Serum level of soluble interleukin-2 receptor is positively correlated with metabolic tumor volume on 18 F-FDG PET/CT in newly diagnosed patients with diffuse large B-cell lymphoma.
ABSTRACT: Diffuse large B-cell lymphoma (DLBCL) is the most frequent subtype of non-Hodgkin lymphoma. High total metabolic tumor volume (TMTV) calculated using 18 F-FDG PET/CT images at diagnosis predicts poor prognosis of patients with DLBCL. However, high cost and poor access to the imaging facilities hamper wider use of 18 F-FDG PET/CT. In order to explore a surrogate marker for TMTV, we evaluated the correlation between the serum levels of soluble interleukin-2 receptor (sIL-2R) and TMTV in 64 patients with DLBCL, and the results were verified in an independent validation cohort of 86 patients. Serum levels of sIL-2R were significantly correlated with TMTV. ROC analysis revealed that the cutoff value of TMTV ?150 cm3 or sIL-2R ? 1300 U/mL could predict failure to achieve EFS24 with areas under the curve (AUC) 0.706 and 0.758, respectively. Each of TMTV ?150 cm3 and sIL-2R ?1300 U/mL was significantly associated with worse 5-year overall survival and event-free survival. Importantly, each of sIL-2R <1300 U/mL or TMTV <150 cm3 identified patients with favorable prognosis among NCCN-IPI high-intermediate and high-risk group. Serum level of sIL-2R represents a convenient surrogate marker to estimate metabolic tumor burden measured by 18 F-FDG PET/CT that can predict treatment outcomes of patients with DLBCL.
Project description:RATIONALE:Evaluation of the feasibility of [18F]EF5-PET/CT scan in identifying hypoxic lesions in ovarian tumors in prospective clinical setting. METHODS:Fifteen patients with a suspected malignant ovarian tumor were scanned with [18F]EF5 and [18F]FDG-PET/CT preoperatively. The distribution of [18F]EF5-uptake, total intraabdominal metabolic tumor volume (TMTV), and hypoxic subvolume (HSV) were assessed. RESULTS:[18F]EF5-PET/CT suggested hypoxia in 47% (7/15) patients. The median HSV was 87?cm3 (31% of TMTV). The [18F]EF5-uptake was detected in primary tumors and in four patients also in intra-abdominal metastases. The [18F]EF5-uptake in cancer tissue was low compared to physiological excretory pathways, complicating the interpretation of PET/CT images. CONCLUSIONS:[18F]EF5-PET/CT is not feasible in ovarian cancer imaging in clinical setting due to physiological intra-abdominal [18F]EF5-accumulation. However, it may be useful when used complementarily to FDG-PET/CT.
Project description:Whether baseline metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) measured by FDG-PET/CT affected prognosis of patients with lymphoma was controversial. We searched PubMed, EMBASE and Cochrane to identify studies assessing the effect of baseline TMTV and TLG on the survival of lymphoma patients. Pooled hazard ratios (HR) for overall survival (OS) and progression-free survival (PFS) were calculated, along with 95% confidence intervals (CI). Twenty-seven eligible studies including 2,729 patients were analysed. Patients with high baseline TMTV showed a worse prognosis with an HR of 3.05 (95% CI 2.55-3.64, p<0.00001) for PFS and an HR of 3.07 (95% CI 2.47-3.82, p<0.00001) for OS. Patients with high baseline TLG also showed a worse prognosis with an HR of 3.44 (95% CI 2.37-5.01, p<0.00001) for PFS and an HR of 3.08 (95% CI 1.84-5.16, p<0.00001) for OS. A high baseline TMTV was significantly associated with worse survival in DLBCL patients treated with R-CHOP (OS, pooled HR = 3.52; PFS, pooled HR = 2.93). A high baseline TLG was significantly associated with worse survival in DLBCL patients treated with R-CHOP (OS, pooled HR = 3.06; PFS, pooled HR = 2.93). The negative effect of high baseline TMTV on PFS was demonstrated in HL (pooled HR = 3.89). A high baseline TMTV was significantly associated with worse survival in ENKL patients (OS, pooled HR = 2.24; PFS, pooled HR = 3.25). A high baseline TLG was significantly associated with worse survival in ENKL patients (OS, pooled HR = 2.58; PFS, pooled HR = 2.99). High baseline TMTV or TLG predict significantly worse PFS and OS in patients with lymphoma. Future studies are warranted to explore whether TMTV or TLG could be integrated into various prognostic models for clinical decision making.
