Interim FDG-PET in Hodgkin lymphoma: a compass for a safe navigation in clinical trials?

Gallamini, Andrea; Kostakoğlu, Lale

doi:10.1182/blood-2012-03-403790

Cited by 60 publications

(31 citation statements)

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“…Prospective and randomized clinical studies evaluating the impact of FDG-PET/CT for response-adapted approaches have been completed. In terms of the question of whether interim FDG-PET/CT is a compass for a safe navigation in HL, 19 the current answer with existing techniques and available data is no. Based on present data, FDG-PET/CT has not been able to discriminate a low-risk earlystage HL group in whom RT may be withheld with respect to acute disease control.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, results of randomized phase 3 clinical trials incorporating response-adapted treatment strategies based on interim FDG-PET/CT to guide treatment decisions have been completed recently in an attempt to answer the question of whether interim FDG-PET/CT is a compass for safe navigation in HL. 19 There are also multiple novel FDG-PET/ CT applications using quantitative techniques, and new imaging modalities are being investigated for the potential incorporation into clinical care for better management of HL patients.…”

Section: Introductionmentioning

confidence: 99%

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The role of FDG-PET in defining prognosis of Hodgkin lymphoma for early-stage disease

Evens

Kostakoğlu

2014

Blood

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Given the excellent survival rates for early-stage Hodgkin lymphoma (HL), the young age of many patients, and concerns regarding acute and late treatment-related toxicities, there is a desire to have a predictive tool that enables therapy to be tailored toward the individual patient. Early (or interim) 18F-fluorodeoxyglucose positron emission tomography with computerized tomography (FDG-PET/CT), as a test of tumor sensitivity to ongoing/planned therapy, has been shown to be prognostic for survival in HL. Based on results of interim FDG-PET/CT, therapy may be subsequently modified through minimization or via intensification for low- and high-risk patient populations, respectively (ie, response-adapted therapy). Important data have been generated to standardize the interpretability and reproducibility of interim FDG-PET/CT (eg, the Deauville 5-point system), and observational and noncontrolled prospective studies have produced evidence supporting the hypothesis that response-adapted therapy may potentially serve as a predictive tool. Furthermore, results from noninferiority phase 3 clinical trials randomizing early-stage HL patients with negative interim FDG-PET/CT to combined modality therapy versus chemotherapy alone have been reported. The current collective findings from these randomized early-stage HL studies have shown that acute relapse rates are lower with combined modality therapy, even in patients with negative interim FDG-PET/CT. Additional randomized response-adapted studies are ongoing and novel FDG-PET/CT applications involving quantitative techniques and innovative imaging modalities are being investigated to identify more robust imaging biomarkers. Treatment of early-stage HL remains a clinical management choice for physicians and patients to make with consideration of acute and long-term outcomes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The role of FDG-PET in defining prognosis of Hodgkin lymphoma for early-stage disease

Evens

Kostakoğlu

2014

Blood

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“…Prospective and randomized clinical studies evaluating the impact of FDG-PET/CT for response-adapted approaches have been completed. In terms of the question of whether interim FDG-PET/CT is a compass for a safe navigation in HL, 19 the current answer with existing techniques and available data is no. Based on present data, FDG-PET/CT has not been able to discriminate a low-risk early-stage HL group in whom RT may be withheld with respect to acute disease control.…”

Section: Discussionmentioning

confidence: 99%

“…[12][13][14][15][16][17][18] Numerous studies have been published over the past decade regarding the clinical utility of FDG-PET/CT in the management of HL. [14][15][16][17][18][19][20][21][22] These include important data that have been produced regarding the standardization of the reproducibility and interpretability of FDG-PET/CT, which are critical for the appropriate incorporation of this modality into routine clinical practice. In addition, observational and noncontrolled prospective studies have generated hypotheses supporting the concept of early (interim) risk assessment using FDG-PET/CT imaging for prognostication and prediction of outcome.…”

Section: Introductionmentioning

confidence: 99%

The role of FDG-PET in defining prognosis of Hodgkin lymphoma for early-stage disease

