Intravascular large B-cell lymphoma appearance on dual-energy computed tomography: a case report.

BACKGROUND: Intravascular large B-cell lymphoma (IVLBCL) is the proliferation of neoplastic B lymphocytes in the vascular space. Since conventional computed tomography (CT) shows nonspecific findings, differentiation between IVLBCL and other lung diseases, such as diffuse interstitial lung disease, is difficult. CASE PRESENTATION: A 73-year-old man presented with dyspnea and hypoxemia. Laboratory findings showed an increased lactate dehydrogenase level of 1690 U/L (normal: 130-235 U/L) and soluble interleukin-2 receptor level of 1140 U/mL (normal: 157-474U/mL). Dual-energy CT iodine mapping showed a significant symmetrical decrease in iodine distribution in the upper lungs, suggesting an unusual distribution of pulmonary hypoperfusion. Therefore, IVLBCL was suspected. A random skin biopsy confirmed the diagnosis of IVLBCL. Due to the severity of the disease, lung biopsy was averted. After admission to the hospital, high-dose methotrexate was administered for central nervous system involvement, due to findings of suspected intracranial infiltration on a brain magnetic resonance imaging and elevated cell counts on lumbar puncture. Subsequently, oxygen demand improved, and rituximab along with cyclophosphamide, doxorubicin, vincristine, and prednisone was added to the patient's regime. Eventually, oxygen administration was terminated, the patient's general condition improved, and the patient was discharged after 47 days of hospitalization. CONCLUSIONS: Since the diagnosis of IVLBCL depends on whether it is possible to suspect IVLBCL, the finding of decreased iodine perfusion demonstrated on dual-energy CT is considered important information for diagnosis. An immediate diagnosis of IVLBCL is needed to avoid rapid disease progression and introduce early treatment for a favorable prognosis. In this case, unique pulmonary hypoperfusion demonstrated by dual-energy CT promoted early diagnosis of IVLBCL.

Prognostic value of metabolic tumor volume and lesion dissemination from baseline PET/CT in patients with diffuse large B-cell lymphoma: Further risk stratification of the group with low-risk and high-risk NCCN-IPI.

PURPOSE: The purpose of this study was to determine the prognostic value of metabolic tumor volume and lesion dissemination from baseline PET/CT in patients with diffuse large B-cell lymphoma (DLBCL) and the prognostic value of them in the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) subgroups. METHODS: A total of 113 patients who underwent 18F-FDG PET/CT examination in our institution were retrospectively collected. The MTV was measured by iterative adaptive algorithm. The location of the lesion was obtained according to its three-dimensional coordinates, and Dmax was obtained. SDmax is derived from Dmax standardized by body surface area (BSA). The X-tile method was used to determine the optimal cut-off values for MTV, Dmax and SDmax. Cox regression analysis was used to perform univariate and multivariate analyses. Patient survival rates were derived from Kaplan-Meier curves and compared using the log-rank test. RESULTS: The median follow-up time was 24 months. The median of MTV was 196.86 cm3 (range 2.54-2925.37 cm3), and the optimal cut-off value was 489 cm3. The median of SDmax was 0.25 m-1 (range 0.12-0.51 m-1), and the best cut-off value was 0.31 m-1. MTV and SDmax were independent prognostic factors of PFS (all P < 0.001). Combined with MTV and SDmax, the patients were divided into three groups, and the difference of PFS among the groups was statistically significant (P < 0.001), and was able to stratify the risk of NCCN-IPI patients in the low-risk (NCCN-IPI < 4) and high-risk (NCCN-IPI ≥ 4) groups (P = 0.001 and P = 0.031). CONCLUSION: MTV and SDmax are independent prognostic factors for PFS in DCBCL patients, which describe tumor burden and tumor dissemination characteristics, respectively. The combination of the two could facilitate risk stratification between the low-risk and high-risk NCCN-IPI groups.

[The Prognosis Assessment Value of Interim 18F-FDG PET/CT Imaging in the Chemotherapy of Diffuse Large B-cell Lymphoma].