Project description:The present study aimed to investigate the prognostic value of baseline <sup>18</sup>F-FDG PET/CT quantitative parameters and interim treatment response, and to assess whether the combination of these could improve the predictive efficacy in patients with diffuse large B-cell lymphoma (DLBCL) receiving R-CHOP chemotherapy. PET/CT images and clinical data of 64 patients with DLBCL who had undergone <sup>18</sup>F-FDG PET/CT scan before and after 3 or 4 cycles of R-CHOP chemotherapy were retrospectively reviewed. The quantitative parameters including standardized uptake value (SUV), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum diameter of the maximum lesion (Dmax) were measured on baseline PET/CT images. Cox proportional hazards model was used to evaluate the influence of baseline PET/CT parameters, clinical indicators and interim treatment response on prognosis. Survival analysis was performed using Kaplan-Meier method. Receiver operating characteristic (ROC) curve analysis was performed to estimate the predictive efficacy of the combination of baseline PET/CT parameters and interim treatment response. Ann Arbor stage, International Prognostic Index (IPI), lactate dehydrogenase (LDH), necrosis, MTVmax, TLGmax, Dmax and interim treatment response showed association with 2-year progression-free survival (PFS, P<0.05). LDH, necrosis, MTVmax, MTVsum, TLGmax, TLGsum, Dmax and interim treatment response showed association with 2-year overall survival (OS, P<0.05). Ann Arbor stage, Dmax and interim treatment response were found to be independent predictors of 2-year PFS (P<0.05), while Dmax and interim treatment response were found to be independent predictors of 2-year OS (P<0.05). The PFS and OS curves of Dmax <5.7 cm group and Dmax ?5.7 cm group, complete response (CR) group and non-CR group were significantly different, respectively (P<0.05). The baseline <sup>18</sup>F-FDG PET/CT parameters and interim treatment response have important prognostic values in DLBCL patients who received R-CHOP chemotherapy. Combined application of Dmax and interim treatment response improved the predictive efficacy of 2-year PFS. It may be helpful to identify patients who are at high-risk of relapse and to guide early clinical intervention of these patients.
Project description:OBJECTIVE::To examine the prognostic value of fluorodeoxyglucose (FDG) and fluorothymidine (FLT) interim positron emission tomography/CT (PET/CT) for diffuse large B-cell lymphoma (DLBCL). METHODS::44 patients with newly diagnosed DLBCL underwent both fluorine 18 FDG (18F-FDG) and 18F-FLT PET/CT scans at baseline and after two cycles of a rituximab-containing chemotherapy regimen. Maximum standard uptake values (SUVmax) and changes in SUV (?SUV) were calculated for both tracers for the predominant lesion of each patient, for prediction of progression-free survival (PFS) and overall survival (OS). RESULTS::The median follow-up period was 71 months. Receiver operating characteristic (ROC) analysis indicated that the best ?SUV cut-off values for FDG (?SUVFDG) and FLT (?SUVFLT) were 79 and 76%, respectively. A ?SUVFLT cut-off of 76% had the highest significance for prediction of PFS (p = 0.003) and OS (p = 0009), with sensitivity, specificity, and accuracy of 80.0, 85.7, and 81.8% respectively in response assessment. CONCLUSION::Interim FLT PET/CT had higher specificity and accuracy than standard FDG PET/CT-based interpretation. ADVANCES IN KNOWLEDGE::This study demonstrated that interim FLT PET/CT had higher accuracy than standardized FDG-based interpretation for therapeutic response assessment in DLBCL. FLT had the advantage of potentially reducing false positive of interim FDG PET/CT.
Project description:11C-methionine (11C-MET) is a new positron emission tomography (PET) tracer for the assessment of disease activity in multiple myeloma (MM) patients, with preliminary data suggesting higher sensitivity and specificity than 18F-fluorodeoxyglucose (18F-FDG). However, the value of tumor burden biomarkers has yet to be investigated. Our goals were to corroborate the superiority of 11C-MET for MM staging and to compare its suitability for the assessment of metabolic tumor burden biomarkers in comparison to 18F-FDG. Twenty-two patients with newly diagnosed, treatment-naïve symptomatic MM who had undergone 11C-MET and 18F-FDG PET/CT were evaluated. Standardized uptake values (SUV) were determined and compared with total metabolic tumor volume (TMTV) for both tracers: total lesion glycolysis (TLG) and total lesion 11C-MET uptake (TLMU). PET-derived values were compared to Revised International Staging System (R-ISS), cytogenetic, and serologic MM markers such as M component, beta 2 microglobulin (B2M), serum free light chains (FLC), albumin, and lactate dehydrogenase (LDH). In 11 patients (50%), 11C-MET detected more focal lesions (FL) than FDG (p < 0.01). SUVmax, SUVmean, SUVpeak, TMTV, and TLMU were also significantly higher in 11C-MET than in 18F-FDG (p < 0.05, respectively). 11C-MET PET biomarkers had a better correlation with tumor burden (bone marrow plasma cell infiltration, M component; p < 0.05 versus p = n.s. respectively). This pilot study suggests that 11C-MET PET/CT is a more sensitive marker for the assessment of myeloma tumor burden than 18F-FDG. Its implications for prognosis evaluation need further investigation.
