Total tumor burden in lymphoma – an evolving strong prognostic parameter

2021 ◽  
pp. 20210448
Author(s):  
Michel Meignan ◽  
Anne-Segolene Cottereau ◽  
Lena Specht ◽  
N. George Mikhaeel

Total metabolic tumor volume (TMTV), a new parameter extracted from baseline FDG-PET/CT, has been recently proposed by several groups as a prognosticator in lymphomas before first-line treatment. TMTV, the sum of the metabolic volume of each lesion, is an index of the metabolically most active part of the tumor and highly correlates with the total tumor burden. TMTV measurement is obtained from PET images processed with different software and techniques, many being now freely available. In the various lymphoma subtypes where it has been measured, such as diffuse large B-cell lymphoma, Hodgkin lymphoma, Follicular Lymphoma, and Peripheral T-cell lymphoma, TMTV has been reported as a strong predictor of outcome (progression-free survival and overall survival) often outperforming the clinical scores, molecular predictors, and results of interim PET. Combined with these scores, TMTV improves the stratification of the populations into risk groups with different outcomes. TMTV cut-off separating the high-risk from the low-risk population impacts the outcome whatever the technique used for its measurement and an international harmonization is ongoing. TMTV is a unique and easy tool that could replace the surrogate of tumor burden included in the prognostic indexes used in lymphoma and help tailor therapy. Other parameters extracted from the baseline PET may give an information on the dissemination of this total tumor volume such as the maximum distance between the lesions. Trials based on TMTV would probably demonstrate its predictive value.

2016 ◽  
Vol 22 (15) ◽  
pp. 3801-3809 ◽  
Author(s):  
Anne-Ségolène Cottereau ◽  
Hélène Lanic ◽  
Sylvain Mareschal ◽  
Michel Meignan ◽  
Pierre Vera ◽  
...  

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4983-4983
Author(s):  
Moo-Kon Song ◽  
Joo-seop Chung ◽  
Ho-Jin Shin ◽  
Joon Ho Moon ◽  
Jeong Ok Lee ◽  
...  

Abstract Abstract 4983 Background: Primary gastrointestinal (GI) lymphoma is the most commonly involved extranodal site and represents 10–15% of all Non-Hodgkin's Lymphoma cases. Recent studies showed that the prognostic value of early 18F-FDG PET using maximum standardized uptake volume (SUVmax) on pretreatment was important prognostic factor in primary GI diffuse large B cell lymphoma (DLBCL). However, initial tumor burden is still an important subject associated with prognosis even extranodal DLBCL. The purpose of this study was to assess the prognostic impact of metabolic tumor volume (MTV) as tumor burden using by PET scan technique compared with initial SUVmax in primary GI DLBCL. Patients and methods: From April, 2006 to July, 2009, 125 stage IE (58 patients) or IIE (67 patients) primary GI DLBCL patients with localized lymph node involvement were enrolled and assigned to 6 or 8 cycles of R-CHOP therapy. Median follow-up was 36 months. Median age was 62 years (range, 20–79 years). Seventy-four patients were male and remainders were female. Numbers of patients above 60 years were 71. Twenty-five patients had an Eastern Cooperative Oncology Group performance status of more than two. Calculatory system by computer automatically delineated a extranodal target lesions above SUV, 2.5 and MTV of GI lesion was 3-dimensional reconstructed by fusion software. The SUVmax was collected from predominant GI lesion and calculated based on the attenuation-corrected images, the amount of injected 18F-FDG and body weight. Results: The extranodal sites of GI tract were included stomach and duodenum (64 patients, 51.2%), jejunum (10 patients, 8%), terminal ileum (30 patients, 24%), cecum (7 patients, 5.6%), ascending colon (8 patients, 6.4%), transverse colon (3 patients, 2.4%) and decending colon (3 patients, 2.4%). We used ROC curve analysis. 158.3cm3 was decided as best ideal cut-off value of MTV and 15.5 was decided as the cut-off value of SUVmax. Several factors (age, sex, disease status and IPI score) between high MTV (≥158.3cm3) and low MTV group (<158.3cm3) were not significantly different. However, SUVmax higher in high MTV group than low MTV group (p<0.001). In response by revised International Workshop Criteria, low MTV group had excellent response rates than high MTV group (CR, p<0.001; PR, p=0.014; SD & PD, p<0.001). Moreover, 3-year PFS was higher in low MTV group than high MTV group (low MTV group, 96.7%; high MTV group, 37.1%; p<0.001) and 3-year OS was also higher in low MTV group than high MTV group (low MTV group, 97.8%; high MTV group, 42.9%; p<0.001). The PFS and OS were higher in low SUVmax group (<15.5) than high SUVmax group (≥15.5) (p<0.001, p<0.001, respectively). In univariate analysis, high IPI score is still important prognostic factor for PFS and OS (PFS: HR, 4.181 [1.844-9.478] p=0.001 & OS: HR, 4.300 [1.801-10.263] p=0.001). High MTV and high SUVmax were also poor prognostic factors for PFS and OS (high MTV; PFS: HR, 26.543 [7.923-88.231] p<0.001 & OS: HR, 32.458 [7.579-139.018] p<0.001) (high SUVmax; PFS: HR, 6.998 [2.399-20.418] p<0.001 & OS: HR, 13.976 [3.257-59.979] p<0.001). In multivariate analysis, high MTV group (PFS: HR, 19.850 [5.193-75.870] p<0.001 & OS: HR, 17.918 [3.694-86.904] p<0.001) and high IPI score (PFS: HR, 2.659 [1.136-6.223] p=0.024 & OS: HR, 2.866 [1.175-6.989] p=0.021) were independent prognostic factors for PFS and OS. However, SUVmax had not significant value for survival. Conclusion: In primary GI DLBCL, high MTV is very important and potential prognostic factor compared with SUVmax for predicting the survival. Therefore, more aggressive treatment strategy would be performed in primary GI DLBCL patients having initial high tumor burden. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1452-1452
Author(s):  
Anne-Ségolène Cottereau ◽  
Hélène Lanic ◽  
Michel Meignan ◽  
Pierre Vera ◽  
Hervé Tilly ◽  
...  