OBJECTIVE: To investigate the prognostic value of interim 18F-FDG PET/CT in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 97 patients with pathologically diagnosed DLBCL at Sichuan Cancer Hospital and Institute from March 2015 to June 2020 were enrolled in this retrospective study. Receiver operating characteristic analysis (ROC) was used to calculate the optimum maximum standard uptake value reduction ratio (△SUVmax%) cut-off value. The prognostic value of △SUVmax% and Deauville five-point scale (5-PS) in patients with DLBCL was compared, and the determined prognostic factors were analyzed. RESULTS: ROC curve indicated that the optimum △SUV max% cut-off value was 74.9%. Patients with △SUVmax%≥74.9% had a lower rate of progression or recurrence than those with △SUVmax% < 74.9% (both P<0.001). Meanwhile, patients with 5-PS score < 4 also had a lower rate of progression or recurrence than those with 5-PS score≥4 (both P<0.001). △SUVmax% and 5-PS had high specificity (83.7% vs 83.7%) and negative predictive value (87.3% vs 84.9%), while low sensitivity (56.0% vs 52.2%) and positive predictive value (53.8% vs 50.0%). △SUVmax% was more sensitive than 5-PS for the corresponding parameters (78.3% vs 76.2%). Univariate analysis showed that Ann Arbor stage, international prognostic index of National Comprehensive Cancer Network (NCCN-IPI), △SUVmax% and 5-PS were associated with TTP and PFS (all P<0.001). Multivariate analysis showed that △SUVmax% was an independent predictor of TTP and PFS (P=0.031, P=0.023). CONCLUSION: Both 5-PS and △SUVmax% can be used to evaluate the prognosis of DLBCL patients, but the predictive value of △SUVmax% is superior to that of 5-PS.

Optimal PET-based radiomic signature construction based on the cross-combination method for predicting the survival of patients with diffuse large B-cell lymphoma.

PURPOSE: To develop and externally validate models incorporating a PET radiomics signature (R-signature) obtained by the cross-combination method for predicting the survival of patients with diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 383 patients with DLBCL from two medical centres between 2011 and 2019 were included. The cross-combination method was used on three types of PET radiomics features from the training cohort to generate 49 feature selection-classification candidates based on 7 different machine learning models. The R-signature was then built by selecting the optimal candidates based on their progression-free survival (PFS) and overall survival (OS). Cox regression analysis was used to develop the survival prediction models. The calibration, discrimination, and clinical utility of the models were assessed and externally validated. RESULTS: The R-signatures determined by 12 and 31 radiomics features were significantly associated with PFS and OS, respectively (P<0.05). The combined models that incorporated R-signatures, metabolic metrics, and clinical risk factors exhibited significant prognostic superiority over the clinical models, PET-based models, and the National Comprehensive Cancer Network International Prognostic Index in terms of both PFS (C-index: 0.801 vs. 0.732 vs. 0.785 vs. 0.720, respectively) and OS (C-index: 0.807 vs. 0.740 vs. 0.773 vs. 0.726, respectively). For external validation, the C-indices were 0.758 vs. 0.621 vs. 0.732 vs. 0.673 and 0.794 vs. 0.696 vs. 0.781 vs. 0.708 in the PFS and OS analyses, respectively. The calibration curves showed good consistency, and the decision curve analysis supported the clinical utility of the combined model. CONCLUSION: The R-signature could be used as a survival predictor for DLBCL, and its combination with clinical factors may allow for accurate risk stratification.

Wernicke encephalopathy with extensive cortical lesions combined with diffuse large B-cell lymphoma.

OBJECTIVE: Wernicke encephalopathy (WE) is an acute or subacute neurologic disorder resulting from thiamine deficiency. A Magnetic Resonance Imaging (MRI) test is useful in addition to the clinical manifestation, which is the main basis for the diagnosis. Typical MRI findings include areas surrounding the aqueduct and third ventricle, as well as those in the medial thalamus, dorsal medulla, tectal plate, and mamillary bodies. We reported a case of WE with extensive cortical lesions. The beneficial effects of thiamine supplementation and low dosage of glucocorticoid did not sustain after discharge. Eventually, we found that the condition he had was brought on by gastric diffuse large B-cell lymphoma. Thiamine supplements combined with glucocorticoids may be a good administration regimen. The etiology of WE is frequently disregarded. In individuals with WE, it is essential to take the underlying illness into account. Malignancy, especially gastrointestinal tract cancer, should be considered. A good administration regimen may include glucocorticoids and thiamine supplements.

A PET in a time of need: toward early PET-adapted therapy in DLBCL in first relapse.

