Total Lesion Glycolysis Improves Tumor Burden Evaluation and Risk Assessment at Diagnosis in Hodgkin Lymphoma

Hodgkin lymphoma (HL) is a hematological malignancy with an excellent prognosis. However, we still need to identify those patients that could experience failed standard frontline chemotherapy. Tumor burden evaluation and standard decisions are based on Ann Arbor (AA) staging, but this approach may be insufficient in predicting outcomes. We aim to study new ways to assess tumor burden through volume-based PET parameters to improve the risk assessment of HL patients. We retrospectively analyzed 101 patients with HL from two hospitals in the Balearic Islands between 2011 and 2018. Higher metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were significantly associated with a higher incidence of III-IV AA stages, B-symptoms, hypoalbuminemia, lymphopenia, and higher IPS. Standardized uptake value (SUVmax) was significantly related to AA stage and hypoalbuminemia. We found that TLG or the combination of SUVmax, TLG, and MTV significantly improved the risk assessment when compared to AA staging. We conclude that TLG is the best single PET/CT-related tumor-load parameter that significantly improves HL risk assessment when compared to AA staging. If confirmed in a larger and validated sample, this information could be used to modify standard frontline therapy and justifies the inclusion of TLG inside an HL prognostic score.

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Risk assessment in the management of newly diagnosed classical Hodgkin lymphoma

Blood ◽

10.1182/blood-2014-07-537480 ◽

2015 ◽

Vol 125 (11) ◽

pp. 1693-1702 ◽

Cited By ~ 26

Author(s):

Joseph M. Connors

Keyword(s):

Risk Assessment ◽

Hodgkin Lymphoma ◽

Dynamic Assessment ◽

Systemic Infection ◽

Scoring Systems ◽

Tumor Burden ◽

Related Factors ◽

Specific Organ ◽

Prognostic Scoring Systems ◽

Careful Assessment

Abstract Treatment of Hodgkin lymphoma is associated with 2 major types of risk: that the treatment may fail to cure the disease or that the treatment will prove unacceptably toxic. Careful assessment of the amount of the lymphoma (tumor burden), its behavior (extent of invasion or specific organ compromise), and host related factors (age; coincident systemic infection; and organ dysfunction, especially hematopoietic, cardiac, or pulmonary) is essential to optimize outcome. Elaborately assembled prognostic scoring systems, such as the International Prognostic Factors Project score, have lost their accuracy and value as increasingly effective chemotherapy and supportive care have been developed. Identification of specific biomarkers derived from sophisticated exploration of Hodgkin lymphoma biology is bringing promise of further improvement in targeted therapy in which effectiveness is increased at the same time off-target toxicity is diminished. Parallel developments in functional imaging are providing additional potential to evaluate the efficacy of treatment while it is being delivered, allowing dynamic assessment of risk during chemotherapy and adaptation of the therapy in real time. Risk assessment in Hodgkin lymphoma is continuously evolving, promising ever greater precision and clinical relevance. This article explores the past usefulness and the emerging potential of risk assessment for this imminently curable malignancy.

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Risk-adapted therapy for advanced-stage Hodgkin lymphoma

Hematology ◽

10.1182/asheducation-2018.1.200 ◽

2018 ◽

Vol 2018 (1) ◽

pp. 200-206 ◽

Cited By ~ 5

Author(s):

Michael A. Spinner ◽

Ranjana H. Advani

Keyword(s):

