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High total metabolic tumor volume at baseline predicts survival independent of response to therapy.

ABSTRACT: Early identification of ultra-risk diffuse large B-cell lymphoma (DLBCL) patients is needed to aid stratification to innovative treatment. Previous studies suggested high baseline total metabolic tumor volume (TMTV) negatively impacts survival of DLBCL patients. We analyzed the prognostic impact of TMTV and prognostic indices in DLBCL patients, aged 60 to 80 years, from the phase 3 REMARC study that randomized responding patients to R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) into maintenance lenalidomide or placebo. TMTV was computed on baseline positron emission tomography/computed tomography using the 41% maximum standardized uptake value method; the optimal TMTV cutoff for progression-free (PFS) and overall survival (OS) was determined and confirmed by a training validation method. There were 301 out of 650 evaluable patients, including 192 patients classified as germinal center B-cell-like (GCB)/non-GCB and MYC/BCL2 expressor. Median baseline TMTV was 238 cm3; optimal TMTV cutoff was 220 cm3. Patients with high vs low TMTV showed worse/higher Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2, stage III or IV disease, >1 extranodal site, elevated lactate dehydrogenase, International Prognostic Index (IPI) 3-5, and age-adjusted IPI 2-3. High vs low TMTV significantly impacted PFS and OS, independent of maintenance treatment. Although the GCB/non-GCB profile and MYC expression did not correlate with TMTV/survival, BCL2 >70% impacted PFS and could be stratified by TMTV. Multivariate analysis identified baseline TMTV and ECOG PS as independently associated with PFS and OS. Even in responding patients, after R-CHOP, high baseline TMTV was a strong prognosticator of inferior PFS and OS. Moreover, TMTV combined with ECOG PS may identify an ultra-risk DLBCL population. This trial was registered at www.clinicaltrials.gov as #NCT01122472.

SUBMITTER: Vercellino L

PROVIDER: S-EPMC7162688 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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High total metabolic tumor volume at baseline predicts survival independent of response to therapy.

Vercellino Laetitia L Cottereau Anne-Segolene AS Casasnovas Olivier O Tilly Hervé H Feugier Pierre P Chartier Loic L Fruchart Christophe C Roulin Louise L Oberic Lucie L Pica Gian Matteo GM Ribrag Vincent V Abraham Julie J Simon Marc M Gonzalez Hugo H Bouabdallah Reda R Fitoussi Olivier O Sebban Catherine C López-Guillermo Armando A Sanhes Laurence L Morschhauser Franck F Trotman Judith J Corront Bernadette B Choufi Bachra B Snauwaert Sylvia S Godmer Pascal P Briere Josette J Salles Gilles G Gaulard Philippe P Meignan Michel M Thieblemont Catherine C

Blood 20200401 16

Early identification of ultra-risk diffuse large B-cell lymphoma (DLBCL) patients is needed to aid stratification to innovative treatment. Previous studies suggested high baseline total metabolic tumor volume (TMTV) negatively impacts survival of DLBCL patients. We analyzed the prognostic impact of TMTV and prognostic indices in DLBCL patients, aged 60 to 80 years, from the phase 3 REMARC study that randomized responding patients to R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristi ...[more]