Salvage chemotherapy and autologous stem cell transplant remain a standard of care in the management of diffuse large B cell lymphoma (DLBCL) at first relapse. However, this paradigm is increasingly being challenged by novel immunotherapies, such as chimeric antigen receptor T-cells (CART-cells). Traditional positron emission tomography-based (PET) prognostication takes place after salvage and before autologous stem cell transplant (ASCT), and while useful, for many patients this information comes too late and at the expense of unnecessary toxicity. In this edition of Leukemia & Lymphoma, two groups present their findings on the use of early quantitative PET markers and the correlation with outcomes in patients embarking on second line salvage chemotherapy. These approaches have the potential to better identify patients who are destined for treatment failure and help guide appropriate sequencing of alternative therapies or the development of PET-adapted clinical trials.

The Role of Interim PET/CT on Survival in Diffuse Large B Cell Lymphoma.

BACKGROUND: Diffuse large B cell lymphoma is the most frequent aggressive non-Hodgkin lymphoma. Predicting response and estimating prognosis earlier makes management of this heterogeneous lymphoma more satisfying. Interim PET response is established in Hodgkin Lymphoma to tailor the therapy but results for non-Hodgkin Lymphoma is unconvincing. In the current study evaluation of interim PET and survival outcomes of 103 DLBCL patients is performed. PATIENTS AND METHODS: About 103 Patients with DLBCL followed up in a single center between 2009 and 2019 were enrolled the study. All patients received R-CHOP chemoimmunotherapy at first line. Interim PET was performed after at least one or more cycles. All PET scans were performed with 18F-FDG isotope as PET/CT. PET scoring results were evaluated according to the 5-Point Deauville Scoring system defined in the National Comprehensive Cancer Network clinical guidelines for iPET and eotPET. 5-P DS of scores of 1 to 3 were defined as negative scans, and scores of 4 to 5 were considered to be positive scans. RESULTS: Forty-six (44.7%) Female and 57 (55.3%) male aged between 25 and 83 (median 57) years newly diagnosed DLBCL patients were enrolled in the study. Median PFS was 21 (interquartile range 8.5-53.7) months and median OS was 33.5 (interquartile range 12.5-62.9) months for the total cohort. Positive predictive value of interim PET according to Deauville scoring system was 65.4% and negative predictive value was 77.9%. CONCLUSION: Our study showed that according to Deauville 5 point scale (D 5PS) scoring system, interim PET-positive patients have shorter both PFS and OS than iPET-negative patients.

Patterns and Predictors of Failure in Recurrent or Refractory Large B-Cell Lymphomas After Chimeric Antigen Receptor T-Cell Therapy.

PURPOSE: Chimeric antigen receptor T-cell (CAR T) therapy is capable of eliciting durable responses in patients with relapsed/refractory (R/R) lymphomas. However, most treated patients relapse. Patterns of failure after CAR T have not been previously characterized, and may provide insights into the mechanisms of resistance guiding future treatment strategies. METHODS AND MATERIALS: This is a retrospective analysis of patients with R/R large B-cell lymphoma who were treated with anti-CD19 CAR T at a National Cancer Institute-designated Comprehensive Cancer Center between 2015 and 2019. Pre- and posttreatment positron emission/computed tomography scans were analyzed to assess the progression of existing (local failures) versus new, nonoverlapping lesions (de novo failures) and identify lesions at a high risk for progression. RESULTS: A total of 469 pretreatment lesions in 63 patients were identified. At a median follow-up of 12.6 months, 36 patients (57%) recurred. Most (n = 31; 86%) had a component of local failure, and 13 patients (36%) exhibited strictly local failures. Even when progressing, 84% of recurrent patients continued to have a subset of pretreatment lesions maintain positron emission/computed tomography resolution. Lesions at a high risk for local failure included those with a diameter ≥5 cm (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.55-3.55; P < .001), maximum standardized uptake value ≥10 (OR, 2.08; 95% CI, 1.38-3.12; P < .001), or those that were extranodal (OR, 1.49; 95% CI, 1.10-2.04; P = .01). In the 69 patients eligible for survival analysis, those with any lesion ≥5 cm (n = 46; 67%) experienced inferior progression-free survival (hazard ratio, 2.41; 95% CI, 1.15-5.04; P = .02) and overall survival (hazard ratio, 3.36; 95% CI, 1.17-9.96; P = .02). CONCLUSIONS: Most patients who recur after CAR T experience a component of local progression. Furthermore, lesions with high-risk features, particularly large size, were associated with inferior treatment efficacy and patient survival. Taken together, these observations suggest that lesion-specific resistance may contribute to CAR T treatment failure. Locally directed therapies to high-risk lesions, such as radiation therapy, may be a viable strategy to prevent CAR T failures in select patients.