Hodgkin Lymphoma ◽

Checkpoint Inhibitors ◽

Intensive Therapy ◽

Metabolic Tumor Volume ◽

Brentuximab Vedotin ◽

Total Lesion Glycolysis ◽

Advanced Stage ◽

Interim Pet ◽

Quantitative Pet ◽

Risk Patients

Abstract More than 80% of patients with advanced-stage Hodgkin lymphoma are now cured with contemporary treatment approaches. The ongoing challenge is how to further improve outcomes by identifying both high-risk patients who may benefit from more intensive frontline therapy to reduce the risk of relapse as well as lower-risk patients who may do just as well with less intensive therapy. Numerous trials have used an interim positron emission tomography (PET) response-adapted approach to evaluate early escalation or deescalation of therapy for patients with a positive or negative interim PET scan, respectively. Recent trials have incorporated novel agents, including brentuximab vedotin (BV) and the immune checkpoint inhibitors, in the frontline setting. Based on results of the ECHELON-1 trial, the Food and Drug Administration approved BV in combination with adriamycin, vinblastine, and dacarbazine chemotherapy for stage III to IV Hodgkin lymphoma. Improved methods to assess higher risk at diagnosis using quantitative PET metrics, such as metabolic tumor volume and total lesion glycolysis, and incorporation of emerging biomarkers may further refine patient selection for more intensive upfront therapy. The ultimate goal is to achieve the highest level of efficacy for an individual patient while minimizing the short- and long-term toxicities.

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Metabolic Tumor Volume for Patients with Lymphomas

Journal of oncology: diagnostic radiology and radiotherapy ◽

10.37174/2587-7593-2021-4-4-40-45 ◽

2021 ◽

Vol 4 (4) ◽

pp. 40-45

Author(s):

Yu. N. Vinogradova ◽

N. V. Ilyin ◽

M. S. Tlostanova ◽

A. A. Ivanova

Keyword(s):

Tumor Volume ◽

Visual Analysis ◽

International Prognostic Index ◽

Prognostic Index ◽

Clinical Importance ◽

Standardized Uptake Value ◽

Metabolic Tumor Volume ◽

Total Lesion Glycolysis ◽

Positron Emission ◽

Pet Ct

Visual analysis of positron emission tomography/computed tomography (PET/CT) scans and semiquantitative parameter of glucose’s standardized uptake value are used in PET/CT with 18F-fluorodeoxyglucose (18F-FDG). Recently some volumetric parameters, which can evaluate metabolic tumor volume for patients with lymphomas and total lesion glycolysis in the tumor sites are established. In our study this problem was analyzed for different types of lymphomas considering clinical importance of these rates and their bond to known factors of international prognostic index.

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Baseline PET-Derived Metabolic Tumor Volume Metrics Did Not Predict Outcomes in Follicular Lymphoma Patients Treated with First-Line Immunochemotherapy and Antibody Maintenance in the Phase III GALLIUM Study

Blood ◽

10.1182/blood-2018-99-117235 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2882-2882 ◽

Cited By ~ 3

Author(s):

Sally F Barrington ◽

Judith Trotman ◽

Deniz Sahin ◽

David Belada ◽

Andrew Davies ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Standardized Uptake Value ◽