Abstract Introduction: The addition of rituximab to the CHOP backbone has improved the outcome of patients with diffuse large B-cell lymphoma (DLBCL). However, over 30% of patients still have a high risk of treatment failure or relapses and cannot be selected accurately by the classic prognostic factors. Molecular profiling has individualized categories with different outcomes. Baseline total metabolic tumor volume seems also to be an important tool to predict outcome in DLBCL, as demonstrated by Casasnovas (Casasnovas et al Hematol Oncol 2015:33,suppl 1) but has not been associated with molecular data. Our study investigated the prognostic impact of baseline PET metrics, including total metabolic tumor volume (TMTV0) and their added value to molecular characteristics (ABC/GCB status, MYC overexpression). Methods: From 2003 to 2009, 81 patients with newly diagnosed DLBCL were retrospectively included. They were treated with rituximab associated with CHOP or ACVBP regimen. All had a baseline FDG-PET/CT. TMTV0 was computed by summing the metabolic volumes of all nodal and extranodal lesions obtained using the 41% SUVmax thresholding method. According to the gene expression profile (GEP), determined using DASL (cDNA-mediated Annealing, Selection, Ligation and extension), a subset of 57 patients was classified in GCB or ABC subtypes. An exploratory analysis was done on MYC expression. Optimal cut points for binary outcome were determined by X-tile" and ROC analysis. Results: 81 patients with a median age of 66 years were enrolled: 80% were stage III/IV, 73% had elevated LDH, 67% IPIaa>1. Median pre-therapy TMTV0 was 320 cm3 (25th-75th percentiles 106-668 cm3). With a median follow-up of 64 months, the 5y-PFS was 60% and the 5y-OS was 63% in the whole population. Using a cut off of 300 cm3, patients with a high TMTV0 (n=43, 53%) had a significantly shorter PFS and OS than those with a low TMTV0 (5y-PFS: 76% vs. 43%, p=0.0023, HR=3.0 and 5y-OS: 78% vs. 46%, p=0.0047, HR=3.0). Patients with a high TMTV0 had a more aggressive disease, with significantly more advanced stage (100%) and higher frequency of IPIaa>1 (93%) than patients with a low TMTV0 (p<0.0001 and p<0.0001 respectively). As expected, ABC status (n=27) was associated with a worse outcome (5y-PFS: 38% vs. 70%, p=0.019, HR=2.4; 5y-OS:37% vs 73%, p=0.0046, HR=3.1). In multivariate analysis, TMTV0 and cells of origin were independent prognostic factors for PFS (p=0.028 and p=0.038 respectively) and OS (p=0.035 and p=0.013). Combining these two factors, TMTV0 allowed a better sub-stratification of ABC/GCB patients (p=0.013 for PFS and p=0.0036 for OS). GCB patients with small TMTV0(n=15) had a 87% 5y-PFS and 86% 5y-OS compared to 53% and 60% for GCB with high TMTV0 (n=15); ABC patients with small TMTV0 (n=11) 50% and 60% compared to 30% and 23% for ABC with high TMTV (n=16) (figure 1). Patients with overexpression of MYC (n=26) had an increased risk of relapse or progression (p=0.0032, HR=3.08) and a reduced survival rates (p=0.0004, HR=4.25). Combining MYC with TMTV0 gave an added prognostic value by splitting the population in 3 risk groups: MYC negative and low TMTV0 (n=16, 5y-PFS of 93% and 5y-OS 93%) ; MYC negative and high TMTV0 (n=15, 45% and 55%) ; MYC positive whatever TMTV0 (n=26, 30% and 30%), p=0.0011 and p=0.0005 respectively. Conclusion: The addition of TMTV0 improved the risk stratification of ABC/GCB subtypes and MYC expression. The combination of molecular and imaging characteristicts at diagnosis could lead to a more accurate selection of patients, in order to increase tailor therapy. Figure 1. Kaplan Meier estimates of progression-free (PFS) and overall survival (OS) according to the baseline total metabolic tumor volume (TMTV0) combining with ABC/GCB Figure 1. Kaplan Meier estimates of progression-free (PFS) and overall survival (OS) according to the baseline total metabolic tumor volume (TMTV0) combining with ABC/GCB Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.