Prognostic significance of bone marrow 2-[18F]-fluoro-2-deoxy-d-glucose uptake in diffuse large B-cell lymphoma: relation to iliac crest biopsy results.

AIM: To investigate the prognostic significance of bone marrow (BM) 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) uptake in relation to posterior iliac crest BM biopsy (BMB) results in diffuse large B-cell lymphoma (DLBCL). MATERIALS AND METHODS: Pretreatment integrated positron-emission tomography(PET)/computed tomography (CT) images of 512 DLBCL patients who underwent BMB and received rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy were analysed retrospectively. BM uptake was assessed visually and by maximum standard uptake value (SUVmax). Associations with lymphoma-specific survival (LSS) were assessed using Kaplan-Meier and Cox regression analyses. RESULTS: FDG(+) BM was observed in 64 cases (41 focal, 12 heterogeneous, 11 diffuse). This finding distinguished iliac crest involvement (positive in 59 and negative in 453) with 89.6% accuracy (459/512) and 93.6% specificity (424/453). In BMB(+) patients, BM-to-liver SUVmax ratio >1.8 concurred perfectly with FDG(+) BM. During 52 months of follow-up, there were 156 lymphoma-related deaths. In the entire population, multivariate analysis revealed high International Prognostic Index (IPI; p<0.001), old age (p=0.003), bulky disease (p=0.011), BMB(+) (p=0.028), and FDG(+) BM (p=0.019) as independent predictors of worse LSS. In the BMB(+) subgroup, high National Comprehensive Cancer Network-revised IPI (NCCN-IPI; p=0.029) and FDG(+) BM (p=0.008) were significant independent predictors. Among BMB(+) patients with low to low-intermediate NCCN-IPI, FDG(+) BM was associated with significantly worse 2-year LSS (33.3% versus 100%; p=0.017). The same was true among those with high-intermediate NCCN-IPI (34.7% versus 76.9%.; p=0.026). CONCLUSION: Increased BM FDG in DLBCL is a predictor of worse LSS independent of BMB results and other prognostic variables including IPI/NCCN-IPI.

Nasopharyngeal diffuse large B-cells lymphoma causing acute airway obstruction amid COVID-19 crisis: an anaesthetist's nightmare.

Acute stridor is often an airway emergency. We present a valuable experience handling an elderly woman who was initially treated as COVID-19 positive during the pandemic in November 2020. She needed an urgent tracheostomy due to nasopharyngeal (NP) diffuse large B-cell lymphoma causing acute airway obstruction. Fortunately, 1 hour later, her NP swab real-time PCR test result returned as SARS-CoV-2 negative. This interesting article depicts the importance of adequate preparations when handling potentially infectious patients with anticipated difficult airway and the perioperative issues associated with it.

Value of 18F-FDG PET/CT for prognostic stratification in patients with primary intestinal diffuse large B cell lymphoma treated with an R-CHOP-like regimen.

PURPOSE: The prognostic value of 18F-FDG PET/CT for primary intestinal diffuse large B-cell lymphoma (PI-DLBCL) patients has not been determined. This prompted us to explore the value of 18F-FDG PET/CT for prognostic stratification in patients with PI-DLBCL treated with an R-CHOP-like regimen. MATERIALS AND METHODS: Seventy-three PI-DLBCL patients who underwent baseline PET/CT between January 2010 and May 2019 were included in this retrospective study. Total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) were computed using the 41% SUVmax thresholding method. Progression-free survival (PFS) and overall survival (OS) were used as endpoints to evaluate prognosis. RESULTS: During the follow-up period of 3-117 months (29.0 ± 25.5 months), high TLG, non-germinal center B-cell-like (non-GCB) and high National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) were significantly associated with inferior PFS and OS. TLG, cell-of-origin and NCCN-IPI were independent predictors of PFS, and both TLG and NCCN-IPI were independent predictors of OS. The grading system was based on the number of risk factors (high TLG, non-GCB, high NCCN-IPI) and patients were divided into 4 risk groups (PFS: χ2 = 33.858, P < 0.001; OS: χ2 = 29.435, P < 0.001): low-risk group (none of the 3 risk factors, 18 patients); low-intermediate risk group (1 risk factor, 24 patients); high-intermediate risk group (2 risk factors, 16 patients); and high-risk group (all 3 risk factors, 15 patients). CONCLUSIONS: High TLG, non-GCB and high NCCN-IPI can identify a subset of PI-DLBCL patients with inferior survival outcomes. Furthermore, the grading system can identify PI-DLBCL patient groups with markedly different prognoses, which might contribute to the adjustment of the therapeutic regime.