Metabolic Tumor Volume ◽

Tumor Burden ◽

Phase Iii ◽

First Line ◽

Employment Equity ◽

Advisory Committees ◽

Equity Ownership

Abstract Introduction: Evidence suggests that baseline 18fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography-derived parameters, such as metabolic tumor volume (MTV) and maximum standardized uptake value (SUVmax), may predict progression-free survival (PFS) in patients (pts) with follicular lymphoma (FL) treated with first-line R-CHOP immunochemotherapy. However, data from pts routinely treated with bendamustine or antibody maintenance are lacking, and several methods have been used to evaluate PET metrics for tumor burden in pts with lymphoma. This prospective exploratory analysis assessed the prognostic value of baseline MTV, total glycolytic activity (TLG), and SUVmax for PFS and overall survival (OS) in pts with FL treated with first-line obinutuzumab (GA101; G) or rituximab (R) plus chemotherapy (chemo) in the Phase III GALLIUM study (NCT01332968; Marcus et al. N Engl J Med 2017), using two published methods for measuring tumor burden. Methods: Pts ≥18 years with previously untreated FL (grade 1-3a) and advanced disease (Stage III/IV or Stage II with tumor diameter ≥7cm) requiring treatment were randomized 1:1 to receive 6-8 cycles of G (1000mg intravenous [IV] on days [D] 1, 8, and 15 of cycle [C] 1 and D1, C2-6 or 8) or R (375mg/m2 IV on D1) plus standard chemo (CHOP, bendamustine, or CVP). Responding pts received the same antibody as maintenance every 2 months for up to 2 years. After an early protocol amendment, PET imaging at baseline and end of induction (EOI) was mandatory in the first 170 pts and optional thereafter. Independent reviewers segmented FDG-avid tumors applying thresholds of I) standardized uptake value (SUV)max ≥2.5, and II) SUVmax ≥41% of lesional maximum SUV and a minimum volume of 1mL, using MIM software. Results were analyzed for the PET intent-to-treat population. MTV, TLG, and SUVmax were split into quartiles: Q1, <25%; Q2, 25-49%; Q3, 50-74%; and Q4, 75-100%, based on their distribution in the available population. Investigator-assessed PFS and OS were estimated using Kaplan-Meier methods (data cut-off, February 12, 2018). Hazard ratios refer to stratified log-rank tests comparing Q2, Q3, and Q4 with Q1, adjusted for the randomization stratification factors FLIPI score and chemo regimen. Multivariable Cox analyses were also undertaken to investigate whether baseline MTV quartiles and other covariates were prognostic for PFS. Statistical significance at 0.05 was determined using the Wald test. Results: Of 1202 enrolled FL pts, 609 had a baseline PET scan and 521 had baseline PET scans available for all quantitative assessments by central review; 303 pts (58%) received bendamustine, 179 (34%) CHOP, and 39 (8%) CVP. After a median follow-up of 57 months, none of the 3 baseline PET parameters (MTV or TLG measured by either method or SUVmax) significantly predicted PFS (Table). Multivariable analysis, which included baseline pt and disease characteristics, confirmed that MTV did not predict PFS. Consistent with the primary analysis, receipt of G-chemo was an independent predictor of improved PFS. Conclusions: Contrary to previous reports, these prospective data from the Phase III GALLIUM study show that baseline quantitative PET metrics do not predict PFS or OS in FL pts receiving first-line immunochemotherapy (of whom the majority received bendamustine) followed by antibody maintenance treatment, irrespective of the measurement method applied. Conversely, a previously reported analysis from GALLIUM suggests that PET-complete metabolic response at EOI assessed using Lugano 2014 criteria is a strong predictor of long-term outcome in these pts. Table. Table. Disclosures Barrington: EPSRC: Research Funding; Department of Health (England): Research Funding; F.Hoffmann-La Roche: Membership on an entity's Board of Directors or advisory committees; National Institute of Health Research: Research Funding; MRC: Research Funding; CRUK: Research Funding. Trotman:Janssen: Other: Unremunerated member of Ad Board, Research Funding; Celgene: Other: Unremunerated member of Ad Board, Research Funding; PCYC: Research Funding; Takeda: Other: Unremunerated member of Ad Board; F. Hoffman-La Roche: Other: Travel to meeting, Unremunerated member of Ad Board, Research Funding; Beigene: Research Funding. Sahin:Roche: Employment, Equity Ownership. Belada:Janssen-Cilag: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Celgene: Research Funding; Roche: Consultancy, Research Funding; Takeda: Consultancy, Research Funding. Davies:Janssen: Consultancy, Honoraria; GSK: Research Funding; Karyopharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Research Funding; Acerta Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; F. Hoffman-La Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Kite: Consultancy; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Honoraria, Research Funding; Pfizer: Research Funding. MacEwan:Consultant Radiologist/ Nuc Med Physician: Consultancy. Owen:Pharmacyclics: Research Funding; F. Hoffmann-La Roche Ltd: Honoraria, Research Funding; Celgene: Research Funding; AstraZeneca: Honoraria, Research Funding; Merck: Honoraria; Janssen: Honoraria, Research Funding; Teva: Honoraria; AbbVie: Research Funding. Ptáčník:F. Hoffman-La Roche: Honoraria. Hiddemann:F. Hoffman-La Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Consultancy, Research Funding. Marcus:Roche: Consultancy, Other: Travel support and lecture fees ; Gilead: Consultancy; F. Hoffman-La Roche: Other: Travel support and lecture fees. Nielsen:F. Hoffmann-La Roche Ltd: Employment, Other: Ownership interests PLC. Mattiello:Roche: Employment. Zeuner:F. Hoffman-La Roche: Employment, Equity Ownership. Meignan:F. Hoffman-La Roche Ltd: Honoraria.

