and 3D analyses. The CT-derived median tumor volumes were 306 cm, 174 cm, 75 cm, 28 cm, and 15 cm at the 5 time points. These volumes were found to associate, for example, with mortality and tumor malignancy. The CT-based tumor volumes showed good correlation with MRI. CONCLUSIONS: Tumor volume quantification is a powerful tool that associates with clinical characteristics and treatment outcome.

Non-Hodgkin lymphoma response evaluation with MRI texture classification.

BACKGROUND: To show magnetic resonance imaging (MRI) texture appearance change in non-Hodgkin lymphoma (NHL) during treatment with response controlled by quantitative volume analysis. METHODS: A total of 19 patients having NHL with an evaluable lymphoma lesion were scanned at three imaging timepoints with 1.5T device during clinical treatment evaluation. Texture characteristics of images were analyzed and classified with MaZda application and statistical tests. RESULTS: NHL tissue MRI texture imaged before treatment and under chemotherapy was classified within several subgroups, showing best discrimination with 96% correct classification in non-linear discriminant analysis of T2-weighted images.Texture parameters of MRI data were successfully tested with statistical tests to assess the impact of the separability of the parameters in evaluating chemotherapy response in lymphoma tissue. CONCLUSION: Texture characteristics of MRI data were classified successfully; this proved texture analysis to be potential quantitative means of representing lymphoma tissue changes during chemotherapy response monitoring.

Response analysis of non-hodgkin lymphoma using magnetic resonance imaging-based volumes.

OBJECTIVE: The aim of this study was to determine the volume of non-Hodgkin lymphomas (NHLs) using semiautomatic segmentation and to correlate these results with clinical findings, treatment, and prognosis in patients with B-cell-type NHL. METHODS: For this study, 29 patients with NHL underwent magnetic resonance imaging at 5 time points after onset of disease. Volumetric analysis of the tumors was accomplished with semiautomatic segmentation by the Anatomatic software. RESULTS: The median tumor volumes from the first to the fifth examination were 468, 256, 90, 38, and 33 cm. Good correlation with 1-dimensional and 2-dimensional measures, used as standard methods in response categorization, was found. Surprisingly, volume reductions in excess of 239 cm after only 1 week of chemotherapy decreased the survival probability. CONCLUSIONS: Volume measurements seem to be highly informative for prognosis in the very early stages of treatment for patients with NHL.

CHOP is superior to CNOP in elderly patients with aggressive lymphoma while outcome is unaffected by filgrastim treatment: results of a Nordic Lymphoma Group randomized trial.

This study was designed to test the hypothesis that administration of granulocyte colony-stimulating factor (G-CSF; filgrastim) during induction chemotherapy with CHOP (cyclophosphamide, vincristine, doxorubicin, prednisone) or CNOP (doxorubicin replaced with mitoxantrone) in elderly patients with aggressive non-Hodgkin lymphoma (NHL) improves time to treatment failure (TTF), complete remission (CR) rate, and overall survival (OS). Furthermore, the efficacy of CHOP versus CNOP chemotherapy was compared. A total of 455 previously untreated patients older than 60 years with stages II to IV aggressive NHL were included in the analysis. Patients (median age, 71 years; range, 60-86 years) were randomized to receive CHOP (doxorubicin 50 mg/m(2)) or CNOP (mitoxantrone 10 mg/m(2)) with or without G-CSF (5 microg/kg from day 2 until day 10-14 of each cycle every 3 weeks; 8 cycles). Forty-seven patients previously hospitalized for class I to II congestive heart failure were randomized to receive CNOP with or without G-CSF (not included in the CHOP versus CNOP analysis). The CR rates in the CHOP/CNOP plus G-CSF and CHOP/CNOP groups were the same, 52%, and in the CHOP with or without G-CSF and CNOP with or without G-CSF groups, 60% and 43% (P <.001), respectively. No benefit of G-CSF in terms of TTF and OS could be shown (P =.96 and P =.22, respectively), whereas CHOP was superior to CNOP (TTF/OS P <.001). The incidences of severe granulocytopenia (World Health Organization grade IV) and granulocytopenic infections were higher in patients not receiving G-CSF. The cumulative proportion of patients receiving 90% or more of allocated chemotherapy was higher (P <.05) in patients receiving G-CSF. Concomitant G-CSF treatment did not improve CR rate, TTF, or OS. Patients receiving CHOP fared better than those given CNOP chemotherapy. The addition of G-CSF reduces the incidence of severe granulocytopenia and infections in elderly patients with aggressive NHL receiving CHOP or CNOP chemotherapy.