A better prediction of progression-free survival in diffuse large B-cell lymphoma by a prognostic model consisting of baseline TLG and %ΔSUVmax.

In the era of rituximab, the International Prognostic Index (IPI) has been inefficient in initial risk stratification for patients with R-CHOP-treated diffuse large B-cell lymphoma (DLBCL). To estimate the predictive values of PET/CT quantitative parameters and three prognostic models consisting of baseline and interim parameters for three-year progression-free survival (PFS), we conducted an analysis of 85 patients in China with DLBCL underwent baseline and interim PET/CT scans and treated at the Department of Hematology of Peking University Third Hospital from November 2012 to November 2017. The PET/CT parameters, viz. the baseline and interim values of standardized uptake value (SUVmax ), total metabolic tumor volume (TMTV), and total lesion glycolysis (TLG), and their rates of change, were analyzed by a receiver operating characteristics curve, Kaplan-Meier analysis, and log-rank test. Besides, the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) was also included in the multivariate Cox hazards model. Owing to the strong correlation between TMTV and TLG at baseline and interim (Pearson's correlation coefficient, r = 0.823, P-value = 0.000, and 0.988, P-value = 0.000, respectively), only TLG was included in the multivariate Cox hazards model, where TLG0  > 1036.61 g and %ΔSUVmax  < 86.02% showed predictive value independently (HR = 10.42, 95% CI 2.35-46.30, P = 0.002, and HR = 4.86, 95% CI 1.27-18.54, P = 0.021, respectively). Replacing TLG in the equation, TMTV0 and TMTV1 both showed significantly predictive abilities like TLG (HR = 8.22, 95% CI 1.86-32.24, P = 0.005, and HR = 2.96, 95% CI 1.16-7.54, P = 0.023, respectively). After dichotomy, NCCN-IPI also gave a significant performance (P = 0.035 and P = 0.010, respectively, in TLG and TMTV models). The baseline variables, that is, TMTV0 , TLG0 and dichotomized NCCN-IPI, and the interim variables TMTV1 and %ΔSUVmax , presented independent prognostic value for PFS. In prognostic model 2 (TLG0  + %ΔSUVmax ), the group with TLG0  > 1036.61 g and %ΔSUVmax  < 86.02% recognized 19 (82.6%) of the relapse or progression events, which showed the best screening ability among three models consisting of baseline and interim PET/CT parameters.

Prognostic value of metabolic tumour volume on baseline 18F-FDG PET/CT in addition to NCCN-IPI in patients with diffuse large B-cell lymphoma: further stratification of the group with a high-risk NCCN-IPI.