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The metabolic parameters based on volume in PET/CT are associated with clinicopathological N stage of colorectal cancer and can predict prognosis

EJNMMI Research ◽

10.1186/s13550-021-00831-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hidenori Kido ◽

Shunsuke Kato ◽

Kimihiko Funahashi ◽

Kazutoshi Shibuya ◽

Yousuke Sasaki ◽

...

Keyword(s):

Colorectal Cancer ◽

Standardized Uptake Value ◽

Threshold Value ◽

Metabolic Tumor Volume ◽

Total Lesion Glycolysis ◽

Metabolic Parameters ◽

Optimal Threshold ◽

Pet Ct ◽

Significant Difference ◽

N Stage

Abstract Background A combination of positron emission tomography and computed tomography (PET/CT) is an important modality for the diagnosis of carcinoma. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) have been reported as metabolic parameters in PET/CT since the late 1990s, and they are expected to be useful in diagnosing diverse cancers and as prognostic biomarkers. We evaluated the potential of these parameters in the prognosis of colorectal cancer (CRC) by comparing them with conventional parameters, including the maximum standardized uptake value (SUVmax). We enrolled 84 patients who underwent surgery for CRC without distal metastasis between April 2015 and April 2019. SUVmax, MTV, and TLG were measured by 18F-fluorodeoxyglucose (FDG)-PET/CT. To find an optimal threshold value related to prognosis, the volume of interest in the primary carcinoma was measured at fixed relative and absolute thresholds based on SUVmax (30%, 40%, and 50%; 2.5, 3.0, and 3.5, respectively), tumor-to-liver standardized uptake ratios, TLR (1.0, 1.5, and 2.0), and SUV normalized to lean body mass, SUL (2.0, 2.5, and 3.0). After classifying the patients into two groups according to pathological N stage, the optimal threshold values of all metabolic parameters were compared between groups using a non-parametric comparison test. Result The most suitable thresholds for MTV were a SUVmax of 3.5 and a TLR 2.0. TLG with a SUVmax value of 40% showed the most significant difference. The MTV standard uptake ratio of 2.0 was significantly associated with pathological N stage. Conclusion Our results suggest that an MTV TLR 2.0 on PET/CT reflects pathological N stage in local patients with CRC.

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Metabolic Tumor Volume Influences Response to Brentuximab-Vedotin in Relapsed Refractory Hodgkin Lymphoma

Blood ◽

10.1182/blood.v126.23.588.588 ◽

2015 ◽

Vol 126 (23) ◽

pp. 588-588

Author(s):

Yassine Al Tabaa ◽

Michel Meignan ◽

Scherman Elodie ◽

Corinne Haioun ◽

Pauline Brice ◽

...

Keyword(s):