2015 ◽  
Vol 5 (7) ◽  
pp. e326-e326 ◽  
Author(s):  
E Malek ◽  
A Sendilnathan ◽  
M Yellu ◽  
A Petersen ◽  
M Fernandez-Ulloa ◽  
...  

2020 ◽  
Vol 4 (14) ◽  
pp. 3268-3276 ◽  
Author(s):  
Erin A. Dean ◽  
Rahul S. Mhaskar ◽  
Hong Lu ◽  
Mina S. Mousa ◽  
Gabriel S. Krivenko ◽  
...  

Abstract High metabolic tumor volume (MTV) predicts worse outcomes in lymphoma treated with chemotherapy. However, it is unknown if this holds for patients treated with axicabtagene ciloleucel (axi-cel), an anti-CD19 targeted chimeric antigen receptor T-cell therapy. The primary objective of this retrospective study was to investigate the relationship between MTV and survival (overall survival [OS] and progression-free survival [PFS]) in patients with relapsed/refractory large B-cell lymphoma (LBCL) treated with axi-cel. Secondary objectives included finding the association of MTV with response rates and toxicity. The MTV values on baseline positron emission tomography of 96 patients were calculated via manual methodology using commercial software. Based on a median MTV cutoff value of 147.5 mL in the first cohort (n = 48), patients were divided into high and low MTV groups. Median follow-up for survivors was 24.98 months (range, 10.59-51.02 months). Patients with low MTV had significantly superior OS (hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.10-0.66) and PFS (HR, 0.40; 95% CI, 0.18-0.89). Results were successfully validated in a second cohort of 48 patients with a median follow-up for survivors of 12.03 months (range, 0.89-25.74 months). Patients with low MTV were found to have superior OS (HR, 0.14; 95% CI, 0.05-0.42) and PFS (HR, 0.29; 95% CI, 0.12-0.69). In conclusion, baseline MTV is associated with OS and PFS in axi-cel recipients with LBCL.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 7562-7562 ◽  
Author(s):  
Erin Dean ◽  
Hong Lu ◽  
Aleksandr Lazaryan ◽  
Gabriel S Krivenko ◽  
Christina A Bachmeier ◽  
...  