Evens

Kostakoğlu

2014

Hematology

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“…TMTV measured on a baseline PET scan in HL is a biomarker of the activity of the microenvironment cells. The early response to treatment expresses the switch-off of activity of these cells under the first two cycles of chemotherapy and is an indirect surrogate of tumour chemosensitivity [17]. In this study both TMTV and ΔSUVmaxPET0-2 were independent predictors of outcome, and each had a strong prognostic value.…”

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confidence: 71%

Baseline metabolic tumour volume in Hodgkin lymphoma: the prognostic value of accessory cells

Meignan

2014

Eur J Nucl Med Mol Imaging

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At the present time Hodgkin lymphoma (HL) can be cured in more than 80 % of all patients [1]. Over 90 % of patients with early-stage HL are cured with contemporary combinedmodality therapy, but there are still 25 -30 % of patients with advanced-stage disease who are not cured with the ABVD regimen alone [1,2]. The International Prognostic Score (IPS) fails to recognize these patients with a high risk of treatment failure since the range of outcomes it delineates has narrowed with treatment improvement [1]. Although clinical prognostic scores continue to be routinely used, the need to identify patients with poorer risk has focused research on the tumoral microenvironment to find valuable prognostic information. Indeed, the tumour tissue in HL is composed of a few scattered neoplastic cells called Hodgkin and ReedSternberg (HRS) cells, which account for less than 1 % of all the cells found in biopsy specimens, that are surrounded by an overwhelming population of nonneoplastic mononuclear bystander cells. These cells (CCR4-expressing cell subsets, including eosinophils, histiocytes, macrophages, plasma cells, and Th2 and Treg lymphocytes) are recruited by chemokines produced by the HRS cells and induce the expression of antiapoptotic proteins in HRS cells and their immortalization via a paracrine loop [3,4]. There is an intimate relationship between the HRS cells and reactive cells of the microenvironment that enables the tumour to thrive and evade immune surveillance. Some recent studies have suggested a prognostic role for the nonneoplastic surrounding cells.In classic HL (CHL) tumour-associated macrophages (TAMs) have been shown to be associated with inferior outcomes [5]. Steidl et al. showed that a macrophage gene expression signature is associated with primary treatment failure in CHL and subsequently showed, using an independent validation cohort, that an increase in CD68-positive macrophages in the microenvironment is associated with inferior outcomes [5]. In the E2496 Intergroup trial, a multicentre phase 3 randomized controlled trial comparing ABVD and Stanford V chemotherapy in 287 patients with locally extensive and advanced stage CHL, increased CD68 or CD163 expression was significantly associated with inferior 5-year failure-free survival (FFS; 64 % vs. 78 % and 63 % vs. 82 %) and 5-year overall survival (OS; 81 % vs. 94 % and 81 % vs. 96 %). Multivariate analysis with clinical and biological factors linked to FFS (lymphocyte count, stage 4 disease) and OS (age ≥45 years) showed that increased CD68 or CD163 expression are significant independent predictors of inferior FFS and OS [6]. However, prognostic indices using these results in routine have not yet been built.HL is a lymphoma showing FDG avidity with 100 % of patients positive at baseline, and FDG PET is currently the most accurate staging modality [7]. It has been shown that different mechanisms of glucose uptake, e.g. via GLUT1 in HRS cells and via GLUT3 in the microenvironment, contribute to PET positivity of the tumour [8]. In a recent study...

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Interim FDG-PET in Hodgkin lymphoma: a compass for a safe navigation in clinical trials?

Cited by 60 publications

References 65 publications

The role of FDG-PET in defining prognosis of Hodgkin lymphoma for early-stage disease

The role of FDG-PET in defining prognosis of Hodgkin lymphoma for early-stage disease

The role of FDG-PET in defining prognosis of Hodgkin lymphoma for early-stage disease

Baseline metabolic tumour volume in Hodgkin lymphoma: the prognostic value of accessory cells

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