Treatment Failure ◽

Hodgkin Lymphoma ◽

Tumor Volume ◽

Visual Analysis ◽

Single Agent ◽

B Cell Lymphoma ◽

Metabolic Tumor Volume ◽

Tumor Burden ◽

Brentuximab Vedotin ◽

Future Research

Abstract Purpose: The total metabolic tumor volume at baseline (T-MTV0) computed on PET has been proposed as a prognostic factor at staging in Hodgkin lymphoma (HL) and diffused large B cell lymphoma (DLBCL). It has also been described to play a role in non-HL treatment by monoclonal antibodies since it could influence antibody exposure and efficacy in a murine model (Dayde D, et al. Blood 2009) that has been confirmed in DLBCL patients study (Casasnovas O, et al. Abstract Lugano 2015). We hypothesized the metabolic tumor burden could influence the efficacy of a monoclonal antibody-drug conjugated (ADC) such as monotherapy based anti-CD30 ADC brentuximab-vedotin (BV). In the present study, we assessed the pre-treatment baseline total metabolic tumor volume based on PET evaluation in the response to BV treatment as a single agent in patients with RR-HL, as well as its prognostic value. Methods: A retrospective multi-center study was built from January 2011 to June 2015. Forty-one consecutive heavily pre-treated patients with a diagnosis of relapsed refractory HL (RR-HL) were included. PET was performed at baseline (PET0) and after 4-6 cycles of BV defining two groups of responders, good responder group achieving a complete metabolic response (CMR group, 23 patients), and non-responder group (no-CMR group, 18 patients), using the revised Lugano classification with the 5-point scale visual analysis PET/CT. T-MTV0 was measured with a semiautomatic method using a 41%-SUVmax-threshold. SUVmax at PET0 (SUVmaxPET0) was measured in each patient and represented the hottest lesion independently from the site. To assess the influence of the T-MTV0 on BV efficacy, we compared the baseline metabolic tumor volume between the two groups. The ROC curve was established to determine the optimal cut-off of T-MTV0 to predict treatment failure. Results: T-MTV0 ranged from 14 cm3 to 213 cm3 in the 41 patients (median 62 cm3; 25th - 75th percentiles 25 - 94 cm3) and SUVmaxPET0 ranged from 4,1 to 19,3 (median 10,4; 25th-75th percentiles 7,8 - 13,7). T-MTV0 was significantly higher in the no-CMR group as compared with the CMR group (median 96 and 30 cm3; 25th-75th percentiles 90 - 139 cm3 and 18 - 38 cm3, respectively; p< 0.01). Considering metabolic sites, the nodal metabolic tumor volume (N-MTV0) represented the main component of T-MTV0 and was significantly higher than the extra nodal metabolic tumor volume (EN-MTV0) in the CMR group (p = 0.025). However, the EN-MTV0 dominated in the no-CMR group and was significantly higher than the N-MTV0 (p = 0.01). SUVmaxPET0 as well as clinical characteristics were not significantly different in the two groups. Furthermore the TMTV0 cut-off value was 62 ml and predictive of treatment failure. Conclusion: In the present study, we demonstrated that tumor metabolic burden and nodal or extra-nodal localizations influence response to BV as a single agent in RR-HL patients, offering some future research directions in the development of new schedules of antibodies administration in anticancer therapy such as the concept of the individual adjustment of treatment dose to tumor burden. This may guide clinicians in their choice of therapeutic strategy. Disclosures Thieblemont: St. Louis Hospital, Paris, France: Employment. Cartron:Sanofi: Honoraria; Gilead: Honoraria; GSK: Honoraria; Roche: Consultancy, Honoraria; Celgene: Honoraria.

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PET/CT Parameters are Useful in Discrimination of Incidental Benign, Premalignant and Malignant Colonic Lesions

Nuklearmedizin ◽

10.1055/a-1084-4723 ◽

2020 ◽

Vol 59 (03) ◽

pp. 235-240

Author(s):

Emine Budak ◽

Ahmet Yanarateş

Keyword(s):

Tumor Volume ◽

Standardized Uptake Value ◽

Metabolic Tumor Volume ◽

Total Lesion Glycolysis ◽

Premalignant Lesions ◽

Benign Lesions ◽

Pet Ct ◽

Malignant Lesions ◽

Fdg Pet Ct

Abstract Aim The present study evaluates the role of PET parameters pertaining to incidentally detected foci of colorectal uptake (IFCU) on FDG PET/CT in the differentiation of benign, premalignant and malignant lesions. Methods This retrospective study included 74 patients. The colonoscopic and histopathological findings were regarded as the reference standards. The results were evaluated on a lesion basis by dividing the lesions into three groups as benign, premalignant and malignant. The maximum standardized uptake value (SUVmax), SUVmean, metabolic tumor volume(MTV) and total lesion glycolysis(TLG) values of the three groups were compared. Results There were 88 IFCU in a total of 74 patients (27 female, 47 male, mean age 65 years). Of the 88 IFCU, 26 were qualified as benign, 42 as premalignant and 20 as malignant. Malignant + premalignant lesions were found in 62/88 (70.4 %) of the IFCU. The SUVmax of the benign lesions was significantly lower than those of the premalignant and malignant lesions; and SUVmean was lower than that of the malignant lesions. The MTV of the malignant lesions was significantly higher than that of the premalignant and benign lesions; and TLG was higher than that of the premalignant lesions. The optimum cut-off value in differentiating between the malignant and non-malignant lesions was 9.15 for SUVmax, 5.05 for SUVmean, 4.7 for MTV and 30.25 for TLG. Conclusion PET parameters can guide the differentiation of benign, premalignant and malignant lesions with IFCU. Besides, patients with IFCU should undergo further evaluation due to high probability of premalignant and malignant lesions.