PMID: 31978225

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Project description:BACKGROUND:Standardized treatment in pediatric patients with Hodgkin's lymphoma (HL) follows risk stratification by tumor stage, erythrocyte sedimentation rate and tumor bulk. We aimed to identify quantitative parameters from pretherapeutic FDG-PET to assist prediction of response to induction chemotherapy. METHODS:Retrospective analysis in 50 children with HL (f:18; m:32; median age, 14.8 [4-18] a) consecutively treated according to EuroNet-PHL-C1 (n = 42) or -C2 treatment protocol (n = 8). Total metabolic tumor volume (MTV) in pretherapeutic FDG-PET was defined using a semi-automated, background-adapted threshold. Metabolic (SUVmax, SUVmean, SUVpeak, total lesion glycolysis [MTV*SUVmean]) and heterogeneity parameters (asphericity [ASP], entropy, contrast, local homogeneity, energy, and cumulative SUV-volume histograms) were derived. Early response assessment (ERA) was performed after 2 cycles of induction chemotherapy according to treatment protocol and verified by reference rating. Prediction of inadequate response (IR) in ERA was based on ROC analysis separated by stage I/II (1 and 26 patients) and stage III/IV disease (7 and 16 patients) or treatment group/level (TG/TL) 1 to 3. RESULTS:IR was seen in 28/50 patients (TG/TL 1, 6/12 patients; TG/TL 2, 10/17; TG/TL 3, 12/21). Among all PET parameters, MTV best predicted IR; ASP was the best heterogeneity parameter. AUC of MTV was 0.84 (95%-confidence interval, 0.69-0.99) in stage I/II and 0.86 (0.7-1.0) in stage III/IV. In patients of TG/TL 1, AUC of MTV was 0.92 (0.74-1.0); in TG/TL 2 0.71 (0.44-0.99), and in TG/TL 3 0.85 (0.69-1.0). Patients with high vs. low MTV had IR in 86 vs. 0% in TG/TL 1, 80 vs. 29% in TG/TL 2, and 90 vs. 27% in TG/TL 3 (cut-off, > 80 ml, > 160 ml, > 410 ml). CONCLUSIONS:In this explorative study, high total MTV best predicted inadequate response to induction therapy in pediatric HL of all pretherapeutic FDG-PET parameters - in both low and high stages as well as the 3 different TG/TL. TRIAL REGISTRATION:Ethics committee number: EA2/151/16 (retrospectively registered).

Project description:ContextMale hypogonadism adversely affects body composition, bone mineral density (BMD), and metabolic health. A previous report showed that pre-treatment testosterone (T) levels of <200 ng/dl is associated with greater improvement in spine BMD with T therapy. However, to date, there is no study that investigates whether baseline T levels also influence body composition and metabolic response to T therapy.ObjectiveThe aim of this study is to determine if there are differences in the changes in body composition, metabolic profile, and bone turnover markers, in addition to BMD, in response to T therapy in men with a baseline T level of <264 ng/dl compared to those with levels ≥264 ng/dl.MethodsThis is a secondary analysis of a single-arm, open-label clinical trial (NCT01378299) on pharmacogenetics of response to T therapy conducted between 2011 and 2016 involving 105 men (40-74 years old), with average morning T < 300 ng/dl, given intramuscular T cypionate 200 mg every 2 weeks for 18 months. Subjects were divided into those with baseline T levels of <264 ng/dl (N = 43) and those with ≥264 ng/dl (N = 57). T and estradiol (E2) were measured by liquid chromatography/mass spectrometry; serum bone turnover markers (C-telopeptide [CTX], osteocalcin, and sclerostin), adiponectin, and leptin were measured by enzyme-linked immunosorbent assay; glycated hemoglobin (HbA1c) was measured by high-performance liquid chromatography; and areal BMD and body composition was measured by dual-energy x-ray absorptiometry (DXA).ResultsMen with T < 264 ng/dl showed greater increases in total fat-free mass (FFM) at 18 months compared to those with T ≥ 264 ng/dl (4.2 ± 4.1 vs. 2.7 ± 3.8%; p = 0.047) and unadjusted appendicular FFM at 6 and 18 months (8.7 ± 11.5 vs. 4.4 ± 4.3%, 7.3 ± 11.6 vs. 2.4 ± 6.8%; p = 0.033 and p = 0.043, respectively). Men with T ≥ 264 ng/dl showed significant decreases in HbA1c at 12 months (-3.1 ± 9.2 vs. 3.2 ± 13.9%; p = 0.005), fasting glucose at 18 months (-4.2 ± 31.9 vs. 13.0 ± 57.3%; p = 0.040), LDL at 6 months (-6.4 ± 27.5 vs. 12.8 ± 44.1%; p = 0.034), and leptin at 18 months (-40.2 ± 35.1 vs. -27.6 ± 31.0%; p = 0.034) compared to those with T < 264 ng/dl. No significant differences in BMD and bone turnover markers were observed.ConclusionT therapy results in improvement in body composition irrespective of baseline T levels but T < 264 ng/dl is associated with greater improvement in FFM, whereas a T level of ≥264 ng/dl favors improvement in metabolic profile.