Project description:<sup>18</sup>F-FDG PET/CT has some limitations in the evaluation of Waldenström macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL), an indolent B-cell lymphoma that primarily involves the bone marrow. Because there is a high level of chemokine receptor 4 expression in the B cells of WM/LPL patients, we performed a prospective cohort study to evaluate the performance of <sup>68</sup>Ga-pentixafor, which targets chemokine receptor 4 in WM/LPL, and to compare it with the performance of <sup>18</sup>F-FDG. <b>Methods:</b> Seventeen patients with WM/LPL were recruited. All patients underwent both <sup>68</sup>Ga-pentixafor PET/CT and <sup>18</sup>F-FDG PET/CT. A positive PET/CT result was defined as the presence of focal lesions with positive PET results or diffuse bone marrow patterns (uptake > liver). The rates of positive results for PET/CT scans of bone marrow, lymph nodes, and other extramedullary involvement were statistically compared. <b>Results:</b> <sup>68</sup>Ga-pentixafor PET/CT had a higher rate of positive results than <sup>18</sup>F-FDG PET/CT (100% vs. 58.8%; <i>P</i> = 0.023) in the recruited WM/LPL patients. The sensitivities of <sup>68</sup>Ga-pentixafor PET/CT and <sup>18</sup>F-FDG PET/CT for detecting bone marrow involvement were 94.1% and 58.8%, respectively (<i>P</i> = 0.077). In terms of detecting lymph node involvement, <sup>68</sup>Ga-pentixafor PET/CT had a significantly higher rate of positive results than <sup>18</sup>F-FDG PET/CT (76.5% vs. 11.8%; <i>P</i> = 0.003). In addition, <sup>68</sup>Ga-pentixafor detected more paramedullary and central nervous system involvement than <sup>18</sup>F-FDG. <b>Conclusion:</b> <sup>68</sup>Ga-pentixafor might be a promising imaging agent for the assessment of WM/LPL.
Project description:Background: We aimed to assess the clinical utility of a previously published score combining the total metabolic tumor volume (TMTV) on baseline FDG-PET/CT and pretreatment derived from the neutrophils to lymphocytes ratio (dNLR) for prognostication in NSCLC patients undergoing first-line immunotherapy (IT). Methods: In this multicenter retrospective study, 63 advanced NSCLC patients with a PD-L1 tumor proportion score (TPS) ?50%, who underwent FDG-PET/CT before first-line IT, treated from January 2017 to September 2019, were enrolled. Associations between this score and the progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and overall response rate (ORR) were evaluated. Results: The median (m) PFS and mOS were 7.7 (95% CI 4.9-10.6) and 12.1 (8.6-15.6) months, respectively, and DCR and ORR were 65% and 58%, respectively. mOS was 17.9 months (14.6 not reached) for the good group versus 13.8 (95%CI 8.4-18.9) and 6.6 (CI 2.0-11.2) months for the intermediate and poor groups, respectively. mPFS was 15.1 (95%CI 12.1-20.0) months for the good group versus 5.2 (1.9-8.5) and 1.9 (95%CI 1.3-2.5) months for the intermediate and poor groups, respectively. The poor prognosis group was associated with DCR and ORR (p < 0.05). Conclusions: The metabolic score combining TMTV on the baseline FDG-PET/CT scan and pretreatment dNLR was associated with the survival and response in a cohort of advanced NSCLC patients with ?50% PD-L1 receiving frontline IT.
Project description: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.
Project description:A 62-year-old man with asthma presented with a 1-month history of wheezing and exertional dyspnea. Although the wheezing symptoms disappeared after systemic corticosteroid therapy, the exertional dyspnea and hypoxemia did not improve. A diagnosis of intravascular large B-cell lymphoma (IVLBCL) with pulmonary involvement was suspected because of the increased serum lactic dehydrogenase (LDH) and soluble interleukin-2 receptor (sIL-2R) level, increased alveolar-arterial oxygen difference (AaDO2), decreased pulmonary diffusing capacity for carbon monoxide (DLCO) and scintigraphic, computed tomography (CT) and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)-CT findings. The patient was diagnosed as having IVLBCL with pulmonary involvement based on a pathological analysis of a random skin biopsy and a transbronchial lung biopsy. IVLBCL should be considered in patients with symptoms of asthma that are refractory to corticosteroid treatment.