PURPOSE: The purpose of this study was to determine the prognostic value of metabolic volumetric parameters as a quantitative index on pre-treatment 18F-FDG PET/CT in addition to the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 103 consecutive patients with DLBCL and baseline FDG PET/CT were retrospectively evaluated. Quantitative metabolic parameters, including total metabolic tumour volume (TMTV) using a standardized uptake value (SUV) of ≥2.5 as the threshold, were estimated. Receiver operating characteristic curve analysis was used to determine the optimal cut-off values for the metabolic parameters. The relationships between study variables and patient survival were tested using Cox regression analysis. Patient survival rates were derived from Kaplan-Meier curves and compared using the log-rank test. RESULTS: Median follow-up was 34 months. In patients with a low TMTV (<249 cm3), the 3-year progression free survival (PFS) rate was 83% and the overall survival (OS) rate was 92%, in contrast to 41% and 57%, respectively, in those with a high TMTV (≥249 cm3). In univariate analysis, a high TMTV and NCCN-IPI ≥4 were associated with inferior PFS and OS (P < 0.0001 for all), as was a high total lesion glycolysis (P = 0.004 and P = 0.005, respectively). In multivariate analysis, TMTV and NCCN-IPI were independent predictors of PFS (hazard ratio, HR, 3.11, 95% confidence interval, CI, 1.37-7.07, P = 0.007, and HR 3.42, 95% CI 1.36-8.59, P = 0.009, respectively) and OS (HR 3.41, 95% CI 1.24-9.38, P = 0.017, and HR 5.06, 95% CI 1.46-17.60, P = 0.014, respectively). TMTV was able to separate patients with a high-risk NCCN-IPI of ≥4 (n = 62) into two groups with significantly different outcomes; patients with low TMTV (n = 16) had a 3-year PFS rate of 75% and an OS rate of 88%, while those with a high TMTV had a 3-year PFS rate of 32% and an OS rate of 47% (χ2 = 7.92, P = 0.005, and χ2 = 8.26, P = 0.004, respectively). However, regardless of TMTV, patients with a low-risk NCCN-IPI of <4 (n = 41) had excellent outcomes (3-year PFS and OS rates of 85% and 95%, respectively). CONCLUSION: Pretreatment TMTV was an independent predictor of survival in patients with DLBCL. Importantly, TMTV had an additive prognostic value in patients with a high-risk NCCN-IPI. Thus, the combination of baseline TMTV with NCCN-IPI may improve the prognostication and may be helpful guide the decision for intensive therapy and clinical trials, especially in DLBCL patients with a high-risk NCCN-IPI.

[Prognostic value of pretreatment (18)F-FDG PET-CT for patients with advanced diffuse large B-cell lymphoma].

Objective: To investigate the prognostic value of the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) measured by pretreatment (18)F-FDG PET-CT in patients with stage Ⅲ~Ⅳ diffuse large B-cell lymphoma (DLBCL). Methods: Clinical data of 72 DLBCL patients with stage Ⅲ~Ⅳ disease undergoing a pretreatment PET-CT scan were retrospectively analyzed. SUVmax, MTV and TLG values of whole-body tumor were calculated from PET-CT images with a threshold of SUVmax 40% of tumor tissues. The optimal cutoff lines of SUVmax, MTV and TLG were obtained by ROC curve analysis. The Kaplan-Meier method and Log-rank test were used to perform univariate survival analysis, while Cox proportional hazards model was done for multivariate analysis. Results: The SUVmax, MTV and TLG of 72 patients were 21.64, 139.48 cm(3) and 1 413.77, respectively. The areas under the ROC curve (AUC) of SUVmax, MTV and TLG were 0.411 (95%CI=0.279~0.544, P=0.195), 0.688 (95%CI=0.566~0.811, P=0.006) and 0.526 (95%CI= 0.469~0.672, P=0.123), respectively. The median SUVmax (21.64) and TLG(1 413.77) were used as the cutoff lines due to smaller AUC. The cutoff point of MTV was 69.71 cm(3). For DLBCL patients of stage Ⅲ~Ⅳ disease, univariate analysis showed that SUVmax and TLG were not associated with the progression-free survival (PFS) and overall survival (OS) (P>0.05 for all). Multivariate analysis showed that National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) but not MTV was the independent prognostic predictor of PFS and OS (P<0.05 for all). And MTV was not the independent prognostic factor of PFS and OS for stage Ⅲ DLBCL (P>0.05 for all). Conclusions: For DLBCL patients with stage Ⅲ~Ⅳ disease, the prognostic value of SUVmax, MTV and TLG before treatment initiation are undetermined, and these indices cannot be used to predict the prognosis.

Analysis of prognostic value of complete response by PET-CT and further stratification by clinical and biological markers in DLBCL patients.

Positron emission tomography-computed tomography (PET-CT) is performed as the standard method for response assessment of diffuse large B cell lymphoma (DLBCL) patients. However, a substantial proportion of patients experience relapse even if they have achieved complete response (CR) defined by PET-CT. We validated the prognostic value of CR by PET-CT and applied the National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) and cell of origin (COO) to patients with CR by PET-CT to evaluate their additional predictive ability for survival outcomes. We retrospectively analyzed DLBCL patients who were treated with R-CHOP or an R-CHOP-like regimen and who achieved CR by PET-CT or CT only. A total of 185 patients were analyzed: 114 patients achieved CR by PET-CT and 71 patients by CT only. Patients with CR by PET-CT had significantly better overall survival (OS) than those with CR by CT (5-year OS, 87.5 vs. 62.4%, P = 0.003). Patients with high risk according to the NCCN-IPI had a dismal outcome despite achieving CR by PET-CT (5-year OS, 61.8%). In contrast, low-, low-intermediate-, and high-intermediate-risk patients had excellent outcomes (5-year OS, 100, 89.7, and 93.5%, respectively). Among patients with CR by PET-CT, patients with germinal center B cell (GCB) DLBCL (n = 40) had significantly better survival than those with non-GCB DLBCL (n = 57) (5-year OS, 96.9 vs. 75.5%, P = 0.039). We demonstrated that CR by PET-CT was a better predictor of survival outcomes than CR by CT only. The NCCN-IPI and COO subtypes could identify a subpopulation of poor-risk patients among those who achieved CR by PET-CT.