Project description:BackgroundCurrent radiological assessments of 18fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging data in diffuse large B-cell lymphoma (DLBCL) can be time consuming, do not yield real-time information regarding disease burden and organ involvement, and hinder the use of FDG-PET to potentially limit the reliance on invasive procedures (e.g. bone marrow biopsy) for risk assessment.MethodsOur aim is to enable real-time assessment of imaging-based risk factors at a large scale and we propose a fully automatic artificial intelligence (AI)-based tool to rapidly extract FDG-PET imaging metrics in DLBCL. On availability of a scan, in combination with clinical data, our approach generates clinically informative risk scores with minimal resource requirements. Overall, 1268 patients with previously untreated DLBCL from the phase III GOYA trial (NCT01287741) were included in the analysis (training: n = 846; hold-out: n = 422).ResultsOur AI-based model comprising imaging and clinical variables yielded a tangible prognostic improvement compared to clinical models without imaging metrics. We observed a risk increase for progression-free survival (PFS) with hazard ratios [HR] of 1.87 (95% CI: 1.31-2.67) vs 1.38 (95% CI: 0.98-1.96) (C-index: 0.59 vs 0.55), and a risk increase for overall survival (OS) (HR: 2.16 (95% CI: 1.37-3.40) vs 1.40 (95% CI: 0.90-2.17); C-index: 0.59 vs 0.55). The combined model defined a high-risk population with 35% and 42% increased odds of a 4-year PFS and OS event, respectively, versus the International Prognostic Index components alone. The method also identified a subpopulation with a 2-year Central Nervous System (CNS)-relapse probability of 17.1%.ConclusionOur tool enables an enhanced risk stratification compared with IPI, and the results indicate that imaging can be used to improve the prediction of central nervous system relapse in DLBCL. These findings support integration of clinically informative AI-generated imaging metrics into clinical workflows to improve identification of high-risk DLBCL patients.Trial registrationRegistered clinicaltrials.gov number: NCT01287741.

Project description:AimTo investigate the respective influence of software tool and total metabolic tumor volume (TMTV0) calculation method on prognostic stratification of baseline 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography ([18F]FDG-PET) in newly diagnosed Hodgkin lymphoma (HL).Methods59 patients with newly diagnosed HL were retrospectively included. [18F]FDG-PET was performed before any treatment. Four sets of TMTV0 were calculated with Beth Israel (BI) software: based on an absolute threshold selecting voxel with standardized uptake value (SUV) >2.5 (TMTV02.5), applying a per-lesion threshold of 41% of the SUV max (TMTV041) and using a per-patient adapted threshold based on SUV max of the liver (>125% and >140% of SUV max of the liver background; TMTV0125 and TMTV0140). TMTV041 was also determined with commercial software for comparison of software tools. ROC curves were used to determine the optimal threshold for each TMTV0 to predict treatment failure.ResultsMedian follow-up was 39 months. There was an excellent correlation between TMTV041 determined with BI and with the commercial software (r = 0.96, p<0.0001). The median TMTV0 value for TMTV041, TMTV02.5, TMTV0125 and TMTV0140 were respectively 160 (used as reference), 210 ([28;154] p = 0.005), 183 ([-4;114] p = 0.06) and 143 ml ([-58;64] p = 0.9). The respective optimal TMTV0 threshold and area under curve (AUC) for prediction of progression free survival (PFS) were respectively: 313 ml and 0.70, 432 ml and 0.68, 450 ml and 0.68, 330 ml and 0.68. There was no significant difference between ROC curves. High TMTV0 value was predictive of poor PFS in all methodologies: 4-years PFS was 83% vs 42% (p = 0.006) for TMTV02.5, 83% vs 41% (p = 0.003) for TMTV041, 85% vs 40% (p<0.001) for TMTV0125 and 83% vs 42% (p = 0.004) for TMTV0140.ConclusionIn newly diagnosed HL, baseline metabolic tumor volume values were significantly influenced by the choice of the method used for determination of volume. However, no significant differences were found in term of prognosis.

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High total metabolic tumor volume at baseline predicts survival independent of response to therapy.

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High total metabolic tumor volume at baseline predicts survival independent of response to therapy.

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