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Improving Evaluation of Disease Burden at Diagnosis in Hodgkin Lymphoma

Blood ◽

10.1182/blood-2020-141875 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 24-25

Author(s):

Ines Herraez ◽

Leyre Bento ◽

Jaume Daumal ◽

Alessandra Repetto ◽

Raquel Del Campo ◽

...

Keyword(s):

Computed Tomography ◽

Survival Analysis ◽

Hodgkin Lymphoma ◽

Fdg Pet ◽

Disease Burden ◽

Conflicts Of Interest ◽

Standardized Uptake Value ◽

Tumor Burden ◽

Bulky Disease ◽

Univariate Survival Analysis

Introduction: Hodgkin lymphoma (HL) is a hematological malignancy, with an inflammatory majority component of reactive cells and a few (1-2%) Reed-Sternberg cells (RSC). A high percentage of patients are cured with conventional strategies but approximately 15-30% relapse or progress. The standard tool to assess disease burden is the Ann Arbor Stage that classically categorizes HL in early (I-II) and advanced stages (III-IV). However, AA staging lacks accuracy in predicting outcome. New ways to asses tumor burden, such as baseline fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT), detect active disease with higher sensitivity in comparison with computed tomography (CT). Additionally, different volumetric parameters, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), may be obtained from FDG PET/TC. We aim to improve disease burden testing using FDG PET/TC-related parameters, to better stratify HL patients at the time of diagnosis. Methods: We retrospectively selected patients with HL, homogeneously treated with ABVD +/- RT, at Son Espases and Son Llatzer University Hospitals in Palma de Mallorca from the databases of Pharmacy, Pathology and Nuclear Medicine Departments, to avoid selection bias. FDG PET/TC was done at baseline. MTV was measured with a semiautomatic method using a 41% maximum standardized uptake value (SUVmax) threshold and represents the sum of metabolic volumes of tumor tissues with increased FDG uptake. TLG was calculated by multiplying MTV and the mean SUV (SUVmean) of the MTV and was representative of the metabolic activity throughout the entire tumor. We used receiver operating curves (ROC) analysis to obtain the optimal cutoff for progression or death of all experimental FDG PET/TC-related variables. Standard clinical prognostic variables were obtained from medical records (age, gender, stage, bulky and ECOG PS) and main prognostic scores (IPS, EORTC and GHSG) were calculated. Progression-free survival (PFS) was considered the time from diagnosis to disease progression or death of any cause. Univariate survival analysis was done using Kaplan-meier plots and comparison between variables with log-rank test. Results: From August-2011 to November-2018, we included 101 patients. Table 1 shows main characteristics of patients. Median age was 37 years (14-83 years), 53% of patients had an advanced stage and 10% had bulky disease. With a median follow-up of 45 months (11-90), median PFS was 78%. The optimal cuttoffs obtained for MTV, TLG and SUVmax were 32.5, 167.8 and 10.4, respectively. In the univariate survival analysis, PFS was significantly influenced by MTV (p=0,007) and TLG (p=0.003), but not AA stage (Table 2). OS was significantly influenced by TLG (p=0.007) and SUVmax (p=0.001). With the three FDG PET/TC-related variables influencing HL survival we designed a FDG PET/TC score as follows: 1 point for high level of MTV, TLG or SUVmax (from 0 to 3). As shown in Table 2, this new FDG PET/TC score had a much better risk assessment that standard AA stage, being able to differentiate three risk groups with 100%, 84% and 65% 4-y PFS and 100%, 84% and 75% OS. Conclusions: The combination of functional 3D measurement of tumor burden (MTV, TLG and SUVmax) obtained from the FDG PET/TC at diagnosis, in HL, could be a valuable tool to better stratify the risk patients from tumor burden at the moment of diagnosis, when compared with standard AA staging. Disclosures No relevant conflicts of interest to declare.