Prognostic value of total lesion glycolysis of baseline 18F-fluorodeoxyglucose positron emission tomography/computed tomography in diffuse large B-cell lymphoma.

PURPOSE: We evaluated the prognostic value of total lesion glycolysis (TLG) measured in baseline 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in diffuse large B-cell lymphoma (DLBCL) treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). METHODS: A total of 91 patients with newly diagnosed DLBCL underwent 18F-FDG PET/CT scans before R-CHOP therapy. Metabolic tumor volume (MTV) was measured with the marginal threshold of normal liver mean standard uptake value (SUVmean) plus 3 standard deviations (SD). TLG was the sum of the products of MTV and SUVmean in all measured lesions. The predictive value was estimated by Log-rank test and Cox-regression analysis. RESULTS: Median follow-up was 30 months (range, 5-124 months). The 5-year estimated progression-free survival (PFS) of the low and high TLG group were 83% and 34%, respectively (p<0.001). The 5-year overall survival (OS) of the same groups were 92% and 67%, respectively (p<0.001). Patients with high TLG level were more likely to relapse than those with low TLG level even though they had got complete or partial remission in R-CHOP therapy (40% versus 9%, p=0.012). Multivariate analysis revealed TLG was the only independent predictor for PFS (Hazard ratio=5.211, 95% confidence interval=2.210-12.288, p<0.001) and OS (Hazard ratio=9.136, 95% confidence interval=1.829-45.644, p=0.002). Other factors including MTV, National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) and Ann Arbor Stage were not independently predictive for survivals. CONCLUSION: Baseline TLG is the only independent predictor for PFS and OS in DLBCL patients treated with R-CHOP therapy.

Prognostic value of interim FDG-PET in R-CHOP-treated diffuse large B-cell lymphoma: Systematic review and meta-analysis.

This study aimed to systematically review and meta-analyze the prognostic value of interim (18)F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). MEDLINE and EMBASE were systematically searched for suitable studies. Included studies were methodologically appraised, and results were summarized both descriptively and meta-analytically. Nine studies, comprising a total of 996 R-CHOP-treated DLBCL patients, were included. Overall, studies were of moderate methodological quality. The area under the summary receiver operating curve (AUC) of interim FDG-PET in predicting treatment failure and death were 0.651 and 0.817, respectively. There was no heterogeneity in diagnostic odds ratios across available studies (I(2)=0.0%). At multivariable analysis, 2 studies reported interim FDG-PET to have independent prognostic value in addition to the International Prognostic Index (IPI) in predicting treatment failure, whereas 3 studies reported that this was not the case. One study reported interim FDG-PET to have independent prognostic value in addition to the IPI in predicting death, whereas 2 studies reported that this was not the case. In conclusion, interim FDG-PET in R-CHOP-treated DLBCL has some correlation with outcome, but its prognostic value is homogeneously suboptimal across studies and it has not consistently proven to surpass the prognostic potential of the IPI. Moreover, there is a lack of studies that compared interim FDG-PET to the recently developed and superior National Comprehensive Cancer Network-IPI. Therefore, at present there is no scientific base to support the clinical use of interim FDG-PET in R-CHOP-treated DLBCL.

Predictive value of F-18 FDG PET/CT quantization parameters for progression-free survival in patients with diffuse large B-cell lymphoma.