7562 Background: Axicabtagene ciloleucel (axi-cel) is an anti-CD19 targeted Chimeric Antigen Receptor (CAR) T-cell therapy for large B-cell lymphoma (LBCL). High tumor burden, by sum of the product of diameters (SPD) in ≥ 6 reference lesions, was associated with lower durable responses rates in the ZUMA-1 trial (Locke F.L. ASCO. 2018). Although metabolic tumor volume (MTV) predicts worse outcomes with chemotherapy in lymphoma (Guo B. PLoSOne. 2019), its prognostic significance remains unclear with axi-cel therapy. Methods: MTV was measured by MIM Software using a 41% SUVmax threshold with manual lesion contour adjustment and radiologist review. Low and high MTV groups were defined based on median cutoff value. Cytokine release syndrome (CRS) was graded by Lee et al. ( Blood. 2014). Neurotoxicity (NT) was graded by CTCAEv4. Toxicities, overall response rate (ORR), and complete response rate (CR) were evaluated via Fisher’s test; PFS and OS via Kaplan-Meier and log-rank test. Results: 48 patients with LBCL, or its variants, that received axi-cel at Moffitt from June 2015 to October 2018 were included. 31 were male, and median age was 63 years (range, 28-76). CRS occurred in 43/47 (91.5%) and NT in 32/47 (68.1%) patients. Grade 3-4 CRS in 2/47 (4.3%) and NT in 12/47 (25.5%). Median follow up for survivors was 8.9 months (range, 1.4- 36.8 months). CR was achieved in 31/48 (64.6 %) and ORR in 39/48 (81.3%). Median for the low MTV group was 35.1 mL (range, 4.24-132.8 mL), and for the high MTV group 455.5 mL (range, 162.2-1221.4 mL). High MTV was not predictive of G1-4 NT or G3-4 NT (OR = 1.14, P = 0.99; OR = 1.66, P = 0.52). Similarly, high MTV was not predictive of G1-4 CRS or G3-4 CRS (OR = 0.29, P = 0.348; OR = 1.05, P = 0.99). Low MTV was predictive of ORR (OR = 11.50, P = 0.026) and CR (OR = 9.8, P = 0.002). Patients with high MTV had inferior PFS (HR = 3.296, 95% CI 1.42-7.64, P = 0.008) and OS (HR = 6.68, 95% CI 2.56-17.32, P = 0.003). Conclusions: High baseline MTV is associated with decreased and less durable response following axi-cel. As survival data mature, future analyses will aim to assess the role of MTV as an independent prognostic tool in axi-cel recipients with LBCL.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5354-5354
Author(s):  
Imran K Tailor ◽  
Bilal Btoosh ◽  
Shaimaa Hamdy ◽  
Shanker Raja ◽  
Mohammed O Alharbi ◽  
...  

Abstract Introduction: Baseline (PETb) and end of therapy (PETe) FDG PET is standard of care in the management of hodgkin's lymphoma (HL) and diffuse large B cell lymphoma (DLBCL). The role of interim PET (PETi) in HL is well established while its role in DLBCL is not well defined. We evaluated the utility of triPET (PETb, PETi and PETe ) in management of these two lymphomas. Methods: Retrospective review of PET archives revealed a total of 37 pts (HL=22, DLBCL=15). TriPET were acquired per accepted protocol. SUVmax and Deauville scores (DSc) were obtained from five target lesions, the average i.e. composite SUVmax & DSc were computed for each pt. Statistical analyses were performed with the composite maxSUV (cSUV) and Deauville scores (cDSc) (using EXCEL). Following statistics were performed (separately and combined in HL and DLBCL); mean+SD, PPV and NPV for complete response (CR) Vs. progressive disease (PD) on PETi using the following variables 1. cSUV and 2. cDSc and 3. delta change (DELT). Median progression free survival (PFS) was the clinical endpoint for response. Results: The mean PFS in our group was 17 and 15 months in HL and DLBCL respectively. Using cut off thresholds for intP to predict CR at cSUV<=2.0, , cDSC<=2.0 and DELT >=80%,. In HL: for cSUV- PPV 67%, NPV 95%; for DELT of cSUV PPV 100%, NPV 95%; for cDSC-PPV 30%, NPV 100%. In DLBCL: for cSUV- PPV 25%, NPV 100%; for DELT of cSUV PPV 33%, NPV 100%; for cDSC- PPV 50%, NPV 100%. Conclusion: The results from our series suggest that PETi has a role not only in HL but in DLBCL as well. Our modest cohort suggests that a negative PETi in DLBCL had a NPV of 100% across cSUV, cDSc and DELT, with regards to CR. Our data also suggests that PETe is not needed if PETi is -ve. While in HL subset, our results concur with results from other groups, this needs to be validated in a larger series. Disclosures No relevant conflicts of interest to declare.


2021 ◽  
pp. 1-11
Author(s):  
Juan Pablo Alderuccio ◽  
Russ A. Kuker ◽  
Priscila Barreto-Coelho ◽  
Bianca M. Martinez ◽  
Feng Miao ◽  
...  

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