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Total metabolic tumor volume as a survival predictor for patients with diffuse large B-cell lymphoma in the GOYA study

Haematologica ◽

10.3324/haematol.2021.278663 ◽

2021 ◽

Author(s):

Lale Kostakoglu ◽

Federico Mattiello ◽

Maurizio Martelli ◽

Laurie H. Sehn ◽

David Belada ◽

...

Keyword(s):

B Cell ◽

Tumor Volume ◽

Standardized Uptake Value ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Metabolic Tumor Volume ◽

Total Lesion Glycolysis ◽

Free Survival ◽

Large B Cell Lymphoma ◽

Large B Cell

This retrospective analysis of the phase III GOYA study investigated the prognostic value of baseline metabolic tumor volume parameters and maximum standardized uptake values for overall and progression-free survival in treatment-naïve diffuse large B-cell lymphoma. Baseline total metabolic tumor volume (determined for tumors >1 mL using a threshold of 1.5 times the mean liver standardized uptake value +2 standard deviations), total lesion glycolysis, and maximum standardized uptake value positron emission tomography data were dichotomized based on receiver operating characteristic analysis and divided into quartiles by baseline population distribution. Of 1,418 enrolled patients, 1,305 had a baseline positron emission tomography scan with detectable lesions. Optimal cut-offs were 366 cm3 for total metabolic tumor volume and 3,004g for total lesion glycolysis. High total metabolic tumor volume and total lesion glycolysis predicted poorer progression-free survival, with associations retained after adjustment for baseline and disease characteristics (high total metabolic tumor volume hazard ratio: 1.71 [95% CI, 1.35–2.18]; total lesion glycolysis hazard ratio: 1.46 [95% CI, 1.15–1.86]). Total metabolic tumor volume was prognostic for progression-free survival in subgroups with International Prognostic Index scores 0–2 and 3–5, and those with different cell-of-origin subtypes. Maximum standardized uptake value had no prognostic value in this setting. High total metabolic tumor volume associated with high International Prognostic Index or non-germinal center B-cell classification identified the highest-risk cohort for unfavorable prognosis. In conclusion, baseline total metabolic tumor volume and total lesion glycolysis are independent predictors of progression-free survival in patients with diffuse large B-cell lymphoma after first-line immunochemotherapy.

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Metabolic Tumor Volume and Soluble Cytokines Levels in Newly Diagnosed Hodgkin Lymphoma: What It Brings into the Staging Precision?

Blood ◽

10.1182/blood-2018-99-115150 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2933-2933 ◽

Cited By ~ 2

Author(s):

VIT K Prochazka ◽

Lenka Henzlova ◽

Marie Lukasova ◽

Veronika Hanackova ◽

Eva Kriegova ◽

...

Keyword(s):