OBJECTIVES: To evaluate the predictive significance of F-18 FDG PET/CT quantization parameters for progression-free survival (PFS) in patients with diffuse large B cell lymphoma (DLBCL) before chemotherapy. METHODS: We conducted a retrospective study involving 60 patients with DLBCL between January 2010 and August 2014 who had undergone F-18 FDG PET/CT scan prior to treatment. Maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and number of enlarged lymph nodes (>2 cm) were measured. The primary outcome measure was PFS. Spearman rank correlation analysis, univariate and multivariate Cox regression models, receiver operating characteristic (ROC) analysis, and Kaplan-Meir survival curves were used. RESULTS: Spearman analysis determined that the MTV and TLG values were positively related to Ann Arbor stage, National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) score, and lactate dehydrogenase (LDH) level. The number of enlarged lymph nodes was positively related only to LDH level. The SUVmax value and clinical characteristics were not related. Univariate Cox regression determined that the MTV and TLG values, number of enlarged lymph nodes, and NCCN-IPI score were predictive factors. Multivariate Cox regression determined that the MTV and TLG values and number of enlarged lymph nodes predicted PFS independently of the NCCN-IPI score. The SUVmax value was not predictive of PFS. According to the cut-off determined from ROC analysis, lower MTV and TLG values were highly predictive of favorable PFS. CONCLUSIONS: In contrast to SUVmax, the MTV and TLG may be significant prognostic markers for PFS in DLBCL.

Tumor necrosis at FDG-PET is an independent predictor of outcome in diffuse large B-cell lymphoma.

PURPOSE: To determine the prognostic performance of tumor necrosis at FDG-PET in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) who are treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. MATERIALS AND METHODS: 108 patients with newly diagnosed DLBCL who underwent FDG-PET before R-CHOP therapy were retrospectively included. Lymphomatous sites at FDG-PET were assessed for the presence of a photopenic area, in keeping with tumor necrosis. Univariate and multivariate Cox regression analyses were performed to determine the associations of tumor necrosis and National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) with progression-free survival (PFS) and overall survival (OS). RESULTS: On univariate Cox regression analysis, both tumor necrosis and higher NCCN-IPI risk groups were significantly associated with PFS (P=0.024 and P<0.001, respectively) and OS (P=0.034 and P<0.001, respectively). On multivariate Cox regression analysis, both tumor necrosis and the NCCN-IPI were independent significant predictors for PFS (P=0.007, hazard ratio: 2.723 [95% confidence interval: 1.324-5.597] and P<0.001, hazard ratio: 2.952 [95% confidence interval: 1.876-4.646], respectively) and OS (P=0.009, hazard ratio: 2.794 [95% confidence interval: 1.305-5.985] and P<0.001, hazard ratio: 2.813 [95% confidence interval: 1.724-4.587], respectively). CONCLUSION: Tumor necrosis at FDG-PET is an NCCN-IPI-independent predictor of outcome in DLBCL.

Brain glucose metabolism in diffuse large B-cell lymphoma patients as assessed with FDG-PET: impact on outcome and chemotherapy effects.

BACKGROUND: There is a lack of data on the effect of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy on brain glucose metabolism of diffuse large B-cell lymphoma (DLBCL) patients, as measured by 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET). Moreover, the prognostic value of brain glucose metabolism measurements is currently unknown. PURPOSE: To investigate the use of FDG-PET for measurement of brain glucose metabolism in R-CHOP-treated DLBCL patients, and to assess its prognostic value. MATERIAL AND METHODS: This retrospective study included DLBCL patients who underwent FDG-PET including the brain. FDG-PET metabolic volume products (MVPs) of the entire brain, cerebral cortex, basal ganglia, and cerebellum were measured, before and after R-CHOP therapy. Whole-body total lesion glycolysis (TLG) was also measured. RESULTS: Thirty-eight patients were included, of whom 18 had an appropriate end-of-treatment FDG-PET scan. There were no significant differences (P > 0.199) between pre- and post-treatment brain glucose metabolism metrics. Low basal ganglia MVP was associated with a significantly worse progression-free survival (PFS) and overall survival (OS) (P = 0.020 and P = 0.032), and low cerebellar MVP was associated with a significantly worse OS (P = 0.034). There were non-significant very weak correlations between pretreatment brain glucose metabolism metrics and TLG. In the multivariate Cox regression, only the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) remained an independent predictor of PFS (hazard ratio 3.787, P = 0.007) and OS (hazard ratio 2.903, P = 0.0345). CONCLUSION: Brain glucose metabolism was not affected by R-CHOP therapy. Low pretreatment brain glucose metabolism was associated with a worse outcome, but did not surpass the predictive value of the NCCN-IPI.