High Risk ◽

Tumor Volume ◽

Metabolic Tumor Volume ◽

Tumor Burden ◽

Pet Ct ◽

Staging Systems ◽

Ann Arbor ◽

Frontline Treatment ◽

Systemic Symptoms ◽

Metabolic Tumor Burden

Abstract Background: Frontline therapy of Hodgkin lymphoma (HL) is strictly stage-adapted. Staging systems used are based on historical variables which only indirectly reflects tumor load (Ann Arbor stage) or lymphoma cytokine activity (systemic symptoms, erytrocyte sedimentation rate). With new, abbreviated interim PET-tailored chemotherapy schemes (2+2) and reduced radiotherapy protocols, there is a clinical need for precise staging tools. Last years have brought new insight into the prognostic role of metabolic quantitative PET parameters and HL-associated biomarkers. Total metabolic tumor volume (TMTV) measured using fluoro-deoxyglucose PET (FDG-PET) was found to be a predictor of therapy failure after frontline treatment (Kanoun 2014). Interestingly, TMTV was found capable of identifying poor responders within one (intermediate) staging group (Akhtari, 2018; Cottereau 2018). Serum concentrations of thymus and activation-regulated chemokine (TARC) and other cytokines have been proved to have prognostic significance in the patients treated both in the frontline and relapse setting (Moskowitz, 2015; Guidetti 2017). A relationship between pretreatment TMTV, baseline cytokines levels, and current staging systems has not been analyzed yet. Aim: To analyzed quantitative metabolic PET parameters and selected soluble biomarkers in the context of the staging systems used in the U.S. and Europe Methods: We have analyzed a prospectively enrolled cohort of forty-eight patients with HL who were diagnosed in two large university medical centers from 5/2015 to 2/2018. All pts have undergone pretreatment FDG-PET/CT with quantitative analysis of TMTV, Total Lesion Glycolysis (TLG), Maximum Standardized Uptake Volume (SUVmax.) and the Largest Tumor Diameter (LD) and were sampled for cytokine analysis within 16 (median) days from the PET/CT. We have analyzed a set of four serum biomarkers: CD30 (sCD30), CD163 (sCD163), TARC, and interleukin 6 (sIL6), which were measured using ELISA assays. Results: A cohort consisted of 22 males and 26 females with median age of 42 years (range 21-75). Histology subtype was known in all but one case: nodular sclerosis in 23, mixed cellularity 15, lymphocyte-rich in 5 and nodular-lymphocyte predominant (NLPHL) in four. Ann Arbor stages were as follows: I in 5, II in 20, III in 13 and IV in 10 of the pts with systemic symptoms in 20 (42%) of them. All pts were classified according to the German Hodgkin Study Group (GHSG) and NCCN staging systems. GHSG stages - limited, intermediate and advanced were seen in 8 (17%), 10 (21%) and 30 (62%) pts, respectively. NCCN stages were distributed into early favorable in 8 (17%), early unfavorable in 17 (35%) and advanced in 23 (48%) of the pts. Chemotherapy was applied in all but four pts using: BEACOPPesc, combined BEACOPP+ABVD, ABVD and ABV/COPP protocols in 7, 15, 16 and six pts respectively. Of four pts without chemo one case was treated with local radiotherapy and three with WaW (all of them with NLPHL). Treatment response was known in 41 (85%) of the cases with CR, PR, and PD in 33 (80.5%), 6 (14.6%) and two (4.9%) pts, respectively. Relationships between disease stages and PET-parameters are summarized in Table 1. Briefly, metabolic tumor burden (TMTV, TLG) identified two markedly different groups: low and intermediate/high risk. Similarly, cytokines levels were significantly lower in low-risk patients compared to those with intermediate-high risk (Table 2). Treatment outcome did not correlate either with GHSG nor NCCN stage. We found correlation of sIL-6 (p=0.03) but not sCD30 (p=0.09), sCD163 (p=0.14) and TARC (p=0.57) with CR achievement. In terms of PET-parameters the high TMTV>104 cm3 (P=0.046) and TLG>798 (P=0.003) were associated with not achieving of CR with NPV, PPV and test accuracy of 94.4, 22.0, 58.5 for TMTV and 100%, 36,4%, 66% for TLG, respectively. Conclusion: Adequate frontline treatment policy is vital for achieving an optimal balance between efficacy and toxicity. Current staging systems have a weak correlation with metabolic tumor burden: one-third of those recognized as advanced stage have the low burden, and vice versa about a half of intermediate-risk pts have high tumor burden. Combination of TMTV/TLG and cytokines can be currently used for decision making in borderline stage cases and probably could serve as a backbone for a new staging system in the future. Acknowledgment: IGA_LF_2018_004, MH CZ-DRO (FNOL, 00098892) Disclosures No relevant conflicts of interest to declare.

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